Dynamic metabolic flux analysis using B-splines to study the effects of temperature shift on CHO cell metabolism.
Metabolic flux analysis (MFA) is widely used to estimate intracellular fluxes. Conventional MFA, however, is limited to continuous cultures and the mid-exponential growth phase of batch cultures. Dynamic MFA (DMFA) has emerged to characterize time-resolved metabolic fluxes for the entire culture period. Here, the linear DMFA approach was extended using B-spline fitting (B-DMFA) to estimate mass balanced fluxes. Smoother fits were achieved using reduced number of knots and parameters. Additionally, computation time was greatly reduced using a new heuristic algorithm for knot placement. B-DMFA revealed that Chinese hamster ovary cells shifted from 37 °C to 32 °C maintained a constant IgG volume-specific productivity, whereas the productivity for the controls peaked during mid-exponential growth phase and declined afterward. The observed 42% increase in product titer at 32 °C was explained by a prolonged cell growth with high cell viability, a larger cell volume and a more stable volume-specific productivity.


Long-acting implants to treat and prevent HIV infection.
Subcutaneous implants are a promising technology to enable long-acting parenteral delivery of antiretroviral drugs (ARV) because they may be able to provide protective drugs concentrations for a year or longer following a single implant. The present review covers the current status of preclinical and clinical development of antiretroviral implants. Over the past three decades, subcutaneous implants have been widely used for long-acting hormonal contraception and the treatment of hormonally-driven malignancies. They are economical and scalable to manufacture, but require special procedures for insertion and removal. They are generally well tolerated, and can remain in place for up to five years. As long-acting delivery of ARV would confer significant advantages, a few investigational implants are under development for the delivery of ARV; most remain at preclinical stages of development. Islatravir, a potent nucleoside analog reverse transcriptase translocation inhibitor that shows particular promise, has entered clinical testing in implant form. Investigational implants containing tenofovir alafenamide and nevirapine, and entecavir (for hepatitis B virus) have been developed and tested in animal models, with varying degrees of success. There is also burgeoning interest in bioerodable implant formulations of established ARVs. LARV implants are a promising new technology, but are in early stages of clinical development. Their potential advantages include more consistent and predictable drug release than that provided by intramuscular injections, the possibility of combining several partner drugs into one implant, and the fact that implants can be removed in the case of a desire to stop treatment or the development of adverse events.


Comparison of the effects of a dexmedetomidine-ketamine-midazolam anesthetic protocol versus isoflurane inhalation anesthesia on echocardiography variables and plasma cardiac troponin I concentration in black-tailed prairie dogs (Cynomys ludovicianus).
To compare the effects of a dexmedetomidine-ketamine-midazolam (DKM) anesthetic protocol versus isoflurane inhalation anesthesia on echocardiographic variables and plasma cardiac troponin 1 (cTnI) concentration in black-tailed prairie dogs (BTPDs; Cynomys ludovicianus). Nine 6-month-old sexually intact male captive BTPDs. Each BTPD was randomly assigned to be anesthetized by IM administration of dexmedetomidine (0.25 mg/kg), ketamine (40 mg/kg), and midazolam (1.5 mg/kg) or via inhalation of isoflurane and oxygen. Three days later, each BTPD underwent the alternative anesthetic protocol. Echocardiographic data and a blood sample were collected within 5 minutes after initiation and just prior to cessation of each 45-minute-long anesthetic episode. Time or anesthetic protocol had no significant effect on echocardiographic variables. For either protocol, plasma cTnI concentration did not differ with time. When administered as the first treatment, neither anesthetic protocol significantly affected plasma cTnI concentration. However, with regard to findings for the second treatments, plasma cTnI concentrations in isoflurane-treated BTPDs (n = 4; data for 1 animal were not analyzed because of procedural problems) were higher than values in DKM-treated BTPDs (4), which was suspected to be a carryover effect from prior DKM treatment. The DKM and isoflurane anesthetic protocols did not have any significant effect on echocardiographic measurements in the BTPDs. Increases in plasma cTnI concentration during the second anesthetic episode were evident when BTPDs underwent the DKM anesthetic protocol as the first of the 2 treatments, suggestive of potential myocardial injury associated with that anesthetic protocol. Clinicians should consider these findings, especially when evaluating BTPDs with known or suspected cardiac disease.


Artificial insemination of pigs reared under smallholder production system in northeastern India: success rate, genetic improvement, and monetary benefit.
The study investigated the success rate, genetic improvement, and monetary benefit of artificial insemination (AI) technology in smallholder backyard pig production system. The pig production system was studied, and performance of nondescript and crossbred pigs under the traditional system was evaluated. Litter size and growth rate of crossbred pig was significantly (P < 0.05) higher compared to the nondescript pigs. Non-availability of superior germplasm to produce crossbred pigs and high mating cost were the major constraints observed in the study in addition to indiscriminate mating and non-availability of breeding boar. For genetic improvement of nondescript local pigs and to produce crossbred pigs, AI delivery mechanism was developed in participatory mode including farmers, village leaders, and key persons in 36 villages. The information system was designed in such a way that AI was carried out at the doorstep of the farmer upon request. A total of 167 estrus sow/gilts were artificially inseminated, and a farrowing rate of 78.44 % was obtained with a mean litter size of 7.86 ± 0.65 following AI, which did not differ significantly from natural service. However, the growth rate of crossbred piglets obtained through AI was significantly higher than the growth rate of piglets born out of natural service. The tribal farmers were benefited by AI in several ways: (1) timely availability of superior germplasm to produce crossbred piglets; (2) saved the mating cost of INR 1,000-1,200 and transport of cost (INR 300-400) of female to the boar premises and (3) controlled mating to prevent inbreeding. The present study clearly demonstrates the feasibility and potential benefit of AI technique to smallholder backyard pig production system in tribal rural areas. In addition to genetic improvement of nondescript local pigs, this technology can help in overcoming breeding constraints in smallholder backyard pig production for increasing productivity.


Review of the teaching of medical ethics in London medical schools.
The study examined the influence of the Pond Report on the teaching of medical ethics in the London medical schools. A questionnaire was given to both medical students and college officers. All medical colleges reported that ethics was included in the curriculum. However, from students' replies, it seems that attendance of optional courses is low and that not all current final year medical students have had any formal teaching in medical ethics. Stronger guidelines are necessary to ensure appropriate ethical training in London medical schools.


Unique pore selectivity for Cs+ and exceptionally high NH4+ exchange capacity of the chalcogenide material K6Sn[Zn4Sn4S17].
Highly selective ion-exchange properties and -exchange capacities of the open framework chalcogenide material K(6)Sn[Zn(4)Sn(4)S(17)] (1) with Cs(+) and NH(4)(+) are reported. Because the structure of this framework is known in great detail, these studies are a rare example where structure/property relationships can be directly drawn. 1 possesses three types of micropore cavities. The largest pore of 1 presents an exact fit for Cs(+) and exhibits high selectivity for this ion, as demonstrated by competitive ion-exchange experiments. The next largest pore has a greater capacity (up to four cations) and is well suited for NH(4)(+) ions. This leads to a high ammonium-exchange capacity for 1 of 3.06 mequiv/gr, which is close to the NH(4)(+)-exchange capacities of natural zeolites. The single-crystal structures of ammonium-exchanged products at various stages reveal an unusual mechanism for the exchange process of 1 which involves diffusion of ammonium cations from the large cavity to the small ones of the framework. Thermal analysis of one of these ammonium-exchanged products, in combination with mass spectroscopy, showed the decomposition of NH(4)(+) cations to NH(3) and H(2)S with the parallel transformation of the exchanged product to a mixture of crystalline phases. Since K(6)Sn[Zn(4)Sn(4)S(17)] can be grown in suitably large crystals (much larger than most zeolites), it defines an excellent model system in which ion-exchange processes and products can be characterized and studied in detail in various reaction stages.


Psychiatric inpatient cost of care before and after admission at a residential subacute step-up/step-down mental health facility.
Residential step-up/step-down services provide transitional care and reintegration into the community for individuals experiencing episodes of subacute mental illness. This study aims to examine psychiatric inpatient admissions, length of stay, and per capita cost of care following the establishment of a step-up/step-down Prevention And Recovery Care (PARC) facility in regional Australia. This was a pragmatic before and after study set within a participatory action research methodology. The target sample comprised patients at a PARC facility over 15 months. Six-month individual level data prior to study entry, during, and over 6-months from study exit were examined using patient activity records. Costs were expressed in 2015-2016AU$. An audit included 192 people experiencing 243 episodes of care represented by males (58%), mean age = 39.3 years (SD = 12.7), primarily diagnosed with schizophrenia (48%) or mood disorders (30%). The cost of 1 day in a psychiatric inpatient unit was found to be comparable to an average of 5 treatment days in PARC; the mean cost difference per-bed day (AU$1,167) was associated with fewer and shorter inpatient stays. Reduced use of inpatient facility translated into an opportunity cost of improved patient flow equivalent to AU$12,555 per resident (bootstrapped 95% CI = $5,680-$19,280). More noticeable outcomes were observed among those who stayed in PARC for longer during index admission (rs = 0.16, p = 0.024), who have had more and lengthy inpatient stays (rs = 0.52, p < 0.001 and rs = 0.69, p < 0.001), and those who stepped-down from the hospital (p < 0.001). This information could be proactively used within step-up/step-down services to target care to patients most likely to benefit. Despite early evidence of positive association, the results warrant further investigation using an experimental study design with alongside economic evaluation. Efforts should be directed toward the adoption of cost-effective alternatives to psychiatric inpatient facilities that provide comparable or improved patient outcomes.


Relationship satisfaction in lesbian and heterosexual couples before and after assisted reproduction: a longitudinal follow-up study.
More and more lesbian couples are planning parenthood through donor insemination and IVF and the number of planned lesbian families is growing in Sweden and other western countries. Research has shown that lesbian couples report as much overall satisfaction in their relationships as do heterosexual couples. However, although parenthood is highly desired, many parents are unaware of the demands of parenthood and the strain on their relationship that the arrival of the baby might bring. The aim of this study was to compare lesbian and heterosexual couples' perceptions of relationship satisfaction at a three-year follow up after assisted reproduction. The present study is a part of the Swedish study on gamete donation, a prospective longitudinal cohort study. The present study constitutes a three-year follow up assessment of lesbian and heterosexual couples after assisted reproduction. Participants requesting assisted reproduction at all fertility clinics performing gamete donation in Sweden, were recruited consecutively during 2005-2008. A total of 114 lesbian women (57 treated women and 57 partners) and 126 heterosexual women and men (63 women and 63 men) participated. Participants responded to the ENRICH inventory at two time points during 2005-2011; at the commencement of treatment (time point 1) and about three years after treatment termination (time point 3). To evaluate the bivariate relationships between the groups (heterosexual and lesbian) and socio-demographic factors Pearson's Chi- square test was used. Kolmogorov-Smirnov test was used for testing of normality, Mann-Whitney U- test to examine differences in ENRICH between the groups and paired samples t-test to examine scores over time. Lesbian couples reported higher relationship satisfaction than heterosexual couples, however the heterosexual couples satisfaction with relationship quality was not low. Both lesbian and heterosexual couples would be classified accordingly to ENRICH-typology as vitalized or harmonious couples. At a follow-up after assisted reproduction with donated sperm, lesbian couples reported stable relationships and a high satisfaction with their relationships, even when treatment was unsuccessful.


Trans-unsaturated fatty acids and acrylamide in food as potential atherosclerosis progression factors. Based on own studies.
Atherosclerosis is a chronic pathological process and it is generelly accepted that lipids, coagulation and inflammatory factors play an important role in its development. Environmental factors such as bed diet and cigarette smoking strongly stimulate initation and progression of atherosclerotic changes in the artery wall. It has been recognized that deeply processed food may be a source of various factors potentiating processes related to atherosclerosis development among which inflammatory processes are of great importance. The aim of our studies was to find out if the trans-unsaturated fatty acids as well as acrylamide present in foods have the potential to provoke pro-inflammatory states in the body and enhance atherosclerosis risk. The results of our in vitro studies have shown that trans fatty acids cause a significant increase in secretion of reactive oxygen species, interleukin-6, tumor necrosis factor a and metalloproteinase-9, and enhance apoptosis. It indicates that in vivo trans-fatty acids may distroy the endothelium integrity and cause plaque rupture. Our in vivo studies in the group of healthy volunteers have shown that the consumption of potato chips rich in acrylamide cause the significant increase in plasma C-reactive protein and homocysteine concentrations. Enhanced CRP and HCY levels are accepted markers of enhanced atherosclerosis risk.


Long term effect of breast feeding: cognitive function in the Caerphilly cohort.
There is evidence suggesting that artificial feeding is associated with a reduction in cognitive function in infants and children, in contrast with breast feeding, but the available evidence suffers from confounding by social and educational factors. An opportunity arose in the Caerphilly cohort study to examine relations between cognitive function in older men and their feeding as infants, when breast feeding was usual. A prospective cohort study. Caerphilly, South Wales, UK, was a deprived coal mining community when the men had been born in 1920-35. Most had been breast fed as infants. 779 men aged 60-74 years when tested. The men had earlier been asked to obtain from their mothers their birth weight, and how they had been fed as infants. Complete data were obtained for 779 men. In those whose birth weight had been at or above the median, the adjusted mean cognitive function was only slightly and non-significantly lower in those who had been artificially fed. In the men whose birth weight had been below the median, having been artificially fed was associated with significantly lower results in both a test of reasoning (the AH4) and word power (the national adult reading test (NART)). Two standard deviations below the median birth weight, artificial feeding was associated with a reduction of six points (70% of a SD) on word power (the NART). In men whose birth weight had been low, having been artificially fed is associated with poorer cognitive function in late adult life.


Segmental kinematic analysis of planovalgus feet during walking in children with cerebral palsy.
Pes planovalgus (flatfoot) is a common deformity among children with cerebral palsy. The Milwaukee Foot Model (MFM), a multi-segmental kinematic foot model, which uses radiography to align the underlying bony anatomy with reflective surface markers, was used to evaluate 20 pediatric participants (30feet) with planovalgus secondary to cerebral palsy prior to surgery. Three-dimensional kinematics of the tibia, hindfoot, forefoot, and hallux segments are reported and compared to an age-matched control set of typically-developing children. Most results were consistent with known characteristics of the deformity and showed decreased plantar flexion of the forefoot relative to hindfoot, increased forefoot abduction, and decreased ranges of motion during push-off in the planovalgus group. Interestingly, while forefoot characteristics were uniformly distributed in a common direction in the transverse plane, there was marked variability of forefoot and hindfoot coronal plane and hindfoot transverse plane positioning. The key finding of these data was the radiographic indexing of the MFM was able to show flat feet in cerebral palsy do not always demonstrate more hindfoot eversion than the typically-developing hindfoot. The coronal plane kinematics of the hindfoot show cases planovalgus feet with the hindfoot in inversion, eversion, and neutral. Along with other metrics, the MFM can be a valuable tool for monitoring kinematic deformity, facilitating clinical decision making, and providing a quantitative analysis of surgical effects on the planovalgus foot.


Assessing childhood maltreatment and mental health correlates of disordered eating profiles in a nationally representative sample of English females.
Previous research suggests that childhood maltreatment is associated with the onset of eating disorders (ED). In turn, EDs are associated with alternative psychopathologies such as depression and posttraumatic stress disorder (PTSD), and with suicidality. Moreover, it has been reported that various ED profiles may exist. The aim of the current study was to examine the profiles of disordered eating and the associations of these with childhood maltreatment and with mental health psychopathology. The current study utilised a representative sample of English females (N = 4206) and assessed for the presence of disordered eating profiles using Latent Class Analysis. Multinomial logistic regression was implemented to examine the associations of childhood sexual and physical abuse with the disordered eating profiles and the associations of these with PTSD, depression and suicidality. Results supported those of previous findings in that we found five latent classes of which three were regarded as disordered eating classes. Significant relationships were found between these and measures of childhood trauma and mental health outcomes. Childhood sexual and physical abuse increased the likelihood of membership in disordered eating classes and these in turn increased the likelihood of adverse mental health and suicidal outcomes.


Evolution of Atg1 function and regulation.
The serine/threonine kinase Atg1 plays an essential role downstream of TOR for the regulation of autophagy. In yeast, where Atg1 was first identified, a complex regulatory mechanism has been described that includes at least seven other interacting proteins and a phosphorylation-dependent switch. Recent findings confirm that the mammalian Atg1 homologues ULK1 and 2 have autophagy regulatory roles. However, we and others have also demonstrated mechanistic differences with the yeast model and between these two Atg1 family members. Here, we elaborate on our growing understanding of Atg1 function, incorporating findings from yeast, C. elegans, D. melanogaster and mammalian cells. We propose that through evolution, Atg1 proteins have adopted additional cellular functions and regulatory mechanisms, which could involve multiple gene family isoforms working within multifunctional protein complexes. The gene family expansion observed in higher eukaryotes might reflect an increased functional diversity of Atg1 proteins in cell growth, differentiation and survival.


Hydrogen motions in defective graphene: the role of surface defects.
Understanding the mobility of H at the surface of carbon nanostructures is one of the essential ingredients for a deep comprehension of the catalytic formation of H2 in interstellar clouds. In this paper, we combine neutron vibrational spectroscopy with DFT molecular dynamics simulations to study the local environment of H structures chemisorbed at the surface of disordered graphene sheets. At 5 K, the ground state is composed of large clusters of hydrogen chemisorbed at sp2 carbon sites, on the edges and in voids of the graphene sheets. At temperatures of ∼300 K, a high degree of dispersion of the clusters is observed, involving the breaking and reforming of covalent bonds which, at low temperatures, is mediated by incoherent tunnelling of hydrogen.


Multilocus sequence analysis and type III effector repertoire mining provide new insights into the evolutionary history and virulence of Xanthomonas oryzae.
Multilocus sequence analysis (MLSA) and type III effector (T3E) repertoire mining were performed to gain new insights into the genetic relatedness of Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc), two major bacterial pathogens of rice. Based on a collection of 45 African and Asian strains, we first sequenced and analysed three housekeeping genes by MLSA, Bayesian clustering and a median-joining network approach. Second, we investigated the distribution of 32 T3E genes, which are known to be major virulence factors of plant pathogenic bacteria, in all selected strains, by polymerase chain reaction and dot-blot hybridization methods. The diversity observed within housekeeping genes, as well as within T3E repertoires, clearly showed that both pathogens belong to closely related, but distinct, phylogenetic groups. Interestingly, these evolutionary groups are differentiated according to the geographical origin of the strains, suggesting that populations of Xoo and Xoc might be endemic in Africa and Asia, and thus have evolved separately. We further revealed that T3E gene repertoires of both pathogens comprise core and variable gene suites that probably have distinct roles in pathogenicity and different evolutionary histories. In this study, we carried out a functional analysis of xopO, a differential T3E gene between Xoo and Xoc, to determine the involvement of this gene in tissue specificity. Altogether, our data contribute to a better understanding of the evolutionary history of Xoo and Xoc in Africa and Asia, and provide clues for functional studies aiming to understand the virulence, host and tissue specificity of both rice pathogens.


Normal glucagon signaling and β-cell function after near-total α-cell ablation in adult mice.
To evaluate whether healthy or diabetic adult mice can tolerate an extreme loss of pancreatic α-cells and how this sudden massive depletion affects β-cell function and blood glucose homeostasis. We generated a new transgenic model allowing near-total α-cell removal specifically in adult mice. Massive α-cell ablation was triggered in normally grown and healthy adult animals upon diphtheria toxin (DT) administration. The metabolic status of these mice was assessed in 1) physiologic conditions, 2) a situation requiring glucagon action, and 3) after β-cell loss. Adult transgenic mice enduring extreme (98%) α-cell removal remained healthy and did not display major defects in insulin counter-regulatory response. We observed that 2% of the normal α-cell mass produced enough glucagon to ensure near-normal glucagonemia. β-Cell function and blood glucose homeostasis remained unaltered after α-cell loss, indicating that direct local intraislet signaling between α- and β-cells is dispensable. Escaping α-cells increased their glucagon content during subsequent months, but there was no significant α-cell regeneration. Near-total α-cell ablation did not prevent hyperglycemia in mice having also undergone massive β-cell loss, indicating that a minimal amount of α-cells can still guarantee normal glucagon signaling in diabetic conditions. An extremely low amount of α-cells is sufficient to prevent a major counter-regulatory deregulation, both under physiologic and diabetic conditions. We previously reported that α-cells reprogram to insulin production after extreme β-cell loss and now conjecture that the low α-cell requirement could be exploited in future diabetic therapies aimed at regenerating β-cells by reprogramming adult α-cells.


Content and processes of postpartum counseling after a distressing birth experience: a review.
A distressing birth experience can produce debilitating symptoms of psychological trauma; however, little is known about the content and processes of counseling interventions to relieve trauma symptoms. This review identifies and examines common content and processes of postpartum counseling interventions to address trauma symptoms following childbirth. A search of major databases (Cinahl 1982-2003; Cochrane 2003; Embase; Proquest; Psychlit; Pubmed/Medline 1966-2003; Sociofile) was conducted, using combinations of the key words of "childbirth,""postpartum,""posttraumatic stress disorder,""anxiety,""trauma,""stress,""debriefing," and "counselling" or "counseling." Identified content and processes were clustered through a thematic analysis. Nineteen publications were retrieved. Counseling strategies provided women with opportunities to talk about their birth experience, express feelings about what happened, have questions answered, address gaps in knowledge or understanding of events, connect the event with emotions and behavior, talk about future pregnancies, and explore existential issues. Descriptions of postpartum counseling and debriefing are generalized and nonspecific; they provide minimal direction for postpartum counseling models, lack necessary detail for replication, may require psychotherapeutic training and therefore be unsuitable for use by caregivers, and are often based on opinion with little empirical evaluation. Few studies have tested specific counseling interventions on a range of maternal outcomes. Further research is needed to develop counseling models for use by health professionals with women who report a distressing birth experience.


Relationships among Doppler-derived umbilical artery absolute velocities, cardiac function, and placental volume blood flow and resistance in fetal sheep.
We hypothesized that umbilical artery (UA) absolute blood flow velocities measured by Doppler ultrasonography reflect placental volume blood flow (Q(UA)) and placental vascular resistance (R(UA)) in a late gestation fetal sheep model. In addition, we examined the relationships between umbilical artery absolute blood flow velocities and parameters of fetal cardiac function. Twenty-six sheep fetuses were instrumented at 112-132 days of gestation. After a 5-day recovery period, experiments were performed under general anesthesia in 16 normal fetuses, in 5 fetuses after maternal administration of phenylephrine, and in 5 fetuses after placental embolization. The Q(UA) and arterial blood pressures were measured using a transit-time ultrasonic flow probe and a catheter placed into the descending aorta, respectively. UA peak systolic velocity (PSV), end-diastolic velocity (EDV), time-averaged maximum velocity (TAMXV), pulsatility index (PI), mean velocity (V(mean)), fetal cardiac output, ventricular ejection forces, and the proportion of isovolumetric relaxation time (IRT%) in the cardiac cycle were measured with the use of Doppler ultrasonography. Significant positive linear correlations were found between UA EDV, TAMXV, and V(mean) versus Q(UA), whereas UA PI had a significant negative correlation with Q(UA). Significant negative correlations were shown between UA EDV, TAMXV, and V(mean) versus R(UA). A significant positive correlation was present between UA PI and R(UA). Doppler-derived UA parameters did not correlate with fetal arterial blood pressures, cardiac output, ventricular ejection forces or IRT%. In fetal sheep, Doppler-derived UA PI and absolute velocities, except PSV, are closely related to directly measured Q(UA) and R(UA), validating the use of noninvasive Doppler velocimetry in the assessment of placental circulation.


Bioinformatics and Drug Discovery.
Bioinformatic analysis can not only accelerate drug target identification and drug candidate screening and refinement, but also facilitate characterization of side effects and predict drug resistance. High-throughput data such as genomic, epigenetic, genome architecture, cistromic, transcriptomic, proteomic, and ribosome profiling data have all made significant contribution to mechanismbased drug discovery and drug repurposing. Accumulation of protein and RNA structures, as well as development of homology modeling and protein structure simulation, coupled with large structure databases of small molecules and metabolites, paved the way for more realistic protein-ligand docking experiments and more informative virtual screening. I present the conceptual framework that drives the collection of these high-throughput data, summarize the utility and potential of mining these data in drug discovery, outline a few inherent limitations in data and software mining these data, point out news ways to refine analysis of these diverse types of data, and highlight commonly used software and databases relevant to drug discovery.


High sensitivity versus low level of vancomycin needs to be concern for another alternative anti- Staphylococcus aureus as the first- line antibiotic.
Vancomycin has been the first-line therapy for MRSA infection disease for many years. According to standard guidelines, the therapeutic vancomycin trough concentration should be above 10 mg/L and optimally between 15-20 mg/L. The aim of this study was to evaluate vancomycin trough level concentration in patients infected with MRSA. This cross- sectional study included a sample of 170 patients admitted to the ICU of Loghman hospital. We used a standard questionnaire, then applied appropriate statistical tests. All collected data had been analyzed and interpreted by IBM SPSS Statistics 19.0. Among this study population, 71.8% was male. Just 20.8% of the patients can reach the therapeutic level trough even after changing the dose. It should be noted that a significant percentage of toxicity was observed after increasing the dose. Even though high sensitivity against vancomycin disc has been seen in antibiogram tests, sufficient efficiency has not been distinguished, in the sense that, just a few patients by low trough level concentration, reached to therapeutic level after the dose change. Based on some sources, because of the side effects and limited safe range of vancomycin, we should consider a new approach to the alternative antibiotics. (www.actabiomedica.it).


CD9 expression as a favorable prognostic marker for patients with malignant mesothelioma.
CD9 is involved in cell growth, adhesion and motility and its expression is reported to be of prognostic significance in various types of human malignancies. We found increased cell migration in the mesothelioma cell lines MSTO-211H and TUM1 following in vitro shRNA-mediated knockdown of CD9 expression. We investigated CD9 expression in 112 malignant pleural mesotheliomas. CD9 expression was observed in 62 of 71 epithelioid, 13 of 20 biphasic and only 1 of 21 sarcomatoid mesotheliomas. Among the epithelioid mesotheliomas (EMs), CD9 expression was observed in all of the 33 cases with a differentiated type (EM-D) and in 29 of the 38 cases with a less-differentiated type (EM-LD). Patients with CD9 expression showed higher 1- and 2-year survival rates (63 and 25%) compared to the patients without CD9 expression (39 and 11%). Univariate analysis revealed that patients with CD9 expression demonstrated a more favorable survival (P=0.0025) along with other clinicopathological factors, including age younger than 60 years, IMIG stage I-II, epithelioid histology, EM-D and patients who underwent extrapleural pneumonectomy or received chemotherapy. Multivariate analysis identified CD9 expression as an independent prognostic factor with a hazard ratio (HR) of 1.99 in the analysis of all mesotheliomas (P=0.0261) and an HR of 2.60 in the analysis of EMs (P=0.0376). CD9 expression is an independent favorable prognostic marker of malignant mesothelioma.


Geography and travel distance impact emergency department visits.
Little has been written about the geographic basis of emergency department (ED) visits. The objective of this study is to describe the impact of geography on ED visits. A retrospective analysis was conducted of ED visits during a 1-year period at a single institution using spatial interaction analysis that models the pattern of flow between a series of origins (census block groups) and a destination (ED). Patients were assigned to census block groups based upon their verified home address. The study hospital is the only Level I trauma, pediatric, and tertiary referral center in the area. There are 11 other hospitals with EDs within a 40-mile radius. Each patient visit within this radius, including repeat visits, was included. Patients with an invalid home address, a post office box address, or those who lived outside a 40-mile radius were excluded. ED visits per 100 population were calculated for each census block group. There were 98,584 (95%) visits by 63,524 patients that met study inclusion criteria. Visit rates decreased with increasing distance from the ED (p < 0.0001). Nineteen percent of patients lived within 2 miles, 48% within 4 miles, and 92% within 12 miles of the ED. The Connecticut border, 7 miles south of the ED (p < 0.0001), the Connecticut River, 1 mile west of the ED (p < 0.0001), and the presence of a competing ED within 1 mile (p < 0.0001) negatively impacted block group ED visit rates. Travel distance was related to the percentage of visits that were high acuity (p < 0.0001), daytime (p < 0.01), or resulted in admission (p < 0.0001). Geography and travel distance significantly impact ED visits.


Erectile dysfunction and its management in patients with diabetes mellitus.
Diabetes can be described as a syndrome of multiple closely related conditions induced by a chronic state of hyperglycaemia resulting from defective insulin secretion, insulin action or both. Chronic complications associated with diabetes (including neuropathy, vascular disease, nephropathy and retinopathy) are common, and of these, erectile dysfunction (ED) deserves special attention. ED and its correlation with cardiovascular disease require careful evaluation and appropriate treatment. PDE5 inhibitors (PDE5is) are an important tool for the treatment of ED, with new drugs coming onto the market since the late 90s. This review offers an overview of PDE5is and their use in treating ED in diabetes. We underline the differences between different types of PDE5i, focusing on available doses, duration of action, T ½, side effects and selectivity profiles in relation to patients with diabetes. We also discuss the link between diabetes and ED in presence of various associated cofactors (obesity, hypertension and its pharmacological treatments, atherosclerosis, hyperhomocysteinaemia, neuropathy, nephropathy, hypogonadism and depression). Finally a number of past and ongoing clinical trials on the use of PDE5is in patients with diabetes are presented to offer an overview of the appropriate treatment of ED in this condition.


Toward a Framework for Islamic Psychology and Psychotherapy: An Islamic Model of the Soul.
A uniquely Islamic theoretical framework for an Islamic psychology has yet to be established. To do so requires that we understand how human beings are conceptualized within the cosmology that characterizes the Islamic tradition. This paper presents a model of the soul from within an Islamic paradigm, generated through a grounded theory analysis of interviews with 18 key informants with relevant academic or religious expertise. The model elaborates aspects of a mechanism for the development of the soul that constitutes a potential foundation for an Islamic theory of human psychology and has particular relevance for Islamic approaches to psychotherapy.


Next-generation sequencing of cervical DNA detects human papillomavirus types not detected by commercial kits.
Human papillomavirus (HPV) is the aetiological agent for cervical cancer and genital warts. Concurrent HPV and HIV infection in the South African population is high. HIV positive (+) women are often infected with multiple, rare and undetermined HPV types. Data on HPV incidence and genotype distribution are based on commercial HPV detection kits, but these kits may not detect all HPV types in HIV + women. The objectives of this study were to (i) identify the HPV types not detected by commercial genotyping kits present in a cervical specimen from an HIV positive South African woman using next generation sequencing, and (ii) determine if these types were prevalent in a cohort of HIV-infected South African women. Total DNA was isolated from 109 cervical specimens from South African HIV + women. A specimen within this cohort representing a complex multiple HPV infection, with 12 HPV genotypes detected by the Roche Linear Array HPV genotyping (LA) kit, was selected for next generation sequencing analysis. All HPV types present in this cervical specimen were identified by Illumina sequencing of the extracted DNA following rolling circle amplification. The prevalence of the HPV types identified by sequencing, but not included in the Roche LA, was then determined in the 109 HIV positive South African women by type-specific PCR. Illumina sequencing identified a total of 16 HPV genotypes in the selected specimen, with four genotypes (HPV-30, 74, 86 and 90) not included in the commercial kit. The prevalence's of HPV-30, 74, 86 and 90 in 109 HIV positive South African women were found to be 14.6%, 12.8%, 4.6% and 8.3% respectively. Our results indicate that there are HPV types, with substantial prevalence, in HIV positive women not being detected in molecular epidemiology studies using commercial kits. The significance of these types in relation to cervical disease remains to be investigated.


Seroprevalences of hepatitis B virus and hepatitis C virus among participants of an Asian health fair in the Lower Mainland, British Columbia.
The seroprevalences of hepatitis B virus (HBV) and hepatitis C virus (HCV) are 0.4% and 0.8%, respectively, in Canada, but varying rates have been reported in different populations. To determine the seroprevalences of HBV and HCV among attendees of an Asian health fair in the Lower Mainland, British Columbia, as well as to correlate questionnaire answers regarding vaccination status to serological profiles. Attendees at an Asian health fair were invited to participate in the present study on a voluntary basis. They provided answers to a questionnaire including ethnicity and vaccination status. Blood was then drawn for HBV and HCV serology. Active HBV was defined as HBV surface antigen (HBsAg) positive while HCV seroprevalence was defined as HCV antibody reactive. Previous exposure to HBV was defined as HBV core antibody (anti-HBc) positive and HBsAg negative. Nonimmunity was defined as anti-HBc negative and HBV surface antibody negative. Only those with correct demographic information matched to serological results were included in the study. There were 192 consenting attendees of the fair, of whom 112 were included in the study. Of the participants, 91% were Chinese. Active HBV infection was found in three participants (2.7% [95% CI 0.6% to 7.6%]) and HCV infection was found in two participants (1.8% [95% CI 0.2% to 6.3%]). More than 40% of participants had been previously exposed to HBV (42% [95% CI 33% to 51%]). Almost 20% demonstrated nonimmunity to HBV (19% [95% CI 12% to 27%]). There was significant discordance when questionnaire answers regarding vaccination status were compared with serological profiles. The seroprevalences of HBV and HCV in this cohort were 2.7% and 1.8%, respectively - higher than nationally reported rates. Our results highlight that the lack of knowledge of HBV infection and vaccination status remains a significant clinical issue in the Asian community of British Columbia.


Meta-analysis of Histological Margin Positivity in the Prediction of Recurrence After Crohn's Resection.
Despite significant advances in the medical management of Crohn's disease, many patients will require intestinal resection during their lifetime. It is disappointing that many will also develop disease recurrence. The current study utilizes meta-analytical techniques to determine the effect of positive histological margins at the time of index resection on disease recurrence. Embase, Medline, PubMed, PubMed Central, and Cochrane databases were searched using a Boolean search algorithm for articles published up to August 2017. Meta-analysis was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Databases were searched for studies reporting the outcomes for patients with Crohn's disease undergoing primary resection that correlated resection margin status with disease recurrence. Results were reported as pooled ORs with 95% CI. A total of 176 citations were reviewed; 18 studies comprising 1833 patients were ultimately included in the analysis, with a mean rate of histopathological margin positivity of 41.7 ± 17.4% and a pooled mean follow-up of 69 ± 39 months. Histopathological margin positivity was associated with a higher rate of overall recurrence (OR, 1.7; 95% CI, 1.3-2.1; p < 0.001), clinical recurrence (OR, 1.7; 95% CI, 1.0-2.8; p = 0.04), and anastomotic recurrence (OR, 1.6; 95% CI, 1.0-2.3; p = 0.03). In studies reporting plexitis specifically at the resection margin, there was an increase in recurrence (OR, 2.3; 95% CI, 1.1-4.9; p = 0.02). The definitions of histological margin positivity and postoperative recurrence vary between the studies and follow-up durations vary. The presence of involved histological margins at the time of index resection in Crohn's disease is associated with recurrence, and plexitis shows promise as a marker of more aggressive disease. Further studies with homogeneity of histopathological and recurrence reporting are required.


A Risk-Based Ecohydrological Approach to Assessing Environmental Flow Regimes.
For several decades there has been recognition that water resource development alters river flow regimes and impacts ecosystem values. Determining strategies to protect or restore flow regimes to achieve ecological outcomes is a focus of water policy and legislation in many parts of the world. However, consideration of existing environmental flow assessment approaches for application in Queensland identified deficiencies precluding their adoption. Firstly, in managing flows and using ecosystem condition as an indicator of effectiveness, many approaches ignore the fact that river ecosystems are subjected to threatening processes other than flow regime alteration. Secondly, many focus on providing flows for responses without considering how often they are necessary to sustain ecological values in the long-term. Finally, few consider requirements at spatial-scales relevant to the desired outcomes, with frequent focus on individual places rather than the regions supporting sustainability. Consequently, we developed a risk-based ecohydrological approach that identifies ecosystem values linked to desired ecological outcomes, is sensitive to flow alteration and uses indicators of broader ecosystem requirements. Monitoring and research is undertaken to quantify flow-dependencies and ecological modelling is used to quantify flow-related ecological responses over an historical flow period. The relative risk from different flow management scenarios can be evaluated at relevant spatial-scales. This overcomes the deficiencies identified above and provides a robust and useful foundation upon which to build the information needed to support water planning decisions. Application of the risk assessment approach is illustrated here by two case studies.


SCARECROW and SHORTROOT control the auxin/cytokinin balance necessary for embryonic stem cell niche specification.
The root apical meristem is established during embryogenesis, when its organizer, the quiescent center, is specified and the stem cell niche is positioned. The SCARECROW-SHORTROOT heterodimer is essential for quiescent center specification and maintenance. As continuous post-embryonic root growth relies upon the SCARECROW-mediated control of the cytokinin/auxin balance, we investigated the role of SCARECROW and SHORTROOT in controlling cytokinin signaling during embryonic quiescent center specification. We found that from embryogenesis onward both SCARECROW and SHORTROOT antagonize cytokinin signaling, thus repressing the expression of the auxin biosynthetic enzyme ANTRANILATHE SYNTHASE BETA 1. This mechanism prevents detrimental and premature high auxin levels in the QC allowing the establishment of a functional embryonic root pole.


Ageratum enation virus-a begomovirus of weeds with the potential to infect crops.
Samples of two Ageratum conyzoides, one Sonchus oleraceus and one turnip (Brassica rapa var. rapa) exhibiting virus-like symptoms were collected from Pakistan and Nepal. Full-length begomovirus clones were obtained from the four plant samples and betasatellite clones from three of these. The begomovirus sequences were shown to be isolates of Ageratum enation virus (AEV) with greater than 89.1% nucleotide sequence identity to the 26 AEV sequences available in the databases. The three betasatellite sequences were shown to be isolates of Ageratum yellow leaf curl betasatellite (AYLCB) with greater than 90% identity to the 18 AYLCB sequences available in the databases. The AEV sequences were shown to fall into two distinct strains, for which the names Nepal (consisting of isolates from Nepal, India, and Pakistan-including the isolates identified here) and India (isolates occurring only in India) strains are proposed. For the clones obtained from two AEV isolates, with their AYLCB, infectivity was shown by Agrobacterium-mediated inoculation to Nicotiana benthamiana, N. tabacum, Solanum lycopersicon and A. conyzoides. N. benthamiana plants infected with AEV alone or betasatellite alone showed no symptoms. N. benthamiana plants infected with AEV with its associated betasatellite showed leaf curl symptoms. The findings show that AEV is predominantly a virus of weeds that has the capacity to infect crops. AYLCB appears to be the common partner betasatellite of AEV and is associated with diseases with a range of very different symptoms in the same plant species. The inability to satisfy Koch's postulates with the cloned components of isolate SOL in A. conyzoides suggests that the etiology may be more complex than a single virus with a single betasatellite.


Cochrane Update: Effect of timing of umbilical cord clamping at birth of term infants on mother and baby outcomes.
Policies for timing of cord clamping vary, with early cord clamping generally carried out in the first 60 seconds after birth, whereas later cord clamping usually involves clamping the umbilical cord greater than one minute after the birth or when cord pulsation has ceased. To determine the effects of different policies of timing of cord clamping at delivery of the placenta on maternal and neonatal outcomes. We searched the Cochrane Pregnancy and Child Birth Group's Trials Register (December 2007). Randomized controlled trials comparing early and late cord clamping. Two review authors independently assessed trial eligibility and quality and extracted data. We included 11 trials of 2,989 mothers and their babies. No significant differences between early and late cord clamping were seen for postpartum hemorrhage or severe postpartum hemorrhage in any of the five trials (2236 women) which measured this outcome (relative risk (RR) for postpartum hemorrhage 500 mls or more 1.22, 95% (CI) 0.96 to 1.55). For neonatal outcomes, our review showed both benefits and harms for late cord clamping. Following birth, there was a significant increase in infants needing phototherapy for jaundice (RR 0.59, 95% CI 0.38 to 0.92; five trials of 1,762 infants) in the late compared with early clamping group. This was accompanied by significant increases in newborn hemoglobin levels in the late cord clamping group compared with early cord clamping (weighted mean difference 2.17 g/dL; 95% CI 0.28 to 4.06; three trials of 671 infants), although this effect did not persist past six months. Infant ferritin levels remained higher in the late clamping group than the early clamping group at six months. One definition of active management includes directions to administer an uterotonic with birth of the anterior shoulder of the baby and to clamp the umbilical cord within 30-60 seconds of birth of the baby (which is not always feasible in practice). In this review delaying clamping of the cord for at least two to three minutes seems not to increase the risk of postpartum hemorrhage. In addition, late cord clamping can be advantageous for the infant by improving iron status which may be of clinical value particularly in infants where access to good nutrition is poor, although delaying clamping increases the risk of jaundice requiring phototherapy.


Multipartite Entanglement in a Microwave Frequency Comb.
Significant progress has been made with multipartite entanglement of discrete qubits, but continuous variable systems may provide a more scalable path toward entanglement of large ensembles. We demonstrate multipartite entanglement in a microwave frequency comb generated by a Josephson parametric amplifier subject to a bichromatic pump. We find 64 correlated modes in the transmission line using a multifrequency digital signal processing platform. Full inseparability is verified in a subset of seven modes. Our method can be expanded to generate even more entangled modes in the near future.


Flybow to Dissect Circuit Assembly in the Drosophila Brain: An Update.
Visualization of single neurons and glia, as well as neural lineages within their complex environment is a pivotal step towards uncovering the mechanisms that control neural circuit development and function. This chapter provides detailed technical information on how to use Drosophila variants of the mouse Brainbow-2 system, called Flybow, for stochastic labeling of individual cells or lineages with different fluorescent proteins in one sample. We describe the genetic strategies and the heat shock regime required for induction of recombination events. Furthermore, we explain how Flybow and the mosaic analysis with a repressible cell marker (MARCM) approach can be combined to generate wild-type or homozygous mutant clones that are positively labeled in multiple colors. This is followed by a detailed protocol as to how to prepare samples for imaging. Finally, we provide specifications to facilitate multichannel image acquisition using confocal microscopy.


Evaluation of irradiance distributions for Fresnel diffraction patterns.
A rotated coordinate system is used to evaluate the irradiance distribution of a Fresnel diffraction pattern. Arbitrary diffracting objects are defined in a bounded input plane. Fresnel patterns for linear chirp functions are simply related to the single-slit pattern. Features of the single-slit pattern are developed for use as optical system design criteria.


Nitazoxanide for chronic hepatitis C.
Hepatitis C infection is a disease of the liver caused by the hepatitis C virus. The estimated number of chronically infected people with hepatitis C virus worldwide is about 150 million people. Every year, another three to four million people acquire the infection. Chronic hepatitis C is a leading cause of liver-related mortality and morbidity. It is estimated that around 5% to 20% of people with the infection will develop liver cirrhosis, which increases the risk of hepatocellular carcinoma and liver failure. Until 2011, the combination therapy of pegylated interferon-alpha (peginterferon) and ribavirin was the approved standard treatment for chronic hepatitis C. In 2011, first-generation direct-acting antivirals have been licensed, for use in combination with peginterferon and ribavirin for treating hepatitis C virus genotype 1 infection. Nitazoxanide is another antiviral drug with broad antiviral activity and may have potential as an effective alternative, or an addition to standard treatment for the treatment of the hepatitis C virus. To assess the benefits and harms of nitazoxanide in people with chronic hepatitis C virus infection. We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (last searched April 2013), The Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 3), MEDLINE (Ovid SP, 1948 to April 2013), EMBASE (Ovid SP, 1980 to April 2013), LILACS (1983 to April 2013), and Science Citation Index EXPANDED (ISI Web of Knowledge, 1900 to April 2013), using the search strategies and the expected time spans. We also scanned reference lists of identified studies.We also searched ClinicalTrials.gov and the World Health Organization's International Clinical Trials Registry Platform search portal for registered trials, either completed or ongoing (April 2013). We included randomised clinical trials that examined the effects of nitazoxanide versus placebo, no intervention, or any other intervention in patients with chronic hepatitis C. We considered any co-intervention, including standard treatment, if delivered to all intervention groups of the randomised trial concerned. Two review authors extracted data independently. We assessed the risk of systematic errors ('bias') by evaluation of bias risk domains. We used Review Manager 5.2 for the statistical analyses of dichotomous outcome data with risk ratio (RR) and of continuous outcome data with mean difference (MD). For meta-analyses, we used a fixed-effect model and a random-effects model, along with an assessment of heterogeneity. We assessed risk of random errors ('play of chance') using trial sequential analysis. We assessed the quality of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to present review results in 'Summary of findings' tables. We included seven randomised clinical trials with a total of 538 participants with chronic hepatitis C. Participants were 18 years of age or older, all diagnosed with chronic hepatitis C genotype 1 or 4. All of the trials had a high risk of bias. All of the trials compared nitazoxanide with placebo or no intervention, and six out of seven of the trials included different antiviral co-interventions administered equally to all intervention groups. Only one trial, comparing nitazoxanide plus peginterferon and ribavirin versus no intervention plus peginterferon and ribavirin, provided information that there were no deaths due to any cause or due to chronic hepatitis C (100 participants, very low quality evidence). The relative effect of nitazoxanide versus placebo or no intervention on adverse events was uncertain (37 out of 179 (21%) versus 30 out of 152 (20%); RR 1.10; 95% CI 0.71 to 1.71; I(2) = 65%; four trials; very low quality evidence). Nitazoxanide decreased the risk of failure to achieve sustained virological response when compared with placebo or no intervention (159 out of 290 (55%) versus 133 out of 208 (64%); RR 0.85; 95% CI 0.75 to 0.97; I(2) = 0%; seven trials; low quality evidence) and also the risk of failure to achieve virological end-of-treatment response (125 out of 290 (43%) versus 110 out of 208 (53%); RR 0.81; 95% CI 0.69 to 0.96; I(2) = 46%; seven trials; low quality evidence). Trial sequential analysis supported the meta-analysis result for sustained virological response, but not the meta-analysis for virological end-of-treatment response. Meta-analysis also showed that nitazoxanide did not decrease the number of participants who showed no improvement in alanine aminotransferase and aspartate aminotransferase serum levels when compared with placebo or no intervention (52 out of 97 (54%) versus 47 out of 95 (49%); RR 1.09; 95% CI 0.84 to 1.42; I(2) = 0%; three trials; very low quality evidence). None of the included trials assessed the effects of nitazoxanide on morbidity or on quality of life. Histological changes were only reported on a subset of three participants out of thirteen participants included in a long term-follow-up trial. We found very low quality, or no, evidence on nitazoxanide for clinically- or patient-relevant outcomes, such as all-cause mortality, chronic hepatitis C-related mortality, morbidity, and adverse events in participants with chronic hepatitis C genotype 1 or 4 infection. Our results of no improvement in alanine aminotransferase and aspartate aminotransferase serum levels were also uncertain. No conclusion could be drawn about liver histology because of a lack of data. Our results indicate that nitazoxanide might have an effect on sustained virological response and virological end-of-treatment response. However, both results could be influenced by systematic errors because all the trials included in the review had a high risk of bias. Furthermore, only the beneficial effect on number of participants achieving sustained virological response was supported when we applied trial sequential analysis. The results on virological end-of-treatment response might, therefore, be caused by a random error. We totally lack information on the effects of nitazoxanide in participants with chronic hepatitis C genotypes 2 or 3 infection. More randomised clinical trials with a low risk of bias are needed to assess the effects of nitazoxanide for chronic hepatitis C.


The "surprise question" for predicting death in seriously ill patients: a systematic review and meta-analysis.
The surprise question - "Would I be surprised if this patient died in the next 12 months?" - has been used to identify patients at high risk of death who might benefit from palliative care services. Our objective was to systematically review the performance characteristics of the surprise question in predicting death. We searched multiple electronic databases from inception to 2016 to identify studies that prospectively screened patients with the surprise question and reported on death at 6 to 18 months. We constructed models of hierarchical summary receiver operating characteristics (sROCs) to determine prognostic performance. Sixteen studies (17 cohorts, 11 621 patients) met the selection criteria. For the outcome of death at 6 to 18 months, the pooled prognostic characteristics were sensitivity 67.0% (95% confidence interval [CI] 55.7%-76.7%), specificity 80.2% (73.3%-85.6%), positive likelihood ratio 3.4 (95% CI 2.8-4.1), negative likelihood ratio 0.41 (95% CI 0.32-0.54), positive predictive value 37.1% (95% CI 30.2%-44.6%) and negative predictive value 93.1% (95% CI 91.0%-94.8%). The surprise question had worse discrimination in patients with noncancer illness (area under sROC curve 0.77 [95% CI 0.73-0.81]) than in patients with cancer (area under sROC curve 0.83 [95% CI 0.79-0.87; p = 0.02 for difference]). Most studies had a moderate to high risk of bias, often because they had a low or unknown participation rate or had missing data. The surprise question performs poorly to modestly as a predictive tool for death, with worse performance in noncancer illness. Further studies are needed to develop accurate tools to identify patients with palliative care needs and to assess the surprise question for this purpose.


Sexual health practices of 16 to 19 year olds in New Zealand: an exploratory study.
INTRODUCTION New Zealand sexual health surveillance data suggest that young people aged 15-19 years are at considerable risk of contracting sexually transmitted infections. Although there is an established body of international research around sexual behaviours and sexual health practices among teenagers, there is a dearth of local research focusing on this age group. AIM The aim of this study was to explore the sexual repertoires and sexual health practices among teenagers in New Zealand with a view to better understanding levels of risk in this age group. METHODS This study comprised a cross-sectional online survey designed to ask questions about sexual behaviours. A convenience sample of young people (n=52) aged 16-19 years living in New Zealand completed the survey. RESULTS Most participants (71.2%) were sexually active, reporting engagement in a range of sexual practices. The most commonly reported sexual behaviours were penis-in-vagina sex (86.5%) and oral sex with a person-with-a-penis (81.1%). Infrequent and inconsistent use of barrier protection across all types of sexual behaviour was also reported. DISCUSSION The findings of this study highlight the importance of ensuring that young people have access to sexual health education that routinely includes health information and advice addressing the full range of sexual practices, regardless of the identity classifications they may use, or that may be attributed to them.


Effects of nicotine on dopaminergic nigrostriatal axons requires stimulation of presynaptic glutamatergic receptors.
An electrophysiological method for evaluating changes in axonal excitability was used to examine presynaptic effects of the local striatal administration of nicotine on nigrostriatal dopaminergic terminal axons in the rat. To eliminate postsynaptic interactions, intrinsic striatal neurons were destroyed with a unilateral kainate lesion performed 10 to 15 days before the recording experiments. Excitability was assessed by determining the striatal stimulus current just sufficient to elicit an antidromic response from the striatal terminal field of a dopaminergic nigral neuron on 95% of the stimulus presentations. Local nicotine infusion (1-100 microM/0.3 microliter) produced a dose-dependent increase in excitability. Previous intrastriatal administration of the nicotine receptor antagonists mecamylamine or chlorisondamine blocked the nicotine effect and subsequent administration reversed the nicotine response. Increased dopamine autoreceptor stimulation, presumably resulting from nicotine-induced dopamine release, appeared to oppose the nicotine-induced increase in excitability. Accordingly, in animals in which dopamine synthesis was blocked with alpha-methyl-p-tyrosine (250 mg/kg, 12 and 2 h before recording), the nicotine-induced increase in terminal excitability was larger than in untreated rats. Simultaneous intrastriatal administration of the glutamate receptor antagonists, 6,7-dinitro-quinoxaline-2,3-dione and 2-amino-7-phosphonoheptanoate, prevented the nicotine-induced increase in excitability in animals with or without alpha-methyl-p-tyrosine pretreatment. We conclude that the nicotine-induced increase in nigrostriatal terminal excitability is an indirect effect resulting from a nicotine-evoked increase in glutamate release and a subsequent increase in the stimulation of presynaptic glutamate heteroreceptors on the dopamine-containing terminals.


Custodial status and self concepts of Nigerian inmates remanded to prison custody.
60 male Nigerian prison inmates (30 with convicted status and 30 awaiting trial) and 210 male noninmates were administered the Tennessee Self-concept Scale to test the hypotheses that (1) inmates with convicted status would obtain higher self-concept scores than those with ¿awaiting trial¿ status, and (2) the self-concept scores of prison inmates generally would be lower than those of noninmates. The two hypotheses were strongly supported for this sample. It was concluded that self-concept scores were not only related to delinquency by also to custodial status.


C-peptide prevents hippocampal apoptosis in type 1 diabetes.
To explore mechanisms underlying central nervous system (CNS) complications in diabetes, we examined hippocampal neuronal apoptosis and loss, and the effect of C-peptide replacement in type 1 diabetic BB/W rats. Apoptosis was demonstrated after 8 months of diabetes, by DNA fragmentation, increased number of apoptotic cells, and an elevated ratio of Bax/Bcl-xL, accompanied by reduced neuronal density in the hippocampus. No apoptotic activity was detected and neuronal density was unchanged in 2-month diabetic hippocampus, whereas insulin-like growth factor (IGF) activities were impaired. In type 1 diabetic BB/W rats replaced with C-peptide, no TdT-mediated dUTP nick-end labeling (TUNEL)-positive cells were shown and DNA laddering was not evident in hippocampus at either 2 or 8 months. C-peptide administration prevented the preceding perturbation of IGF expression and reduced the elevated ratio of Bax/Bcl-xL. Our data suggest that type 1 diabetes causes a duration-dependent programmed cell death of the hippocampus, which is partially prevented by C-peptide.


Slicing embryos gently with laser light sheets.
Light sheet microscopy is an easy to implement and extremely powerful alternative to established fluorescence imaging techniques such as laser scanning confocal, multi-photon and spinning disk microscopy. By illuminating the sample only with a thin slice of light, photo-bleaching is reduced to a minimum, making light sheet microscopy ideal for non-destructive imaging of fragile samples over extended periods of time. Millimeter-sized samples can be imaged rapidly with high resolution and high depth penetration. A large variety of instruments have been developed and optimized for a number of different samples: Bessel beams form thin light sheets for single cells, and selective plane illumination microscopy (SPIM) offers multi-view acquisition to image entire embryos with isotropic resolution. This review explains how light sheet microscopy involves a conceptually new microscope design and how it changes modern imaging in biology.


Defining a new ethical standard for human in vitro embryos in the context of stem cell research.
This iBrief discusses some of the social, ethical and legal considerations surrounding the use of unimplanted, in vitro embryos in stem cell research. It proposes that a new ethical standard be elucidated for these embryos. The iBrief gives an overview of two proposals for such a standard at opposite ends of the spectrum: treating the in vitro embryo as a legal person versus treating it as mere property. It argues against both approaches. The former can have undesirable social implications including undue interference with female reproductive autonomy, while the latter would objectify potential human life and reproductive potential. The iBrief proposes an intermediate approach that treats the embryo as a special entity. It warns against a model whereby the respect accorded to embryos is made dependent on the attainment of various qualitative or developmental criteria. The complexities surrounding human life, it argues, are too uncertain. What is certain is the embryo's unique potential for human life, at any developmental stage. This, the iBrief proposes, should be the sole criterion for an embryo's special status, a status that should be confined within constitutional limits.


HCF-2 inhibits cell proliferation and activates differentiation-gene expression programs.
HCF-2 is a member of the host-cell-factor protein family, which arose in early vertebrate evolution as a result of gene duplication. Whereas its paralog, HCF-1, is known to act as a versatile chromatin-associated protein required for cell proliferation and differentiation, much less is known about HCF-2. Here, we show that HCF-2 is broadly present in human and mouse cells, and possesses activities distinct from HCF-1. Unlike HCF-1, which is excluded from nucleoli, HCF-2 is nucleolar-an activity conferred by one and a half C-terminal Fibronectin type 3 repeats and inhibited by the HCF-1 nuclear localization signal. Elevated HCF-2 synthesis in HEK-293 cells results in phenotypes reminiscent of HCF-1-depleted cells, including inhibition of cell proliferation and mitotic defects. Furthermore, increased HCF-2 levels in HEK-293 cells lead to inhibition of cell proliferation and metabolism gene-expression programs with parallel activation of differentiation and morphogenesis gene-expression programs. Thus, the HCF ancestor appears to have evolved into a small two-member protein family possessing contrasting nuclear versus nucleolar localization, and cell proliferation and differentiation functions.


Axillary nerve injury: diagnosis and treatment.
Axillary nerve injury is infrequently diagnosed but is not a rare occurrence. Injury to the nerve may result from a traction force or blunt trauma applied to the shoulder. The most common zone of injury is just proximal to the quadrilateral space. Atraumatic causes of neuropathy include brachial neuritis and quadrilateral space syndrome. The vast majority of patients recover with non-operative treatment. Baseline electromyographic and nerve conduction studies should be obtained within 4 weeks after injury, with a follow-up evaluation at 12 weeks. If no clinical or electromyographic improvement is noted, surgery may be appropriate. The results of operative repair are best if surgery is performed within 3 to 6 months from the injury. Surgical options include neurolysis, nerve grafting, and neurotization. The results of repair of axillary nerve injuries have been good compared with treatment of other peripheral nerve lesions, due to the monofascicular composition of the nerve and the relatively short distance between the zone of injury and the motor end-plate.


Carotenoid depletion and ovarian dysfunction in common bully exposed to a New Zealand pulp mill effluent.
In a previous cumulative impacts assessments of fish populations along the Waikato River, New Zealand, reduced ovary pigmentation was observed in the common bully (Gobiomorphus cotidianus) with an associated reduction in recruitment in the pulp mill-impacted Kopakorahi Arm of Lake Maraetai compared to an upstream reference site. Carotenoid pigments are typically responsible for the yellow to red colouration of fish eggs and a number of functions for these pigments such as pro-vitamins and antioxidants have been proposed. The purpose of the current study was first to quantify the observed pigment reduction and then to establish possible consequences of carotenoid deficiency. Significantly lower levels of all measured carotenoids were observed in the ovaries of fish from below the mill outfall compared to the reference site. Using in vitro incubations of ovarian follicles, it was also found that these fish had a significantly reduced ability to produce the sex steroids testosterone and estradiol. This study demonstrates changes in ovarian carotenoids associated with pulp mill effluent exposure. Significantly reduced biosynthetic capacity of ovarian follicles demonstrates reproductive endocrine disruption potential associated with exposure to this particular effluent. These results may provide an important link between reproductive dysfunction, oxidative stress and food chain modifications in pulp mill-impacted systems.


Review of preclinical studies on pediatric general anesthesia-induced developmental neurotoxicity.
Thousands of infants and children undergo complicated surgical procedures that require prolonged periods of anesthesia and/or sedation each year. A growing body of preclinical research suggests pediatric anesthetics are harmful to the developing brain; yet, the extent to which these effects generalize to the clinical setting remains unclear. As there will be a continuing need for surgical and other interventions requiring sedation and/or anesthesia during the neonatal period, it seems clear that research efforts should focus on determining the extent to which general anesthetics can affect the developing brain as well as determining strategies for preventing or ameliorating the adverse effects associated with exposure to such agents. The purpose of this paper is to provide a review of the preclinical literature examining the effects of general anesthesia on brain and behavioral development. This paper will detail the effects of different anesthetic agents on various indices of neurotoxicity and functional outcomes as well as provide a review of potential protective compounds and suggestions for areas of future research.


Microbiological aspects of public health planning and preparedness for the 2012 Olympic Games.
Although communicable diseases have hitherto played a small part in illness associated with Olympic Games, an outbreak of infection in a national team, Games venue or visiting spectators has the potential to disrupt a global sporting event and distract from the international celebration of athletic excellence. Preparation for hosting the Olympic Games includes implementation of early warning systems for detecting emerging infection problems. Ensuring capability for rapid microbiological diagnoses to inform situational risk assessments underpins the ability to dispel rumours. These are a prelude to control measures to minimize impact of any outbreak of infectious disease at a time of intense public scrutiny. Complex multidisciplinary teamwork combined with laboratory technical innovation and efficient information flows underlie the Health Protection Agency's preparation for the London 2012 Olympic and Paralympic Games. These will deliver durable legacies for clinical and public health microbiology, outbreak investigation and control in the coming years.


CH(3)NH(3)PbI(3) perovskite / silicon tandem solar cells: characterization based optical simulations.
In this study we analyze and discuss the optical properties of various tandem architectures: mechanically stacked (four-terminal) and monolithically integrated (two-terminal) tandem devices, consisting of a methyl ammonium lead triiodide (CH(3)NH(3)PbI(3)) perovskite top solar cell and a crystalline silicon bottom solar cell. We provide layer thickness optimization guidelines and give estimates of the maximum tandem efficiencies based on state-of-the-art sub cells. We use experimental complex refractive index spectra for all involved materials as input data for an in-house developed optical simulator CROWM. Our characterization based simulations forecast that with optimized layer thicknesses the four-terminal configuration enables efficiencies over 30%, well above the current single-junction crystalline silicon cell record of 25.6%. Efficiencies over 30% can also be achieved with a two-terminal monolithic integration of the sub-cells, combined with proper selection of layer thicknesses.


Effects of early IL-17A neutralization on disease induction in a primate model of experimental autoimmune encephalomyelitis.
We report on the effect of antibody-mediated neutralization of interleukin (IL)-17A in a non-human primate experimental autoimmune encephalomyelitis (EAE) model induced with recombinant human myelin oligodendrocyte glycoprotein (rhMOG). We tested a human-anti-human IL-17A-antibody in two doses (3 and 30 mg/kg) against placebo (PBS). The treatment was started 1 day before EAE induction and continued throughout the experiment. Although all monkeys developed clinically evident EAE, the onset of neurological signs was delayed in some monkeys from both treatment groups. Total CNS lesion volumes, demyelination, or inflammation did not differ between the different groups. Immune profiling revealed an altered distribution of IL-17A producing cells in the lymphoid organs of antibody-treated monkeys. Comparable numbers of IL-17A producing cells were observed in the brain. RhMOG-induced T cell proliferation in the lymph nodes was slightly reduced after anti-IL-17A antibody treatment. To summarize, we found that anti-IL-17A antibody as a single treatment from disease induction effects a trend towards delayed neurological disease progression in the marmoset EAE model, although the effect did not reach statistical significance. This suggests a role of IL-17A in late stage disease in the marmoset EAE model, but IL-17A may not be the dominant pathogenic cytokine.


Anxiety and depression in patients with coronary heart disease: a study in a tertiary hospital.
Anxiety and depression could reduce the quality of life, and exacerbate physical symptoms and even mortality amongst patients with coronary heart disease (CHD). The aim of this study was to investigate the incidence of anxiety and depression in patients with acute CHD. In a period from March to December 2008, the views of 108 CHD patients, hospitalized in a tertiary hospital, were solicited using Hospital Anxiety and Depression Scale (HADS) and sociodemographic questionnaires. Patients with CHD had a low level anxiety and depression scores. There was significant differences in the total HADS score of participants stratified for marital status (P=0.027) or co-morbidity of diseases (P=0.012). Also, there were significant differences in the scores of depression subscale stratified for marital status (P=0.021) or co-morbidity of disease (P=0.007). However, there was no significant difference between the total HADS score or depression subscale score of the participants stratified based on age, gender, race, education, or income. Moreover, unmarried CHD respondents possessed higher depression level compared to the married respondents, and CHD respondents with co-morbid diseases showed a high level of depression. The findings might be taken as evidence to suggest that CHD patients should be evaluated early for the detection of anxiety and depression for appropriate referral and support.


Antialarmins for treatment of asthma: future perspectives.
Recent studies have highlighted the role of alarmins in asthma pathophysiology and tested the roles of these cytokines in asthmatic patients. This review will discuss the recent advances in the role of alarmins in asthma and the potential of future targeted therapies in asthma. Epithelial-derived cytokines can be released upon exposure to external stimuli, causing damage to the epithelial barrier and resulting in tissue inflammation. Of these cytokines, IL-25, IL-33 and thymic stromal lymphopoeitin (TSLP), have been associated with asthma. These alarmins are all not only overexpressed in asthmatic airways, particularly in airway epithelial cells, but also in other structural and immune cells. Furthermore, all three alarmins drive type-2 pro-inflammatory responses in several immune cells that have been identified as key players in the pathogenesis of asthma, including innate lymphoid type-2 cells. Clinical trials testing therapeutics that block pathways of the alarmins are in progress. To-date, only TSLP blockade has been reported in human clinical trials, and this approach has shown efficacy in asthmatic patients. Current body of evidence suggests that alarmins are useful upstream targets for treatment of asthma.


Molecular systematics of European Hyalodaphnia: the role of contemporary hybridization in ancient species.
We examined phylogenetic relationships among Daphnia using mitochondrial DNA (mtDNA) sequences from the small subunit ribosomal RNA (12S), cytochrome c oxidase subunit I and nuclear DNA sequences from the first and second internal transcribed spacer representing 1612 base positions. Phylogenetic analyses using several species of the three main Daphnia subgenera, Ctenodaphnia, Hyalodaphnia and Daphnia, revealed that the Hyalodaphnia are a monophyletic sister group of the Daphnia. Most Hyalodaphnia species occur on one continent, whereas only three are found in North America and Europe. Endemicity of species is associated with variation in thermal tolerance and habitat differentiation. Although many species of the Hyalodaphnia are known to hybridize in nature, mtDNA divergence is relatively high ca. 9%) compared to other hybridizing arthropods (ca. 3%). Reproductive isolation in Daphnia seems to evolve significantly slower than genetic isolation. We related these findings to what is known about the ecology and genetics of Daphnia in order to better understand the evolutionary diversification of lineages. The relationship of these data to phylogenetic patterns is discussed in the context of speciation processes in Daphnia.


Paraquat and nitrofurantoin inhibit growth of Escherichia coli by inducing stringency.
The herbicide paraquat and the antibiotic nitrofurantoin (redox-active compounds that can transfer electrons singly to oxygen) induced intracellular accumulation of the regulatory inhibitor guanosine tetraphosphate (stringency) in Escherichia coli. This mechanism is sufficient to account for the rapid bacteristasis produced in minimal medium by these agents. The growth inhibition and stringency induction were prevented by inclusion of specific amino acids in the medium. Stringency was first reported to result from amino acid starvation, with unloaded transfer ribonucleic acids (tRNAs) acting as the trigger. Previously, inhibition of growth of E. coli by paraquat and hyperbaric oxygen were shown to be prevented by inclusion in the medium of a nearly identical profile of specific amino acids, including branched-chain amino acids, which were required because of poisoning of their biosynthesis at the dihydroxyacid dehydratase site, and stringency has been induced by hyperbaric oxygen poisoning. Thus, stringency induction via a common poisoned site in branched-chain amino acid biosynthesis appears to be a shared mechanism of toxicity for these agents and hyperbaric oxygen, which also share the propensity for one-electron-transfer, free-radical reactions in cells.


Urban affinity and its associated traits: A global analysis of bats.
Urbanization is a major contributor to the loss of biodiversity. Its rapid progress is mostly at the expense of natural ecosystems and the species inhabiting them. While some species can adjust quickly and thrive in cities, many others cannot. To support biodiversity conservation and guide management decisions in urban areas, it is important to find robust methods to estimate the urban affinity of species (i.e. their tendency to live in urban areas) and understand how it is associated with their traits. Since previous studies mainly relied on discrete classifications of species' urban affinity, often involving inconsistent assessments or variable parameters, their results were difficult to compare. To address this issue, we developed and evaluated a set of continuous indices that quantify species' urban affinity based on publicly available occurrence data. We investigated the extent to which a species' position along the urban affinity gradient depends on the chosen index and how this choice affects inferences about the relationship between urban affinity and a set of morphological, sensory and functional traits. While these indices are applicable to a wide range of taxonomic groups, we examined their performance using a global set of 356 bat species. As bats vary in sensitivity to anthropogenic disturbances, they provide an interesting case study. We found that different types of indices resulted in different rankings of species on the urban affinity spectrum, but this had little effect on the association of traits with urban affinity. Our results suggest that bat species predisposed to urban life are characterized by low echolocation call frequencies, relatively long call durations, small body size and flexibility in the selection of the roost type. We conclude that simple indices are appropriate and practical, and propose to apply them to more taxa to improve our understanding of how urbanization favours or filters species with particular traits.


Amygdalar atrophy in panic disorder patients detected by volumetric magnetic resonance imaging.
It has been suggested that the pathophysiology of panic disorder (PD) may involve abnormalities in several brain structures, including the amygdala. To date, however, no study has used quantitative structural neuroimaging techniques to examine amygdalar anatomy in this disorder. Volumetric magnetic resonance imaging (MRI) studies of the amygdalas, hippocampi, and temporal lobes were conducted in 12 drug-free, symptomatic PD patients (six females and six males), and 12 case-matched healthy comparison subjects. Volumetric MRI data were normalized for brain size. PD patients were found to have smaller left-sided and right-sided amygdalar volumes than controls. No differences were found in either hippocampi or temporal lobes. These findings provide new evidence of changes in amygdalar structure in PD and warrant further anatomical and MRI brain studies of patients with this disorder.


Photoconductance and inverse photoconductance in films of functionalized metal nanoparticles.
In traditional photoconductors, the impinging light generates mobile charge carriers in the valence and/or conduction bands, causing the material's conductivity to increase. Such positive photoconductance is observed in both bulk and nanostructured photoconductors. Here we describe a class of nanoparticle-based materials whose conductivity can either increase or decrease on irradiation with visible light of wavelengths close to the particles' surface plasmon resonance. The remarkable feature of these plasmonic materials is that the sign of the conductivity change and the nature of the electron transport between the nanoparticles depend on the molecules comprising the self-assembled monolayers (SAMs) stabilizing the nanoparticles. For SAMs made of electrically neutral (polar and non-polar) molecules, conductivity increases on irradiation. If, however, the SAMs contain electrically charged (either negatively or positively) groups, conductivity decreases. The optical and electrical characteristics of these previously undescribed inverse photoconductors can be engineered flexibly by adjusting the material properties of the nanoparticles and of the coating SAMs. In particular, in films comprising mixtures of different nanoparticles or nanoparticles coated with mixed SAMs, the overall photoconductance is a weighted average of the changes induced by the individual components. These and other observations can be rationalized in terms of light-induced creation of mobile charge carriers whose transport through the charged SAMs is inhibited by carrier trapping in transient polaron-like states. The nanoparticle-based photoconductors we describe could have uses in chemical sensors and/or in conjunction with flexible substrates.


Screening mammography in older women: a review.
Guidelines recommend individualizing screening mammography decisions for women aged 75 years and older. However, little pragmatic guidance is available to help counsel patients. To provide an evidence-based approach for individualizing decision-making about screening mammography in older women. We searched PubMed for English-language studies in peer-reviewed journals published from January 1, 1990, to February 1, 2014, to identify risk factors for late-life breast cancer in women aged 65 years and older and to quantify the benefits and harms of screening mammography for women aged 75 years and older. Age is the major risk factor for developing and dying from breast cancer. Breast cancer risk factors that reflect hormonal exposures in the distant past, such as age at first birth or age at menarche, are less predictive of late-life breast cancer than factors indicating recent hormonal exposures such as high bone mass or obesity. Randomized trials of the benefits of screening mammography did not include women older than 74 years. Thus it is not known if screening mammography benefits older women. Observational studies favor extending screening mammography to older women who have a life expectancy of more than 10 years. Modeling studies estimate 2 fewer breast cancer deaths/1000 women who in their 70s continue biennial screening for 10 years instead of stopping screening at age 69. Potential harms of continued screening over 10 years include false-positive mammograms in approximately 200/1000 women screened and overdiagnosis (ie, finding breast cancer that would not have clinically surfaced otherwise) in approximately 13/1000 women screened. Providing information about life expectancy along with potential benefits and harms of screening may help older women's decision-making about screening mammography. For women with less than a 10-year life expectancy, recommendations to stop screening mammography should emphasize increased potential harms from screening and highlight health promotion measures likely to be beneficial over the short term. For women with a life expectancy of more than 10 years, deciding whether potential benefits of screening outweigh harms becomes a value judgment for patients, requiring a realistic understanding of screening outcomes.


Does the Partners in Health scale allow meaningful comparisons of chronic condition self-management between men and women? Testing measurement invariance.
To determine if the Partners in Health scale, pertinent to assessing patient chronic condition self-management, operates equivalently for men and women. There are distinct gender-based differences in self-management behaviours and health perceptions. This may introduce non-invariance in self-report measures. Testing of measurement invariance is a recommended practice in nursing science to ensure robust metrics. A representative cross-sectional population survey in South Australian. In 2014, 940 people responded to the South Australian Health Omnibus Survey, a battery of health-related questions. MI and estimation of heterogeneity was tested using Bayesian confirmatory factor analysis. Findings showed self-management constructs were interpreted equivalently between men and women. Observed population heterogeneity associated lower education levels with poorer illness and treatment knowledge, smokers with poorer treatment partnerships and mental health problems with lower coping capacity. Approximate measurement invariance was achieved between men and women for Partners in Health scale. There is a lack of well-validated generic instruments, including investigation into gender variability, for measuring chronic condition self-management behaviours. Lower education levels were found to connect with poorer knowledge of health condition and treatment. Mental health problems attenuated ability to cope with the effect of the condition. Findings can facilitate the development of better tailored interventions for self-management of patients' chronic condition/s.


Evaluation of the importance of maternal history of diabetes and of mitochondrial variation in the development of NIDDM.
In 79 South Indian nuclear pedigrees ascertained via probands with NIDDM and both parents living, parental diabetic status was established through previously diagnosed NIDDM (n = 97) or oral glucose tolerance testing (n = 61). There was no significant difference between diabetes prevalence in mothers and fathers (60 vs 53 (76% vs 67%), respectively, p = 0.22). 'Age at diabetes diagnosis' survival curves did differ according to parental gender (p = 0.02) but this may reflect gender differences in health provision rather than pathophysiology. No maternal excess effects of the magnitude evident in previous studies were detected, suggesting either ethnic differences or overestimation of the maternal effect when reported histories of parental diabetes have been used. The tRNA(Leu(UUR) gene region was studied for diabetes-associated variation given the role of mutations in this gene in some pedigrees displaying maternal transmission of NIDDM. None of 142 unrelated South Indian NIDDM subjects displayed the MELAS mutation at nt3243. However, sequencing identified two variants of potential importance: (a) at nt3290 in the tRNA(Leu(UUR) gene, seen in 7/142 diabetic and 1/85 control subjects (p = 0.11), (b) at nt3316 in the ND1 gene (4/142 vs 1/85 subjects, respectively (p = 0.51)). Further studies are needed to determine the relevance of these variants to the development of NIDDM.


Impact of progression at baseline and on-treatment progression events in three large prostate cancer trials.
There is a discussion about the optimal timing to initiate or switch treatment in metastatic castration-resistant prostate cancer (mCRPC). This post hoc analysis of 3 large trials for men with mCRPC examined the influence of the type of progression at initiation of first-line chemotherapy, as well as the type of progression during treatment, on treatment outcomes. Data from the phase III studies VENICE (n = 1224), TAX327 (n = 1006) and FIRSTANA (n = 1168) were used as independent data sets. Type of progression was defined as follows: prostate-specific antigen (PSA) only (group 1), radiological (±PSA) (group 2) or pain (±PSA, ± radiological) progression (group 3). The impact of baseline type of progression on overall survival (OS) was evaluated in multivariate Cox regression analysis with backward elimination, stratified for the Eastern Cooperative Oncology Group performance score and treatment arm. The median OS (arms combined) from treatment initiation in VENICE was 28.6, 26.3 and 16.9 months for G1, G2 and G3, respectively (hazard ratio: 1.14 [95% confidence interval {CI}: 0.92-1.41%] in G2 and 2.13 [95% CI: 1.75-2.59%] in G3 compared with G1). Multivariate analysis (arms combined) showed that pain progression at baseline was an independent predictor of poor OS. Similar findings were observed in the TAX327 and FIRSTANA data sets. During treatment, pain or radiological progression preceded PSA progression in ~55% of the patients. The retrospective characteristic of this study is a limitation. The type of progression at baseline strongly predicts OS in men with mCRPC treated with first-line chemotherapy. During treatment, pain and/or radiological progression preceded PSA progression as the first progression event in ~55% of the patients. This finding has the prospect to be incorporated in clinical guidelines and to be practice changing because it implies the need for regular imaging and not to rely on PSA progression alone.


Conservation in the first internal transcribed spacer (ITS1) region of Hematodinium perezi (genotype III) from Callinectes sapidus .
Hematodinium spp. infections have been reported from blue crabs Callinectes sapidus in high-salinity waters of the USA from New Jersey to Texas. Recently, H. perezi (genotype III) has been proposed as the parasite species and genotype infecting blue crabs from Virginia; however, it is unknown whether this same genotype is present in blue crabs from other locations. To address this question, we collected 317 blue crabs from Massachusetts, Virginia, Georgia, Florida, Louisiana, and Texas to test for the presence of H. perezi (III) using a specific PCR assay targeting the first internal transcribed spacer (ITS1) region of the ribosomal RNA gene complex. To examine the genetic variation within H. perezi (III), ITS1 region sequences from the parasite in blue crabs from multiple locations were compared to each other and to those of H. perezi (III) found in alternate hosts from Virginia. In total, 34 distinct ITS1 sequence variants of the parasite were identified from blue crabs alone, and 38 distinct variants were identified when alternate hosts were included. However, a single ITS1 sequence variant appeared in all geographic regions and hosts, and also in blue crabs sampled from a previous study. The high similarity among all the ITS1 region sequences examined (>98%) and the observation of a single variant found throughout a large geographic range, strongly suggests that a single species and genotype of Hematodinium, specifically H. perezi (III), infects blue crabs from Virginia to Texas and multiple alternate host species in Virginia.


Social domain dysfunction and disorganization in borderline personality disorder.
Social dysfunction in personality disorder is commonly ascribed to abnormal temperamental traits but may also reflect deficits in social processing. In this study, we examined whether borderline and avoidant personality disorders (BPD, APD) may be differentiated by deficits in different social domains and whether disorganization of social domain functioning uniquely characterizes BPD. Patients were recruited from psychiatric clinics in Pittsburgh, USA, to provide a sample with BPD, APD and a no-personality disorder (no-PD) comparison group. Standardized assessments of Axis I and Axis II disorders and social domain dysfunction were conducted, including a new scale of 'domain disorganization' (DD). Pervasive social dysfunction was associated with a 16-fold increase in the odds of an Axis II disorder. Both APD and BPD were associated with elevated social dysfunction. Romantic relationship dysfunction was associated specifically with BPD symptoms and diagnosis. DD was associated specifically with a categorical BPD diagnosis and with a dimensional BPD symptom count. A focus on the inherently interpersonal properties of personality disorders suggests specific mechanisms (within and across interpersonal domains) that may help to account for the origins and maintenance of some disorders. In particular, BPD reflects disturbances in romantic relationships, consistent with a role for attachment processes, and in the organization of functioning across social domains.