A comparison of removal performance of volatile organic and sulfurous compounds between odour abatement systems.
Three types of odour abatement systems in sewer networks in Australia were studied for 18 months to determine the removals of different compounds. Six volatile sulfurous compounds and seven volatile organic compounds (VOCs) were further investigated. All types of odour abatement systems exhibited good removal of hydrogen sulfide with the biotrickling filters (BTFs) showing the highest consistent removal. Biofilters outperformed BTFs and activated carbon (AC) filters in the removal of dimethyl mono-, di- and tri-sulfide species at the low inlet concentrations typically found. AC filters exhibited little VOC removal with no compound consistently identified as having a removal greater than 0%. Biofilters outperformed BTFs in VOC removal, yet both had high removal variability.


Targeted Capture of Hundreds of Nuclear Genes Unravels Phylogenetic Relationships of the Diverse Neotropical Palm Tribe Geonomateae.
The tribe Geonomateae is a widely distributed group of 103 species of Neotropical palms which contains six ecologically important understory or subcanopy genera. Although it has been the focus of many studies, our understanding of the evolutionary history of this group, and in particular of the taxonomically complex genus Geonoma, is far from complete due to a lack of molecular data. Specifically, the previous Sanger sequencing-based studies used a few informative characters and partial sampling. To overcome these limitations, we used a recently developed Arecaceae-specific target capture bait set to undertake a phylogenomic analysis of the tribe Geonomateae. We sequenced 3,988 genomic regions for 85% of the species of the tribe, including 84% of the species of the largest genus, Geonoma. Phylogenetic relationships were inferred using both concatenation and coalescent methods. Overall, our phylogenetic tree is highly supported and congruent with taxonomic delimitations although several morphological taxa were revealed to be non-monophyletic. It is the first time that such a large genomic dataset is provided for an entire tribe within the Arecaceae. Our study lays the groundwork not only for detailed macro- and micro-evolutionary studies within the group, but also sets a workflow for understanding other species complexes across the tree of life.


Interactome analysis of Bag-1 isoforms reveals novel interaction partners in endoplasmic reticulum-associated degradation.
Bag-1 is a multifunctional protein that regulates Hsp70 chaperone activity, apoptosis, and proliferation. The three major Bag-1 isoforms have different subcellular localizations and partly non-overlapping functions. To identify the detailed interaction network of each isoform, we utilized mass spectrometry-based proteomics and found that interactomes of Bag-1 isoforms contained many common proteins, with variations in their abundances. Bag-1 interactomes were enriched with proteins involved in protein processing and degradation pathways. Novel interaction partners included VCP/p97; a transitional ER ATPase, Rad23B; a shuttling factor for ubiquitinated proteins, proteasome components, and ER-resident proteins, suggesting a role for Bag-1 also in ER-associated protein degradation (ERAD). Bag-1 pull-down from cells and tissues from breast cancer patients validated these interactions and showed cancer-related prominence. Using in silico predictions we detected hotspot residues of Bag-1. Mutations of these residues caused loss of binding to protein quality control elements and impaired proteasomal activity in MCF-7 cells. Following CD147 glycosylation pattern, we showed that Bag-1 downregulated VCP/p97-dependent ERAD. Overall, our data extends the interaction map of Bag-1, and broadens its role in protein homeostasis. Targeting the interaction surfaces revealed in this study might be an effective strategy in the treatment of cancer.


Mortality patterns among critically ill children in a Pediatric Intensive Care Unit of a developing country.
Advances in biomedical technology have made medical treatment to be continued beyond a point, at which it does not confer an advantage but may increase the suffering of patients. In such cases, continuation of care may not always be useful, and this has given rise to the concept of limitation of life-sustaining treatment. Our aim was to study mortality patterns over a 6-year period in a Pediatric Intensive Care Unit (PICU) in a developing country and to compare the results with published data from other countries. Retrospective cohort study was conducted in a PICU of a tertiary care hospital in Pakistan. Data were drawn from the medical records of children aged 1-month - 16 years of age who died in PICU, from January 2007 to December 2012. A total of 248 (from an admitted number of 1919) patients died over a period of 6 years with a mortality rate 12.9%. The median age of children who died was 2.8 years, of which 60.5% (n = 150) were males. The most common source of admission was from the emergency room (57.5%, n = 143). The most common cause of death was limitation of life-sustaining treatment (63.7%, n = 158) followed by failed cardiopulmonary resuscitation (28.2%, n = 70) and brain death (8.1%, n = 20). We also found an increasing trend of limitation of life-sustaining treatment do-not-resuscitate (DNR) over the 6-year reporting period. We found limitation of life support treatment (DNR + Withdrawal of Life support Treatment) to be the most common cause of death, and parents were always involved in the end-of-life care decision-making.


Stenotrophomonas rhizophila sp. nov., a novel plant-associated bacterium with antifungal properties.
A polyphasic taxonomic study was performed on 16 Stenotrophomonas strains from environmental and clinical sources. A group of three plant-associated isolates were shown to be phenotypically different from the other strains. This group formed a separate physiological cluster (B1) with 42% heterogeneity to the other isolates. The defining characteristics of the new species were as follows: growth at 4 degrees C and the absence of growth at 40 degrees C; the utilization of xylose as a carbon source; lower osmolytic tolerance (< 4.5% NaCl, w/v), although the isolates can produce trehalose and glucosylglycerol as osmoprotective substances; the absence of lipase and beta-glucosidase production; and antifungal activity against plant-pathogenic fungi. The whole-cell fatty acid profile of this group was different and characterized by the main fatty acids iso-C15:0 and anteiso-C15:0. Numerical analysis of the fatty acid profiles of the strains examined supports the differentiation of the physiological B1 group. By 16S rDNA analysis, three clusters were distinguished. The three strains of the B1 group formed a separate environmental cluster (E1). They showed a mean similarity of 99.5% within the cluster, and differed from strains of a second environmental cluster (E2) by 2.2% and from the clinical cluster (C) by about 3.0%. DNA-DNA hybridization data supported the taxonomic differentiation. All results led to the proposal of a new species, Stenotrophomonas rhizophila sp. nov., with strain e-p10(T) (= DSM 14405(T) = ATCC BAA-473(T)) as the type strain.


Regulation of proto-oncogenic dbl by chaperone-controlled, ubiquitin-mediated degradation.
The dbl proto-oncogene product is a prototype of a growing family of guanine nucleotide exchange factors (GEFs) that stimulate the activation of small GTP-binding proteins from the Rho family. Mutations that result in the loss of proto-Dbl's amino terminus produce a variant with constitutive GEF activity and high oncogenic potential. Here, we show that proto-Dbl is a short-lived protein that is kept at low levels in cells by efficient ubiquitination and degradation. The cellular fate of proto-Dbl is regulated by interactions with the chaperones Hsc70 and Hsp90 and the protein-ubiquitin ligase CHIP, and these interactions are mediated by the spectrin domain of proto-Dbl. We show that CHIP is the E3 ligase responsible for ubiquitination and proteasomal degradation of proto-Dbl, while Hsp90 functions to stabilize the protein. Onco-Dbl, lacking the spectrin homology domain, cannot bind these regulators and therefore accumulates in cells at high levels, leading to persistent stimulation of its downstream signaling pathways.


Gait analysis in chronic heart failure: The calf as a locus of impaired walking capacity.
Reduced walking capacity, a hallmark of chronic heart failure (CHF), is strongly correlated with hospitalization and morbidity. The aim of this work was to perform a detailed biomechanical gait analysis to better identify mechanisms underlying reduced walking capacity in CHF. Inverse dynamic analyses were conducted in CHF patients and age- and exercise level-matched control subjects on an instrumented treadmill at self-selected treadmill walking speeds and at speeds representing +20% and -20% of the subjects' preferred speed. Surprisingly, no difference in preferred speed was observed between groups, possibly explained by an optimization of the mechanical cost of transport in both groups (the mechanical cost to travel a given distance; J/kg/m). The majority of limb kinematics and kinetics were also similar between groups, with the exception of greater ankle dorsiflexion angles during stance in CHF. Nevertheless, over two times greater ankle plantarflexion work during stance and per distance traveled is required for a given triceps surae muscle volume in CHF patients. This, together with a greater reliance on the ankle compared to the hip to power walking in CHF patients, especially at faster speeds, may contribute to the earlier onset of fatigue in CHF patients. This observation also helps explain the high correlation between triceps surae muscle volume and exercise capacity that has previously been reported in CHF. Considering the key role played by the plantarflexors in powering walking and their association with exercise capacity, our findings strongly suggest that exercise-based rehabilitation in CHF should not omit the ankle muscle group.


Synthesis, molecular modeling and biological evaluation of aza-flavanones as α-glucosidase inhibitors.
An efficient acid catalyzed methodology has been employed to synthesize a variety of aza-flavanones and their α-glucosidase inhibitory activity is evaluated using acarbose, miglitol and voglibose as reference standards. Molecular modeling studies were performed for all compounds to identify the important binding modes responsible for the inhibition activity of α-glucosidase which helped find key interactions between the enzyme and the active compounds. Among all the compounds 5g, 5r and 5w have shown high α-glucosidase inhibition activity compared to standard reference drugs and have been identified as promising potential antidiabetic agents. This study is the first biological evaluation of aza-flavanones as α-glucosidase inhibitors.


Cultural and Digital Health Literacy Appropriateness of App- and Web-Based Systems Designed for Pregnant Women With Gestational Diabetes Mellitus: Scoping Review.
The prevalence of women diagnosed with gestational diabetes mellitus (GDM) is increasing dramatically. Mobile technologies to enhance patient self-management offer many advantages for women diagnosed with GDM. However, to our knowledge, although mobile health (mHealth) and telemedicine systems for GDM management exist, evidence on their cultural and digital health literacy appropriateness levels is limited. This review aimed to search and assess the literature on mHealth and telemedicine systems designed for women diagnosed with GDM. Our assessment of these technologies focused on their cultural and digital health literacy appropriateness as well as the systems' effectiveness in improving glycemic control and maternal and infant outcomes. We conducted a scoping review using a framework adapted from Arksey and O'Malley. Four electronic databases were searched for relevant studies: PubMed, MEDLINE (EBSCO), Web of Science, and Scopus. The databases were searched between January 2010 and January 2022. The inclusion criteria were pregnant women diagnosed with GDM, use of telemedicine for monitoring and management, and vulnerable or disadvantaged patients. We used terms related to mobile apps and telemedicine: GDM, vulnerable populations, periphery, cultural appropriateness, and digital health literacy. Studies were screened and selected independently by 2 authors. We extracted the study data on a Microsoft Excel charting table and categorized them into final themes. The results were categorized according to the cultural and digital health literacy features presented. We identified 17 studies that reported on 12 telemedicine and mHealth app interventions. We assessed the studies in three domains: cultural appropriateness, digital health literacy, and maternal and infant outcomes. In the literature, we found that existing digital technologies may improve glycemic control and diabetes self-management. However, there is a lack of assessment of cultural and digital health literacy appropriateness for pregnant women diagnosed with GDM. Considerations in app design regarding cultural appropriateness were found in only 12% (2/17) of the studies, and only 25% (3/12) of the interventions scored ≥3 out of 5 in our assessment of digital health literacy. mHealth and telemedicine can be an effective platform to improve the clinical management of women with GDM. Although studies published on the use of mHealth and telemedicine systems exist, there is a limited body of knowledge on the digital health literacy and cultural appropriateness of the systems designed for women diagnosed with GDM. In addition, as our study was restricted to the English language, relevant studies may have been excluded. Further research is needed to evaluate, design, and implement better tailored apps regarding cultural and digital literacy appropriateness for enhancing pregnant women's self-management as well as the effectiveness of these apps in improving maternal and infant health outcomes.


HIV-1 Gag shares a signature motif with annexin (Anx7), which is required for virus replication.
Genetic and biochemical analyses of the Gag protein of HIV-1 indicate a crucial role for this protein in several functions related to viral replication, including viral assembly. It has been suggested that Gag may fulfill some of the functions by recruiting host cellular protein(s). In our effort to identify structural and functional homologies between Gag and cellular cytoskeletal and secretory proteins involved in transport, we observed that HIV-1 Gag contains a unique PGQM motif in the capsid region. This motif was initially noted in the regulatory domain of synexin the membrane fusion protein of Xenopus laevis. To evaluate the functional significance of the highly conserved PGQM motif, we introduced alanine (A) in place of individual residues of the PGQM and deleted the motif altogether in a Gag expression plasmid and in an HIV-1 proviral DNA. The proviral DNA containing mutations in the PGQM motif showed altered expression, assembly, and release of viral particles in comparison to parental (NL4-3) DNA. When tested in multiple- and single-round replication assays, the mutant viruses exhibited distinct replication phenotypes; the viruses containing the A for the G and Q residues failed to replicate, whereas A in place of the P and M residues did not inhibit viral replication. Deletion of the tetrapeptide also resulted in the inhibition of replication. These results suggest that the PGQM motif may play an important role in the infection process of HIV-1 by facilitating protein-protein interactions between viral and/or viral and cellular proteins.


Mitf cooperates with Rb1 and activates p21Cip1 expression to regulate cell cycle progression.
The controls that enable melanoblasts and melanoma cells to proliferate are likely to be related, but so far no key regulator of cell cycle progression specific to the melanocyte lineage has been identified. The microphthalmia-associated transcription factor Mitf has a crucial but poorly defined role in melanoblast and melanocyte survival and in differentiation. Here we show that Mitf can act as a novel anti-proliferative transcription factor able to induce a G1 cell-cycle arrest that is dependent on Mitf-mediated activation of the p21(Cip1) (CDKN1A) cyclin-dependent kinase inhibitor gene. Moreover, cooperation between Mitf and the retinoblastoma protein Rb1 potentiates the ability of Mitf to activate transcription. The results indicate that Mitf-mediated activation of p21Cip1 expression and consequent hypophosphorylation of Rb1 will contribute to cell cycle exit and activation of the differentiation programme. The mutation of genes associated with melanoma, such as INK4a or BRAF that would affect either Mitf cooperation with Rb1 or Mitf stability respectively, would impair Mitf-mediated cell cycle control.


Molecular cloning and characterization of a novel esophageal cancer related gene.
We previously identified four novel cDNA fragments related to human esophageal cancer. One of the fragments was named esophageal cancer related gene 2 (ECRG2). We report here the molecular cloning, sequencing, and expression of the ECRG2 gene. The ECRG2 cDNA comprises a 258 bp nucleotide sequence which encodes for 85 amino acids with a predicted molecular weight of 9.2 kDa. Analysis of the protein sequence reveals the presence at the N terminus of a signal peptide followed by 56 amino acids with a significant degree of sequence similarity with the conserved Kazal domain which characterizes the serine protease inhibitor family. Pulse-chase experiments showed that ECRG2 protein was detected in both cell lysates and culture medium, indicating that the ECRG2 protein was extracellularly secreted after the post-translational cleavage. In vitro uPA/plasmin activity analysis showed the secreted ECRG2 protein inhibited the uPA/plasmin activity, indicating that ECRG2 may be a novel serine protease inhibitor. Northern blot analysis revealed the presence of the major band corresponding to a size of 569 kb throughout the fetal skin, thymus, esophagus, brain, lung, heart, stomach, liver, spleen, colon, kidney, testis, muscle, cholecyst tissues and adult esophageal mucosa, brain, thyroid tissue and mouth epithelia. However, ECRG2 gene was significantly down-regulated in primary esophageal cancer tissues. Taken together, these results indicate that ECRG2 is a novel member of the Kazal-type serine protease inhibitor family and may function as a tumor suppressor gene regulating the protease cascades during carcinogenesis and migration/invasion of esophageal cancer.


Evaluation of Distortion Product Otoacoustic Emissions (DPOAEs) among workers at an Industrial Company exposed to different industrial noise levels in 2014.
Noise-induced hearing loss (NIHL) is usually one of the main problems in industrial settings. The aim of this study was to determine whether changes in the signal-to-noise ratio (SNR) in different DPOAE are caused by exposure to different levels of noise at different time intervals among workers exposed to noise. This case-control study was conducted in the autumn of 2014 on 45 workers at Gol Gohar Mining and Industrial Company, which is located in Sirjan in southeast Iran. The workers were divided into three groups based on their noise exposure, i.e., 1) 15 office workers as a control group with exposure to low levels of noise, 2) 15 workers from manufacturing departments who were exposed to a medium level of noise, and 3) 15 workers from manufacturing departments who were exposed to high levels of noise. The SNRs at the frequencies of 1000, 2000, 3000, 4000, and 6000 Hz were measured in both ears at three different time intervals during the shift work. SNRs of 6 or greater were considered as inclusion criterion. Repeated measures, the Spearman rank-order correlation test, and paired t-test analyses were used with α = 0.05 being the level of significance. For all frequencies in the right and left ears, the SNR values were more than 6, thus all SNR values were considered as acceptable responses. The effects of time and sound pressure level (SPL) on SNR were significant for the right and left ears (p = 0.027 and < 0.001, respectively). There was a statistically significant correlation between the SNR values in the right and left ears for the time intervals 7:30-8:00 A.M. and 13:30-14:00 P.M., which implied that an increase in the duration of exposure led to reduced SNR values (p = 0.024, r = 0.948). The comparison of the SNR values in the right and left ears (for all frequencies and the three different SPLs) indicated that the values decreased during the shift work.


Characterization of antimicrobial-resistant Salmonella isolated from imported foods.
Two-hundred eight Salmonella isolates recovered from over 5,000 imported foods entering the United States in 2001 were tested for antimicrobial susceptibilities and further characterized for quinolone resistance mechanisms, integron carriage, and genetic relatedness. Salmonella Weltevreden (20%), Salmonella Newport (6%), Salmonella Lexington (5%), and Salmonella Thompson (4%) were the four most common serotypes recovered. Twenty-three (11%) isolates were resistant to at least one antimicrobial, and seven (3.4%) to three or more antimicrobials. Resistance was most often observed to tetracycline (9%), followed by sulfamethoxazole (5%), streptomycin (4%), nalidixic acid (3%), and trimethoprim/sulfamethoxazole (2%). One Salmonella Schwarzengrund isolate recovered from squid imported from Taiwan exhibited resistance to eight antimicrobials, including ampicillin, chloramphenicol, gentamicin, kanamycin, nalidixic acid, sulfamethoxazole, tetracycline, and trimethoprim/sulfamethoxazole. Six isolates (Salmonella Bareilly, Salmonella Derby, Salmonella Ohio and three Salmonella Schwarzengrund) contained class 1 integrons, which carried several resistance genes including dhfrI/dhfrXII, aadA, pse-1, and sat1, conferring resistance to trimethoprim/sulfamethoxazole, streptomycin, ampicillin, and streptothricin, respectively. Five of six nalidixic acid-resistant isolates possessed DNA point mutations at either Ser83 or Asp87 in DNA gyrase. One ciprofloxacin-resistant isolate possessed double mutations in DNA gyrase at positions Ser83 and Asp87 as well as a single mutation at Ser80 in parC. The top three serotypes identified, Salmonella Weltevreden (n = 41), Salmonella Newport (n = 13), and Salmonella Lexington (n = 11), were further characterized for genetic relatedness by pulsed-field gel electrophoresis. Fifty-five distinct pulsed-field gel electrophoresis patterns were observed among the 65 isolates, indicating extensive genetic diversity among these Salmonella serotypes contaminating imported foods.


Psychosocial safety climate buffers effects of job demands on depression and positive organizational behaviors.
In a general population sample of 2343 Australian workers from a wide ranging employment demographic, we extended research testing the buffering role of psychosocial safety climate (PSC) as a macro-level resource within the health impairment process of the Job Demands-Resources (JD-R) model. Moderated structural equation modeling was used to test PSC as a moderator between emotional and psychological job demands and worker depression compared with control and social support as alternative moderators. We also tested PSC as a moderator between depression and positive organizational behaviors (POB; engagement and job satisfaction) compared with control and social support as moderators. As expected we found PSC moderated the effects of job demands on depression and further moderated the effects of depression on POB with fit to the data that was as good as control and social support as moderators. This study has shown that PSC is a macro-level resource and safety signal for workers acting to reduce demand-induced depression. We conclude that organizations need to focus on the development of a robust PSC that will operate to buffer the effects of workplace psychosocial hazards and to build environments conducive to worker psychological health and positive organizational behaviors.


Laparoscopically inserted button colostomy as a venting stoma and access port for the administration of antegrade enemas in African degenerative leiomyopathy.
African degenerative leiomyopathy (ADL) is a rare incurable disorder seen in African children, predominantly in southern and south-eastern Africa. ADL presents as chronic intestinal pseudo-obstruction. Management is traditionally conservative, with surgery restricted to the management of complications. We have placed Malone antegrade continence enema (MACE) stomas in the grossly dilated colon to vent accumulated gas and administer antegrade bowel enemas. This is done mainly for relief of gaseous distension and constipation in an attempt to provide symptomatic relief and improve quality of life. In this article, we present our preliminary results of laparoscopically assisted technique to insert a Mic-Key gastrostomy device as a 'button colostomy' in 8 patients over the past 6½ years.


Assessing longitudinal quality of life in prostate cancer patients and their spouses: a multilevel modeling approach.
This study aimed at examining the relationship between quality of life (QOL) in prostate cancer (PCa) patients and partners and how baseline demographics, cancer-related factors, and time-varying psychosocial and symptom covariates affect their QOL over time. Guided by a modified Stress-Coping Model, this study used multilevel modeling to analyze longitudinal data from a randomized clinical trial that tested a family-based intervention to improve QOL in couples managing PCa. Patients and partners from the usual-care control group (N = 134 dyads) independently completed the measurements at baseline, and at 4-, 8-, and 12-month follow-ups. Correlations of QOL between patients and partners over time were small to moderate. Patients' lower education level, partners' older age, higher family income, and localized cancer at baseline were associated with better QOL in couples. Over time, couples' QOL improved as their social support and cancer-related dyadic communication increased and as couples' uncertainty, general symptoms, and patients' prostate cancer-related sexual and hormonal symptoms decreased. Evidence indicates that couples' QOL during cancer survivorship is affected by multiple contextual factors (e.g., baseline demographics and time-varying psychosocial factors and symptoms). Intervention research is needed to explore comprehensive strategies to improve couples' QOL during the continuum of PCa survivorship.


Clinical outcomes and nephrotoxicity associated with vancomycin trough concentrations during treatment of deep-seated infections.
Higher vancomycin concentrations are thought necessary for treatment of deep-seated methicillin-resistant Staphylococcus aureus (MRSA) infection, yet this may result in greater risk of nephrotoxicity. We evaluated the relationship of serum vancomycin trough concentration with clinical outcomes and nephrotoxicity for patients with deep-seated MRSA infection. A retrospective cohort study evaluated adults with MRSA pneumonia, endocarditis or osteomyelitis who received vancomycin for > or = 5 days from June 2005 to June 2007. Patients were stratified by mean vancomycin trough level [low (< 15 mg/l), high (> or = 15 mg/l)]. Outcomes were clinical response, mortality, length of stay (LOS) and nephrotoxicity. Three definitions of nephrotoxicity were used: i) rise in serum creatinine (SCr) > or = 0.5 mg/dl; ii) 50% increase in SCr; and iii) 25% decrease in estimated creatinine clearance. Fifty-five patients experiencing MRSA pneumonia (n = 28), endocarditis (n = 9), osteomyelitis (n = 20) and multiple infections (n = 2) were stratified into low (n = 39) and high (n = 16) groups. High group patients were more likely to be septic (p = 0.01) and have a higher APACHE II score (p = 0.01). After adjustment for APACHE II score, clinical response rates among survivors did not differ significantly. Risk of death was not significantly different between the high (19%) and low (5%) group patients (p = 0.1). LOS did not differ significantly between groups (p = 0.7). Nephrotoxicity occurred in the low and high groups, respectively, for 10 and 31% (p = 0.04) with definition 1, 10 and 31% (p = 0.04) with definition 2, and 13 and 25% (p = 0.1) with definition 3. After adjustment for APACHE II score, odds of nephrotoxicity based on definitions 1 or 2 were increased among the high versus low groups (OR = 3.27, 95% CI: 0.7 - 15.25, p = 0.1), although not statistically significant. Clinical outcomes did not differ significantly between high and low trough groups for deep-seated MRSA infections. Nephrotoxicity was consistently higher in the high trough group, regardless of the definition used.


Adaptation to diverse nitrogen-limited environments by deletion or extrachromosomal element formation of the GAP1 locus.
To study adaptive evolution in defined environments, we performed evolution experiments with Saccharomyces cerevisiae (yeast) in nitrogen-limited chemostat cultures. We used DNA microarrays to identify copy-number variation associated with adaptation and observed frequent amplifications and deletions at the GAP1 locus. GAP1 encodes the general amino acid permease, which transports amino acids across the plasma membrane. We identified a self-propagating extrachromosomal circular DNA molecule that results from intrachromosomal recombination between long terminal repeats (LTRs) flanking GAP1. Extrachromosomal DNA circles (GAP1(circle)) contain GAP1, the replication origin ARS1116, and a single hybrid LTR derived from recombination between the two flanking LTRs. Formation of the GAP1(circle) is associated with deletion of chromosomal GAP1 (gap1Δ) and production of a single hybrid LTR at the GAP1 chromosomal locus. The GAP1(circle) is selected following prolonged culturing in L-glutamine-limited chemostats in a manner analogous to the selection of oncogenes present on double minutes in human cancers. Clones carrying only the gap1Δ allele were selected under various non-amino acid nitrogen limitations including ammonium, urea, and allantoin limitation. Previous studies have shown that the rate of intrachromosomal recombination between tandem repeats is stimulated by transcription of the intervening sequence. The high level of GAP1 expression in nitrogen-limited chemostats suggests that the frequency of GAP1(circle) and gap1Δ generation may be increased under nitrogen-limiting conditions. We propose that this genomic architecture facilitates evolvability of S. cerevisiae populations exposed to variation in levels and sources of environmental nitrogen.


Recovery after nasal surgery vs. tonsillectomy: discriminant validation of the Postoperative Quality of Recovery Scale.
Initial validation and feasibility of the Post-Operative Quality of Recovery Scale (PQRS) was published in 2010. Ongoing validation includes studies to determine whether this scale can discriminate differences in recovery in similar patients having different surgery. A prospective observational study included 89 patients undergoing nasal surgery and 46 patients undergoing tonsillectomy as the primary surgical procedure. Patients were assessed using the PQRS. Assessments were performed pre-surgery, at 15 and 40 min, 1 and 3 days, and 3 months after surgery. Tonsillectomy patients were younger [25.0 standard deviation (SD) 17.8 vs. 32.1 SD 18.0 years, P = 0.031] and had shorter anaesthesia duration (29.5 SD 12.6 vs. 42.7 SD 15.8 min, P < 0.01). Tonsillectomy patients had worse recovery in the nociceptive (pain and nausea; P < 0.001), activities of daily living (P < 0.001) and overall recovery (P = 0.025) domains, but were not different in the cognitive, emotive (depression and anxiety) or physiological recovery domains. Complete satisfaction was lower for tonsillectomy (P < 0.001). At 3 months, there was equivalence between groups in all assessments. The study shows the ability of the PQRS to discriminate recovery in different domains. Tonsillectomy has a worse recovery profile over the first 3 days in nociceptive, activities of daily living and overall recovery, which is associated with poorer satisfaction than nasal surgery.


Comparative jaw muscle anatomy in kangaroos, wallabies, and rat-kangaroos (marsupialia: macropodoidea).
The jaw muscles were studied in seven genera of macropodoid marsupials with diets ranging from mainly fungi in Potorous to grass in Macropus. Relative size, attachments, and lamination within the jaw adductor muscles varied between macropodoid species. Among macropodine species, the jaw adductor muscle proportions vary with feeding type. The relative mass of the masseter is roughly consistent, but grazers and mixed-feeders (Macropus and Lagostrophus) had relatively larger medial pterygoids and smaller temporalis muscles than the browsers (Dendrolagus, Dorcopsulus, and Setonix). Grazing macropods show similar jaw muscle proportions to "ungulate-grinding" type placental mammals. The internal architecture of the jaw muscles also varies between grazing and browsing macropods, most significantly, the anatomy of the medial pterygoid muscle. Potoroines have distinctly different jaw muscle proportions to macropodines. The masseter muscle group, in particular, the superficial masseter is enlarged, while the temporalis group is relatively reduced. Lagostrophus fasciatus is anatomically distinct from other macropods with respect to its masticatory muscle anatomy, including enlarged superficial medial pterygoid and deep temporalis muscles, an anteriorly inflected masseteric process, and the shape of the mandibular condyle. The enlarged triangular pterygoid process of the sphenoid bone, in particular, is distinctive of Lagsotrophus.


Neurochemical dynamics of acute orofacial pain in the human trigeminal brainstem nuclear complex.
The trigeminal brainstem sensory nuclear complex is the first central relay structure mediating orofacial somatosensory and nociceptive perception. Animal studies suggest a substantial involvement of neurochemical alterations at such basal CNS levels in acute and chronic pain processing. Translating this animal based knowledge to humans is challenging. Human related examining of brainstem functions are challenged by MR related peculiarities as well as applicability aspects of experimentally standardized paradigms. Based on our experience with an MR compatible human orofacial pain model, the aims of the present study were twofold: 1) from a technical perspective, the evaluation of proton magnetic resonance spectroscopy at 3 T regarding measurement accuracy of neurochemical profiles in this small brainstem nuclear complex and 2) the examination of possible neurochemical alterations induced by an experimental orofacial pain model. Data from 13 healthy volunteers aged 19-46 years were analyzed and revealed high quality spectra with significant reductions in total N-acetylaspartate (N-acetylaspartate + N-acetylaspartylglutamate) (-3.7%, p = 0.009) and GABA (-10.88%, p = 0.041) during the pain condition. These results might reflect contributions of N-acetylaspartate and N-acetylaspartylglutamate in neuronal activity-dependent physiologic processes and/or excitatory neurotransmission, whereas changes in GABA might indicate towards a reduction in tonic GABAergic functioning during nociceptive signaling. Summarized, the present study indicates the applicability of 1H-MRS to obtain neurochemical dynamics within the human trigeminal brainstem sensory nuclear complex. Further developments are needed to pave the way towards bridging important animal based knowledge with human research to understand the neurochemistry of orofacial nociception and pain.


Induction of proinflammatory responses in macrophages by the glycosylphosphatidylinositols of Plasmodium falciparum: cell signaling receptors, glycosylphosphatidylinositol (GPI) structural requirement, and regulation of GPI activity.
The glycosylphosphatidylinositol (GPI) anchors of Plasmodium falciparum have been proposed to be the major factors that contribute to malaria pathogenesis through their ability to induce proinflammatory responses. In this study we identified the receptors for P. falciparum GPI-induced cell signaling that leads to proinflammatory responses and studied the GPI structure-activity relationship. The data show that GPI signaling is mediated mainly through recognition by TLR2 and to a lesser extent by TLR4. The activity of sn-2-lyso-GPIs is comparable with that of the intact GPIs, whereas the activity of Man(3)-GPIs is about 80% that of the intact GPIs. The GPIs with three (intact GPIs and Man(3)-GPIs) and two fatty acids (sn-2-lyso-GPIs) appear to differ considerably in the requirement of the auxiliary receptor, TLR1 or TLR6, for recognition by TLR2. The former are preferentially recognized by TLR2/TLR1, whereas the latter are favored by TLR2/TLR6. However, the signaling pathways initiated by all three GPI types are similar, involving the MyD88-dependent activation of extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 and NF-kappaB-signaling pathways. The signaling molecules of these pathways differentially contribute to the production of various cytokines and nitric oxide (Zhu, J., Krishnegowda, G., and Gowda, D. C. (2004) J. Biol. Chem. 280, 8617-8627). Our data also show that GPIs are degraded by the macrophage surface phospholipases predominantly into inactive species, indicating that the host can regulate GPI activity at least in part by this mechanism. These results imply that macrophage surface phospholipases play important roles in the GPI-induced innate immune responses and malaria pathogenesis.


Female house mice avoid fertilization by t haplotype incompatible males in a mate choice experiment.
The t haplotype in house mice is a well-known selfish genetic element with detrimental, nonadditive fitness consequences to its carriers: recessive lethal mutations cause t/t homozygotes to perish in utero. Given the severe genetic incompatibility imposed by the t haplotype, we predict females to avoid fertilization by t haplotype incompatible males. Indeed, some of the strongest evidence for compatibility mate choice is related to the t haplotype in house mice. However, all previous evidence for compatibility mate choice in this system is based on olfactory preference. It is so far unknown how general these preferences are and whether they are relevant in an actual mating context. Here, we assess female compatibility mate choice related to t haplotypes in a setting that--for the first time--allowed females to directly interact and mate with males. This approach enabled us to analyse female behaviour during the testing period, and the resulting paternity success and fitness consequences of a given choice. We show that genetic incompatibilities arising from the t haplotype had severe indirect fitness consequences and t females avoided fertilization by t incompatible males. The results are inconclusive whether this avoidance of t fertilization by t females was caused by pre- or post-copulatory processes.


Systemic MCP-1 Levels Derive Mainly From Injured Liver and Are Associated With Complications in Cirrhosis.
Background and Aims: Monocyte chemotactic protein-1 (MCP-1) is a potent chemoattractant for monocytes. It is involved in pathogenesis of several inflammatory diseases. Hepatic MCP-1 is a readout of macrophage activation. While inflammation is a major driver of liver disease progression, the origin and role of circulating MCP-1 as a biomarker remains unclear. Methods: Hepatic CC-chemokine ligand 2 (CCL2) expression and F4/80 staining for Kupffer cells were measured and correlated in a mouse model of chronic liver disease (inhalative CCl4 for 7 weeks). Next, hepatic RNA levels of CCL2 were measured in explanted livers of 39 patients after transplantation and correlated with severity of disease. Changes in MCP-1 were further evaluated in a rat model of experimental cirrhosis and acute-on-chronic liver failure (ACLF). Finally, we analyzed portal and hepatic vein levels of MCP-1 in patients receiving transjugular intrahepatic portosystemic shunt insertion for complications of portal hypertension. Results: In this mouse model of fibrotic hepatitis, hepatic expression of CCL2 (P = 0.009) and the amount of F4/80 positive cells in the liver (P < 0.001) significantly increased after induction of hepatitis by CCl4 compared to control animals. Moreover, strong correlation of hepatic CCL2 expression and F4/80 positive cells were seen (P = 0.023). Furthermore, in human liver explants, hepatic transcription levels of CCL2 correlated with the MELD score of the patients, and thus disease severity (P = 0.007). The experimental model of ACLF in rats revealed significantly higher levels of MCP-1 plasma (P = 0.028) and correlation of hepatic CCL2 expression (R = 0.69, P = 0.003). Particularly, plasma MCP-1 levels did not correlate with peripheral blood monocyte CCL2 expression. Finally, higher levels of MCP-1 were observed in the hepatic compared to the portal vein (P = 0.01) in patients receiving TIPS. Similarly, a positive correlation of MCP-1 with Child-Pugh score was observed (P = 0.018). Further, in the presence of ACLF, portal and hepatic vein levels of MCP-1 were significantly higher compared to patients without ACLF (both P = 0.039). Conclusion: Circulating levels of MCP-1 mainly derive from the injured liver and are associated with severity of liver disease. Therefore, liver macrophages contribute significantly to disease progression. Circulating MCP-1 may reflect the extent of hepatic macrophage activation.


A global view of shifting cultivation: Recent, current, and future extent.
Mosaic landscapes under shifting cultivation, with their dynamic mix of managed and natural land covers, often fall through the cracks in remote sensing-based land cover and land use classifications, as these are unable to adequately capture such landscapes' dynamic nature and complex spectral and spatial signatures. But information about such landscapes is urgently needed to improve the outcomes of global earth system modelling and large-scale carbon and greenhouse gas accounting. This study combines existing global Landsat-based deforestation data covering the years 2000 to 2014 with very high-resolution satellite imagery to visually detect the specific spatio-temporal pattern of shifting cultivation at a one-degree cell resolution worldwide. The accuracy levels of our classification were high with an overall accuracy above 87%. We estimate the current global extent of shifting cultivation and compare it to other current global mapping endeavors as well as results of literature searches. Based on an expert survey, we make a first attempt at estimating past trends as well as possible future trends in the global distribution of shifting cultivation until the end of the 21st century. With 62% of the investigated one-degree cells in the humid and sub-humid tropics currently showing signs of shifting cultivation-the majority in the Americas (41%) and Africa (37%)-this form of cultivation remains widespread, and it would be wrong to speak of its general global demise in the last decades. We estimate that shifting cultivation landscapes currently cover roughly 280 million hectares worldwide, including both cultivated fields and fallows. While only an approximation, this estimate is clearly smaller than the areas mentioned in the literature which range up to 1,000 million hectares. Based on our expert survey and historical trends we estimate a possible strong decrease in shifting cultivation over the next decades, raising issues of livelihood security and resilience among people currently depending on shifting cultivation.


Milk protein polymorphisms in cattle (Bos indicus), mithun (Bos frontalis) and yak (Bos grunniens) breeds and their hybrids indigenous to Bhutan.
In the current study, milk protein variation was examined in cattle (Bos indicus), mithun (Bos frontalis), yak (Bos grunniens) and their hybrid populations in Bhutan to estimate genetic variability, conduct genetic characterization and assess the possibility of gene flow between mithun and cattle. Isoelectric focusing of 372 milk samples from 11 populations detected four molecular types of β-lactoglobulin (A, B, E and M), five molecular types of α(S1) -casein (A, B, C, E and X) and three molecular types of k-casein (A, B and X). Mithun and yak shared alleles but were found to exhibit different allele frequencies for the proteins studied. The degree of genetic variability within populations was measured by average heterozygosity and ranged from 24-40% in cattle, 26% for yak and 33% for mithun. We also resolved the traditional mithun and cattle hybridization system via principal component analysis. Our results suggested secondary introgression of mithun genes to the village Thrabum population, and a close genetic relationship between Bhutanese indigenous cattle and Indian cattle.


Discovery of Brigatinib (AP26113), a Phosphine Oxide-Containing, Potent, Orally Active Inhibitor of Anaplastic Lymphoma Kinase.
In the treatment of echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase positive (ALK+) non-small-cell lung cancer (NSCLC), secondary mutations within the ALK kinase domain have emerged as a major resistance mechanism to both first- and second-generation ALK inhibitors. This report describes the design and synthesis of a series of 2,4-diarylaminopyrimidine-based potent and selective ALK inhibitors culminating in identification of the investigational clinical candidate brigatinib. A unique structural feature of brigatinib is a phosphine oxide, an overlooked but novel hydrogen-bond acceptor that drives potency and selectivity in addition to favorable ADME properties. Brigatinib displayed low nanomolar IC50s against native ALK and all tested clinically relevant ALK mutants in both enzyme-based biochemical and cell-based viability assays and demonstrated efficacy in multiple ALK+ xenografts in mice, including Karpas-299 (anaplastic large-cell lymphomas [ALCL]) and H3122 (NSCLC). Brigatinib represents the most clinically advanced phosphine oxide-containing drug candidate to date and is currently being evaluated in a global phase 2 registration trial.


Regulation of human telomerase activity: repression by normal chromosome 3 abolishes nuclear telomerase reverse transcriptase transcripts but does not affect c-Myc activity.
Telomerase is required for the complete replication of chromosomal ends. In tumors, the human telomerase reverse transcriptase subunit (hTERT) is up-regulated, thereby removing a critical barrier for unlimited cell proliferation. To understand more about hTERT regulation, we measured hTERT RNA levels by quantitative reverse transcription (RT)-PCR. Telomerase-positive cell lines were found to contain between 0.2 and 6 molecules of spliced hTERT RNA per cell, whereas in telomerase-negative cells, the number of molecules was below the sensitivity of the assay (<0.004 molecules/cell). Intron-containing, immature hTERT RNA was observed only in nuclei of telomerase-positive cells, which suggests that hTERT RNA levels are transcriptionally regulated. Microcell transfer of a normal chromosome 3 into the human breast carcinoma cell line (21NT) abolishes telomerase activity and induces senescence. Endogenous hTERT transcripts were undetectable in the nuclei of 21NT-chromosome 3 hybrids, even in cells permanently expressing a transfected hTERT cDNA. However, chromosome 3 transfer did not affect the expression of green fluorescent protein reporter constructs driven by up to 7.4 kb of noncoding DNA flanking the 5' end of the hTERT gene. Because direct up-regulation of hTERT through c-Myc overexpression had previously been reported, we investigated whether chromosome 3 transfer affected c-Myc activity. An at least 30-fold reduction of immature intron-containing hTERT RNA was observed after the introduction of a normal chromosome 3, but expression levels of c-Myc, Mad1, and other c-Myc target genes were unchanged. Our results suggest that telomerase is regulated primarily at the level of hTERT transcription by complex mechanisms involving regulatory elements distant from the 5' flanking region, and that the putative hTERT repressor on chromosome 3 does not regulate the expression of hTERT through c-Myc or one of its coregulators.


Vif determines the requirement for CBF-β in APOBEC3 degradation.
APOBEC3 (apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3) proteins are cellular DNA deaminases that restrict a broad spectrum of lentiviruses. This process is counteracted by Vif (viral infectivity factor) of lentiviruses, which binds APOBEC3s and promotes their degradation. CBF-β (core binding factor subunit β) is an essential co-factor for the function of human immunodeficiency virus type 1 Vif to degrade human APOBEC3s. However, the requirement for CBF-β in Vif-mediated degradation of other mammalian APOBEC3 proteins is less clear. Here, we determined the sequence of feline CBFB and performed phylogenetic analyses. These analyses revealed that mammalian CBFB is under purifying selection. Moreover, we demonstrated that CBF-β is dispensable for feline immunodeficiency virus Vif-mediated degradation of APOBEC3s of its host. These findings suggested that primate lentiviruses have adapted to use CBF-β, an evolutionary stable protein, to counteract APOBEC3 proteins of their hosts after diverging from other lentiviruses.


Psychometric Properties of the Memory Binding Test: Test-Retest Reliability and Convergent Validity.
Episodic memory testing is fundamental for the diagnosis of Alzheimer's disease (AD). Although the Free and Cued Selective Reminding Test (FCSRT) is widely used for this purpose, it may not be sensitive enough for early detection of subtle decline in preclinical AD. The Memory Binding Test (MBT) intends to overcome this limitation. To analyze the test-retest reliability of the MBT and its convergent validity with the FCRST. 36 cognitively healthy participants of the ALFA Study, aged 45 to 65, were included for the test-retest study and 69 for the convergent analysis. They were visited twice in a period of 6 ± 2 weeks. Test-retest reliability was determined by the calculation of the intra-class correlation coefficient (ICC). Score differences were studied by computing the mean percentage of score variation between visits and visualized by Bland-Altman plots. Convergent validity was determined by Pearson's correlations. ICC values in the test-retest reliability analysis of the MBT direct scores ranged from 0.64 to 0.76. Subjects showed consistent practice effects, with mean amounts of score increasing between 10% and 26%. Pearson correlation between MBT and FCSRT direct scores showed r values between 0.40 and 0.53. The FCSRT displayed ceiling effects not observed in the MBT. The MBT shows adequate test-retest reliability and overall moderate convergent validity with the FCSRT. Unlike the FCSRT, the MBT does not have ceiling effects and it may therefore be especially useful in longitudinal studies, facilitating the measurement of subtle memory performance decline and the detection of very early AD.


What Is the Optimal Device Length and Insertion Site for Needle Thoracostomy in UK Military Casualties? A Computed Tomography Study.
Significant lessons to inform best practice in trauma care should be learned from the last decade of conflict in Afghanistan and Iraq. This study used radiological data collated in the UK Military Hospital in Camp Bastion, Afghanistan, to investigate the most appropriate device length for needle chest decompression of tension pneumothorax (TP). We reviewed the optimal length of device and site needed for needle decompression of a tension pneumothorax in a UK military population and found no significant difference between sites for needle chest decompression (NCD). As a result, we do not recommend use of devices longer than 60mm for UK service personnel.


Nonalcoholic fatty liver disease: a nutritional approach.
Nonalcoholic fatty liver disease (NAFLD) is among the most common causes of chronic liver disease in many countries, and its prevalence is increasing. NAFLD is often considered to be a hepatic component of metabolic syndrome, and studies have established that insulin resistance plays a major role in the pathogenesis of NAFLD. Treatments for NAFLD primarily target insulin resistance. Interestingly, the most common environmental cause of insulin resistance is diet. This article examines the correlations between NAFLD and diet and provides some diet recommendations based on the most current data available.


Innovative programming in a community service center.
A Community Center in a downtown urban area offers comprehensive services that provide continuity and choice to homeless and poor people. Emphasis is on outreach, through a Day Treatment Program for severely, persistently mentally ill homeless, a mobile outreach team, and neighborhood services, and/or employment, including a restaurant and Employment Reintegration Program. The Center is an example of how professionals, community and business leaders, and citizens can unite to assist clients and how programs can evolve from clients' requests and participation in services. The Center's programming can be followed in any community in this health care reform era.


3-Chlorotyrosine, a specific marker of myeloperoxidase-catalyzed oxidation, is markedly elevated in low density lipoprotein isolated from human atherosclerotic intima.
Oxidation of LDL may be of pivotal importance in atherogenesis, but the mechanisms that promote oxidation in vivo remain poorly understood. We have explored the possibility that one pathway involves myeloperoxidase, a heme protein secreted by phagocytes. Myeloperoxidase is the only human enzyme known to generate hypochlorous acid (HOCl), a potent oxidizing agent, at physiological halide concentrations. LDL exposed to the complete myeloperoxidase-H2O2-Cl- system underwent chlorination of its protein tyrosyl residues. Treatment of LDL with reagent HOCl resulted in 3-chlorotyrosine formation, implicating HOCl as an intermediate in the enzymatic reaction pathway. In contrast, 3-chlorotyrosine was undetectable in LDL oxidized by hydroxyl radical, copper, iron, hemin, glucose, peroxynitrite, horseradish peroxidase, lactoperoxidase, or lipoxygenase. These results indicate that 3-chlorotyrosine is a specific marker for LDL oxidation by myeloperoxidase. To address the role of myeloperoxidase in promoting LDL oxidation in vivo, we used stable isotope dilution gas chromatography-mass spectrometry to quantify 3-chlorotyrosine in human aortic tissue and in LDL isolated from atherosclerotic lesions. The level of 3-chlorotyrosine in atherosclerotic tissue obtained during vascular surgery was sixfold higher than that of normal aortic intima. Moreover, the level of 3-chlorotyrosine was 30-fold higher in LDL isolated from atherosclerotic intima compared with circulating LDL. The detection of 3-chlorotyrosine in human atherosclerotic lesions indicates that halogenation reactions catalyzed by the myeloperoxidase system of phagocytes constitute one pathway for protein oxidation in vivo. These findings raise the possibility that the myeloperoxidase-H2O2-Cl- system plays a critical role in converting LDL into an atherogenic form.


Comparative biochemical and immunological studies of the glycine betaine synthesis pathway in diverse families of dicotyledons.
Members of the Chenopodiaceae can accumulate high levels (>100 μmol·(g DW)(-1)) of glycine betaine (betaine) in leaves when salinized. Chenopodiaceae synthesize betaine by a two-step oxidation of choline (choline→betaine aldehyde→ betaine), with the second step catalyzed by betaine aldehyde dehydrogenase (BADH, EC 18.104.22.168). High betaine levels have also been reported in leaves of species from several distantly-related families of dicotyledons, raising the question of whether the same betaine-synthesis pathway is used in all cases.Fast atom bombardment mass spectrometry showed that betaine levels of >100 μmol·(g DW)(-1) are present in Lycium ferocissimum Miers (Solanaceae), Helianthus annuus L. (Asteraceae), Convolvulus arvensis L. (Convolvulaceae), and Amaranthus caudatus L. (Amaranthaceae), that salinization promotes betaine accumulation in these plants, and that they can convert supplied choline to betaine aldehyde and betaine. Nicotiana tabacum L. and Lycopersicon lycopersicum (L.) Karst. ex Farw. (Solanaceae), Lactuca sativa L. (Asteraceae) and Ipomoea purpurea L. (Convolvulaceae) also contained betaine, but at a low level (0.1-0.5 μmol·(g DW)(-1). Betaine aldehyde dehydrogenase activity assays, immunotitration and immunoblotting demonstrated that the betaine-accumulating species have a BADH enzyme recognized by antibodies raised against BADH from Spinacia oleracea L. (Chenopodiaceae), and that the Mr of the BADH monomer is in all cases close to 63 000. These data indicate that the choline→betaine aldehyde→betaine pathway may have evolved by vertical descent from an early angiosperm ancestor, and might be widespread (albeit not always strongly expressed) among flowering plants. Consistent with these suggestions, Magnolia x soulangiana was found to have a low level of betaine, and to express a protein of Mr 63 000 which cross-reacted with antibodies to BADH from Spinacia oleracea.


Drivers of Intensity and Prevalence of Flea Parasitism on Small Mammals in East African Savanna Ecosystems.
The relative importance of environmental factors and host factors in explaining variation in prevalence and intensity of flea parasitism in small mammal communities is poorly established. We examined these relationships in an East African savanna landscape, considering multiple host levels: across individuals within a local population, across populations within species, and across species within a landscape. We sampled fleas from 2,672 small mammals of 27 species. This included a total of 8,283 fleas, with 5 genera and 12 species identified. Across individual hosts within a site, both rodent body mass and season affected total intensity of flea infestation, although the explanatory power of these factors was generally modest (<10%). Across host populations in the landscape, we found consistently positive effects of host density and negative effects of vegetation cover on the intensity of flea infestation. Other factors explored (host diversity, annual rainfall, anthropogenic disturbance, and soil properties) tended to have lower and less consistent explanatory power. Across host species in the landscape, we found that host body mass was strongly positively correlated with both prevalence and intensity of flea parasitism, while average robustness of a host species to disturbance was not correlated with flea parasitism. Cumulatively, these results provide insight into the intricate roles of both host and environmental factors in explaining complex patterns of flea parasitism across landscape mosaics.


Glucose indices are associated with cognitive and structural brain measures in young adults.
To evaluate the possible early consequences of impaired glucose metabolism on the brain by assessing the relationship of diabetes, fasting blood glucose (FBG) levels, and insulin resistance with cognitive performance and brain integrity in healthy young and middle-aged adults. The sample included dementia-free participants (mean age 40 ± 9 years; 53% women) of the Framingham Heart Study third-generation cohort with cognitive testing of memory, abstract reasoning, visual perception, attention, and executive function (n = 2,126). In addition, brain MRI examination (n = 1,597) was used to determine white matter, gray matter, and white matter hyperintensity (WMH) volumes and fractional anisotropy measures. We used linear regression models to assess relationships between diabetes, FBG, and insulin resistance with cognition, lobar gray matter, and WMH volumes as well as voxel-based microstructural white matter integrity and gray matter density, adjusting for potential confounders. Mediating effect of brain lesions on the association of diabetes with cognitive performance was also tested. Diabetes was associated with worse memory, visual perception, and attention performance; increased WMH; and decreased total cerebral brain and occipital lobar gray matter volumes. The link of diabetes with attention and memory was mediated through occipital and frontal atrophy, and the latter also through hippocampal atrophy. Both diabetes and increased FBG were associated with large areas of reductions in gray matter density and fractional anisotropy on voxel-based analyses. We found that hyperglycemia is associated with subtle brain injury and impaired attention and memory even in young adults, indicating that brain injury is an early manifestation of impaired glucose metabolism.


Effects of Protein Supplementation Combined with Exercise Intervention on Frailty Indices, Body Composition, and Physical Function in Frail Older Adults.
Aging poses a high risk of lean mass loss, which can be effectively improved through resistance exercise training (RET), or multicomponent exercise training (MET) as well as nutrition supplementation, such as protein supplementation (PS). This study investigated the effects of PS plus exercise training on frail older individuals. A comprehensive search of online databases was performed to identify randomized controlled trials (RCTs) that reported the efficacy of PS combined with RET or MET in frail older individuals. The included RCTs were analyzed through a meta-analysis and risk-of-bias assessment. We finally included 22 RCTs in the meta-analysis, with a mean (range/total) Physiotherapy Evidence Database score of 6.7 (4⁻9/10). PS plus exercise training significantly improved the frailty status (odds ratio = 2.77; p = 0.006), lean mass (standard mean difference (SMD) = 0.52; p < 0.00001), leg strength (SMD = 0.37; p < 0.00001), and walking speed (SMD = 0.32; p = 0.002). Subgroup analyses revealed that PS plus MET exert significant effects on frailty indices, whereas PS plus RET further improves lean mass. Our findings suggest that PS plus RET as well as MET is effective in improving frailty status, lean mass, muscle strength, and physical mobility in frail older individuals.


Dissociable contributions of ventromedial prefrontal and posterior parietal cortex to value-guided choice.
Two long-standing traditions have highlighted cortical decision mechanisms in the parietal and prefrontal cortices of primates, but it has not been clear how these processes differ, or when each cortical region may influence behaviour. Recent data from ventromedial prefrontal cortex (vmPFC) and posterior parietal cortex (PPC) have suggested one possible axis on which the two decision processes might be delineated. Fast decisions may be resolved primarily by parietal mechanisms, whereas decisions made without time pressure may rely on prefrontal mechanisms. Here, we report direct evidence for such dissociation. During decisions under time pressure, a value comparison process was evident in PPC, but not in vmPFC. Value-related activity was still found in vmPFC under time pressure. However, vmPFC represented overall input value rather than compared output value. In contrast, when decisions were made without time pressure, vmPFC transitioned to encode a value comparison while value-related parameters were entirely absent from PPC. Furthermore, under time pressure, decision performance was primarily governed by PPC, while it was dominated by vmPFC at longer decision times. These data demonstrate that parallel cortical mechanisms may resolve the same choices in differing circumstances, and offer an explanation of the diverse neural signals reported in vmPFC and PPC during value-guided choice.


[Corrigendum] Structure‑activity relationship of three synthesized benzimidazole‑based oligosaccharides in human platelet activation.
Following the publication of the above paper, the authors noted that the third author affiliation was presented incorrectly. The third author affiliation should have been written as 'Department of Pharmacology, School of Medicine, College of Medicine, and Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan'. Therefore, the author and affiliation details for this paper should have been presented as follows (the changes are highlighted in bold): YI CHANg1‑3*, WEN‑HsIEN HsU2,4*, WEN‑BIN YANg5, THANAsEKARAN JAYAKUMAR3, TZU‑YIN LEE3, JOEN‑RONg sHEU3, WAN‑JUNg LU3,6 and JIUN‑YI LI3,7. 1Department of Anesthesiology, Shin Kong Wu Ho‑Su Memorial Hospital, Taipei 111; 2School of Medicine, Fu‑Jen Catholic University, Xin Zhuang, New Taipei City 242; 3Department of Pharmacology, School of Medicine, College of Medicine, and Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110; 4Department of Surgery, Wan‑Fang Hospital, Taipei Medical University, Taipei 116; 5Genomics Research Center, Academia Sinica, Taipei 115; 6Department of Medical Research and Translational Laboratory, Research Department, Taipei Medical University Hospital, Taipei 110; 7Department of Cardiovascular Surgery, Mackay Memorial Hospital, and Mackay Medical College, Taipei 104, Taiwan, R.O.C.. The authors regret that the error with the third author affiliation was not noticed prior to the publication of their paper, and apologize for any inconvenience caused. [The original article was published in International Journal of Molecular Medicine 40: 1520‑1528, 2017; DOI: 10.3892/ijmm.2017.3133].


Evolution of dispersal distance.
The problem of how often to disperse in a randomly fluctuating environment has long been investigated, primarily using patch models with uniform dispersal. Here, we consider the problem of choice of seed size for plants in a stable environment when there is a trade off between survivability and dispersal range. Ezoe (J Theor Biol 190:287-293, 1998) and Levin and Muller-Landau (Evol Ecol Res 2:409-435, 2000) approached this problem using models that were essentially deterministic, and used calculus to find optimal dispersal parameters. Here we follow Hiebeler (Theor Pop Biol 66:205-218, 2004) and use a stochastic spatial model to study the competition of different dispersal strategies. Most work on such systems is done by simulation or nonrigorous methods such as pair approximation. Here, we use machinery developed by Cox et al. (Voter model perturbations and reaction diffusion equations 2011) to rigorously and explicitly compute evolutionarily stable strategies.


Humidity affects the extensibility of an orb-weaving spider's viscous thread droplets.
The prey-capture threads found in most spider orb webs rely on viscous droplets for their stickiness. Each droplet is formed of a central mass of viscoelastic glycoprotein glue surrounded by an aqueous covering, both of which incorporate hydrophilic components. We found that the extensibility of droplets on Larinioides cornutus threads increased as humidity increased. However, the deflection of the droplets' supporting axial lines did not change, indicating that atmospheric water uptake increases glycoprotein plasticity, but not glycoprotein adhesion. The extensibility of droplets, along with that of the thread's supporting axial fibers, is responsible for summing the adhesion of multiple thread droplets. Therefore, daily changes in humidity have the potential to significantly alter the performance of viscous threads and orb webs.


Baicalein, a Natural Anti-Cancer Compound, Alters MicroRNA Expression Profiles in Bel-7402 Human Hepatocellular Carcinoma Cells.
Baicalein has been shown to possess significant anti-hepatoma activity by inhibiting cell proliferation. Whether the anti-proliferative effect of baicalein is related to its modulation of miRNA expression in hepatocellular carcinoma (HCC) is still unknown. The anti-proliferative effects of baicalein on HCC cell line Bel-7402 was assessed by detecting the proliferation activity, cell cycle distribution, expression changes of p21/CDKN1A, P27/CDKN1B, total Akt and phosphoryted AKT. Microarray analysis was conducted to determine the miRNA expression profiles in baicalein-treated or untreated Bel-7402 cells and then validated by qRT-PCR in two HCC cell lines (Bel-7402 and Hep3B). The gain-of-function of miR-3127-5p was performed by detecting anti-proliferative effects after transfecting miRNA mimics in cells. Finally, the expression level of miR-3127-5p in different HCC cell lines was determined by qRT-PCR. Baicalein was able to inhibit the proliferation of Bel-7402 cells by inducing cell cycle arrest at the S and G2/M phase via up-regulating the expression of p21/CDKN1A and P27/CDKN1B and suppressing the PI3K/Akt pathway. Baicalein could alter the miRNA expression profiles in Bel-7402 cells. Putative target genes for differentially expressed miRNAs could be enriched in terms of cell proliferation regulation, cell cycle arrest and were mainly involved in MAPK, PI3K-Akt, Wnt, Hippo and mTOR signaling pathways. MiR- 3127-5p, one of up-regulated miRNAs, exhibits low expression level in several HCC cell lines and its overexpression could inhibit cell growth of Bel-7402 and Hep3B cell lines by inducing S phase arrest by up-regulating the expression of p21and P27 and repressing the PI3K/Akt pathway. Modulation of miRNA expression may be an important mechanism underlying the anti-hepatoma effects of baicalein.


Allometries and the morphogenesis of the molluscan shell: a quantitative and theoretical model.
This article explores the close relationships between growth rate and allometries of molluscan shells. After reviewing the previous theoretical approaches devoted to the understanding of shell form and its morphogenesis, we present a free-form vector model which can simulate apertural shape changes and nonlinear allometries. Shell morphology is generated by iteratively adding a growth increment onto the last computed aperture. The first growth increment defines so-called growth vectors which are assumed to be constant in direction (relative to the last computed aperture position) during a simulation of a shell (ontogeny). These growth vectors are uniformly scaled at each time step according to various growth rate curves that are used to simulate the mantle growth over time. From the model, we derive morphometric variables that illustrate the ontogenetic trajectories in time-size-shape space. We investigate the effects of changing the growth curves types, growth rate parameters and growth vector maps on the direction, speed and patterns of ontogenetic allometries. Because this model focuses the issue on time, it highlights a plausible effect of growth rate on shell shape and illustrates some fundamental geometrical properties of the logarithmic spiral, in particular the close relationship between the size and the geometry of growth increments. This model could be used to develop a mathematically data-driven approach where experimentally obtained growth curves could be used as inputs in the model. More generally, our study recalls the role of growth rates in the generation of allometries.


Neighboring cells override 3D hydrogel matrix cues to drive human MSC quiescence.
Physical properties of modifiable hydrogels can be tuned to direct stem cell differentiation in a role akin to that played by the extracellular matrix in native stem cell niches. However, stem cells do not respond to matrix cues in isolation, but rather integrate soluble and non-soluble signals to balance quiescence, self-renewal and differentiation. Here, we encapsulated single cell suspensions of human mesenchymal stem cells (hMSC) in hyaluronic acid-based hydrogels at high and low densities to unravel the contributions of matrix- and non-matrix-mediated cues in directing stem cell response. We show that in high-density (HD) cultures, hMSC do not rely on hydrogel cues to guide their fate. Instead, they take on characteristics of quiescent cells and secrete a glycoprotein-rich pericellular matrix (PCM) in response to signaling from neighboring cells. Preventing quiescence precluded the formation of a glycoprotein-rich PCM and forced HD cultures to differentiate in response to hydrogel composition. Our observations may have important implications for tissue engineering as neighboring cells may act counter to matrix cues provided by scaffolds. Moreover, as stem cells are most regenerative if activated from a quiescent state, our results suggest that ex vivo native-like niches that incorporate signaling from neighboring cells may enable the production of clinically relevant, highly regenerative cells.


[Mood congruent effects by music on word cognition].
Two studies investigated the mood congruent effects of music on word cognition. In both studies, bright or sad music was used in order to induce elated or depressed mood, and subjects were assigned to either the bright or the sad music condition. In Study 1, positive and negative personality trait words and non-words were presented with the music to examine the effect on incidental recall. Thirty-one subjects were asked to judge whether the words were positive or negative as quickly and accurately as possible. In Study 2, 37 subjects were presented with ambiguous personality trait words without and with music to examine how their interpretations of ambiguous stimuli were affected by music. The results showed the mood congruent effects on recall, interpretation, and response time, and these findings agreed with those obtained from other studies of the mood effects on cognition, especially on recall. It was suggested that music induces a certain mood, which influences on cognitive processes of other stimuli.


Effect of smoking status on total energy expenditure.
Individuals who smoke generally have a lower body mass index (BMI) than nonsmokers. The relative roles of energy expenditure and energy intake in maintaining the lower BMI, however, remain controversial. We tested the hypothesis that current smokers have higher total energy expenditure than never smokers in 308 adults aged 40-69 years old of which 47 were current smokers. Energy expenditure was measured by doubly labeled water during a two week period in which the subjects lived at home and performed their normal activities. Smoking status was determined by questionnaire. There were no significant differences in mean BMI (mean ± SD) between smokers and never smokers for either males (27.8+5.1 kg/m2 vs. 27.5+4.0 kg/m2) or females (26.5+5.3 kg/m2 vs. 28.1+6.6 kg/m2), although the difference in females was of similar magnitude to previous reports. Similarly, total energy expenditure of male smokers (3069+764 kcal/d) was not significantly different from that of never smokers (2854+468 kcal/d), and that of female smokers (2266+387 kcal/d) was not different from that of never smokers (2330+415 kcal/d). These findings did not change after adjustment for age, fat-free mass and self-reported physical activity. Using doubly labeled water, we found no evidence of increased energy expenditure among smokers, however, it should be noted that BMI differences in this cohort also did not differ by smoking status.


Macroinvertebrate community responses to hydrological controls and groundwater abstraction effects across intermittent and perennial headwater streams.
Intermittent rivers comprise a significant proportion of river networks globally and their spatial extent is predicted to increase with rising water abstraction pressures. Despite this, the ecological implications of hydrological modifications within intermittent rivers have received limited research attention. This paper examines macroinvertebrate assemblages across intermittent and perennial sections of headwater streams within the Hampshire Avon catchment (United Kingdom) over a five-year period. The composition of faunal assemblages was quantified in relation to four hydrological metrics: the duration of flowing conditions, the geographical proximity to the nearest perennial source along each watercourse (two observed flow parameters) and two modelled groundwater abstraction influences. The results highlight that macroinvertebrate communities inhabiting sites which dry periodically and are positioned at greater distances (>c. 2.5km) above the perennial source (the most upstream point of permanent flow within a given year) possessed the highest conservation values. These sites supported species that are rare in many areas of Europe (e.g. Ephemeroptera: Paraletophlebia werneri) or with limited geographical distribution across the United Kingdom (e.g. Trichoptera: Limnephilus bipunctatus). A range of faunal community diversity indices were found to be more sensitive to the antecedent flow duration and distance from the perennial source, rather than any effects of groundwater abstraction. Taxonomic richness responded most strongly to these observed flow parameters and varied more markedly with the distance from the perennial source compared to the antecedent flow duration. Several taxa were significantly associated with the observed flow parameters, particularly those predominantly inhabiting perennially flowing systems. However, the distance that such fauna could migrate into intermittent reaches varied between taxa. This research demonstrates the overriding importance of antecedent flow durations and the geographical proximity to perennial sources on macroinvertebrate communities within intermittent and perennial headwater streams.


Proteome Profiling Outperforms Transcriptome Profiling for Coexpression Based Gene Function Prediction.
Coexpression of mRNAs under multiple conditions is commonly used to infer cofunctionality of their gene products despite well-known limitations of this "guilt-by-association" (GBA) approach. Recent advancements in mass spectrometry-based proteomic technologies have enabled global expression profiling at the protein level; however, whether proteome profiling data can outperform transcriptome profiling data for coexpression based gene function prediction has not been systematically investigated. Here, we address this question by constructing and analyzing mRNA and protein coexpression networks for three cancer types with matched mRNA and protein profiling data from The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC). Our analyses revealed a marked difference in wiring between the mRNA and protein coexpression networks. Whereas protein coexpression was driven primarily by functional similarity between coexpressed genes, mRNA coexpression was driven by both cofunction and chromosomal colocalization of the genes. Functionally coherent mRNA modules were more likely to have their edges preserved in corresponding protein networks than functionally incoherent mRNA modules. Proteomic data strengthened the link between gene expression and function for at least 75% of Gene Ontology (GO) biological processes and 90% of KEGG pathways. A web application Gene2Net (http://cptac.gene2net.org) developed based on the three protein coexpression networks revealed novel gene-function relationships, such as linking ERBB2 (HER2) to lipid biosynthetic process in breast cancer, identifying PLG as a new gene involved in complement activation, and identifying AEBP1 as a new epithelial-mesenchymal transition (EMT) marker. Our results demonstrate that proteome profiling outperforms transcriptome profiling for coexpression based gene function prediction. Proteomics should be integrated if not preferred in gene function and human disease studies.


DEPRES II (Depression Research in European Society II): a patient survey of the symptoms, disability and current management of depression in the community. DEPRES Steering Committee.
The first pan-European survey of depression in the community (DEPRES I) demonstrated that 17% of the general population suffer from depression (major depression, minor depression, or depressive symptoms). This article describes findings from a second phase of DEPRES (DEPRES II), in which detailed interviews based on a semi-structured questionnaire (78 questions) were conducted with 1884 DEPRES I participants who had suffered from depression and who consulted a healthcare professional about their symptoms during the previous 6 months. The mean time from onset of depression was 45 months, and the most commonly experienced symptoms during the latest period were low mood (76%), tiredness (73%) and sleep problems (63%). During the previous 6 months, respondents had been unable to undertake normal activities because of their depression for a mean of 30 days, and a mean of 20 days of work had been lost to depression by those in paid employment. Approximately one-third of respondents (30%) had received an antidepressant during the latest period of depression. Significantly more respondents given a selective serotonin reputake inhibitor found that their treatment made them feel more like their normal self than those given a tricyclic antidepressant, and fewer reported treatment-related concentration lapses, weight problems, and heavy-headedness (all P < 0.05). Approximately two-thirds of respondents (70%) had received no antidepressant therapy during the latest period of depression, and prescription of benzodiazepines alone, which are not effective against depression, was widespread (17%). There is a need for education of healthcare professionals to encourage appropriate treatment of depression.


Energetic requirement of insulin secretion distal to calcium influx.
A number of agents that inhibit oxidative phosphorylation by different mechanisms (carbonyl cyanide mchlorophenylhydrazone [CCCP], sodium azide, oligomycin) induced an increase of cytoplasmic Ca2+ concentration ([Ca2+]i) in pancreatic beta-cells, as measured by microfluorimetry with digital imaging. All three agents are known inhibitors of insulin secretion, and the secretory response to 20 mmol/l glucose was found to be abolished in spite of elevated [Ca2+]i. Two reasons could account for this dissociation between increase of [Ca2+]i and insulin secretion: 1) the increase did not take place at a site critical for exocytosis, 2) a threshold concentration of a metabolism-derived factor like ATP exists for the induction of exocytosis. The increase of [Ca2+]i by CCCP and sodium azide involved release of Ca2+ from internal stores, whereas oligomycin induced a slow D 600-inhibitable Ca2+ influx. Because CCCP and sodium azide, but not oligomycin, decreased the mitochondrial membrane potential concomitantly with the increase of [Ca2+]i, release of Ca2+ from the mitochondria most probably plays a decisive role for the internal mobilization. A Ca2+ influx induced by 40 mmol/l K+ or 250 micromol/l tolbutamide was unimpaired in the presence of oligomycin, but oligomycin completely abolished insulin secretion in response to these agents. While CCCP and sodium azide opened ATP-sensitive K+ channels, oligomycin was virtually ineffective, although it could be shown to significantly reduce beta-cell ATP production. By comparison of the effects of different inhibitors of oxidative phosphorylation, we conclude that the initiation of exocytosis in beta-cells is particularly sensitive to a decrease of energy metabolism, more than ATP-sensitive K+ channels or voltage-dependent Ca2+ channels. Thus, any increase of [Ca2+]i in beta-cells that occurs in a situation of a decreased ATP supply is unlikely to elicit a secretory response.


Acute high-level toluene exposure decreases hippocampal neurogenesis in rats.
Toluene is an organic solvent that is used in various industrial applications. Despite its usefulness, toluene has toxic effects on the brain and is a substance that is commonly abused. Toluene causes behavioral and functional abnormalities such as decreased memory capacity, cognitive impairment, and depression-like symptoms. However, the target sites and toxic mechanisms of inhaled toluene in the brain are poorly understood. In this study, we subjected Sprague-Dawley (SD) rats to acute high-level toluene exposure (7000 ppm) to investigate its neuronal toxicity, and in particular, its effect on neurogenesis in the hippocampus. In order to assay the effects of inhaled toluene on hippocampal neurogenesis, we measured the levels of neurogenesis markers Ki-67 and doublecortin (DCX) in the hippocampus 1, 2, 5, and 8 days after cessation of toluene exposure. In addition to assaying clinical signs, body weight, and bronchoalveolar lavage fluid, the liver, lungs, and kidneys were subjected to histopathological examination to investigate the toxic effects of high-level toluene exposure. Although abnormal neurological signs were observed after toluene exposure, these disappeared within 24 h and no toluene-related toxicological effects were observed in the liver, lungs, or kidneys. The animals exposed to toluene showed significantly decreased hippocampal neurogenesis, which persisted until the 8th and final day of measurement. Thus, acute high-level toluene exposure inhibited hippocampal neurogenesis and produced transient abnormal neurological signs, but did not produce toxicity in the other organs studied.


Diffusion tensor imaging and voxel based morphometry study in early progressive supranuclear palsy.
A comprehensive characterisation of grey and white matter changes in progressive supranuclear palsy (PSP), the second most common extrapyramidal syndrome after Parkinson disease, is still not available. To evaluate grey and white matter changes in mild PSP patients by voxel based morphometry (VBM) and diffusion tensor imaging (DTI), respectively. 14 mild PSP patients and 14 healthy controls entered the study and underwent a clinical and neuropsychological evaluation according with a standardised assessment. Each subject had a structural magnetic resonance imaging (MRI) study. Processing analysis of MRI data was carried out according to optimised VBM and fractional anisotropy was determined. Compared with the controls, in PSP patients VBM analysis showed a significant clusters of reduced grey matter in premotor cortex, frontal operculum, anterior insula, hippocampus, and parahippocampal gyrus, bilaterally. With regard to subcortical brain regions, the pulvinar, dorsomedial and anterior nuclei of the thalamus, and superior and inferior culliculum were affected bilaterally. A bilateral decrease in fractional anisotropy in superior longitudinal fasciculus, anterior part of corpus callosum, arcuate fascicolus, posterior thalamic radiations, and internal capsule, probably involving the cortico-bulbar tracts, was present in PSP patients. These data provide evidence for both grey and white matter degeneration in PSP from the early disease stage. These structural changes suggest that atrophy of cortical and subcortical structures and neurodegeneration of specific fibre tracts contribute to neurological deficits in PSP.


Reproductive health in humanitarian settings in Lebanon and Iraq: results from four cross-sectional studies, 2014-2015.
Reproductive health is an important component of humanitarian response. Displaced women need access to family planning, antenatal care, and the presence of a skilled birth attendant at delivery. Since the beginning of the Syrian conflict in 2011, Lebanon and Iraq have been hosting large numbers of refugees, thereby straining local capacities to provide these services. In order to identify salient health needs, Médecins Sans Frontières conducted a survey in several sites hosting refugees and internally displaced persons across the region. Here we describe the reproductive health profile of Syrian refugees, Iraqi displaced persons, and vulnerable Lebanese and their use of services. We conducted four cross-sectional surveys in 2014-2015 in two sites in Lebanon and two sites in Iraq. Depending on the site, two-stage cluster sampling or systematic sampling was intended, but non-probability methods were employed at the second stage due to implementation challenges. We collected information on overall health (including reproductive health) and demographic information from heads of households on the basis of a standardized questionnaire. Pearson chi-square tests were used to compare proportions, and generalized linear models were used to calculate odds ratios with regard to risk factors. All analyses were performed using the survey suite of commands in Stata version 14.1. A total of 23,604 individuals were surveyed, including 5925 women of childbearing age. Overall, it was reported that 7.5% of women were currently pregnant and 12.8% had given birth within the previous 12 months. It was reported that pregnancy was unplanned for 57% of currently pregnant women and 66.7% of women who had delivered in the previous year. A slight majority of women from both groups had accessed antenatal care at least once. Amongst women who had delivered in the previous year, 84.5% had done so with a skilled birth attendant and 22.1% had had a cesarean section. Location and head of household education were predictors of unplanned pregnancy in multivariable analysis. Head of household education was also significantly associated with higher uptake of antenatal care. Considering the large number of pregnant women and women having recently delivered in these settings, addressing their sexual and reproductive health needs emerges as a crucial aspect of humanitarian response. This study identified unmet needs for family planning and high cesarean section rates at all sites, suggesting both lack of access to certain services (contraception, antenatal care), but also over-recourse to cesarean section. These specific challenges can impact directly on maternal and child health and need today to be kept high on the humanitarian agenda.


Regional bond strength to lateral walls in class I and II ceramic inlays luted with four resin cements and glass-ionomer luting agent.
To investigate regional shear bond strength to lateral walls of ceramic inlays in occlusal and occlusoproximal cavities using etch-and-rinse and self-adhesive resin cements and a glass-ionomer luting agent. IPS e.max Press ceramic inlays were made in 50 Class I and 50 Class II standardized cavities in intact extracted human molars and divided into 5 luting agent subgroups (n = 10): Variolink II (VL); Multilink Sprint (MLS); Multilink Automix (MLA); RelyX Unicem (RLX), and Ketac Cem Aplicap (KC). Inlays were pre-etched with IPS Ceramic etching gel for 60s. After 48 h, two disks of ca 1.0 mm thickness, one of superficial and the other of deep dentin, were push-out tested in a universal testing machine at a crosshead speed of 1.0 mm/min. The mode of failure was determined under a stereomicroscope at 20X. Data were analyzed with one way ANOVA, and Scheffé's test was used for post-hoc comparisons (α = 0.05). There were no significant differences in shear bond strength between Class I and Class II cavities for the dual-curing system in light-curing mode (VL=MLS=RLX), except that RLX demonstrated greater bond strength to deep dentin in Class II cavities. Bond strength values were significantly higher on deep than on superficial dentin. KC showed the worst result. Failures were mixed (adhesive/cohesive) for the resin luting cements and solely adhesive (cement/ceramic) for the glass-ionomer luting agent. Dual-curing etch-and-rinse or self-etching self-adhesive resin luting cements achieved greater bond strength when light curing was applied, with no differences between Class I and Class II cavities but higher values for deep vs superficial dentin. The weakest adhesion was obtained with glass-ionomer luting agent in both cavity types.


Analysis of goalkeepers' game performances at the 2016 European Football Championships.
Despite a substantial body of literature on the physical and technical demands of outfield players in football, there is little information regarding the performance of goalkeepers. The aim of this study was to analyse the game performance profiles of goalkeepers at the 2016 European Football Championships. A total of 30 goalkeepers from 15 games played during the 2016 European Football Championships were analysed using the InStat® video tracking system. The results showed that goalkeepers covered a mean total distance of 4819 m, ranging from 4036 m to 6640 m. Overall, 68% of distance travelled was attributed to walking, whereas 0.8% was due to high-intensity activities. The goalkeepers of teams that lost matches covered significantly (p < 0.05) longer distances while sprinting than those of teams that drew or won the matches. Goalkeepers of teams that drew significantly (p < 0.05) had a greater number of passes than those goalkeepers of teams that won or lost. The current results have implications for soccer coaches to structure training sessions and tactical strategies for goalkeepers. The ability of goalkeepers to meet the physical and technical demands of a match could directly influence the successful execution of skills and the outcome of the competition.


Dosimetric evaluation of nuclear interaction models in the Geant4 Monte Carlo simulation toolkit for carbon-ion radiotherapy.
We tested the ability of two separate nuclear reaction models, the binary cascade and JQMD (Jaeri version of Quantum Molecular Dynamics), to predict the dose distribution in carbon-ion radiotherapy. This was done by use of a realistic simulation of the experimental irradiation of a water target. Comparison with measurement shows that the binary cascade model does a good job reproducing the spread-out Bragg peak in depth-dose distributions in water irradiated with a 290 MeV/u (per nucleon) beam. However, it significantly overestimates the peak dose for a 400 MeV/u beam. JQMD underestimates the overall dose because of a tendency to break a nucleus into lower-Z fragments than does the binary cascade model. As far as shape of the dose distribution is concerned, JQMD shows fairly good agreement with measurement for both beam energies of 290 and 400 MeV/u, which favors JQMD over the binary cascade model for the calculation of the relative dose distribution in treatment planning.


Bottom-up Electrosynthesis of Highly Active Tungsten Sulfide (WS3-x) Films for Hydrogen Evolution.
Transition metal dichalcogenides have been extensively studied as promising earth-abundant electrocatalysts for hydrogen evolution reaction (HER). However, despite the intention to achieve sustainable energy generation, conventional syntheses typically use environmentally damaging reagents and energy-demanding preparation conditions. Hence, we present electrochemical synthesis as a green and versatile alternative to traditional methods. In this fundamental study, we demonstrated the bottom-up synthesis of a mixed WS2/WS3 film-like material via cyclic voltammetry (CV). The film-like material can be directly electrosynthesized on any conductive substrates and renders the catalyst immobilization step redundant. Through stepwise analysis of deposition voltammograms facilitated by straightforward modification of CV conditions, and characterization using X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS), a two-step mechanism involving the initial WS3 deposition and subsequent partial reduction to WS2 was proposed. The WS2/WS3 material was determined to possess composition of WS2.64. Compared to non-electrosynthesized WSx materials, its predominantly basal orientation limited the heterogeneous electron transfer rate toward surface-sensitive redox couples. However, WS2.64 demonstrated excellent HER activity, with the lowest Tafel slope of 43.7 mV dec(-1) to date; this was attributed to different metal-chalcogen binding strengths within WS2.64. Fundamental understanding of the electrosynthesis process is crucial for green syntheses of inexpensive and highly electrocatalytically active materials for sustainable energy production. Albeit, the process may be different for a myriad of nanomaterials, this study can be exploited for its analyses from which the conclusions were made, to empower electrochemical synthesis as the prime fabrication approach for HER electrocatalyst development.


Conservation through different lenses: reflection, responsibility, and the politics of participation in conservation advocacy.
This essay considers the arenas of advocacy, politics, and self-reflection in strengthening conservation and resource management initiatives. It frames key questions that reflective conservation practitioners may address in seeking to enhance the results of conservation projects, including equity and more inclusive participation by nonprivileged groups. The essay touches on the importance of understanding conservation work within particular political and historic dynamics, including the need to understand non-Western and/or indigenous or traditional perspectives on conservation. The author makes the case that Western or privileged conservation practitioners are uniquely situated to advocate effectively for change.


[Nutritional status, metabolic syndrome and insulin resistance in children from Santiago (Chile)].
The origin of most non-communicable diseases (NCDs) is in early life. Consequently obtaining information on risk factors for NCDs is important for preventive purposes. However, there is no information available on the prevalence of obesity, metabolic syndrome (MS) and insulin resistance (IR) in Chilean children. To determine the prevalence of nutritional status, MS and IR, and secondly, to study the associations among them. Cross-sectional study conducted during 2009-2011 in 20 public schools of Puente Alto County, Santiago, Chile. Anthropometry, blood pressure and pubertal status were assessed. A blood sample was obtained for determination of lipids, blood glucose and insulin. Abnormal Homeostasis model assessment index (HOMA-IR) was based on a national standard. 3325 children had a mean age of 11.4 ± 1 years old (range 10-15 years). The prevalence of obesity, MS and IR was 16.1%, 7.3% and 25.9%, respectively. The prevalence of IR and MS was higher in obese children. MS and IR were strongly associated with an OR of 8.0 (95% CI= 5.9-10.7). Multivariate analysis showed that all MS components were associated to IR. There is a relatively high prevalence of risk factors in this sample of children. The strong positive association between nutritional status, IR and MS points out the need to early identify risk factors for NCDs allowing for prevention.