Corticosteroid as an Adjunct in the Treatment of Endobronchial Tuberculosis: A Systematic Review & Meta-analysis.
Corticosteroid exerts anti-inflammatory action and can prevent tissue damage resulting from various causes. Studies have shown that corticosteroids may prevent the damaging effect of tuberculosis (TB) in various organs, but there is no published meta-analysis specifically looking for the effect of corticosteroid in endobronchial TB. To synthesize the evidence regarding the usefulness of corticosteroid in endo-bronchial TB. A comprehensive search was performed of the major electronic databases till 30th November 2018. Randomized trials comparing treatment with corticosteroid as an adjunct to antitubercular drugs (ATT) versus placebo/no treatment in endobronchial TB were included. Three authors independently applied eligibility criteria, assessed the studies for methodological quality, and extracted data. The review is registered at PROSPERO database [CRD42016047063]. Out of 525 search results, 4 trials including 205 patients (151 children) were eligible for inclusion. Oral prednisolone was used in various dose schedules. Rifampicin containing ATT regimen was used in 3 trials. The bronchoscopy findings showed no significant improvement at 1 month (effect size could not be calculated due to 0 event in the intervention group, p = 0.05), 2 months (RR 1.26, 95% CI 0.89 to 1.8), and at completion of ATT (RR 0.63, 95% CI 0.1 to 4.14) in steroid-treated group compared to the control group. The need for repeat bronchoscopy was significantly decreased in the steroid group (RR 0.13, 95% CI 0.02 to 0.9). Among the adverse events, the infection rate was significantly lesser in the steroid group (RR 0.53, 95% CI 0.29 to 0.97); but other adverse events (mortality, hypertension, and abdominal distension) showed no significant difference between the two groups. The GRADE evidence generated was of very low quality. The present meta-analysis showed that oral steroid does not help patients with endobronchial tuberculosis. However, the quality of evidence was very low. Future trials with robust design and a larger sample size would be required to provide any firm recommendation regarding the use of oral prednisolone in endobronchial tuberculosis.


Trends and outcomes associated with serum albumin concentration among incident dialysis patients in the United States.
Serum albumin concentrations are associated with mortality, and respond to nutritional and inflammatory states. To explore whether changing demographics and practice patterns in dialysis have influenced serum albumin concentrations, we analyzed trends in serum albumin among incident patients on dialysis from 1995 through 2004. Mean serum albumin concentrations declined significantly over time, even after accounting for changes in age, diabetes, body size, and other factors. Although laboratory assays were not uniform within or across years, serum albumin declined over time, regardless of the reported laboratory lower limit of normal. Moreover, serum albumin retained its potent association with mortality over time. Lower serum albumin was especially hazardous among younger patients and blacks, and was less hazardous among persons with diabetes as a primary cause of kidney disease. Despite higher body weights and the initiation of dialysis earlier in the course of progressive chronic kidney disease, hypoalbuminemia remains common and hazardous to persons starting dialysis.


A decade of progress in juvenile idiopathic athritis treatments and outcomes in Canada: results from ReACCh-Out and the CAPRI registry.
To assess changes in juvenile idiopathic arthritis (JIA) treatments and outcomes in Canada, comparing a 2005-2010 and a 2017-2021 inception cohorts. Patients enrolled within three months of diagnosis in the Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh-Out) and the Canadian Alliance of Pediatric Rheumatology Investigators Registry (CAPRI) cohorts were included. Cumulative incidences of drug starts and outcome attainment within 70 weeks of diagnosis were compared with Kaplan Meier survival analysis and multivariable Cox regression. The 2005-2010 and 2017-2021 cohorts included 1128 and 721 patients, respectively. JIA category distribution and baseline clinical juvenile idiopathic arthritis disease activity (cJADAS10) scores at enrolment were comparable. By 70 weeks, 6% of patients (95% CI 5, 7) in the 2005-2010 and 26% (23, 30) in the 2017-2021 cohort had started a biologic DMARD (bDMARD), and 43% (40, 47) and 60% (56, 64) had started a conventional DMARD (cDMARD), respectively. Outcome attainment was 64% (61, 67) and 83% (80, 86) for Inactive disease (Wallace criteria), 69% (66, 72) and 84% (81, 87) for minimally active disease (cJADAS10 criteria), 57% (54, 61) and 63% (59, 68) for pain control (<1/10), and 52% (47, 56) and 54% (48, 60) for a good health-related quality of life. Although baseline disease characteristics were comparable in the 2005-2010 and 2017-2021 cohorts, cDMARD and bDMARD use increased with a concurrent increase in minimally active and inactive disease. Improvements in parent and patient reported outcomes were smaller than improvements in disease activity.


Identification of developmental stage and anatomical fraction contributions to cell wall recalcitrance in switchgrass.
Heterogeneity within herbaceous biomass can present important challenges for processing feedstocks to cellulosic biofuels. Alterations to cell wall composition and organization during plant growth represent major contributions to heterogeneity within a single species or cultivar. To address this challenge, the focus of this study was to characterize the relationship between composition and properties of the plant cell wall and cell wall response to deconstruction by NaOH pretreatment and enzymatic hydrolysis for anatomical fractions (stem internodes, leaf sheaths, and leaf blades) within switchgrass at various tissue maturities as assessed by differing internode. Substantial differences in both cell wall composition and response to deconstruction were observed as a function of anatomical fraction and tissue maturity. Notably, lignin content increased with tissue maturity concurrently with decreasing ferulate content across all three anatomical fractions. Stem internodes exhibited the highest lignin content as well as the lowest hydrolysis yields, which were inversely correlated to lignin content. Confocal microscopy was used to demonstrate that removal of cell wall aromatics (i.e., lignins and hydroxycinnamates) by NaOH pretreatment was non-uniform across diverse cell types. Non-cellulosic polysaccharides were linked to differences in cell wall response to deconstruction in lower lignin fractions. Specifically, leaf sheath and leaf blade were found to have higher contents of substituted glucuronoarabinoxylans and pectic polysaccharides. Glycome profiling demonstrated that xylan and pectic polysaccharide extractability varied with stem internode maturity, with more mature internodes requiring harsher chemical extractions to remove comparable glycan abundances relative to less mature internodes. While enzymatic hydrolysis was performed on extractives-free biomass, extractible sugars (i.e., starch and sucrose) comprised a significant portion of total dry weight particularly in stem internodes, and may provide an opportunity for recovery during processing. Cell wall structural differences within a single plant can play a significant role in feedstock properties and have the potential to be exploited for improving biomass processability during a biorefining process. The results from this work demonstrate that cell wall lignin content, while generally exhibiting a negative correlation with enzymatic hydrolysis yields, is not the sole contributor to cell wall recalcitrance across diverse anatomical fractions within switchgrass.


Endogenous calcium in sickle cells does not activate polyphosphoinositide phospholipase C.
Sickle-cell-anaemia erythrocytes (SS cells) are known to have a high Ca2+ content (particularly the dense cell fraction) and to take up Ca2+ on deoxygenation. It has been reported that this high Ca2+ was responsible for the activation of the Ca2+-dependent K+ loss, and of the Ca2+-sensitive polyphosphoinositide phospholipase C (PIC) in dense SS cells. We found that, either in the total population of SS cells or in the light or dense fractions, the content of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] was not changed, whereas that of phosphatidylinositol 4-phosphate was increased and that of phosphatidic acid (PtdOH) was decreased compared with normal (AA) erythrocytes. Deoxygenation-induced Ca2+ entry into SS cells did not change the concentration or, in 32P-prelabelled cells, the radioactivity of polyphosphoinositides and PtdOH. It also failed to induce the formation of inositol 1,4,5-trisphosphate, the product of PtdIns(4,5)P2 hydrolysis by PIC, which was measured by an original method using ion-pair reverse-phase h.p.l.c. Thus there was no evidence of an endogenous Ca2+ effect on the PIC activity in SS cells, in agreement with the demonstration that the excess Ca2+ in SS cells is compartmentalized into internal vesicles and unavailable as free Ca2+. The 32P incorporation in polyphosphoinositides and PtdOH was markedly higher in SS than in AA cells, but this increase was the same in both dense and light SS cells. The increase in the turnover of these phospholipids in SS cells is consistent either with an activation of the lipid kinases and phosphatases or with perturbation in the metabolic compartmentation of these lipids.


Enhancing capacity among faith-based organizations to implement evidence-based cancer control programs: a community-engaged approach.
Evidence-based interventions (EBIs) to promote cancer control among Latinos have proliferated in recent years, though adoption and implementation of these interventions by faith-based organizations (FBOs) is limited. Capacity building may be one strategy to promote implementation. In this qualitative study, 18 community key informants were interviewed to (a) understand existing capacity for health programming among Catholic parishes, (b) characterize parishes' resource gaps and capacity-building needs implementing cancer control EBIs, and (c) elucidate strategies for delivering capacity-building assistance to parishes to facilitate implementation of EBIs. Semi-structured qualitative interviews were conducted. Key informants concurred about the capacity of Catholic parishes to deliver health programs, and described attributes of parishes that make them strong partners in health promotion initiatives, including a mission to address physical and mental health, outreach to marginalized groups, altruism among members, and existing engagement in health programming. However, resource gaps and capacity building needs were also identified. Specific recommendations participants made about how existing resources might be leveraged to address challenges include to: establish parish wellness committees; provide "hands-on" learning opportunities for parishioners to gain program planning skills; offer continuous, tailored, on-site technical assistance; facilitate relationships between parishes and community resources; and provide financial support for parishes. Leveraging parishes' existing resources and addressing their implementation needs may improve adoption of cancer control EBIs.


Dicetyl phosphate-tetraethylenepentamine-based liposomes for systemic siRNA delivery.
Dicetyl phosphate-tetraethylenepentamine (DCP-TEPA) conjugate was newly synthesized and formed into liposomes for efficient siRNA delivery. Formulation of DCP-TEPA-based polycation liposomes (TEPA-PCL) complexed with siRNA was examined by performing knockdown experiments using stable EGFP-transfected HT1080 human fibrosarcoma cells and siRNA for GFP. An adequate amount of DCP-TEPA in TEPA-PCL and N/P ratio of TEPA-PCL/siRNA complexes were determined based on the knockdown efficiency. Then, the biodistribution of TEPA-PCL modified with poly(ethylene glycol) (PEG) was examined in BALB/c mice. As a result, TEPA-PCL modified with PEG6000 avoided reticuloendothelial system uptake and showed long circulation in the bloodstream. On the other hand, PEGylation of TEPA-PCL/siRNA complexes caused dissociation of a portion of the siRNA from the liposomes. However, we found that the use of cholesterol-conjugated siRNA improved the interaction between TEPA-PCL and siRNA, which allowed PEGylation of TEPA-PCL/siRNA complexes without siRNA dissociation. In addition, TEPA-PCL complexed with cholesterol-conjugated siRNA showed potent knockdown efficiency in stable luciferase-transfected B16-F10 murine melanoma cells. Finally, the biodistribution of cholesterol-conjugated siRNA formulated in PEGylated TEPA-PCL was examined by performing near-infrared fluorescence imaging in Colon26 NL-17 murine carcinoma-bearing mice. Our results showed that tumor targeting with siRNA via systemic administration was achieved by using PEGylated TEPA-PCL combined with active targeting with Ala-Pro-Arg-Pro-Gly, a peptide used for targeting angiogenic endothelium.


Management of postpneumonectomy empyema and bronchopleural fistula.
Empyema after pneumonectomy is often associated with a bronchopleural fistula (BDF) and has a significant mortality. Management options include systemic antibiotics and observation, adequate pleural drainage, appropriate parenteral antibiotics, removal of necrotic tissue, and obliteration of residual pleural space. We prefer to treat the empyema with the procedure originally described by Clagett and Geraci in 1963. They demonstrated that postpneumonectomy empyema could be successfully treated by open pleural drainage, frequent wet-to-dry dressing changes, and when the thorax was clean, secondary chest wall closure with obliteration of the pleural cavity with an antibiotic solution. Failure was most often caused by a persistent or recurrent fistula. Because of this, when a BPF is present, the original Clagett technique was modified to include transposition of a well-vascularized muscle to cover the stump at the time of open drainage to prevent further ischemia and necrosis. Our preference is intrathoracic transposition of extrathoracic skeletal muscle. The goals of therapy for postpneumonectomy empyema remain a healthy patient with a a healed chest wall and no evidence of drainage or infection. Excellent results can be obtained in more than 80% of patients by using the Clagett procedure and intrathoracic muscle transposition when a BPF is present.


Outcome of three screening questions for temporomandibular disorders (3Q/TMD) on clinical decision-making.
Patients with temporomandibular disorders (TMD) seem to go undetected and not adequately managed within dentistry. To identify these patients, three screening questions (3Q/TMD) have been introduced within dentistry in parts of Sweden. It is not known whether 3Q/TMD affects the clinical decision-making for these patients. The aim of this study was to evaluate the outcome of 3Q/TMD on the clinical decision-making and to analyse whether gender, age and the fee system the individual was assigned to were related to prescribed TMD treatment. This cohort study was carried out within the Public Dental Health service in Västerbotten, Sweden. As part of the routine dental check-up, a health declaration including 3Q/TMD was completed. The study population was randomly selected based on their 3Q/TMD answers. In total, 300 individuals with an affirmative answer to any of the 3Q/TMD, and 500 individuals with all negative answers were selected. The 3Q/TMD includes questions on weekly jaw-face-temple pain (Q1), pain on function (Q2) and catching/locking of the jaw (Q3). The 3Q/TMD was analysed in relation to prescribed treatment assessed from dental records. There was significantly more treatment performed or recommended for 3Q-positives (21·5%), compared to 3Q-negatives (2·2%) (P < 0·001). The odds ratio for TMD-related treatment for 3Q-positives versus 3Q-negatives was 12·1 (95% CI: 6·3-23·4). Although affirmative answers to the 3Q/TMD was related to TMD treatment, the majority of individuals with a screen positive still did not, according to dental records, receive assessment or treatment. Further studies are needed to better understand the clinical decision-making process for patients with TMD.


The collaborative health care team: the role of individual and group expertise.
Increasing costs of health care and rapid knowledge growth have led to collaboration among health care professionals to share knowledge and skills. To characterize the qualitative nature of team interaction and its relation to training health professionals, drawing on theoretical and analytical frameworks from the sociocognitive sciences. Activities in a primary care unit were monitored using observational field notes, hospital documents, and audio recordings of interviews and clinical interactions. The demarcation of responsibilities and roles of personnel within the team became fuzzy in practice. Continuous care was provided by primary care providers and specialized care by intermittent consultants. The nature of individual expertise required was a function of the patient problem and the interaction goal. These team characteristics contributed to the reduction of unnecessary and redundant interactions. Distributed responsibilities allow the team to process massive amounts of patient information, reducing the cognitive load on individuals. The uniqueness of individual professional expertise as it contributes to the accomplishment of team goals is highlighted, suggesting emphasis on conceptual competence in the development of individual professional education programs.


Evidence for direct physical association between a K+ channel (Kir6.2) and an ATP-binding cassette protein (SUR1) which affects cellular distribution and kinetic behavior of an ATP-sensitive K+ channel.
Structurally unique among ion channels, ATP-sensitive K+ (KATP) channels are essential in coupling cellular metabolism with membrane excitability, and their activity can be reconstituted by coexpression of an inwardly rectifying K+ channel, Kir6.2, with an ATP-binding cassette protein, SUR1. To determine if constitutive channel subunits form a physical complex, we developed antibodies to specifically label and immunoprecipitate Kir6.2. From a mixture of Kir6.2 and SUR1 in vitro-translated proteins, and from COS cells transfected with both channel subunits, the Kir6.2-specific antibody coimmunoprecipitated 38- and 140-kDa proteins corresponding to Kir6.2 and SUR1, respectively. Since previous reports suggest that the carboxy-truncated Kir6.2 can form a channel independent of SUR, we deleted 114 nucleotides from the carboxy terminus of the Kir6.2 open reading frame (Kir6.2deltaC37). Kir6.2deltaC37 still coimmunoprecipitated with SUR1, suggesting that the distal carboxy terminus of Kir6.2 is unnecessary for subunit association. Confocal microscopic images of COS cells transfected with Kir6.2 or Kir6.2deltaC37 and labeled with fluorescent antibodies revealed unique honeycomb patterns unlike the diffuse immunostaining observed when cells were cotransfected with Kir6.2-SUR1 or Kir6.2deltaC37-SUR1. Membrane patches excised from COS cells cotransfected with Kir6.2-SUR1 or Kir6.2deltaC37-SUR1 exhibited single-channel activity characteristic of pancreatic KATP channels. Kir6.2deltaC37 alone formed functional channels with single-channel conductance and intraburst kinetic properties similar to those of Kir6.2-SUR1 or Kir6.2deltaC37-SUR1 but with reduced burst duration. This study provides direct evidence that an inwardly rectifying K+ channel and an ATP-binding cassette protein physically associate, which affects the cellular distribution and kinetic behavior of a KATP channel.


Saving the split: the benefits of VATS thymectomy.
With the advent of minimally invasive techniques, the standard approaches to many surgeries have changed. We compared the financial costs and health care outcomes between standard thymectomy via sternotomy and video assisted thoracoscopic surgery (VATS). A 3-year review [2010-2012] of the National Inpatient Sample (NIS) was performed. All patients undergoing thymectomy were included. Patients undergoing VATS thymectomy were identified. Outcomes measured were hospital length of stay (LOS), hospital charges, and mortality. Univariate and multivariate analyses were performed to control for demographics and comorbidities. The results of 2,065 patients who underwent thymectomy were analyzed, of which 373 (18.1%) had VATS thymectomy and 1,692 (81.9%) had standard thymectomy. Mean age was 52.8±16, 42.5% were male, and 65.5% were Caucasian. There was a significant interval increase in number of patients undergoing VATS thymectomy (10% in 2010 vs. 19.2% in 2012, P<0.001). Patients undergoing standard thymectomy had longer hospital LOS (6.8±6.6 vs. 3.3d±3.4 d, P<0.001), hospital charges $88,838±$120,892 vs. $57,251±$54,929) and hospital mortality (0.9% vs. 0%, P=0.01). In multivariate analysis, thymectomy via sternotomy was independently associated with increased hospital LOS B =1.6 d, P<0.001) and charges (B = $13,041, P=0.041). Our study demonstrates decreased hospital length of stay and reduced hospital charges in patients undergoing VATS thymectomy compared to standard thymectomy. Our data demonstrates that the prevalence of VATS thymectomies is increasing, likely related to improved healthcare and financial outcomes.


Fatigue in patients receiving maintenance dialysis: a review of definitions, measures, and contributing factors.
Fatigue is a debilitating symptom or side effect experienced by many patients on long-term dialysis therapy. Fatigue has a considerable effect on patient health-related quality of life and is viewed as being more important than survival by some patients. Renal providers face many challenges when attempting to reduce fatigue in dialysis patients. The lack of a reliable, valid, and sensitive fatigue scale complicates the accurate identification of this symptom. Symptoms of daytime sleepiness and depression overlap with fatigue, making it difficult to target specific therapies. Moreover, many chronic health conditions common in the long-term dialysis population may lead to the development of fatigue and contribute to the day-to-day and diurnal variation in fatigue in patients. Key to improving the assessment and treatment of fatigue is improving our understanding of potential mediators, as well as potential therapies. Cytokines have emerged as an important mediator of fatigue and have been studied extensively in patients with cancer-related fatigue. In addition, although erythropoietin-stimulating agents have been shown to mitigate fatigue, the recent controversy regarding erythropoietin-stimulating agent dosing in patients with chronic kidney disease suggests that erythropoietin-stimulating agent therapy may not serve as the sole therapy to improve fatigue in this population. In conclusion, fatigue is an important and often underrecognized symptom in the dialysis population. Possible interventions for minimizing fatigue in patients on long-term dialysis therapy should aim at improving health care provider awareness, developing improved methods of measurement, understanding the pathogenesis better, and managing known contributing factors.


Left ventricular assist devices in the elderly: Marching forward with cautions.
Congestive heart failure is highly prevalent in the elderly population and left ventricular assist device (LVAD) has been increasingly used in this population. LVAD therapy is more costly than medical treatment but it increases the survival and quality of life of the elderly patients with low disease acuity. Therefore careful selection of candidates and implementation of LVAD therapy earlier in the course of the disease is crucial to improve outcomes. With the technical advances and improvement in clinical management, the financial burden of LVAD therapy in the elderly will become less, making this therapy more economically feasible.


Isolated canine mastocytoma cells: propagation and characterization of two cell lines.
Five different dog mastocytoma tumors were successfully transplanted and propagated in BALB/c nude mice. Cells from two of these tumors were passaged serially through at least four generations of mice without morphological or functional change. The average yield from a 2-cm tumor harvested from a mouse was 1.2 +/- 2.8 X 10(9) mast cells with greater than 90% viability. Cells of one line were larger and more heavily granulated than the other, and contained 1.29 +/- 0.74 pg histamine/cell (mean +/- SD). Calcium ionophore A23187 and compound 48/80 caused dose dependent histamine release with no significant difference in release from generation to generation. The smaller cells contained 0.06 +/- 0.06 pg histamine/cell. Histamine release after calcium ionophore or compound 48/80 was dose dependent and unchanged through serial passages. Following passive sensitization antigen caused dose-dependent histamine release confirming the presence of IgE receptors on these cells. In both cell lines histamine release was inhibited by terbutaline, dibutyryl adenosine 3',5'-cyclic monophosphate, or isobutylmethylxanthine. These methods provide a morphologically and functionally stable population of nearly pure canine mast cells for biochemical and physiological studies.


Effect of protein structure changes during different power ultrasound thawing on emulsification properties of common carp (Cyprinus carpio) myofibrillar protein.
The impact of ultrasound thawing (UT) at different power (0 W, 100 W/0.132 W·cm-2, 300 W/1.077 W·cm-2, and 500 W/1.997 W·cm-2, namely WT, UT-100, UT-300, and UT-500) on protein structure, aggregation, and emulsifying properties of common carp (Cyprinus carpio) myofibrillar protein were investigated in the present study. The result showed that the reactive sulfhydryl content, total sulfhydryl content, protein solubility, and absolute potential of UT-300 samples were obviously higher than those of other thawed samples, while the turbidity of UT-300 samples was lower (P < 0.05), which indicated that proper UT power was beneficial to inhibit protein aggregation caused by thawing, while too low (100 W) or too high (500 W) ultrasonic power had poor effect. The Ca2+-ATPase activity and thermal stability of UT-300 samples were much higher than those of other thawed samples (P < 0.05), indicating that UT-300 inhibited myosin denaturation and thermal stability reduction of thawed products. The α-helix content of UT-300 samples was higher than that of other thawed samples, while the β-sheet content was significantly lower than that of other thawed samples (P < 0.05). The fluorescence intensity of UT-300 samples was higher than that of other thawed samples, and the λmax of UT-300 samples and UT-100 samples were lower than that of other thawed samples, which indicated that UT-300 could effectively inhibit the alteration of protein secondary structure and tertiary structure during thawing. The emulsifying activity of UT-300 samples was significantly higher than that of WT samples, and the droplet diameter of UT-300 samples was also lower than that of WT samples (P < 0.05), which indicated that UT-300 inhibited the decrease of emulsifying property during thawing. Overall, moderate ultrasonic power (300 W) could effectively inhibit the protein aggregation and structural changes during thawing, led to the decrease of emulsifying activity.


Expectations towards alcohol consumption in school children between 8 and 12 years of age: a descriptive study.
The World Health Organization (WHO) indicates that the consumption of alcoholic beverages at social gatherings is common in many parts of the world and can have negative health and social consequences. Early initiation of alcohol use is a major risk factor for the development of patterns of abusive consumption of alcohol. To analyze the expectations towards alcohol consumption and to identify the age of onset of alcohol use in school children between 8 and 12 years of age. The study was exploratory, descriptive and cross-sectional. Data were collected from February to March, 2016, at the elementary schools Prof. Claudio Cortés Castro and Manuel Prieto Diaz in the city of Villahermosa, Tabasco. The questionnaire of expectations towards alcohol for children was applied. Sample size was 203 children. Twenty eight percent of children had consumed alcohol once in life; mean age of consumption onset was between 8 and 9 years old. Most frequently, the drink was beer, mostly provided by the father in places of family life. Among alcohol consumption expectations, dimensions scoring higher were aggressiveness and sociability and the dimension scoring lower was that of negative states. With respect to expectations towards alcohol consumption, children think that consuming alcohol promotes aggressive behavior followed by swear words, disturbing other people and discussing with them. In contrast, there are situations produced by alcohol consumption that children fail to appreciate, such as sadness and shame.


What are the major correlates of macronutrient selection in Western populations?
In order to better understand the factors that may influence and regulate the intake of the macronutrients carbohydrate, fat and protein a 7 d diet diary technique was employed to study eating behaviour in the natural environment of free-living human subjects. In general, factors that promote energy intake tend to promote fat and protein intake to a greater extent than carbohydrate intake. This increased intake occurs as the result of: environmental factors such as social facilitation and the time of day, week or lunar phase; subjective factors such as hunger and elation; individual difference factors such as obesity, restraint and ageing. There are indications that the intake of macronutrients is regulated by negative feedback systems. In the short term, the amount of protein remaining in the stomach at the onset of a meal appears to have a restraining effect on intake, especially protein intake. Over several days, macronutrient intake appears to be affected by a nutrient-specific delayed negative feedback. Protein intake during 1 d is negatively associated with protein intake 2 and 3 d later, while carbohydrate intake is negatively related to later carbohydrate intake, and fat intake to later fat intake; both peaking after a 2 d delay. Studies of the intakes of twins suggested that many aspects of the control of macronutrient intake are influenced by inheritance; these factors include the overall amounts ingested, the before-meal stomach contents and the responsiveness of the subject to the negative impact of the stomach contents. The results indicate that macronutrient intakes are regulated by multiple persistent processes that are to a large extent inherited.


Continuous attractors with morphed/correlated maps.
Continuous attractor networks are used to model the storage and representation of analog quantities, such as position of a visual stimulus. The storage of multiple continuous attractors in the same network has previously been studied in the context of self-position coding. Several uncorrelated maps of environments are stored in the synaptic connections, and a position in a given environment is represented by a localized pattern of neural activity in the corresponding map, driven by a spatially tuned input. Here we analyze networks storing a pair of correlated maps, or a morph sequence between two uncorrelated maps. We find a novel state in which the network activity is simultaneously localized in both maps. In this state, a fixed cue presented to the network does not determine uniquely the location of the bump, i.e. the response is unreliable, with neurons not always responding when their preferred input is present. When the tuned input varies smoothly in time, the neuronal responses become reliable and selective for the environment: the subset of neurons responsive to a moving input in one map changes almost completely in the other map. This form of remapping is a non-trivial transformation between the tuned input to the network and the resulting tuning curves of the neurons. The new state of the network could be related to the formation of direction selectivity in one-dimensional environments and hippocampal remapping. The applicability of the model is not confined to self-position representations; we show an instance of the network solving a simple delayed discrimination task.


Changes in plasma urea concentration can be used to determine protein requirements of two populations of pigs with different protein accretion rates.
The experiment had two objectives: 1) to determine the protein requirements of two strains of growing-finishing pigs based on growth performance, carcass characteristics, tissue accretion rates, and organ weights and 2) to evaluate whether protein requirements can be determined from changes in plasma urea concentration. Forty-six Gene Pool (GP) and 46 Hampshire (H) gilts with an initial BW of 28.5 kg were used. Pigs were allotted to two trials of a randomized complete block experiment with a 2 x 6 factorial arrangement of treatments. Five pigs from each strain were randomly selected and slaughtered at the beginning of each of the two trials. The remaining 72 pigs were individually penned and allotted to one of six dietary treatments (10, 13, 16, 19, 22, or 25% CP). Pigs remained on the experiment until the mean weight of a treatment group within each strain reached 115 kg (16 wk for GP and 14 wk for H), at which time all pigs of that strain were slaughtered. The only strain x protein level interactions that were detected were for carcass protein and water accretion rates. Gene Pool pigs grew less rapidly and utilized feed less efficiently than H pigs (P < .001). Average daily gain (quadratic, P < .05) and ADG/ADFI (quadratic, P < .05) were increased as protein level increased until a plateau was reached. Backfat depths were decreased (linear, P < .001) and longissimus muscle areas were increased (linear, P < .001) as protein level increased. Protein accretion rate was lower (P < .01) and fat accretion was higher (P < .01) in GP pigs than in H pigs. Protein accretion increased (quadratic, P < .001) and fat accretion decreased (linear, P < .001) with increasing dietary protein level. Examination of the response of plasma urea concentration over time suggested that GP pigs required 13% CP from 30 to 80 kg and 10% CP thereafter, whereas H pigs required 19% CP from 30 to 45 kg, 16% CP from 45 to 100 kg, and 13% CP thereafter.


Excretion of NaCl and KCl loads in mosquitoes. 2. Effects of the small molecule Kir channel modulator VU573 and its inactive analog VU342.
The effect of two small molecules VU342 and VU573 on renal functions in the yellow fever mosquito Aedes aegypti was investigated in vitro and in vivo. In isolated Malpighian tubules, VU342 (10 μM) had no effect on the transepithelial secretion of Na(+), K(+), Cl(-), and water. In contrast, 10 μM VU573 first stimulated and then inhibited the transepithelial secretion of fluid when the tubules were bathed in Na(+)-rich or K(+)-rich Ringer solution. The early stimulation was blocked by bumetanide, suggesting the transient stimulation of Na-K-2Cl cotransport, and the late inhibition of fluid secretion was consistent with the known block of AeKir1, an Aedes inward rectifier K(+) channel, by VU573. VU342 and VU573 at a hemolymph concentration of about 11 μM had no effect on the diuresis triggered by hemolymph Na(+) or K(+) loads. VU342 at a hemolymph concentration of 420 μM had no effect on the diuresis elicited by hemolymph Na(+) or K(+) loads. In contrast, the same concentration of VU573 significantly diminished the Na(+) diuresis by inhibiting the urinary excretion of Na(+), Cl(-), and water. In K(+)-loaded mosquitoes, 420 μM VU573 significantly diminished the K(+) diuresis by inhibiting the urinary excretion of K(+), Na(+), Cl(-), and water. We conclude that 1) the effects of VU573 observed in isolated Malpighian tubules are overwhelmed in vivo by the diuresis triggered with the coinjection of Na(+) and K(+) loads, and 2) at a hemolymph concentration of 420 μM VU573 affects Kir channels systemically, including those that might be involved in the release of diuretic hormones.


Gold Nanoparticles sensitize pancreatic cancer cells to gemcitabine.
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest solid cancers with dismal prognosis. Several mechanisms that are mainly responsible for aggressiveness and therapy resistance of PDAC cells include epithelial to mesenchymal transition (EMT), stemness and Mitogen Activated Protein Kinase (MAPK) signaling. Strategies that inhibit these mechanisms are critically important to improve therapeutic outcome in PDAC. In the current study, we wanted to investigate whether gold nanoparticles (AuNPs) could sensitize pancreatic cancer cells to the chemotherapeutic agent gemcitabine. We demonstrated that treatment with AuNPs of 20 nm diameter inhibited migration and colony forming ability of pancreatic cancer cells. Pre-treatment with AuNPs sensitized pancreatic cancer cells to gemcitabine in both viability and colony forming assays. Mechanistically, pre-treatment of pancreatic cancer cells with AuNPs decreased gemcitabine induced EMT, stemness and MAPK activation. Taken together, these findings suggest that AuNPs could be considered as a potential agent to sensitize pancreatic cancer cells to gemcitabine.


Purification from Tetrahymena thermophila of DNA polymerase and a protein which modifies its activity.
Two proteins, which may be involved in DNA replication, have been isolated and characterized from the eukaryote Tetrahymena thermophila. One of these proteins, DNA polymerase, has been purified to apparent homogeneity. The enzyme has a native molecular weight of approximately 90 000 in the presence of salt and aggregates to higher-molecular-weight forms in the absence of salt. Purified preparations of the enzyme yield a major subunit of Mr 45 000 when the protein is analyzed by denaturing electrophoresis. Tetrahymena DNA polymerase requires a divalent cation for catalysis and prefers gapped template-primers over denatured and native DNAs. A template-primer such as poly(dT) . oligo(A) can also be elongated by the DNA polymerase. However, the enzyme will not use poly(A) . oligo(dT) as a template-primer. Sulfhydryl-blocking reagents, such as N-ethylmaleimide, inhibit Tetrahymena DNA polymerase. The DNA polymerase lacks assayable levels of both single and double-stranded deoxyribonuclease activity. Throughout the early stages of purification the DNA polymerase chromatographs together with a protein of molecular weight 100 000. This protein, which yields a single major polypeptide of Mr 25 000 when analyzed by denaturing electrophoresis, has single-stranded-DNA-binding properties and has the ability to stimulate both the rate and extent of DNA-polymerase-catalyzed DNA synthesis in vitro. By virtue of this latter ability, the protein has been referred to as the M (for 'modifying') protein. Maximum stimulation of DNA polymerase was achieved with template-primers, which contained large stretches of single-stranded template such as poly(dA) . (dT)10 mixed in a template-to-primer ratio of one to one. Stimulation of DNA polymerase activity by M protein in vitro appears to involve formation of longer product DNA.


Biochemistry of S-layers.
During evolution prokaryotes have developed different envelope structures exterior to the cell wall proper. Among these surface components are regularly arranged S-layers and capsules. The structural characterization and the detailed chemical analysis of these surface molecules is a prerequisite to understand their biosynthesis and functional role(s) at the molecular level. Of particular interest are the glycosylated S-layer proteins which belong to the first prokaryotic glycoproteins ever described. Their characterization was performed on strains belonging to the thermophilic Bacillaceae and included structural studies and experiments to learn about the pathways for the glycan biosynthesis of S-layer glycoproteins. As an example for non-glycosylated S-layer proteins those of Lactobacillus helveticus strains are described in detail. Recently, a novel type of bacterial glycoconjugate was observed in the cell envelope of the extremely halophilic archaeon Natronococcus occultus which consists of a glycosylated polyglutamyl polymer. Beside the conventional biochemical techniques for the analysis new sophisticated instrumental methods such as X-ray photoelectron spectroscopy and matrix-assisted laser desorption ionization or electrospray ionization mass spectrometry have been introduced for the analysis of the protein and glycan portions of these cell surface macromolecules.


Transitional community adherence support for people leaving incarceration in South Africa: a pragmatic, open-label, randomised controlled trial.
People released from correctional facilities face multifactorial barriers to continuing HIV treatment. We hypothesised that barriers faced in the first 6 months of community re-entry would be decreased by a multilevel group-based and peer-led intervention, the Transitional Community Adherence Club (TCAC). We did a pragmatic, open-label, individually randomised controlled trial in five correctional facilities in Gauteng, South Africa. Participants aged 18 years and older and receiving antiretroviral therapy (ART) in correctional facilities were enrolled before release and randomly assigned (1:2) to either passive referral (usual care) or TCACs. TCACs followed a 12-session curriculum over 6 months and were facilitated by trained peer and social workers. Participants were followed up by telephone and in person to assess the primary outcome: post-release enrolment in HIV treatment services at 6 months from the date of release. We did an intention-to-treat analysis to determine the effectiveness of TCACs compared with usual care. The trial was registered with the South African National Clinical Trials Register (DOH-27-0419-605) and ClinicalTrials.gov (NCT03340428). This study is completed and is listed as such on ClinicalTrials.gov. From March 1, to Dec 13, 2019, we screened 222 individuals and enrolled 176 participants who were randomly assigned 1:2 to the usual care group (n=59) or TCACs (n=117). 175 participants were included in the final analysis. In the usual care group, 21 (36%) of 59 participants had enrolled in HIV treatment services at 6 months, compared with 71 (61%) of 116 in the TCAC group (risk ratio 1·7, 95% CI 1·2-2·5; p=0·0010). No adverse events were reported. We found strong evidence that a differentiated service delivery model with curriculum and peer support designed specifically to address the needs of people with HIV returning from incarceration improved the primary outcome of enrolment in HIV treatment services. Our approach is a reasonable model to build further HIV treatment continuity interventions for individuals in the criminal justice system in South Africa and elsewhere. National Institute of Mental Health.


A new species of Didogobius (Teleostei: Gobiidae) from the Canary Islands.
Didogobius helenae is described from the Canary Islands. It has a sensory papillae pattern that is consistent with the current diagnosis for Didogobius, but lacks all head canals and pores that are present in other members of the genus. Pores, in general, are replaced by large papillae. The species is defined by first dorsal fin VI; second dorsal fin I,10; anal fin I,9; pectoral fin 16-17; pelvic fin I,5 and disk shaped; lateral scales 28-30, cycloid at anterior, becoming ctenoid posteriorly; cycloid scales present on belly and posterior breast; predorsal region, cheek, operculum and base of pectoral fin without scales; lower most scale on the caudal fin-base with elongate, thickened ctenii along the upper and lower posterior edges. Color in life consists of four mottled, wide brown-orange bars separated by narrower white bars on the trunk, the cheek whitish with 5 more or less circular blotches of orange, outlined in dark brown and a black spot on ventral operculum. A key to the species is provided.


Methodological issues in cardiovascular epidemiology: the risk of determining absolute risk through statistical models.
During the past years there has been increasing interest in the development of cardiovascular disease functions that predict future events at individual level. However, this effort has not been so far very successful, since several investigators have reported large differences in the estimation of the absolute risk among different populations. For example, it seems that predictive models that have been derived from U.S. or north European populations overestimate the incidence of cardiovascular events in south European and Japanese populations. A potential explanation could be attributed to several factors such as geographical, cultural, social, behavioral, as well as genetic variations between the investigated populations in addition to various methodological, statistical, issues relating to the estimation of these predictive models. Based on current literature it can be concluded that, while risk prediction of future cardiovascular events is a useful tool and might be valuable in controlling the burden of the disease in a population, further work is required to improve the accuracy of the present predictive models.


[Diagnosis of labyrinthine fistula in patients suffering from otitis media purulenta chronica with cholesteatoma: informative value of different methods].
Informative content of different methods of labyrinthine fistulas (LF) diagnosis was assessed in 118 patients suffering from otitis media purulenta chronica (OMPC) with cholesteatoma which ran for 20 years and longer in 82.2% patients, 83.9% had fistula symptom. Unilateral hypoacusis was diagnosed in 68 (57.6%), bilateral--in 50 (42.4%) patients. Severity of vestibular disorders correlated positively with LF size and duration of the disease. Advanced LF was detected in 65 (55.1%) patients, multiple--in 7 (5.9%). Computed tomography of the temporal bone detected LF in all 29 OMPC examinees including "silent" fistulas. Thus, the disease history, clinically manifest fistula symptom and CT of the temporal bone are most informative for diagnosis of LF in OMPC with cholesteatoma.


Cytokine inhibitors and graft-versus-host disease.
Graft-versus-host disease (GVHD) remains the major complication of allogeneic bone marrow transplantation. T cells in donor bone marrow recognize and react to host alloantigens and thereby initiate GVHD, but the precise mechanisms by which host tissues are damaged remain unclear. Recently, several convergent lines of evidence suggested that inflammatory cytokines act as mediators of acute GVHD. Most of the clinical manifestations of GVHD may, in fact, be due to the dysregulated production of cytokines by T cells and other inflammatory cells. The complex interactions among cytokines and their cellular targets suggest that individual cytokines may play an important and distinctive role in the pathophysiology of GVHD. Perturbation of the cytokine network may function as a final common pathway of target organ damage, and the rapid onset of severe, acute GVHD can be considered a "cytokine storm."


Toward the single-hour high-quality genome.
Today, resequencing of a human genome can be performed in approximately a week using a single instrument. Thanks to a steady logarithmic rate of increase in performance for DNA sequencing platforms over the past seven years, DNA sequencing is one of the fastest developing technology fields. As the process becomes faster, it opens up possibilities within health care, diagnostics, and entirely new fields of research. Immediate genetic characterization of contagious outbreaks has been exemplified, and with such applications for the direct benefit of human health, expectations of future sensitive, rapid, high-throughput, and cost-effective technologies are steadily growing. Simultaneously, some of the limitations of a rapidly growing field have become apparent, and questions regarding the quality of some of the data deposited into databases have been raised. A human genome sequenced in only an hour is likely to become a reality in the future, but its definition may not be as certain.


The triggering of myocardial infarction by fine particles is enhanced when particles are enriched in secondary species.
Previous studies have reported an increased risk of myocardial infarction (MI) associated with acute increases in PM concentration. Recently, we reported that MI/fine particle (PM2.5) associations may be limited to transmural infarctions. In this study, we retained data on hospital discharges with a primary diagnosis of acute myocardial infarction (using International Classification of Diseases ninth Revision [ICD-9] codes), for those admitted January 1, 2004 to December 31, 2006, who were ≥ 18 years of age, and were residents of New Jersey at the time of their MI. We excluded MI with a diagnosis of a previous MI and MI coded as a subendocardial infarction, leaving n = 1563 transmural infarctions available for analysis. We coupled these health data with PM2.5 species concentrations predicted by the Community Multiscale Air Quality chemical transport model, ambient PM2.5 concentrations, and used the same case-crossover methods to evaluate whether the relative odds of transmural MI associated with increased PM2.5 concentration is modified by the PM2.5 composition/mixture (i.e., mass fractions of sulfate, nitrate, elemental carbon, organic carbon, and ammonium). We found the largest relative odds estimates on the days with the highest tertile of sulfate mass fraction (OR = 1.13; 95% CI = 1.00, 1.27), nitrate mass fraction (OR = 1.18; 95% CI = 0.98, 1.35), and ammonium mass fraction (OR = 1.13; 95% CI = 1.00 1.28), and the lowest tertile of EC mass fraction (OR = 1.17; 95% CI = 1.03, 1.34). Air pollution mixtures on these days were enhanced in pollutants formed through atmospheric chemistry (i.e., secondary PM2.5) and depleted in primary pollutants (e.g., EC). When mixtures were laden with secondary PM species (sulfate, nitrate, and/or organics), we observed larger relative odds of myocardial infarction associated with increased PM2.5 concentrations. Further work is needed to confirm these findings and examine which secondary PM2.5 component(s) is/are responsible for an acute MI response.


Intelligence and Verbal Short-Term Memory/Working Memory: Their Interrelationships from Childhood to Young Adulthood and Their Impact on Academic Achievement.
Although recent developmental studies exploring the predictive power of intelligence and working memory (WM) for educational achievement in children have provided evidence for the importance of both variables, findings concerning the relative impact of IQ and WM on achievement have been inconsistent. Whereas IQ has been identified as the major predictor variable in a few studies, results from several other developmental investigations suggest that WM may be the stronger predictor of academic achievement. In the present study, data from the Munich Longitudinal Study on the Genesis of Individual Competencies (LOGIC) were used to explore this issue further. The secondary data analysis included data from about 200 participants whose IQ and WM was first assessed at the age of six and repeatedly measured until the ages of 18 and 23. Measures of reading, spelling, and math were also repeatedly assessed for this age range. Both regression analyses based on observed variables and latent variable structural equation modeling (SEM) were carried out to explore whether the predictive power of IQ and WM would differ as a function of time point of measurement (i.e., early vs. late assessment). As a main result of various regression analyses, IQ and WM turned out to be reliable predictors of academic achievement, both in early and later developmental stages, when previous domain knowledge was not included as additional predictor. The latter variable accounted for most of the variance in more comprehensive regression models, reducing the impact of both IQ and WM considerably. Findings from SEM analyses basically confirmed this outcome, indicating IQ impacts on educational achievement in the early phase, and illustrating the strong additional impact of previous domain knowledge on achievement at later stages of development.


Intronic Alus influence alternative splicing.
Examination of the human transcriptome reveals higher levels of RNA editing than in any other organism tested to date. This is indicative of extensive double-stranded RNA (dsRNA) formation within the human transcriptome. Most of the editing sites are located in the primate-specific retrotransposed element called Alu. A large fraction of Alus are found in intronic sequences, implying extensive Alu-Alu dsRNA formation in mRNA precursors. Yet, the effect of these intronic Alus on splicing of the flanking exons is largely unknown. Here, we show that more Alus flank alternatively spliced exons than constitutively spliced ones; this is especially notable for those exons that have changed their mode of splicing from constitutive to alternative during human evolution. This implies that Alu insertions may change the mode of splicing of the flanking exons. Indeed, we demonstrate experimentally that two Alu elements that were inserted into an intron in opposite orientation undergo base-pairing, as evident by RNA editing, and affect the splicing patterns of a downstream exon, shifting it from constitutive to alternative. Our results indicate the importance of intronic Alus in influencing the splicing of flanking exons, further emphasizing the role of Alus in shaping of the human transcriptome.


Interventions for maintenance of surgically induced remission in Crohn's disease: a network meta-analysis.
Crohn's disease (CD) is a chronic disease of the gut. About 75% of people with CD undergo surgery at least once in their lifetime to induce remission. However, as there is no known cure for the disease, patients usually experience a recurrence even after surgery. Different interventions are routinely used in maintaining postsurgical remission. There is currently no consensus on which treatment is the most effective. To assess the effects and harms of interventions for the maintenance of surgically induced remission in Crohn's disease and rank the treatments in order of effectiveness. We searched the Cochrane IBD Group Specialized Register, CENTRAL, MEDLINE, and Embase from inception to 15 January 2019. We also searched reference lists of relevant articles, abstracts from major gastroenterology meetings, ClinicalTrials.gov, and the WHO ICTRP. There was no restriction on language, date, or publication status. We considered for inclusion randomised controlled trials (RCTs) that compared different interventions used for maintaining surgically induced remission in people with CD who were in postsurgical remission. Participants had to have received maintenance treatment for at least three months. We excluded studies assessing enteral diet, diet manipulation, herbal medicine, and nutritional supplementation. Two review authors independently selected relevant studies, extracted data, and assessed the risk of bias. Any disagreements were resolved by discussion or by arbitration of a third review author when necessary. We conducted a network meta-analysis (NMA) using a Bayesian approach through Markov Chain Monte Carlo (MCMC) simulation. For the pairwise comparisons carried out in Review Manager 5, we calculated risk ratios (RR) with their corresponding 95% confidence intervals (95% CI). For the NMA, we presented hazard ratios (HR) with corresponding 95% credible intervals (95% CrI) and reported ranking probabilities for each intervention. For the NMA, we focused on three main outcomes: clinical relapse, endoscopic relapse, and withdrawals due to adverse events. Data were insufficient to assess time to relapse and histologic relapse. Adverse events and serious adverse events were not sufficiently or objectively reported to permit an NMA. We used CINeMA (Confidence in Network Meta-Analysis) methods to evaluate our confidence in the findings within networks, and GRADE for entire networks. We included 35 RCTs (3249 participants) in the review. The average age of study participants ranged between 33.6 and 38.8 years. Risk of bias was high in 18 studies, low in four studies, and unclear in 13 studies. Of the 35 included RCTs, 26 studies (2581 participants; 9 interventions) were considered eligible for inclusion in the NMA. The interventions studied included 5-aminosalicylic acid (5-ASA), adalimumab, antibiotics, budesonide, infliximab, probiotics, purine analogues, sulfasalazine, and a combination of sulfasalazine and prednisolone. This resulted in 30 direct contrasts, which informed 102 mixed-treatment contrasts.The evidence for the clinical relapse network (21 studies; 2245 participants) and endoscopic relapse (12 studies; 1128 participants) were of low certainty while the evidence for withdrawal due to adverse events (15 studies; 1498 participants) was of very low certainty. This assessment was due to high risk of bias in most of the studies, inconsistency, and imprecision across networks. We mainly judged individual contrasts as of low or very low certainty, except 5-ASA versus placebo, the evidence for which was judged as of moderate certainty.We ranked the treatments based on effectiveness and the certainty of the evidence. For clinical relapse, the five most highly ranked treatments were adalimumab, infliximab, budesonide, 5-ASA, and purine analogues. We found some evidence that adalimumab (HR 0.11, 95% Crl 0.02 to 0.33; low-certainty evidence) and 5-ASA may reduce the probability of clinical relapse compared to placebo (HR 0.69, 95% Crl 0.53 to 0.87; moderate-certainty evidence). However, budesonide may not be effective in preventing clinical relapse (HR 0.66, 95% CrI 0.27 to 1.34; low-certainty evidence). We are less confident about the effectiveness of infliximab (HR 0.36, 95% CrI 0.02 to 1.74; very low-certainty evidence) and purine analogues (HR 0.75, 95% CrI 0.55 to 1.00; low-certainty evidence). It was unclear whether the other interventions reduced the probability of a clinical relapse, as the certainty of the evidence was very low.Due to high risk of bias and limited data across the network, we are uncertain about the effectiveness of interventions for preventing endoscopic relapse. Whilst there might be some evidence of prevention of endoscopic relapse with adalimumab (HR 0.10, 95% CrI 0.01 to 0.32; low-certainty evidence), no other intervention studied appeared to be effective.Due to high risk of bias and limited data across the network, we are uncertain about the effectiveness of interventions for preventing withdrawal due to adverse events. Withdrawal due to adverse events appeared to be least likely with sulfasalazine (HR 1.96, 95% Crl 0.00 to 8.90; very low-certainty evidence) and most likely with antibiotics (HR 53.92, 95% Crl 0.43 to 259.80; very low-certainty evidence). When considering the network as a whole, two adverse events leading to study withdrawal (i.e. pancreatitis and leukopenia) occurred in more than 1% of participants treated with an intervention. Pancreatitis occurred in 2.8% (11/399) of purine analogue participants compared to 0.17% (2/1210) of all other groups studied. Leukopenia occurred in 2.5% (10/399) of purine analogue participants compared to 0.08% (1/1210) of all other groups studied. Due to low-certainty evidence in the networks, we are unable to draw conclusions on which treatment is most effective for preventing clinical relapse and endoscopic relapse. Evidence on the safety of the interventions was inconclusive, however cases of pancreatitis and leukopenia from purine analogues were evident in the studies. Larger trials are needed to further understand the effect of the interventions on endoscopic relapse.


Is advanced maternal age an independent risk factor for uteroplacental insufficiency?
To determine whether maternal age 35 years or older is an independent risk factor for uteroplacental insufficiency and thus an independent indication for antepartum testing. A retrospective cohort analysis was performed of all deliveries at Los Angeles County-University of Southern California Women's and Children's Hospital between August 1, 1995, and September 1, 2003. Women with documented indications for antepartum testing, fetal anomalies, or delivery prior to 34 weeks were excluded from analysis. Markers of uteroplacental insufficiency included stillbirth, birth weight less than the 10th percentile, fetal distress, cesarean section for fetal distress, oligohydramnios, meconium passage, and 5-minute Apgar score less than 7. Indications for antepartum testing were significantly more common in women 35 years or older (33.2% versus 27.0%). After excluding women with indications for antepartum testing, anomalous fetuses, and women delivering prior to 34 weeks, stillbirth was twice as common in women 35 years and older. However, among stillbirths, growth restriction occurred with similar frequency in the older (28.6%) and younger (25.0%) cohorts. Among live births, 2 markers of uteroplacental insufficiency, intrapartum fetal distress (5.7% versus 4.1%) and cesarean delivery for fetal distress (4.0% versus 2.4%) were significantly more common in the older cohort. All other markers of uteroplacental insufficiency were observed with similar frequency in the 2 groups. After excluding women with other indications for antepartum testing, fetal anomalies, and delivery prior to 34 weeks, stillbirth was twice as common in women 35 years of age or older as in those younger than 35 years. The increased rate of stillbirth does not appear to be explained by a higher rate of uteroplacental insufficiency.


Obesity, weight loss, and the polycystic ovary syndrome: effect of treatment with diet and orlistat for 24 weeks on insulin resistance and androgen levels.
To investigate the combined effect of diet and orlistat, for 24 weeks, on anthropometric features, hormonal parameters, and indices of insulin resistance in obese women with polycystic ovary syndrome (PCOS) and in obese women without the syndrome. Prospective clinical study. Department of obstetrics and gynecology in a major university in Greece. Eighteen selected women with PCOS were matched for age and body mass index with 14 obese control women. Subjects were prescribed an energy-restricted diet, and orlistat (120 mg, 3 times per d) was administered to all subjects for 24 weeks. At baseline, week 12, and week 24, after an overnight fast, blood samples were collected, and serum levels of FSH, LH, PRL, T, Delta(4)A, DHEAS, 17 alpha-hydroxyprogesterone, sex hormone-binding globulin, glucose, and insulin were measured. Testosterone levels were significantly decreased with treatment in women with PCOS; this decrease was attributed to the first trimester, whereas T levels did not change during the second 12-week period. In women with PCOS, insulin levels and HOMA-IR values were decreased during the first 12 weeks, whereas no significant change was observed during the second trimester. Orlistat administration, combined with diet, for 24 weeks, resulted in significant weight loss and improvement of insulin resistance in obese women, with or without PCOS. Moreover, T levels were significantly decreased in women with PCOS. There appears to be a trend during the first 12-week period for greater improvement of metabolic and hormonal parameters in women with PCOS.


Opinions and practices of clinicians associated with continuation of exclusive breastfeeding.
The American Academy of Pediatrics recommends exclusive breastfeeding for the first 6 months of life. Recent statistics indicate that initiation and maintenance of exclusive breastfeeding are low in the United States. Unfortunately, little information is available on how clinicians and health care organizations can best promote continuation of exclusive breastfeeding. To identify clinicians' opinions and management practices that are associated with continuation of exclusive breastfeeding. We conducted a prospective cohort study of low-risk mother-newborn pairs in a large, multispecialty group practice in which the mother was breastfeeding at 4 weeks. Mothers completed telephone interviews at 4 and 12 weeks postpartum, and their data were linked with their obstetric and pediatric clinicians' responses to a cross-sectional mailed survey conducted during the same time period. Obstetric and pediatric clinicians included medical doctors, nurse practitioners, and nurse midwives. Overall response rates were 63% for mothers and 82% for clinicians (54 obstetric and 67 pediatric clinicians). Bivariate and multivariate analyses were conducted to identify the characteristics of clinicians and mothers that predicted exclusive breastfeeding at 12 weeks. Of the 288 mothers who were breastfeeding at 4 weeks and had a complete 12-week interview, 152 (53%) were exclusively breastfeeding their infants at 12 weeks. Mothers who discontinued exclusive breastfeeding were more likely to have experienced problems with their infant latching on or sucking (odds ratio [OR]: 3.8; 95% confidence interval [CI]: 1.5-9.7) or report that a health care provider recommended formula supplementation (OR: 2.3; 95% CI: 1.1-5.0). Clinicians reported limited time during preventive visits to address breastfeeding problems as a very important barrier to promoting breastfeeding. Obstetric providers were least confident in resolving problems with mothers not producing enough breast milk. Pediatric providers were least confident in resolving problems with breast pain or tenderness or cracked or painful nipples. In the final multivariate model, mothers whose pediatric providers recommended formula supplementation if an infant was not gaining enough weight (OR: 3.2; 95% CI: 1.04, 9.7) or who considered their advice to mothers on breastfeeding duration to be not very important (OR: 2.2; 95% CI: 1.2-3.9) were more likely to have discontinued exclusive breastfeeding by 12 weeks postpartum. Black mothers were significantly more likely to discontinue exclusive breastfeeding by 12 weeks. Clinicians' practices regarding formula supplementation of healthy infants and their opinions about the importance of their breastfeeding advice are associated with the likelihood that mothers will continue exclusive breastfeeding. Policies to enhance clinicians' abilities to address breastfeeding problems within the constraints of busy practices could improve their ability to support exclusive breastfeeding.


Electrically induced potentiation of eighth nerve responses.
Whole-nerve potentials were recorded from a total of 42 anesthetized cats using a 25-micron electrode in the 8th nerve as it exits from the internal auditory meatus, in response to acoustic clicks across an 80-db range. Biphasic electric pulses, 0.5 msec in duration, 100/sec for 5-10 min, at 100 microamps, were delivered by the 8th nerve electrode. Potentiation of responses to acoustic clicks was observed in amplitude, latency, and duration when comparing sets of pre- vs post-stimulation output. High consistency was achieved. These data were corroborated by recording output also from the round window, and by auditorily evoked brainstem far field potentials with a subcutaneous electrode. Control experiments such as ablation of AI, AII, EP, and IT, resection of the inferior colliculus, the crossed olivocochlear bundle, and middle-ear muscles, determined that electric potentiation was a local effect. Furthermore, the usual electric pulses applied to an electrode on the round window had no potentiating effect. Electric stimulation had a significant effect at the .001 level in increasing amplitude of response. Latency of N1 was shortened by 0.2 msec. Potentiation persisted for up to 3 hrs. An unexpected result was potentiation of 8th nerve and brainstem nuclei responses after acoustic stimulation of the contralateral ear; electric stimulation may induce a more active involvement of efferent activity originating in the superior olive or more rostrally. The interpretation of how such changes might affect perception after, for example, long term stimulation of neurons by a prosthesis is difficult to make without behavioral corroboration. The amplitude change of the whole-nerve action potentials are rough indicators of relative loudness. Thus an accentuated loudness may be experienced over time as equivalent intensities tend, as in these cats, to elicit greater response. The long time constancy of the decay, on the other hand, could tend to maintain a consistency of such potentiated responses and thus create no real variability in perception over time. The shortened latency could mean an involvement of higher frequency perception, but how this might be translated into a change in, for example, intelligibility of speech it is not possible to infer at this time.


Urban vegetation and heat-related mortality in Seoul, Korea.
Urban areas are particularly vulnerable to heat-related health outcomes. Simultaneous trends of climate change and urbanization may increase the urban heat-related health burden. We investigated the effects of urban vegetation on heat-related mortality, and evaluated whether different levels of vegetation and individuals' characteristics affect the temperature-mortality associations within Seoul, Korea 2000-2009. We used Normalized Difference Vegetation Index (NDVI) to assess the urban vegetation within Seoul. We applied an overdispersed Poisson generalized linear model with interaction term between temperature and indicator of NDVI group (categorized in 3 levels) to assess the effect modification of the temperature-mortality association by urban vegetation. We conducted stratified analysis to explore whether associations are affected by individual characteristics of sex and age. The association between total mortality and a 1°C increase in temperature above the 90th percentile (25.1°C) (the "heat effect") was the highest for gus with low NDVI. The heat effect was a 4.1% (95% confidence interval (CI) 2.3, 5.9%), 3.0% (95% CI 0.2, 5.9%), and 2.2% (95% CI -0.5, 5.0%) increase in mortality risk for low, medium, and high NDVI group, respectively. Estimated risks showed similar effects by sex and age. Our findings suggest a higher mortality effect of high temperature in areas with lower vegetation in Seoul, Korea.


Purification capability of tobacco transformed with enzymes from a methylotrophic bacterium for formaldehyde.
Plants have the ability to remediate environmental pollution. Especially, they have a high purification capability for airpollution. We have measured the purification characteristics of foliage plants for indoor airpollutants--for example, formaldehyde (HCHO), toluene, and xylene--using a tin oxide gas sensor. HCHO is an important intermediate for biological fixation of C1 compounds in methylotrophs. The ribulose monophosphate pathway of HCHO fixation is inherent in many methylotrophic bacteria, which can grow on Cl compounds. Two genes for the key enzymes, HPS and PHI, from the methylotrophic bacterium Mycobacterium gastri MB19 were introduced into tobacco. In this article, the HCHO-removal characteristic of the transformant was examined by using the gas sensor in order to evaluate quantitatively. The purification characteristics of the transformant for toluene, xylene, and styrene were also measured. The results confirmed an increase of 20% in the HCHO-removal capability. The differences of the purification capabilities for toluene, xylene, and styrene were not recognized.


Arthritis associated with gluten-sensitive enteropathy.
A 15-year-old girl, with synovitis of the knees and ankles for 3 years before a diagnosis of gluten-sensitive enteropathy, is described. The enteropathy was confirmed histologically and on the basis of a clinical response to a gluten-free diet. The arthritis also resolved promptly, suggesting that it was associated with the bowel disorder.


Dpp-induced Egfr signaling triggers postembryonic wing development in Drosophila.
The acquisition of flight contributed to the success of insects and winged forms are present in most orders. Key to understanding the origin of wings will be knowledge of the earliest postembryonic events promoting wing outgrowth. The Drosophila melanogaster wing is intensely studied as a model appendage, and yet little is known about the beginning of wing outgrowth. Vein (Vn) is a neuregulin-like ligand for the EGF receptor (Egfr), which is necessary for global development of the early Drosophila wing disc. vn is not expressed in the embryonic wing primordium and thus has to be induced de novo in the nascent larval wing disc. We find that Decapentaplegic (Dpp), a Bone Morphogenetic Protein (BMP) family member, provides the instructive signal for initiating vn expression. The signaling involves paracrine communication between two epithelia in the early disc. Once initiated, vn expression is amplified and maintained by autocrine signaling mediated by the E-twenty six (ETS)-factor PointedP2 (PntP2). This interplay of paracrine and autocrine signaling underlies the spatial and temporal pattern of induction of Vn/Egfr target genes and explains both body wall development and wing outgrowth. It is possible this gene regulatory network governing expression of an EGF ligand is conserved and reflects a common origin of insect wings.


[From a mammographic station to the organization of the Federal Mammologic Center].
The history of radiation application for breast cancer diagnosis in Russia is illustrated by an experience gained at the Center. It was concerned with designing specialized X-ray equipment as well as development of Standards to be used at mammographic stations. Teaching programs were devised for training X-ray diagnosis specialists with all necessary qualification to operate high-tech equipment of a mammographic station and to use a wide range of radiation and invasive procedures.


Efficacy of an Empowerment-Based, Group-Delivered HIV Prevention Intervention for Young Transgender Women: The Project LifeSkills Randomized Clinical Trial.
The incidence of HIV infection among transgender women in the United States is extremely high, with young transgender women (YTW) at highest risk; condomless sex is the primary risk behavior for transmission. However, there are no published randomized clinical trials to date examining interventions to reduce sexual risk for HIV acquisition and transmission within this group. To determine the efficacy of a culturally specific, empowerment-based, and group-delivered behavioral prevention intervention to reduce sexual risk for HIV acquisition and transmission in sexually active YTW aged 16 to 29 years. Randomized clinical efficacy trial of Project LifeSkills, a group-delivered, behavioral HIV prevention intervention, vs standard of care conducted among 190 sexually active YTW between March 26, 2012, and August 15, 2016, at community-based locations in Boston, Massachusetts, and Chicago, Illinois, to reduce sexual risk for HIV acquisition or transmission. Data analysis was by a modified intention-to-treat approach. Participants were randomized (approximately 2:2:1) to the LifeSkills intervention (n = 116), standard of care only (n = 74), or a diet and nutrition time- and attention-matched control (attention control) arm (n = 43). The attention control arm was dropped during active enrollment per the Data Safety and Monitoring Board's recommendation. The LifeSkills intervention was delivered in six 2-hour sessions spanning a 3-week period. Primary outcome was change in the number of self-reported condomless anal or vaginal sex acts in the 4 months before the baseline assessment and that reported at the 4-, 8-, and 12-month visits. Of the 190 study participants, the mean (SD) age was 23.4 (3.4) years (range, 16-29 years); 47 (24.7%) were white, 83 (43.7%) were black or African American, 25 (13.2%) were Hispanic or Latina, and 35 (18.4%) were another race/ethnicity. From baseline to 4 months, the LifeSkills group had a 30.8% greater mean (SE) reduction in condomless sex acts (2.26 [0.40] at baseline vs 1.22 [0.22] at 4 months) compared with the standard of care group (2.69 [0.59] at baseline vs 2.10 [0.47] at 4 months) (risk ratio [RR], 0.69; 95% CI, 0.60-0.80; P < .001). Similarly, the LifeSkills group had a 39.8% greater mean (SE) reduction in condomless sex acts at the 12-month follow-up visit compared with the standard of care group (0.71 [0.13] vs 1.40 [0.32]; RR, 0.60; 95% CI, 0.50-0.72; P < .001). Among YTW at sexual risk of HIV acquisition or transmission, the LifeSkills intervention resulted in a 39.8% greater mean reduction in condomless sex acts during the 12-month follow-up in comparison to the standard of care group. This trial is the first to date to demonstrate evidence of efficacy for a behavioral intervention to reduce sexual risk in YTW. ClinicalTrials.gov Identifier: NCT01575938.


Large-scale linkage analysis of 1302 affected relative pairs with rheumatoid arthritis.
Rheumatoid arthritis is the most common systematic autoimmune disease and its etiology is believed to have both strong genetic and environmental components. We demonstrate the utility of including genetic and clinical phenotypes as covariates within a linkage analysis framework to search for rheumatoid arthritis susceptibility loci. The raw genotypes of 1302 affected relative pairs were combined from four large family-based samples (North American Rheumatoid Arthritis Consortium, United Kingdom, European Consortium on Rheumatoid Arthritis Families, and Canada). The familiality of the clinical phenotypes was assessed. The affected relative pairs were subjected to autosomal multipoint affected relative-pair linkage analysis. Covariates were included in the linkage analysis to take account of heterogeneity within the sample. Evidence of familiality was observed with age at onset (p << 0.001) and rheumatoid factor (RF) IgM (p << 0.001), but not definite erosions (p = 0.21). Genome-wide significant evidence for linkage was observed on chromosome 6. Genome-wide suggestive evidence for linkage was observed on chromosomes 13 and 20 when conditioning on age at onset, chromosome 15 conditional on gender, and chromosome 19 conditional on RF IgM after allowing for multiple testing of covariates.


Genetic structure and demographic history of new world screwworm across its current geographic range.
The phylogeographical history of the pest fly screwworm, Cochliomyia hominivorax (Coquerel), was studied using partial mitochondrial DNA sequences of the control region, Cytochrome c oxidase (CO) subunit I and CO subunit II from 361 individuals collected across its current geographic range. Analyses showed marked genetic differentiation on a macrogeographic scale. The genetic diversity in the species is structured into four main "regional groups," corresponding to Cuba, the Dominican Republic, and the North and South Amazon region. Results indicated that the distribution of screwworm genetic diversity was mainly shaped by historical events, i.e., colonization of Caribbean islands, vicariance in the Amazon region and population expansion. Demographic history analyses revealed that the population expansion started approximately 20-25,000 yr ago and recently increased exponentially. We hypothesized that the initial period of expansion was probably associated with environmental amelioration in the late Pleistocene and the exponential increase with resource availability in recent times. The population expansion is probably responsible for the low divergence and the lack of genetic and geographic correlation in the South Amazon region but did not erase the genetic structure pattern on a continental scale. The screwworm is one of the most damaging livestock pests in South and Central America, and the pattern of genetic variability distribution reported here suggests that the Caribbean area and the North and South Amazon regions could be considered as independent units for future pest control programs.


Differential regulation of HIC1 target genes by CtBP and NuRD, via an acetylation/SUMOylation switch, in quiescent versus proliferating cells.
The tumor suppressor gene HIC1 encodes a transcriptional repressor involved in regulatory loops modulating P53-dependent and E2F1-dependent cell survival, growth control, and stress responses. Despite its importance, few HIC1 corepressors and target genes have been characterized thus far. Using a yeast two-hybrid approach, we identify MTA1, a subunit of the NuRD complex, as a new HIC1 corepressor. This interaction is regulated by two competitive posttranslational modifications of HIC1 at lysine 314, promotion by SUMOylation, and inhibition by acetylation. Consistent with the role of HIC1 in growth control, we demonstrate that HIC1/MTA1 complexes bind on two new target genes, Cyclin D1 and p57KIP2 in quiescent but not in growing WI38 cells. In addition, HIC1/MTA1 and HIC1/CtBP complexes differentially bind on two mutually exclusive HIC1 binding sites (HiRE) on the SIRT1 promoter. SIRT1 transcriptional activation induced by short-term serum starvation coincides with loss of occupancy of the distal sites by HIC1/MTA1 and HIC1/CtBP. Upon longer starvation, both complexes are found but on a newly identified proximal HiRE that is evolutionarily conserved and specifically enriched with repressive histone marks. Our results decipher a mechanistic link between two competitive posttranslational modifications of HIC1 and corepressor recruitment to specific genes, leading to growth control.


Interobserver variability in angiographic measurement and morphologic characterization of intracranial aneurysms: a report from the International Study of Unruptured Intracranial Aneurysms.
To determine the variability in assessment of the principal inherent characteristics of intracranial aneurysms through the evaluation of interobserver variability for material with uniform quality. Blinded interpretations of a single set of cerebral arteriograms of 55 aneurysms were evaluated by several statistical approaches. Excellent correlations were found for the detection and measurement of aneurysms after adjusting for geometric distortion caused by magnification. Progressively decreasing correspondence was found for factors that characterized morphology, including, in order, determination of margins, assessment of accessory appendages, and identification of a neck. Correction for geometric distortion was the most critical factor that influenced uniform measurement of size. Standards for measurement and morphologic characteristics were subsequently established for use in the International Study of Unruptured Intracranial Aneurysms.


Microplastics in Tampa Bay, Florida: Abundance and variability in estuarine waters and sediments.
This study provides the first measurement of microplastic abundance and distribution in surface waters and sediments in Tampa Bay, FL. Microplastic concentrations in discrete water samples ranged from 0.25 to 7.0 particles/L with an average of 0.94 (±0.52) particles/L. Samples taken with a 330 μm plankton net had 1.2-18.1 particles/m3 with an average of 4.5 (±2.3) particles/m3. Discrete samples were 200 times higher than net samples, suggesting substantial losses or undersampling with the net. For both discrete and plankton tow samples, there were no significant differences in concentrations between stations or regions. Intense rainfall events in the summer always preceded samples with substantially higher counts. Most (>75%) microplastics were fibers. Using an average value of 1 particle/L, Tampa Bay contains ~4 billion microplastic particles. Surface sediments had an average of 280 (±290) particles/kg, ranging from 30 to 790 particles/kg. Highest concentrations of microplastics were found in sediments close to industrial sources; lowest values in Middle and Lower Tampa Bay are consistent with shorter residence times.


A psychoanalytic concept of metaphor.
Metaphor is defined as seeing something in terms of something else. Psychoanalysis sees the present in terms of the past and the past in terms of the present. It therefore relates past and present metaphorically to each other, which implies that both metaphor parts change each other. This view entails a broadening of the linguistic metaphor concept towards a supralinguistic, here psychoanalytic, one: metaphor is not only a phenomenon of language but of mentation; its units are not only words but psychodynamics. Familiar concepts of psychoanalytic theory are recast in the light of this psychoanalytic concept of metaphor. Symptoms are seen as the analysand's damaged ability to metaphorise past and present. Using interpretation the analyst helps the analysand to restore metaphorical processes that have been interrupted in their flow from the past to the present and from the present to the past. Metaphor restores the polysemy that is lost in neurotic suffering. The metaphorical processes within psychoanalysis are seen as common to all psychoanalytic schools that focus on the analysis of transference. The increasing attention the concept of metaphor is receiving within psychoanalysis is seen as related to a trend in today's science to more from objective categories to experiential ones.


A study of 2D GeI2/InTe van der Waals hetero bilayer as a photocatalyst material.
The computational study of the van der Waals hetero (vdW) bilayer GeI2/InTe has been carried out in present study. The isolated monolayer GeI2 and InTe have been studied first and the results were compared to the previous studies. The possible stackings are considered after the vdW interaction correction is applied in the structure relaxation. The vdW hetero bilayer stability has been checked from the phonon dispersion and Ab-initio Molecular Dynamics (AIMD) calculations. The charge transfer from InTe to GeI2 monolayer. Type-II indirect band gap (1.98, 2.01 eV) is verified by the projected band structure and band alignment calculations. The vdW hetero bilayer is a superior photocatalyst for the pH value up to pH = 0 to 11. The optical properties are calculated from the complex dielectric constant. The absorption coefficient shows the enhance absorption of light in the visible and ultraviolet regions. The vdW hetero bilayer has shown low reflectivity (37%) and a high refractive index (2.80) in the visible region. The enhanced optical properties have shown its possible applications in optoelectronic devices.&#xD.


Foliar aphid feeding recruits rhizosphere bacteria and primes plant immunity against pathogenic and non-pathogenic bacteria in pepper.
Plants modulate defence signalling networks in response to different biotic stresses. The present study evaluated the effect of a phloem-sucking aphid on plant defence mechanisms in pepper (Capsicum annuum) during subsequent pathogen attacks on leaves and rhizosphere bacteria on roots. Plants were pretreated with aphids and/or the chemical trigger benzothiadiazol (BTH) 7 d before being challenged with two pathogenic bacteria, Xanthomonas axonopodis pv. vesicatoria (Xav) as a compatible pathogen and X. axonopodis pv. glycines (Xag) as an incompatible (non-host) pathogen. Disease severity was noticeably lower in aphid- and BTH + aphid-treated plants than in controls. Although treatment with BTH or aphids alone did not affect the hypersensitive response (HR) against Xag strain 8ra, the combination treatment had a synergistic effect on the HR. The aphid population was reduced by BTH pretreatment and by combination treatment with BTH and bacterial pathogens in a synergistic manner. Analysis of the expression of the defence-related genes Capsicum annum pathogenesis-related gene 9 (CaPR9), chitinase 2 (CaCHI2), SAR8·2 and Lipoxygenase1 (CaLOX1) revealed that aphid infestation resulted in the priming of the systemic defence responses against compatible and incompatible pathogens. Conversely, pre-challenge with the compatible pathogen Xav on pepper leaves significantly reduced aphid numbers. Aphid infestation increased the population of the beneficial Bacillus subtilis GB03 but reduced that of the pathogenic Ralstonia solanacearum SL1931. The expression of defence-related genes in the root and leaf after aphid feeding indicated that the above-ground aphid infestation elicited salicylic acid and jasmonic acid signalling throughout the whole plant. The findings of this study show that aphid feeding elicits plant resistance responses and attracts beneficial bacterial populations to help the plant cope with subsequent pathogen attacks.


Reduced brain gray matter concentration in patients with obstructive sleep apnea syndrome.
To investigate differences in brain gray matter concentrations or volumes in patients with obstructive sleep apnea syndrome (OSA) and healthy volunteers. Optimized voxel-based morphometry, an automated processing technique for MRI, was used to characterize structural differences in gray matter in newly diagnosed male patients. University hospital. The study consisted of 36 male OSA and 31 non-apneic male healthy volunteers matched for age (mean age, 44.8 years). Using the t-test, gray matter differences were identified. The statistical significance level was set to a false discovery rate P < 0.05 with an extent threshold of k(E) > 200 voxels. The mean apnea-hypopnea index (AHI) of patients was 52.5/h. On visual inspection of MRI, no structural abnormalities were observed. Compared to healthy volunteers, the gray matter concentrations of OSA patients were significantly decreased in the left gyrus rectus, bilateral superior frontal gyri, left precentral gyrus, bilateral frontomarginal gyri, bilateral anterior cingulate gyri, right insular gyrus, bilateral caudate nuclei, bilateral thalami, bilateral amygdalo-hippocampi, bilateral inferior temporal gyri, and bilateral quadrangular and biventer lobules in the cerebellum (false discovery rate P < 0.05). Gray matter volume was not different between OSA patients and healthy volunteers. The brain gray matter deficits may suggest that memory impairment, affective and cardiovascular disturbances, executive dysfunctions, and dysregulation of autonomic and respiratory control frequently found in OSA patients might be related to morphological differences in the brain gray matter areas.


A Systematic Review of Cognitive Functioning After Traumatic Brain Injury in Individuals Aged 10-30 Years.
Given the importance of the period of life from 10 to 30 years in terms of cognitive development and education, combined with the high incidence of traumatic brain injury (TBI) during this period, and limited consensus as to the pattern and degree of cognitive impairment post TBI during this period, we conducted a systematic review to investigate cognitive performance across a range of domains among individuals between the ages of 10 and 30 years who had sustained a TBI. We searched five databases and identified 799 unique records; 52 met our inclusion criteria. These studies reported cognitive function for intelligence, attention, memory, processing speed, and executive function. The majority of the studies reported significant effects, suggesting that TBI is associated with cognitive impairments in these domains. Nine of the studies used physiological tests (EEG and fMRI), the outcomes of which supported behaviorally demonstrated cognitive deficits. In the studies we reviewed, individuals aged 10-30 years who had experienced a TBI performed worse than healthy controls on cognitive function measures-specifically for attention, memory, processing speed, and executive function. In the studies that subjected the individuals with TBI to EEG and fMRI, atypical activation in associated brain regions was demonstrated while the individuals were undergoing cognitive tasks. However, caution should be taken when interpreting the overall results due to the high risk of bias across the majority of the studies. The broader implications of reduced cognitive performance after TBI across this age range are yet to be fully understood.


Do gene variants influencing adult adiposity affect birth weight? A population-based study of 24 loci in 4,744 Danish individuals.
Several obesity risk alleles affecting adult adiposity have been identified by the recent wave of genome wide association studies. We aimed to examine the potential effect of these variants on fetal body composition by investigating the variants in relation to birth weight and ponderal index of the newborn. Midwife records from the Danish State Archives provided information on mother's age, parity, as well as birth weight, birth length and prematurity of the newborn in 4,744 individuals of the population-based Inter99 study. Twenty-four risk alleles showing genome-wide associations with adult BMI and/or waist circumference were genotyped. None of the 24 risk variants tested showed an association with birth weight or ponderal index after correction for multiple testing. Birth weight was divided into three categories low (≤10(th) percentile), normal (10(th)-90(th) percentile) and high birth weight (≥90th percentile) to allow for non-linear associations. There was no difference in the number of risk alleles between the groups (p = 0.57). No interactions between each risk allele and birth weight in the prediction of adult BMI were observed. An obesity risk score was created by summing up risk alleles. The risk score did not associate with fetal body composition. Moreover there was no interaction between the risk score and birth weight/ponderal index in the prediction of adult BMI. 24 common variants associated with adult adiposity did not affect or interact with birth weight among Danes suggesting that the effects of these variants predominantly arise in the post-natal life.


Recombinant human milk proteins - an opportunity and a challenge.
Several human milk proteins have physiologic functions in infants. These proteins are involved in defense against infectious agents and in the optimization of nutrient uptake from milk. Therefore, interest in producing recombinant human milk proteins to use in infant formula has been growing. Microorganisms and transgenic animals can now be used for the production of bioactive proteins. However, the benefits of each protein must be evaluated in cells, animal models, and infants before claims can be made that adding them to formula improves the health or nutrition of infants. Once benefits are shown, proper manufacturing conditions must be developed for introducing the protein or proteins into formula. Processing conditions must be evaluated to ensure that biologic activity is maintained. Dry blending, aseptic processing, sterile filtration, and other techniques will likely be necessary for introducing proteins that require specific tertiary structure for activity. The importance of posttranslational modifications must also be considered: some proteins may require proper glycosylation or phosphorylation for physiologic activity.


Molecular and serological characterization of species B2 adenovirus strains isolated from children hospitalized with acute respiratory disease in Buenos Aires, Argentina.
Between September 2000 and November 2005, approximately 10% of the retrospectively examined human adenovirus (HAdV)-positive pediatric cases of acute respiratory disease (ARD) requiring hospitalization at the Hospital Nacional de Pediatria Juan P. Garrahan in Buenos Aires, Argentina, were found to have a HAdV-B2 infection. To characterize genetically and antigenically the HAdV-B2 virus isolates. Restriction enzyme analysis (REA), hexon and fiber gene sequencing and virus neutralization assays (VN) were carried out on 8 HAdV-B2 respiratory virus isolates. REA showed that the 8 examined HAdV-B2 virus isolates were HAdV11, belonging to two genomic variants: HAdV11a and a BclI variant of HAdV11c which we designated 11c4. Molecular analysis of the hexon genes showed that both REA variants had a HAdV11-like hexon gene. Confirming previous reports, the 7 HAdV11a virus isolates were found to have HAdV14-like fiber genes and therefore are HAdV H11/F14. The fiber gene of the HAdV11c4 virus isolates most closely resembled that of various strains of HAdV7. In VN assays, the 4 tested HAdV11a strains were serotyped as HAdV11-14. The HAdV11c4 strain was serotyped as HAdV11 but also showed a weak but significant reactivity with antiserum to HAdV7. Compared with the other HAdV-positive cases in our study, infection with HAdV11 caused a similarly severe disease. Our results provide evidence to the long term world-wide circulation of HAdV H11/F14 as a causative agent of ARD. Combined, our molecular and serology data support the rationale to base the molecular typing and designation of recombinant viruses on the sequences of the hexon and fiber genes.


Mitochondrial oxidative stress causes chromosomal instability of mouse embryonic fibroblasts.
Reactive oxygen species are an inevitable by-product of mitochondrial respiration. It has been estimated that between 0.4 and 4% of molecular oxygen is converted to the radical superoxide (O2*-) and this level is significantly influenced by the functional status of the mitochondria. It is well established that exogenous oxidative stress and high doses of mitochondrial poisons such as paraquat and carbonyl cyanide 4 (trifluoromethoxy) phenylhydrazone (FCCP) can lead to genomic instability. In this report we show for the first time that endogenous mitochondrial oxidative stress in standard cell culture conditions results in nuclear genomic instability in primary mouse embryonic fibroblasts (MEFs). We show that lack of mitochondrial superoxide dismutase in MEFs leads to a severe increase of double strand breaks, end-to-end fusions, chromosomal translocations, and loss of cell viability and proliferative capacity. Our results predict that endogenous mitochondrial oxidative stress can induce genomic instability, and therefore may have a profound effect in cancer and aging.