Epidemiology of vancomycin-resistant Enterococcus faecalis: a case-case-control study.
Although much is known about vancomycin-resistant (VR) Enterococcus faecium, little is known about the epidemiology of VR Enterococcus faecalis. The predilection of VR E. faecalis to transfer the vancomycin resistance determinant to Staphylococcus aureus is much greater than that of VR E. faecium. The epidemiology of VR E. faecalis has important implications regarding the emergence of vancomycin-resistant S. aureus (VRSA); 8 of 13 reported VRSA cases have been from Michigan. A retrospective case-case-control study was conducted at the Detroit Medical Center, located in southeastern Michigan. Unique patients with VR E. faecalis infection were matched to patients with strains of vancomycin-susceptible (VS) E. faecalis and to uninfected controls at a 1:1:1 ratio. Five hundred thirty-two VR E. faecalis cases were identified and were matched to 532 VS E. faecalis cases and 532 uninfected controls. The overall mean age of the study cohort (n = 1,596) was 63.0 ± 17.4 years, and 747 (46.8%) individuals were male. Independent predictors for the isolation of VR E. faecalis (but not VS E. faecalis) compared to uninfected controls were an age of ≥65 years, nonhome residence, diabetes mellitus, peripheral vascular disease, exposure to cephalosporins and fluoroquinolones in the prior 3 months, and immunosuppressive status. Invasive procedures and/or surgery, chronic skin ulcers, and indwelling devices were risk factors for both VR E. faecalis and VS E. faecalis isolation. Cephalosporin and fluoroquinolone exposures were unique, independent predictors for isolation of VR E. faecalis. A majority of case patients had VR E. faecalis present at the time of admission. Control of VR E. faecalis, and ultimately VRSA, will likely require regional efforts focusing on infection prevention and antimicrobial stewardship.


Risk assessment for recrudescence of avian influenza in caged layer houses following depopulation: the effect of cleansing, disinfection and dismantling of equipment.
Following an outbreak of highly pathogenic avian influenza virus (HPAIV) in a poultry house, control measures are put in place to prevent further spread. An essential part of the control measures based on the European Commission Avian Influenza Directive 2005/94/EC is the cleansing and disinfection (C&D) of infected premises. Cleansing and disinfection includes both preliminary and secondary C&D, and the dismantling of complex equipment during secondary C&D is also required, which is costly to the owner and also delays the secondary cleansing process, hence increasing the risk for onward spread. In this study, a quantitative risk assessment is presented to assess the risk of re-infection (recrudescence) occurring in an enriched colony-caged layer poultry house on restocking with chickens after different C&D scenarios. The risk is expressed as the number of restocked poultry houses expected before recrudescence occurs. Three C&D scenarios were considered, namely (i) preliminary C&D alone, (ii) preliminary C&D plus secondary C&D without dismantling and (iii) preliminary C&D plus secondary C&D with dismantling. The source-pathway-receptor framework was used to construct the model, and parameterisation was based on the three C&D scenarios. Two key operational variables in the model are (i) the time between depopulation of infected birds and restocking with new birds (TbDR) and (ii) the proportion of infected material that bypasses C&D, enabling virus to survive the process. Probability distributions were used to describe these two parameters for which there was recognised variability between premises in TbDR or uncertainty due to lack of information in the fraction of bypass. The risk assessment estimates that the median (95% credible intervals) number of repopulated poultry houses before recrudescence are 1.2 × 104 (50 to 2.8 × 106), 1.9 × 105 (780 to 5.7 × 107) and 1.1 × 106 (4.2 × 103 to 2.9 × 108) under C&D scenarios (i), (ii) and (iii), respectively. Thus for HPAIV in caged layers, undertaking secondary C&D without dismantling reduces the risk by 16-fold compared to preliminary C&D alone. Dismantling has an additional, although smaller, impact, reducing the risk by a further 6-fold and thus around 90-fold compared to preliminary C&D alone. On the basis of the 95% credible intervals, the model demonstrates the importance of secondary C&D (with or without dismantling) over preliminary C&D alone. However, the extra protection afforded by dismantling may not be cost beneficial in the context of reduced risk of onward spread.


The way from pen and paper to electronic documentation in a German emergency department.
Some of the advantages of implementing electronic emergency department information systems (EDIS) are improvements in data availability and simplification of statistical evaluations of emergency department (ED) treatments. However, for multi-center evaluations, standardized documentation is necessary. The AKTIN project ("National Emergency Department Register: Improvement of Health Services Research in Acute Medicine in Germany") has used the "German Emergency Department Medical Record" (GEDMR) published by the German Interdisciplinary Association of Intensive and Emergency Care as the documentation standard for its national data registry. Until March 2016 the documentation standard in ED was the pen-and-paper version of the GEDMR. In April 2016 we implemented the GEDMR in a timeline-based EDIS. Related to this, we compared the availability of structured treatment information of traumatological patients between pen-and-paper-based and electronic documentation, with special focus on the treatment time. All 796 data fields of the 6 modules (basic data, severe trauma, patient surveillance, anesthesia, council, neurology) were adapted for use with the existing EDIS configuration by a physician working regularly in the ED. Electronic implementation increased availability of structured anamnesis and treatment information. However, treatment time was increased in electronic documentation both immediately (2:12 ± 0:04 h; n = 2907) and 6 months after implementation (2:18 ± 0:03 h; n = 4778) compared to the pen-and-paper group (1:43 ± 0:02 h; n = 2523; p < 0.001). We successfully implemented standardized documentation in an EDIS. The availability of structured treatment information was improved, but treatment time was also increased. Thus, further work is necessary to improve input time.


Deficient post-error slowing in children with ADHD is limited to the inattentive subtype.
Post-error slowing (i.e., slowing of a response on correct trials following an error) is thought to reflect adaptive behavior that may be impaired in Attention-Deficit/Hyperactivity Disorder (ADHD). The current study examined post-error slowing in children with ADHD and typically developing controls on two cognitive tasks. Fifty-one ADHD-Combined type, 53 ADHD-Inattentive type, and 47 controls completed a Choice Discrimination and Stop Signal Task with incentive and event rate manipulations. Linear mixed models were used to examine reaction times surrounding errors (trial-by-trial). Pre-error speeding and pre- to post-error slowing occurred on both tasks. Impaired post-error slowing was only present on the Choice Discrimination Task for the ADHD-Inattentive type. Post-error slowing is impaired in children with ADHD-Inattentive type, but not ADHD-Combined type, on a simple attention task. These findings highlight the importance of considering task demands and ADHD subtype when examining post-error slowing and also provide a novel approach to quantifying post-error slowing.


Utilization of health care services by depressed patients attending the general out-patients department of the Jos University Teaching Hospital, Jos, Nigeria.
Depression is a common psychiatric disorder in primary health care throughout the world with increasing incidence and prevalence. It is often under-treated and under-diagnosed. Consequently, several studies have revealed that patients with depression are high utilizers of medical services. The study was aimed at determining the frequency of consultation and the utilization of investigative procedures by the depressed and non-depressed patients in the last 12 months. This was a cross-sectional descriptive study among 200 consecutive patients attending the General Out-Patient Department of the Jos University Teaching Hospital between November 2006 and March 2007. A semi-structured questionnaire was used to collect socio-demographic data and health services utilization indices. Structured Clinical Interview for DSM-IV axis-1 Disorders (SCID) was used for diagnosis of depression. The study found that 51(25.5%) of the respondents met DSM-IV criteria for the diagnosis of major depression while 149 (74.5%) did not. Depressed patients significantly had more number of consultations with their doctors (P=0.000), had consulted more number of hospitals (P=0.000), stayed longer on admission (P=0.000) and had consumed more types of medicine (P=0.005) in the last 12 months compared with the non-depressed. The depressed patients also had significantly higher mean of different types of investigations compared with non-depressed; urinalysis (1.69 vs 0.55, P=0.000), chest X-ray (0.57 vs 0.21, P=0.000) and Widal test (1.92 vs 0.39, P=0.000). Others are HIV screening (0.39vs0.11, P=0.000) urine mcs (0.94 vs 0.18, P=0.000), stool mcs (1.24 vs 0.20, P=0.000). The study demonstrated that patients who suffer from depression are higher utilizers of health care resources compared with the non-depressed. Therefore, it is recommended that general practitioners and other health workers need to be better equipped to deal with the diagnosis and management of depression.


Evaluating Complex Health and Social Care Program Using Multi-Criteria Decision Analysis: A Case Study of "Better Together in Amsterdam North".
Multi-criteria decision analysis (MCDA) has been recommended to support policy making in healthcare. However, practical applications of MCDA are sparse. One potential use for MCDA is for the evaluation of programs for complex and vulnerable patients. These complex patients benefit from integrated care programs that span healthcare and social care and aim to improve more than just health outcomes. MCDA can evaluate programs that aim to improve broader outcomes because it allows the evaluation of multiple outcomes alongside each other. In this study, we evaluate an innovative integrated care program in the Netherlands using MCDA. We used an innovative MCDA framework with broad outcomes of health, well-being, and cost to evaluate the Better Together in Amsterdam North (BSiN) program using preferences of patients, partners, providers, payers, and policy makers in the Netherlands. BSiN provides case management support for a period of 6 months. Seven outcomes that previous research has deemed important to complex patients were measured, including physical functioning and social relationships and participation. We find that the program improved the overall MCDA score marginally, and, thus, after 6 and after 12 months, BSiN was preferred to usual care by all stakeholders. BSiN was preferred to usual care, mostly owing to improvements in psychological well-being and social relationships and participation. The integrated healthcare and social care program BSiN in the Netherlands was preferred to usual care according to an MCDA evaluation. MCDA seems a useful method to evaluate complex programs with benefits beyond health.


The spirochetal chpK-chromosomal toxin-antitoxin locus induces growth inhibition of yeast and mycobacteria.
Toxin-antitoxin systems encoded by bacterial plasmids and chromosomes typically consist of a toxin that inhibits growth of the host cell and a specific antitoxin. In this report, the chpK gene from the chromosomal toxin-antitoxin locus of the spirochete Leptospira interrogans was studied in both prokaryotic and eukaryotic systems. Cloning of the the spirochetal chpK gene into a mycobacterial expressing vector led to dramatic reductions of transformation efficiency in both Mycobacterium smegmatis and Mycobacterium bovis BCG. However, few mycobacterial transformants were obtained. This result could be due to plasmid structural modifications leading to disruption of chpK expression, suggesting that L. interrogans ChpK is highly toxic for mycobacteria. Presence of the L. interrogans chpK gene was also found to inhibit cell growth of the yeast Saccharomyces cerevisiae. These results show that ChpK possesses a broad activity against both prokaryotes and eukaryotes, suggesting that the cellular target of the toxin is conserved in these organisms.


Anaerobic growth of Escherichia coli K12 with fumarate as terminal electron acceptor. Genetic studies with menaquinone and fluoroacetate-resistant mutants.
Fifteen independent menaquinone biosynthesis mutants (men) of Escherichia coli K12, selected for their inability to use fumarate as terminal electron acceptor, were investigated. Two nutritionally distinct groups were detected. The major group (13 mutants) responded to 1,4-dihydroxy-2-naphthoate (DHN), 2-succinylbenzoate (SB) and its dilactone, whereas the minor group (2 mutants) only responded to DHN. DHN was at least five times more effective than SB but it inhibited growth at concentrations greater than 10 microM. For anaerobic growth on glucose minimal medium the auxotrophs responded to much lower concentrations of DHN and SB and these intermediates could be replaced by uracil. Anaerobic growth tests showed that glycerol, formate and H2 are good substrates for E. coli when fumarate is the ultimate electron acceptor but growth with lactate or with fumarate alone is poor. All 15 men mutations were located between glpT and purF at approximately 49 min in the E. coli linkage map. Cotransduction frequencies with relevant markers were: nalA (21%), glpT (35%) and purF (15%). The presence of at least three genetically distinct classes (menC and menD, SB-requirers; menB, DHN-requirers) was indicated using abortive transduction as a complementation test and three-factor genetic analysis. The relative orientation nalA...menC-(D,B)...purF was indicated. Fluoroacetate-resistant mutants were isolated and four different classes were identified: ack, lacking acetate kinase; pta, lacking phosphotransacetylase; facA, lacking both of these activities; and facB, which retained both of these enzyme activities. Some of the pta mutants and all of the facA mutants failed to grow on media containing fumarate as terminal electron acceptor or anaerobically on glucose minimal medium. All four types had genetic lesions clustered between the men and purF sites. Average cotransduction frequencies with relevant markers were: nalA (4%), men (27 to 35%) and purF (71 to 80%).


Serum selenoprotein P levels in patients with type 2 diabetes and prediabetes: implications for insulin resistance, inflammation, and atherosclerosis.
The dysregulation of hepatokines may be associated with the pathogenesis of insulin resistance and type 2 diabetes. A recent study has suggested that selenoprotein P (SeP), a novel hepatokine, may play a role in the regulation of glucose metabolism and insulin sensitivity. We examined the relationship between circulating SeP levels and clinical parameters associated with insulin resistance in humans. We compared serum SeP concentrations in 100 subjects with diverse glucose tolerance statuses. Furthermore, we evaluated the relationship between SeP and cardiometabolic risk factors including insulin resistance, high-sensitivity C-reactive protein, and carotid intima-media thickness. Serum SeP concentrations were significantly higher in patients with type 2 diabetes or prediabetes than those with normal glucose tolerance (all P < 0.01) and decreased in a stepwise manner [1032.4 (495.9-2149.4) vs. 867.3 (516.3-1582.7) vs. 362.0 (252.5-694.5), P = 0.004]. In addition, overweight and obese subjects had significantly increased SeP levels compared with lean subjects (P = 0.002). Spearman's partial correlation analysis adjusted for age and gender showed a significant relationship between SeP and cardiometabolic factors including body mass index, waist circumference, systolic blood pressure, triglycerides, glucose, hemoglobin A1c, aspartate aminotransferase, and insulin resistance. Furthermore, in multiple regression analyses, SeP showed an independent association with carotid intima-media thickness as well as high-sensitivity C-reactive protein, even after adjustment for other confounding factors. Circulating SeP concentrations were elevated in patients with glucose metabolism dysregulation and were related to various cardiometabolic parameters including insulin resistance, inflammation, and atherosclerosis.


Capecitabine as a Radiosensitizer in Adjuvant Chemoradiotherapy for Pancreatic Cancer: A Retrospective Study.
Pancreatic cancer remains one of the deadliest cancer diagnoses and is the fourth leading cause of cancer-related deaths in the U.S. Surgery is the mainstay of treatment for the 20% for whom the tumor is resectable, however, controversy exists over the appropriate adjuvant therapy where local recurrence rates remain strikingly high (50-85%). We aimed to evaluate the safety and efficacy of adding capecitabine (a known radiosensitizer by direct and abscopal effects) to concurrent radiation in the adjuvant setting after resection of pancreatic adenocarcinoma. We conducted a retrospective study of 63 patients diagnosed from 2004-2013 with histopathologically-confirmed stage I/II pancreatic cancer treated with a surgical resection followed by adjuvant concurrent chemoradiation to at least 45 Gy using 3D planning and capecitabine at 1,600 mg/m(2)/day (Monday-Friday) for 6 weeks. This was combined with either 4 months of gemcitabine at 1,000 mg/m(2) weekly for 3 out of 4 weeks or capecitabine at 2,000 mg/m(2) for 14 days every 3 weeks for a total of 4 months. The majority of patients were over 65 years old (71%), male (60%), had negative surgical margins (79%), had pancreatic head or neck involvement (71%), Eastern Cooperative Oncology Group performance score of 1 (71%), and a cancer antigen 19-9 in the range of 11-100 U/ml at the time of diagnosis (51%). Of the 63 patients reviewed, 61 patients (97%) completed concurrent chemoradiotherapy. Treatment was halted in one patient due to gastritis and a second for gastrointestinal bleeding. Otherwise, adverse reactions during concurrent chemoradiotherapy were well-tolerated and the majority were Common Terminology Criteria for Adverse Events grades 1 and 2. Grade 3 toxicity was anorexia (n=2) and hand and foot syndrome (n=2) and GI bleeding (n=1). The only grade 4 toxicities were anorexia (n=1) and fatigue (n=1). The median follow-up of patients at the time of analysis was 36 months. The median survival of the entire cohort was 23.5 (range=8.5-42) months. The 1-, 2- and 3-year survival rates were 80%, 35% and 25%, respectively. Concurrent chemoradiation using capecitabine as a radiosensitizer in the adjuvant setting for pancreatic cancer was completed by the vast majority of patients in this series. Treatment was relatively well-tolerated, and its efficacy seems comparable to that for historical controls. This study probably represents the largest yet reported using capecitabine in this setting. Future studies including an increased sample size are required.


Progression of myocardial fibrosis in hypertrophic cardiomyopathy: mechanisms and clinical implications.
Myocardial fibrosis as detected by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is a powerful prognostic marker in hypertrophic cardiomyopathy (HCM) and may be progressive. The precise mechanisms underlying fibrosis progression are unclear. We sought to assess the extent of LGE progression in HCM and explore potential causal mechanisms and clinical implications. Seventy-two HCM patients had two CMR (CMR1-CMR2) at an interval of 5.7 ± 2.8 years with annual clinical follow-up for 6.3 ± 3.6 years from CMR1. A combined endpoint of heart failure progression, cardiac hospitalization, and new onset ventricular tachycardia was assessed. Cine and LGE imaging were performed to assess left ventricular (LV) mass, function, and fibrosis on serial CMR. Stress perfusion imaging and cardiac energetics were undertaken in 38 patients on baseline CMR (CMR1). LGE mass increased from median 4.98 g [interquartile range (IQR) 0.97-13.48 g] to 6.30 g (IQR 1.38-17.51 g) from CMR1 to CMR2. Substantial LGE progression (ΔLGE ≥ 4.75 g) occurred in 26% of patients. LGE increment was significantly higher in those with impaired myocardial perfusion reserve (<MPRI 1.40) and energetics (phosphocreatine/adenosine triphosphate <1.44) on baseline CMR (P ≤ 0.01 for both). Substantial LGE progression was associated with LV thinning, increased cavity size and reduced systolic function, and conferred a five-fold increased risk of subsequent clinical events (hazard ratio 5.04, 95% confidence interval 1.85-13.79; P = 0.002). Myocardial fibrosis is progressive in some HCM patients. Impaired energetics and perfusion abnormalities are possible mechanistic drivers of the fibrotic process. Fibrosis progression is associated with adverse cardiac remodelling and predicts an increased risk of subsequent clinical events in HCM.


C-MYC rearrangements are frequent in aggressive mature B-Cell lymphoma with atypical morphology.
Diagnosis and classification of aggressive mature B-cell lymphoma with atypical morphology remains a challenge. To identify factors that may contribute to the atypical morphology, we selected eight such cases and evaluated their morphologic, immunophenotypic and cytogenetic features and clinical outcomes. The neoplastic cells showed a diffuse monotonous infiltrating pattern with a spectrum of morphology including: 1) L1 lymphoblastic; 2) centroblastic; 3) immunoblastic; and 4) mixed centroblastic and immunoblastic. The lymphoma cells in most cases were positive for CD10 and/or BCL6, and showed BCL2 expression. 6 of 8 cases showed C-MYC rearrangements, and interestingly, all 6 cases demonstrated a proliferation index of < or =90%. 3 of the 6 cases also demonstrated t(14;18). Clinical follow-up indicated that aggressive mature B-cell lymphoma may benefit from more intensified chemotherapeutic regimens used for BL. Our study suggests that aggressive mature B-cell lymphoma with atypical morphology may be another "grey zone lymphoma" lying in the spectrum between Burkitt lymphoma and diffuse large B-cell lymphoma.


Examining the Association Between Comorbidity Indexes and Functional Status in Hospitalized Medicare Fee-for-Service Beneficiaries.
Medicare data from acute hospitals do not contain information on functional status. This lack of information limits the ability to conduct rehabilitation-related health services research. The purpose of this study was to examine the associations between 5 comorbidity indexes derived from acute care claims data and functional status assessed at admission to an inpatient rehabilitation facility (IRF). Comorbidity indexes included tier comorbidity, Functional Comorbidity Index (FCI), Charlson Comorbidity Index, Elixhauser Comorbidity Index, and Hierarchical Condition Category (HCC). This was a retrospective cohort study. Medicare beneficiaries with stroke, lower extremity joint replacement, and lower extremity fracture discharged to an IRF in 2011 were studied (N=105,441). Data from the beneficiary summary file, Medicare Provider Analysis and Review (MedPAR) file, and Inpatient Rehabilitation Facility-Patient Assessment Instrument (IRF-PAI) file were linked. Inpatient rehabilitation facility admission functional status was used as a proxy for acute hospital discharge functional status. Separate linear regression models for each impairment group were developed to assess the relationships between the comorbidity indexes and functional status. Base models included age, sex, race/ethnicity, disability, dual eligibility, and length of stay. Subsequent models included individual comorbidity indexes. Values of variance explained (R(2)) with each comorbidity index were compared. Base models explained 7.7% of the variance in motor function ratings for stroke, 3.8% for joint replacement, and 7.3% for fracture. The R(2) increased marginally when comorbidity indexes were added to base models for stroke, joint replacement, and fracture: Charlson Comorbidity Index (0.4%, 0.5%, 0.3%), tier comorbidity (0.2%, 0.6%, 0.5%), FCI (0.4%, 1.2%, 1.6%), Elixhauser Comorbidity Index (1.2%, 1.9%, 3.5%), and HCC (2.2%, 2.1%, 2.8%). Patients from 3 impairment categories were included in the sample. The 5 comorbidity indexes contributed little to predicting functional status. The indexes examined were not useful as proxies for functional status in the acute settings studied.


Can Non-HLA Single Nucleotide Polymorphisms Help Stratify Risk in TrialNet Relatives at Risk for Type 1 Diabetes?
Genome-wide association studies identified >50 type 1 diabetes (T1D) associated non-human leukocyte antigens (non-HLA) loci. The purpose of this study was to assess the contribution of non-HLA single nucleotide polymorphisms (SNPs) to risk of disease progression. The TrialNet Pathway to Prevention Study follows relatives of T1D patients for development of autoantibodies (Abs) and T1D. Using the Immunochip, we analyzed 53 diabetes-associated, non-HLA SNPs in 1016 Ab-positive, at-risk non-Hispanic white relatives. Effect of SNPs on the development of multiple Abs and T1D. Cox proportional analyses included all substantial non-HLA SNPs, HLA genotypes, relationship to proband, sex, age at initial screening, initial Ab type, and number. Factors involved in progression from single to multiple Abs included age at screening, relationship to proband, HLA genotypes, and rs3087243 (cytotoxic T lymphocyte antigen-4). Significant factors for diabetes progression included age at screening, Ab number, HLA genotypes, rs6476839 [GLIS family zinc finger 3 (GLIS3)], and rs3184504 [SH2B adaptor protein 3 (SH2B3)]. When glucose area under the curve (AUC) was included, factors involved in disease progression included glucose AUC, age at screening, Ab number, relationship to proband, HLA genotypes, rs6476839 (GLIS3), and rs7221109 (CCR7). In stratified analyses by age, glucose AUC, age at screening, sibling, HLA genotypes, rs6476839 (GLIS3), and rs4900384 (C14orf64) were significantly associated with progression to diabetes in participants <12 years old, whereas glucose AUC, sibling, rs3184504 (SH2B3), and rs4900384 (C14orf64) were significant in those ≥12. In conclusion, we identified five non-HLA SNPs associated with increased risk of progression from Ab positivity to disease that may improve risk stratification for prevention trials.


Who are the male partners of adolescent girls and young women in Swaziland? Analysis of survey data from community venues across 19 DREAMS districts.
Adolescent girls and young women (AGYW, ages 15-24) are at high risk of HIV in Swaziland. Understanding more about their male sexual partners can inform HIV prevention efforts for both. Using the PLACE methodology across all 19 DREAMS implementation districts, 843 men ages 20-34 were surveyed between December 2016-February 2017. Surveys were conducted at 182 venues identified by community informants as places where AGYW and men meet/socialize. Descriptive and multivariate analyses examined characteristics and risk behaviors of male partners of AGYW. Men's average age was 25.7. Sixty-three percent reported female partners ages 15-19, and 70% reported partners ages 20-24 in the last year; of those, 12% and 11% respectively had five or more such partners. Among the 568 male partners of AGYW, 36% reported consistent condom use with their current/last partner. Forty-two percent reported testing for HIV in the last year; 6% were HIV-positive, and of those, 97% were currently on treatment. One-third (37%) reported being circumcised; among uncircumcised, 81% were not considering it. In multivariate analyses, men who reported three or more AGYW partners in the last year were more likely to be HIV-positive (aOR 3.2, 95% CI 1.1,8.8). Men were also less likely to disclose their HIV status to adolescent versus older partners (aOR 0.6, 95% CI 0.4,0.9) and partners more than 5 years younger than themselves (aOR 0.6, 95% CI 0.4,0.9). Results also revealed relatively high unemployment and mobility, substantial financial responsibilities, and periodic homelessness. Most men identified through community venues reported relationships with AGYW, and these relationships demonstrated substantial HIV risk. Challenging life circumstances suggest structural factors may underlie some risk behaviors. Engaging men in HIV prevention and targeted health services is critical, and informant-identified community venues are promising intervention sites to reach high-risk male partners of AGYW.


Carotid-cavernous fistula as a mimicker of myasthenia gravis.
A carotid-cavernous fistula (CCF) is an abnormal communication between the carotid arterial system and the cavernous sinus. Common symptoms of CCFs include proptosis and ophthalmoplegia, but fluctuating diplopia and presence of ptosis are not typical. We present an unusual case of CCF with fluctuating binocular diplopia and ptosis, mimicking myasthenia gravis. Electrodiagnostic testing, which included repetitive nerve stimulation and single-fiber electromyography, was normal. Magnetic resonance imaging of the brain and orbits was initially normal, but later magnetic resonance angiography revealed enlargement of the left superior ophthalmic vein along with a left CCF. Patient underwent a successful left cavernous sinus embolization. Fluctuating ophthalmic symptoms are a typical presentation of myasthenia gravis; however, there may be an association of these symptoms with a CCF. Repetitive nerve stimulation and single-fiber electromyography played a key role in diagnosis of this case, as the normal result led to further investigations revealing a CCF.


Consistency in the supply of larval fishes among coral reefs in French Polynesia.
For marine fishes with a bipartite life cycle, pelagic larval dispersal can shape the distribution, connectivity, composition and resilience of adult populations. Numerous studies of larval dispersal, and associated settlement and recruitment processes, have examined the relationship between population connectivity and oceanographic features. However, relatively little is known about spatial and temporal variation in the abundance of larvae settling among different reefs and the extent to which the species assemblage of larvae settling at one location is reflective of the assemblage in neighbouring areas. Here, using crest nets, which provide a non-selective measure of the total abundance and assemblage of larvae settling to a reef (i.e. larval supply), we collected larval coral reef fishes at five locations surrounding two spatially disparate French Polynesian islands: Moorea and Nengo-Nengo. Overall, larval settlement patterns were correlated with the lunar cycle, with larval abundance peaking during the new moon. Although there were some spatial differences in larval supply among the five monitored sites, settlement patterns were largely consistent, even at the species level, irrespective of factors such as coastline orientation or distance between sites. This study provides further insights into the mechanisms driving patterns of dispersal and settlement of larval fishes over large spatial scales.


Microfluidic device to study cell transmigration under physiological shear stress conditions.
The development of new drug therapies relies on studies of cell transmigration in in vitro systems. Migration has traditionally been studied using two methods, the Boyden chamber and a shear flow chamber assay. Though, commonly applied in cell transmigration studies, they are far from imitating a natural migration process. Here we describe a novel in vitro cell transmigration microfluidic assay, which mimicks physiological shear flow conditions in blood vessels. The device was designed to incorporate the principles of both the Boyden chamber and the shear flow chamber assay, i.e. migration through the membrane under flow conditions. The 3D environment of migrating cells is imitated by injecting cell adhesion proteins to coat the membrane in the device. We tested the developed device with Jurkat cells migration towards medium supplemented with serum, and with chemokine induced lymphocytes migration. The applied continuous flow of cell suspension and chemoattractant ensures that the concentration gradient is maintained in time and space. The cell adhesion proteins used to enhance cell migration in the device were fibronectin and VCAM-1. We successfully observed a multistep transmigration process by means of the developed microfluidic migration assay. The presented device is inexpensive, easy to fabricate and disposable, having a potential to be applied in basic research as well as in the drug development process.


Conventional pulmonary vein isolation compared with the "box isolation" method: a randomized clinical trial.
Esophageal injury is a potential complication with radiofrequency ablation in the posterior wall of the left atrium (LA). The "box isolation" method isolates the posterior LA wall including the pulmonary veins without ablation on the posterior LA wall. This study compares the acute and long-term efficacy of the box isolation method with conventional circumferential pulmonary vein isolation (PVI) for catheter ablation of AF. Twenty-nine patients (age 60 ± 9 years, 62% male, 79% paroxysmal) with drug refractory AF underwent catheter ablation. Sixteen of the 29 patients (55%) underwent box isolation. Recurrence of AF was detected by checking the daily recorded rhythm strip on a portable home ECG monitor, irrespective of the symptoms. Mean follow-up duration was 10 ± 2 months. Complete isolation of the posterior LA using box isolation lesions was achieved in three of 16 (19%) patients. The other 13 patients underwent creation of additional lesions until all PVs were isolated. Of the 16 patients who underwent box isolation, four patients (25%) had complete success, six patients (38%) had improvement, and the remaining six patients (37%) had failure. Of the 13 patients who underwent the standard PV isolation, two patients (15%) had complete success, eight patients (62%) had improvement, and the remaining three patients (23%) had failure (p = 0.44). In this pilot study, the efficacy of box isolation is similar to the circumferential PVI for catheter ablation of AF. Few patients achieved PVI with box method alone. Based on these results, we do not recommend the box isolation strategy.


Detecting Neurodevelopmental Effects of Early-Gestation Ethanol Exposure: A Nonhuman Primate Model of Ethanol Drinking During Pregnancy.
Gestational ethanol (EtOH) exposure is associated with multiple developmental abnormalities, collectively termed fetal alcohol spectrum disorder (FASD). While the majority of women abstain from EtOH following knowledge of pregnancy, one contributing factor to the high FASD prevalence is that pregnancy is not detected until 4 to 6 weeks. Thus, EtOH consumption continues during the initial stages of fetal development. An experimental protocol is described in which rhesus macaques self-administer 1.5 g/kg/d EtOH (or isocaloric maltose dextrin) prior to pregnancy and through the first 60 days of a 168-day gestation term. Menstrual cycles were monitored, including measurements of circulating estradiol and progesterone levels. The latency to consume 1.5 g/kg EtOH and blood EtOH concentration (BEC) was measured. Twenty-eight fetuses (14 EtOH and 14 controls) were generated in this study. EtOH did not affect menstrual cycles or the probability of successful breeding. No EtOH-induced gross adverse effects on pregnancy were observed. Individual variability in latency to complete drinking translated into variability in BEC, measured 90 minutes following session start. Drinking latencies in controls and EtOH drinkers were longer in the second gestational month than in the first. All pregnancies reached the planned experimental time point of G85, G110, or G135, when in utero MRIs were performed, fetuses were delivered by caesarean section, and brains were evaluated with ex vivo procedures, including slice electrophysiology. Fetal tissues have been deposited to the Monkey Alcohol Tissue Research Resource. This FASD model takes advantage of the similarities between humans and rhesus macaques in gestational length relative to brain development, as well as similarities in EtOH self-administration and metabolism. The daily 1.5 g/kg dose of EtOH through the first trimester does not influence pregnancy success rates. However, pregnancy influences drinking behavior during the second month of pregnancy. Future publications using this model will describe the effect of early-gestation EtOH exposure on anatomical and functional brain development at subsequent gestational ages.


The discovery of long-term potentiation.
This paper describes circumstances around the discovery of long-term potentiation (LTP). In 1966, I had just begun independent work for the degree of Dr medicinae (PhD) in Per Andersen's laboratory in Oslo after an eighteen-month apprenticeship with him. Studying the effects of activating the perforant path to dentate granule cells in the hippocampus of anaesthetized rabbits, I observed that brief trains of stimuli resulted in increased efficiency of transmission at the perforant path-granule cell synapses that could last for hours. In 1968, Tim Bliss came to Per Andersen's laboratory to learn about the hippocampus and field potential recording for studies of possible memory mechanisms. The two of us then followed up my preliminary results from 1966 and did the experiments that resulted in a paper that is now properly considered to be the basic reference for the discovery of LTP.


Directional Solvent Vapor Annealing for Crystal Alignment in Solution-Processed Organic Semiconductors.
A unified approach of directional solvent vapor annealing for crystal alignment in solution-processed organic semiconductors is proposed. Highly crystalline molecular self-assembly of the drop-cast technique is further enhanced by postprocessing scheme of the solvent vapor annealing with additional benefit of alignment of the crystalline domains. In this technique, a mixture of carrier gas and solvent vapors are made to flow in a certain direction and in the close proximity of the surface of the substrates carrying the solution. Flow of the carrier gas imparts directionality to the semiconducting crystalline ribbons, whereas the influx of the solvent vapors improves the crystalline order in the semiconducting film. The flow rate of the carrier gas and the position of the substrate in the interaction chamber are the primary regulating factors, which have the ability to provide a semiconducting layer with a well-aligned and interconnected assembly of long ribbons. These favorable film properties further materialize in the form of electrical performance of the corresponding field-effect transistors. The versatility of this technique makes it a viable alternative for the solution processing of organic semiconductors.


Quality of care among patients undergoing lower extremity revascularization.
Compliance with guidelines for treating patients with peripheral artery disease (PAD) lags compliance for treating patients with coronary artery disease. We assessed the gap between guidelines and practice for patients with PAD who underwent lower extremity revascularization (LER) at our institution from 2007 to 2010. Quality of care (QoC) was calculated by measuring provider performance on four indicators (antiplatelet therapy, dyslipidemia management, control of hypertension, and diabetes) derived from the ACCF/AHA PAD guidelines. The QoC score was calculated at the time of admission and at time of discharge for each patient, and reflects the proportion of indicated treatments received. Patients (n = 734, mean age 70±11, female 51%) were followed for a mean of 2.0±1.4 years (range 0-5.7) following LER. The indication for LER was claudication (24.8%), rest pain (16.7%), and tissue loss (58.4%). The percentage of patients with a perfect QoC score increased significantly during hospital admission (11% to 21%, p < 0.001). Significant multivariate predictors of perfect QoC score included race/ethnicity, Charlson score, severity of LE ischemia, and observation period (admission, discharge). Multivariate analysis demonstrated that age>75 years, heart failure, chronic kidney disease, rest pain, and tissue loss-but not compliance with four guideline-based therapies-were associated with decreased freedom from the composite endpoint of major amputation, repeat revascularization, and death. Although adherence to guidelines improved over time, we found a significant gap between guidelines and practice for this cohort of patients at increased risk for adverse cardiovascular events.


The nuclear receptor genes HR3 and E75 are required for the circadian rhythm in a primitive insect.
Insect circadian rhythms are generated by a circadian clock consisting of transcriptional/translational feedback loops, in which CYCLE and CLOCK are the key elements in activating the transcription of various clock genes such as timeless (tim) and period (per). Although the transcriptional regulation of Clock (Clk) has been profoundly studied, little is known about the regulation of cycle (cyc). Here, we identify the orphan nuclear receptor genes HR3 and E75, which are orthologs of mammalian clock genes, Rorα and Rev-erbα, respectively, as factors involved in the rhythmic expression of the cyc gene in a primitive insect, the firebrat Thermobia domestica. Our results show that HR3 and E75 are rhythmically expressed, and their normal, rhythmic expression is required for the persistence of locomotor rhythms. Their RNAi considerably altered the rhythmic transcription of not only cyc but also tim. Surprisingly, the RNAi of HR3 revealed the rhythmic expression of Clk, suggesting that this ancestral insect species possesses the mechanisms for rhythmic expression of both cyc and Clk genes. When either HR3 or E75 was knocked down, tim, cyc, and Clk or tim and cyc, respectively, oscillated in phase, suggesting that the two genes play an important role in the regulation of the phase relationship among the clock genes. Interestingly, HR3 and E75 were also found to be involved in the regulation of ecdysis, suggesting that they interconnect the circadian clock and developmental processes.


Results From a Randomized, Placebo-Controlled Clinical Trial of a RBX2660-A Microbiota-Based Drug for the Prevention of Recurrent Clostridium difficile Infection.
Despite advancements, recurrent Clostridium difficile infections (CDI) remain an urgent public health threat with insufficient response rates to currently approved antibiotic therapies. Microbiota-based treatments appear effective, but rigorous clinical trials are required to optimize dosing strategies and substantiate long-term safety. This randomized, double-blind, placebo-controlled phase 2B trial enrolled adults with 2 or more CDI recurrences to receive: 2 doses of RBX2660, a standardized microbiota-based drug (group A); 2doses of placebo (group B); or 1 dose of RBX2660 followed by 1 dose of placebo (group C). Efficacy was defined as prevention of recurrent CDI for 8 weeks following treatment. Participants who had a recurrence within 8 weeks were eligible to receive up to 2 open-label RBX2660 doses. The primary endpoint was efficacy for group A compared to group B. Secondary endpoints included the efficacy of group C compared to group B, combined efficacy in the blinded and open-label phases, and safety for 24 months. The efficacy for groups A, B, and C were 61%, 45%, and 67%, respectively. The primary endpoint was not met (P = .152). One RBX2660 dose (group C) was superior to placebo (group B; P = .048), and the overall efficacy (including open-label response) for RBX2660-treated participants was 88.8%. Adverse events did not differ significantly among treatment groups. One, but not 2, doses of RBX2660 was superior to placebo in this randomized, placebo-controlled trial. These data provide important insights for a larger phase 3 trial and continued clinical development of RBX2660. NCT02299570.


Non-steroidal anti-inflammatory drugs and risk of Parkinson's disease in the elderly population: a meta-analysis.
Several studies have explored the impact of non-steroidal anti-inflammatory drugs (NSAIDs) and the risk of Parkinson disease (PD). However, the extent to which NSAIDs may increase or decrease the risk of PD remains unresolved. We, therefore, performed a meta-analysis of relevant studies to quantify the magnitude of the association between NSAID use and PD risk in the elderly population. The electronic databases such as PubMed, EMBASE, Scopus, Google Scholar, and Web of Science were used to search the relevant articles published between January 1990 and December 2017. Large (n ≥ 1000) observational design studies with a follow-up at least 1 year were considered. Two authors independently extracted information from the included studies. Random effect model was used to calculate risk ratios (RRs) with 95% confidence interval (Cl). A total of 17 studies with 2,498,258 participants and nearly 14,713 PD patients were included in the final analysis. The overall pooled RR of PD was 0.95 (95%CI 0.860-1.048) with significant heterogeneity (I2 = 63.093, Q = 43.352, p < 0.0001). In the subgroup analysis, the overall pooled RR of PD was 0.90 (95%CI 0.738-1.109), 0.96 (95%CI 0.882-1.055), and 0.99 (95%CI 0.841-0.982) from the studies of North America, Europe, and Asia. Additionally, long-term use, study design, individual NSAID use, and risk of PD were also evaluated. Despite the neuroprotective potential of NSAIDs demonstrated in some experimental studies, our findings suggest that there is no association between NSAIDs and the risk of Parkinson disease at the population level. Until further evidence is established, clinicians need to be vigilant ensuring that the use of NSAIDs remains restricted to their approved anti-inflammatory and analgesic effect.


Association of interleukin-1 gene polymorphisms with Alzheimer's disease.
Interleukin-1 (IL-1) is markedly overexpressed in Alzheimer's disease. We found the IL-1A 2,2 genotype in 12.9% of 232 neuropathologically confirmed Alzheimer's disease patients and 6.6% of 167 controls from four centers in the United Kingdom and United States (odds ratio, 3.0; controlled for age and for ApoE [apolipoprotein E] genotype). Homozygosity for both allele 2 of IL-1A and allele 2 of IL-1B conferred even greater risk (odds ratio, 10.8). IL-1 genotypes may confer risk for Alzheimer's disease through IL-1 overexpression and IL-1-driven neurodegenerative cascades.


[Surgical treatment of combined injuries of the anterior and posterior segment of the eye with intraocular metallic foreign body].
The aim of this study was to establish anatomical and functional results of combined injuries of the anterior and posterior segment of the eye caused by penetration of the metallic foreign body. The group consisted of 25 eyes with penetrating injury caused by metallic intraocular body. The age at time of the injury in the group was 14-68 years (36.8 +/- 10.9) and the average follow up period was 21.0 +/- 10.7 months. All injuries were treated by means of suture of the entering wound with immediate or postponed treatment of the pathologic findings in both segments during one or more procedures. The metallic foreign bodies were extracted with forceps or endomagnetic device during the pars plana vitrectomy. Traumatic changes of the retina were treated by means of endodiathermy and endolaser. Silicone oil tamponade was performed, where indicated. The partial or total traumatic cataract was removed by phacoemulsification through the scleral admittance or by endophaco fragmentation with or without intraocular lens implantation. The most common pathological findings were the penetrating wound of the cornea (72%) and traumatic changes of the iris (56%). The total cataract was present in 56 % of cases. In the posterior segment, vitreous hemorrhage was most frequent (36%). Signs of endophtalmitis were present in 12% of cases. The period between the primary suture and combined procedure at the anterior and posterior segment was mostly 5-14 days (56%). In ten cases (40%), the intraocular lens (IOL) was implanted, 9 times in the posterior and once in the anterior chamber. Out of the early postoperative complications, the fibrin in the anterior chamber was noticed most frequently (16%), and out of the late ones, the retinal detachment (32%) and proliferative vitreoretinopathy (24) were most common. Anatomical and functional result of the combined injury with the foreign intraocular body depends not only on the choice of the surgical technique, but predominantly on the extent of the initial injury and risk of the present infection's spreading.


Substance abuse and criminal activities following traumatic brain injury in childhood, adolescence, and early adulthood.
Use a longitudinal birth cohort to evaluate the association of traumatic brain injury at ages 0 to 5, 6 to 15, and 16 to 21 years with drug and alcohol abuse and engagement in criminal activities. Follow-up over 21 to 25 years using self-report of drug and alcohol use, arrests, and violent and property offenses. Outcomes were assessed for 2 levels of severity (inpatient, hospitalized; outpatient, seen by general practitioner or at emergency department). Members of the Christchurch Health and Development Study, a longitudinal birth cohort. Christchurch, New Zealand. Adjusted for child and family factors, compared with noninjured individuals, inpatients injured at 0 to 5 years or 16 to 21 years were more likely to have symptoms consistent with drug dependence. All inpatient groups had increased risk of arrest, with the age groups of 0 to 5 and 6 to 15 years more likely to be involved in violent offenses and the age group of 0 to 5 years more likely to engage in property offenses. Outpatient group had an increased risk of violent offenses for first injury 0 to 5 years, arrests and property offenses for injury 6 to 15 years, and increased risk of arrests and violent offenses for injury 16 to 21 years of age. However, when alcohol dependence and drug dependence were added as an additional covariate, traumatic brain injury was no longer associated with criminal behavior for the age group of 0 to 5 years. Traumatic brain injury is associated with increased criminal behavior and may represent a risk factor for offending. However, early substance use is a mediating factor for those injured early in life.


Mono-nuclear copper complexes mimicking the intermediates for the binuclear copper center of the subunit II of cytochrome oxidase: a peptide based approach.
Three stable copper complexes of peptides derived from the copper ion binding loop of the subunit II of cytochrome c oxidase have been prepared and characterized by various spectroscopic techniques. These stable copper complexes of peptides were found to exhibit cysteine, histidine and/or methionine ligation, which has predominant σ-contribution in the Cys-Cu charge transfer. The copper(ii) peptide complexes showed type-2 EPR spectra, which is uncommon in copper-cysteinate complexes. UV-visible spectra, Raman and EPR results support a tetragonal structure of the coordination geometry around the copper ion. The copper complex of the 9-amino acid peptide suggested the formation of a 'red' copper center while the copper complexes of the 12- and 11-amino acid peptides showed the formation of a 'green' copper center. The results provide insights on the first stable models of the copper complexes formed in the peptide scaffold that mimic the mono-nuclear copper bound protein intermediates proposed during the formation of the binuclear Cu2S2 core of the enzyme. These three copper complexes of peptides derived from the metal ion binding loop of the CuA center of the subunit II of cytochrome c oxidase showed novel spectroscopic properties which have not so far been reported in any stable small complex.


Bodily illusions in health and disease: physiological and clinical perspectives and the concept of a cortical 'body matrix'.
Illusions that induce a feeling of ownership over an artificial body or body-part have been used to explore the complex relationships that exist between the brain's representation of the body and the integrity of the body itself. Here we discuss recent findings in both healthy volunteers and clinical populations that highlight the robust relationship that exists between a person's sense of ownership over a body part, cortical processing of tactile input from that body part, and its physiological regulation. We propose that a network of multisensory and homeostatic brain areas may be responsible for maintaining a 'body-matrix'. That is, a dynamic neural representation that not only extends beyond the body surface to integrate both somatotopic and peripersonal sensory data, but also integrates body-centred spatial sensory data. The existence of such a 'body-matrix' allows our brain to adapt to even profound anatomical and configurational changes to our body. It also plays an important role in maintaining homeostatic control over the body. Its alteration can be seen to have both deleterious and beneficial effects in various clinical populations.


Representation of Women With Industry Ties in Ophthalmology.
Women in ophthalmology are growing in number and have made strides in traditional metrics of professional achievement. Professional ties to industry represent another potential means of career advancement, recognition, and income. To report the representation of women among ophthalmologists receiving industry remuneration for research, consulting, honoraria, grants, royalties, and faculty/speaker roles. In this observational, retrospective study, the Centers for Medicare and Medicaid Services Open Payments database for payments to ophthalmologists by biomedical companies was reviewed for representation, median payments, and mean payments by women and men for industry relationships in 2013 and 2014. The analysis was performed from July 2015 to November 2015. The primary outcome measures were percentage representation of women vs men overall and in industry research, consulting, speaking roles, royalties and licenses, grants, services other than consulting, and honoraria. Secondary outcome measures included mean and median payments from industry to female vs male ophthalmologists. In 2013, 4164 of 21 380 (19.5%) ophthalmologists were women, and of 1204 ophthalmologists analyzed for industry payments, 176 (4.2%) women had industry ties compared with 1028 (6%) men (P < .001). Mean payments to women were $11 419 compared with $20 957 for men (P = .001), and median payments to women were $3000 compared with $4787 for men (P = .007). In 2013, women were underrepresented among ophthalmologists receiving industry payments for research (49 of 462 [10.6%]), consulting (96 of 610 [15.7%]), honoraria (3 of 47 [6.4%]), industry grants (1 of 7 [14.3%]), royalties and licenses (1 of 13 [7.7%]), and faculty/speaker roles (2 of 48 [4.2%]). In 2014, 4352 of 21 531 (20.2%) of ophthalmologists were women. Of 1518 ophthalmologists analyzed for industry payments, 255 (6%) women had industry ties compared with 1263 (7.4%) men (P < .001). Mean payments to women were $14 848 compared with $30 513 for men (P = .004), and median payments to women were $3750 compared with $5000 for men (P = .005). Women remained underrepresented among ophthalmologists receiving industry payments for research (25 of 241 [10.4%]), consulting (145 of 921 [15.7%]), honoraria (14 of 11 [12.6%]), industry grants (3 of 25 [12.0%]), royalties and licenses (1 of 22 [4.6%]), and faculty/speaker roles (21 of 189 [11.1%]) in 2014. Women make up a minority of ophthalmologists with professional industry relationships, and the average woman partnering with industry earns less than her male colleagues. The reasons for differences are multifactorial and could not be determined by this study.


Pulsed-field gel electrophoresis analysis of Bordetella pertussis isolates circulating in Europe from 1998 to 2009.
Between 1998 and 2009, Bordetella pertussis clinical isolates were collected during three periods, i.e., 1998 to 2001 (n = 102), 2004 to 2005 (n = 154), and 2007 to 2009 (n = 140), from nine countries with distinct vaccination programs, i.e., Denmark, Finland, France, Germany, The Netherlands, Norway, Poland, Sweden, and the United Kingdom. Pulsed-field gel electrophoresis (PFGE) analysis was performed according to standardized recommendations for epidemiological typing of B. pertussis. There were 81 different PFGE profiles, five of which (BpSR3, BpSR5, BpSR10, BpSR11, and BpSR12) were observed in 61% of the 396 isolates and shown to be predominant in almost all countries. The major profile, BpSR11, showed a decreasing trend from 25% to 30% in 1998 to 2005 to 13% in 2007 to 2009, and there were increases in BpSR3 and BpSR10 from 0% and 8% to 21% and 22%, respectively. One difference between these profiles is that BpSR11 contains isolates harboring the fim3-2 allele and BpSR3 and BpSR10 contain isolates harboring the fim3-1 allele. The total proportion of the five predominant profiles increased from 44% in 1998 to 2001 to 63% in 2004 to 2005 to 70% in 2007 to 2009. In conclusion, common PFGE profiles were identified in B. pertussis populations circulating in European countries with different vaccination programs and different vaccine coverages. These prevalent isolates contain the novel pertussis toxin promoter ptxP3 allele. However, there is evidence for diversifying selection between ptxP3 strains characterized by distinct PFGE profiles. This work shows that, even within a relatively short time span of 10 years, successful isolates which spread through Europe and cause large shifts in B. pertussis populations may emerge.


Dietary intake of fish, omega-3, omega-6 polyunsaturated fatty acids and vitamin D and the prevalence of psychotic-like symptoms in a cohort of 33,000 women from the general population.
Low intake of fish, polyunsaturated fatty acids (PUFA) and vitamin D deficiency has been suggested to play a role in the development of schizophrenia. Our aim was to evaluate the association between the intake of different fish species, PUFA and vitamin D and the prevalence of psychotic-like symptoms in a population-based study among Swedish women. Dietary intake was estimated using a food frequency questionnaire among 33,623 women aged 30-49 years at enrollment (1991/92). Information on psychotic-like symptoms was derived from a follow-up questionnaire in the years 2002/03. Participants were classified into three predefined levels: low, middle and high frequency of symptoms. The association between diet and psychotic-like symptoms was summarized in terms of relative risks (RR) and corresponding 95% confidence intervals and was evaluated by energy-adjusted multinomial logistic regression. 18,411 women were classified as having a low level of psychotic-like symptoms, 14 395 as middle and 817 as having a high level. The risk of high level symptoms was 53% (95% CI, 30-69%) lower among women who ate fish 3-4 times per week compared to women who never ate fish. The risk was also lower for women with a high intake of omega-3 and omega-6 PUFA compared to women with a lower intake of these fatty acids. The effect was most pronounced for omega-6 PUFAs. The RR comparing the highest to the lowest quartile of omega-6 PUFAs intake was 0.78 (95% CI, 0.64-0.97). The associations were J-shaped with the strongest reduced risk for an intermediate intake of fish or PUFA. For fatty fish (herring/mackerel, salmon-type fish), the strongest inverse association was found for an intermediate intake (RR: 0.81, 95% CI, 0.66-0.98), whereas a high intake of fatty fish was associated with an increased risk of psychotic-like symptoms (RR: 1.90, 95% CI, 1.34-2.70). Women in the highest compared with the lowest quartile of vitamin D consumption experienced a 37% (95% CI, 22-50%) lower risk of psychotic-like symptoms. Our findings raise a possibility that adult women with a high intake of fish, omega-3 or omega-6 PUFA and vitamin D have a lower rate of psychotic-like symptoms.


Surface modification of a POSS-nanocomposite material to enhance cellular integration of a synthetic bioscaffold.
Polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane (POSS-PCU) is a versatile nanocomposite biomaterial with growing applications as a bioscaffold for tissue engineering. Integration of synthetic implants with host tissue can be problematic but could be improved by topographical modifications. We describe optimization of POSS-PCU by dispersion of porogens (sodium bicarbonate (NaHCO3), sodium chloride (NaCl) and sucrose) onto the material surface, with the principle aim of increasing surface porosity, thus providing additional opportunities for improved cellular and vascular ingrowth. We assess the effect of the porogens on the material's mechanical strength, surface chemistry, wettability and cytocompatibilty. Surface porosity was characterized by scanning electron microscopy (SEM). There was no alteration in surface chemistry and wettability and only modest changes in mechanical properties were detected. The size of porogens correlated well with the porosity of the construct produced and larger porogens improved interconnectivity of spaces within constructs. Using primary human bronchial epithelial cells (HBECs) we demonstrate moderate in vitro cytocompatibility for all surface modifications; however, larger pores resulted in cellular aggregation. These cells were able to differentiate on POSS-PCU scaffolds. Implantation of the scaffold in vivo demonstrated that larger pore sizes favor cellular integration and vascular ingrowth. These experiments demonstrate that surface modification with large porogens can improve POSS-PCU nanocomposite scaffold integration and suggest the need to strike a balance between the non-porous surfaces required for epithelial coverage and the porous structure required for integration and vascularization of synthetic scaffolds in future construct design.


Penetrating or stricturing diseases are the major determinants of time to first and repeat resection surgery in Crohn's disease.
About 80% of patients with Crohn's disease (CD) require bowel resection and up to 65% will undergo a second resection within 10 years. This study reports clinical risk factors for resection surgery (RS) and repeat RS. Retrospective cohort study, using data from patients included in the Swiss Inflammatory Bowel Disease Cohort. Cox regression analyses were performed to estimate rates of initial and repeated RS. Out of 1,138 CD cohort patients, 417 (36.6%) had already undergone RS at the time of inclusion. Kaplan-Meier curves showed that the probability of being free of RS was 65% after 10 years, 42% after 20 years, and 23% after 40 years. Perianal involvement (PA) did not modify this probability to a significant extent. The main adjusted risk factors for RS were smoking at diagnosis (hazard ratio (HR) = 1.33; p = 0.006), stricturing with vs. without PA (HR = 4.91 vs. 4.11; p < 0.001) or penetrating disease with vs. without PA (HR = 3.53 vs. 4.58; p < 0.001). The risk factor for repeat RS was penetrating disease with vs. without PA (HR = 3.17 vs. 2.24; p < 0.05). The risk of RS was confirmed to be very high for CD in our cohort. Smoking status at diagnosis, but mostly penetrating and stricturing diseases increase the risk of RS.


The fibromyalgia bladder index.
The aim of this study was to determine whether an existing outcome measure, the Interstitial Cystitis Symptom and Problem Index (ICSI/ICPI), is a valid, reliable, and clinically relevant instrument to assess the sensory urinary symptoms in women with fibromyalgia syndrome (FM). Ninety women with American College of Rheumatology 90 FM and who had at least two sensory bladder symptoms participated in the study. All underwent urological screening to exclude lower urinary tract pathology. All participants completed the following: ICSI/ICPI, Fibromyalgia Impact Questionnaire (FIQ), Medical Outcome Study Short Form 36, King's Health Questionnaire (KHQ), and Vulval Symptom Assessment Scale. Assessment was made for internal consistency reliability, test-retest reliability, and concurrent validity. Factor analysis was used to assess the internal structure of the scale. Factor analysis displayed two separate components of symptom and problem combinations as distinct from the original ICSI/ICPI developed for the interstitial cystitis population. The eight items of the index configured differently and formed two subscales of a newly developed Fibromyalgia Bladder Index. The two subscales of this index include the Bladder Urgency and Pain Subscale and the Bladder Frequency and Nocturia Subscale. This index has high internal consistency reliability (Cronbach's alpha coefficient of 0.81), test-retest reliability showing intraclass correlation of 0.85, and high concurrent validity through correlations between the Fibromyalgia Bladder Index and the KHQ (0.735, p = 0.000) and the FIQ (0.433, p = 0.000). This more specific configuration of the ICSI/ICPI better reflects FM bladder symptomatology. The Fibromyalgia Bladder Index is a validated FM-specific instrument that captures information about the sensory bladder symptoms and their impact in this fibromyalgia population. This instrument should allow for better understanding and management of this important fibromyalgia-associated problem.


Swamp rice farming: possible effects on endemicity of schistosomiasis mansoni and haematobia in a population in Liberia.
To obtain a better understanding of the possible influence of swamp rice farming on the patterns of Schistosoma mansoni and Schistosoma haematobium infections, the populations of two communities in rural liberia were studied. In one village, Balama (population of 435), swamp rice farms were initiated six years before the survey; in the other nearby community, Gbarta (population of 216), swamp rice farms had not yet been initiated. The prevalence of S. mansoni infection in Balama was 87% vs. 9% in Gbarta (P less than 0.01). The geometric and arithmetic mean egg counts for all infected subjects in Balama were respectively 263 and 671/g feces. in Gbarta, the geometric and arithmetic mean egg counts were 150 and 129/g feces. S. haematobium eggs were detected in 42% of subjects in Balama vs. 11% in Gbarta (P less than 0.01). Hematuria correlated with the presence of S. haematobium eggs in urine. These data indicate that there is a significantly higher prevalence and intensity of schistosomiasis mansoni and haematobia in a community where swamp rice farming has been utilized for 6 years compared to a nearby village where this water irrigation and drainage practice has not yet been implemented.


Molecular correlates of social dominance: a novel role for ependymin in aggression.
Theoretical and empirical studies have sought to explain the formation and maintenance of social relationships within groups. The resulting dominance hierarchies have significant fitness and survival consequences dependent upon social status. We hypothesised that each position or rank within a group has a distinctive brain gene expression profile that correlates with behavioural phenotype. Furthermore, transitions in rank position should determine which genes shift in expression concurrent with the new dominance status. We used a custom cDNA microarray to profile brain transcript expression in a model species, the rainbow trout, which forms tractable linear hierarchies. Dominant, subdominant and submissive individuals had distinctive transcript profiles with 110 gene probes identified using conservative statistical analyses. By removing the dominant, we characterised the changes in transcript expression in sub-dominant individuals that became dominant demonstrating that the molecular transition occurred within 48 hours. A strong, novel candidate gene, ependymin, which was highly expressed in both the transcript and protein in subdominants relative to dominants, was tested further. Using antibody injection to inactivate ependymin in pairs of dominant and subdominant zebrafish, the subdominant fish exhibited a substantial increase in aggression in parallel with an enhanced competitive ability. This is the first study to characterise the molecular signatures of dominance status within groups and the first to implicate ependymin in control of aggressive behaviour. It also provides evidence for indirect genetic effect models in which genotype/phenotype of an individual is influenced by conspecific interactions within a group. The variation in the molecular profile of each individual within a group may offer a new explanation of intraspecific variation in gene expression within undefined groups of animals and provides new candidates for empirical study.


Candiduria in catheterized intensive care unit patients: emerging microbiological trends.
Urinary tract infection (UTI) as a result of Candida spp. is becoming increasingly common in hospitalized setting. Clinicians face dilemma in differentiating colonization from true infection and whether to treat candiduria or not. The objective of the present study was to look into the significance of candiduria in catheterized patients admitted in the ICUs and perform microbiological characterization of yeasts to guide treatment protocols. One hundred consecutive isolates of Candida spp. from the urine sample of 70 catheterized patients admitted in the ICU were collected and stocked for further characterization. A proforma was maintained containing demographic and clinical details. Blood cultures were obtained from all these 70 patients and processed. Species identification of yeasts was done on VITEK. Candiduria was more common at extremes of age. The mean duration of catheter days was 11.1 ± 6 days. Other associated risk factors such as diabetes mellitus and antibiotic usage were seen in 38% and 100% of our study group. Concomitant candidemia was seen in 4.3% of cases. Non-albicans Candida spp. (71.4%) emerged as the predominant pathogen causing nosocomial UTI. The present study reiterates the presence of candiduria in catheterized patients, especially in the presence of diabetes and antibiotic usage. Non-albicans Candida spp. are replacing Candida albicans as the predominant pathogen for nosocomial UTI. Hence, we believe that surveillance for nosocomial candiduria should be carried out in hospitalized patients.


Effectiveness of YouTube as a Source of Medical Information on Heart Transplantation.
In this digital era, there is a growing tendency to use the popular Internet site YouTube as a new electronic-learning (e-learning) means for continuing medical education. Heart transplantation (HTx) remains the most viable option for patients with end-stage heart failure or severe coronary artery disease. There are plenty of freely accessible YouTube videos providing medical information about HTx. The aim of the present study is to determine the effectiveness of YouTube as an e-learning source on HTx. In order to carry out this study, YouTube was searched for videos uploaded containing surgical-related information using the four keywords: (1) "heart transplantation", (2) "cardiac transplantation", (3) "heart transplantation operation", and (4) "cardiac transplantation operation". Only videos in English (with comments or subtitles in English language) were included. Two experienced cardiac surgeons watched each video (N=1800) and classified them as useful, misleading, or recipients videos based on the HTx-relevant information. The kappa statistic was used to measure interobserver variability. Data was analyzed according to six types of YouTube characteristics including "total viewership", "duration", "source", "days since upload", "scores" given by the viewers, and specialized information contents of the videos. A total of 342/1800 (19.00%) videos had relevant information about HTx. Of these 342 videos, 215 (62.8%) videos had useful information about specialized knowledge, 7/342 (2.0%) were found to be misleading, and 120/342 (35.1%) only concerned recipients' individual issues. Useful videos had 56.09% of total viewership share (2,175,845/3,878,890), whereas misleading had 35.47% (1,375,673/3,878,890). Independent user channel videos accounted for a smaller proportion (19% in total numbers) but might have a wider impact on Web viewers, with the highest mean views/day (mean 39, SD 107) among four kinds of channels to distribute HTx-related information. YouTube videos on HTx benefit medical professionals by providing a substantial amount of information. However, it is a time-consuming course to find high-quality videos. More authoritative videos by trusted sources should be posted for dissemination of reliable information. With an improvement of ranking system and content providers in future, YouTube, as a freely accessible outlet, will help to meet the huge informational needs of medical staffs and promote medical education on HTx.


Diet Assessment Based on Rumen Contents: A Comparison between DNA Metabarcoding and Macroscopy.
Dietary choices are central to our understanding of ecology and evolution. Still, many aspects of food choice have been hampered by time consuming procedures and methodological problems. Faster and cheaper methods, such as DNA metabarcoding, have therefore been widely adopted. However, there is still very little empirical support that this new method is better and more accurate compared to the classic methods. Here, we compare DNA metabarcoding to macroscopic identifications of rumen contents in two species of wild free-ranging ungulates: roe deer and fallow deer. We found that the methods were comparable, but they did not completely overlap. Sometimes the DNA method failed to identify food items that were found macroscopically, and the opposite was also true. However, the total number of taxa identified increased using DNA compared to the macroscopic analysis. Moreover, the taxonomic precision of metabarcoding was substantially higher, with on average 90% of DNA-sequences being identified to genus or species level compared to 75% of plant fragments using macroscopy. In niche overlap analyses, presence/absence data showed that both methods came to very similar conclusions. When using the sequence count data and macroscopic weight, niche overlap was lower than when using presence-absence data yet tended to increase when using DNA compared to macroscopy. Nevertheless, the significant positive correlation between macroscopic quantity and number of DNA sequences counted from the same plant group give support for the use of metabarcoding to quantify plants in the rumen. This study thus shows that there is much to be gained by using metabarcoding to quantitatively assess diet composition compared to macroscopic analysis, including higher taxonomic precision, sensitivity and cost efficiency.


Prevalence of Listeria spp. and Molecular Characterization of Listeria monocytogenes Isolates from Broilers at the Abattoir.
Products from three broiler abattoirs were sampled for Listeria species to evaluate the changes in the prevalence and contamination rates at two stages of processing. Sampling was performed at the evisceration stage and at the end of processing after packaging and refrigerating at 4°C for 24 h. A total of 212 samples were collected; 52 were from abattoir A, and 80 samples each were collected from abattoirs B and C. Among all samples, 99 (46.7%) tested positive for Listeria, including L. monocytogenes 19 (8.9%), L. innocua 69 (32.5%), L. grayi 10 (4.7%), and L. welshimeri 1 (0.5%). The L. monocytogenes contamination rate varied from 5% to 11.5% in the 3 abattoirs. L. innocua was the most common species identified and was found in 8.8% of the samples from abattoir A and 33.7% of the samples from both abattoirs B and C. Twenty-six of the L. monocytogenes isolates obtained from positive samples were subjected to serotyping by multiplex polymerase chain reaction and characterization by the pulsed-field gel electrophoresis (PFGE) method using two cutting enzymes, ApaI and AscI. Three molecular serogroups were identified: IIa, IIb, and IVb. Serogroup IIa was common to all abattoirs, and serogroups IIb and IVb were found only in abattoir C. The 10 different obtained PFGE profiles were grouped into 7 clusters; some of these clusters were common to the 3 abattoirs, and others were specific to the abattoirs in which they were identified. This study revealed a high prevalence of Listeria spp., particularly L. monocytogenes, in raw broilers. This high incidence presents a risk to consumers due to the potential occurrence of cross-contamination with other foods in domestic refrigerators and the ability of these microorganisms to survive in undercooked products.


A trajectory towards partnership in care--Patient experiences of autonomy in intensive care: A qualitative study.
The aim of this study was to describe and elucidate patient experiences of autonomy in an intensive care context from a caring perspective. Patients in intensive care units (ICUs) are critically ill and in a dependent and vulnerable position. There is thus a risk of staff taking command not only of the patients' vital functions but also of their decision-making. A qualitative design was selected. Individual interviews were conducted with 11 adult patients with an intensive care episode of two days or more at six Swedish ICUs. The data were analysed using Inductive Content Analysis. Patient autonomy in intensive care was shown to be 'A trajectory towards partnership in care depending on state of health and mutual understanding'. It was experienced through acknowledged dependence, being recognised as a person, invited participation and becoming a co-partner in care. Patients in need of intensive care wanted to be involved in making decisions about their care as this creates a trusting and healthy care environment. Greater awareness is required about the ICU patient not only being a passive care recipient but also an active agent and where involvement in decision-making and participation in care are crucial.


Microbiology in complicated head and neck infections.
To identify the pathogens associated with complicated ear, throat and sinus infections and to link the relevant susceptibility patterns to the empirical therapy currently advised in the Dutch guidelines. Retrospective, descriptive study of consecutive cases. Tertiary referral centre. All consecutive patients with a complicated ear, nose and throat infection who underwent surgery at a tertiary referral centre during a six-year period. The term 'complicated' was used to define infections that had spread outside the primary region of infection (middle ear cavity, pharyngeal mucosa, or paranasal sinus) and which therefore, under our policy, required surgical intervention. Microbiological culture and susceptibility pattern A total of 96 patients were included in this study. The predominant causative organisms for the infections were Streptococcus pneumonia, beta hemolytic streptococci and Streptococcus milleri for ear, throat, and sinus infections, respectively. These were all susceptible to the recommended empirical therapy. Cultures from 6 patients yielded coagulase-negative staphylococci resistant to frequently used antibiotics. The mortality rate in our series was 13% for ear infections. This was caused by complicated infections in young children and patients with cholesteatoma. Ten per cent of the ear infections in adults yielded Pseudomonas aeruginosa and 25% yielded anaerobes. Ear infections in young children and in patients with cholesteatoma should be treated aggressively. Our results suggest that patients with intracranial complications stemming from ear infections should preferably be treated with a combination therapy including antibiotics targeting gram negatives and anaerobes. The role of coagulase-negative staphylococci, especially in neck abscesses, may be more important than has been thought until now.


Development of a Human Immunodeficiency Virus Risk Prediction Model Using Electronic Health Record Data From an Academic Health System in the Southern United States.
Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) is underutilized in the southern United States. Rapid identification of individuals vulnerable to diagnosis of HIV using electronic health record (EHR)-based tools may augment PrEP uptake in the region. Using machine learning, we developed EHR-based models to predict incident HIV diagnosis as a surrogate for PrEP candidacy. We included patients from a southern medical system with encounters between October 2014 and August 2016, training the model to predict incident HIV diagnosis between September 2016 and August 2018. We obtained 74 EHR variables as potential predictors. We compared Extreme Gradient Boosting (XGBoost) versus least absolute shrinkage selection operator (LASSO) logistic regression models, and assessed performance, overall and among women, using area under the receiver operating characteristic curve (AUROC) and area under precision recall curve (AUPRC). Of 998 787 eligible patients, 162 had an incident HIV diagnosis, of whom 49 were women. The XGBoost model outperformed the LASSO model for the total cohort, achieving an AUROC of 0.89 and AUPRC of 0.01. The female-only cohort XGBoost model resulted in an AUROC of 0.78 and AUPRC of 0.00025. The most predictive variables for the overall cohort were race, sex, and male partner. The strongest positive predictors for the female-only cohort were history of pelvic inflammatory disease, drug use, and tobacco use. Our machine-learning models were able to effectively predict incident HIV diagnoses including among women. This study establishes feasibility of using these models to identify persons most suitable for PrEP in the South.


Islet regeneration during the reversal of autoimmune diabetes in NOD mice.
Nonobese diabetic (NOD) mice are a model for type 1 diabetes in humans. Treatment of NOD mice with end-stage disease by injection of donor splenocytes and complete Freund's adjuvant eliminates autoimmunity and permanently restores normoglycemia. The return of endogenous insulin secretion is accompanied by the reappearance of pancreatic beta cells. We now show that live donor male or labeled splenocytes administered to diabetic NOD females contain cells that rapidly differentiate into islet and ductal epithelial cells within the pancreas. Treatment with irradiated splenocytes is also followed by islet regeneration, but at a slower rate. The islets generated in both instances are persistent, functional, and apparent in all NOD hosts with permanent disease reversal.


Testing a new cognitive behavioural treatment for obesity: A randomized controlled trial with three-year follow-up.
It is remarkably difficult for people with obesity to maintain a new lower weight following weight loss. The aim of the present study was to examine the immediate and longer-term effects of a new cognitive behavioural treatment that was explicitly designed to minimise this post-treatment weight regain. One hundred and fifty female participants with obesity were randomized to the new treatment, behaviour therapy (the leading alternative psychological treatment) or guided self-help (a minimal intervention). Both of the main treatments resulted in an average weight loss of about ten percent of initial weight whereas weight loss was more modest with guided self-help. The participants were subsequently followed-up for three years post-treatment. The great majority regained almost all the weight that they had lost with the new treatment being no better than the behavioural treatment in preventing weight regain. These findings lend further support to the notion that obesity is resistant to psychological methods of treatment, if anything other than a short-term perspective is taken. It is suggested that it is ethically questionable to claim that psychological treatments for obesity "work" in the absence of data on their longer-term effects.


Moderating effects of age on the alcohol and sexual risk taking association: an online daily diary study of men who have sex with men.
Men who have sex with men (MSM) account for the majority of HIV/AIDS diagnoses and data suggest infection rates are rising. Identification of factors that increase the risk of infection is key to the development of effective prevention programs. Previous research has been inconsistent regarding the link between alcohol consumption and sexual risk taking among MSM. Daily reports of alcohol consumption and sexual behavior were completed for up to 30 days by 143 HIV negative MSM recruited online. This resulted in 2,887 daily reports of number of sex partners and 549 episodes of sex. Independent variables included age, number of standard drinks consumed, and partner type. Outcome variables included sex with a partner, a composite sexual risk variable, and unprotected anal intercourse (UAI). Alcohol consumption significantly increased the odds of having sex and had a significant positive association with the sexual risk composite variable. Age was a significant moderator of the association between alcohol consumption and sexual risk taking, with the effects of alcohol increasing with age. For example, at the 75%tile of age (37 years old), the odds of UAI increase from approximately 0.2 to 0.35 as the number of alcoholic drinks increases from zero to seven. Partner type did not have significant effects. Daily reports of alcohol consumption had a significant within-person association with sexual risk behaviors, particularly among older MSM. Findings highlight the importance of measuring individual differences as moderators of the association between alcohol and risky sexual behavior.


A randomized, double-blind, placebo-controlled trial of olanzapine in the treatment of trichotillomania.
Trichotillomania has been considered as part of the obsessive-compulsive disorder spectrum; however, trichotillomania treatment with obsessive-compulsive disorder medications has largely been unsuccessful. To determine whether a dopaminergic treatment as used in tics and Tourette's syndrome would be effective in trichotillomania. Twenty-five participants with DSM-IV trichotillomania participated in a 12-week, randomized, double-blind, placebo-controlled trial of flexible-dose olanzapine for trichotillomania. Recruitment occurred between August 2001 and December 2005, and follow-up was completed in February 2006. The primary outcome measure was the Clinical Global Impressions-Improvement (CGI-I) scale, and secondary measures of efficacy included the Yale-Brown Obsessive Compulsive Scale for Trichotillomania (TTM-YBOCS) and the Clinical Global Impressions-Severity of Illness (CGI-S) scale. Eleven of 13 participants (85%) in the olanzapine group and 2 of 12 (17%) in the placebo group were considered responders according to the CGI-I (P = .001). There was a significant change from baseline to end point in the TTM-YBOCS (P < .01) and the CGI-S (P < .001). The mean ± SD dose of olanzapine at end point was 10.8 ± 5.7 mg/d. Twenty-one of 25 patients (84%) reported at least 1 adverse event, but no adverse events resulted in early withdrawal from the study. Olanzapine seems to be a safe and effective treatment for primary DSM-IV trichotillomania. clinicaltrials.gov Identifier: NCT00182507.


Ring-closing metathesis of unprotected peptides in water.
Ring-closing metathesis (RCM) is an attractive reaction for the preparation of artificially designed peptides. Until now, RCM has been used for fully or partially protected peptides. Herein, the first RCM of unprotected peptides in water was achieved using a water-soluble Ru catalyst.


Role of Mycobacterium tuberculosis copper-zinc superoxide dismutase.
Superoxide dismutases (SODs) play an important role in protection against oxidative stress and have been shown to contribute to the pathogenicity of many bacterial species. To determine the function of the mycobacterial copper and zinc-cofactored SOD (CuZnSOD), we constructed and characterized Mycobacterium tuberculosis and Mycobacterium bovis BCG CuZnSOD null mutants. Both strains were more sensitive to superoxides and hydrogen peroxide than were their respective parental strains. The survival of M. bovis BCG in unstimulated as well as activated mouse bone marrow-derived macrophages was not affected by the loss of CuZnSOD. The survival of CuZnSOD deficient-M. tuberculosis in guinea pig tissues was comparable to that of its parental strain. These results indicate that the mycobacterial CuZnSOD is not essential for intracellular growth within macrophages and does not detectably contribute to the pathogenicity of M. tuberculosis.


The C. elegans par-4 gene encodes a putative serine-threonine kinase required for establishing embryonic asymmetry.
During the first cell cycle of Caenorhabditis elegans embryogenesis, asymmetries are established that are essential for determining the subsequent developmental fates of the daughter cells. The maternally expressed par genes are required for establishing this polarity. The products of several of the par genes have been found to be themselves asymmetrically distributed in the first cell cycle. We have identified the par-4 gene of C. elegans, and find that it encodes a putative serine-threonine kinase with similarity to a human kinase associated with Peutz-Jeghers Syndrome, LKB1 (STK11), and a Xenopus egg and embryo kinase, XEEK1. Several strong par-4 mutant alleles are missense mutations that alter conserved residues within the kinase domain, suggesting that kinase activity is essential for PAR-4 function. We find that the PAR-4 protein is present in the gonads, oocytes and early embryos of C. elegans, and is both cytoplasmically and cortically distributed. The cortical distribution begins at the late 1-cell stage, is more pronounced at the 2- and 4-cell stages and is reduced at late stages of embryonic development. We find no asymmetry in the distribution of PAR-4 protein in C. elegans embryos. The distribution of PAR-4 protein in early embryos is unaffected by mutations in the other par genes.


Selective Roles of Vertebrate PCF11 in Premature and Full-Length Transcript Termination.
The pervasive nature of RNA polymerase II (Pol II) transcription requires efficient termination. A key player in this process is the cleavage and polyadenylation (CPA) factor PCF11, which directly binds to the Pol II C-terminal domain and dismantles elongating Pol II from DNA in vitro. We demonstrate that PCF11-mediated termination is essential for vertebrate development. A range of genomic analyses, including mNET-seq, 3' mRNA-seq, chromatin RNA-seq, and ChIP-seq, reveals that PCF11 enhances transcription termination and stimulates early polyadenylation genome-wide. PCF11 binds preferentially between closely spaced genes, where it prevents transcriptional interference and consequent gene downregulation. Notably, PCF11 is sub-stoichiometric to the CPA complex. Low levels of PCF11 are maintained by an auto-regulatory mechanism involving premature termination of its own transcript and are important for normal development. Both in human cell culture and during zebrafish development, PCF11 selectively attenuates the expression of other transcriptional regulators by premature CPA and termination.


When and Where Birth Spacing Matters for Child Survival: An International Comparison Using the DHS.
A large body of research has found an association between short birth intervals and the risk of infant mortality in developing countries, but recent work on other perinatal outcomes from highly developed countries has called these claims into question, arguing that previous studies have failed to adequately control for unobserved heterogeneity. Our study addresses this issue by estimating within-family models on a sample of 4.5 million births from 77 countries at various levels of development. We show that after unobserved maternal heterogeneity is controlled for, intervals shorter than 36 months substantially increase the probability of infant death. However, the importance of birth intervals as a determinant of infant mortality varies inversely with maternal education and the strength of the relationship varies regionally. Finally, we demonstrate that the mortality-reducing effects of longer birth intervals are strong at low levels of development but decline steadily toward zero at higher levels of development. These findings offer a clear way to reconcile previous research showing that birth intervals are important for perinatal outcomes in low-income countries but are much less consequential in high-income settings.


[Teratogenic effect of potato glycoalkaloids].
Potato glycoalkaloids were extracted from potato sprout and then analyzed to determine their purity by using TLC and HPLC methods and compare with pure alpha-Solanine and alpha-Chaconine of Sigma. The result indicated that the purity of potato glycoalkaloids is 78. 31%, which contains 73.64% alpha-Solanine and 4.67% alpha-Chaconine. The LD50 of mice was 44.721 +/- 5.860 4 mg/kg. In order to determine the toxicity and teratogenicity of potato glycoalkaloids, the effect of potato glycoalkaloids on Kunming pregnant mice were studied. The results showed that: (1) potato glycoalkaloids have teratogenic effects on embryos of mice. It could induce neural tube defects (NTDs), and may be an important teratogen of NTDs. (2) potato glycoalkaloids have embryo toxicity. It could cause the death of embryos and result in absorbed and dead fetuses. (3) potato glycoalkaloids could evidently affect the development of embryos and lead to intrauterine growth retardation (IUGR). An interesting phenomena which just like the clinical manifestation of miscarriage in human being was noticed. If potato glycoalkaloids were given to the pregnant mice on the 5th or 6th day of gestation intraabdominally, vaginal bleeding and abortion would occur, and this has not been reported yet. The animal model of NTDs in this experiments supported our hypothesis that sprouted potato could be a teratogen of NTDs.


Long-term outcome of isolated limb perfusion with tumour necrosis factor-α for patients with melanoma in-transit metastases.
The use of tumour necrosis factor (TNF) α in isolated limb perfusion (ILP) for in-transit melanoma metastasis is not uniformly accepted. This article reports the long-term results of adding TNF-α to standard melphalan-based ILP (TM-ILP) for treatment of melanoma in-transit metastases. Data for patients treated between 1991 and 2005 were retrieved from a prospectively maintained database. Hyperthermic ILP was performed with 1-4 mg TNF-α. With a median potential follow-up of 13 years, response rates, time to local progression and disease-specific survival were analysed in relation to standard baseline factors. Some 118 TM-ILPs were analysed in 105 patients, 54 for stage IIIA, 50 for stage IIIAB and 14 for stage IV disease. The overall response rate was 93·2 per cent; the response was complete in 67·8 per cent and partial in 25·4 per cent. The response rate was significantly influenced by stage of disease (IIIA versus IIIAB; P = 0·006). The complete response was maintained until the end of follow-up in 35 patients (33·3 per cent), and local control was achieved with one additional intervention in 12 others (11·4 per cent). Local progression occurred after 66 ILPs (55·9 per cent). Number of in-transit metastases (P = 0·008) and complete response after ILP (P < 0·001) were strong prognostic factors for time to local progression. The 5-year disease-specific survival rate was 27·3 per cent; survival was positively influenced by age, stage of disease, previous ILP and complete response after ILP. ILP with TNF-α may obtain long-term local control in selected patients with in-transit metastases from melanoma.


On the fractal patterns of language structures.
Natural Language Processing (NLP) makes use of Artificial Intelligence algorithms to extract meaningful information from unstructured texts, i.e., content that lacks metadata and cannot easily be indexed or mapped onto standard database fields. It has several applications, from sentiment analysis and text summary to automatic language translation. In this work, we use NLP to figure out similar structural linguistic patterns among several different languages. We apply the word2vec algorithm that creates a vector representation for the words in a multidimensional space that maintains the meaning relationship between the words. From a large corpus we built this vectorial representation in a 100-dimensional space for English, Portuguese, German, Spanish, Russian, French, Chinese, Japanese, Korean, Italian, Arabic, Hebrew, Basque, Dutch, Swedish, Finnish, and Estonian. Then, we calculated the fractal dimensions of the structure that represents each language. The structures are multi-fractals with two different dimensions that we use, in addition to the token-dictionary size rate of the languages, to represent the languages in a three-dimensional space. Finally, analyzing the distance among languages in this space, we conclude that the closeness there is tendentially related to the distance in the Phylogenetic tree that depicts the lines of evolutionary descent of the languages from a common ancestor.