Datasets:

krana

/

pubmed_processed

like 0

### Question: Is prostate cancer genetic-susceptibility locus on chromosome 20q13 amplified and coupled to androgen receptor-regulation in metastatic tumors? ### Context: The 20q13 chromosomal region has been previously identified as the hereditary prostate cancer genetic-susceptibility locus on chromosome 20 (HPC20). In this study, the 20q13 region was shown to be frequently co-amplified with the androgen receptor (AR) in metastatic prostate cancer. Furthermore, the AR signaling axis, which plays an essential role in the pathogenesis of prostate cancer, was demonstrated to be central to the regulation of the 20q13 common amplified region (CAR). High-resolution mapping analyses revealed hot spots of AR recruitment to response elements in the vicinity of most genes located on the 20q13 CAR. Moreover, amplification of AR significantly co-occurred with CAR amplification on 20q13 and it was confirmed that the majority of AR-bound genes on the 20q13 CAR were indeed regulated by androgens. These data reveal that amplification of the AR is tightly linked to amplification of the AR-regulated CAR region on 20q13. These results suggest that the cross-talk between gene amplification and gene transcription is an important step in the development of castration-resistant metastatic disease. ### Long_Answer: These novel results are a noteworthy example of the cross-talk between gene amplification and gene transcription in the development of advanced prostate cancer. ### Final_Prediction: yes

### Question: Do plasma albumin levels correlate with decreased microcirculation and the development of skin defects in hemodialyzed patients? ### Context: Difficulty healing wounds and skin defects is a frequent problem in patients on chronic hemodialysis (HD) because of malnutrition, inflammation, and atherosclerosis (MIA) syndrome. The aim of the present study was to estimate the influence of peripheral blood flow changes during HD on the development of foot defects and its relationship to plasma albumin levels.Peripheral skin blood flow was measured using a laser Doppler line scanner in 10 different areas of the dorsal part of the instep and the toes of each foot before and during HD with ultrafiltration (897 +/- 465 mL/procedure) in 31 HD patients (10 female, 21 male; age 36-79 y, body mass index = 28 +/- 5.0). No skin defects or apparent acute disease or infection were detected in any patient at the time of laser Doppler line scanner measurement. The feet of the patients were clinically re-examined carefully over the next 18 mo.We found a significant and constant decrease of skin blood flow during the HD procedure (P < 0.001). Skin blood flow was significantly correlated with serum albumin level both before HD (r = 0.36, P = 0.05) and during HD (r = 0.47, P = 0.007). Skin defects developed in 11 patients, with significantly lower skin blood flow during the 18-mo follow-up period. A significantly larger number of patients who had normal perfusion remained defect-free in comparison to patients with critical perfusion (93% versus 38%, P = 0.002, Kaplan-Meier analysis). ### Long_Answer: Skin blood flow may be impaired in HD patients. The apparent malnutrition and inflammation in HD patients are likely responsible for the decreased skin blood flow and the development of the difficulty to heal skin defects and wounds. ### Final_Prediction: yes

### Question: Do combination of IFNγ and chemotherapeutic agents increase TRAIL sensitivity of neuroblastoma cell lines? ### Context: Aim of the study was to further evaluate the role of caspase 8 and death receptors (DR) in the TRAIL-induced apoptosis of neuroblastoma (NB) cell lines.Caspase 8 mRNA expression was monitored by RT-PCR. Caspase 8, DR5 and DR4 protein expression were monitored by Western blot analysis. The effects of IFNγ, TRAIL, IFNγ+TRAIL, caspase 8 inhibitor+TRAIL and IFNγ+chemotherapeutic agents+TRAIL on the growth and apoptosis of NB cells were detected with MTT and flow cytometry. The relative caspase 8 activity was measured with colorimetric assay.Caspase 8 expression was induced by IFNγ in the NB cell line SKNDZ. TRAIL alone did not induce apoptosis compared with controls but a combination of IFNγ+TRAIL and IFNγ+chemotherapeutic agents+TRAIL significantly induced cell apoptosis in SY5Y cells. Etoposide and doxorubicin induced DR5 but not DR4 in NB cell lines. SKNDZ cells expressing caspase 8 after treatment with IFNγ were still resistant to TRAIL but sensitive to TRAIL after the induction of DR5. ### Long_Answer: Sensitization of NB cells to TRAIL may be mediated by the upregulation of caspase 8 with IFNγ and DR5 with chemotherapeutic agents. This suggests that caspase 8 and death receptors play a very important role in TRAIL-induced apoptosis of NB cells and a combination of IFNγ, TRAIL and chemotherapeutic agents may be a new and interesting anticancer treatment strategy for NB. ### Final_Prediction: yes

### Question: Do pulmonary function tests overestimate chronic pulmonary disease in patients with severe aortic stenosis? ### Context: Pulmonary dysfunction is an important risk factor for postoperative complications after cardiac surgery, and severe chronic obstructive pulmonary disease (COPD) is considered a relative contraindication to aortic valve replacement. Pulmonary function tests may mistakenly diagnose patients as having COPD, when in fact they have pulmonary dysfunction due to heart failure that potentially will improve with valve replacement.Between January 2009 and July 2011, 214 consecutive patients underwent pulmonary function testing as part of their preoperative screening. Based on the testing, 143 patients were identified as having COPD (52 mild, 42 moderate, and 49 severe), according to The Society of Thoracic Surgery definition. A total of 71 patients had follow-up tests performed at 6 to 12 months postprocedure.A recent smoking history was present in 55 of 214 (25.7%) patients. Aortic valve replacement was performed in 13.6% (29 of 214) of patients by a conventional surgical approach, in 39.3% (84 of 214) by a transfemoral approach, and in 47.2% (101 of 214) by a transapical approach. Mortality was not significantly different in patients with COPD (12 of 71, 16.9%) compared with patients without COPD (37 of 143, 25.9%), p = 0.141. Logistic regression analyses failed to identify preoperative COPD severity category (p = 0.332) as a predictor for mortality. Comparison of pre- and postprocedure tests revealed that 42% (30 of 71) of patients with COPD showed improvement of one COPD severity category or more, including 40% (12 of 30) of patients in the mild group, 43% (9 of 21) of patients in the moderate group, and 45% (9 of 20) of patients in the severe category. ### Long_Answer: Abnormal pulmonary function improves in a significant number of patients with severe aortic stenosis after valve replacement. ### Final_Prediction: yes

### Question: Is a strong pelvic floor associated with higher rates of sexual activity in women with pelvic floor disorders? ### Context: We evaluated the associations between pelvic floor muscle strength and tone with sexual activity and sexual function in women with pelvic floor disorders.This was a secondary analysis of a multicenter study of women with pelvic floor disorders from the USA and UK performed to validate the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR). Participants were surveyed about whether they were sexually active and completed the PISQ-IR and the Female Sexual Function Index (FSFI) questionnaires to assess sexual function. Physical examinations included assessment of pelvic floor strength by the Oxford Grading Scale, and assessment of pelvic floor tone as per ICS guidelines.The cohort of 585 women was middle-aged (mean age 54.9 ± 12.1) with 395 (67.5 %) reporting sexual activity. Women with a strong pelvic floor (n = 275) were more likely to report sexual activity than women with weak strength (n = 280; 75.3 vs 61.8 %, p < 0.001), but normal or hypoactive pelvic floor tone was not associated with sexual activity (68.8 vs 60.2 %, normal vs hypoactive, p = 0.08). After multivariable analysis, a strong pelvic floor remained predictive of sexual activity (OR 1.89, CI 1.18-3.03, p < 0.01). Among sexually active women (n = 370), a strong pelvic floor was associated with higher scores on the PISQ-IR domain of condition impact (parameter estimate 0.20± 0.09, p = 0.04), and the FSFI orgasm domain (PE 0.51 ± 0.17, p = 0.004). ### Long_Answer: A strong pelvic floor is associated with higher rates of sexual activity as well as higher sexual function scores on the condition impact domain of the PISQ-IR and the orgasm domain of the FSFI. ### Final_Prediction: yes

### Question: Does functional strength training of the leg in subacute stroke improve physical performance? ### Context: To examine the effect of functional strength training in subacute stroke.A single-blinded randomized controlled trial.Two rehabilitation units.Eighteen patients in the subacute phase post stroke, randomly allocated to a functional strength training (intervention) group (n = 8) and a training-as-usual (comparison) group (n = 10).The functional strength training group participated in functional progressive strength training of the affected lower extremity. The training-as-usual group had traditional training, excessive muscle power being avoided to prevent associated reactions. All trained 50 minutes five days a week for four weeks.Maximum weight-bearing in standing (primary outcome), isometric muscle strength, gait speed and items of Motor Assessment Scale.Maximum weight-bearing on the affected leg improved more in the functional strength training group (mean 17.4% of body weight) than in the training-as-usual group (mean 5.6% of body weight), but taking test data at inclusion into consideration, the difference in change was not statistically significant (P = 0.056). More patients in the functional strength training group (57%) could weight-bear on the affected leg while stepping forward, than in the training-as-usual group (17%). Improvement was clinically significant in 7 of 9 outcome measures in the functional strength training group (effect size>or = 0.80, large), but in only 3 of 9 in the training-as-usual group. All patients in the functional strength training group and 70% of the patients in the training-as-usual group rated their overall status as 'much' or 'very much' improved. ### Long_Answer: This pilot study indicates that functional strength training of lower extremities improves physical performance more than traditional training. ### Final_Prediction: nan

### Question: Does catheter-based radio-frequency renal nerve denervation lower blood pressure in obese hypertensive swine model? ### Context: Radio-frequency renal denervation (RDN) therapy is under investigation for the treatment of uncontrolled hypertension. Data in hypertensive, drug-naïve large animal models using RDN is limited.A cohort of Ossabaw swine (N = 9) was implanted with telemetry monitors, enrolled on a high calorie-feed regimen and randomly assigned to RDN. Blood pressure (BP) data were separated and analyzed according to the following epoch definitions: 24-h (h), most-active-h, light-h, and dark-h.The mean weight increased by 45% from 86.5 ± 2.5 kg at telemetry implant (day 87) to 125.2 ± 4.5 kg at time of RDN therapy (day 227). Hypertension developed in all swine (24-h BP: 169.5/128.3 ± 5.8/5.1 mmHg pre-RDN). RDN resulted in significant reductions in noradrenaline kidney tissue concentration by 63%. Significant BP reductions were documented at 45 days post-RDN in all defined interday epochs, except for the dark-h period. The most pronounced SBP/DBP reduction was 12.4/11.2 mmHg (P < 0.05), observed during the most-active-h period. Animals continued to gain weight after the RDN procedure to the end of the study at 90 days (125.2 ± 4.5-138.5 ± 6.6 kg, P < 0.001). At 90 days post-RDN, the mean 24-h BP returned near pre-RDN baseline values. Given the strong relationship of BP to weight (R = 0.87, P < 0.001), group mean SBP/DBP was normalized by weight resulting in significant and continued reductions at both 45 and 90 days post-RDN across all intradaily epochs. ### Long_Answer: Catheter-based RDN, using a multielectrode system, resulted in a significant reduction in 24-h BP in this drug-naïve, hypertensive animal model. ### Final_Prediction: yes

### Question: Is loss of the 14-3-3σ tumor suppressor a critical event in ErbB2-mediated tumor progression? ### Context: 14-3-3σ is a putative tumor suppressor involved in cell-cycle progression and epithelial polarity. We demonstrate that loss of one or both copies of the conditional 14-3-3σ allele results in accelerated mammary and salivary tumorigenesis in mice expressing an activated erbB2 oncogene under the endogenous erbB2 promoter. Significantly, the majority of tumors bearing a single conditional 14-3-3σ allele lose expression of the remaining 14-3-3σ allele, which is associated with epigenetic methylation of the 14-3-3σ locus. In addition to accelerated tumor onset, in a mouse mammary tumor virus-driven ErbB2 tumor model, loss of 14-3-3σ results in enhanced metastatic phenotype that is correlated with loss of cellular junctions. Taken together, these results provide compelling evidence that 14-3-3σ is a potent tumor suppressor involved in ErbB2-driven breast cancer initiation and metastasis. ### Long_Answer: 14-3-3σ has been identified as a normal mammary epithelial cell marker frequently downregulated during neoplastic development. Consistent with its potential role as a tumor suppressor, we demonstrate that targeted disruption of 14-3-3σ in a number of epithelial tissues can profoundly impact both the initiation and metastatic phases of ErbB2-mediated tumor progression through modulation of a number of distinct signaling networks. ### Final_Prediction: yes

### Question: Are elevated peripheral blood natural killer cells effectively downregulated by immunoglobulin G infusion in women with recurrent spontaneous abortions? ### Context: We investigated the hypothesis that elevated peripheral blood natural killer cells (NK) are decreased by immunoglobulin G infusion (IVIg) therapy in women with recurrent spontaneous abortions (RSA) and elevated NK cells.Seventy-three women with RSA and elevated NK cells received IVIg therapy (400 mg/Kg/day for 3 days ever 4 wks) and anticoagulation treatment. Peripheral blood immunophenotype assay by flow cytometry was done prospectively prior to and 7 days after first IVIg therapy, every 2 wks until 20 wks gestation and then monthly. Controls were 95 women with RSA and normal NK cells who received anticoagulation treatment.(1) 86.3% of women with elevated NK cells who received the IVIg and anticoagulation therapy had a successful pregnancy outcome; (2) Peripheral blood CD56+ NK cells and CD56+/16+ NK cells were significantly suppressed 7 days post IVIg infusion (P < 0.0005); (3) Pre-IVIg infusion levels of other lymphocyte subsets were not different as compared with those of 7 days post-IVIg therapy; (4) Women who delivered a liveborn infant with IVIg therapy demonstrated downregulation of peripheral blood NK cells (CD56+, CD56+/16+) during early pregnancy when compared to women who miscarried the index pregnancy (P < 0.05); (5) Women with normal NK cells who miscarried while on anticoagulation therapy demonstrated significantly elevated CD56+ NK cells during early pregnancy as compared with that of women who delivered a liveborn infant (P < 0.05); (6) CD19+ B cells were significantly downregulated during pregnancy in women with anticoagulation and IVIg therapy when compared to women with anticoagulation therapy (P < 0.05). ### Long_Answer: Downregulation of NK cells in women with RSA is associated with a favorable pregnancy outcome. Peripheral blood NK cells (CD56+, CD56+/16+) are effectively suppressed after IVIg therapy. Women with RSA and high NK cells benefit from IVIg therapy and experience suppression of CD56+ and CD56+/16+ NK cells. ### Final_Prediction: yes

### Question: Bladder pain syndrome: do the different morphological and cystoscopic features correlate? ### Context: For the diagnosis of bladder pain syndrome (BPS), the International Society for the Study of Bladder Pain Syndrome (ESSIC) recommends a specific diagnostic work-up using cystoscopy with hydrodistension and bladder biopsies. This study evaluates the correlation between the histological findings in bladder biopsies handled following ESSIC recommendations, as well as the importance of the histological features in BPS compared with the cystoscopic findings.The study included 15 men and 93 women. All patients underwent cystoscopy with hydrodistension, and at least three deep biopsies including detrusor muscle were taken. For the cell count the Leder stain was used most frequently. A cut-off point of 28 mast cells/mm(2) was used for detrusor mastocytosis.Significant correlations were found between urothelial damage and inflammatory infiltrate (p<0.001). Detrusor mastocytosis was significantly more elevated in biopsies with normal urinary epithelium (Tukey corrected p<0.0001) than in biopsies where the urothelium was damaged. No other correlations were found between histological findings or between histological and cystoscopic findings. ### Long_Answer: Both cystoscopy with hydrodistension and histology can be used to illustrate different pathophysiological mechanisms in patients with BPS. These results favour the use of both in the classification of BPS patients. ### Final_Prediction: nan

### Question: Should lower limb fractures be treated surgically in patients with chronic spinal injuries? ### Context: To report the outcomes of surgical treatment of lower limb fractures in patients with chronic spinal cord injuries.A total of 37 lower limb fractures were treated from 2003 to 2010, of which 25 fractures were treated surgically and 12 orthopaedically.Patients of the surgical group had better clinical results, range of motion, bone consolidation, and less pressure ulcers and radiological misalignment. No differences were detected between groups in terms of pain, hospital stay, and medical complications.There is no currently consensus regarding the management of lower limb fractures in patients with chronic spinal cord injuries, but the trend has been conservative treatment due to the high rate of complications in surgical treatment. ### Long_Answer: Chronic spinal cord injuries patients with lower limb fractures who are treated surgically achieved a more reliable consolidation, practically a free range of motion, low rate of cutaneous complications, and pain associated with the fracture. This allows a quick return to the previous standard of living, and should be considered as an alternative to orthopaedic treatment in these patients. ### Final_Prediction: yes

### Question: Small bowel lymphangiectasia and angiodysplasia: a positive association; novel clinical marker or shared pathophysiology? ### Context: Small bowel angiodysplasia accounts for 30 to 40% of cases of obscure gastrointestinal bleeding and is associated with significant morbidity and mortality. Identifying lesions can be difficult. Small bowel capsule endoscopy (SBCE) is a significant advance on earlier diagnostic techniques. The cause of angiodysplasia is unknown and the natural history poorly understood. Many lesions are thought to arise from a degenerative process associated with ageing, local vascular anomalies, and tissue hypoxia. Nonpathologic lymphangiectasias are commonly seen throughout the small bowel and are considered a normal finding.To determine whether there is an association between lymphangiectasias, angiodysplasia, and atherosclerosis related conditions.Relevant information was collected from a dedicated SBCE database. Logistic regression analysis was used to examine associations between angiodysplasia, lymphangiectasia, patient demographics, and comorbidity.In all, 180 patients underwent SBCE during the study period, 46 (25%) had angiodysplasia and 47 (26%) lymphangiectasia. Lymphangiectasia were seen in 24 (52%) of 46 with angiodysplasia, in 16 (19%) of 84 with obscure gastrointestinal bleeding without angiodysplasia and in 7 (14%) of 50 without gastrointestinal bleeding. Logistic regression analysis confirmed a strong positive association between angiodysplasia and lymphangiectasia; odds ratio 4.42, P<0.003. Angiodysplasias were also associated with increasing age; odds ratio 1.1. There was no correlation with any other patient characteristic. ### Long_Answer: Lymphangiectasia are strongly associated with the presence of small intestinal angiodysplasia and may represent a useful clinical marker for this condition. Angiodysplasia are also associated with increasing age. Conditions associated with systemic atherosclerosis did not increase the risk of angiodysplasia. ### Final_Prediction: nan

### Question: Are structural and biomechanical alterations in rabbit thoracic aortas associated with the progression of atherosclerosis? ### Context: Atherosclerosis is a diffuse and highly variable disease of arteries that alters the mechanical properties of the vessel wall through highly variable changes in its cellular composition and histological structure. We have analyzed the effects of acute atherosclerotic changes on the mechanical properties of the descending thoracic aorta of rabbits fed a 4% cholesterol diet.Two groups of eight male New Zealand White rabbits were randomly selected and fed for 8 weeks either an atherogenic diet (4% cholesterol plus regular rabbit chow), or regular chow. Animals were sacrificed after 8 weeks, and the descending thoracic aortas were excised for pressure-diameter tests and histological evaluation to examine the relationship between aortic elastic properties and atherosclerotic lesions.All rabbits fed the high-cholesterol diet developed either intermediate or advanced atherosclerotic lesions, particularly American Heart Association-type III and IV, which were fatty and contained abundant lipid-filled foam cells (RAM 11-positive cells) and fewer SMCs with solid-like actin staining (HHF-35-positive cells). In contrast, rabbits fed a normal diet had no visible atherosclerotic changes. The atherosclerotic lesions correlated with a statistically significant decrease in mean vessel wall stiffness in the cholesterol-fed rabbits (51.52 ± 8.76 kPa) compared to the control animals (68.98 ± 11.98 kPa), especially in rabbits with more progressive disease. ### Long_Answer: Notably, stiffness appears to decrease with the progression of atherosclerosis after the 8-week period. ### Final_Prediction: yes

### Question: Does response to mitotane predict outcome in patients with recurrent adrenal cortical carcinoma? ### Context: Adrenal cortical carcinoma (ACC) is a rare disease in which recurrence after surgery is common. Mitotane is the primary systemic treatment for recurrent ACC; data are limited regarding the impact of mitotane on recurrent ACC.We reviewed the records of all patients who underwent surgery for ACC evaluated at our institution from 1991 to 2006.The median disease-free survival for all 186 patients was 12 months and the median overall survival (OS) was 37 months. Higher stage at presentation (P = .002) and tumor cortisol production (P = .007) were associated with a worse OS. Mitotane was given to 67 evaluable patients with recurrent ACC. A response to mitotane was observed in 13 (19%) of the 67 patients. For patients with stable or responding disease to mitotane, the median OS from date of recurrence was 18 months, compared with 9 months (P = .01) for those who progressed. ### Long_Answer: Patients with recurrent ACC who have stable or responding disease to mitotane have a more favorable prognosis than those who progress. Mitotane should be considered in most patients with recurrent ACC, including as preoperative therapy for those with recurrent disease considered for surgical resection. ### Final_Prediction: yes

### Question: Is definition of medical event to be based on the total source strength for evaluation of permanent prostate brachytherapy : A report from the American Society for Radiation Oncology? ### Context: The Nuclear Regulatory Commission deems it to be a medical event (ME) if the total dose delivered differs from the prescribed dose by 20% or more. A dose-based definition of ME is not appropriate for permanent prostate brachytherapy as it generates too many spurious MEs and thereby creates unnecessary apprehension in patients, and ties up regulatory bodies and the licensees in unnecessary and burdensome investigations. A more suitable definition of ME is required for permanent prostate brachytherapy.The American Society for Radiation Oncology (ASTRO) formed a working group of experienced clinicians to review the literature, assess the validity of current regulations, and make specific recommendations about the definition of an ME in permanent prostate brachytherapy.The working group found that the current definition of ME in §35.3045 as "the total dose delivered differs from the prescribed dose by 20 percent or more" was not suitable for permanent prostate brachytherapy since the prostate volume (and hence the resultant calculated prostate dose) is dependent on the timing of the imaging, the imaging modality used, the observer variability in prostate contouring, the planning margins used, inadequacies of brachytherapy treatment planning systems to calculate tissue doses, and seed migration within and outside the prostate. If a dose-based definition for permanent implants is applied strictly, many properly executed implants would be improperly classified as an ME leading to a detrimental effect on brachytherapy. The working group found that a source strength-based criterion, of >20% of source strength prescribed in the post-procedure written directive being implanted outside the planning target volume is more appropriate for defining ME in permanent prostate brachytherapy. ### Long_Answer: ASTRO recommends that the definition of ME for permanent prostate brachytherapy should not be dose based but should be based upon the source strength (air-kerma strength) administered. ### Final_Prediction: yes

### Question: Does apolipoprotein E modulate establishment of HSV-1 latency and survival in a mouse ocular model? ### Context: To evaluate and compare the neuroinvasiveness and neurovirulence after ocular HSV-1 infection in ApoE knockout (ApoE-/-) and control C57BL/6 (ApoE+/+) mice.Age-matched (14 weeks of age) C57BL/6J (ApoE+/+) female mice and female ApoE knockout (ApoE-/-) mice were inoculated by corneal scarification with HSV-1 strain 17Syn+. Analysis of HSV-1 replication in the mouse cornea was assessed through infectious virus assays of ocular (tear film) swabs at 1 to 5 days postinoculation (PI), slit-lamp examination (SLE) of corneas at PI days 1 to 7, and survival of infected mice. The contribution of apoE to the efficient establishment of latency was measured by real-time PCR quantitation of the latent viral genome in the trigeminal ganglia (TG) of infected mice.These studies showed that HSV-1 strain 17Syn+ replicates efficiently in the eyes, regardless of the host ApoE genotype. Neither the scoring of corneal pathology via SLE nor the infectious virus assay of the tear film resulted in any statistical differences between ApoE knockout (-/-) mice or the C57BL/6 (ApoE+/+) mice. In mice latently infected with HSV-1, our real-time PCR data showed significantly lower viral copy numbers of HSV-1 DNA in ApoE knockout (ApoE-/-) mice compared with C57BL/6 (ApoE+/+) mice. C57BL/6 (ApoE+/+) mice are more susceptible to the neurovirulence of HSV-1 strain 17Syn+ than female ApoE knockout (-/-) mice, as demonstrated by the fact that 50% (7/14) of the female C57BL/6 (ApoE+/+) mice inoculated with 17Syn+ died, as opposed to none (0/14) of the age- and sex-matched ApoE knockout mice. ### Long_Answer: These data indicate that age (14 weeks) and sex-matched (female) wild mice with an ApoE null background (ApoE-/-) are more resistant and less efficient in the establishment of latency compared with ApoE+/+ mice in the C57BL/6 background. ### Final_Prediction: yes

### Question: Does etanercept reduce neuroinflammation and lethality in mouse model of Japanese encephalitis? ### Context: Japanese encephalitis virus (JEV) is a neurotropic flavivirus that causes Japanese encephalitis (JE), which leads to high fatality rates in human. Tumor necrosis factor alpha (TNF-α) is a key factor that mediates immunopathology in the central nervous system (CNS) during JE. Etanercept is a safe anti-TNF-α drug that has been commonly used in the treatment of various human autoimmune diseases.The effect of etanercept on JE was investigated with a JEV-infected mouse model. Four groups of mice were assigned to receive injections of phosphate-buffered saline, etanercept, JEV, or JEV plus etanercept. Inflammatory responses in mouse brains and mortality of mice were evaluated within 23 days post infection.The in vitro assay with mouse neuron/glia cultures showed that etanercept treatment reduced the inflammatory response induced by JEV infection. In vivo experiments further demonstrated that administration of etanercept protected mice from JEV-induced lethality. Neuronal damage, glial activation, and secretion of proinflammatory cytokines were found to be markedly decreased in JEV-infected mice that received etanercept treatment. Additionally, etanercept treatment restored the integrity of the blood-brain barrier and reduced viral load in mouse brains. ### Long_Answer: Etanercept effectively reduces the inflammation and provides protection against acute encephalitis in a JEV-infected mouse model. ### Final_Prediction: yes

### Question: Are the conventional cutoff values adequate to define hypertension in young women? ### Context: Women have lower systolic blood pressure (SBP) levels than men during early adulthood. Diastolic blood pressure (DBP) tends to be just marginally lower in women than men regardless of age.Aims of this study were (i) to determine 95th percentile value of SBP, DBP, and mean arterial blood pressure in healthy women, and (ii) to evaluate the effects of basal demographic and anthropometric features on blood pressure.Six hundred and fifty-four consecutive participants (18-35 years old) were initially enrolled in the study but among them 54 (8.2%) cases were excluded. Demographic features, relevant personal and family history data about hypertension, smoking habits, and use of medications were interviewed using a questionnaire. Blood pressure, height, weight, and waist circumference of every case were measured.Of the 600 patients (mean age, 24.6±4.0 years), 124 (20.7%) were currently smokers, 20 (3.3%) had history of hypertension during pregnancy, and 291 (48.5%) had family history of hypertension in women (mean age, 61.0±9.51 years). Reference ranges of 5th and 95th percentile values for SBP were determined as 74 and 115 mmHg, for mean arterial blood pressure as 57 and 85 mmHg, for DBP as 45 and 72 mmHg, respectively. ### Long_Answer: In conclusion, cutoff values of hypertension in healthy women, which were determined by our study, are lower than the standard cutoff values for definition of hypertension in adults. However, clinical importance of these findings should be investigated in further studies involving larger population with prospective follow-up. ### Final_Prediction: nan

### Question: Do high and low schizotypal female subjects differ in spatial memory abilities in a virtual reality task? ### Context: Schizotypy is a psychological construct related to schizophrenia. The exact relationship between both entities is not clear. In recent years, schizophrenia has been associated with hippocampal abnormalities and spatial memory problems. The aim of this study was to determine possible links between high schizotypy (HS) and low schizotypy (LS) and spatial abilities, using virtual reality tasks. We hypothesised that the HS group would exhibit a lower performance in spatial memory tasks than the LS group.Two groups of female students were formed according to their score on the ESQUIZO-Q-A questionnaire. HS and LS subjects were tested on two different tasks: the Boxes Room task, a spatial memory task sensitive to hippocampal alterations and a spatial recognition task.Data showed that both groups mastered both tasks. Groups differed in personality features but not in spatial performance. These results provide valuable information about the schizotypy-schizophrenia connections. ### Long_Answer: Schizotypal subjects are not impaired on spatial cognition and, accordingly, the schizotypy-schizophrenia relationship is not straightforward. ### Final_Prediction: no

### Question: Is exposure to media intended for preschool children associated with less parent-child shared reading aloud and teaching activities? ### Context: To determine whether electronic media exposure is associated with decreased parental reading and teaching activities in the homes of preschool children.A convenience sample presenting for well-child care to an urban hospital pediatric clinic was enrolled. Inclusion criteria were: child's age 3 to 5 years and not yet in kindergarten. Electronic media exposure (TV, movies/video, computer/video games) was assessed with a 24-hour recall diary and characterized on the basis of industry ratings. Reading aloud and teaching activities were assessed with the StimQ-Preschool READ and PIDA (Parental Involvement in Developmental Advance) subscales, respectively.A total of 77 families were assessed. Children were exposed to a mean (SD) of 200.8 (128.9) minutes per day of media, including 78.2 (63.7) minutes of educational young child-oriented, 62.0 (65.6) minutes of noneducational young child-oriented, 14.8 (41.4) minutes of school age/teen-oriented, and 29.2 (56.6) minutes of adult-oriented media, as well as to 16.6 (47.5) minutes of media of unknown type. A total of 79.2% watched 2 or more hours per day. Noneducational young child-oriented exposure was associated with fewer reading (semipartial correlation coefficient [SR] = -0.24, P = .02) and teaching (SR = -0.27, P = .01) activities; similar relationships were not found for other media categories. Children exposed to 2 or more hours of total electronic media per day had 1.6 (95% confidence interval, 0.4-2.9) fewer days per week of reading than children exposed to less than 2 hours (SR = -0.27, P = .01). ### Long_Answer: This study found an association between increased exposure to noneducational young child-oriented media and decreased teaching and reading activities in the home. This association represents a mechanism by which media exposure could adversely affect development. ### Final_Prediction: nan

### Question: Does anal vector volume analysis complement endoanal ultrasonographic assessment of postpartum anal sphincter injury? ### Context: The aim of this study was to determine the role of anal vector manometry in the assessment of postpartum anal sphincter injury and to establish the most suitable method of anal vector volume analysis for identifying significant external anal sphincter (EAS) injury in an at-risk parous population.A total of 101 consecutive women with a history of instrumental or traumatic vaginal delivery was recruited. Anal ultrasonography and anal vector manometry were performed. Receiver-operator characteristic curves were used to determine the usefulness of anal manometry and anal vector volume analysis in the identification of significant EAS disruption (full thickness, more than one quadrant involved) detected by ultrasonography.Seventeen women had significant EAS disruption identified by anal ultrasonography. Anal vector manometry provided complementary functional information. Anal vector symmetry index (VSI), determined by analysis of mean maximum squeeze pressure, yielded 100 per cent sensitivity for significant EAS disruption, with a positive predictive value of 61 per cent. ### Long_Answer: Anal vector manometry complements endoanal ultrasonography. VSI, determined by means of the squeeze pressure profile, correlates best with significant EAS disruption identified at anal ultrasonography. ### Final_Prediction: yes

### Question: Does aT1 receptor blockade regulate the local angiotensin II system in cerebral microvessels from spontaneously hypertensive rats? ### Context: Blockade of angiotensin II AT1 receptors in cerebral microvessels protects against brain ischemia and inflammation. In this study, we tried to clarify the presence and regulation of the local renin-angiotensin system (RAS) in brain microvessels in hypertension.Spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) controls were treated with an AT1 receptor antagonist (candesartan, 0.3 mg/kg per day) via subcutaneous osmotic minipumps for 4 weeks. The expression and localization of RAS components and the effect of AT1 receptor blockade were assessed by Affymetrix microarray, qRT-PCR, Western blots, immunohistochemistry and immunofluorescence.We found transcripts of most of RAS components in our microarray database, and confirmed their expression by qRT-PCR. Angiotensinogen (Aogen), angiotensin-converting enzyme (ACE) and AT1 receptors were localized to the endothelium. There was no evidence of AT2 receptor localization in the microvascular endothelium. In SHR, (pro)renin receptor mRNA and AT1 receptor mRNA and protein expression were higher, whereas Aogen, ACE mRNA and AT2 receptor mRNA and protein expression were lower than in WKY rats. Candesartan treatment increased Aogen, ACE and AT2 receptor in SHR, and increased ACE and decreased Aogen in WKY rats, without affecting the (pro)renin and AT1 receptors. ### Long_Answer: Increased (pro)renin and AT1 receptor expression in SHR substantiates the importance of the local RAS overdrive in the cerebrovascular pathophysiology in hypertension. AT1 receptor blockade and increased AT2 receptor stimulation after administration of candesartan may contribute to the protection against brain ischemia and inflammation. ### Final_Prediction: yes

### Question: Does pentoxifylline inhibit WNT Signalling in β-Cateninhigh Patient-Derived Melanoma Cell Populations? ### Context: The heterogeneity of melanoma needs to be addressed and combination therapies seem to be necessary to overcome intrinsic and acquired resistance to newly developed immunotherapies and targeted therapies. Although the role of WNT/β-catenin pathway in melanoma was early demonstrated, its contribution to the lack of the melanoma patient response to treatment was only recently recognized. Using patient-derived melanoma cell populations, we investigated the influence of pentoxifylline on melanoma cells with either high or low expression of β-catenin.Our results indicate that pentoxifylline inhibits the activity of the canonical WNT pathway in melanoma cell populations with high basal activity of this signalling. This is supported by lowered overall activity of transcription factors TCF/LEF and reduced nuclear localisation of active β-catenin. Moreover, treatment of β-cateninhigh melanoma cell populations with pentoxifylline induces downregulation of genes that are targets of the WNT/β-catenin pathway including connective tissue growth factor (CTGF) and microphthalmia-associated transcription factor (MITF-M), a melanocyte- and melanoma cell-specific regulator. ### Long_Answer: These results suggest that pentoxifylline, a drug approved by the FDA in the treatment of peripheral arterial disease, might be tested in a subset of melanoma patients with elevated activity of β-catenin. This pharmaceutical might be tested as an adjuvant drug in combination therapies when the response to immunotherapy is prevented by high activity of the WNT/β-catenin pathway. ### Final_Prediction: yes

### Question: Does hepatic Encephalopathy be Associated With Mortality in Patients With Cirrhosis Independent of Other Extrahepatic Organ Failures? ### Context: Although survival times have increased for patients with cirrhosis, hepatic encephalopathy (HE) remains a major complication and its relative contribution toward mortality in North America is unclear. We investigated whether HE is associated with mortality independent of extrahepatic organ failures (EHOFs).We collected data from the North American Consortium for Study of End-stage Liver Disease database of hospitalized patients with cirrhosis at tertiary-care centers. EHOFs were defined as need for ventilation (respiratory failure), dialysis (renal failure), or shock (circulatory failure). We analyzed in-hospital and 30-day mortality for patients with varying HE grades and EHOF using adjusted models.We analyzed data from 1560 patients, 516 with HE (371 grade 1-2 and 145 grade 3-4). Patients with maximum HE grade 3-4 HE during hospitalization had a higher median model for end-stage liver disease (MELD) score (22) than patients with HE grade 1-2 (MELD score, 19) or no HE (MELD score, 18) (P < .0001). Thirty-day mortality for patients with HE grade 3-4 was significantly higher (38%) than for patients with HE grade 1-2 (8%) or no HE (7%). A total of 107 patients had 2 or more EHOFs, with or without HE; 151 had 1 EHOF and 1302 had no organ failure. Unadjusted mortality was highest for patients with HE of grade 3-4 with 2 EHOFs (n = 44). On regression analysis, HE severity was significantly associated with in-hospital and 30-day mortality, independent of any EHOF, white blood cell count, systemic inflammatory response syndrome, or MELD score (odds ratio, 3.3; P < .0001). ### Long_Answer: In an analysis of more than 1500 patients hospitalized for cirrhosis, HE of grade 3 or 4 was associated with higher in-hospital and 30-day mortality, independently of failure of other organs. ### Final_Prediction: yes

### Question: Does lentivirus-delivered ZEB-1 small interfering RNA inhibit lung adenocarcinoma cell growth in vitro and in vivo? ### Context: To explore the relationship between the expression of ZEB1 gene and the proliferation ability of lung adenocarcinoma cells.Immunohistochemistry, Western blot and Real-time PCR were used to detect the expression of ZEB1 gene in lung adenocarcinoma tissue and cell lines compared with adjacent noncancerous region and the human lung fibroblast cell HLF cells. The lentivirus RNA interference technique was used to knock down the expression of ZEB1 in lung adenocarcinoma A549 and H1299 cell lines. Cell cycle and cell apoptosis were measured by FCM assay. In vivo, four groups of 4-week-old nude mice were subcutaneously injected with the stably transfected (ZEB-si, scr-si) cells at a single site to investigate the effect of ZEB1-siRNA in the nude mice tumor growth. In situ apoptosis was detection by TUNEL assay.ZEB-1 was highly expressed in lung adenocarcinoma tissue and cell lines compared with adjacent noncancerous region and the human lung fibroblast cell HLF cells. ZEB1-siRNA could decrease lung adenocarcinoma cell proliferation by delaying S-phase entry and induce cell apoptosis, which led to the inhibition of the tumorigenicity of A549 and H1299 cell lines. Further investigation showed that injecting the ZEB1-siRNA cells into the nude mice could significantly decrease the tumor growth. ### Long_Answer: Knockdown of ZEB-1 expression by lentivirus-delivered siRNA may provide a novel therapeutic target for the treatment of lung cancer. ### Final_Prediction: yes

### Question: Does ambulatory monitoring predict development of drug-treated hypertension in subjects with high normal blood pressure? ### Context: High normal blood pressure (HNBP), i.e. blood pressure (BP) > or = 130/85 mmHg and <140/90 mmHg, is an important predictor of progression to established hypertension.The purpose of this retrospective study was the evaluation of the predictive value of ambulatory blood pressure monitoring (ABPM) for the development of drug-treated hypertension in subjects with HNBP and other risk factors.We studied 127 subjects (69 M, 58 F, age 50 +/- 14 years): 59 subjects had normal BP (NBP: < 130/85 mmHg), 68 subjects had systolic and/or diastolic HNBP. All the subjects underwent ABPM. There were 21/68 (30.9%) subjects in the HNBP group vs. 1/59 (1.7%) in the NBP group with an elevated (>135/85 mmHg) daytime ambulatory blood pressure (ABP) (p < 0.01).After an average follow-up of 103 +/- 28 months, 27 subjects (39.7%) in the HNBP group and 4 subjects (6.8%) in the NBP group developed drug-treated hypertension (p < 0.01). An elevated daytime ABP correctly predicted development of drug-treated hypertension in 17/21 subjects (81%) of the HNBP group and in the only subject of the NBP group. Development of drug-treated hypertension was associated with higher office and ambulatory BP (p < 0.01) and pulse pressures (p < 0.05), longer follow-up (p < 0.05) and higher prevalence of hypercholesterolaemia and smoking (p < 0.01). ### Long_Answer: We conclude that ABPM correctly predicts development of drug-treated hypertension in most subjects who were identified early as having a daytime mean ABP >135/85 mmHg. ABPM appears to be a useful clinical tool in the early diagnosis of hypertension in subjects with metabolic risk factors and smoking. ### Final_Prediction: yes

### Question: Does operant self-administration of a sigma ligand improve nociceptive and emotional manifestations of neuropathic pain? ### Context: The treatment of neuropathic pain is unsatisfactory at the present moment and the sigma 1 receptor has been identified as a new potential target for neuropathic pain. The aim of this study was to use an operant self-administration model to reveal the potential interest of a new sigma 1 receptor antagonist, S1RA, in chronic pain that was developed in mice by a partial ligation of the sciatic nerve.Once that chronic pain had reached a steady state, mice were trained to maintain an operant behaviour to self-administer S1RA. The possible abuse liability of the analgesic compound was determined by evaluating operant self-administration in sham-operated mice. The influence of S1RA on the anhedonic state related to chronic pain was also evaluated by measuring the preference for palatable drink (2% sucrose solution) using a recently validated and highly sensitive behavioural device.Nerve-injured mice, but not sham-operated animals, acquired the operant responding to obtain S1RA (6 mg/kg/infusion). After 10 days of S1RA self-administration, neuropathic pain was significantly reduced in nerve-injured mice. In addition, an anhedonic state was revealed in nerve-injured mice by a decreased consumption of palatable drink, which was significantly attenuated by S1RA (25 mg/kg). ### Long_Answer: These results reveal the analgesic efficacy of the sigma antagonist, S1RA, in neuropathic pain associated with an improvement of the emotional negative state and that was devoided of reinforcing effects. The operant responses evaluated in this new mouse model can have a high predictive value to estimate the clinical benefit/risk ratio of new analgesic compounds to treat chronic pain, such as S1RA. ### Final_Prediction: yes

### Question: Is dual HER2 inhibition in combination with anti-VEGF treatment active in heavily pretreated HER2-positive breast cancer? ### Context: Preclinical data indicate that dual HER2 inhibition overcomes trastuzumab resistance and that use of an HER2 inhibitor with an anti-angiogenic agent may augment responses.We conducted a dose-escalation, phase I study of a combination of trastuzumab, lapatinib and bevacizumab. The subset of patients with metastatic breast cancer was analyzed for safety and response.Twenty-six patients with metastatic breast cancer (median = 7 prior systemic therapies) (all with prior trastuzumab; 23 with prior lapatinib; one with prior bevacizumab) received treatment on a range of dose levels. The most common treatment-related grade 2 or higher toxicities were diarrhea (n = 11, 42%) and skin rash (n = 2, 8%). The recommended phase 2 dose was determined to be the full Food and Drug Administration (FDA) approved doses for all the three agents (trastuzumab 8 mg/kg loading dose, 6 mg/kg maintenance dose, intravenously every 3 weeks; lapatinib 1250 mg daily, bevacizumab 15 mg/kg intravenously every 3 weeks). The overall rate of stable disease (SD) ≥6 months and partial or complete remission (PR/CR) was 50% (five patients with SD ≥6 months; seven PRs (including one unconfirmed); one CR). The rate of SD ≥6 months/PR/CR was not compromised in patients who had previously received study drugs, those with brain metastases, and patients treated at lower dose levels. ### Long_Answer: The combination of trastuzumab, lapatinib and bevacizumab was well-tolerated at maximally approved doses of each drug, and its activity in heavily pretreated patients with metastatic breast cancer suggests that it warrants further investigation. ### Final_Prediction: yes

### Question: Does surgery result in exaggerated and persistent cognitive decline in a rat model of the Metabolic Syndrome? ### Context: Postoperative cognitive decline can be reproduced in animal models. In a well-validated rat model of the Metabolic Syndrome, we sought to investigate whether surgery induced a more severe and persistent form of cognitive decline similar to that noted in preliminary clinical studies.In rats that had been selectively bred for low and high exercise endurance, the low capacity runners (LCR) exhibited features of Metabolic Syndrome (obesity, dyslipidemia, insulin resistance, and hypertension). Tibial fracture surgery was performed under isoflurane anesthesia in LCR and high capacity runner (HCR) rats and cognitive function was assessed postoperatively in a trace-fear conditioning paradigm and Morris Water Maze; non-operated rats were exposed to anesthesia and analgesia (sham). Group sizes were n = 6.On postoperative D7, LCR rats had shorter freezing times than postoperative HCR rats. Five months postoperatively, LCR rats had a flatter learning trajectory and took longer to locate the submerged platform than postoperative HCR rats; dwell-time in the target quadrant in a probe trial was shorter in the postoperative LCR compared to HCR rats. LCR and HCR sham rats did not differ in any test. ### Long_Answer: Postoperatively, LCR rats diverged from HCR rats exhibiting a greater decline in memory, acutely, with persistent learning and memory decline, remotely; this could not be attributed to changes in locomotor or swimming performance. This Metabolic Syndrome animal model of surgery-induced cognitive decline corroborates, with high fidelity, preliminary findings of postoperative cognitive dysfunction in Metabolic Syndrome patients. ### Final_Prediction: yes

### Question: Does periadventitial fat-derived nitric oxide play a role in improved saphenous vein graft patency in patients undergoing coronary artery bypass surgery? ### Context: The saphenous vein is commonly used for coronary artery bypass surgery but its patency is poor. Vascular damage occurs during conventional surgery. However, patency improves when the graft is harvested with minimal surgical trauma, partly due to preservation of vascular endothelial nitric oxide synthase (eNOS) and tissue sources of nitric oxide (NO), a factor possessing both dilatory and anti-proliferative properties. Apart from these grafts exhibiting an intact luminal endothelium they are harvested complete with a surrounding cushion of tissue, much of which is fat.Immunostaining for eNOS was performed on vein graft sections and reverse-transcriptase polymerase chain reaction and Western blotting were used to identify eNOS mRNA and protein. NO synthase activity was measured using the citrulline assay.Immunohistochemistry identified eNOS staining of vein graft segments, including dense staining of the cushion of perivascular fat and associated structures surrounding the vein. eNOS protein was confirmed in both the vein and surrounding fat by Western blot analysis. Using the citrulline assay, the perivascular fat and underlying vein possessed comparable NO synthase activity. ### Long_Answer: Our observations suggest that perivascular fat-derived NO plays a beneficial role in saphenous veins harvested atraumatically and used as grafts in patients undergoing coronary artery bypass surgery. ### Final_Prediction: nan

### Question: Is nutritional status associated with health-related quality of life in children with cystic fibrosis aged 9-19 years? ### Context: The impact of improved nutritional status on health-related quality of life (HRQOL) is unknown for children with cystic fibrosis (CF).Associations between nutritional status and HRQOL were examined over 2 years in 95 children, aged 9-19 years, who were followed in the Wisconsin Newborn Screening Project. HRQOL was assessed using the Cystic Fibrosis Questionnaire (CFQ). Associations between height z-score (HtZ), BMI z-score (BMIZ) and seven CFQ dimensions were evaluated.Mean values of at least 80 were observed for all CFQ dimensions except respiratory symptoms and treatment burden. Treatment burden was significantly worse in patients with meconium ileus (57) compared to pancreatic insufficient (65) and sufficient (78) subjects, p<0.0001. HtZ and BMIZ were positively associated with physical functioning and body image (p<0.05). ### Long_Answer: Better nutritional status was associated with increased HRQOL scores. Early diagnosis through newborn screening and improved nutrition provides an opportunity to enhance quality of life and body image perception. ### Final_Prediction: yes

### Question: Is coracoacromial arch angle a predisposing factor for rotator cuff tears? ### Context: The aim of the present study was to investigate whether coracoacromial arch angle is a predisposing factor for rotator cuff tears.Shoulder magnetic resonance imaging (MRI) examinations of 40 patients having shoulder arthroscopy due to rotator cuff tears and 28 patients with normal MRI findings were evaluated retrospectively. Acromio-humeral distance, coraco-humeral distance, the angle between the longitudinal axis of the coracoacromial ligament and longitudinal axis of the acromion (coracoacromial arch angle), and thickness of the coracoacromial ligament were measured.In patients with rotator cuff pathology the mean coraco-humeral distance was 7.88±2.37 mm, the mean acromio-humeral distance was 7.89±2.09 mm, and the mean coracoacromial arch angle was 132.38°±6.52° compared to 11.67±1.86 mm, 11.15±1.84 mm, and 116.95°±7.66° in the control group, respectively (P<0.001, for all). In regression analysis, all three parameters were found to be significant predictors of rotator cuff tears. The mean thickness of the coracoacromial ligament was not significantly different between the patient and control groups (0.95±0.30 mm vs. 1.00±0.33 mm, P>0.05). ### Long_Answer: Acromio-humeral and coraco-humeral distances are narrower than normal limits in patients with rotator cuff tears. In addition, coracoacromial arch angle may be a predisposing factor for rotator cuff tears. ### Final_Prediction: nan

### Question: Is the long-term behavior of lightweight and heavyweight meshes used to repair abdominal wall defects determined by the host tissue repair process provoked by the mesh? ### Context: Although heavyweight (HW) or lightweight (LW) polypropylene (PP) meshes are widely used for hernia repair, other alternatives have recently appeared. They have the same large-pore structure yet are composed of polytetrafluoroethylene (PTFE). This study compares the long-term (3 and 6 months) behavior of meshes of different pore size (HW compared with LW) and composition (PP compared with PTFE).Partial defects were created in the lateral wall of the abdomen in New Zealand White rabbits and then repaired by the use of a HW or LW PP mesh or a new monofilament, large-pore PTFE mesh (Infinit). At 90 and 180 days after implantation, tissue incorporation, gene and protein expression of neocollagens (reverse transcription-polymerase chain reaction/immunofluorescence), macrophage response (immunohistochemistry), and biomechanical strength were determined. Shrinkage was measured at 90 days.All three meshes induced good host tissue ingrowth, yet the macrophage response was significantly greater in the PTFE implants (P < .05). Collagen 1/3 mRNA levels failed to vary at 90 days yet in the longer term, the LW meshes showed the reduced genetic expression of both collagens (P < .05) accompanied by increased neocollagen deposition, indicating more efficient mRNA translation. After 90-180 days of implant, tensile strengths and elastic modulus values were similar for all 3 implants (P > .05). ### Long_Answer: Host collagen deposition is mesh pore size dependent whereas the macrophage response induced is composition dependent with a greater response shown by PTFE. In the long term, macroporous meshes show comparable biomechanical behavior regardless of their pore size or composition. ### Final_Prediction: yes

### Question: Is atypical cortical drive during activation of the paretic and nonparetic tibialis anterior related to gait deficits in chronic stroke? ### Context: The role of cortical drive in stroke recovery for the lower extremity remains ambiguous. The purpose of this study was to investigate the relationship between cortical drive and gait speed in a group of stroke survivors.Eighteen individuals with stroke were dichotomized into fast or slow walking groups. Transcranial magnetic stimulation (TMS) was used to collect motor evoked potentials (MEPs) from the tibialis anterior of each lower extremity during rest, paretic muscle contractions, and nonparetic muscle contractions. An asymmetry-index (AI) was calculated using motor thresholds and compared between groups. The average MEP of the paretic leg during TMS at maximal intensity (MEP100) for each condition was compared within and between groups.A significant positive correlation was found between AI and walking speed. Slow-walkers had greater MEP100s during the nonparetic contraction than during the paretic contraction or rest conditions. In contrast, fast-walkers had greatest MEP100s during the paretic contraction. ### Long_Answer: Alterations in the balance of corticomotor excitability occur in the lower extremity of individuals with poor motor recovery post-stroke. This atypical cortical drive is dependent on activation of the unaffected hemisphere and contraction of the nonparetic leg. ### Final_Prediction: yes

### Question: Do manufacturer changes lead to clinically important differences between two editions of the TNO stereotest? ### Context: Stereoacuity tests used in clinical practice should be repeatable and reproducible. However, it has been observed in a clinical setting that new editions of the TNO stereotest appear to give different values from those obtained using previous versions. The purpose of the present research was to investigate this observation.One hundred and twenty-one Dutch subjects, 88 (73%) females and 33 (27%) males, with an average age of 34.0 years (range 18-55) had their stereoacuity measured using two different versions of the TNO stereoacuity test (TNO 13 and TNO 15). The TNO was tested in a counterbalanced order so that consecutive subjects started with alternate editions to avoid bias.There was a significant difference (p < 0.001) between the median value for stereoacuity measured with TNO 13 (30 s of arc) and TNO 15 (60 s of arc). The bias between the two test versions was -0.23 Log arcseconds (95% limits of the differences: 0.15 to -0.60 Log arcseconds). ### Long_Answer: This study reveals that results obtained with two different editions of a commonplace stereoacuity test are not comparable. New versions come on the market at regular intervals and the assumption that they will give the same results as previous versions may not be valid. Besides the statistically significant difference between the TNO 13 and TNO 15, the Bland-Altman plot also showed a considerable bias and the 95% limits of the differences between the TNO 13 and TNO 15 are more than two steps on the Log arcsecond scale. This difference between two editions of the TNO stereotests is not clinically acceptable and therefore it is inappropriate to use the two versions of the test interchangeably. It is important in both research and clinical records to specify the edition of the TNO test used. ### Final_Prediction: yes

### Question: Does retinoic acid have different effects on UCP1 expression in mouse and human adipocytes? ### Context: Increased adipose thermogenesis is being considered as a strategy aimed at preventing or reversing obesity. Thus, regulation of the uncoupling protein 1 (UCP1) gene in human adipocytes is of significant interest. Retinoic acid (RA), the carboxylic acid form of vitamin A, displays agonist activity toward several nuclear hormone receptors, including RA receptors (RARs) and peroxisome proliferator-activated receptor δ (PPARδ). Moreover, RA is a potent positive regulator of UCP1 expression in mouse adipocytes.The effects of all-trans RA (ATRA) on UCP1 gene expression in models of mouse and human adipocyte differentiation were investigated. ATRA induced UCP1 expression in all mouse white and brown adipocytes, but inhibited or had no effect on UCP1 expression in human adipocyte cell lines and primary human white adipocytes. Experiments with various RAR agonists and a RAR antagonist in mouse cells demonstrated that the stimulatory effect of ATRA on UCP1 gene expression was indeed mediated by RARs. Consistently, a PPARδ agonist was without effect. Moreover, the ATRA-mediated induction of UCP1 expression in mouse adipocytes was independent of PPARγ coactivator-1α. ### Long_Answer: UCP1 expression is differently affected by ATRA in mouse and human adipocytes. ATRA induces UCP1 expression in mouse adipocytes through activation of RARs, whereas expression of UCP1 in human adipocytes is not increased by exposure to ATRA. ### Final_Prediction: yes

### Question: Is serum microRNA-21 a novel biomarker in patients with esophageal squamous cell carcinoma? ### Context: It was recently revealed that microRNAs (miRNAs) can stably exist in serum and may affect the pathogenesis of several diseases. However, there are few reports that have demonstrated the significance of miRNAs in the serum of patients with esophageal squamous cell carcinoma (ESCC). Thus, the aims of this study were to clarify the status of miRNA-21 in serum of ESCC patients and to reveal the usefulness of this molecule as a biomarker.We measured the miRNA-21 levels in serum samples from 71 ESCC patients and 39 healthy controls by using real-time RT-PCR. We also evaluated the changes in the miRNA-21 level during operation and chemotherapy.We found that serum concentration of miRNA-21 in ESCC patients was significantly higher than that in healthy controls (P < 0.001). A significant reduction in the serum miR-21 levels was observed in the postoperative samples versus the preoperative samples (P = 0.003). Furthermore, miRNA-21 levels were significantly reduced in ESCC patients who responded to chemotherapy (P = 0.003), whereas no significant change was observed in the non-responders. ### Long_Answer: Serum miRNA-21 is considered to be a novel biomarker for diagnosing ESCC, and it can also be used as a response marker during chemotherapy for ESCC patients. ### Final_Prediction: yes

### Question: Can the cardiovascular family history reported by our patients be trusted? ### Context: Family history (FH) is used as a marker for inherited risk. Using FH for this purpose requires the FH to reflect true disease in the family. The aim was to analyse the concordance between young and middle-aged ischaemic stroke patients' reported FH of cardiovascular disease (CVD) with their parents' own reports.Ischaemic stroke patients aged 15-60 years and their eligible parents were interviewed using a standardized questionnaire. Information of own CVD and FH of CVD was registered. Concordance between patients and parents was tested by kappa statistics, sensitivity, specificity, predictive values and likelihood ratios. Regression analyses were performed to identify patient characteristics associated with non-concordance of replies.There was no difference in response rate between fathers and mothers (P = 0.355). Both parents responded in 57 cases. Concordance between patient and parent reports was good, with kappa values ranging from 0.57 to 0.7. The patient-reported FH yielded positive predictive values of 75% or above and negative predictive values of 90% or higher. The positive likelihood ratios (LR+) were 10 or higher and negative likelihood ratios (LR-) were generally 0.5 or lower. Interpretation regarding peripheral arterial disease was limited due to low parental prevalence. Higher age was associated with impaired concordance between patient and parent reports (odds ratio 1.05; 95% confidence interval 1.01-1.09; P = 0.020). ### Long_Answer: The FH provided by young and middle-aged stroke patients is in good concordance with parental reports. FH is an adequate proxy to assess inherited risk of CVD in young stroke patients. ### Final_Prediction: nan

### Question: Does zBTB33 bound unmethylated regions of the genome associated with actively expressed genes? ### Context: DNA methylation and repressive histone modifications cooperate to silence promoters. One mechanism by which regions of methylated DNA could acquire repressive histone modifications is via methyl DNA-binding transcription factors. The zinc finger protein ZBTB33 (also known as Kaiso) has been shown in vitro to bind preferentially to methylated DNA and to interact with the SMRT/NCoR histone deacetylase complexes. We have performed bioinformatic analyses of Kaiso ChIP-seq and DNA methylation datasets to test a model whereby binding of Kaiso to methylated CpGs leads to loss of acetylated histones at target promoters.Our results suggest that, contrary to expectations, Kaiso does not bind to methylated DNA in vivo but instead binds to highly active promoters that are marked with high levels of acetylated histones. In addition, our studies suggest that DNA methylation and nucleosome occupancy patterns restrict access of Kaiso to potential binding sites and influence cell type-specific binding. ### Long_Answer: We propose a new model for the genome-wide binding and function of Kaiso whereby Kaiso binds to unmethylated regulatory regions and contributes to the active state of target promoters. ### Final_Prediction: yes

### Question: Does endothelin-1 stimulate oral fibroblasts to promote oral cancer invasion? ### Context: The aims of this study were to examine the role of endothelin-1 (ET-1), a pleiotropic peptide found at elevated levels in a number of malignancies and which has been shown to influence oral cancer cell behaviour via paracrine signalling pathways, on the phenotype of oral fibroblasts.The effect of ET-1 on proliferation and migration of human primary oral fibroblasts was assessed using MTS and scratch assays, respectively. The ability of ET-1 to affect fibroblast contractility was analysed using type-I collagen gels. Changes in gene expression in oral fibroblasts exposed to ET-1 were examined using quantitative PCR. The invasiveness of oral cancer cells in the presence of conditioned media collected from ET-1 treated fibroblasts was determined using 2D Matrigel assays.Here we provide evidence that ET-1 increases the migration of oral fibroblasts and induces a more contractile phenotype which is not associated with changes in gene expression indicative of myofibroblast transdifferentiation. In addition we provide evidence that conditioned medium of ET-1-stimulated oral fibroblasts promotes invasion of OSCC cells in vitro. ### Long_Answer: In oral squamous cell carcinoma, a frequently fatal and increasingly common epithelial malignancy of the oral cavity, ET-1 is known to contribute to pro-migratory paracrine signalling between stromal fibroblasts and cancer cells. The ability of ET-1 to modulate the phenotype of human oral stromal fibroblasts, however, has not previously been reported. The findings presented here suggest that targeting the stromal endothelin system may be a viable and novel therapeutic strategy for invasive oral cancer. ### Final_Prediction: yes

### Question: Are surveillance CT scans a source of anxiety and fear of recurrence in long-term lymphoma survivors? ### Context: We aimed to assess anxiety and the psychological impact of routine surveillance scans in long-term survivors of adult aggressive lymphoma.In this cross-sectional observational study of 70 survivors of curable adult aggressive lymphoma, we measured anxiety and the doctor-patient relationship and performed a qualitative interview (n = 30) focused on patient perception of routine follow-up imaging studies.Participants were diagnosed with aggressive lymphoma a median of 4.9 years (2.4-38.0 years) before enrollment. Thirty-seven percent of patients were found to meet criteria for clinically significant anxiety, which was not associated with years since diagnosis. In multivariate analysis, history of relapse and a worse doctor-patient relationship were independently associated with higher anxiety levels. Despite representing a largely cured population, in qualitative interviews patients reported fear of recurrence as a major concern and considerable anxiety around the time of a follow-up imaging scan. ### Long_Answer: Routine surveillance scans exacerbate underlying anxiety symptoms and fear of recurrence in survivors of aggressive lymphoma. Strategies to minimize follow-up imaging and to improve doctor-patient communication should be prospectively evaluated to address these clinically significant issues. ### Final_Prediction: yes

### Question: Are serum interleukin-18 levels associated with physical activity in Japanese men? ### Context: To investigate the link between serum interleukin-18 (IL-18) levels and physical activity in Japanese men.A total of 81 men (45.7±17.6 years old) was enrolled in this cross-sectional investigation study. We assessed anthropometric and body composition parameters. Serum IL-18 levels, physical activity by uniaxial accelerometers, peak oxygen uptake and metabolic risk parameters were also evaluated.Serum IL-18 levels were 179.4±84.7 pg/mL. Physical activity evaluated by Σ[metabolic equivalents × h per week (METs⋅h/w)]was significantly and negatively correlated with serum IL-18 levels (r = -0.252, p = 0.0235). These associations remained even after adjusting for age, peak oxygen uptake and other confounding factors. ### Long_Answer: Serum IL-18 levels were closely associated with physical activity independent of peak oxygen uptake in Japanese men. ### Final_Prediction: yes

### Question: Does direct immunofluorescence testing result in cases of premalignant and malignant oral lesions? ### Context: Oral premalignant and malignant lesions may mimic oral lichen planus (OLP) clinically and microscopically. OLP often shows basement membrane fibrinogen positivity on direct immunofluorescence testing (DIF). This study examined fibrinogen positivity in oral premalignant lesions and squamous cell carcinoma.The University of Florida Oral Pathology Biopsy Service records were searched for the years 2003 to 2013 for oral premalignant lesions and squamous cell carcinoma with concurrent DIF testing. Demographic, clinical, and DIF or histologic information was collected and analyzed.Sixty-eight fibrinogen positive lesions were identified within a total of 164 cases. Low-grade dysplasia and premalignant verrucous lesions made up the majority of the fibrinogen positive lesions (combined n = 43; 63.2%), and the most common locations in positive cases were the buccal mucosa, tongue, and gingiva. A lichenoid distribution of the inflammatory infiltrate significantly predicted fibrinogen positivity (P < .0005). ### Long_Answer: Fibrinogen positivity may be seen in premalignant and malignant oral lesions increasing the risk of misdiagnosis. ### Final_Prediction: yes

### Question: Does severity of femoral trochlear dysplasia affect outcome in patellofemoral instability treated by medial patellofemoral ligament reconstruction and anterior tibial tuberosity transfer? ### Context: Medial patellofemoral ligament (MPFL) reconstruction associated to anterior tibial tuberosity transfer (ATTT) is recommended in objective patellofemoral instability (PFI). Efficacy, however, has not been precisely determined in trochlear dysplasia with spur. A case-control study was performed in a PFI population, comparing groups with trochlear dysplasia with and without spur (S+ vs. S-) to assess the impact of trochlear dysplasia on (1) patellofemoral stability, (2) functional results and complications, and (3) patellofemoral cartilage status on MRI.Trochlear spur does not affect outcome in PFI managed by MPFL reconstruction and ATTT.Twenty-eight knees (26 patients) with PFI were analyzed retrospectively and divided into 2 groups of 14 knees each according to presence of trochlear spur (S+ vs. S-). All 28 knees had undergone ATTT and MPFL reconstruction by semitendinosus autograft. Results were assessed on Lille and IKDC functional scores, and cartilage status was determined on MRI at last follow-up.At a mean 24 months' follow-up (range, 12-52 months), there was no recurrence of dislocation. IKDC and Lille scores tended to improve in both groups, although the only significant improvement was in IKDC score (S- gain, 21.3±16; S+ gain, 18.1±14) (P=0.01). IKDC scores at last follow-up were better in the S+ than S- group (79±19 [range, 21-92] vs. 68±13 [range, 35-84], respectively; P=0.012). Lille scores showed no significant inter-group differences in mean gain (P=0.492) or mean value (P=0.381). The S+ group showed more cartilage lesions (n=14/14 knees, including 12/14 with grade≥2 lesions) than the S- group (n=9/14 knees, all grade≤2). ### Long_Answer: MPFL reconstruction with ATTT provided good short-term patellofemoral stability independently of the severity of trochlear dysplasia. Functional results and gain on IKDC, however, were poorer in case of dysplasia with trochlear spur. This is probably due to cartilage lesions, observed more frequently pre- and post-operatively in the spur group, especially as there was no significant difference in Lille Score, which highlights stability. ### Final_Prediction: nan

### Question: Do gingival fibroblasts from periodontitis patients exhibit inflammatory characteristics in vitro? ### Context: Gingival fibroblasts (GFs) are an important regulatory cell type in the progression of periodontitis. This study aimed to compare the expression levels of genes associated with inflammation, extracellular matrix degradation and bone destruction in GFs isolated from healthy and periodontitis subjects in the absence and presence of Porphyromonas gingivalis.Primary GFs from healthy (n=10) and periodontitis subjects (n=10) were stimulated in vitro with viable P. gingivalis ATCC 49417 and 3 clinical isolates of P. gingivalis with type II fimbriae from one healthy subject (KUMC-H1) and two periodontitis patients (KUMC-P1, -P2). The mRNA expression of proinflammatory cytokines (interleukin (IL)-6, IL-8, IL-1B), anti-inflammatory cytokines (IL-4, IL-10), matrix metalloproteinase (MMP)-1 and 2, tissue inhibitor matrix metalloproteinase (TIMP)-3 and osteoprotegerin (OPG) were assessed using real-time PCR. The levels of IL-6, IL-1β and TIMP-3 protein were measured by an enzyme-linked immunosorbent assay.The mRNA expression of IL-6, IL-1B and TIMP-3 was higher in the periodontitis group compared with the healthy group, whereas IL-4 expression was higher in the healthy group both in the absence and presence of the P. gingivalis strains. The expression levels of IL-6, IL-1β and TIMP-3 protein were also higher in the periodontitis group in the absence and/or presence of the P. gingivalis strains. There was inter-strain variability among P. gingivalis strains in the ability to induce expression of the proinflammatory cytokines, MMPs and OPG and in the ability to degrade IL-6 protein. ### Long_Answer: High expression of proinflammatory cytokines and TIMP-3 and low expression of IL-4 can be a signature of GFs associated with periodontitis. ### Final_Prediction: yes

### Question: Does induction of microRNA-1 by myocardin in smooth muscle cells inhibit cell proliferation? ### Context: Myocardin is a cardiac- and smooth muscle-specific transcription co-factor that potently activates the expression of downstream target genes. Previously, we demonstrated that overexpression of myocardin inhibited the proliferation of smooth muscle cells (SMCs). Recently, myocardin was reported to induce the expression of microRNA-1 (miR-1) in cardiomyocytes. In this study, we investigated whether myocardin induces miR-1 expression to mediate its inhibitory effects on SMC proliferation.Using tetracycline-regulated expression (T-REx) inducible system expressing myocardin in human vascular SMCs, we found that overexpression of myocardin resulted in significant induction of miR-1 expression and inhibition of SMC proliferation, which was reversed by miR-1 inhibitors. Consistently, introduction of miR-1 into SMCs inhibited their proliferation. We isolated spindle-shaped and epithelioid human SMCs and demonstrated that spindle-shaped SMCs were more differentiated and less proliferative. Correspondingly, spindle-shaped SMCs had significantly higher expression levels of both myocardin and miR-1 than epithelioid SMCs. We identified Pim-1, a serine/threonine kinase, as a target gene for miR-1 in SMCs. Western blot and luciferase reporter assays further confirmed that miR-1 targeted Pim-1 directly. Furthermore, neointimal lesions of mouse carotid arteries displayed downregulation of myocardin and miR-1 with upregulation of Pim-1. ### Long_Answer: Our data demonstrate that miR-1 participates in myocardin-dependent of SMC proliferation inhibition. ### Final_Prediction: yes

### Question: Do cognitively impaired stroke patients do benefit from admission to an acute rehabilitation unit? ### Context: To determine whether cognitively impaired stroke patients benefit (defined as having an improved level of functional independence and capable of being discharged home) from admission to an acute rehabilitation unit.Retrospective analysis of data from a historical cohort of patients with acute stroke within the last 4 weeks or less.Acute stroke rehabilitation unit.The study sample was divided into 4 distinct groups based on admission Mini-Mental State Examination (MMSE) scores: cognitively intact (MMSE score range, > or =25 points), mild cognitive impairment (MMSE score range, 21-24), moderate cognitive impairment (MMSE score range, 10-20), and severe cognitive impairment (MMSE score range, < or =9 points).Not applicable.Primary outcome measures were: change in total FIM instrument score, cognitive FIM subscore, length of stay (LOS), FIM efficiency, and discharge disposition (home vs not-to-home).Based on the MMSE cut scores, there were 233 cognitively intact patients and 435 cognitively impaired (mild, n=139; moderate, n=165; severe, n=131) patients. The cognitively intact and the 3 cognitively impaired groups were similar in age, sex, and ethnicity. The data show that the 3 cognitively impaired groups of patients had delayed onset to acute rehabilitation admission and greater stroke severity and disability. The change in FIM total score and FIM efficiency was similar between the cognitively intact and the 3 cognitively impaired groups (P=.058). There were, however, statistically significant changes in the FIM cognitive subscore favoring the cognitively impaired groups (P<.001). Similarly, patients in the cognitively intact group had a shorter LOS (P<.001) and more home discharges (P<.001). ### Long_Answer: Our results suggest that despite severe neurologic impairment(s) and disability, cognitively impaired stroke patients make significant functional gains while undergoing rehabilitation and many can be discharged home. Based on these results, stroke patients with cognitive impairments benefit from rehabilitation and should be given the same access to acute rehabilitation services as stroke patients who are cognitively intact. ### Final_Prediction: yes

### Question: Is the activity profile in international Taekwondo competition modulated by weight category? ### Context: To examine the activity profiles of elite male competitors during international Taekwondo competition in relation to fin, feather, and heavy weight categories.Twelve male Taekwondo competitors equally representing fin, feather, and heavy weight divisions were studied during the 2005 World Taekwondo Championships using a time-motion system developed to analyze the activities and activity phases. The frequency and duration of activities were recorded and assimilated into four independent activity phases: fighting activity, preparatory activity, nonpreparatory activity and stoppage activity. The total number of exchanges and kicks were also calculated for each combat.For all weight groupings the mean ± SD fighting time was 1.7 ± 0.3 s, preparatory time 6.4 ± 2.1 s, nonpreparatory time 3.0 ± 0.6 s, referee stoppage time 2.8 ± 0.9 s and 28 ± 6 exchanges and 31 ± 7 kicks were performed. Differences in the mean fighting time (fin: 1.4 ± 0.2 s vs heavy: 1.8 ± 0.3 s; P = .03; effect size [ES] = 1.57), preparatory time (fin: 5.3 ± 1.0 s vs feather: 8.2 ± 2.6 s; P = .03; ES = 1.47) and the total number of exchanges (feather: 24 ± 6 vs heavy: 32 ± 5; P = .03; ES = 1.44) were identified between the weight categories. ### Long_Answer: The activity profile in international Taekwondo competition was modulated by competitors' weight category. These findings suggest that conditioning sessions may need to be specialized to the requirements of specific weight categories. ### Final_Prediction: yes

### Question: Does niacin result in reduced monocyte adhesion in patients with type 2 diabetes mellitus? ### Context: Patients with type 2 diabetes have increased expression of cell adhesion molecules (CAMs). CAMs and monocyte adhesion mediate essential processes in atherogenesis. It remains unclear if monocytes from patients on niacin have reduced adhesion function.We studied the variation of monocyte adhesion in patients with type 2 diabetes and low HDL-cholesterol, taking either extended release niacin (Niaspan®, Abbott Laboratories) or controls not on niacin. Biochemical parameters including adiponectin, CAMs and fresh monocytes from whole blood for adhesion assays, were studied at baseline and 12-weeks.Niacin 1500 mg daily raised HDL-cholesterol from 0.8 mmol/l (95% CI: 0.7-0.9) to 0.9 mmol/l (95% CI: 0.8-1.1), p=0.10, and significantly reduced PECAM-1 by 24.9% (95% CI: 10.9-39.0; p<0.05), increased adiponectin by 30.5% (95% CI: 14.1-47.0; p<0.05), with monocyte adhesion reduced by 9.2% (95%CI: 0.7-17.7; p<0.05) in endothelial cells treated in basal conditions, and 7.8% (95% CI: 3.1-12.5; p<0.05) after TNF-α stimulation. ### Long_Answer: Monocytes isolated from patients on niacin had reduced adhesion to endothelial cells. Our findings suggest niacin has broad range of effects apart from lipid-modification, and these could be important in cardiovascular risk reduction. ### Final_Prediction: yes

### Question: Does mild folate deficiency induce genetic and epigenetic instability and phenotype changes in prostate cancer cells? ### Context: Folate (vitamin B9) is essential for cellular proliferation as it is involved in the biosynthesis of deoxythymidine monophosphate (dTMP) and s-adenosylmethionine (AdoMet). The link between folate depletion and the genesis and progression of cancers of epithelial origin is of high clinical relevance, but still unclear. We recently demonstrated that sensitivity to low folate availability is affected by the rate of polyamine biosynthesis, which is prominent in prostate cells. We, therefore, hypothesized that prostate cells might be highly susceptible to genetic, epigenetic and phenotypic changes consequent to folate restriction.We studied the consequences of long-term, mild folate depletion in a model comprised of three syngenic cell lines derived from the transgenic adenoma of the mouse prostate (TRAMP) model, recapitulating different stages of prostate cancer; benign, transformed and metastatic. High-performance liquid chromatography analysis demonstrated that mild folate depletion (100 nM) sufficed to induce imbalance in both the nucleotide and AdoMet pools in all prostate cell lines. Random oligonucleotide-primed synthesis (ROPS) revealed a significant increase in uracil misincorporation and DNA single strand breaks, while spectral karyotype analysis (SKY) identified five novel chromosomal rearrangements in cells grown with mild folate depletion. Using global approaches, we identified an increase in CpG island and histone methylation upon folate depletion despite unchanged levels of total 5-methylcytosine, indicating a broad effect of folate depletion on epigenetic regulation. These genomic changes coincided with phenotype changes in the prostate cells including increased anchorage-independent growth and reduced sensitivity to folate depletion. ### Long_Answer: This study demonstrates that prostate cells are highly susceptible to genetic and epigenetic changes consequent to mild folate depletion as compared to cells grown with supraphysiological amounts of folate (2 microM) routinely used in tissue culture. In addition, we elucidate for the first time the contribution of these aspects to consequent phenotype changes in epithelial cells. These results provide a strong rationale for studying the effects of folate manipulation on the prostate in vivo, where cells might be more sensitive to changes in folate status resulting from folate supplementation or antifolate therapeutic approaches. ### Final_Prediction: yes

### Question: Is health-related quality of life associated with upper and lower airway inflammation in asthmatics? ### Context: Allergic diseases impair health-related quality of life (HR-QoL). However, the relationship between airway inflammation and HR-QoL in patients with asthma and rhinitis has not been fully investigated. We explored whether the inflammation of upper and lower airways is associated with HR-QoL.Twenty-two mild allergic asthmatics with concomitant rhinitis (10 males, 38 ± 17 years) were recruited. The Rhinasthma was used to identify HR-QoL, and the Asthma Control Test (ACT) was used to assess asthma control. Subjects underwent lung function and exhaled nitric oxide (eNO) test, collection of exhaled breath condensate (EBC), and nasal wash.The Rhinasthma Global Summary score (GS) was 25 ± 11. No relationships were found between GS and markers of nasal allergic inflammation (% eosinophils: r = 0.34, P = 0.24; ECP: r = 0.06, P = 0.87) or bronchial inflammation (pH of the EBC: r = 0.12, P = 0.44; bronchial NO: r = 0.27, P = 0.22; alveolar NO: r = 0.38, P = 0.10). The mean ACT score was 18. When subjects were divided into controlled (ACT ≥ 20) and uncontrolled (ACT<20), the alveolar NO significantly correlated with GS in uncontrolled asthmatics (r = 0.60, P = 0.04). ### Long_Answer: Upper and lower airways inflammation appears unrelated to HR-QoL associated with respiratory symptoms. These preliminary findings suggest that, in uncontrolled asthma, peripheral airway inflammation could be responsible for impaired HR-QoL. ### Final_Prediction: nan

### Question: Does the ANK3 bipolar disorder gene regulate psychiatric-related behaviors that are modulated by lithium and stress? ### Context: Ankyrin 3 (ANK3) has been strongly implicated as a risk gene for bipolar disorder (BD) by recent genome-wide association studies of patient populations. However, the genetic variants of ANK3 contributing to BD risk and their pathological function are unknown.To gain insight into the potential disease relevance of ANK3, we examined the function of mouse Ank3 in the regulation of psychiatric-related behaviors using genetic, neurobiological, pharmacological, and gene-environment interaction (G×E) approaches. Ank3 expression was reduced in mouse brain either by viral-mediated RNA interference or through disruption of brain-specific Ank3 in a heterozygous knockout mouse.RNA interference of Ank3 in hippocampus dentate gyrus induced a highly specific and consistent phenotype marked by decreased anxiety-related behaviors and increased activity during the light phase, which were attenuated by chronic treatment with the mood stabilizer lithium. Similar behavioral alterations of reduced anxiety and increased motivation for reward were also exhibited by Ank3+/- heterozygous mice compared with wild-type Ank3+/+ mice. Remarkably, the behavioral traits of Ank3+/- mice transitioned to depression-related features after chronic stress, a trigger of mood episodes in BD. Ank3+/- mice also exhibited elevated serum corticosterone, suggesting that reduced Ank3 expression is associated with elevated stress reactivity. ### Long_Answer: This study defines a new role for Ank3 in the regulation of psychiatric-related behaviors and stress reactivity that lends support for its involvement in BD and establishes a general framework for determining the disease relevance of genes implicated by patient genome-wide association studies. ### Final_Prediction: yes

### Question: Is homeobox C9 potentially related to congenital heart disease in Chinese patients? ### Context: Congenital heart disease (CHD) is one of the most common human birth defects. The etiology and pathogenesis of CHD are complex and involve several genes as well as multiple changes in signaling pathways. The aim of this study was to identify potential pathological mutations in the Homeobox C9 (Hoxc9) gene in 350 Chinese children with CHD to further understand the etiology of CHD.Sequence analysis of the Hoxc9 gene in 350 nonsyndromic patients with CHD Result: We did not identify any nonsynonymous variants in the coding regions of Hoxc9 in the patients with CHD. We found one synonymous variant c.C564T (p. his188his) in one ventricular septal defect patient. We also identified four previously reported polymorphisms (rs56368105, rs12817092, rs34079606, and rs2241820) in CHD. ### Long_Answer: We did not find any diagnostic alterations in the coding regions of Hoxc9 among the patients with CHD. Nevertheless, to our knowledge, this is the first study of Hoxc9 in nonsyndromic CHD and has expanded our overall knowledge of the etiology of this disease. ### Final_Prediction: no

### Question: Is it possible for "traditional" laparoscopic surgery to leave "invisible" scars? ### Context: Improved cosmesis is widely recognized as the main benefit of single-port laparoscopy (SPL). Recently, some centers have started to perform SPL in infants and neonates. However, in our experience, the cosmetic result following traditional laparoscopic surgery in this age range is excellent. This study assessed infants' postoperative scars following traditional laparoscopic surgery.Ten successive patients who previously underwent transperitoneal dismembered pyeloplasty were invited to attend for photographs of their abdominal wounds. All patients had had a 5-mm infra-umbilical port and two 3.5-mm ports (epigastrium and iliac fossa). Photographs were all taken in the hospital's medical photography studio by the same medical photographer. Life-size photographs were then shown to 10 junior doctors who were asked to identify any visible scars and rate the cosmetic result.Six patients with a median age at surgery of 8 months (range, 4-15 months) attended for photographs a median of 13 months postoperatively (range, 8-19 months). None of the junior doctors was able to identify all three scars on any photo. No individual scar was identifiable by all reviewers. No scars were identified in over half (31) of the total of 60 photograph reviews. Of 180 scar reviews, only 37 (21%) were identified. The umbilical scars were least noticeable (3/60), followed by iliac fossa scars (11/60) and epigastric scars (23/60). Where any scars were correctly identified, the cosmetic result was always rated good (44%) or excellent (56%). ### Long_Answer: Traditional laparoscopic surgery in infants can have an excellent cosmetic result with "invisible" scars. The cosmetic benefit and thus the role of SPL in infants are therefore questionable. ### Final_Prediction: nan

### Question: Do dietary treatments enriched in olive and safflower oils regulate seric and placental matrix metalloproteinases in maternal diabetes? ### Context: Matrix metalloproteinases (MMPs) are proteolytic enzymes involved in placental development and function, although related to the pro-inflammatory environment when produced in excess. Previous studies have identified MMP-2 and MMP-9 overactivities in the placenta from diabetic rats. In this study, we aimed to determine whether diets supplemented with olive and safflower oil, enriched in natural PPAR ligands, are able to regulate MMP-2 and MMP-9 activities in the placenta and serum from diabetic rats.Diabetes was induced in rat neonates by streptozotocin administration (90mg/kg s.c.). Control and diabetic rats were fed with 6% olive oil- or 6% safflower oil-supplemented diets from days 0.5-13.5 of gestation.On day 13.5 of gestation, placentas and sera were isolated for further determination of matrix metalloproteinases (MMPs) 2 and 9 activities by zymography. Placental MMP-2 and MMP-9 protein concentration and immunolocalization were also determined.Sera from diabetic pregnant animals showed MMP-2 and MMP-9 overactivities when compared to controls. Serum MMP-9 activity was significantly decreased when the diabetic animals received the olive and safflower oil dietary treatments. Placentas from diabetic rats showed increased MMP-2 and MMP-9 activities and protein concentrations, and both were decreased when diabetic rats received the olive and safflower dietary treatments. ### Long_Answer: This study demonstrates that both olive and safflower oil-supplemented diets were able to prevent MMPs overactivities in the placenta from diabetic rats, and that these beneficial effects are reflected in rat sera. ### Final_Prediction: yes

### Question: Does anti-VEGF antibody suppress primary tumor growth and metastasis in an experimental model of Wilms ' tumor? ### Context: Vascular endothelial growth factor (VEGF) has been shown previously to correlate with tumor growth and metastasis in an experimental model of anaplastic Wilms' tumor. The authors hypothesized that treatment with anti-VEGF antibodies would suppress both primary tumor growth and metastasis in this model.Tumors were induced in the right kidneys of nude mice by the injection of cultured Wilms' tumor cells. After 1 week, anti-VEGF treatment was begun with injection of either vehicle or an anti-VEGF antibody intraperitoneally. Mice were killed after 4.5 weeks of treatment and tumor weights and the incidence of metastases evaluated.Anti-VEGF treatment resulted in a greater than 95% reduction in tumor weight (P < .0001). Anti-VEGF treatment also abolished the establishment of lung metastases (40% in control animals, P < .003). Cessation of treatment resulted in rebound tumor growth. ### Long_Answer: Anti-VEGF therapy can suppress both primary tumor growth and the establishment of metastases in experimental anaplastic Wilms' tumor. ### Final_Prediction: yes

### Question: Fatigued elderly patients with chronic heart failure: do patient reports and nurse recordings correspond? ### Context: To compare descriptions of fatigue from interviews with elderly people with chronic congestive heart failure (CHF) and data recorded by nurses at an outpatient heart failure clinic.Patients (N = 158) were screened for moderate to severe CHF and interviewed using a revised form of the Fatigue Interview Schedule (FIS). Seventy-nine of these patients were offered visits at a nurse-monitored heart failure clinic. Nursing documentation of fatigue in patient records (n = 56) at the heart failure clinic was compared to the patient interviews.Results indicated poor concordance between patients' descriptions and record content concerning fatigue. Decreased libido was linked to fatigue according to the patients but not to the nurses' notes. Cognitive characteristics of fatigue were rarely recorded, but were more frequent in patient interviews. ### Long_Answer: Nurses must recognize characteristics and factors related to fatigue in patients and develop strategies to help patients cope with their restricted ability in daily life. ### Final_Prediction: nan

### Question: Do cervicovaginal fluid and semen block the microbicidal activity of hydrogen peroxide produced by vaginal lactobacilli? ### Context: H2O2 produced by vaginal lactobacilli is believed to protect against infection, and H2O2-producing lactobacilli inactivate pathogens in vitro in protein-free salt solution. However, cervicovaginal fluid (CVF) and semen have significant H2O2-blocking activity.We measured the H2O2 concentration of CVF and the H2O2-blocking activity of CVF and semen using fluorescence and in vitro bacterial-exposure experiments.The mean H2O2 measured in fully aerobic CVF was 23 +/- 5 microM; however, 50 microM H2O2 in salt solution showed no in vitro inactivation of HSV-2, Neisseria gonorrhoeae, Hemophilus ducreyii, or any of six BV-associated bacteria. CVF reduced 1 mM added H2O2 to an undetectable level, while semen reduced 10 mM added H2O2 to undetectable. Moreover, the addition of just 1% CVF supernatant abolished in vitro pathogen-inactivation by H2O2-producing lactobacilli. ### Long_Answer: Given the H2O2-blocking activity of CVF and semen, it is implausible that H2O2-production by vaginal lactobacilli is a significant mechanism of protection in vivo. ### Final_Prediction: yes

### Question: Increased anti-KIR4.1 antibodies in multiple sclerosis: could it be a marker of disease relapse? ### Context: Screening of putative autoimmune targets in multiple sclerosis (MS) revealed a proportion of patients carrying antibodies (Abs) against KIR4.1, a potassium channel that shares functional properties with AQP4. Both are localized at the perivascular astrocytic processes.To measure anti-KIR4.1 Abs in the serum of MS and neuromyelitis optica (NMO) patients, and to identify the clinical and laboratory characteristics of patients harboring anti-KIR4.1 Abs.We measured anti-KIR4.1 Abs in serum, using the peptide KIR4.1 (83-120) enzyme-linked immunosorbent assay (ELISA).Serum levels of anti-KIR4.1 Abs were significantly higher in MS and NMO patients than in healthy controls (HCs); with Abs detected in 21 of 80, 10 of 45, and 2 of 32 individuals, respectively (MS versus HC, p<0.05). The level of anti-KIR4.1 Abs was significantly higher during MS relapse, versus remission (p = 0.04). The clinical characteristics of our study patients did not vary based on KIR4.1 positivity. ### Long_Answer: Anti-KIR4.1 Abs were found in similar proportions of patients with MS and NMO, at a significantly higher level than observed in HCs; consequently, the presence of Abs does not discriminate between these demyelinating diseases. However, anti-KIR4.1 Ab levels differed in MS patients during relapse and remission; as such, they may represent a marker of disease exacerbation. ### Final_Prediction: nan

### Question: Are racial differences in vaginal pH explained by vaginal flora? ### Context: The study assessed racial differences in vaginal pH among women without bacterial vaginosis.Data from the Vaginal Infections and Prematurity (VIP) Study were analyzed. From 1984 to 1989, 13,917 largely low-income women were enrolled during routine prenatal visits from 23 to 26 weeks' gestation. Vaginal cultures, Gram stains, and pH levels were collected. Comparisons of pH by race were made among women with Gram stain scores<7 and without trichomoniasis before and after adjustment for actual Gram stain score.Among women with Gram stain scores<7, there was a modest but statistically significant racial difference in vaginal pH level. However, after controlling for difference in Gram stain score, age, and study site, there was no longer a significant difference in vaginal pH. ### Long_Answer: There is no significant difference in vaginal pH level between black and white women after controlling for differences in confounding factors, particularly vaginal flora. ### Final_Prediction: nan

### Question: Does the level of physical activity in university students influence development and progression of myopia? ### Context: To study whether physical activity has a protective effect on the development and progression of myopia in medical students.In a 2-year longitudinal cohort study, 156 Caucasian first-year medical students from the University of Copenhagen were enrolled. The baseline examination included visual acuity, subjective refraction, Maddox Wing test (Clement Clarke International Ltd., Harlow, UK), partial coherence interferometry, slit lamp examination, automated refraction in cycloplegia, an oral questionnaire, and a cycle ergometer test. Measurements were repeated at the follow-up. A total of 151 (97%) participants completed the study.The prevalence of myopia (spherical equivalent [SE]<or= -0.5 D) increased from 37% (95% confidence interval [CI]: 29.1-44.9) to 43% (95% CI: 34.6-50.8, P<0.001). The incidence rate of myopia was 6.1/100 person years of observation. The mean refractive error (SE) decreased from -0.50 (1.81) to -0.74 (1.95) D (P<0.001), and the mean axial length increased from 23.81 (1.06) to 23.94 (1.09) mm (P<0.001). In a multiple regression analysis, time spent reading scientific literature (P = 0.024) and younger age (P = 0.022) were associated with a refractive change toward myopia, whereas physical activity was inversely associated with a refractive change toward myopia (P = 0.015). Myopic eyes progressed significantly more than did emmetropic and hyperopic eyes (P = 0.002). ### Long_Answer: An association between physical activity and myopia was observed, suggesting a protective effect of physical activity on the development and progression of myopia in university students. The results confirm that intensive studying is a risk factor of myopia and that myopic progression or development is more likely in medical students in their early 20s than in their late 20s. ### Final_Prediction: nan

### Question: Are hNF1β and S100A1 useful biomarkers for distinguishing renal oncocytoma and chromophobe renal cell carcinoma in FNA and core needle biopsies? ### Context: Morphologic overlap between renal oncocytoma (RO) and chromophobe renal cell carcinoma (ChRCC) can pose diagnostic challenges, especially in biopsy samples in which tumor quantity may be limited, architectural features are not well represented, and gross examination is not possible. It has been demonstrated that immunohistochemistry (IHC) for HNF1α, HNF1β, and S100A1 are differentially expressed in RO and ChRCC in resection specimens. We evaluated the utility of these markers in FNA and core biopsies of RO and ChRCC.IHC for HNF1α, HNF1β, and S100A1 were performed on 61 RO specimens (36 FNA biopsies and 25 core biopsies) and on 14 ChRCC specimens (10 FNA biopsies and 4 core biopsies), and results were scored semiquantitatively for staining intensity (0-3: negative, weak, moderate, strong) and staining extent (0-4: 0%, 1-25%, 26-50%, 51-75%, 76-100%).Forty-four (44) of 60 (73%) RO displayed moderate-to-strong nuclear reactivity for HNF1β compared to 3 of 14 (21%) ChRCC (P < .001). Staining was present in >50% of tumor cells in 34 of 60 (57%) RO and in 2 of 14 (14%) ChRCC (P = .004). S100A1 was moderately-to-strongly positive in 45 of 56 (80%) RO and in 1 of 13 (8%) ChRCC (P < .001), with 39 of 56 (70%) and 2 of 13 (15%) cases, respectively showing positivity in >50% of tumor cells (P< .001). No ChRCCs were positive for both markers. There was no statistically significant difference in intensity or extent of HNF1α staining between RO and ChRCC. ### Long_Answer: HNF1β and S100A1 positivity was observed in a significantly greater proportion of RO than ChRCC. IHC for both markers can thus aid in the differential diagnosis. Accurate distinction is of increasing importance as tumor-ablative procedures and active surveillance become more widely adopted. ### Final_Prediction: yes

### Question: Does hypoglycemic and hypolipidemic effects of Bersama engleriana leave in nicotinamide/streptozotocin-induced type 2 diabetic rats? ### Context: The present investigation was aimed at evaluating the hypoglycemic and hypolipidemic properties of the aqueous and methanolic extracts from Bersama engleriana leaves in streptozotocin/nicotinamide (STZ-NA)-induced type 2 diabetic rats.Animals were orally treated for 4 consecutive weeks with Bersama engleriana extracts at doses of 300 or 600 mg/kg. The anti-diabetic effect was examined by measuring blood glucose (BG) at 0, 1, 14 and 28 days after STZ-NA treatment and, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and triglycerides (TG) levels at sacrifice (day 29). Glibenclamide (0.25 mg/kg) was used for comparison.STZ-NA-induced diabetic rats showed moderate to significant increases in the levels of BG, TG, TC, LDL-C while body weight, HDL-C levels and relative weights of liver and pancreas were decreased compared to controls (non diabetic rats). Administration of the plant extracts to STZ-NA diabetic rats resulted in a significant decrease in BG, TG, TC and LDL-C and the dose 600 mg/kg of the methanolic extract was the most effective; HDL-C level was markedly increased after four weeks compared to untreated diabetic rats. A dose-dependent increase in the relative weights of the diabetogenic organs was observed in the Bersama engleriana groups. It can be also noticed that the methanolic extract, especially the dose 600 mg/kg (p<0.001), produced more effects than glibenclamide and aqueous extract. Rats treated with glibenclamide (0.25 mg/kg) generally gave lower results compared to groups treated with plant extracts. ### Long_Answer: Results of the present study showed that Bersama engleriana extracts and especially its methanolic extract possess antidiabetogenic properties and beneficial effects on diabetic hyperlipidemia. All these effects could be due to the bioactive components revealed in the Bersama engleriana extracts such as triterpenes and phenols and which could justify its ethnomedical use. ### Final_Prediction: yes

### Question: Does photodynamic therapy selectively enhance liposomal doxorubicin uptake in sarcoma tumors to rodent lungs? ### Context: In specific conditions, photodynamic therapy (PDT) can enhance the distribution of macromolecules across the endothelial barrier in solid tumors. It was recently postulated that tumor neovessels were more responsive to PDT than the normal vasculature. We hypothesized that Visudyne(R)-mediated PDT could selectively increase liposomal doxorubicin (Liporubicin) uptake in sarcoma tumors to rodent lungs while sparing the normal surrounding tissue.Sarcoma tumors were generated subpleurally in the left lower lung lobe of 66 Fischer rats. Ten days following sarcoma implantation, tumors underwent different pre-treatment schemes: no PDT (controls), low-dose PDT (0.0625 mg/kg Visudyne(R), 10 J/cm(2) and 35 mW/cm(2)) and high-dose PDT (0.125 mg/kg Visudyne(R), 10 J/cm(2) and 35 mW/cm(2)). Liporubicin was then administered and allowed to circulate for 1, 3, or 6 hours. At the end of each treatment scheme, we assessed the uptake of Liporubicin in tumor and lung tissues by high-performance liquid chromatography and fluorescence microscopy.In all PDT-treated groups, there was a significant enhancement of Liporubicin uptake in tumors compared to controls after 3 and 6 hours of drug circulation. In addition, Liporubicin distribution within the normal lung tissue was not affected by PDT. Thus, PDT pre-treatment significantly enhanced the ratio of tumor-to-lung drug uptake compared to controls. Finally, fluorescence microscopy revealed a well-detectable Liporubicin signaling throughout PDT-treated tumors but not in controls. ### Long_Answer: PDT is a tumor-specific enhancer of Liporubicin distribution in sarcoma lung tumors which may find a translation in clinics. ### Final_Prediction: yes

### Question: Does recombinant thrombomodulin improve the visceral microcirculation by attenuating the leukocyte-endothelial interaction in a rat LPS model? ### Context: Abnormalities in vascular endothelial function play an important role in the development of septic organ dysfunction. The aim of this study was to examine the effect of recombinant thrombomodulin (rTM) on leukocyte-endothelial interaction and subsequent malcirculation in endotoxemia.Wistar rats were administered with either low, medium or high dose of rTM (n=7 each) 2hours after lipopolysaccharide (LPS) infusion. Mesenteric microcirculation after the treatment was observed under the intravital microscopy. In another series (n=5 each), plasma levels of high-mobility group box 1 (HMGB1) levels were measured at 5hours after LPS infusion.Microscopic findings revealed suppression in leukocyte adhesion, thrombus formation and endothelial damage with the treatment by rTM. However, high-dose rTM tended to increase the bleeding events. Thus, blood flow was better maintained with medium-dose rTM (P<0.05). The increase in HMGB1 level was significantly suppressed by medium and high-dose rTM (P<0.05, respectively). ### Long_Answer: rTM demonstrated a protective effect on microcirculation through the inhibition of leukocyte-endothelial interaction and suppression of HMGB1. ### Final_Prediction: yes

### Question: Are long-term psychiatric patients causing more crisis consultations outside office hours in mental health care? ### Context: As well as an improvement in community services, the de-institutionalization of patients receiving long-term psychiatric care can lead to marginally staffed mental health services, more homelessness, rising admission rates and more people in prison cells. It is assumed that an imbalance between community and hospital care for chronic patients puts pressure on crisis services.In this study, the central question is whether patients receiving long-term psychiatric care in Amsterdam do indeed put pressure on the city's emergency mental health services. We compare the pressure exerted by this group with the pressure resulting from the use of these services by all registered patients.Data were taken from the client registration systems of three mental health organizations in Amsterdam in the period from 2000 to 2004. Inclusion criteria for long-term psychiatric patients were age above 19 years and uninterrupted receipt of mental health care for a minimum of two successive years.Annually, 6%-8% of all non-long-term patients experienced a crisis outside office hours in the period under investigation; this was 4%-6% for long-term patients. The non-long-term patients accounted for 83% of crisis contacts outside office hours over the entire study period, with long-term patients accounting for 17%. ### Long_Answer: The assumption that crises are more prevalent in long-term patients in the community seems to be an example of stigmatization rather than an observation based on fact. ### Final_Prediction: nan