Long term cimetidine therapy for the prevention of recurring peptic ulcer: a multicenter study.
The aim of this study was to gain experience regarding the efficacy and safety of cimetidine 400 mg nightly for the long-term maintenance treatment of peptic ulcers three years. The trial was carried out in 44 centres in 12 countries. 1988 patients with endoscopically-proven peptic ulceration initially underwent an acute treatment over 6-12 weeks (open study) with 1000 mg cimetidine-the dosage could be increased to 1600 mg daily if necessary. After 6 weeks, 81% of patients had healed ulcers and the cumulative healing rate after 12 weeks rose to 95%. The statistical analysis of the subsequent long-term maintenance treatment was based on data from 1726 patients (82% with healed pyloric or duodenal ulcers; 16% with ulcus ventriculi and 2% with ulcers subsequent to stomach surgery) who received 400 mg cimetidine nightly over 3 years. Based on life-table analysis, patients who received 400 mg cimetidine nightly during the entire length of the study showed relapse rates of 25%, 36% and 45% after 1, 2 and 3 years respectively. The effect of various prognostic factors on the ulcer relapse rate was examined. Patients who smoked or who were younger than 50 years suffered significantly more relapses and patients with duodenal ulcers also relapsed more frequently. After the open-design long-term maintenance treatment study had been continued over 2 years, one-fifth of the patients who had remained relapse-free were randomly assigned to placebo for one year. In the 3rd year, 36% in the placebo group and 16% of the patients who had continued with cimetidine had relapsed. This difference is statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)


Impella assisted transradial coronary intervention in patients with acute coronary syndromes and cardiogenic shock: case series.
Operators may feel apprehension when considering the transradial approach in patients with cardiogenic shock due to concerns of the need for femoral access for mechanical support. There is however potential benefit of transradial approach in this setting by reducing bleeding complications in patients on potent anticoagulant and antiplatelet agents. We report three cases of patients with cardiogenic shock with successful transradial intervention (TRI) whilst using unilateral femoral access for Impella (ABIOMED, Danvers, MA) mechanical support. In two cases, the need for mechanical support was not clear at the beginning of the procedure, and in the third there was a clear need to combine femoral and radial access due to pre-existing anatomic issues. Two patients required transfusion of red blood cells but otherwise there were no vascular access complications.


Control of synthesis of wall teichoic acid during balanced growth of Bacillus subtilis W23.
Enzymes involved in the synthesis of teichoic acid and its linkage to the wall in Bacillus subtilis W23 were measured in chemostat cultures growing at equilibrium at a dilution rate of 0.2 h-1 in different concentrations of inorganic phosphate. All the enzymes, except teichoic acid glucosyl transferase, which was insensitive to changes in phosphate concentration, were almost undetectable at 0.5 mM-phosphate. At higher phosphate concentrations the changes in activity of the enzymes of linkage unit synthesis were sufficient to account for the changes in the rate of incorporation of teichoic acid into the wall in vivo. Between 3.5 and 4.5 mM-phosphate the amount of teichoic acid synthesized in vivo increased, but no increase in the ability of toluenized bacteria to synthesize teichoic acid could be detected. Allosteric regulation might therefore be important at high phosphate concentrations. Bacteria maintained a constant ATP content and a constant adenylate energy charge during chemostat growth at all phosphate concentrations.


Analysis of preformed xenoreactive antibodies in the discordant guinea pig to rat model using a guinea pig fibroblast-like cell line.
In the discordant guinea pig (gp) to rat model of xenotransplantation, circulating xenoreactive natural antibodies (XNA) recognizing gp antigens are usually determined by an ELISA using membrane extracts of gp platelets. We analysed the lung-derived, fibroblast-like cell line JH 4 to detect XNA by ELISA or immunoblot, which was compared to primary gp cells, i.e. platelets, liver- and spleen cells. All membrane extracts proved to be useful to detect rat XNA directed against gp antigens by ELISA. In general, IgM responses of Lewis or C6 deficient PVG rats (PVG/C6-) were higher as compared to IgG responses. However, we observed great inter-individual variabilities. The strongest IgM response of Lewis rat sera was observed when the JH 4 cell line or gp liver cells were used as antigen. JH 4 cells also showed the strongest xenoreactivity with sera from PVG/C6- rats. These data demonstrate that JH 4 cells prove useful as antigen source for XNA ELISA. In immunoblot, individual sera of the two different rat strains showed the same antigen patterns using a gp membrane extract of one particular cell type. However, the different gp cell types showed a distinct pattern of antigen expression. Whereas the JH 4 cells, platelets and spleen cells express xenoreactive proteins of the same size, a unique pattern of proteins was detected in liver cells.


The Molecular Tweezer CLR01 Stabilizes a Disordered Protein-Protein Interface.
Protein regions that are involved in protein-protein interactions (PPIs) very often display a high degree of intrinsic disorder, which is reduced during the recognition process. A prime example is binding of the rigid 14-3-3 adapter proteins to their numerous partner proteins, whose recognition motifs undergo an extensive disorder-to-order transition. In this context, it is highly desirable to control this entropy-costly process using tailored stabilizing agents. This study reveals how the molecular tweezer CLR01 tunes the 14-3-3/Cdc25CpS216 protein-protein interaction. Protein crystallography, biophysical affinity determination and biomolecular simulations unanimously deliver a remarkable finding: a supramolecular "Janus" ligand can bind simultaneously to a flexible peptidic PPI recognition motif and to a well-structured adapter protein. This binding fills a gap in the protein-protein interface, "freezes" one of the conformational states of the intrinsically disordered Cdc25C protein partner and enhances the apparent affinity of the interaction. This is the first structural and functional proof of a supramolecular ligand targeting a PPI interface and stabilizing the binding of an intrinsically disordered recognition motif to a rigid partner protein.


ETS transcription factor ELF3 (ESE-1) is a cell cycle regulator in benign and malignant prostate.
This study aimed to elucidate the role of ELF3, an ETS family member in normal prostate growth and prostate cancer. Silencing ELF3 in both benign prostate (BPH-1) and prostate cancer (PC3) cell lines resulted in decreased colony-forming ability, inhibition of cell migration and reduced cell viability due to cell cycle arrest, establishing ELF3 as a cell cycle regulator. Increased ELF3 expression in more advanced prostate tumours was shown by immunostaining of tissue microarrays and from analysis of gene expression and genetic alteration studies. This study indicates that ELF3 functions not only as a part of normal prostate epithelial growth but also as a potential oncogene in advanced prostate cancers.


How to use… serum creatinine, cystatin C and GFR.
Glomerular filtration rate (GFR) is the best overall measure of kidney function. The GFR is relatively low at birth but increases through infancy and early childhood to reach adult levels of approximately 120 mL/min/1.73 m2 by age 2. While GFR can be measured most accurately by the urinary clearance of an exogenous ideal filtration marker such as inulin, it is more clinically useful to estimate GFR using a single serum measurement of an endogenous biomarker such as creatinine or cystatin C. When in steady state, there is an inverse relationship between creatinine/cystatin C and GFR, allowing GFR to be estimated from either using simple equations. Because of the non-linear relationship between creatinine/cystatin C and GFR, relatively small initial increases in these markers represent significant decreases in GFR. While cystatin C is produced by all nucleated cells, creatinine is a waste product of muscle metabolism and is therefore influenced by diet and muscle mass/body habitus. Decreased GFR is used to diagnose and stage chronic kidney disease (CKD) using the Kidney Disease: Improving Global Outcomes system. A diagnosis of CKD requires GFR <60 mL/min/1.73 m2 for more than 3 months; higher GFR also represents CKD if evidence of kidney damage (such as albuminuria or abnormal imaging) is present. Changes in serum creatinine and urine output are used to diagnose acute kidney injury. It is possible to calculate a kinetic GFR when the creatinine is changing rapidly, though more complex calculations are required.


Development and Usability Evaluation of Web-Based Telerehabilitation Platform for Patients After Myocardial Infarction.
Cardiac rehabilitation (CR) is a multidisciplinary intervention that improves quality of life and reduces the risk of recurrent heart attack. Unlike all known benefits for CR, the patient participation in CR is low. Telerehabilitation has the potential to improve lifestyle and helps patients having long-term compliance with clinician advice. The objective of this study was the development of a web-based cardiac telerehabilitation platform to engage the post-myocardial infarction (MI) patients in self-management of disease. Development process of creating and evaluating a telerehabilitation platform included four phases: (1) need assessment, (2) design the prototype, (3) implement the cardiac telerehabilitation platform, (4) usability evaluation. Cardiac telerehabilitation platform consists of an Android-based application for patients and web-based dashboard for rehabilitation mentors. The modules of the application are daily self-assessment, weekly self-assessment, educational content, stress and sleep improvement skills, medication reminder, online chat, prescribed diet, prescribed physical activity and rehabilitation records. The self-assessment modules allow users to enter the data such as physical activity, diet, blood pressure, heart rate, and body weight. The patient data entries are interpreted in the system knowledge base and colored symbol feedbacks display for patients and mentors. In the dashboard, the mentors review the patient data entries and set the rehabilitation plan for next week. In a beta test of usability evaluation, the mean of SUS score for patients was 75.16, for clinicians was 73.33 and for medical informatics specialist was 72.33. These results showed that the usability of our system was at an acceptable level. The cardiac telerehabilitation platform is a convenient tool for post-MI patients who cannot attend at outpatient cardiac rehabilitation centers for any reason.


[Cytotoxic effect of lymphotoxin on a culture of macrophages].
Results of study of the cytotoxic effect of the lymphotoxin on the monolayer culture of the peritoneal macrophages used as target cells are presented. The lymphotoxin was obtained following an 18-hour incubation of the lymph node cells of guinea pigs with delayed hypersensitivity to tuberculoproteins, in the presence of the specific antigen (tuberculin). It was shown that only on the 5th--6th day of cultivation did the supernatants destroy more than half of the macrophages in 70% of the experiments. The death of the macrophages during the later periods of cultivation, in comparing with the L-cells, suggests a different resistance of these target-cells to the cytotoxic effect of the lymphotoxin.


Rapid effects of a protective O-polysaccharide-specific monoclonal IgA on Vibrio cholerae agglutination, motility, and surface morphology.
2D6 is a dimeric monoclonal immunoglobulin A (IgA) specific for the nonreducing terminal residue of Ogawa O-polysaccharide (OPS) of Vibrio cholerae. It was previously demonstrated that 2D6 IgA is sufficient to passively protect suckling mice from oral challenge with virulent V. cholerae O395. In this study, we sought to define the mechanism by which 2D6 IgA antibody protects the intestinal epithelium from V. cholerae infection. In a mouse ligated-ileal-loop assay, 2D6 IgA promoted V. cholerae agglutination in the intestinal lumen and limited the ability of the bacteria to associate with the epithelium, particularly within the crypt regions. In vitro fluorescence digital video microscopy analysis of antibody-treated V. cholerae in liquid medium revealed that 2D6 IgA not only induced the rapid (5- to 10-min) onset of agglutination but was an equally potent inhibitor of bacterial motility. Scanning electron microscopy showed that 2D6 IgA promoted flagellum-flagellum cross-linking, as well as flagellar entanglement with bacterial bodies, suggesting that motility arrest may be a consequence of flagellar tethering. However, monovalent 2D6 Fab fragments also inhibited V. cholerae motility, demonstrating that antibody-mediated agglutination and motility arrest are separate phenomena. While 2D6 IgA is neither bactericidal nor bacteriostatic, exposure of V. cholerae to 2D6 IgA (or Fab fragments) resulted in a 5-fold increase in surface-associated blebs, as well an onset of a wrinkled surface morphotype. We propose that the protective immunity conferred by 2D6 IgA is the result of multifactorial effects on V. cholerae, including agglutination, motility arrest, and possibly outer membrane stress.


Validation of the Tiba Medical Ambulo 2400 ambulatory blood pressure monitor to the ISO Standard and BHS protocol.
We evaluated the Tiba Medical Ambulo 2400 ambulatory blood pressure monitor accuracy by both the International Standards Organization (ISO) Standard and the British Hypertension Society (BHS) protocol. We tested children, adolescents, and adults. The requirements for both ISO and BHS were completed for 85 individuals each. The Ambulo 2400 passed both ISO and BHS criteria. For ISO method 1, the mean±SD for the difference between device and manual systolic blood pressure (SBP) was -1.8±6.5 mmHg; for diastolic blood pressure (DBP) the values were 0.7±7.3 mmHg. For the method 2 analyses, the differences were -1.8±4.7 and 0.7±6.3 mmHg for SBP and DBP, respectively. The percentage of differences within 5, 10, and 15 mmHg were 60, 86, and 98% for SBP, and 60, 85, and 96% for DBP. The Ambulo 2400 passed all phases of the ISO testing and achieved an A grade for both SBP and DBP per BHS analyses. There was no decrease in accuracy in either high or low BP ranges. The Ambulo 2400 integrates activity monitoring for assigning actual awake and asleep times. There are software features that are particularly beneficial to monitor children and adolescents.


Healthcare utilization for pain in children and adolescents: a prospective study of laboratory and non-laboratory predictors of care-seeking.
Few studies have focused on identifying predictors of medical consultation for pain in healthy children and adolescents. This investigation sought to identify parent and child laboratory and non-laboratory predictors of pediatric healthcare utilization for pain problems. Participants were 210 healthy children and adolescents (102 girls), aged 8-17 years who took part in a laboratory pain session. Three months after the laboratory session, participants were contacted by telephone to ascertain whether they had experienced pain and whether they had seen a healthcare professional for pain. Zero-order correlations among sociodemographic status, child laboratory pain responses, parent physical/mental health status and medical consultation for pain were conducted to identify relevant correlates of pediatric healthcare utilization; these correlates were subjected to multivariate analyses. Bivariate analyses indicated that higher anticipated pain and bother for the cold pressor task, as well as poorer parent physical health status, were associated with pediatric medical consultation for pain, but only among girls. Sequential logistic regression analyses controlling for child age indicated that only parent physical health status, not the laboratory indicators, significantly predicted healthcare consultation for pain among girls. No parent or child correlates of care-seeking for pain emerged for boys. The findings suggest that parents' perceived physical health plays a role in determining whether medical care is sought for pain complaints in healthy girls. These results suggest that interventions to assist parents in managing their own physical health problems could lead to reductions in medical consultation for girls' pain.


Myeloid SENP3 deficiency protects mice from diet and age-induced obesity via regulation of YAP1 SUMOylation.
Obesity is characterized by chronic low-grade inflammation, which is driven by macrophage infiltration in adipose tissue and leads to elevated cytokines such as interleukin-1β (IL-1β) in the circulation and tissues. Previous studies demonstrate that SENP3, a redox-sensitive SUMO2/3-specific protease, is strongly implicated in the development and progression of cancer and cardiovascular diseases. However, the role of SENP3 in obesity-associated inflammation remains largely unknown. To better understand the effects of SENP3 on adipose tissue macrophage (ATM) activation and function within the context of obesity, we generated mice with myeloid-specific deletion of SENP3 (Senp3flox/flox;Lyz2-Cre mice). We found that the expression of SENP3 is dramatically increased in ATMs during high-fat diet (HFD)-induced obesity in mice. Senp3flox/flox;Lyz2-Cre mice show lower body weight gain and reduced adiposity and adipocyte size after challenged with HFD and during aging. Myeloid-specific SENP3 deletion attenuates macrophage infiltration in adipose tissue and reduces serum levels of inflammatory factors during diet and age-induced obesity. Furthermore, we found that SENP3 knockout markedly inhibits cytokine release from macrophage after lipopolysaccharide and palmitic acid treatment in vitro. Mechanistically, in cultured peritoneal macrophages, SENP3 protein level is enhanced by IL-1β, in parallel with the upregulation of Yes-associated protein 1 (YAP1). Moreover, we demonstrated that SENP3 modulates de-SUMO modification of YAP1 and SENP3 deletion abolishes the upregulation of YAP1 induced by IL-1β. Most importantly, SENP3 deficiency reduces YAP1 protein level in adipose tissue during obesity. Our results highlight the important role of SENP3 in ATM inflammation and diet and age-induced obesity.


In vitro and in vivo induction of heme oxygenase 1 in mouse macrophages following melanocortin receptor activation.
RAW264.7 cell incubation with adrenocorticotrophin (ACTH) led to a time-dependent (4-24 h) and concentration-related (1-100 ng/ml) induction of heme oxygenase (HO)-1, and this was a specific effect, because the pattern of expression of other cellular proteins (HO-2, heat shock proteins 70 and 90) was not modified by ACTH. Combined RT-PCR and Western blot analyses revealed expression of the melanocortin receptor (MC-R) types 1 and 3, but not 4, in these cells. However, use of more selective agonists (including melanotan (MTII)) indicated a predominant role for MC3-R in the induction of HO-1 expression and activity. Relevantly, ACTH and MTII incubation with primary peritoneal macrophages (Mphi) also induced HO-1 expression. The potential link between MC3-R dependent cAMP formation and HO-1 induction was ascertained by the following: 1) ACTH and MTII produced a concentration-dependent accumulation of cAMP in RAW264.7 cells, and 2) whereas a selective inhibitor of cAMP-dependent protein kinase A abrogated ACTH- and MTII-induced HO-1 expression, a soluble cAMP derivative promoted HO-1 induction both in RAW264.7 cells and primary Mphi. HO-1 induction in peritoneal Mphi was also detected following in vivo administration of MTII, and appeared to be functionally related to the antimigratory effect of this melanocortin, as determined with a specific inhibitor (zinc protoporphyrin IX). In conclusion, this study highlights a biochemical link between MC-R activation and HO-1 induction in the Mphi, and proposes that this may be of functional relevance in determining MC-R-dependent control of the host inflammatory response.


Intestinal calcium transport: the role of sodium.
The role of sodium in intestinal calcium transport was investigated in everted rat intestine. Ethacrynic acid, but not ouabain, inhibited calcium transport. However, ouabain did inhibit net water transport and, therefore, sodium transport, establishing the dissociation of the two transport processes. In addition to a magnesium-dependent adenosine triphosphatase (activated by sodium and potassium), a phosphatase dependent on sodium and calcium was localized to the lateral and basal membrane fractions of the mucosal cell. Activity of the latter phosphatase, similar to calcium transport in intact tissue, was inhibited by ethacrynic acid and not by ouabain. Sodium, therefore, may participate in the calcium transport process by activating an enzyme complex, dependent on adenosine triphosphate, that mediates calcium transport.


Gliosarcoma with prominent smooth muscle component (gliomyosarcoma): a report of 10 cases.
Gliosarcoma (GS) is an uncommon malignant tumor of the brain, consisting of malignant glial, usually a glioblastoma (GB), as well as sarcomatous component; the latter is usually in the form of fibrosarcoma. We report a series of 10 GSs with prominent smooth muscle component, which is a rare occurrence. Out of a series of 225 cases of GB admitted in our hospital, 10 were diagnosed as GS with prominent smooth muscle component, gliomyosarcoma (GMS). This is an observational study based on the experience with 225 cases of GB, encountered between 1995 and 2008, in our hospital. The tumors showing prominent spindle cell component were stained with reticulin and 20 with strongly positive reticulin stain were diagnosed as GS. They were further studied by immunohistochemical staining for glial fibrillary acidic protein (GFAP), smooth muscle actin (SMA), desmin and factor VIII antigen. Out of 225 cases of GB, 20 were diagnosed as GS. Ten of these showed prominent smooth muscle component and were diagnosed as GMS. They revealed varying degrees of SMA and factor VIII Ag positivity. In the sarcomatous component, SMA and factor VIII positive cells were seen close to the vessel walls as well as away from them. GMS containing prominent smooth muscle component may not be as rare as has been reported in the literature. Both GS and GMS appear to arise from the vessel wall at least in some cases, suggesting their possible vascular origin.


Improving menopausal symptoms through promoting physical activity: a pilot Web-based intervention study among Asian Americans.
Based on previous studies, a Web-based physical activity promotion program with educational modules on menopausal symptoms and physical activity has been developed for Asian American midlife women to reduce their menopausal symptoms through increasing their physical activity. The purpose of this pilot randomized intervention study was to determine the efficacy of the Web-based program in improving menopausal symptom experience of Asian American midlife women. This was a randomized repeated measures pretest/posttest (pretest, post 1 month, and post 3 months) control group study among 29 Asian American midlife women. Multiple instruments were used, including the Midlife Women's Symptom Index and the Kaiser Physical Activity Survey. The data were analyzed using a mixed-model growth curve analysis. Over time, total severity scores decreased for the control group (-0.53, P < 0.10), whereas they did not exhibit a meaningful change for the intervention group. Both study groups experienced improvement in active living habits over time, but such an improvement was greater for the intervention group (β = 0.29, P < 0.001) than for the control group (β = 0.08, P < 0.10). The time × group interactions for total severity scores were not statistically significant anymore after controlling for physical activity (-0.34 for the control group, P = 0.10). The findings supported the feasibility of a 3-month Web-based intervention for menopausal symptom management among Asian American midlife women and the preliminary efficacy of the program in increasing their physical activity.


Can a participatory organizational intervention improve social capital and organizational readiness to change? Cluster randomized controlled trial at five Danish hospitals.
This study investigates the effect of a participatory organizational intervention on social capital and organizational readiness for change. Cluster randomized controlled trial. In 2016, 27 departments from five hospitals in Denmark were randomly allocated at the department level to 1 year of participatory intervention (14 clusters, 316 healthcare workers) or a control group (13 clusters, 309 healthcare workers). The participatory intervention consisted of 2 × 2 hr workshops, where managers, 2-5 healthcare workers from each department, and the hospital's health and safety staff, developed action plans for implementing solutions for improving the use of assistive devices at the department throughout the 1-year intervention period. Workplace social capital: (a) within teams (bonding); (b) between teams and nearest leaders (linking A); and (c) between teams and distant leaders (linking B) and organizational readiness for change were measured using questionnaires at baseline, 6, and 12 months. No group-by-time interaction occurred for any of the outcome measures. However, explorative post hoc analysis showed within-group improvements in bonding and linking B social capital and organizational readiness for change following the participatory intervention. Participatory organizational interventions may improve social capital within teams and between teams and distant leaders and organizational readiness for change. Implementing participatory interventions at the workplace may be a cost-effective strategy as they provide additional benefits, e.g., increased social capital and improved organizational readiness for change, that exceed the primary outcome of the intervention. ClinicalTrials.gov (NCT02708550) March 2016.


Visual simulations, artificial animals and virtual ecosystems.
This review is about a field that does not traditionally belong to biological sciences. A branch of computer animation has its mission to create active self-powered objects living artificial lives in the theoretical biology zone. Selected work, of particular interest to biologists, is presented here. These works include animated simulations of legged locomotion, flexible-bodied animals swimming and crawling, artificial fish in virtual ecosystems, automated learning of swimming and the evolution of virtual creatures with respect to morphology, locomotion and behaviour. The corresponding animations are available for downloading via the Internet. I hope that watching these intriguing pieces of visual simulation will stimulate digitally oriented biologists to seize the interactive methods made possible by ever-increasing computing power.


Apparent low absorbers of cyclosporine microemulsion have higher requirements for tacrolimus in renal transplantation.
Bioavailability and exposure of cyclosporine microemulsion and tacrolimus in renal transplantation are governed by many complex factors. Failure to achieve therapeutic two-h post-dose (C(2)) levels despite adequate doses of cyclosporine ("low absorbers") may merit conversion to tacrolimus. We compared tacrolimus dose requirements in "low absorbers" (n = 15) with a random control group of de novo tacrolimus patients (n = 14). Low absorbers failed to reach target C(2) despite increasing dose from 10.1 to 16.2 mg/kg/d. At conversion the mean C(2) was 969 ng/mL (95% CI: 684-1255; target 1700 ng/mL). Low absorbers tended to be younger, heavier, and diabetic. Despite a similar initial tacrolimus dose (0.17-0.18 mg/kg/d), low absorbers required a much higher daily dose to achieve target; 0.25 vs. 0.16 mg/kg/d (p = 0.016). Furthermore, daily maintenance tacrolimus remained much higher in low absorbers at three wk (0.22 vs. 0.13 mg/kg/d, p = 0.012). Although not statistically significant, this group experienced an acute rejection rate of 33%, compared with 21% in the control group. Patients treated with cyclosporine as initial immunosuppression who fail to reach target C(2) levels in a timely fashion are at risk for impaired bioavailability of tacrolimus. Based on our data, a starting dose of 0.25 mg/kg/d in divided doses may be warranted for low absorbers converting to tacrolimus; however, we encourage larger studies with formal pharmacokinetic analysis in this population.


Measurement properties of the Disability Rating Index in patients undergoing hip replacement.
The aim of this study was to establish and validate the measurement properties of the Disability Rating Index (DRI) in a population of adults undergoing hip replacement. One hundred and twenty-six adults participating in a randomized controlled trial completed the Oxford Hip Score, Harris Hip Score, DRI and EuroQol Group-Five Dimensions (EQ-5D) questionnaires at four time points. The structural validity of the DRI was assessed using principal component analysis. Cronbach's α was used to determine the internal consistency and scale reliability was also assessed. Correlation between the DRI and the other functional and health-related quality of life scales was used to check criterion validity. DRI responsiveness was estimated and the interpretability of the scale was also assessed by checking for edge effects. Results of analyses showed that the DRI was internally consistent (Cronbach's α = 0.92), had good association with both function-specific and general health-related quality of life scores and was sensitive to change (smallest detectable change = 2.7). No evidence of edge effects was found. Furthermore, structural assessment of the DRI revealed two novel subscales representing simple tasks and difficult tasks. The DRI is structurally valid, responsive and concurs with functional assessment in adults undergoing hip replacement.


Seromucinous Hamartoma of the Sinonasal Cavity.
Benign tumors or malignant neoplasms must be evaluated in patients with unilateral nasal cavity mass lesions. The 3 most prevalent unilateral benign mass lesions in such individuals are nasal polyps (NPs) and inverted papillomas (IPs). Although rare, it should be kept in mind that sinonasal hamartomas can be occasionally diagnosed as well. Among sinonasal hamartomas, respiratory epithelial adenomatoid hamartoma is more prevalent, with seromucinous hamartoma (SMH) being the second most common. Unlike NPs, sinonasal hamartomas are benign tumors with growth potential, which means it should not be undertreated and warrants surgical removal for treatment. However, sinonasal hamartomas do not have local invasion or malignant transformation potential like IPs; hence, it is vital not to overtreat them. Therefore, understanding the histopathology of SMH and thereby establishing proper surgical planning prior to the surgery remains crucial in such cases. Here, we present a successfully treated case of SMH with a distinctive radiographic, gross, and pathological clinical image of SMH.


Applications of LC-MS in PET radioligand development and metabolic elucidation.
Positron emission tomography (PET) is a very sensitive molecular imaging technique that when employed with an appropriate radioligand has the ability to quantititate physiological processes in a non-invasive manner. Since the imaging technique detects all radioactive emissions in the field of view, the presence and biological activity of radiolabeled metabolites must be determined for each radioligand in order to validate the utility of the radiotracer for measuring the desired physiological process. Thus, the identification of metabolic profiles of radiolabeled compounds is an important aspect of design, development, and validation of new radiopharmaceuticals and their applications in drug development and molecular imaging. Metabolite identification for different chemical classes of radiopharmaceuticals allows rational design to minimize the formation and accumulation of metabolites in the target tissue, either through enhanced excretion or minimized metabolism. This review will discuss methods for identifying and quantitating metabolites during the pre-clinical development of radiopharmaceuticals with special emphasis on the application of LC/MS.


"Cheating under pressure: A self-protection model of workplace cheating behavior": Correction to Mitchel et al. (2017).
Reports an error in "Cheating Under Pressure: A Self-Protection Model of Workplace Cheating Behavior" by Marie S. Mitchell, Michael D. Baer, Maureen L. Ambrose, Robert Folger and Noel F. Palmer (Journal of Applied Psychology, Advanced Online Publication, Aug 14, 2017, np). In the article, the fit statistics in Study 3 were reported in error. The fit of the measurement model is: Χ²(362) = 563.66, p = .001; CFI = .94; SRMR = .05; RMSEA = .04. The fit of the SEM model is: Χ²(362) = 563.66, p = .001; CFI = .94; SRMR = .05; RMSEA = .04. (The following abstract of the original article appeared in record 2017-34937-001.) Workplace cheating behavior is unethical behavior that seeks to create an unfair advantage and enhance benefits for the actor. Although cheating is clearly unwanted behavior within organizations, organizations may unknowingly increase cheating as a byproduct of their pursuit of high performance. We theorize that as organizations place a strong emphasis on high levels of performance, they may also enhance employees' self-interested motives and need for self-protection. We suggest that demands for high performance may elicit performance pressure-the subjective experience that employees must raise their performance efforts or face significant consequences. Employees' perception of the need to raise performance paired with the potential for negative consequences is threatening and heightens self-protection needs. Driven by self-protection, employees experience anger and heightened self-serving cognitions, which motivate cheating behavior. A multistudy approach was used to test our predictions. Study 1 developed and provided validity evidence for a measure of cheating behavior. Studies 2 and 3 tested our predictions in time-separated field studies. Results from Study 2 demonstrated that anger mediates the effects of performance pressure on cheating behavior. Study 3 replicated the Study 2 findings, and extended them to show that self-serving cognitions also mediate the effects of performance pressure on cheating behavior. Implications of our findings for theory and practice are provided. (PsycINFO Database Record


The rub family of ubiquitin-like proteins. Crystal structure of Arabidopsis rub1 and expression of multiple rubs in Arabidopsis.
Several proteins with significant identity to ubiquitin have been characterized recently. In contrast to ubiquitin's main role in targeting proteins for degradation, a described function of one family of ubiquitin-related proteins, the Rub family, is to serve as a stable post-translational modification of a complex involved in the G1-to-S cell cycle transition. Rub proteins have been found in animals, plants, and fungi and consist of 76 residues with 52-63% identity to ubiquitin. In this study three different RUB proteins within the plant Arabidopsis are identified; two differ by only 1 amino acid, while the third is only 77.6% identical to the other two. Genes encoding all three are expressed in multiple organs. In addition, we report the crystal structure of higher plant RUB1 at 1.7-A resolution to help elucidate the functional differences between Rub and ubiquitin. RUB1 contains a single globular domain with a flexible COOH-terminal extension. The overall RUB1 structure is very similar to ubiquitin. The majority of the amino acid differences between RUB1 and ubiquitin map to the surface. These changes alter the electrostatic surface potential in two regions and likely confer specificity between ubiquitin and RUB1 and their ubiquitin-activating enzyme (E1) or E1-like activating enzymes.


The impact of vaccines and vaccinations: Challenges and opportunities for modelers.
This review focuses on how infectious diseases and their prevention and control by development of vaccines and widespread vaccination has shaped evolution of human civilization and of the animals and plants that humans depend on for food, labor and companionship. After describing major infectious diseases and the current status for control by vaccination, the barriers to infection and the attributes of innate and acquired immunity contributing to control are discussed. The evolution in types of vaccines is presented in the context of developing technologies and in improving adjuvants to engender enhanced vaccine efficacy. The special concerns and needs in vaccine design and development are discussed in dealing with epidemics/pandemics with special emphasis on influenza and current global problems in vaccine delivery.


[CASC5</I> Gene Expression Changes Correlate with Targeted Mutations in Leukemia].
Dysfunction of genes that control mitosis and are responsible for the correct segregation of sister chromatids in anaphase is often accompanied by aneuploidy, which is frequently detected in leukemia. One of the components of the kinetochore complex, namely, the AF15q14/KNL1/CASC5 protein, is an important factor ensuring the correct binding of the pericentromeric region of chromosomes with the spindle microtubules. As shown recently, in some leukemias, the gene of this protein can be involved in the generation of the chromosomal translocation t(11;15)(q23;q14) or a variant of the chimeric MLL-AF15Q14 oncogene, which serves as a biomarker of poor prognosis. Despite the implication of mRNA of the CASC5 gene in oncogenesis of solid tumors, expression of this gene in hematopoietic neoplasms has not been studied. We analyzed expression levels of the CASC5 gene and the nearest regulatory genes, including WT1, APOBEC3A (A3A), and N-MYC. A pronounced decrease in CASC5 expression in bone marrow cells of primary leukemia patients compared with healthy donors was found. It was also shown that reduced expression of the CASC5 gene correlates with the detection of targeted mutations in patients composed two prognostic subgroups (favorable, unfavorable) with a significance level (p <0.05). It was noted that the change in the expression level of the CASC5 gene in acute myeloid leukemia is associated with overexpression of the genes WT1, A3A, and in some cases N-MYC and SPT16, which is consistent with the resistance to chemotherapy and leukemia progression. However, the question of which regulatory gene initiates leukemogenesis remains open.


Superhard monoclinic polymorph of carbon.
We report a novel phase of carbon possessing a monoclinic C2/m structure (8 atoms/cell) identified using an ab initio evolutionary structural search. This polymorph, which we call M-carbon, is related to the (2x1) reconstruction of the (111) surface of diamond and can also be viewed as a distorted (through sliding and buckling of the sheets) form of graphite. It is stable over cold-compressed graphite above 13.4 GPa. The simulated x-ray diffraction pattern and near K-edge spectroscopy are in satisfactory agreement with the experimental data [W. L. Mao, Science 302, 425 (2003)10.1126/science.1089713] on overcompressed graphite. The hardness and bulk modulus of this new carbon polymorph are calculated to be 83.1 and 431.2 GPa, respectively, which are comparable to those of diamond.


Total and LDL cholesterol are associated with glomerular filtration rate in normoalbuminuric type 1 diabetic patients.
Studies have generally suggested a positive association between dyslipidemia and chronic kidney disease, but sparse data are available on the relation of lipids and glomerular filtration rate in patients with normal renal function. We investigated the associations of serum lipids, including total, LDL, HDL, VLDL cholesterol, and triglyceride levels with estimated glomerular filtration rate (eGFR) in type 1 diabetic patients. Study included 313 normoalbuminuric type 1 diabetic patients with normal or mild decrease (eGFR > 60 mL/min per 1.73 m2) renal function and before any interventions with statins, ACE inhibitors or angiotensin II receptor blockers. eGFR was significantly associated with total, LDL, and HDL cholesterol (r = -0.21, -0.18, and -0.17, respectively, for all p < 0.05). Stratifying serum lipids for degree of eGFR, levels of total, LDL, and HDL cholesterol were inversely related to eGFR, but trends were significant only for total (5.1 vs 5.0 and 4.6 mmol/L) and LDL cholesterol (2.9 vs 2.8 and 2.4 mmol/L). We have detected an association between eGFR and lipid abnormalities in type 1 diabetes in early stages. The study was conducted in patients with no therapeutic intervention. This may suggest that lipid abnormalities may play a role in the pathogenesis of renal impairment in type 1 diabetic patients.


Lidocaine attenuation testing: An in vivo investigation of putative LQT3-associated variants in the SCN5A-encoded sodium channel.
Long QT syndrome type 3 (LQT3) accounts for 5%-10% of long QT syndrome and results from gain-of-function mutations in the SCN5A-encoded sodium channel. Approximately 2% of healthy individuals host rare SCN5A variants of uncertain significance (VUS). Distinction of true LQT3-causative mutations from background genetic noise is essential. The purpose of this study was to assess the use of the lidocaine attenuation test (LAT) in evaluating patients with possible LQT3. We reviewed the LAT results and medical records for 25 patients with a possible LQT3-associated SCN5A variant. The LAT involved a loading dose of 1 mg/kg of intravenous lidocaine followed by continuous infusion at 50 μg/(kg⋅min) for 20 minutes. If the corrected QT interval shortened by ≥30 ms, the LAT was defined as positive. Sixteen patients (64%) had a positive LAT, 6 of which demonstrated the E1784K variant. A positive LAT correlated in 86% of cases with abnormal in vitro channel function (mean corrected QT interval attenuation 43 ± 3 ms vs 25 ± 5 ms for wild-type variants; P = .03). Four of 5 patients (80%) with a VUS had a positive LAT (T1304M [2 patients], L1786P, and R800L). The T1304M variant demonstrated abnormal in vitro function and a positive LAT, opening the door for a potential variant promotion from VUS to likely pathogenic. The LAT may help distinguish true LQT3-causative mutations from an otherwise noncontributory VUS. Given that lidocaine acts as a late sodium current blocker, a positive LAT may enable the early identification of a pathological accentuation of the late sodium current that could be targeted therapeutically.


Age moderates non-genetic influences on the initiation of cannabis use: a twin-sibling study in Dutch adolescents and young adults.
To examine the heritability of cannabis initiation, the influence of a possible twin-specific environment and the influence of age on the effects of genes and environment in Dutch adolescents and young adults. Genetic structural equation modelling was used to partition the variance in the liability to cannabis initiation into genetic and environmental components. All participants were registered with the Netherlands Twin Register. A total of 6,208 twins (age 13-20) and 1,545 siblings (age 11-25) from 3,503 families participated in this study. Self-reported cannabis use was assessed prospectively with the Dutch Health Behavior Questionnaire. At the median age of the sample (16.5), genetic factors explained 40% of the individual differences in liability to cannabis initiation. Twins resembled each other more than non-twin siblings, which could not be attributed to the age difference between non-twin siblings. Environmental influences increased with age. This increase applied to environmental factors shared by twins (47% of the variance), environmental factors shared by twins and siblings (24%) and environmental factors unique to an individual (13%). The heritability of the liability for cannabis initiation is higher in adolescents than in young adults due to a larger contribution of environmental factors in young adults. This is due mainly to environmental factors only shared by twins and those shared by all offspring growing up in the same family, but the contribution of environmental factors specific to individuals is also larger in young adults.


Early disruptions to syringe services programs during the Russian invasion of Ukraine.
The widespread HIV epidemic in Ukraine is concentrated among people who inject drugs (PWID), making access to sterile injection paraphernalia (SIP) like sterile needles and syringes a critical method of HIV/AIDS prevention; however, the Russian invasion has threatened to disrupt the operations of syringe services programs (SSPs), creating a risk of HIV outbreaks among PWID. We conducted 10 semi-structured interviews with outreach workers from SSPs. Interviews were purposively sampled to cover three prototypic regions of Ukraine: temporarily Russian-controlled, frontline, and destination. Qualitative results from interviews were then compared against a standardized, nationwide harm reduction database. We found that the Russian invasion triggered both supply and demand challenges for SSPs. Demand increased for all regions due to client transitions from pharmacies that closed to SSPs, increases in illicit drug use, greater client openness to NGO support, and displacement of clients to destination regions. Supply decreased for all areas (except for remote destination regions) due to battle-related barriers like curfews, roadblocks, and Internet disruptions; diminished deliveries of SIP and funding; and staff displacement. Time series plots of the number of unique clients accessing harm reduction services showed that an initial decrease in service provision occurred at the start of the war but that most regions recovered within several months except for Russian-controlled regions, which continued to provide services to fewer clients relative to previous years. To ensure continued scale-up of SIP and other HIV prevention services, the SyrEx database should be leveraged to serve as a streamlined harm reduction locator that can inform workers and clients of open site locations and other pertinent information.


Optimized tPA: A non-neurotoxic fibrinolytic agent for the drainage of intracerebral hemorrhages.
Intracerebral hemorrhage (ICH) is the most severe form of stroke. Catheter-delivered thrombolysis with recombinant tissue-type plasminogen activator (rtPA) for the drainage of ICH is currently under evaluation in a phase III clinical trial (MISTIE III). However, in a pig model of ICH, in situ fibrinolysis with rtPA was reported to increase peri-lesional edema by promoting N-methyl-D-aspartate (NMDA)-dependent excitotoxicity. In the present study, we engineered a non-neurotoxic tPA variant, OptPA, and investigated its safety and efficacy for in situ fibrinolysis in a rat model of ICH. Magnetic resonance imaging analyses of hematoma and edema volumes, behavioral tasks and histological analyses were performed to measure the effects of treatments. In vitro, OptPA was equally fibrinolytic as rtPA without promoting NMDA-dependent neurotoxicity. In vivo, in situ fibrinolysis using OptPA reduced hematoma volume, like rtPA, but it also reduced the evolution of peri-hematomal neuronal death and subsequent edema progression. Overall, this preclinical study demonstrates beneficial effects of OptPA compared to rtPA for the drainage of ICH.


"Can Do, Do Do" Quadrants and 6-Year All-Cause Mortality in Patients With COPD.
Physical capacity (PC; "can do") and physical activity (PA; "do do") are prognostic indicators in COPD and can be used to subdivide patients with COPD into four exclusive subgroups (the so-called "can do, do do" quadrants). This concept may be useful to understand better the impact of PC and PA on all-cause mortality in patients with COPD. What is the 6-year all-cause mortality risk of the "can do, do do" quadrants of patients with COPD? This retrospective study used data from patients with COPD who underwent a comprehensive assessment at their first-ever outpatient consultation. PC was assessed using the 6-min walk distance and physical activity was assessed using an accelerometer (steps per day). All-cause mortality data were obtained from the Municipal Personal Records Database. Receiver operating characteristic curves were used to determine threshold values for PC and PA to predict 6-year all-cause mortality. Using the derived threshold values, male and female patients were divided into the four "can do, do do" quadrants. Data from 829 patients were used for analyses. Best discriminatory values for 6-year mortality were 404 m and 4,125 steps/day for men and 394 m and 4,005 steps/day for women. During a median follow-up of 55 months (interquartile range, 37-71 months), 129 patients (15.6%) died. After controlling for established prognostic factors, patients in the "can do, don't do" quadrant and "can do, do do" quadrant showed significantly lower mortality risk compared with patients in the "can't do, don't do" quadrant: hazard ratios of 0.36 (95% CI, 0.14-0.93) and 0.24 (95% CI, 0.09-0.61) for men and 0.37 (95% CI, 0.38-0.99) and 0.29 (95% CI, 0.10-0.87) for women, respectively. No significant differences were found between the "can't do, do do" and "can't do, don't do" quadrants. Patients with COPD with a preserved PC seem to have a significantly lower 6-year mortality risk compared with patients with a decreased PC, regardless of physical activity level.


Platelet-to-Lymphocyte Ratio as a New Predictive Index of Neurological Outcomes in Patients with Acute Intracranial Hemorrhage: A Retrospective Study.
BACKGROUND Systemic inflammation plays a critical role in the pathophysiological process of intracranial hemorrhage (ICH). Recently, the platelet-to-lymphocyte ratio (PLR) has become a research focus that indicates inflammation in various diseases. Thus, this study aimed to investigate the predictive value of PLR in patients with acute ICH. MATERIAL AND METHODS This study was performed in a single teaching hospital. Glasgow coma scale at hospital discharge (GCSdis) and modified Rankin score (MRS) at 6 months were recorded as short-term and long-term neurological outcomes. Ordered and binary logistic regression methods were used to explore the associations. RESULTS Finally, data on 183 ICH patients were included. A knot of PLR around 100 was detected and applied in the extended ordered logistic regression models. For PLR >100, PLR on ICU admission was significantly associated with worse GCSdis (from Model 1: OR: 1.004, 95% CI 1.001-1.007 to Model 4: OR: 1.006, 95% CI 1.002-1.009) while the PLR on Emergency Department (ED) admission was insignificant. For PLR ≤100, neither the PLR on ICU or ED admission was associated with GCSdis level. In the quartile grouping analysis, PLR Q2 was used as a reference level. Both Q3 and Q4 on ICU admission were significantly associated with lower GCSdis level (OR, 3.30; 95%CI 1.38-7.88; and OR, 3.79; 95%CI 1.54-9.33, respectively), while Q1 was insignificant. All 4 quartiles of PLR on ED admission were not associated with GCSdis. CONCLUSIONS Only higher PLR value on ICU admission but not on ED admission was associated with worse GCSdis.


Can Engagement Go Awry and Lead to Burnout? The Moderating Role of the Perceived Motivational Climate.
In this study, we propose that when employees become too engaged, they may become burnt out due to resource depletion. We further suggest that this negative outcome is contingent upon the perceived motivational psychological climate (mastery and performance climates) at work. A two-wave field study of 1081 employees revealed an inverted U-shaped relationship between work engagement and burnout. This finding suggests that employees with too much work engagement may be exposed to a higher risk of burnout. Further, a performance climate, with its emphasis on social comparison, may enhance-and a mastery climate, which focuses on growth, cooperation and effort, may mitigate the likelihood that employees become cynical towards work-an important dimension of burnout.


Patterns of Care Partner Communication for Persons Living with Dementia in the Emergency Department.
Nearly half of all persons living with dementia (PLwD) will visit the emergency department (ED) in any given year and ED visits by PLwD are associated with short-term adverse outcomes. Care partner engagement is critical in the care of PLwD, but little is known about their patterns of communication with ED clinicians. We performed a retrospective electronic health record (EHR) review of a random sampling of patients ≥ 65 years with a historical diagnosis code of dementia who visited an ED within a large regional health network between 1/2014 and 1/2022. ED notes within the EHRs were coded for documentation of care partner communication and presence of a care partner in the ED. Logistic regression was used to identify patient characteristics associated with the composite outcome of either care partner communication or care partner presence in the ED. A total of 460 patients were included. The median age was 83.0 years, 59.3% were female, 11.3% were Black, and 7.6% Hispanic. A care partner was documented in the ED for 22.4% of the visits and care partner communication documented for 43.9% of visits. 54.8% of patients had no documentation of care partner communication nor evidence of a care partner at the bedside. In multivariate logistic regression, increasing age (OR, (95% CI): 1.06 (1.04-1.09)), altered mental status (OR: 2.26 (1.01-5.05)), and weakness (OR: 3.38 (1.49-7.65)) significantly increased the probability of having care partner communication documented or a care partner at the bedside. More than half of PLwD in our sample did not have clinician documentation of communication with a care partner or a care partner in the ED. Further studies are needed to use these insights to improve communication with care partners of PLwD in the ED.


Phase II trial of sorafenib in combination with carboplatin and paclitaxel in patients with metastatic uveal melanoma: SWOG S0512.
Sorafenib, a multikinase inhibitor of cell proliferation and angiogenesis, inhibits the mitogen-activated protein kinase pathway that is activated in most uveal melanoma tumors. This phase II study was conducted by the SWOG cooperative group to evaluate the efficacy of sorafenib in combination with carboplatin and paclitaxel (CP) in metastatic uveal melanoma. Twenty-five patients with stage IV uveal melanoma who had received 0-1 prior systemic therapy were enrolled. Treatment included up to 6 cycles of carboplatin (AUC = 6) and paclitaxel (225 mg/m(2)) administered IV on day 1 plus sorafenib (400 mg PO twice daily), followed by sorafenib monotherapy until disease progression. The primary endpoint was objective response rate (ORR); a two-stage design was used with the study to be terminated if no confirmed responses were observed in the first 20 evaluable patients. Secondary efficacy endpoints included progression-free survival (PFS) and overall survival (OS). No confirmed objective responses occurred among the 24 evaluable patients (ORR = 0% [95% CI: 0-14%]) and the study was terminated at the first stage. Minor responses (tumor regression less than 30%) were seen in eleven of 24 (45%) patients. The median PFS was 4 months [95% CI: 1-6 months] and the 6-month PFS was 29% [95% CI: 13%-48%]. The median OS was 11 months [95% CI: 7-14 months]. In this study, the overall efficacy of CP plus sorafenib in metastatic uveal melanoma did not warrant further clinical testing when assessed by ORR, although minor tumor responses and stable disease were observed in some patients. ClinicalTrials.govNCT00329641.


Distinct molecular signatures in pediatric infratentorial glioblastomas defined by aCGH.
Glioblastomas (GBM) are rare in children, but reportedly have more varied outcome which suggests differences in tumor etiology compared to typical GBM of adults. To investigate this we performed high resolution array comparative genomic hybridization (aCGH) analysis on three pediatric infratentorial GBM, ages 3.5, 7 and 14 years. Two of these tumors occurred in the brainstem and one in the spinal cord. While histologically typical, one brainstem tumor showed mainly pleomorphic astrocytic cells, whereas the other brainstem and spinal tumors showed a GFAP positive small cell component. Whole chromosomal gains (#1 and #2) and loss (#20) were seen only in the pleomorphic brainstem GBM, which also showed a high level of segmental genomic copy number changes. Segmental loss involving chromosome 8 was seen in all three tumors (Chr8;133039446-136869494, Chr8;pter-3581577, and Chr8;pter-30480019 respectively), whereas loss involving chromosome 16 was seen in only 2 cases with small cell components (Chr16;31827239-qter and Chr16;pter-29754532). Segmental gain of chromosome 7 was shared only between the 2 brainstem cases (Chr7;17187166-qter and Chr7;69824947-qter). Chromosome 17 showed segmental gain of 17q in the backdrop of loss of 17p only in case 1. Segmental gain of chromosome 1q was seen only in case 2. The spinal GBM showed a relatively stable karyotype with a unique loss of Chr19;32848902-qter. None of the frequent losses, gains and amplifications known to occur in adult GBM were identified, suggesting that pediatric infratentorial glioblastomas show a molecular karyotype that was more characteristic of pediatric embryonal tumors than adult GBM.


Perioperative morbidity of laparoscopic radical prostatectomy compared with open radical retropubic prostatectomy.
The objective of the study was to compare the perioperative complication rates of our initial 60 laparoscopic radical prostatectomy (LRP) patients and our most recent 60 sequential open radical retropubic prostatectomy (RRP) patients. Sixty sequential LRP and 60 sequential RRP patients treated between March 2000 and March 2002 were retrospectively evaluated. Patients who received neo-adjuvant hormonal therapy or had metastatic disease and 3 LRP patients converted to open RRP were excluded. Estimated blood loss (EBL), transfusion rates, hemoglobin level, serum and drain fluid creatinine levels, hospital stay and complication rates were analyzed. There were 15 (25%) and 11 (18.3%) complications in the LRP and RRP cohorts, respectively. There were 3 (ulnar neuropathy, ureteral stricture, anastomotic leak with ureteral obstruction requiring reoperation), and 4 [2 bladder neck contractures (BNC) and 2 deep venous thromboses (DVT)] major complications, respectively. Minor complications included rectus hematoma, superficial wound infections, ileus and anastomotic urine leaks. A higher incidence of the latter (10 patients) was noted in the LRP cohort. One (1.7%) LRP and 31 (52%) RRP cohort patients received intraoperative or postoperative transfusions. The mean (median) EBL was 317 (250) and 1355 (1100) for the LRP and RRP cohorts, respectively. A transient, insignificant increase in serum creatinine from a median of 1.0 to 1.2 mg/dL was observed only in the LRP cohort. We concluded that our initial 60 LRP patients had a similar, but not improved, rate of perioperative complications when compared with 60 sequential open RRP patients of nearly identical age, preoperative PSA and prostate size. The types of complications differed between the LRP and RRP cohorts.


Phonon bandgap engineering of strained monolayer MoS₂.
The phonon band structure of monolayer MoS₂ is characteristic of a large energy gap between acoustic and optical branches, which protects the vibration of acoustic modes from being scattered by optical phonon modes. Therefore, the phonon bandgap engineering is of practical significance for the manipulation of phonon-related mechanical or thermal properties in monolayer MoS₂. We perform both phonon analysis and molecular dynamics simulations to investigate the tension effect on the phonon bandgap and the compression induced instability of the monolayer MoS₂. Our key finding is that the phonon bandgap can be narrowed by the uniaxial tension, and is completely closed at ε = 0.145; while the biaxial tension only has a limited effect on the phonon bandgap. We also demonstrate the compression induced buckling for the monolayer MoS₂. The critical strain for buckling is extracted from the band structure analysis of the flexure mode in the monolayer MoS₂ and is further verified by molecular dynamics simulations and the Euler buckling theory. Our study illustrates the uniaxial tension as an efficient method for manipulating the phonon bandgap of the monolayer MoS₂, while the biaxial compression as a powerful tool to intrigue buckling in the monolayer MoS₂.


[Simian adenovirus 20 genome. I. DNA mapping using restriction enconucleases BamHI, EcoRi, XbaI, HindIII].
The effect of specific restriction endonuclease on the simian adenovirus SV20 DNA was studied. It was shown that endonucleases SalI, XbaI, EcoRI, BamHI, HindIII cleaved the viral DNA into 3, 4, 5, 5, 8 specific fragments respectively. The sequence of fragments (physical map) was determined and found to be B-C-A for enzyme SalI, C-D-B-A--for enzyme Xbal, E-A-C-D-B--for enzyme EcoRI, B-E-C-A-D--for enzyme BamHI and B-E-A-C-(GH)-D-F--for enzyme HindIII. The G-C content of specific fragments was studied. The "right"-"left" orientation of the physical map of the simian adenovirus 20 DNA based on the G-C content was made in respect with the nomenclature of human adenoviruses.


[Contribution of clinical biology in the etiological exploration and follow-up of urolithiasis].
Urolithiasis is a frequent pathology with a constantly increasing prevalence in industrial countries. The relapse frequency is around 50 % with a risk of complications. The laboratory input is essential in the determination of the etiology and in the therapeutic monitoring. The morphoconstitutional analysis of the stone is the most important element. It comprises the examination of the stone with binocular loupes and the simultaneous analysis of its crystalline composition. This can be done by different techniques but infrared spectrophotometry is the most powerful. The chemical analysis should be definitely proscribed. The analysis of crystalluria includes the search, the identification and the counting of crystals in fresh morning urines. It is useful for the diagnosis and for the patient follow-up. Finally, the biochemical analyses in urine and serum, in first line or on the basis of the stone composition, are an important part of the etiological exploration and therapeutic monitoring.


Shape transformations of a compartmentalized fluid surface.
A surface model on compartmentalized spheres is studied by using the Monte Carlo simulation technique with dynamical triangulations. We found that the model exhibits a variety of phases: The spherical phase, the tubular phase, the planar phase, the wormlike planar phase, the wormlike long phase, the wormlike short phase, and the collapsed phase. We also demonstrated that almost all phases are separated from their neighboring phases by first-order transitions. Mechanical strength of the surface is given only by elastic skeletons, which are the compartment boundaries, and therefore vertices diffuse freely inside the compartments. We confirm that the cytoskeletal structure and the lateral diffusion of vertices are origins of such a variety of phases.


Investigation of the simian polyomavirus SV40 as a potential causative agent of human neurological disorders in AIDS patients.
Neurological diseases and a variety of neoplasms frequently occur in AIDS patients. Human JC and BK polyomaviruses have been associated with neurological disorders in such patients. SV40 polyomavirus sequences have been detected in human brain tumours, other neoplasms and normal tissues. JCV, BKV and SV40 DNA sequences were investigated in cerebrospinal fluid (CSF) samples from 12 AIDS patients affected by different neurological disorders, by PCR assay and filter hybridisation with specific internal oligoprobes, and DNA sequencing. Three of the 12 CSF samples were positive for JCV (one sample) or SV40 (one) DNA, or both (one). No sample was positive for BKV DNA. JCV- and SV40-specific genomic regions were confirmed by DNA sequencing. CSF samples from the two patients diagnosed clinically as having progressive multifocal leukoencephalopathy (PML) contained either JCV (one sample) or SV40 (one) DNA. The CSF found to contain both JCV and SV40 DNA originated from a patient with a cerebral mass lesion of unknown aetiology. These results suggest that SV40 may be involved in the aetiology of PML in AIDS patients, and raise the possibility that SV40 and JCV may act synergically in vivo to enhance their pathogenicity.


Gender Equity in Transplantation: A Report from the Women in Transplantation Workshop of The Transplantation Society of Australia and New Zealand.
The exponential growth of young talented women choosing science and medicine as their professional career over the past decade is substantial. Currently, more than half of the Australian medical doctoral graduates and early career researchers are comprised of women, but less than 20% of all academic professorial staff are women. The loss of female talent in the hierarchical ladder of Australian academia is a considerable waste of government investment, productivity, and scientific innovation. Gender disparity in the professional workforce composition is even more striking within the field of transplantation. Women are grossly underrepresented in leadership roles, with currently no female heads of unit in any of the Australian and New Zealand transplanting centers. At the same time, there is also gender segregation with a greater concentration of women in lower-status academic position compared with their male counterparts. Given the extent and magnitude of the disparity, the Women in Transplantation Committee, a subcommittee of The Transplantation Society of Australia and New Zealand established a workshop comprising 8 female clinicians/scientists in transplantation. The key objectives were to (i) identify potential gender equity issues within the transplantation workforce; (ii) devise and implement potential strategies and interventions to address some of these challenges at a societal level; (iii) set realistic and achievable goals to enhance and facility gender equality, equity, and diversity in transplantation.


Associations between drug use and behavioral repertoire in urban youths.
Converging with psycho-social research findings, animal and human laboratory studies indicate that behavioral alternatives are important determinants of drug-taking. To investigate associations between how early adolescents spend their time, i.e. their behavioral repertoire and drug use (use of marijuana, crack/cocaine or inhalants), we analyzed data from an epidemiological sample of 1516 urban middle-school students who had completed private interviews in spring 1993. The interview included a 36-item questionnaire to assess how frequently the youth engaged in different activities; history of drug-taking was assessed separately. Multiple logistic regression was used to estimate associations between drug use and each of seven behavioral domains as well as sex, age and racial-ethnic status. Youths spending a great deal of time working for pay and assuming other adult-like roles were more likely to have initiated drug use (estimated odds ratio, OR = 3.49; p = 0.002). Those who spent much time in religious activities were less likely (OR = 0.2, p <0.001). An exploratory search for interactions disclosed other associations that merit attention in future research. These results corroborate evidence on the potential etiological significance of behavioral repertoire in relation to risk of drug use.


Comparison of Clinical Trial and Systematic Review Outcomes for the 4 Most Prevalent Eye Diseases.
Suboptimal overlap in outcomes reported in clinical trials and systematic reviews compromises efforts to compare and summarize results across these studies. To examine the most frequent outcomes used in trials and reviews of the 4 most prevalent eye diseases (age-related macular degeneration [AMD], cataract, diabetic retinopathy [DR], and glaucoma) and the overlap between outcomes in the reviews and the trials included in the reviews. This cross-sectional study examined all Cochrane reviews that addressed AMD, cataract, DR, and glaucoma; were published as of July 20, 2016; and included at least 1 trial and the trials included in the reviews. For each disease, a pair of clinical experts independently classified all outcomes and resolved discrepancies. Outcomes (outcome domains) were then compared separately for each disease. Proportion of review outcomes also reported in trials and vice versa. This study included 56 reviews that comprised 414 trials. Although the median number of outcomes per trial and per review was the same (n = 5) for each disease, the trials included a greater number of outcomes overall than did the reviews, ranging from 2.9 times greater (89 vs 30 outcomes for glaucoma) to 4.9 times greater (107 vs 22 outcomes for AMD). Most review outcomes, ranging from 14 of 19 outcomes (73.7%) (for DR) to 27 of 29 outcomes (93.1%) (for cataract), were also reported in the trials. For trial outcomes, however, the proportion also named in reviews was low, ranging from 19 of 107 outcomes (17.8%) (for AMD) to 24 of 89 outcomes (27.0%) (for glaucoma). Only 1 outcome (visual acuity) was consistently reported in greater than half the trials and greater than half the reviews. Although most review outcomes were reported in the trials, most trial outcomes were not reported in the reviews. The current analysis focused on outcome domains, which might underestimate the problem of inconsistent outcomes. Other important elements of an outcome (ie, specific measurement, specific metric, method of aggregation, and time points) might have differed even though the domains overlapped. Inconsistency in trial outcomes may impede research synthesis and indicates the need for disease-specific core outcome sets in ophthalmology.


Development and validation of a HPLC method for the determination of trans-resveratrol in spiked human plasma.
A simple, accurate, precise, sensitive, and reproducible high-performance liquid chromatography method was developed for the determination of Resveratrol (trans-3, 4',5-trihydroxystilbene) in human plasma using liquid-liquid extraction. Caffeine was employed as an internal standard (IS). However, little information is known about its distribution in the organism generally because of the lack of accurate and precise detection methods. The chromatographic separation was achieved on a Phenomenex C18 column (250 mm × 4.6 mm, 5 μm) at room temperature in isocratic mode, and the column effluent was monitored by UV detector at 306 nm. The mobile phase used was methanol: phosphate buffer (pH 6.8 adjusted with 0.5% (v/v) orthophosphoric acid solution in Milli-Q water) (63:37%, v/v) at a flow rate of 1.0 ml/min. Nominal retention times of trans-resveratrol and IS were 3.94 and 7.86 minutes, respectively. Limits of detection and Limits of quantification of trans-resveratrol were 0.006 μg/ml and 0.008 μg/ml, respectively. This method was linear over the range of 0.010 to 6.4 μg/ml with regression coefficient greater than 0.9998. The inter- and intra-day precisions in the samples, 0.010, 3.2 and 6.4 μg/ml of trans-resveratrol was in the range 0.63 to 2.12% relative standard deviation (RSD) and 0.46 to 1.02% RSD, respectively. Resveratrol was found to be stable for a period of 15 days on storage at -20°C. The method was found to be precise, accurate, and specific during the study.


A case of a shrunken multilocular mediastinal cyst that developed into thymic carcinoma with lung metastases 13 years later.
Multilocular thymic cysts (MTC) are acquired multilocular cysts caused by inflammation. The rarity of such lesions and a lack of recognition make diagnosis and treatment difficult. Herein, we present our experience with a multilocular mediastinal cyst that resulted in the development of thymic cancer with metastasis over a period of 13 years. Computed tomography findings revealed an anterior mediastinal mass that was suspected to be an MTC in a 49-year-old man. The mass shrank gradually over a period of 7 years; however, growth was observed at 10 years after initial detection. At 13 years after detection, thymic carcinoma with multiple lung metastases was diagnosed. Resection was recommended during the follow-up period, but the patient refused treatment. A multilocular wall and location are factors that indicate MTC. However, even if a definitive diagnosis is not made, resection of multilocular anterior mediastinal cysts should be considered as determining the preoperative diagnosis is difficult. Nevertheless, our case suggests that the coexistence of tumors with cysts is possible, and the potential for malignant tumor development exists.


Connections between variation principles at the interface of wave-function and density-functional theories.
A recently proposed variation principle [N. I. Gidopoulos, Phys. Rev. A 83, 040502(R) (2011)] for the determination of Kohn-Sham effective potentials is examined and extended to arbitrary electron-interaction strengths and to mixed states. Comparisons are drawn with Lieb's convex-conjugate functional, which allows for the determination of a potential associated with a given electron density by maximization, yielding the Kohn-Sham potential for a non-interacting system. The mathematical structure of the two functionals is shown to be intrinsically related; the variation principle put forward by Gidopoulos may be expressed in terms of the Lieb functional. The equivalence between the information obtained from the two approaches is illustrated numerically by their implementation in a common framework.


Decreased regional cortical thickness and thinning rate are associated with inattention symptoms in healthy children.
Children with attention-deficit/hyperactivity disorder (ADHD) have delayed cortical maturation, evidenced by regionally specific slower cortical thinning. However, the relationship between cortical maturation and attention capacities in typically developing children is unknown. This study examines cortical thickness correlates of inattention symptoms in a large sample of healthy children. Data from 357 healthy subjects (6.0-18.4 years of age) were obtained from the NIH MRI Study of Normal Brain Development. In cross-sectional analysis (first visit, n = 257), Child Behavior Checklist Attention Problems (AP) scores were linearly regressed against cortical thickness, controlling for age, gender, total brain volume, and site. For longitudinal data (up to three visits, n = 357/672 scans), similar analyses were performed using mixed-effects linear regressions. Interactions of AP with age and gender were tested. A cross-sectional "AP by age" interaction was found in bilateral orbito-frontal cortex, right inferior frontal cortex, bilateral ventromedial prefrontal cortex, bilateral dorsolateral prefrontal cortex, and several additional attention network regions. The interaction was due to negative associations between AP and thickness in younger subjects (6-10 years of age) that gradually disappeared over time secondary to slower cortical thinning. Similar trends were present in longitudinal analyses. Higher AP scores were associated with thinner cortex at baseline and slower cortical thinning with aging in multiple areas involved in attention processes. Similar patterns have been identified in ADHD, suggesting a dimensional component to the link between attention and cortical maturation. The identified association between cortical maturation and attention in healthy development will help to inform studies of neuroimaging biomarkers of ADHD.


Molecular characterization of a hydroxymethylglutaryl-CoA reductase gene from mulberry (Morus alba L.).
The genus Morus consists of trees and shrubs, which are distributed in temperate and subtropical regions. Commonly known as mulberry, a few of the Morus species are valued for their foliage, which constitutes the chief feed for mulberry silkworms. Steroids and isoprenoid compounds present in the foliage not only add nutritive factors to the feed but also contribute greatly to silkworm health and silk production. Mevalonate synthesis, which is the first step in isoprenoid biosynthesis, is catalyzed by the enzyme hydroxymethylglutaryl-CoAreductase (HMGR). A genomic clone, Mahmg1, was isolated from Morus alba and its expression characterized in mulberry and transgenic tobacco. In mulberry, Mahmg1 transcripts were highest in young leaves and flowers. The promoter region of the Mahmg1 gene was fused to the beta-glucuronidase (GUS) reporter gene and the fusion introduced into tobacco. In imbibed embryos, GUS expression was limited to the cotyledons, epicotyl, and root elongation zone. Later, GUS staining was observed in floral tissues, guard cells, and the heads of trichomes on the stem and petioles. Mahmg1::GUS activity increased 3-4-fold by treatment with 100 microM abscisic acid and 15-80-fold in dark-grown versus light-grown seedlings. These results show that expression of the Mahmg1 gene is differentially regulated by developmental and environmental cues, suggesting that its HMGR isozyme a may provide a precursor for synthesis of specific isoprenoids during mulberry growth and development.


[Long-term survival and spontaneous tumor regression in stage IV melanoma: possible role of adrenalectomy and massive tumor antigen release].
Mean survival for stage IV melanoma patients is 6 to 8 months. Long-term survival is rare and spontaneous regression even more unusual. A 46-year-old woman underwent amputation of the left thumb for subungual melanoma in 1997. In 2002, lobectomy was performed for a single pulmonary metastasis. In June 2006, a seemingly isolated adrenal metastasis was detected, and was rapidly complicated by acute abdominal symptoms due to metastatic rupture that required emergency adrenalectomy. During surgery, peritoneal metastases were observed macroscopically and confirmed histologically. One month later, then every six months until July 2009, clinical and laboratory tests, and in particular positron emission tomodensitometry (PET) scans, revealed no further tumoural lesions. No treatment was given. Screening for signs of autoimmunity revealed isolated appearances of anticardiolipin antibodies starting in June 2006. This rare case suggests the existence of specific factors resulting in tumour control. The favourable prognostic value of autoimmune signs has been discussed in stage III and IV melanoma. A number of studies have also suggested a link between prolonged survival and adrenalectomy for single and multiple adrenal metastases, with rare cases of complete regression of residual tumour following non-oncological surgery, as occurred in our patient. Other possible mechanisms include massive release of tumour antigens following metastatic rupture possibly resulting in massive stimulation of antitumour immune response, as suggested in certain animal models. Laboratory tests to validate these hypotheses have been indicated and could open up fresh therapeutic horizons.


Discovery and genetic mapping of single nucleotide polymorphisms in candidate genes for pathogen defence response in perennial ryegrass (Lolium perenne L.).
Susceptibility to foliar pathogens commonly causes significant reductions in productivity of the important temperate forage perennial ryegrass. Breeding for durable disease resistance involves not only the deployment of major genes but also the additive effects of minor genes. An approach based on in vitro single nucleotide polymorphism (SNP) discovery in candidate defence response (DR) genes has been used to develop potential diagnostic genetic markers. SNPs were predicted, validated and mapped for representatives of the pathogenesis-related (PR) protein-encoding and reactive oxygen species (ROS)-generating gene classes. The F(1)(NA(6) x AU(6)) two-way pseudo-test cross population was used for SNP genetic mapping and detection of quantitative trait loci (QTLs) in response to a crown rust field infection. Novel resistance QTLs were coincident with mapped DR gene SNPs. QTLs on LG3 and LG7 also coincided with both herbage quality QTLs and candidate genes for lignin biosynthesis. Multiple DR gene SNP loci additionally co-located with QTLs for grey leaf spot, bacterial wilt and crown rust resistance from other published studies. Further functional validation of DR gene SNP loci using methods such as fine-mapping and association genetics will improve the efficiency of parental selection based on superior allele content.


Who uses a prescription drug monitoring program and how? Insights from a statewide survey of Oregon clinicians.
Prescription drug monitoring programs (PDMPs) are relatively new but potentially useful tools to enhance prudent prescribing of controlled substances. However, little is known about the types of clinicians who make the most use of PDMPs, how these programs are incorporated into clinicians' work flow, or how clinicians and patients respond to the information. We therefore surveyed a random sample of Oregon providers, with 1,065 respondents. Clinicians in emergency medicine, primary care, and pain and addiction specialties were the largest number of registrants, but many frequent prescribers of controlled substances were not registered to use the PDMP. Among users, 95% reported accessing the PDMP when they suspected a patient of abuse or diversion, but fewer than half would check it for every new patient or every time they prescribe a controlled drug. Nearly all PDMP users reported that they discuss worrisome PDMP data with patients; 54% reported making mental health or substance abuse referrals, and 36% reported sometimes discharging patients from the practice. Clinicians reported frequent patient denial or anger and only occasional requests for help with drug dependence. More research is needed to optimize how clinicians use PDMPs across settings and how clinicians and patients respond to the data. This study examined differences between PDMP users and nonusers and how clinicians in various specialties use PDMPs in practice. A better understanding of effective PDMP use will facilitate access to treatment for patients with pain while curbing the prescription drug epidemic and may ultimately reduce abuse, misuse, and overdose death.


An enigmatic brainstem posterior fossa ganglioglioma in an adult.
Ganglioglioma is a rare central nervous system neoplasm representing 0.4% to 1.7% of all brain tumors and most frequently occurs in the pediatric population with an incidence of 7.6%. These tumors are usually slow-growing and well-circumscribed solid or cystic lesions. Gangliogliomatosis infrequently occurs in the frontal lobe, pineal gland, basal ganglia, hypothalamus, and optic chiasm, with very few reports of brainstem ganglioglioma. We report a case of a 35-year-old female who initially presented with headache, vertigo, ataxia, saccadic dysfunction, dysarthria, and dysmetria for several years due to an unknown etiology. Her brain imaging showed multiple lesions in the pons and the cerebellum with cystic changes and size reduction and enlargement over the next few years while her neurological symptoms continued to worsen. The patient received courses of steroid treatment that improved her neurological symptoms, suggesting an inflammatory component of her disease. Extensive workup for an inflammatory or infectious etiology was unfruitful and two brain biopsies were inconclusive. A third biopsy showed atypical glial nuclei, binucleated cells, and Rosenthal fibers and the presence of BRAF V600E mutation was detected. The diagnosis of gangliogliomatosis was consequently established. This case illustrates that gangliogliomatosis may present with the waxing-and-waning neurological signs and symptoms. It can masquerade inflammatory processes in the central nervous system on brain imaging and deserves careful consideration in the diagnosis of patients with an indolent course of neurological deterioration.


Induction of hepatic heme oxygenase-1 and ferritin in rats by cancer chemopreventive dithiolethiones.
Treatment of rats with the cancer chemopreventive agent 1,2-dithiole-3-thione (D3T) resulted in a significant increase in hepatic heme oxygenase (HO) activity, which corresponded to increased protein levels of HO-1. Upon further analysis of proteins related to heme metabolism, the level of ferritin, the major iron storage protein in liver, was also found to be elevated. Diminished levels of intracellular free iron were monitored by EPR spectroscopy at times after administration of D3T that suggested that increased ferritin content sequesters intracellular iron. The increased levels of protein were associated with increased levels of steady-state RNA of HO-1 and the light (FL) and heavy (FH) subunits of ferritin. A direct relationship between enhanced rates of gene transcription and elevated levels of HO-1 and ferritin RNA was found. The inductions of FL and FH, but not HO-1, were sensitive to cycloheximide, suggesting that in vivo these genes are regulated by distinct D3T-responsive transcriptional mechanisms. The known protective roles for induced HO-1 and ferritin in cellular stress have been suggested to include increased levels of the antioxidant bilirubin and enhanced sequestration of intracellular iron into ferritin, which can effectively reduce iron-mediated reactive oxygen generation. Thus, protective actions of D3T against the cytotoxic and carcinogenic consequences of chemicals that exert electrophilic or oxidative stresses may be mediated, in part, by the induction of HO-1, FL and FH.


Individual and contextual factors associated with appropriate healthcare seeking behavior among febrile children in Tanzania.
Fever in malaria endemic areas, has been shown to strongly predict malaria infection and is a key symptom influencing malaria treatment. WHO recommended confirmation testing for Plasmodium spp. before initiation of antimalarials due to increased evidence of the decrease of morbidity and mortality from malaria, decreased malaria associated fever, and increased evidence of high prevalence of non-malaria fever. To immediately diagnose and promptly offer appropriate management, caretakers of children with fever should seek care where these services can be offered; in health facilities. This study was conducted to describe healthcare seeking behaviors among caretakers of febrile under five years, in Tanzania. And to determine children's, household and community-level factors associated with parents' healthcare seeking behavior in health facilities. Secondary data analysis was done using the Tanzania HIV and Malaria Indicator Surveys (THMIS) 2011-2012. Three-level mixed effects logistic regression was used to assess children's, household and community-level factors associated with appropriate healthcare seeking behavior among care takers of febrile children as well as differentiating between household and community variabilities. Of the 8573 children under the age of five years surveyed, 1,675(19.5%) had a history of fever two weeks preceding the survey. Of these, 951 (56.8%) sought appropriate healthcare. Febrile children aged less than a year have 2.7 times higher odds of being taken to the health facilities compared to children with two or more years of age. (OR: 2.7; 95%CI: 1.50-4.88). Febrile children from households headed by female caretakers have almost three times higher odds of being taken to the health facilities (OR: 2.85; 95%CI; 1.41-5.74) compared to households headed by men. Febrile children with caretakers exposed to mass media (radio, television and newspaper) have more than two times higher odds of being taken to health facilities compared to those not exposed to mass media. Febrile children from regions with malaria prevalence above national level have 41% less odds of being taken to health facilities (OR: 0.49; 95%CI: 0.29-0.84) compared to those febrile children coming from areas with malaria prevalence below the national level. Furthermore, febrile children coming from areas with higher community education levels have 57% (OR: 1.57; 95%CI: 1.14-2.15) higher odds of being taken to health facilities compared to their counterparts coming from areas with low levels of community education. To effectively and appropriately manage and control febrile illnesses, the low proportion of febrile children taken to health facilities by their caretakers should be addressed through frequent advocacy of the importance of appropriate healthcare seeking behavior, using mass media particularly in areas with high malaria prevalence. Multifaceted approach needs to be used in malaria control and eradication as multiple factors are associated with appropriate healthcare seeking behavior.


[Efficacy of the use of remnant stomach in esophagoplasty].
In the period from 2001 till 2010 there were 117 extirpations of the oesophagus with single-stage plasty of the stomach in 94 patients and plasty of the large intestine--in 23 cases. Gastric resections were performed earlier in 50 (42.7%) patients, though gastrectomy took place in 39 (78%) patients. The accumulated experience allowed making an assessment of immediate and long-term results of esophagoplasty to patients, who had earlier the gastric resection. The incompetence of oesophagogastric anastomosis was noted in 2 times more frequent and the formation of stenosis of given anastomosis in 3 times more often. I order to improve the results of esophagoplasty, the method of serousmyotomy was applied in the cases of remnant stomach.


Unbiased High-Precision Cell Mechanical Measurements with Microconstrictions.
We describe a quantitative, high-precision, high-throughput method for measuring the mechanical properties of cells in suspension with a microfluidic device, and for relating cell mechanical responses to protein expression levels. Using a high-speed (750 fps) charge-coupled device camera, we measure the driving pressure Δp, maximum cell deformation εmax, and entry time tentry of cells in an array of microconstrictions. From these measurements, we estimate population averages of elastic modulus E and fluidity β (the power-law exponent of the cell deformation in response to a step change in pressure). We find that cell elasticity increases with increasing strain εmax according to E ∼ εmax, and with increasing pressure according to E ∼ Δp. Variable cell stress due to driving pressure fluctuations and variable cell strain due to cell size fluctuations therefore cause significant variability between measurements. To reduce measurement variability, we use a histogram matching method that selects and analyzes only those cells from different measurements that have experienced the same pressure and strain. With this method, we investigate the influence of measurement parameters on the resulting cell elastic modulus and fluidity. We find a small but significant softening of cells with increasing time after cell harvesting. Cells harvested from confluent cultures are softer compared to cells harvested from subconfluent cultures. Moreover, cell elastic modulus increases with decreasing concentration of the adhesion-reducing surfactant pluronic. Lastly, we simultaneously measure cell mechanics and fluorescence signals of cells that overexpress the GFP-tagged nuclear envelope protein lamin A. We find a dose-dependent increase in cell elastic modulus and decrease in cell fluidity with increasing lamin A levels. Together, our findings demonstrate that histogram matching of pressure, strain, and protein expression levels greatly reduces the variability between measurements and enables us to reproducibly detect small differences in cell mechanics.


Taurine: evidence of physiological function in the retina.
Taurine is a free amino acid found in high millimolar concentrations in mammalian tissue and is particularly abundant in the retina. Mammals synthesize taurine endogenously with varying abilities, with some species more dependent on dietary sources of taurine than others. Human children appear to be more dependent on dietary taurine than adults. Specifically, it has been established that visual dysfunction in both human and animal subjects results from taurine deficiency. Moreover, the deficiency is reversed with simple nutritional supplementation with taurine. The data suggest that taurine is an important neurochemical factor in the visual system. However, the exact function or functions of taurine in the retina are still unresolved despite continuing scientific study. Nevertheless, the importance of taurine in the retina is implied in the following experimental findings: (1) Taurine exhibits significant effects on biochemical systems in vitro. (2) The distribution of taurine is tightly regulated in the different retinal cell types through the development of the retina. (3) Taurine depletion results in significant retinal lesions. (4) Taurine release and uptake has been found to employ distinct regulatory mechanisms in the retina.


A blood-based, 7-metabolite signature for the early diagnosis of Alzheimer's disease.
Accurate blood-based biomarkers of Alzheimer's disease (AD) could constitute simple, inexpensive, and non-invasive tools for the early diagnosis and treatment of this devastating neurodegenerative disease. We sought to develop a robust AD biomarker panel by identifying alterations in plasma metabolites that persist throughout the continuum of AD pathophysiology. Using a multicenter, cross-sectional study design, we based our analysis on metabolites whose levels were altered both in AD patients and in patients with amnestic mild cognitive impairment (aMCI), the earliest identifiable stage of AD. UPLC coupled to mass spectrometry was used to independently compare the levels of 495 plasma metabolites in aMCI (n = 58) and AD (n = 100) patients with those of normal cognition controls (NC, n = 93). Metabolite alterations common to both aMCI and AD patients were used to generate a logistic regression model that accurately distinguished AD from NC patients. The final panel consisted of seven metabolites: three amino acids (glutamic acid, alanine, and aspartic acid), one non-esterified fatty acid (22:6n-3, DHA), one bile acid (deoxycholic acid), one phosphatidylethanolamine [PE(36:4)], and one sphingomyelin [SM(39:1)]. Detailed analysis ruled out the influence of potential confounding variables, including comorbidities and treatments, on each of the seven biomarkers. The final model accurately distinguished AD from NC patients (AUC, 0.918). Importantly, the model also distinguished aMCI from NC patients (AUC, 0.826), indicating its potential diagnostic utility in early disease stages. These findings describe a sensitive biomarker panel that may facilitate the specific detection of early-stage AD through the analysis of plasma samples.


Isolated systolic hypertension and incident heart failure in older adults: a propensity-matched study.
The association between isolated systolic hypertension (ISH) and incident heart failure (HF) has not been prospectively studied in a propensity-matched population of ambulatory older adults. Of the 5795 participants in the public-use copy of the Cardiovascular Health Study data set, 5248 had diastolic blood pressure <90 mm Hg and were free of HF at baseline. Of these, 2000 (38%) had ISH, defined as average seated systolic blood pressure > or =140 mm Hg. Propensity scores for baseline ISH were calculated for each participant (based on 64 baseline covariates) and were used to match 1260 pairs of participants with and without ISH. Matched Cox regression models were used to estimate the association of ISH with incident HF during a mean follow-up of 8.7 years. Matched participants (n=2520) had a mean (+/-SD) age of 74 (+/-6) years, 60% were women, 16% were nonwhites, 18% developed new-onset HF, and 35% died. Incident HF developed in 20% (rate: 242/10,000 person-years) and 16% (rate: 194/10,000 person-years) of participants with and without ISH, respectively (matched hazard ratio when ISH was compared with no ISH: 1.26; 95% CI: 1.04 to 1.51; P=0.016). Prematch unadjusted, multivariable-adjusted, and propensity-adjusted hazard ratios (95% CIs) for ISH-associated incident HF were, respectively, 1.72 (1.51 to 1.97; P<0.0001), 1.35 (1.18 to 1.56; P<0.0001), and 1.22 (1.04 to 1.44; P=0.016). ISH had no association with all-cause mortality (matched hazard ratio: 1.03; 95% CI: 0.88 to 1.19; P=0.732). In conclusion, in a propensity-matched cohort of community-dwelling older adults who were well balanced in 64 baseline covariates, ISH was associated with increased risk of incident HF but had no association with all-cause mortality.


Microvesicles derived from mesenchymal stem cells enhance survival in a lethal model of acute kidney injury.
Several studies demonstrated that treatment with mesenchymal stem cells (MSCs) reduces cisplatin mortality in mice. Microvesicles (MVs) released from MSCs were previously shown to favor renal repair in non lethal toxic and ischemic acute renal injury (AKI). In the present study we investigated the effects of MSC-derived MVs in SCID mice survival in lethal cisplatin-induced AKI. Moreover, we evaluated in vitro the effect of MVs on cisplatin-induced apoptosis of human renal tubular epithelial cells and the molecular mechanisms involved. Two different regimens of MV injection were used. The single administration of MVs ameliorated renal function and morphology, and improved survival but did not prevent chronic tubular injury and persistent increase in BUN and creatinine. Multiple injections of MVs further decreased mortality and at day 21 surviving mice showed normal histology and renal function. The mechanism of protection was mainly ascribed to an anti-apoptotic effect of MVs. In vitro studies demonstrated that MVs up-regulated in cisplatin-treated human tubular epithelial cells anti-apoptotic genes, such as Bcl-xL, Bcl2 and BIRC8 and down-regulated genes that have a central role in the execution-phase of cell apoptosis such as Casp1, Casp8 and LTA. In conclusion, MVs released from MSCs were found to exert a pro-survival effect on renal cells in vitro and in vivo, suggesting that MVs may contribute to renal protection conferred by MSCs.