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FedML_PubMedQA_instruction_stf_dataset

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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: Crohn's disease (CD) is a chronic idiopathic inflammatory bowel disease involving the whole gastrointestinal tract. TNFSF15 has been proved as a susceptibility gene for CD, but there are few reports about the association between TNFSF15 single nucleotide polymorphisms (SNPs) and the clinical course of CD. To investigate the association between TNFSF15 genotypes and the clinical course of CD in Koreans. A total of 906 CD patients having TNFSF15 genotype data and clinical information were recruited from CD registry database of a tertiary referral center. The association between five TNFSF15 SNPs (rs4574921, rs3810936, rs6478108, rs6478109, and rs7848647) and various clinical parameters including stricture, non-perianal penetrating complications, bowel resection, and reoperation was investigated. Among the five SNPs, rs6478108 CC genotype was associated with the development of stricture and non-perianal penetrating complications during follow-up (HR for stricture=1.706, 95% confidence interval 1.178-2.471, P=0.005; HR for non-perianal penetrating complications=1.667, 95% confidence interval 1.127-2.466, P=0.010), and rs4574921 CC genotype was associated with the development of perianal fistula (HR=2.386, 95% confidence interval 1.204-4.727, P=0.013) by multivariate analysis. However, there was no significant association of cumulative operation and reoperation rate with 5 SNPs of TNFSF15. Question: Is tNFSF15 an independent predictor for the development of Crohn 's disease-related complications in Koreans? <|endoftext|> <|assistant|> In Korean patients with CD, non-risk allele homozygotes of TNFSF15 SNPs rs6478108 and rs4574921 are independent genetic predictive factors for the development of strictures/non-perianal penetrating complications and perianal fistula, respectively.

<|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: Oztag is an Australian tag rugby code in which opponents are 'tackled' by removing Velcro tabs from their shorts. It is assumed to be safer than other higher-contact rugby codes. Oztag-related hand injuries were identified by a word search of the electronic emergency department records of Concord Repatriation General Hospital from January 2011 to October 2013. Clinical records were retrospectively reviewed. Twenty-eight presentations were identified. Mean age of patients was 24 years (range 13-38). Injuries included fractures, dislocations and ligamentous injuries, in isolation or combination. The most common injuries were middle phalangeal fractures (six), all of which required operative fixation. No tendon avulsions were identified. The most common mechanism of injury was attempted tackle, which was much more likely to require operative management than any other mechanism (70% versus 14%, P = 0.010). Question: Oztag: high risk for hand injuries? <|endoftext|> <|assistant|> While the prevalence of Oztag-related hand injuries may be low, the occurrence of potentially debilitating injuries in a young, working population raises concern. The 'tag' tackle, which involves players running at speed with outstretched fingers, is particularly high risk. Prospective audit of injuries is required and players and organizers should be made aware of the dangers of this 'low-contact' sport.

<|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: Exogenous catecholamine exposure has been associated with p38 mitogen-activated protein kinase (MAPK) and cardiac hypertrophy. In this study, we investigated the regulation of p38 MAPK in cardiac remodeling elicited by endogenous adrenergic mechanisms. Transgenic male and female mice with fourfold phospholamban (PLB) overexpression exhibited enhanced circulating norepinephrine (NE), as a physiological compensatory mechanism to attenuate PLB's inhibitory effects. This enhanced noradrenergic state resulted in left ventricular hypertrophy/dilatation and depressed function. Male transgenics exhibited ventricular hypertrophy and mortality at 15 months, concurrent with cardiac p38 MAPK activation. Female transgenics, despite similar contractile dysfunction, displayed a temporal delay in p38 activation, hypertrophy, and mortality (22 months), which was associated with sustained cardiac levels of MAP Kinase Phosphatase-1 (MKP-1), a potent inhibitor of p38. At 22 months, decreases in cardiac MKP-1 were accompanied by increased levels of p38 activation. In vitro studies indicated that preincubation with 17-beta-estradiol induced high MKP-1 levels, which precluded NE-induced p38 activation. Question: Does differential regulation of p38 mitogen-activated protein kinase mediate gender-dependent catecholamine-induced hypertrophy? <|endoftext|> <|assistant|> These findings suggest that norepinephrine-induced hypertrophy is linked closely with p38 MAP kinase activation, which can be endogenously modulated through estrogen-responsive regulation of MKP-1 expression.

<|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 indicate that direct cell-to-cell interaction is involved in transdifferentiation of adult stem cells into cardiomyocytes. We investigated whether transdifferentiation of human adipose-tissue-derived stem cells could be achieved by transfecting the cells with a nuclear neonatal cardiomyocyte extract using a liposome-based transfection system. In this study, we isolated stem cells derived from human subcutaneous adipose tissue. These cells were transfected with nuclear protein extracts from either isolated cardiomyocytes or whole hearts of neonatal rats. Results. We found that transfection induced expression of the cardiac markers alpha-sarcomeric actin, Nkx2.5, troponin I and troponin T after 1-3 weeks. Whole-heart protein extracts showed the additional capacity to induce differentiation into endothelial-like and smooth muscle-like cells. Question: Does liposome-mediated transfection with extract from neonatal rat cardiomyocytes induce transdifferentiation of human adipose-derived stem cells into cardiomyocytes? <|endoftext|> <|assistant|> We demonstrate that transfection with nuclear protein extracts from neonatal rat cardiomyocytes can induce a cardiomyogenic differentiation pathway in human stem cells.

<|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: Antheraea mylitta cytoplasmic polyhedrosis virus (AmCPV), a cypovirus of Reoviridae family, infects non mulberry Indian silk worm, Antheraea mylitta, and contains eleven segmented double stranded RNA in its genome (S1-S11). Some of its genome segments (S1-S3, and S6-S11) have been previously characterized but genome segment encoding the viral guanylyltransferase which helps in RNA capping has not been characterized. In this study genome segment 5 (S5) of AmCPV was converted to cDNA, cloned and sequenced. S5 consisted of 2180 nucleotides, with one long ORF of 1818 nucleotides and could encode a protein of 606 amino acids with molecular mass of ~65 kDa (p65). Bioinformatics analysis showed presence of KLRS and HxnH motifs as observed in some other reoviral guanylyltransferase and suggests that S5 may encodes viral guanylyltransferase. The ORF of S5 was expressed in E. coli as 65 kDa his tagged fusion protein, purified through Ni-NTA chromatography and polyclonal antibody was raised. Immunoblot analysis of virion particles with the purified antibody showed specific immunoreactive band and suggests p65 as a viral structural protein. Functional analysis showed that recombinant p65 possesses guanylyltransferase activity, and transfers GMP moiety to the 5' diphosphate (A/G) ended viral RNA after the formation of p65-GMP complex for capping. Kinetic analysis showed K(m) of this enzyme for GTP and RNA was 34.24 uM and 98.35 nM, respectively. Site directed mutagenesis at K21A in KLRS motif, and H93A or H105A in HxnH motif completely abolished the autoguanylylation activity and indicates importance of these residues at these sites. Thermodynamic analysis showed p65-GTP interaction was primarily driven by enthalpy (ΔH = -399.1 ± 4.1 kJ/mol) whereas the p65-RNA interaction by favorable entropy (0.043 ± 0.0049 kJ/ mol). Question: Does genome segment 5 of Antheraea mylitta cytoplasmic polyhedrosis virus encode a bona fide guanylyltransferase? <|endoftext|> <|assistant|> Viral capping enzymes play a critical role in the post transcriptional or post replication modification in case of RNA virus. Our results of cloning, sequencing and functional analysis of AmCPV S5 indicates that S5 encoded p65 through its guanylyltransferase activity can transfer guanine residue to the 5' end of viral RNA for capping. Further studies will help to understand complete capping process of cypoviral RNA during viral replication within the viral capsid.

<|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 assessed the cellular proliferation of clinically localized prostate cancer by immunohistochemistry using the monoclonal antibody MIB to Ki-67 antigen in an attempt to identify associations between proliferative indexes and disease progression following radical prostatectomy. Ki-67 proliferative antigen was evaluated using MIB 1 monoclonal antibody in archival paraffin embedded radical prostatectomy specimens from 180 patients followed for 1 to 9 years (mean 4.4). The percentage of tumor nuclei expressing Ki-67 antigen was measured and assigned and MIB 1 score (none or rare--negative, 1+--low score and 2 to 4+--high score) and analyzed for prostate specific antigen, stage, age, race, grade and serological recurrence postoperatively. There was a significant association between MIB 1 score and nuclear grade (p < 0.001), Gleason score (p < 0.001) and pathological stage (p = 0.01). Patients with a high MIB 1 score had earlier progression and a lower 5-year recurrence-free survival rate (44%) than those with negative MIB 1 scores (71%, p < 0.001). In multivariate Cox regression analysis with backward elimination, pathological stage (p < 0.01), pretreatment prostate specific antigen (p = 0.04) and MIB 1 score (p = 0.05) were statistically significant predictors of disease-free survival, and patients with a high MIB 1 score were 3.1 times as likely to have recurrence as those with a negative score. Controlling for stage, patients with organ confined disease and a high MIB 1 score had a lower 5-year disease-free survival rate (68%) than those with a low MIB 1 score (95%, p < 0.01). Question: Is ki-67 expression a prognostic marker of prostate cancer recurrence after radical prostatectomy? <|endoftext|> <|assistant|> Proliferative activity as measured by the Ki-67 proliferative antigen, MIB 1, appears to be a prognostic marker of recurrent prostate cancer after radical prostatectomy.

<|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 IgG4 levels in a cohort of consecutive patients with primary Sjögren's syndrome (SS) and other autoimmune diseases and explore whether they associate with distinct clinical, serologic, and histopathologic features. Serum IgG4 levels were measured in 133 primary SS patients and 49 healthy donors (HDs). Seventy-four lupus and 54 rheumatoid arthritis (RA) patients served as disease controls. Immunohistochemical IgG4 analysis was performed in paraffin-embedded minor salivary gland (MSG) tissues. Raised IgG4 serum levels (>135 mg/dl) were detected in 10 (7.5%) of 133 primary SS patients (high-IgG4 group), in 8 (10.8%) of 74 lupus patients, in 7 (12.9%) of 54 RA patients, and in 1 (2%) of 49 HDs. Compared to the normal-IgG4 (<135 mg/dl) primary SS group, high-IgG4 patients exhibited increased prevalence of IgG4-related features (autoimmune cholangitis, autoimmune pancreatitis, and interstitial nephritis), lower rates of antinuclear antibody positivity, and higher IgG2 and IgE levels. Positive staining for IgG4+ plasma cells with an IgG4:IgG ratio ≥40% was detected in 3 of 6 available MSG tissues in the high-IgG4 group. Criteria of possible or definite IgG4-related disease (IgG4-RD) were fulfilled by 10 (7.5%) of 133 of our primary SS cohort. Question: Elevated IgG4 serum levels among primary Sjögren's syndrome patients: do they unmask underlying IgG4-related disease? <|endoftext|> <|assistant|> Raised IgG4 serum levels were detected in 7.5% of primary SS patients in association with IgG4RD-reminiscent clinical, serologic, and histopathologic features. Whether this high-IgG4 primary SS group represents a misclassified IgG4-RD group or a distinct primary SS subtype remains to be further explored in future 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: Topical beta antagonists are prescribed for glaucoma in approximately 500 000 people in the United Kingdom. The authors have previously shown that topical beta antagonists are associated with an excess incidence of airways obstruction. They examined whether selective topical beta antagonists are associated with excess airways obstruction. A historical cohort study was performed to determine the incidence of airways obstruction in subjects with no previous history of airways obstruction, following treatment with topical beta antagonists for glaucoma for the period 1993-7. Cases were defined as having received a first prescription of a drug specifically used in the management of airways obstruction. For selective topical beta antagonists 12 of 324 treated subjects developed airways obstruction, compared with 112 of 9094 controls (adjusted hazard rate 3.0 (95% confidence interval (95% CI) 1.6 to 5.4)). For non-selective topical beta antagonists, the corresponding figures were 69 of 2321 subjects compared with the same control group (adjusted hazard rate 2.2 (1.6 to 3.0)). There was no significant difference between groups (p = 0.47, chi(2)), both being associated with a significantly increased risk of airways obstruction. Question: Do selective topical beta antagonists for glaucoma have respiratory side effects? <|endoftext|> <|assistant|> Selective topical beta antagonists do appear to have an excess risk of airways obstruction in this population setting and should be subject to the same prescribing caveats as unselective topical beta antagonists.

<|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 prognosis in patients with hyperdynamic septic shock correlates with the presence and the severity of septic encephalopathy. However, the neurological evaluation is considerably influenced by the use of analgesia sedation during mechanical ventilation. An early concentration peak of the neuroprotein S-100B in serum reflects both cellular damage at an increased permeability of the blood-brain-barrier and a delayed renal elimination. Thus, the objective of this study was to analyze the effect of continuous veno-venous hemofiltration (CVVH) on early S-100B serum levels in septic shock patients, who were treated with either stress doses of hydrocortisone or placebo. Twenty-four consecutive patients, who met the ACCP / SCCM criteria for septic shock, were enrolled in this prospective, randomised, double-blind, single-center trial. The severity of illness at recruitment was graded using the APACHE II and SAPS II scoring systems; the MODS was described by the SOFA score. All patients were prospectively randomised to receive either stress doses of hydrocortisone or placebo. Hydrocortisone was started in 12 patients with a loading dose of 100 mg and followed by a continuous infusion of 0.18 mg/kg/h for 6 days. Median S-100B serum levels of the hydrocortisone group decreased from 0.32 ng/ml (0.19-3.60) at study entry to 0.07 ng/ml (0.04 - 0.32) 6 days later without significant differences compared to the placebo group. Patients undergoing CVVH showed significantly higher S-100B serum values compared to patients without CVVH (p<0.001). However, initial median S-100B serum levels of the CVVH group even increased from 0.92 ng/ml (0.16 - 4.63) to 2.33 ng/ml (0.59 - 2.44) 30 hours after study entry, reaching data ranges already known in patients with out-of-hospital cardiac arrest or severe traumatic brain injury. Question: Does hemofiltration influence early S-100B serum levels in septic shock patients receiving stress doses of hydrocortisone or placebo? <|endoftext|> <|assistant|> Early S-100B serum levels in septic shock patients receiving either stress doses of hydrocortisone or placebo were not influenced by CVVH. For the first time, we observed a similar extent of S-100B serum increase in CVVH patients, who had significantly higher S-100B serum values compared to those without CVVH, as reported for out-of-hospital cardiac arrest or severe traumatic brain injury. Hypercortisolemia induced by the infusion of stress doses of hydrocortisone did not significantly reduce early S-100B serum concentrations with time.

<|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 long QT syndrome type 1 (LQT1), the location and type of mutations have been shown to affect the clinical outcome. Although haploinsufficiency, including stop-codon and frameshift mutations, has been associated with a lower risk of cardiac events in patients with LQT1, nonsense mutations have been presumed functionally equivalent. The purpose of this study was to evaluate clinical differences between patients with nonsense mutations. The study sample comprised 1090 patients with genetically confirmed mutations. Patients were categorized into 5 groups, depending on mutation type and location: missense not located in the high-risk cytoplasmic loop (c-loop) (n = 698), which is used as reference; missense c-loop (n = 192); stop-codon (n = 67); frameshift (n = 39); and others (n = 94). The primary outcome was a composite end point of syncope, aborted cardiac arrest, and long QT syndrome-related death (cardiac events). Outcomes were evaluated using the multivariate Cox proportional hazards regression analysis. Standard patch clamp techniques were used. Compared to patients with missense non-c-loop mutations, the risk of cardiac events was reduced significantly in patients with stop-codon mutations (hazard ratio [HR] 0.57; 95% confidence interval [CI] 0.34-0.96; P = .035), but not in patients with frameshift mutations (HR 1.01; 95% CI 0.58-1.77; P = .97). Our data suggest that currents of the most common stop-codon mutant channel (Q530X) were larger than those of haploinsufficient channels (wild type: 42 ± 6 pA/pF, n = 20; Q530X+wild type: 79 ± 14 pA/pF, n = 20; P < .05) and voltage dependence of activation was altered. Question: Are stop-codon and C-terminal nonsense mutations associated with a lower risk of cardiac events in patients with long QT syndrome type 1? <|endoftext|> <|assistant|> Stop-codon mutations are associated with a lower risk of cardiac events in patients with LQT1, while frameshift mutations are associated with the same risk as the majority of the missense mutations. Our data indicate functional differences between these previously considered equivalent mutation subtypes.

<|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: Vitamin B12 deficiency could be associated with cardiovascular autonomic neuropathy (CAN) in diabetes patients. We aim to investigate the association between serum levels of vitamin B12 and CAN in type 2 diabetes patients. 469 ambulatory type 2 diabetes patients (mean diabetes duration 10.0years (IQR 5.0;17.0), mean age 59.0years (SD 11.6), 63% men, mean B12 289.0pmol/l (IQR 217;390)) were screened for CAN using three cardiovascular reflex tests, five minute resting heart rate (5min RHR) and heart rate variability indices. Serum levels of vitamin B12 were significantly lower in patients treated with metformin and/or proton pump inhibitors (PPIs) compared with patients not treated (p<0.001). A 25pmol/l higher level of vitamin B12 was associated with an odds ratio of the CAN diagnosis of 0.94 (95% CI 0.88; 1.00, p=0.034), an increase in E/I-ratio of 0.21% (95% CI 0.01; 0.43, p=0.038), and a decrease in 5min RHR of 0.25 beats per minute (95% CI -0.47; -0.03, p=0.025). Question: Is vitamin B12 deficiency associated with cardiovascular autonomic neuropathy in patients with type 2 diabetes? <|endoftext|> <|assistant|> Vitamin B12 may be inversely associated with CAN in patients with type 2 diabetes. Confirmatory studies investigating a causal role of vitamin B12 for the development of diabetic CAN are warranted.

<|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: Mild forms of HIV-associated neurocognitive disorders (HAND) remain prevalent in the era of combination antiretroviral therapy (cART). Although elevated lipopolysaccharide (LPS) and immune activation are implicated in HAND pathogenesis, relationships of LPS and inflammatory markers to mild forms of HAND or impairment in specific cognitive domains are unknown. To examine these relationships, we compared plasma soluble CD14 (sCD14), CCL2, and LPS levels with neurocognitive test scores in a cART era cohort. We analyzed plasma from HIV+ subjects (n = 97) with nadir CD4 counts <300 and high frequency of hepatitis C virus coinfection and illicit drug use for relationships between sCD14, CCL2, and LPS levels and neurocognitive test scores. Plasma sCD14 levels were higher in subjects with test scores indicating global impairment (P = 0.007), particularly in attention and learning domains (P = 0.015 and P = 0.03, respectively), regardless of HAND diagnosis. Plasma sCD14 levels correlated inversely with global, attention, and learning T scores (P = 0.036, 0.047, and 0.007, respectively) and yielded higher area under receiver operating characteristic values for predicting impaired scores than single-marker models based on plasma or cerebrospinal fluid viral load or CD4 count (area under receiver operating characteristic values = 0.71, 0.81, and 0.71, respectively) and in 4-marker models based on plasma sCD14 and 3 conventional markers compared with the 3-marker models. Question: Is plasma sCD14 a biomarker associated with impaired neurocognitive test performance in attention and learning domains in HIV infection? <|endoftext|> <|assistant|> Plasma sCD14 is a biomarker associated with impaired neurocognitive testing in attention and learning domains in HIV-infected individuals with advanced disease, suggesting involvement of cortical and limbic pathways by inflammatory processes in the cART era. Plasma sCD14 is a potential biomarker to monitor HAND progression and therapeutic responses.

<|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: Auditory and visual deviant stimuli evoke mismatch negativity (MMN) responses, which can be recorded with electroencephalography (EEG) and magnetoencephalography (MEG). However, little is known about the role of neuronal oscillations in encoding of rare stimuli. We aimed at verifying the existence of a mechanism for the detection of deviant visual stimuli on the basis of oscillatory responses, so-called visual mismatch oscillatory response (vMOR). Peripheral visual stimuli in an oddball paradigm, standard vs. deviant (7:1), were presented to twenty healthy subjects. The oscillatory responses to an infrequent change in the direction of moving peripheral stimuli were recorded with a 60-channel EEG system. In order to enhance the detection of oscillatory responses, we used the common spatial pattern (CSP) algorithm, designed for the optimal extraction of changes in the amplitude of oscillations. Both standard and deviant visual stimuli produced Event-Related Desynchronization (ERD) and Synchronization (ERS) primarily in the occipito-parietal cortical areas. ERD and ERS had overlapping time-courses and peaked at about 500-730 ms. These oscillatory responses, however, were significantly stronger for the deviant than for the standard stimuli. A difference between the oscillatory responses to deviant and standard stimuli thus reflects the presence of vMOR. Question: Do visual deviant stimuli produce mismatch responses in the amplitude dynamics of neuronal oscillations? <|endoftext|> <|assistant|> The present study shows that the detection of visual deviant stimuli can be reflected in both synchronization and desynchronization of neuronal oscillations. This broadens our knowledge about the brain mechanisms encoding deviant sensory stimuli.

<|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: Nitric oxide is a major inhibitory neurotransmitter in the enteric nervous system. Loss or dysfunction of nitrinergic neurons is associated with serious disruptions of motility, intractable symptoms, and long-term suffering. The aim of this study was to evaluate the effect of intrapyloric transplantation of neural stem cells (NSCs) on gastric emptying and pyloric function in nNOS-/- mice, a well-established genetic model of gastroparesis. NSCs were isolated from embryonic mice transgenically engineered to express green fluorescent protein and transplanted into the pylorus of nNOS-/- mice. Grafted cells were visualized in pyloric sections and further characterized by immunofluorescence staining. One week posttransplantation, gastric emptying to a non-nutrient meal was measured using the phenol red method and pyloric function was assessed by measuring the relaxation of pyloric strips in an organ bath in response to electrical field stimulation (EFS) under nonadrenergic, noncholinergic conditions. One week following implantation, grafted NSCs differentiated into neurons and expressed neuronal nitric oxide synthase. Gastric emptying was significantly increased in mice that received NSCs as compared with vehicle-injected controls (49.67% vs 35.09%; P < .01 by Student t test). EFS-induced relaxation of pyloric strips was also significantly increased (P < .01 by 2-way analysis of variance). The nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester and the neuronal blocker tetrodotoxin blocked the EFS-induced relaxation, indicating that the observed effect is NO mediated and neuronally derived. Question: Does neural stem cell transplantation in the stomach rescue gastric function in neuronal nitric oxide synthase-deficient mice? <|endoftext|> <|assistant|> Our results support the potential of NSC transplantation as a viable therapeutic option for neuroenteric disorders.

<|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 phenomenon of cross-talk has been noted that electrical stimulation of one part of the gut affects another part of the gut. This study was designed to investigate whether the effect of electrical stimulation of one part of the gut on another part of the gut was related to the organ or the distance between the stimulation site and the affected organ, and the mechanism of ileum electrical stimulation on rectal tone. This study was performed in 13 healthy dogs (16-28 kg) in the fasting state. Experiments were performed to study 1) effects of gastric electrical stimulation, duodenal electrical stimulation, ileum electrical stimulation, and colonic electrical stimulation on rectal tone, and 2) the sympathetic and nitrergic pathways involved in the effects of ileum electrical stimulation on rectal tone. A computerized barostat was used to assess rectal tone. All methods of stimulations significantly inhibited rectal tone. Duodenal electrical stimulation was least effective in reducing rectal tone. The percentage of increase in rectal volume was distance-related with duodenal electrical stimulation, ileum electrical stimulation, and colonic electrical stimulation but organ-specific with gastric electrical stimulation. The inhibitory effect of ileum electrical stimulation on rectal tone was abolished by N omega-nitro-L-arginine but not guanethidine. Question: Are inhibitory effects of gastrointestinal electrical stimulation on rectal tone both organ-specific and distance-related in dogs? <|endoftext|> <|assistant|> Electrical stimulation of the stomach, intestine, or colon with long pulses has an inhibitory effect on rectal tone. This inhibitory effect is organ-specific as well as associated with the distance between stimulation site and affected organs. The inhibitory effect of ileum electrical stimulation on rectal tone is mediated by the nitrergic but not sympathetic pathway.

<|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 antioxidant and antiapoptotic effects of U-74389G on ischemic brain in rats. Right focal cerebral ischemia and reperfusion was induced by suturing in 103 male SD rats weighing 280-310 g. To determine LPO in the cortex and striatum, we randomly divided 78 rats into 5 groups: group 1, sham-operative group (6 rats); group 2, control (18); group 3, U-74389G administration before ischemia (18); group 4, U-74389G administration before reperfusion; group 5, CS-4 vehicle as negative control. Groups 2-5 were further divided into 3 subgroups according to the duration of reperfusion. Another 25 rats were similarly grouped (5) to detect apoptosis with TUNEL stain. The concentrations of MDA in groups 3 and 4 were reduced and the activities of SOD and concentrations of GSH were partially restored as compared with the control group. These effects were more significant in group 3 than in group 4. Otherwise, CS-4 can not provide protective effects. The number of apoptotic cells in groups 3 (P < 0.01) and 4 (P < 0.05) was significantly reduced as compared with the control group. Question: Does u-74389G suppress lipid peroxidation and apoptosis following focal cerebral ischemia and reperfusion in rats? <|endoftext|> <|assistant|> U-74389G has antioxidant and antiapoptotic effects on ischemic brain in rats. The administration of U-74389G before the onset of ischemia was more useful than that before the onset of reperfusion.

<|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: Most of our knowledge about how antiretrovirals and host immune responses influence the HIV-1 protease gene is derived from studies of subtype B virus. We investigated the effect of protease resistance-associated mutations (PRAMs) and population-based HLA haplotype frequencies on polymorphisms found in CRF01_AE pro. We used all CRF01_AE protease sequences retrieved from the LANL database and obtained regional HLA frequencies from the dbMHC database. Polymorphisms and major PRAMs in the sequences were identified using the Stanford Resistance Database, and we performed phylogenetic and selection analyses using HyPhy. HLA binding affinities were estimated using the Immune Epitope Database and Analysis. Overall, 99% of CRF01_AE sequences had at least 1 polymorphism and 10% had at least 1 major PRAM. Three polymorphisms (L10 V, K20RMI and I62 V) were associated with the presence of a major PRAM (P < 0.05). Compared to the subtype B consensus, six additional polymorphisms (I13 V, E35D, M36I, R41K, H69K, L89M) were identified in the CRF01_AE consensus; all but L89M were located within epitopes recognized by HLA class I alleles. Of the predominant HLA haplotypes in the Asian regions of CRF01_AE origin, 80% were positively associated with the observed polymorphisms, and estimated HLA binding affinity was estimated to decrease 19-40 fold with the observed polymorphisms at positions 35, 36 and 41. Question: Do protease polymorphisms in HIV-1 subtype CRF01_AE represent selection by antiretroviral therapy and host immune pressure? <|endoftext|> <|assistant|> Polymorphisms in CRF01_AE protease gene were common, and polymorphisms at residues 10, 20 and 62 most likely represent selection by use of protease inhibitors, whereas R41K and H69K were more likely attributable to recognition of epitopes by the HLA haplotypes of the host 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: To assess the reliability of nasal inspiratory peak flow (NIPF) in providing a clinically accurate objective measure following functional septorhinoplasty by comparing it to the validated disease-specific quality-of-life questionnaire, SNOT-22. Studies so far have demonstrated poor correlation between bilateral NIPF and symptom-specific nasal questionnaires following septorhinoplasty. To perform a prospective comparative analysis between NIPF and the validated disease-specific quality-of-life questionnaire SNOT-22 and to determine whether a correlation exists following septorhinoplasty surgery. The Royal National Throat Nose and Ear Hospital, London. A total of 122 patients (78 males, 44 females; mean age 33.5 ± 12.2 years) were recruited from the senior authors rhinology clinic and underwent functional septorhinoplasty surgery. Preoperative and postoperative nasal inspiratory peak flow (NIPF) measurements were performed in addition to the completion of three subjective quality-of-life and symptom assessment tool questionnaires; Sinonasal Outcome Test 22 (SNOT-22), Nasal Obstruction Symptom Evaluation (NOSE) and Visual Analogue Scale (VAS: 0-10). The mean preoperative NIPF was 88.2 L/min, and the postoperative value was 101.6 L/min and showed a significant improvement following surgery (P = 0.0064). The mean total SNOT-22 score improved significantly from 48.6 to 26.6 (P<0.0001); the NOSE score from 14.1 to 6.6 (P<0.0001); and the Visual Analogue Scale (VAS) blockage score from 6.9 to 3.2 (P<0.0001). All individual domains assessed showed improvements postoperatively, but no correlation was found between the NIPF and SNOT-22 score. Equally, we did not find a correlation between NIPF and the symptom-specific NOSE questionnaire and the nasal blockage domain on the Visual Analogue Scale (VAS) scale. Question: The need for an objective measure in septorhinoplasty surgery: are we any closer to finding an answer? <|endoftext|> <|assistant|> We have demonstrated that NIPF does not correlate with the SNOT-22 disease-specific questionnaire, although both outcomes significantly improve postoperatively. At present, we are still lacking a clinically accurate objective measure of nasal function for the evaluation of patients undergoing septorhinoplasty surgery.

<|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: Immediate treatment has been shown to decrease the recurrence of cerebrovascular accidents following transient ischemic attacks (TIA), prompting the use of a specialized neurologic emergency department (Neuro ED) to triage patients. Despite these findings, there is little evidence supporting the notion that hospital admission improves post-TIA outcomes. Through the lens of a Neuro ED, this retrospective chart review of TIA patients examines whether hospital admission improves 90-day outcomes. Two hundred sixty charts of patients discharged with TIA diagnosis were reviewed. These charts encompassed patients with TIA who presented to a main emergency department (ED) or Neuro ED from January 2014 to April 2015. Demographic information, admission ABCD(2) scores, admission National Institutes of Health Stroke Scale scores, and admission Modified Rankin Scale, and reason for any return visits within 90 days were collected. This review shows that patients triaged by the Neuro ED were admitted at a lower rate than those seen by the standard ED. Further, patients triaged by the Neuro ED experienced lower readmission and recurrence of stroke or TIA within 90 days. Question: An Analysis of Transient Ischemic Attack Practices: Does Hospital Admission Improve Patient Outcomes? <|endoftext|> <|assistant|> These results provide preliminary support for the notion that discharging appropriate TIA patients, with adequate follow-up, will not adversely affect the recurrence of TIA or stroke within 90 days.

<|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: Leukocytes rapidly accumulate in the heart early in reperfusion after ischemia, contributing to reperfusion injury. The purpose of this study was to determine whether treatment with the selectin blocker fucoidin (FCN) would attenuate early leukocyte retention in coronary venules and capillaries during low flow reperfusion. Isolated rat hearts subjected to 30 minutes of 37 degrees C, no-flow ischemia were initially reperfused with blood containing labeled leukocytes, followed by reperfusion with a Krebs red cell solution. The deposition of leukocytes in coronary capillaries and venules was observed using intravital microscopy. Three groups were studied: nonischemic control hearts, untreated postischemic hearts reperfused at low flow, and postischemic hearts reperfused at low flow, where both the hearts and the blood reperfusate were pretreated with FCN (0.36 mg/mL blood). In the ischemia-reperfusion group, we observed a rapid and significant increase in leukocyte accumulation in both capillaries and venules. Treatment with FCN significantly reduced the leukocyte accumulation in both capillaries and venules (p<0.05). In addition, FCN significantly reduced the persistence of leukostasis in both capillaries and venules, indicating that FCN affected a transient adhesion process. Question: Does fucoidin reduce coronary microvascular leukocyte accumulation early in reperfusion? <|endoftext|> <|assistant|> These results suggest that the selectin family of leukocyte-endothelial cell adhesion proteins mediates the initial retention of leukocytes in both coronary capillaries and venules during reperfusion. Selectin blockade may be effective in reducing the contribution of leukocytes to early reperfusion injury.

<|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 was undertaken to compare the rate of abnormal glucose levels measured after 1 hour (>140 mg%) with those measured after 2 hours (>120 mg%) postprandially in women with gestational diabetes mellitus (GDM). Sixty-eight women were included in this study. All had GDM based on the criteria of Carpenter-Coustan. Women with fasting glucose levels of 105 mg% or more were excluded from the study. All women were initially treated by diet. All women measured daily capillary blood glucose levels when fasting as well as 1 hour and 2 hours postprandially for 1 week, immediately after diagnosis of GDM. Glucose levels were obtained by memory-based glucometers. All women were followed in a specialized gestational-diabetes clinic throughout the pregnancy. Insulin therapy was started on an individual basis according to common clinical criteria. Epidemiologic and perinatal data were collected from medical charts. The average age of the women was 30.8 +/- 5.4 years. Thirty-five percent of participants were primipara. The mean gestational age at diagnosis was 28.8 +/- 5.4 weeks. Glucose measurements included 618 readings during fasting and 2730 either 1 hour or 2 hours postprandial. Rates of abnormal glucose (>95 mg% when fasting;>140 mg% 1 hour or>120 mg% 2 hours after each meal) per person were the following: fasting, 27.1% abnormal glucose measurements; postbreakfast, 22.4% abnormal levels after 1 and 8.5% after 2 hours (P<.01); postlunch, 16.4% abnormal levels after 1 hour and 18.2% after 2 hours (not significant); postdinner, 16.3% abnormal levels after 1 hour and 30.1% after 2 hours (P<.01). Question: One or two hours postprandial glucose measurements: are they the same? <|endoftext|> <|assistant|> The rate of abnormal values was 2.5-fold greater 1 hour postbreakfast than 2 hours postbreakfast, in contrast to an opposite ratio of a 2-fold increase in the rate of abnormal values 2 hours postdinner versus 1 hour postdinner. Therefore, differential measurement (1 hour after breakfast and 2 hours after dinner) might impose stricter criteria for controlling blood glucose levels. Further clinical research should explore whether differential measurements might reduce the rate of diabetes-associated complications.

<|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 Stroke Eastern Saxony Network (SOS-NET) provides telecare for acute stroke patients. Stroke neurologists recommend intravenous thrombolysis based on clinical assessment and cerebral computed tomography (CT) evaluation using Alberta Stroke Program Early CT score (ASPECTS). We sought to assess whether ASPECTS misinterpretation by stroke neurologists was associated with thrombolysis-related symptomatic intracranial hemorrhage (sICH). We retrospectively analyzed consecutive SOS-NET patients treated with thrombolytics from July 2007 to July 2012. Experienced neuroradiologists re-evaluated CT scans blinded to clinical information providing reference standard. We defined ASPECTS underestimation as ASPECTS stroke neurologist--ASPECTS neuroradiologist more than 1 point. Primary outcome was sICH by European Cooperative Acute Stroke Study II criteria. Secondary outcome was unfavorable outcome at discharge defined as modified Rankin Scale scores 3 or more. Of 1659 patients with acute ischemic stroke, thrombolysis was performed in 657 patients. Complete primary outcome and imaging data were available for 432 patients (median age, 75; interquartile range [IQR], 12 years; National Institutes of Health Stroke Scale score, 12 [IQR, 11]; 52.8% women). Nineteen patients (4.4%) had sICH, and 259 patients (60.0%) had an unfavorable outcome at discharge. Interobserver agreement between ASPECTS assessment was fair (κ = .51). ASPECTS underestimation was neither associated with sICH (adjusted odds ratio (OR), 1.32; 95% confidence interval (CI), .36-4.83, P = .68) nor unfavorable outcome (adjusted OR, 1.10; 95% CI, .47-2.54; P = .83). Question: Is telemedical Brain Computed Tomography Misinterpretation by Stroke Neurologists Associated with Thrombolysis-Related Intracranial Hemorrhage? <|endoftext|> <|assistant|> Despite fair interrater agreement between stroke neurologists and expert neuroradiologists, underestimation of ASPECTS by the former was not associated with thrombolysis-related sICH in our telestroke network.

<|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: Raf kinase inhibitory protein (RKIP) is an inhibitor of the Raf/MEK/MAP kinase signaling cascade and a suppressor of cancer metastasis. But its function in pancreatic cancer was not yet clarified completely. The aim of this study was to investigate the involvement of RKIP in pancreatic cancer. RKIP expression was investigated retrospectively by immunohistochemistry in paraffin-embedded primary tumor tissue samples from a series (n = 99) of consecutive patients with pancreatic cancer. Survival was calculated using Kaplan-Meier curves. Parameters found to be of prognostic significance in univariate analysis were verified in a multivariate Cox regression model. RKIP expression was high in normal pancreatic epithelium and retained to varying degrees in pancreatic cancer tissues. However, in tumor tissues with lymph node metastasis (P = 0.008) and high UICC stage (P = 0.006), RKIP expression was highly significantly reduced or lost. Furthermore, the reduced expression of RKIP significantly correlated with both poor overall and disease-free survival (P = 0.008 and 0.01, respectively). Multivariate analyses revealed RKIP to be an independent prognosticator. Question: Does reduced expression of Raf kinase inhibitor protein correlate with poor prognosis in pancreatic cancer? <|endoftext|> <|assistant|> These findings suggest that RKIP could be a promising marker for predicting a better prognosis in pancreatic 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: Group A Streptococcus (GAS) causes acute tonsillopharyngitis in children, and approximately 20% of this population are chronic carriers of GAS. Antibacterial therapy has previously been shown to be insufficient at clearing GAS carriage. Bacterial biofilms are a surface-attached bacterial community that is encased in a matrix of extracellular polymeric substances. Biofilms have been shown to provide a protective niche against the immune response and antibiotic treatments, and are often associated with recurrent or chronic bacterial infections. The objective of this study was to test the hypothesis that GAS is present within tonsil tissue at the time of tonsillectomy. Blinded immunofluorescent and histological methods were employed to evaluate palatine tonsils from children undergoing routine tonsillectomy for adenotonsillar hypertrophy or recurrent GAS tonsillopharyngitis. Immunofluorescence analysis using anti-GAS antibody was positive in 11/30 (37%) children who had tonsillectomy for adenotonsillar hypertrophy and in 10/30 (33%) children who had tonsillectomy for recurrent GAS pharyngitis. Fluorescent microscopy with anti-GAS and anti-cytokeratin 8 & 18 antibodies revealed GAS was localized to the tonsillar reticulated crypts. Scanning electron microscopy identified 3-dimensional communities of cocci similar in size and morphology to GAS. The characteristics of these communities are similar to GAS biofilms from in vivo animal models. Question: Does detection of group A Streptococcus in tonsils from pediatric patients reveal high rate of asymptomatic streptococcal carriage? <|endoftext|> <|assistant|> Our study revealed the presence of GAS within the tonsillar reticulated crypts of approximately one-third of children who underwent tonsillectomy for either adenotonsillar hypertrophy or recurrent GAS tonsillopharyngitis at the Wake Forest School of Medicine.

<|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: Cervical artery dissection (CAD) is a common cause of ischemic stroke in young adults. Alteration in the structure of the vascular extracellular matrix has been described in CAD. Matrix metalloproteinases (MMPs) degrade extracellular matrix proteins and can lead to vascular damage. We tested 2 different MMP-9 DNA polymorphisms, a CA repeat and a cytosine to thymidine transition in the promotor sequence, for frequency in 52 patients with CAD. We compared the results with those of 52 healthy controls. No differences were found in the allelic distribution of either polymorphism. Question: Are mMP-9 polymorphisms associated with spontaneous cervical artery dissection? <|endoftext|> <|assistant|> Alleles of these well-characterized functional polymorphisms of MMP-9 gene are not associated with structural alterations in the matrix of vessels of patients with CAD.

<|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 study was conducted at the University of Aberdeen Dental School. UCAS forms for course applicants were reviewed and assigned a pre-admission score (PAS) and a tariff given for the UCAS personal statement (UCAS). Individuals ranked highest were invited to attend multiple mini-interviews (MMI), which were scored. Data was correlated with academic performance reported as the University Common Assessment Scale (0-20). Comparisons were also made between the first degree and subsequent educational achievement. Data were analysed by multiple linear regression, Pearson correlation and unstacked ANOVA (IBM SPSS Statistics 19). Data were obtained for 75 students (F: 50; M: 25). A correlation between performance at MMI and CAS scores was identified (r = 0.180, p = 0.001, df = 538). A correlation was also noted between each student's first degree and the CAS scores (F = 4.08, p = 0.001, df = 9). Question: The admissions process in a graduate-entry dental school: can we predict academic performance? <|endoftext|> <|assistant|> This study suggests that candidate performance at MMI might be a stronger predictor of academic and clinical performance of graduate-entry dental students compared to other pre-interview selection criteria. The first degree for such a programme also appears to be significant.

<|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: Transfusion-related immunomodulation consists of both proinflammatory and anti-inflammatory responses after transfusion of blood products. Stored red blood cells (RBCs) suppress human T-cell proliferation in vitro, but the mechanism remains unknown. We hypothesized that cytokine synthesis by T cells may be inhibited when stored RBCs are present and that suppression between fresh and stored RBCs would be different. Purified human T cells were stimulated to proliferate with anti-CD3/anti-CD28 and then exposed to stored or fresh RBCs. Cells were placed in culture for 5 days. Cell culture supernatants were analyzed for the production of typical T-cell cytokines using multianalyte ELISArray kits. Stimulated T cells proliferated. RBC exposure markedly suppressed this proliferation. Interleukin 10, interleukin 17a, interferon γ, tumor necrosis factor α, and granulocyte macrophage colony-stimulating factor were increased in response to stimulation but depressed in the presence of stored RBCs. The use of fresh RBCs also resulted in depression of these cytokines when compared with stimulated T cells with no RBCs; however, this depression was less pronounced. Question: Does in vitro transfusion of red blood cells result in decreased cytokine production by human T cells? <|endoftext|> <|assistant|> T-cell activation is associated with both proinflammatory and anti-inflammatory cytokine release, comparable with patterns seen in trauma and acute injury. All of these responses are depressed by an exposure to stored RBCs. Decreased levels of these cytokines after RBC transfusion represents a potential contributor to the immunosuppressive complications seen in trauma patients after transfusion. This provides insight for future mechanistic studies to delineate the role of RBC transfusion in transfusion-related immunomodulation.

<|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 development of atherosclerosis may be enhanced by iron accumulation in macrophages. Hepcidin-25 is a key regulator of iron homeostasis, which downregulates the cellular iron exporter ferroportin. In haemodialysis (HD) patients, hepcidin-25 levels are increased. Therefore, it is conceivable that hepcidin-25 is associated with all-cause mortality and/or fatal and non-fatal cardiovascular (CV) events in this patient group. The aim of the current analysis was to study the relationship between hepcidin-25 and all-cause mortality and both fatal and non-fatal CV events in chronic HD patients. Data from 405 chronic HD patients included in the CONvective TRAnsport STudy (NCT00205556) were studied (62% men, age 63.7 ± 13.9 years [mean ± SD]). The median (range) follow-up was 3.0 (0.8-6.6) years. Hepcidin-25 was measured with mass spectrometry. The relationship between hepcidin-25 and all-cause mortality or fatal and non-fatal CV events was investigated with multivariate Cox proportional hazard models. Median (interquartile range) hepcidin-25 level was 13.8 (6.6-22.5) nmol/L. During follow-up, 158 (39%) patients died from any cause and 131 (32%) had a CV event. Hepcidin-25 was associated with all-cause mortality in an unadjusted model [hazard ratio (HR) 1.14 per 10 nmol/L, 95% CI 1.03-1.26; P = 0.01], but not after adjustment for all confounders including high-sensitive C-reactive protein (HR 1.02 per 10 nmol/L, 95% CI 0.87-1.20; P = 0.80). At the same time, hepcidin-25 was significantly related to fatal and non-fatal CV events in a fully adjusted model (HR 1.24 per 10 nmol/L, 95% CI 1.05-1.46, P = 0.01). Question: Is hepcidin-25 related to cardiovascular events in chronic haemodialysis patients? <|endoftext|> <|assistant|> Hepcidin-25 was associated with fatal and non-fatal CV events, even after adjustment for inflammation. Furthermore, inflammation appears to be a significant confounder in the relation between hepcidin-25 and all-cause mortality. These findings suggest that hepcidin-25 might be a novel determinant of CV disease in chronic HD 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: The hospital environment contributes to the spread of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-PE) during outbreaks. We aimed to assess the rate of environmental contamination in rooms occupied by ESBL carriers or infected children and to identify risk factors associated with contamination. Five environmental surface samples were systematically performed in rooms occupied by ESBL-PE carrier or infected children. Forty-six Escherichia coli and 48 Klebsiella infected/carrier patients were included in the study. Nineteen (4%) of the 470 environmental samples performed yielded ESBL-PE. Klebsiella spp was the most frequent species isolated (16, 89%), whereas E coli and Citrobacter freundii were reported twice and once, respectively. Ten of the 19 (52%) isolates were identical to the corresponding strains isolated from children. Multivariate analysis highlighted ESBL-producing Klebsiella carriage/infection as the only risk factor significantly associated with surface contamination (P = .024). Question: Environmental contamination with extended-spectrum β-lactamases: is there any difference between Escherichia coli and Klebsiella spp? <|endoftext|> <|assistant|> Our data suggest that hospital environmental contamination is more frequent in instances of fecal carriage or infection with ESBL-producing Klebsiella than ESBL-producing E coli. Reinforcing hygiene measures around ESBL-producing Klebsiella might be necessary to reduce the spread of ESBL-PE in hospital 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 diagnosis of Whipple's disease (WD) is commonly confirmed by histology demonstrating Periodic Acid Schiff (PAS)-positive macrophages in the duodenal mucosa. Analysis of intestinal tissue or other specimens using polymerase chain reaction (PCR) is a more sensitive method. However, the relevance of positive PCR findings is still controversial. Therefore, we evaluated the relevance of histology and PCR findings to establishing the diagnosis of WD in a series of WD patients initially presenting with suspected rheumatic diseases. Between 2006 and 2014, 20 patients with seronegative rheumatic diseases tested positive for Tropheryma whipplei (Tw) by PCR and/or histology and were enrolled in a retrospective analysis of the diagnostic value of both procedures. Seven of the 20 cases (35%) were diagnosed with 'classic' WD as indicated by PAS-positive macrophages. In the remaining 13 patients, the presence of Tw was detected by intestinal (n = 10) or synovial PCR analysis (n = 3). Two of the 20 patients (10%) with evidence of Tw did not respond to antibiotic therapy. They were not considered to suffer from WD. Therefore, relying only on histological findings of intestinal biopsies would have missed 11 (61%) of the 18 patients with WD in our cohort. In comparison, PCR of intestinal biopsies detected Tw-DNA in 14 (93%) of the 15 WD patients evaluated. Patients with a positive histology did not differ from PCR-positive patients with regard to sex, age, or duration of disease, but more often presented with gastrointestinal symptoms. Question: Is pCR analysis superior to histology for diagnosis of Whipple 's disease mimicking seronegative rheumatic diseases? <|endoftext|> <|assistant|> A substantial number of WD patients present without typical intestinal histology findings. Additional PCR analysis of intestinal tissue or synovial fluid increased the sensitivity of the diagnostic evaluation and should be considered particularly in patients presenting with atypical seronegative rheumatic diseases and a high-risk profile for WD.

<|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: It has been suggested that thrombospondin-1 (TSP-1) plays a role in angiogenesis in many cancers. In addition, TSP-1 has been shown to suppress tumor growth by activating transforming growth factor-β (TGF-β). Recent studies have shown that Ski protein suppresses TGF-β signaling. The aim of this study was to investigate the role of TSP-1 and Ski expression in advanced gastric cancer. Sixty-five recurrent patients who underwent resection of advanced gastric cancer (n = 62) or who had unresectable tumors (n = 3) between March 2003 and October 2007 participated in this study. All patients were treated with chemotherapy after collection of the tumor tissue. Twenty-three of them were also treated with chemotherapy before collection of the tumor specimen. The TSP-1, Ski, vascular endothelial growth factor (VEGF) and TGF-β protein expression were examined by immunohistochemical staining, and microvessels in the tumor were counted. There were 17 (26.2%) gastric cancers with positive staining for TSP-1. There was no relationship between TSP-1 expression and clinicopathological factors. TSP-1 expression had positive association with VEGF expression, microvessel density (MVD) and TGF-β expression. However, there was no relationship between TSP-1 and Ski expression. TSP-1 correlated with good survival in advanced gastric cancer, and Ski correlated with poor survival in the patients with TGF-β-positive advanced gastric cancer. Question: Are expression of thrombospondin-1 and Ski prognostic factors in advanced gastric cancer? <|endoftext|> <|assistant|> This study shows that TSP-1 enhances angiogenesis due to its positive correlation with VEGF and MVD, and is a good prognostic factor for survival in advanced gastric cancer. This study also shows that Ski inhibits the prolonged effects of TGF-β for survival in advanced gastric 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: In vivo airway hyperresponsiveness has been demonstrated following inhalation of specific cytokines in normal individuals. Whether this airway hyperresponsiveness results from a direct effect of cytokines on airway smooth muscle contractility, or via changes in airway wall structure is not known. The aim of the present study was to determine the effect of the pro-inflammatory cytokines interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) on airway smooth muscle contractility in vitro. Ovine tracheal smooth muscle strips were incubated for 18 h at room temperature in Dulbecco's modified Eagle's medium, supplemented with antibiotics, with IL-1beta (10 ng/mL) and TNF-alpha (100 ng/mL), in an atmosphere of 5%CO2:95%O2. Following incubation cumulative concentration-response curves to acetylcholine (ACh) and neurokinin A (NKA) were obtained. Antagonist affinity studies were performed to determine whether the cytokine-induced enhanced contractility to ACh and NKA resulted from a functional alteration to specific M3 and NK2 receptors. Cumulative concentration-response curves to NKA were performed in the presence of phosphoramidon to determine if the enhanced contractility to NKA following cytokine exposure was due to a reduction in endogenous neutral endopeptidase activity. To assess the calcium dependence of the hyperresponsiveness, cumulative concentration-responses to ACh were conducted in calcium-free Krebs'-Henseleit solution. Pre-incubation with TNF-alpha and IL-1beta caused a significant leftward shift, and an increase in the magnitude, of the concentration-response curves to both ACh and NKA. No difference in M3 and NK2 receptor antagonist affinity (pA2) values between the control and cytokine-treated tissue was observed. Neurokinin A contractility in the presence of phosphoramidon indicated that the enhanced contractility following cytokine exposure was not due to a reduction in endogenous neutral endopeptidase activity. Removal of extracellular calcium ions attenuated the contractile response to low concentrations of ACh in the control and cytokine-pretreated tissue. However, enhanced contractility following TNF-alpha and IL-1beta pretreatment was still present. Question: Do cytokines enhance airway smooth muscle contractility in response to acetylcholine and neurokinin A? <|endoftext|> <|assistant|> Pro-inflammatory cytokines induce in vitro hyperresponsiveness in normal airway smooth muscle via a mechanism involving intracellular calcium mobilization.

<|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 investigates the dietary intake of African American women in public housing as related to cancer risk and explores the sociodemographic factors that hinder healthy dietary intake in this population. Demographic and dietary data for this cross-sectional study were collected as part of a Breast Health Education Study. Trained interviewers conducted face-to-face interviews with study participants to assess the frequency of consumption of specified food items. Study participants included 202 women 35-79 years old residing in six public housing facilities in Atlanta, Georgia. Univariate analyses were performed to report age, marital status, education level, employment status, income level, and frequencies of food items consumed. Correlation coefficients and multivariate logistic regression were used to analyze the association between the frequency of food item consumption and selected sociodemographic characteristics. Overall, only 33.7% and 17.9% of the women consumed fruit and vegetables on a daily basis, respectively. Almost two thirds consumed meat daily, while less than a third consumed whole wheat bread and bran cereals daily. A significant proportion of women had a daily consumption of fats, oils, and sweets (13.4%-49.5%). Three sociodemographic factors - young age, low income, and low education--were associated with unhealthy dietary intake. Question: Dietary intake to reduce cancer risk among African American women in public housing: do sociodemographic factors make a difference? <|endoftext|> <|assistant|> Strategies to promote healthy dietary intake should be implemented for women in public housing communities to help reduce cancer morbidity and mortality in this population. These strategies should address the barriers to healthy dietary consumption that are faced by women in this setting.

<|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: Artemisia capillaris, also called "InJin" in Korean, has been widely used to treat various hepatic disorders in traditional Oriental medicine. The purpose of this study is to evaluate the hepatoprotective effect of Artemisia capillaris (aqueous extract, WAC) on alcoholic liver injury. Liver injury was induced by oral administration of 30% alcohol (10 mL/kg, twice per day) plus pyrazole (PRZ, 30 mg/kg) with/without WAC (50, 100mg/kg, orally once per day) or silymarin (50mg/kg) for 10 days. The hepatoprotective effects were assessed by observing histopathological changes, hepatic transaminase enzymes, hepatic oxidation and antioxidant parameters, inflammatory cytokines, and alcohol metabolic enzymes in serum and hepatic gene expression level, respectively. Alcohol-PRZ treatment drastically increased the serum levels of aspartate transaminase (AST), alanine transaminase (ALT), and malondialdehyde (MDA) levels in serum and liver tissues while these changes were significantly ameliorated by WAC administration (p<0.05 or 0.01). The prominent microvesicular steatosis and mild necrosis in hepatic histopathology were induced by alcohol-PRZ treatment, but notably attenuated by WAC administration. Moreover, the alcohol-PRZ treatment-induced depletions of the antioxidant components including glutathione content, total antioxidant capacity (TAC), activities of glutathione peroxidase (GSH-Px), reductase (GSH-Rd), catalase, and superoxide dismutase (SOD) were significantly ameliorated by WAC administration (p<0.05, except GSH-Rd). These results were in accordance with the modulation of NF-E2-related factor (Nrf2) and heme oxygenase-1 (HO-1) gene expression. Alcohol-PRZ treatment increased the levels of tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) in hepatic tissues. However they were significantly normalized by WAC administration (p<0.05 or 0.01). In addition, WAC administration significantly attenuated the alterations of aldehyde dehydrogenase (ALDH) level in serum and hepatic gene expressions of ALDH and alcohol dehydrogenase (ADH). Question: Does aqueous extract of Artemisia capillaris exert hepatoprotective action in alcohol-pyrazole-fed rat model? <|endoftext|> <|assistant|> These results support the relevance in clinical use of Artemisia capillaris for alcohol-associated hepatic disorders. The underlying mechanisms may involve both enhancement of antioxidant activities and modulation of proinflammatory cytokines.

<|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: Cholestasis complicates total parenteral nutrition (TPN) in preterm infants. Ursodeoxycholic acid (UDCA) is used for several cholestatic problems. The hypothesis of this study was that intravenous UDCA prevents TPN-induced cholestasis by (1) maintaining normal basal and stimulated bile flow, (2) altering bile composition, and (3) changing hepatocyte membrane composition and Na+,K(+)-adenosine triphosphatase (ATPase) activity. Three groups of piglets were studied: group 1 received sow's milk, groups 2 and 3 received TPN, and group 3 also received 100 mumol.kg-1.day-1 UDCA intravenously. After 3 weeks, basal and stimulated bile flow were measured. Cholesterol, bile acids, phospholipids, and phospholipid fatty acids were analyzed in bile, and fluidity, phospholipid fatty acid composition, and Na+,K(+)-ATPase were analyzed in hepatocyte membranes. Bile acid secretion and basal and stimulated bile flow were similar in control and UDCA-treated animals but reduced to < 50% in the TPN group. Bile acid-dependent and -independent bile flow were lower in the TPN group. UDCA did not normalize abnormalities in TPN-induced bile composition. Sinusoidal but not canalicular membrane fluidity was different in TPN than in control and UDCA-treated animals. UDCA also increased Na+,K(+)-ATPase activity. Bile and membrane phospholipid fatty acids reflected dietary fatty acids. Question: Does intravenous ursodeoxycholic acid reduce cholestasis in parenterally fed newborn piglets? <|endoftext|> <|assistant|> Intravenous UDCA improves bile flow and reduces bilirubin levels in the serum and liver in piglets with TPN-induced cholestasis.

<|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: It is unknown whether the route of administration influences dendritic cell (DC)-based immunotherapy. We compared the effect of intradermal versus intranodal administration of a DC vaccine on induction of immunologic responses in melanoma patients and examined whether concomitant administration of interleukin (IL)-2 increases the efficacy of the DC vaccine. HLA-A2.1(+) melanoma patients scheduled for regional lymph node dissection were vaccinated four times biweekly via intradermal or intranodal injection with 12 × 10⁶ to 17 × 10⁶ mature DCs loaded with tyrosinase and gp100 peptides together with keyhole limpet hemocyanin (KLH). Half of the patients also received low-dose IL-2 (9 MIU daily for 7 days starting 3 days after each vaccination). KLH-specific B- and T-cell responses were monitored in blood. gp100- and tyrosinase-specific T-cell responses were monitored in blood by tetramer analysis and in biopsies from delayed-type hypersensitivity (DTH) skin tests by tetramer and functional analyses with (51)Cr release assays or IFNγ release, following coculture with peptide-pulsed T2 cells or gp100- or tyrosinase-expressing tumor cells. In 19 of 43 vaccinated patients, functional tumor antigen-specific T cells could be detected. Although significantly more DCs migrated to adjacent lymph nodes upon intranodal vaccination, this was also highly variable with a complete absence of migration in 7 of 24 intranodally vaccinated patients. Intradermal vaccinations proved superior in inducing functional tumor antigen-specific T cells. Coadministration of IL-2 did not further augment the antigen-specific T-cell response but did result in higher regulatory T-cell frequencies. Question: Does route of administration modulate the induction of dendritic cell vaccine-induced antigen-specific T cells in advanced melanoma patients? <|endoftext|> <|assistant|> Intradermal vaccination resulted in superior antitumor T-cell induction when compared with intranodal vaccination. No advantage of additional IL-2 treatment could be shown.

<|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 modifiable risk factors for anastomotic leak in patients undergoing low anterior resection. In total 233 patients undergoing low anterior resection for benign and malignant disease over a 10-year period at a single surgical unit were identified from a prospective database. The relationships between anastomotic leak and 17 variables were examined, including patient demographics, operative technique, tumour pathology, preoperative physiological function and smoking status. The majority (91%) of operations were carried out for rectal cancers, and 24 procedures (10%) were performed with laparoscopic assistance. The overall anastomotic leak rate was 14% (33/233). Patients with anastomotic leak had higher 30-day mortality (6%vs 1%, P<0.05) and stayed significantly longer in hospital (median 23 vs 10 days, P<0.001). On multivariate analysis, current smokers (OR 3.68, 95% CI 1.38-9.82, P=0.009) and patients with evidence of metastatic malignant disease (OR 3.43, 95% CI 1.29-9.13, P=.013) were at increased risk of anastomotic leak. Question: Is smoking a major risk factor for anastomotic leak in patients undergoing low anterior resection? <|endoftext|> <|assistant|> Smoking and the presence of metastatic disease are major risk factors for the development of anastomotic leak following low anterior resection.

<|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 nuclear receptor estrogen receptor α (ERα) is one of the key players in energy balance, insulin resistance, and trophoblast differentiation. We tested the hypothesis that gestational diabetes mellitus (GDM) alters expression of placental ERα in a cell type-specific manner and that this regulation may involve epigenetic changes. Expression of ERα was analyzed by immunohistochemistry using the semiquantitative immunoreactive score in 80 placentas (40 GDM/40 controls). Quantitative real-time polymerase chain reaction (PCR) measured ERα messenger RNA (mRNA) in decidual tissue. Methylation-specific PCR was performed to analyze cytosine-phosphatidyl-guanine-island methylation of the ERα promoter. Expression of ERα protein is upregulated (P = .011) in GDM in extravillous trophoblasts but not in syncytiotrophoblast. Gestational diabetes mellitus downregulated ERα in decidual vessels only in pregnancies with male but not female fetuses. Furthermore, mRNA of the ERα encoding gene estrogen receptor gene 1 (ESR1) was increased (+1.77 fold) in GDM decidua when compared to controls (P = .024). In parallel, the promoter of ESR1 was methylated only in decidua of healthy control individuals but not in GDM. Question: Does gDM alter Expression of Placental Estrogen Receptor α in a Cell Type and Gender-Specific Manner? <|endoftext|> <|assistant|> Gestational diabetes mellitus affects expression of placental ERα in a cell type-dependent way, on epigenetic level. These data link GDM with epigenetic deregulations of ERα expression and open new insights into the intrauterine programming hypothesis of GDM.

<|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: Overaggressive fluid resuscitation in elderly patients requiring pancreatectomy can delay recovery and increase morbidity. Despite advancements, no accurate and reproducible methods exist to evaluate effective intravascular volume status in the postoperative setting. We hypothesized that sequential measurement of currently available serum proteins will indicate fluid balance. Clinicopathologic (n = 44) and echocardiogram (echo) data (n = 18) were collected on patients receiving pancreatectomy or diagnostic laparoscopy (n = 5). Measured fluid balance, serum BUN, creatinine (CR), and brain natriuretic peptide (BNP) levels were recorded on postoperative days (POD) 1 to 7 (only POD1 for diagnostic laparoscopy). ANOVA and bivariate random effect models examined the correlation between BNP and BUN/CR and fluid balance. Linear mixed-effect models examined the correlation between factors associated with vascular stiffness and BNP, BUN/CR, and fluid balance. On POD1 after diagnostic laparoscopy, the fluid balance was positive by 3,265 mL and was accompanied by a >300-point increase in BNP (p = 0.0083). After pancreatectomy, a similar increase in BNP (250 pg/mL) and fluid balance (4,492 mL) on POD1 was observed. During the return to euvolemia, the change in serum BNP levels correlated with fluid balance changes during POD 1 to 3 (p = 0.039), and BUN/CR levels correlated with fluid balance during POD 4 to 7. Patients with risk factors associated with cardiovascular stiffness or echo evidence of poor compliance experienced higher BNP during the postoperative period. Question: Do serum brain naturietic peptide measurements reflect fluid balance after pancreatectomy? <|endoftext|> <|assistant|> Fluid loading at surgery is accompanied by an increase in serum BNP, and return to a balanced fluid state after pancreatectomy is paralleled by changes in BNP and BUN/CR levels.

<|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: Interleukin (IL)-12 is believed to modulate local T-cell response in human colitis. A direct functional relationship between IL-12 and tissue injury in human intestine has not been reported. The aim of this study was to examine changes that take place in explant cultures of human fetal gut after stimulation of T cells with anti-CD3 in the presence of exogenous IL-12/IL-18. T cells in explants of fetal gut were activated with anti-CD3 antibody and/or IL-12 or IL-18. Mucosal pathology was determined by immunohistochemistry. Quantitative reverse-transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay were used to determine cytokine synthesis, and the production of matrix metalloproteinases was analyzed by RT-PCR and Western blotting. Activation of T cells in explants with anti-CD3 antibody elicited very little interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha production and no tissue injury. Addition of graded doses of IL-12 with anti-CD3 resulted in a significant increase in both IFN-gamma and TNF-alpha. This change was associated with a massive increase in stromelysin-1 expression and severe tissue injury, which was inhibitable by a stromelysin-1 inhibitor. Costimulation of explants with anti-CD3 and IL-18 induced only IFN-gamma and no tissue injury. Question: Does enhancing Lamina propria Th1 cell responses with interleukin 12 produce severe tissue injury? <|endoftext|> <|assistant|> IL-12 can convert a physiological T-cell signal into a strong signal with the downstream effect of elevating tissue stromelysin-1 concentration and mucosal degradation.

<|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 outcome of implant treatment in periodontally compromised partially edentulous patients has not been completely clarified. Therefore, the aim of the present study was to perform, applying a systematic methodology, a comprehensive and critical review of the prospective studies published in English up to and including August 2006, regarding the short-term (<5 years) and long-term (>or=5 years) prognosis of osseointegrated implants placed in periodontally compromised partially edentulous patients. Using The National Library Of Medicine and Cochrane Oral Health Group databases, a literature search for articles published up to and including August 2006 was performed. At the first phase of selection the titles and abstracts and at the second phase full papers were screened independently and in duplicate by the three reviewers (I. K. K., S. K., I. F.). The search provided 2987 potentially relevant titles and abstracts. At the first phase of evaluation, 2956 publications were rejected based on title and abstract. At the second phase, the full text of the remaining 31 publications was retrieved for more detailed evaluation. Finally, 15 prospective studies were selected, including seven short-term and eight long-term studies. Because of considerable discrepancies among these studies, meta-analysis was not performed. Question: Do a comprehensive and critical review of dental implant prognosis in periodontally compromised partially edentulous patients? <|endoftext|> <|assistant|> No statistically significant differences in both short-term and long-term implant survival exist between patients with a history of chronic periodontitis and periodontally healthy individuals. Patients with a history of chronic periodontitis may exhibit significantly greater long-term probing pocket depth, peri-implant marginal bone loss and incidence of peri-implantitis compared with periodontally healthy subjects. Even though the short-term implant prognosis for patients treated for aggressive periodontitis is acceptable, on a long-term basis the matter is open to question. Alterations in clinical parameters around implants and teeth in aggressive periodontitis patients may not follow the same pattern, in contrast to what has been reported for chronic periodontitis patients. However, as only three studies comprising patients treated for aggressive periodontitis were selected, more studies, specially designed, are required to evaluate implant prognosis in this subtype of periodontitis. As the selected publications exhibited considerable discrepancies, more studies, uniformly designed, preferably longitudinal, prospective and controlled, would be important.

<|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: It is of great importance to assess progression of aortic valvar stenosis (AVS) when cardiac surgery is planned for other indications when established criteria for aortic valve replacement are not fulfilled at that moment. These considerations have often been ignored in prospective planning of treatment, necessitating a second cardiac surgical intervention just a few years later. The aim of this study was to establish criteria for estimating the rate of progression of AVS. Clinical, echocardiographic and haemodynamic data were analysed for 169 patients with aortic valvar stenosis (169 men, 88 women; mean age at first cardiac catheterization [CC] 55.2 +/- 15.7 years, at second CC 63.4 +/- 15.6 years. The degree of AVS increases exponentially in relation to the extent of calcification (graded 0-3) and the fall in transaortic gradient (TG), from a TG>0.6 mmHg/ml stroke volume and can be sufficiently predictable for clinical purposes. But neither age, sex nor the aetiology/pathology of the valvar defect have a sustained influence on the progression of AVS. Question: Is the estimation of the progression of valvular aortic stenosis possible? <|endoftext|> <|assistant|> These data indicate that knowing the current reduction in TG and the degree of calcification makes it possible to assess the likely progression of previously asymptomatic AVS and thus greatly facilitate the decision of whether or not to combine aortic valve replacement with another indicated cardiac operation.

<|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: Neutrophil elastase (NE) concentration is associated with progression of acute pancreatitis (AP), but measuring total NE concentration includes biologically inactive NE. This study aims to investigate the relationship between NE activity and the aetiology and severity of AP and associated organ failure. Seventy-five patients admitted to our surgery department with a first episode of AP during 2004-2005 were age- and sex-matched to 20 healthy volunteers (controls). NE activity was assessed using venous blood samples obtained on patient admission and after 1, 2 and 14 days. One sample was also taken from each control. ANOVA was used for statistical comparison between groups. Baseline NE activity (geometric mean; 95% confidence intervals) differed between patients (58.6 nM of substrate 7-amino-4-methylcoumarin [AMC]/hour; 48.52-70.72) and controls (31.5 nM AMC/hour; 25.5-39.0) (p = 0.0003), and did not correlate with time between symptom onset and admission. Patients with alcohol-induced AP demonstrated higher mean activity (59.1 nM AMC/h; 44.7-78.2) than those with gallstone-induced AP (41.7 nM AMC/h; 33.9-51.4) (p = 0.0496). NE activity was higher overall in patients with predicted severe AP (60.9 nM AMC/h; 48.0-77.2) than in those with predicted mild AP (42.1 nM AMC/h; 34.9-50.8) (p = 0.027). Patients with respiratory failure had higher NE activity (82.5 nM AMC/h; 57.5-118.4) than those without (43.9 nM AMC/h; 37.6-51.3) (p = 0.0024). Question: Does activity of neutrophil elastase reflect the progression of acute pancreatitis? <|endoftext|> <|assistant|> NE activity was associated with predicted severity of AP and AP-associated respiratory failure. Specific NE inhibitors may have therapeutic potential in acute pancreatitis.

<|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: Growth and differentiation factor-5 (GDF-5) is a multifunctional protein that regulates the development and repair in many tissues. The purpose of this study was to investigate whether GDF-5 may influence the proliferation, differentiation, and collagen turnover of human dental pulp cells. Human dental pulp cells were treated with different concentrations of GDF-5 (0-500 ng/mL). Morphology of pulp cells was observed under a microscope. Cell proliferation was evaluated by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. Immunofluorescent assay was used to observe the percentages of cell mitosis. Collagen content was measured by Sircol collagen assay. Tissue inhibitor of metalloproteinase-1 level in the culture medium was measured with enzyme-linked immunosorbent assay and Western blotting. Cell differentiation was evaluated by alkaline phosphatase (ALP) staining and ALP enzyme activity assay. After exposure of dental pulp cells to various concentrations of GDF-5, cell number was up-regulated significantly in dose-dependent manner. GDF-5 also stimulated mitosis of dental pulp cells as indicated by an increased percentage of binucleated cells from 28% to 35%-45%. GDF-5 did not affect the collagen content and tissue inhibitor of metalloproteinase-1 level of pulp cells. GDF-5 decreased the ALP activity of pulp cells as analyzed by ALP staining and enzyme activity assay, with 14%-44% of inhibition. Question: Does growth and differentiation factor-5 regulate the growth and differentiation of human dental pulp cells? <|endoftext|> <|assistant|> GDF-5 revealed mitogenic and proliferative activity to dental pulp cells. GDF-5 showed inhibitory effect on ALP activity but little effect on the collagen turnover. These events are crucial in specific stages of dental pulp repair and regeneration. GDF-5 may be potentially used for tissue engineering of pulp-dentin complex.

<|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 elderly population has suffered from hypothermia for thousands of years. This report analyzes the first documented case of hypothermia as described in the Bible. The sentence "Now King David was old and stricken in years, and they covered him with clothes, but he gained no warmth" indicates that hypothermia afflicted the biblical King David, the second and the greatest of Israel's kings, who ruled the country 3000 years ago. Environmental factors did not play a significant role in the development of hypothermia. Among various diseases, the most likely to cause immobility and subsequent hypothermia are dementia, senile osteoporosis, hyperparathyroidism, and malignancy. Among these diseases, malignancy is the most likely. Question: Was the biblical King David affected by hypothermia? <|endoftext|> <|assistant|> Viewed by a modern physician, the story of King David unfolds as possibly the earliest description of a patient affected by hypothermia, features of which have changed little through the ages. This report shows that the roots of contemporary geriatrics lead back to biblical times.

<|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 patients with A(H1N1)pdm09 infection, severe lung involvement requiring admission to intensive care units (ICU) has been reported. Mutations at the hemagglutinin (HA) receptor binding site (RBS) have been associated with increased virulence and disease severity, representing a potential marker of critical illness. To assess the contribution of HA-RBS variability in critically ill patients, A(H1N1)pdm09 virus from adult patients with severe infection admitted to ICU for extracorporeal membrane oxygenation support (ECMO) during influenza season 2009-2011 in Piemonte (4·2 million inhabitants), northwestern Italy, was studied. We retrospectively analyzed HA-RBS polymorphisms in ICU patients and compared with those from randomly selected inpatients with mild A(H1N1)pdm09 disease and outpatients with influenza from the local surveillance program. By HA-RBS direct sequencing of respiratory specimens, D222G and D222N viral variants were identified in a higher proportion in ICU patients (n=8/24, 33·3%) than in patients with mild disease (n=2/34, 6%) or in outpatients (n=0/44) (Fisher's exact test P<0·0001; OR 38·5; CI 95% 4·494-329·9). Eleven ICU patients died (42%), three of them carrying the D222G variant, which was associated with RBS mutation S183P in two. D222G and D222N mutants were identified in upper and lower respiratory samples. Question: Are a ( H1N1 ) pdm09 hemagglutinin D222G and D222N variants frequently harbored by patients requiring extracorporeal membrane oxygenation and advanced respiratory assistance for severe A ( H1N1 ) pdm09 infection? <|endoftext|> <|assistant|> A(H1N1)pdm09 HA substitutions D222G and D222N were harbored in a significantly higher proportion by patients with acute respiratory distress for A(H1N1)pdm09 severe infection requiring ICU admission and ECMO. These data emphasize the importance of monitoring viral evolution for understanding virus-host adaptation aimed at the surveillance of strain circulation and the study of viral correlates of disease severity.

<|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: Angiogenesis is crucial in RA disease progression. Lymphotoxin β receptor (LTβR)-induced activation of the non-canonical nuclear factor-κB (NF-κB) pathway via NF-κB-inducing kinase (NIK) has been implicated in this process. Consequently, inhibition of this pathway may hold therapeutic potential in RA. We describe a novel three-dimensional (3D) model of synovial angiogenesis incorporating endothelial cells (ECs), RA fibroblast-like synoviocytes (RAFLSs) and RA synovial fluid (RASF) to further investigate the contributions of NF-κB in this process. Spheroids consisting of RAFLSs and ECs were stimulated with RASF, the LTβR ligands LTβ and LIGHT, or growth factor bFGF and VEGF, followed by quantification of EC sprouting using confocal microscopy and digital image analysis. Next, the effects of anginex, NIK-targeting siRNA (siNIK), LTβR-Ig fusion protein (baminercept) and a novel pharmacological NIK inhibitor were investigated. RASF significantly promoted sprout formation, which was blocked by the established angiogenesis inhibitor anginex (P < 0.05). LTβ and LIGHT induced significant sprouting (P < 0.05), as did bFGF/VEGF (P < 0.01). siNIK pre-treatment of ECs led to reductions in LTβR-induced vessel formation (P < 0.05). LTβR-Ig not only blocked LTβ- or LIGHT-induced sprouting, but also RASF-induced sprouting (P < 0.05). The NIK inhibitor blocked angiogenesis induced by LTβ, LIGHT, growth factors (P < 0.05) and RASF (P < 0.01). Question: Does targeting non-canonical nuclear factor-κB signalling attenuate neovascularization in a novel 3D model of rheumatoid arthritis synovial angiogenesis? <|endoftext|> <|assistant|> We present a novel 3D model of synovial angiogenesis incorporating RAFLSs, ECs and RASF that mimics the in vivo situation. Using this system, we demonstrate that non-canonical NF-κB signalling promotes neovascularization and show that this model is useful for dissecting relative contributions of signalling pathways in specific cell types to angiogenic responses and for testing pharmacological inhibitors of angiogenesis.

<|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: Nitric oxide (NO), produced by normal vascular endothelial cells, reduces platelet aggregation and thrombus formation. NO-releasing biopolymers have the potential to prolong vascular graft and stent patency without adverse systemic vasodilation. 5-mm polyurethane vascular grafts coated with a polymer containing the NO-donor dialkylhexanediamine diazeniumdiolate were implanted for 21 days in a sheep arteriovenous bridge-graft model. Eighty percent (4/5) of grafts coated with the NO-releasing polymer remained patent through the 21 day implantation period, compared to fifty percent (2/4) of sham-coated grafts and no (0/3) uncoated grafts. Thrombus-free surface area (+/-SEM) of explanted grafts was significantly increased in NO-donor coated grafts (98.2% +/- 0.9%) compared with sham-coated (79.2% +/- 8.6%) and uncoated (47.2% +/- 5.4%) grafts ( P = .00046). Examination of the graft surface showed no adherent thrombus or platelets and no inflammatory cell infiltration in NO-donor coated grafts, while control grafts showed adherent complex surface thrombus consisting of red blood cells in an amorphous fibrin matrix, as well as significant red blood cell and inflammatory cell infiltration into the graft wall. Question: Do nitric oxide-releasing biopolymers inhibit thrombus formation in a sheep model of arteriovenous bridge grafts? <|endoftext|> <|assistant|> In this study we determined that local NO release from the luminal surface of prosthetic vascular grafts can reduce thrombus formation and prolong patency in a model of prosthetic arteriovenous bridge grafts in adult sheep. These findings may translate into improved function and improved primary patency rates in small-diameter prosthetic vascular grafts.

<|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: Gastroschisis associated intestinal dysmotility (GAID) is poorly understood. Animal experiments suggest that interstitial cells of Cajal (ICC), play an important role. Infants with gastroschisis (GS) and GAID (time to full feed >42days) were selected. Age matched GS and control (NEC, ileal atresia, malrotation, and volvulus) samples from primary (T1) and secondary (T2) time points underwent standard histopathology and immunohistochemistry for identification of ICC, followed by evaluation of ICC numbers, distribution, morphology, relation to ganglion cells, and myenteric plexus architecture. Groups were compared using parametric and nonparametric tests. Twelve patients had samples available for histopathological evaluation. GAID patients had a significantly lower total number of ICCs than controls (3 vs. 8, P<0.0029). ICC number at T1 was 2.5 vs. 6 (P=0.0629) and significantly lower at T2. (3.5 vs. 11, P=0.0124). GAID patients did not show a significant increase of ICC from T1 to T2. Controls showed a significant increase of ICC over time (6 vs. 11, P=0.0408). Question: Are interstitial cells of Cajal decreased in patients with gastroschisis associated intestinal dysmotility? <|endoftext|> <|assistant|> Intestinal samples from infants with GAID who underwent stoma formation demonstrated fewer ICC than controls. There was no improvement or cell recovery during the study period. The ability to modulate ICC may have significant implications for the management of GAID.

<|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: Ingestion of sycamore seeds (Acer pseudoplatanus) is the likely source of hypoglycin A in atypical myopathy (AM) but ingestion of seedlings in spring might also contribute to intoxication. To test for hypoglycin A in seeds and seedlings collected on pastures where AM cases were reported and compare its concentration in serum of affected and healthy horses. Field investigation of clinical cases. Whenever present, samaras (the winged nuts that each contain one seed) and/or seedlings were collected from pastures of 8 AM cases and 5 unaffected horses from different premises. Two AM cases were each co-grazing with an apparently healthy horse. Acylcarnitines and hypoglycin A were quantified in blood samples of all horses involved in the study. Hypoglycin A was detected in serum of AM (5.47 ± 1.60 μmol/l) but not in healthy controls pasturing where A. pseudoplatanus trees were not present. However, hypoglycin A was detected at high concentrations (7.98 μmol/l) in serum of a clinically healthy horse grazing a pasture with seedlings and samaras and also in the 2 healthy horses co-grazing with AM cases (0.43 ± 0.59 μmol/l). Hypoglycin A was detected in all samples of seeds and spring seedlings of A. pseudoplatanus. Question: Are samaras and seedlings of Acer pseudoplatanus potential sources of hypoglycin A intoxication in atypical myopathy without necessarily inducing clinical signs? <|endoftext|> <|assistant|> Atypical myopathy can be associated with the ingestion of sycamore samaras and also ingestion of seedlings. Hypoglycin A can be detected in the blood of horses with no detectable clinical signs at pasture in which there is A. pseudoplatanus. Determination of hypoglycin A concentration in blood is useful for screening for exposure in suspected cases of AM.

<|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: Ethanol (EtOH) exposure alters gene expression in the cerebral cortex (CCx); however, mechanisms of EtOH-induced gene regulation are not well understood. We hypothesized that EtOH regulates gene expression by differentially altering histone modifications at gene promoters that are up- and down-regulated by EtOH. Such epigenetic mechanisms may ultimately contribute to EtOH-induced neuro-adaptations that underlie tolerance, dependence, and EtOH-use disorders. Eight-week-old, male C57BL/6J mice were treated with 3 g/kg EtOH (intraperitoneally) or saline and sacrificed 6 hours after injection; the CCx and hippocampus (HC) were immediately removed and flash frozen. Chromatin immunoprecipitation was used to study the association of model gene promoters with histone modifications. Western blot was used to detect global changes in the histone modifications studied. We also used a polymerase chain reaction (PCR) array to identify changes in expression of chromatin-modifying enzymes. In CCx, acute EtOH decreased expression of Gad1, Hdac2, and Hdac11, which was associated with decreased histone acetylation at the Gad1 and Hdac2 promoters; we also identified increased expression of Mt1, Mt2, Egr1, which was associated with increased H3K4me3 levels at the Mt2 promoter and decreased H3K27me3 levels at the Mt1 promoter. We identified an increase in global levels of H3K4me3 in CCx as well as a global increase in H3K9ac and H3K14ac in HC. The PCR array identified decreased expression of Csrp2 bp, Hdac2, and Hdac11 as well as increased expression of Kat2b in CCx. Question: Does acute ethanol alter multiple histone modifications at model gene promoters in the cerebral cortex? <|endoftext|> <|assistant|> Acute EtOH induces chromatin remodeling at model up- and down-regulated genes in CCx. Different patterns of histone modifications at these gene promoters indicate that EtOH may be acting through multiple histone-modifying enzymes to alter gene expression; in particular, differential expression of Kat2b, Hdac2, Hdac11, and Csrp2 bp in CCx may mediate EtOH-induced chromatin remodeling. Additional studies are necessary to determine the relationship between EtOH-induced changes in histone-modifying enzymes, specific EtOH-induced histone modifications, and gene expression.

<|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: Percutaneous endoscopic gastrostomy (PEG) is often used for the feeding of patients with malnutrition due to dysphagia, and despite more than 30 years experience, numerous questions on its benefit remain. This was a prospective observational study to assess the safety of PEG. One hundred and nineteen patients mean age 63 years (21-91 years) who were admitted to the Hannover Medical School between November 2010 and March 2012 and had an indication for PEG according to the German guidelines were included. Primary endpoints were the following: reason for indication, date of in-hospital mortality after PEG insertion, death within 3 months after PEG placement, and complications. Most patients (54.6%) received PEG for dysphagia caused by tumors and second (29.4%) for neurologic diseases with a minor proportion of dementia (3%). About 73% of our patients had no complications at all and only 10% suffered severe effects. We saw only 1 case of aspiration, which did not lead to pneumonia. The 30-day mortality was 10%, and no patient died as a result of the PEG procedure. Significantly more patients with neurologic disorders died within 24 weeks of PEG placement than tumor patients (60% versus 27.7%, respectively, p = 0.002, n = 100). Question: Are complication and mortality rate after percutaneous endoscopic gastrostomy low and indication-dependent? <|endoftext|> <|assistant|> It is important to select patients receiving PEG very carefully. The patients' indications, their primary disease, and their capability for mental cooperation are essential. If these aspects are taken into account, PEG is a safe method with few mainly mild complications.

<|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 beneficial effects of angiotensin converting enzyme (ACE)-inhibitors are in part mediated through the inhibition of the degradation of the vasodilator bradykinin. The bradykinin effect is counteracted by cyclooxygenase-inhibitors. Angiotensin receptor blockers (ARBs) do not affect bradykinin. To test the hypothesis that renal counteraction from a cyclooxygenase-inhibitor, diclofenac, is different in subjects treated with an ACE-inhibitor, enalapril compared with an ARB, losartan. Twelve elderly, healthy, slightly over-hydrated subjects received diclofenac orally after pre-treatment with a diuretic, bendroflumethiazide, and enalapril or bendroflumethiazide and losartan, in a double-blind cross-over fashion, with a wash-out period of at least 1 week. Diclofenac reduced GFR significantly from 81(64-98) ml/min at first observations after dose for enalapril to 29(16-42) and from 76(64-88) after losartan to 35(24-46). There was no significant difference between enalapril and losartan in GFR. Diclofenac induced decreases in urine flow, excretion rates and clearances of sodium, osmolality clearance and free water clearance, irrespective of treatment with enalapril or losartan. However, serum potassium and handling of potassium were significantly lower after losartan-treatment. Question: Are treatments with losartan or enalapril equally sensitive to deterioration in renal function from cyclooxygenase inhibition? <|endoftext|> <|assistant|> The negative renal effects of diclofenac administration in subjects with activation of the renin-angiotensin system and enalapril treatment are the same in subjects with activation of the renin-angiotensin system and losartan 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: It has been shown in the rat that endogenous cholecystokinin (CCK), released in response to the non-nutrient trypsin inhibitor camostat, reduces food intake at meals and increases Fos-like immunoreactivity (Fos-LI; a marker for neuronal activation) in the dorsal vagal complex (DVC) of the hindbrain but not the myenteric plexus of the duodenum and jejunum. Experiment 1: We examined Fos-LI in the myenteric and the submucosal plexuses of the gut in response to orogastric gavage of camostat in rats. As we reported previously, camostat failed to increase Fos-LI in the myenteric plexus. We show here that camostat increased Fos-LI in the submucosal plexus of the duodenum and jejunum. Camostat also increased Fos-LI in the DVC. Experiment 2: Pretreatment with devazepide, a specific CCK(1) receptor antagonist abolished camostat-induced Fos-LI in the submucosal plexus and the DVC. Experiment 3: Bilateral subdiaphragmatic vagotomy reduced camostat-induced Fos-LI in the submucosal plexus approximately 40% and abolished it in the DVC. Question: Does activation of submucosal but not myenteric plexus of the gastrointestinal tract accompany reduction of food intake by camostat? <|endoftext|> <|assistant|> Activation of the submucosal plexus by cholecystokinin at the CCK(1) receptor accompanies stimulation of the dorsal vagal complex of the hindbrain and inhibition of food intake. Unlike the submucosal plexus, activation of the myenteric plexus is not necessary for cholecystokinin's influence on the dorsal vagal complex and food intake. The lack of activation in the myenteric plexus after camostat stimulation, in contrast to nutrient releasers of CCK such as oleate, suggests that intestinal stimulants can either release different amounts of CCK or cause release of CCK from I cells with different molecular forms of CCK. This would suggest that CCK-8 is released by camostat and is not able to travel to the myenteric plexus while a more stable form of CCK such as CCK-58 can travel to this site that is further away from the I cell.

<|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: PRV-1 mRNA is overexpressed by neutrophils from polycythemia vera patients and is homologous to NB1 a gene overexpressed in reactive neutrophilia. These investigations were designed to confirm searches of genome databases suggesting that PRV-1 and NB1 are alleles of the same gene, CD177, and confirm a pseudogene adjacent to CD177. Methods included polymerase chain reaction (PCR), cloning, sequencing, and fluorescent hybridization studies. The coding region of PRV-1 was PCR-amplified from human fetal RNA, cloned, and used to screen the RPCI-11 bacterial artificial chromosome (BAC) library. Five BACs were reactive with the PRV-1 probe. PCR analysis of the BACs with primers encompassing PRV-1 exons, containing four known single-nucleotide polymorphisms, followed by sequencing rendered amplicons identical to PRV-1 in all five BACs. Analysis of all five by restriction digestion yielded fragments possible only if both the gene and the pseudogene are present. End sequencing of the BACs localized them to the same chromosome region. G-banding and fluorescence in situ hybridization at the 400- and 850-band levels of resolution mapped one BAC to chromosome band 19q13.2 and sublocalized the BAC to band 19q13.31, respectively. Question: Are the gene overexpressed in polycythemia rubra vera , PRV-1 , and the gene encoding a neutrophil alloantigen , NB1 , alleles of a single gene , CD177 , in chromosome band 19q13.31? <|endoftext|> <|assistant|> PRV-1 and NB1 are alleles of the same gene now referred to as CD177. Changes in CD177 expression may be a marker of increased or decreased myelopoiesis and are therefore an effect of, rather than a cause of, myeloproliferative disorders.

<|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: Preclinical research has suggested that the endocannabinoid system may be involved in the etiology and/or treatment of depression; however, there are no published studies examining circulating endocannabinoid content in patients with clinical depression. This study examined the endocannabinoids (anandamide; AEA) and 2-arachidonylglycerol (2-AG) in serum from ambulatory, medication-free female patients diagnosed with minor or major depression, and in controls matched for demographic characteristics. Serum 2-AG content was significantly decreased in patients diagnosed with major depression, and this decrease was correlated significantly and negatively with duration of the depressive episode, such that 2-AG content was progressively lower the longer the depressive episode. While AEA was not associated with major depression PER SE, a strong negative correlation was found between serum AEA content and Hamilton ratings for cognitive and somatic anxiety, suggesting that AEA content may relate to the anxiety dimension of affective disorders. In subjects with minor depression, serum AEA was significantly elevated, with 2-AG content demonstrating a similar, but statistically insignificant trend. Question: Is serum endocannabinoid content altered in females with depressive disorders : a preliminary report? <|endoftext|> <|assistant|> These are the first clinical data to indicate that the endocannabinoid system may be disturbed in affective disease, and suggest that future research is required to determine the relevance of these changes with respect to disease manifestation and pharmacotherapy.

<|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: Proinflammatory cytokines may contribute to clinical complications in heart transplant (HTx) recipients. Previous studies have shown immunomodulating effects of omega-3 fatty acids, but the results are somewhat conflicting. In this study, we examined plasma levels of tumor necrosis factor alpha (TNF-alpha), interleukin (IL) 10, and their relations to antioxidant vitamins in 45 HTx recipients before and after treatment with omega-3 fatty acids or placebo. The patients were long-time survivors of heart transplantation, randomized in a double-blind fashion to receive omega-3 fatty acids (3.4 g/day) or placebo for 1 year. Plasma levels of cytokines were measured by enzyme immunoassays and vitamin A, vitamin E, and beta-carotene by high-performance liquid chromatography. In the omega-3, but not in the placebo group, there was a rise in the proinflammatory cytokine TNF-alpha (P<0.05), a decrease in the anti-inflammatory cytokine IL-10 (P=0.07), and a rise in TNF/IL-10 ratio (P<0.05) after 12 months, suggesting a proinflammatory net effect. In the omega-3 group, the increase in TNF-alpha was associated with an increase in eicosapentaenoic acid in plasma (r=0.58, P<0.02). During omega-3 fatty-acid treatment, but not during placebo, there was a decrease in vitamin E (P<0.05) and beta-carotene (P<0.05) levels, and the decrease in vitamin E was inversely correlated with the increase in TNF-alpha (r= -0.56, P<0.01). The rise in TNF-alpha levels during omega-3 fatty acids treatment was most pronounced in those patients with transplant coronary artery disease (P<0.04). Question: Do omega-3 fatty acids enhance tumor necrosis factor-alpha levels in heart transplant recipients? <|endoftext|> <|assistant|> Our data suggest that omega-3 fatty acids in HTx recipients may change the balance between proinflammatory and anti-inflammatory cytokines in an inflammatory direction, possibly related to prooxidative effects of these fatty acids.

<|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: Atherosclerotic plaque thrombogenicity is a critical factor that affects thrombus formation and the onset of acute myocardial infarction (AMI). The aim of this study was to identify the vascular factors involved in thrombus formation and AMI onset. Culprit lesions in 40 coronary arteries with thrombi at autopsy after lethal AMI and non-cardiac death (asymptomatic plaque disruption) were analyzed on histology. Thrombus size, ratio of thrombus to lumen area, length of plaque disruption, and immunopositive areas for tissue factor (TF) and hexokinase (HK)-II were significantly larger in coronary arteries with AMI than with asymptomatic plaque disruption. The size of coronary thrombus positively correlated with the length of plaque disruption (r=0.80) and with immunopositive areas for TF (r=0.38) and HK-II (r=0.40). Because both M1 and M2 macrophages express TF and HK-II in symptomatic plaques, we assessed TF and HK-II expression in M1- and M2-polarized macrophages. The expression of TF was increased and that of HK-II was decreased in M2-, compared with M1-polarized THP-1 macrophages. Inhibiting glycolysis enhanced TF expression in the macrophages partly via hypoxia inducible factor-1α. Question: Is human coronary thrombus formation associated with degree of plaque disruption and expression of tissue factor and hexokinase II? <|endoftext|> <|assistant|> The degree of plaque disruption and expression of TF and HK-II appear to be important vascular factors for AMI onset, and polarized macrophages make a distinct contribution to thrombogenicity and glucose metabolism.

<|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: Whole genome association studies have identified many loci associated with the risk of prostate cancer (PC). However, very few of the genes associated with these loci have been related to specific processes of prostate carcinogenesis. Therefore I inferred biological functions associated with these risk genes using gene expression correlation analysis. PC risk genes reported in the literature were classified as having high (P<10(-6)), medium (P<10(-4)), or low (P<10(-2)) statistical confidence. Correlation coefficients of the expression levels between the risk genes and other genes in cancerous prostates samples were compared against those in normal prostates using a microarray dataset from Gene Expression Omnibus. Overall, significant decrease of correlations in PC was observed between the levels of expression of the high-confidence genes and other genes in the microarray dataset, whereas correlation between low-confidence genes and other genes in PC showed smaller decrease. Genes involved in developmental processes were significantly correlated with all risk gene categories. Ectoderm development genes, which may be related to squamous metaplasia, and genes enriched in fetal prostate stem cells (PSCs) showed strong association with the high-confidence genes. The association between the PSC genes and the low-confidence genes was weak, but genes related to neural system genes showed strong association with low-confidence genes. Question: Does gene expression correlation analysis predict involvement of high- and low-confidence risk genes in different stages of prostate carcinogenesis? <|endoftext|> <|assistant|> The high-confidence risk genes may be associated with an early stage of prostate carcinogenesis, possibly involving PSCs and squamous metaplasia. The low-confidence genes may be involved in a later stage of carcinogenesis.

<|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: Focal neurodegeneration of the optic nerve in Leber hereditary optic neuropathy (LHON) is primarily due to a maternally inherited mitochondrial DNA mutation. However, the markedly reduced penetrance of LHON and segregation pattern of visual failure within families implicates an interacting nuclear genetic locus modulating the phenotype. Folate deficiency is known to cause bilateral optic neuropathy, and defects of folate metabolism have been associated with nonarteritic ischemic optic neuropathy. Methylenetetrahydrofolate reductase (MTHFR) catalyzes a critical step in folate metabolism, and genetic variation in MTHFR has been associated with several late-onset neurodegenerative diseases. We therefore determined whether functional genetic variants in MTHFR could account for the reduced penetrance in LHON by studying 414 LHON mtDNA mutation carriers. We found no evidence of association between visual failure in LHON and MTHFR polymorphisms or the MTHFR haplotype. Question: Does genetic variation in the methylenetetrahydrofolate reductase gene , MTHFR , alter the risk of visual failure in Leber 's hereditary optic neuropathy? <|endoftext|> <|assistant|> Genetic variation in MTHFR does not provide an explanation for the variable phenotype in LHON.

<|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 quantitatively evaluate the time course of macular choroidal blood flow velocity in acute central serous chorioretinopathy (CSC). This retrospective observational case series included 21 eyes of 20 patients (17 men, 3 women; mean age, 53.0 years) with treatment-naïve acute CSC. Laser speckle flowgraphy was performed to calculate macular mean blur rate (MBR), an indicator of relative blood flow velocity at the first visit, 3 and 6 months thereafter. Changes in average MBR values were compared with visual improvement at 6 months. Subretinal fluid completely resolved in all eyes within 6 months, while best-corrected visual acuity (BCVA) significantly improved at 6 months compared to the initial BCVA. During the follow-up period, the average MBR significantly decreased to 92.8% and 82.3% at 3 and 6 months, respectively, against baseline (100%). Importantly, there was a negative correlation between the BCVA recovery and the MBR decrease, showing the possible association of MBR increase with poor visual prognosis. Multiple regression analysis demonstrated no significant correlation between MBR and ocular perfusion pressure. Question: Does macular choroidal blood flow velocity decrease with regression of acute central serous chorioretinopathy? <|endoftext|> <|assistant|> These results indicate that macular choroidal blood flow velocity decreases concurrently with regression of CSC, suggesting a validity of choroidal blood flow elevation in the pathogenesis of acute CSC.

<|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 describe the prevalence of joint stiffness and associated comorbidities in community-living older adults and to determine whether joint stiffness, independent of pain, contributes to new and worsening disability. Population-based cohort. Urban and suburban communities in the Boston, Massachusetts, area. Adults aged 70 and older (N = 765) underwent a baseline home interview and clinic examination, 680 participants completed the 18-month follow-up. Morning joint stiffness on most days in the past month was assessed in the arms, back, hips, and knees. Mobility limitations were measured using self-reported difficulty and the Short Physical Performance Battery (SPPB). The home interview and clinic examination included extensive health measures. Four hundred one participants reported morning joint stiffness, half of these with one site of stiffness and the other half with multisite stiffness. Twenty percent of participants with multisite stiffness and 50% with single site stiffness did not have a major stiffness-associated condition. After adjustment for pain severity and other covariates, multisite stiffness was associated with a 64% greater risk of developing new or worsening mobility difficulty (relative risk = 1.64, 95% confidence interval = 1.05-2.79). Those with multisite stiffness had declined more quickly in physical performance over the 18-month follow up. Question: A stiff price to pay: does joint stiffness predict disability in an older population? <|endoftext|> <|assistant|> Older adults with multisite stiffness are more likely to be at risk of disability than those without joint stiffness after accounting for pain severity and the presence of stiffness-associated conditions. Better assessment, along with strategies to prevent and treat multisite joint stiffness is needed to prevent or slow the progression of disability in elderly adults.

<|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: Calumenin, a molecular chaperone, exerts a regulatory effect on the vitamin K-dependent γ-carboxylation redox cycle that inhibits transfer of the reduced vitamin K from VKORC1, the pharmacological target of warfarin, to the γ-carboxylase. Because of its polymorphic structure and central role in the warfarin metabolic pathway, a contributory role for calumenin to warfarin dose variability has been posited. The current study sought to validate modulation of therapeutic dosing requirements by a single nucleotide polymorphisms (SNP) occurring in the calumenin gene (CALU) reported in previous studies. The CALU SNP was further modeled to detect interaction with SNPs occurring in VKORC1, CYP2C9, and CYP4F2 genes and characterize any additional contribution to variability in therapeutic warfarin dose requirement. The study was undertaken in an established, well-characterized cohort of subjects treated with warfarin in the Anticoagulation Clinic of Marshfield Clinic in Marshfield, Wisconsin. Subjects (N=491) previously genotyped for SNPS known to contribute variability to therapeutic warfarin dose requirement were genotyped for CALU SNP rs1043550, using TaqMan assays. Contribution of CALU SNP rs1043550 was modeled relative to other genotypic and phenotypic characteristics including gender, diagnosis, age, body surface area, underlying indication for warfarin, comorbidities, and pharmacological exposures. Interaction between SNPs impacting on warfarin dose requirements and calumenin SNPs was also modeled. Small differences in warfarin dosing requirements detected among individuals encoding the mutant G allele in the calumenin SNP were not statistically or clinically significant relative to therapeutic warfarin dose requirement and did not independently contribute significantly to the warfarin dosing model. Interaction between calumenin and VKORC1 SNPs contributed only minor additional variability to that ascribed to the wild type VKORC1 genotype. Question: Does CALU SNP rs1043550 contribute variability to therapeutic warfarin dosing requirements? <|endoftext|> <|assistant|> The impact of the CALU SNP on warfarin dose variability was minor and did not contribute significantly to therapeutic warfarin dose requirement in our study cohort. While no contribution was noted for the SNP examined in the present study, further examination of interaction between genetic elements contributing major impact on therapeutic warfarin dose requirements and genes exhibiting a lesser contribution is warranted.

<|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 studied the prevalence of endocrine dysfunction in subjects with idiopathic Parkinson's disease (IPD) on newer dopaminergic agents (DA). DA are also used in endocrine hypersecretory states in small doses and we hypothesized that endocrine dysfunction was likely in IPD where DA were used in comparatively much higher dosage. Twenty-five subjects with IPD, established on DA, were recruited to this cross-sectional study. We measured insulin-like growth factor-1, prolactin, luteinizing hormone, follicle stimulating hormone, thyroid function, oestradiol or testosterone and cortisol levels following a short synacthen test. We studied 18 males and 7 females, whose median age was 72 years, and whose median time from diagnosis, and duration of treatment was 27 months (interquartile range 17-45 and 13-39 months, respectively). (1) Endocrine tests were normal in 19 of 25 subjects at recruitment. Minor abnormalities reverted to normal on repeat testing in three of six with initial abnormalities; two had persistent abnormalities and the third subject could not be further investigated. Therefore, 22 of 24 (92%) with IPD on DA therapy had normal endocrine profiles. (2) The cortisol response to ACTH was normal in 24 of 25 subjects (96%). (3) Eleven subjects (44%) had isolated PRL suppression. There were no differences between the suppressed PRL and "normal" PRL groups. However, a higher number of them were on non-ergoline-derived DA (83% vs 31%; P < 0.05). Question: Do newer dopaminergic agents cause minimal endocrine effects in idiopathic Parkinson 's disease? <|endoftext|> <|assistant|> We have demonstrated that newer non-ergoline DA therapy caused only minimal endocrine perturbations in subjects with IPD. Their clinical significance can only be speculative currently. The cortisol response to ACTH was normal in almost all but a significant minority had suppressed prolactin levels.

<|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 association of low vitamin D status with autoimmune thyroid disease (AITD), which includes Hashimoto's thyroiditis (HT) and Graves' disease (GD), is controversial. The aim of this study was to investigate the correlation between vitamin D insufficiency and AITD, HT, and GD. Our cross-sectional study included patients who visited a tertiary hospital for thyroid evaluation or follow-up. A total of 776 patients in whom serum 25-hydroxyvitamin D [25(OH)D], thyroid function, and anti-thyroid antibodies had been measured were analyzed retrospectively. Vitamin D insufficiency was defined as serum 25(OH)D level <75 nmol/L. The prevalence of vitamin D insufficiency was significantly higher in the 369 patients with AITD than in the 407 without AITD (46.1% vs. 37.1%, p=0.011), and higher in the 221 patients with HT than in those with GD or non-AITD (48.9% vs. 41.9%, 37.1%, p=0.017). Among HT cases, patients with overt hypothyroidism had a significantly higher prevalence of vitamin D insufficiency (60.4% vs. 44.1%, 21.7%, 37.1%, respectively, p <0.001) and lower 25(OH)D levels (80.1 ± 47.7 vs. 99.34 ± 61.2, 110.3 ± 69.9, 99.6 ± 53.7 nmol/L, respectively, p=0.009) compared with those with euthyroidism and subclinical hypothyroidism or those without AITD. Serum 25(OH)D levels were significantly negatively correlated with serum thyroid stimulating hormone (TSH) levels after adjustment for age, sex, body mass index, and sampling season (r= -0.127, p=0.013). Question: Is low vitamin D status associated with hypothyroid Hashimoto 's thyroiditis? <|endoftext|> <|assistant|> Vitamin D insufficiency was associated with AITD and HT, especially overt hypothyroidism. Low serum vitamin D levels were independently associated with high serum TSH levels.

<|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: microRNAs have recently been identified as powerful biomarkers of human disease. Reliable polymerase chain reaction (PCR)-based quantification of nucleic acids in clinical samples contaminated with polymerase inhibitor heparin requires deheparinization. However, the effects of deheparinization procedure on quantification of nucleic acids remain largely unknown. The aim of this study was to determine whether the deheparinization procedure completely eliminates the inhibition of amplification, while maintaining RNA integrity and technical variability of the measured microRNA levels. Heparinized plasma from 9 patients undergoing coronary artery bypass grafting (CABG) and the heparin-free plasma from 58 rats were spiked with a synthetic RNA oligonucleotide and total RNA was extracted. The RNA solutions were then treated with heparinase I to remove contaminating heparin prior to reverse transcription. Levels of synthetic spike-in RNA oligonucleotide, as well as endogenous hsa-miR-1-3p and hsa-miR-208a-3p, were measured using quantitative reverse transcription PCR (RT-qPCR). The amplification efficiency and presence of inhibitors in individual samples were directly determined using calibration curves. In contrast to RNA samples from rat plasma, RNA samples derived from the CABG patient plasma contained inhibitors, which were completely eliminated by treatment with heparinase. The procedure caused a decrease in the amount of detected RNA; however, the technical variability of the measured targets did not change, allowing for the quantification of circulating endogenous hsa-miR-1-3p and hsa-miR-208a-3p in the plasma of CABG patients. Question: Does heparinase treatment of heparin-contaminated plasma from coronary artery bypass grafting patients enable reliable quantification of microRNAs? <|endoftext|> <|assistant|> The heparinase treatment procedure enables utilization of RT-qPCR for reliable microRNA quantification in heparinized plasma.

<|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: It has been shown that killing of suspended cells by low-intensity ultrasound (0.08-0.11 W/cm(2)) can be enhanced by a mild non-lethal hypotonic (146 mOsm) medium. In this study we wished to determine whether hypotonia-induced cell swelling of suspension cells was directly related to enhancement of ultrasound-mediated cell killing, and to verify whether similar effects could be observed on circulating and attached cells. U937 cells under mild hypotonia were exposed to ultrasound for different times with real-time monitoring of cell size using a particle-size-distribution analyzer. To study the effect on attached cells, HeLa cells were exposed to ultrasound while under hypotonia in an in vivo-simulated set-up. The result showed that the enhanced cell killing (up to more than twice) was directly proportional to hypotonia-induced cell swelling. Similar membrane damage based on PI staining could be observed on HeLa cells treated with hypotonia. An in vivo-simulated circulating system also showed similar findings for hypotonia-enhanced ultrasound cell killing. Question: Does hypotonia-induced cell swelling enhance ultrasound-induced mechanical damage to cancer cells? <|endoftext|> <|assistant|> These findings showed that mild hypotonia can be used to augment the effect of ultrasound in the treatment of cancers, particularly leukemia. The results showing that such enhancement is related to cell swelling could guide us toward proper timing of sonication while under hypotonic 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 purpose of this study was to determine whether the dynamic cause for mitral systolic anterior motion (SAM) is a Venturi or a flow drag (pushing) mechanism. In obstructive hypertrophic cardiomyopathy (HCM), if SAM were caused by the Venturi mechanism, high flow velocity in the left ventricular outflow tract (LVOT) should be found at the time of SAM onset. However, if the velocity was found to be normal, this would support an alternative mechanism. We studied with echocardiography 25 patients with obstructive HCM who had a mean outflow tract gradient of 82 +/- 6 mm Hg. We compared mitral valve M-mode echocardiogram tracings with continuous wave (CW) and pulsed wave (PW) Doppler tracings recorded on the same study. A total of 98 M-mode, 159 CW, and 151 PW Doppler tracings were digitized and analyzed. For each patient we determined the LVOT CW velocity at the time of SAM onset. This was done by first determining the mean time interval from Q-wave to SAM onset from multiple M-mode tracings. Then, CW velocity in the outflow tract was measured at that same time interval following the Qwave. Systolic anterior motion began mean 71 +/- 5 ms after Q-wave onset. Mean CW Doppler velocity in the LVOT at SAM onset was 89 +/- 8 cm/s. In 68% of cases SAM began before onset of CW and PW Doppler LV ejection. Question: Does systolic anterior motion begin at low left ventricular outflow tract velocity in obstructive hypertrophic cardiomyopathy? <|endoftext|> <|assistant|> Systolic anterior motion begins at normal LVOT velocity. At SAM onset, though Venturi forces are present in the outflow tract, their magnitude is much smaller than previously assumed; the Venturi mechanism cannot explain SAM. These velocity data, along with shape, orientation and temporal observations in patients, indicate that drag, the pushing force of flow, is the dominant hydrodynamic force that causes SAM.

<|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: Mucinous carcinoma of the colon and rectum (mucinous CRC) is a histological subtype of colorectal adenocarcinoma for which there is little data on chemotherapy responsiveness. The purpose of this study was to investigate specifically the efficacy of fluorouracil-based first-line chemotherapy in patients with advanced mucinous CRC. All patients with advanced mucinous CRC enrolled in three prospective randomized trials evaluating infused 5-fluorouracil as first-line treatment were compared with patients with non-mucinous subtypes enrolled in the same trials in a case-control study. Prognostic factors associated with overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were identified using univariate and multivariate logistic and/or Cox proportional hazards analyses. The study included 135 patients (45 cases and 90 controls). The response rates for cases and controls were 22% [95% confidence interval (CI), 11% to 38%] and 47% (95% CI, 36.1% to 58.2%), respectively (P=0.0058). Median OS for the mucinous CRC patients was 11.8 months (95% CI, 8.87-14.8) compared with 17.9 months (95% CI, 13.38-22.39) in the control group (univariate analysis, P=0.056); after correcting for significant prognostic factors by multivariate Cox regression analysis, P=0.0372 and hazard ratio (HR)=1.497 (1.02-2.19). Question: Does mucinous histology predict for reduced fluorouracil responsiveness and survival in advanced colorectal cancer? <|endoftext|> <|assistant|> Patients with advanced mucinous CRC have a poorer response to fluorouracil-based first-line chemotherapy and reduced survival compared with patients with non-mucinous CRC.

<|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 SAH gene locus has recently been proposed to be involved in obesity-related hypertension in Japanese individuals. To replicate independently the initial findings in another ethnic group, we scanned the entire SAH gene in 190 Caucasian chromosomes. A total of 651 patients with essential hypertension and 776 controls (PEGASE Study) were genotyped for all identified variants using allele-specific oligonucleotides, and single nucleotide polymorphism as well as haplotype analyses were carried out. We also performed transient transfection experiments, northern and western blots, immunoprecipitation, and acyl-coenzyme A synthetase activity assays. We identified five polymorphisms in the promoter region (C-1808T, G-1606A, -962ins/del, G-451A, T-67C), two in introns 5 and 7 (T+9/In5C, A+20/In7T), and one missense variant (K359N). Carriage of the -1606A allele was significantly associated with hypertension [odds ratio (OR) 1.28, P = 0.049] as was 359N (OR 1.35, P = 0.048) compared with non-carriers. Conversely, for -962del, the OR for hypertension was 0.80 (P = 0.042). The SAH alleles -1606A and 359N, but not -962ins/del, displayed a raising effect on body mass index (BMI; P = 0.004 and P = 0.030, respectively) in hypertensive as well as in control individuals. After adjustment for BMI in hypertensive individuals, only the OR associated with -962ins/del remained significant (OR 0.77, P = 0.028). Functional analyses in BHK did not reveal differences for SAH 359N or 359K-containing constructs, formally excluding K359N as the functional variant. Question: Are sAH gene variants associated with obesity-related hypertension in Caucasians : the PEGASE Study? <|endoftext|> <|assistant|> We confirm recent evidence that the SAH locus is associated with obesity-related hypertension, in which pathophysiological context SAH variants affecting blood pressure remain, however, to be shown.

<|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 Instability Severity Index Score (ISIS) includes preoperative clinical and radiological risk factors to select patients who can benefit from an arthroscopic Bankart procedure with a low rate of recurrence. Patients who underwent an arthroscopic Bankart for anterior shoulder instability with an ISIS lower than or equal to four were assessed after a minimum of 5-year follow-up. Forty-five shoulders were assessed at a mean of 79 months (range 60-118 months). Average age was 29.4 years (range 17-58 years) at the time of surgery. Postoperative functions were assessed by the Walch and Duplay and the Rowe scores for 26 patients; an adapted telephonic interview was performed for the 19 remaining patients who could not be reassessed clinically. A failure was defined by the recurrence of an anterior dislocation or subluxation. Patients were asked whether they were finally very satisfied, satisfied or unhappy. The mean Walch and Duplay score at last follow-up was 84.3 (range 35-100). The final result for these patients was excellent in 14 patients (53.8 %), good in seven cases (26.9 %), poor in three patients (11.5 %) and bad in two patients (7.7 %). The mean Rowe score was 82.6 (range 35-100). Thirty-nine patients (86.7 %) were subjectively very satisfied or satisfied, and six (13.3 %) were unhappy. Four patients (8.9 %) had a recurrence of frank dislocation with a mean delay of 34 months (range 12-72 months). Three of them had a Hill-Sachs lesion preoperatively. Two patients had a preoperative ISIS at 4 points and two patients at 3 points. Question: Results of 45 arthroscopic Bankart procedures: Does the ISIS remain a reliable prognostic assessment after 5 years? <|endoftext|> <|assistant|> The selection based on the ISIS allows a low rate of failure after an average term of 5 years. Lowering the limit for indication to 3 points allows to avoid the association between two major risk factors for recurrence, which are valued at 2 points. The existence of a Hill-Sachs lesion is a stronger indicator for the outcome of instability 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: Mammographic density adversely affects diagnostic accuracy and may be a risk factor for breast cancer. Mammographic density is affected by hormone replacement therapy (HRT). To assess mammographic density in postmenopausal women with and without HRT. Part I. Mammographic density was determined in 1232 postmenopausal women attending a breast screening clinic. Density was compared between HRT users and nonusers in three age groups. When available, previous mammograms were assessed for interval density change. Part II. Density change in 162 women during transition from premenopause to postmenopause was recorded. HRT effect was assessed. Part I. There was no density difference between postmenopausal HRT-users and nonusers younger than age 55. Thereafter, the density was significantly less in nonusers. In the majority of HRT-users the density remained at pretreatment levels but density increased in 8% of women after HRT was started. Part II. Of 117 HRT nonusers followed over menopause 38% had a density decrease before age 55. Of those started on HRT, 80% had no density change, 18% decreased density and 2% increased density. Question: Mammographic density changes in perimenopausal and postmenopausal women: is effect of hormone replacement therapy predictable? <|endoftext|> <|assistant|> The density decreases significantly after age 55 with the greatest change occurring between age 55 and 64. This decrease does not occur in the majority of HRT-users. Usually HRT maintains the density present at the time HRT is started. Density decreases after HRT is started in some women suggesting refractoriness to hormones. In fewer than 8% of women density increases commensurate with HRT. Any adverse effect of HRT may depend on the receptivity of the epithelial elements which, in turn, may be reflected by the mammographic density at the time HRT is started.

<|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 ileal conduit is held to be the safest and simplest form of urinary diversion. There are few reports about long-term problems after ileal conduit formation, especially intractable urinary incontinence in females. We reviewed long-term stomal complications in patients with an ileal conduit. Notes on 93 consecutive patients in whom an ileal conduit was created were reviewed. Information was collected on patient demographics, indications for an ileal conduit and long-term complications, in particular parastomal and incisional hernias, stomal retraction, stenosis or prolapse and the development of a redundant loop. Mean followup available was 63.4 months (range 1 to 434). A total of 33 males with a mean age of 60.1 years (range 2 to 78) and 60 females with a mean age of 48.2 years (range 4 to 79) underwent ileal conduit diversion. The main indications for an ileal conduit were intractable incontinence in 44 patients (47%), cancer in 31 (33%) and interstitial cystitis in 8 (9%). In male, continent female and incontinent female patients A parastomal hernia developed in 3 (9%), 2 (9.5%) and 12 (31%), an incisional hernia developed in 1 (3%), 1 (4.8%) and 2 (5%), stomal retraction developed in 0, 2 (9.5%) and 12 (31%), stomal stenosis developed in 0 (0%), 1 (4.8%) and 6 (15.4%), and a redundant loop developed in 0 (0%), 2 (9.5%) and 5 (12.8%), respectively. A total of 23 patients (24.7%) required further surgery for stomal problems with 13 (57%) requiring more than 1 reoperation, of whom 9 were incontinent females. Question: Are stomal complications of ileal conduits significantly higher when formed in women with intractable urinary incontinence? <|endoftext|> <|assistant|> An ileal conduit is associated with a stomal complication rate of 34.4% (61% in incontinent females and 18% in other patients) and a 4.3% incisional hernia rate. Reoperation is required for stomal complications in 24.7% of cases. Stomal complication rates and reoperation rates vary by sex and the indication for ileal conduit, and they are significantly higher for those performed for intractable urinary incontinence in females.

<|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 satisfaction of the intensive care unit staff with a computerized physician order entry and to compare the concept of the computerized physician order entry relevance among intensive care unit healthcare workers. We performed a cross-sectional survey to assess the satisfaction of the intensive care unit staff with the computerized physician order entry in a 30-bed medical/surgical adult intensive care unit using a self-administered questionnaire. The questions used for grading satisfaction levels were answered according to a numerical scale that ranged from 1 point (low satisfaction) to 10 points (high satisfaction). The majority of the respondents (n=250) were female (66%) between the ages of 30 and 35 years of age (69%). The overall satisfaction with the computerized physician order entry scored 5.74±2.14 points. The satisfaction was lower among physicians (n=42) than among nurses, nurse technicians, respiratory therapists, clinical pharmacists and diet specialists (4.62±1.79 versus 5.97±2.14, p<0.001); satisfaction decreased with age (p<0.001). Physicians scored lower concerning the potential of the computerized physician order entry for improving patient safety (5.45±2.20 versus 8.09±2.21, p<0.001) and the ease of using the computerized physician order entry (3.83±1.88 versus 6.44±2.31, p<0.001). The characteristics independently associated with satisfaction were the system's user-friendliness, accuracy, capacity to provide clear information, and fast response time. Question: Is the ICU staff satisfied with the computerized physician order entry? <|endoftext|> <|assistant|> Six months after its implementation, healthcare workers were satisfied, albeit not entirely, with the computerized physician order entry. The overall users' satisfaction with computerized physician order entry was lower among physicians compared to other healthcare professionals. The factors associated with satisfaction included the belief that digitalization decreased the workload and contributed to the intensive care unit quality with a user-friendly and accurate system and that digitalization provided concise information within a reasonable time frame.

<|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 relative expressions of matrix metalloprotease (MMP) genes pro-MMP1 and pro-MMP3 in the cartilage of rabbits with experimentally induced osteoarthritis (OA), and to assess the role of the chondrocyte in this process. OA was induced in rabbits after partial medial meniscectomy. Rabbits were killed at 4 weeks or 8 weeks, and total cellular RNA was prepared from cartilage and probed by Northern blotting with pro-MMP 32P-labeled complementary DNA. Monolayer chondrocytes were used to assess MMP-inducing activity of chondrocyte factor(s). Pro-MMP messenger RNAs (mRNAs) were up-regulated in experimental OA cartilage; pro-MMP3 mRNA expression exceeded that of pro-MMP1. Conditioned medium from OA-derived chondrocytes up-regulated pro-MMP mRNAs in normal chondrocytes. Question: Are prostromelysin and procollagenase genes differentially up-regulated in chondrocytes from the knees of rabbits with experimental osteoarthritis? <|endoftext|> <|assistant|> Up-regulation of MMP genes in this OA model may contribute to cartilage degradation. Chondrocytes up-regulate MMP genes via an autocrine pathway.

<|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: Methamphetamine addiction is believed to primarily result from increased dopamine release and the inhibition of dopamine uptake. Some evidence suggests that hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play important roles in the functional modulation of dopaminergic neurons and the pathophysiology of related diseases. However, little is known about the effects of HCN channels on methamphetamine addiction. The present study investigated the role of brain HCN channels in methamphetamine addiction. Acute intracerebroventricular (i.c.v.) injection or bilateral intra-accumbens microinjections of non-selective HCN channel blocker ZD7288 (0.3125 and 0.625 μg) significantly reduced both methamphetamine (0.0125 or 0.05 mg/kg/infusion)-induced self-administration under fixed ratio 2 reinforcement and the breakpoint of methamphetamine (0.05 mg/kg/infusion) under progressive ratio reinforcement in rats. Moreover, compared with i.c.v. injection, bilateral intra-accumbens microinjections of ZD7288 exerted stronger inhibitory effects, suggesting that blockade of HCN channels in the nucleus accumbens reduced the reinforcing effects of and motivation for methamphetamine. We also found that ZD7288 (0.625 and 1.25 μg, i.c.v.) significantly decreased methamphetamine (1 mg/kg, intraperitoneal (i.p.))-induced hyperactivity with no effect on the spontaneous activity in rats. Finally, in vivo microdialysis experiments showed that the HCN channel blockade using ZD7288 (0.625 and 1.25 μg, i.c.v.) decreased methamphetamine (1 mg/kg, i.p.)-induced elevation of extracellular dopamine levels in the nucleus accumbens. Question: Do nucleus accumbens hyperpolarization-activated cyclic nucleotide-gated channels modulate methamphetamine self-administration in rats? <|endoftext|> <|assistant|> These results indicate that HCN channels in the nucleus accumbens are involved in the reinforcing properties of methamphetamine and highlight the importance of HCN channels in the regulation of dopamine neurotransmission underlying methamphetamine addiction.

<|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 success of induction of labor in twin gestations using standard protocols for misoprostol and oxytocin designed for singleton gestations. This retrospective cohort study involved all diamniotic twin gestations that were induced at>or = 32 weeks' gestation with intact membranes. Two singleton pregnancies were matched for each twin pregnancy. Use of intravaginal misoprostol and low-dose intravenous oxytocin was based on ACOG management guidelines. A small proportion (40 of 430 [9.3%]) of twins met the inclusion criteria for an induction of labor. Misoprostol was utilized less frequently with twins than with singletons (55% vs. 78%, p = 0.02) because of the higher preinduction Bishop score. Doses of oxytocin were comparable between the 2 groups. A high rate of vaginal delivery was seen in the twin and singleton groups (85.0% vs. 80.0%, p = 0.62) with similar neonatal outcomes. Question: Is the protocol for induction of labor in singletons applicable to twin gestations? <|endoftext|> <|assistant|> A standard protocol of labor induction for singleton gestations would apply for twins with overall favorable intrapartum 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: The incidence and risk factors of central nervous system (CNS) involvement in peripheral T-cell lymphomas (PTCLs) are still unclear. We analyzed 228 patients with PTCLs, excluding cases of extranodal natural killer/T-cell lymphoma and primary cutaneous T-cell lymphoma, by retrospectively collecting the clinical features and outcomes of the patients. Twenty events (8.77%, 20/228) of CNS involvement were observed during a median follow-up period of 13.9 months (range 0.03-159.43). Based on univariate analysis, elevated serum lactate dehydrogenase (LDH) level [P = 0.019, relative risk (RR) 5.904, 95% confidence interval (CI) 1.334-26.123] and involvement of the paranasal sinus (P = 0.032, RR 3.137, 95% CI 1.105-8.908) adversely affect CNS involvement. In multivariate analysis, both were independently poor prognostic factors for CNS relapse [elevated LDH level: P = 0.011, hazard ratio (HR) 6.716, 95% CI 1.548-29.131; involvement of the paranasal sinus: P = 0.008, HR 3.784, 95% CI 1.420-10.083]. The survival duration of patients with CNS involvement was significantly shorter than that of the patients without CNS involvement (P = 0.009), with median overall survival of 7.60 months (95% CI of 4.92-10.28) versus 27.43 months (95% CI of 0.00-57.38), respectively. Question: Are elevated LDH and paranasal sinus involvement risk factors for central nervous system involvement in patients with peripheral T-cell lymphoma? <|endoftext|> <|assistant|> Elevated LDH level and involvement of the paranasal sinus are two risk factors for CNS involvement in patients with PTCLs. Considering the poor prognoses after CNS relapse, prophylaxis should be considered with the presence of any risk factor.

<|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: Asthma is a chronic inflammatory disease of the airway that is mediated by T-helper 2(TH2) cells. Thymic stromal lymphopoietin (TSLP) can aggravate asthmatic lung inflammation by activating dendritic cells (DCs) to promote TH2 differentiation. TSLP promoter polymorphisms are associated with susceptibility to bronchial asthma in Japanese population. We sought to determine whether single nucleotide polymorphisms (SNPs) in TSLP gene are associated with asthma in Chinese Han population. To analyze the polymorphism of the two SNPs Rs2289276 and Rs2289278 in TSLP gene and to evaluate the association between the two SNPs and asthma susceptibility in Chinese Han population by using case-control study. five hundred and thirty one asthmatic patients and 540 age-sex matched normal controls were collected and DNA were extracted from peripheral blood, then the genotypes of SNPs Rs2289276 and Rs2289278 in TSLP gene were detected with polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP), genotype and allele frequencies were calculated and analyzed with Chi-square test. Frequencies of CC/CT/TT genotypes at Rs2289276 site were 0.4706/0.4392/0.0902 in the asthmatic patients and 0.5604/0.3800/0.0595 in the healthy controls. Frequencies of CC/CG/GG genotypes at Rs2289278 site were 0.6502/0.2966/0.0532 in the asthmatic patients and 0.5795/0.3428/0.0777 in the healthy controls. The genotype and allele frequencies of the two SNPs in asthma patients were significantly different from those in the healthy controls. Rs2289278 C allele was correlated with decreased FEV(1): FVC (P ≤ .05). Question: Are two single nucleotide polymorphisms in TSLP gene associated with asthma susceptibility in Chinese Han population? <|endoftext|> <|assistant|> TSLP variants are significantly associated with bronchial asthma. TSLP might be a new therapeutic target molecule for asthma.

<|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: Adult-onset autoimmune diabetes is prevalent in China, in contrast to childhood-onset type 1 diabetes mellitus. Islet autoantibodies are the most important immune biomarkers to diagnose autoimmune diabetes. We assayed four different islet autoantibodies in recently diagnosed adult non-insulin-requiring diabetes Chinese subjects to investigate the best antibody assay strategy for the correct diagnosis of these subjects. LADA China study is a nation-wide multicenter study conducted in diabetes patients from 46 university-affiliated hospitals in China. Non-insulin-treated newly diagnosed adult diabetes patients (n = 2388) were centrally assayed for glutamic acid decarboxylase autoantibody (GADA), protein tyrosine phosphatase-2 autoantibody (IA-2A), and zinc transporter 8 autoantibody (ZnT8A) by radioligand assay and insulin autoantibody (IAA) by microtiter plate radioimmunoassay. Clinical data were determined locally. Two hundred and six (8.63 %) subjects were autoantibody positive, of which GADA identified 5.78 % (138/2388) of the total, but only 67 % (138/206) of the autoimmune cases. IA-2A, ZnT8A, and IAA were found in 1.51, 1.84, and 1.26 % of the total study subjects, respectively. When assaying three islet autoantibodies, the most effective strategy was the combination of GADA, ZnT8A, and IAA, which could identify 92.2 % (190/206) autoimmune diabetes patients. The clinical data showed that those subjects with positive GADA had lower random C-peptide than autoantibody negative subjects (P < 0.05). Question: Are glutamic acid decarboxylase autoantibodies dominant but insufficient to identify most Chinese with adult-onset non-insulin requiring autoimmune diabetes : LADA China study 5? <|endoftext|> <|assistant|> As with Europeans, GADA is the dominant autoantibody in this form of autoimmune diabetes in China, but in contrast to Europeans, screening should include other diabetes-associated autoantibodies.

<|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: Prolongation of anticoagulant treatment might reduce subsequent cardiac events in patients with unstable coronary artery disease. Multilead ST-segment monitoring identifies patients with a high risk of adverse outcome. The aim was to assess the value of multilead ST-monitoring in prospectively identifying patients who respond to extended anticoagulant treatment with low-molecular weight heparin when treated by a primarily non-invasive strategy. In this substudy of the FRISC II trial, ST-monitoring with a continuous 12-lead ECG or vectorcardiography was performed for 24 h in 629 patients with unstable coronary artery disease randomized to receive either the low-molecular weight heparin dalteparin, or placebo for 3 months after at least 5 days' dalteparin treatment in all patients. Ischaemic episodes were detected in 34% during ST-monitoring. In the group with ischaemic episodes, the extended dalteparin treatment was associated with a lower rate of death, myocardial infarction, or revascularization (35.2% vs 53.4%, relative risk reduction: 34%, P=0.01). In patients without ischaemic episodes, long-term dalteparin treatment had no effect. Question: Does continuous multilead ST-monitoring identify patients with unstable coronary artery disease who benefit from extended antithrombotic treatment? <|endoftext|> <|assistant|> In patients with unstable coronary artery disease treated primarily with a non-invasive strategy, ischaemic episodes revealed while on multilead ST-monitoring identifies patients who benefit most from extended treatment with anticoagulants.

<|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 correlate the baseline and change of chromogranin A (CgA) levels with patient survival and tumor response in Asian patients with advanced gastro-enteropancreatic neuroendocrine tumors (GEP-NETs). Sixty patients with advanced GEP-NET treated in a medical center between April 2010 and April 2013 were enrolled retrospectively. Plasma CgA level was analyzed for correlation with the patient's clinical outcome and tumor response. Multivariate analysis showed that independent favorable prognostic factors for overall survival were: Eastern Cooperative Oncology Groups performance score 0-1, World Health Organization tumor grade 1-2, single organ metastasis and less than twice the upper normal range of baseline CgA levels. Percentage changes in paired CgA tests (ΔCgA) of more than 17% can predict partial response or stable disease from progressive disease with 91.2% sensitivity and 82.9% specificity. Question: Do plasma chromogranin A levels predict survival and tumor response in patients with advanced gastroenteropancreatic neuroendocrine tumors? <|endoftext|> <|assistant|> Baseline plasma CgA levels predicted overall survival and ΔCgA predicted treatment response in Asian patients with GEP-NETs.

<|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: Increased blood glucose and impaired pressure reactivity (PRx) after traumatic brain injury (TBI) are both known to correlate with unfavorable patient outcome. However, the relationship between these two variables is unknown. To test the hypothesis that increased blood glucose leads to increased PRx, we retrospectively analyzed data from 86 traumatic brain injured patients admitted to the Neurocritical Care Unit. Data analyzed included arterial glucose concentration, intracranial pressure (ICP), cerebral perfusion pressure (CPP) and end-tidal CO2. PRx was calculated as the moving correlation coefficient between averaged (10 seconds) arterial blood pressure and ICP. One arterial glucose concentration and one time-aligned PRx value were obtained for each patient, during each day until the fifth day after ictus. Mean arterial glucose concentrations during the first 5 days since ictus were positively correlated with mean PRx (Pearson correlation coefficient = 0.25, p = 0.02). The correlation was strongest on the first day after injury (Pearson correlation coefficient = 0.47, p = 0.008). Question: Is increased blood glucose related to disturbed cerebrovascular pressure reactivity after traumatic brain injury? <|endoftext|> <|assistant|> Our preliminary findings indicate that increased blood glucose may impair cerebrovascular reactivity, potentially contributing to a mechanistic link between increased blood glucose and poorer outcome after TBI.

<|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: : Regarding safety, we investigated the effect of prenatal probiotic and 6 months of pro- and prebiotic supplementation of infants on their hematologic values at 6 months and 2 years and factors affecting these values. : In a prospective randomized controlled probiotic intervention trial in infants at high risk for allergy, we obtained blood samples consecutively from 98 infants at 6 months and from 658 children at 2 years to measure hematologic values. We collected fecal samples at 3 and 6 months to measure immunologic development by calprotectin, alpha-1-antitrypsin, tumor necrosis factor-alpha, and immunoglobulin A. : At 6 months, infants in the probiotic group had significantly lower hemoglobin (Hb) values than did the placebo group, mean (SD): 119.8 g/L (6.3) versus 123.3 g/L (8.4), P = 0.025. Adjustment for factors that might affect Hb values (breast-feeding duration, solid-food introduction, and sex), revealed no need for adjustment. A significant negative correlation emerged between Hb values at 6 months and fecal calprotectin at age 3 months r = -0.301, P = 0.009, which was affected neither by breast-feeding, sex, nor study group. At 2 years, hematologic values in both groups became similar. Question: Does pro- and prebiotic supplementation induce a transient reduction in hemoglobin concentration in infants? <|endoftext|> <|assistant|> : Probiotics cause a gut mucosal inflammation with decreased Hb values during intervention, corrected after halting the supplementation.

<|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: Computed tomography enterography (CTE) is a promising modality for small bowel imaging. However, the role of CTE in the evaluation of obscure gastrointestinal bleeding (OGIB) has not been established. We investigated the efficacy of CTE in diagnosing OGIB and the long-term outcomes based on CTE findings, with special reference to negative CTE. A total of 63 consecutive patients who had undergone CTE for OGIB were enrolled, and their pre- and post-CTE clinical data were collected. "Specific treatments" were defined as treatments directly aimed at resolving presumed bleeding causes, including hemostasis and operation, while "non-specific treatments" were defined as symptomatic treatments for anemia. Among 60 patients for whom long-term follow-up data were available, positive lesions were found in 16 patients (26.7%). The overall rebleeding rate was 21.7% during a mean follow up of 17.6 ± 4.7 months. There was no significant difference in the cumulative rebleeding rates between patients with positive and negative CTE results (P = 0.241). All patients who received specific treatments after CTE did not rebleed (0/8). In positive CTE patients, specific treatments significantly reduced the rebleeding rate (P = 0.023). Question: Long-term outcomes of obscure gastrointestinal bleeding after CT enterography: does negative CT enterography predict lower long-term rebleeding rate? <|endoftext|> <|assistant|> CTE has a high rate of detecting overt OGIB. However, negative CTE results do not predict lower long-term rebleeding, and such patients with OGIB should be closely observed. In patients with positive CTE, more vigorous management significantly reduces the incidence of rebleeding.

<|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: Specialized brood pollination systems involve both mutualism and antagonism in the overall interaction and have led to diversification in both plants and insects. Although largely known for mutualism, the role of the antagonistic side of the interaction in these systems has been overlooked. Specialization may be driven by plant defenses to feeding by the insect larvae that consume and kill developing plant ovules. The interaction among yuccas and yucca moths is cited as a classic example of the importance of mutualism in specialization and diversification. Pollinators moths are very host specific, but whether this specificity is due to adult pollination ability or larval feeding ability is unclear. Here, I test the potential role of antagonism in driving specialization among yuccas and yucca moths. I examined the ability of the most-polyphagous yucca moth pollinator, Tegeticula yuccasella, to pollinate and develop on five Yucca species used across its range. Yucca species endemic to the Great Plains and Texas were transplanted to a common garden in Syracuse, New York and exposed to the local pollinator moth population over 3 years. Local moths visited all but one of the Yucca species, but had drastically lower rates of successful larval development on non-natal Yucca species in comparison to the local host species. Question: Specialization in the yucca-yucca moth obligate pollination mutualism: A role for antagonism? <|endoftext|> <|assistant|> Specialization in many brood pollination systems may be strongly influenced by the antagonistic rather than the mutualistic side of the overall interaction, suggesting that antagonistic coevolution is a possible source of diversification.

<|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: Uterine serous carcinoma (USC) is a subtype of endometrial cancer associated with chemoresistance and poor outcome. Overexpression of tubulin-β-III and p-glycoprotein has been linked to paclitaxel resistance in many cancers but has been undercharacterized among USCs. Epothilones have demonstrated activity in certain paclitaxel-resistant malignancies. In this study, relationships are clarified, in USCs relative to ovarian serous carcinomas (OSCs), between tubulin-β-III and p-glycoprotein expression, clinical outcome, and in vitro chemoresponsiveness to epothilone B, ixabepilone, and paclitaxel. Tubulin-β-III and p-glycoprotein were quantified by real-time polymerase chain reaction in 48 fresh-frozen tissue samples and 13 cell lines. Copy number was correlated with immunohistochemistry and overall survival. Median inhibitory concentration (IC50 ) was determined using viability and metabolic assays. Impact of tubulin-β-III knockdown on IC50 was assessed with small interfering RNAs. USC overexpressed tubulin-β-III but not p-glycoprotein relative to OSC in both fresh-frozen tissues (552.9 ± 106.7 versus 202.0 ± 43.99, P = .01) and cell lines (1701.0 ± 376.4 versus 645.1 ± 157.9, P = .02). Tubulin-β-III immunohistochemistry reflected quantitative real-time polymerase chain reaction copy number and overexpression stratified patients by overall survival (copy number ≤ 400: 615 days; copy number > 400: 165 days, P = .049); p-glycoprotein did not predict clinical outcome. USCs remained exquisitely sensitive to patupilone in vitro despite tubulin-β-III overexpression (IC50,USC 0.245 ± 0.11 nM versus IC50,OSC 1.01 ± 0.13 nM, P = .006). Question: Is tubulin-β-III overexpression by uterine serous carcinomas a marker for poor overall survival after platinum/taxane chemotherapy and sensitivity to epothilones? <|endoftext|> <|assistant|> Tubulin-β-III overexpression in USCs discriminates poor prognosis, serves as a marker for sensitivity to epothilones, and may contribute to paclitaxel resistance. Immunohistochemistry reliably identifies tumors with overexpression of tubulin-β-III, and a subset of individuals likely to respond to patupilone and ixabepilone. Epothilones warrant clinical investigation for treatment of USCs.

<|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: Endothelial dysfunction, specifically endothelium-derived contracting factors have been implicated in the development of arterial conduit vasospasm. The potent vasoconstrictor endothelin-1 (ET-1) has received much attention in this regard. The present study was designed to evaluate the role of ET-1 in the development of endothelial dysfunction in human internal mammary arteries (IMA). To this aim, we examined the effects of specific and non-specific ET-receptor antagonists on endothelial function (assessed using acetylcholine (ACh)-induced vasodilation) in segments of IMA obtained during coronary artery bypass graft (CABG) surgery. Vascular segments of IMA were obtained from 51 patients undergoing elective coronary artery bypass graft (CABG) surgery and in vitro endothelium-dependent and -independent responses to ACh and sodium nitroprusside (SNP) were assessed. Isometric dose response curves (DRC) to ACh and SNP were constructed in pre-contracted rings in the presence and absence of bosentan (ET(A/B) receptor antagonist, 3 microM), BQ-123 (ET(A) antagonist, 1 microM) and BQ-788 (ET(B) antagonist, 1 microM) using the isolated organ bath apparatus. Percent maximum relaxation (%E(max)) and sensitivity (pEC(50)) were compared between interventions. ACh caused dose-dependent endothelium-mediated relaxation in IMA (%E(max) 43+/-4, pEC(50) 6. 74+/-0.12). In the presence of bosentan, BQ-123 and BQ-788 ACh-induced relaxation was significantly augmented (%E(max) bosentan 60+/-3, BQ-123 56+/-4, BQ-788 53+/-5 vs. control 43+/-4, P<0.05) without affecting sensitivity. The effects of these antagonists were endothelium-specific since endothelium-independent responses to SNP remained unaltered. Furthermore, the beneficial effects were independently and maximally mediated by ET(A) and ET(B) receptors (%E(max) BQ-123 56+/-4 vs. BQ-788 53+/-5 vs. bosentan 60+/-3, P>0. 05). Question: Does endothelin receptor blockade improve endothelial function in human internal mammary arteries? <|endoftext|> <|assistant|> These data uncover, for the first time, beneficial effects of ET receptor blockade on endothelial-dependent vasorelaxation in human IMA.

<|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 cryopreservation of yam is constrained with many challenges. This study tested the effects of melatonin on shoot tips of D. alata and D. cayenensis accessions exposed to water and liquid nitrogen (LN) stresses. Sucrose pretreatment (0.3 M) was applied for 48 h before cryopreservation. Shoot tips were encapsulated in beads loaded with 0.75 M sucrose, with and without melatonin and desiccated over sterile dry silica gel for 0 - 9 h. The beads moisture content declined from 100% to ~ 13% after 9 h. The 3 h desiccation period without melatonin produced a significantly higher regeneration compared to 6 h and 9 h. Shoot tips with melatonin had significantly higher regeneration after 3 - 6 h desiccation compared to 9 h and the regeneration of all accessions after 6 h was >80%. Regeneration following 6 h desiccation and LN was significantly greater for melatonin-treated shoot tips compared to non-treated ones. Question: Do melatonin-loaded alginate beads improve cryopreservation of yam ( Dioscorea alata and D. cayenensis )? <|endoftext|> <|assistant|> The results indicate that melatonin significantly increased regeneration from 15% to 35%.

<|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 prospective study, brain ultrasound scans were performed in 42 newborns (median birth weight 1700 g, range 1020-3720 g; gestational age 32 weeks, 26-36) to reveal peri-intraventricular haemorrhage (PIVH) (grades I-IV) as well as echodensities (ED) and/or periventricular leucomalacia (PVL). ECG and arterial blood pressure were recorded on magnetic tape at 8-h intervals during the first 24 h of life for further computer analysis. Heart rate (HR) and its variability (HRV) indices RMSM (long-term variability) and RMSSD (short-term variability), together with their coefficients of variation, were computed. Systolic (SBP), diastolic (DBP), and mean blood pressures (MBP) were detected as average values for 2-min stationary segments together with the respective minima and maxima. The indices of variability and their coefficients of variation were computed for the arterial pressure. PIVH was found in 12 newborns and ED in 8 (of whom two developed PVL). The remaining 22 served as controls. Neither HR, HRV nor BP variability differed between the groups. DBP was higher in the group with PIVH (39 mmHg) when compared to both the controls (33 mmHg, P < 0.05) and the ED group (32 mmHg, P < 0.01). MBP behaved respectively (45 mmHg, 38 mmHg, 37 mmHg, P < 0.01). SBP behaved also similarly when gestational age and birth weight were used as covariates (57 mmHg, 48 mmHg, 47 mmHg, P < 0.01). Question: Is elevated arterial blood pressure associated with peri-intraventricular haemorrhage? <|endoftext|> <|assistant|> Our results suggest that elevated diastolic, mean and systolic blood pressure are significantly associated with peri-intraventricular haemorrhage in preterm newborn infants.

<|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: Fabry disease, a lysosomal storage disease caused by deficient lysosomal alpha-galactosidase A activity, is characterized by globotriaosylceramide (GL-3) accumulation in multiple cell types, particularly the vasculature, leading to end organ failure. Accumulation in the kidney is responsible for progressive decline in renal function in male patients with the classical phenotype, resulting in renal failure in their third to fifth decades of life. With the advent of recombinant protein synthesis technology, enzyme replacement therapy has become a viable alternative to dialysis or renal transplantation, previously the only available treatment options for end-stage renal disease. The pre- and post-treatment renal biopsies were analyzed from fifty-eight Fabry patients enrolled in a Phase 3 double-blind, randomized, placebo-controlled trial followed by a six-month open label extension study of the recombinant human enzyme, alpha-galactosidase A (r-halphaGalA), administered IV at 1 mg/kg biweekly. The purpose of this investigation was to detail the pathologic changes in glycosphingolipid distribution and the pattern of post-treatment clearance in the kidney. Baseline evaluations revealed GL-3 accumulations in nearly all renal cell types including vascular endothelial cells, vascular smooth muscle cells, mesangial cells and interstitial cells, with particularly dense accumulations in podocytes and distal tubular epithelial cells. After 11 months of r-halphaGalA treatment there was complete clearance of glycolipid from the endothelium of all vasculature as well as from the mesangial cells of the glomerulus and interstitial cells of the cortex. Moderate clearance was noted from the smooth muscle cells of arterioles and small arteries. Podocytes and distal tubular epithelium also demonstrated evidence for decreased GL-3, although this clearance was more limited than that observed in other cell types. No evidence of immune complex disease was found by immunofluorescence despite circulating anti-r-halphaGalA IgG antibodies. Question: Is globotriaosylceramide accumulation in the Fabry kidney cleared from multiple cell types after enzyme replacement therapy? <|endoftext|> <|assistant|> These findings indicate a striking reversal of renal glycosphingolipid accumulation in the vasculature and in other renal cell types, and suggest that long-term treatment with r-halphaGalA may halt the progression of pathology and prevent renal failure in patients with Fabry disease.

<|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: With a theoretical link between stent insertion and increased risk of tumour seeding, there is concern about long-term survival after the use of self-expanding metallic stents (SEMS) as a "bridge to surgery" in the treatment of left-sided obstructing colorectal cancer. This cohort study aims to determine if preoperative stenting adversely affects long-term survival by comparing a group of patients having preoperative stenting (group A) with a group of patients having elective surgery (group B) in a single centre. The study is retrospective. Survival was calculated with Kaplan-Meier analysis and compared using the log-rank test. Other group characteristics were compared with Fisher's exact test. From November 1998 to November 2008, 15 patients had preoperative SEMS and were entered in group A. This represented 11.5 % of a total of 130 patients undergoing SEMS insertion in the same period. Group B included 88 consecutive patients undergoing elective left-sided colonic resection for Dukes' B and C cancer excluding mid and low rectal tumours between January 2003 and December 2007. The 30-day mortality rate for groups A and B was 6.7 % (one patient) and 5.7 % (five patients), respectively. The 5-year survival rate was 60 % and 58 %, respectively, with a p value of 0.96. Question: Does stenting of left-sided colorectal cancer as a "bridge to surgery" adversely affect oncological outcomes? <|endoftext|> <|assistant|> In our own practice, patients undergoing SEMS as a "bridge to surgery" have the same long-term survival with those undergoing elective surgery. This finding needs to be confirmed in larger scale 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: Myelin protein zero (MPZ) is a critical structural component of myelin in the peripheral nervous system. The MPZ gene is regulated, in part, by the transcription factors SOX10 and EGR2. Mutations in MPZ, SOX10, and EGR2 have been implicated in demyelinating peripheral neuropathies, suggesting that components of this transcriptional network are candidates for harboring disease-causing mutations (or otherwise functional variants) that affect MPZ expression. We utilized a combination of multi-species sequence comparisons, transcription factor-binding site predictions, targeted human DNA re-sequencing, and in vitro and in vivo enhancer assays to study human non-coding MPZ variants. Our efforts revealed a variant within the first intron of MPZ that resides within a previously described SOX10 binding site is associated with decreased enhancer activity, and alters binding of nuclear proteins. Additionally, the genomic segment harboring this variant directs tissue-relevant reporter gene expression in zebrafish. Question: Does a rare myelin protein zero ( MPZ ) variant alter enhancer activity in vitro and in vivo? <|endoftext|> <|assistant|> This is the first reported MPZ variant within a cis-acting transcriptional regulatory element. While we were unable to implicate this variant in disease onset, our data suggests that similar non-coding sequences should be screened for mutations in patients with neurological disease. Furthermore, our multi-faceted approach for examining the functional significance of non-coding variants can be readily generalized to study other loci important for myelin structure and function.

<|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: MCPIP is a novel CCCH zinc finger protein described as an RNase engaged in the regulation of immune responses. The regulation of expression of the gene coding for MCPIP - ZC3H12A is poorly explored. Here we report that the proinflammatory cytokine IL-1beta rapidly induces the synthesis of MCPIP in primary monocyte-derived macrophages and HepG2 cells. This up-regulation takes place through the MAP kinase pathway and following activation of the transcription factor Elk-1. Using a ZC3H12A reporter construct we have shown that a ZC3H12A promoter region, stretching from -76 to +60, mediates activation by IL-1beta. This region contains binding sites for Elk-1 and its partner SRF. Chromatin immunoprecipitation analysis confirms in vivo binding of both transcription factors to this region of the ZC3H12A promoter. Question: Are transcription factors Elk-1 and SRF engaged in IL1-dependent regulation of ZC3H12A expression? <|endoftext|> <|assistant|> We conclude that the transcription factor Elk-1 plays an important role in the activation of ZC3H12A expression in response to IL-1beta stimulation.

<|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 was conducted to determine if oral triiodothyronine supplementation could prevent the decrease of serum triiodothyronine levels that commonly occurs after cardiopulmonary bypass for pediatric congenital heart surgery. Secondary objectives included identifying any significant adverse effects of oral triiodothyronine supplementation, including any effects on the thyroid/pituitary axis. Randomized, placebo-controlled, doubleblind clinical trial Operating room and ICU. Infants and children younger than 2 years of age undergoing congenital heart surgery using cardiopulmonary bypass (n = 43). Subjects were assigned to placebo (n = 15, group A) or one of two treatment groups: a low-dose group (group B, n = 14, 0.5 mcg/kg triiodothyronine orally every 24 hr for 3 d) or a high-dose group (group C, n = 14, 0.5 mcg/kg triiodothyronine orally every 12 hr for 3 d). Thyroid hormone, including total and free triiodothyronine levels at predetermined time points, potential side effects indicating hyperthyroidism, indicators of the thyroid-pituitary axis, and clinical endpoints. Oral triiodothyronine supplementation twice-daily maintained serum triiodothyronine levels within normal limits in group C, whereas serum levels progressively declined in groups A and B. A statistically significant difference in triiodothyronine levels between the treatment groups occurred between 18 and 36 hours post cross-clamp release, with the largest difference in serum levels between group C and group A noted at 36 hours post cross-clamp release (total triiodothyronine, 0.71 ± 0.15 [0.34-1.08] ng/mL [p < 0.01]; free triiodothyronine, 2.56 ± 0.49 [1.33-3.79] pg/mL [p < 0.01]). There was no evidence of hyperthyroidism or suppression of the pituitary-thyroid axis in either treatment group Question: Does oral triiodothyronine normalize triiodothyronine levels after surgery for pediatric congenital heart disease*? <|endoftext|> <|assistant|> Oral triiodothyronine supplementation at a dose of 0.5 mcg/kg every 12 hours for 3 days can maintain total and free triiodothyronine levels within normal limits after open-heart surgery using cardiopulmonary bypass for congenital heart disease.

<|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, our aim was to investigate how different immunohistochemical techniques may influence the result of BCL6 positivity and categorization in germinal center (GC) and non-GC derived diffuse large B-cell lymphoma (DLBCL), as it has been proposed that classification of DLBCL according to cell-of-origin by immunohistochemistry may be performed as a routine procedure in the diagnostic work-up. However, a number of technical issues need to be solved before introducing this as a standard technique. Tumor specimens from 122 patients with de novo stage II-IV disease, adequately treated with anthracycline-containing chemotherapy regimens were collected. Immunohistochemical expression of BCL6, CD10, and MUM-1/IRF4 was examined using a tissue microarray (TMA) technique. BCL6 and CD10 were also evaluated on whole tissue sections. Due to profound tissue heterogeneity, BCL6 showed a wide range of positivity, with a high number of false negative results by TMA (25% positive), compared to 53% on whole tissue sections (WTS). CD10 was more homogeneously expressed, and TMA results corresponded better to WTS. Consequently, the results from categorization into GC and non-GC DLBCL differed considerably by use of the two methods, and resulted in very different outcome in terms of overall survival. Question: Is tissue microarray inappropriate for analysis of BCL6 expression in diffuse large B-cell lymphoma? <|endoftext|> <|assistant|> Immunohistochemical GC-status determined on TMA is not reliable enough to be used for individual treatment decisions in DLBCL, mostly due to difficulties in interpreting BCL6 status.

<|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 coagulation protein von Willebrand Factor (VWF) is known to be elevated in pregnancy. However, the timing and nature of changes in VWF and associated parameters throughout pregnancy are not well understood. To better understand the changes in VWF provoked by pregnancy, we studied VWF-associated parameters in samples collected over the course of healthy pregnancies. We measured VWF antigen (VWF:Ag), VWF propeptide (VWFpp), Factor VIII (FVIII), and ADAMTS13 activity in samples collected from 46 women during pregnancy and at non-pregnant baseline. We also characterized pregnant vs. non-pregnant VWF multimer structure in 21 pregnancies, and performed isoelectric focusing (IEF) of VWF in two pregnancies which had samples from multiple trimesters. VWF:Ag and FVIII levels were significantly increased during pregnancy. ADAMTS13 activity was unchanged. VWFpp levels increased much later in pregnancy than VWF:Ag, resulting in a progressive decrease in VWFpp:Ag ratios. FVIII:VWF ratios also decreased in pregnancy. Most pregnancies exhibited a clear loss of larger VWF multimers and altered VWF triplet structure. Further evidence of acquired VWF qualitative changes in pregnancy was found in progressive, reversible shifts in VWF IEF patterns over gestation. Question: Are complex changes in von Willebrand factor-associated parameters acquired during uncomplicated pregnancy? <|endoftext|> <|assistant|> These data support a new view of pregnancy in which VWF can acquire qualitative changes associated with advancing gestational age. Modeling supports a scenario in which both increased VWF production and doubling of the VWF half-life would account for the data observed. We propose that gestation induces a prolongation in VWF survival, which likely contributes to increased total VWF levels and altered VWF structure.

<|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: Clinical supervision is regarded as a central component in developing mental health nursing practices, but the evidence supporting positive outcomes of clinical supervision in psychiatric nursing is not convincing. The study was designed as a randomized controlled trial. All permanently employed nursing staff members at three general psychiatric wards at a Danish university hospital (n = 83) were allocated to either an intervention group (n = 40) receiving the meta-supervision in addition to attending usual supervision or to a control group (n = 43) attending usual supervision. Self-reported questionnaire measures of clinical supervision effectiveness and benefits were collected at base line in January 2012 and at follow-up completed in February 2013. In addition, a prospective registration of clinical supervision participation was carried out over 3 months subsequent to the intervention. The main result was that it was possible to motivate staff in the intervention group to participate significantly more frequently in sessions of the ongoing supervision compared with the control group. However, more frequent participation was not reflected in the experienced effectiveness of the clinical supervision or in the general formative or restorative benefits. Question: Is it possible to strengthen psychiatric nursing staff's clinical supervision? <|endoftext|> <|assistant|> The intervention had a positive effect on individuals or wards already actively engaged in clinical supervision, which suggested that individuals and wards without well-established supervision practices may require more comprehensive interventions targeting individual and organizational barriers to clinical supervision.

<|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: Saccharomyces cerevisiae, a nonpathogenic yeast, has been used previously as a vehicle to elicit immune responses to foreign antigens, and tumor-associated antigens, and has been shown to reduce tumor burden in mice. Studies were designed to determine if vaccination of human carcinoembryonic antigen (CEA)-transgenic (CEA-Tg) mice (where CEA is a self-antigen) with a recombinant S. cerevisiae construct expressing human CEA (yeast-CEA) elicits CEA-specific T-cell responses and antitumor activity. CEA-Tg mice were vaccinated with yeast-CEA, and CD4(+) and CD8(+) T-cell responses were assessed after one and multiple administrations or vaccinations at multiple sites per administration. Antitumor activity was determined by tumor growth and overall survival in both pulmonary metastasis and s.c. pancreatic tumor models. These studies demonstrate that recombinant yeast can break tolerance and that (a) yeast-CEA constructs elicit both CEA-specific CD4(+) and CD8(+) T-cell responses; (b) repeated yeast-CEA administration causes increased antigen-specific T-cell responses after each vaccination; (c) vaccination with yeast-CEA at multiple sites induces a greater T-cell response than the same dose given at a single site; and (d) tumor-bearing mice vaccinated with yeast-CEA show a reduction in tumor burden and increased overall survival compared to mock-treated or control yeast-vaccinated mice in both pulmonary metastasis and s.c. pancreatic tumor models. Question: Does vaccination with a recombinant Saccharomyces cerevisiae expressing a tumor antigen breaks immune tolerance and elicit therapeutic antitumor responses? <|endoftext|> <|assistant|> Vaccination with a heat-killed recombinant yeast expressing the tumor-associated antigen CEA induces CEA-specific immune responses, reduces tumor burden, and extends overall survival in CEA-Tg mice. These studies thus form the rationale for the incorporation of recombinant yeast-CEA and other recombinant yeast constructs in cancer immunotherapy protocols.

<|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: Cartilage oligomeric matrix protein (COMP) is a structural component of cartilage, where it catalyzes collagen fibrillogenesis. Elevated amounts of COMP are found in serum during increased turnover of cartilage associated with active joint disease, such as rheumatoid arthritis (RA) and osteoarthritis (OA). This study was undertaken to investigate the ability of COMP to regulate complement, a capacity that has previously been shown for some other cartilage proteins. Regulation of complement by COMP was studied using functional in vitro assays. Inter-actions between complement proteins and COMP were investigated by direct binding assay and electron microscopy. Circulating COMP and COMP-C3b complexes in serum and synovial fluid from RA and OA patients and healthy controls were measured with a novel enzyme-linked immunosorbent assay. We found in vivo evidence of complement activation by released COMP in the general circulation of patients with RA, but not patients with OA. COMP induced activation and deposition of C3b and C9 specifically via the alternative pathway of complement, which was attributable to direct interaction between COMP and properdin. Furthermore, COMP inhibited the classical and the lectin complement pathways due to direct interaction with the stalk region of C1q and mannose-binding lectin, respectively. Question: Does regulation of complement by cartilage oligomeric matrix protein allow for a novel molecular diagnostic principle in rheumatoid arthritis? <|endoftext|> <|assistant|> COMP is the first extracellular matrix protein for which an active role in inflammation has been demonstrated in vivo. It can activate one complement pathway at the same time as it has the potential to inhibit another. The net outcome of these interactions is most likely determined by the type of released COMP fragments, which may be disease specific.