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<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: In human breast cancers, amplification of chromosome 11q13 correlates with lymph node metastasis and increased mortality. To date, two genes located within this amplicon, CCND1 and EMS1, were considered to act as oncogenes, because overexpression of both proteins, respectively cyclin D1 and cortactin, correlated well with 11q13 amplification. Cyclin D1 is involved in cell cycle regulation and the F-actin-binding protein cortactin in cytoskeletal dynamics and cell migration. To study the role of cortactin in mammary gland tumorigenesis, we examined mouse mammary tumor virus (MMTV)-cortactin transgenic mice and MMTV-cortactin/-MMTV-cyclin D1 bitransgenic mice. MMTV-cortactin transgenic mice were generated and intercrossed with previously described MMTV-cyclin D1 transgenic mice. Immunohistochemical, Northern and Western blot analyses were performed to study the expression of human transgene cortactin during mammary gland development and in mammary tumors. For tumor incidence studies, forced-bred, multiparous mice were used to enhance transgene expression in the mammary gland. Microscopical examination was performed using haematoxylin and eosin staining. Mammary gland tumors arose stochastically (incidence 21%) with a mean age of onset at 100 weeks. This incidence, however, did not exceed that of aged-matched control FVB/N mice (38%), which unexpectedly, also developed spontaneous mammary gland tumors. We mimicked 11q13 amplification by generating MMTV-cortactin/-MMTV-cyclin D1 bitransgenic mice but did not observe any synergistic effect of cortactin on cyclin D1-induced mammary hyperplasias or carcinomas, nor development of distant metastasis. Question: Do transgenic mice with mammary gland targeted expression of human cortactin develop ( pre-malignant ) breast tumors : studies in MMTV-cortactin and MMTV-cortactin/-cyclin D1 bitransgenic mice? <|endoftext|> <|assistant|> From this study, we conclude that development of (pre-malignant) breast tumors in either wild type or MMTV-cyclin D1 mice was not augmented due to mammary gland targeted overexpression of human cortactin.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Samples analyzed in proteomic studies by nanoelectrospray ionization (nanoESI) are extremely limited in quantity requiring careful sample handling to prevent loss upon transfer and to maintain sample concentration. To alleviate the operational process and reduce the cost of nanoESI, it is essential to develop more robust, simple and sensitive analytical variants of the process. Membrane funnel-based spray was developed for analysis of proteins/peptides in this study. The membrane funnel was fabricated from thin flexible membrane by a punching method using a homemade device. The performance of the membrane funnel-based spray was demonstrated by analyzing peptides, proteins and trypsin-digested samples in comparison of nanoESI and the Teflon sheet based microfunnel. Compared with the microfunnel, the membrane funnel can be fabricated easily by punching a thin flexible membrane using a sharp needle. Only 50 nL of sample was required for an analysis. The membrane funnel enhanced the spray sensitivity 100-fold. A total of 5 amol of on-spot sample loading was sufficient to provide a measurable signal on a 9.4 Tesla Fourier transform ion cyclotron resonance mass spectrometry system. High-mass proteins (up to 66 kDa) could be analyzed using this funnel-based spray system. Good sequence coverage was obtained for tryptic digested samples. Question: Do membrane funnel-based spray ionization for protein/peptide analysis by Fourier transform ion cyclotron resonance mass spectrometry? <|endoftext|> <|assistant|> A rapid, simple and cheap membrane funnel-based sample plate fabrication method was developed. The membrane funnel-based spray is a promising new variant of nanoESI capable of fast and sensitive analysis of peptides/proteins with great potential that could be extended to other applications, including quantitative analysis at high throughput and imaging mass spectrometry.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: To determine the relationship between stroke and lower esophageal dysfunction with vomiting and to identify an optimal nutrition protocol based on our findings. The lower and upper esophageal sphincter functions were assessed in 35 patients who had an acute stroke to determine whether gastric or jejunal enteral feeding was the optimal route. Stroke was due to unilateral ischemia in 20 patients, unilateral intracerebral hemorrhage in 8 patients, and global ischemia in 7 patients. Our study consisted of 18 men and 17 women with an average age of 64 years. Using standard esophageal manometric definitions, the lower esophageal sphincter function was below normal in 24 patients: 3 had global anoxia, 5 had unilateral hemorrhage, and 16 had unilateral ischemia. The upper esophageal sphincter function was low in 30 patients: 6 had global anoxia, 7 had unilateral hemorrhage, and 17 had unilateral ischemia. Based on lower esophageal sphincter pressure, 7 patients underwent tube gastrostomy and 13 patients underwent tube jejunostomy placement. All tolerated enteral alimentation well. Prior to lower esophageal sphincter assessment, 4 patients had percutaneous endoscopy gastrostomy feedings that led to aspiration pneumonitis and consultation for tracheostomy; 2 terminally ill patients were referred to the ethics service, and 2 were converted to feeding via jejunostomy tube at the time of tracheostomy and did well. Question: Does lower esophageal sphincter dysfunction often preclude safe gastric feeding in stroke patients? <|endoftext|> <|assistant|> Vomiting with aspiration due to lower esophageal sphincter dysfunction is common after acute strokes. Esophageal manometry serves as a guide to find the optimal feeding route.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Multiple abnormalities in pain processing have been reported in patients with chronic musculoskeletal pain syndromes. These changes include mechanical and thermal hyperalgesia, decreased thresholds to mechanical and thermal stimuli (allodynia), and central sensitization, all of which are fundamental to the generation of clinical pain. Therefore, we hypothesized that quantitative sensory tests may provide useful predictors of clinical pain intensity of such patients. Our previous studies of fibromyalgia (FM) patients have shown statistically significant correlations of quantitative sensory test results with clinical pain intensity, including mechanical spatial summation, number of pain areas, wind-up, and wind-up aftersensations. Although these tests predicted up to 59% of the variance in FM clinical pain intensity, their expense and technical complexities limited widespread use in clinical practice and trials. Thus, we developed practical tests of primary (mechanical) and secondary (heat) hyperalgesia that also strongly predict clinical pain intensity in patients with chronic musculoskeletal pain disorders. Thirty-six individuals with FM, 24 with local musculoskeletal pain, and 23 normal controls underwent testing of mechanical and heat hyperalgesia at the shoulders and hands. All subjects rated experimental pains using an electronic visual analog scale. Using either heat or pressure pain ratings as well as tender point counts and negative affect as predictors, up to 49.4% of the patients' variance of clinical pain intensity could be estimated. Results of this study emphasize the important contributions of peripheral and central factors to both local and widespread chronic pain. Overall, measures of mechanical and heat hyperalgesia in combination with tender point and negative affect provided powerful predictors of clinical pain intensity in chronic musculoskeletal pain patients that can be readily used in clinical practice and trials. Question: Do mechanical and heat hyperalgesia highly predict clinical pain intensity in patients with chronic musculoskeletal pain syndromes? <|endoftext|> <|assistant|> Simple tests of mechanical and heat hyperalgesia can predict large proportions of the variance in clinical pain intensity of chronic musculoskeletal pain patients and thus are feasible to be included in clinical practice and clinical trials.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Observational study of 46 consecutive patients with the diagnosis of active GCA and abnormal high FDG uptake in the aorta and other large arteries suggestive for GCA. 15 of the 46 GCA patients had abnormal high FDG uptake within the extending from the V0 to V3 segment in 13 and confined to single segments in 2 patients. In 2 patients high FDG uptake in one VA was the onIy PET abnormality. In 13 patients high FDG uptake was also found in other large arteries (carotid n = 10, subclavian/axillary artery n = 12, thoracic aorta n = 12). Abnormal PET was detectable in 5 patients despite glucocorticoid (GC) treatment. Nuchal and occipital pain and ischemic stroke or TIA in the posterior circulation (n = 3) were found in 10 patients with high VA FDG uptake. US detected halos of the V0-2 segments in 8/46 patients (5/15 VA PET positive and 3/31 VA PET negative patients). Biopsies were available in 10/15 VA PET positive patients with evidence of active GCA in 7 cases. Question: Vertebral arteries: a target for FDG-PET imaging in giant cell arteritis? <|endoftext|> <|assistant|> In patients with severe GCA and a high TVS the extracranial VA are a good target for PET imaging in active GCA with abnormal findings in 33% of patients with a positive PET. VA abnormalities can be an early and isolated finding in active GCA. PET is superior to US for the detection of active VA-GCA. A strong correlation between VA abnormalities and associated clinical abnormalities existed in 2/3 of patients. PET abnormalities of the VA could be detected in some cases after GC treatment has been started even at high doses.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: 'Hami' melon is susceptible to softening during postharvest storage at ambient temperature, which enhances postharvest deterioration and limits transportation and storage. To look for a method of softening control, the effect of 1-methylcyclopropene (1-MCP) on regulating postharvest softening of 'Hami' melon fruit was investigated. 1-MCP treatment at 1 µL L(-1) significantly reduced ethylene production and maintained higher levels of fruit firmness. It also markedly inhibited the accumulation of 1-aminocyclopropane-1-carboxylic acid (ACC) and maintained lower activities of ACC synthase and ACC oxidase. In addition, 1-MCP treatment reduced the activities of fruit-softening enzymes such as pectin methyl esterase, polygalacturonase, endo-1,4-β-glucanase and β-galactosidase. Question: Does 1-MCP suppress ethylene biosynthesis and delays softening of 'Hami ' melon during storage at ambient temperature? <|endoftext|> <|assistant|> 1-MCP was effective in suppressing ethylene production and delaying fruit softening in 'Hami' melon by decreasing the activities of ethylene biosynthesis enzymes and inhibiting fruit-softening enzymes.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Previously the angiotensin II receptor blocker Irbesartan has been demonstrated to reduce the risk for progression from microalbuminuria to macroalbuminuria in type 2 diabetic patients. The purpose of this study was to evaluate the effect of treatment with Irbesartan in type 2 diabetic patients with microalbuminuria on the urinary proteome. High-resolution capillary-electrophoresis coupled to mass-spectrometry (CE-MS) was used to profile the low-molecular-weight proteome in urine of a subgroup of patients from a two year randomized irbesartan versus placebo therapy trial, which included hypertensive type 2 diabetic patients with microalbuminuria on ongoing antihypertensive medication (IRMA2-substudy). We demonstrate that the therapy with 300 mg Irbesartan daily over a period of two years results in significant changes of the urinary proteome. Both, a classifier developed previously that consists of urinary peptides indicative of chronic kidney disease, as well as several individual peptides changed significantly after treatment. These changes were not observed in the placebo-treated individuals. Most prominent are changes of urinary collagen fragments associated with progression of diabetic nephropathy, indicating normalization in urinary peptides. Question: Does urinary proteome analysis enable assessment of renoprotective treatment in type 2 diabetic patients with microalbuminuria? <|endoftext|> <|assistant|> CE-MS analysis of urine enabled identification of peptides as potential surrogate markers for renoprotection in microalbuminuric type 2 diabetic patients, which show persistent improvement after longterm treatment with Irbesartan. The results suggest that a major benefit of treatment by Irbesartan may be improvement of collagen turnover, reduction of fibrosis. They further suggest that urinary proteome analysis could be utilized to assess potential benefit of therapeutic intervention, providing statistically significant results even on a small population.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Calcium phosphate cements (CPCs) are promising for dental and craniofacial repairs. The objectives of this study were to: (1) develop an injectable cell delivery system based on encapsulation of induced pluripotent stem cell-derived mesenchymal stem cells (iPSMSCs) in microbeads; (2) develop a novel tissue engineered construct by dispersing iPSMSC-microbeads in CPC to investigate bone regeneration in an animal model for the first time. iPSMSCs were pre-osteoinduced for 2 weeks (OS-iPSMSCs), or transduced with bone morphogenetic protein-2 (BMP2-iPSMSCs). Cells were encapsulated in fast-degradable alginate microbeads. Microbeads were mixed with CPC paste and filled into cranial defects in nude rats. Four groups were tested: (1) CPC-microbeads without cells (CPC control); (2) CPC-microbeads-iPSMSCs (CPC-iPSMSCs); (3) CPC-microbeads-OS-iPSMSCs (CPC-OS-iPSMSCs); (4) CPC-microbeads-BMP2-iPSMSCs (CPC-BMP2-iPSMSCs). Cells maintained good viability inside microbeads after injection. The microbeads were able to release the cells which had more than 10-fold increase in live cell density from 1 to 14 days. The cells exhibited up-regulation of osteogenic markers and deposition of minerals. In vivo, new bone area fraction (mean±SD; n=5) for CPC-iPSMSCs group was (22.5±7.6)%. New bone area fractions were (38.9±18.4)% and (44.7±22.8)% for CPC-OS-iPSMSCs group and CPC-BMP2-iPSMSCs group, respectively, 2-3 times the (15.6±11.2)% in CPC control at 12 weeks (p<0.05). Cell-CPC constructs accelerated scaffold resorption, with CPC-BMP2-iPSMSCs having remaining scaffold material that was 7-fold less than CPC control. Question: Do a self-setting iPSMSC-alginate-calcium phosphate paste for bone tissue engineering? <|endoftext|> <|assistant|> Novel injectable CPC-microbead-cell constructs promoted bone regeneration, with OS-iPSMSCs and BMP2-iPSMSCs having 2-3 fold the new bone of CPC control. Cell delivery accelerated scaffold resorption, with CPC-BMP2-iPSMSC having remaining scaffold material that was 7-fold less than CPC control. Therefore, CPC-microbead-iPSMSC is a promising injectable material for orthopedic, dental and craniofacial bone regenerations.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: The differential diagnosis of early-stage pancreatic cancer and mass-forming pancreatitis is still unsettled. The purpose of the present study was to define the differential feature of focal mass-forming pancreatitis and malignant mass using aspects of clinical, laboratory and imaging features on pancreatogram or computed tomography (CT). Between April 1995 and May 2003, 15 patients confirmed as inflammatory mass after surgical resection for pancreatic mass and 21 patients with early-stage pancreatic adenocarcinoma among the patients diagnosed as pancreatic malignancy were included in our study. Hospital records, laboratory results, findings of imaging studies and pathological findings were reviewed retrospectively. Regarding the clinical characteristics, the history of previous pancreatitis was distinguished in group with mass-forming pancreatitis. Incidence of jaundice was higher in the group with adenocarcinoma than in the mass-forming pancreatitis group. For laboratory results, CA19-9 level and alkaline phosphatase level were significantly elevated in the malignant group. Findings such as hyperattenuation on portal venous phase of CT scans and gradual tapering stricture on pancreatogram were differential diagnostic markers between the two groups. A portion of patients with mass-forming pancreatitis demonstrated the pathologic characteristics of autoimmune pancreatitis. Question: Is there any clinical or radiologic feature as a preoperative marker for differentiating mass-forming pancreatitis from early-stage pancreatic adenocarcinoma? <|endoftext|> <|assistant|> Our 9-year experience suggests that imaging findings such as attenuation pattern on the delayed phase of CT scan and tapering pattern of pancreatic ductal stricture on pancreatogram can help to differentiate mass-forming pancreatitis from early-stage pancreatic adenocarcinoma.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: The objectives of the study were to investigate the effects of 36 h of sleep deprivation on the discrete mood states of anger, depression, anxiety, confusion, fatigue, and vigour in healthy adolescents. Twelve healthy adolescent good sleepers (six male), aged 14-18 years (M = 16.17, standard deviation (SD) = 0.83), spent three consecutive nights in the sleep laboratory of the Centre for Sleep Research: two baseline nights with 10-h sleep opportunities and one night of total sleep deprivation. Every 2 h during wakefulness, they completed the Profile of Mood States - Short Form. Mood across two baseline days was compared to mood at the same clock time (0900 h to 1900 h) following one night without sleep. The subscales of depression, anger, confusion, anxiety, vigour, and fatigue were compared across days. All mood states significantly worsened following one night without sleep. Females showed a greater vulnerability to mood deficits following sleep loss, with greater depressed mood and anxiety following sleep deprivation only witnessed among female participants. While both males and females reported more confusion following sleep deprivation, the magnitude of this effect was greater for females. Question: Does sleep deprivation lead to mood deficits in healthy adolescents? <|endoftext|> <|assistant|> This study provides empirical support for the notion that sleep loss can causally affect mood states in healthy adolescents, with females having heightened vulnerability. Understanding the detrimental effects of insufficient sleep during adolescence is important, as it is a stage where sleep loss and mood dysregulation are highly prevalent. These findings escalate the importance of promoting sleep for the well-being of adolescents at this critical life phase.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: To determine the effect of climatic factors on immune markers in children with Dermatophagoides farinae induced asthma. Serum concentrations of macrophage migration inhibitory factor (MIF), eosinophil cationic protein (ECP) and D. farinae-specific immunoglobulin E (DF-sIgE), together with peripheral blood eosinophil counts, were measured in children with D. farinae induced (n = 75) or non-D. farinae-induced asthma (n = 17), and in healthy controls (n = 30). Mean temperature and relative humidity in the month before enrolment were calculated from meteorological data. MIF, ECP and eosinophil counts were significantly higher in children with D. farinae-induced asthma than in controls, but comparable with non-D. farinae-induced asthma. Children with D. farinae-induced asthma in a low temperature (< 16 °C) or low relative humidity (< 70%) climate had significantly lower DF-sIgE, MIF, ECP and eosinophil counts than those in a high temperature or high humidity climate. DF-sIgE correlated positively with MIF, ECP and eosinophil count in D. farinae-induced asthma. Question: Do climatic factors correlate with innate immune response in children with Dermatophagoides farinae-induced allergic asthma? <|endoftext|> <|assistant|> Temperature and humidity influenced MIF, ECP, eosinophil count and DF-sIgE in D. farinae-induced asthma. Understanding this relationship may provide new strategies for asthma prevention and treatment.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: The pistillody mutant wheat (Triticum aestivum L.) plant HTS-1 exhibits homeotic transformation of stamens into pistils or pistil-like structures. Unlike common wheat varieties, HTS-1 produces three to six pistils per floret, potentially increasing the yield. Thus, HTS-1 is highly valuable in the study of floral development in wheat. In this study, we conducted RNA sequencing of the transcriptomes of the pistillody stamen (PS) and the pistil (P) from HTS-1 plants, and the stamen (S) from the non-pistillody control variety Chinese Spring TP to gain insights into pistil and stamen development in wheat. Approximately 40 Gb of processed reads were obtained from PS, P, and S. De novo assembly yielded 121,210 putative unigenes, with a mean length of 695 bp. Among these high-quality unigenes, 59,199 (48.84%) had at least one significant match with an existing gene model. A total of 23, 263, and 553 differentially expressed genes were identified in PS vs. P, PS vs. S, and P vs. S, respectively, with differences in expression greater than five-fold. Among the differentially expressed genes, 206 were highly correlated with stamen and pistil development. These genes include WM27B, DL, YAB1, YABBY4, WM 5, CER 1, and WBLH1, which have been implicated in flower development. The expression patterns of 25 differentially expressed genes were confirmed through quantitative real-time reverse transcription PCR. Question: Does pistillody mutant reveal key insights into stamen and pistil development in wheat ( Triticum aestivum L. )? <|endoftext|> <|assistant|> Analysis of this transcriptome resource enabled us to characterize gene expression profiles, examine differential gene expression, and produce a candidate gene list related to wheat stamen and pistil development. This work is significant for the development of genomic resources for wheat, and provides important insights into the molecular mechanisms of wheat stamen and pistil development.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: The purpose of this study was to evaluate whether consolidation chemotherapy (CCT) after concurrent chemo-radiotherapy is beneficial for patients with locally advanced non-small-cell lung cancer (LA-NSCLC). We systematically searched PubMed for phase II/III trials published before December 31, 2011, examining survival of LA-NSCLC treated with concurrent chemo-radiotherapy. Median overall survival and other study characteristics were collected from each study and pooled. We extracted log-transformed hazards and standard errors under the assumption that survival follows an exponential distribution, and computed a pooled median overall survival and a 95% confidence interval (CI) using random-effects model. Collected trial arms were categorized as having CCT or not having it, CCT+ and CCT-, respectively. Forty-one studies were identified including seven phase III studies and 34 phase II studies with 45 arms (CCT+: 25; CCT-: 20). Clinical data were comparable for clinical stage, performance status, cancer histology, sex, and median age between the two groups. There was no statistical difference in pooled mOS between CCT+ (19.0 month; 95% CI, 17.3-21.0) and CCT- (17.9 month; 95% CI, 16.1-19.9). Predicted hazard ratio of CCT+ to CCT- was 0.94 (95% CI, 0.81-1.09; p = 0.40). There were no differences between the two groups with regard to grade 3-5 toxicities in pneumonitis, esophagitis, and neutropenia. These models estimated that addition of CCT could not lead to significant survival prolongation or risk reduction in death for LA-NSCLC patients. Question: Is consolidation chemotherapy after concurrent chemo-radiotherapy beneficial for patients with locally advanced non-small-cell lung cancer? <|endoftext|> <|assistant|> The pooled analysis based on a publication basis failed to provide evidence that CCT yields significant survival benefit for LA-NSCLC.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: The response to hypoxia is primarily mediated by the transcription factor hypoxia-inducible factor-1 (HIF-1) which leads to the induction of a variety of adaptive gene products including vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS). This study was designed to test the hypothesis that HIF-1 and its target genes would be upregulated in the ventricular myocardium of infants with cyanotic congenital cardiac defects. 14 infants with cyanotic (n = 7) or acyanotic cardiac defects (n = 7) were investigated. Samples from the right ventricular myocardium taken immediately after aortic clamping were studied for protein expression and DNA-binding activity. Protein levels of HIF-1alpha were significantly elevated in patients with cyanotic compared to acyanotic congenital heart disease and inversely correlated with the degree of hypoxemia. This response was accompanied by significantly enhanced HIF-1 DNA binding activity. Furthermore, protein levels of VEGF and eNOS were significantly higher in the myocardium of cyanotic than of acyanotic infants. To test the potential involvement of upstream regulatory pathways, activation of MAP kinases was determined. Intramyocardial levels of phosphorylated p38 MAP kinase, but not of ERK1/2 were significantly higher in infants with cyanotic compared to those with acyanotic congenital heart disease and inversely correlated to hypoxemia. Question: Does the hypoxia-inducible factor HIF-1 promote intramyocardial expression of VEGF in infants with congenital cardiac defects? <|endoftext|> <|assistant|> These findings show that chronic hypoxemia is associated with the induction and stabilization of the transcription factor HIF-1 as well as its target genes VEGF and eNOS in the myocardium of infants with cyanotic cardiac defects. Thus, stabilization of HIF-1 and induction of the adaptive hypoxia response could particularly participate in myocardial remodeling in children with congenital cardiac defects and chronic hypoxemia.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: A new modality is necessary to prevent recurrence of superficial bladder cancer after complete transurethral resection because of the high recurrence rate even with current prophylaxis protocols. In order to analyze the predictive value of cyclooxygenase-2 (COX-2) expression and tumor infiltrating lymphocytes (TILs) in recurrence of this disease tumor specimens from 127 patients with solitary papillary non-muscle invasive bladder cancer (NMIBC), 78 with recurrent disease and 49 without recurrence during follow up of minimum 5 years, were retrieved for tissue microarrays construction and immunohistochemical analysis. COX-2 expression was scored according to Allred's scoring protocol, while presence of TILs was categorized as absent (no) or present (yes) on whole tissue sections. COX-2 immunoreactivity was presented in 70 (71%), weak in 16% and strong in 55% of cases, while 29 (29%) tumors were negative. TILs were present in 64 (58%) NMIBC, while 44 cases (41%) did not reveal mononuclear infiltration in tumoral stroma. Statistical analysis demonstrated a higher proportion of patients with recurrence in the group with the COX-2 score 0, and lower in the group with score 2 (p=0.0001, p=0.0101, respectively). In addition, a higher proportion of recurrent patients in the group with no TILs, and lower proportion in the group with TILs were found (p=0.009, p=0.009, respectively). Univariate and multivariate analysis revealed overexpression of COX-2 and presence of TILs as negative predictors. Question: Is lower cyclooxygenase-2 expression associated with recurrence of solitary non-muscle invasive bladder carcinoma? <|endoftext|> <|assistant|> Patients with lower COX-2 expression and absence of TILs in NMIBC need to be followed up more vigorously and probably selected for adjuvant therapy.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Despite the compulsory use of faceguards in hurling, serious and sight-threatening eye injuries are still occurring. The purpose of this study is to highlight a number of key areas where there is still a high risk of serious ocular injury. A case series study. Distinct patterns of injuries are being observed in both playing and non-playing staff in the following areas: in the pre-match 'warm up' period and during training drills, situations historically where faceguards or eye protection has not been worn. Moreover, significant injuries are being observed in matches due to either modification of or defective faceguards. Question: Eye safety in hurling: a few remaining blind spots? <|endoftext|> <|assistant|> It is incumbent upon the Gaelic Athletic Association to expand current safety regulations to eliminate injuries in these key areas. This should include mandatory checks of faceguards by match officials prior to the commencement of matches. Finally, there needs to be more robust data collection by the association to ascertain the true extent of long-term ocular morbidity following these types of injuries.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: To prospectively evaluate whether TRUS guided biopsy associated with Color Doppler (CD) imaging improves the detection of PCa. From January 2008 to December 2010, 144 subjects, with an increased PSA value or with a suspect digital rectal examination, were enrolled. Transrectal grey-scale Ultrasound (US) and CD examination were performed in all patients. CD US was considered positive or negative on the basis of the presence or absence of vascular abnormality. Prostate biopsy was performed immediately after grey-scale and Doppler evaluation, with a mean of 10 core-biopsy for each patient as well as a selective biopsy of all US abnormal areas (hypoechoic lesion or CD abnormality areas). PCa has been detected in 71 (49.3%) patients. 58 of the 71 patients had a hypoechoic area at US scan and 27 had a CD abnormality. The PSA value was<4 ng/ml in 11 patients (Group 1), in 63 patients PSA ranged between 4 and 10 ng/ml (Group 2) and in 70 patients PSA was greater than 10 ng/ml (Group 3). The detection rate was 36.7, 36.5 and 62.8% respectively. In Group 1 we detected 5 hypoechoic areas and 4 CD abnormal areas. Moreover 6 of 11 patients had a positive DRE. In the Group 2, 20 patients were positive to DRE; we visualized 21 hypoechoic areas and 7 CD abnormality. In the Group 3, 38 patients had a positive DRE, with 32 hypoechoic areas and 16 CD abnormalities found. We obtained 1537 total bioptic cores, 1440 randomly from peripheral gland, 70 from hypoechoic areas and 27 from abnormal CD flow areas. The detection rate was 17.1, 65.7 and 22.2% respectively. Question: Does transrectal color Doppler ultrasound improve the diagnosis of prostate cancer? <|endoftext|> <|assistant|> CD US showed to be a complement to grey-scale imaging of prostate unless insufficiently sensitive to replace the standard systematic 8-12 core random peripherally biopsy. Furthermore it should be associated routinely to TRUS to easily focus suspect areas.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: epsilon-Poly-l-lysine (epsilon-PLL) is a polypeptide comprising approximately 30 l-lysine subunits generated by bond formation between alpha-carboxy and epsilon-amino groups. It is an approved antimicrobial food preservative in Japan. However, the efficacy of epsilon-PLL as an antibacterial additive for storage of human platelet concentrates (PCs) is not known. Staphylococcus aureus, Bacillus cereus, and Klebsiella oxytoca (20 colony-forming units/mL) were inoculated into 100% plasma PCs or PCs containing 80% platelet (PLT) additive solution with 5.0 mmol/L potassium and 1.5 mmol/L magnesium (PAS-IIIM) and 20% plasma (PAS-IIIM PCs). Next, a range of epsilon-PLL concentrations up to 200 and 50 microg/mL were added to plasma PCs and PAS-IIIM PCs, respectively, and the bacterial count was determined on Days 1, 2, 5, and 8. The quality of the PCs was also determined. Bacterial growth was inhibited at epsilon-PLL concentrations of 200 and 50 microg/mL in the plasma and PAS-IIIM PCs after 8 days of incubation. The percentage of CD62P-positive PLTs was higher in plasma PCs treated with 200 microg/mL epsilon-PLL and in PAS-IIIM PCs treated with 50 microg/mL epsilon-PLL than in the respective controls without epsilon-PLL. There were no remarkable differences in the other variables, that is, PLT number, mean PLT volume, pH, aggregability, percentage of PAC-1-positive cells, lactate dehydrogenase release, and plasma K and Na concentrations between the epsilon-PLL-treated PCs and the controls. Question: Does application of the bactericidal activity of epsilon-poly-l-lysine to the storage of human platelet concentrate? <|endoftext|> <|assistant|> epsilon-PLL inhibited the growth of bacteria in the PCs and did not considerably affect the quality of PCs, except CD62P expression. Further studies are required to estimate the in vivo effectiveness and safety of epsilon-PLL-treated PCs.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Intracellular transport involves the movement of organelles along microtubules (MTs) or actin filaments (AFs) by means of opposite-polarity MT motors or actin-dependent motors of the myosin family. The correct delivery of organelles to their different destinations involves a precise coordination of the two transport systems. Such coordination could occur through regulation of the densities of the two cytoskeletal systems or through regulation of the activities of the cytoskeletal motors by signaling mechanisms. To investigate the mechanisms of switching between MT and AF-dependent transport, we examine the influence of the densities of the MT and AF network on pigment transport in fish melanophores. We also change signaling by using activators and inhibitors of Protein Kinase A (PKA). We find that the key parameters characterizing pigment granule transport along MTs do not depend on MT density and are not significantly altered by complete disruption of AFs. In contrast, the kinetics of changes in these parameters correlate with the kinetics of changes in the intracellular levels of cAMP and are affected by the inhibitors of PKA, suggesting the regulation of MT- and AF-dependent motors by cAMP-induced signaling. Furthermore, perturbation of cAMP levels prevents the transfer of pigment granules from MTs onto AFs. Question: Does switching between microtubule- and actin-based transport systems in melanophores is control by cAMP levels? <|endoftext|> <|assistant|> We conclude that the switching of pigment granules between the two major cytoskeletal systems is independent of the densities of MT or AF but is tightly controlled by signaling events.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: In 1838, Edward Cock described the anatomic findings in 4 inner ears with a widely patent communication between the cochlea and the vestibule that is now frequently referred to as the "common cavity deformity" and is often confused with Michel's "otocyst deformity." Little is known about the anatomic characteristics, including the presence of neural elements in this malformation. Light microscopy and 2-dimensional and computerized 3-dimensional reconstructions were used to determine the histopathology and spiral ganglion cell counts in 7 temporal bones with a widely patent cochleovestibular communication. In all 7 specimens, the cochlea, vestibule, and semicircular canals were distinguishable and a bony defect resulting in an abnormal communication of perilymphatic space between the cochlea and vestibule was present. The ductus reuniens was abnormally wide in all. The cochlear duct varied from less than 1 turn to up to 2 turns. The mean spiral ganglion cells were estimated as a percentage of age-matched normal controls at 2.3%, 16.5%, and 26.8% when the cochlea was approximately 1, 1(1/2), and 2 turns, respectively (p = .007). The cribrose area consisted of a thin membrane in 2 specimens, and Rosenthal's canal openly communicated with the cerebrospinal fluid space in 3 specimens. The stapes footplate was abnormal in all 7 specimens and consisted of a central defect bridged by a thin membrane in 4 specimens. The facial nerve was dehiscent in 5 specimens (71%) and also followed an anomalous course in 2 specimens (28%). Question: Is the widely patent cochleovestibular communication of Edward Cock a distinct inner ear malformation : implications for cochlear implantation? <|endoftext|> <|assistant|> The widely patent cochleovestibular communication is a distinct inner ear malformation, recognition of which may have important clinical implications. Estimates of spiral ganglion cells can be predicted from the number of cochlear turns. Although cochlear implantation is feasible in patients with this malformation, a higher risk of cerebrospinal fluid gushers, facial nerve injuries, meningitis, and poor performance would be predicted. A better understanding of the anatomy will allow more effective surgical planning and techniques and may have a significant impact in improving outcomes.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Gene therapeutic strategies with suicide genes are currently investigated in clinical trials for brain tumors. Previously, we have shown that lentiviral vectors delivering the suicide gene HSV-Tk to experimental brain tumors promote a highly significant treatment effect and thus are promising vectors for clinical translation. In the present study, we tested lentiviral vectors delivering the suicide gene HSV-Tk.007, a highly active mutant of HSV-Tk, to rat brains as a preclinical toxicity study. We injected 10(6) vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped functional lentiviral particles harboring the suicide gene HSV-Tk.007 into the brain of healthy, immunocompetent rats. During prodrug treatment with ganciclovir (GCV), we measured weight and assessed the behavior of the rats in an open field test. After 14 days of GCV treatment, we analyzed HSV-Tk.007 expression in different brain cell populations, as well as inflammatory responses and apoptosis. During prodrug treatment with GCV, behavior experiments did not reveal differences between the treated rats and the control groups. Analysis of HSV-Tk expression in different brain cell populations showed that transduced normal brain cells survived GCV treatment. There were no statistically significant differences in the number of transduced cells between treatment and control groups. Furthermore, inflammatory responses and apoptosis of brain cells were not observed. Question: Is lentiviral HSV-Tk.007-mediated suicide gene therapy toxic for normal brain cells? <|endoftext|> <|assistant|> We show that HSV-Tk.007-mediated suicide gene therapy is not toxic to normal brain cells. This observation is of high relevance for the translation of lentivirus-mediated suicide gene therapies into the clinic for the treatment of brain tumor patients. Copyright © 2016 John Wiley & Sons, Ltd.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Previous research suggests greater risk of coronary heart disease with lower levels of the adrenal steroid dehydroepiandrosterone sulfate (DHEAS). No studies have examined the association between DHEAS and risk of ischemic stroke. DHEAS may influence ischemic stroke risk through atherosclerotic-related mechanisms (endothelial function and smooth muscle cell proliferation) or insulin resistance. Between 1989 and 1990, 32 826 women without prior stroke in the Nurses' Health Study, an observational cohort, provided blood samples and were followed up for cardiovascular events. Among this sample, using a nested case-control design, 461 ischemic strokes were confirmed by medical records by 2006. Cases were matched to controls free of stroke at the time of the index case and by age, race, menopausal status, postmenopausal hormone use, smoking status, and date of sample collection. Multivariable conditional logistic regression was used. Median DHEAS levels did not differ between cases (median=58.7) and controls (median=66.0; P=0.10). Conditional on matching factors, the lowest DHEAS quartile exhibited a relative risk of 1.30 for ischemic stroke (95% confidence interval, 0.88-1.94), compared with the highest quartile and marginally unchanged when adjusted for confounders (relative risk=1.33; 95% confidence interval, 0.87-2.02). When modeled as a binary variable dichotomized at the lowest quartile, women with low DHEAS (≤the lowest quartile) had a significantly increased multivariable adjusted risk of ischemic stroke compared with those with higher levels (relative risk=1.41; 95% confidence interval, 1.03-1.92). Question: Is low dehydroepiandrosterone sulfate associated with increased risk of ischemic stroke among women? <|endoftext|> <|assistant|> Lower DHEAS levels were associated with a greater risk of ischemic stroke, even after adjustment for potential confounders. These novel observations warrant confirmation in other populations.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: The aim of this study was to study the effect of the embryo freezing method on the birth weight of newborns from frozen embryo transfer (FET) cycles, and the pregnancy results of cleavage stage embryos cryopreserved by slow freezing or vitrification. This is a retrospective cohort study undertaken in a University Hospital IVF unit using concurrently both the slow-freezing and the vitrification techniques. All frozen-thawed and vitrified-warmed day 2 and day 3 embryo transfers during the time period from 1 April 2009 to 31 November 2013 were included in the study. There was no statistically significant weight difference between newborns from vitrified or slow-frozen embryos (3588 vs 3670 g). A higher post-thaw viability rate was achieved after cryopreservation by the vitrification technique compared to the slow-freezing protocol (83.4 vs 61.4%). The miscarriage rate was lower in the vitrification group (15.7 vs 29.0%). The live birth rates were similar (19.5 vs 19.1%) in the slow-freezing and vitrification groups, respectively. Among vitrified embryos, 7.4 embryos needed to be thawed to produce one delivery; in the slow-freezing group, that number was 11.9. Question: Does the freezing method of cleavage stage embryos have no impact on the weight of the newborns? <|endoftext|> <|assistant|> The freezing method has no impact on the weight of the newborn. With lower post-thaw survival rates and higher miscarriage rates, the slow-freezing cryopreservation protocol is inferior to the vitrification technique.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Ventromedial hypothalamic (VMH) lesions cause an increase in DNA content in the rat pancreas. This study examined the role of cell proliferation in the mitotic response of the rat pancreas after VMH lesion formation. Alterations in rat pancreatic DNA content, DNA synthesis, and labeling indices using antiproliferation cell nuclear antigen molecular antibody were measured 0,1,3, and 7 days after VMH lesion formation. Additionally, the effects of vagotomy, atropine, or anti-insulin antibody on VMH lesion-induced alterations in DNA synthesis were examined. Pancreatic samples were also treated with double immunostaining: first for PCNA and then for insulin, glucagon, and somatostatin. Pancreatic weight, DNA content, and DNA synthesis increased in animals receiving VMH lesions. Proliferation was primarily observed in islet B and acinar cells beginning 1 day after VMH lesion formation, reaching a maximum rate after 3 days. VMH lesion-induced stimulation of DNA synthesis was completely inhibited by vagotomy or atropine administration but not by anti-insulin antibody. Question: Does ventromedial hypothalamic lesion-induced vagal hyperactivity stimulate rat pancreatic cell proliferation? <|endoftext|> <|assistant|> Vagal hyperactivity produced by VMH lesions stimulated cell proliferation of rat pancreatic islet B and acinar cells primarily through a cholinergic receptor mechanism.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Patients derived from the TraumaRegister DGU(®) database between 2002 and 2010 were analyzed. First, patients were allocated into the four classes of hypovolaemic shock by matching the combination of heart rate (HR), systolic blood pressure (SBP) and Glasgow Coma Scale (GCS) according to ATLS. Second, patients were classified by only one parameter (HR, SBP or GCS) according to the ATLS classification and the corresponding changes of the remaining two parameters were assessed within these four groups. Analyses of demographic, injury and therapy characteristics were performed as well. 36,504 patients were identified for further analysis. Only 3411 patients (9.3%) could be adequately classified according to ATLS, whereas 33,093 did not match the combination of all three criteria given by ATLS. When patients were grouped by HR, there was only a slight reduction of SBP associated with tachycardia. The median GCS declined from 12 to 3. When grouped by SBP, GCS dropped from 13 to 3 while there was no relevant tachycardia observed in any group. Patients with a GCS=15 presented normotensive and with a HR of 88/min, whereas patients with a GCS<12 showed a slight reduced SBP of 117mmHg and HR was unaltered. Question: A critical reappraisal of the ATLS classification of hypovolaemic shock: does it really reflect clinical reality? <|endoftext|> <|assistant|> This study indicates that the ATLS classification of hypovolaemic shock does not seem to reflect clinical reality accurately.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: SMAD4 is a gastrointestinal malignancy-specific tumor suppressor gene found mutated in one third of colorectal cancer specimens and half of pancreatic tumors. SMAD4 inactivation by allelic deletion or intragenic mutation mainly occurs in the late stage of human pancreatic ductal adenocarcinoma (PDAC). Various studies have proposed potential SMAD4-mediated anti-tumor effects in human malignancy; however, the relevance of SMAD4 in the PDAC molecular phenotype has not yet been fully characterized. The AsPC-1, CFPAC-1 and PANC-1 human PDAC cell lines were used. The restoration or knockdown of SMAD4 expression in PDAC cells were confirmed by western blotting, luciferase reporter and immunofluorescence assays. In vitro cell proliferation, xenograft, wound healing, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry analysis were conducted using PDAC cells in which SMAD4 was either overexpressed or knocked down. Here, we report that re-expression of SMAD4 in SMAD4-null PDAC cells does not affect tumor cell growth in vitro or in vivo, but significantly enhances cells migration in vitro. SMAD4 restoration transcriptionally activates the TGF-β1/Nestin pathway and induces expression of several transcriptional factors. In contrast, SMAD4 loss in PDAC leads to increased expression of E-cadherin, vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR) and CD133. Furthermore, SMAD4 loss causes alterations to multiple kinase pathways (particularly the phosphorylated ERK/p38/Akt pathways), and increases chemoresistance in vitro. Finally, PDAC cells with intact SMAD4 are more sensitive to TGF-β1 inhibitor treatment to reduced cell migration; PDAC cells lacking SMAD4 showed decreased cell motility in response to EGFR inhibitor treatment. Question: Does sMAD4 loss trigger the phenotypic changes of pancreatic ductal adenocarcinoma cells? <|endoftext|> <|assistant|> This study revealed the molecular basis for SMAD4-dependent differences in PDAC with the aim of identifying the subset of patients likely to respond to therapies targeting the TGF-β or EGFR signaling pathways and of identifying potential therapeutic interventions for PDAC patients with SMAD4 defects.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Visceral adiposity is linked with sleep-disordered breathing (SDB) (called Syndrome Z), and both correlate with coronary artery disease (CAD). The aim of the present study was to determine the significance of excess visceral fat, SDB and circulating levels of biomarkers in CAD in Japanese men. SDB, visceral fat area (VFA), and circulating levels of biomarkers were assessed in 60 Japanese male patients who underwent coronary angiography and overnight cardiorespiratory monitoring. Age-adjusted logistic analysis showed a significant relationship between CAD and diabetes, hypertension, dyslipidemia, SDB (AHI ≥5 events/hour), visceral fat accumulation (VFA ≥100 cm(2)), the combination of visceral fat accumulation and hypertension or dyslipidemia, as well as the combination of visceral fat accumulation and SDB. Patients with VFA ≥100 cm(2) and SDB had significantly lower serum adiponectin levels and higher serum soluble CD40 ligand levels than those with VFA<100 cm(2) and SDB. The prevalence of CAD was significantly higher in patients with VFA ≥100 cm(2) and SDB than in patients with VFA <100 cm(2) and AHI <5 events/hour, patients with VFA<100 cm(2) and AHI ≥5 events/hour or patients with VFA ≥100 cm(2) and AHI <5 events/hour (93% versus 14%, p <0.001, 53%, p <0.01 or 63%, p <0.01, respectively). Question: Does coexistence of visceral fat accumulation and sleep-disordered breathing correlate with coronary artery disease? <|endoftext|> <|assistant|> The present study indicates that patients with both visceral fat accumulation and SDB develop CAD in association with hypoadiponectinemia and inflammatory activity.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: To investigate the epidemiology of a steep decrease in the incidence of suicide deaths in Australia. National data on suicide deaths and deliberate self-harm for the period 1994-2007 were obtained from the Australian Institute of Health and Welfare. We calculated attempt and death rates for five major methods and the lethality of these methods. Negative binomial regression was used to estimate the size and significance of method-specific time-trends in attempts and lethality. Hanging, motor vehicle exhaust and firearms were the most lethal methods, and together accounted for 72% of all deaths. The lethality of motor vehicle exhaust attempts decreased sharply (RR = 0.94 per year, 95% CI 0.93-0.95) while the motor vehicle exhaust attempt rate changed little; this combination of motor vehicle exhaust trends explained nearly half of the overall decline in suicide deaths. Hanging lethality also decreased sharply (RR = 0.96 per year, 95% CI 0.956-0.965) but large increases in hanging attempts negated the effect on death rates. Firearm lethality changed little while attempts decreased. Question: Do declines in the lethality of suicide attempts explain the decline in suicide deaths in Australia? <|endoftext|> <|assistant|> Declines in the lethality of suicide attempts-especially attempts by motor vehicle exhaust and hanging-explain the remarkable decline in deaths by suicide in Australia since 1997.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Recent studies have suggested that AD may reflect a chronic process that begins many years before the clinical expression of dementia. The current study examines premorbid Benton Visual Retention Test (BVRT) and Wechsler Adult Intelligence Scale-vocabulary (WAIS-voc) test scores in order to determine whether long-term deficits in these tests can predict the development of AD decades later in the Baltimore Longitudinal Study of Aging (BLSA). Participants are volunteers from the BLSA, a multidisciplinary study of normal aging conducted by the National Institute on Aging. A total of 1,425 BLSA participants who were older than 60 years were included in the analyses. Cox proportional hazards models were used to estimate the relative risk of developing AD associated with BVRT and WAIS-voc scores at different time periods up to 20 years before the diagnosis of AD. The relative risks for 6 or more BVRT errors vs less than 6 errors at 1 to 3, 3 to 5, 5 to 10, and 10 to 15 years before the diagnosis of AD were 5.69, 2.11, 1.76, and 1.83 (p < 0.05). The relative risk for 15 or more years before diagnosis was not significant (p > 0.10). WAIS-voc scores were not significantly associated with the risk of AD in any time period. Question: Does visual memory predict Alzheimer 's disease more than a decade before diagnosis? <|endoftext|> <|assistant|> A greater number of errors on the BVRT is associated with an increased risk of AD up to 15 years later. Poor visual memory performance may represent an early expression of AD years before diagnosis. This result suggests the need to continue to revise views on the natural history of AD and the possibility of an increased window of opportunity for preventive treatment before definitive diagnosis.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: In this study, circulating serum betatrophin levels were quantitated and their relationships with insulin resistance (IR) and other metabolic parameters in Chinese subjects with varying degrees of obesity and glucose tolerance were examined. Serum betatrophin levels were determined using ELISA in 60 subjects with normal glucose tolerance (NGT: 17 lean, 23 overweight, and 20 obese subjects) and 56 subjects with type 2 diabetes mellitus (T2DM: 14 lean, 23 overweight, and 19 obese subjects). The associations of serum betatrophin levels with adiposity, glucose, lipid profile, and hepatic enzyme parameters were studied. Serum betatrophin concentrations were significantly higher in overweight subjects in both the NGT and T2DM groups; however, no significant difference between lean and obese participants was observed. No significant difference was found between males and females or between NGT and T2DM subjects. Serum betatrophin concentrations correlated positively with fasting insulin, homeostasis model assessment-estimated insulin resistance (HOMA-IR), γ-glutamyl transpeptidase (γ-GT), and alanine aminotransferase (ALT) in all subjects. Serum betatrophin concentrations showed an independent association with γ-GT and HOMA-IR. Question: Are serum betatrophin concentrations significantly increased in overweight but not in obese or type 2 diabetic individuals? <|endoftext|> <|assistant|> Serum betatrophin levels were significantly increased in overweight individuals but not in individuals with obesity or T2DM. Serum betatrophin concentrations were significantly associated with IR, but not with lipid profiles, glucose homeostasis, or diabetes.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: A substantial number of adult patients with asthma are inadequately controlled despite the availability of effective asthma treatment. Patients and physicians seem to overestimate the level of asthma control. The current study explores whether valid differentiation is possible between asthma patients with controlled and uncontrolled asthma symptoms, on the basis of the Asthma Control Questionnaire (ACQ). In this multi-centre, cross-sectional study, patients were classified according to Global Initiative for Asthma criteria into levels of asthma symptom control based on a diary card registration. We defined Step 1 ('well controlled' asthma symptoms), Step 2 ('moderately controlled'), Step 3 ('poorly controlled') and Step 4 ('very poorly controlled'). These control steps were related with the sum score of the ACQ. From 108 asthma patients complete data were obtained. The Step 1 subgroup comprised 17 patients; Step 2, 12 patients; Step 3, 22 patients; and Step 4, 57 patients. Receiver Operating Characteristic curve analysis showed that the optimal ACQ sum score cut-off value to differentiate between Step 1 and Steps 2, 3 and 4 was three points (sensitivity: 84%, specificity: 76%). For Steps 1 and 2 versus Steps 3 and 4, this was four points (sensitivity: 77%, specificity: 59%). For Steps 1, 2 and 3 versus Step 4, this was six points (sensitivity: 70%, specificity: 74%). Question: Can the Asthma Control Questionnaire be used to differentiate between patients with controlled and uncontrolled asthma symptoms? <|endoftext|> <|assistant|> Our results show that discrimination between asthma patients with controlled and uncontrolled asthma symptoms, based on the ACQ, is possible with a reasonable margin of test inaccuracy. Thus, the ACQ may be an important tool for health care professionals who aim to optimize the level of asthma control in their patient population.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: We evaluated and quantified the levels of sarcoglycans present in the detrusor muscle layer of rabbits with partial bladder outlet obstruction. Rabbits underwent surgery, as previously described, to partially obstruct the urethra. One, 3, 7 and 14 days after obstruction the detrusor muscle layer was dissected free of the remaining bladder tissue and extracted with detergent to isolate the transmembrane components of the dystroglycan-glycoprotein complex. Several components of the dystroglycan-glycoprotein complex were characterized and quantified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting. Upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis several bands were noted on gels with a molecular weight (43 and 35 kDa, respectively) corresponding to beta and gamma-sarcoglycan. As obstruction progressed longitudinally, the levels of beta and gamma-sarcoglycan showed progressive decrease at the protein level with beta-sarcoglycan levels recovering at later time points. Bladders with a functional physiology that showed more advanced symptoms of dysfunction had a greater decrease in beta and gamma-sarcoglycan protein. Question: Are beta and gamma-sarcoglycans decreased in the detrusor smooth muscle cells of the partially obstructed rabbit bladder? <|endoftext|> <|assistant|> The levels of beta and gamma-sarcoglycan progressively change with obstruction with greater changes occurring in the levels of gamma-sarcoglycan. It is likely that alterations in the dystroglycan-glycoprotein complex are responsible for some of the changes in muscle physiology that occur as a consequence of obstruction.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Although cases of acute mad honey intoxication have been reported earlier, chronic mad honey intoxication (CMHI) syndrome has not been described and we address this issue only in this study. We prospectively evaluated the history of non-commercial honey intake in all patients referred to our institution for investigation of slow heart rate or atrioventricular (AV) conduction abnormalities. Between April 2008 and December 2008, 173 patients were referred to our institution for assessment of sinus bradycardia and various degrees of AV block and/or permanent pacemaker implantation. All patients were questioned about history of honey intake. Detailed evaluation revealed a history of daily honey intake for a long period of time in five of the patients (2.8%). This non-commercial honey was made by different amateur beekeepers in eastern Back Sea region of Turkey. Discontinuation of honey intake resulted in prompt normalization of conduction and significant symptomatic improvement. None of the patients were admitted to hospital and all were asymptomatic during 3 months follow-up. Holter monitoring for 24-h revealed no abnormality at first and third month. Question: Chronic mad honey intoxication syndrome: a new form of an old disease? <|endoftext|> <|assistant|> This is the first report of CMHI. This issue should be suggested during assessment of patients with unexpected conduction abnormalities, because abandonment of honey intake results in prompt symptomatic and electrocardiographic improvement.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Gender differences have been found in the development of hypertension. The role of estrogen in the association between hyperinsulinemia/insulin resistance and hypertension was investigated in an insulin-induced, insulin-resistant, and hypertensive model. Ovariectomized or sham operated female Wistar rats were chronically treated with insulin and/or estrogen via subcutaneous implants (insulin, 2 U/day; 17beta-estradiol 0.5 mg/pellet, 60-day release). Systolic blood pressure was monitored at weeks 0, 3, and 6. At week 7, an oral glucose tolerance test was performed. Ovariectomy resulted in the development of insulin resistance and blood pressure elevation in chronically insulin-treated female rats. Chronic estrogen treatment prevented the elevation in blood pressure and the development of insulin resistance. Question: Does chronic estrogen treatment modify insulin-induced insulin resistance and hypertension in ovariectomized rats? <|endoftext|> <|assistant|> The results indicate that chronic estrogen treatment modifies the insulin-induced hypertension by increasing insulin sensitivity in ovariectomized rats.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: BACKGROUND. Adults born small for gestational age (SGA) are at increased risk for the metabolic syndrome and cardiovascular disease. Impaired short-term blood pressure regulation may contribute to the development of hypertension in patients born SGA. In all, 43 patients born SGA (18 female, age 19.4 +/- 0.3 years) were evaluated by beat-to-beat blood pressure and heart rate registration during rest and mental and orthostatic stress. The study group was divided into Group 1 with normal resting blood pressure (n=32) and Group 2 with slightly elevated blood pressure (n=11). Baroreceptor sensitivity (BRS) was calculated. Fasting insulin as well as lipid levels were correlated with hemodynamic parameters. Eleven of the 43 study patients (25%) had a slightly elevated resting systolic blood pressure (SBP) rising during mental and orthostatic stress. Body mass index (BMI) and fasting insulin levels correlated strongly with SBP in Group 2. Baroreceptor sensitivity was lower in Group 2 at rest (p<0.05). Question: Young adults born small for gestational age: is reduced baroreceptor sensitivity a risk factor for hypertension? <|endoftext|> <|assistant|> Three components of metabolic syndrome (elevated BP, high BMI, elevated insulin levels) correlate strongly in young adolescents born SGA; BRS is reduced in prehypertensive patients. Close follow-up is warranted during adult life as they are predisposed for developing a metabolic syndrome with elevated cardiovascular risk.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: In a murine model of AA amyloidosis, it has been demonstrated that perlecan, the basement membrane heparan sulfate proteoglycan, is co-deposited with AA amyloid as it forms in various tissues. The objectives of this study were to determine whether the accumulation of perlecan during amyloidogenesis is associated with induction of perlecan gene expression and, if so, to define the temporal relationship of this induction to the onset of amyloid formation. Accelerated splenic AA amyloidosis was stimulated in mice by concomitant administration of subcutaneous silver nitrate as an inflammatory stimulus and amyloid-enhancing factor. A kinetic analysis of splenic perlecan mRNA levels during amyloid formation in the spleen was conducted using a reverse transcription-polymerase chain reaction assay. Amyloid deposits were detected histochemically with the Congo red stain and by immunohistochemistry using anti-AA antisera. Perlecan mRNA levels increased significantly during amyloidogenesis, increasing 4.1-fold within 72 hours of the amyloidogenic stimulus and subsequently falling to steady-state levels. A 2.0-fold induction of perlecan mRNA occurred by 24 hours post-stimulation, a time at which amyloid was not detectable by either histochemistry or immunohistochemistry. In contrast, control animals administered either the inflammatory stimulus or AEF alone showed no significant change in perlecan mRNA levels. Question: Does induction of perlecan gene expression precede amyloid formation during experimental murine AA amyloidogenesis? <|endoftext|> <|assistant|> Increased perlecan mRNA levels account, at least in part, for the accumulation of perlecan in murine splenic AA amyloid deposits. This induction of perlecan gene expression occurs before the onset of amyloid formation, supporting a role for perlecan in the earliest stages of amyloid fibrillogenesis.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: The clinical use of chromatin-modulating drugs, such as histone deacetylase inhibitors, for the treatment of bone marrow failure and hematopoietic malignancies has increased dramatically over the last few years. Nonetheless, little is currently known concerning their effects on myelopoiesis. We utilized an ex vivo differentiation system in which umbilical cord blood-derived CD34(+) cells were treated with trichostatin A, sodium butyrate and valproic acid to evaluate the effect of histone deacetylase inhibitor treatment on myeloid lineage development, colony-forming potential, proliferation, and terminal neutrophil differentiation. Trichostatin A treatment modestly reduced progenitor proliferation, while sodium butyrate and valproic acid resulted in concentration-dependent effects on proliferation and apoptosis. Addition of valproic acid uniquely stimulated CD34(+) proliferation. Sodium butyrate treatment inhibited terminal neutrophil differentiation both quantitatively and qualitatively. Addition of 100 microM valproic acid resulted in increased numbers of mature neutrophils with a block in differentiation at increasing concentrations. Sodium butyrate and valproic acid treatment resulted in increased acetylation of histones 3 and 4 while trichostatin A, sodium butyrate and valproic acid had differential effects on the acetylation of non-histone proteins. Question: Does histone deacetylase inhibition modulate cell fate decisions during myeloid differentiation? <|endoftext|> <|assistant|> Individual histone deacetylase inhibitors had specific effects on cell fate decisions during myeloid development. These data provide novel insights into the effects of histone deacetylase inhibitors on the regulation of normal hematopoiesis, which is of importance when considering utilizing these compounds for the treatment of myeloid malignancies and bone marrow failure syndromes.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: The aims of this study were to identify and evaluate the frequency of drugs involved in adverse drug reactions (ADRs) for which recommendations of the Summary of Product Characteristics (SPC) had not been respected and to compare the percentages of drugs suspected of being the cause of ADRs when correctly and incorrectly used. All ADRs reported to the Regional Pharmacovigilance Centre of Tours (RPC) over a period of 5 months were analysed to identify drugs used "incorrectly" defined by drug use beyond the recommendations of the SPC, i.e. drugs used when contra-indicated and/or drugs used for an off-label indication, and/or drugs used at an inappropriate dose, and/or inappropriate duration of treatment, and/or drugs used in the presence of a potentially or definitely interacting drug. Included in the study were 182 ADRs involving 182 patients. Of 642 drugs, 169 (26%) were incorrectly used and for 81 patients (44.5%) ADRs involved at least one "incorrectly" used drug. These included 10% (64 of 642) drug interactions, 7.3% (47 of 642) off-licence indications, 5% (32 of 642) inadequate dosage, 3% (20 of 642) incorrect duration of treatment and 1% (6 of 642) contraindications. "Correctly" used drugs appeared to be less often the cause of the ADRs than "incorrectly" used drugs (59.4% versus 75%, P=0.0001). Question: Are incorrectly used drugs more frequently involved in adverse drug reactions? <|endoftext|> <|assistant|> "Incorrectly" used drugs were more often causally linked to ADR than correctly used drugs. A meaningful number of ADRs could probably be avoided if SPC guidelines for a safe and effective drug use are carefully adhered to.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: To investigate the impact of endoscopic esophageal tumor length on survival for patients with resected esophageal squamous cell carcinoma (ESCC). We retrospectively reviewed the clinicopathologic characteristics of 244 ESCC patients who underwent curative resection as the primary treatment at Taipei Veterans General Hospital between January 2000 and November 2010. The endoscopic tumor length was defined as a uniform measurement before completion of the esophagectomy. The impact of endoscopic tumor length on a patient's overall survival (OS) and disease-free survival (DFS) were assessed. A Cox regression model was used to identify prognostic factors. The 1-, 3-, and 5-year OS rates were 81.2, 48.2, and 39.6%, respectively, with a median survival time of 18.0 months. The 1-, 3-, and 5-year DFS rates were 66.2, 34.7, and 32.4%, respectively, with a median DFS of 15.0 months. Endoscopic tumor length correlated with pathologic tumor length [Pearson correction (r)=0.621; P<0.001] Regression trees analyses suggested an optimum cutoff point of >4 cm to identify patients with decreased long-term survival. In multivariate survival analysis, endoscopic tumor length (more or less than 4 cm) remained an independent prognostic factor for both OS (P=0.006) and DFS (P=0.002). Question: Is endoscopic tumor length an independent prognostic factor in esophageal squamous cell carcinoma? <|endoftext|> <|assistant|> Endoscopic tumor length could have a significant impact on both the OS and DFS of patients with resected ESCC and may provide additional prognostic value to the current tumor, node, and metastasis staging system before patients receive any cancer-specific treatment.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: This study sought to determine whether cyclooxygenase products modulate angiotensin II-induced contractions of human placental arteries. Ring segments of chorionic plate arteries (3 to 5 mm inner diameter) were obtained after normal vaginal deliveries. Active force in response to 10(-6) mol/L angiotensin II or 10(-4) mol/L arachidonic acid was measured in the presence or absence of 10(-6) mol/L indomethacin to inhibit cyclooxygenase. The response of K+ contracted arteries to the stable prostacyclin analog iloprost was also tested to determine whether prostacyclin relaxes these vessels. Statistical differences were assessed by analysis of variance, Wilcoxon sign rank test, or Student t test with Bonferroni correction for multiple comparisons. Successive applications of angiotensin II produced significantly less contraction than the original dose (angiotensin II tachyphylaxis). Angiotensin II tachyphylaxis was unaffected by indomethacin. Arachidonic acid caused an indomethacin-sensitive contraction and iloprost failed to relax the arteries. Question: Do cyclooxygenase products modulate angiotensin II-induced contractions of human chorionic plate arteries? <|endoftext|> <|assistant|> These results suggest that cyclooxygenase products do not mediate angiotensin II tachyphylaxis in these vessels.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Intravenous cytostatic agents as second-line treatment of epithelial ovarian carcinoma have been withheld from many elderly patients because of fear of toxicity. The purpose of the study is to compare the toxicity and efficacy between elderly (older than 65 years of age) and younger (younger than 65 years of age) patients receiving intravenous second-line treatment of epithelial ovarian carcinoma. This study was a retrospective analysis of 286 consecutive patients with primary epithelial ovarian carcinoma. Inclusion criteria included histopathologically documented International Federation of Gynecology and Obstetrics (FIGO) Stage IC-IV epithelial ovarian carcinoma; first-line treatment with paclitaxel and a platinum analog; intravenous second-line treatment with topotecan 1.0 mg/m(2)/day for 5 days, every 3 weeks or paclitaxel (175 mg/m(2)) and carboplatin (AUC 5), every 3 weeks. One hundred two patients fulfilled the inclusion criteria receiving topotecan (n = 57) or paclitaxel-carboplatin (n = 45) because of refractory or recurrent disease. The patients' age at start of second-line treatment in the younger (n = 68) and the elderly (n = 34) group were median 54.0 years (range, 34.7-64.3) and 69.5 years (range, 65.1-77.2), respectively. In the patient group aged younger than 65 years, initial performance status was more favorable than in patients aged older than 65 years (P = 0.007) whereas the groups were similar in relation to other potential prognostic factors (P > 0.05). For patients aged younger than 65 years, the overall response rate of 50% (95% confidence interval [CI], 37-63%) was similar to the response rate of 44% (95% CI, 27-62%) in patients aged older than 65 years (P = 0.29). The overall survival from the first day of second-line treatment in patients aged younger and older than 65 years were median 13.3+ months (range, 1.2-38.3+) and 11.8+ months (range, 2.0-41.0+), respectively (P = 0.25). In a multivariate Cox analysis, performance status at time of first-line treatment (0 vs.1-2; P = 0.013; hazard ratio [HR], 2.12), performance status at time of second-line treatment (0 vs. 1-2; P = 0.004; HR, 2.47), and response to second-line treatment (CR + PR vs. NC + PD; P < 0.001; HR, 4.38) were found to be independent significant factors for overall survival whereas age (younger than 65 years vs. older than 65 years) yielded no independent information (P = 0.90). No differences in the rate of postponement of treatment, neutropenia Grade 4, thrombocytopenia Grade 3-4, nor hypersensitivity reaction to either cytostatic agent between older and younger patients were noticed (P > 0.05). Question: Is performance status rather than age the key prognostic factor in second-line treatment of elderly patients with epithelial ovarian carcinoma? <|endoftext|> <|assistant|> Modality of second-line treatment of epithelial ovarian carcinoma should be determined more by assessment of performance status than age per se. Second-line treatment with topotecan or paclitaxel-carboplatin can be safely administered in the aged.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: To investigate cardiorespiratory and inflammatory responses in male workers following exposure to welding fumes and airborne particles in actual workplace conditions. We measured blood leukocytes and their differential counts, platelet count, hemoglobin, sensitive C-reactive protein, fibrinogen, E-selectin, IL-(interleukin)1β, IL-6, IL-8, tumor necrosis factor alpha (TNF-α) and endothelin-1 in blood samples of twenty workers before and after their working day. We also studied peak expiratory flow (PEF), forced expiratory volume in one second (FEV1), and exhaled nitric oxide (NO). We assessed heart rate variability (HRV) by obtaining 24-hour ambulatory electrocardiograms. The total blood leukocytes and neutrophils increased after the work shift, whereas IL-1β and E-selectin decreased significantly. There were no statistically significant changes in exhaled NO, FEV1, PEF or HRV. Question: Does inflammatory response to acute exposure to welding fume during the working day? <|endoftext|> <|assistant|> Occupational exposure to welding fumes and particles caused a slight, acute inflammatory effect estimated based on the increased values of leukocytes and neutrophils in blood and a decrease in the interleukin 1β and E-selectin values, but no changes in the pulmonary function (exhaled NO, FEV1, PEF) or HRV during the working day were observed.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Recurrent or persistent defects in the rotator cuff after its repair are common. Short- and medium-term surveys have revealed, after open repair, patients with an intact rotator cuff have increased function and ROM. However, no long-term studies have verified cuff integrity on MR arthrography or correlated it with clinical and functional outcomes. We evaluated long-term cuff integrity and fatty infiltration after open repair using MR arthrography and determined whether these findings correlated with clinical and functional results. Using MR arthrography, we retrospectively evaluated 67 patients (48 men, 19 women) who underwent open rotator cuff repair between 1980 and 1989. Their mean age at surgery was 52 years. Minimum followup was 16 years (mean, 20 years; range, 16-25 years). The retear rate was 94%, and mean size of rerupture was 3.5 × 3.6 cm (ranges, 0.5-5.0 cm × 0.5-5.2 cm; median, 4 × 4 cm). The remaining four patients had a partial supraspinatus tendon tear. Fatty infiltration was marked in the supraspinatus and infraspinatus tendons. Cuff integrity correlated with clinical results: active external rotation and forward flexion, and flexion, abduction, and external rotation strengths, were better in patients with an intact rotator cuff or a small retear of 4 cm(2) or less than in patients with larger tears. Cuff integrity also correlated with functional results. Question: Does rotator cuff integrity correlate with clinical and functional results at a minimum 16 years after open repair? <|endoftext|> <|assistant|> Rotator cuff integrity was lost in 94% of patients after a minimum followup of 16 years. Cuff integrity correlates well with clinical and functional results even several years postoperatively. A large retear seems to be the most important factor in deteriorating long-term clinical and functional results after open rotator cuff repair.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Patients with treated Human Immunodeficiency Virus-1 (HIV) infection are at increased risk of cardiovascular events. Traditionally much of this risk has been attributed to metabolic and anthropometric abnormalities associated with HIV, which are similar to the metabolic syndrome (MS), an established risk factor for cardiovascular mortality. It remains unclear whether treated HIV infection is itself associated with increased risk, via increase vascular stiffness. 226 subjects (90 with HIV) were divided into 4 groups based on HIV and MS status: 1) HIV-ve/MS-ve, 2) HIV-ve/MS + ve, 3) HIV + ve/MS-ve and 4)HIV + ve/MS + ve. CMR was used to determine aortic pulse wave velocity (PWV) and regional aortic distensibility (AD). PWV was 11% higher and regional AD up to 14% lower in the HIV + ve/MS-ve group when compared to HIV-ve/MS-ve (p < 0.01 all analyses). PWV and AD in the HIV + ve/MS-ve group was similar to that observed in the HIV-ve/MS + ve group (p > 0.99 all analyses). The HIV + ve/MS + ve group had 32% higher PWV and 30-34% lower AD than the HIV-ve/MS-ve group (all p < 0.001), and 19% higher PWV and up to 31% lower AD than HIV + ve/MS-ve subjects (all p < 0.05). On multivariable regression, age, systolic blood pressure and treated HIV infection were all independent predictors of both PWV and regional AD. Question: Is hIV an independent predictor of aortic stiffness? <|endoftext|> <|assistant|> Across multiple measures, treated HIV infection is associated with increased aortic stiffness and is also an independent predictor of both PWV and regional AD. The magnitude of the effect of treated HIV and MS are similar, with additive detrimental effects on central vascular elasticity.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Testicular development is arrested in the hypogonadal (hpg) mouse due to a congenital deficiency in hypothalamic gonadotropin-releasing hormone (GnRH) synthesis. Chronic treatment of male hpg mice with estradiol induces FSH synthesis and secretion, and causes testicular maturation and qualitatively normal spermatogenesis. As estradiol negative feedback normally inhibits FSH production in the male, this study tested whether this paradoxical response to estradiol in the male hpg mouse might be due to inadequate masculinisation or incomplete defeminization in the neonatal period. Previous studies have demonstrated that treatment of hpg mice with testosterone propionate in the immediate neonatal period is necessary to allow full reproductive behaviors to be expressed following suitable endocrine stimulation at adult ages. Hpg mice were treated with 100 mug testosterone propionate or vehicle on postnatal day 2. At 35 days of age, subgroups of these mice were treated with silastic implants containing estradiol or cholesterol. Reproductive behavior was scored in tests with steroid-primed female mice, then testicular development was assessed histologically, and measures of pituitary FSH content made at 85 days of age. The neonatal testosterone propionate treatment successfully defeminized female litter mates, as revealed by impaired vaginal opening and deficiencies in lordosis behavior, and it allowed appropriate male reproductive behavior to be expressed in a proportion of the hpg males when tested at an adult age. However, neonatal androgen supplementation did not block or even reduce the subsequent actions of estradiol in increasing pituitary FSH content, nor did it affect the ability of estradiol to induce qualitatively normal spermatogenesis. Question: Does neonatal androgenization of hypogonadal ( hpg ) male mice abolish estradiol-induced FSH production and spermatogenesis? <|endoftext|> <|assistant|> The ability of the hpg male to show a "female" neuroendocrine response to estradiol is not a result of inadequate androgenization during neonatal development, and thus the actions of estradiol revealed in this rodent model are not an artefact of incomplete sexual differentiation, but reflect a physiological role of estradiol occurring during a specific early temporal window of male reproductive development.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: To evaluate the relationship between the intensity of murmurs and severity of mitral and aortic regurgitation. Consecutive patients with chronic isolated aortic (n = 40) or mitral (n = 170) regurgitation undergoing echocardiographic quantitation of regurgitation between 1990 and 1991 were studied. Regurgitant volume and fraction were measured using two simultaneous methods (quantitative Doppler echocardiography and quantitative two-dimensional echocardiography); the intensity of the regurgitant murmur (grade 0 to 6) was noted by physicians unaware of the study. Correlations between murmur intensity and regurgitant volume and fraction were good in aortic regurgitation (r = .60 and r = .67, respectively; P < 0.001) and mitral regurgitation (r = .64 and r = .67, respectively; P < 0.001) but weaker (r = .47 and r = .45, respectively) in the subset of mitral regurgitation of ischemic or functional cause. Murmur intensity grades > or = 3 for aortic regurgitation and > or = 4 for mitral regurgitation predicted severe regurgitation (regurgitant fraction > or = 40%) in 71% and 91% of patients, respectively. Murmur grades < or = 1 for aortic regurgitation and < or = 2 for mitral regurgitation predicted "not severe" regurgitation in 100% and 88% of patients, respectively. Murmur grades 2 for aortic regurgitation and 3 for mitral regurgitation were not correlated to degree of regurgitation. The severity of regurgitation was the most powerful determinant of intensity of murmur. Question: Does intensity of murmurs correlate with severity of valvular regurgitation? <|endoftext|> <|assistant|> Murmur intensity correlates well with the degree of chronic organic aortic and mitral regurgitation, and can be used as a predictor of regurgitation severity and as a simple guideline for diagnostic testing in these patients.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Antidepressants are used by 10% of the US population. Amongst these users, most will stop their antidepressant at some point, and about half--over a million people--will experience withdrawal effects, given usual taper rates. Moreover, recent data suggest that relapse rates (in patients with depression, panic disorder, or bipolar disorder) are higher with shorter tapers. How long is long enough? Recent data from narcolepsy research suggest that the physiologic processes associated with antidepressant discontinuation last over three months. Antidepressants have long been used in control of narcolepsy with cataplexy, but their sustained efficacy in this role has been in question. Thus prior to a trial of a new medication for cataplexy, antidepressants were carefully tapered and cataplexy rates monitored. Patients who had never received antidepressants were used as controls. Antidepressant discontinuation was associated with a dramatic increase in cataplexy rates, as anticipated; but importantly, these rates did not normalize, relative to the never-exposed patients, for over 3 months. Question: Tapering antidepressants: is 3 months slow enough? <|endoftext|> <|assistant|> These cataplexy data suggest that common antidepressant taper rates may be far too brief. Patients who are doing well and ready to discontinue their antidepressant might experience fewer withdrawal effects and fewer relapses with rates much longer than those now routinely used.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: To assess the influence of age at a cardiac procedure of children, who underwent elective cardiac surgery or interventional cardiac catheterisation for treatment of congenital cardiac defects between 3 months and 7 years of age, on the longitudinal development of psychological distress and styles of coping of their parents. We used the General Health Questionnaire to measure psychological distress, and the Utrecht Coping List to measure styles of coping. Parents completed questionnaires on average respectively 5 weeks prior to, and 18.7 months after, cardiac surgery or catheter intervention for their child. Apart from one exception, no significant influence was found of the age at which children underwent elective cardiac surgery or catheter intervention on the pre- to postprocedural course of psychological distress and the styles of coping of their parents. Across time, parents of children undergoing surgery reported, on average, significantly higher levels of psychological distress than parents of children who underwent catheter intervention. After the procedure, parents of children who underwent either procedure reported significantly lower levels of psychological distress, and showed a weaker tendency to use several styles of coping, than did their reference groups. Question: Does age at the time of elective cardiac surgery or catheter intervention in children influence the longitudinal development of psychological distress and styles of coping of parents? <|endoftext|> <|assistant|> Age of the children at the time of elective cardiac surgery or catheter intervention did not influence the course of psychological distress of their parents, nor the styles of coping used by the parents. Future research should investigate in what way the age at which these cardiac procedures are performed influences the emotional and cognitive development of the children.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Kawasaki disease (KD) is an acute self-limited panvasculitis, primarily affecting young children, with an outstanding risk of cardiovascular complications. Fibroblast Growth Factor-23 (FGF23) is the latest member of the FGF family, acting on phosphate metabolism, which has been shown to display a potential role in the vascular remodelling. The aim of our study was to test the hypothesis that circulating serum levels of FGF23 might be related to the occurrence of coronary artery abnormalities (CAA) in children with KD. Serum of 109 consecutive KD patients (median age 30.5 months) were collected for the evaluation of intact FGF23 by ELISA test. Sixty sex/age-matched healthy children were studied as controls, after having excluded rheumatic, endocrinological and chronic renal diseases. In all these subjects a familiar predisposition to atherosclerosis was excluded. FGF23 levels resulted significantly higher in patients with KD than in controls (72±40 pg/ml vs. 12.3±3.2 pg/ml; p=0.01). Twenty-eight/109 KD patients having developed CAA (aneurysms or dilatations) presented significantly higher FGF23 levels than those without any coronary artery damage (120±40 pg/ml vs. 38.2±5 pg/ml; p<0.0001). Multiple logistic regression analysis showed that only serum FGF23 levels, among different general clinical and biochemical variables, were suggestive of coronary artery damage (OR=4.86). Question: Can fibroblast growth factor (FGF)-23 circulating levels suggest coronary artery abnormalities in children with Kawasaki disease? <|endoftext|> <|assistant|> Based on this preliminary investigation, high serum FGF23 levels would seem suggestive of the potential occurrence of cardiac vascular complications in children with KD.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: The existence of a 'critical period' early in life characterized by a high susceptibility to melanoma initiation due to excessive ultraviolet (UV) radiation has been suggested by various authors based on epidemiological findings from migration studies and some case-control studies. However, the evidence so far is controversial as several epidemiological investigations failed to corroborate these results. Objective To compare the increase in melanoma risk due to excessive UV radiation between different periods in life. In a multicentre case-control study we recruited 603 melanoma cases and 627 population controls in seven European countries. We obtained data on the history of sunburns during 'childhood' (</= 15 years) and 'adulthood' (> 15 years), respectively, in standardized personal interviews. We employed logistic regression analyses to estimate the impact of the exposure factors under study, while simultaneously controlling for the effect of a variety of confounding variables. We found a very similar upward gradient of melanoma risk in exposure categories related to the frequency of sunburns during both periods in life. More than five sunburns doubled the melanoma risk, irrespective of their timing in life. Question: Does timing of excessive ultraviolet radiation and melanoma : epidemiology support the existence of a critical period of high susceptibility to solar ultraviolet radiation- induced melanoma? <|endoftext|> <|assistant|> Our data do not provide supporting evidence for the existence of a 'critical period'. The hazardous impact of sunburns seems to persist lifelong and thus activities concerned with melanoma prevention should be directed to the entire population rather than being focused only on younger age groups.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: To determine the effect of postpartum length of stay on newborn readmission. Secondary data set consisting of newborns born in Washington state in 1989 and 1990. The data set contains information about the characteristics of the newborn and its parents, physician, hospital, and insurance status. Analysis of the effect of length of stay on the probability of newborn readmission using hour of birth and method of delivery as instrumental variables (IVs) to account for unobserved heterogeneity. Of approximately 150,000 newborns born in Washington in 1989 and 1990, 108,551 (72 percent) were included in our analysis. Newborns with different lengths of stay differ in unmeasured characteristics, biasing estimates based on standard statistical methods. The results of our analyses show that a 12-hour increase in length of stay is associated with a reduction in the newborn readmission rate of 0.6 percentage points. This is twice as large as the estimate obtained using standard statistical (non-IV) methods. Question: Do longer postpartum stays reduce newborn readmissions? <|endoftext|> <|assistant|> An increase in the length of postpartum hospital stays may result in a decline in newborn readmissions. The magnitude of this decline in readmissions may be larger than previously thought.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Epigallocatechin-3-gallate (EGCG), a major catechin found in green tea, displays a variety of pharmacological properties and recently received attention as a prospective dietary intervention in cardiovascular diseases (CVD). This study was conducted to test the hypothesis that EGCG was able to inhibit tumor necrosis factor-α (TNF-α)-induced production of monocyte chemoattractant protein-1 (MCP-1) in human umbilical vein endothelial cells (HUVECs) and investigated the underlying molecular mechanisms. The inhibitory effect of EGCG on TNF-α-induced expression of MCP-1 was measured using ELISA and RT-qPCR. The effect of EGCG on TNF-α-induced nuclear factor-kappa B (NF-κB) activation was investigated by western blot and luciferase assays. Monocyte adhesion assay was detected by microscope. EGCG significantly suppressed the TNF-α-induced protein and mRNA expression of MCP-1. Investigation of the mechanism suggested that EGCG suppressed the TNF-α-mediated NF-κB activation. In addition, the 67-kD laminin receptor (67LR) was involved in EGCG-mediated suppression of MCP-1 generation. Furthermore, EGCG potently inhibited monocyte adhesion to activated HUVECs. Question: Does green tea polyphenol epigallocatechin-3-gallate inhibit TNF-α-induced production of monocyte chemoattractant protein-1 in human umbilical vein endothelial cells? <|endoftext|> <|assistant|> EGCG suppresses TNF-α-induced MCP-1 expression in HUVECs. This effect was mediated by 67LR and was via the inhibition of NF-κB activation. Our results demonstrated that EGCG might be a possible medicine for CVD prevention and treatment.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: The prognostic impact of complete response (CR) achievement in multiple myeloma (MM) has been shown mostly in the context of autologous stem-cell transplantation. Other levels of response have been defined because, even with high-dose therapy, CR is a relatively rare event. The purpose of this study was to analyze the prognostic impact of very good partial response (VGPR) in patients treated with high-dose therapy. All patients were included in the Intergroupe Francophone du Myelome 99-02 and 99-04 trials and treated with vincristine, doxorubicin, and dexamethasone (VAD) induction therapy followed by double autologous stem-cell transplantation (ASCT). Best post-ASCT response assessment was available for 802 patients. With a median follow-up of 67 months, median event-free survival (EFS) and 5-year EFS were 42 months and 34%, respectively, for 405 patients who achieved at least VGPR after ASCT versus 32 months and 26% in 288 patients who achieved only partial remission (P = .005). Five-year overall survival (OS) was significantly superior in patients achieving at least VGPR (74% v 61% P = .0017). In multivariate analysis, achievement of less than VGPR was an independent factor predicting shorter EFS and OS. Response to VAD had no impact on EFS and OS. The impact of VGPR achievement on EFS and OS was significant in patients with International Staging System stages 2 to 3 and for patients with poor-risk cytogenetics t(4;14) or del(17p). Question: Is achievement of at least very good partial response a simple and robust prognostic factor in patients with multiple myeloma treated with high-dose therapy : long-term analysis of the IFM 99-02 and 99-04 Trials? <|endoftext|> <|assistant|> In the context of ASCT, achievement of at least VGPR is a simple prognostic factor that has importance in intermediate and high-risk MM and can be informative in more patients than CR.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Ovarian serous carcinoma (OSC) is a fatal gynecologic malignancy usually presenting with bilateral localization and malignant peritoneal effusion. Programmed cell death 4 (PDCD4) is a tumor suppressor gene whose expression is directly controlled by microRNA-21 (miR-21). Exosomes are small cell-derived vesicles that participate in intercellular communication, delivering their cargo of molecules to specific cells. Exosomes are involved in several physiological and pathological processes including oncogenesis, immunomodulation, angiogenesis, and metastasis. The current study analyzed the expression of PDCD4 and miR-21 in resected OSC specimens and in cells and exosomes from OSC peritoneal effusions. PDCD4 was immunohistochemically examined in 14 normal ovaries, 14 serous cystadenoma (CA), and 14 OSC cases. Quantitative reverse transcriptase-polymerase chain reaction analysis of PDCD4 and miR-21 expression was performed in CA and OSC cases and in cells and exosomes obtained from 10 OSC and 10 nonneoplastic peritoneal effusions. miR-21 was also evaluated by in situ hybridization. Immunohistochemistry demonstrated a gradual PDCD4 loss from normal ovaries to CA and OSC specimens. Quantitative reverse transcriptase-polymerase chain reaction displayed higher PDCD4 messenger RNA levels in CA specimens compared with OSC cases and highlighted miR-21 overexpression in OSC specimens. In situ hybridization detected miR-21 only in OSC cells. This PDCD4 and miR-21 inverse expression was also noted in cells and exosomes from OSC peritoneal effusions compared with nonneoplastic effusions. Question: Is programmed cell death 4 and microRNA 21 inverse expression maintained in cells and exosomes from ovarian serous carcinoma effusions? <|endoftext|> <|assistant|> PDCD4 and miR-21 are involved in OSC oncogenesis. The transfer of miR-21 by exosomes could promote oncogenic transformation in target cells distant from the primary tumor without direct colonization by cancer cells and could be used as a diagnostic tool.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Primary Sjögren's syndrome (pSS) is an autoimmune disease affecting the exocrine glands and internal organs including the central nervous system (CNS). The fms-related tyrosine kinase 3 ligand (Flt3L) is a maturation factor essential for brain homeostasis. Blood levels of Flt3L are increased in inflammatory diseases including the inflamed salivary glands in pSS. The present study evaluated the role of Flt3L in the CNS of patients with pSS and in two non-autoimmune conditions, fibromyalgia (FM) and Alzheimer's disease (AD). Levels of Flt3L were measured in cerebrospinal fluid (CSF) and serum of patients with pSS (n = 15), FM (n = 29), and AD (n = 39) and related to CNS symptoms and to markers of inflammation and degeneration. Levels of CSF Flt3L in pSS and AD were significantly lower than in FM (p = 0.005 and p = 0.0003, respectively). Flt3L in pSS correlated to tau proteins [total tau (T-tau), r = 0.679; phosphorylated tau (P-tau), r = 0.646] and to a marker for microglia activation, monocyte chemoattractant protein 1 (MCP-1). Similar correlations were present in FM and AD patients. One-third of pSS patients had low levels of CSF Flt3L. This group had decreased levels of amyloid precursor protein metabolites (Aβ40 and Aβ42) in CSF, which was not seen in FM patients. Question: Does cerebrospinal Flt3 ligand correlate to tau protein levels in primary Sjögren 's syndrome? <|endoftext|> <|assistant|> This study shows a strong correlation between CSF Flt3L and tau proteins in pSS patients suggesting ongoing degradation/remodelling in the CNS. In pSS patients, low levels of Flt3L were linked to changes in amyloid turnover and may represent processes similar to those in AD.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: In current practice, minimal invazive interventions such as percutaneous drainage and laparoscopic surgery in adjunct treatment with benzimidazoles have been gaining acceptance in treatment of hydatid cystic disease with minimal morbidity and mortality. In this prospective study, the efficacy and validity of primary medical therapy in the treatment of hydatid cystic disease has been investigated. Sixty-five patients with hepatic cystic disease were treated with albendazole alone between January 2004 and June 2007. All of the patients were administrated albendazole as 10 mg kg(-1) day(-1) divided into two equal doses for 6 months with ultrasonography (USG), serological tests, full-blood cell count and hepatic function tests performed in 2 months intervals in the course of treatment. Fifty of the patients were female and 15 were male with a mean age of 47.0+/-16.9 (17-80). A total number of 106 cysts were present in 65 patients. Mean cystic diameter was 5.5+/-3.6 (1-16). In 41 of the patients, cysts were solitary and in remaining 24 patients cysts were multiple. Mean follow-up period was 28.3+/-8.6 (12-42) months. The overall success rate of albendazole therapy was 18% (12/65) in the study. Question: Is albendazole effective for primary treatment of hepatic hydatid cysts? <|endoftext|> <|assistant|> Albendazole therapy for hepatic hydatidosis is not effective in the vast majority of patients and, therefore, should not be used as the primary therapy for patients who are surgical candidates.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Angiopoietin-like protein 3, a liver-derived plasma protein, increases plasma triglycerides (TG) in mice by suppressing the activity of lipoprotein lipase, a key enzyme in plasma TG clearance. Uremic dyslipidemia is characterized by increased TG-rich lipoproteins such as very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL), lowered high-density lipoprotein (HDL), and TG-enrichment of low-density lipoprotein (LDL) and HDL. Since the role of angiopoietin-like protein 3 (ANGPTL3) in uremic dyslipidemia is unknown, we examined its possible association with the lipoprotein abnormalities in patients with chronic renal failure (CRF). The subjects were 202 hemodialysis patients, 44 predialysis patients with CRF and 148 healthy control subjects comparable in age and sex. Fasting plasma ANGPTL3 was measured by enzyme-linked immunoassay, and lipoproteins were fractioned by ultracentrifugation. Median (25th-75th percentile range) ANGPTL3 levels were 523 (409-645) and 393 (308-511)ng/mL in hemodialysis and predialysis patients, respectively, which were significantly lower than the control level of 700 (570-875)ng/mL. In the total subjects, ANGPTL3 was inversely correlated with VLDL- and IDL-cholesterol levels, and positively with HDL-cholesterol. ANGPTL3 correlated inversely with TG/cholesterol ratios of both LDL and HDL. In multiple regression models, these associations, excluding TG/cholesterol ratio of LDL, remained significant and independent of possible confounders including age, sex, body mass index, insulin resistance index (HOMA-IR), and adiponectin, whereas the associations of ANGPTL3 with the lipoprotein parameters were less significant when apoC-II/C-III ratio was included in the models. Question: Is plasma angiopoietin-like protein 3 ( ANGPTL3 ) concentration associated with uremic dyslipidemia? <|endoftext|> <|assistant|> The reduced ANGPTL3 level in hemodialysis patients was consistently associated with the major components of uremic dyslipidemia. ANGPTL3 may be a novel factor contributing to uremic dyslipidemia.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: National guidance documents advise that tissue obtained from treatment of miscarriage should be submitted for histological examination to exclude trophoblastic disease and ectopic pregnancy, and require sensitive disposal of human tissue. The aim of this study was to determine the extent to which health professionals have adopted these recommendations. Fifteen Scottish Obstetric and Gynaecology services participated in an audit of early pregnancy loss care. Three audit tools were used. In a case note review, 484 women completed medical or surgical treatment for miscarriage. 71% of records contained evidence of histological examination of tissue. Documentation of discussion of disposal of tissue with the woman was found in 29% of records. In a patient survey, 648 women with threatened or confirmed miscarriage returned questionnaires. Active treatment occurred in 134 cases. Only 55%, 50.9% and 47.4% reported being 'informed', 'consented' and 'involved', respectively, with decisions about tissue disposal. In a staff survey, a postal questionnaire was administered to 224 gynaecologists, with 144 replies. Self reported practice as 'seldom' or 'occasional' for sending tissue for histological examination was 34% for surgical evacuation and 57% for medical management. Reporting of 'seldom' or 'occasional' discussion of disposal of tissue with the woman was 42% and 49% for surgical and medical treatment, respectively. Question: Are national recommendations regarding examination and disposal of products of miscarriage being followed? <|endoftext|> <|assistant|> National guidance on these issues was found to be contentious and implementation was variable. Wide consultation with stakeholders is needed prior to the publication of revised guidance.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: To review the childhood course of glucocorticoid-remediable aldosteronism (GRA) in order to provide management guidelines for hypertension in children. Records for 20 children with GRA (aged 1 month to 18 years; 16 with hypertension) were retrospectively reviewed. Of the 16 children with GRA who developed hypertension, 50% had moderate-severe hypertension (blood pressure [BP] >99th centile for age and sex); 32% had mild hypertension (BP >95th and <99th centile), and 18% had borderline normal BP (BP >90th and <95th centile). Eight of 16 children with hypertension who received directed monotherapy (glucocorticoid suppression or aldosterone receptor/sodium epithelial channel antagonists) maintained BP below the 90th centile. Three additional subjects receiving a combination of directed therapies or a combination of directed therapies and nifedipine were unable to achieve BP control. At GRA diagnosis, 5 of 8 children were normokalemic, and plasma renin activity was suppressed in 5 of 5 subjects. Question: Is glucocorticoid-remediable aldosteronism associated with severe hypertension in early childhood? <|endoftext|> <|assistant|> Clinicians should have a high index of suspicion for GRA, especially in children with severe hypertension and a positive family history of early-onset hypertension and/or premature hemorrhagic stroke. Directed monotherapy is often successful in controlling BP in GRA.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: To examine differences in end-of-life decision-making in patients dying at home, in a hospital or in a care home. A death certificate study: certifying physicians from representative samples of death certificates, taken between June 2001 and February 2002, were sent questionnaires on the end-of-life decision-making preceding the patient's death. Four European countries: Belgium (Flanders), Denmark, Sweden, and Switzerland (German-speaking part). The incidence of and communication in different end-of-life decisions: physician-assisted death, alleviation of pain/symptoms with a possible life-shortening effect, and non-treatment decisions. Response rates ranged from 59% in Belgium to 69% in Switzerland. The total number of deaths studied was 12 492. Among all non-sudden deaths the incidence of several end-of-life decisions varied by place of death. Physician-assisted death occurred relatively more often at home (0.3-5.1%); non-treatment decisions generally occurred more often in hospitals (22.4-41.3%), although they were also frequently taken in care homes in Belgium (26.0%) and Switzerland (43.1%). Continuous deep sedation, in particular without the administration of food and fluids, was more likely to occur in hospitals. At home, end-of-life decisions were usually more often discussed with patients. The incidence of discussion with other caregivers was generally relatively low at home compared with in hospitals or care homes. Question: End-of-life decision-making in Belgium, Denmark, Sweden and Switzerland: does place of death make a difference? <|endoftext|> <|assistant|> The results suggest the possibility that end-of-life decision-making is related to the care setting where people die. The study results seem to call for the development of good end-of-life care options and end-of-life communication guidelines in all settings.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Influenza accounts for a large proportion of hospitalizations and deaths among older adults, resulting in substantial health care expenses. Influenza vaccinations are effective in reducing respiratory infections in younger populations, but it is less certain whether they reduce costs associated with respiratory infections among older adults. The purpose of this study was to determine whether influenza vaccination of older adult Medicare beneficiaries reduced costs associated with acute and chronic respiratory conditions during 3 recent influenza seasons. This study analyzed the relationship between influenza vaccination and costs for respiratory conditions among Medicare beneficiaries>or=55 years of age in influenza seasons (October-May) between 2002 and 2005 using data from the Medicare Current Beneficiary Survey. Two-part multiple regressions of vaccination status were estimated on the probability and cost of treating respiratory conditions in each influenza season controlling for influenza risk factors and other covariates. Various sensitivity tests were conducted by type of service, subgroup analysis for specific population risk segments, propensity score-matched comparisons, and difference equations. The study sample included 13,402 Medicare beneficiaries for the 3 influenza seasons examined. Vaccination rates varied between 67.3% and 74.9% over the 3 influenza seasons. In unadjusted comparisons, no significant difference in the cost of treating respiratory conditions was found between vaccinated and unvaccinated beneficiaries in 2002/2003 (-$104), but vaccinated beneficiaries had significantly higher mean cost differentials in the more recent influenza seasons ($258 in 2003/2004, P = 0.012; $254 in 2004/2005, P = 0.003). Based on 2-part multiple regressions of vaccine status over the 3 seasons combined, costs of respiratory conditions were $142 dollars higher on average for vaccinated beneficiaries (P = 0.014). The base regression models showed no significant cost savings from vaccination in any year. Results of 2 of the 54 sensitivity tests that were conducted indicated significant savings from vaccination (inpatient costs for 2002/2003 and difference in total costs for persons unvaccinated in 2002/2003 but vaccinated in 2003/2004). Question: Does influenza vaccination of older adult Medicare beneficiaries lower treatment costs for acute and chronic respiratory disease? <|endoftext|> <|assistant|> In this study of older adults, no significant cost savings were found with influenza vaccines in the 3 influenza seasons examined (2002-2005) when the outcome was measured in terms of differential spending for acute and chronic respiratory conditions.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Mentorship programs are perceived as valuable, yet little is known about the effect of program design on mentoring effectiveness. We developed a program focused on mentoring relationship quality and evaluated how subsequent relationships compared to preexisting informal pairings. Faculty members were invited by e-mail to participate in a new mentoring program. Participants were asked to complete a biography, subsequently provided to second- and third-year internal medicine residents. Residents were instructed to contact available mentors, and ultimately designate a formal mentor. All faculty and residents were provided a half-day workshop training, written guidelines, and e-mails. Reminders were e-mailed and announced in conferences approximately monthly. Residents were surveyed at the end of the academic year. Thirty-seven faculty members completed the biography, and 70% (26 of 37) of residents responded to the survey. Of the resident respondents, 77% (20 of 26) chose a formal mentor. Of the remainder, most had a previous informal mentor. Overall, 96% (25 of 26) of the residents had identified a mentor of some kind compared to 50% (13 of 26) before the intervention (P < .001), and 70% (14 of 20) who chose formal mentors identified them as actual mentors. Similar numbers of residents described their mentors as invested in the mentorship, and there was no statistical difference in the number of times mentors and mentees met. Question: Results of a Formal Mentorship Program for Internal Medicine Residents: Can We Facilitate Genuine Mentorship? <|endoftext|> <|assistant|> Facilitated selection of formal mentors produced relationships similar to preexisting informal ones. This model may increase the prevalence of mentorship without decreasing quality.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: To determine whether arterial spin-labeling (ASL) magnetic resonance (MR) imaging findings at baseline and early during antiangiogenic therapy can predict later resistance to therapy. Protocol was approved by an institutional animal care and use committee. Caki-1, A498, and 786-0 human renal cell carcinoma (RCC) xenografts were implanted in 39 nude mice. Animals received 80 mg sorafenib per kilogram of body weight once daily once tumors measured 12 mm. ASL imaging was performed at baseline and day 14, with additional imaging performed for 786-0 and A498 (3 days to 12 weeks). Mean blood flow values and qualitative differences in spatial distribution of blood flow were analyzed and compared with histopathologic findings for viability and microvascular density. t Tests were used to compare differences in mean tumor blood flow. Bonferroni-adjusted P values less than .05 denoted significant differences. Baseline blood flow was 80.1 mL/100 g/min +/- 23.3 (standard deviation) for A498, 75.1 mL/100 g/min +/- 28.6 for 786-0, and 10.2 mL/100 g/min +/- 9.0 for Caki-1. Treated Caki-1 showed no significant change (14.9 mL/100 g/min +/- 7.6) in flow, whereas flow decreased in all treated A498 on day 14 (47.9 mL/100 g/min +/- 21.1) and in 786-0 on day 3 (20.3 mL/100 g/min +/- 8.7) (P = .003 and .03, respectively). For A498, lowest values were measured at 28-42 days of receiving sorafenib. Regions of increased flow occurred on days 35-49, 17-32 days before documented tumor growth and before significant increases in mean flow (day 77). Although 786-0 showed new, progressive regions with signal intensity detected as early as day 5 that correlated to viable tumor at histopathologic examination, no significant changes in mean flow were noted when day 3 was compared with all subsequent days (P>.99). Question: Does arterial spin-labeling MR imaging-measured tumor perfusion correlate with renal cell cancer response to antiangiogenic therapy in a mouse model? <|endoftext|> <|assistant|> ASL imaging provides clinically relevant information regarding tumor viability in RCC lines that respond to sorafenib.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: The immunoregulatory enzyme indoleamine 2,3-dioxygenase, which catalyzes the conversion of tryptophan into kynurenine, is expressed in a significant subset of patients with acute myeloid leukemia, resulting in the inhibition of T-cell proliferation and the induction of regulatory T cells. Acute myeloid leukemia cells can be differentiated into dendritic cells, which have increased immunogenicity and have been proposed as vaccines against leukemia. Leukemic dendritic cells were generated from acute myeloid leukemia cells and used as stimulators in functional assays, including the induction of regulatory T cells. Indoleamine 2,3-dioxygenase expression in leukemic dendritic cells was evaluated at molecular, protein and enzymatic levels. We demonstrate that, after differentiation into dendritic cells, both indoleamine 2,3-dioxygenase-negative and indoleamine 2,3-dioxygenase-positive acute myeloid leukemia samples show induction and up-regulation of indoleamine 2,3-dioxygenase gene and protein, respectively. Indoleamine 2,3-dioxygenase-positive acute myeloid leukemia dendritic cells catabolize tryptophan into kynurenine metabolite and inhibit T-cell proliferation through an indoleamine 2,3-dioxygenase-dependent mechanism. Moreover, indoleamine 2,3-dioxygenase-positive leukemic dendritic cells increase the number of allogeneic and autologous CD4(+)CD25(+) Foxp3(+) T cells and this effect is completely abrogated by the indoleamine 2,3-dioxygenase-inhibitor, 1-methyl tryptophan. Purified CD4(+)CD25(+) T cells obtained from co-culture with indoleamine 2,3-dioxygenase-positive leukemic dendritic cells act as regulatory T cells as they inhibit naive T-cell proliferation and impair the complete maturation of normal dendritic cells. Importantly, leukemic dendritic cell-induced regulatory T cells are capable of in vitro suppression of a leukemia-specific T cell-mediated immune response, directed against the leukemia-associated antigen, Wilms' tumor protein. Question: Do indoleamine 2,3-dioxygenase-expressing leukemic dendritic cells impair a leukemia-specific immune response by inducing potent T regulatory cells? <|endoftext|> <|assistant|> These data identify indoleamine 2,3-dioxygenase-mediated catabolism as a tolerogenic mechanism exerted by leukemic dendritic cells and have clinical implications for the use of these cells for active immunotherapy of leukemia.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Survival of metastatic colon cancer (mCC) patients has considerably improved with optimization of new drugs regimen. Inactivation of TP53 pathway by TP53 mutations is observed in nearly half of colorectal tumors. The impact of such mutations has been poorly studied in the metastatic setting. The files of 254 mCC treated in a single institution at Saint-Louis hospital between January 1999 and April 2011 were retrospectively reviewed. Tissue samples for analysis of TP53 mutations were available for 68 patients, performed using FASAY. The prognostic value of TP53 status was evaluated by comparing progression free survival (PFS) and overall survival (OS) in the group of TP53-mutated and wild type patients. PFS was 6.9 months and OS 21.7 months in the whole population. There was no statistical difference in TP53-mutated and wild type groups in term of PFS (HR=1.04; IC 95%=0.6-1.79) and OS (HR=0.99; IC 95%=0.53-1.55) whatever the chemotherapy regimen (oxaliplatin- or irinotecan-based). Only BRAF V600 mutation was demonstrated to be a poor prognostic factor for PFS and OS, and CEA level for OS. Question: Do functional TP53 mutations have no impact on response to cytotoxic agents in metastatic colon cancer? <|endoftext|> <|assistant|> Routine determination of TP53 mutations, even with a highly sensitive method, cannot be recommended to predict chemotherapy response in mCC.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Constipation is a common affliction affecting the general population, with dyssynergic defaecation accounting for a large proportion of tertiary referrals. We sought to review the results of our patients with dyssynergic defaecation treated with biofeedback therapy in order to determine its efficacy. All patients who were referred to the anorectal physiology laboratory of our tertiary unit for biofeedback therapy for dyssynergic defaecation were reviewed. Patients diagnosed with secondary constipation and slow-transit constipation were excluded. A defaecating proctogram was used to exclude anatomical abnormalities causing outlet obstruction. Patients underwent a four-session, structured biofeedback exercise programme under the supervision of trained nurses. The effectiveness of biofeedback treatment was assessed using the validated Eypasch's Gastrointestinal Quality of Life Index (GIQLI). 226 patients (85 male, 141 female; median age 48 years) underwent biofeedback treatment. Post treatment, improvement was observed in the overall total score of the GIQLI, with gastrointestinal symptom (68.6%), emotion (61.0%) and physical function (57.9%) components showing the most improvement. These improvements were also reflected in the mean scores of each component and the mean total score. All components, except for social function and medication, and the overall total score showed significant improvement post treatment. At the one-year follow-up, 160 (71%) patients reported that improvements were maintained. Question: Is biofeedback an effective treatment for patients with dyssynergic defaecation? <|endoftext|> <|assistant|> Biofeedback is an effective treatment for patients with dyssynergic defaecation. Patients with chronic constipation not improved by fibre and laxatives should be referred to a tertiary centre with facilities for further anorectal physiological assessment.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Despite recent concerns about potential overuse of tympanostomy tube (TT) placement to treat otitis media in children, utilization of this common procedure in the U.S. has been shown to be relatively less common among minority children. It is not known if the indications for TT differ by child race/ethnicity and/or socioeconomic status (SES). Our objective is to analyze the association of patient- and neighborhood-level demographics and SES with clinical indications for TT. We conducted a retrospective chart review of children who underwent TT at single urban academic tertiary pediatric care center in a 6-month period (8/2013-3/2014). Children with congenital anomalies or syndromic diagnoses were excluded (50/137 children, 36.5%). Children were grouped by primary TT indication, recurrent acute otitis media (RAOM) or chronic otitis media with effusion (OME). Group characteristics were compared using t-tests and chi-square analyses, and logistic regression was performed to assess the association between demographics and TT indication. 87 children were included in this analysis (mean age = 2.8 years, 1-6 years). The most common indication for TT was RAOM (53%), and these children had a mean of 6 AOM episodes/year. Indications for TT varied significantly by the patient's neighborhood SES (median neighborhood income $70,969.09-RAOM vs $58, 844.95-OME, p-value = 0.009). Those undergoing TT for RAOM were less likely to live in a high-poverty neighborhood (OR = 0.36,p-value = 0.02), whereas children who underwent TT for OME were more likely to live in a high-poverty neighborhood. There was no significant difference in indication by race/ethnicity or insurance type. Question: Do race/ethnicity or socioeconomic status affect why we place ear tubes in children? <|endoftext|> <|assistant|> In this population, TT indications differed by SES. Among children receiving tubes, those from high poverty areas were more likely than those from low poverty neighborhoods to receive tubes for the indication of OME as opposed to RAOM. This finding suggests that concerns for appropriate use of TT in the setting of RAOM may be specific to a more affluent population. Future prospective patient-centered research will evaluate cultural and economic influences for families pursuing TT placement, as well as factors considered by physicians who make surgical recommendations.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Epigenetic modification plays a critical role in regulating gene expression. To understand how epigenetic modification alters miRNA expression in monocyte-derived dendritic cells (moDCs) in different environments, we analyzed the connections between H3K4me3 and H3K27me3 modification and the expression of miRNAs in LPS- and TGF-β-conditioned moDCs. In moDCs, H3K4me3 modification was strongly associated with the expression of activating miRNAs, whereas H3K27me3 was related to repressive miRNAs. The regulation of miRNA expression by H3K4me3 and H3K27me3 was further confirmed by silencing or inhibiting methyltransferases or methylation-associated factors in LPS- and TGF-β-conditioned moDCs. siRNAs targeting H3K4me3-associated mixed lineage leukemia (MLL) and retinoblastoma binding protein 5 (RBBP5) reduced H3K4me3 enrichment and downregulated miRNA expression; conversely, silencing H3K27me3-associated enhancer of zeste homolog 2 (EZH2) and embryonic ectoderm development (EED) genes upregulated the DC-associated miRNAs. However, LPS-mediated miRNAs were often associated with H3K4me3 redistribution from the transcription start site (TSS) to the miRNA-coding region. Silencing LPS-associated NF-κB p65 and CBP/p300 not only inhibited H3K4m3 redistribution but also reduced miRNA expression. LPS-upregulated RBBP4 and RBBP7, which are involved in chromatin remodeling, also affected the redistribution of H3K4me3 and reduced the expression of miRNAs. Question: Are dendritic cell-associated miRNAs modulated via chromatin remodeling in response to different environments? <|endoftext|> <|assistant|> In LPS- and TGF-β-conditioned moDCs, miRNAs may be modulated not only by H3K4m3 and H3K27me3 modification but also by redistribution of H3K4me3 around the transcriptional start site of miRNAs. Thus, H3K4me3 and H3K27me3 epigenetic modification may play an important role in regulating DC differentiation and function in the presence of tumor or inflammatory environments.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: The objective of this study is to test the hypothesis that the number of functional somatic syndromes (FSSs) predicts new, additional FSSs. In a recent case-control study of interstitial cystitis/painful bladder syndrome (IC/PBS), we used symptom-based consensus definitions to identify these FSSs: fibromyalgia (FM), chronic fatigue syndrome (CFS), irritable bowel syndrome (IBS), chronic pelvic pain, migraine, sicca syndrome and panic disorder. Those present before the incidence year were called antecedent FSSs; those with onset during the incidence year were called incident FSSs. In each of two groups, 312 IC/PBS cases and 313 controls, rates of incident FSSs were compared among those with 0, 1, 2, or ≥3 antecedent FSSs. Confounding was assessed using logistic regression analyses that included the individual antecedent FSSs, published correlates of these FSSs, and demographic variables. The incidence of a new FSS increased with the number of antecedent FSSs, as did that of incident FM, CFS and IBS studied separately. These findings were not confounded by other variables. The presence of multiple antecedent FSSs generally had the highest odds ratio for new, different, incident FSSs. Question: Is the number of existing functional somatic syndromes ( FSSs ) an important risk factor for new , different FSSs? <|endoftext|> <|assistant|> This study revealed that the number of antecedent FSSs was among the strongest risk factors for other FSSs, especially incident FM, CFS and IBS. This suggests that the FSSs are linked through a polysyndromic phenotype. If each FSS is heterogeneous, to seek a pathogenesis common to all FSSs, individuals with multiple FSSs should be sought; to seek a pathogenesis unique to a specific FSS, mature persons who have only that FSS should be studied.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: This study aimed to assess the influence of knee joint cooling on the in vivo mechanical properties of the patellar tendon. Twenty young, healthy women volunteered for the study. B-mode ultrasonography was used to record patellar tendon elongation during isometric ramp contraction of the knee extensors (5-7 s, 90° knee angle) and calculate tendon stiffness. Skin temperature was measured by infrared thermometry. Data were acquired before and after 30 min of local icing of the knee joint and compared by paired samples t-tests. After cold exposure, skin temperature as measured over the patellar tendon dropped by 16.8 ± 2.0 °C. Tendon stiffness increased from 2189 ± 551 to 2705 ± 902 N mm(-1) (+25 %, p = 0.007). Tendon strain decreased by 9 % (p = 0.004). A small, albeit significant reduction in maximum tendon force was observed (-3.3 %, p = 0.03). Question: Does knee joint cooling change in vivo patellar tendon mechanical properties? <|endoftext|> <|assistant|> Knee cooling is associated with a significant increase in patellar tendon stiffness. The observed tendon stiffening may influence the operating range of sarcomeres, possibly limiting the maximal force generation capacity of knee extensor muscles. In addition, a stiffer tendon might benefit rate of force development, thus countering the loss in explosiveness typically described for cold muscles.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Cardiac resynchronization therapy (CRT) diminishes cardiac apoptosis and improves systolic function in heart failure (HF) patients with ventricular dyssynchrony. Plasma annexin A5 (AnxA5), a protein related to cellular damage, is associated with systolic dysfunction. We investigated whether the response to CRT is associated with plasma AnxA5. We also studied AnxA5 overexpression effects in HL-1 cardiomyocytes. AnxA5 ELISA was performed in plasma from 57 patients with HF and ventricular dyssynchrony at baseline and after 1 year of CRT. Patients were categorized as responders if they presented both a reduction in left ventricular (LV) end-systolic volume index (LVESVi) >10% and an increase in LV ejection fraction (LVEF) >10%. HL-1 cells were transfected with human AnxA5 cDNA, and AnxA5, PKC, Akt, p38MAPK, Bcl-2, mitochondrial integrity, caspase-3, and ATP were assessed. At baseline, an increased plasma AnxA5 level was associated with decreased LVEF and increased LVEDVi values (P < 0.05). No differences in baseline AnxA5 were observed between responders and non-responders. After CRT, AnxA5 decreased (P = 0.001) in responders but remained unchanged in non-responders. Final values of AnxA5 were independently associated with LVEF (r = -0.387, P = 0.003) and LVESVi (r = 0.403, P = 0.004) in all patients. Compared with control cells, AnxA5-transfected cells exhibited AnxA5 overexpression, decreased PKC and Akt and increased p38MAPK and Bcl-2 phosphorylation, loss of mitochondrial integrity, caspase-3 activation, and decreased ATP. Question: Is cardiac resynchronization therapy-induced left ventricular reverse remodelling associated with reduced plasma annexin A5? <|endoftext|> <|assistant|> CRT-induced LV reverse remodelling is associated with reduction in plasma AnxA5. The excess of AnxA5 is detrimental for HL-1 cardiomyocytes. Collectively, these data suggest that the beneficial effects of CRT might be related to an AnxA5 decrease.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: The mosquito Anopheles gambiae is broadly distributed throughout sub-Saharan Africa and this contributes to making it the most efficient vector of malaria on the continent. The pervasiveness of this species is hypothesized to originate in local adaptations facilitated by inversion polymorphisms. One inversion, named 2La, is strongly associated with aridity clines in West and Central Africa: while 2La is fixed in arid savannas, the 2L+a arrangement is predominantly found in the rainforest. Ability to survive high temperature exposure is an essential component of aridity tolerance, particularly in immature stages that are restricted to shallow puddles. Toward deciphering the role of the 2La inversion in local adaptation, the present investigation focused on variation in larval and pupal thermo-tolerance in two populations dissimilar solely in 2La arrangement. A laboratory colony of A. gambiae that is polymorphic for 2La but standard for all other known inversions was used to create 2 homokaryotypic populations (2L+a and 2La). The survival of 4th instar larvae and pupae from both populations was then tested following exposure to thermal stress with and without prior heat hardening. Larvae responded identically to a 40 degrees C heat stress, with about 50% of larvae dying after 1.5-2 h and few larvae surviving a 3 h stress. When heat hardened prior to the thermal stress, thermo-tolerance of both larval populations increased, with 2La 24 h survival significantly exceeding that of 2L+a. Pupae were generally more thermo-tolerant than larvae, although 2La pupae were less so than 2L+a. Heat hardening had no positive effect on pupal thermo-tolerance. Question: Does 2La chromosomal inversion enhance thermal tolerance of Anopheles gambiae larvae? <|endoftext|> <|assistant|> The increased thermo-tolerance observed in 2La larvae following heat hardening suggests higher responsiveness (i.e., thermal sensitivity) of the inverted karyotype. By responding more drastically to the heat shock, 2La larvae are better equipped to resist the potentially lethal temperatures that occur in arid habitats. The lower survival of 2La pupae compared with 2L+a may reflect the cost of this sensitivity, whereby the thermal resistance mechanisms prevent successful completion of metamorphosis. The costs and benefits of thermal resistance are discussed in light of the climates characterizing either end of the 2La frequency cline.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: We sought to test whether the mechanical dyssynchrony assessed by tissue Doppler imaging (TDI) is a predictor of cardiac events in patients with congestive heart failure (CHF) and QRS duration < or =120 ms. The prevalence and prognostic value of mechanical dyssynchrony in patients with CHF and normal QRS duration have not been well clarified. A total of 106 patients (age 63 +/- 11 years) with CHF and ejection fraction (EF) <35% were followed serially; TDI was performed using four basal and four mid-left ventricular segments to assess the time to peak systolic point from R-wave on electrocardiogram (Ts). The standard deviation of Ts (Ts-SD) and the maximal temporal difference of Ts (Ts-diff) of eight segments were used as an indicator of mechanical dyssynchrony. Clinical events included readmission due to worsening of CHF, cardiac transplantation, and death. After 17 +/- 11 months of follow-up, the clinical event rate was 33% including all-cause mortality of 19%. Prolonged Ts-SD (>37 ms) and Ts-diff (>91 ms) were associated with a significant increase in all clinical events. By multivariate analysis, Ts-diff (>91 ms) was an independent risk factor of clinical events and mortality regardless of age, EF, QRS duration, and use of beta-blocking agents. Mean event-free survival was 16.3 months (95% confidence interval [CI] 11.9 to 20.7) in patients with Ts-diff >91 ms and 31.6 months (95% CI 28.0 to 35.1) in those with Ts-diff < or =91 ms, respectively (p < 0.001). Question: Is mechanical dyssynchrony assessed by tissue Doppler imaging a powerful predictor of mortality in congestive heart failure with normal QRS duration? <|endoftext|> <|assistant|> Myocardial dyssynchrony assessed by TDI is a powerful predictor of clinical events in CHF with normal QRS.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: The TOlerabilidad de LERcanidipino 20 mg frente a Amlodipino y Nifedipino en CondicionEs normales de uso study was aimed to compare the tolerability of high doses of lercanidipine with amlodipine and nifedipine gastro-intestinal therapeutic system (GITS) in the treatment of hypertension in daily clinical practice. Essential hypertensives >or= 18 years, treated during at least 1 month with lercanidipine 20 mg, amlodipine 10 mg or nifedipine GITS 60 mg, after a previous treatment course of at least 1 month with half the dose of the corresponding drugs were included. We present the data of the subgroup of patients with metabolic syndrome (MetS). Three hundred and thirty-seven of the 650 study population fulfilled criteria of MetS, 233 (69.1%) on lercanidipine and 104 (30.9%) on amlodipine/nifedipine GITS. Overall, a significantly lower proportion of lercanidipine-treated patients showed adverse reactions (ARs) when compared with patients receiving other-dihydropyridines (DHPs) (60.1% vs. 73.1%, p = 0.003). Similarly, the most common vasodilation-related ARs (oedema, swelling, flushing and headache) were significantly less frequent in lercanidipine group (all p < 0.01). Question: Are high doses of lercanidipine better tolerated than other dihydropyridines in hypertensive patients with metabolic syndrome : results from the TOLERANCE study? <|endoftext|> <|assistant|> In conclusion, lercanidipine appears to exhibit a better tolerability profile and less vasodilation-related ARs compared with other DHPs in hypertensive patients with MetS.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: To study the value of the cervical length (CL) measurement at 11-14 weeks in predicting second trimester miscarriage occurring at 16-24 weeks. Prospective study in routine obstetric population using transvaginal ultrasound examination to measure the length of the endocervical canal at 11-14 weeks. The study group consisted of 2836 singleton pregnancies. Eleven (0.0038%) women miscarried between 16 and 24 weeks whereas 2825 delivered after 34 weeks. CL was significantly shorter (Mann-Whitney U test, p = 0.001), in women that had a second trimester miscarriage in comparison to those who delivered after 34 weeks (median CL 28 mm versus 32 mm, respectively). First trimester CL was predictive of a late miscarriage (OR = 0.7093304, R(2 )= 0.1211, AUC = 0.7838, p < 0.001). The detection rate was 63.64% for 20% screen positive rate. Question: Is first trimester cervical length associated with mid-trimester loss? <|endoftext|> <|assistant|> First trimester endocervix is significantly shorter in women destined to miscarry between 16 and 24 weeks. In low risk singleton pregnancies, first trimester CL can be useful in predicting second trimester miscarriage.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Arthritis is the most frequent manifestation of Blau syndrome, an autoinflammatory disorder caused by the genetic mutation of NOD2. However, detailed information on arthritis in Blau syndrome on which the therapeutic strategy should be based on is lacking. This multi-center study aimed to accurately characterize the articular manifestation of Blau syndrome and also to demonstrate the utility of musculoskeletal ultrasound in Blau syndrome. Patients who had been diagnosed with Blau syndrome by genetic analysis of NOD2 were recruited. A total of 102 synovial sites in 40 joints were assessed semiquantitatively by ultrasound for gray-scale synovitis and synovial power Doppler (PD) signal. In total, 10 patients whose age ranged from 10 months to 37 years enrolled in this study. Although only 4 joints (0.8%) were tender on physical examination, 81 joints (16.9%) were clinically swollen. Moreover, 240 (50.0%), and 124 (25.8%) joints showed gray-scale (GS) synovitis and synovial PD signal on ultrasound, respectively. Importantly, GS synovitis was present in 168 out of 399 non-swollen joints, in which 61 also exhibited synovial PD signal. Among 40 joint regions, the ankle, the wrist, and the proximal interphalangeal joints were the most frequently and severely affected joints. Comparisons between different synovial tissues demonstrated a significantly higher proportion of the joints with tenosynovitis as compared with that with intra-articular synovitis (41.5% versus 27.9%, P < 0.0001). In respect of age and treatment, synovial PD signals were minimal in the youngest patient and in the oldest two patients, and were relatively mild in patients receiving treatment with methotrexate plus TNF antagonists. In two patients who underwent the second ultrasound examination, total PD scores markedly decreased after initiating the treatment with a tumor necrosis factor (TNF) antagonist. Question: Does ultrasonographic assessment reveal detailed distribution of synovial inflammation in Blau syndrome? <|endoftext|> <|assistant|> The detailed information on synovial inflammation obtained by ultrasound confirms the dissociation between pain and inflammation and the frequently involved joint regions and synovial tissue in the arthritis of Blau syndrome. Our data also demonstrate that ultrasonography can be a potent tool in monitoring the activity of synovial inflammation and in investigating the pathophysiology of arthritis in this rare but archetypical autoinflammatory condition.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Acute stress triggers transient alterations in the synaptic release and metabolism of brain monoamine neurotransmitters. These rapid changes are essential to activate neuroplastic processes aimed at the appraisal of the stressor and enactment of commensurate defensive behaviors. Threat evaluation has been recently associated with the dendritic morphology of pyramidal cells in the orbitofrontal cortex (OFC) and basolateral amygdala (BLA); thus, we examined the rapid effects of restraint stress on anxiety-like behavior and dendritic morphology in the BLA and OFC of mice. Furthermore, we tested whether these processes may be affected by deficiency of monoamine oxidase A (MAO-A), the primary enzyme catalyzing monoamine metabolism. Following a short-term (1-4h) restraint schedule, MAO-A knockout (KO) and wild-type (WT) mice were sacrificed, and histological analyses of dendrites in pyramidal neurons of the BLA and OFC of the animals were performed. Anxiety-like behaviors were examined in a separate cohort of animals subjected to the same experimental conditions. In WT mice, short-term restraint stress significantly enhanced anxiety-like responses, as well as a time-dependent proliferation of apical (but not basilar) dendrites of the OFC neurons; conversely, a retraction in BLA dendrites was observed. None of these behavioral and morphological changes were observed in MAO-A KO mice. Question: Is monoamine Oxidase A Required for Rapid Dendritic Remodeling in Response to Stress? <|endoftext|> <|assistant|> These findings suggest that acute stress induces anxiety-like responses by affecting rapid dendritic remodeling in the pyramidal cells of OFC and BLA; furthermore, our data show that MAO-A and monoamine metabolism are required for these phenomena.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Abnormalities in brain organic osmolytes are associated with hepatic encephalopathy and with chronic hyponatremia. In spite of the high frequency of hyponatremia in acute and chronic hepatic failure, its role in the development of neurological complications in liver disease is poorly understood. We aimed to study the effect of prior hyponatremia on the development of ammonia-induced brain edema in rats after portacaval anastomosis. In this model, brain swelling is mediated in part through an increase in brain glutamine, an organic osmolyte. Hyponatremia was induced in rats with 1-desamino-8-D-arginine vasopressin (DDAVP) administered through an osmotic minipump for 1 week. This was followed by performance of a portacaval anastomosis and ammonia infusion. At the end of the infusion, brain water (density gradient) and key brain organic osmolytes (HPLC) were measured. Rats with hyponatremia showed a decrease in all three brain organic osmolytes measured: glutamine, myo-inositol and taurine. Hyperammonemia resulted in the expected rise in glutamine, with a reduction of myo-inositol and taurine. In the combined group (hyponatremia plus hyperammonemia), the rise in brain glutamine induced by ammonia infusion was attenuated (10.6+/-0.9 mM/kg vs. 15.5+/-0.8 mM/kg hyperammonemia alone; p<0.05). In spite of this limited rise in brain glutamine, ammonia infusion to hyponatremic rats exacerbated brain swelling (82.3+/-0.3% vs. 80.6+/-0.1%; p<0.05). Question: Does chronic hyponatremia exacerbate ammonia-induced brain edema in rats after portacaval anastomosis? <|endoftext|> <|assistant|> Hyponatremia worsens brain swelling in a model of ammonia-induced brain edema. The decrease in the concentration of brain organic osmolytes induced by hyponatremia does not protect the brain from the development of ammonia-induced brain edema.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Fragrance allergy is the most common cause of cosmetic contact dermatitis. Many occult sources of fragrance exist. Those which cause the most concern are some "fragrance-free" products that contain fragrance raw ingredients. Thus, the very patients requiring fragrance-free items may be exposed to potential perfume allergens or cross-reactors in seemingly safe products. Additionally, medications dermatologists recommend, both prescription and over-the-counter, sometimes contain fragrance. This report describes a patient with chronic hand dermatitis sensitized to multiple fragrance ingredients including rose oil, present in the "fragrance-free" soap she used. Additionally, the tar soaks recommended to her also contained fragrance. Question: Is it really fragrance-free? <|endoftext|> <|assistant|> It is no longer sufficient to recommend the use of products labeled fragrance-free to fragrance-sensitive patients. These patients must be educated to read labels and look for plant extracts that are potential perfume sensitizers and cross-reactors. Rose oil, which has been felt to be a rare sensitizer, may be a more common allergen than previously recognized, perhaps because of its existence in a popular "fragrance-free" soap and, conceivably, in many "all-natural" products. Further testing with rose oil should be conducted in the future. Finally, manufacturers need to be more forthright in the labeling of their products.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: We undertook this study to examine the effects of estradiol on chondrogenesis of human bone marrow-derived mesenchymal stem cells (MSCs), with consideration of sex-dependent differences in cartilage repair. Bone marrow was obtained from the iliac crest of young men. Density-gradient centrifugation-separated human MSCs proliferated as a monolayer in serum-containing medium. After confluence was achieved, aggregates were created and cultured in a serum-free differentiation medium. We added different concentrations of 17beta-estradiol (E2) with or without the specific estrogen receptor inhibitor ICI 182.780, membrane-impermeable E2-bovine serum albumin (E2-BSA), ICI 182.780 alone, G-1 (an agonist of G protein-coupled receptor 30 [GPR-30]), and G15 (a GPR-30 antagonist). After 21 days, the aggregates were analyzed histologically and immunohistochemically; we quantified synthesized type II collagen, DNA content, sulfated glycosaminoglycan (sGAG) concentrations, and type X collagen and matrix metalloproteinase 13 (MMP-13) expression. The existence of intracellular and membrane-associated E2 receptors was shown at various stages of chondrogenesis. Smaller aggregates and significantly lower type II collagen and sGAG content were detected after treatment with E2 and E2-BSA in a dose-dependent manner. Furthermore, E2 enhanced type X collagen and MMP-13 expression. Compared with estradiol alone, the coincubation of ICI 182.780 with estradiol enhanced suppression of chondrogenesis. Treatment with specific GPR-30 agonists alone (G-1 and ICI 182.780) resulted in a considerable inhibition of chondrogenesis. In addition, we found an enhancement of hypertrophy by G-1. Furthermore, the specific GPR-30 antagonist G15 reversed the GPR-30-mediated inhibition of chondrogenesis and up-regulation of hypertrophic gene expression. Question: Does estradiol inhibit chondrogenic differentiation of mesenchymal stem cells via nonclassic signaling? <|endoftext|> <|assistant|> The experiments revealed a suppression of chondrogenesis by estradiol via membrane receptors (GPR-30). The study opens new perspectives for influencing chondrogenesis on the basis of classic and nonclassic estradiol signaling.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: To compare hospital pharmacy practice in France and Canada by identifying similarities and differences in the two institution's pharmacy activities, resources, drug dispensing processes and responsibilities. Centre hospitalier universitaire Sainte-Justine (SJ), Montréal, Québec, Canada and Hôpital Robert Debré (RD), Paris, France, are two maternal-child teaching hospitals. They share a similar mission focused on patient care, teaching and research. The data were gathered from annual reports, department strategic plans and by direct observation. The description and comparison of the legal environment, hospital demographics, pharmacy department data, drug dispensing processes and pharmacist activities in the two institutions. The Centre hospitalier universitaire Sainte-Justine and Hôpital Robert Debré are similar with respect to their mission and general demographics; number of beds, annual hospital expenditures, number of admissions, visits and childbirths. The respective pharmacy departments differ in allocated resources. The main operational differences concern compounding, quality control programs and clinical activities. The French department also manages medical devices, medical gases, blood derivatives and the sterilisation unit. These comparisons highlight the more patient-oriented Canadian hospital pharmacy practice against the more product-oriented French hospital practice Factors contributing to these differences include academic curriculum, the attention paid to the legal environment by professional bodies, staffing patterns and culture. Question: Comparison of hospital pharmacy practice in France and Canada: can different practice perspectives complement each other? <|endoftext|> <|assistant|> There are differences between the hospital pharmacy practice in the studied hospitals in Canada and France. Hospital pharmacy practice in France seems to be more product oriented, and the practice in Canada seems more patient oriented.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: The ABCD(2) score predicts the early risk of stroke after transient ischemic attack (TIA). However, data on the severity of recurrent events would also be useful. Do patients with high scores also have more severe early recurrent strokes, perhaps further justifying hospital admission? Do patients with low scores have a low early risk of recurrent TIA as well as recurrent stroke? We completed a prospective, population-based study in Oxfordshire, England, of 500 consecutive patients presenting with TIA from April 1, 2002, by using multiple methods of case ascertainment (Oxford Vascular Study). Recurrent TIA, minor stroke, and major stroke (National Institutes of Health Stroke Scale score >3 at the time of first assessment) were identified by face-to-face follow-up. Predictive value was expressed as the area under the receiver operating characteristic curve. Of 500 patients with TIA, 55 had a recurrent TIA (11.0%; 95% CI, 8.3% to 13.7%) and 50 had a recurrent stroke (10.0%; 95% CI, 7.5% to 12.0%) within 7 days. The ABCD(2) score was highly predictive of major recurrent stroke (area under the receiver operating characteristic curve=0.80; 95% CI, 0.72 to 0.87, P<0.0001), weakly predictive of minor stroke (area under the receiver operating characteristic curve=0.57; 95% CI, 0.43 to 0.71, P=0.26), and inversely related to risk of recurrent TIA (area under the receiver operating characteristic curve=0.37; 95% CI, 0.29 to 0.44, P=0.001) (overall heterogeneity, P<0.0001). The score predicted stroke-related disability, length of stay for recurrent stroke, and hence, overall acute hospital care costs. Question: Does aBCD2 score predict severity rather than risk of early recurrent events after transient ischemic attack? <|endoftext|> <|assistant|> The ABCD(2) score predicts severity of recurrent events after TIA, high scores being associated with major recurrent stroke and low scores with high rates of recurrent TIA. These findings have implications for cost-benefit analyses of policies on hospital admission for patients with high scores and for the advice given to patients with low scores.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Antenatal screening for depressive/anxiety symptoms could be biased by worries surrounding the first ultrasound (US). Therefore, we examined the potential influence of worries surrounding the first US on systematic screening for depressive/anxiety symptoms during pregnancy. We obtained data from 573 women screened consecutively in midwifery practices and hospitals in the Netherlands. Data included the Edinburgh Depression Scale (EDS), having had an US, and its perceived influence on women's worries. In total, 18% had EDS scores ≥10 (n = 105). Among 392 women who underwent an US, currently existing worries, introduced or unaltered by the US, predicted depressive/anxiety symptoms (aOR: 3.41, P < 0.001). Among 181 women who did not undergo an US, expected continuation of existing worries after the US predicted depressive/anxiety symptoms (aOR: 18.84, P = 0.046), in contrast to worries which were expected to subside. Question: Do worries surrounding the first ultrasound bias the screening for depressive and anxiety symptoms during pregnancy? <|endoftext|> <|assistant|> In our cohort, depressive and/or anxiety symptoms were not associated with transient worries, reduced by a first US, suggesting no bias. If true, antenatal screening for anxiety/depressive symptoms should not depend on the timing of this US examination.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Overweight, particularly obesity is a major risk factor for several important diseases, especially hypertension, coronary heart diseases and diabetes mellitus. Our aim is to determine the prevalence of obesity and central obesity among Omani adults aged > or =20 years, and to identify the socio-demographic and health variables that correlate to obesity and central obesity in a community based survey (National Health Survey, 2000). A community based cross-sectional survey representing all parts of Oman was designed in the year 2000. A part of the survey was a door to door interviews including demographic data, weight, height, hip and waist measurements, blood pressure and fasting blood glucose and serum cholesterol for adults aged > or =20 years. The crude prevalence of overweight and obesity (body mass index >25 kg/m2) was 47.9% for the whole sample, and 46.2% for males, 49.5% for females. The crude prevalence of central obesity (abnormal weight hips ratio) was 49.3% for the whole sample, 31.5% for males, and 64.6% for females. Obesity and central obesity were less prevalent among younger age groups and highly educated subjects. Both obesity and central obesity increased the odds of having diabetes, hypertension and hyperchlostremia. Question: Does prevalence and correlate of obesity and central obesity among Omani adults? <|endoftext|> <|assistant|> The prevalence of obesity and central obesity is quietly high in Oman. Launching nutritional programs and promotional life style modification programs are recommended.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: The key role of serum estradiol (E2) for bone health in men is well established. The effect of serum sex steroids on bone microstructure, measured by high-resolution peripheral quantitative computed tomography, remains unknown in elderly men. The objective of the study was to examine the associations between serum sex steroids and bone microstructural parameters in older men. Trabecular and cortical bone microstructure at the tibia was measured by high-resolution peripheral quantitative computed tomography in 440 men (mean 80 y of age) participating in the population-based Osteoporotic Fractures in Men Sweden cohort. Serum levels of E2 and T were analyzed with mass spectrometry and free E2 and free T levels were calculated using law-of-mass-action equations. Age-adjusted models demonstrated that E2 and free E2 but not T or free T associated significantly inversely with cortical porosity. The associations between E2 and free E2 and cortical porosity remained significant after further adjustment for height, weight, physical activity, calcium intake, and smoking. Models including both serum E2 and T demonstrated that E2 (standardized β = -.12, P < .05) but not T associated independently with cortical porosity. A similar independent association was found for free E2 (standardized β = -.12, P < .05) but not free T. Free E2 associated significantly with trabecular bone volume fraction in the age-adjusted models, but this association did not remain significant after further adjustment. Question: Are serum estradiol levels inversely associated with cortical porosity in older men? <|endoftext|> <|assistant|> Serum E2 levels associated inversely with cortical porosity in 80-year-old men. We propose that low serum E2 may reduce cortical bone strength, at least partly, by increasing cortical porosity and thereby increase fracture risk in older men.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Polyamines affect proliferation, differentiation, migration and apoptosis of cells, indicating their potential as a target for cancer chemotherapy. Ornithine decarboxylase converts ornithine to putrescine and is the rate-limiting step in polyamine synthesis.alpha-Difluoromethylornithine (DFMO) irreversibly inhibits ornithine decarboxylase and MDA-MB-435 human breast cancer metastasis to the lung without blocking orthotopic tumor growth. This study tested the effects of DFMO on orthotopic tumor growth and lung colonization of another breast cancer cell line (MDA-MB-231) and the effects on bone metastasis of MDA-MB-435 cells. MDA-MB-231 cells were injected into the mammary fat pad of athymic mice. DFMO treatment (2% per orally) began at the day of tumor cell injection or 21 days post injection. Tumor growth was measured weekly. MDA-MB-231 cells were injected into the tail vein of athymic mice. DFMO treatment began 7 days prior to injection, or 7 or 14 days post injection. The number and incidence of lung metastases were determined. Green fluorescent protein-tagged MDA-MB-435 cells were injected into the left cardiac ventricle in order to assess the incidence and extent of metastasis to the femur. DFMO treatment began 7 days prior to injection. DFMO treatment delayed MDA-MB-231 orthotopic tumor growth to a greater extent than growth of MDA-MB-435 tumors. The most substantial effect on lung colonization by MDA-MB-231 cells occurred when DFMO treatment began 7 days before intravenous injection of tumor cells (incidence decreased 28% and number of metastases per lung decreased 35-40%). When DFMO treatment began 7 days post injection, the incidence and number of metastases decreased less than 10%. Surprisingly, treatment initiated 14 days after tumor cell inoculation resulted in a nearly 50% reduction in the number of lung metastases without diminishing the incidence. After intracardiac injection, DFMO treatment decreased the incidence of bone metastases (55% vs 87%) and the area occupied by the tumor (1.66 mm2 vs 4.51 mm2, P < 0.05). Question: Is metastasis of hormone-independent breast cancer to lung and bone decreased by alpha-difluoromethylornithine treatment? <|endoftext|> <|assistant|> Taken together, these data demonstrate that DFMO exerts an anti-metastatic effect in more than one hormone-independent breast cancer, for which no standard form of biologically-based treatment exists. Importantly, the data show that DFMO is effective against metastasis to multiple sites and that treatment is generally more effective when administered early.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Adrenal vein sampling (AVS) is used for determining treatment options for primary aldosteronism (PA), but is a difficult procedure. Adrenocorticotropic hormone (ACTH) infusion or bolus has been reported to improve AVS success rates by increasing cortisol secretion, but effects on lateralization are controversial. We therefore assessed the effects of ACTH in regard to AVS success and lateralization in our unit, after a change in protocol to ACTH-stimulated AVS. AVS was performed after overnight recumbency in patients with PA confirmed by fludrocortisone suppression testing. Bilateral sequential sampling was performed before and after an intravenous bolus of 250 mcg of ACTH. Lateralization was defined as an aldosterone/cortisol ratio in one adrenal vein at least twice peripheral, combined with a contralateral adrenal ratio no higher than peripheral (contralateral suppression). In 47 AVS procedures, the median adrenal/peripheral cortisol gradient increased on the left (11·6 vs 18·2 μg/100 ml, P<0·001) and right (15·6 vs 31·5 μg/100 ml, P<0·001) after ACTH. A total of 34 of 47 studies were diagnostic pre-ACTH (six failing because of low aldosterone levels bilaterally and seven failing to cannulate one or both sides) vs 44 of 47 (P = 0·011) studies diagnostic post-ACTH (failure to cannulate one or both sides in 3). Concordance between diagnostic studies pre- and post-ACTH was 91%, but two bilateral cases became unilateral after ACTH and one unilateral case before ACTH was bilateral afterwards. Question: Does ACTH improve the diagnostic performance of adrenal vein sampling for subtyping primary aldosteronism? <|endoftext|> <|assistant|> ACTH improved cortisol gradients and aldosterone secretion, resulting in a reduction in the proportion of nondiagnostic studies. There was a low proportion of discordance between pre- and post-ACTH diagnoses, the significance of which is unclear.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Ovarian cancer is the seventh most common cancer in women worldwide, with nearly a quarter of a million women diagnosed every year. The serum tumor markers cancer antigens CA 125, CA 19-9, and carcinoembryonic antigen (CEA) are potentially of clinical value for the diagnosis of ovarian cancer. A diagnostic tool that is noninvasive, simple to perform, and specific is needed to predict primary ovarian cancer. The purpose of this study was to evaluate the diagnostic sensivitity and specificity of vaginal-washing tumor markers CA 125, CA 19-9, and CEA for diagnosis of primary ovarian cancer. In the current prospective study, 30 patients with advanced primary ovarian cancer and 30 patients with benign ovarian cysts were enrolled. The vaginal-washing fluid samples were obtained the day before surgery and were immediately centrifuged and stored at -80 degrees C until analysis. Measurements of CA 125, CA 19-9, and CEA were determined using fully-automated chemiluminescent microparticle immunoassays. The vaginal fluid concentrations of CA 125, CA 19-9, and CEA in patients with primary ovarian carcinoma were significantly higher (p<0.001) compared to those in patients with benign adnexal masses (p<0.001). In the ROC curve analysis, the optimal cut-off values for the detection of primary ovarian cancer were>295 for CA 125 (p<0.001),>101 for CA 19-9 (p<0.001), and>135 for CEA (p<0.001). Question: New method: Are tumor markers in vaginal-washing fluid significant in the diagnosis of primary ovarian carcinoma? <|endoftext|> <|assistant|> Vaginal-washing tumor markers CA 125, CA 19-9, and CEA are simple, noninvasive, and reliable diagnostic tests for the detection of primary ovarian cancer.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: The present study investigated tissue-specific responses of muscle and mammary gland to a 10 week intervention of German Holstein cows (n = 18) with three different dietary fat supplements (saturated fat; linseed oil or sunflower oil plus docosahexaenoic acid-rich algae) by analysing fatty acid profiles and quality parameters of meat and milk. Plant oil/algae intervention affected neither fat content nor quality parameters of meat but decreased fat content and saturated fatty acid amounts of milk. Linseed oil/algae intervention caused significantly higher concentrations of C18:3n-3 (meat, 1.0 g per 100 g; milk, 1.2 g per 100 g) and C22:6n-3 (meat, 0.3 g per 100 g; milk, 0.14 g per 100 g). Sunflower oil/algae intervention increased n-6 fatty acid contents in milk (4.0 g per 100 g) but not in meat. Elevated amounts of C18:1trans isomers and C18:1trans-11 were found in meat and especially in milk of plant oil/algae-fed cows. C18:1cis-9 amounts were found to be increased in milk but decreased in meat after plant oil/algae intervention. Question: Does dietary fatty acid intervention of lactating cows simultaneously affect lipid profiles of meat and milk? <|endoftext|> <|assistant|> The present study demonstrated that dietary fatty acid manipulation substantially shifted the fatty acid profiles of milk and to a lesser extent of meat, whereas meat quality traits were not affected. Indications of tissue-specific responses of mammary gland and muscle were identified.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: The purpose of this paper was to examine if pain and functioning can be distinguished in the Oxford Knee Score (OKS) in a meaningful way. This was done by (1) conducting exploratory factor analysis to explore the factorial structure of the OKS and (2) conducting confirmatory factor analysis to examine whether a two-factor solution is superior to a one-factor solution. Secondary data analysis of four independent datasets containing OKS scores on 161,973 patients was performed. Four independent datasets contained data on: (1) 156, 788 patients from the NHS HES/PROMS dataset, (2) 2,405 consecutive patients from the South West London Elective Operating Centre, (3) 2,353 patients enrolled in the Knee Arthroplasty Trial and (4) 427 consecutive patients listed for knee replacement surgery at the Nuffield Orthopaedic Centre in Oxford. Factor extraction methods suggested that, depending on the method employed, both one- and two-factor solutions are meaningful. Overall and in each data set some cross-loading occurred and item loadings were consistent across two factors. On confirmatory factor analysis, both one- and two-factor models had acceptable fit indices. This allowed the creation of the 'OKS pain component' and the 'OKS functional component' subscales. Question: Can pain and function be distinguished in the Oxford Knee Score in a meaningful way? <|endoftext|> <|assistant|> Factor analysis confirmed the original conceptual basis of the OKS but offered an option to perform additional analyses using pain and functional subscales. Further research should focus on providing further evidence on construct validity and responsiveness of the newly derived subscales.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Preterm birth is closely associated with neurocognitive impairment in childhood including increased risk for social difficulties. Eye tracking objectively assesses eye-gaze behaviour in response to visual stimuli, which permits inference about underlying cognitive processes. We tested the hypothesis that social orienting in infancy is altered by preterm birth. Fifty preterm infants with mean (range) gestational age (GA) at birth of 29(+1) (23(+2) -33(+0) ) weeks and 50 term infants with mean (range) GA at birth 40(+2) (37(+0) -42(+3) ) weeks underwent eye tracking at median age of 7 months. Infants were presented with three categories of social stimuli of increasing complexity. Time to first fixate (TFF) and looking time (LT) on areas of interest (AoIs) were recorded using remote eye tracking. Preterm infants consistently fixated for a shorter time on social content than term infants across all three tasks: face-scanning (fixation to eyes minus mouth 0.61s vs. 1.47s, p = .013); face pop-out task (fixation to face 0.8s vs. 1.34s, p = .023); and social preferential looking (1.16s vs. 1.5s p = .02). Time given to AoIs containing social content as a proportion of LT at the whole stimulus was lower in preterm infants across all three tasks. These results were not explained by differences in overall looking time between the groups. Question: Is preterm birth associated with atypical social orienting in infancy detected using eye tracking? <|endoftext|> <|assistant|> Eye tracking provides early evidence of atypical cognition after preterm birth, and may be a useful tool for stratifying infants at risk of impairment for early interventions designed to improve outcome.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Central periodic breathing (CPB) is common following acute stroke, but its prognostic significance is uncertain. We determined the frequency of CPB on admission with stroke and assessed whether it was related to outcome. We measured arterial oxygen saturation (SaO2), chest wall movements and nasal airflow continually with portable monitoring equipment in a large cohort of acute stroke patients, from arrival at hospital through acute assessment to reaching the ward. Baseline neurological examination and 3-month outcome (modified Rankin scale, MRS) were assessed blind to recordings. CPB was defined as cyclical rises and falls in ventilation, with intermittent reduced respiratory airflow or total apnoea. CPB was common in acute stroke (33/138, 24%), but was poorly recognised by clinical staff. Patients with CPB were more likely to have a total anterior circulation syndrome and higher National Institutes of Health Stroke Scale scores than those without (both p<0.01). Patients with CPB had significantly higher median SaO2 than those without (p<0.01), unrelated to whether they received oxygen or not. At 3-month follow-up: 91% of patients with CPB were dead or dependent (MRS>or=3) compared with 53% of those without (OR 8.8; 95% CI 2.5-30.5); the association remained statistically significant after adjusting for covariates (OR 5.9; 95% CI 1.4-25.4). Question: Is central periodic breathing observed on hospital admission associated with an adverse prognosis in conscious acute stroke patients? <|endoftext|> <|assistant|> CPB is independently associated with poor outcome after stroke, but is not by association with hypoxia. Further work is required to identify causes, effects and interventions that might improve effects of CPB.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: To investigate the effect of peritonization at cesarean section on postoperative vital signs which was thought to be an indirect finding secondary to increased sympathetic activity originated from pain caused by stretched peritoneum. One hundred and thirty-three pregnant women were randomized to four groups; Closure of parietal peritoneum only (group 1; n = 32), closure of visceral and parietal peritoneums (group 2; n = 32), no closure of peritoneums (group 3; n = 32) and closure of the visceral peritoneum only (group 4; n = 32). All participants were monitored for blood pressure, pulse activity and hourly urinary output during the first postoperative 24 h. Postoperative pain was measured using a Visual Analogue Scale 6th and 24th hours after surgery. Return of bowel function was measured from the end of the operation to the first passage of flatus. Operating time, pre- and postoperative hemoglobin, postoperative complications, length of hospital stay and postoperative urine osmolarity were noted. The mean surgery duration was significantly longer in group 2. Diuresis was found significantly decreased in group 2. Pulse rate and systolic and diastolic blood pressure were significantly higher in group 2. Closure of both peritoneums was associated with higher post-operative pain as assessed using Visual analogue scale score analyses in group 2. Question: Effects of closure versus non-closure of the visceral and parietal peritoneum at cesarean section: does it have any effect on postoperative vital signs? <|endoftext|> <|assistant|> Both visceral and parietal membrane closure in cesarean section should be avoided in women with hypertensive disorders, renal function abnormalities and autonomic dysfunction because of increased postoperative pain and associated sympathetic overactivity.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: To evaluate whether there is any histologic progression from radical prostatectomy (RP) to local recurrence in patients with clinically isolated local recurrence following RP. A total of 43 patients with clinically isolated, biopsy proven, local recurrence following RP were retrospectively analyzed with respect to the change in Gleason score (GS) from RP to local recurrence. Central pathology review was undertaken for both RP and local recurrence biopsy specimens. The changes in primary and secondary Gleason grade (GG), and any potential correlation between the extent of GS change and other variables were also examined. Median age at the time of local recurrence was 67 years (range: 55-78). Median interval between RP and local recurrence was 3.6 years (range: 0.3-17.7). Eight had a short course (<3 months) of hormone therapy prior to RP. Initial GS of RP specimens was 5, 6, 7, 8, and 9 in 1, 3, 29, 1, and 9 patients, respectively. At the time of local recurrence, GS was upgraded in 13, unchanged in 23, and downgraded in 7. The extent of GS change was correlated with the interval between RP and local recurrence, but not with pathological T stage or age. Question: Is there a progression of histologic grade from radical prostatectomy to local recurrence in patients with clinically isolated local recurrence following surgery? <|endoftext|> <|assistant|> There was no statistically significant change in GS from RP to local recurrence, although there was a trend toward a higher GS at the time of local recurrence. The extent of GS change was associated positively with the elapsed time to local recurrence.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Proteasomes are nonlysosomal proteolytic structures that have been implicated in cell growth and differentiation. Abnormal expression levels of proteasomes have been described in tumor cells, and proteasomes can be detected and measured in plasma. The objective of this study was to characterize differences in proteasome levels between normal, healthy donors and patients with neoplastic disease and to correlate the findings with clinical status and other biologic markers of disease spread. Plasma proteasome levels were measured using a sandwich enzyme-linked immunosorbent assay in normal donors (n = 73 donors) and in patients with solid tumors (n = 20 patients), acute leukemia (n = 35 patients), myeloproliferative (n = 37 patients) and myelodysplastic (n = 19 patients) syndromes, chronic lymphocytic leukemia (n = 44 patients), non-Hodgkin lymphoma (n =104 patients), Hodgkin disease (n = 14 patients), other lymphoid disorders (n = 17 patients), and multiple myeloma (n = 27 patients). In the normal donors, the plasma proteasome concentration was 2356 ng/mL +/- 127 ng/mL. Patients with solid tumors exhibited a significantly higher value (7589 ng/mL +/- 2124 ng/mL), similar to the patients with myeloproliferative (4099 ng/mL +/- 498 ng/mL) and myelodysplastic (2922 ng/mL +/- 322 ng/mL) syndromes. Patients with lymphoproliferative disorders, in contrast, had significantly lower values than normal donors (1751 ng/mL +/- 107 ng/mL), except those in aggressive phase of the disease. This low level persisted in patients who were in complete remission. Proteasome levels decreased during the initial phase of treatment. Although there was a significant correlation with serum lactic dehydrogenase levels, frequent discrepancies were noted. There was no correlation with C-reactive protein or beta2-microglobulin levels, even in the group of patients with multiple myeloma. Question: Is plasma proteasome level a potential marker in patients with solid tumors and hemopoietic malignancies? <|endoftext|> <|assistant|> The plasma proteasome level is a potential new tool for the monitoring of patients with neoplastic disease. It is not correlated solely with cell lysis and may be involved in the pathophysiology of disease progression.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Allergen immunotherapy offers an alternative for drug treatment in the management of allergic diseases. Because immunotherapy often induces side-effects, less allergenic preparations would be beneficial. The purpose of this study was to examine whether the allergenicity of a cow-derived lipocalin allergen, Bos d 2, could be diminished by substituting or deleting carboxy-terminal amino acids including the cysteine which forms a disulphide bond with a cysteine inside the molecule. Four recombinant mutants of Bos d 2 were created by substituting or deleting the four most carboxy-terminal amino acids. The immunological characteristics of the mutant preparations were compared with the unmodified rBos d 2 by Western blotting, ELISA inhibition, skin prick tests, and the proliferative responses of allergen-specific T-cell clones. In Western blot, one of the two monoclonal antibodies showed reduced binding to the preparations without the terminal cysteine. In contrast, the other monoclonal antibody, human IgE and rabbit immune serum bound equally well to all the preparations. ELISA inhibition analyses revealed, however, that the preparations without the terminal cysteine bound antibody less efficiently. They were needed 15-38 times more than the unmodified rBos d 2 to cause the same level of inhibition. Surprisingly, one of the mutants with the terminal cysteine but a mutated adjacent amino acid turned out to be the weakest in inducing skin reactivity. All the preparations stimulated well allergen-specific T-cell clones. Question: Are mutant derivatives of the main respiratory allergen of cow less allergenic than the intact molecule? <|endoftext|> <|assistant|> The results show that the allergenicity of a lipocalin allergen, Bos d 2, can be diminished by modifying the carboxy-terminal end of the molecule. Modifications in the area which encompasses a disulphide bond impaired the antibody binding without affecting the T-cell stimulatory capacity. It was also shown that in vivo tests are necessary for determining the allergenicity of a modified allergen.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: General population studies have shown a strong association between alcohol intake and death from alcoholic cirrhosis, but whether this is a dose-response or a threshold effect remains unknown, and the relation among alcohol misusers has not been studied. A cohort of 6152 alcohol misusing men and women aged 15-83 were interviewed about drinking pattern and social issues and followed for 84,257 person-years. Outcome was alcoholic cirrhosis mortality. Data was analyzed by means of Cox-regression models. In this large prospective cohort study of alcohol misusers there was a 27 fold increased mortality from alcoholic cirrhosis in men and a 35 fold increased mortality from alcoholic cirrhosis in women compared to the Danish population. Number of drinks per day was not significantly associated with death from alcoholic cirrhosis, since there was no additional risk of death from alcoholic cirrhosis when exceeding an average daily number of five drinks (>60 g/alcohol) in neither men nor women. Question: Alcohol and cirrhosis: dose--response or threshold effect? <|endoftext|> <|assistant|> The results indicate that alcohol has a threshold effect rather than a dose-response effect on mortality from alcoholic cirrhosis in alcohol misusers.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: The assessment of workplace physical load is highly resource intensive. This study tested whether a single-item measure asking individuals about perceived physical strain (PPS) at work was an acceptable proxy for physical load. The study was conducted in a subset of the GAZEL cohort (n = 2612) undergoing assessment of exposure to 38 occupational biomechanical constraints (representing eight domains) in 1994. Test-retest reliability analyses compared PPS in 1994 and 1995. Validity analyses compared PPS in 1994 to concurrent strains assessed in the more extensive measure. The measure showed adequate test-retest reliability. Within and across domains of physical load, linear relationships (P<0.0001) existed between n exposures and PPS. Domains considered more strenuous (carrying loads, pulling objects) showed the highest PPS. Question: Can a single-item measure assess physical load at work? <|endoftext|> <|assistant|> Perceived physical strain approximates physical load in the absence of detailed measures. Perceived physical strain could be used in nonoccupational epidemiologic studies.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: We investigated the effects of consensus interferon (IFN-alphaCon1), a nonnaturally occurring type I interferon with higher specific activity than other type I IFNs, on the growth of human liver cancer cells. The effect of IFN-alphaCon1 on the proliferation of 13 liver cancer cell lines was investigated in vitro. Hepatocellular carcinoma (HCC) cells (KIM-1 and HAK-1B) were transplanted subcutaneously into the back of nude mice, then IFN-alphaCon1 was subcutaneously administered to the mice once a day for 2 weeks, and tumor volume and histology were examined. IFN-alphaCon1 expressed a dose-dependent growth inhibitory effect in all cell lines in vitro. KIM-1 tumor volume in mice that received 0.01 microg (10(4)IU)/mouse/day of IFN-alphaCon1 (similar to the clinical dose for chronic hepatitis C) was 62% of the control, 0.1microg/mouse/day resulted in 26%, and 1 microg/mouse/day resulted in 10%. HAK-1B tumor volume under the same treatment was 61, 24 and 0% of the control, respectively. The number of apoptotic cells significantly increased and the number of blood vessels significantly decreased with the increase in IFN-alphaCon1 dose. Question: Does interferon-alphaCon1 suppress proliferation of liver cancer cell lines in vitro and in vivo? <|endoftext|> <|assistant|> IFN-alphaCon1 suppressed HCC growth in nude mice. These data indicate the potential clinical application of IFN-alphaCon1 in the prevention and treatment of HCC.

<|system|> You are an biomedical AI assistant that follows instruction extremely well, Your task is to answer biomedical questions precisely and truthfully using the given abstract <|endoftext|> <|prompter|> Abstract: Regulation of anabolic and catabolic factors is considered essential in maintaining the homoeostasis of healthy articular cartilage. In this study we investigated the influence of RNA binding proteins (RNABPs) in this process. Using small interfering RNA (siRNA), RNABP expression was knocked down in SW1353 chondrosarcoma cells and human articular chondrocytes. Gene expression and messenger RNA (mRNA) decay of anabolic (SOX9, Aggrecan) and catabolic (matrix metalloproteinase (MMP)13) factors were analysed using reverse transcription quantitative polymerase chain reaction (RT-qPCR). RNA-electromobility shift assays (EMSAs) were used to investigate RNABP interactions with the SOX9 mRNA 3' untranslated region (UTR). Immunohistochemical localisation of MMP13 and the RNABP human antigen R (HuR) was performed in E13.5 and E16.5 mouse embryo sections. SOX9 mRNA, mRNA half-life and protein expression were increased with siRNA targeting the RNABP tristetraprolin (TTP) in both HACs and SW1353s. TTP knockdown also stimulated aggrecan mRNA expression but did not affect its stability. RNA-EMSAs demonstrated that adenine uracil (AU)-rich elements in the SOX9 mRNA 3'UTR interacted with chondrocyte proteins with three specific elements interacting with TTP. HuR knockdown significantly increased MMP13 expression and also regulated the expression of a number of known transcriptional repressors of MMP13. HuR was ubiquitously expressed within mouse embryos yet displayed regional down-regulation within developing skeletal structures. Question: Do rNA binding proteins regulate anabolic and catabolic gene expression in chondrocytes? <|endoftext|> <|assistant|> This study demonstrates for the first time how RNABPs are able to affect the balance of anabolic and catabolic gene expression in human chondrocytes. The post-transcriptional mechanisms controlled by RNABPs present novel avenues of regulation and potential points of intervention for controlling the expression of SOX9 and MMP13 in chondrocytes.