PTH transiently increases the percent mobile fraction of Npt2a in OK cells as determined by FRAP.
Renal sodium-dependent phosphate transporter 2a (Npt2a) binds to a number of PDZ adaptor proteins including sodium-hydrogen exchanger regulatory factor-1 (NHERF-1), which regulates its retention in the apical membrane of renal proximal tubule cells and the response to parathyroid hormone (PTH). The present experiments were designed to study the lateral mobility of enhanced green fluorescent protein (EGFP)-Npt2a in proximal tubule-like opossum kidney (OK) cells using fluorescence recovery after photobleaching (FRAP) and to determine the role of PDZ binding proteins in mediating the effects of PTH. The mobile fraction of wild-type Npt2a (EGFP-Npt2a-TRL) under basal conditions was approximately 17%. Treatment of the cells with Bis(sulfosuccinimidyl) suberate, a water-soluble cross-linker, abolished recovery nearly completely, indicating that recovery represented lateral diffusion in the plasma membrane and not the exocytosis or synthesis of unbleached transporter. Substitution of the C-terminal amino acid PDZ binding sequence TRL with AAA (EGFP-Npt2a-AAA) resulted in a nearly twofold increase in percent mobile fraction of Npt2a. Treatment of cells with PTH resulted in a rapid increase in the percent mobile fraction to >30% followed by a time-dependent decrease to baseline or below. PTH had no effect on the mobility of EGFP-Npt2a-AAA expressed in native OK cells or on wild-type EGFP-Npt2a-TRL expressed in OK-H cells deficient in NHERF-1. These findings indicate that the association of Npt2a with PDZ binding proteins limits the lateral mobility of the transporter in the apical membrane of renal proximal tubule cells. Treatment with PTH, presumably by dissociating NHERF-1/Npt2a complexes, transiently increases the mobility of Npt2a, suggesting that freeing of Npt2a from the cytoskeleton precedes PTH-mediated endocytosis.


Detection of Quiescent Radioresistant Epithelial Progenitors in the Adult Thymus.
Thymic aging precedes that of other organs and is initiated by the gradual loss of thymic epithelial cells (TECs). Based on in vitro culture and transplantation assays, recent studies have reported on the presence of thymic epithelial progenitor cells (TEPCs) in young adult mice. However, the physiological role and properties of TEPC populations reported to date remain unclear. Using an in vivo label-retention assay, we previously identified a population of quiescent but non-senescent TECs. The goals of this study were therefore (i) to evaluate the contribution of these quiescent TECs to thymic regeneration following irradiation-induced acute thymic injury and (ii) to characterize their phenotypic and molecular profiles using flow cytometry, immunohistology, and transcriptome sequencing. We report that while UEA1+ cells cycle the most in steady state, they are greatly affected by irradiation, leading to cell loss and proliferative arrest following acute thymic involution. On the opposite, the UEA1- subset of quiescent TECs is radioresistant and proliferate in situ following acute thymic involution, thereby contributing to thymic regeneration in 28- to 30-week-old mice. UEA1- quiescent TECs display an undifferentiated phenotype (co-expression of K8 and K5 cytokeratins) and express high levels of genes that regulate stem cell activity in different tissues (e.g., Podxl and Ptprz1). In addition, two features suggest that UEA1- quiescent TECs occupy discrete stromal niches: (i) their preferential location in clusters adjacent to the cortico-medullary junction and (ii) their high expression of genes involved in cross talk with mesenchymal cells. The ability of UEA1- quiescent TECs to participate to TEC regeneration qualifies them as in vivo progenitor cells particularly relevant in the context of regeneration following acute thymic injury.


Morphological, Morphometric, and Molecular Characterization of Intraspecific Variations within Indian Populations of Meloidogyne graminicola.
Fourteen populations of Meloidogyne graminicola were collected from different agroecological regions of India. Morphological and morphometrical comparisons were made for various nematode life stages. Three populations (Hisar, New Delhi, and Samastipur) were different from typical M. graminicola on the basis of the length of eggs; J2 length, a-value, hyaline tail portion; male length, distance up to excretory pore, spicule and gubernaculum lengths; female length and width, stylet length, distance up to excretory pore, EPST (distance of excretory pore from anterior end / stylet length [females]) ratio, and vulval length. Morphological and morphometrical comparison with closely related species M. graminis, M. oryzae, M. salasi, M. triticoryzae, and M. lini clustered these populations into two groups: Anand, Bhubaneswar, Hyderabad, Jammu, Jorhat, Kalyani, Kanpur, Ludhiana, Mandya, Palampur, Vellayani grouped with M. graminicola, M. triticoryzae and M. salasi; whereas, Hisar, New Delhi, Samastipur grouped with M. oryzae and M. graminis. Molecular phylogenetic analysis using internal transcribed spacer (ITS) suggested that in spite of morphological differences, these populations belonged to M. graminicola.


Maternal and neonatal individual risks and benefits associated with caesarean delivery: multicentre prospective study.
To assess the risks and benefits associated with caesarean delivery compared with vaginal delivery. Prospective cohort study within the 2005 WHO global survey on maternal and perinatal health. 410 health facilities in 24 areas in eight randomly selected Latin American countries; 123 were randomly selected and 120 participated and provided data 106,546 deliveries reported during the three month study period, with data available for 97,095 (91% coverage). Maternal, fetal, and neonatal morbidity and mortality associated with intrapartum or elective caesarean delivery, adjusted for clinical, demographic, pregnancy, and institutional characteristics. Women undergoing caesarean delivery had an increased risk of severe maternal morbidity compared with women undergoing vaginal delivery (odds ratio 2.0 (95% confidence interval 1.6 to 2.5) for intrapartum caesarean and 2.3 (1.7 to 3.1) for elective caesarean). The risk of antibiotic treatment after delivery for women having either type of caesarean was five times that of women having vaginal deliveries. With cephalic presentation, there was a trend towards a reduced odds ratio for fetal death with elective caesarean, after adjustment for possible confounding variables and gestational age (0.7, 0.4 to 1.0). With breech presentation, caesarean delivery had a large protective effect for fetal death. With cephalic presentation, however, independent of possible confounding variables and gestational age, intrapartum and elective caesarean increased the risk for a stay of seven or more days in neonatal intensive care (2.1 (1.8 to 2.6) and 1.9 (1.6 to 2.3), respectively) and the risk of neonatal mortality up to hospital discharge (1.7 (1.3 to 2.2) and 1.9 (1.5 to 2.6), respectively), which remained higher even after exclusion of all caesarean deliveries for fetal distress. Such increased risk was not seen for breech presentation. Lack of labour was a risk factor for a stay of seven or more days in neonatal intensive care and neonatal mortality up to hospital discharge for babies delivered by elective caesarean delivery, but rupturing of membranes may be protective. Caesarean delivery independently reduces overall risk in breech presentations and risk of intrapartum fetal death in cephalic presentations but increases the risk of severe maternal and neonatal morbidity and mortality in cephalic presentations.


Postpancreatitis Diabetes Confers Higher Risk for Pancreatic Cancer Than Type 2 Diabetes: Results From a Nationwide Cancer Registry.
Pancreatitis and diabetes are established risk factors for pancreatic cancer. However, to date, studies have investigated only the risk associated with either of them alone. The aim of this study was to investigate the effect of pancreatitis and diabetes combined, as well as their temporal relationship, on the risk of pancreatic cancer. Nationwide cancer registry was linked to hospital discharge and mortality data from 1998 to 2015 in New Zealand. Incidence of primary pancreatic cancer in the four study groups (type 2 diabetes [T2D] alone, pancreatitis alone, T2D followed by pancreatitis, and postpancreatitis diabetes mellitus [PPDM]) was identified. Multivariable Cox regression analyses were conducted, with T2D as the reference group. A head-to-head comparison between the T2D followed by pancreatitis and PPDM groups was also performed. Among 139,843 individuals (735,541 person-years), 913 (0.7%) were diagnosed with pancreatic cancer. The proportion of pancreatic cancer was 3.1%, 2.3%, 2.0%, and 0.6% in individuals with PPDM, T2D followed by pancreatitis, pancreatitis alone, and T2D alone, respectively. PPDM (hazard ratio [HR] 6.94; 95% CI 4.09-11.77) and T2D followed by pancreatitis (HR 5.35; 95% CI 3.52-8.14) were associated with significantly higher risks of pancreatic cancer compared with T2D alone. In the head-to-head comparison, PPDM was associated with a higher risk of pancreatic cancer compared with T2D followed by pancreatitis (HR 2.35; 95% CI 1.12-4.93). Pancreatitis significantly increases the risk of pancreatic cancer in individuals with diabetes. In particular, PPDM poses the highest risk for pancreatic cancer.


"Let's get moving: let's get praising:" promoting health and hope in an African American church.
Stroke and cardiovascular disease are major health problems for African Americans. This article describes challenges, strategies employed, and successes in implementing a combination "faith-based" and "faith-placed" health promotion program called the BLESS Project in a small rural church in North Carolina. The project was implemented by a congregational nurse who teaches nursing at a nearby HBCU and students with a grant from a local agency and partnerships with local health-care agencies. Despite numerous challenges in implementing the project, it was successful in increasing awareness of stroke and heart disease and the need for improving diet and increasing physical activity. Research is needed to test the efficacy of combining faith-based and faith-placed activities in preventing cardiovascular disease in African Americans.


CDCP1 drives triple-negative breast cancer metastasis through reduction of lipid-droplet abundance and stimulation of fatty acid oxidation.
Triple-negative breast cancer (TNBC) is notoriously aggressive with high metastatic potential, which has recently been linked to high rates of fatty acid oxidation (FAO). Here we report the mechanism of lipid metabolism dysregulation in TNBC through the prometastatic protein, CUB-domain containing protein 1 (CDCP1). We show that a "low-lipid" phenotype is characteristic of breast cancer cells compared with normal breast epithelial cells and negatively correlates with invasiveness in 3D culture. Using coherent anti-Stokes Raman scattering and two-photon excited fluorescence microscopy, we show that CDCP1 depletes lipids from cytoplasmic lipid droplets (LDs) through reduced acyl-CoA production and increased lipid utilization in the mitochondria through FAO, fueling oxidative phosphorylation. These findings are supported by CDCP1's interaction with and inhibition of acyl CoA-synthetase ligase (ACSL) activity. Importantly, CDCP1 knockdown increases LD abundance and reduces TNBC 2D migration in vitro, which can be partially rescued by the ACSL inhibitor, Triacsin C. Furthermore, CDCP1 knockdown reduced 3D invasion, which can be rescued by ACSL3 co-knockdown. In vivo, inhibiting CDCP1 activity with an engineered blocking fragment (extracellular portion of cleaved CDCP1) lead to increased LD abundance in primary tumors, decreased metastasis, and increased ACSL activity in two animal models of TNBC. Finally, TNBC lung metastases have lower LD abundance than their corresponding primary tumors, indicating that LD abundance in primary tumor might serve as a prognostic marker for metastatic potential. Our studies have important implications for the development of TNBC therapeutics to specifically block CDCP1-driven FAO and oxidative phosphorylation, which contribute to TNBC migration and metastasis.


Mass spectrometry insights into a tandem ubiquitin-binding domain hybrid engineered for the selective recognition of unanchored polyubiquitin.
Unanchored polyubiquitin chains are emerging as important regulators of cellular physiology with diverse roles paralleling those of substrate-conjugated polyubiquitin. However tools able to discriminate unanchored polyubiquitin chains of different isopeptide linkages have not been reported. We describe the design of a linker-optimized ubiquitin-binding domain hybrid (t-UBD) containing two UBDs, a ZnF-UBP domain in tandem with a linkage-selective UBA domain, which exploits avidity effects to afford selective recognition of unanchored Lys48-linked polyubiquitin chains. Utilizing native MS to quantitatively probe binding affinities we confirm cooperative binding of the UBDs within the synthetic protein, and desired binding specificity for Lys48-linked ubiquitin dimers. Furthermore, MS/MS analyses indicate that the t-UBD, when applied as an affinity enrichment reagent, can be used to favor the purification of endogenous unanchored Lys48-linked polyubiquitin chains from mammalian cell extracts. Our study indicates that strategies for the rational design and engineering of polyubiquitin chain-selective binding in nonbiological polymers are possible, paving the way for the generation of reagents to probe unanchored polyubiquitin chains of different linkages and more broadly the 'ubiquitome'. All MS data have been deposited in the ProteomeXchange with identifier PXD004059 (http://proteomecentral.proteomexchange.org/dataset/PXD004059).


Competition for glutathione precursors between the immune system and the skeletal muscle: pathogenesis of chronic fatigue syndrome.
The chronic fatigue syndrome (CFS) is typically associated or follows a recognized or presumed infection. Abnormalities of both humoral and cellular immunity have been demonstrated in a substantial proportion of patients with CFS. The most consistent findings are of impaired lymphocyte responses to mitogen. As an antioxidant, glutathione (GSH) is essential for allowing the lymphocyte to express its full potential without being hampered by oxiradical accumulation. Hence, protracted challenge of the immunocytes may lead to cellular GSH depletion. Because GSH is also essential to aerobic muscular contraction, an undesirable competition for GSH precursors between the immune and muscular systems may develop. It is conceivable that the priority of the immune system for the survival of the host has drawn to this vital area the ever-diminishing GSH precursors, thus depriving the skeletal muscle of adequate GSH precursors to sustain a normal aerobic metabolism resulting in fatigue and eventually myalgia.


Ocean acidification disrupts the innate ability of fish to detect predator olfactory cues.
While ocean acidification is predicted to threaten marine biodiversity, the processes that directly impact species persistence are not well understood. For marine species, early life history stages are inherently vulnerable to predators and an innate ability to detect predators can be critical for survival. However, whether or not acidification inhibits predator detection is unknown. Here, we show that newly hatched larvae of the marine fish Amphiprion percula innately detect predators using olfactory cues and this ability is retained through to settlement. Aquarium-reared larvae, not previously exposed to predators, were able to distinguish between the olfactory cues of predatory and non-predatory species. However, when eggs and larvae were exposed to seawater simulating ocean acidification (pH 7.8 and 1000 p.p.m. CO2) settlement-stage larvae became strongly attracted to the smell of predators and the ability to discriminate between predators and non-predators was lost. Newly hatched larvae were unaffected by CO2 exposure and were still able to distinguish between predatory and non-predatory fish. If this impairment of olfactory preferences in settlement-stage larvae translates to higher mortality as a result of increased predation risk, there could be direct consequences for the replenishment and the sustainability of marine populations.


"Superficial infiltration to treat white hypomineralized defects of enamel: clinical trial with 12-month follow-up.
Hypomineralization represents one of the most common defects in tooth crowns. Thanks to a wide understanding of aesthetics, patients request a treatment to resolve these defects. Different techniques are available, such as crowns/veneers, traditional restorative treatments, microabrasion, whitening, remineralizing agents and infiltration technique. The objective of this trial is to assess the effectiveness of superficial infiltration with Icon (DMG, Hamburg, Germany) on the attenuation of crown hypomineralized lesions of various etiological origins with a 12-month follow-up. Seventeen patients with white defects of enamel in the aesthetic sector were selected. The infiltration procedure was carried out following the manufacturer's instructions. Intraoral photographs were taken before and directly after treatment in order to document the immediate change in colour. Check-ups were performed 1 and 12 months later. All the defects which were treated showed a degree of attenuation. The teeth affected by molar incisor hypomineralization (MIH) showed partial attenuation in 8 cases, and only in one case the defect disappeared. Regarding the post-trauma cases, 6 were partially attenuated and 2 disappeared. The post orthodontic defects disappeared in 6 cases and were attenuated in 5. All incipient caries defects were completely hidden. Four out of 6 cases of fluorosis disappeared. Diagnosis plays a key role in guiding the dental clinical selection of treatment. While it has always been possible to achieve a high level of attenuation in cases of fluorosis and lesions of caries origin, cases of MIH should probably be treated using more invasive techniques. Post-trauma lesions should be infiltrated with caution, and only after having informed the patient of the possible ineffective outcome.


The role of lipid geometry in designing liposomes for the solubilisation of poorly water soluble drugs.
Liposomes are well recognised for their ability to improve the delivery of a range of drugs. More commonly they are applied for the delivery of water-soluble drugs, but given their structural attributes, they can also be employed as solubilising agents for low solubility drugs as well as drug targeting agents. To further explore the potential of liposomes as solubilising agents, we have investigated the role of bilayer packaging in promoting drug solubilisation in liposome bilayers. The effect of alkyl chain length and symmetry was investigated to consider if using 'mis-matched' phospholipids could create 'voids' within the bilayers, and enhance bilayer loading capacity. Lipid packing was investigated using Langmuir studies, which demonstrated that increasing the alkyl chain length enhanced lipid packing, with condensed monolayers forming, whilst asymmetric lipids formed less condensed monolayers. However, this more open packing did not translate into improved drug loading, with the longer chain, condensed bilayers formed from long-chain, saturated lipids offering higher drug loading capacity. These studies demonstrate that liposomes formulated from longer chain, saturated lipids offer enhanced solubilisation capacity. However the molecular size, rather than lipophilicity, of the drug to be incorporated was also a key factor dominating bilayer incorporation efficiency.


Rapamycin Impairs Antitumor CD8+ T-cell Responses and Vaccine-Induced Tumor Eradication.
The metabolic sensor mTOR broadly regulates cell growth and division in cancer cells, leading to a significant focus on studies of rapamycin and its analogues as candidate anticancer drugs. However, mTOR inhibitors have failed to produce useful clinical efficacy, potentially because mTOR is also critical in T cells implicated in immunosurveillance. Indeed, recent studies using rapamycin have demonstrated the important role of mTOR in differentiation and induction of the CD8+ memory in T-cell responses associated with antitumor properties. In this study, we demonstrate that rapamycin harms antitumor immune responses mediated by T cells in the setting of cancer vaccine therapy. Specifically, we analyzed how rapamycin affects the antitumor efficacy of a human papilloma virus E7 peptide vaccine (CyaA-E7) capable of eradicating tumors in the TC-1 mouse model of cervical cancer. In animals vaccinated with CyaA-E7, rapamycin administration completely abolished recruitment of CD8+ T cells into TC-1 tumors along with the ability of the vaccine to reduce infiltration of T regulatory cells and myeloid-derived suppressor cells. Moreover, rapamycin completely abolished vaccine-induced cytotoxic T-cell responses and therapeutic activity. Taken together, our results demonstrate the powerful effects of mTOR inhibition in abolishing T-cell-mediated antitumor immune responses essential for the therapeutic efficacy of cancer vaccines.


Analysis of SOX9 expression in colorectal cancer.
Our purpose was to investigate the role of SOX9, a novel downstream molecule of beta-catenin, in colorectal cancer. Expression of SOX9 and beta-catenin was detected by immunostaining, quantitative real-time reverse transcription-polymerase chain reaction (Q-PCR), and Western blot in colorectal cancer. The correlation between SOX9 or beta-catenin expression and clinicopathologic parameters was also analyzed. Immunostaining, Q-PCR, and Western blot consistently confirmed SOX9 up-regulation in colorectal cancer compared with normal mucosa (P < .05). Immunostaining showed more SOX9+ cells in the lower zone of colonic crypts than in the upper zone (P < .05). Cancers with strong SOX9 immunostaining were significantly associated with a lower 5-year overall survival (40% [17/43] vs low expression, 69% [66/95]; P < .01). The Cox proportional hazards model showed that strong SOX9 expression was an independent adverse prognosticator in colorectal cancer (P < .05). The detection of SOX9 expression might contribute to predicting clinical outcomes for patients with colorectal cancer.


Magnetoelectric inversion of domain patterns.
The inversion of inhomogeneous physical states has great technological importance; for example, active noise reduction relies on the emission of an inverted sound wave that interferes destructively with the noise of the emitter1, and inverting the evolution of a spin system by using a magnetic-field pulse enables magnetic resonance tomography2. In contrast to these examples, inversion of a distribution of ferromagnetic or ferroelectric domains within a material is surprisingly difficult: field poling creates a single-domain state, and piece-by-piece inversion using a scanning tip is impractical. Here we report inversion of entire ferromagnetic and ferroelectric domain patterns in the magnetoelectric material Co3TeO6 and the multiferroic material Mn2GeO4, respectively. In these materials, an applied magnetic field reverses the magnetization or polarization, respectively, of each domain, but leaves the domain pattern intact. Landau theory indicates that this type of magnetoelectric inversion is universal across materials that exhibit complex ordering, with one order parameter holding the memory of the domain structure and another setting its overall sign. Domain-pattern inversion is only one example of a previously unnoticed effect in systems such as multiferroics, in which several order parameters are available for combination. Exploring these effects could therefore advance multiferroics towards new levels of functionality.


Season matters when sampling streams for swine CAFO waste pollution impacts.
Concentrated (or confined) animal feed operations (CAFOs) are the principal means of livestock production in the United States, and such facilities pollute nearby waterways because of their waste management practices; CAFO waste is pumped from the confinement structure into a cesspit and sprayed on a field. Stocking Head Creek is located in eastern North Carolina, a state with >9,000,000 head of swine confined in CAFOs. This watershed contains 40 swine CAFOs; stream water quality was investigated at seven sites during 2016, with five sampling dates in early spring and five in summer. Geometric mean fecal coliform counts were in the thousands/100 mL at five sites in spring and all seven sites in summer. Excessive nitrate pollution was widespread with concentrations up to >11.0 mg N/L. Seasonality played an important role in pollutant concentrations. In North Carolina, spraying animal waste on adjoining fields is permissible from March 1 through September 30. Seasonal data showed significantly higher (p < 0.01) concentrations of conductivity, nitrate, total nitrogen, total organic carbon, and fecal bacteria in summer as opposed to early spring. Thus, sampling performed only in winter-early spring would significantly underestimate impacts from swine CAFO spray fields on nearby waterways.


Population studies of native grass-endophyte symbioses provide clues for the roles of host jumps and hybridization in driving their evolution.
Fungal endophytes in the genera Epichloë and Neotyphodium, collectively termed the epichloae, have fascinated biologists for decades. These intriguing fungi, also referred to as 'class 1 or clavicipitaceous endophytes', spend the large majority, or even their entire life cycle, within the tissues of their cool-season grass hosts without eliciting any symptoms of infection. While all epichloae reside within the intercellular spaces of aboveground vegetative grass tissues, the species at the symbiotic extreme are known as Neotyphodium, and the intimacy of their interaction extends to the reproductive (flowering) stage. At this point, fungal filaments (hyphae) nondestructively invade the developing ovaries of their host and are incorporated into perfectly viable, healthy seeds. Thus, these endophytes live solely within the tissues of their host plants and are transmitted maternally from generation to generation. A second life history characteristic of interest is that while all Epichloë and some Neotyphodium species are haploid, a great many of the strictly seed-transmitted Neotyphodium spp. are interspecific hybrids. This phenomenon may be critical for the success of these symbioses over longer spans of evolutionary time and will be discussed in greater detail below. A third characteristic, and one of the primary reasons these grass endophytes have received so much attention over the last three decades, is the strong mutualistic nature these relationships often exhibit. In exchange for photosynthetically derived carbon, the endophytes protect their cool-season grass hosts from grazing herbivores and a variety of abiotic stresses. It has been hypothesized that these three biological phenomena are related (Schardl & Craven 2003), perhaps with the former two driving the third, and it is here that the recent article in Molecular Ecology entitled 'Genetic diversity in epichloid endophytes of Hordelymus europaeus suggests repeated host jumps and interspecific hybridizations', by Oberhofer & Leuchtmann (2012), provides critical clues to linking these traits together. While the large majority of studies have focused on documenting the ever-increasing list of mutualistic qualities attributed to these fungi, very few have taken an exhaustive population-level approach to document plant and endophyte genotypes within a naturally occurring system (Faeth et al. 2010; Jani et al. 2010; Tintjer & Rudgers 2006). Such information is crucial to more fully elucidate the factors shaping grass-endophyte symbioses and those often driving these relationships to mutualistic extremes.


Radiation-induced meningioma: a distinct molecular genetic pattern?
Radiation-induced meningiomas arise after low-dose irradiation treatment of certain medical conditions and are recognized as clinically separate from sporadic meningioma. These tumors are often aggressive or malignant, they are likely to be multiple, and they have a high recurrence rate following treatment compared with sporadic meningiomas. To understand the molecular mechanism by which radiation-induced meningioma (RIM) arise, we compared genetic changes in 7 RIM and 8 sporadic meningioma (SM) samples. The presence of mutations in the 17 exons of the neurofibromatosis type 2 (NF2) gene, which has been shown to be inactivated in sporadic meningiomas, was analyzed in RIM and SM using single-strand conformation polymorphism (SSCP) and DNA sequencing. In contrast to SM, which showed NF2 mutations in 50% of specimens, no mutations were found in RIM. In addition, Western blot analysis of schwannomin/merlin protein, the NF2 gene product, demonstrated protein levels comparable to normal brain in 4/4 RIM tumor samples analyzed. Loss of heterozygosity (LOH) of genomic regions, which were reported for SM, was also analyzed in all cases of RIM using 22 polymorphic DNA markers. Allele losses were found on chromosomes 1p (4/7), 9p (2/7), 19q (2/7), 22q (2/7), and 18q (1/7). From these observations we conclude that unlike sporadic meningiomas, NF2 gene inactivation and chromosome 22q deletions are far less frequent in RIM, and their role in meningioma development following low dose irradiation is less significant. Other chromosomal lesions, especially loss of 1p, possibly induced by irradiation, may be more important in the development of these tumors.


Habitual coffee intake reduces all-cause mortality by decreasing heart rate.
It is well known that subjects with metabolic syndrome show an elevated resting heart rate. We previously reported that elevated heart rate was significantly related to all-cause mortality, and that coffee consumption was inversely associated with metabolic syndrome. We hypothesized that higher coffee consumption may decrease all-cause mortality by reducing resting heart rate. We performed a longitudinal epidemiological study in Tanushimaru (a cohort of the Seven Countries Study). A total of 1920 residents aged over 40 years received health checkups in 1999. We measured components of metabolic syndrome, and eating and drinking patterns were evaluated by a food frequency questionnaire. We followed up the participants annually for 15 years. During the follow-up period, 343 of the participants died. Of these, 102 subjects died of cancer, 48 of cerebro-cardiovascular diseases, and 44 of infectious diseases. Multivariate analyses revealed that higher coffee consumption was inversely associated with resting heart rate. Kaplan-Meier curves found lower mortality rates in the higher coffee consumption groups. In the lower coffee consumption groups, elevated hazard ratios of all-cause death were observed in the increased heart rate quintiles, whereas heart rate was not associated with all-cause death in the higher coffee consumption groups. These significant associations remained after further adjustment for confounders. This prospective study suggests that higher coffee consumption may have a protective effect against all-cause death due to reducing resting heart rate.


Evaluating the ecological impacts of salvage logging: can natural and anthropogenic disturbances promote coexistence?
Salvage logging following windthrow is common throughout forests worldwide even though the practice is often considered inimical to forest recovery. Because salvaging removes trees, crushes seedlings, and compacts soils, many warn this practice may delay succession, suppress diversity, and alter composition. Here, over 8 yr following windthrow, we experimentally evaluate how salvaging affects tree succession across 11 gaps in Eastern deciduous forests of Pennsylvania, wherein each gap was divided into salvaged and control (unsalvaged) halves. Our gaps vary in size and windthrow severity, and we explicitly account for this variation as well as variation in soil disturbance (i.e., scarification) resulting from salvaging so that our results would be generalizable. Salvage logging had modest and ephemeral impacts on tree succession. Seedling richness and density declined similarly over time in both salvaged and unsalvaged areas as individuals grew into saplings. The primary impact of salvaging on succession occurred where salvaging scarified soils. Here, salvaging caused 41 to 82% declines in sapling abundance, richness, and diversity, but these differences largely disappeared within 5 yr. Additionally, we documented interactions between windthrow severity and scarification. Specifically, low-severity windthrow and scarification combined reinforced dominance by shade-tolerant and browse-tolerant species (Acer pensylvanicum, Fagus grandifolia). In contrast, high windthrow severity and scarification together reduced the density of a fast-growing pioneer tree (Prunus pensylvanica) and non-tree vegetation cover by 75% and 26%, respectively. This reduction enhanced the recruitment of two mid-successional tree species, Acer rubrum and Prunus serotina, by 2 and 3-fold, respectively. Thus, our findings demonstrate that salvaging creates novel microsites and mitigates competing vegetation, thereby enhancing establishment of important hardwoods and promoting tree species coexistence. Our results, coupled with an assessment of 27 published post-windthrow salvage studies, suggest short-term studies may overestimate the impact of salvaging on regeneration. We conclude that the ecological costs and benefits of salvaging depend upon the variation in canopy and soil disturbance severity as well as the timescale at which effects are evaluated. Thus, our findings are inconsistent with the view that salvaging inexorably undermines plant diversity; rather we suggest salvaging can promote tree species coexistence within various contexts.


Few eligible for the newly recommended short course MDR-TB regimen at a large Mumbai private clinic.
India has the world's highest tuberculosis burden, and Mumbai is particularly affected by multidrug resistant tuberculosis (MDR-TB). WHO recommends short, intensive treatment ("Short Course") for previously untreated pulmonary MDR-TB patients but does not require universal drug susceptibility testing (DST) before Short Course. DST would likely screen out many MDR-TB patients in places like Mumbai with significant drug resistance. MDR-TB patients at a private clinic were recruited for a prospective observational cohort. Short Course eligibility was evaluated by clinical criteria and DST results. Eligibility by DST was classified as rifampin monoresistance (as tested by Xpert MTB/RIF), rifampin, fluoroquinolones, and 2nd-line injectable drugs resistance (as tested by line probe assays) and resistance to other drugs. Of 559 participants with MDR-TB, 33% met clinical eligibility for Short Course. DST for rifampin, fluoroquinolones, and 2nd-line injectable drugs excluded 74.7% of participants. Complete phenotypic DST excluded 96.6% of participants. Prior treatment with either 1st or 2nd-line drugs did not significantly affect eligibility. In a global MDR-TB hotspot, < 5% of participants with MDR-TB were appropriate for Short Course by clinical characteristics and DST results. Rapid molecular testing would not sufficiently identify drug resistance in this population. Eligibility rates were not significantly reduced by prior TB treatment.


"How do you try to have anyone comply or at least be pliable with you if that person's not even medicated?": Perspectives on the use of psychiatric medication within recovery-oriented practice.
Objective: Medication is particularly important to advocates within the mental health recovery movement and this movement is founded upon a resistance to coercive treatment. Given this history, we explored the perspectives of providers and service users engaged in the recovery-oriented practice Person-Centered Care Planning (PCCP) to understand (a). How providers trained in PCCP understand the role of psychiatric medication and (b). How service users receiving services from providers trained in PCCP understand and experience the role of psychiatric medication in treatment. Method: This study comprises data from the qualitative phase of an NIMH-funded randomized trial of PCCP, an evidence-based recovery-oriented practice. Data were collected from 22 focus groups of providers and service users across seven community mental health centers. Interviews were analyzed using thematic analysis. Results: Qualitative themes from the provider focus groups included "promoting adherence" and "medication as a precondition." Providers expressed that service users need to be adherent to medication and their symptoms managed before recovery-oriented practices could be pursued. Service user themes included "we were cattle" and medication as "my saving grace." While many experienced medication as helpful, they found providers' focus on adherence to be inflexible and, at times, coercive. Conclusion and Implications for Practice: These results suggest that even within agencies actively implementing recovery-oriented practices, there are aspects of treatment, namely medication management, that are more impervious to recovery principles. Agency level trainings in PCCP and other recovery-oriented practices would benefit from the inclusion of all staff, including psychiatrists and other prescribers. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


General solvothermal approach to synthesize telluride nanotubes for thermoelectric applications.
One-dimensional tellurides are good candidates for thermoelectric applications, but the fabrication of telluride nanotubes is still challenging. To this end, the solvothermal approach is proposed to synthesize Bi2Te3, PbTe, CuxTe and Ag2Te nanotubes. In this scheme, single-crystal Te nanotubes are produced first and then used as the sacrificed template for epitaxial growth of metal telluride. It was demonstrated that polycrystalline telluride nanotubes are produced. Considering Bi2Te3 nanotubes as an example, the pellets are prepared by spark plasma sintering, and the thermoelectric properties are measured. Compared to the nanowire counterpart, the higher-energy barrier to electrons at the grain boundaries (GBs) leads to an optimized power factor of 1.04 mW m-1 K-2 at 373 K in the nanotube samples. Furthermore, the thermal conductivity of nanotubes is in the range of 0.503-0.617 W m-1 K-1, which is much smaller than that of the nanowires. The ultralow thermal conductivity could be attributed to both the higher potential barrier of GBs and the additional scattering of phonons at the side walls of the nanotubes. In all, a ZT value of 0.74 was obtained at 373 K, which is much higher than that of nanowires. This synthesis route is ready to be extended to other telluride nanotubes.


Phyllodes tumor of the breast: stromal overgrowth and histological classification are useful prognosis-predictive factors for local recurrence in patients with a positive surgical margin.
The local recurrence rate of phyllodes tumors is high and ensuring a sufficient surgical margin is considered important for local control. However, the preoperative diagnosis rate of phyllodes tumors is low and we often encounter cases in which a sufficient surgical margin is not achieved, since in routine medical practice the lesion may not be diagnosed as phyllodes tumor until postoperative biopsy of a mammary mass. Furthermore, there are no established therapeutic guidelines for surgical stump-positive phyllodes tumors. We reviewed the outcomes of excision of phyllodes tumors to investigate factors involved in local recurrence and to determine the indication for re-excision in stump-positive cases. The subjects were 45 patients treated for phyllodes tumors at our institution from January 1980 to July 2005. Age, tumor size, surgical method, stromal cellular atypia, mitotic activity, stromal overgrowth, histological classification and surgical stump status were analyzed. Median age was 45 years old (range 28-75) and tumor size was 1-17 cm (median 3.5 cm). Pathologic diagnoses were benign, borderline and malignant in 31, five and nine cases, respectively, and the surgical stump was negative in 27 lesions and positive in 15. Median follow-up was 101 months (range 1-273), with local recurrence in six cases and distant metastasis in one. The local recurrence-free rate was 88, 88 and 84% and the disease-free rate was 85, 85 and 81% after 5, 10 and 15 years, respectively. Overall 10-year survival was 97%. In univariate analysis, a positive surgical margin, stromal overgrowth and histological classification were predictive factors for local recurrence after breast-conservation surgery (P = 0.0034, 0.0003, 0.026). A positive surgical stump was the only independent predictor of local recurrence in multivariate analysis (RR 0.086; 95% CI 0.01-0.743, P = 0.012). Stromal overgrowth was a predictive factor for local recurrence in cases with a positive surgical margin (P = 0.0139). Wide excision is the preferred therapy for phyllodes tumor and preoperative diagnosis is important for good local control. Re-excision is recommended in cases with a positive surgical margin and stromal overgrowth and malignancy.


Crystal structure of a Trypanosoma brucei metacaspase.
Metacaspases are distantly related caspase-family cysteine peptidases implicated in programmed cell death in plants and lower eukaryotes. They differ significantly from caspases because they are calcium-activated, arginine-specific peptidases that do not require processing or dimerization for activity. To elucidate the basis of these differences and to determine the impact they might have on the control of cell death pathways in lower eukaryotes, the previously undescribed crystal structure of a metacaspase, an inactive mutant of metacaspase 2 (MCA2) from Trypanosoma brucei, has been determined to a resolution of 1.4 Å. The structure comprises a core caspase fold, but with an unusual eight-stranded β-sheet that stabilizes the protein as a monomer. Essential aspartic acid residues, in the predicted S1 binding pocket, delineate the arginine-specific substrate specificity. In addition, MCA2 possesses an unusual N terminus, which encircles the protein and traverses the catalytic dyad, with Y31 acting as a gatekeeper residue. The calcium-binding site is defined by samarium coordinated by four aspartic acid residues, whereas calcium binding itself induces an allosteric conformational change that could stabilize the active site in a fashion analogous to subunit processing in caspases. Collectively, these data give insights into the mechanistic basis of substrate specificity and mode of activation of MCA2 and provide a detailed framework for understanding the role of metacaspases in cell death pathways of lower eukaryotes.


Isoproterenol-Dependent Activation of TRPM7 Protects Against Neurotoxin-Induced Loss of Neuroblastoma Cells.
Neuronal function and their survival depend on the activation of ion channels. Loss of ion channel function is known to induce neurodegenerative diseases such as Parkinson's that exhibit loss of dopaminergic neurons; however, mechanisms that could limit neuronal loss are not yet fully identified. Our data suggest that neurotoxin-mediated loss of neuroblastoma SH-SY5Y cells is inhibited by the addition of β-adrenergic receptor (β-AR) agonist isoproterenol. The addition of isoproterenol to SHSY-5Y cells showed increased Mg2+ influx and cell survival in the presence of neurotoxin especially at higher concentration of isoproterenol. Importantly, isoproterenol potentiated transient receptor potential melastatin-7 (TRPM7) channel activation that leads to an increase in intracellular Mg2+ levels. The addition of 2APB, which is a known TRPM7 channel blocker, significantly decreased the TRPM7 function and inhibited isoproterenol-mediated protection against neurotoxins. Moreover, neurotoxins inhibited TRPM7 expression and function, but the restoration of TRPM7 expression increased neuroblastoma cell survival. In contrast, TRPM7 silencing increased cell loss, decreased Mg2+ homeostasis, and inhibited mitochondrial function. Moreover, isoproterenol treatment prevented neurotoxin-mediated loss of TRPM7 expression and inhibited Bax expression that induces cell survival. These effects were dependent on the neurotoxin-induced increase in oxidative stress, which inhibits TRPM7 expression and function. Together, our results suggest a positive role for β-AR in activating TRPM7 channels that regulate Mg2+ homeostasis and are essential for the survival of SH-SY5Y cells from neurotoxin.


First-derivative spectroscopic determination of acetaminophen and sodium salicylate in tablets.
A first-derivative spectroscopic method for the simultaneous determination of acetaminophen and sodium salicylate in tablets was developed. Solutions of this drug combination in acidic ethanol were analyzed using their respective spectral responses at 258.5 and 317.0 nm. The method, which can be used for tablet composite assay and content uniformity analysis, is linear for acetaminophen concentrations ranging from 0.0 to 21.6 micrograms/mL, and for sodium salicylate concentrations ranging from 0.0 to 36.0 micrograms/mL. Relative standard deviations for the assay of both drugs in commercial tablets were less than 2%, and recoveries of acetaminophen and sodium salicylate from spiked samples were 99.7 and 100.1%, respectively. The results obtained by first-derivative spectroscopy were in agreement with the results of a liquid chromatographic procedure for acetaminophen and a fluorometric method for sodium salicylate. The technique used for the selection of wavelengths for analysis is also described.


Characterization of novel LMW-GS genes at Glu-D3 locus on chromosome 1D in Aegilops tauschii.
The objectives of this study were to clarify the relationship between LMW-GS Glu-D3 gene of Ae. tauschii registered in GenBank and the six Glu-D3 genes including 12 allelic variants of common wheat characterized in our previous studies, and identify novel Glu-D3 genes and haplotypes from Ae. tauschii using gene specific PCR amplification. By searching the NCBI database, 13 LMW-GS genes/pseudogenes of Ae. tauschii were retrieved and classified into five gene families based on their nucleotide similarity with the six Glu-D3 genes of common wheat. Of them, four Ae. tauschii genes, AY585350, AY585354, AY585355 and AY585356 matched GluD3-4, GluD3-5, GluD3-1 and GluD3-2 of common wheat, respectively, and one pseudogene AY585351 matched to GluD3-6, but none of them matched to GluD3-3. In order to identify the Glu-D3 genes from Ae. tauschii corresponding to GluD3-3 and GluD3-6 of common wheat, gene specific primers were developed to amplify 8-18 Ae. tauschii entries. As a result, two novel Glu-D3 genes, designated as GluDt3-3 and GluDt3-6, were identified. GluDt3-3 showed seven allelic variants or haplotypes at the DNA level in eight Ae. tauschii entries, designated as GluDt3-31, GluDt3-32, GluDt3-33, GluDt3-34, GluDt3-35, GluDt3-36 and GluDt3-37, respectively. Two to eight SNPs were found among the seven haplotypes and 1-4 amino acid substitutions among the deduced peptides. Multiple sequence alignments showed that the DNA similarity was 99.6-99.9% among the seven GluDt3-3 haplotypes, and 99.4-99.7% between these haplotypes and those of common wheat GluD3-3 gene. GluDt3-6 presented seven haplotypes in 18 Ae. tauschii entries, designated as GluDt3-61, GluDt3-62, GluDt3-63, GluDt3-64, GluDt3-65, GluDt3-66 and GluDt3-67, respectively. GluDt3-61 from Ae. tauschii entry Ae38 was the only one haplotype with complete coding sequence, and the other six were all pseudogenes. Compared with GluD3-6 gene of common wheat, GluDt3-61 exhibited a 3-bp insertion, a 42-bp deletion and 11 base substitutions, leading to a glutamine insertion in position 52, 14 amino acid deletion in position 84-97 and 10 amino acid mutations in its deduced peptide; GluDt3-62 and GluDt3-63 showed a 6-bp insertion, a 24-bp deletion and 15-21 base substitutions in coding region, of which a nonsense mutation from C to T at position 622 resulted in pseudogenes; GluDt3-64 had five base substitution, including a nonsense mutation at the position 742. GluDt3-65, GluDt3-66 and GluDt3-67 all had a base deletion at position 247, as well as 7-8 base substitutions, which resulted in frameshift mutations in the three haplotypes. The results indicated that Ae. tauschii also contains six Glu-D3 genes and their allelic variants are even richer than those in common wheat.


Multimodal micro, nano, and size conversion ultrasound agents for imaging and therapy.
Ultrasound (US) is one of the most commonly used clinical imaging techniques. However, the use of US and US-based intravenous agents extends far beyond imaging. In particular, there has been a surge in the fabrication of multimodality US contrast agents and theranostic US agents for cancer imaging and therapy. The unique interaction of US waves with microscale and nanoscale agents has attracted much attention in the development of contrast agents and drug-delivery vehicles. The dimensions of the agent not only dictate how it behaves in vivo, but also how it interacts with US for imaging and drug delivery. Furthermore, these agents are also unique due to their ability to convert from the nanoscale to the microscale and vice versa, having imaging and therapeutic utility in both dimensions. Here, we review multimodality and multifunctional US-based agents, according to their size, and also highlight recent developments in size conversion US agents. WIREs Nanomed Nanobiotechnol 2016, 8:796-813. doi: 10.1002/wnan.1398 For further resources related to this article, please visit the WIREs website.


Health needs assessment.
THIS PAPER TAKES A PUBLIC HEALTH APPROACH TO BRIEFLY EXAMINE: (i) the concept of community health care need assessment; (ii) the roles of academic institutions in health needs assessment; (iii) Jazan study to address the health care needs in Jazan region, Saudi Arabia. The methods included an analysis of the literature, distillation of experience from the recently Jazan Health Need Assessment Survey, and WHO reports. The most important perceived health problems in Jazan region are shortage of health care providers, increased prevalence of communicable diseases and poor environmental health. The academic institutions, Ministry of Health and other health care institutions need to work together to look for innovative approaches, especially to increase the awareness of the society on public health issues, and give more support to increase national and regional funding for community based studies.The findings of the assessment of the health needs of Jazan presented in this review could be utilized as a baseline and reference information for policy formulation, subsequent planning and cost effective intervention programs. It could also be utilized for the curriculum development or review for a community oriented medical schools.


The critical role of respiratory sinus arrhythmia on temporal cardiac dynamics.
Temporal cardiac properties provide alternative information in analyzing heart rate variability (HRV), which may be disregarded by the standard HRV analyses. Patients with congestive heart failure (CHF) are known to have distinct temporal features from the healthy individuals. However, the underlying mechanism leading to the variation remains unclear. Whether or not these parameters can finely classify the severity for CHF patients is uncertain as well. In this work, an electrocardiogram was monitored in advanced CHF patients using 24-h Holter in four conditions, including baseline, one and three months after atenolol therapy, and healthy individuals. Slope and area under the curve (AUC) of multiscale entropy (MSE) curve over short (scales 1-5) and long (scales 6-20) scales, and detrended fluctuation analysis (DFA) scaling exponents at short (4-11 beats) and intermediate (>11 beats) window sizes were calculated. The results show that short-time scale MSE-derived parameters (slope: -0.08 ± 0.10, -0.03 ± 0.10, 0.02 ± 0.06, 0.08 ± 0.06; AUC: 4.03 ± 2.11, 4.69 ± 1.28, 4.73 ± 0.94, and 6.17 ± 1.23) and short-time scale DFA exponent (0.79 ± 0.16, 0.95 ± 0.22, 1.11 ± 0.19, and 1.35 ± 0.20) can hierarchically classify all four conditions. More importantly, simulated R-R intervals with different fractions and amplitude of respiratory sinus arrhythmia (RSA) components were examined to validate our hypothesis regarding the essentiality of RSA in the improvement of cardiovascular function, and its tight association with unpredictability and fractal property of HRV, which is in line with our hypothesis that RSA contributes significantly to the generation of the unpredictability and fractal behavior of HR dynamics.NEW & NOTEWORTHY Temporal cardiac properties provide useful diagnostic parameters for patients with congestive heart failure (CHF). Our study hierarchically classified CHF patients with β-blocker treatment by using multiscale entropy and detrended fluctuation analysis. Also, we provided the evidence to validate the critical role of respiratory sinus arrhythmia in the fractal properties of heart rate variability.


A bloodspot-based diagnostic test for fibromyalgia syndrome and related disorders.
The aim of this study was to investigate the ability of a rapid biomarker-based method for diagnosis of fibromyalgia syndrome (FM) using mid-infrared microspectroscopy (IRMS) to differentiate patients with FM from those with osteoarthritis (OA) and rheumatoid arthritis (RA), and to identify molecular species associated with the spectral patterns. Under IRB approval, blood samples were collected from patients diagnosed with FM (n = 14), RA (n = 15), or OA (n = 12). Samples were prepared, placed onto a highly reflective slide, and spectra were collected using IRMS. Spectra were analyzed using multivariate statistical modeling to differentiate groups. Aliquots of samples also were subjected to metabolomic analysis. IRMS separated subjects into classes based on spectral information with no misclassifications among FM and RA or OA patients. Interclass distances of 15.4 (FM vs. RA), 14.7 (FM vs. OA) and 2.5 (RA vs. OA) among subjects, demonstrating the ability of IRMS to achieve reliable resolution of unique spectral patterns specific to FM. Metabolomic analysis revealed that RA and OA groups were metabolically similar, whereas biochemical differences were identified in the FM that were quite distinctive from those found in the other two groups. Both IRMS and metabolomic analysis identified changes in tryptophan catabolism pathway that differentiated patients with FM from those with RA or OA.


Clinical severity in forecasting platelet to lymphocyte ratio in Crimean-Congo hemorrhagic fever patients.
Crimean-Congo hemorrhagic fever (CCHF) is a life-threatening disease that develops as a result of infection by a member of the Nairovirus genus of the Bunyaviridae family, and its initial symptoms are not specific. In patients with severe clinical progression, in particular, the neutrophil rate is high, whereas lymphocyte and monocyte levels are low. A total of 149 patients, in whom the diagnosis was confirmed with reverse transcriptase PCR, were included in the study. In order to compare patient clinical progression severity, we divided the patients into two groups. For group 1, Çevik's severity score was used. The patients who had a platelet/lymphocyte ratio (PLR) <41 constituted group 2. Of 149 patients, 20 (13.4 %) were determined as group 1 (Çevik's classification) and 38 (25.5 %) were determined as group 2 (PLR <41). Of 11 deaths, 4 (36.4 %) patients were from group 1 and 7 (63.6 %) were from group 2. This is the first study to our knowledge to analyse the relationship between severity and PLR in patients with CCHF. PLR is a simple laboratory test that can aid in determining the prognosis of individuals with this disease.


Fertility is a key predictor of the double burden of malnutrition among women of child-bearing age in sub-Saharan Africa.
The ongoing nutrition transition in sub-Saharan Africa (SSA) is exhibiting spatial heterogeneity and temporal variability leading to different forms of malnutrition burden across SSA, with some regions exhibiting the double burden of malnutrition. This study aimed to develop a predictive understanding of the malnutrition burden among women of child-bearing age. Data from 34 SSA countries were acquired from the Demographic and Health Survey, World Bank, and Swiss Federal Institute of Technology. The SSA countries were classified into malnutrition classes based on their national prevalence of underweight, overweight, and obesity using a 10% threshold. Next, random forest analysis was used to examine the association between country-level demographic variables and the national prevalence of underweight, overweight and obesity. Finally, random forest analysis and multinomial logistic regression models were utilized to investigate the association between individual-level social and demographic variables and Body Mass Index (BMI) categories of underweight, normal weight, and combined overweight and obesity. Four malnutrition classes were identified: Class A had 5 countries with ≥10% of the women underweight; Class B had 11 countries with ≥10% each of underweight and overweight; Class C1 had 7 countries with ≥10% overweight; and Class C2 had 11 countries with ≥10% obesity. At the country-level, fertility rate predicted underweight, overweight and obesity prevalence, but economic indicators were also important, including the gross domestic product per capita - a measure of economic opportunity that predicted both overweight and obesity prevalence, and the GINI coefficient - a measure of economic inequality that predicted both underweight and overweight prevalence. At the individual-level, parity was a risk factor for underweight in underweight burdened countries and a risk factor for overweight/obesity in overweight/obesity burdened countries, whereas age and wealth were protective factors for underweight but risk factors for overweight/obesity. Beyond the effect of economic indicators, this study revealed the important role of fertility rate and parity, which may represent risk factors for both underweight and combined overweight and obesity among women of child-bearing age. Health professionals should consider combining reproductive health services with nutritional programs when addressing the challenge of malnutrition in SSA.


Use of the counter selectable marker PheS* for genome engineering in Staphylococcus aureus.
The gold standard method for the creation of gene deletions in Staphylococcus aureus is homologous recombination using allelic exchange plasmids with a temperature-sensitive origin of replication. A knockout vector that contains regions of homology is first integrated into the chromosome of S. aureus by a single crossover event selected for at high temperatures (non-permissive for plasmid replication) and antibiotic selection. Next, the second crossover event is encouraged by growth without antibiotic selection at low temperature, leading at a certain frequency to the excision of the plasmid and the deletion of the gene of interest. To detect or encourage plasmid loss, either a beta-galactosidase screening method or, more typically, a counterselection step is used. We present here the adaptation of the counter-selectable marker pheS*, coding for a mutated subunit of the phenylalanine tRNA synthetase, for use in S. aureus. The PheS* protein variant allows for the incorporation of the toxic phenylalanine amino acid analogue para-chlorophenylalanine (PCPA) into proteins and the addition of 20-40 mM PCPA to rich media leads to drastic growth reduction for S. aureus and supplementing chemically defined medium with 2.5-5 mM PCPA leads to complete growth inhibition. Using the new allelic exchange plasmid pIMAY*, we delete the magnesium transporter gene mgtE in S. aureus USA300 LAC* (SAUSA300_0910/SAUSA300_RS04895) and RN4220 (SAOUHSC_00945) and demonstrate that cobalt toxicity in S. aureus is mainly mediated by the presence of MgtE. This new plasmid will aid the efficient and easy creation of gene knockouts in S. aureus.


Six 'biases' against patients and carers in evidence-based medicine.
Evidence-based medicine (EBM) is maturing from its early focus on epidemiology to embrace a wider range of disciplines and methodologies. At the heart of EBM is the patient, whose informed choices have long been recognised as paramount. However, good evidence-based care is more than choices. We discuss six potential 'biases' in EBM that may inadvertently devalue the patient and carer agenda: limited patient input to research design, low status given to experience in the hierarchy of evidence, a tendency to conflate patient-centred consulting with use of decision tools; insufficient attention to power imbalances that suppress the patient's voice, over-emphasis on the clinical consultation, and focus on people who seek and obtain care (rather than the hidden denominator of those that do not seek or cannot access care). To reduce these 'biases', EBM should embrace patient involvement in research, make more systematic use of individual ('personally significant') evidence, take a more interdisciplinary and humanistic view of consultations, address unequal power dynamics in healthcare encounters, support patient communities, and address the inverse care law.


A Randomized, Double-blind, Placebo-controlled Clinical Study to Investigate the efficacy of Herring Roe Oil for treatment of Psoriasis.
The effect of omega-3 polyunsaturated fatty acid supplements in patients with psoriasis vulgaris has previously been investigated, but interventions varied in source, composition, dose, administration route and duration of treatment. The observed beneficial effects in patients with psoriasis vulgaris using herring roe oil as a dietary supplement prompted this investigation. This randomised, double-blind and placebo-controlled study was designed and performed to explore the efficacy and safety of herring roe oil supplementation in 64 patients with plaque psoriasis (ClinicalTrials.gov: NCT03359577). The primary end-point was comparing the change in mean Psoriasis Area Severity Index (PASI) scores in the herring roe oil treatment group and the placebo group from baseline to week 26. In the intention-to-treat population, a statistically significant improvement in the mean PASI score was observed with herring roe oil compared to placebo at 26 weeks. In the recruited patient group, the measured improvement was greatest in patients with a PASI score from 5.5-9.9 at baseline.


Daily rhythmicity of clock gene transcripts in atlantic cod fast skeletal muscle.
The classical notion of a centralized clock that governs circadian rhythmicity has been challenged with the discovery of peripheral oscillators that enable organisms to cope with daily changes in their environment. The present study aimed to identify the molecular clock components in Atlantic cod (Gadus morhua) and to investigate their daily gene expression in fast skeletal muscle. Atlantic cod clock genes were closely related to their orthologs in teleosts and tetrapods. Synteny was conserved to varying degrees in the majority of the 18 clock genes examined. In particular, aryl hydrocarbon receptor nuclear translocator-like 2 (arntl2), RAR-related orphan receptor A (rora) and timeless (tim) displayed high degrees of conservation. Expression profiling during the early ontogenesis revealed that some transcripts were maternally transferred, namely arntl2, cryptochrome 1b and 2 (cry1b and cry2), and period 2a and 2b (per2a and per2b). Most clock genes were ubiquitously expressed in various tissues, suggesting the possible existence of multiple peripheral clock systems in Atlantic cod. In particular, they were all detected in fast skeletal muscle, with the exception of neuronal PAS (Per-Arnt-Single-minded) domain-containing protein (npas1) and rora. Rhythmicity analysis revealed 8 clock genes with daily rhythmic expression, namely arntl2, circadian locomotor output cycles kaput (clock), npas2, cry2, cry3 per2a, nuclear receptor subfamily 1, group D, member 1 (nr1d1), and nr1d2a. Transcript levels of the myogenic genes myogenic factor 5 (myf5) and muscleblind-like 1 (mbnl1) strongly correlated with clock gene expression. This is the first study to unravel the molecular components of peripheral clocks in Atlantic cod. Taken together, our data suggest that the putative clock system in fast skeletal muscle of Atlantic cod has regulatory implications on muscle physiology, particularly in the expression of genes related to myogenesis.


Association of dietary vitamin C and e intake and antioxidant enzymes in type 2 diabetes mellitus patients.
Diabetes mellitus consist of a various metabolic diseases such as hyperglycemia, increase glycosylated hemoglobin (HbA1c) and disorder in antioxidant enzymes activity, hence supplementing with antioxidant nutrients, mainly vitamin C and E seems to reduce oxidative injure in patients with type 2 diabetes mellitus (T2DM). To evaluate outcome of vitamin C and E supplementation on type 2 DM patients. The study was completed in 170 T2DM on consumption of vitamin C, E, combination of C & E and placebo. The cases groups of this study consist of two major groups, which were named supplementation and placebo group. The group of supplementation consisted of 3 sub-groups, which received three capsules per day for a phase of three months. The parameters such as HbA1c, glucose, superoxide dismutase (SOD) and glutathione peroxides (GSH) were evaluated in baseline and after three months with supplementation. The statistical analyses were evaluated with the use of mean ± SD, ANOVA-test and paired-sample t-test. Mean age of 170 patients, 84 male and 86 female were 53.82±5.26 in the range of 30-60 years. The blood pressure results showed significant differences between the all supplement groups in baseline as compared to after receiving supplements (p<0.05). Use of vitamin C, E, and E & C showed significant differences in concentration of plasma FBS and HbA1c (p<0.05 & <0.001), but there was no significant differences in placebo groups. SOD and GSH enzymes levels showed a significant increased after consumption of vitamins in supplementation groups (p<0.001). This research confirmed that subjects with T2DM after three months supplementation of vitamins demonstrated significantly low level of hypertension, decrease levels of blood glucose, and increase SOD and GSH enzyme activity that can probably reduce insulin resistance by enhanced lowering oxidative stress parameters.


Impaired neuromuscular transmission and response to acetylcholinesterase inhibitors in centronuclear myopathies.
Many clinical features of autosomal centronuclear myopathies (CNM) and X-linked myotubular myopathy (XLMTM) are common to congenital myasthenic syndromes (CMS). We describe three children whose clinical and electrophysiological findings originally suggested CMS, in whom CNM was diagnosed pathologically, though not yet genetically characterised. A fourth case, with XLMTM, also showed electrophysiological features of a neuromuscular transmission defect. Three (including the XLMTM case) showed improved strength with acetylcholinesterase inhibitor treatment. We also studied neuromuscular junction structure and function in the MTM1 knockdown zebrafish model of XLMTM, demonstrating abnormal neuromuscular junction organization; anticholinesterase therapy resulted in marked clinical response. These observations suggest that a neuromuscular transmission defect may accompany CNM and contribute to muscle weakness. Muscle biopsy should be considered in infants suspected to have CMS, especially if treatment response is incomplete, or no CMS gene mutation is identified. Treatment with acetylcholinesterase inhibitors may benefit some CNM patients. This warrants further confirmation.


Cortical feedback controls the frequency and synchrony of oscillations in the visual thalamus.
Thalamic circuits have an intrinsic capacity to generate state-dependent oscillations of different frequency and degrees of synchrony, but little is known of how synchronized oscillation is controlled in the intact brain or what function it may serve. The influence of cortical feedback was examined using slice preparations of the visual thalamus and computational models. Cortical feedback was mimicked by stimulating corticothalamic axons, triggered by the activity of relay neurons. This artificially coupled network had the capacity to self-organize and to generate qualitatively different rhythmical activities according to the strength of corticothalamic feedback stimuli. Weak feedback (one to three shocks at 100-150 Hz) phase-locked the spontaneous spindle oscillations (6-10 Hz) in geniculate and perigeniculate nuclei. However, strong feedback (four to eight shocks at 100-150 Hz) led to a more synchronized oscillation, slower in frequency (2-4 Hz) and dependent on GABA(B) receptors. This increase in synchrony was essentially attributable to a redistribution of the timing of action potential generation in lateral geniculate nucleus cells, resulting in an increased output of relay cells toward the cortex. Corticothalamic feedback is thus capable of inducing highly synchronous slow oscillations in physiologically intact thalamic circuits. This modulation may have implications for a better understanding of the descending control of thalamic nuclei by the cortex, and the genesis of pathological rhythmical activity, such as absence seizures.


Quantification of the Cost and Potential Environmental Effects of Unused Pharmaceutical Products in Cataract Surgery.
Pharmaceutical products, including unused portions, may contribute to financial and environmental costs in the United States. Because cataract surgery is performed millions of times each year in the United States and throughout the rest of the world, understanding these financial and environmental costs associated with cataract surgery is warranted. To investigate the financial and environmental costs of unused pharmaceutical products after phacoemulsification surgery. This descriptive qualitative study included 4 surgical sites in the northeastern United States (a private ambulatory care center, private tertiary care center, private outpatient center, and federally run medical center for veterans). Prices and data for use of services and pharmaceuticals were obtained for the tertiary care and outpatient centers from January 1 through April 30, 2016; for the ambulatory care center from June 1, 2017, through March 31, 2018; and the federal medical center from November 1, 2017, through February 28, 2018. Data were collected from routine phacoemulsification surgical procedures without vitreous loss or other complications. Volume or weight of medications remaining after surgery was measured. Total and mean costs of medications per case and month were calculated. Environmental effects were estimated using economic input-output life cycle assessment methods. Data were analyzed from December 1, 2017, through June 30, 2018. Cost of unused pharmaceutical products (in US dollars) and kilogram equivalents of carbon emissions (carbon dioxide [CO2-e]), air pollution (fine particulate matter emissions of ≤10 μm in diameter [PM10-e]), and eutrophication potential (nitrogen [N-e]). A total of 116 unique drugs were surveyed among the 4 centers. Assuming unmeasured medications had no materials left unused, a cumulative mean 83 070 of 183 304 mL per month (45.3%) of pharmaceuticals were unused by weight or volume across all sites. Annual unused product cost estimates reached approximately $195 200 per site. A larger percentage of eyedrops (65.7% by volume) were unused compared with injections (24.8%) or systemic medications (59.9%). Monthly unused quantities at the ambulatory care center (65.9% by volume [54 971 of 83 440 mL]), tertiary care center (21.3% [17 143 of 80 344 mL]), federal medical center (38.5% [265 of 689 mL]), and outpatient center (56.8% [10 691 of 18 832 mL]) resulted in unnecessary potential emissions at each center of 2135, 2498, 418, and 711 kg CO2-e/mo, respectively. Unnecessary potential air pollution between sites varied from 0.8 to 4.5 kg PM10-e/mo, and unnecessary eutrophication potential between sites varied from 0.07 to 0.42 kg N-e/mo. This study suggests that unused pharmaceutical products during phacoemulsification result in relatively high financial and environmental costs. If these findings can be substantiated and shown to be generalizable in the United States or elsewhere, reducing these costs may be of value.


Survival of syngeneic and allogeneic iPSC-derived neural precursors after spinal grafting in minipigs.
The use of autologous (or syngeneic) cells derived from induced pluripotent stem cells (iPSCs) holds great promise for future clinical use in a wide range of diseases and injuries. It is expected that cell replacement therapies using autologous cells would forego the need for immunosuppression, otherwise required in allogeneic transplantations. However, recent studies have shown the unexpected immune rejection of undifferentiated autologous mouse iPSCs after transplantation. Whether similar immunogenic properties are maintained in iPSC-derived lineage-committed cells (such as neural precursors) is relatively unknown. We demonstrate that syngeneic porcine iPSC-derived neural precursor cell (NPC) transplantation to the spinal cord in the absence of immunosuppression is associated with long-term survival and neuronal and glial differentiation. No tumor formation was noted. Similar cell engraftment and differentiation were shown in spinally injured transiently immunosuppressed swine leukocyte antigen (SLA)-mismatched allogeneic pigs. These data demonstrate that iPSC-NPCs can be grafted into syngeneic recipients in the absence of immunosuppression and that temporary immunosuppression is sufficient to induce long-term immune tolerance after NPC engraftment into spinally injured allogeneic recipients. Collectively, our results show that iPSC-NPCs represent an alternative source of transplantable NPCs for the treatment of a variety of disorders affecting the spinal cord, including trauma, ischemia, or amyotrophic lateral sclerosis.


Combinatorial effects of odorant mixes in olfactory cortex.
In mammals, each odorant is detected by a combination of different odorant receptors. Signals from different types of receptors are segregated in the nose and the olfactory bulb, but appear to be combined in individual neurons in the olfactory cortex. Here, we report that binary odorant mixes stimulate cortical neurons that are not stimulated by their individual component odorants. We propose that cortical neurons require combinations of receptor inputs for activation and that merging the receptor codes of two odorants provides novel combinations of receptor inputs that stimulate neurons beyond those activated by the single odorants. These findings may explain why odorant mixtures can elicit novel odor percepts in humans.


Household food insecurity is associated with depressive symptoms among low-income pregnant Latinas.
Latinas experience high rates of poverty, household food insecurity and prenatal depression. To date, only one USA study has examined the relationship between household food insecurity and prenatal depression, yet it focused primarily on non-Latina white and non-Latina black populations. Therefore, this study examined the independent association of household food insecurity with depressive symptoms among low-income pregnant Latinas. This cross-sectional study included 135 low income pregnant Latinas living in Hartford, Connecticut. Women were assessed at enrolment for household food security during pregnancy using an adapted and validated version of the US Household Food Security Survey Module. Prenatal depressive symptoms were assessed using the Center for Epidemiological Studies Depression Scale. A cut-off of ≥21 was used to indicate elevated levels of prenatal depressive symptoms (EPDS). Multivariate backwards stepwise logistic regression was used to identify risk factors for EPDS. Almost one third of participants had EPDS. Women who were food insecure were more likely to experience EPDS compared to food secure women (OR = 2.59; 95% CI = 1.03-6.52). Being primiparous, experiencing heartburn and reporting poor/fair health during pregnancy, as well as having a history of depression were also independent risk factors for experiencing EPDS. Findings from this study suggest the importance of assessing household food insecurity when evaluating depression risk among pregnant Latinas.


Effects of centrally administered losartan on deoxycorticosterone-salt hypertension rats.
To investigate whether brain AT1 receptor stimulation contributes as a hypertensive mechanism to deoxycorticosterone acetate (DOCA)-salt hypertension, losartan (1 mg/4 microL) or artificial cerebrospinal fluid (aCSF) was injected into the lateral cerebral ventricle in conscious control uninephrectomized Wistar rats or rats with DOCA-salt for 2 or 4 weeks, and mean arterial pressure (MAP) and heart rates (HR) were recorded. In rats with DOCA-salt treatment, resting MAP increased to 144+/-6 mmHg after 2 weeks and to 170+/-5 mmHg after 4 weeks versus 115- 120 mmHg in controls. In rats with 2 week DOCA-salt treatment, MAP started declining at 4 hr after intracerebroventricular (icv) injection of losartan, and significant decreases in MAP were found at 18 and 24 hr. In rats with 4 week DOCA-salt treatment, MAP was significantly decreased at 4, 18 and 24 hr. In both groups MAP decreased to that of control rats. In control rats, icv losartan had no effect on MAP and HR. Icv aCSF did not significantly change MAP and HR in either DOCA-salt hypertensive rats or control rats. Normalization of MAP after icv administration of the AT1 receptor antagonist suggests a significant role for brain AT1 receptor stimulation in the development and maintenance of hypertension in the DOCA-salt hypertensive rat model.


Hypoxia and Transforming Growth Factor β Cooperate to Induce Fibulin-5 Expression in Pancreatic Cancer.
The deposition of extracellular matrix (ECM) is a defining feature of pancreatic ductal adenocarcinoma (PDA), where ECM signaling can promote cancer cell survival and epithelial plasticity programs. However, ECM signaling can also limit PDA tumor growth by producing cytotoxic levels of reactive oxygen species. For example, excess fibronectin stimulation of α5β1 integrin on stromal cells in PDA results in reduced angiogenesis and increased tumor cell apoptosis because of oxidative stress. Fibulin-5 (Fbln5) is a matricellular protein that blocks fibronectin-integrin interaction and thus directly limits ECM-driven reactive oxygen species production and supports PDA progression. Compared with normal pancreatic tissue, Fbln5 is expressed abundantly in the stroma of PDA; however, the mechanisms underlying the stimulation of Fbln5 expression in PDA are undefined. Using in vitro and in vivo approaches, we report that hypoxia triggers Fbln5 expression in a TGF-β- and PI3K-dependent manner. Pharmacologic inhibition of TGF-β receptor, PI3K, or protein kinase B (AKT) was found to block hypoxia-induced Fbln5 expression in mouse embryonic fibroblasts and 3T3 fibroblasts. Moreover, tumor-associated fibroblasts from mouse PDA were also responsive to TGF-β receptor and PI3K/AKT inhibition with regard to suppression of Fbln5. In genetically engineered mouse models of PDA, therapy-induced hypoxia elevated Fbln5 expression, whereas pharmacologic inhibition of TGF-β signaling reduced Fbln5 expression. These findings offer insight into the signaling axis that induces Fbln5 expression in PDA and a potential strategy to block its production.


[Awareness of health and welfare planning for elderly and methods to increase awareness: based on social marketing].
To clarify the socio-psychological factors affecting awareness of health and welfare planning for the elderly, a survey of community residents was performed in the Tokyo metropolitan area. The results obtained were as follows: 1. There were three factors which affected awareness concern about health and welfare services for the elderly as a social issue: concern about the local community; and concern about the local government. 2. Two other factors which did not affect the level of awareness were: anxiety about the health and welfare services for the elderly as a personal issue; and having personal experience of nursing care. From these results, a method to increase awareness was studied based on social marketing methods. Two primary target groups for increasing awareness were identified. One target was people who have the socio-psychological factors described above. Another target was people who have the potential need for health and welfare services but who were not aware of it. That is, they have relatively high anxiety about health and welfare services for the elderly as a personal issue and have personally experienced nursing care. The method of approach for these targets were studied. For the first group, the amount of the information available seemed to be important because these persons are ready to recognize the need for planning. Therefore, efficient information channels should be selected. For the second group, approaches that generate greater consumer participation by presenting this as an efficient method for solution of the problem should be adopted.


Reflective Practice: How the World Bank Explored Its Own Biases?
While many international organisations have independent evaluations, including the International Monetary Fund (IMF) and World Health organization (WHO), uniquely the World Bank in its 2015 World Development Report sought to ascertain the potential biases that influence how its staff interpret evidence and influence policy. Here, we describe the World Bank's study design, including experiments to ascertain the impact on Bank staff's judgements of complexity, confirmation bias, sunk cost bias, and an understanding of the wishes of those whom they seek to help. We then review the Bank's proposed mechanisms to minimise the impact of the biases they identified. We argue that this approach, that we refer to as 'reflective practice,' deserves to be adopted more widely among institutions that seek to use evidence from research to inform policy and practice.


Predictors of decline in MMSE scores among older Mexican Americans.
The purpose of this analysis was to examine the association of sociodemographic variables and health-related conditions with 5-year declines in cognitive function among Mexican American elderly persons. The cognitive function of 1759 participants was assessed by using the Mini-Mental State Examination (MMSE) in 1993/1994 and again in 1998/1999. Cognitive decline was defined by two sets of criteria: (1) a drop to 17 or below on the MMSE at follow-up, and (2) a decline of at least three points, the mean change in MMSE scores among respondents who obtained scores at or above the 5th percentile distribution at baseline. Cognitive decline was significantly associated with sociodemographic variables including age, education, marital status, and household composition. In addition, respondents with reported vision impairment, stroke, and diabetes were at increased risk for cognitive decline after controlling for multiple potential confounders. Although age and education have been reported as the more salient predictors of cognitive deterioration, other sociodemographic and several medical conditions including stroke and diabetes should be considered as part of cognitive aging studies among Mexican American elders.


Dynamics and selection of many-strain pathogens.
Strain structure is of fundamental importance in the underlying dynamics of a number of pathogens. However, previous models have been too complex to accommodate many strains. This paper offers a solution to this problem, in the form of a simple model that is capable of capturing the dynamics of a large number of antigenic types that interact via host cross-immunity. We derive the structure of the model, which can manage the complexity of many strains by using a status-based formulation, assuming polarized immunity and cross-immunity act to reduced transmission probability. We then apply the model to address basic questions in strain dynamics, focusing particularly on the interpandemic dynamics of influenza. This model shows that strains have a tendency to "cluster." For a long infectious period, relative to host lifetime, clusters may coexist. By contrast, a short infectious period leads to a single dominant cluster at any given time. We show how the speed of cluster replacement depends on the specificity of cross-immunity and on the underlying pathogen mutation rate.


Measuring depression in adolescence: Evaluation of a hierarchical factor model of the Children's Depression Inventory and measurement invariance across boys and girls.
One of the most widely used instruments to measure depression in childhood and adolescence is Kovacs's Children's Depression Inventory (CDI). Even though this particular measure sparked massive interest among researchers, there is no clear consensus about its factorial structure. It has been suggested that inconsistencies in findings can be partly ascribed to the cultural context. The aim of this study was a) to examine and verify the factor structure of CDI in the Czech population and b) to assess gender-related psychometric differences using the mean and covariance structure (MACS) approach and differential item functioning (DIF) analysis. The research sample consisted of 1,515 adolescents (ages 12 to 16 years, 53.7% female) from a non-clinical general population. Based on exploratory factor analysis (EFA) on a random subsample (N = 500), we proposed a model that was subsequently tested on the rest of the sample (N = 1,015) using confirmatory factor analysis (CFA). Following the MACS procedure, we assessed measurement invariance in boys and girls. The between-group comparison was further supplemented by a DIF analysis. The proposed hierarchical four-factor model (General Symptoms, Negative Self-Concept, Inefficiency, and Social Anhedonia) with a second-order factor of depression fitted the data reasonably well (χ2 = 1281.355; df = 320; RMSEA = 0.054, CFI = 0.925). Regarding gender differences, we found no substantial signs of measurement invariance using the MACS approach. Boys and girls differed in first-order latent means (girls scored higher on General Symptoms with a standardized mean difference of 0.52 and on Negative Self-Concept with a standardized mean difference of 0.31). DIF analysis identified three items with differential functioning. However, the levels of differential functioning were only marginal (in two items) or marginal/moderate and the presence of DIF does not substantially influence scoring of CDI. In the general adolescent population in the Czech Republic, the CDI can be considered a reliable instrument for screening purposes in clinical settings and for use in research practice. Instead of the originally proposed five-factor model, we recommend using the newly established four-factor structure. The measure seems to show only marginal psychometric differences with respect to gender, and overall measurement invariance in boys and girls seems to be a tenable assumption.


The preservative propionic acid differentially affects survival of conidia and germ tubes of feed spoilage fungi.
Propionic acid is widely used as a preservative in (poultry) feed. In this study we have isolated and identified fungal strains from nine samples poultry feed originating from different countries. The majority of the strains were Aspergilli with a eurotium-morph, such as Aspergillus proliferans and A. chevalieri. These and three other species were selected and tested for their sensitivity towards the feed preservative propionic acid, among them Penicillium lanosocoeruleum. The determined MIC values of 6.1-31 mM of these poultry feed specific fungi were well in the range as described in literature. Propionic acid (at 31 mM) damages conidia (spores) in a species dependent fashion after a 24-hour-treatment. The majority of the conidia (over 70%) of P. lanosocoeruleum germinated within 60 h on agar medium, while 50 and 80% of the A. chevalieri and A. proliferans conidia did not, respectively. Dependent on the species, cell damage was visible after incubation with propionic acid. Germ tubes of P. lanosocoeruleum in a biofilm showed extensive (85%) cell death after a 30 min treatment with propionic acid and slightly lower sensitivity was observed with A. proliferans (62% cell death). Microscopic analysis of these fungal biofilms revealed extensive damage to the cell membrane and showed distorted intracellular structures. Fluorescent life-dead staining of the germ tubes showed a clear dose response of propionic acid indicating a fungicidal effect on these growing cells. These results show that conidia can be inactivated by propionic acid, but that germ tubes show a much higher sensitivity. These observations shed new light on the mode of action of this important preservative to prevent fungal contamination of feed.


The risks, reasons, and costs for 30- and 90-day readmissions after fusion surgery for adolescent idiopathic scoliosis.
With the continued evolution of bundled payment plans, there has been a greater focus within orthopedic surgery on quality metrics up to 90 days of care. Although the Centers for Medicare and Medicaid Services does not currently penalize hospitals based on their pediatric readmission rates, it is important to understand the drivers for unplanned readmission to improve the quality of care and reduce costs. The National Readmission Database provides a nationally representative sample of all discharges from US hospitals and allows follow-up across hospitals up to 1 calendar year. Adolescents (age 10-18 years) who underwent idiopathic scoliosis surgery from 2012 to 2015 were included. Patients were separated into those with and those without readmission within 30 days or between 31 and 90 days. Demographics, operative conditions, hospital factors, and surgical outcomes were compared using the chi-square test and t-test. Independent predictors for readmissions were identified using stepwise multivariate logistic regression. A total of 30,677 patients underwent adolescent idiopathic scoliosis surgery from 2012 to 2015. The rates of 30- and 90-day readmissions were 2.9% and 1.4%, respectively. The mean costs associated with the index admission and 30- and 90-day readmissions were $60,680, $23,567, and $16,916, respectively. Common risk factors for readmissions included length of stay > 5 days, obesity, neurological disorders, and chronic use of antiplatelets or anticoagulants. The index admission complications associated with readmissions were unintended durotomy, syndrome of inappropriate antidiuretic hormone, and superior mesenteric artery syndrome. Hospital factors, discharge disposition, and operative conditions appeared to be less important for readmission risk. The top reasons for 30-day and 90-day readmissions were wound infection (34.7%) and implant complications (17.3%), respectively. Readmissions requiring a reoperation were significantly higher for those that occurred between 31 and 90 days after the index readmission. Readmission rates were low for both 30- and 90-day readmissions for adolescent idiopathic scoliosis surgery patients. Nevertheless, readmissions are costly and appear to be associated with potentially modifiable risk factors, although some risk factors remain potentially unavoidable.


Exploring time-resolved photoluminescence for nanowires using a three-dimensional computational transient model.
Time-resolved photoluminescence (TRPL) has been implemented experimentally to measure the carrier lifetime of semiconductors for decades. For the characterization of nanowires, the rich information embedded in TRPL curves has not been fully interpreted and meaningfully mapped to the respective material properties. This is because their three-dimensional (3-D) geometries result in more complicated mechanisms of carrier recombination than those in thin films and analytical solutions cannot be found for those nanostructures. In this work, we extend the intrinsic power of TRPL by developing a full 3-D transient model, which accounts for different material properties and drift-diffusion, to simulate TRPL curves for nanowires. To show the capability of the model, we perform TRPL measurements on a set of GaAs nanowire arrays grown on silicon substrates and then fit the measured data by tuning various material properties, including carrier mobility, Shockley-Read-Hall recombination lifetime, and surface recombination velocity at the GaAs-Si heterointerface. From the resultant TRPL simulations, we numerically identify the lifetime characteristics of those material properties. In addition, we computationally map the spatial and temporal electron distributions in nanowire segments and reveal the underlying carrier dynamics. We believe this study provides a theoretical foundation for interpretation of TRPL measurements to unveil the complex carrier recombination mechanisms in 3-D nanostructured materials.


Adaptive transforms for image coding using spatially varying wavelet packets.
We introduce a novel, adaptive image representation using spatially varying wavelet packets (WPs), Our adaptive representation uses the fast double-tree algorithm introduced previously (Herley et al., 1993) to optimize an operational rate-distortion (R-D) cost function, as is appropriate for the lossy image compression framework. This involves jointly determining which filter bank tree (WP frequency decomposition) to use, and when to change the filter bank tree (spatial segmentation). For optimality, the spatial and frequency segmentations must be done jointly, not sequentially. Due to computational complexity constraints, we consider quadtree spatial segmentations and binary WP frequency decompositions (corresponding to two-channel filter banks) for application to image coding. We present results verifying the usefulness and versatility of this adaptive representation for image coding using both a first-order entropy rate-measure-based coder as well as a powerful space-frequency quantization-based (SPQ-based) wavelet coder introduced by Xiong et al. (1993).


A Look into the Cell: Honey Storage in Honey Bees, Apis mellifera.
Honey bees, Apis species, obtain carbohydrates from nectar and honeydew. These resources are ripened into honey in wax cells that are capped for long-term storage. These stores are used to overcome dearth periods when foraging is not possible. Despite the economic and ecological importance of honey, little is known about the processes of its production by workers. Here, we monitored the usage of storage cells and the ripening process of honey in free-flying A. mellifera colonies. We provided the colonies with solutions of different sugar concentrations to reflect the natural influx of nectar with varying quality. Since the amount of carbohydrates in a solution affects its density, we used computer tomography to measure the sugar concentration of cell content over time. The data show the occurrence of two cohorts of cells with different provisioning and ripening dynamics. The relocation of the content of many cells before final storage was part of the ripening process, because sugar concentration of the content removed was lower than that of content deposited. The results confirm the mixing of solutions of different concentrations in cells and show that honey is an inhomogeneous matrix. The last stage of ripening occurred when cell capping had already started, indicating a race against water absorption. The storage and ripening processes as well as resource use were context dependent because their dynamics changed with sugar concentration of the food. Our results support hypotheses regarding honey production proposed in earlier studies and provide new insights into the mechanisms involved.


Depression case management by practice nurses in primary care: an audit.
Introduction Depression is a common and debilitating condition. A body of evidence exists about improving depression outcomes in primary care, using collaborative care models. Such approaches, however, have not been routinely adopted within general practice settings. In this paper we outline the results of an audit of an enhanced care initiative that trained practice nurses to deliver such approaches.Method An audit of symptom outcome and satisfaction was conducted in depression case-management clinics run by practice nurses. Results were then benchmarked against appropriate randomised trial data. The cost of practice nurse time devoted to the delivery of the service was estimated by multiplying time by unit cost.Results A mean change of 9.07 (standard deviation (SD) 6.67, 95% confidence interval (CI) 7.93-10.22, P < 0.001) points on the Patient Health Questionnaire (PHQ9) score was observed in those who were using/had used the service. Clinical change demonstrated a shift from moderate-to-severe to mild depression. The results reflect the changes seen in randomised controlled trial data from similar interventions in similar samples, and are superior to expected treatment as usual outcomes. Overall, respondents were 'very satisfied' with the service on offer. The mean cost of practice nurse time was estimated at £45 per patient.Discussion While acknowledging the limitations of audit data, practice nurses in general practice appear to be able to offer effective and acceptable case management to patients experiencing depression.