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### Question: Do prostaglandin analogs affect eyelid position and motility? ### Context: The authors aim at investigating the possible clinical effects of topical Prostaglandin Analogs on eyelid position and motility with this single masked protocol in a cross-sectional study.A group (group A) of 182 patients on treatment for glaucoma with prostaglandin analogs (latanoprost, travoprost, and bimatoprost) and a group of 191 age-matched normal controls (group B) were enrolled in the study. Group A was subdivided into 3 subgroups according to the prostaglandin analogs used by the patients. Group A1: 84 patients on latanoprost, group A2: 56 patients on travoprost, and group A3: 42 patients on bimatoprost. Two positive control groups (group H of 115 patients with lower lid involutional entropion or ectropion secondary to horizontal lid laxity (HLL), and a group P of 137 patients with involutive aponeurotic blepharoptosis) were also enrolled in the study. For the upper eyelid, the following parameters were measured: margin-reflex distance (MRD), upper lid crease position, levator function. For the lower lid, the following parameters were used: HLL and lower lid excursion (LLE). Statistical analysis of the data was done to assess whether there was any statistical significant difference for each of the parameter between group A (and its subgroups) and, respectively, groups B, H, and P. Similarly, it was also compared with group B, with group H, and then with group P. Analysis of variance of the eyelid parameters was also carried out in the 3 subgroups A1, A2, and A3.There was no statistically significant difference for each studied parameter between group B and, respectively, groups A1, A2, A3 and group A, nor there was any statistically significant variance between parameters in the 3 subgroups A1, A2, and A3. The accuracy of the eyelid parameters was confirmed while obtaining statistically significant differences in LLE (P<0.05) and in HLL (P<0.001) comparing group A (and its subgroups) and group H and also in MRD and upper lid crest (P<0.001) comparing group A (and its subgroups) and group P. ### Long_Answer: There is no evidence that prostaglandin analogs significantly affect the eyelids' tissues to produce eyelid malposition. ### Final_Prediction: nan

### Question: Is illicit drug use a significant risk factor for loss to follow up in patients with HIV-1 infection at a large urban HIV clinic in Tokyo? ### Context: Loss to follow up (LTFU) is an important prognostic factor in patients with HIV-1 infection. The impact of illicit drug use on LTFU of patients with HIV-1 infection is unknown in Japan.A single center observational study was conducted to elucidate the impact of illicit drug use on LTFU at a large HIV clinic in Tokyo. LTFU was defined as those who discontinued their visits to the clinic for at least 12 months and were not known to be under the care of other facilities or have died within 12 months of their last visit. Patients who first visited the clinic between January 2005 and August 2010 were enrolled. Information on illicit drug use was collected in a structured interview and medical charts. Comparison of the effects of illicit drug use and no use on LTFU was conducted by uni- and multi-variate Cox hazards models as the primary exposure.The study subjects were 1,208 patients, mostly Japanese men, of relatively young age, and infected through homosexual contact. A total of 111 patients (9.2%) were LTFU (incidence: 24.9 per 1,000 person-years). Among illicit drug users and non users, 55 (13.3%) and 56 (7.1%) patients, respectively, were LTFU, with incidence of 35.7 and 19.2 per 1,000 person-years, respectively. Uni- and multi-variate analyses showed that illicit drug use was a significant risk for LTFU (HR=1.860; 95% CI, 1.282-2.699; p=0.001) (adjusted HR=1.544; 95% CI, 1.028-2.318; p=0.036). Multivariate analysis also identified young age, high CD4 count, no antiretroviral therapy, and no health insurance as risk factors for LTFU. ### Long_Answer: The incidence of LTFU among illicit drug users was almost twice higher than that among non users. Effective intervention for illicit drug use in this population is warranted to ensure proper treatment and prevent the spread of HIV. ### Final_Prediction: yes

### Question: Is the 6-minute pegboard and ring test correlated with upper extremity activity of daily living in chronic obstructive pulmonary disease? ### Context: Upper-extremity exercise is for pulmonary rehabilitation. The 6-minute pegboard and ring test (6PBRT) was developed to evaluate arm exercise capacity in patients with chronic obstructive pulmonary disease (COPD). The purpose of this study was to characterize the 6PBRT and evaluate its relationship with upper-extremity activities of daily living (ADLs) in COPD patients.Twenty outpatients with mild to very severe COPD underwent the 6PBRT and spirometry, and their maximal inspiratory and expiratory pressures and grip strength were measured. For the 6PBRT, subjects were asked to move as many rings as possible in 6 minutes, and the score was the number of moved rings during the 6-minute period. Upper-extremity ADLs were evaluated with the upper extremity activities subdomain of the modified Pulmonary Functional Status and Dyspnea Questionnaire. Upper-extremity ADLs were also measured objectively by using a wrist accelerometer every day for 1 week.There was a positive correlation between 6PBRT score and inspiratory capacity (r = 0.71, P < 0.001), inspiratory capacity/total lung capacity predicted (r = 0.68, P < 0.01), and forced vial capacity (r = 0.57, P < 0.01). There was also a positive correlation between 6PBRT score and accelerometer count (r = 0.54, P < 0.05) and a negative correlation between 6PBRT score and arm activity score (ρ = -0.49, P < 0.05). ### Long_Answer: The 6PBRT may be a predictive test to maintain and improve upper-extremity ADL during pulmonary rehabilitation in patients with COPD. ### Final_Prediction: yes

### Question: Corneal topography bow-tie pattern: artifact of videokeratoscopy? ### Context: To test the hypothesis that the bow-tie corneal topography pattern results from corneal asphericity in the presence of astigmatism.Astigmatic color-coded power maps using different shape factors were computer generated. Each simulation was based on the calculation of dioptric power at 20 points along each of 180 hemimeridia, for a total of 3600 points. The calculations were made independent of the capture or measurement of video-keratographs. These simulations were compared to power maps taken from clinical records.A shape factor of 1.00 resulted in a spherocylinder color-coded map with straight-edged sectors of power. The familiar bow-tie pattern was generated using an elliptical model with a shape factor of less than 1.00. This pattern was reversed by modeling the cornea as an oblate ellipsoid using a shape factor greater than 1.00. ### Long_Answer: By simple alteration of the amount of corneal asphericity through manipulation of the shape factor, computer simulation showed that this surface characteristic is responsible for the bow-tie pattern observed in corneal topography power maps. ### Final_Prediction: nan

### Question: Does c-Maf Transcription Factor regulate ADAMTS-12 Expression in Human Chondrogenic Cells? ### Context: ADAMTS (a disintegrin and metalloproteinase with thrombospondin type-1 motif) zinc metalloproteinases are important during the synthesis and breakdown of cartilage extracellular matrix. ADAMTS-12 is up-regulated during in vitro chondrogenesis and embryonic limb development; however, the regulation of ADAMTS-12 expression in cartilage remains unknown. The transcription factor c-Maf is a member of Maf family of basic ZIP (bZIP) transcription factors. Expression of c-Maf is highest in hypertrophic chondrocytes during embryonic development and postnatal growth. We hypothesize that c-Maf and ADAMTS-12 are co-expressed during chondrocyte differentiation and that c-Maf regulates ADAMTS-12 expression during chondrogenesis.Promoter analysis and species alignments identified potential c-Maf binding sites in the ADAMTS-12 promoter. c-Maf and ADAMTS-12 co-expression was monitored during chondrogenesis of stem cell pellet cultures. Luciferase expression driven by ADAMTS-12 promoter segments was measured in the presence and absence of c-Maf, and synthetic oligonucleotides were used to confirm specific binding of c-Maf to ADAMTS-12 promoter sequences.In vitro chondrogenesis from human mesenchymal stem cells revealed co-expression of ADAMTS-12 and c-Maf during differentiation. Truncation and point mutations of the ADAMTS-12 promoter evaluated in reporter assays localized the response to the proximal 315 bp of the ADAMTS-12 promoter, which contained a predicted c-Maf recognition element (MARE) at position -61. Electorphoretic mobility shift assay confirmed that c-Maf directly interacted with the MARE at position -61. ### Long_Answer: These data suggest that c-Maf is involved in chondrocyte differentiation and hypertrophy, at least in part, through the regulation of ADAMTS-12 expression at a newly identified MARE in its proximal promoter. ### Final_Prediction: yes

### Question: Does hyaluronan induce scarless repair in mouse limb organ culture? ### Context: Wounded fetal mouse limbs harvested from two distinct time points in gestation heal differently in organ culture. The healing of a gestational day 14 limb is by scarless repair, whereas gestational day 18 (gd 18) limbs heal by scarring. The persistence of elevated levels of hyaluronic acid (HA) is a major difference in the extracellular matrix of scarless repair. The purpose of this study was to demonstrate that chronic additions of HA to incisional wounds of gd 18 limbs induces scarless repair.Time-dated pregnant CD-1 mice (term, 20 days) were killed on gestational day 18 and fetuses were harvested via laparotomy. A through and through stab wound was made in each forelimb with a 1-mm microscapel, and the wound was closed with a single 10-0 nylon suture. The forelimbs were amputated at the level of the shoulder and placed in organ culture. Daily medium changes with 1 mL of BGJb (devoid of serum) were made. Half the cultures received 10 microL of HA (4 mg/mL) directly to the wound site with each medium change. The other half of the cultures received 10 microL of phosphate-buffered saline (PBS-control). At day 7, the limbs were harvested, fixed in methyl Carnoys solution, paraffin embedded, and 5-microm serial sections cut. The sections were stained with H&E or Sirius red/fast green. The sections were viewed in a blinded fashion by two observers. Suture defined the wound site, and the sections were graded for healing by scarring.Minimal limb growth occurred in both control and HA-treated limbs. Grossly, both control and treated limbs healed incisional wounds by 7 days in culture. Limbs from both treatment and control groups showed viability by microscopic analysis. The limbs treated with HA had no appreciable scar morphologically in sections in which epithelial dimpling and suture were evident. The orientation of the collagen fiber bundles in the control wounds were in parallel arrays perpendicular to the incision. The orientation of the collagen fiber bundles in the HA-treated limbs had a basket weave pattern that was indistinguishable from unwounded dermis. The direct repeated additions of HA to healing organ cultured limb explants of gestational day 18 fetal mice promoted scarless repair. ### Long_Answer: This result demonstrates that chronic elevation of HA in the microenvironment of a wound affects healing by promoting the deposition of a more dermal-like connective tissue matrix in the wound site. The maintenance of elevated levels of HA could have utility in the clinical setting to improve the organization of connective tissue, leading to the reduction of scar complications. ### Final_Prediction: yes

### Question: Is strictureplasty an effective option in the operative management of duodenal Crohn 's disease? ### Context: Duodenal Crohn's disease requiring surgery has traditionally been managed with a bypass procedure. We compared our experience with duodenal strictureplasty with this traditional approach.Records of patients operated on for duodenal Crohn's disease since 1980 were retrospectively reviewed. Patients having strictureplasty or bypass were compared with regard to demographics, indications, complications, and outcome.Since 1980, 34 patients were operated on for duodenal Crohn's disease. Mean age was 38.9 (range, 16-68) years, and 20 of 34 patients were females, with no significant differences between operative groups. Obstruction was the presenting symptom in 33 of 34 patients, and all had strictures. The basis for diagnosis of duodenal Crohn's disease was macroscopic appearance and the presence of Crohn's elsewhere in 29 of 34 patients, with only 5 of 34 having either duodenal or contiguous antral granulomas. Thirty-seven strictures were present in the 34 patients; 24 were in the proximal duodenum (8 strictureplasty, 16 bypass), 9 were in the midduodenum (4 strictureplasty, 5 bypass), and 4 were in the distal duodenum (3 strictureplasty, 1 bypass). Bypass was performed in 21 patients, with two operative complications, and at a mean follow-up of 8 years, 1 of 21 patients required reoperation for recurrent disease. Strictureplasty was performed in 13 patients, with two operative complication, and at a mean follow-up of 3.6 years, 1 patient required reoperation for recurrence also. Vagotomy was performed in 16 of 21 bypasses and 7 of 13 strictureplasties. ### Long_Answer: Although follow-up is shorter, strictureplasty is a safe and effective operation for duodenal Crohn's disease and should be considered when feasible. ### Final_Prediction: yes

### Question: Does cesarean section before the scheduled date increase the risk of neonatal morbidity? ### Context: Previous studies led to the recommendation to schedule planned elective cesarean deliveries at or after 39 weeks of gestation and not before 38 weeks. The question is whether this practice is appropriate in face of possible risks to the newborn should the pregnancy have to be ended by cesarean section before the scheduled date.To compare the outcomes of newborn infants who were delivered on their scheduled day by elective cesarean section versus those who required delivery earlier.This single-center retrospective study was based on medical records covering a period of 18 months. We compared the neonatal outcomes of 272 infants delivered by elective cesarean section as scheduled (at 38.8 +/- 0.8 weeks gestation)and 44 infants who had to be delivered earlier than planned j(at 37.9 +/- 1.1 weeks).We found no morbidity directly related to delivery by cesarean section before the scheduled date. There were no significant differences in the need for resuscitation after delivery. Although more of the infants who were delivered early were admitted to intensive care and overall stayed longer in the hospital (5.8 +/- 7.3 vs. 3.9 +/- 0.8 days, P<0.02), their more severe respiratory illness and subsequent longer hospitalization was the result of their younger gestational age. Transient tachypnea of the newborn was associated with younger gestational age at delivery in both groups. ### Long_Answer: We suggest continuing with the current recommendation to postpone elective cesarean singleton deliveries beyond 38-39 weeks of gestation whenever possible. ### Final_Prediction: nan

### Question: Does gain-of-function FHF1 mutation cause early-onset epileptic encephalopathy with cerebellar atrophy? ### Context: Voltage-gated sodium channel (Nav)-encoding genes are among early-onset epileptic encephalopathies (EOEE) targets, suggesting that other genes encoding Nav-binding proteins, such as fibroblast growth factor homologous factors (FHFs), may also play roles in these disorders.To identify additional genes for EOEE, we performed whole-exome sequencing in a family quintet with 2 siblings with a lethal disease characterized by EOEE and cerebellar atrophy. The pathogenic nature and functional consequences of the identified sequence alteration were determined by electrophysiologic studies in vitro and in vivo.A de novo heterozygous missense mutation was identified in the FHF1 gene (FHF1AR114H, FHF1BR52H) in the 2 affected siblings. The mutant FHF1 proteins had a strong gain-of-function phenotype in transfected Neuro2A cells, enhancing the depolarizing shifts in Nav1.6 voltage-dependent fast inactivation, predicting increased neuronal excitability. Surprisingly, the gain-of-function effect is predicted to result from weaker interaction of mutant FHF1 with the Nav cytoplasmic tail. Transgenic overexpression of mutant FHF1B in zebrafish larvae enhanced epileptiform discharges, demonstrating the epileptic potential of this FHF1 mutation in the affected children. ### Long_Answer: Our data demonstrate that gain-of-function FHF mutations can cause neurologic disorder, and expand the repertoire of genetic causes (FHF1) and mechanisms (altered Nav gating) underlying EOEE and cerebellar atrophy. ### Final_Prediction: yes

### Question: Does the hospitalization after a cancer diagnosis modify adherence to process indicators of diabetes care quality? ### Context: This study was designed to answer the question whether surgery due to newly diagnosed cancer may modify quality of diabetes' management, as suggested by current guidelines.Adherence to guideline composite indicator (GCI), a process indicator including one annual assessment of HbA1c and at least two among eye examination, serum lipids measurement and microalbuminuria, was evaluated between years 2011-2012 and 2014-2015 in 158,069 diabetic patients living in Tuscany, Italy, on 1 January 2011 and surviving on 31 December 2015, of whom 661 were hospitalized in index year 2013 for a surgery procedure due to a newly incident cancer. Difference in GCI modification (DELTA_GCI) of these patients was compared with that of diabetic people without cancer, strictly matched for main confounders by means of a propensity score.In diabetic patients with cancer, GCI adherence increased by about 8 % between years 2011-2012 and 2014-2015. When compared with controls, DELTA_GCI increased by 6 % in cancer group compared with controls (p < 0.05), but any significance was lost after matching the groups by propensity score (3 %; p = NS). ### Long_Answer: Our study suggests that a hospitalization for a surgical procedure due to a newly diagnosed cancer does not influence the compliance to a quality process indicator of diabetes care such as GCI. ### Final_Prediction: nan

### Question: Do type D personality and diabetes predict the onset of depressive symptoms in patients after percutaneous coronary intervention? ### Context: Depression is common in cardiac patients and has been associated with adverse clinical outcome. However, little is known about predictors of the onset of depressive symptoms. We examined predictors of the onset of depressive symptoms at 12 months post-percutaneous coronary intervention (PCI) in patients treated in the drug-eluting stent era.Unselected patients, free from depressive symptoms at 6 months with a depression score at 12 months treated with PCI with either drug-eluting or bare stent implantation as part of the RESEARCH registry qualified for inclusion in the current study. Patients completed the Hospital Anxiety and Depression Scale at 6 and 12 months and the Type D Personality Scale (DS14) at 6 months post-PCI. Six months was used as the baseline assessment.Of 542 patients, 41 (8%) had developed significant depressive symptoms at 12 months. The occurrence of a new cardiac event between 6 and 12 months post-index event did not influence the incidence of depressive symptoms at 12 months. Depressive patients were more likely to have a type D personality (34% vs 16%, P = .003) and diabetes (24% vs 11%, P = .01) than nondepressive patients. Type D personality (odds ratio 3.04, 95% CI 1.50-6.16) and diabetes (odds ratio 2.75, 95% CI 1.25-6.05) were independent predictors of the onset of depressive symptoms 12 months post-PCI in adjusted analyses. In patients with neither risk factors (type D or diabetes), the incidence of depression was 5.1% with the incidence more than doubling to 13.2% and 30% for each additional risk factor. ### Long_Answer: Type D personality and diabetes comprise risk factors for the onset of depressive symptoms post-PCI. In clinical practice, patients with these risk factors should be identified and considered for psychosocial intervention targeting depression to enhance secondary prevention. ### Final_Prediction: yes

### Question: Is presence of the metabolic syndrome associated with shorter time to castration-resistant prostate cancer? ### Context: Metabolic syndrome (MS) is a set of risk factors that includes obesity and insulin resistance and has been implicated in the development of prostate cancer. Its impact on androgen deprivation therapy (ADT) efficacy has not been studied.Retrospective study of prostate cancer patients seen from 1998 to 2005 in a medical oncology clinic. MS, as defined by modified Adult Treatment Panel III criteria, was assessed at the time of initiation of ADT. The study end points were time to prostate-specific antigen (PSA) progression and overall survival (OS) from time of starting ADT.Eighty-two patients treated with ADT and data to assess for presence of MS were identified. Median age in men with and without MS was 70 years and 49% of the patients evaluated met criteria for MS. Median time to PSA progression for patients with MS was 16 versus 36 months without MS (P=0.003). The median OS for patients with MS was 36.5 months after commencing ADT compared with 46.7 months for those patients without MS (P=0.061). ### Long_Answer: This preliminary data suggest that MS is a risk factor for earlier development of castration-resistant prostate cancer and support the need for a prospective evaluation of this finding. ### Final_Prediction: yes

### Question: Peripheral neuropathy associated with leflunomide: is there a risk patient profile? ### Context: (i) To monitor the potential clinical neurotoxic symptoms in patients treated with leflunomide in daily practice and (ii) to describe the characteristics of patients presenting with this peripheral nervous system symptoms.All patients treated with leflunomide between May 2000 and April 2003 and followed in the rheumatology department of the University Hospital participated in the study. Data concerning treatment patterns with leflunomide, demographic and disease characteristics were obtained from clinical charts. Neuropathy was diagnosed with nerve conduction study (NCS). Cases of neuropathy were described and then compared to other patients using univariate analyses.One hundred and thirteen patients were included in the study. M/F sex ratio was 0.45. Mean age at start of treatment was 55.6 years (range = 27-81). During the study period, eight incident cases of peripheral neuropathy and two cases of worsening of preexisting neuropathy were reported (incidence: 9.8%). Compared with other patients, neuropathy cases were older (69 vs. 54 years, p = 0.0006), more often diabetic (30% vs. 2.9%, p = 0.009) and more often treated with potentially neurotoxic drugs (20% vs. 1.9%, p = 0.039). At least one risk factor (potentially neurotoxic drug or diabetes) was found in 50% of patients with neuropathy versus 4% of patients without neuropathy (56% PPV, 96% NPV). ### Long_Answer: Cases of toxic neuropathy have been observed during treatment of rheumatoid arthritis with leflunomide. Their occurrence seems to be associated with known risk factors. Careful monitoring of the patient's neurological status during leflunomide treatment is therefore mandatory. ### Final_Prediction: nan

### Question: Does h3 receptor blockade by thioperamide enhance cognition in rats without inducing locomotor sensitization? ### Context: Attention deficit hyperactivity disorder (ADHD) is currently treated with psychomotor stimulants, including methylphenidate and amphetamine. Several adverse effects are associated with these drugs, however, such as agitation and abuse. H(3) receptor antagonists are under clinical investigation for ADHD.To investigate the potential of thioperamide, a prototypical H(3) receptor antagonist, to enhance learning and attention while inducing no effects on locomotor stimulation and sensitization, or alterations in ACTH levels.Thioperamide (1, 3, 10, 30 mg/kg) was administered prior to testing in a multi-trial, inhibitory avoidance response in rat pups (five trials separated by 1 min) to evaluate attention/cognition. Locomotor sensitization and cross-sensitization was assessed following administration of methylphenidate (3 mg/kg), cocaine (10 mg/kg), or thioperamide (1, 3, 10 mg/kg).Thioperamide significantly enhanced performance of the five-trial inhibitory avoidance response with efficacy similar to that previously reported for methylphenidate. Administration of amphetamine, methylphenidate and cocaine produced significant locomotor sensitization, however. In contrast, thioperamide did not induce locomotor stimulation or sensitization, nor did it cross-sensitize to the stimulant effects of amphetamine or cocaine. The repeated administration of methylphenidate significantly elevated ACTH levels, while thioperamide did not affect this neuroendocrine endpoint. ### Long_Answer: H(3) receptor blockade may offer a safer alternative to psychomotor stimulants for the treatment of ADHD. ### Final_Prediction: yes

### Question: Does the Amsterdam preoperative anxiety and information scale provide a simple and reliable measure of preoperative anxiety? ### Context: To compare three anxiety scales; the anxiety visual analogue scale (VAS), the anxiety component of the Amsterdam preoperative anxiety and information scale (APAIS), and the state portion of the Spielburger state-trait anxiety inventory (STAI), for assessment of preoperative anxiety levels in same day admission patients.Patients completed the three anxiety assessment scales both before and after seeing the anesthesiologist preoperatively. The scales used were the STAI, the six-question APAIS, and the VAS. APAIS was further subdivided to assess anxiety about anesthesia (sum A), anxiety about surgery (sum S) and a combined anxiety total (i.e., sum C = sum A + sum S). These scales were compared to one another. Pearson's correlation (pair-wise deletion) was used for validity testing. Cronbach's alpha analysis was used to test internal validity of the various components of the APAIS scale. A correlation co-efficient (r) > or = 0.6 and P < 0.05 were considered significant.Four hundred and sixty three scale sets were completed by 197 patients. There was significant and positive correlation between VAS and STAI r = 0.64, P < 0.001), VAS and APAIS r = 0.6, P < 0.001), sum C and STAI r = 0.63, P < 0.001) and between VAS and sum C r = 0.61, P < 0.001). Sum C and STAI r value were consistent with repeated administration. Cronbach's alpha-levels for the anxiety components of the APAIS (sum C) and desire for information were 0.84 and 0.77 respectively. ### Long_Answer: In addition to VAS, the anxiety component of APAIS (sum C) is a promising new practical tool to assess preoperative patient anxiety levels. ### Final_Prediction: yes

### Question: Does vitamin D antagonize negative effects of preeclampsia on fetal endothelial colony forming cell number and function? ### Context: Endothelial dysfunction is a primary feature of preeclampsia, a pregnancy complication associated with an increased future cardiovascular risk for mother and offspring. Endothelial colony forming cells (ECFC) are endothelial progenitor cells that participate in vasculogenesis and endothelial repair.We hypothesized that the number and functional properties of fetal cord blood-derived ECFCs are reduced in preeclampsia compared to uncomplicated pregnancy (controls), and asked if adverse effects of preeclampsia on ECFC function are reversed by 1,25 (OH)2 vitamin D3.This was a nested, case-control study. Forty women with uncomplicated pregnancy and 33 women with PE were recruited at Magee-Womens Hospital (USA) or at Hannover Medical School (Germany).Time to ECFC colony appearance in culture, and number of colonies formed, were determined. Functional abilities of ECFCs were assessed in vitro by tubule formation in Matrigel assay, migration, and proliferation. ECFC function was tested in the presence or absence of 1,25 (OH)2 vitamin D3, and after vitamin D receptor (VDR) or VEGF signaling blockade.The number of cord ECFC colonies was lower (P = 0.04) in preeclampsia compared to controls. ECFCs from preeclampsia showed reduced proliferation (P<0.0001), formed fewer tubules (P = 0.02), and migrated less (P = 0.049) than control. Vitamin D3 significantly improved preeclampsia ECFC functional properties. VDR- or VEGF blockade reduced tubule formation, partially restorable by vitamin D3. ### Long_Answer: Fetal ECFCs from preeclamptic pregnancies are reduced in number and dysfunctional. Vitamin D3 had rescuing effects. This may have implications for the increased cardiovascular risk associated with preeclampsia. ### Final_Prediction: yes

### Question: Is serum arylhydrocarbon receptor transactivating activity elevated in type 2 diabetic patients with diabetic nephropathy? ### Context: Evidence is emerging that exposure to persistent organic pollutants (POPs) is a risk factor for obesity-related diseases and for diabetes mellitus (DM). We found that POPs could be measured by a cell-based arylhydrocarbon receptor (AhR)-dependent reporter assay. We tested if serum AhR transactivating (AHRT) activities are a risk factor for diabetic nephropathy in people with type 2 diabetes.We enrolled diabetic patients with normoalbuminuria (n = 36), microalbuminuria (n = 29), macroalbuminuria (n = 8) and end-stage renal disease (n = 31). Sera were tested for their AHRT activities, which were standardized by an AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and expressed as TCDD equivalents (TCDDeq pmol/L).Mean serum AHRT activities were higher in patients with microalbuminuria (40.1 ± 7.1 pmol/L), macroalbuminuria (37.4 ± 5.5 pmol/L) and end-stage renal disease (59.1 ± 20.0 pmol/L) than in subjects with normoalbuminuria (12.7 ± 5.4 pmol/L; P < 0.05 for all comparisons). Serum AhR ligands showed a correlation with estimated glomerular filtration rate (eGFR; r = -0.663, P < 0.001), serum creatinine level (r = 0.635, P < 0.001), systolic blood pressure (r = 0.223, P = 0.026), glycated hemoglobim (r = 0.339, P < 0.001) and diabetic duration (r = 0.394, P < 0.001). In a multiple regression analysis, diabetic nephropathy was found to be an independent risk factor for higher AHRT activity after controlling for the confounding factors. ### Long_Answer: The present findings suggest serum AHRT activity, thus serum AhR ligands, is a risk factor for diabetic nephropathy. Further studies are required to clarify if an accumulation of POPs in the body is causally related to diabetic nephropathy. ### Final_Prediction: yes

### Question: Is kidney function decline after a non-dialysis-requiring acute kidney injury associated with higher long-term mortality in critically ill survivors? ### Context: The adverse consequences of a non-dialysis-requiring acute kidney injury (AKI) are unclear. This study aimed to assess the long-term prognoses for critically ill patients experiencing a non-dialysis-requiring AKI.This retrospective observational cohort study investigated non-dialysis-requiring AKI survivors in surgical intensive care units between January 2002 and June 2010. All longitudinal post-discharge serum creatinine measurements and information regarding end-stage renal disease (ESRD) and death were collected. We assessed the long-term outcomes of chronic kidney disease (CKD), ESRD and all-cause mortality beyond discharge.Of the 922 identified critically ill patients with a non-dialysis-requiring AKI, 634 (68.8%) patients who survived to discharge were enrolled. A total of 207 patients died after a median follow-up of 700.5 days. The median intervals between the onset of the AKI and the composite endpoints "stage 3 CKD or death", "stage 4 CKD or death", "stage 5 CKD or death", and "ESRD or death" were 685, 1319, 1743, and 2048 days, respectively. This finding shows a steady long-term decline in kidney function after discharge. Using the multivariate Cox proportional hazard model, we found that every 1 mL/min/1.73 m2 decrease from baseline estimated glomerular filtration rate (eGFR) of individuals who progressed to stage 3, 4, and 5 CKD increased the risks of long-term mortality by 0.7%, 2.3%, and 4.1%, respectively (all p < 0.05). This result indicates that the mortality risk increased significantly in a graded manner as kidney function declined from the baseline eGFR to advanced stages of CKD during the follow-up period. ### Long_Answer: In critically ill patients who survive a non-dialysis-requiring AKI, there is a need for continuous monitoring and kidney function protection beyond discharge. ### Final_Prediction: yes

### Question: Are increased levels of tumor necrosis factor-alpha and decreased levels of interleukin-12 p 70 in tracheal aspirates , within 2 hrs after birth , associated with mortality among ventilated preterm infants? ### Context: To determine the association of antibacterial interleukin (IL)-12 p 70 levels as well as the pathogen-induced proinflammatory cytokine response in tracheal aspirate (TA) to respiratory failure and mortality among ventilated preterm infants.A prospective observational clinical cohort study with measurements of cytokine levels and microbial cultures of TA from ventilated preterm neonates. Interleukin (IL)-1 beta, IL-8, IL-6, IL-10, IL-12 p 70, and tumor necrosis factor (TNF)-alpha were measured in TA within 2 hrs of birth, and comorbidity characteristics were recorded prospectively. The association between cytokine levels in TA and neonatal mortality was determined, with correction for comorbidity factors by means of multivariate stepwise logistic regression.A single tertiary neonatal intensive care unit at the University Hospital of Antwerp, Belgium.One hundred forty-one neonates born before a gestational age of 31 wks and who required ventilation were enrolled in the study; 31 (22%) died and 37 (26%) had airway colonization.The airway colonization rate was significantly greater among deceased neonates (45% vs. 21%; chi-square, 7.4; p=.007). Neonates who died had a significantly lower IL-12 p 70 cytokine level (6 pg/mL vs. 11 pg/mL; p<.05) in their TA. Neonates with a low IL-12 p 70 cytokine level had more pronounced respiratory failure (significantly higher oxygenation index, higher degree of radiologic respiratory distress syndrome, higher critical index for babies score, and more surfactant use). Multivariate analysis revealed that, after correction for severity of disease by critical index for babies score, the degree of intraventricular hemorrhage (odds ratio, 5.0 [95% confidence interval, 2.6-9.7]), low IL-12 p 70 levels (odds ratio, 4.9 [95% confidence interval, 2.1-11.7]), and high TNF-alpha levels in TA (odds ratio, 3.5 [95% confidence interval, 1.6-7.5]) were significantly associated with neonatal mortality. ### Long_Answer: Pathogen-induced excessive production of the proinflammatory cytokine TNF-alpha and lack of antibacterial IL-12 p 70 response in the TA are associated with increased neonatal mortality among ventilated preterm infants. ### Final_Prediction: yes

### Question: Do protease inhibitor levels in hair strongly predict virologic response to treatment? ### Context: Antiretroviral (ARV) therapies fail when behavioral or biologic factors lead to inadequate medication exposure. The currently available methods to assess ARV exposure are limited. Levels of ARVs in hair reflect plasma concentrations over weeks to months, and may provide a novel method for predicting therapeutic responses.The Women's Interagency HIV Study, a prospective cohort of HIV-infected women, provided the basis for developing and assessing methods to measure commonly prescribed protease inhibitors (lopinavir/ritonavir and atazanavir) in small hair samples. We examined the association between hair protease inhibitor levels and initial virologic responses to therapy in multivariate logistic regression models.ARV concentrations in hair were strongly and independently associated with treatment response for 224 women starting a new protease inhibitor-based regimen. For participants initiating lopinavir/ritonavir, the odds ratio (OR) for virologic suppression was 39.8 [95% confidence interval (CI) = 2.8-564] for those with lopinavir hair levels in the top tertile (>1.9 ng/mg) compared to the bottom (</=0.41 ng/mg) when controlling for self-reported adherence, age, race, starting viral load and CD4 cell count, and prior experience with protease inhibitors. For women starting atazanavir, the adjusted OR for virologic success was 7.7 (95% CI = 2.0-29.7) for those with hair concentrations in the top tertile (>3.4 ng/mg) compared to the lowest (</=1.2 ng/mg). ### Long_Answer: Protease inhibitor levels in small hair samples were the strongest independent predictor of virologic success in a diverse group of HIV-infected adults. This non-invasive method for determining ARV exposure may have particular relevance for the epidemic in resource-poor settings due to the ease of collecting and storing hair. ### Final_Prediction: yes

### Question: Is younger gestational age associated with worse neurodevelopmental outcomes after cardiac surgery in infancy? ### Context: Evaluate the impact of near-term delivery on neurodevelopmental (ND) outcomes in children with congenital heart disease (CHD).Secondary analysis of data from a study of genetic polymorphisms and ND outcomes after cardiac surgery in infants. The effect of gestational age (GA) as a continuous variable on ND outcomes was evaluated using general linear regression models. GA was also evaluated as a categorical variable to seek a threshold for better outcomes. ND domains tested at 4 years of age included cognition, language skills, attention, impulsivity, memory, executive function, social competence, visual-motor, and fine-motor skills.ND outcomes and GA were available for 378 infants. Median GA was 39 weeks (range, 28-42 weeks) with 351 born at 36 weeks or more (near-term/term). In univariate analysis of the near-term/term subgroup, older GA predicted better performance for cognition, visual-motor, and fine-motor skills. After covariate adjustment, older GA predicted better performance for fine-motor skills (P = .018). Performance for cognition, language, executive function, social skills, visual-motor, and fine-motor skills was better for those born at 39 to 40 weeks of GA or more versus those born at less than 39 weeks (all P < .05). ### Long_Answer: These findings are consistent with the hypothesis that delivery before 39 to 40 weeks of GA is associated with worse outcomes in patients with CHD. Early delivery of a child with CHD is often indicated because of maternal or fetal health issues. In the absence of these concerns, these data suggest that elective (or spontaneous) delivery at 39 to 40 weeks of GA is associated with better ND outcomes. ### Final_Prediction: yes

### Question: Is location of pulmonary metastasis in pediatric osteosarcoma predictive of outcome? ### Context: The 3-year survival after pulmonary metastasectomy for osteosarcoma (OS) is approximately 30%. Resection of metastatic disease can prolong life in pediatric patients with OS. Our objective is to assess the outcome of pediatric patients with pulmonary metastases located centrally as compared with peripheral lesions.A retrospective review of patients 0 to 21 years old with a diagnosis of OS with pulmonary metastases on computed tomographic scan between 1985 and 2000 was completed. Demographics, metastasis location, survival, morbidity, and mortality were evaluated.Of 115 patients who had pulmonary metastasis secondary to OS, there were 96 wedge resections and 13 lobectomy/pneumonectomies in 84 patients. The morbidity of wedge resection was 9% and lobectomy/pneumonectomy was 8%. There were no deaths from surgery. The median survival for patients undergoing lobectomy compared with wedge resection was 0.61 and 1.14 years, respectively, but did not reach statistical significance. The median overall survival for the entire cohort was 0.75 years. The median overall survival after initial detection of metastatic disease was 1.06 years among the patients with peripheral disease, compared with 0.38 years in patients with central disease (P = .008). ### Long_Answer: Patients with central pulmonary metastases in OS have a very poor prognosis, even after operative treatment, compared with those with peripheral disease. Patients with central lesions may benefit from other nonsurgical treatment options. ### Final_Prediction: yes

### Question: Does extracorporeal photochemotherapy induce a significant increase in CD36+ circulating monocytes in patients with mycosis fungoides? ### Context: In patients with Sezary syndrome undergoing extracorporeal photochemotherapy it is currently thought that photodamage of a congruent number of pathogenic circulating T cells is a necessary condition for a specific anticlonal response to be induced against these cells by the immune system. However other mechanisms of action, such as the induction of release by photoirradiated monocytes of some cytokines, are thought to cooperate in the induction of a therapeutic response.We investigated the effects of extracorporeal photochemotherapy on peripheral blood mononuclear cells in seven stage Ib cutaneous T cell lymphoma patients.Samples of peripheral blood were taken before starting extracorporeal photochemotherapy (baseline), and before the 3rd and 6th cycle of treatment, and then incubated with specific monoclonal antibodies.The results showed a significant increase of CD8+ and CD36+ and a significant decrease of CD25+ in all the treated patients. ### Long_Answer: Our results show that extracorporeal photochemotherapy is able to induce an increase of CD36+ cell in peripheral blood of patients with mycosis fungoides in its early stages. This subset of monocytes could be involved in the complex mechanism of action of extracorporeal photochemotherapy. ### Final_Prediction: yes

### Question: Are morningness-eveningness preferences of emergency medicine residents skewed toward eveningness? ### Context: To determine the morningness-eveningness (ME) distribution of emergency medicine (EM) residents.A voluntary, modified ME questionnaire was administered to all EM residents in the United States at the time of the 1995 American Board of Emergency Medicine's annual In-Training Examination.Seventy-eight percent (2,047/2,614) of the surveys were returned. ME scores ranged from 24 to 76, with a median score of 49 (interquartile range 44, 56). The scores were distributed differently from those of the normal population (p < 0.001), being skewed toward eveningness. There was a correlation (r = 0.13, p < 0.0001) between resident age and ME score, with older residents being more morning-oriented. Males were more morning-oriented than females (p = 0.005), and respondents with children living at home also were significantly more morning-oriented (p < 0.001). Stepwise logistic regression showed that the influence of age, gender, and children was cumulative (r = 0.19) but accounted for only 4% of the observed variability. ### Long_Answer: EM residents are distributed differently from the normal population in terms of their ME preferences, tending slightly toward eveningness. The importance of this distribution in EM residents in unknown. A longitudinal follow-up of this cohort may help to determine the association of ME preference with overall practice satisfaction, tolerance of shift work, and career longevity. ### Final_Prediction: yes

### Question: Does topical application of Sadat-Habdan mesenchymal stimulating peptide ( SHMSP ) accelerate wound healing in diabetic rabbits? ### Context: Diminished wound healing is a common problem in diabetic patients due to diminished angiogenesis. SHMSP was found to promote angiogenesis. The present study was carried out to examine the effect of this peptide in healing of wounds in diabetic rabbits.Twenty male New Zealand rabbits were used in this study. Diabetes mellitus was induced and the rabbits were randomly divided into two equal groups: control group and peptide group. A-full thickness punch biopsy was made to create a wound of about 10 mm on the right ears of all rabbits. Every day, the wound was cleaned with saline in control groups. In the peptide group, 15 mg of SHMSP was applied after cleaning. On day 15th, all animals were sacrificed, and the wounds were excised with a rim of 5 mm of normal surrounding tissue. Histo-pathological assessment of wound healing, inflammatory cell infiltration, blood vessel proliferation, and collagen deposition was performed.There were no deaths among the groups. There was significant increase in wound healing, blood vessel proliferation and collagen deposition, and significant decrease in inflammatory cell infiltration in the peptide group compared to the control group. ### Long_Answer: Topical application of SHMSP improves wound healing in diabetic rabbits. ### Final_Prediction: yes

### Question: Are hospital characteristics associated with parental views of pediatric inpatient care quality? ### Context: Patient assessments of care are increasingly being considered an important dimension of quality of care. Few studies have examined the types and extent of problems identified by parents in the care of hospitalized children and whether hospital characteristics are associated with some of these problems. The objective of this study was to describe the quality of pediatric inpatient care as perceived by parents of hospitalized children and test whether hospital characteristics (academic status, market competition, freestanding children's hospital) are associated with variations in quality.We performed a cross-sectional analysis of surveys from 6030 parents of children who were discharged for a medical condition from 38 hospitals that used the Picker Institute's Pediatric Inpatient Survey. The Pediatric Inpatient Survey measures 7 dimensions of inpatient care quality: partnership, coordination, information to parent, information to child, physical comfort, confidence and trust, and continuity and transition. Our main outcome measures included an overall quality of care rating (1 = poor, 5 = excellent), as well as overall and dimension-specific problem scores (0 = no problems, 100 = problems with 100% of processes asked about in the survey). We used Pearson correlation to determine the strength of association between the overall quality of care rating and dimension problem scores. We tested for associations between hospital characteristics and problem scores using linear regression models, controlling for patient health status and other socioeconomic status variables.Parents on average rated their child's care as very good (mean: 4.2) but reported problems with 27% of the survey's hospital process measures. Information to the child (33%) and coordination of care (30%) had the highest problem rates. Parent communication problems correlated most strongly with overall quality of care ratings (r = -0.49). Parents of children who were hospitalized at academic health centers (AHCs) reported 4% more problems overall (29.8% vs 25.5%) and almost 9% more problems with coordination of care (34.1% vs 25.6%) compared with those at non-AHCs. Parents in more competitive markets reported almost 3% more problems than those in the less competitive ones (28.9% vs 26.3%). The freestanding children's hospital classification was not associated with overall problem scores. We found wide variation in problem scores by hospital, even among AHCs. Hospital and patient characteristics explained only 6% of the variance in problem scores. ### Long_Answer: Despite high subjective ratings of quality of care, measures of specific processes of care reveal significant variations among hospitals and identify areas with opportunities for improvement. Improving the quality of communication with the parent of a hospitalized child may have the most positive impact on a hospital's overall quality of care rating. AHCs and hospitals in more competitive markets may be more prone to problems. With wide variation in parental perceptions of hospital quality of care, a systems analysis of individual hospitals may provide strategies for hospitals to deliver higher quality care. ### Final_Prediction: nan

### Question: Does sphingosine kinase 1 gene transfer reduce postoperative peritoneal adhesion in an experimental model? ### Context: Recovery of the surgically damaged mesothelial cell layer is a major process in reducing postoperative peritoneal adhesions. Sphingosine kinase (SPK) 1 is a signalling molecule involved in the regulation of proliferation and migration of various cell types. This study determined the effect of SPK-1 gene transfer on the recovery of damaged mesothelial cells and on peritoneal adhesion formation after surgery.Rat mesothelial cells were isolated and characterized by their expression of cytokeratin and vimentin. Their migration was determined by scratch wound motility assay. Cellular SPK-1 activity was measured by [gamma-32P]adenosine 5'-triphosphate incorporation. Wistar rats underwent laparotomy with subsequent caecum or uterine horn abrasion. Rats were randomized to either SPK-1 gene (Ad-SPK-1) transfer or control groups. The animals were killed 14 days after operation and peritoneal adhesions were graded.Adenovirus-mediated SPK-1 gene transfer increased the cellular SPK-1 activity of mesothelial cells, leading to enhanced migration. Median adhesion scores were significantly lower in the Ad-SPK-1 group than in controls in both rat caecum (0.98 versus 2.60; P < 0.001) and rat uterine horn (0.28 versus 1.83; P < 0.001) models. ### Long_Answer: Adenovirus-mediated SPK-1 gene transfer promotes recovery of the surgically damaged mesothelial cell layer and prevents postoperative peritoneal adhesion formation. ### Final_Prediction: yes

### Question: Smoking in the workplace: do smoking patterns and attitudes reflect the legislative environment? ### Context: With regard to the workplace, to examine restrictions on smoking, smoking at work, attitudes toward and reactions to restrictions, and workplace programmes in the context of the legislative environment.Population-based telephone interview survey of adult residents of the jurisdictions of Metropolitan Toronto, Ontario, Canada.Workers within the City of Toronto (n = 374) were compared with other workers (n = 536), because their legislative environments with regard to workplace smoking were markedly different, with workplaces in the City of Toronto being covered by a much more stringent bylaw.In comparison with other workers, City of Toronto workers reported workplace restrictions to be more common and widespread. These workers were also less likely to smoke at work, and more likely to smoke less at work and to have cut down on smoking at work. Quit-smoking rates, however, were similar. There was evidence of some compensatory smoking outside work, but additional compensation in association with more stringent restrictions was not found. City workers and other workers were similar in their support for smoke-free workplaces, in their attitudes to the role of governments in regulating workplace smoking, and in their perceptions of conflict between smokers and non-smokers. Reports of quit-smoking programmes and educational interventions in the workplace were similarly uncommon, although both groups of workers indicated strong support for the role of business and industry in helping people quit. ### Long_Answer: Restrictions on smoking and smoking patterns reflected the legislative environment; a more stringent environment was associated with more restrictions and less smoking at work. ### Final_Prediction: nan

### Question: Does increased baseline temperature improve the acquisition of contact heat evoked potentials after spinal cord injury? ### Context: To investigate the effect of increasing the skin surface baseline temperature for contact heat evoked potentials (CHEPs).CHEPs were studied in healthy subjects and subjects with chronic cervical spinal cord injury (SCI) using a conventional 35°C (condition 1) or increased 42-45°C baseline temperature (condition 2). A third condition was used to standardize the contact heat stimulus duration from the different baseline temperatures. Changes in peak latency and N2P2 amplitude of the CHEPs and rating of perceived intensity were examined between conditions.In healthy subjects, increasing the baseline temperature for contact heat stimulation significantly increased the rating of perceived intensity (conditions 2 and 3), as well as the amplitude of CHEPs (condition 2 only). Following SCI, an increased baseline temperature facilitated perception of contact heat stimulation and evoked potentials could be recorded from dermatomes that were insensitive to contact heat from a conventional baseline temperature. ### Long_Answer: Enhancing the acquisition of CHEPs can be achieved by increasing the baseline temperature. This effect can be attributed, in part, to shortening the stimulation duration. ### Final_Prediction: yes

### Question: Do emergency department abdominal x-rays have a poor diagnostic yield and their usefulness is questionable? ### Context: To determine the prevalence and nature of new clinically significant abdominal x-ray (AXR) findings and the proportion of patients receiving additional imaging in the emergency department (ED).This was a retrospective audit of consecutive adult patients, who presented to a tertiary referral ED (annual census 70,000) between September and December 2008. Data were extracted from radiologist reports and the medical records of patients with new significant AXR findings. The electronic radiology record was further interrogated to determine which patients received additional imaging and whether this correlated with the original AXR findings.Of 997 cases that met the inclusion criteria, 121 (12.1%, 95% CI 10.2 to 14.4) and 43 (4.3%, 95% CI 3.2 to 5.8) had new clinically significant and insignificant AXR findings, respectively. Among the significant findings, the predominant diagnoses were bowel obstruction (72.7%), renal calculi (14.0%) and sigmoid volvulus (5.0%). Patient signs and symptoms were poorly associated with significant AXR findings. In all, 334 (33.5%, 95% CI 30.6 to 36.5) cases had additional imaging after the AXR. However, more patients with clinically significant AXR findings went on to have additional imaging (difference in proportions 23.0%, 95% CI 13.2 to 32.9, p<0.001). ### Long_Answer: The yield for clinically useful information from the AXR is low and this investigation may be overused. Positive findings are associated mostly with bowel obstruction. As the proportion of patients ordered additional imaging was considerable, the utility of the preliminary AXR is questionable, especially in cases where the diagnosis is clear. Guidelines for AXR imaging are recommended to assist clinicians with investigation ordering. ### Final_Prediction: yes

### Question: Does predictors and economic burden of serious workplace fall in health care? ### Context: To examine the demographic and workplace risk factors of serious falls and associated economic burden in Canadian health care workers.Fall injury data during 2005-2008 from a workplace health and safety surveillance system were linked with workers' compensation claims and payroll records. The costs for treatment and wage loss and days lost for accepted time-loss claims were calculated. Demographic and work-related factors were identified to distinguish the risk for more serious falls from less serious falls.Nine hundred and thirty-eight fall injury claims were captured among 48 519 full-time equivalent workers. Workers >60 years, part time or employed in the long-term care sector sustained a higher proportion of serious falls (>70%). Over 75% of falls were serious for care aides, facility support service workers and community health workers. In the multivariate analysis, the risk of serious falls remained higher for workers in the long-term care sector [odds ratio (OR) 1.71; P < 0.05] compared with those in acute care and for care aides (OR 1.72; P < 0.05), facility support service workers (OR 2.58; P < 0.01) and community health workers (OR 3.61; P < 0.001) compared with registered nurses (RNs). The median number of days lost was higher for females, long-term care workers, licensed practical nurses and care aides. Females, long-term care workers, RNs, licensed practical nurses, care aides and maintenance workers had the most costly falls. ### Long_Answer: Reducing work-related serious fall injuries would be expected to bring about significant benefits in terms of reduced pain and suffering, improved workplace productivity, reduced absenteeism and reduced compensation costs. ### Final_Prediction: yes

### Question: Does prenatal diagnosis influence the morbidity associated with left in situ nonfunctioning or poorly functioning renal moiety after endoscopic puncture of ureterocele? ### Context: We compared long-term morbidity associated with left in situ nonfunctioning or poorly functioning renal moiety of a duplex system in children with prenatal vs postnatal diagnosis of ureterocele who underwent endoscopic puncture.A total of 48 children underwent primary endoscopic puncture of duplex system ureterocele. Of the cases 35 (73%) were diagnosed prenatally (group 1) and 13 (27%) postnatally (group 2). Median age at time of puncture was 4 months in group 1 and 3.5 years in group 2. A total of 20 patients in group 1 (57%) and 8 in group 2 (62%) presented with intravesical ureterocele, while 15 in group 1 (43%) and 5 in group 2 (38%) had ectopic ureterocele. A total of 20 children in group 1 (57%) and 7 in group 2 (54%) had a nonfunctioning renal moiety, and 15 in group 1 (43%) and 6 in group 2 (46%) had a poorly functioning ureterocele moiety. Vesicoureteral reflux (VUR) was present in 23 children in group 1 (66%) comprising 30 renal refluxing units (RRUs), and in 12 in group 2 (92%) comprising 14 RRUs. Median followup was 9 years (range 1 to 15) for both groups.Preoperative urinary tract infection (UTI) was common in group 2 (92%) vs group 1 (20%). No patient in group 1 had development of UTI after puncture, while 23% of the children in group 2 presented with UTI. Four children (2 from each group) with ectopic ureterocele required secondary puncture resulting in satisfactory drainage. A total of 14 RRUs (47%) showed spontaneous resolution of VUR in group 1 compared to 3 (21%) in group 2. Four RRUs (13%) required endoscopic correction due to high grade VUR in group 1. Two RRUs (17%) were treated with endoscopic correction and 2 (17%) with ureteral reimplantation due to UTI in group 2. Only 1 patient in group 1 underwent nephrectomy due to nonfunctioning kidney, while 2 patients in group 2 required partial nephrectomy due to UTI. ### Long_Answer: Our data reveal that prenatal diagnosis of duplex system ureterocele is associated with fewer UTIs, and early endoscopic management may decrease UTI and the need for additional surgery. Nonfunctioning or poorly functioning renal moieties left in situ following successful endoscopic decompression of ureterocele are not associated with additional morbidity and do not require partial nephrectomy in the majority of the cases. ### Final_Prediction: nan

### Question: Analysis of morbidity in patients with endometrial cancer: is there a commitment to offer laparoscopy? ### Context: Benefits of laparoscopy over laparotomy in patients with endometrial cancer (EC) are well known. As many patients with EC carry co-morbid conditions, surgery is exposing them to increased risk of complications. A review of the patients with EC recruited so far in a clinical trial comparing laparoscopy to laparotomy was performed. The goal was to identify patients carrying specific risk factors for complications, who would most benefit of laparoscopy and be the ideal candidates for this surgical approach.Between July 1995 and December 2002, 122 patients with uterine cancer entered the study. Sixty-three patients were allocated to the laparoscopy (LPS) arm (group A), while 59 were allocated to the laparotomy (LPT) arm (group B). Rate and type of intra-, early and late post-operative complications were prospectively recorded. Risk factors for complications are analyzed to define a group of patients truly benefiting from laparoscopy.Overall, 12 patients out of 122 (9.8%) have experienced intra-operative, 43 patients out of 122 (35.2%) early post-operative and 25 patients out of 122 (20.4%) late post-operative complications. Rate of intra-operative complications was 4.7% in group A (3 patients out of 63) vs. 15.2% in group B (9 patients out of 59), P = 0.082. Early post-operative complications rate was 23.8% in group A (15 out of 63) and 47.4% in group B (28 out of 59), P = 0.011. Rate of late post-operative complications was 7.9% (5 out of 63) in group A vs. 35.5% (21 out of 59), P = 0.001. Univariate analysis shows co-morbid medical conditions, weight>80 kg, Quetelet index>30 and age>65 years to be predictive of complications and, in fact, a subgroup of patients presenting with these characteristics (n = 57, 30 in group A and 27 in group B) has been recognized to accumulate 60% of the overall complications. In these patients, multivariate analysis identifies the surgical technique (LPS vs. LPT) to be the only significant risk factor for complications. ### Long_Answer: At least one third of the patients with EC carry serious co-morbidities with an increased surgical risk for complications. For this subgroup of patients, a laparoscopic-vaginal approach significantly reduces the rate of complications and should be the standard of surgical treatment. ### Final_Prediction: nan

### Question: Does high DNA methylation pattern intratumoral diversity imply weak selection in many human colorectal cancers? ### Context: It is possible to infer the past of populations by comparing genomes between individuals. In general, older populations have more genomic diversity than younger populations. The force of selection can also be inferred from population diversity. If selection is strong and frequently eliminates less fit variants, diversity will be limited because new, initially homogeneous populations constantly emerge.Here we translate a population genetics approach to human somatic cancer cell populations by measuring genomic diversity within and between small colorectal cancer (CRC) glands. Control tissue culture and xenograft experiments demonstrate that the population diversity of certain passenger DNA methylation patterns is reduced after cloning but subsequently increases with time. When measured in CRC gland populations, passenger methylation diversity from different parts of nine CRCs was relatively high and uniform, consistent with older, stable lineages rather than mixtures of younger homogeneous populations arising from frequent cycles of selection. The diversity of six metastases was also high, suggesting dissemination early after transformation. Diversity was lower in DNA mismatch repair deficient CRC glands, possibly suggesting more selection and the elimination of less fit variants when mutation rates are elevated. ### Long_Answer: The many hitchhiking passenger variants observed in primary and metastatic CRC cell populations are consistent with relatively old populations, suggesting that clonal evolution leading to selective sweeps may be rare after transformation. Selection in human cancers appears to be a weaker than presumed force after transformation, consistent with the observed rarity of driver mutations in cancer genomes. Phenotypic plasticity rather than the stepwise acquisition of new driver mutations may better account for the many different phenotypes within human tumors. ### Final_Prediction: yes

### Question: Is hypermethylation of the somatostatin promoter a common , early event in human esophageal carcinogenesis? ### Context: The promoter of somatostatin (SST), a primary inhibitor of gastrin-stimulated gastric acid secretion, is hypermethylated in 80% of human colon cancers. The aim of the current study was to investigate whether and at what stage promoter hypermethylation of SST is involved in human esophageal carcinogenesis.SST promoter hypermethylation was examined by real-time methylation-specific polymerase chain reaction (PCR) (MSP) in 260 human esophageal tissue specimens. Real-time reverse-transcriptase PCR and MSP were also performed on esophageal cancer cell lines before and after treatment with 5-aza-2'-deoxycytidine (5-Aza-dC).SST hypermethylation showed highly discriminative receiver-operator characteristic curve profiles, clearly distinguishing esophageal squamous cell carcinomas (ESCC) and esophageal adenocarcinomas (EAC) from normal esophagus (NE) (P < .01). Both SST methylation frequency and normalized methylation value (NMV) were significantly higher in Barrett metaplasia without dysplasia or EAC (BE), low-grade and high-grade (HGD) dysplasia occurring in BE, EAC, and ESCC than in NE (P < .01). SST hypermethylation frequency was significantly lower in NE (9%) than in BE (70%), HGD (71.4%), or EAC (71.6%), whereas 14 (53.8%) of 26 ESCCs exhibited SST hypermethylation. There was a significant relation between SST hypermethylation and BE segment length, a known clinical risk factor for neoplastic progression. Demethylation of KYSE220 ESCC and OE33 EAC cells with 5-Aza-dC reduced SST methylation and increased SST mRNA expression. SST mRNA levels in native unmethylated EACs were significantly higher than in native methylated EACs (P < .05). ### Long_Answer: SST promoter hypermethylation is a common event in human esophageal carcinomas and is related to early neoplastic progression in Barrett esophagus. ### Final_Prediction: yes

### Question: Are 3 cycles of bleomycin, etoposide and cisplatin or 4 cycles of etoposide and cisplatin equivalent optimal regimens for patients with good risk metastatic germ cell tumors of the testis? ### Context: Standard chemotherapy for good prognosis metastatic nonseminomatous germ cell tumors of the testis currently includes etoposide and cisplatin. The optimal number of cycles and the need for bleomycin remain matters of debate. Three cycles of bleomycin, etoposide and cisplatin (BEP) or 4 cycles of etoposide and cisplatin are supposed to represent equivalent optimal regimens.We analyzed the therapeutic outcome of 75 patients with good risk metastatic nonseminomatous germ cell tumor of the testis who were routinely treated at our institute. The chemotherapy regimens consisted of 4 cycles of BEP in 17 patients, 3 cycles of BEP in 23 patients, and 4 cycles of etoposide and cisplatin in 35 patients.All 75 patients achieved a complete or partial response with normal serum tumor markers. After a median followup of 3.5 years (range 2 to 7.5) the overall no evidence of disease rate was 91% (100, 96 and 83% in patients treated with 4 cycles of BEP, 3 cycles of BEP, and 4 cycles of etoposide and cisplatin, respectively). When considering the number of adverse events in each treatment group, that is the number of surgical complete responses or relapses after complete remission, results appeared similar with 3 or 4 cycles of BEP (2 and 3, respectively) but lower in patients who received 4 cycles of etoposide and cisplatin (11 adverse events). Of the 35 patients treated with etoposide and cisplatin 4 (11%) died of disease while only 1 of the 40 (3%) treated with BEP died of disease. ### Long_Answer: Four cycles of etoposide and cisplatin could yield inferior results compared to 3 cycles of BEP in patients with good risk nonseminomatous germ cell tumor of the testis. Our results highlight the need for a randomized trial addressing the question of therapeutic equivalence between these 2 chemotherapy regimens. ### Final_Prediction: nan

### Question: Does de novo transcriptomic analysis of Chlorella sorokiniana reveal differential genes expression in photosynthetic carbon fixation and lipid production? ### Context: Microalgae, which can absorb carbon dioxide and then transform it into lipid, are promising candidates to produce renewable energy, especially biodiesel. The paucity of genomic information, however, limits the development of genome-based genetic modification to improve lipid production in many microalgae. Here, we describe the de novo sequencing, transcriptome assembly, annotation and differential expression analysis for Chlorella sorokiniana cultivated in different conditions to reveal the change of genes expression associated with lipid accumulation and photosynthetic carbon fixation.Six cultivation conditions were selected to cultivate C. sorokiniana. Lipid content of C. sorokiniana under nitrogen-limited condition was 2.96 times than that under nitrogen-replete condition. When cultivated in light with nitrogen-limited supply, C. sorokiniana can use carbon dioxide to accumulate lipid. Then, transcriptome of C. sorokiniana was sequenced using Illumina paired-end sequencing technology, and 244,291,069 raw reads with length of 100 bp were produced. After preprocessed, these reads were de novo assembled into 63,811 contigs among which 23,528 contigs were found homologous sequences in public databases through Blastx. Gene expression abundance under six conditions were quantified by calculating FPKM value. Ultimately, we found 385 genes at least 2-fold up-regulated while 71 genes at least 2-fold down-regulated in nitrogen-limited condition. Also, 204 genes were at least 2-fold up-regulated in light while 638 genes at least 2-fold down-regulated. Finally, 16 genes were selected to conduct RT-qPCR and 15 genes showed the similar results as those identified by transcriptomic analysis in term of differential expression. ### Long_Answer: De novo transcriptomic analyses have generated enormous information over C. sorokiniana, revealing a broad overview of genomic information related to lipid accumulation and photosynthetic carbon fixation. The genes with expression change under different conditions are highly likely the potential targets for genetic modification to improve lipid production and CO ### Final_Prediction: yes

### Question: Does [ siRNA-mediated CDK6 knockdown suppress nasopharyngeal carcinoma cell growth and cell cycle transition in vitro ]? ### Context: To assess the effect of small interfering RNA (siRNA)-mediated suppression of CDK6 expression on the proliferation and cell cycles of nasopharyngeal carcinoma (NPC) cells in vitro.QRT-PCR was used to examine the differential expression of CDK6 in 30 NPC tissues and 18 normal nasopharyngeal tissues. A siRNA targeting CDK6 was transfected in NPC CNE2 cells, and MTT assay and flow cytometry were used to analyze the changes in cell proliferation and cell cycle distribution. Western blotting was used to examine the expressions of the cell cycle-related factors.Compared with normal nasopharyngeal tissues, NPC tissues showed an increased expression of CDK6 mRNA. Knocking down CDK6 expression obviously inhibited tumor cell growth and cell cycle transition from G1 to S phase and caused reduced expressions of CDK4, CCND1, and E2F1 and enhanced expression of the tumor suppressor p21. ### Long_Answer: NPC tissues overexpress CDK6. Knocking down CDK6 expression inhibits the growth and cell cycle transition of NPC cells in vitro by inhibiting the expressions of CDK4, CCND1, and E2F1 and upregulating tumor suppressor p21 expression. ### Final_Prediction: yes

### Question: Does bariatric surgery reduce cancer risk in morbidly obese patients? ### Context: To assess the effect of bariatric surgery on the cancer risk of patients with morbid obesity because evidence is mounting of an association between obesity and cancer.We performed an observational 2-cohort study. The treatment cohort (n = 1035) included patients who had undergone bariatric surgery from 1986 to 2002. The control group (n = 5746) included age- and gender-matched morbidly obese patients who had not undergone weight-reduction surgery and who were identified from a single-payor administrative database. The subjects with physician or hospital visits for a cancer-related diagnosis or treatment within the 6 months previous to the beginning of the study were excluded. The cohorts were followed up for a maximum of 5 years from study inception.Bariatric surgery resulted in a significant reduction in the mean percentage of excess weight loss (67.1%, P <.001). The surgery patients had significantly fewer physician/hospital visits for all cancer diagnoses (n = 21, 2.0%) compared with the controls (n = 487, 8.45%; relative risk .22, 95% confidence interval .143-.347; P = .001). The physician/hospital visits for common cancers such as breast cancer were significantly reduced in the surgery group (P = .001). For all other cancers, the physician/hospital visits showed a trend toward being lower in the surgery group. Because of the low frequencies, statistical significance could not be demonstrated for individual cancer diagnoses. ### Long_Answer: The data suggest that bariatric surgery improves the cancer outcomes in some morbidly obese patients. ### Final_Prediction: yes

### Question: Is the lifetime prevalence of abdominal aortic aneurysms among siblings of aneurysm patients eightfold higher than among siblings of spouses : an analysis of 187 aneurysm families in Nova Scotia , Canada? ### Context: Abdominal aortic aneurysms (AAAs) are frequently familial. The aim of this study was to compare the prevalence of AAA among the siblings of AAA patients with that in the spouses' siblings.The siblings of 375 AAA patients and the siblings of the spouses of the AAA patients were included in this study and offered ultrasonography screening for AAA. Participants were asked to complete a questionnaire to collect demographic and general health information. Statistical analysis was done with Fisher's exact test. Odds ratios and 95% confidence intervals were also calculated.Abdominal ultrasonography examinations were done for 309 individuals. The results indicated that 11 (11.2%) of 98 brothers of AAA patients, 4 (2.7%) of 147 sisters, and none of the 64 siblings of the spouses of the AAA patients were found to have an AAA. Combining the information from the ultrasonography screening and medical records on already known cases of AAA in these families, altogether 29.0% (44/152) of the brothers of AAA patients, 11.1% (20/181) of the sisters of AAA patients, and 2.3% (2/88) of the siblings of the spouses had an AAA. ### Long_Answer: There was a significant difference between the siblings of the AAA patients and those of the spouses both in the frequency of AAA detected by ultrasonography screening and in the overall prevalence of AAA. The overall prevalence of AAA in the siblings of AAA patients was about eight times that observed among the siblings of their spouses (19.2% vs 2.3%). These findings confirmed previous reports on high prevalence of AAA among siblings of AAA patients and emphasized the importance of an ultrasonography screening program for siblings of AAA patients. ### Final_Prediction: yes

### Question: Does estrogen receptor alpha deletion enhance the metastatic phenotype of Ron overexpressing mammary tumors in mice? ### Context: The receptor tyrosine kinase family includes many transmembrane proteins with diverse physiological and pathophysiological functions. The involvement of tyrosine kinase signaling in promoting a more aggressive tumor phenotype within the context of chemotherapeutic evasion is gaining recognition. The Ron receptor is a tyrosine kinase receptor that has been implicated in the progression of breast cancer and evasion of tamoxifen therapy.Here, we report that Ron expression is correlated with in situ, estrogen receptor alpha (ERα)-positive tumors, and is higher in breast tumors following neoadjuvant tamoxifen therapy. We also demonstrate that the majority of mammary tumors isolated from transgenic mice with mammary specific-Ron overexpression (MMTV-Ron mice), exhibit appreciable ER expression. Moreover, genetic-ablation of ERα, in the context of Ron overexpression, leads to delayed mammary tumor initiation and growth, but also results in an increased metastasis. ### Long_Answer: Ron receptor overexpression is associated with ERα-positive human and murine breast tumors. In addition, loss of ERα on a Ron overexpressing background in mice leads to the development of breast tumors which grow slower but which exhibit more metastasis and suggests that targeting of ERα, as in the case of tamoxifen therapy, may reduce the growth of Ron overexpressing breast cancers but may cause these tumors to be more metastatic. ### Final_Prediction: yes

### Question: Does range of motion physiotherapy reduce the force deficit in antagonists to denervated rat muscles? ### Context: We used a rat hindlimb model of tibial nerve transection to determine if a loss of mechanical function exists in innervated antagonists compared with denervated muscles. We tested two hypotheses: (1) denervation of the rat ankle plantar flexors results in decreased force production of the ankle dorsiflexors, and (2) daily passive ankle range of motion (ROM) physiotherapy prevents or reduces the force deficit.Adult Lewis rats were assigned to one of three groups: (1) a sham (S) group, in which the tibial nerve was exposed but not transected; (2) a no rehabilitation (NR) group, in which a 2-cm segment of tibial nerve was excised at midthigh to denervate the ankle plantar flexors; or (3) a rehabilitation (R) group, in which a 2-cm segment of tibial nerve was excised and the animals were subjected to ankle passive ROM physiotherapy for two 5-min sessions each day. After 14 days, maximum isometric tetanic force (F(0)) and specific force (sF(0)) were measured in the extensor digitorum longus (EDL) muscle, an ankle dorsiflexor.Compared with those from animals in the S group, EDL muscles from animals in the NR group demonstrated a 22% decrease in both F(0) and sF(0). In the EDL from animals in the R group, daily passive ROM physiotherapy diminished the deficit in F(0) but not in sF(0). ### Long_Answer: These data support the hypotheses that nerve injuries result in impaired mechanical function in the innervated antagonists to denervated muscles and that passive ROM physiotherapy can improve force production in these muscles. ### Final_Prediction: yes

### Question: Is saikosaponin b2 a naturally occurring terpenoid that efficiently inhibits hepatitis C virus entry? ### Context: A vaccine against hepatitis C virus (HCV) is unavailable and cost-effective antivirals that prevent HCV infection and re-infection, such as in the transplant setting, do not exist. In a search for novel and economical prophylactic agents, we examined the antiviral activity of saikosaponins (SSa, SSb2, SSc, and SSd) from Bupleurum kaoi root (BK) as entry inhibitors against HCV infection.Infectious HCV culture systems were used to examine the effect of saikosaponins on the complete virus life cycle (entry, RNA replication/translation, and particle production). Antiviral activity against various HCV genotypes, clinical isolates, and infection of primary human hepatocytes were also evaluated.BK and the saikosaponins potently inhibited HCV infection at non-cytotoxic concentrations. These natural agents targeted early steps of the viral life cycle, while leaving replication/translation, egress, and spread relatively unaffected. In particular, we identified SSb2 as an efficient inhibitor of early HCV entry, including neutralization of virus particles, preventing viral attachment, and inhibiting viral entry/fusion. Binding analysis, using soluble viral glycoproteins, demonstrated that SSb2 acted on HCV E2. Moreover, SSb2 inhibited infection by several genotypic strains and prevented binding of serum-derived HCV onto hepatoma cells. Finally, treatment with the compound blocked HCV infection of primary human hepatocytes. ### Long_Answer: Due to its potency, SSb2 may be of value for development as an antagonist of HCV entry and could be explored as prophylactic treatment during the course of liver transplantation. ### Final_Prediction: yes

### Question: Do poor Muscle Strength and Low Physical Activity Are the Most Prevalent Frailty Components in Community-Dwelling Older Adults? ### Context: To determine the prevalence of five physical frailty phenotype components and to assess the relationship between them and other clinical factors.A population-based cross-sectional study was performed. Subjects 75 years and older were randomly selected from primary care databases (with sampling stratified by gender). Physical frailty phenotypes were assessed using Fried's criteria. Sociodemographic data, comorbidities, nutritional status, and functional capacity were assessed.126 subjects were recruited (47% women). Prevalence rates were poor muscle strength: 50%; low physical activity: 29%; slow gait: 28%; exhaustion: 27%; and weight loss: 5%. Prefrailty and frailty prevalence rates were 35.7% and 29.4%, respectively. Poor muscle strength and low physical activity showed a close relationship and concordance (kappa = 0.92). Most frailty components were associated with outdoor activity, hours walked daily, and certain comorbidities. ### Long_Answer: Poor muscle strength was the most prevalent frailty component and was closely associated with physical activity, suggesting that training programs may revert or prevent the frailty process. ### Final_Prediction: yes

### Question: Is rapid aneuploidy screening used alone acceptable in prenatal diagnosis? ### Context: The objectives of this study were to use a factual basis to: (1) determine the number, nature, and probable phenotypic consequences of karyotype anomalies that would probably be missed (structural anomalies, uncommon aneuploidies and mosaic aneuploidies) by rapid aneuploidy screening (RAS), and (2) appraise whether RAS can replace traditional karyotyping when amniocenteses are performed for increased risk of Down's syndrome by maternal serum screening or advanced maternal age in the absence of ultrasound abnormality.This retrospective cohort study analysed the indications, results and outcomes of 5,713 consecutive amniocenteses over a 5-year period at a single prenatal diagnosis centre in Paris.Advanced maternal age and increased Down's risk with maternal serum marker were the most common indications. Chromosome abnormalities were detected in 3.64% of the pregnancies tested, and unexpected structural anomalies in 0.63% (n = 36). Translocations were more likely to be reciprocal, balanced and of parental origin. There were 6 mosaic gonosomal aneuploidies. Overall, 4 mosaic autosomal aneuploidies and 36 structural aberrations would not have been recognised by RAS alone. Of the 4 mosaic autosomal aneuploidies, all were terminated, one had major malformations and the others had discrete signs that a good quality ultrasound examination would probably not detect. Of the 36 structural aberrations, 24 would be undetected by ultrasound scan, from which 6 would be associated with a significant risk of an abnormal phenotype outcome. ### Long_Answer: In conclusion, our data do not provide evidence that RAS can replace the traditional karyotype. It is probably impossible to arrive in a universal conclusion of which approach (karyotype or RAS) is definitely better than the other. Each prenatal centre could have its own approach depending on the local data analysis, including quality control of ultrasounds. ### Final_Prediction: nan

### Question: Does posterior Cruciate Ligament Retention or Substitution During Total Knee Arthroplasty Affect Long-Term Bone Mineral Density or Quality? ### Context: Physical activity is recognized as one of the factors that influence bone mineral density (BMD) and bone quality after total knee arthroplasty (TKA). According to biomechanical analyses after posterior cruciate ligament (PCL) retaining (PCLR) and substituting (PCLS) TKA, each implant design has different kinematics and kinetics. The purposes of this study were: (1) to perform within-patient comparisons of the midterm and long-term effects of PCL retention in mobile-bearing TKA on proximal femur and tibia BMD and calcaneus bone quality measured using ultrasound and (2) to identify correlations between them.A prospective, quasi-randomized design was used. Thirty-seven patients (74 knees) who underwent bilateral TKA (PCLR on one side and PCLS on the other) were evaluated. Mean follow-up periods were 118 months (standard deviation 40) and 117 months (standard deviation 36) in knees with PCLR and PCLS implants, respectively. The BMDs of the total hip and proximal tibia and broadband ultrasound attenuation (BUA; dB/MHz) through the calcaneus were measured.The mean BMD of PCLR and PCLS were equivalent at the proximal hip and tibia. The BUA of the calcaneus was also the same between implants. There were significant correlations between the 3 anatomic sites. ### Long_Answer: When measured approximately 10 years after TKA, PCL retention had no substantial effect on the BMD of the proximal femur and tibia, or on the bone quality of the calcaneus. The measurement of noninvasive BUA may predict BMD, although further analysis is required. ### Final_Prediction: no

### Question: Does tumor necrosis factor-alpha mediate diabetes-induced vascular inflammation in mice? ### Context: Vascular inflammation is a key feature of both micro- and macrovascular complications in diabetes. Several lines of evidence have implicated the cytokine tumor necrosis factor (TNF) alpha as an important mediator of inflammation in diabetes. In the present study we evaluated the role of TNF alpha in streptozotocin (STZ)-induced diabetes on vascular inflammation in C57BL/6 wild-type and apoE-/- mice.Diabetes increased the expression of vascular cell adhesion molecule (VCAM)-1 in cerebral arteries 150 m in diameter as well as the macrophage accumulation in aortic root atherosclerotic plaques in apoE-/- mice. A more pronounced vascular inflammatory response was observed in diabetic TNF alpha-deficient apoE-/- mice. These mice were also characterized by increased accumulation of IgG and IgM autoantibodies in atherosclerotic lesions. Diabetes also increased VCAM-1 expression and plaque formation in apoE-competent TNF alpha -/- mice, whereas no such effects were observed in C57BL/6 wild-type mice. ### Long_Answer: The present findings suggest that TNF alpha does not mediate diabetic-induced vascular inflammation in mice and reveal an unexpected protective role for TNF alpha. These effects are partly attributable to a direct antiinflammatory role of TNF alpha, but may also reflect a defective development of the immune system in these mice. ### Final_Prediction: no

### Question: The use of exfoliative cytology for the early diagnosis of oral cancers: is there a role for it in education and private practice? ### Context: Early detection of oral cancers is not easy, because oral precancerous lesions and early oral cancers can mimic many benign conditions in the mouth, leading to delays in diagnosis and treatment. There is a need to emphasize the early diagnosis of oral cancers in order to reduce the unacceptably high morbidity and mortality.A survey regarding oral exfoliative cytology was completed by 132 dentists in Virginia who were randomly chosen from a mailing list.Less than half of the dentists (41.7%) had been taught how to obtain a cytologic smear, and only 26.0% knew the clinical indications for doing so. Only 9.2% of the dentists had ever obtained a cytologic smear in private practice. Of the 13 dentists in the survey who had done so, 12 had been trained in the technique. Interest in learning the cytologic technique and getting the needed supplies was indicated by 79.2% of the dentists. ### Long_Answer: Diagnostic aids in the evaluation of oral mucosal lesions can serve an important role by identifying lesions that need to be biopsied in spite of a "benign" appearance. Exfoliative cytology, as well as vital staining, may aid in this goal. This has implications regarding undergraduate and postdoctoral education. ### Final_Prediction: nan

### Question: Are cXXC4 mRNA levels associated with clinicopathological parameters and survival of myelodysplastic syndrome patients? ### Context: The CXXC domain protein 4 (CXXC4) functions as a negative regulator of Wnt signaling and also regulates expression of the ten-eleven translocation 2 (TET2) protein for DNA methylation. This study detected levels of CXXC4 and TET2 mRNA to determine their association with survival of patients with myelodysplastic syndrome (MDS).Levels of TET2 and CXXC4 mRNA were analyzed in bone marrow samples from 154 MDS patients and 50 control subjects using qRT-PCR and subsequently associated these levels with clinicopathological characteristics and survival of MDS patients.Levels of TET2 and CXXC4 mRNA were significantly lower in MDS patients than that in controls (P=0.009 and P<0.001, respectively). Patients with advanced WHO subtypes (e.g., RAEB-1 and RAEB-2) exhibited a higher level of CXXC4 mRNA (P=0.020) compared to those with early stage subtypes (i.e., RA, RARS, RCMD, RCMD-RS, 5q-syndrome, and MDS-U). Moreover, levels of CXXC4 mRNA were associated with marrow blast levels (P=0.014) and neutrophil counts (P=0.039). Levels of CXXC4 mRNA and hemoglobin and IPSS cytopenias were associated with the overall survival (P=0.025) but not with the leukemia-free survival of MDS patients. The multivariate analysis demonstrated that the age of patients and levels of hemoglobin and marrow blast were independent risk factors for survival of MDS patients. ### Long_Answer: This study demonstrated that the age of patients and levels of CXXC4 mRNA, hemoglobin, and marrow blast associated with survival of MDS patients. ### Final_Prediction: yes

### Question: Does preoperative DVT chemoprophylaxis in spinal surgery affect the incidence of thromboembolic complications and spinal epidural hematomas? ### Context: Deep venous thrombosis (DVT) and pulmonary embolus (PE) remain common surgical complications, often affecting patients without any prior warning. Postoperative spinal epidural hematomas (SEH) may have a devastating impact on a patient's recovery from a routine procedure. The effect of preoperative DVT prophylaxis administration on elective spinal patients has not previously been studied.Retrospective cohort analysis.To correlate the incidence of preoperative DVT prophylaxis administration and the rate of postoperative DVT, PE, and SEH after elective spinal surgery.Earlier studies have shown a postoperative DVT rate in elective spinal patients of between 0.3% and 31%, a PE rate of 0.2% to 0.9%, and a SEH rate of approximately 0.1%.About 3870 patient notes, from 2004 to 2008 elective spinal procedures, were reviewed. DVT, PE, and SEH rates were compared between those patients receiving and not receiving preoperative DVT prophylaxis.The 36.9% of patients received preoperative DVT prophylaxis, and 19 patients suffered and DVT and/or PE. Nine of these had received preoperative prophylaxis, giving an odds ratio of 0.91. Sixteen patients suffered a SEH, and this gave an odds ratio of 1.33. The SEH's presented with a median postoperative time of 4 days. ### Long_Answer: Preoperative DVT prophylaxis does not influence the rate of postoperative DVT or PE among elective spinal patients. It probably does not influence SEH rate, and it is noted that SEH may present quite late, in contrast to currently accepted time courses. ### Final_Prediction: nan

### Question: Is hospital volume a determinant of postoperative complications , blood transfusion and length of stay after radical or partial nephrectomy? ### Context: We examined the impact of hospital volume on short-term outcomes after nephrectomy for nonmetastatic renal cell carcinoma.Using the Nationwide Inpatient Sample we identified 48,172 patients with nonmetastatic renal cell carcinoma treated with nephrectomy (1998 to 2007). Postoperative complications, blood transfusions, prolonged length of stay and in-hospital mortality were examined. Stratification was performed according to teaching status, nephrectomy type (partial vs radical nephrectomy) and surgical approach (open vs laparoscopic). Multivariable logistic regression models were fitted.Patients treated at high volume centers were younger and healthier at nephrectomy. High hospital volume predicted lower blood transfusion rates (8.5% vs 9.7% vs 11.8%), postoperative complications (14.4% vs 16.6% vs 17.2%) and shorter length of stay (43.1% vs 49.8% vs 54.0%, all p <0.001). In multivariable analyses stratified according to teaching status, nephrectomy type and surgical approach, high hospital volume was an independent predictor of lower rates of postoperative complications (OR 0.73-0.88), blood transfusions (OR 0.71-0.78) and prolonged length of stay (OR 0.76-0.89, all p <0.001). Exceptions were postoperative complications at nonteaching centers (OR 0.94, p >0.05) and blood transfusions in nephrectomies performed laparoscopically (OR 0.68, p >0.05). ### Long_Answer: On average, high hospital volume results in more favorable outcomes during hospitalization after nephrectomy. ### Final_Prediction: yes

### Question: Do accurate prediction tools in prostate cancer require consistent assessment of included variables? ### Context: The aim of this study was to create a preoperative prediction model predicting extraprostatic tumour growth in men with clinically organ-confined disease from a prospectively collected Swedish cohort.The study used data from 3386 men in the prospective multi-centre Laparoscopic Prostatectomy Robot Open (LAPPRO) trial, with 14 participating urological departments. External validation was performed using a cohort of 634 men from the largest study centre with patients who underwent surgery before and after the inclusion period of the LAPPRO study. External validation of the updated Partin table was used for comparison. The prediction models were created by multivariable logistic regression. Nomogram prediction performance, internal, internal-external and external validation are presented as the area under the receiver operating characteristic curve (AUC).The nomogram reached a prediction performance with an AUC of 0.741, with internal and external validation of 0.738 and 0.698, respectively. Internal-external validation showed great divergence between centres, with AUCs ranging from 0.476 to 0.892, indicating inconsistencies in pathological staging or one or more of the included variables in the regression model. When including centre as a variable in the multivariable model it was significantly associated with the outcome of pT3 (p < 0.001). AUC for external validation of the Partin table was 0.694. ### Long_Answer: Accurate prediction tools in prostate cancer require consistent assessment of included variables, and local validation is needed before the use of such tools in clinical practice. ### Final_Prediction: yes

### Question: Do influenza virus haemagglutinin-derived peptides inhibit T-cell activation induced by HLA-DR4/1 specific peptides in rheumatoid arthritis? ### Context: To investigate whether influenza virus haemagglutinin (HA)-derived altered peptide ligands (APLs) could abrogate T-cell responses to wild type HA308-317 or type II collagen (CII) 263-272 peptides and explore the potential inhibitory effects of the altered HA308-317 peptides on T-cell activation in rheumatoid arthritis (RA).Altered HA308-317 peptides containing substitutions of T-cell receptor (TCR)-contact residues were synthesized. Peripheral blood mononuclear cells (PBMC) were obtained from 27 HLA-DR4/1-positive RA patients. Impact of the altered HA308-317 peptides on T-cell responses and the inhibitory effects on T-cell activation were determined by using PBMC from RA.The results showed that the altered HA308-317 peptides could bind to HLA-DR4/1 on cell surface and had no effects on T-cell proliferation and CD25 expression. Moreover, all the altered HA308-317 peptides inhibited T-cell proliferative responses to wild type HA308-317 or CII263-272. In addition, Th1 type cytokine profile was found when PBMC were cultured with wild type HA308-317 or CII263-272, but not the altered HA 308-317 peptides. ### Long_Answer: It is suggested that altered HA308-317 peptides bind to the RA-associated HLA-DR4/1 with no stimulating effects on T cells and might be potentially important in inhibition of T-cell activation in RA. ### Final_Prediction: yes

### Question: Is progesterone receptor negativity an independent risk factor for relapse in patients with early stage endometrioid endometrial adenocarcinoma? ### Context: In endometrioid endometrial adenocarcinoma (EEA), the currently established prognostic factors in clinical guidelines are stage and grade. Many guidelines include lymphovascular invasion (LVI) and tumor size as prognostic factors. Although several studies have associated lack of estrogen (ER) and progesterone receptor (PR) expression with reduced outcome, the prognostic use of these markers is uncommon. Better prognostication of clinical behavior would be useful in patients with early stage (I-II) disease. In this study we evaluated ER and PR as prognostic factors in EEA, and compared their expression with other potential biomarkers and clinical parameters.Tissue microarrays were constructed from 182 patients with stages I-II EEA. ER, PR, p53, Ki-67, PTEN, MLH and HER-2 expression were assessed by immunohistochemical staining and HER-2 was confirmed with SISH. The results were correlated with clinicopathologic parameters and to disease-free survival.Eleven patients (6%) developed recurrent disease during a median follow up time of 62.8 months. In univariate analysis FIGO grade (p=0.019), positive expression of p53 (p=0.010) and negative PR expression (p=0.001) were associated with a shorter disease-free survival. In multivariate analysis only negative PR expression (p=0.019) was significantly associated with a shorter disease-free survival. LVI and tumor size where not of prognostic value. ### Long_Answer: Lack of PR expression is a strong, independent risk factor for tumor recurrence in patients with stages I-II endometrioid endometrial cancer. The use of this easily measurable biomarker as a prognostic factor in the clinical context should be considered and tested in a larger patient population. ### Final_Prediction: yes

### Question: Is anemia a predictor of graft loss but not cardiovascular events and all-cause mortality in renal transplant recipients : follow-up data from the ALERT study? ### Context: It is well established that post-transplantation anemia (PTA) in renal transplant recipients (RTRs) is associated with reduced graft survival. However, there is an uncertainty of the effect of PTA on cardiovascular events and all-cause mortality. We examined prospectively in a large cohort of erythropoietin-naive patients the effects of PTA on cardiovascular morbidity, patient survival, and graft survival.A prospective cohort study of RTRs (n = 2102) included in the ALERT study. Cox regression models were used to evaluate the impact of PTA on study endpoints: first occurrence of a major adverse cardiac event, all-cause death, and the incidence of death-censored graft loss. Mean follow-up was 6.7 yr. All endpoints were adjudicated by an independent endpoint committee.Twenty-nine percent of women and 30% of men were anemic. Hemoglobin levels were not associated with any effect on cardiovascular morbidity and mortality (HR 0.97 [0.90-1.05] per g/dL, p = 0.48) or all-cause death (HR 0.96 [0.90-1.03] per g/dL, p = 0.24) after extensive multivariate adjustments for clinical and demographic factors. Hemoglobin levels were negatively associated with graft loss (HR 0.86 [0.80-0.92] per g/dL, p < 0.001). ### Long_Answer: PTA was not associated with an increased incidence of cardiovascular morbidity and mortality or all-cause mortality. ### Final_Prediction: yes

### Question: Are increases in thyrotropin within the near-normal range associated with increased triiodothyronine but not increased thyroxine in the pediatric age group? ### Context: TSH has been shown in vitro to increase conversion of T4 to T3 and to preferentially increase thyroidal T3 secretion. Whether or not these effects are significant in vivo, other than in obesity, is unclear.To test whether the incremental relationships between free T4 (FT4), free T3 (FT3), and TSH are compatible with TSH enhancement of a preferential increase in serum FT3.A large database of pediatric and adolescent thyroid test results drawn in community clinics from children and adolescents without known thyroid disease was analyzed.RESULTS of FT3, FT4, and TSH were studied anonymously. They were crossed with electronic charts to exclude a history of positive thyroid autoantibodies and use of thyroid hormone preparations, antithyroid medication, or drugs known to affect thyroid function. All samples from patients appearing more than once in the database were removed. After exclusions, 3276 samples remained. FT4, FT3, and the FT3/FT4 ratios were correlated with TSH for the entire group, and the same parameters were segregated by TSH quartile. RESULTS were stratified for body mass index and studied separately in a normal-weight subgroup.Stepwise correlations of FT4, FT3, and FT3/FT4 ratios with TSH.There was a significant positive linear correlation of TSH with FT3 and FT3/FT4 ratios (R = 0.12; P < .0001 in both), but not with FT4. ### Long_Answer: Within the near-euthyroid range, increasing TSH levels are associated with increasing FT3 levels, without an increase in FT4. This provides in vivo support for TSH enhancing preferentially T3 production and/or secretion. ### Final_Prediction: yes

### Question: Does cNAP ( ® ) reliably detect minimal or maximal arterial blood pressures during induction of anaesthesia and tracheal intubation? ### Context: CNAP(®) provides continuous non-invasive arterial pressure (AP) monitoring. We assessed its ability to detect minimal and maximal APs during induction of general anaesthesia and tracheal intubation.Fifty-two patients undergoing surgery under general anaesthesia were enrolled. Invasive pressure monitoring was established at the radial artery, and CNAP monitoring using a finger sensor recording was begun before induction. Statistical analysis was conducted with the Bland-Altman method for comparison of repeated measures and intraclass correlation coefficient (ICC).Patients' median age was 67 years [interquartile range (59-76)], median American Society of Anesthesiologists score was 3 [interquartile range (2-3)]. Bias was 5 and -7 mmHg for peak and nadir systolic AP (SAP), with upper and lower limits of agreement of (42:-32) and (27;-42), respectively. The corresponding ICC values were 0.74 [95% confidence interval (CI) = 0.57-0.84] and 0.60 (95% CI = 0.44-0.73). Time lags to reach these values were 7.5 s (95% CI = -10.0 to 60.0) for the highest SAP and 10 s (95% CI = -12.5 to 72.5) for the lowest SAP. Bias, lower and upper limits of agreement for diastolic, and mean AP were -14 (-36 to 9) and -12 (-37 to 13) for the nadir value and -7 (-29 to 15) and -2 (-28 to 25) for the peak value. ### Long_Answer: The CNAP monitor could detect acute change in AP within a reasonable time lag. Precision of its measurements is not satisfactory, and therefore, it could only serve as a clue to the occurrence of changes in AP. ### Final_Prediction: no

### Question: Superficial acral fibromyxoma: a clinicopathological study of new 41 cases from the U.K.: should myxoma (NOS) and fibroma (NOS) continue as part of 21st-century reporting? ### Context: Superficial acral fibromyxoma (SAF) remains poorly recognized by general pathologists and dermatopathologists, partly attributable to its relatively uncommon occurrence and recent documentation.To examine a series of SAF and document the U.K. experience with this new entity.We reviewed 771 tumours reported between 1970 and 2006 in seven different U.K. hospitals and coded as myxoma, not otherwise specified (NOS), fibroma (NOS) or dermatofibroma (NOS) presenting at acral sites. Forty-one cases of SAF were studied.The patients comprised 27 men and 14 women, age range 19-91 years (mean 50, median 47), presenting with a solitary mass or nodule with a mean size of 1.92 cm. The common clinical sites were the toes (n=29) and fingers (n=11) as well as the palm (n=1), with more than 75% of cases close to or involving the nail bed. All cases presented with a painless mass except for four cases where pain was the presenting complaint. A history of trauma was reported in only two cases. Histologically, all cases presented as proliferation of spindle-shaped and/or stellate cells with a storiform and fascicular pattern embedded in a fibromyxoid/collagenous stroma with conspicuous mast cells. Multinucleated cells were observed (n=22), increased number of blood vessels in the stroma and extravasation of red blood cells (n=4). The characteristic immunophenotype was CD34+, CD99+/-, epithelial membrane antigen+ focally/-, S100-, desmin-, smooth muscle actin-, HMB45- and cytokeratin-. ### Long_Answer: We describe a large series of 41 cases of SAF showing that it is a distinct entity with typical clinical, histological and immunohistochemical features. Follow-up was available only in 12 patients, precluding a firm comment on recurrence. However, complete excision and follow-up review is recommended. ### Final_Prediction: nan

### Question: Does urokinase-type plasminogen activator deficiency in bone marrow-derived cells augment rupture of angiotensin II-induced abdominal aortic aneurysms? ### Context: Abdominal aortic aneurysms (AAAs) are associated with fragmentation of extracellular matrix during development of aortic dilation and rupture. Therefore, it is important to identify specific protease systems involved in extracellular matrix degradation during AAA formation. The present study determined the contribution of the urokinase system to AAA formation and rupture.Angiotensin II (Ang II)-induced AAAs were associated with increased aortic abundance of both urokinase-type plasminogen activator receptor (uPAR) and urokinase-type plasminogen activator (uPA) proteins. However, this increased presence was unrelated to AAA formation because deficiencies of either uPAR or uPA had no effect on either the incidence or size of Ang II-induced AAAs in both normolipidemic mice and low-density lipoprotein receptor-/- mice fed a saturated fat-enriched diet. Although uPA deficiency did not affect development of AAAs, there was an effect of increasing mortality rate from AAA rupture in hypercholesterolemic mice. Bone marrow transplantation demonstrated that enhanced aneurysmal rupture was attributable to deficiency of uPA in leukocytes. uPA deficiency led to an increased propensity for impaired resolution of the thrombotic material within the aneurysmal tissue. Neither uPAR nor uPA deficiency had any effect on Ang II-induced atherosclerosis in low-density lipoprotein receptor-/- mice. ### Long_Answer: The uPA-uPAR axis has no effect on the formation of Ang II-induced AAAs, but uPA deficiency promotes aneurysmal rupture. ### Final_Prediction: yes

### Question: Does staphylococcal enterotoxin P predict bacteremia in hospitalized patients colonized with methicillin-resistant Staphylococcus aureus? ### Context: Methicillin-resistant Staphylococcus aureus (MRSA) colonization predicts later infection, with both host and pathogen determinants of invasive disease.This nested case-control study evaluates predictors of MRSA bacteremia in an 8-intensive care unit (ICU) prospective adult cohort from 1 September 2003 through 30 April 2005 with active MRSA surveillance and collection of ICU, post-ICU, and readmission MRSA isolates. We selected MRSA carriers who did (cases) and those who did not (controls) develop MRSA bacteremia. Generating assembled genome sequences, we evaluated 30 MRSA genes potentially associated with virulence and invasion. Using multivariable Cox proportional hazards regression, we assessed the association of these genes with MRSA bacteremia, controlling for host risk factors.We collected 1578 MRSA isolates from 520 patients. We analyzed host and pathogen factors for 33 cases and 121 controls. Predictors of MRSA bacteremia included a diagnosis of cancer, presence of a central venous catheter, hyperglycemia (glucose level, >200 mg/dL), and infection with a MRSA strain carrying the gene for staphylococcal enterotoxin P (sep). Receipt of an anti-MRSA medication had a significant protective effect. ### Long_Answer: In an analysis controlling for host factors, colonization with MRSA carrying sep increased the risk of MRSA bacteremia. Identification of risk-adjusted genetic determinants of virulence may help to improve prediction of invasive disease and suggest new targets for therapeutic intervention. ### Final_Prediction: yes

### Question: Does proteomic analysis reveal novel proteins associated with progression and differentiation of colorectal carcinoma? ### Context: The objective of this study is to characterize differential proteomic expression among well-differentiation and poor-differentiation colorectal carcinoma tissues and normal mucous epithelium.The study is based on quantitative 2-dimensional gel electrophoresis and analyzed by PDquest.Excluding redundancies due to proteolysis and posttranslational modified isoforms of over 600 protein spots, 11 proteins were revealed as regulated with statistical variance being within the 95th confidence level and were identified by peptide mass fingerprinting in matrix assisted laser desorption/ionization time-of-flight mass spectrometry. Progression-associated proteins belong to the functional complexes of tumorigenesis, proliferation, differentiation, metabolism, and the regulation of major histocompatibility complex processing and other functions. Partial but significant overlap was revealed with previous proteomics and transcriptomics studies in CRC. Among various differentiation stage of CRC tissues, we identified calreticulin precursor, MHC class I antigen (human leukocyte antigen A ), glutathione S-transferase pi1, keratin 8, heat shock protein 27, tubulin beta chain, triosephosphate, fatty acid-binding protein, hemoglobin (deoxy) mutant with val b 1 replaced by met (HBB), and zinc finger protein 312 (FEZF2). ### Long_Answer: Their functional networks were analyzed by Ingenuity systems Ingenuity Pathways Analysis and revealed the potential roles as novel biomarkers for progression in various differentiation stages of CRC. ### Final_Prediction: yes

### Question: Does direct observation during surgery show preservation of cerebral microcirculation in patients with traumatic brain injury? ### Context: To describe the alterations of the cortical microcirculation of the brain (blood flow and vessel density) in TBI patients who and compare them with a control group.Prospective and observational study in a third-level university hospital. Cortical microcirculation in the brain was directly observed using sidestream dark-field (SDF) imaging in 14 patients who underwent surgery: 5 subdural hematomas (SDH) and 9 parenchymal lesions (contusions/hematomas). In this last set of patients, images were recorded in the "pericontusional" areas and in the "surrounding" brain (areas that were as far from the lesion as the craniotomy allowed). These patients were compared to five patients who underwent craniotomy for a disease that did not affect the cortex.There were fewer "pericontusional" images that could be analyzed due to the presence of subarachnoid hemorrhage. The proportion or perfused vessels was similar in all groups: control 99.5% ± 1.3%; SDH 98.6% ± 2.4%; "pericontusional" area 98.2% ± 2.4%; "surrounding" area 98.4% ± 2.5% (p = 0.145). The perfused vessel density index was smaller in the "pericontusional" area: control 6.5 ± 1.6 l/mm; SDH 6.5 ± 2.5 l/mm; "pericontusional" area 5.4 ± 2.6 l/mm; "surrounding" 6.6 ± 2.1 l/mm (p = 0.07). ### Long_Answer: Although the analysis of pericontusional zone was difficult, there were fewer vessels than in the controls and there was no change in the flow. In the surrounding zone and in patients with SDH, we did not document alterations in the microcirculation. Direct imaging of cerebral microcirculation in TBI patients showed that despite serious brain injury the cerebral microcirculation was remarkably well preserved. ### Final_Prediction: yes

### Question: Does propofol block human skeletal muscle sodium channels in a voltage-dependent manner? ### Context: Propofol decreases muscle tone in the absence of neuromuscular blocking drugs. This effect probably cannot be attributed solely to central nervous depression. We studied the effects of propofol on heterologously expressed skeletal muscle sodium channels. Our hypothesis was that the decrease in muscle tone may partly be attributed to an interaction of propofol with sarcolemmal sodium channels. Cells were voltage clamped and whole-cell sodium inward currents were recorded in the absence and presence of propofol. When depolarizing pulses to 0 mV were started from a holding potential close to the normal resting potential of muscle (-70 mV), or when a 2.5-s prepulse inducing slow inactivation was applied before the test pulse at -100 mV, a significant reduction in the peak current amplitude was achieved by 10 and 5 microM propofol, respectively (P < 0.001). Half-maximum blocking concentrations with these protocols were 23 and 22 microM. Blocking potency increased at depolarized membrane potentials with the fraction of inactivated channels; the estimated dissociation constant K(d) from the inactivated state was 4.6 microM. These results suggest that propofol significantly blocks sarcolemmal sodium channels at clinically relevant concentrations while maintaining potentials close to the physiological resting potential. ### Long_Answer: Voltage-gated sodium channels mediate the initiation and propagation of action potentials along the sarcolemma. Results from our study show that those channels are targeted and blocked in a concentration- and voltage-dependent manner by propofol. This mechanism may contribute to the reduction in muscle excitability. ### Final_Prediction: yes

### Question: Is arterial Blood , Rather Than Venous Blood , a Better Source for Circulating Melanoma Cells? ### Context: CTCs provide prognostic information and their application is under investigation in multiple tumor types. Of the multiple variables inherent in any such process, none is more important to outcome than the appropriateness of the sample source. To address this question, we investigated CTCs in paired peripheral venous and arterial blood specimens obtained from stage IV uveal melanoma patients.Blood specimens were obtained from both common femoral arteries and antecubital veins in 17 uveal melanoma patients with multiple hepatic metastases for CTC measurements.CTCs were detectable with greater frequency (100%) and in larger numbers (median 5, range 1 to 168) in all arterial blood specimens than in venous samples (52.9%; median 1, range 0 to 8). Patients with hepatic as well as extra-hepatic metastasis showed higher number of arterial CTCs, compared to patients with liver-only metastasis (p = 0.003). There was no significant association between the number of arterial CTCs and the tumor burden within the liver in patients who had liver-only metastases. ### Long_Answer: Our data indicate that arterial blood specimens might be a better source of circulating uveal melanoma cells. Although less conveniently processed, perhaps arterial blood should be evaluated as sample source for measurement of CTCs. ### Final_Prediction: yes

### Question: Diabetes-related knowledge and sources of information among periodontal patients: is there a role for dental hygienists? ### Context: Although there is a bidirectional relationship between periodontal disease and diabetes, little is known about the diabetes-related knowledge of periodontal patients. This study examines what patients with periodontal disease know about diabetes and its association with periodontitis. It also examines their sources of diabetes-related information.Patients (n=111) with or at risk for diabetes who were receiving care at a university-based periodontics and implant clinic completed a written survey assessing their socio-demographic characteristics, health-related activities, diabetes knowledge and sources of diabetes-related information. Survey results were summarized using descriptive statistics. Fisher's exact tests were used to compare patients who had and had not been diagnosed with diabetes according to responses on diabetes-related knowledge items and sources of diabetes information.Although respondents endorsed various diabetes-related information sources, including family and friends and health care providers, respondents demonstrated very limited knowledge about the diabetes and periodontal disease association. There were no statistically significant differences between patients who had, and had not been diagnosed with diabetes regarding their diabetes-related knowledge. As compared with patients not diagnosed with diabetes, patients with diabetes were significantly more likely to have learned about diabetes from a health care provider (p=0.05) and significantly less likely to have learned about it from friends or family (p=0.05). ### Long_Answer: Periodontal patients need education about the periodontitis-diabetes relationship. Dental hygienists' regular and ongoing involvement with these patients and their primary role in the patients' periodontal care places them in an optimal position to provide this education. ### Final_Prediction: nan

### Question: Are structural and functional changes of carotid wall properties in patients with acromegaly restored after 1 year of GH/IGF1 normalization? ### Context: Vascular changes are common in acromegaly (ACM). Current therapies can normalise the levels of both growth hormone (GH) and insulin-like growth factor (IGF1).To establish whether the ACM vascular changes in patients with effectively managed disease are different from those in patients with an active condition.64 ACM patients were tested for serum GH (random and during an oral glucose tolerance test) and IGF1. Ultrasonography of the right common carotid (RCC) explored structural (the carotid diameter and intima-media thickness index (IMT)) and functional (the augmentation index (AIx), elastic modulus (Ep), and local pulse wave velocity (PWV)) arterial parameters in the ACM patients (groups A and B) and an age- and sex-matched control group of 21 patients without acromegaly (group C).The ACM patients were divided into 2 subgroups that had similar cardiovascular risk factor profiles: A (n=10, with controlled ACM), and B (n=54, with active ACM). The AIx was higher in groups A (27.7% [2.2-54.3]) and B (20.0% [ - 38.2-97.1]) than in group C (3.5% [ - 11.3-31.1]), p=0.01 and 0.002, respectively. The group B patients presented with poorer functional carotid wall parameters than the control subjects: Ep-95.5 [33-280] KPa vs. 77.5 [39-146] KPa, p=0.01; and PWV-6 [3.6-10.4] m/s vs. 5.4 [3.9-7.2] m/s, p=0.03.The ACM patients had greater RCC diameters (6.4 ± 0.6 mm vs. 5.7 ± 0.6 mm, p<0.001) and IMT values (0.72 ± 0.13 mm vs. 0.58 ± 0.08 mm, p<0.001) than the subjects in group C. ### Long_Answer: Both the controlled and active ACM patients showed structural arterial changes. After 1 year of disease control, the patients with controlled ACM showed improvements in the functional, but not the structural, arterial parameters compared with the patients with an active condition. ### Final_Prediction: no

### Question: Are nUDT15 and TPMT genetic polymorphisms related to 6-mercaptopurine intolerance in children treated for acute lymphoblastic leukemia at the Children 's Cancer Center of Lebanon? ### Context: Interindividual variability in thiopurine-related toxicity could not be completely explained by thiopurine S-methyltransferase (TPMT) polymorphisms, as a number of patients who are homozygous wild type or normal for TPMT still develop toxicity that necessitates 6-mercaptopurine (MP) dose reduction or protocol interruption. Recently, few studies reported on an inherited nucleoside diphosphate-linked moiety X motif 15 (NUDT15) c.415C>T low-function variant that is associated with decreased thiopurine metabolism and leukopenia in childhood acute lymphoblastic leukemia (ALL) and other diseases.The aim of this study is to measure the frequency of TPMT and NUDT15 polymorphisms and assess whether they are predictors of MP intolerance in children treated for ALL. One hundred thirty-seven patients with ALL of whom 121 were Lebanese were evaluated. MP dose intensity was calculated as the ratio of the tolerated MP dose to planned dose during continuation phase to maintain an absolute neutrophil count (ANC) dose above 300 per μl.One patient was NUDT15 heterozygous TC and tolerated only 33.33% of the planned MP dose, which was statistically significantly different from the median-tolerated MP dose intensity of the rest of the cohort (76.00%). Three patients had the TPMT*3A haplotype and tolerated 40.00-66.66% of the planned MP dose, which was also statistically significantly different from the rest of the cohort. ### Long_Answer: This is the first report on the association of TPMT and NUDT15 polymorphisms with MP dose intolerance in Arab patients with ALL. Genotyping for additional polymorphisms may be warranted for potential gene/allele-dose effect. ### Final_Prediction: yes

### Question: Is minor trauma an unrecognized contributor to poor fetal outcomes : a population-based study of 78,552 pregnancies? ### Context: Fetal outcomes after minor injury (MI) to pregnant women are difficult to study because these patients are discharged after emergency room evaluation and not entered in trauma registries. The purpose of this study was to determine the association of both minor and severe injury on fetal demise and prematurity/low birth weight (LBW) in a large population-based study using robust state databases.The Tennessee State Fetal Birth and Death Data Systems were merged with the Tennessee State Hospital Discharge Data System using patient identifiers. All women with an e-code requiring inpatient admission during their pregnancy were considered severely injured, whereas those discharged after emergency room evaluation were considered to have MI. The impact of trauma on unintended fetal demise and premature birth/LBW was assessed using multivariable logistic regression.In 2005, there were 376 fetal deaths and 78,176 viable deliveries of which 11,817 were premature/LBW. Severe injury was significantly associated with fetal demise and prematurity/LBW. Unexpectedly, first- and second-trimester MI was associated with both fetal demise and prematurity/LBW. ### Long_Answer: As expected, fetal mortality and morbidity increased after severe injury. Surprisingly, MI was associated with fetal demise, premature delivery, and LBW. Pregnant women who sustain MI should be told that they are at increased risk for an adverse outcome. ### Final_Prediction: yes

### Question: Is nonalcoholic steatohepatitis associated with altered hepatic MicroRNA expression? ### Context: The expression of microRNA in nonalcoholic steatohepatitis (NASH) and their role in the genesis of NASH are not known. The aims of this study were to: (1) identify differentially expressed microRNAs in human NASH, (2) tabulate their potential targets, and (3) define the effect of a specific differentially expressed microRNA, miR-122, on its targets and compare these effects with the pattern of expression of these targets in human NASH. The expression of 474 human microRNAs was compared in subjects with the metabolic syndrome and NASH versus controls with normal liver histology. Differentially expressed microRNAs were identified by the muParaflo microRNA microarray assay and validated using quantitative real-time polymerase chain reaction (PCR). The effects of a specific differentially expressed miRNA (miR-122) on its predicted targets were assessed by silencing and overexpressing miR-122 in vitro. A total of 23 microRNAs were underexpressed or overexpressed. The predicted targets of these microRNAs are known to affect cell proliferation, protein translation, apoptosis, inflammation, oxidative stress, and metabolism. The miR-122 level was significantly decreased in subjects with NASH (63% by real-time PCR, P < 0.00001). Silencing miR-122 led to an initial increase in mRNA levels of these targets (P < 0.05 for all) followed by a decrease by 48 hours. This was accompanied by an increase in protein levels of these targets (P < 0.05 for all). Overexpression of miR-122 led to a significant decrease in protein levels of these targets. ### Long_Answer: NASH is associated with altered hepatic microRNA expression. Underexpression of miR-122 potentially contributes to altered lipid metabolism implicated in the pathogenesis of NASH. ### Final_Prediction: yes

### Question: Does in utero and postnatal exposure to isoflavones result in a reduced responsivity of the mammary gland towards estradiol? ### Context: Exposure scenarios during different stages of development of an organism are discussed to trigger adverse and beneficial effects of isoflavones (ISO). The aim of this study was to investigate how in utero and postnatal ISO exposure modulates the estrogen sensitivity of the mammary gland and to identify the underlying molecular mechanisms.Therefore, rats were exposed to either ISO-free (IDD), ISO-rich (IRD) or genistein-rich diet (GRD), up to young adulthood. Proliferative activity (PCNA expression) in the mammary gland at different ages and the estrogen sensitivity of the mammary gland to estradiol (E₂) or genistein (GEN) in adult ovariectomized animals was determined and compared with different treatments. Treatment with E₂ resulted in a significant lower proliferative and estrogenic response of the mammary gland in IRD and GRD compared with IDD. This correlates to a change in the gene expression pattern and a decrease in the ratio of estrogen receptor alpha (ERα) beta (ERβ ### Long_Answer: Our results provide evidence that in utero and postnatal exposure to a diet rich in ISO but also to GEN reduces the sensitivity of the mammary gland toward estrogens and support the hypothesis that in utero and postnatal ISO exposure reduces the risk to develop breast cancer. ### Final_Prediction: yes

### Question: Are lipid disorders involved in the predominance of human T-lymphotropic virus-1 infections in women? ### Context: The human T-lymphotropic virus-1 (HTLV-1) is associated with chronic inflammatory diseases such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a chronic inflammatory disease. Disturbances in lipid metabolism are involved in inflammatory and demyelinating diseases.Plasma levels of triglycerides, total cholesterol, and fractions of HTLV-1-infected individuals of both sexes with different clinical progressions were determined.Elevated levels of triglyceride and very low-density lipoproteins (VLDL) were exclusively detected in HTLV-1-infected women from asymptomatic and HAM/TSP groups compared with uninfected individuals (p = 0.02). ### Long_Answer: Elevated triglyceride and VLDL levels in HTLV-1-infected women may be related to the predominance of HAM/TSP in women. ### Final_Prediction: nan

### Question: Is child sexual abuse largely hidden from the adult society . An epidemiological study of adolescents ' disclosures? ### Context: The aim of this study was to investigate disclosure rates and disclosure patterns and to examine predictors of non-disclosure in a sample of male and female adolescents with self-reported experiences of sexual abuse.A sample of 4,339 high school seniors (2,324 girls, 2,015 boys) was examined with a questionnaire concerning sexual experiences in this study with a focus on disclosure of sexual abuse (non-contact, contact or penetrating abuse, and including peer abuse).Of the sample, 1,505 girls (65%) and 457 boys (23%) reported experience of sexual abuse. The disclosure rate was 81% (girls) and 69% (boys). Girls and boys disclosed most often to a friend of their own age. Few had disclosed to professionals. Even fewer said that the incident had been reported to the authorities. Logistic regression showed that it was less likely for girls to disclose if they had experienced contact sexual abuse with or without penetration, abuse by a family member, only a single abuse occasion or if they had perceived their parents as non-caring. Boys were less likely to disclose if they studied a vocational program, lived with both parents or had perceived their parents as either caring and overprotective or non-caring and not overprotective. ### Long_Answer: Disclosing sexual abuse is a complex process. Much is hidden from the adult society, especially from professionals and the legal system. Since peers are the most common receivers of abuse information, programs for supporting peers ought to be developed. Differences in disclosure patterns for girls and boys indicate that a gender perspective is helpful when developing guidelines for professionals. ### Final_Prediction: yes

### Question: Do antidepressants influence the disease course in inflammatory bowel disease? ### Context: Depression, like adverse events and psychological stress, can trigger relapse in inflammatory bowel disease (IBD); however, the effects of psychoactive drugs on disease course are unclear.Using retrospective electronic case note review, after exclusion of five patients on low-dose tricyclic antidepressants we compared the course of IBD in 29 patients (14 ulcerative colitis and 15 Crohn's disease), during the years before (year 1) and after (year 2) they were started on an antidepressant for a concomitant mood disorder to that of controls matched for age, sex, disease type, medication at baseline, and relapse rate in year 1.Patients had fewer relapses and courses of steroids in the year after starting an antidepressant than in the year before (1 [0-4] (median [range]) vs. 0 [0-4], P = 0.002; 1 [0-3]vs. 0 [0-4], P<0.001, respectively); the controls showed no changes between years 1 and 2 in relapses (1 [0-4] vs. 1 [0-3], respectively) or courses of steroids (1 [0-2] vs. 0 [0-3]). Although there were no differences in the use of other relapse-related medications, outpatient attendances, or hospital admissions, the number of endoscopies fell significantly in the antidepressant group in year 2 compared with year 1 (P<0.01). No such changes were seen in the controls. ### Long_Answer: Antidepressants, when used to treat concomitant mood disorders in IBD, seem to reduce relapse rates, use of steroids, and endoscopies in the year after their introduction. These results suggest the need for a prospective controlled trial to evaluate their effects on disease course in patients with IBD. ### Final_Prediction: nan

### Question: Does Sitagliptin Affect the Rate of Osteoporotic Fractures in Type 2 Diabetes? ### Context: Type 2 diabetes and osteoporosis are both common, chronic, and increase with age, whereas type 2 diabetes is also a risk factor for major osteoporotic fractures (MOFs). However, different treatments for type 2 diabetes can affect fracture risk differently, with metaanalyses showing some agents increase risk (eg, thiazolidinediones) and some reduce risk (eg, sitagliptin).To determine the independent association between new use of sitagliptin and MOF in a large population-based cohort study.A sitagliptin new user study design employing a nationally representative Unites States claims database of 72 738 insured patients with type 2 diabetes. We used 90-day time-varying sitagliptin exposure windows and controlled confounding by using multivariable analyses that adjusted for clinical data, comorbidities, and time-updated propensity scores.We compared the incidence of MOF (hip, clinical spine, proximal humerus, distal radius) in new users of sitagliptin vs nonusers over a median 2.2 years follow-up.At baseline, the median age was 52 years, 54% were men, and median A1c was 7.5%. There were 8894 new users of sitagliptin and 63 834 nonusers with a total 181 139 person-years of follow-up. There were 741 MOF (79 hip fractures), with 53 fractures (4.8 per 1000 person-years) among new users of sitagliptin vs 688 fractures (4.0 per 1000 person-years) among nonusers (P = .3 for difference). In multivariable analyses, sitagliptin was not associated with fracture (adjusted hazard ratio 1.1, 95% confidence interval 0.8-1.4; P = .7), although insulin (P<.001), sulfonylureas (P<.008), and thiazolidinedione (P = .019) were each independently associated with increased fracture risk. ### Long_Answer: Even in a young population with type 2 diabetes, osteoporotic fractures were not uncommon. New use of sitagliptin was not associated with fracture, but other commonly used second-line agents for type 2 diabetes were associated with increased risk. These data should be considered when making treatment decisions for those with type 2 diabetes at particularly high risk of fractures. ### Final_Prediction: nan

### Question: Does 2-5A antisense directed against telomerase RNA produce apoptosis in ovarian cancer cells? ### Context: RNase L is converted to an active form upon binding short 2',5'-oligoadenylates (2-5A). To direct RNase L to an RNA target, 2-5A is attached to an antisense oligonucleotide (2-5A antisense). This chimera can be directed against telomerase-an RNA-protein complex that elongates telomeric DNA and is involved in cellular immortalization. Our objective is to investigate the effect of 2-5A antisense by targeting telomerase RNA (hTR) in the ovarian cancer cell line, HEY-1B.Baseline RNase L levels and telomerase activities were measured in both HEY-1B and normal ovarian epithelial cells (NOE). Cells were treated daily with chimeric oligonuclotides (ODN) directed against four different hTR sites, or control ODNs including nonchimeric antisense, 2-5A fused to a mismatched sequence, or inactive 2-5A fused to antisense. At 48 h, apoptosis was evaluated using the TUNEL assay. After six daily ODN administrations, telomerase activity was redetermined, and at 7 days viability counts were obtained.Both cell lines expressed similar levels of RNase L. Hey-1B displayed telomerase activity while NOE did not. After 7 days of transfection, 2-5A antisense ODNs caused profound cell death in the HEY-1B cells, but not in the NOE cells. This effect was seen regardless of hTR target site, and ODN controls showed no significant decrease in cell viability in either cell line. HEY1B cells treated with 2-5A antisense against hTR showed a decrease in telomerase activity and a profound induction of programmed cell death. ### Long_Answer: The results suggest that 2-5A antisense directed against telomerase RNA results in apoptotic cell death in ovarian cancer cells, but not normal ovarian epithelial cells. The 2-5A antisense strategy may hold a considerable advantage over the conventional antisense approach in targeting cancer-causing genes. ### Final_Prediction: yes

### Question: Does craniocervical extension improve the specificity and predictive value of the Mallampati airway evaluation? ### Context: The modified Mallampati (MMP) classification is a standard airway examination that assesses mouth opening and structures within the oral cavity. Recent data suggest that maximal mouth opening (as measured by interdental distance) is possible only with extension of the craniocervical junction. Because the MMP examination is performed with the head in a neutral position, the airway may appear worse because of submaximal interdental distance. We hypothesized that adding craniocervical extension to the MMP would allow for greater mouth opening, lower scores, and less false positives than the traditional MMP examination.Multiple clinicians with at least 1 yr of airway experience evaluated adult airways (n = 60) with the MMP examination (with head in neutral position). The same examination was then repeated with the addition of craniocervical extension (Extended Mallampati Score, EMS).On average, craniocervical extension decreased the MMP class (P < 0.002). The EMS improved specificity from 70% to 80% and positive predictive value from 24% to 31% when compared with the traditional MMP. The sensitivity (83%) was the same for MMP and EMS. ### Long_Answer: Craniocervical extension improves the specificity and positive predictive value of the MMP airway evaluation while retaining sensitivity of the traditional MMP examination. The introduction of the EMS into clinical practice should be considered. ### Final_Prediction: yes

### Question: Does beta-1 blocker improve survival of septic rats through preservation of gut barrier function? ### Context: Since recent study demonstrated beneficial effects of β-adrenergic blocker in sepsis, we tested the hypothesis that infusion of selective β1-blocker, esmolol, improves outcome in sepsis by modulating inflammatory responses and gut barrier function.Prospective randomized animal study.University research laboratory.Male Wistar rats.To assess the effects of esmolol infusion on survival time, 19 animals that underwent cecal ligation and perforation were randomized into control (n = 9) or esmolol (n = 10) groups, the latter of which received esmolol infusion (15 mg/kg/h) throughout the study period. In an additional 20 animals, levels of tumor necrosis factor-α (TNF-α) in both plasma and intraperitoneal fluid were measured, and mesenteric lymph nodes (MLNs) and ileum were excised for evaluation of bacterial translocation and mucosal injury at the 18-h study period.Mean survival time in the esmolol group was significantly longer compared with the control group (69.5 ± 26.8 versus 28.6 ± 11.0 h). Plasma TNF-α was not detectable in either group, while intraperitoneal fluid TNF-α level was elevated in the control group but significantly depressed in the esmolol group (16.8 ± 10.7 versus 5.4 ± 7.1 pg/ml, P < 0.05). Simultaneously, the Escherichia coli positive rate of MLNs was higher (100% versus 44%, P < 0.05) and the gut mucosal injury score was elevated (4.1 ± 0.6 versus 2.8 ± 0.6, P < 0.01) in the control compared with the esmolol group. ### Long_Answer: Beta-1 blocker therapy improves outcome in sepsis possibly through modulation of gut mucosal integrity and local inflammatory response. ### Final_Prediction: yes

### Question: Is latent Epstein-Barr virus infection an unlikely event in the pathogenesis of immunoproliferative small intestinal disease? ### Context: The observed seasonal and geographic variations in the incidence of immunoproliferative small intestinal disease (IPSID) suggest that environmental factors contribute to its pathogenesis. One such environmental factor, the Epstein-Barr virus (EBV), has been associated with other B-cell lymphoproliferative disorders.IPSID tissues obtained at the time of initial diagnosis were retrieved from the American University of Beirut pathology archives (1972-1983) and examined for EBV genetic information by colorimetric in situ hybridization (ISH) and polymerase chain reaction (PCR). Eight patients were identified, four of whom also had serologic and immunohistochemical evidence of alpha-heavy chain disease. Thirteen tissue samples from these eight patients were available for study: eight were intestinal and five were nodal. Non-Hodgkin's B-cell lymphoma cases (nine) were randomly selected from the same archive to serve as a control for EBV in that geographic location. The ISH method used a probe to the "W" repetitive region of EBV, with the human placental DNA probe as a control for sample preparation. The PCR method amplified a 110 base pair region in the long internal direct repeat with amplification of beta-actin as control for DNA preservation. Both assays used formalin fixed paraffin embedded Raji cells as a positive control.Neither ISH nor PCR demonstrated EBV in any of the eight patients with IPSID: The results for one of seven control blocks with adequate DNA preservation were positive when PCR was used but were negative when ISH was used. ### Long_Answer: These findings do not support a role for EBV in the induction of B-cell proliferation in IPSID: ### Final_Prediction: yes

### Question: Does reduction of magnetic resonance imaging-related heating in deep brain stimulation lead using a lead management device? ### Context: To evaluate the ability of a lead management device to reduce magnetic resonance imaging (MRI)-related heating of deep brain stimulation (DBS) leads and thereby to decrease the risks of exposing patients with these implants to MRI procedures.Experiments were performed using the Activa series (Medtronic, Inc., Minneapolis, MN) DBS systems in an in vitro, gelled-saline head and torso phantom. Temperature change was recorded using fluoroptic thermometry during MRI performed using a transmit-and-receive radiofrequency body coil at 1.5 T and a transmit-and-receive radiofrequency head coil at 3 T. A cranial model placed in the phantom was used to test a custom-designed burr hole device that permitted the placement of small-diameter, concentric loops around the burr hole at the DBS lead as it exited the cranium.A total of 41 scans were performed, with absolute temperature changes ranging from 0.8 to 10.3 degrees C. Depending on the MRI system tested and the side of the phantom on which the hardware was placed, loop placement resulted in reductions in temperature rise of 41 to 74%. The effect was linearly related to the number of loops formed (P < 0.01) over the range tested (0-2.75 loops). ### Long_Answer: Small, concentric loops placed around the burr hole seem to reduce MRI-related heating for these implants. Although the mechanism is still not fully understood, a device such as that used in the present study could permit a wider range of clinical scanning sequences to be used at 1.5 and 3 T in patients with DBS implants, in addition to increasing the margin of safety for the patient. ### Final_Prediction: yes

### Question: Does thoracic epidural anesthesia with ropivacaine compromise the tolerance of acute normovolemic anemia in pigs? ### Context: The initial treatment of an acute blood loss with acellular fluids leads to the dilution of the red cell mass remaining in the vasculature, that is, to acute normovolemic anemia. Whether the compensation and, thus, the tolerance of acute anemia, are affected by sympathetic block induced by thoracic epidural anesthesia has not yet been investigated.Eighteen anesthetized and mechanically ventilated pigs were instrumented with thoracic epidural catheters and randomly assigned to receive an epidural injection of either 5-ml ropivacaine 0.2% (n = 9) aiming for a Th5-Th10 block or saline (n = 9) followed by continuous epidural infusion of 5 ml/h of either fluid. Subsequently, acute normovolemic anemia was induced by replacement of whole blood with 6% hydroxyethyl starch solution until a "critical" limitation of oxygen transport capacity was reached as indicated by a sudden decrease in oxygen consumption. The critical hemoglobin concentration quantified at this time point was the primary endpoint; secondary endpoints were hemodynamic and oxygen transport parameters.Thoracic epidural anesthesia elicited only a moderate decrease in mean arterial pressure and cardiac index and a transient decrease in oxygen extraction ratio. During progressive anemia, the compensatory increases in cardiac index and oxygen extraction ratio were not compromised by thoracic epidural anesthesia. Critical hemoglobin concentration was reached at identical levels in both groups (ropivacaine group: 2.5 ± 0.6 g/dl, saline group: 2.5 ± 0.6 g/dl). ### Long_Answer: Thoracic epidural anesthesia with ropivacaine 0.2% does not decrease the tolerance to acute normovolemic anemia in healthy pigs. The hemodynamic compensation of acute anemia is fully preserved despite sympathetic block, and the critical hemoglobin concentration remains unaffected. ### Final_Prediction: no

### Question: Is platelet response to corneal abrasion necessary for acute inflammation and efficient re-epithelialization? ### Context: Adhesion molecules play a critical role in leukocyte emigration to wound sites, but differences are evident in different vascular beds. In this study, the contributions of P-selectin to neutrophil emigration into the cornea after central epithelial abrasion were investigated.Re-epithelialization, neutrophil influx, and platelet accumulation were assessed in C57BL/6 mice after removal of a 2-mm diameter area of central corneal epithelium that did not directly injure the limbal vessels or the avascular stroma of the cornea. Comparisons were made between wild-type (WT) mice and mice with targeted deletions of genes for P-selectin, CD18, or CD54, or mice with antibody-induced neutropenia or thrombocytopenia.After central corneal epithelial abrasion, platelets localized in the limbal vessels and neutrophils emigrated from the limbal vessels to the region of the epithelial wound. There was temporal correspondence of platelet and neutrophil localization, peaking within 12 hours of wounding. Platelet accumulation, neutrophil emigration and corneal epithelial healing as measured by wound closure, basal epithelial cell density, and epithelial cell division were significantly reduced in P-selectin-deficient mice (P-sel(-/-)). Anti-GP1balpha antibody-induced thrombocytopenia in WT mice significantly reduced platelet and neutrophil accumulation and wound healing. Passive transfer of wild-type platelets into P-sel(-/-) mice significantly restored platelet localization in limbal vessels, neutrophil emigration, epithelial cell division, and epithelial cell migration into the abraded region of the cornea. ### Long_Answer: Platelet localization in the limbus of abraded corneas contributes to re-epithelialization, and P-selectin provides a necessary step in this process. ### Final_Prediction: yes

### Question: Does quercetin reduce obesity-induced hepatosteatosis by enhancing mitochondrial oxidative metabolism via heme oxygenase-1? ### Context: Obesity-induced hepatic lipid accumulation causes lipotoxicity, mitochondrial dysfunction, oxidative stress, and insulin resistance, and is implicated in non-alcoholic hepatic pathologies such as steatohepatitis and fibrosis. Heme oxygenase-1 (HO-1), an important antioxidant enzyme catalyzing the rate-limiting step in heme degradation, protects against oxidative stress, inflammation, and metabolic dysregulation. Here, we demonstrate that the phytochemical, quercetin, a natural polyphenol flavonoid, protects against hepatic steatosis in obese mice fed a high-fat diet, and that it does so by inducing HO-1 and stimulating increased hepatic mitochondrial oxidative metabolism.Male C57BL/6 mice were fed a regular diet (RD), a high-fat diet (HFD), and an HFD supplemented with quercetin for 9 weeks. Levels of mitochondrial biogenesis and oxidative metabolic transcripts/proteins were measured by real-time PCR and/or Western blotting. HO-1 transcripts/proteins were measured real-time PCR and/or Western blotting.Quercetin upregulated genes involved in mitochondrial biogenesis and oxidative metabolism in lipid-laden hepatocytes and the livers of HFD-fed obese mice, and this was accompanied by increased levels of the transcription factor, nuclear erythroid 2-related factor 2 (Nrf-2), and HO-1 protein. The HO-1 inducer hemin and the HO-1 byproduct carbon monoxide (CO) also enhanced hepatic oxidative metabolism in HFD-fed obese mice. Moreover, the metabolic changes and the lipid-lowering effects of quercetin were completely blocked by the HO-1 inhibitor ZnPP and by deficiency of Nrf-2. ### Long_Answer: These findings suggest that quercetin stimulates hepatic mitochondrial oxidative metabolism by inducing HO-1 via the Nrf-2 pathway. Quercetin may be useful in protecting against obesity-induced hepatosteatosis. ### Final_Prediction: yes

### Question: Do socioeconomic Factors Are Associated With Readmission After Lobectomy for Early Stage Lung Cancer? ### Context: Data regarding risk factors for readmissions after surgical resection for lung cancer are limited and largely focus on postoperative outcomes, including complications and hospital length of stay. The current study aims to identify preoperative risk factors for postoperative readmission in early stage lung cancer patients.The National Cancer Data Base was queried for all early stage lung cancer patients with clinical stage T2N0M0 or less who underwent lobectomy in 2010 and 2011. Patients with unplanned readmission within 30 days of hospital discharge were identified. Univariate analysis was utilized to identify preoperative differences between readmitted and not readmitted cohorts; multivariable logistic regression was used to identify risk factors resulting in readmission.In all, 840 of 19,711 patients (4.3%) were readmitted postoperatively. Male patients were more likely to be readmitted than female patients (4.9% versus 3.8%, p < 0.001), as were patients who received surgery at a nonacademic rather than an academic facility (4.6% versus 3.6%; p = 0.001) and had underlying medical comorbidities (Charlson/Deyo score 1+ versus 0; 4.8% versus 3.7%; p < 0.001). Readmitted patients had a longer median hospital length of stay (6 days versus 5; p < 0.001) and were more likely to have undergone a minimally invasive approach (5.1% video-assisted thoracic surgery versus 3.9% open; p < 0.001). In addition to those variables, multivariable logistic regression analysis identified that median household income level, insurance status (government versus private), and geographic residence (metropolitan versus urban versus rural) had significant influence on readmission. ### Long_Answer: The socioeconomic factors identified significantly influence hospital readmission and should be considered during preoperative and postoperative discharge planning for patients with early stage lung cancer. ### Final_Prediction: yes

### Question: Can the Application of Fluoride Iontophoresis Improve Remineralisation of Early Caries Lesions? ### Context: To determine the optimal electric current intensity of fluoride iontophoresis (FI) for remineralisation of early caries lesions in vitro.Sixty specimens were made from bovine incisors and immersed in a demineralising gel for 96 h. Specimens were divided into control (conventional fluoride application) and experimental (FI) groups. All of the specimens were covered with fluoride for 4 min every day. Different electric current intensities (100, 200, 300 and 400 μA) were applied in the FI groups using the FI device. The concentration of KOH-soluble fluoride was determined to evaluate the amount of CaF2 formed on the tooth surface. The reduction in lesion depth was measured by polarised light microscopy.The concentration of KOH-soluble fluoride was the highest in the specimens of the 300 μA FI group. However, there was no significant difference in the reduction of lesion depth between the experimental groups and the control group. ### Long_Answer: Variations in the electric current intensity influenced the amount of CaF2 formed on the enamel surface, with the greatest amount found for 300 μA. ### Final_Prediction: nan

### Question: Does open access publishing increase the impact of scientific articles? ### Context: Some studies suggest that open access articles are more often cited than non-open access articles. However, the relationship between open access and citations count in a discipline such as intensive care medicine has not been studied to date. The present article analyzes the effect of open access publishing of scientific articles in intensive care medicine journals in terms of citations count.We evaluated a total of 161 articles (76% being non-open access articles) published in Intensive Care Medicine in the year 2008. Citation data were compared between the two groups up until April 30, 2011. Potentially confounding variables for citation counts were adjusted for in a linear multiple regression model.The median number (interquartile range) of citations of non-open access articles was 8 (4-12) versus 9 (6-18) in the case of open access articles (p=0.084). In the highest citation range (>8), the citation count was 13 (10-16) and 18 (13-21) (p=0.008), respectively. The mean follow-up was 37.5 ± 3 months in both groups. In the 30-35 months after publication, the average number (mean ± standard deviation) of citations per article per month of non-open access articles was 0.28 ± 0.6 versus 0.38 ± 0.7 in the case of open access articles (p=0.043). Independent factors for citation advantage were the Hirsch index of the first signing author (β=0.207; p=0.015) and open access status (β=3.618; p=0.006). ### Long_Answer: Open access publishing and the Hirsch index of the first signing author increase the impact of scientific articles. The open access advantage is greater for the more highly cited articles, and appears in the 30-35 months after publication. ### Final_Prediction: yes

### Question: Does antiplatelet loading improve behavioral outcome in a rabbit model of stroke? ### Context: No approved acute therapy exists for thousands of patients with ischemic stroke who present ineligible for thrombolytics. The purpose of this proof-of-concept study was to evaluate the efficacy of acute antiplatelet loading on stroke outcome in the rabbit small clot embolic model.Sixty male New Zealand white rabbits were embolized via small clots into the middle cerebral artery. Two hours later, animals were treated with (1) aspirin (5 mg/kg; n=20); (2) usual dual antiplatelet loading (aspirin 10 mg/kg+clopidogrel 10 mg/kg; n=20); or (3) high-dose dual antiplatelet loading (aspirin 10 mg/kg+clopidogrel 30 mg/kg; n=20). The coprimary outcomes were as follows: (1) platelet inhibition and (2) behavioral outcome as measured by the P50 (milligrams of clot that leads to neurological dysfunction in 50% of animals in a group).There was a significant difference in 3-hour arachidonic acid and ADP (P<0.011); 6-hour collagen and ADP (P<0.01, P<0.01); and 24-hour collagen, arachidonic acid, and ADP (P=0.02, P<0.01, P<0.01) platelet inhibition. The behavioral outcome was significantly better in the usual dual antiplatelet loading versus aspirin group (P=0.02). ### Long_Answer: This study suggests that usual dual antiplatelet loading is clinically beneficial in a validated model of acute stroke. Study of usual dual antiplatelet loading in acute stroke is warranted to provide treatment to stroke victims ineligible for current therapies. ### Final_Prediction: yes

### Question: Does surgical technique influence bowel function after low anterior resection and sigmoid colectomy? ### Context: Since June 1996, we have changed surgical strategies to preserve the pelvic autonomic nerve and abandon high ligation of the inferior mesenteric artery. The aim of this study was to clarify the influence of this surgical technique on subjective bowel function of patients with low anterior resection and sigmoid colectomy for cancer.Forty-eight patients who underwent low anterior resection or sigmoid colectomy for cancer during June 1996 and February 2000 replied to the questionnaire which consisted of eight categories of bowel symptoms. Subjective bowel function and operative data of these patients were compared with those obtained from 84 patients with low anterior resection or sigmoid colectomy during April 1984 and May 1996.When recent series were compared with previous series, the frequency of bowel movement at night (21% vs. 60%, p < 0.01) and patient's own judgment as fair or poor (0% vs. 29%, p < 0.01) was decreased in patients with low anterior resection; whereas the frequency of defecation > 2 per day (5% vs. 34%, p < 0.01), difficulty in emptying (32% vs. 71%, p < 0.01), and incomplete evacuation (32% vs. 66%, p < 0.05) was decreased in patients with sigmoid colectomy. Patient judged as poor bowel function was less frequent in the recent group after low anterior resection (25% vs. 71%, p < 0.01) and sigmoid colectomy (18% vs. 42%, p < 0.05) compared with the previous group. Operative data including volume of blood loss, frequency of transfusion, and length of resected specimen were also different between the two groups. ### Long_Answer: Surgical technique had a significant impact on bowel function following low anterior resection and sigmoid colectomy for cancer. When high ligation of the inferior mesenteric artery is abandoned and the pelvic autonomic nerve is preserved by careful technique, postoperative bowel dysfunction in patients with rectosigmoid colon cancer can be minimized. ### Final_Prediction: yes

### Question: Does the prevalence of the c-kit exon 10 variant , M541L , in aggressive fibromatosis differ from the general population? ### Context: The frequency of the c-kit exon 10 variant, M541L, (c.1621 A>C) in aggressive fibromatosis (AF) was recently determined to be 2.5-fold higher than in healthy controls. It was thus hypothesised that M541L could be associated with the development of AF.42 cases of sporadic AF were investigated for c-kit exon 10 alterations, by traditional sequencing. Subsequently, the AF cases and 126 healthy volunteers were screened for the M541L by pyrosequencing.Genotype frequency of M541L in AF was 16.7% (allele frequencies: A, 0.92 and C, 0.08), which did not differ from the control group. Moreover the M541L variant was found to be not tumour specific. ### Long_Answer: The result classifies the M541L variant of c-kit exon 10 as a single nucleotide polymorphism. Because its prevalence does not differ between the AF and general populations, an association with AF tumourigenesis is unlikely. ### Final_Prediction: no

### Question: Does a subanesthetic dose of ketamine in the Rhesus monkey reduce the occurrence of anticipatory saccades? ### Context: It has been shown that antagonism of the glutamatergic N-methyl-D-aspartate (NMDA) receptor with subanesthetic doses of ketamine perturbs the perception of elapsed time. Anticipatory eye movements are based on an internal representation of elapsed time. Therefore, the occurrence of anticipatory saccades could be a particularly sensitive indicator of abnormal time perception due to NMDA receptors blockade.The objective of this study was to determine whether the occurrence of anticipatory saccades could be selectively altered by a subanesthetic dose of ketamine.Three Rhesus monkeys were trained in a simple visually guided saccadic task with a variable delay. Monkeys were rewarded for making a visually guided saccade at the end of the delay. Premature anticipatory saccades to the future position of the eccentric target initiated before the end of the delay were not rewarded. A subanesthetic dose of ketamine (0.25 mg/kg) or a saline solution of the same volume was injected i.m. during the task.We found that the injected dose of ketamine did not induce sedation or abnormal behavior. However, in ∼4 min, ketamine induced a strong reduction of the occurrence of anticipatory saccades but did not reduce the occurrence of visually guided saccades. ### Long_Answer: This unexpected reduction of anticipatory saccade occurrence could be interpreted as resulting from an altered use of the perception of elapsed time during the delay period induced by NMDA receptors antagonism. ### Final_Prediction: yes

### Question: Could the Breast Prognostic Biomarker Status Change During Disease Progression? ### Context: Prognostic biomarkers in breast cancer are routinely investigated in the primary tumors to guide further management. However, it is proposed that the expression may change during the disease progression, and may result in a different immune profile in the metastatic nodes. This work aimed to investigate the expression of breast prognostic biomarkers in primary tumors and in its axillary nodal metastasis, to estimate the possible discordant expression.60 paired primary and axillary nodal metastasis samples were collected from patients with primary breast cancer with positive nodal deposits, diagnosed at the Maadi Military Hospital, Cairo, Egypt, during the year 2013. ER, PR and HER2 expression was assessed by immunohistochemistry in all samples48.3% of the included cases showed concordant results for both ER and PR receptors between the primary tumor and its nodal metastasis while 51.7% showed discordant results and the discordance level was statistically significant. On the other hand, 70% of the cases showed concordant Her2 results between the primary tumors and the nodal deposits, 30% showed discordant results and the difference was significant. ### Long_Answer: The study indicated that the discordance in ER and PR receptor expression between the primary breast tumor and their nodal metastasis may be significant. The possible switch in the biomarker status during the disease progression is worth noting and may change the patient therapeutic planning. So, whether the treatment selection should be based on biomarkers in the lymph node is a topic for further studies and future clinical trials. ### Final_Prediction: nan

### Question: Does widespread cortical thinning characterize patients with MS with mild cognitive impairment? ### Context: Although cognitive dysfunction affects a relevant portion of patients with multiple sclerosis (MS), its pathologic substrate has not been clarified and it does not seem entirely explained by white matter changes.A total of 100 consecutive patients with relapsing remitting MS (RRMS) and 42 normal controls (NC) were enrolled in the study. Cognitive performance was assessed by Rao's Brief Repeatable Battery of Neuropsychological Tests (BRB). Regional cortical thickness (CTh) was evaluated by Freesurfer.Thirty-one patients with RRMS failed 1 or 2 tests of BRB and were considered to have a mild cognitive impairment (mCI-RRMS), while 8 patients failed at least 3 tests and were classified as markedly impaired (sCI-RRMS). The mean CTh of mCI-RRMS and sCI-RRMS group was significantly lower than in NC (p < 0.001) and cognitively normal patients with RRMS (CN-RRMS) (p < 0.001). The regional analysis revealed significant cortical thinning in frontal and temporal regions (frontotemporal thinning) of CN-RRMS compared to NC, while a widespread pattern of cortical thinning was observed in mCI-RRMS and in sCI-RRMS compared to both CN-RRMS and NC. A correlation was observed between cognitive score (CS) and the mean CTh (r = -0.69, p < 0.001) and between CS and CTh of almost all the cortical areas analyzed (r value between -0.20 and -0.65, p < 0.01). A correlation was found between T2-WM-LV and mean CTh (r = -0.31, p = 0.004) or CS (r = 0.21, p = 0.031). The multivariate analysis confirmed a widespread cortical thinning as the best predictor of cognitive impairment. ### Long_Answer: A widespread pattern of cortical thinning characterizes patients with cognitive dysfunction, suggesting such dysfunction as expression of a more aggressive and widespread cortical pathology. ### Final_Prediction: yes

### Question: Does [ Designing a surgical device for harvesting autologous fascia lata graft as a minimal invasive procedure ]? ### Context: Fascia lata is used in different shapes and sizes as a graft material in surgical procedures. The conventional method of harvesting a fascia lata graft is through a long skin incision on the lateral aspect of the thigh. Minimal invasive procedures have been established to reduce the disadvantages of an extensive surgical approach for obtaining the autotransplant. However, they do not facilitate to suture the remaining fascia after harvesting the transplant and therefore bear the risk of a symptomatic herniation of the muscle belly. The aim of this study was to design a surgical device to harvest a fascia lata graft and close the resulting fascia defect as a minimal invasive procedure.The prototype was tested in 11 human cadaver specimens. It was introduced subcutanously via two small skin incisions. The device contained a special fixation- and working mechanism which enabled the fascial closure using a continuous suture. After the harvest procedure, both the transplant and the sutured fascia lata were examined.The experiments demonstrated the suitability of this method for minimal invasive harvesting of fascia lata. The removed transplants complied in all experiments with the expected dimensions. The continuous suture of the femoral fascia ran with accurate gaps between the sutures and constant tension without dehiscence. Neither the transplant nor the tissue in the region of harvest have shown unduly macroscopic damage due to the use of the device. ### Long_Answer: The designed prototype can be used for harvesting a fascia lata graft and repairing the resulting defect minimal invasively. Clinical implementation seems possible. However, improvements could be made mainly concerning the handling of the device. ### Final_Prediction: yes

### Question: Does reduced cystatin B activity correlate with enhanced cathepsin activity in progressive myoclonus epilepsy? ### Context: Loss-of-function mutations in the gene encoding cystatin B (CSTB) underlie an inherited neurodegenerative disorder, progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1). CSTB is an inhibitor of several papain-family cysteine proteases, the lysosomal cathepsins. Its physiological function and the molecular pathways leading to the clinical EPM1 phenotype are unknown.To elucidate the role of CSTB and different cathepsins in pathogenesis of EPM1.We determined the total papain inhibitory (cystatin) and papain-like (cathepsin) activity as well as specific activities of cathepsins B, H, L and S in lymphoblastoid cells of EPM1 patients, carriers and controls.In EPM1 patients, who express reduced levels of CSTB mRNA, the papain inhibitory activity was significantly decreased or absent. This reduction was correlated with significant increase in general cathepsin activity. The increase in cathepsin B, L and S activities was highly significant, whereas the increase in cathepsin H activity was not. ### Long_Answer: This is the first demonstration of cysteine protease activity being regulated by CSTB activity in a biological context. The effects of decreased CSTB activity in EPM1 pathogenesis may, at least in part, be mediated by cathepsins through increased activity of cathepsins S and L. ### Final_Prediction: yes

### Question: Is renal cell carcinoma in adults 40 years old or less : young age an independent prognostic factor for cancer-specific survival? ### Context: Renal cell carcinoma (RCC) is uncommon in young adults. Based on the few studies published to date, it is difficult to determine whether this tumour has a particular progression pattern. This retrospective, multicentre study analysed RCC in young patients, defined as </=40 yr old, compared to RCC in older patients.Between 1988 and 2000, 1233 patients, 93 under 40 yr old and 1140 older (mean ages, 34.2 and 61.9 years, respectively) underwent surgery for RCC in four teaching hospitals. Clinical and biologic parameters at diagnosis were compared and subjected to univariate and multivariate analyses to study survival. Mean follow-up was 4.5 yr for young and 4.1 yr for older patients.When comparing younger to older patients, respectively, they had a lower male-to-female ratio (1.2 vs. 2.5), lower stage (84.9% vs. 67.4% pT1-pT2N0M0; p=0.001), and fewer clear-cell carcinomas (73.1% vs. 82%), but more papillary carcinomas (20.4% vs. 11.4%; p=0.01) and better 5-yr cancer-specific survival rates (90.8% vs. 78.3%; p=0.005). Independent prognostic factors for survival, in the order of decreasing impact, were tumor stage (p<0.0001), Fuhrman nuclear grade (p<0.0001), and age </=40 yr at diagnosis (risk ratio 0.4, p<0.047). Young patients tended to have a better 5-yr progression-free survival (80.5% vs. 70.7%; p=0.05). ### Long_Answer: RCC in young adults was more often localised at diagnosis and had a better prognosis than the disease in older subjects. Age under 40 yr old was an independent prognostic factor for survival. ### Final_Prediction: yes

### Question: Is cD8 membrane expression down-regulated by transforming growth factor ( TGF ) -beta 1 , TGF-beta 2 , and prostaglandin E2? ### Context: CD8 T-cells are present at a lower frequency in human decidua than in peripheral blood. Because transforming growth factor (TGF)-beta 2 down-regulates CD4 membrane expression, its contribution, as well as the contribution of TGF-beta 1 and prostaglandin (PG) E2, to the modulation CD8 expression was studied using human peripheral blood lymphocytes (PBLs).PBLs were cultured with TGF-beta 1, TGF-beta 2, PGE 2, PGI 2, or day-12 rabbit blastocoelic fluid (BF) that was or was not depleted of TGF-beta 2 and/or PGE 2. Quantum Simply Cellular Microbeads were then used to evaluate CD8 membrane expression levels.This study is the first demonstration that treatment of PBLs with TGF-beta 1, TGF-beta 2, and PGE 2 leads to a dose-dependent decrease in CD8 expression. A significant inhibition was observed at 2.5 mg/mL for TGF-beta 2, 5 ng/mL for TGF-beta 1, and 10 ng/mL for PGE 2. In contrast, PGI 2 had no effect. Treatment of PBLs with BF day-12 decreased CD8 expression. This effect, however, was not observed when BF was depleted of TGF-beta 2 and/or PGE 2. ### Long_Answer: Our results suggest that TGF-beta s and PGE 2 are important modulators of CD8 membrane expression in human lymphocytes. Because TGF-beta 1, TGF-beta 2, and PGE 2 are produced by the conceptus and by uterine cells and because the effect is observed after only 3 days of treatment, the present data suggest that these substances can locally modulate the phenotype of lymphocytes at the fetomaternal interface. Such modulation may explain, at least partly, the changes observed in the population of decidual lymphocytes during pregnancy. ### Final_Prediction: yes

### Question: Is dTP with or after measles vaccination associated with increased in-hospital mortality in Guinea-Bissau? ### Context: The sequence of routine immunisations may be important for childhood mortality. Three doses of diphtheria-tetanus-pertussis vaccine (DTP) should be given at 6, 10, and 14 weeks and measles vaccine (MV) at 9 months of age. The sequence is not always respected. We examined in-hospital mortality of children having received DTP with or after measles vaccine.The only paediatric ward in Bissau, Guinea-Bissau.Children hospitalised during two periods in 1990-1996 and 2001-2002 who had received MV prior to hospitalisation.The all-cause case fatality at the hospital for children aged 6-17 months.The case fatality was increased for children who had received DTP with or after measles vaccine compared with children who had received measles vaccine as the most recent vaccine, the ratio being 2.53 (1.37-4.67) and 1.77 (0.92-3.41) in the two periods, respectively. The combined estimate was 2.10 (1.34-3.28). These results were not explained by differences in nutritional status, number of doses of DTP or discharge policy. ### Long_Answer: Administration of DTP with, or after MV, may reduce the beneficial effect of MV. ### Final_Prediction: yes

### Question: Does wNT5A-NFAT signaling mediate resistance to apoptosis in pancreatic cancer? ### Context: WNT5A belongs to the Wnt family of secreted signaling molecules. Using transcriptional profiling, we previously identified WNT5A as target of the antiapoptotic transcription factor CUX1 and demonstrated high expression levels in pancreatic cancer. However, the impact of WNT5A on drug resistance and the signaling pathways employed by WNT5A remain to be elucidated.This project aims to decipher the impact of WNT5A on resistance to apoptosis and the signaling pathways employed by WNT5A in pancreatic cancer.The impact of WNT5A and its downstream effectors on tumor growth and drug resistance was studied in vitro and in xenograft models in vivo. Tissue microarrays of pancreatic cancer specimens were employed for immunohistochemical studies.Knockdown of WNT5A results in a significant increase in drug-induced apoptosis. In contrast, overexpression of WNT5A or addition of recombinant WNT5A mediates resistance to apoptosis in vitro. In our attempt to identify downstream effectors of WNT5A, we identified the transcription factor nuclear factor of activated T cells c2 (NFATc2) as transcriptional target of WNT5A signaling. NFATc2 confers a strong antiapoptotic phenotype mediating at least in part the effects of WNT5A on drug resistance and tumor cell survival. In vivo, WNT5A expression leads to resistance to gemcitabine-induced apoptosis in a xenograft model, which is paralleled by up-regulation of NFATc2. Both WNT5A and NFATc2 proteins are highly expressed in human pancreatic cancer tissues and their expression levels correlated significantly. ### Long_Answer: We identified the WNT5A-NFATc2 axis as important mediator of drug resistance in pancreatic cancer. ### Final_Prediction: yes

### Question: Does donor-recipient gender mismatch affect early graft loss after kidney transplantation? ### Context: We sought to determine the risk factors influencing the occurrence of early graft loss among kidney transplant recipients.One hundred forty-six potential donors and 230 kidney recipients were included in the study. Prior to organ procurement we collected demographic data as well as hemodynamic data of mean arterial pressure, central venous pressure, pulmonary capillary wedge pressure, systemic vascular resistance index acquired by means of a thermodilution method. The recipient data included age, gender, prior hemodialysis period, panel-reactive antibodies, cold ischemia time, renal insufficiency cause, and donor-recipient gender mismatch. We assessed the influence of the data on graft loss at 30 days after renal transplantation. To confirm the relationships, we performed statistical analyses using chi-square, Fisher exact, and V. Cramer tests.There were no significant relationships between the analyzed parameters and early graft loss in the study group except for gender mismatch. The 71 female recipients of male kidneys showed the lowest graft survival: donor/recipient male/female 89%; donor/recipient female/male 97%; no mismatch 97% (P=.01). ### Long_Answer: Female recipients of male kidneys may experience a greater risk of early graft loss compared with all other gender combinations. ### Final_Prediction: yes

### Question: Does prevalence and cardiovascular disease correlate of low cardiorespiratory fitness in adolescents and adults? ### Context: Population surveys indicate that physical activity levels are low in the United States. One consequence of inactivity, low cardiorespiratory fitness, is an established risk factor for cardiovascular disease (CVD) morbidity and mortality, but the prevalence of cardiorespiratory fitness has not been quantified in representative US population samples.To describe the prevalence of low fitness in the US population aged 12 through 49 years and to relate low fitness to CVD risk factors in this population.Inception cohort study using data from the cross-sectional nationally representative National Health and Nutrition Examination Survey 1999-2002. Participants were adolescents (aged 12-19 years; n = 3110) and adults (aged 20-49 years; n = 2205) free from previously diagnosed CVD who underwent submaximal graded exercise treadmill testing to achieve at least 75% to 90% of their age-predicted maximum heart rate. Maximal oxygen consumption (VO2max) was estimated by measuring the heart rate response to reference levels of submaximal work.Low fitness defined using percentile cut points of estimated VO2max from existing external referent populations; anthropometric and other CVD risk factors measured according to standard methods.Low fitness was identified in 33.6% of adolescents (approximately 7.5 million US adolescents) and 13.9% of adults (approximately 8.5 million US adults); the prevalence was similar in adolescent females (34.4%) and males (32.9%) (P = .40) but was higher in adult females (16.2%) than in males (11.8%) (P = .03). Non-Hispanic blacks and Mexican Americans were less fit than non-Hispanic whites. In all age-sex groups, body mass index and waist circumference were inversely associated with fitness; age- and race-adjusted odds ratios of overweight or obesity (body mass index > or =25) ranged from 2.1 to 3.7 (P<.01 for all), comparing persons with low fitness with those with moderate or high fitness. Total cholesterol levels and systolic blood pressure were higher and levels of high-density lipoprotein cholesterol were lower among participants with low vs high fitness. ### Long_Answer: Low fitness in adolescents and adults is common in the US population and is associated with an increased prevalence of CVD risk factors. ### Final_Prediction: yes

### Question: Are renovascular effects of sympathetic cotransmitters ATP and NPY age-dependent in spontaneously hypertensive rats? ### Context: Hypertension is characterized by sympathetic overactivity. Neuropeptide Y (NPY) and ATP are cotransmitters of norepinephrine (NE) and regulate renovascular resistance. The present study analyzes sympathetic nonadrenergic neurotransmission in hypertensive (SH-SP) and normotensive (WKY) rats. In addition, adult and young hypertensive rats were compared to investigate the role of aging on sympathetic nonadrenergic cotransmission in hypertensive disease.Pressor responses to renal nerve stimulations (RNS) and drugs were measured on isolated perfused kidneys of young (8-10 weeks) and adult (18-24 weeks) WKY, and SH-SP rats.RNS evoked contractions at 1 Hz were resistant to blockade by the alpha-adrenoceptor antagonist phentolamine (1 microM) but abolished by the P2 receptor blocker suramin (100 microM). Compared to adult WKY, RNS-induced pressor responses were unchanged in adult SH-SP and young WKY, but significantly greater in young SH-SP rats. The NPY-Y1 receptor antagonist BIBP3226 (1 microM) reduced phentolamine-resistant pressor responses in adult and young WKY, young SH-SP, but not in adult SH-SP rats. In contrast to WKY and young SH-SP rats, exogenously perfused NPY (0.1 microM) was unable to potentiate RNS-induced, phentolamine-resistant pressor responses in adult SH-SP rats. NE and the stable ATP analogue alpha,beta-mATP increased the perfusion pressor response more potently in adult SH-SP than in WKY rats. ### Long_Answer: Neuronally released NPY plays a major role in potentiating RNS-induced nonadrenergic pressor responses in kidneys of WKY and young SH-SP rats. In adult SH-SP rats NPY fails to enhance these responses. In this hypertensive model ageing seems to be associated with a loss of a modulatory role of renal NPY Y1 receptors. Since pressor responses to NE and ATP are higher in SH-SP animals, functional NPY-Y1 receptor downregulation might be an adaptive mechanism. ### Final_Prediction: yes