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### Question: Is duration of postoperative fasting associated with infection and prolonged length of stay in surgical patients? ### Context: Verify whether the postoperative fasting period increases the risk for infection and prolonged length of stay.Prospective cohort study. Elective surgery patients were included. Excluded: those with no conditions for nutritional assessment, admitted in minimal care units, as well as with<72h in-hospital stay. Postoperative fasting was recorded from the days of no nutrition therapy. The length of stay was considered prolonged when above the average according to the specialty and type of surgery. Logistic regression was used to assess associations and adjust for confounding factors.521 patients were analyzed, 44.1% were fasted for a period ≥1 day, 91% for ≥3 days and 5.6% for more than 5 days. Patients with more than 5 days fasting were more eutrophic, more admitted to intensive care units, and had more postoperative surgical complications. After adjustment for confounding variables, it was noted that ≥1 day of postoperative fasting increased the infection risk by 2.04 (CI95%: 1.20 to 3.50), ≥3 days 2.81 (CI95%: 1.4-5.8), and in fasting for more than 5 days the infection risk was 2.88 times higher (CI95%: 1.17 to 7.16). The risk for prolonged hospitalization was 2.4 (CI95%: 1.48 to 3.77) among patients who had ≥1 day fasting, 4.44 (CI95%: 2.0 to 9.8)and 4.43 times higher (CI95%: 1.73 to 11.3) among patients with ≥3 days fasting and more than 5 days, respectively. ### Long_Answer: The longer duration of postoperative fasting was an independent risk factor both for infection and for prolonged hospital stay. ### Final_Prediction: nan

### Question: Does maximal leg-strength training improve cycling economy in previously untrained men? ### Context: This study examined cycling economy before and after 8 wk of maximal leg-strength training.Seven previously untrained males (25 +/- 2 yr) performed leg-strength training 3 d.wk(-1) for 8 wk using four sets of five repetitions at 85% of one repetition maximum (1RM). Body mass, lean-leg muscle mass (LLM), percentage of body fat, and leg strength (1RM) were measured at 0, 4, and 8 wk of training. Cycling economy was calculated as the deltaVO2/deltaWR (change in the O2 cost of exercise divided by the change in the power between two different power outputs).There were significant increases in LLM and 1RM from 0 to 4 wk of training (LLM: 25.8 +/- 0.7 to 27.2 +/- 0.8 kg; 1RM: 138 +/- 9 to 215 +/- 9 kg). From 4 to 8 wk of training, 1RM continued to increase significantly (215 +/- 9 to 266 +/- 8 kg) with no further change observed in LLM. Peak power during incremental cycling increased significantly (305 +/- 14 to 315 +/- 16 W), whereas the power output achieved at the gas-exchange threshold (GET) remained unchanged. Peak O2 uptake and the O2 uptake achieved at the GET also remained unchanged following training. Cycling economy improved significantly when the power output was increased from below the GET to above the GET but not for power outputs below the GET. ### Long_Answer: Maximal leg-strength training improves cycling economy in previously untrained subjects. Increases in leg strength during the final 4 wk of training with unchanged LLM suggest that neural adaptations were present. ### Final_Prediction: yes

### Question: Does high tissue-transglutaminase antibody level predict small intestinal villous atrophy in adult patients at high risk of celiac disease? ### Context: Duodenal biopsy may be unnecessary to confirm celiac disease in patients with high tissue-transglutaminase antibody level.To define a cut-off value of tissue-transglutaminase antibody with high positive likelihood ratio for duodenal atrophy in patients with suspected celiac disease.We retrospectively identified 945 patients with suspected celiac disease and classified according to the method used for tissue-transglutaminase antibody assay: Group A (n=393, Eu-tTG® Eurospital), Group B (n=263; Eu-tTG® Eurospital) and Group C (n=289; Celikey® Phadia). Duodenal histology was graded according to Marsh. Sensitivity, specificity, and positive likelihood ratio were used to evaluate cut-off points of tissue-transglutaminase antibody as predictor of villous atrophy.100% specificity and ∞ positive likelihood ratio for duodenal atrophy was observed at a cut-off value of tissue-transglutaminase antibody 5 times higher than the upper limit of normal. CD diagnosis was confirmed by concordance with antiendomysial antibodies, and by reduction of t-TG titre in all patients and improvement of duodenal histology in 80% during gluten-free diet. ### Long_Answer: Tissue-transglutaminase antibody level 5-folds the upper limit of normal is 100% specific for duodenal atrophy and using this cut-off biopsy could by avoided in 1/3 of patients. Diagnostic criteria of celiac disease in adults need revision. ### Final_Prediction: yes

### Question: Does radiologic progression of pulmonary infiltrates predict a worse prognosis in severe community-acquired pneumonia than bacteremia? ### Context: It remains unknown whether bacteremia and rapid radiologic progression of pulmonary infiltrates increase the risk of shock and mortality in ICU patients with community-acquired pneumonia (CAP). The objective of this study was to investigate the relative importance of these two factors in the outcome of patients with severe CAP (sCAP).A secondary analysis in a multicenter observational study was conducted in 457 patients with CAP admitted to the ICU. Patients were classified into four groups: group RB, rapid radiographic spread of pulmonary infiltrates and bacteremia (n = 48); group R, rapid radiographic spread but no bacteremia (n = 183); group B, bacteremia but without rapid radiographic spread (n = 39); and group C, neither rapid radiographic spread nor bacteremia (n = 187).Logistic regression analysis showed that group RB and group R had a greater risk for shock than group C (adjusted odds ratio [aOR], 8.9; 95% confidence interval [CI], 4.0 to 19.7; and aOR, 3.8; 95% CI, 2.5 to 5.9; respectively), while patients in group B had no increased risk. In addition, compared to group C, group RB and group R had an increased risk of ICU death (aOR, 3.4; 95% CI, 1.4 to 8.1; and aOR, 3.1; 95% CI, 1.7 to 5.7, respectively), while patients in group B had none. ### Long_Answer: In this cohort of patients with severe CAP, radiologic progression of pulmonary infiltrates in the first 48 h is a significant adverse prognostic feature. In contrast, bacteremia does not affect outcomes. ### Final_Prediction: yes

### Question: Does inhibition of type 5 phosphodiesterase counteract β2-adrenergic signalling in beating cardiomyocytes? ### Context: Compartmentalization of cAMP and PKA activity in cardiac muscle cells plays a key role in maintaining basal and enhanced contractility stimulated by sympathetic nerve activity. In cardiomyocytes, activation of adrenergic receptor increases cAMP production, which is countered by the hydrolytic activity of selective phosphodiesterases (PDEs). The intracellular regional dynamics of cAMP production and hydrolysis modulate downstream signals resulting in different biological responses. The interplay between beta receptors (βARs) signalling and phosphodiesterase 5 (PDE5) activity remains to be addressed.Using combined strategies with pharmacological inhibitors and genetic deletion of PDEs and βAR isoforms, we revealed a specific pool of cAMP that is under dual regulation by PDE2 and, indirectly, PDE5 activity. Inhibition of PDE5 with sildenafil produces a cGMP-dependent activation of PDE2 that attenuates cAMP generation induced by βAR agonists, with concomitant modulation of stimulated contraction rate and calcium transients. PDE2 haploinsufficiency abolished the effects of sildenafil. The negative chronotropic effect of PDE5 inhibition through PDE2 activation was also observed in sinoatrial node tissue from adult mice. PDE5 inhibition selectively lowered contraction rate stimulated by β2AR, but not β1AR activation, supporting a compartmentalization of the cGMP-modulated pool of cAMP. ### Long_Answer: These data identify a new effect of PDE5 inhibitors on the modulation of cardiomyocyte response to adrenergic stimulation via PDE5-PDE2-mediated cross-talk. ### Final_Prediction: yes

### Question: Does life style modification improve insulin resistance and liver histology in patients with non-alcoholic fatty liver disease? ### Context: To study the effect of regular aerobic exercise on insulin resistance, serum aminotransferase and liver histology in nonalcoholic fatty liver disease (NAFLD) patients.Sixty (mean age 40.0 ± 8.5 years, 75% male) NAFLD patients were included in the study. After baseline anthropometric measurement i.e., body mass index (BMI), waist circumference (WC); all patients were advised regular aerobic exercise for 30 min/d, for at least 5 d/wk and trained to achieve around 70% of his maximal heart rate. In addition, moderately energy restricted diet was advised to patients with high BMI (> 25 kg/m(2)). Monthly follow up was done by measuring BMI, WC, aspartate aminotransferase, and alanine aminotransferase (ALT). Insulin resistance was calculated using homeostasis model assessment (HOMA) of insulin resistance (HOMA-IR) model, at baseline and after 6 mo. Insulin resistance was arbitrarily considered altered when it was ≥ 2. Liver biopsy was done in a section of patients at baseline and after 6 mo.Seventy percent (42/60) patients were overweight or obese; 95% (57/60) had central obesity (WC > 90 cm in men, > 80 cm in women). In the 45 exercise compliant patients insulin resistance decreased from 6.4 ± 6.1 to 1.3 ± 1.0, BMI from 26.7 ± 3.3 kg/m(2) to 25.0 ± 3.3 kg/m(2), WC from 95.7 ± 8.9 cm to 90.8 ± 7.3 cm and ALT from 84.8 ± 43.5 U/L to 41.3 ± 18.2 U/L (P < 0.01). In 15 exercise noncompliant patient's insulin resistance, BMI, WC and ALT did not show significant change at 6 mo follow up. Six of 8 patients in compliant group on repeat liver biopsy showed significant change in steatosis and necroinflammation. Nonalcoholic steatohepatitis scores improved form 5.3 ± 1.5 to 3.35 ± 1.5. The decline in insulin resistance correlated with decline in ALT (P = 0.01, r(s) = 0.90) and liver histology (P = 0.03, r(s) = 0.73). ### Long_Answer: Life style modification improves insulin resistance resulting in improvement in ALT and liver histology in NAFLD patients. ### Final_Prediction: yes

### Question: Does doxycycline block gastric ulcer by regulating matrix metalloproteinase-2 activity and oxidative stress? ### Context: To examine the effect of doxycycline on the activity of matrix metalloproteinases (MMPs) and oxidative stress in gastric tissues of rats following gastric injury.Gastric ulcers were generated in rats by administration of 70% ethanol, and activity of doxycycline was tested by administration 30 min prior to ethanol. Similarly, the effect of doxycycline was tested in an indomethacin-induced gastric ulcer model. The activities and expression of MMPs were examined by zymography and Western blot analysis.Gastric injury in rats as judged by elevated ulcer indices following exposure to ulcerogen, either indomethacin or ethanol, was reversed significantly by doxycycline. Indomethacin-induced ulcerated gastric tissues exhibited about 12-fold higher proMMP-9 activity and about 5-fold higher proMMP-3 activity as compared to control tissues. Similarly, ethanol induced about 22-fold and about 6-fold higher proMMP-9 and proMMP-3 activities, respectively, in rat gastric tissues. Both proMMP-9 and MMP-3 activities were markedly decreased by doxycycline in ulcerogen treated rat gastric tissues. In contrast, the reduced MMP-2 activity in ulcerated tissues was increased by doxycycline during ulcer prevention. On the other hand, doxycycline inhibited significantly proMMP-9, -2 and -3 activities in vitro. In addition, doxycycline reduced oxidative load in gastric tissues and scavenged H₂O₂ in vitro. Our results suggest a novel regulatory role of doxycycline on MMP-2 activity in addition to inhibitory action on MMP-9 and MMP-3 during prevention of gastric ulcers. ### Long_Answer: This is the first demonstration of dual action of doxycycline, that is, regulation of MMP activity and reduction of oxidative stress in arresting gastric injury. ### Final_Prediction: yes

### Question: Does rat granulation tissue maturation involve gap junction communications? ### Context: Wound healing, a coordinated process, proceeds by sequential changes in cell differentiation and terminates with the deposition of a new connective tissue matrix, a scar. Initially, there is the migratory fibroblast, followed by the proliferative fibroblast, then the synthetic fibroblast, which transforms into the myofibroblast, and finally the apoptotic fibroblast. Gap junction intercellular communications are proposed to coordinate the stringent control of fibroblast phenotypic changes. Does added oleamide, a natural fatty acid that blocks gap junction intercellular communications, alter the phenotypic progression of wound fibroblasts?Pairs of polyvinyl alcohol sponges attached to Alzet pumps, which constantly pumped either oleamide or vehicle solvent, were implanted subcutaneously into three rats. On day 8, implants were harvested and evaluated histologically and biochemically.The capsule of oleamide-treated sponge contained closely packed fibroblasts with little connective tissue between them. The birefringence intensity of that connective tissue was reduced, indicating a reduced density of collagen fiber bundles. Myofibroblasts, identified immunohistologically by alpha-smooth muscle actin-stained stress fibers, were reduced in oleamide-treated implants. Western blot analysis showing less alpha-smooth muscle actin confirmed the reduced density of myofibroblasts. ### Long_Answer: It appears that oleamide retards the progression of wound repair, where less connective tissue is deposited, the collagen is less organized, and the appearance of myofibroblasts is impaired. These findings support the hypothesis that gap junction intercellular communications between wound fibroblasts in granulation tissue play a role in the progression of repair and the maturation of granulation tissue into scar. ### Final_Prediction: nan

### Question: Does vitamin B-complex application promote secondary palate development in a palate organ model of the A/WySnJ mouse? ### Context: This study analyzed the direct influence of vitamin B-complex supplements (Polybion N, Merck Pharma GmbH, Germany) in medium on secondary palatal development in palatal organ cultures of A/WySnJ mice. Because of positive clinical experiences with prophylactic vitamin B substitution in mothers of cleft-related families, the direct influence of the vitamin B-complex on palatal tissue was analyzed.The inbred A/WySnJ mouse strain shows a highly spontaneous, genetically determined clefting rate of 20% to 44%. One hundred seventy-seven A/WySnJ fetuses were microdissected on gestational day 14.3 before the occurrence of palatal fusion. Palatal organ cultures were prepared and incubated in chemically defined serum-free medium with different concentrations (0.1% and 1.0%) of the vitamin B-complex Polybion N for 72 hours. Palatal development was analyzed microscopically according to the 6-step visual scale that describes the approximation of palatal shelves during development.At the beginning of the experiment (gestational day 14.3), the palatal development of all specimens used for in vitro organ culture showed a clear approach of the palatal shelves at stage II (2.25±0.78). Seventy-two hours after in vitro cultivation, the palatal shelves of the organ cultures supplemented with the vitamin B-complex showed significant growth (0.1%, P=.00017; 1.0%, P=.00078), whereas the untreated control group remained at initial developmental stage II (P=.291). ### Long_Answer: The results of this in vitro study suggest a significant positive influence of vitamin B supplementation on palatal shelf development in organ culture. Further studies will focus on the vitamin B concentration in the amniotic fluid of dams with or without cleft in their offspring. ### Final_Prediction: yes

### Question: Can iterative reconstruction improve imaging quality for lower radiation CT perfusion? ### Context: Initial results using IR for CT of the head showed satisfactory subjective and objective imaging quality with a 20-40% radiation dose reduction. The aim of our study was to compare the influence of IR and FBP algorithms on perfusion parameters at standard and lowered doses of CTP.Forty patients with unilateral carotid stenosis post-carotid stent placement referred for follow-up CTP were divided into 2 groups (tube currents were 100 mAs in group A and 80 mAs in group B). Datasets were reconstructed with IR and FBP algorithms; and SNRs of gray matter, white matter, and arterial and venous ROIs were compared. CBF, CBV, and MTT means and SNRs were evaluated by using linear regression, and qualitative imaging scores were compared across the 2 algorithms.The mean effective radiation dose of group B (2.06 mSv) was approximately 20% lower than that of group A (2.56 mSv). SNRs for ROIs in the dynamic contrast-enhanced images were significantly higher than those for the FBP images. Correlations of the SNRs for CBF, CBV, and MTT across the 2 algorithms were moderate (R² = 0.46, 0.23, and 0.44, respectively). ROIs in gray matter rather than the IR algorithm predicted increasing SNRs in all CBF, CBV, and MTT maps. Two cases of significant restenosis were confirmed in both algorithms. CBV, CBF, and MTT imaging scores did not differ significantly across algorithms or groups. ### Long_Answer: Lower dose CTP (20% below normal dose) without IR can effectively identify oligemic tissue in poststenting follow-up. IR does not alter the absolute values or increase the SNRs of perfusion parameters. Other methods should be attempted to improve SNRs in settings with low tube currents. ### Final_Prediction: nan

### Question: Is the involvement of human amnion in histologic chorioamnionitis an indicator that a fetal and an intra-amniotic inflammatory response is more likely and severe : clinical implications? ### Context: Amnionitis (inflammation of the amnion) is the final stage of extra-placental chorioamniotic inflammation. We propose that patients with "amnionitis", rather than "chorionitis" have a more advanced form of intra-uterine inflammation/infection and, thus, would have a more intense fetal and intra-amniotic inflammatory response than those without "amnionitis".The relationship between the presence of amnionitis, and a fetal and an intra-amniotic inflammatory response was examined in 290 singleton preterm births (<or=36 weeks) with histologic chorioamnionitis. The fetal inflammatory response was determined by plasma C-reactive protein (CRP) concentrations in umbilical cord and the presence of funisitis. The intra-amniotic inflammatory response was assessed by matrix metalloproteinase-8 (MMP-8) concentration and white blood cell (WBC) count in 156 amniotic fluid (AF) samples obtained within 5 days of birth. AF was cultured for aerobic and anaerobic bacteria and genital mycoplasmas. The CRP concentration was measured with a highly sensitive immunoassay.(1) Amnionitis was present in 43.1% of cases with histologic chorioamnionitis. (2) Patients with amnionitis had a significantly higher rate of funisitis and positive AF culture and a higher median umbilical cord plasma CRP, AF MMP-8 level and AF WBC count than those without amnionitis (p<0.001 for each). (3) Among cases with amnionitis, the presence or absence of funisitis was not associated with significant differences in the median cord plasma CRP, AF MMP-8 level and AF WBC count. (4) However, the presence of amnionitis in cases with funisitis was associated with a higher median umbilical cord plasma CRP, AF MMP-8 level and AF WBC count than the absence of amnionitis in those with funisitis (p<0.05 for each). (5) Multiple logistic regression analysis demonstrated that amnionitis was a better independent predictor of proven or suspected early-onset neonatal sepsis (odds ratio 3.8, 95% confidence interval (CI) 1.1-13.2, p<0.05) than funisitis (odds ratio 1.8, 95% CI 0.5-6.1, not significant) after correction for the contribution of other potential confounding variables. ### Long_Answer: The involvement of the amnion in the inflammatory process of the extraplacental membranes is associated with a more intense fetal and intra-amniotic inflammatory response than chorionitis alone. This observation has clinical implications because it allows staging of the severity of the inflammatory process and assessment of the likelihood of fetal involvement. ### Final_Prediction: yes

### Question: Does galectin-1 deficiency improve axonal swelling of motor neurones in SOD1 ( G93A ) transgenic mice? ### Context: Galectin-1, a member of the β-galactoside-binding lectin family, accumulates in neurofilamentous lesions in the spinal cords of both sporadic and familial amyotrophic lateral sclerosis (ALS) patients with a superoxide dismutase 1 gene (SOD1) mutation (A4V). The aim of this study was to evaluate the roles of endogenous galectin-1 in the pathogenesis of ALS.Expression of galectin-1 in the spinal cord of mutant SOD1 transgenic (SOD1(G93A) ) mice was examined by pathological analysis, real-time RT-PCR and Western blotting. The effects of galectin-1 deficiency were evaluated by cross-breeding SOD1(G93A) mice with galectin-1 null (Lgals1(-/-) ) mice.Before ALS-like symptoms developed in SOD1(G93A) /Lgals1(+/+) mice, strong galectin-1 immunoreactivity was observed in swollen motor axons and colocalized with aggregated neurofilaments. Electron microscopic observations revealed that the diameters of swollen motor axons in the spinal cord were significantly smaller in SOD1(G93A) /Lgals1(-/-) mice, and there was less accumulation of vacuoles compared with SOD1(G93A) /Lgals1(+/+) mice. In symptomatic SOD1(G93A) /Lgals1(+/+) mice, astrocytes surrounding motor axons expressed a high level of galectin-1. ### Long_Answer: Galectin-1 accumulates in neurofilamentous lesions in SOD1(G93A) mice, as previously reported in humans with ALS. Galectin-1 accumulation in motor axons occurs before the development of ALS-like symptoms and is associated with early processes of axonal degeneration in SOD1(G93A) mice. In contrast, galectin-1 expressed in astrocytes may be involved in axonal degeneration during symptom presentation. ### Final_Prediction: yes

### Question: Does [ Down-regulation of CT120A by RNA interference suppress lung cancer cells growth ]? ### Context: To validate our obtained outcomes and clarify the relationship between CT120A, a novel human plasma membrane-associated gene, and proliferation of lung cancer cells.A vector-based small hairpin RNA (shRNA) was transfected into the human lung adenocarcinoma SPC-A-1 cells to specifically target CT120A cDNA. RT-PCR and Western blotting were used to analyze the CT120A expression. The cell proliferation rate was analyzed by BrdU-TdR incorporation assay, the ability of cells to grow in soft agarose and the tumorigenicity in nude mice were measured. Flow cytometry was performed to analyze cell apoptosis.When compared with the scrambled control cell line, CT120A transcripts were reduced by 70% and 50% in two shRNA-H stable transfectants, H2 and H3 clones, respectively. The protein of CT120A was reduced by about 80% in both the H2 and H3 clones. By BrdU incorporation assay, up to the 6th day a dramatic decrease in the cell growth rate (30% to 40%) was observed in the shRNA-H2 and shRNA-H3 cell lines. The colony formation rate in soft agarose of the two cell lines was about one half that of the control cells. In addition, a remarkable reduction of tumorigenicity of the two cell lines was observed as compared with that of the control. The suppression of CT120A expression also sensitized cells to ultraviolet-induced apoptosis. ### Long_Answer: Down-regulation of CT120A by RNA interference suppresses lung cancer cell growth. The successful knockdown of CT120A expression by RNA interference implicates that CT120A may be a new candidate of drug target for treatment of lung cancers. ### Final_Prediction: yes

### Question: Is the radio-sensitizing effect of xanthohumol mediated by STAT3 and EGFR suppression in doxorubicin-resistant MCF-7 human breast cancer cells? ### Context: Chemotherapeutic drug resistance remains a clinical obstacle in cancer management. Drug-resistant cancer cells usually exhibit cross-resistance to ionizing radiation, which has devastating consequences for patients. With a better understanding of the molecular mechanisms, it will be possible to develop strategies to overcome this cross-resistance and to increase therapeutic sensitivity.Natural and synthetic flavonoid compounds including xanthohumol, the principal flavonoid in hops, were investigated for its radio-sensitizing activity on human breast cancer MCF-7 and adriamycin-resistant MCF-7 (MCF-7/ADR) cells. Chemo-sensitizing or radio-sensitizing effect was analyzed by tetrazolium-based colorimetric assay and flow cytometry. Western blot analysis, confocal microscopy, gene silencing with siRNA transfection and luciferase reporter gene assay were performed to examine signaling molecule activation.Among the tested flavonoid compounds, pretreatment of the cells with xanthohumol significantly sensitized MCF-7/ADR cells to the radiation treatment by inducing apoptosis. In MCF-7/ADR cells, treatment with xanthohumol alone or with gamma-rays significantly decreased levels of anti-apoptotic proteins. Multi-drug resistance 1 (MDR1), epidermal growth factor receptor (EGFR) and signal transducer and activator of transcription 3 (STAT3) expression levels in MCF-7/ADR cells were suppressed by xanthohumol treatment. In addition, xanthohumol treatment increased death receptor (DR)-4 and DR5 expression. The xanthohumol-induced changes of these resistance-related molecules in MCF-7/ADR cells were synergistically increased by gamma-ray treatment. ### Long_Answer: Xanthohumol restored sensitivity of MCF-7/ADR cells to doxorubicin and radiation therapies. ### Final_Prediction: yes

### Question: Is p300 amplitude insensitive to working memory load in schizophrenia? ### Context: Working memory (WM) tasks usually elicit a P300 ERP component, whose amplitude decreases with increasing WM load. So far, this effect has not been studied in schizophrenics (SZs), a group that is considered to have an aberrant brain connectivity and impairments in WM capacity. The aim of this study was to determine the dependency of the P300 component on WM load in a sample of SZ subjects.We recorded 26 subjects (13 SZ patients and their matched controls) with an 80-channel electroencephalogram. Subjects performed an N-back task, a WM paradigm that manipulates the number of items to be stored in memory.In healthy subjects, P300 amplitude was highest in the low WM load condition, and lowest in both the attentional control condition and the high WM load condition. In contrast, SZs evidenced low P300 amplitude in all conditions. A significant between group difference in P300 amplitude was evidenced only at the low WM load condition (1 -back), being smaller in SZs. ### Long_Answer: SZ subjects display a lower than normal P300 amplitude, which does not vary as a function of memory load. These results are consistent with a general impairment in WM capacity in these patients. ### Final_Prediction: yes

### Question: Is admission hyperglycaemia associated with higher mortality in patients with hip fracture? ### Context: To determine the proportion of hip-fracture patients with admission hyperglycaemia, and, when present, whether it was associated with a worse outcome (i.e. increased length of hospital stay, admission to ICU, or mortality).Over a 2-year period, we retrospectively analysed records of patients with a primary diagnosis of hip fracture (ICD-9-CM 820.x). The records were retrieved from an electronic hospital database.An admission blood sugar level (aBSL) greater than 140 mg/dl was observed in 34% of the patients and was associated with a higher in-hospital mortality (P=0.042). ICU admissions and length of stay did not differ for patients having an aBSL above or below the 140 mg/dl cut-off. ### Long_Answer: Hyperglycaemia is common in hip-fracture patients. A high aBSL might serve as a prognostic indicator in hip-fracture patients. To our knowledge, this is the first report of hyperglycaemia-associated mortality in less severely traumatised patients, who generally are not admitted to an ICU. ### Final_Prediction: yes

### Question: Are extreme urinary betaine losses in type 2 diabetes combined with bezafibrate treatment associated with losses of dimethylglycine and choline but not with increased losses of other osmolytes? ### Context: Betaine deficiency is a probable cardiovascular risk factor and a cause of elevated homocysteine. Urinary betaine excretion is increased by fibrate treatment, and is also often elevated in diabetes. Does fibrate further increase betaine excretion in diabetes, and does it affect the plasma concentrations and excretions of related metabolites and of other osmolytes?Samples from a previous study of type 2 diabetes were selected if participants were taking bezafibrate (n = 32). These samples were compared with participants matched for age and gender and not on a fibrate (comparator group, n = 64). Betaine, related metabolites, and osmolytes were measured in plasma and urine samples from these 96 participants.Median urinary betaine excretion in those on bezafibrate was 5-fold higher than in the comparator group (p < 0.001), itself 3.5-fold higher than the median reported for healthy populations. In the bezafibrate group, median dimethylglycine excretion was higher (9-fold, p < 0.001). Excretions of choline, and of the osmolytes myo-inositol, taurine and glycerophosphorylcholine, were not significantly different between groups. Some participants excreted more betaine than usual dietary intakes. Several betaine fractional clearances were >100 %. Betaine excretion correlated with excretions of the osmolytes myo-inositol and glycerophosphorylcholine, and also with the excretion of choline and N,N-dimethylglycine, but it was inconclusive whether these relationships were affected by bezafibrate therapy. ### Long_Answer: Increased urinary betaine excretions in type 2 diabetes are further increased by fibrate treatment, sometimes to more than their dietary intake. Concurrent betaine supplementation may be beneficial. ### Final_Prediction: yes

### Question: Does evidence suggest there was not a `` resurgence '' of kernicterus in the 1990s? ### Context: Although some have suggested that kernicterus disappeared in the United States in the 1970s to 1980s and dramatically reappeared in the 1990s, population-based data to support such a resurgence are lacking.We used diagnosis codes on data collection forms from the California Department of Developmental Services (DDS) to identify kernicterus cases among children born from 1988 to 1997. We examined kernicterus mortality trends in the United States from 1979 to 2006 using death certificate data from the National Center for Health Statistics.We identified 25 cases of physician-diagnosed kernicterus. This figure was augmented to reflect estimates of cases lost to infant mortality, yielding incidence estimates of 1 in 200 000 California live births, 1 in 2500 among children who received services from DDS, and 1 in 400 children with cerebral palsy. There was no significant trend in kernicterus incidence from 1988 to 1997 (P = .77). Incidence before and after the 1994 publication of the AAP practice parameter for hyperbilirubinemia in healthy term infants was not significantly different (P = .92). Nationally, there were 3 reported infant deaths from kernicterus in 1994 and 2 or fewer in the other 28 years from 1979 to 2006 (0.28 deaths per million live births): there was no significant increase in kernicterus mortality over this period. ### Long_Answer: Data from California do not support a resurgence of kernicterus in the 1990s. Deaths from kernicterus in the United States have remained rare, with no apparent increase during the last 25 years. ### Final_Prediction: yes

### Question: Does motor performance deteriorate with simultaneously performed cognitive tasks in geriatric patients? ### Context: To investigate whether simultaneous cognitive tasks influence maximal motor performance in frail geriatric patients with a history of injurious falls and different levels of cognitive function.Experimental 3-group design.Geriatric rehabilitation hospital.Twenty-two healthy, young adults (mean age +/- standard deviation, 27.7 +/- 9y) and 23 geriatric patients (mean age, 80.9 +/- 5.4y) with a history of injurious falls with (Mini-Mental State Examination [MMSE] score, 20.5 +/- 1.6) and without (MMSE score, 28.1 +/- 1.2) cognitive impairment.Not applicable.Motor performance: peak and integral of maximal isometric strength of leg extensors. Cognition: semiautomated calculation steps (serial 2 forward) and nonautomated calculation steps derived from the MMSE (serial 7 retro). Motor and cognitive performances were examined as single and dual tasks.In frail geriatric patients, especially in patients with cognitive impairment, maximal motor performance decreased significantly during all dual tasks. Cognitive performance was reduced, depending on the task and group. ### Long_Answer: In frail or cognitively impaired geriatric patients, additional tasks can substantially decrease maximal motor performance. Insufficient resources on dual tasking may thus be a link in connecting the high incidence of falls with frailty and cognitive impairment in geriatric patients with a history of injurious falls. ### Final_Prediction: yes

### Question: Do ingestion of casein and whey proteins result in muscle anabolism after resistance exercise? ### Context: Determination of the anabolic response to exercise and nutrition is important for individuals who may benefit from increased muscle mass. Intake of free amino acids after resistance exercise stimulates net muscle protein synthesis. The response of muscle protein balance to intact protein ingestion after exercise has not been studied. This study was designed to examine the acute response of muscle protein balance to ingestion of two different intact proteins after resistance exercise.Healthy volunteers were randomly assigned to one of three groups. Each group consumed one of three drinks: placebo (PL; N = 7), 20 g of casein (CS; N = 7), or whey proteins (WH; N = 9). Volunteers consumed the drink 1 h after the conclusion of a leg extension exercise bout. Leucine and phenylalanine concentrations were measured in femoral arteriovenous samples to determine balance across the leg.Arterial amino acid concentrations were elevated by protein ingestion, but the pattern of appearance was different for CS and WH. Net amino acid balance switched from negative to positive after ingestion of both proteins. Peak leucine net balance over time was greater for WH (347 +/- 50 nmol.min(-1).100 mL(-1) leg) than CS (133 +/- 45 nmol.min(-1).100 mL(-1) leg), but peak phenylalanine balance was similar for CS and WH. Ingestion of both CS and WH stimulated a significantly larger net phenylalanine uptake after resistance exercise, compared with the PL (PL -5 +/- 15 mg, CS 84 +/- 10 mg, WH 62 +/- 18 mg). Amino acid uptake relative to amount ingested was similar for both CS and WH (approximately 10-15%). ### Long_Answer: Acute ingestion of both WH and CS after exercise resulted in similar increases in muscle protein net balance, resulting in net muscle protein synthesis despite different patterns of blood amino acid responses. ### Final_Prediction: yes

### Question: Does human acellular dermal matrix for ventral hernia repair reduce morbidity in transplant patients? ### Context: Organ transplantation is widely accepted as the treatment of choice for native organ failure. Due to required immunosuppression, however, organ recipients are prone to wound infections, incisional hernias, and fascial dehiscence. These complications are especially dangerous in this patient population, as they can compromise the survival of the transplanted organ. Various methods have been employed to repair ventral and incisional hernias in these patients. These include primary repair, synthetic mesh, biologic mesh, tensor fascia lata grafts (TFL), component separation, flaps from the thighs, or a combination of these. The goal of this study was to review the experience at our institution with ventral hernia repair in transplant patients and to compare outcomes of the various repair techniques.Patients with liver, renal, or pancreas transplants requiring immunosuppression who underwent a ventral or incisional hernia repair at the University of Maryland from 2000-2005 were reviewed retrospectively. Factors examined include type and location of hernia, type of repair, post operative infection, hernia recurrence, reoperation, mesh removal, and length of follow up. Complication rates were compared using odds ratio and chi-square.A total of 104 patients met the criteria with a mean length of follow up of 26 months. Of these, 34 patients had repair with human acellular dermal matrix (HADM), 26 had synthetic mesh, 25 had primary repair, and 9 had TFL. Rates of wound infection in these groups were 15, 65, 8, and 11% respectively (χ (2) = 28, P < 0.001). Rates of recurrence were 24, 77, 36, and 11% respectively (χ (2) = 22, P < 0.001). The rate of mesh removal with HADM and synthetic mesh were 12 and 69%, respectively (χ (2) = 14, P < 0.001). When comparing HADM and synthetic mesh, the odds ratio for wound infection is 11 (95% CI 3.2-38) and for mesh removal is 8.7 (95% CI 2.6-28). ### Long_Answer: When repairing ventral or incisional hernias in immunosuppressed transplant patients, HADM provides significantly reduced morbidity from reduced rates of infection, recurrence, and need for operative removal of mesh. ### Final_Prediction: yes

### Question: Is mRI-guided region-of-interest delineation comparable to manual delineation in dopamine transporter SPECT quantification in patients : a reproducibility study? ### Context: A particularly sensitive step in the quantification of SPECT images of the dopamine transporter (DAT) is a correct delineation of the region of interest (ROI). In this study, we primarily compared the reproducibility of the following different approaches for ROI delineation in SPECT images of the DAT: the use of manual delineation (MD) on high-count striatal slides directly on the SPECT image, ROI delineation based on individual MR images (MRD), and oversized striatal ROIs-that is, the striatal volume of interest (SVI), as described previously. We also assessed the ability of the different approaches to identify striatal pathology in patients with parkinsonism.Eight patients with highly variable reductions in cerebral DAT availability were SPECT-scanned twice with (123)I-labeled N-(3-iodoprop-(2E)-enyl)-2beta-carboxymethoxy-3beta-(4'-methylphenyl) nortropane bolus infusion setup and once with an MRI scanner. For SPECT/MRI coregistration, we used external fiducial markers visible on both MRI and SPECT. With the MD and MRD methods, the outcome parameters for DAT availability were the binding potentials and the ratio at equilibrium of specifically bound radioligand to nondisplaceable radioligand in tissue (BP(ND)). For the SVI method, the outcome parameter was the specific binding ratio (SBR).No statistically significant difference in striatal BP(ND) intraobserver reproducibility was seen among any of the 3 methods. The intraobserver reproducibility average +/- SD for MD was 7.0% +/- 4.1%; for MRD, 5.7% +/- 5.4%; and for SVI, 6.7% +/- 6.0%. Mean intrasubject variability, as determined from the test-retest scans, did not differ with the 3 delineation methods used. The average (+/-SD) intrasubject variability of striatal BP(ND) was 11.9% +/- 10.0% with MD and 14.6% +/- 15.3% with MRD. With the SVI method, the intrasubject variability of striatal specific binding ratio was 10.0% +/- 10.2%. BP(ND) values obtained with the MD and MRD methods were similar (paired t test, P > 0.4). ### Long_Answer: In patients with reduced striatal DAT binding, the reproducibility of the outcome from ROI MD is comparable to both that obtained by delineation of ROI on individual MR images, followed by coregistration to the SPECT image, and that obtained with the SVI-based approach. ### Final_Prediction: yes

### Question: Does acute TSH stimulation in vivo alter serum PCSK9 levels? ### Context: It is now recognized that TSH can act on targets other than the thyroid, including the liver. Elevated serum TSH levels in euthyroid subjects were recently reported to correlate with high values of serum proprotein convertase subtilisin/kexin type 9 (PCSK9). This protein, expressed and secreted by hepatocytes, promotes higher LDL-cholesterol levels. We tested whether an acute increase of TSH levels following administration of TSH in vivo would raise PCSK9 levels in patients who had previously undergone total thyroidectomy and radioablation for thyroid cancer.TSH levels rose from 0.64 ± 1.02 mU/L on day 1 to 98.66 ± 4.83 mU/L on day 3, following injections of recombinant human TSH (on days 1 and 2). PCSK9 levels were 330 ± 99 ng/ml on day 1, and did not change on days 3 or 5 in response to TSH stimulation. ### Long_Answer: Although a positive correlation between TSH and PCSK9 in euthyroid subjects has raised the possibility that TSH might act on the liver to raise PCSK9 values, our data show that PCSK9 levels are not affected by acute elevations of TSH levels. Whether chronic elevations of TSH are needed to upregulate PCSK9 remains to be determined. ### Final_Prediction: no

### Question: Is c-index associated with functional outcomes after laparoscopic partial nephrectomy? ### Context: The C-index is a morphometric descriptor of renal masses that incorporates tumor size and site. We examined associations of the C-index with kidney function after laparoscopic partial nephrectomy.We retrospectively reviewed the records of 131 patients who underwent laparoscopic partial nephrectomy for a single kidney tumor. We calculated the C-index from preoperative contrast enhanced computerized tomography images. Estimated glomerular filtration rate was calculated using the modification of diet in renal disease 2 equation. Nadir estimated glomerular filtration rate was calculated using peak serum creatinine within 7 days of surgery.The median C-index was 2.7 (range 0.7 to 9.6). The median preoperative and nadir estimated glomerular filtration rate was 78 (range 23 to 148) and 54 ml/minute/1.73 m2 (range 15 to 127, p<0.001). The mean±SD total glomerular filtration rate decrease was 28%±16%. On univariate analysis we noted a positive correlation between log C-index and the nadir estimated glomerular filtration rate (r=0.29, p=0.002), and a negative correlation between log C-index and the percent decrease in the estimated glomerular filtration rate (r=-0.4, p<0.001). On multivariate analysis the estimated glomerular filtration rate percent decrease was significantly associated with log C-index (p=0.005) and warm ischemia time (p<0.001) but not with tumor diameter or the preoperative estimated glomerular filtration rate. Of patients with a C-index of 2.5 or less 70% showed a 30% or greater decrease in the estimated glomerular filtration rate vs 32% of those with a C-index of greater than 2.5 (RR 2.2, p<0.001). ### Long_Answer: The C-index is associated with the postoperative nadir estimated glomerular filtration rate and the percent decrease in the estimated glomerular filtration rate after laparoscopic partial nephrectomy. A C-index of less than 2.5 correlated with a 2.2-fold increased risk of a 30% or greater estimated glomerular filtration rate decrease after laparoscopic partial nephrectomy. ### Final_Prediction: yes

### Question: Is serum cystatin C a poor biomarker for diagnosing acute kidney injury in critically-ill children? ### Context: Accurate diagnosis of acute kidney injury (AKI) is problematic especially in critically-ill patients in whom renal function is in an unsteady state.Our aim was to evaluate the role of serum (S.) cystatin C as an early biomarker of AKI in critically-ill children.S. creatinine and S. cystatin C were measured in 32 critically-ill children who were at risk for developing AKI. AKI was defined by both: Risk,-injury,-failure,-loss, and-endstage renal disease (RIFLE) classification and glomerular filtration rate (GFR) <80 ml/min/1.73 m(2). GFR was estimated by both Schwartz formula and S. cystatin C-based equation.S. cystatin C was not statistically higher in AKI patients compared with non-AKI by RIFLE classification (median 1.48 mg/l vs. 1.16 mg/l, P = 0.1) while S. creatinine was significantly higher (median 0.8 mg/dl vs. 0.4 mg/dl, P = 0.001). On estimating GFR by the two equations we found, a lag between rise of S. cystatin C and creatinine denoted by lower GFR by Schwartz formula in four patients, on other hand, six patients had elevated S. cystatin C with low GFR despite normal creatinine and GFR, denoting poor concordance between the two equations and the two markers. The ability of S. creatinine in predicting AKI was superior to S. cystatin with area under the curve (AUC) 0.95 with sensitivity and specificity (100% and 84.6%, respectively) using the RIFLE classification. The same findings were found when using Schwartz formula. ### Long_Answer: S. cystatin C is a poor biomarker for diagnosing AKI in critically-ill children. ### Final_Prediction: yes

### Question: Do liver transplantation-induced antihistone H1 autoantibodies suppress mixed lymphocyte reaction? ### Context: In a rat model of orthotopic liver transplantation (OLT), recipient serum after OLT (post-OLT serum) has been reported to prevent allograft rejection. However, the molecular identities of immunosuppressive factors, which are in the early stage of post-OLT, remain elusive. This study was aimed to identify immunodominant suppressive factors present in early post-OLT serum.The immunosuppressive activities of post-OLT serum, immunoglobulin (Ig) G-depleted serum, and purified IgG were evaluated in vitro by inhibition of the mixed lymphocyte reaction (MLR). Autoantigens recognized by the MLR-inhibitory IgG in early post-OLT serum were identified by the internal protein sequencing.Recipient post-OLT serum inhibited MLR, and its immunosuppressive activity vanished by means of the elimination of OLT-inducible IgG. IgG from post-OLT sera (2-3 weeks) specifically reacted to 31-, 34-, and 73-kDa autoantigens on splenic cells. The internal sequences of the doublet 31- and 34-kDa antigens coincided completely with those of histone H1 molecules. The levels of histone H1-specific antibodies were transiently increased to a plateau around 2 to 3 weeks after OLT but decreased in the later tolerogenic phase. Immunodepletion of antihistone H1 autoantibodies from early post-OLT serum abolished the MLR-inhibitory activity. Furthermore, rabbit polyclonal antibody-directed histone H1 not only suppressed MLR but also prolonged allograft survival. ### Long_Answer: In this article, the authors provide evidence that autoreactive antibodies against histone H1, which are transiently induced at the early stage by liver transplantation, are a major OLT-induced graft survival factor. ### Final_Prediction: yes

### Question: Does clonidine inhibit anti-non-Gal IgM xenoantibody elicited in multiple pig-to-primate models? ### Context: Survival of vascularized xenografts is dependent on pre-emptive inhibition of the xenoantibody response against galactosyltransferase knockout (GTKO) porcine organs. Our analysis in multiple GTKO pig-to-primate models of xenotransplantation has demonstrated that the anti-non-gal-α-1,3-gal (anti-non-Gal) xenoantibody response displays limited structural diversity. This allowed our group to identify an experimental compound which selectively inhibited induced anti-non-Gal IgM xenoantibodies. However, because this compound had an unknown safety profile, we extended this line of research to include screening small molecules with known safety profiles allowing rapid advancement to large animal models.The NIH clinical collections of small molecules were screened by ELISA for their ability to inhibit xenoantibody binding to GTKO pig endothelial cells. Serum collected from non-immunosuppressed rhesus monkeys at day 14 post-injection with GTKO pig endothelial cells was utilized as a source of elicited xenoantibody for initial screening. Virtual small molecule screening based on xenoantibody structure was used to assess the likelihood that the identified small molecules bound xenoantibody directly. As a proxy for selectivity, ELISAs against tetanus toxoid and the natural antigens laminin, thyroglobulin, and single-stranded DNA (ssDNA) were utilized to assess the ability of the identified reagents to inhibit additional antibody responses. The identified inhibitory small molecules were further tested for their ability to inhibit xenoantibody elicited in multiple settings, including rhesus monkeys pre-treated with an anti-non-Gal selective anti-idiotypic antibody, non-immunosuppressed rhesus monkeys immunized with wild-type fetal pig isletlike cell clusters, and non-immunosuppressed baboons transplanted with GTKO multiple transgenic pig kidneys.Four clinically relevant small molecules inhibited anti-non-Gal IgM binding to GTKO pig endothelial cells in vitro. Three of these drugs displayed a limited region of structural similarity suggesting they may inhibit xenoantibody by a similar mechanism. One of these, the anti-hypertensive agent clonidine, displayed only minimal inhibition of antibodies elicited by vaccination against tetanus toxoid or pre-existing natural antibodies against laminin, thyroglobulin, or ssDNA. Furthermore, clonidine inhibited elicited anti-non-Gal IgM from all animals that demonstrated a xenoantibody response in each experimental setting. ### Long_Answer: Clinically relevant small molecule drugs with known safety profiles can inhibit xenoantibody elicited against non-Gal antigens in diverse experimental xenotransplantation settings. These molecules are ready to be tested in large animal models. However, it will first be necessary to optimize the timing and dosing required to inhibit xenoantibodies in vivo. ### Final_Prediction: yes

### Question: Are preoperative radiographic factors and surgeon experience associated with cortical breach of C2 pedicle screws? ### Context: A retrospective review study.In this study, we attempt to identify radiographic variables associated with likelihood of intraoperative breach during C2 pedicle screw placement. In addition, we attempt to correlate surgeon experience with breach rate.Pedicle screws have emerged as an effective approach for obtaining fixation of the axis, yet placement of C2 pedicle screws is technically demanding and poses the risk of injury to the vertebral artery. Given the evidence for substantial variation in C2 anatomy, preoperative assessment of computed tomography (CT) scans may indicate, which patients are at increased risk for cortical breach during the pedicle screw placement.A retrospective review of all patients undergoing C2 pedicle screw fixation at a single institution over the last 6 years was conducted. Radiographic cortical breaches were defined on postoperative CT scans as visualization of the screw beyond the cortical edge. Radiographic measurements were determined from preoperative CT scans and were then correlated with breaches via Student t test. The association of breach rate with surgeon experience was evaluated using univariate linear regression.Ninety-three patients underwent placement of 170 screws. Cortical breach was detected on postoperative CT scans in 43 screws (25.3%). One clinically significant breach occurred with damage to the left vertebral artery intraoperatively. On axial CT sections, mean pedicle isthmus diameter was significantly smaller in patients with breach than in patients without breach for both left and right sides, P=0.006 and P=0.010, respectively. Specifically, a diameter of less than 6 mm was associated with a nearly 2-fold increase in risk of cortical breach (37% vs. 21%). Surgeons with greater experience in placing C2 pedicle screws were noted to have a lower breach incidence (P=0.004). ### Long_Answer: During placement of C2 pedicle screws, likelihood of cortical breach may be associated with size of pedicle and surgeon experience. Extensive preoperative evaluation of CT scans and consideration of technical demands of procedure may help avoid complications with such internal fixation. ### Final_Prediction: yes

### Question: Is diabetic peripheral neuropathic pain a stronger predictor of depression than other diabetic complications and comorbidities? ### Context: To investigate the independent effect on depression of painless diabetic polyneuropathy, painful diabetic polyneuropathy, and general and diabetes-related comorbidities.In 181 patients, the presence of painless diabetic polyneuropathy, painful diabetic polyneuropathy, comorbidities and depression was assessed using the Michigan Neuropathy Screening Instrument Questionnaire, the Michigan Diabetic Neuropathy Score, nerve conduction studies, the Douleur Neuropathique en 4 Questions, the Charlson Comorbidity Index and the Beck Depression Inventory-II.In all, 46 patients met the criteria of confirmed painless diabetic polyneuropathy and 25 of painful diabetic polyneuropathy. Beck Depression Inventory-II scores indicative of mild-moderate-severe depression were reached in 36 patients (19.7%). In a multiple logistic regression analysis (including age, sex, body mass index, being unemployed, duration, haemoglobin A1c, insulin treatment, systolic blood pressure, nephropathy, retinopathy, Charlson Comorbidity Index and painful diabetic polyneuropathy), female sex (odds ratio: 5.9, p = 0.005) and painful diabetic polyneuropathy (odds ratio: 4.6, p = 0.038) were the only independent predictors of depression. Multiple regression analysis, including Douleur Neuropathique en 4 Questions and Michigan Diabetic Neuropathy Score instead of painful diabetic polyneuropathy, showed that Douleur Neuropathique en 4 Questions, in addition to female sex, was a significant predictor of depressive symptoms severity (p =0.005). ### Long_Answer: Painful diabetic polyneuropathy is a greater determinant of depression than other diabetes-related complications and comorbidities. Painful symptoms enhance depression severity more than objective insensitivity. ### Final_Prediction: yes

### Question: Does the genotype of the transporter associated with antigen processing gene affect susceptibility to colorectal cancer in Japanese? ### Context: Although colorectal cancer (CRC) is one of the most frequent malignancies in Japan, the associated genetic factors remain to be elucidated. Functional loss of the transporter associated with antigen processing (TAP) 1 gene induces carcinogenesis. We investigated whether single nucleotide polymorphisms (SNPs) in the TAP1 gene (rs735883) are associated with susceptibility to CRC in a Japanese population.The study participants were 143 cases and 243 clinical controls. After extracting DNA from their peripheral blood cells, genotyping was conducted by the polymerase chain reaction-restriction fragment length polymorphism method.Participants with a mutated allele had an increased risk for CRC. The adjusted odds ratios for the C/T, T/T, and the mutation type (C/T + T/T) compared to that of wild type (C/C) were 2.27 [95 % confidence interval (CI), 1.43-3.67], 1.95 (95 % CI, 0.88-4.30), and 2.22 (95 % CI, 1.42-3.55), respectively. Furthermore, a significant trend in the rate of cases was observed with an increasing number of mutated alleles (P for trend = 0.0068). ### Long_Answer: The genotype of the TAP1 gene is associated with susceptibility to CRC. ### Final_Prediction: yes

### Question: Does [ CTLA4-Ig interfere and downregulates the proinflammatory activities of rheumatoid synovial macrophages in monoculture ]? ### Context: CTLA4-Ig, a biologic agent employed in rheumatoid arthritis (RA) treatment, downregulates the immune response and exerts anti-inflammatory effects acting on different cells including dendritic/T cells interaction and directly on osteoclasts. We investigated the anti-inflammatory effects of CTLA4-Ig in primary monocultures of RA synovial macrophages (SM).SM were obtained, from 8 RA patients (7 F, 1 M; DAS28>5.2) who underwent therapeutic arthroscopic synoviectomy and were cultured in the absence and in the presence of CTLA4-Ig at the concentration of [500 microg/ml], the most reliable dose related to the previous pharmacological clinical and experimental experiences. Inflammatory cytokine (IL-6, TNFalpha, IL-1beta) expression was evaluated by immunocytochemistry (ICC with relative image analysis), western blot (WB), and quantitative real-time polymerase chain reaction (qRT-PCR).ICC analysis revealed that CTLA4-Ig treatment significantly downregulated cytokine expression (p<0.001 for IL-6, TNFalpha and IL-1beta) when compared to untreated RA SM. WB and qRT-PCR confirmed partially the data. ### Long_Answer: CTLA4-Ig was found to exert a direct and significant anti-inflammatory effect on primary monocultures of RA SM, suggesting a therapeutic power in different phases of the disease activity. ### Final_Prediction: yes

### Question: Are monitor units predictive of neutron dose for high-energy IMRT? ### Context: Due to the substantial increase in beam-on time of high energy intensity-modulated radiotherapy (>10 MV) techniques to deliver the same target dose compared to conventional treatment techniques, an increased dose of scatter radiation, including neutrons, is delivered to the patient. As a consequence, an increase in second malignancies may be expected in the future with the application of intensity-modulated radiotherapy. It is commonly assumed that the neutron dose equivalent scales with the number of monitor units.Measurements of neutron dose equivalent were performed for an open and an intensity-modulated field at four positions: inside and outside of the treatment field at 0.2 cm and 15 cm depth, respectively.It was shown that the neutron dose equivalent, which a patient receives during an intensity-modulated radiotherapy treatment, does not scale with the ratio of applied monitor units relative to an open field irradiation. Outside the treatment volume at larger depth 35% less neutron dose equivalent is delivered than expected. ### Long_Answer: The predicted increase of second cancer induction rates from intensity-modulated treatment techniques can be overestimated when the neutron dose is simply scaled with monitor units. ### Final_Prediction: no

### Question: Is polymorphisms of GSTP1 associated with differences of chemotherapy response and toxicity in breast cancer? ### Context: Although chemotherapy is one of the most important treatments of breast cancer, it is limited by significant inter-individual variations in response and toxicity. The metabolism of epirubicin (EPI) and cyclophosphamide (CTX) is mainly mediated by cytochrome P450s (CYPs) and glutathione S-transferases (GSTs). It has been well-known that the activities of these enzymes are polymorphic in population due to their genetic polymorphisms. The aim of this research was to examine the effects of genetic polymorphisms in CYP3A, GSTP1 and MDR1 genes on treatment response and side-effects of breast cancer patients receiving EPI/CTX chemotherapy.One hundred and twenty patients with stage II or III invasive breast cancer were recruited and treated with three to four cycles of EPI 80 mg/m(2) and CTX 600 mg/m(2) every two weeks. The AJCC TNM staging system (sixth edition) was used to evaluate the pathological response of primary tumor and axillary lymph nodes. The genotypes of gene polymorphisms were determined by using PCR-restriction fragment length polymorphism methods.Patients carrying GSTP1 (105)Ile/Val or (105)Ile/Ile genotype were more likely to have good response (OR, 0.40; 95%CI, 0.16 - 0.96; P = 0.024) and light toxicity (OR, 0.35; 95%CI, 0.13 - 0.78; P = 0.006) than those carrying (105)Val/Val genotypes. The response to the treatment was not correlated with estrogen receptor, progesterone receptor and Her2/neu status of tumors. No correlation was found between toxicity effect and patient's age, tumor staging, menopause status, and dose intensity of the drugs. ### Long_Answer: GSTP1 polymorphism was associated with the chemotherapy response or adverse effects of EPI and CTX regimens. ### Final_Prediction: yes

### Question: Can upfront systemic chemotherapy replace stereotactic radiosurgery or whole brain radiotherapy in the treatment of non-small cell lung cancer patients with asymptomatic brain metastases? ### Context: The optimal treatment for non-small cell lung cancer (NSCLC) patients with asymptomatic brain metastasis is still controversial. This study aimed to analyze the outcome for various treatment modalities including chemotherapy only, upfront whole brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS) in NSCLC patients with asymptomatic brain metastases.We retrospectively reviewed the medical records of patients with histopathologically proven NSCLC and synchronous asymptomatic brain metastasis between January 2003 and December 2007.From the database, 741 NSCLC patients were identified to have been diagnosed of brain metastases during initial staging or follow-up between January 2003 and December 2007. Of 741 NSCLC patients, 135 (18%) NSCLC patients were identified to have synchronous brain metastasis without associated symptoms. Of the 129 patients included in the analysis, 78 (57.8%) patients received systemic chemotherapy only, 27 (20.0%) upfront WBRT followed by chemotherapy and 24 (17.8%) patients received upfront SRS and chemotherapy. There was no significant difference in overall survival among three groups (systemic chemotherapy alone, 13.9 versus upfront SRS followed by chemotherapy, 22.4 versus upfront WBRT followed by chemotherapy, 17.7 months, respectively; P=0.86). Subset analysis of 110 adenocarcinoma patients showed that the median OS for patients treated with upfront SRS was longer than those of upfront WRBT (29.3 months versus 17.7 months; P=0.01) or chemotherapy alone (29.3 months versus 14.6 months; P=0.04). ### Long_Answer: This study suggested a potential role of systemic chemotherapy alone or upfront SRS followed by chemotherapy instead of WBRT as an initial treatment of NSCLC patients with synchronous, asymptomatic brain metastases. The optimal treatment modality, however, needs to be defined in prospective trials for this subset of patients. ### Final_Prediction: nan

### Question: Does the glutathione depleting agent diethylmaleate prolong renal allograft survival? ### Context: Intercellular adhesion molecule 1 (ICAM-1) plays an important role in mediating allograft rejection through its role in cellular trafficking and as an important costimulatory signal mediating T cell activation. We have previously reported that systemic administration of the glutathione (GSH) depleting agent diethylmaleate (DEM) prevents upregulation of ICAM-1 in various inflammatory models, suggesting that this agent may offer benefit in preventing allograft rejection. Thus we evaluated the effects of DEM in a murine model of renal transplantation.Kidneys from C57BL/6 mice were transplanted into MHC incompatible C3H mice. Donors were treated with DEM 1 h prior to sacrifice, whereas recipients received DEM 1 h following transplantation. Animals were followed until the time of death. In separate studies, renal ICAM-1 mRNA expression was evaluated by polymerase chain reaction and the CD4(+) T cell cytokine profile evaluated in a mixed lymphocyte reaction using C3H responder splenocytes and C57BL/6 stimulator cells.Pretreatment with DEM increased survival from 18.9 +/- 3.6 to 30.6 +/- 10 days (P < 0.05). This increase in survival was associated with a reduction in renal ICAM-1 mRNA expression. Mixed lymphocyte cultures derived from animals pretreated with DEM demonstrated a reduction in the Th1 cytokines IFN-gamma and IL-2 and an increase in the Th2 cytokines IL-4 and IL-10. ### Long_Answer: Administration of DEM with consequent systemic GSH depletion significantly reduces allograft ICAM-1 expression and prolongs graft survival. Although speculative, a shift from a Th1 to a Th2 cytokine response raises the possibility that tolerance induction plays a role in prolonged allograft survival. ### Final_Prediction: yes

### Question: Do colorectal cancer cases and relatives of cases indicate similar willingness to receive and disclose genetic information? ### Context: Recent developments in genetic testing allow us to detect individuals with inherited susceptibility to some cancers. Genetic testing to identify carriers of cancer-related mutations may help lower risk by encouraging preventive behaviors and surveillance. This study assessed willingness of colon cancer cases and relatives to receive genetic information that may indicate an increased risk for cancer, to whom they would disclose genetic information, and whether receiving genetic test results may influence future prevention behaviors among individuals enrolled in the Seattle Colorectal Cancer Family Registry.Incident invasive colorectal cancer cases were identified from the Puget Sound Surveillance Epidemiology and End Results (SEER) registry. In 2007, a sequential sample of cases and relatives (n = 147) were asked to respond to a questionnaire addressing study aims. The questionnaire was administered during a baseline or 5-year follow-up interview.Patterns of response to each statement were similar between colorectal cancer cases and relatives. Both colorectal cases (95%) and relatives (95%) reported willingness to receive genetic information. Nearly all participants would tell their doctor the results of a genetic test (99% of cases; 98% of relatives), and all married participants would tell their spouses. Cases (96%) anticipated being slightly more likely than relatives (90%) to change their cancer screening behavior, but this difference was not statistically significant (p = 0.33). ### Long_Answer: A high percentage of both colorectal cancer cases and relatives sampled from the Seattle Colorectal Cancer Family Registry are interested in identifying their genetic status, discussing their genetic status with their family and doctor, and adopting behavioral changes that may reduce cancer risk. ### Final_Prediction: yes

### Question: Are gastric precancerous lesions associated with gene variants in Helicobacter pylori-susceptible ethnic Malays? ### Context: To identify genes associated with gastric precancerous lesions in Helicobacter pylori (H. pylori)-susceptible ethnic Malays.Twenty-three Malay subjects with H. pylori infection and gastric precancerous lesions identified during endoscopy were included as "cases". Thirty-seven Malay subjects who were H. pylori negative and had no precancerous lesions were included as "controls". Venous blood was collected for genotyping with Affymetrix 50K Xba1 kit. Genotypes with call rates < 90% for autosomal single nucleotide polymorphisms (SNPs) were excluded. For each precancerous lesion, associated SNPs were identified from Manhattan plots, and only SNPs with a χ² P value < 0.05 and Hardy Weinberg Equilibrium P value > 0.5 was considered as significant markers.Of the 23 H. pylori-positive subjects recruited, one sample was excluded from further analysis due to a low genotyping call rate. Of the 22 H. pylori-positive samples, atrophic gastritis only was present in 50.0%, complete intestinal metaplasia was present in 18.25%, both incomplete intestinal metaplasia and dysplasia was present in 22.7%, and dysplasia only was present in 9.1%. SNPs rs9315542 (UFM1 gene), rs6878265 (THBS4 gene), rs1042194 (CYP2C19 gene) and rs10505799 (MGST1 gene) were significantly associated with atrophic gastritis, complete intestinal metaplasia, incomplete metaplasia with foci of dysplasia and dysplasia, respectively. Allele frequencies in "cases" vs "controls" for rs9315542, rs6878265, rs1042194 and rs10505799 were 0.4 vs 0.06, 0.6 vs 0.01, 0.6 vs 0.01 and 0.5 vs 0.02, respectively. ### Long_Answer: Genetic variants possibly related to gastric precancerous lesions in ethnic Malays susceptible to H. pylori infection were identified for testing in subsequent trials. ### Final_Prediction: yes

### Question: Is 99mTc-phytate better than 99mTc-human serum albumin as a radioactive tracer for sentinel lymph node biopsy in breast cancer? ### Context: Several radioactive agents are used for sentinel lymph node biopsy (SLNB) in breast cancer, but we are still unsure which of these is best. We retrospectively compared the effectiveness of two radioactive agents, 99mTc-phytate and 99mTc-human serum albumin (HSA), when used in combination with blue dye.A consecutive series of 533 clinically node-negative patients with a collective 539 breast carcinomas were divided into two groups for treatment with SLNB. The HSA-group consisted of 264 patients (with a collective 266 breast cancers) and the P-group consisted of 269 patients (with a collective 273 breast cancers) treated with 99mTc-HSA and 99mTc-phytate, respectively, in combination with blue dye. We analyzed the identification and radioactivity of SLNs in the two groups.The identification rate of SLN was significantly higher in the P-group than in the HSA-group. The same results were produced by analysis using the radioactive agent alone, but not by using the blue dye alone. Most importantly, the highest radioactivity of SLNs per case was more than five times higher in the P-group than in the HSA-group, and this difference was significant. ### Long_Answer: Our historical analysis of the two radioactive agents used in different periods could not exclude the influence of the improved skill of the surgeons. However, because the specific accumulation of phytate in SLNs was greater than that of HSA, phytate might result in a higher SLN identification rate. Thus, 99mTc-phytate is better than 99mTc-HSA as a radioactive agent for SLNB in breast cancer. ### Final_Prediction: yes

### Question: Is visfatin associated with inflammatory markers in patients on hemodialysis? ### Context: Cardiovascular events are a major cause of death in patients with end-stage renal disease. Endothelial dysfunction represents a key event in atherosclerosis development and has been implicated in the pathophysiology of different forms of cardiovascular disease, including chronic kidney disease. In recent years, visfatin, a ubiquitous adipokine, has been described as a potent marker of endothelial inflammation and dysfunction. The aim of the study was to investigate the association of visfatin with well-known markers of inflammation and endothelial dysfunction.Serum and plasma samples from 66 patients (40 males and 26 females) treated by hemodialysis were analysed for visfatin, fibrinogen, CRP, PAI-1 levels. Visfatin was determined by ELISA method while CRP, fibrinogen and PAL-1 were obtained by standard laboratory methods.We observed statistically significant correlation between visfatin level and fibrinogen (r = 0.51; p = 0.008) and the time on dialysis in female patients (r = 0.70; p < 0.001). PAI-1 and CRP did not correlate with visfatin in males nor in females. ### Long_Answer: Visfatin is correlated with time on dialysis and with fibrinogen only in female dialysis patients. To confirm this, further studies are needed with a higher number of patients. ### Final_Prediction: no

### Question: Does dexamethasone protect neonatal hypoxic-ischemic brain injury via L-PGDS-dependent PGD2-DP1-pERK signaling pathway? ### Context: Glucocorticoids pretreatment confers protection against neonatal hypoxic-ischemic (HI) brain injury. However, the molecular mechanism remains poorly elucidated. We tested the hypothesis that glucocorticoids protect against HI brain injury in neonatal rat by stimulation of lipocalin-type prostaglandin D synthase (L-PGDS)-induced prostaglandin D2 (PGD2)-DP1-pERK mediated signaling pathway.Dexamethasone and inhibitors were administered via intracerebroventricular (i.c.v) injections into 10-day-old rat brains. Levels of L-PGD2, D prostanoid (DP1) receptor, pERK1/2 and PGD2 were determined by Western immunoblotting and ELISA, respectively. Brain injury was evaluated 48 hours after conduction of HI in 10-day-old rat pups.Dexamethasone pretreatment significantly upregulated L-PGDS expression and the biosynthesis of PGD2. Dexamethasone also selectively increased isoform pERK-44 level in the neonatal rat brains. Inhibitors of L-PGDS (SeCl4), DP1 (MK-0524) and MAPK (PD98059) abrogated dexamethasone-induced increases in pERK-44 level, respectively. Of importance, these inhibitors also blocked dexamethasone-mediated neuroprotective effects against HI brain injury in neonatal rat brains. ### Long_Answer: Interaction of glucocorticoids-GR signaling and L-PGDS-PGD2-DP1-pERK mediated pathway underlies the neuroprotective effects of dexamethasone pretreatment in neonatal HI brain injury. ### Final_Prediction: yes

### Question: Does renal artery revascularization improve heart failure control in patients with atherosclerotic renal artery stenosis? ### Context: Renal artery stenosis (RAS) impacts the pathogenesis and control of heart failure (HF) and may further contribute to increased cardiovascular morbidity and mortality in HF patients. However, the long-term effects of renal artery revascularization on cardiovascular outcomes in HF patients are not well studied.The prevalence of HF and its effects on all-cause mortality were studied in 163 consecutive patients with systemic hypertension and chronic kidney disease (serum creatinine >2 mg/dL) who underwent percutaneous transluminal renal angioplasty (PTRA) with stenting for atherosclerotic RAS. In addition, in 100 patients with RAS and coexistent HF, we compared the impact of medical treatment (n = 50) versus PTRA (n = 50) on clinical outcomes.HF (predominantly normal ejection fraction) was present in 50/163 (31%) patients with systemic hypertension and chronic kidney disease (serum creatinine >2 mg/ dL) undergoing PTRA for RAS and represented the major predictor of all-cause mortality in these patients. When compared with sex-matched RAS and HF patients treated medically, PTRA with stenting was associated with a significant decrease in the New York Heart Association Functional Class (1.9 +/- 0.8 versus 2.6 +/- 1.0, P < 0.04) and a 5-fold reduction in the number of hospitalizations. However, renal artery revascularization did not impact mortality. ### Long_Answer: HF was present in one-third of patients with renal dysfunction and atherosclerotic RAS who were referred for PTRA. The presence of HF was associated with a significantly increased risk of death after PTRA with stenting. Renal artery revascularization resulted in improved HF control and a reduction in HF hospitalizations. ### Final_Prediction: yes

### Question: Does protease inhibitor therapy improve protein catabolism in prepubertal children with HIV infection? ### Context: Past studies in adults have reported that loss of lean tissue mass (LTM) is associated with accelerated rates of protein catabolism. To date, studies of protein kinetics from pediatric patients infected by HIV have not been published; however, poor linear growth and weight loss are well-documented. The first aim of this study was to test the hypothesis that protein catabolism is high in pediatric patients with HIV. Protease inhibitors (PI) have proven to be effective therapy for pediatric HIV patients. One action of these drugs is that of lowering the viral burden, and several studies suggest that these drugs result in increased growth and weight velocity. Our second aim was to determine whether PI therapy improves protein catabolism.We studied eight children infected with HIV (ages 2.9-6.2 years, Tanner stage I, CD4 counts 100,000-300,000, 5 F/3 M) and eight healthy age- and gender-matched controls. Measures of protein turnover were conducted using the stable isotope [1-(13C)]leucine. Body composition was measured by dual X-ray absorptiometry (DXA) scan for determination of LTM, and indirect calorimetry for measurement of resting energy expenditure. Children with HIV infection were studied at baseline and after 6 weeks of PI therapy; control children were studied only once.Protein catabolism, represented as leucine rate of appearance (Ra) in the fasted state, was higher in the HIV-infected children at baseline compared to control children. After 6 weeks of PI therapy, leucine Ra decreased, but not to the range found in control children. Leucine Ra correlated with viral burden. LTM significantly improved in all patients. ### Long_Answer: These results suggest that similar to HIV-infected adults, HIV-infected children have higher than normal protein catabolism. Furthermore, our measures suggest that short-term PI therapy results in improved protein catabolism and LTM. ### Final_Prediction: yes

### Question: Is anal human papillomavirus infection associated with HIV acquisition in men who have sex with men? ### Context: Human papillomavirus (HPV) is a common sexually transmitted agent that causes anogenital cancer and precancer lesions that have an inflammatory infiltrate, may be friable and bleed. Our aim was to determine the association between anal HPV infection and HIV acquisition.A prospective cohort study.We recruited 1409 HIV-negative men who have sex with men from a community-based setting in Boston, Denver, New York and San Francisco. We used Cox proportional hazards regression modeling and assessed the independent association of HPV infection with the rate of acquisition of HIV infection.Of 1409 participants contributing 4375 person-years of follow-up, 51 HIV-seroconverted. The median number of HPV types in HPV-infected HIV-seroconverters was 2 (interquartile range 1-3) at the time of HIV seroconversion. After adjustment for sexual activity, substance use, occurrence of other sexually transmitted infections and demographic variables, there was evidence (P = 0.002) for the effect of infection with at least two HPV types (hazard ratio 3.5, 95% confidence interval 1.2-10.6) in HIV seroconversion. ### Long_Answer: Anal HPV infection is independently associated with HIV acquisition. Studies that incorporate high-resolution anoscopy to more accurately identify HPV-associated disease are needed to determine the relationship between HPV-associated disease and HIV seroconversion. ### Final_Prediction: yes

### Question: Is dyslipidemia in rat fed with high-fat diet associated with PCSK9-LDL-receptor pathway but ageing? ### Context: Obesity is associated with unfavorable alternations in plasma lipid profile and a broad spectrum of cardio-metabolic disorders. Proprotein convestase subtilisin kexin type 9 (PCSK9) is a novel circulating protein that promotes hypercholesterolemia by decreasing hepatic low lipoprotein density receptor (LDLR) protein. However, the relationship between PCSK9 concentration and lipid profile in an obesity condition has less been investigated.To examine the changes of plasma PCSK9 concentration in a rat model fed with high fat diet (HFD) and its correlation to lipid profile, body weight and ageing.Twenty male Sprague Dawley (SD) rats were divided into two groups, control group (fed with normal pellet for 4 weeks), and high-fat diet group (fed with 3% cholesterol enrich diet for 4 weeks). Blood samples of rats were obtained before and at days 14, 21, and 28 in both groups. The body weight, plasma metabolic parameters (glucose, lipid profile) and PCSK9 were determined at indicated time points.The body weights were significantly increased in rats fed with HFD compared to that in rats with normal pellets at day 28. Additionally, total cholesterol (TC), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C) levels in rat fed with HFD were also higher than that in rats fed with control diet while decreased high density lipoprotein cholesterol (HDL-C) levels were found in rats with HFD at day 28. More interesting, there were no differences of plasma PCSK9 concentrations as well as hepatic expression of LDLR between the two groups at day 28. ### Long_Answer: Although the body weight and LDL-C were significantly increased in rats fed with HFD at 4 weeks, there were no differences of changes in plasma PCSK9 concentration and LDLR expression of liver tissue in both groups at baseline and day 28, suggesting that dyslipidemia in the rat model with HFD appears not to be associated with PCSK9-LDLR pathway but ageing. ### Final_Prediction: no

### Question: Social support among African Americans with heart failure: is there a role for community health advisors? ### Context: The study had 2 objectives: (1) to gather the observations of community health advisors (CHAs) on the role of social support in the lives of African Americans; and (2) to develop a lay support intervention framework, on the basis of the existing literature and observations of CHAs, depicting how social support may address the needs of African American patients with heart failure.Qualitative data were collected in semistructured interviews among 15 CHAs working in African American communities in Birmingham, Alabama.Prominent themes included the challenge of meeting clients' overlapping health care and general life needs, the variation in social support received from family and friends, and the opportunities for CHAs to provide multiple types of social support to clients. CHAs also believed that their support activities could be implemented among populations with heart failure. ### Long_Answer: The experience of CHAs with social support can inform a potential framework of a lay support intervention among African Americans with heart failure. ### Final_Prediction: nan

### Question: Does the Z-cad dual fluorescent sensor detect dynamic changes between the epithelial and mesenchymal cellular states? ### Context: The epithelial to mesenchymal transition (EMT) has been implicated in metastasis and therapy resistance of carcinomas and can endow cancer cells with cancer stem cell (CSC) properties. The ability to detect cancer cells that are undergoing or have completed EMT has typically relied on the expression of cell surface antigens that correlate with an EMT/CSC phenotype. Alternatively these cells may be permanently marked through Cre-mediated recombination or through immunostaining of fixed cells. The EMT process is dynamic, and these existing methods cannot reveal such changes within live cells. The development of fluorescent sensors that mirror the dynamic EMT state by following the expression of bona fide EMT regulators in live cells would provide a valuable new tool for characterizing EMT. In addition, these sensors will allow direct observation of cellular plasticity with respect to the epithelial/mesenchymal state to enable more effective studies of EMT in cancer and development.We generated a lentiviral-based, dual fluorescent reporter system, designated as the Z-cad dual sensor, comprising destabilized green fluorescent protein containing the ZEB1 3' UTR and red fluorescent protein driven by the E-cadherin (CDH1) promoter. Using this sensor, we robustly detected EMT and mesenchymal to epithelial transition (MET) in breast cancer cells by flow cytometry and fluorescence microscopy. Importantly, we observed dynamic changes in cellular populations undergoing MET. Additionally, we used the Z-cad sensor to identify and isolate minor subpopulations of cells displaying mesenchymal properties within a population comprising predominately epithelial-like cells. The Z-cad dual sensor identified cells with CSC-like properties more effectively than either the ZEB1 3' UTR or E-cadherin sensor alone. ### Long_Answer: The Z-cad dual sensor effectively reports the activities of two factors critical in determining the epithelial/mesenchymal state of carcinoma cells. The ability of this stably integrating dual sensor system to detect dynamic fluctuations between these two states through live cell imaging offers a significant improvement over existing methods and helps facilitate the study of EMT/MET plasticity in response to different stimuli and in cancer pathogenesis. Finally, the versatile Z-cad sensor can be adapted to a variety of in vitro or in vivo systems to elucidate whether EMT/MET contributes to normal and disease phenotypes. ### Final_Prediction: yes

### Question: Are alterations in plasma protease concentrations during labor associated with poor obstetric outcomes? ### Context: The purpose of this study was to assess the association between abnormal connective tissue remodeling during labor as reflected by plasma concentrations of extracellular matrix remodeling proteolytic enzymes and adverse obstetric outcomes.A prospective observational study of 176 nulliparous women who attended the antenatal clinics at the Mercy Hospital for Women (Melbourne, Australia) from 1999 to 2000.Patients with a prolonged second stage (>120 minutes) had a significantly increased plasma concentration of matrix metalloproteinase 9 after delivery compared with control subjects (P<.001); patients in labor who underwent an emergency caesarean delivery had a significantly lower concentration (P<.001). Patients with a prolonged duration of labor (>11 hours) had a significantly lower urokinase plasminogen activator plasma concentration compared with control subjects (P<.01). ### Long_Answer: Altered plasma concentrations of extracellular matrix remodeling proteolytic enzymes, matrix metalloproteinase 9, and urokinase plasminogen activator were found to be associated with abnormal labor and delivery outcomes. This finding may provide a useful predictor of abnormal obstetric outcomes. ### Final_Prediction: nan

### Question: Does systolic blood pressure in childhood predict hypertension and metabolic syndrome later in life? ### Context: The goal was to link hypertension and the metabolic syndrome in adulthood directly to blood pressures measured decades earlier for the same individuals as children and to establish criterion values for blood pressure that predict hypertension and the metabolic syndrome later in life.We analyzed serial data for 240 men and 253 women in the Fels Longitudinal Study. We derived age- and gender-specific childhood blood pressures that predict hypertension and the metabolic syndrome in adulthood, and we validated these criterion values in a larger sample.Blood pressure diverged between adults with and without the metabolic syndrome beginning at age 5 for boys and age 8 for girls. The odds ratios for developing hypertension at > or = 30 years of age ranged from 1.1 for 14- to 18-year-old boys to 3.8 for 5- to 7-year-old boys and from 2.7 for 8- to 13-year-old girls to 4.5 for 5- to 7-year-old girls, if their blood pressure exceeded criterion values at a single examination in childhood. The corresponding odds ratios for the metabolic syndrome, with or without hypertension, ranged from 1.2 for 14- to 18-year-old boys to 2.6 for 8- to 13-year-old boys and from 1.5 for 14- to 18-year-old girls to 3.1 for 5- to 7-year-old girls. The relative risk of adult hypertension ranged from 1.5 to 3.8 for boys and from 1.5 to 4.7 for girls, and that of the metabolic syndrome ranged from 1.1 to 1.8 for boys and from 1.2 to 5.6 for girls. These relative risks varied directly with the number of examinations at which systolic blood pressure exceeded criterion values. ### Long_Answer: Children with systolic blood pressures above the criterion values established in this longitudinal study are at increased risk of hypertension and the metabolic syndrome later in life. ### Final_Prediction: yes

### Question: Is there any relationship between plasma antioxidant capacity and lung function in smokers and in patients with chronic obstructive pulmonary disease? ### Context: It has been suggested that oxidative stress is an important factor in the pathogenesis of chronic obstructive pulmonary disease (COPD). We have shown that an oxidant/antioxidant imbalance occurs in the distal air spaces of smokers and in patients with COPD which is reflected systemically in the plasma. A study was undertaken to determine whether plasma antioxidant status correlated with lung function as assessed by forced expiratory volume in one second (FEV(1)) and forced vital capacity (FVC) in smokers and patients with COPD.Plasma antioxidant capacity, assessed by the Trolox equivalent antioxidant capacity (TEAC) as an index of overall systemic oxidative stress, and protein thiol levels were measured in 95 patients with stable COPD, in 82 healthy smokers, and in 37 healthy non-smokers.Mean (SE) plasma TEAC levels were significantly decreased in patients with COPD (0.81 (0.03) mmol/l, p<0.001) and in healthy smokers (0.87 (0.04) mmol/l, p<0. 001) compared with healthy non-smokers (1.31 (0.11) mmol/l). The mean differences in plasma antioxidant capacity (mM) were (0.81, 95% confidence interval (CI) 0.22 to 1.48), (0.87, 95% CI 0.2 to 1.46), and (1.31, 95% CI 1.09 to 1.58) in patients with COPD, healthy smokers, and healthy non-smokers, respectively. This reduction was associated with a 29% (95% CI 18 to 38) and a 30% (95% CI 19 to 40) decrease in plasma protein thiol levels in COPD patients and smokers, respectively. Current smoking was not the main contributor to the reduction in antioxidant capacity in patients with COPD as those patients who were still smokers had similar TEAC levels (mean (SE) 0. 78 (0.05); n = 25) to those who had stopped smoking (0.84 (0.02); n = 70). No significant correlations were found between spirometric data measured as FEV(1) % predicted or FEV(1)/FVC % predicted and the plasma levels of TEAC in patients with COPD, healthy smokers, or healthy non-smokers. Similarly, there was no significant correlation between FEV(1) % predicted or FEV(1)/FVC % predicted and the levels of plasma protein thiols in the three groups. ### Long_Answer: These data confirm decreased antioxidant capacity in smokers and patients with COPD, indicating the presence of systemic oxidative stress. However, no relationship was found between protein thiols or TEAC levels and measurements of airflow limitation in either smokers or in patients with COPD. ### Final_Prediction: nan

### Question: Is overabundant FANCD2 , alone and combined with NQO1 , a sensitive marker of adverse prognosis in breast cancer? ### Context: Defective DNA repair is central to the progression and treatment of breast cancer. Immunohistochemically detected DNA repair markers may be good candidates for novel prognostic and predictive factors that could guide the selection of individualized treatment strategies.We have analyzed nuclear immunohistochemical staining of BRCA1, FANCD2, RAD51, XPF, and PAR in relation to clinicopathological and survival data among 1240 paraffin-embedded breast tumors, and additional gene expression microarray data from 76 tumors. The antioxidant enzyme NQO1 was analyzed as a potential modifier of prognostic DNA repair markers.RAD51 [hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.70-0.94, P = 0.0050] and FANCD2 expression (HR 1.50, 95% CI 1.28-1.76, P = 1.50 × 10(-7)) were associated with breast cancer survival. High FANCD2 expression correlated with markers of adverse prognosis but remained independently prognostic in multivariate analysis (HR 1.27, 95% CI 1.08-1.49, P = 0.0043). The FANCD2-associated survival effect was most pronounced in hormone receptor positive, HER2-negative tumors, and in tumors with above-median NQO1 expression. In the NQO1-high subset, patients belonging to the highest quartile of FANCD2 immunohistochemical scores had a threefold increased risk of metastasis or death (HR 3.10, 95% CI 1.96-4.92). Global gene expression analysis indicated that FANCD protein overabundance is associated with the upregulation of proliferation-related genes and a downregulated nucleotide excision repair pathway. ### Long_Answer: FANCD2 immunohistochemistry is a sensitive, independent prognostic factor in breast cancer, particularly when standard markers indicate relatively favorable prognosis. Taken together, our results suggest that the prognostic effect is linked to proliferation, DNA damage, and oxidative stress; simultaneous detection of FANCD2 and NQO1 provides additional prognostic value. ### Final_Prediction: yes

### Question: Is rotavirus-induced murine biliary atresia mediated by nuclear factor-kappaB? ### Context: Intraperitoneal inoculation of rhesus rotavirus (RRV) was shown to cause atretic-appearing segments of the extrahepatic bile ducts (EHBDs) in a murine model. The factors responsible for the injury of bile ducts, however, remain unknown. In this study, the morphologic status of nuclear factor- kappa B (NF- kappa B) activation in the liver and in the EHBDs from murine model of biliary atresia induced by intraperitoneal injection of rotavirus was investigated.Within the first 24 hours of life, the newborn mice were infected through intraperitoneal route with a volume of 50 microL containing different titers of RRV. The pups were killed on days 5, 10, 15, 21, and 28 after inoculation and prepared under a dissecting microscope with photographic documentation. Consecutive sections of specimens were stained with H & E and used for histopathologic studies. The methods of modified Vision immunohistochemical staining was used to detect viral antigen of VP7 and active NF- kappa B. The distribution and intensity of staining were analyzed by image analysis software (GT-2 model, Huakang Co, Chengdu, China).The viral antigen was detected by immunohistochemical staining in specimens from experimental groups on day 5 after infection. The occlusion of the EHBDs could be visualized after intraperitoneal injection of 10(7) plaque-forming unit (pfu) of RRV, whereas the incidence of cholestasis was reduced with an infection dosage of 10(6) pfu or less. Obliteration of the EHBDs did not occur when the injection dosage of RRV was reduced to 10(5) pfu or when inoculation of 10(7) pfu of RRV was combined with pyrolidine dithiocarbamate (PDTC), a chemical inhibitor of active NF- kappa B. The antigen of active NF- kappa B was detected by immunohistochemical staining in the liver and in the EHBDs from pups after inoculation of 10(7), 10(6), and 10(5) pfu RRV. Low or no expression of active NF- kappa B was noted in the specimens obtained from the control group. As the inflammatory reaction in the liver and in the EHBDs gradually subsided on day 28 after inoculation, the expression of active NF- kappa B also decreased. The expression of active NF- kappa B after injection of RRV combined with PDTC was similar to the expression in the control group on days 5 and 10 after infection. ### Long_Answer: The authors found that occlusion of the EHBDs could be noted in pups after inoculation of 10(7) pfu RRV. Meanwhile, the expression of active NF- kappa B in the liver and in the EHBDs was increased after inoculation of RRV. Simultaneous intraperitoneal injection of PDTC, however, was shown to prevent the obstruction of EHBDs secondary to inoculation of RRV. These results show that the murine biliary atresia induced by RRV is mediated by active NF- kappa B. ### Final_Prediction: yes

### Question: Cogan I syndrome: too often detected too late? ### Context: Cogan's syndrome is an uncommon disease characterized by ocular inflammation, vestibuloauditory dysfunction and symptoms of systemic disease. The etiology is unknown, however there is evidence for an autoimmune pathogenesis. The "typical" Cogan's syndrome presents as bilateral interstitial keratitis and progressing vestibuloauditory dysfunction. The presence of other inflammatory manifestations in addition of keratitis has been termed as "atypical" Cogan's syndrome.We report on six patients presenting with typical as well as atypical ocular manifestations between 1982 and 1994. Typically, the illness was accompanied by systemic symptoms. Each patient had audiovestibular involvement, that was the initial presentation in 4 cases. Vestibular dysfunction often preceded hearing loss. Five of our patients not only presented with keratitis but also demonstrated signs of ocular inflammation diagnosed as scleritis or episcleritis. In two patients these ocular symptoms were the first signs of Cogan's syndrome, recurred periodically and did not respond to corticosteroids.In 3 patients that were diagnosed early and treatment with corticosteroids was initiated early, hearing could be stabilized, in the remaining patients total bilateral deafness could not be prevented. ### Long_Answer: The importance of being aware that vestibuloauditory dysfunction may occur in patients with ocular inflammation, and the fact that early immunotherapy may prevent the risk of deafness, has to be emphasized. ### Final_Prediction: nan

### Question: Is the vasodilatory response of skin microcirculation to local heating subject to desensitization? ### Context: In humans, local heating increases skin perfusion by mechanisms dependent on nitric oxide (NO). Because the vascular effects of NO may be subject to desensitization, we examined whether a first local thermal stimulus would attenuate the hyperemic response to a second one applied later.Twelve healthy young men were studied. Skin blood flow (SkBF) was measured on forearm skin with laser Doppler imaging. Local thermal stimuli (temperature step from 34 to 41 degrees C maintained for 30 minutes) were applied with temperature-controlled chambers. We also tested the influence of prior local heating on the vasodilation induced by sodium nitroprusside (SNP), a donor of NO.On reheating the same spot after two hours, the response of SkBF (i.e., plateau SkBF at 30 minutes minus SkBF at 34 degrees C) was lower than during the first stimulation (mean+/-SD 404+/-212 perfusion units [PU] vs. 635+/-100 PU; P<0.001). There was no such difference when reheating after four hours (654+/-153 vs. 645+/-103 PU; P=NS). Two, but not four, hours after local heating, the response of SkBF to SNP was reduced. ### Long_Answer: The NO-dependent hyperemic response induced by local heating in human skin is subject to desensitization. At least one part of the mechanism implicated consists of a desensitization to the effects of NO itself. ### Final_Prediction: yes

### Question: Are nurse-facilitated preparation and life completion interventions acceptable and feasible in the Australian palliative care setting : results from a phase 2 trial? ### Context: Existential/spiritual needs of advanced cancer patients are not always met in healthcare. Potential barriers for health professionals exploring existential concerns include lack of time, training, tools, and confidence. Yet patients with life-threatening illnesses require holistic care, and interest in their existential/spiritual needs is growing. Preparation and life completion interventions have shown positive results in the existential/spiritual care of hospice-eligible patients in the United States. Nurses are in the ideal position to deliver such interventions, but have not been previously evaluated in this context.The objective of this study was to explore the acceptability and feasibility of a nurse-facilitated preparation and life completion intervention (Outlook) in an Australian palliative care patient population.Patients discussed their life story, forgiveness, and heritage and legacy over 3 audiotaped sessions. Preintervention/postintervention outcome measures included the Memorial Symptom Assessment Scale, Functional Assessment of Cancer Therapy-Spirituality Well-being, Profile of Mood States, Quality of Life at End of Life Scale, and Center for Epidemiological Depression Scale. Participant feedback was subjected to thematic analysis to understand the patient experience of receiving the intervention.Ten palliative care patients with advanced cancer completed the study. Patients reported the intervention and assessments to be acceptable and feasible and to be overall positively received although with nonsignificant improvements in measures of "meaning and peace" and "preparation for end of life." ### Long_Answer: A nurse-facilitated preparation and life completion intervention is acceptable and feasible for palliative care patients with advanced cancer in Australia. ### Final_Prediction: yes

### Question: Is jNK suppression essential for 17β-Estradiol inhibits prostaglandin E2-Induced uPA and MMP-9 expressions and cell migration in human LoVo colon cancer cells? ### Context: Epidemiological studies demonstrate that the incidence and mortality rates of colorectal cancer in women are lower than in men. However, it is unknown if 17β-estradiol treatment is sufficient to inhibit prostaglandin E2 (PGE2)-induced cellular motility in human colon cancer cells.We analyzed the protein expression of urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA), matrix metallopeptidases (MMPs), plasminogen activator inhibitor-1 (PAI-1) and tissue inhibitor of metalloproteinases (TIMPs), and the cellular motility in PGE2-stimulated human LoVo cells. 17β-Estradiol and the inhibitors including LY294002 (Akt activation inhibitor), U0126 (ERK1/2 inhibitor), SB203580 (p38 MAPK inhibitor), SP600125 (JNK1/2 inhibitor), QNZ (NFκB inhibitor) and ICI 182 780 were further used to explore the inhibitory effects of 17β-estradiol on PGE2-induced LoVo cell motility. Student's t-test was used to analyze the difference between the two groups.Upregulation of urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA) and matrix metallopeptidases (MMPs) is reported to associate with the development of cancer cell mobility, metastasis, and subsequent malignant tumor. After administration of inhibitors including LY294002, U0126, SB203580, SP600125 or QNZ, we found that PGE2 treatment up-regulated uPA and MMP-9 expression via JNK1/2 signaling pathway, thus promoting cellular motility in human LoVo cancer cells. However, PGE2 treatment showed no effects on regulating expression of tPA, MMP-2, plasminogen activator inhibitor-1 (PAI-1), tissue inhibitor of metalloproteinase-1, -2, -3 and -4 (TIMP-1, -2, -3 and -4). We further observed that 17β-estradiol treatment inhibited PGE2-induced uPA, MMP-9 and cellular motility by suppressing activation of JNK1/2 in human LoVo cancer cells. ### Long_Answer: Collectively, these results suggest that 17β-estradiol treatment significantly inhibits PGE2-induced motility of human LoVo colon cancer cells. ### Final_Prediction: yes

### Question: Do psychiatric disorders and their association with burn-related factors in children with burn injury? ### Context: The aim of this study was to assess psychiatric disorders and their association with burn-related factors in a population of Turkish children with burns.Thirty-one children admitted to the Cerrahpasa Medical Faculty Burn Unit between January 2013 and August 2013 were first assessed by the plastic surgeon, and then those with psychological symptoms were referred to a child psychiatrist, and the records were analyzed retrospectively.The percentage of burned area to Total Body Surface Area (TBSA) ranged between 2-60% (mean, 17.3%). Nineteen patients (61.3%) had a psychiatric diagnosis, which included acute stress disorder (ASD) (n=15), depression (n=3), posttraumatic stress disorder (n=2, comorbid with depression), and delirium (n=1). The percentage of burned area to TBSA was associated with the presence of psychopathology and ASD. Further, psychopathology was associated with the number of burned major body regions. ### Long_Answer: Pediatric burn patients are at risk of developing psychopathology. The children with a greater percentage of burned area to TBSA and more burned body regions have the greatest risk of psychopathology. Surgeons have an important role in patient referral for psychiatric interventions, so that psychiatric disorders can be prevented as early as possible. ### Final_Prediction: yes

### Question: Is low-molecular-weight heparin more effective than aspirin in preventing early neurologic deterioration and improving six-month outcome? ### Context: We evaluated the efficacy of low-molecular-weight heparin (LMWH) relative to aspirin in preventing early neurologic deterioration (END), venous thromboembolism (VTE), and outcomes at 6 months.Patients were randomly assigned to receive either subcutaneous enoxaparin 4000 anti-factor Xa IU/0.4 mL twice daily or oral aspirin 200 mg daily for 10 days. After day 10, all subjects received aspirin 100 mg once daily for 6 months. We assessed whether LMWH was superior to aspirin in preventing END and VTE within the first 10 days after index stroke and evaluated 6-month outcomes.Of the total 1368 patients, 7.89% suffered from END, and 2.85% suffered from deep-vein thrombosis during the first 10 days, with a significance difference between the LMWH group and aspirin group (3.95%, 1.46% versus 11.82%, 4.23%, respectively). At 6 months, there was a significant difference in the frequency of good outcomes among patients over the median age of 70 years (LMWH 63.8% versus aspirin 44.6%). The benefit of LMWH was also significant in patients with symptomatic stenosis of the posterior circulation and basilar artery (75.2% and 82% for LMWH versus 40.5% and 48% for aspirin, respectively). ### Long_Answer: For patients with acute ischemic stroke, treatment with LMWH within 48 hours of stroke until 10 days later may reduce END and deep-vein thrombosis during the first 10 days. LMWH appears to have advantages over aspirin in certain subgroups, such as elderly patients and patients with posterior circulation and basilar artery stenosis. ### Final_Prediction: yes

### Question: Apical versus Non-Apical Lead: Is ICD Lead Position Important for Successful Defibrillation? ### Context: We aim to compare the acute and long-term success of defibrillation between non-apical and apical ICD lead position.The position of the ventricular lead was recorded by the implanting physician for 2,475 of 2,500 subjects in the Shockless IMPLant Evaluation (SIMPLE) trial, and subjects were grouped accordingly as non-apical or apical. The success of intra-operative defibrillation testing and of subsequent clinical shocks were compared. Propensity scoring was used to adjust for the impact of differences in baseline variables between these groups. There were 541 leads that were implanted at a non-apical position (21.9%). Patients implanted with a non-apical lead had a higher rate of secondary prevention indication. Non-apical location resulted in a lower mean R-wave amplitude (14.0 vs. 15.2, P<0.001), lower mean pacing impedance (662 ohm vs. 728 ohm, P<0.001), and higher mean pacing threshold (0.70 V vs. 0.66 V, P = 0.01). Single-coil leads and cardiac resynchronization devices were used more often in non-apical implants. The success of intra-operative defibrillation was similar between propensity score matched groups (89%). Over a mean follow-up of 3 years, there were no significant differences in the yearly rates of appropriate shock (5.5% vs. 5.4%, P = 0.98), failed appropriate first shock (0.9% vs. 1.0%, P = 0.66), or the composite of failed shock or arrhythmic death (2.8% vs. 2.3% P = 0.35) according to lead location. ### Long_Answer: We did not detect any reduction in the ICD efficacy at the time of implant or during follow-up in patients receiving a non-apical RV lead. ### Final_Prediction: nan

### Question: Does symptom burden predict nursing home admissions among older adults? ### Context: Symptom burden has been associated with functional decline in community-dwelling older adults and may be responsive to interventions. Known predictors of nursing home (NH) admission are often nonmodifiable.To determine if symptom burden independently predicted NH admission among community-dwelling older adults over an eight and a half-year follow-up period.A random sample of community-dwelling Medicare beneficiaries in Alabama, stratified by race, gender, and rural/urban residence had baseline in-home assessments of sociodemographic measurements, Charlson comorbidity count, and symptoms. Symptom burden was derived from a count of 10 patient-reported symptoms. Nursing home admissions were determined from telephone interviews conducted every six months over the eight and a half years of study. Cox proportional hazard modeling was used to examine the significance of symptom burden as a predictor for NH admission after adjusting for other variables.The mean ± SD age of the sample (N = 999) was 75.3 ± 6.7 years, and the sample was 51% rural, 50% African American, and 50% male. Thirty-eight percent (n = 380) had symptom burden scores ≥2. Seventy-five participants (7.5%) had confirmed dates for NH admission during the eight and a half years of follow-up. Using Cox proportional hazard modeling, symptom burden remained an independent predictor of time to NH placement (hazard ratio = 1.11; P = 0.02), even after adjustment for comorbidity count, race, sex, and age. ### Long_Answer: Symptom burden is an independent risk factor for NH admission. Aggressive management of symptoms in older adults may reduce or delay NH admission. ### Final_Prediction: yes

### Question: Does [ Eosinophilic esophagitis lead to dysphagia in a 18-year-old boy -- case report ]? ### Context: Eosinophilic esophsgitis (EE) is a chronic inflammatory disease of the esophagus which is characterized by isolated eosinophilic infiltrations within squamous esophageal epithelium and by macroscopic lesions which lead to clinical symptoms of the disease. The aim of the work is presentation of the case of EE in a boy, together with discussion of epidemiology, pathophysiology, clinical symptoms and treatment basing on current literature. A case of a 18-years old boy with a allergy and dysphagia lasting since 6 months in whom eosinophilic esophagitis was recognized is presented. ### Long_Answer: The authors emphasize necessity of extensive diagnostic, including histopatological study of esophagus mucosa specimens in pediatric patients in whom dysphagia is observed. It seems that there is a need for prospective studies in children, which would allow for determination of esinophilic esophagitis in Polish population. ### Final_Prediction: yes

### Question: Is passive expiratory flow-volume curve an accurate method to measure the respiratory time constant in rabbits? ### Context: In mechanically ventilated patients, inspiration is forced by an externally applied positive pressure whereas expiration remains passive and depends on the time constant of the total respiratory system (tau), which constitutes an important determinant of mechanical ventilation. The end-inspiratory occlusion technique is one of the easiest methods to obtain tau values in ventilated patients, especially infants, but its accuracy is not well established. The aim of this study was to compare in anesthetized, paralyzed rabbits tau values given by the end-inspiratory occlusion technique (tau(rs)) to tau values obtained by references methods for measurements (i.e. the product of static lung compliance by airway resistance: tau(ref)) during carbachol-induced bronchospasm eliciting marked modifications of the respiratory mechanics.Comparisons were made in the basal state and after carbachol-induced bronchoconstriction in seven New Zealand adult rabbits. This procedure resulted in a wide range of expiratory time constants. A pneumotachograph was used to measure expiratory flow and volume before and after end-inspiratory occlusion. The slope of the flow volume curve gave tau(rs). Then tau(rs) was compared with tau(ref) (which ranged from 0.30 to 1.96 s).Statistical analysis revealed a weak correlation between the two methods, and a size-dependent bias of tau(rs) measurements. ### Long_Answer: The end-inspiratory occlusion technique leads to a systemic bias in measurements of respiratory time constant, especially when the resistance of the respiratory system is elevated. ### Final_Prediction: no

### Question: Does false-positive meconium test result for fatty acid ethyl esters secondary to delayed sample collection? ### Context: Meconium analysis for fatty acid ethyl esters (FAEEs) is a validated method for identifying heavy prenatal ethanol (EtOH) exposure. This study investigated whether delayed sample collection can result in false-positive test results for FAEEs because of collection of samples potentially contaminated with postnatally produced stool.Serial excretions were prospectively collected from neonates born to nondrinking mothers to capture the transition from meconium to postnatal stool. These were analyzed for FAEEs using headspace-solid phase microextraction and gas chromatography-mass spectrometry. Experiments involving incubation of samples with glucose or EtOH were performed to explore a potential mechanism of FAEE elevation.A total of 136 samples were collected from 30 neonates during their first few days of life (median of 4 samples/baby over a mean period of 68.5 hours postpartum). Although the first-collected meconium sample tested negative for FAEEs in all babies, later samples tested above the 2 nmol/g positive cutoff in 19 of 30 babies. Median time to appearance of FAEE-positive samples was 59.2 hours postpartum. In vitro experiments demonstrated that FAEE levels can be further increased in late samples (likely containing postnatal stool) after incubation with glucose, and that FAEEs are readily formed in meconium in the presence of EtOH. ### Long_Answer: Collection of samples excreted later in the postpartum period can lead to false-positive test results for FAEEs, which could be because of contamination with dietary components of postnatally produced stool and EtOH-producing microorganisms. Clinically, it is critical to collect the earliest possible excretion for determination of FAEEs to ensure that the FAEE content is representative of in utero EtOH exposure. ### Final_Prediction: yes

### Question: Is 17β Hydroxysteroid dehydrogenase type 12 ( HSD17B12 ) a marker of poor prognosis in ovarian carcinoma? ### Context: 17β-hydroxysteroid dehydrogenase isoform 12 (HSD17B12) overexpression is associated with poor clinical outcome in invasive ductal carcinoma of the breast. Here, we evaluated HSD17B12 overexpression and its activity in ovarian carcinoma (OvCa) to determine its role in the growth and progression of this tumor.Immunohistochemical analysis of HSD17B12 expression was performed in 100 tissue samples of untreated OvCa and was correlated with clinicopathologic characteristics and patient outcome. In A2780 OvCa cell line expressing HSD17B12, siRNA knockdown of the enzyme was performed, and its effects on tumor cell growth and Annexin V binding were determined.HSD17B12 expression was detected in all tumor samples, but the staining intensity was variable. Normal ovarian epithelium was negative. Patients with tumor showing weak/moderate expression of HSD17B12 had a better overall survival than those with strongly positive tumors (p<0.001). The time to first recurrence was longer for patients with tumors with heterogeneous staining relative to patients with tumors that were uniformly positive (p<0.001). Upon silencing of HSD17B12 in tumor cells, their growth was inhibited (p<0.005) and apoptosis was increased (p<0.05). Arachidonic acid but not estradiol reversed the growth inhibition mediated by HSD17B12 knockdown. ### Long_Answer: HSD17B12 overexpression is shown to be a marker of poor survival in patients with OvCa. Expression in the tumor and function of this enzyme facilitates OvCa progression. ### Final_Prediction: yes

### Question: Does melatonin reduce Cataract Formation and Aldose Reductase Activity in Lenses of Streptozotocin-induced Diabetic Rat? ### Context: The relationship between the high activity of aldose reductase (AR) and diabetic cataract formation has been previously investigated. The purpose of the present study was to determine the preventing effect of melatonin on streptozotocin (STZ)-induced diabetic cataract in rats.34 adult healthy male Sprague-Dawely rats were divided into four groups. Diabetic control and diabetic+melatonin received a single dose of STZ (50 mg/kg, intraperitoneally), whereas the normal control and normal+melatonin received vehicle. The melatonin groups were gavaged with melatonin (5 mg/kg) daily for a period of 8 weeks, whereas the rats in the normal control and diabetic control groups received only the vehicle. The rats' eyes were examined every week and cataract formation scores (0-4) were determined by slit-lamp microscope. At the end of the eighth week, the rats were sacrificed and markers of the polyol pathway and antioxidative (Glutathione, GSH) in their lens were determined. The levels of blood glucose, HbA1c and plasma malondialdhyde (MDA), as a marker of lipid peroxidation, were also measured.Melatonin prevented STZ-induced hyperglycemia by decreased blood glucose and HbA1c levels. Slit lamp examination indicated that melatonin delayed cataract progression in diabetic rats. The results revealed that melatonin feeding increased the GSH levels, decreased the activities of AR and sorbitol dehydrogenase (SDH) and sorbitol formation in catractous lenses as well as plasma MDA content. ### Long_Answer: In summary, for the first time we demonstrated that melatonin delayed the formation and progression of cataract in diabetic rat lenses. ### Final_Prediction: yes

### Question: Does whole-body biodistribution and radiation dosimetry estimate for the PET dopamine transporter probe 18F-FECNT in non-human primates? ### Context: 2 beta-Carbomethoxy-3-(4-chlorophenyl)-8-(2-[18F]fluoroethyl)nortropane (18F-FECNT) is a selective radioligand for the in vivo quantification of dopamine transporters by using positron emission tomography. The aim of the current study was to quantify the distribution of radioactivity in three rhesus monkeys after the injection of approximately 185 MBq (5 mCi) of 18F-FECNT.Whole-body images were acquired at 23-30 time points for a total of 220 min following injection of the radioligand. Source organs were identified at each time point from planar images.The peak activities in planar images in the six identified source organs (expressed as per cent injected dose (%ID)) were lungs (16.5%ID at 2 min), kidneys (12.5%ID at 3 min), brain (9.5%ID at 6 min), liver (7.5%ID at 3 min), red bone marrow (3.5%ID at 12 min), and urinary bladder (2%ID at 98 min). Radiation absorbed doses were calculated using the gastrointestinal tract model in two ways: (1) assuming no urine voiding, and (2) using a dynamic bladder model with voiding intervals of 2.4 and 4.8 h. Using the gastrointestinal tract model and dynamic bladder model with a voiding interval 4.8 h, the three organs with highest exposure (in mu Gy.MBq(-1) (mrad.mCi(-1)) were kidneys 75.68 (280), lungs 44.86 (166) and urinary bladder 58.38 (216). Effective doses estimated with and without urine voiding were in the range 21.35-22.70 mu Gy.MBq(-1) (79-84 mrad.mCi(-1)). ### Long_Answer: The estimated radiation burden of 18F-FECNT is relatively modest and would allow multiple scans per research subject per year. ### Final_Prediction: yes

### Question: Is galectin-1 part of human trophoblast invasion machinery -- a functional study in vitro? ### Context: Interactions of glycoconjugates with endogenous galectins, have been long proposed to participate in several reproductive processes including implantation. In human placenta gal-1, gal-3, gal-8, and gal-13 proteins are known to be present. Each of them has been proposed to play multiple functions, but so far no clear picture has emerged. We hypothesized that gal-1 participates in trophoblast invasion, and conducted Matrigel invasion assay using isolated cytotrophoblast from first trimester placenta and HTR-8/SVneo cell line to test it.Function blocking anti-gal-1 antibody was employed to assess participation of endogenous gal-1 in cell adhesion, cell invasion of HTR-8/SVneo cells. When gal-1 was blocked in isolated trophoblast cell invasion was reduced to 75% of control (SEM ± 6.3, P<0.001) and to 66% of control (SEM ± 1.7, P<0.001) in HTR-8/SVneo cell line. Increased availability of gal-1, as two molecular forms of recombinant human gal-1 (CS-gal-1 and Ox-gal-1), resulted in increased cell invasion by cytotrophoblast to 151% (SEM ± 16, P<0.01) with 1 ng/ml of CS-gal-1, and to 192% (SEM ± 51, P<0.05) with 1 µg/ml of Ox-gal-1. Stimulation was also observed in HTR-8/SVneo cells, to 317% (SEM ± 58, P<0.001) by CS-gal-1, and to 200% (SEM ± 24, P<0.001) by Ox-gal-1 at 1 µg/ml. Both sets of results confirmed involvement of gal-1 in trophoblast invasion. Galectin profile of isolated cytotrophoblast and HTR-8/SVneo cells was established using RT-PCR and real-time PCR and found to consist of gal-1, gal-3 and gal-8 for both cell types. Only gal-1 was located at the trophoblast cell membrane, as determined by FACS analysis, which is consistent with the results of the functional tests. ### Long_Answer: These findings qualify gal-1 as a member of human trophoblast cell invasion machinery. ### Final_Prediction: yes

### Question: Is 15 mm size criterion for lacunar infarction still valid? ### Context: The 'lacunar hypothesis' has been challenged, since small (diameter<15 mm) subcortical infarcts can be produced by middle cerebral artery disease (MCAD) or cardioembolism (CE), while a larger infarct can occur without evidence of MCAD or CE. We sought to assess whether the lacunar hypothesis based on size is still valid.We studied 118 patients who were admitted within 72 h after stroke onset and had acute deep subcortical MCA territory infarcts detected by diffusion-weighted MRI, and who had undergone angiography (mostly MR angiography). Stroke mechanisms were arbitrarily categorized regardless of lesion size: (1) MCAD when there was a corresponding MCA lesion; (2) internal carotid artery disease (ICAD) when there was a significant (>50%) ipsilateral ICAD; (3) CE when there was emboligenic heart disease without MCAD or ICAD, and (4) small vessel disease (SVD) when there was neither CE nor MCAD. SVD was further divided into definite SVD (dSVD, longest diameter<15 mm) or probable SVD (pSVD, longest diameter>or =15 mm).Seventy-three patients (62%) had SVD, of which 38 (32%) had pSVD and 35 (30%) dSVD. Thirty-three patients (28%) had MCAD, five (4%) CE, and seven (6%) ICAD. The infarct diameter in MCAD was not larger than in SVD (p = 0.35), and there was no difference in clinical features or risk factors between MCAD and SVD, or between pSVD and dSVD. CE was distinguished from SVD by its larger size and cortical symptoms. ### Long_Answer: There are no clinical and lesion-size differences between MCAD and SVD, suggesting that there seems to be no rationale for the 15 mm size criterion for lacunar or small-vessel infarction. ### Final_Prediction: nan

### Question: Does hydrolysed protein accelerate the gastrointestinal transport of formula in preterm infants? ### Context: Vomiting, large gastric residuals and abdominal distension are common in very immature infants on formula feeding. The present trial investigated whether a protein hydrolysate formula reduces the gastrointestinal transit time in preterm infants. Fifteen preterm infants (median gestational age 29 (24-32) wk, birthweight 1241 (660-1900) g, postnatal age 18 (5-54) d) on full enteral feeds (>150 ml/kg*d) were enrolled. It was hypothesized that the gastrointestinal transit time is at least 2 h shorter when protein hydrolysate formula is fed compared with standard preterm formula. In a randomized cross-over design study, each formula was fed for 5 d. On days 4 and 9 the gastrointestinal transit time was estimated using carmine red. The protein hydrolysate formula had a markedly shorter gastrointestinal transit time (9.8 h) than the standard formula (19 h) (p = 0.0022, two-sided Mann-Whitney U test). ### Long_Answer: The hydrolysate protein formula accelerated gastrointestinal transit of milk and stools, but whether hydrolysate formulas enable a more rapid establishment of full enteral feeding in preterm infants needs to be investigated. ### Final_Prediction: yes

### Question: Does helicobacter pylori tumor necrosis factor-α inducing protein promote cytokine expression via nuclear factor-κB? ### Context: To study the effects of Helicobacter pylori (H. pylori) tumor necrosis factor-α (TNF) inducing protein (Tip-α) on cytokine expression and its mechanism.We cloned Tip-α from the H. pylori strain 26695, transformed Escherichia coli with an expression plasmid, and then confirmed the expression product by Western blotting. Using different concentrations of Tip-α that affected SGC7901 and GES-1 cells at different times, we assessed cytokine levels using enzyme-linked immunosorbent assay. We blocked SGC7901 cells with pyrrolidine dithiocarbamate (PDTC), a specific inhibitor of nuclear factor κB (NF-κB). We then detected interleukin (IL)-1β and TNF-α levels in SGC7901 cells.Western blot analysis using an anti-Tip-α antibody revealed a 23-kDa protein, which indicated that recombinant Tip-α protein was recombined successfully. The levels of IL-1β, IL-8 and TNF-α were significantly higher following Tip-α interference, whether GES-1 cells or SGC-7901 cells were used (P < 0.05). However, the levels of cytokines (including IL-1β, IL-8 and TNF-α) secreted by SGC-7901 cells were greater than those secreted by GES-1 cells following treatment with Tip-α at the same concentration and for the same duration (P < 0.05). After blocking NF-κB with PDTC, the cells (GES-1 cells and SGC-7901 cells) underwent interference with Tip-α. We found that IL-1β and TNF-α levels were significantly decreased compared to cells that only underwent Tip-α interference (P < 0.05). ### Long_Answer: Tip-α plays an important role in cytokine expression through NF-κB. ### Final_Prediction: yes

### Question: Are macaca fascicularis highly susceptible to an RT-SHIV following intravaginal inoculation : a new model for microbicide evaluation? ### Context: Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is a major target for antiretroviral strategy to block or curtail HIV infection. A suitable RT-SHIV/macaque model is urgently needed for the evaluation of HIV/AIDS therapies and microbicides specifically targeting HIV-1 RT.Fifteen cynomolgus macaques (Macaca fascicularis) were divided into three groups (n = 5) and intravaginally inoculated with 4800, 1200, or 300 TCID(50) of RT-SHIVtc. Systemic infections of RT-SHIVtc exposed macaques were determined by both virological and immunologic parameters during 24 weeks post-challenge.Within 2 weeks post-inoculation, 13 of 15 macaques became infected as confirmed by virus isolation, plasma viral RNA, proviral DNA, declined CD4(+)T cell counts in peripheral blood and seroconversion. ### Long_Answer: Results serve to validate the infectivity and pathogenicity of RT-SHIVtc following vaginal exposure in M. fascicularis. This RT-SHIVtc/macaque model could be suitable for the pre-clinical evaluation of non-nucleoside RT inhibitor-based anti-HIV microbicides. ### Final_Prediction: yes

### Question: Does beta-adrenergic receptor 1 selective antagonism inhibit norepinephrine-mediated TNF-alpha downregulation in experimental liver cirrhosis? ### Context: Bacterial translocation is a frequent event in cirrhosis leading to an increased inflammatory response. Splanchnic adrenergic system hyperactivation has been related with increased bacterial translocation. We aim at evaluating the interacting mechanism between hepatic norepinephrine and inflammation during liver damage in the presence of bacterial-DNA.Forty-six mice were included in a 16-week protocol of CCl(4)-induced cirrhosis. Laparotomies were performed at weeks 6, 10, 13 and 16. A second set of forty mice injected with a single intraperitoneal dose of CCl(4) was treated with saline, 6-hydroxidopamine, Nebivolol or Butoxamine. After 5 days, mice received E. coli-DNA intraperitoneally. Laparotomies were performed 24 hours later. Liver bacterial-DNA, norepinephrine, TNF-alpha, IL-6 and beta-adrenergic receptor levels were measured.Bacterial-DNA translocation was more frequent in CCl(4)-treated animals compared with controls, and increased as fibrosis progressed. Liver norepinephrine and pro-inflammatory cytokines were significantly higher in mice with vs without bacterial-DNA (319.7 ± 120.6 vs 120.7 ± 68.6 pg/g for norepinephrine, 38.4 ± 6.1 vs 29.7 ± 4.2 pg/g for TNF-alpha, 41.8 ± 7.4 vs 28.7 ± 4.3 pg/g for IL-6). Only beta-adrenergic receptor-1 was significantly increased in treated vs control animals (34.6 ± 7.3 vs 12.5 ± 5.3, p=0.01) and correlated with TNF-alpha, IL-6 and norepinephrine hepatic levels in animals with bacterial-DNA. In the second set of mice, cytokine levels were increased in 6-hydroxidopamine and Nebivolol (beta-adrenergic receptor-1 antagonist) treated mice compared with saline. Butoxamine (beta-adrenergic receptor-2 antagonist) didn't inhibit liver norepinephrine modulation of pro-inflammatory cytokines. ### Long_Answer: Beta-adrenergic receptor-1 mediates liver norepinephrine modulation of the pro-inflammatory response in CCl(4)-treated mice with bacterial-DNA. ### Final_Prediction: yes

### Question: Does the extent of prebending affect the stability of femoral shaft fractures stabilized by titanium elastic nails? ### Context: Elastic stable intramedullary nailing (ESIN) is a common procedure for stabilization of femoral shaft fractures in childhood. Prebending of the nail is generally recommended to achieve optimal nail tension at the fracture site. To our knowledge there are no published data on the effects of prebending on stability. The purpose of this biomechanical study was to compare the effects of different degrees of prebending on the stability of transverse femoral fractures after ESIN using a bone model.Standardized transverse midshaft fractures were created in 20 synthetic, biomechanically validated adolescent bones (4th Generation Composite Femur--Sawbones Europe AB, Sweden) that were stabilized with 2 titanium nails (TEN) each (4 mm diameter, Synthes) and inserted in standardized retrograde technique. The 4 test series addressed nail prebending at 0 degree, 30 degrees, 45 degrees, and 60 degrees. The models were tested biomechanically in 4-point bending in the coronal and sagittal planes, relative stiffness was determined and analyzed statistically. The level of significance was set at P<0.05.Comparison of the individual groups showed no significant differences in stiffness for different degrees of prebending in the coronal plane. Significantly reduced stiffness was found in the sagittal plane for the group with 60-degree prebending compared with the 0-degree, 30-degree, and 45-degree prebending groups. Intragroup comparison in the coronal and sagittal planes yielded a significantly reduced stiffness in the sagittal plane compared with the coronal plane in the group with 60-degree prebending. The 45-degree prebending group showed a similar tendency and in the 0-degree and 30-degree prebending groups there were no significant differences. ### Long_Answer: On a synthetic bone model, prebending of TEN was found to affect the stability of transverse fractures of the femoral shaft, whereby indiscriminate prebending will reduce stability in the sagittal plane.Despite limited extrapolation of the findings to the in vivo situation, it can be stated that prebending of TEN by 0 to 30 degrees offers the greatest stability in the coronal and sagittal planes for transverse fractures of the femoral shaft. ### Final_Prediction: nan

### Question: Is 25-hydroxyvitamin D deficiency a risk factor for symptoms of postoperative hypocalcemia and secondary hyperparathyroidism after minimally invasive parathyroidectomy? ### Context: Patients with primary hyperparathyroidism who undergo minimally invasive parathyroidectomy (MIP) may have postoperative symptoms of hypocalcemia or secondary hyperparathyroidism. This study sought to identify factors predictive of these events.Between 1998 and 2004, 190 patients with primary hyperparathyroidism underwent MIP with excision of a single adenoma. Age, gender, race, prior head and neck surgery, use of preoperative thyroid hormone or calcium-channel blockers, preoperative levels of calcium, 25-hydroxyvitamin D (25[OH]D) and intact parathyroid hormone (iPTH), the presence of osteopenia or osteoporosis, intraoperative iPTH levels, and adenoma weight were evaluated by univariate analysis as predictors of postoperative symptoms of hypocalcemia and secondary hyperparathyroidism.None of the following were predictors of postoperative symptoms of hypocalcemia: age, gender, race, prior head and neck surgery, preoperative medications, preoperative calcium and iPTH levels, osteopenia or osteoporosis, intraoperative iPTH levels, or adenoma weight. However, patients with postoperative symptoms of hypocalcemia had significantly lower preoperative 25[OH]D levels (P = .01). Further, higher preoperative iPTH levels (P < .01) and lower preoperative 25[OH]D levels (P = .05) were associated with secondary hyperparathyroidism postoperatively. ### Long_Answer: A low preoperative 25[OH]D level is associated with postoperative symptoms of hypocalcemia and secondary hyperparathyroidism in patients undergoing MIP. One might consider instituting empiric calcium supplementation postoperatively in patients with low 25[OH]D levels. ### Final_Prediction: yes

### Question: Does triple combination therapy for hepatitis C with telaprevir exhibit greater early antiviral activity than with boceprevir? ### Context: Achievement of early viral suppression is important in patients with chronic HCV infection treated with telaprevir (TLV) or boceprevir (BOC) to avoid selection of drug resistance and attain cure. No head-to-head studies comparing TLV and BOC have been performed so far.All consecutive individuals who initiated triple HCV therapy with TLV or BOC outside clinical trials at three European clinics were evaluated. Rapid virological response (RVR) was defined as unquantifiable HCV RNA (<25 IU/ml) at week 4 for TLV and at week 8 for BOC (4 weeks after lead-in).A total of 106 patients were evaluated, 33 treated with BOC and 73 with TLV. Median age, gender, body mass index, baseline HCV RNA, HCV subtype 1a (45% versus 42%) and IL28B-CC alleles (29% versus 23%) did not differ significantly in BOC and TLV groups, respectively. HIV coinfection was more prevalent in patients on TLV than BOC (24% versus 44%). Conversely, more patients on BOC than TLV had previously failed pegylated interferon plus ribavirin (82% versus 64%). RVR was achieved by 82% of patients on TLV versus 59% on BOC (P=0.001). Multivariate logistic regression analysis confirmed that TLV use was the strongest predictor of RVR (OR 3.54 [95% CI 1.23, 10.24]; P=0.02), others being HCV subtype 1b versus 1a (OR 3.26 [95% CI 1.17, 9.09]; P=0.02) and low baseline HCV RNA (OR 0.41 [95% CI 0.16, 1.03]; P=0.06). Prior interferon exposure, HIV coinfection or absence of advanced liver fibrosis did not influence the likelihood of RVR. ### Long_Answer: Compared to BOC, triple therapy with TLV produces greater RVR rates. TLV might be a better option in more difficult-to-cure patients, such as those with high baseline HCV RNA and/or HCV 1a subtype. HIV coinfection does not influence early HCV RNA responses. ### Final_Prediction: yes

### Question: Is prolonged resuscitation of metabolic acidosis after trauma associated with more complications? ### Context: Optimal patterns for fluid management are controversial in the resuscitation of major trauma. Similarly, appropriate surgical timing is often unclear in orthopedic polytrauma. Early appropriate care (EAC) has recently been introduced as an objective model to determine readiness for surgery based on the resuscitation of metabolic acidosis. EAC is an objective treatment algorithm that recommends fracture fixation within 36 h when either lactate <4.0 mmol/L, pH ≥ 7.25, or base excess (BE) ≥-5.5 mmol/L. The aim of this study is to better characterize the relationship between post-operative complications and the time required for resuscitation of metabolic acidosis using EAC.At an adult level 1 trauma center, 332 patients with major trauma (Injury Severity Score (ISS) ≥16) were prospectively treated with EAC. The time from injury to EAC resuscitation was determined in all patients. Age, race, gender, ISS, American Society of Anesthesiologists score (ASA), body mass index (BMI), outside hospital transfer status, number of fractures, and the specific fractures were also reviewed. Complications in the 6-month post-operative period were adjudicated by an independent multidisciplinary committee of trauma physicians and included infection, sepsis, pulmonary embolism, deep venous thrombosis, renal failure, multiorgan failure, pneumonia, and acute respiratory distress syndrome. Univariate analysis and binomial logistic regression analysis were used to compare complications between groups.Sixty-six patients developed complications, which was less than a historical cohort of 1,441 patients (19.9% vs. 22.1%). ISS (p < 0.0005) and time to EAC resuscitation (p = 0.041) were independent predictors of complication rate. A 2.7-h increase in time to resuscitation had odds for sustaining a complication equivalent to a 1-unit increase on the ISS. ### Long_Answer: EAC guidelines were safe, effective, and practically implemented in a level 1 trauma center. During the resuscitation course, increased exposure to acidosis was associated with a higher complication rate. Identifying the innate differences in the response, regulation, and resolution of acidosis in these critically injured patients is an important area for trauma research. ### Final_Prediction: yes

### Question: Is 18F-FDG uptake assessed by PET/CT in abdominal aortic aneurysms associated with cellular and molecular alterations prefacing wall deterioration and rupture? ### Context: Rupture of abdominal aortic aneurysms (AAAs) leads to a significant morbidity and mortality in aging populations, and its prediction would be most beneficial to public health. Spots positive for uptake of (18)F-FDG detected by PET are found in 12% of AAA patients (PET+), who are most often symptomatic and at high rupture risk. Comparing the (18)F-FDG-positive site with a negative site from the same aneurysm and with samples collected from AAA patients with no (18)F-FDG uptake should allow the discrimination of biologic alterations that would help in identifying markers predictive of rupture.Biopsies of the AAA wall were obtained from patients with no (18)F-FDG uptake (PET0, n = 10) and from PET+ patients (n = 8), both at the site positive for uptake and at a distant negative site of the aneurysmal wall. Samples were analyzed by immunohistochemistry, quantitative real-time polymerase chain reaction, and zymography.The sites of the aneurysmal wall with a positive (18)F-FDG uptake were characterized by a strikingly increased number of adventitial inflammatory cells, highly proliferative, and by a drastic reduction of smooth muscle cells (SMCs) in the media as compared with their negative counterpart and with the PET0 wall. The expression of a series of genes involved in the maintenance and remodeling of the wall was significantly modified in the negative sites of PET+, compared with the PET0 wall, suggesting a systemic alteration of the aneurysmal wall. Furthermore, a striking increase of several matrix metalloproteinases (MMPs), notably the MMP1 and MMP13 collagenases, was observed in the positive sites, mainly in the adventitia. Moreover, PET+ patients were characterized by a higher circulating C-reactive protein. ### Long_Answer: Positive (18)F-FDG uptake in the aneurysmal wall is associated with an active inflammatory process characterized by a dense infiltrate of proliferating leukocytes in the adventitia and an increased circulating C-reactive protein. Moreover, a loss of SMC in the media and alterations of the expression of genes involved in the remodeling of adventitia and collagen degradation potentially participate in the weakening of the aneurysmal wall preceding rupture. ### Final_Prediction: yes

### Question: Is the vitamin B12 analog cobinamide an effective hydrogen sulfide antidote in a lethal rabbit model? ### Context: Hydrogen sulfide (H2S) is a highly toxic gas for which no effective antidotes exist. It acts, at least in part, by binding to cytochrome c oxidase, causing cellular asphyxiation and anoxia. We investigated the effects of three different ligand forms of cobinamide, a vitamin B12 analog, to reverse sulfide (NaHS) toxicity.New Zealand white rabbits received a continuous intravenous (IV) infusion of NaHS (3 mg/min) until expiration or a maximum 270 mg dose. Animals received six different treatments, administered at the time when they developed signs of severe toxicity: Group 1-saline (placebo group, N = 9); Group 2--IV hydroxocobalamin (N = 7); Group 3--IV aquohydroxocobinamide (N = 6); Group 4--IV sulfitocobinamide (N = 6); Group 5--intramuscular (IM) sulfitocobinamide (N = 6); and Group 6-IM dinitrocobinamide (N = 8). Blood was sampled intermittently, and systemic blood pressure and deoxygenated and oxygenated hemoglobin were measured continuously in peripheral muscle and over the brain region; the latter were measured by diffuse optical spectroscopy (DOS) and continuous wave near infrared spectroscopy (CWNIRS).Compared with the saline controls, all cobinamide derivatives significantly increased survival time and the amount of NaHS that was tolerated. Aquohydroxocobinamide was most effective (261.5 ± 2.4 mg NaHS tolerated vs. 93.8 ± 6.2 mg in controls, p < 0.0001). Dinitrocobinamide was more effective than sulfitocobinamide. Hydroxocobalamin was not significantly more effective than the saline control. ### Long_Answer: Cobinamide is an effective agent for inhibiting lethal sulfide exposure in this rabbit model. Further studies are needed to determine the optimal dose and form of cobinamide and route of administration. ### Final_Prediction: yes

### Question: Do older adults prioritize postural stability in the anterior-posterior direction to regain balance following volitional lateral step? ### Context: Postural control in the medial-lateral (ML) direction is of particular interest regarding the assessment of changes in postural control, as it is highly related to the risk of falling.To determine the postural strategies used to regain balance following a voluntary lateral step and compare these strategies between young and older adults.Sixteen older adults (60-90 years) and 14 young adults (20-40 years) were asked to stand quietly for 30s, walk in place and then take a lateral step and stand quietly (30s). Balance Post was divided into 10s intervals. Center of pressure displacement (CoP) and velocity (VCoP) in the anterio-posterior (AP) and ML directions were analyzed.In both groups, CoP and VCoP in AP and ML increased in Post1 compared to Pre (P<0.001). Dissimilar to young adults, VCoP-Post2, Post3 ML were larger than Pre (P=0.01) in older adults. Age correlated with all VCoP (Pre and Post) in both ML (P<0.05) and AP directions (P<0.01). ### Long_Answer: Dissimilar to young adults, older adults use different postural strategies in ML and AP directions and prioritized postural stability in the AP direction to recover balance after completing a lateral step. In the ML direction, older adults took up to 30s to regain balance. Considering that age was related to larger CoP displacement and velocity, the AP strategy to recover postural balance following a lateral step could become less efficient as older adults age and therefore increasing the risk of falls. ### Final_Prediction: yes

### Question: Is Two Really Better Than One? ### Context: Periprocedural stroke after carotid endarterectomy increases long-term mortality. Intraoperative monitoring with electroencephalography (EEG) and somatosensory-evoked potentials (SSEPs) helps predict perioperative stroke risk. However, the sensitivity of each technique when used independently still remains low. The aim of this study is to determine whether multimodal monitoring leads to an increase in sensitivity and diagnostic accuracy.Relevant literature was obtained through a search of Embase, PubMed, and Web of Science databases and data were extracted. Data from the University of Pittsburgh Medical Center hospital records for the 2000-2012 period were included. Pooled estimates of sensitivity, specificity, and diagnostic odds ratio were obtained for single and multimodality neurophysiologic monitoring. A McNemar test was used to evaluate for any statistically significant differences in the sensitivities and false-positive rates.The diagnostic odds ratio of dual modality monitoring was found to be 17.4. The specificity of concurrent EEG and SSEP changes in predicting perioperative strokes was calculated to be 96.8% (95% confidence interval 94.1%-98.3%). The sensitivity of combined monitoring with a change in either modality designated as significant was 58.9% (95% confidence interval 41.2%-74.7%). Multimodality monitoring with a change in either EEG or SSEP as the alarm criteria was 1.32 times more sensitive than EEG alone and 1.26 times more sensitive than SSEP alone. ### Long_Answer: The odds of having a change in either EEG or SSEP are 17 times more in patients with perioperative strokes. Dual modality monitoring is more sensitive at predicting perioperative deficits than EEG or SSEP used independently. ### Final_Prediction: nan

### Question: Is ultrasonographic strain imaging superior to conventional non-invasive measures of vascular stiffness in the detection of age-dependent differences in the mechanical properties of the common carotid artery? ### Context: Elastic properties of large arteries have been shown to deteriorate with age and in the presence of atherosclerotic vascular disease. In this study, the performance of ultrasonographic strain measurements was compared with conventional measures of vascular stiffness in the detection of age-dependent differences in the elastic properties of the common carotid artery (CCA).In 10 younger (25-28 years, four women) and 10 older (50-59 years, four women) healthy individuals, global and regional circumferential, and radial strain variables were measured in the short-axis view of the right CCA using ultrasonographic two-dimensional (2D) strain imaging with recently introduced speckle tracking technique. Conventional elasticity variables, elastic modulus (E(p)), and beta stiffness index, were calculated using M-mode sonography and non-invasive blood pressure measurements. Global and regional circumferential systolic strain and strain rate values were significantly higher (P < 0.01 for regional late systolic strain rate, P < 0.001 otherwise) in the younger individuals, whereas the values of conventional stiffness variables in the same group were lower (P < 0.05). Among all strain and conventional stiffness variables, principal component analysis and its regression extension identified only circumferential systolic strain variables as contributing significantly to the observed discrimination between the younger and older age groups. ### Long_Answer: Ultrasonographic 2D-strain imaging is a sensitive method for the assessment of elastic properties in the CCA, being in this respect superior to the conventional measures of vascular stiffness. The method has potential to become a valuable non-invasive tool in the detection of early atherosclerotic vascular changes. ### Final_Prediction: yes

### Question: Does melatonin reduce the expression of chemokines in rat with trinitrobenzene sulfonic acid-induced colitis? ### Context: To investigate the effect of melatonin on the colon inflammatory injury of rats with colitis and determine whether this effect is associated with inhibition of chemoattractant molecules interleukin (IL-8) and monocyte chemoattractant protein (MCP-1).The study was designed and implemented in JingMen No.1 People's Hospital, HuBei Province, from May 2006 to April 2007. It involved 72 animals divided into 6 groups of 12 each: normal group, model group, 5-aminosalisalicylic acid group,and melatonin group (dose of 2.5, 5.0, and 10.0mg/kg). Rat colitis model was established by 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) enema. Interlukin-8 and MCP-1 proteins in colon tissue were examined by immunohistochemistry and western blot. The messenger-RNA expressions of chemokines were determined by reverse transcription polymerase chain reaction analysis.Trinitrobenzene sulfonic acid enema resulted in pronounced pathological changes of colonic mucosa in model rats, which were in accordance with the significantly elevated myeloperoxidase activity. Expressions of chemokines were up-regulated in colitis. Melatonin treatment reduced colonic lesions and improved colitis symptom, and decreased the protein and mRNA expressions of IL-8 and MCP-1 significantly in colon tissues of rats with colitis. ### Long_Answer: Chemokines IL-8 and MCP-1 are elevated in mucosal tissues in colitis and play an important role in the perpetuation of tissue destructive inflammatory processes; melatonin reduces colonic inflammatory injury of rats colitis through down-regulating the expressions of chemokines. Melatonin can be considered as a novel therapeutic alternative for the treatment of inflammatory bowel disease. ### Final_Prediction: yes

### Question: Do bioflavonoids attenuate renal proximal tubular cell injury during cold preservation in Euro-Collins and University of Wisconsin solutions? ### Context: Cold ischemia and reperfusion during kidney transplantation are associated with release of free oxygen radicals and damage of renal tubular cells. Bioflavonoids may diminish cold storage-induced injury due to antioxidant and iron chelating activities. This study was designed to delineate the renoprotective mechanisms of bioflavonoids and to define the structural features conferring cytoprotection from cold injury.LLC-PK1 cells were preincubated for three hours with bioflavonoids and cold stored in University of Wisconsin (UW)- or Euro-Collins (EC)-solution for 20 hours. After rewarming, cell viability was assessed by the lactate dehydrogenase (LDH) release, MTT-test, and amino acid transport activity. Lipid peroxidation was assessed from the generation of thiobarbituric acid-reactive substances.Twenty-hours of cold storage of LLC-PK1 cells resulted in a substantial loss of cell integrity that was more pronounced in the EC (LDH release, 93.6 +/- 1.6%) than the UW solution (67.2 +/- 6.9%; P < 0.0001). Pretreatment with quercetin significantly enhanced cell survival (LDH release, 5.4 +/- 2.7% for UW and 8.4 +/- 4.2% for EC) in a concentration dependent manner. Structure-activity studies revealed similar renoprotection for kaempferol, luteolin and fisetin, unlike myricetin, morin, apigenin, naringenin, catechin, silibinin and rutin. Lipid peroxidation was reduced (UW alone, 2.7 +/- 1.2 vs. UW+quercetin 0.5 +/- 0.2 nmol/mg protein, P < 0.01), and l-threonine uptake completely sustained by pretreatment with quercetin, kaempferol, luteolin, and fisetin. However, renoprotection by fisetin was rapidly lost during rewarming. Protective properties of bioflavonoids were governed by the number and arrangement of hydroxyl substitutes, electron-delocalization, sterical planarity, and lipophilicity of the basic diphenylpyran skeleton. ### Long_Answer: Cold storage-induced renal tubular cell injury is ameliorated by bioflavonoids. Renoprotective effects of bioflavonoids are defined by structure, suggesting that flavonoids are incorporated into membrane lipid bilayers and interfere with membrane lipid peroxidation. ### Final_Prediction: yes

### Question: Recent trends of ophthalmic diseases in Italy: are official data reliable? ### Context: The aim of the study was to investigate the epidemiological trends of ocular diseases using hospital discharge forms as our data source.We examined official Italian Statistical Institute (ISTAT) data concerning patients discharged from ophthalmologic wards. Our analysis was limited to the years when ISTAT managed health service data (1986, 1990 and 1994); whilst currently this duty has been transferred to the Ministry of Health.The diseases encountered most frequently were cataract, glaucoma and retinal detachment. Patients over 65 years of age represented 54% in 1986 and 67% in 1994. We observed a general trend toward shorter hospital stays (10.5 days in 1986 and 6.4 days in 1994). We applied an indirect analysis that included masculinity and chi 2 homogeneity that were aimed to evaluate results de spite the questionable reliability of ISTAT gross data. ### Long_Answer: The results of indirect analysis (masculinity and chi 2 homogeneity, of data combined with the significant number of charts presenting incomplete diagnostic information strongly question the reliability of official documentation. The increase of hospitalisation for ophthalmic surgery and a higher average age of affected subjects were confirmed. We observed a reduction of mean hospital stay per admission, indicating a positive achievement in terms of cost reduction. ### Final_Prediction: nan

### Question: Does lamotrigine protect hippocampal CA1 neurons from ischemic damage after cardiac arrest? ### Context: Lamotrigine (LTG) is an anticonvulsant drug whose mechanism of action may involve the inhibition of glutamate release by blocking voltage-dependent sodium channels. Glutamate neurotoxicity may contribute to cerebral ischemic damage after recovery from cardiac arrest. Thus, LTG may prevent the brain damage associated with global cerebral ischemia by reducing the release of glutamate from presynaptic vesicles during the ischemic insult or the early recovery period.LTG was studied in cardiac arrest-induced global cerebral ischemia with reperfusion in rats. In the first set of experiments, LTG (100 mg/kg, p.o.) was administered before induction of ischemia; and in the second experiment, LTG (10 mg/kg, i.v.) was given 15 minutes after ischemia and a second dose (10 mg/kg,i.v.) was given 5 hours later.In both experiments LTG reduced the damage to the hippocampal CA1 cell population by greater than 50%. Neuroprotection was not associated with changes in brain temperature or plasma glucose concentration. Plasma concentrations of LTG ranged between 8 and 13 micrograms/mL. Patients taking LTG as a monotherapy for epilepsy typically have plasma levels of LTG in the 10 to 15 micrograms/mL range. ### Long_Answer: These data suggest that LTG may be effective in preventing brain damage after recovery from cardiac arrest. Patients on LTG monotherapy for epilepsy have plasma concentrations very similar to those found to be neuroprotective in this study. Although difficult to extrapolate, our data suggest that LTG at neuroprotective doses may be well tolerated by humans. ### Final_Prediction: yes

### Question: Customised birthweight percentiles: does adjusting for maternal characteristics matter? ### Context: The objective of this study was to determine whether the improved prediction of risk for perinatal mortality obtained with the use of a customised birthweight standard can also be obtained with the use of a non-customised but intrauterine-based standard.Population-based cohort study.Sweden.Births in the Swedish Medical Birth Register between 1992 and 2001 (n = 782 303) with complete data on birthweight, gestational age, sex, maternal age, pre-pregnancy body mass index, height, parity, and ethnicity.We calculated the relative risks (RRs) of stillbirth and early neonatal mortality among small-for-gestational-age (SGA) births as established by (1) a customised standard, (2) a population standard based on birthweights, and (3) a population standard based on a best estimate of intrauterine weights.Stillbirth and early neonatal mortality (<7 days).The RRs of stillbirth and early neonatal mortality among SGA births as classified by the intrauterine standard were similar to those among SGA births as classified by the customised standard and much higher than those among SGA births as classified by the birthweight standard. ### Long_Answer: A non-customised but intrauterine-based standard has a similar ability to predict risk for stillbirth and early neonatal mortality as a customised birthweight standard. The process of customising population weight-for-gestational-age standards to account for maternal characteristics does little to improve prediction of perinatal mortality. ### Final_Prediction: nan

### Question: Is first-line eradication for Helicobacter pylori-positive gastritis by esomeprazole-based triple therapy influenced by CYP2C19 genotype? ### Context: To evaluate the effect of first line esomeprazole (EPZ)-based triple therapy on Helicobacter pylori (H. pylori) eradication.A total of 80 Japanese patients with gastritis who were diagnosed as positive for H. pylori infection by endoscopic biopsy-based or (13)C-urea breath tests were included in this study. The average age of the patients was 57.2 years (male/female, 42/38). These patients were treated by first-line eradication therapy with EPZ 40 mg/d, amoxicillin 1500 mg/d, and clarithromycin 400 mg/d for 7 d. All drugs were given twice per day. Correlations between H. pylori eradication, CYP2C19 genotype, and serum pepsinogen (PG) level were analyzed. This study was registered with the UMIN Clinical Trials Registry (UMIN000009642).The H. pylori eradication rates by EPZ-based triple therapy evaluated by intention-to-treat and per protocol were 67.5% and 68.4%, respectively, which were similar to triple therapies with other first-generation proton pump inhibitors (PPIs). The eradication rates in three different CYP2C19 genotypes, described as extensive metabolizer (EM), intermediate metabolizer, and poor metabolizer, were 52.2%, 72.1%, and 84.6%, respectively. The H. pylori eradication rate was significantly lower in EM than non-EM (P < 0.05). The serum PG I level and PG I/II ratio were significantly increased after eradication of H. pylori (P < 0.01), suggesting that gastric atrophy was improved by H. pylori eradication. Thus, first-line eradication by EPZ-based triple therapy for patients with H. pylori-positive gastritis was influenced by CYP2C19 genotype, and the eradication rate was on the same level with other first-generation PPIs in the Japanese population. ### Long_Answer: The results from this study suggest that there is no advantage to EPZ-based triple therapy on H. pylori eradication compared to other first-generation PPIs. ### Final_Prediction: yes

### Question: Does Adenotonsillectomy really reduced clinic visits for pediatric upper respiratory tract infections? ### Context: To investigate whether adenotonsillectomy reduces upper respiratory tract infections (URIs) in the pediatric population.We identified 415 children, aged ≤18 years who had undergone adenoidectomy and/or tonsillectomy during the period from 1999 to 2006, from the Taiwan National Health Insurance Research Database. The comparison group consisted of 1630 children without the surgery randomly selected from the same database frequency matched with sex, age and the surgery date (index date). Changes in physician visits for URIs 2-year period before and 2-year period after the index date were compared between the two groups of children.The number of outpatient visits for URIs decreased with time, children with tonsillectomy and/or adenoidectomy had a greater reduction than comparison children (mean changes, -14 times and -6 times, respectively) in the 2-year period after the index date. Multivariate analyses using generalized estimated equation revealed a significant effect in reducing URIs visits from the surgery (relative ratio=0.85, p<0.0001), strongest for children undergoing both tonsillectomy and adenoidectomy (relative ratio=0.76, p<0.0001). The association between surgery and the decrease in URIs was more pronounced for children aged 12 years and less. ### Long_Answer: This population-based study suggests that tonsillectomy and/or adenoidectomy is associated with fewer physician visits for URIs. The association is weakened in old children. ### Final_Prediction: nan

### Question: Perforated peptic ulcer: is the form of methamphetamine known as "crystal meth" a new risk factor? ### Context: The emergence of new synthetic drugs related to peptic ulcer perforation has been reported. Recently an increase in the use of inhaled methamphetamine has been observed and we have described an association of frequent use with peptic disease symptomatology and perforation.To determine whether methamphetamine use is a factor related to peptic acid disease and perforation and to establish its demographic variables.A retrospective, comparative, descriptive, and observational study was carried out through the evaluation of medical records of patients admitted to the Surgery Service with perforated ulcer, within the time frame of January 2002 to March 2005. A descriptive analysis was carried out, along with the Z test, odds ratio, confidence interval, p value and the Student's t test.Forty-two patients were divided into 2 groups: methamphetamine users (n=25) and nonusers (n=17). There was a statistically significant difference in relation to age, which was lower in the methamphetamine user group (38,7 years vs 58,88 years, p=0.0001). In addition, there was a trend in the user group to develop peptic ulcer perforation at earlier ages compared with the nonuser group (p=0.0001). There were no statistically significant differences between the two groups in regard to clinical presentation. ### Long_Answer: Methamphetamine use is related to ulcer perforation in age groups of younger patients when compared with nonuser patients. ### Final_Prediction: nan

### Question: Is severity of cough in idiopathic pulmonary fibrosis associated with MUC5 B genotype? ### Context: A polymorphism (rs35705950) in the promoter region of the mucin MUC5B is associated with both familial and sporadic forms of idiopathic pulmonary fibrosis. (IPF) We hypothesize that this common MUC5B variant will impact the expression of cough, a frequent disabling symptom seen in subjects with IPF.We genotyped 136 subjects with IPF. All living subjects were provided with a Leicester Cough Questionnaire (LCQ) to measure cough severity. We assessed allele effects of the MUC5B polymorphism on the LCQ scores using SAS General Linear Models (GLM) in the patients with IPF.In the 68 of the total 136 IPF patients who returned the LCQ, MUC5B minor allele frequency (T) is consistent with prior published studies (31%). We found a significant independent effect of the T allele on the LCQ score (p = 0.002 for subjects with IPF). This effect is independent of other common causes of cough, including gastroesophogeal reflux disease and upper airway cough syndrome. ### Long_Answer: Cough severity, a common disabling phenotypic component of IPF, is significantly associated with the presence of the minor allele of a MUC5B promoter polymorphism. This study highlights a possible genetic mechanism for phenotypic heterogeneity in pulmonary fibrosis. ### Final_Prediction: yes

### Question: Delayed-Type Hypersensitivity to Metals of Environmental Burden in Patients with Takotsubo Syndrome - Is There a Clinical Relevance? ### Context: Takotsubo syndrome (TS) is a heart condition characterised by a sudden transient left ventricular dysfunction; its pathophysiology is probably associated with elevated levels of catecholamines but the exact mechanism is not known as yet. Literature and clinical experience suggest that TS affects persons with various comorbidities. This pilot work aims to evaluate the frequency of comorbidities with potential pathological immune reactivity, and to evaluate the potential association between TS and hypersensitivity to metals assessed by LTT-MELISA®.A total of 24 patients (23 women, 1 man) with a history of TS attack and 27 healthy controls were evaluated. Hypersensitivity was evaluated by a lymphocyte transformation test (LTT-MELISA®); a questionnaire of environmental burden was used to select evaluated metals. A total of 19 patients (79%) had at least one condition that might potentially be associated with pathological immune reactivity (autoimmune thyroid disease, drug allergy, bronchial asthma, cancer, contact dermatitis, rheumatoid arthritis). Hypersensitivity to metals was identified significantly more frequently in TS patients than in healthy controls (positive reaction to at least one metal was identified in 95.8% of TS patients and in 59.3% of controls; p = 0.003); the difference was statistically significant for mercury (45.8% and 14.8%, respectively; p = 0.029). ### Long_Answer: Our work shows that conditions with pathological immune reactivity occur frequently in TS patients, and our data suggest a possible association between TS and hypersensitivity to metals (mercury in particular) evaluated by LTT-MELISA®. We also suggest that apart from the triggering stress factor, potential existence of other serious conditions should be considered when taking medical history of TS patients. ### Final_Prediction: nan

### Question: Depression and cardiovascular mortality: a role for n-3 fatty acids? ### Context: Recent studies indicate that depression plays an important role in the occurrence of cardiovascular diseases (CVDs). The underlying mechanisms are not well understood.We investigated whether dietary intake of the n-3 fatty acids (FAs) eicosapentaenic acid and docosahexaenoic acid could explain the relation between depressive symptoms and cardiovascular mortality.The Zutphen Elderly Study is a prospective cohort study conducted in the Netherlands. Depressive symptoms were measured in 1990 with the Zung Self-rating Depression Scale in 332 men aged 70-90 y and free from CVD and diabetes. Dietary factors were assessed with a cross-check dietary history method in 1990. Mortality data were collected between 1990 and 2000. Logistic and Cox regression analyses were performed, with adjustment for demographics and CVD risk factors.Compared with a low intake (x: 21 mg/d), a high intake (x: 407 mg/d) of n-3 FAs was associated with fewer depressive symptoms [odds ratio: 0.46; 95% CI: 0.22, 0.95; P for trend = 0.04] at baseline and no significant reduced risk of 10-y CVD mortality [hazard ratio (HR): 0.88; 95% CI: 0.51, 1.50]. The adjusted HR for an increase in depressive symptoms with 1 SD for CVD mortality was 1.28 (95% CI: 1.03, 1.57) and did not change after additional adjustment for the intake of n-3 FAs. ### Long_Answer: An average intake of approximately 400 mg n-3 FA/d may reduce the risk of depression. Our results, however, do not support the hypothesis that the intake of n-3 FAs explains the relation between depression and CVD. ### Final_Prediction: nan

### Question: Do adverse rearing experiences enhance responding to both aversive and rewarding stimuli in juvenile rhesus monkeys? ### Context: While adverse rearing is thought to alter threat responding, the effects on appetitive behavior remains minimally explored. This study examines the effects that early life emotional adversity has on response to both threatening and appetitive stimuli in juvenile rhesus monkeys.Twenty-four, 2-year-old monkeys with differential rearing histories were tested for fear-potentiated startle responding and consumption of an artificially sweetened solution.Relative to monkeys reared under typical conditions, monkeys removed from their mothers at birth and reared with peers demonstrated both increases in reward responding, as evidenced by greater consumption of a palatable solution in a free choice test, and increased threat responding, as evidenced by enhanced fear-potentiated startle responding. ### Long_Answer: Findings suggest that early rearing impacts juvenile manifestations of both appetitive and aversive emotional systems. Results are discussed in the context of development, anxiety, depression, and substance abuse. ### Final_Prediction: yes

### Question: Does interval training attenuate the metabolic disturbances in type 1 diabetes rat model? ### Context: This study investigated the effect of interval training on blood biochemistry and immune parameters in type 1 diabetic rats.Male Wistar rats were divided into four groups: sedentary (SE, n = 15), interval training (IT, n = 17), diabetic sedentary (DSE, n = 17), diabetic interval training (DIT, n = 17). Diabetes was induced by i.v. injection of streptozotocin (60 mg/kg). Swimming Interval Training consisted of 30-s exercise with 30-s rest, for 30 minutes, during 6 weeks, four times a week, with an overload of 15% of body mass. Plasma glucose, lactate, triacylglycerol and total cholesterol concentrations, phagocytic capacity, cationic vesicle content, and superoxide anion and hydrogen peroxide production by blood neutrophils and peritoneal macrophages were evaluated. Proliferation of mesenteric lymphocytes was also estimated.Interval training resulted in attenuation of the resting hyperglycemic state and decreased blood lipids in the DIT group. Diabetes increased the functionality of blood neutrophils and peritoneal macrophages in the DSE group. Interval training increased all functionality parameters of peritoneal macrophages in the IT group. Interval training also led to a twofold increase in the proliferation of mesenteric lymphocytes after 6 weeks of exercise in the DIT group. ### Long_Answer: Low-volume high-intensity physical exercise attenuates hyperglycemia and dislipidemia induced by type 1 diabetes, and induces changes in the functionality of innate and acquired immunity. ### Final_Prediction: yes

### Question: Is liposome-encapsulated hemoglobin ( hemoglobin-vesicle ) transferred from mother to fetus at the late stage of pregnancy in the rat model? ### Context: Liposome-encapsulated hemoglobin (hemoglobin vesicles: HbV; diameter 250 nm) is reconstructed from human hemoglobin and developed as an artificial oxygen carrier for use as a transfusion alternative. Previous studies using rodent models closely investigated the safety of daily repeated infusions (DRI) of HbV and reported that the reticuloendothelial system was physiologically capable of degrading HbV to maintain plasma clinical chemistry within normal ranges. The present study examined the effect of DRI of HbV on the pregnant rat mother and fetal development, focusing on placental transfer of HbV in pregnancy.Pregnant rats intravenously received HbV bolus injections at 2 ml/kg/day for the last 7 consecutive days till term. The cumulative infusion volume (14 ml/kg) was equal to 25% of the whole blood volume (56 ml/kg).Maternal DRI of HbV had no obvious side effects on the pregnant mother or on fetal development. Maternal vital signs, plasma clinical chemistry, and blood gas parameters were overall normal after DRI of HbV. In addition, maternal/fetal transfer of HbV was limited to the placenta and HbV did not reach the fetus. Histopathological examination with human hemoglobin antibody detected HbV accumulation in the maternal spleen, liver, kidney, and placenta, but not in the fetuses. These results were also confirmed by a pharmacokinetic study using (125)I-labeled HbV. ### Long_Answer: This safety study of HbV use in the pregnant mother and fetus will contribute to a possible application of HbV as a potential treatment for fetal hypoxia by supplying oxygen through the placenta. ### Final_Prediction: no

### Question: Does somatostatin receptor type 2 contribute to the self-renewal of murine embryonic stem cells? ### Context: The roles of G-protein coupled receptors (GPCRs) in stem cell biology remain unclear. In this study, we aimed to identify GPCRs that might contribute to the self-renewal of mouse embryonic stem cells (mESCs).The expression levels of pluripotent genes and GPCR gene were detected in E14 mESCs using PCR array and RT-PCR. Immunofluorescent staining was used to examine the expression of pluripotent markers and the receptor translocation. Western blot analysis was used to detect phosphorylation of signal proteins. Knock-down of receptor was conducted to confirm its role in pluripotency maintenance.In leukemia inhibitory factor (LIF)-free medium, mESCs lost the typical morphology of pluripotency, accompanied by markedly decreases in expression of somatostatin receptor type 2 (SSTR2), as well as the pluripotency biomarkers Oct4, Sox2, Rex1 and Nanog. Addition of the SSTR2 agonist octreotide or seglitide (0.1-30 μmol/L) in LIF-free medium dose-dependently promoted the self-renewal of mESCs, whereas the SSTR2 antagonist S4 (0.03-3 μmol/L) dose-dependently blocked octreotide-induced self-renewal. Knock-down of SSTR2 significantly decreased the self-renewal of mESCs even in the presence of LIF. Addition of LIF (1000 U/mL) or octreotide (1 μmol/L) in LIF-free medium significantly increased both phosphorylation and nuclear ocalization of STAT3. ### Long_Answer: The activation of SSTR2 contributes to the self-renewal of mESCs via activation of the STAT3 pathway. ### Final_Prediction: yes

### Question: Does awarding a medical degree with honours act as a motivator or demotivator to student learning? ### Context: To look at students' support for, and perception of, the effects of awarding a degree with honours.Questionnaires were given to all medical students from those entering year 1 to those graduating, i.e. six cohorts. We performed quantitative and qualitative analyses on the responses.University of Manchester.Medical students.Of 1618 students, 1290 responded (80%). The majority of students thought that we should have a system to award a degree with honours (968/1290[75%]), but this support was related to a number of variables. When asked to rate their agreement to a series of statements, students from the later years were more likely to disagree that an honours system is a helpful motivator for students to learn (Kruskal-Wallis; P<0.0001). In contrast, those students with 'points' counting towards an honours degree were more likely to agree that there should be an honours system (chi2[1]=18.7, P<0.0001). ### Long_Answer: Most students supported the honours system. However, there was less support from students in later years. The qualitative analysis showed a mixture of views. There was a relationship between the probability of being awarding a degree with honours and support of the system. ### Final_Prediction: nan

### Question: Does twenty Questions game performance on medical school entrance predict clinical performance? ### Context: This study is based on the premise that the game of 'Twenty Questions' (TQ) tests the knowledge people acquire through their lives and how well they organise and store it so that they can effectively retrieve, combine and use it to address new life challenges. Therefore, performance on TQ may predict how effectively medical school applicants will organise and store knowledge they acquire during medical training to support their work as doctors.This study was designed to determine whether TQ game performance on medical school entrance predicts performance on a clinical performance examination near graduation.This prospective, longitudinal, observational study involved each medical student in one class playing a game of TQ on a non-medical topic during the first week of medical school. Near graduation, these students completed a 14-case clinical performance examination. Performance on the TQ task was compared with performance on the clinical performance examination.The 24 students who exhibited a logical approach to the TQ task performed better on all senior clinical performance examination measures than did the 26 students who exhibited a random approach. Approach to the task was a better predictor of senior examination diagnosis justification performance than was the Medical College Admission Test (MCAT) Biological Science Test score and accounts for a substantial amount of score variation not attributable to a co-relationship with MCAT Biological Science Test performance. ### Long_Answer: Approach to the TQ task appears to be one reasonable indicator of how students process and store knowledge acquired in their everyday lives and may be a useful predictor of how they will process the knowledge acquired during medical training. The TQ task can be fitted into one slot of a mini medical interview. ### Final_Prediction: yes

### Question: Are the daily diary and the questionnaire equivalent for the evaluation of bowel habits? ### Context: It is unclear whether questionnaires and diary cards, which are widely used to collect data on bowel habits, provide analogous information.We verified the concordance between the data provided by a daily diary and a retrospective questionnaire.A 4-week diary (DIARY) concerning bowel habits was compiled by 221 subjects. They were also asked to fill out a questionnaire on their bowel habits before (BEF) and after (AFT) the diary period.Concerning bowel movements, no significant difference was detected in the concordance between BEF and DIARY (rho: 0.80), AFT and DIARY (rho: 0.84), or BEF and AFT (rho: 0.84). The mean concordance in the other defecation-related parameters between BEF and DIARY (K: 0.62) and between DIARY and AFT (K: 0.63) were both significantly lower than that seen between BEF and AFT (K: 0.80; p<0.01). ### Long_Answer: A considerable discrepancy between the two methods of assessment was found. The higher concordance between BEF and AFT than between DIARY and AFT regarding defecation-related parameters suggests that when a subject recalls events, even those from the recent past, he/she tends to generalize, reporting more or less the same data for different periods of time. These two instruments cannot be viewed as interchangeable, and their inherent differences must be taken into account when deciding which one to employ in different settings. ### Final_Prediction: no

### Question: Do a mixture of feature experts approach for protein-protein interaction prediction? ### Context: High-throughput methods can directly detect the set of interacting proteins in model species but the results are often incomplete and exhibit high false positive and false negative rates. A number of researchers have recently presented methods for integrating direct and indirect data for predicting interactions. These methods utilize a common classifier for all pairs. However, due to missing data and high redundancy among the features used, different protein pairs may benefit from different features based on the set of attributes available. In addition, in many cases it is hard to directly determine which of the data sources contributed to a prediction. This information is important for biologists using these predications in the design of new experiments.To address these challenges we propose a Mixture-of-Feature-Experts method for protein-protein interaction prediction. We split the features into roughly homogeneous sets of feature experts. The individual experts use logistic regression and their scores are combined using another logistic regression. When combining the scores the weighting of each expert depends on the set of input attributes available for that pair. Thus, different experts will have different influence on the prediction depending on the available features. ### Long_Answer: We applied our method to predict the set of interacting proteins in yeast and human cells. Our method improved upon the best previous methods for this task. In addition, the weighting of the experts provides means to evaluate the prediction based on the high scoring features. ### Final_Prediction: yes

### Question: Does the external rotation immobilisation reduce recurrence rates or improve quality of life after primary anterior shoulder dislocation : a systematic review and meta-analysis? ### Context: Conducting a systematic review and meta-analysis of prospective randomised controlled trials directly comparing (1) the rates of recurrence and (2) patient-based quality-of-life assessments after the external rotation (ER) or internal rotation (IR) immobilisation after primary anterior shoulder dislocation.PubMed, EMBASE, the Cochrane Library and ISI Web of Science were searched up to January 2013, using the Boolean operators as follows: (bankart lesion OR shoulder anterior dislocation) AND ((external rotation AND internal rotation) OR immobilisation). All prospective randomised controlled trials directly comparing recurrence rate and patient-based quality-of-life assessments between the ER and IR immobilisations were retrieved. No limitation of the language or publication year existed in our analysis.Seven of 896 studies involving 663 patients were included, 338 in the ER group and 325 in the IR group. No significant difference was observed in the recurrence rate at all ages (risk ratio (RR)=0.65; 95% confidence interval, 0.41-1.03; p=0.067), at the age stratum of ≤30 years (RR=0.70; 95% confidence interval, 0.38-1.29; p=0.250) and >30 years (RR=0.86; 95% confidence interval, 0.38-1.97; p=0.722). Four trials adopted quality-of-life assessments, using the Constant-Murlay functional scoring system, the Rowe scoring system, the Western Ontario Shoulder Instability index (WOSI), the Disabilities of arm, shoulder and hand (DASH) and the American Shoulder and Elbow Surgeons evaluation form (ASES). Only one trial demonstrated borderline statistical significance (p=0.05) and probable superiority of the ER group based on the ASES. No significant difference was observed in other three trials. ### Long_Answer: Based on the results of our analysis, the ER immobilisation could not reduce the rates of recurrence after primary anterior shoulder dislocation or improve the quality of life compared with the IR immobilisation. More rigorous and adequately powered prospective randomised controlled trials with long-term follow-ups are required to elucidate a more objective outcome. ### Final_Prediction: no