The role of spatial dynamics in the stability, resilience, and productivity of an estuarine fish population.
Understanding mechanisms that support long-term persistence of populations and sustainability of productive fisheries is a priority in fisheries management. Complex spatial structure within populations is increasingly viewed as a result of a plastic behavioral response that can have consequences for the dynamics of a population. We incorporated spatial structure and environmental forcing into a population model to examine the consequences for population stability (coefficient of variation of spawning-stock biomass), resilience (time to recover from disturbance), and productivity (spawning-stock biomass). White perch (Morone americana) served as a model species that exhibits simultaneous occurrence of migratory and resident groups within a population. We evaluated the role that contingents (behavioral groups within populations that exhibit divergent life histories) play in mitigating population responses to unfavorable environmental conditions. We used age-structured models that incorporated contingent-specific vital rates to simulate population dynamics of white perch in a sub-estuary of Chesapeake Bay, USA. The dynamics of the population were most sensitive to the proportion of individuals within each contingent and to a lesser degree to the level of correlation in recruitment between contingents in their responses to the environment. Increased representation of the dispersive contingent within populations resulted in increased productivity and resilience, but decreased stability. Empirical evidence from the Patuxent River white perch population was consistent with these findings. A high negative correlation in resident and dispersive contingent recruitment dynamics resulted in increased productivity and stability, with little effect on resilience. With high positive correlation between contingent recruitments, the model showed similar responses in population productivity and resilience, but decreased stability. Because contingent structure involves differing patterns of nursery habitat use, spatial management that conserves sets of habitats rather than the single most productive nursery habitat would be expected to contribute to long-term population stability.


Maternal protein intake is not associated with infant blood pressure.
Animal data show that low protein intake in pregnancy programs higher offspring blood pressure, but similar data in humans are limited. We examined the associations of first and second trimester maternal protein intake with offspring blood pressure (BP) at the age of six months. In a prospective US cohort study, called Project Viva, pregnant women completed validated semi-quantitative food-frequency questionnaires (FFQ) to measure gestational protein intake. Among 947 mother-offspring pairs with first trimester dietary data and 910 pairs with second trimester data, we measured systolic blood pressure (SBP) up to five times with an automated device in the offspring at the age of six months. Controlling for blood pressure measurement conditions, maternal and infant characteristics, we examined the effect of energy-adjusted maternal protein intake on infant SBP using multivariable mixed effects models. Mean daily second trimester maternal protein intake was 17.6% of energy (mean 2111 kcal/day). First trimester nutrient intakes were similar. Mean SBP at age 6 months was 90.0 mm Hg (SD 12.9). Consistent with prior reports, adjusted SBP was 1.94 mm Hg lower [95% confidence interval (CI) -3.45 to -0.42] for each kg increase in birth weight. However, we did not find an association between maternal protein intake and infant SBP. After adjusting for covariates, the effect estimates were 0.14 mm Hg (95% CI 20.12 to 20.40) for a 1% increase in energy from protein during the second trimester, and 20.01 mm Hg (95% CI 20.24 to -0.23) for a 1% increase in energy from protein in the first trimester. Variation in maternal total protein intake during pregnancy does not appear to program offspring blood pressure.


Conjunctival rhinosporidiosis: a case report from a Congolese patient.
This report describes a case of conjunctival rhinosporidiosis. A 10-year old Congolese boy (from DR Congo), presented in May 2003 with a history of a growing mass of the conjunctiva protruding through the palpebral aperture. Examination showed conjunctival polypoid mass with muco-purulent discharge from the affected eye. After surgical excision of the lesion, the microscopic diagnosis was rhinosporidiosis. Rhinosporidiosis is a condition which both clinicians and pathologists should keep in mind when managing patients living in or coming from endemic countries with conjunctival masses.


Quality of antenatal care and client satisfaction in Kenya and Namibia.
Despite much progress in maternal health service coverage, the quality of care has not seen parallel improvement. This study assessed the quality of antenatal care (ANC), an entry point to the health system for many women. The study used data from recent Service Provision Assessment (SPA) surveys of nationally representative health facilities in Kenya and Namibia. Kenya and Namibia represent the situation in much of sub-Saharan Africa, where ANC is relatively common but maternal mortality remains high. The SPA comprised an inventory of health facilities that provided ANC, interviews with ANC providers and clients, and observations of service delivery. Not applicable. Quality was measured in terms of structure and process of service provision, and client satisfaction as the outcome of service provision. Wide variations in structural and process attributes of quality of care existed in both Kenya and Namibia; however, better structural quality did not translate to better service delivery process or greater client satisfaction. Long waiting time was a common problem and was generally more serious in hospitals and health centers than in clinics and smaller facilities; it was consistently associated with lower client satisfaction. The study also indicates that the provider's technical preparedness may not be sufficient to provide good-quality services and to ensure client satisfaction. Findings highlight important program implications, including improving ANC services and promoting their use at health clinics and lower-level facilities, and ensuring that available supplies and equipment are used for service provision.


Shared and unique proteins in human, mouse and rat saliva proteomes: Footprints of functional adaptation.
The overall goal of our study was to compare the proteins found in the saliva proteomes of three mammals: human, mouse and rat. Our first objective was to compare two human proteomes with very different analysis depths. The 89 shared proteins in this comparison apparently represent a core of highly-expressed human salivary proteins. Of the proteins unique to each proteome, one-half to 2/3 lack signal peptides and probably are contaminants instead of less highly-represented salivary proteins. We recently published the first rodent saliva proteomes with salivas collected from the genome mouse (C57BL/6) and the genome rat (BN/SsNHsd/Mcwi). Our second objective was to compare the proteins in the human proteome with those we identified in the genome mouse and rat to determine those common to all three mammals as well as the specialized rodent subset. We also identified proteins unique to each of the three mammals because differences in the secreted protein constitutions can provide clues to differences in the evolutionary adaptation of the secretions in the three different mammals.


AgeAnnoMO: a knowledgebase of multi-omics annotation for animal aging.
Aging entails gradual functional decline influenced by interconnected factors. Multiple hallmarks proposed as common and conserved underlying denominators of aging on the molecular, cellular and systemic levels across multiple species. Thus, understanding the function of aging hallmarks and their relationships across species can facilitate the translation of anti-aging drug development from model organisms to humans. Here, we built AgeAnnoMO (https://relab.xidian.edu.cn/AgeAnnoMO/#/), a knowledgebase of multi-omics annotation for animal aging. AgeAnnoMO encompasses an extensive collection of 136 datasets from eight modalities, encompassing 8596 samples from 50 representative species, making it a comprehensive resource for aging and longevity research. AgeAnnoMO characterizes multiple aging regulators across species via multi-omics data, comprehensively annotating aging-related genes, proteins, metabolites, mitochondrial genes, microbiotas and age-specific TCR and BCR sequences tied to aging hallmarks for these species and tissues. AgeAnnoMO not only facilitates a deeper and more generalizable understanding of aging mechanisms, but also provides potential insights of the specificity across tissues and species in aging process, which is important to develop the effective anti-aging interventions for diverse populations. We anticipate that AgeAnnoMO will provide a valuable resource for comprehending and integrating the conserved driving hallmarks in aging biology and identifying the targetable biomarkers for aging research.


Shape changes and reduced calcium level in the surface membrane region of human platelets exposed to manganese in vitro.
The effect of exogenous manganese ions upon human platelets in vitro has been studied. Morphological changes reported include the loss of discoid shape, increase in filopodia and close apposition of platelet surfaces. Electron microscope X-ray microanalysis of thin-sectioned material revealed a significant decrease in the bound calcium levels of the surface membrane as a result of manganese treatment. Analysis of whole platelet homogenates using atomic absorption spectrophotometry indicated that the total internal platelet calcium content had increased significantly. It is suggested that manganese induces the observed changes by displacing calcium from the regulatory system of an actomyosin-like protein complex at the periphery of the platelet.


Seqpare: a self-consistent metric of similarity between genomic interval sets.
Searching genomic interval sets produced by sequencing methods has been widely and routinely performed; however, existing metrics for quantifying similarities among interval sets are inconsistent. Here we introduce Seqpare, a self-consistent and effective metric of similarity and tool for comparing sequences based on their interval sets. With this metric, the similarity of two interval sets is quantified by a single index, the ratio of their effective overlap over the union: an index of zero indicates unrelated interval sets, and an index of one means that the interval sets are identical. Analysis and tests confirm the effectiveness and self-consistency of the Seqpare metric.


The chromatin-modifying protein HUB2 is involved in the regulation of lignin composition in xylem vessels.
PIRIN2 (PRN2) was earlier reported to suppress syringyl (S)-type lignin accumulation of xylem vessels of Arabidopsis thaliana. In the present study, we report yeast two-hybrid results supporting the interaction of PRN2 with HISTONE MONOUBIQUITINATION2 (HUB2) in Arabidopsis. HUB2 has been previously implicated in several plant developmental processes, but not in lignification. Interaction between PRN2 and HUB2 was verified by β-galactosidase enzymatic and co-immunoprecipitation assays. HUB2 promoted the deposition of S-type lignin in the secondary cell walls of both stem and hypocotyl tissues, as analysed by pyrolysis-GC/MS. Chemical fingerprinting of individual xylem vessel cell walls by Raman and Fourier transform infrared microspectroscopy supported the function of HUB2 in lignin deposition. These results, together with a genetic analysis of the hub2 prn2 double mutant, support the antagonistic function of PRN2 and HUB2 in deposition of S-type lignin. Transcriptome analyses indicated the opposite regulation of the S-type lignin biosynthetic gene FERULATE-5-HYDROXYLASE1 by PRN2 and HUB2 as the underlying mechanism. PRN2 and HUB2 promoter activities co-localized in cells neighbouring the xylem vessel elements, suggesting that the S-type lignin-promoting function of HUB2 is antagonized by PRN2 for the benefit of the guaiacyl (G)-type lignin enrichment of the neighbouring xylem vessel elements.


Feasibility and acceptability of group music therapy vs wait-list control for treatment of patients with long-term depression (the SYNCHRONY trial): study protocol for a randomised controlled trial.
Depression is of significant global concern. Despite a range of effective treatment options it is estimated that around one in five diagnosed with an acute depressive episode continue to experience enduring symptoms for more than 2 years. There is evidence for effectiveness of individual music therapy for depression. However, no studies have as yet looked at a group intervention within an NHS context. This study aims to assess the feasibility of conducting a randomised controlled trial of group music therapy for patients with long-term depression (symptom durations of 1 year or longer) within the community. This is a single-centre randomised controlled feasibility trial of group music therapy versus wait-list control with a nested process evaluation. Thirty participants will be randomised with unbalanced allocation (20 to receive the intervention immediately, 10 as wait-list controls). Group music therapy will be offered three times per week in a community centre with a focus on songwriting. Data will be collected post-intervention, 3 and 6 months after the intervention finishes. We will examine the feasibility of recruitment processes including identifying the number of eligible participants, participation and retention rates and the intervention in terms of testing components, measuring adherence and estimation of the likely intervention effect. A nested process evaluation will consist of treatment fidelity analysis, exploratory analysis of process measures and end-of-participation interviews with participants and referring staff. Whilst group music therapy is an option in some community mental health settings, this will be the first study to examine group music therapy for this particular patient group. We will assess symptoms of depression, acceptability of the intervention and quality of life. We anticipate potential challenges in the recruitment and retention of participants. It is unclear whether offering the intervention three times per week will be acceptable to participants, particularly given participants' enduring symptoms and impact upon motivation. This study will provide data to inform both development of the intervention and to assess and inform the design of a full trial. ISRCTN.com, ISRCTN18164037 . Registered on 26 September 2016.


The influence of microplastics pollution on the feeding behavior of a prominent sandy beach amphipod, Orchestoidea tuberculata (Nicolet, 1849).
Pollution by microplastics has become a global threat affecting coastal habitats such as sandy beaches and their resident macrofauna. The goal of this study was to assess the influence of microplastics on the feeding behavior and growth rate of a widespread sandy beach amphipod, Orchestoidea tuberculata. These organisms were exposed to artificial food prepared with Poly(styrene-co-divinylbenzene) microspheres (8 μm particle size) at 3 different concentrations (0%, 5% and 10%). The amphipods consumed significantly more food when the concentration of microplastics was 0% and significantly less when the concentration was 10%, both in trials in which they had a choice (preference experiments) and those in which they did not have a food choice. In contrast to this, the amphipod's absorption efficiency and estimated growth rates were not significantly affected by the concentration of microplastics. Combined, these results indicate that high microplastics concentrations (e.g. 10%) cause a reduction in the amphipod's consumption rates and, indirectly, may affect the role of this species as a main consumer of stranded seaweeds in sandy beaches ecosystems.


The development of a new type of rechargeable batteries based on hybrid electrolytes.
Lithium ion batteries (LIBs), which have the highest energy density among all currently available rechargeable batteries, have recently been considered for use in hybrid electric vehicles (HEVs), plug-in hybrid electric vehicles (PHEVs), and pure electric vehicles (PEV). A major challenge in this effort is to increase the energy density of LIBs to satisfy the industrial needs of HEVs, PHEVs, and PEVs. Recently, new types of lithium-air and lithium-copper batteries that employ hybrid electrolytes have attracted significant attention; these batteries are expected to succeed lithium ion batteries as next-generation power sources. Herein, we review the concept of hybrid electrolytes, as well as their advantages and disadvantages. In addition, we examine new battery types that use hybrid electrolytes.


Skin reactions to foods in patients with atopic dermatitis.
Thirty-seven patients with moderate or severe persistent atopic dermatitis gave a history of skin reactions following the ingestion of certain foods. These reactions fell into three groups: immediate reactions (within one hour) which included angio-oedema, contact urticaria, generalised itching and erythema, or urticaria; late reactions, where patients experienced late urticaria, late angio-oedema, itching, or exacerbation of the dermatitis; dual reactions where immediate reactions were followed by exacerbation of the atopic dermatitis. The foods implicated were either potential allergens or recognised nonimmunological histamine-release agents. Foods which caused an IgE-mediated reaction tended to produce early or dual reactions whereas histamine releasing foods tended to result in late reactions.


Bone marrow transplantation for refractory Langerhans' cell histiocytosis.
Langerhans' cell histiocytosis (LCH) is an uncommon disorder of childhood, formerly referred to histiocytosis X. A significant proportion of children with disseminated disease may undergo progression to a fatal outcome despite chemotherapy with single or multiple agents. Only six cases of LCH treated with BMT have been reported in the literature, including two cases of autologous BMT. Of them, only one was less than 14 years of age. We describe a 4-year-old child whose disseminated, refractory Langerhans' cell histiocytosis was not controlled by front-line monotherapy with etoposide, nor by rescue treatment with combined chemotherapy (vinblastine and etoposide) and immunotherapy (steroids and cyclosporine). Due to the high risk of fatal progressive disease, he underwent bone marrow transplantation from his HLA-identical sister who was heterozigous for beta-thalassemia. On day 24 after transplantation marrow reconstitution was evident, with WBC count 2.3 x 10(9)/L, neutrophil count > 0.5 x 10(9)/L, and platelet count 72 x 10(9)/L. Engraftment was demonstrated by PCR DNA analysis. The patient was discharged on day 25. After transplantation he experienced fever for 11 days and developed signs of grade I cutaneous and intestinal graft-versus-host disease, that was treated with methylprednisolone from days 11 to day 68 (1 mg/kg/day for 18 days, then tapered). He became transfusion independent on day 24; the hemoglobin value was 7.5 g/dL on day 54 and has remained > 10 g/dL since day 200. Features of heterozygous beta-thalassemia have been evident since then. Bone marrow aspirate was normal on days 25 and 94. At the time of this writing he remains in excellent condition, disease and treatment free, 25 months after transplantation. Although limited, current experience suggests that bone marrow transplantation has the potential to cure refractory Langerhans' cell histiocytosis.


Twelve tips on how to motivate healthcare professions students and their supervisors for Interprofessional Education.
This article was migrated. The article was marked as recommended. Special efforts in rotations are necessary to have students from different professions learn with, from and about each other to improve their collaboration and the quality of care. The twelve tips derived from the lived experiences and research from the authors, are intended to stimulate motivation for interprofessional education in students and their supervisors. Internalization of the value students place on interprofessional learning will improve their readiness for future interprofessional collaboration. While creating an autonomy-supportive learning environment, supervisors are capable of both scaffolding the learning of students from all professions, and learning themselves from these authentic situations. The authors promote a central place for the clinical reasoning of each profession in both the profession specific skills as well as in the communication, collaboration and team skills, thus enhancing the 'T shaped-professional' ( Visser, 2018).


Acute lymphoblastic leukaemia cells produce large extracellular vesicles containing organelles and an active cytoskeleton.
Extracellular vesicles have been described in non-paracrine cellular interactions in cancer. We report a similar phenomenon in B-cell precursor (BCP) acute lymphoblastic leukaemia (ALL). Using advanced microscopy and high throughput screening, we further characterise a subset of large vesicles (LEVs) identified in cell lines, murine models of human BCP-ALL and clinical samples. Primary ALL blasts and cell lines released heterogeneous anucleate vesicles <6 micron into extracellular fluids. Larger LEVs were enclosed in continuous membranes, contained intact organelles and demonstrated an organised cytoskeleton. An excess of circulating CD19-positive LEVs were observed in diagnostic samples and isolated from mice engrafted with BCP-ALL primary cells. LEVs exhibited dynamic shape change in vitro and were internalised by other leukaemic cell lines leading to phenotypic transformation analogous to the cell of origin. In patient-derived xenografts, LEVs were released by primary ALL cells into extracellular spaces and internalised by murine mesenchymal cells in vivo. Collectively these data highlight the heterogeneity but accessibility of LEVs in clinical samples and their potential to provide a unique insight into the biology of the cell of origin and to their development as novel biomarkers to aid diagnosis and improve therapeutic outcomes.


[New aspects of echography using during delivery].
The paper presents some aspects of the use of echography in obstetrics for the prediction and early diagnosis of labour abnormalities just before delivery and its first period. Prediction and early diagnosis of the nature of labour are made on the studies of changes in the myometrial thickness in the first period of delivery and myometrial echo structural features before and during delivery. Proceeding from the findings, labour abnormalities were corrected and the efficiency of drug therapy was evaluated.


An enhanced heterologous virus-like particle for human papillomavirus type 16 tumour immunotherapy.
Cervical cancer is caused by high-risk, cancer-causing human papillomaviruses (HPV) and is the second highest cause of cancer deaths in women globally. The majority of cervical cancers express well-characterized HPV oncogenes, which are potential targets for immunotherapeutic vaccination. Here we develop a rabbit haemorrhagic disease virus (RHDV) virus-like particle (VLP)-based vaccine designed for immunotherapy against HPV16 positive tumours. An RHDV-VLP, modified to contain the universal helper T cell epitope PADRE and decorated with an MHC I-restricted peptide (aa 48-57) from the HPV16 E6, was tested for its immunotherapeutic efficacy against the TC-1 HPV16 E6 and E7-expressing tumour in mice. The E6-RHDV-VLP-PADRE was administered therapeutically for the treatment of a pre-existing TC-1 tumour and was delivered with antibodies either to deplete regulatory T cells (anti-CD25) or to block T cell suppression mediated through CTLA-4. As a result, the tumour burden was reduced by around 50% and the median survival time of mice to the humane endpoint was almost doubled the compared to controls. The incorporation of PADRE into the RHDV-VLP was necessary for an E6-specific enhancement of the anti-tumour response and the co-administration of the immune modifying antibodies contributed to the overall efficacy of the immunotherapy. The E6-RHDV-VLP-PADRE shows immunotherapeutic efficacy, prolonging survival for HPV tumour-bearing mice. This was enhanced by the systemic administration of immune-modifying antibodies that are commercially available for use in humans. There is potential to further modify these particles for even greater efficacy in the path to development of an immunotherapeutic treatment for HPV precancerous and cancer stages.


Intrapartum asphyxia and cerebral palsy.
Signs of presumed hypoxia/asphyxia of the fetus are not uncommon and can be detected during labor, in the delivery room, and during the early neonatal period. Virtually no single sign or symptom has sufficient correlation to enable prediction of later cerebral palsy with a reasonable degree of medical certainty. To attribute cerebral palsy to prior asphyxia with reasonable certainty, there must be evidence that a substantial hypoxic injury occurred and that a sequence of events ensued which would prove the clinical impact of that hypoxic insult. Few cases of cerebral palsy meet these criteria.


One-pot chemoenzymatic synthesis of chiral 1,3-diols using an enantioselective aldol reaction with chiral Zn2+ complex catalysts and enzymatic reduction using oxidoreductases with cofactor regeneration.
We previously reported on enantioselective aldol reactions of acetone and some aldehydes catalyzed by chiral Zn(2+) complexes of L-prolyl-pendant [12]aneN(4) (L-ZnL(1)) and L-valyl-pendant [12]aneN(4) (L-ZnL(2)) in aqueous solution. Here, we report on the one-pot chemoenzymatic synthesis of chiral 1,3-diols in an aqueous solvent system at room temperature by a combination of enantioselective aldol reactions catalyzed by Zn(2+) complexes of L- and D-phenylalanyl-pendant [12]aneN(4) (L-ZnL(3) and D-ZnL(3) ) and the successive enantioselective reduction of the aldol products using oxidoreductases with the regeneration of the NADH (reduced form of nicotinamine adenine dinucleotide) cofactor. The findings indicate that all four stereoisomers of 1,3-diols can be produced by appropriate selection of a chiral Zn(2+)-complex and an oxidoreductase commercially available from the "Chiralscreen OH" kit.


Ozone inactivation of norovirus surrogates on fresh produce.
Preharvest contamination of produce by foodborne viruses can occur through a variety of agents, including animal feces/manures, soil, irrigation water, animals, and human handling. Problems of contamination are magnified by potential countrywide distribution. Postharvest processing of produce can involve spraying, washing, or immersion into water with disinfectants; however, disinfectants, including chlorine, have varying effects on viruses and harmful by-products pose a concern. The use of ozone as a disinfectant in produce washes has shown great promise for bacterial pathogens, but limited research exists on its efficacy on viruses. This study compares ozone inactivation of human norovirus surrogates (feline calicivirus [FCV] and murine norovirus [MNV]) on produce (green onions and lettuce) and in sterile water. Green onions and lettuce inoculated with FCV or MNV were treated with ozone (6.25 ppm) for 0.5- to 10-min time intervals. Infectivity was determined by 50% tissue culture infectious dose (TCID(50)) and plaque assay for FCV and MNV, respectively. After 5 min of ozone treatment, >6 log TCID(50)/ml of FCV was inactivated in water and ∼2-log TCID(50)/ml on lettuce and green onions. MNV inoculated onto green onions and lettuce showed a >2-log reduction after 1 min of ozone treatment. The food matrix played the largest role in protection against ozone inactivation. These results indicate that ozone is an alternative method to reduce viral contamination on the surface of fresh produce.


[Selective microsurgical therapy in vascular-induced erectile impotence].
Patients with erectile dysfunction should be subjected to a complex and complete diagnostic procedure, including selective pharmaco-phalloangiography and dynamic pharmacocavernosonography only when SKAT has failed and after the exclusion of neurological disorders. Patients being offered these invasive procedures should be highly motivated and willing to undergo surgical correction of the vascular origin of their erectile impotence. If peripheral vascular occlusive disease is found affecting the pelvic arteries, the best operative technique must be selected. In our opinion, this decision should be made intraoperatively after visualization of the dissected dorsal penile vessels. Use of the Doppler probe can be extremely helpful during the operation. Intraoperative findings on the degree of arteriosclerosis and arterial flow can differ from those allowed by preoperative diagnostic procedures. Penile erectile function was restored in seven of nine patients after penile revascularization performed under microsurgical conditions. We used the operative methods described by Virag and Hauri, applying our own modification of the Hauri procedure in two patients. With careful selection of patients and methods it should be possible to resolve individual patients' problems with peripheral occlusion, even though the exact hemodynamic pathology remains obscure.


Transcriptional and functional consequences of Oncostatin M signaling on young Dnmt3a-mutant hematopoietic stem cells.
Age-associated clonal hematopoiesis (CH) occurs due to somatic mutations accrued in hematopoietic stem cells (HSCs) that confer a selective growth advantage in the context of aging. The mechanisms by which CH-mutant HSCs gain this advantage with aging are not comprehensively understood. Using unbiased transcriptomic approaches, we identified Oncostatin M (OSM) signaling as a candidate contributor to age-related Dnmt3a-mutant CH. We found that Dnmt3a-mutant HSCs from young adult mice (3-6 months old) subjected to acute OSM stimulation do not demonstrate altered proliferation, apoptosis, hematopoietic engraftment, or myeloid differentiation. Dnmt3a-mutant HSCs from young mice do transcriptionally upregulate an inflammatory cytokine network in response to acute in vitro OSM stimulation as evidenced by significant upregulation of the genes encoding IL-6, IL-1β, and TNFα. OSM-stimulated Dnmt3a-mutant HSCs also demonstrate upregulation of the anti-inflammatory genes Socs3, Atf3, and Nr4a1. In the context of an aged bone marrow (BM) microenvironment, Dnmt3a-mutant HSCs upregulate proinflammatory genes but not the anti-inflammatory genes Socs3, Atf3, and Nr4a1. The results from our studies suggest that aging may exhaust the regulatory mechanisms that HSCs employ to resolve inflammatory states in response to factors such as OSM.


Genetic and physiological activation of osmosensitive gene expression mimics transcriptional signatures of pathogen infection in C. elegans.
The soil-dwelling nematode C. elegans is a powerful system for comparative molecular analyses of environmental stress response mechanisms. Infection of worms with bacterial and fungal pathogens causes the activation of well-characterized innate immune transcriptional programs in pathogen-exposed hypodermal and intestinal tissues. However, the pathophysiological events that drive such transcriptional responses are not understood. Here, we show that infection-activated transcriptional responses are, in large part, recapitulated by either physiological or genetic activation of the osmotic stress response. Microarray profiling of wild type worms exposed to non-lethal hypertonicity identified a suite of genes that were also regulated by infection. Expression profiles of five different osmotic stress resistant (osr) mutants under isotonic conditions reiterated the wild type transcriptional response to osmotic stress and also showed substantial similarity to infection-induced gene expression under isotonic conditions. Computational, transgenic, and functional approaches revealed that two GATA transcription factors previously implicated in infection-induced transcriptional responses, elt-2 and elt-3, are also essential for coordinated tissue-specific activation of osmosensitive gene expression and promote survival under osmotically stressful conditions. Together, our data suggest infection and osmotic adaptation share previously unappreciated transcriptional similarities which might be controlled via regulation of tissue-specific GATA transcription factors.


A three-component dicamba O-demethylase from Pseudomonas maltophilia, strain DI-6: gene isolation, characterization, and heterologous expression.
Dicamba O-demethylase is a multicomponent enzyme from Pseudomonas maltophilia, strain DI-6, that catalyzes the conversion of the widely used herbicide dicamba (2-methoxy-3,6-dichlorobenzoic acid) to DCSA (3,6-dichlorosalicylic acid). We recently described the biochemical characteristics of the three components of this enzyme (i.e. reductase(DIC), ferredoxin(DIC), and oxygenase(DIC)) and classified the oxygenase component of dicamba O-demethylase as a member of the Rieske non-heme iron family of oxygenases. In the current study, we used N-terminal and internal amino acid sequence information from the purified proteins to clone the genes that encode dicamba O-demethylase. Two reductase genes (ddmA1 and ddmA2) with predicted amino acid sequences of 408 and 409 residues were identified. The open reading frames encode 43.7- and 43.9-kDa proteins that are 99.3% identical to each other and homologous to members of the FAD-dependent pyridine nucleotide reductase family. The ferredoxin coding sequence (ddmB) specifies an 11.4-kDa protein composed of 105 residues with similarity to the adrenodoxin family of [2Fe-2S] bacterial ferredoxins. The oxygenase gene (ddmC) encodes a 37.3-kDa protein composed of 339 amino acids that is homologous to members of the Phthalate family of Rieske non-heme iron oxygenases that function as monooxygenases. Southern analysis localized the oxygenase gene to a megaplasmid in cells of P. maltophilia. Mixtures of the three highly purified recombinant dicamba O-demethylase components overexpressed in Escherichia coli converted dicamba to DCSA with an efficiency similar to that of the native enzyme, suggesting that all of the components required for optimal enzymatic activity have been identified. Computer modeling suggests that oxygenase(DIC) has strong similarities with the core alphasubunits of naphthalene 1,2-dioxygenase. Nonetheless, the present studies point to dicamba O-demethylase as an enzyme system with its own unique combination of characteristics.


Synaptic connections of axo-axonic (chandelier) cells in human epileptic temporal cortex.
The human temporal cortex contains a type of interneuron, identified by Golgi impregnation which, like the axo-axonic or chandelier cells found in animals, establishes Gray's type II synaptic contacts exclusively with the axon initial segments of pyramidal cells. Each terminal segment is composed of 3-12 boutons to form a "chandelier"-like appearance. For the two human axo-axonic cells analysed in this study we could identify 269 and 86 bouton rows respectively, which represents an equivalent number of postsynaptic pyramidal cells. A terminal bouton row from one of these Golgi-impregnated cells was shown to be in synaptic contact with the axon initial segment of a Golgi-impregnated pyramidal cell. The very specific nature of the target of axo-axonic cells, together with their highly divergent axonal arborization, means that they are ideally placed to control the output of a large population of pyramidal cells. Since previous studies in animals have shown the GABAergic nature of axo-axonic cells it is possible that human axo-axonic cells could be involved in the generation of epileptic activity or in the control of its propagation.


Liver transplantation from non-heart beating donors in rats: influence of viscosity and temperature of initial flushing solutions on graft function.
We evaluated the effect of warm (37 degrees C) versus cold (4 degrees C) solutions as the initial flush for liver preservation from non-heart beating donors in rats. An initial flush was performed just before donor hepatectomy with cold or warm University of Wisconsin solution (UW), UW without hydroxyethyl starch, sodium lactobionate sucrose solution, or lactated Ringer's solution as the control group. A separate group also used as control received no initial flushing. Liver transplantation was performed, and the graft function was determined by survival and assessment of enzyme release. The viscosity of each solution and the vascular resistance of the graft were measured. The 7-day survival rate was 83% and 100% in the warm and cold sodium lactobionate sucrose solution groups and 60% and 50% in the warm and cold lactated Ringer's solution groups, respectively. In the no-initial-flush group, rats did not survive. The 7-day survival rate was 67% and 0% in the warm and cold UW groups, respectively. Eliminating the hydroxyethyl starch from the cold UW improved the survival to 67%. Serum alanine aminotransferase levels 1 day after transplantation in the no-initial-flush and the cold UW groups were significantly higher than those of the remaining groups. At 4 degrees C the viscosity was higher in the UW (86.2 cp) compared to hydroxyethyl starch-free UW solution (30.9 cp), lactated Ringer's solution (24.5 cp), and sodium lactobionate sucrose solution (32.7 cp). The viscosity of UW at 37 degrees C was 34.7 cp. Vascular resistance correlated well with the viscosity. Livers flushed with solutions with a low viscosity showed lower vascular resistance than those flushed with cold UW and led to better survival. These data suggest that the viscosity of the initial flushing solution may play an important role in determining the outcome of organ procurement from non-heart beating donors.


A transcriptional activator, FleQ, regulates mucin adhesion and flagellar gene expression in Pseudomonas aeruginosa in a cascade manner.
Previous work has demonstrated that fleR, the gene for a transcriptional activator belonging to the NtrC subfamily of response regulators, is involved in the regulation of mucin adhesion and flagellar expression by Pseudomonas aeruginosa. This report describes the identification and characterization of fleQ, the gene for another transcriptional regulator which also regulates mucin adhesion and motility in this organism. The complete nucleotide sequence of the fleQ gene was determined on both DNA strands, and an open reading frame (ORF) consisting of 1,493 nucleotides was identified. This ORF coded for a gene product of predicted molecular weight, as confirmed by the overexpression of the fleQ gene as a fusion protein under an inducible promoter. The fleQ gene is flanked by a flagellar operon, fliDSorf126, at the 5' end and the fleSR operon on the 3' end. FleQ also had striking homology to a number of proteins belonging to the NtrC subfamily of response regulators, which work in concert with the alternate sigma factor RpoN (sigma54) to activate transcription. However, FleQ lacks the residues corresponding to Asp-54 and Lys-104 of the NtrC protein which are conserved in most of the members belonging to this subfamily of regulators. In addition, unlike some of the other transcriptional activators of this group, FleQ does not appear to have a cognate sensor kinase. A chromosomal insertional mutation in the fleQ gene abolished mucin adhesion and motility of P. aeruginosa PAK and PAK-NP. Both of these functions were regained by providing the complete fleQ gene on a multicopy plasmid. The location of fleQ immediately upstream of the fleSR operon, which is also necessary for the same process, suggested that these regulators may interact in some way. We therefore examined the regulation of the fleSR operon by fleQ and vice versa. Promoter fusion experiments showed that the fleSR operon was regulated by RpoN and FleQ. On the other hand, the fleQ promoter was independent of RpoN and FleR. FleQ, thus, adds another level of regulation to motility and adhesion in P. aeruginosa, above that of fleSR. We therefore propose the existence of a regulatory cascade which consists of at least two transcriptional regulators, FleQ and FleR, in the control of motility and adhesion in P. aeruginosa.


Common heritable effects underpin concerns over norm maintenance and in-group favoritism: evidence from genetic analyses of right-wing authoritarianism and traditionalism.
Research has shown that in-group favoritism is associated with concerns over the maintenance of social norms. Here we present two studies examining whether genetic factors underpin this association. A classical twin design was used to decompose phenotypic variance into genetic and environmental components in two studies. Study 1 used 812 pairs of adult U.S. twins from the nationally representative MIDUS II sample. Study 2 used 707 pairs of middle-age twins from the Minnesota Twin Registry. In-group favoritism was measured with scales tapping preferences for in-group (vs. out-group) individuals; norm concerns were measured with the Multidimensional Personality Questionnaire-Traditionalism (Study 1) and Right-Wing Authoritarianism (RWA; Study 2) scales. In Study 1, heritable effects underlying traditionalism were moderately (c. 35%) overlapping with the genetic variance underpinning in-group favoritism. In Study 2, heritable influences on RWA were entirely shared with the heritable effects on in-group favoritism. Moreover, we observed that Big Five Openness shared common genetic links to both RWA and in-group favoritism. These results suggest that, at the genetic level, in-group favoritism is linked with a system related to concern over normative social practices, which is, in turn, partially associated with trait Openness.


Convergent Structures Illuminate Features for Germline Antibody Binding and Pan-Lassa Virus Neutralization.
Lassa virus (LASV) causes hemorrhagic fever and is endemic in West Africa. Protective antibody responses primarily target the LASV surface glycoprotein (GPC), and GPC-B competition group antibodies often show potent neutralizing activity in humans. However, which features confer potent and broadly neutralizing antibody responses is unclear. Here, we compared three crystal structures of LASV GPC complexed with GPC-B antibodies of varying neutralization potency. Each GPC-B antibody recognized an overlapping epitope involved in binding of two adjacent GPC monomers and preserved the prefusion trimeric conformation. Differences among GPC-antibody interactions highlighted specific residues that enhance neutralization. Using structure-guided amino acid substitutions, we increased the neutralization potency and breadth of these antibodies to include all major LASV lineages. The ability to define antibody residues that allow potent and broad neutralizing activity, together with findings from analyses of inferred germline precursors, is critical to develop potent therapeutics and for vaccine design and assessment.


Korean guidelines for the diagnosis and management of dry eye: development and validation of clinical efficacy.
To evaluate the clinical efficacy of newly developed guidelines for the diagnosis and management of dry eye. This retrospective, multi-center, non-randomized, observational study included a total of 1,612 patients with dry eye disease who initially visited the clinics from March 2010 to August 2010. Korean guidelines for the diagnosis and management of dry eye were newly developed from concise, expert-consensus recommendations. Severity levels at initial and final visits were determined using the guidelines in patients with 90 ± 7 days of follow-up visits (n = 526). Groups with different clinical outcomes were compared with respect to clinical parameters, treatment modalities, and guideline compliance. Main outcome measures were ocular and visual symptoms, ocular surface disease index, global assessment by patient and physician, tear film break-up time, Schirmer-1 test score, ocular surface staining score at initial and final visits, clinical outcome after three months of treatment, and guideline compliance. Severity level was reduced in 47.37% of patients treated as recommended by the guidelines. Younger age (odd ratio [OR], 0.984; p = 0.044), higher severity level at initial visit, compliance to treatment recommendation (OR, 1.832; p = 0.047), and use of topical cyclosporine (OR, 1.838; p = 0.011) were significantly associated with improved clinical outcomes. Korean guidelines for the diagnosis and management of dry eye can be used as a valid and effective tool for the treatment of dry eye disease.


[Structual and functional dynamics of the ATP receptor channel P2X(2)].
ATP is known to function as a neurotransmitter. There are 2 major families of ATP receptors-the ion channel-type P2X receptors and metabotropic P2Y receptors. P2X receptors are known to possess unique properties of pore dilation that depends on the time lapse after ATP application; further, they exert their functions by directly interacting with nicotinic ACh receptors. These properties suggest the flexibility of the pore formed by these receptors. We studied the biophysical properties of P2X(2) receptor by using in vitro expression systems and focused on various dynamic regulations and structural rearrangements. Firstly, the pore property clearly depended on the expression levels of the P2X(2) receptors on the membrane. When the expression level was high, inward rectification was weak, and pore dilation was clearly observed. We also clarified that the key feature of the pore property is not the number of channels expressed but the number of open channels on the membrane. Secondly, we focused on the regulation of these channels by phosphoinositides (PIP(ns)). PIP(ns) are known to regulate the activity of various ion channels, but in the case of P2X(2), we observed that PIP(ns) regulate not only the activity but also the processes of pore dilation and desensitization. The binding of PIP(ns) to P2X(2) in the pore dilated state was observed to be less stable. Application of a reagent, which decreases the levels of PIP(ns), and mutation of the binding site facilitated desensitization of P2X(2) in the pore dilated state. Thirdly, we analyzed the voltage-dependent gating of these channels. Although P2X(2) lacks a canonical voltage-sensor domain, it undergoes voltage-dependent activation upon hyperpolarization. Further, we observed that the voltage-dependent gating depends on ATP concentration; conductance-voltage relationship curve shifted toward depolarization potential with increase in ATP concentration. We found that the ATP-binding site and the extracellular sideus of the transmembrane region were critical for the voltage-dependent gating. These results show that P2X(2) channel pore is exceptionally flexible, and that the channel activity is dynamically regulated by various factors, including not only ATP but also PIP(ns) and membrane potential.


Markedly Increased Mean Platelet Volume in Bacterial Meningitis.
Differentiating bacterial and viral meningitis is crucial, and this study explored the potential of mean platelet volume (MPV) as a marker for differentiation. Blood samples were collected from patients with central nerve system related manifestations, and MPV was tested. Cerebrospinal fluid samples were obtained and bacterial culture and the FilmArray ME panel were performed. The distribution of MPV was compared between groups. The study included 8 patients in the bacterial meningitis group and 12 patients in the viral meningitis group. The bacterial meningitis group showed a significantly higher median MPV of 10.9 (9.2 - 11.6) fL compared to the viral meningitis group with 8.4 (8.1 - 8.8) fL (p < 0.0001). MPV could serve as a diagnostic indicator to differentiate between bacterial and viral meningitis. Larger studies are needed to validate these findings.


Resistance to TGF-beta1 correlates with a reduction of TGF-beta type II receptor expression in Burkitt's lymphoma and Epstein-Barr virus-transformed B lymphoblastoid cell lines.
The pleiotropic cytokine TGF-beta1 is a member of a large family of related factors involved in controlling cell proliferation, differentiation and apoptosis. TGF-beta ligands interact with a complex of type I and type II transmembrane serine/threonine kinases and they transmit their signals to the nucleus via a family of Smad proteins. A panel of over 20 Burkitt's lymphoma (BL) cell lines has been compiled including those that are Epstein-Barr virus (EBV) negative, those that carry EBV with a restricted pattern of EBV latent gene expression (group I) and those that express the full range of latent EBV genes (group III), together with selected EBV-transformed lymphoblastoid cell lines (LCLs). Most of the EBV-negative and group I BL cell lines underwent apoptosis or a G(1) arrest in response to TGF-beta1 treatment. In contrast, group III cell lines and LCLs were completely refractory to these effects of TGF-beta1. All of the cell lines expressed the TGF-beta pathway Smads and the TGF-beta type I receptor. Lack of responsiveness to TGF-beta1 appears to correlate with a down-regulation of TGF-beta type II receptor expression. Studies of EBV-converted and stably transfected BL cell lines demonstrated that the EBV gene LMP-1 is neither necessary nor sufficient to block the TGF-beta1 response.


Alcohol and the Risk of Injury.
Globally, almost four and a half million people died from injury in 2019. Alcohol's contribution to injury-related premature loss of life, disability and ill-health is pervasive, touching individuals, families and societies throughout the world. We conducted a review of research evidence for alcohol's causal role in injury by focusing on previously published systematic reviews, meta-analyses and where indicated, key studies. The review summarises evidence for pharmacological and physiological effects that support postulated causal pathways, highlights findings and knowledge gaps relevant to specific forms of injury (i.e., violence, suicide and self-harm, road injury, falls, burns, workplace injuries) and lays out options for evidence-based prevention.


Two types of sensorimotor strategies for whole-body movement in individuals with stroke: a pilot study.
This study compared the sensory-motor interactions and strategies for whole-body movement in individuals with stroke who had damaged motor system area or sensory system area in the brain. Participants with hemiparesis were asked to perform sit-to-stand movements while their vision was restricted, which can affect completion of the task. The participants were divided into two groups. The first group had no history of lesions in the sensory system area but did have a history of lesions in the motor system area (no damaged sensory-system: NDS). The second group had a history of lesions in the sensory system area of the brain (damaged sensory-system: DS). Center-of-pressure (COP) trajectories were measured to evaluate balance control in participants with and without vision, and numbers of sub-movements (i.e. numbers of segmented movements which reflect the degree of use of the feedback loops) were measured to evaluate feedforward and feedback control. Movement times were also measured. When vision was restricted, NDS participants showed increased variability in mediolateral COP trajectories during movement and utilized mainly feedforward control. In contrast, DS participants showed reduced variability in mediolateral COP trajectories during movement and utilized additional feedback control. These results demonstrate two types of strategies for whole-body movements in individuals with stroke. These differences may be attributed to whether the individual can compensate for vision with somatic senses and whether appropriate processing of somatosensory information has been lost. Individuals with hemiparesis created dexterous and flexible strategies to execute tasks successfully, depending on the characteristics of their sensorimotor disorders.


Effects of enhanced adsorption haemofiltration versus haemoadsorption in severe, refractory septic shock with high levels of endotoxemia: the ENDoX bicentric, randomized, controlled trial.
Endotoxin adsorption is a promising but controversial therapy in severe, refractory septic shock and conflicting results exist on the effective capacity of available devices to reduce circulating endotoxin and inflammatory cytokine levels. Multiarm, randomized, controlled trial in two Swiss intensive care units, with a 1:1:1 randomization of patients suffering severe, refractory septic shock with high levels of endotoxemia, defined as an endotoxin activity ≥ 0.6, a vasopressor dependency index ≥ 3, volume resuscitation of at least 30 ml/kg/24 h and at least single organ failure, to a haemoadsorption (Toraymyxin), an enhanced adsorption haemofiltration (oXiris) or a control intervention. Primary endpoint was the difference in endotoxin activity at 72-h post-intervention to baseline. In addition, inflammatory cytokine, vasopressor dependency index and SOFA-Score dynamics over the initial 72 h were assessed inter alia. In the 30, out of 437 screened, randomized patients (10 Standard of care, 10 oXiris, 10 Toraymyxin), endotoxin reduction at 72-h post-intervention-start did not differ among interventions (Standard of Care: 12 [1-42]%, oXiris: 21 [10-51]%, Toraymyxin: 23 [10-36]%, p = 0.82). Furthermore, no difference between groups could be observed neither for reduction of inflammatory cytokine levels (p = 0.58), nor for vasopressor weaning (p = 0.95) or reversal of organ injury (p = 0.22). In a highly endotoxemic, severe, refractory septic shock population neither the Toraymyxin adsorber nor the oXiris membrane could show a reduction in circulating endotoxin or cytokine levels over standard of care. Trial registration ClinicalTrials.gov. NCT01948778. Registered August 30, 2013. https://clinicaltrials.gov/study/NCT01948778.


Recovery from high-intensity training sessions in female soccer players.
This study quantified the performance recovery time requirements after training sessions using high-intensity soccer drills with and without the ball in National Collegiate Athletic Association Division I female soccer players. Recovery time periods (24, 48, 72 hours of rest) from high-intensity soccer training sessions using drills with and without the ball were evaluated. Markers of recovery were each individual's performance relative to baseline performance in countermovement jump (CMJ) height, 5 bound jumps for distance (5BT), 20-m sprint (20SP), session rating of perceived effort (S-RPE), and heart rate (HR). Repeated-measures analysis of variance revealed a significant difference in CMJ performance (p < 0.04) and S-RPE (p < 0.02) after 24 hours of rest but not at 48 or 72 hours compared to baseline. There were no significant differences in 20SP, 5BT, or HR after 24, 48, or 72-hour recovery (p > 0.05). Therefore, high-intensity training drills produced a sufficient conditioning stimulus with little chance of underrecovery for the performance measures we tested. Countermovement jump and S-RPE may be more sensitive performance recovery indicators.


Small-angle x-ray scattering studies of metastable intermediates of beta-lactoglobulin isolated after heat-induced aggregation.
Small-angle x-ray scattering was used for studying intermediate species, isolated after heat-induced aggregation of the A variant of bovine beta-lactoglobulin. The intermediates were separated in two fractions, the heated metastable dimer and heated metastable oligomers larger than the dimer. The pair distance distribution functions for the two intermediate fractions as well as for the native protein have been obtained by indirect Fourier transformation. In addition, the scattering intensity data for samples of the native protein at different concentrations were fitted using a combination of monomer and dimer form factors, which provides an estimate of the amount of monomer in solutions. By subtracting the contribution from the monomer, the scattering intensity from the dimer of the native protein can be determined and compared with the results for the metastable dimer. An ellipsoidal model was used to fit the data for the metastable dimer, and for comparison the same analysis was performed on the dimer of the native protein. The results show that the metastable dimer is more elongated than the dimer of the native protein and it occupies a volume 1.4-fold larger, in agreement with a more loose, partially unfolded conformation. The same ellipsoidal model was used to analyze the data for the fraction of larger metastable oligomers. In this case, an even more elongated ellipsoid was obtained, suggesting a linear association of monomers in the oligomers.


Do societal wealth, family affluence and gender account for trends in adolescent cannabis use? A 30 country cross-national study.
To examine cross-national changes in frequent adolescent cannabis use (40+ times consumed over life-time at age 15) over time and relate these trends to societal wealth, family affluence and gender. Data from three cycles (2002, 2006, 2010) of the Health Behaviour in School-aged Children (HBSC) Study were used for cross-sectional and trend analyses of adolescent cannabis use. Representative surveys in 30 European and North American countries. A total of 160 606 15-year-old students. Respondents' life-time cannabis use, demographics, family affluence (FAS) and frequency of peer contacts were measured individually. Indicators of wealth (gross domestic product per capita, GDP) and perceived availability of cannabis were obtained from national public data bases. The frequency of life-time cannabis use decreased over time among adolescents in Europe and North America, particularly in western European countries and the United States (relative risk (RR) = 0.86: confidence interval (CI) 0.79-0.93). This trend was not observed consistently in rapidly developing countries in eastern, central and southern Europe. Over time (2002-10), cannabis use became: (i) less characteristic of high GDP countries in contrast to lower GDP countries (RR = 0.74: CI 0.57-0.95); (ii) less characteristic of youth from high FAS families in contrast to youth from low FAS families (RR = 0.83: CI 0.72-0.96); and (iii) characterized by an increasing gender gap, i.e. consumption was higher among males (RR 1.26: CI 1.04-1.53). Perceived availability of cannabis and peer contacts remained strong predictors of frequent cannabis use. Among 30 European and North American countries, cannabis use appears to have 'trickled down' over time, with developing countries taking on the former (heavier) use pattern of richer countries, and less affluent youth taking on the former (heavier) use pattern of more affluent youth. Cannabis use continues to be more common among adolescent males than females.


Activation of a novel metabolic gene regulatory pathway by chronic stimulation of skeletal muscle.
To determine whether expression of a nuclear gene encoding a mitochondrial fatty acid oxidation enzyme is regulated in parallel with skeletal muscle fibre-type-specific energy substrate preference, expression of the gene encoding medium-chain acyl-CoA dehydrogenase (MCAD) was delineated in canine latissimus dorsi muscle subjected to chronic motor nerve stimulation. In predominantly fast-twitch canine latissimus dorsi muscle, MCAD mRNA levels were regulated by chronic stimulation in a biphasic pattern. During the 1st wk of stimulation, steady-state MCAD mRNA levels decreased to 50% of unstimulated levels. MCAD mRNA levels began to increase during the 3rd wk of stimulation to reach a level 3.0-fold higher than levels in unstimulated contralateral control muscle by day 70. Immunodetectable MCAD mRNA levels throughout the stimulation period. The temporal pattern and magnitude of MCAD mRNA accumulation in response to muscle stimulation was distinct from that of mRNAs encoding other enzymes known to be regulated by this stimulus, including glyceraldehyde phosphate dehydrogenase, citrate synthase, and sarcoplasmic reticulum Ca-ATPase, but paralleled the protein levels of the peroxisome proliferator-activated receptor (PPAR), an orphan member of the nuclear hormone receptor superfamily known to regulate genes encoding fatty acid oxidation enzymes in liver. The skeletal muscle expression pattern of PPAR was also similar to that of MCAD in unstimulated rat skeletal muscles with distinct fiber-type compositions. These results demonstrate that a nuclear gene encoding a mitochondrial beta-oxidation enzyme is dynamically regulated in a pattern that parallels skeletal muscle fiber-type-specific energy substrate utilization and implicate an orphan nuclear receptor transcription factor as a candidate transducer of this response.


Plasmid-mediated 16S rRNA methylases conferring high-level aminoglycoside resistance in Escherichia coli and Klebsiella pneumoniae isolates from two Taiwanese hospitals.
This study was conducted to investigate the occurrence of 16S rRNA methylases that confer high-level aminoglycoside resistance in Klebsiella pneumoniae and Escherichia coli isolates from two Taiwanese hospitals and the characteristics of these isolates. A total of 1624 K. pneumoniae and 2559 E. coli isolates consecutively collected over an 18 month period from a university hospital and seven E. coli and eight K. pneumoniae isolates that were resistant to amikacin from a district hospital were analysed. Two 16S rRNA methylase genes, armA and rmtB, were detected by PCR-based assays. beta-Lactamase characteristics were determined by phenotypic and genotypic methods. Overall, 28 armA-positive and seven rmtB-positive isolates were identified, and extended-spectrum beta-lactamases (ESBLs) were detected in 33 (94.3%) isolates. The prevalence rates of armA and rmtB at the university hospital were 0.9% (n=15) and 0.3% (n=5) in K. pneumoniae and 0.4% (n=10) and 0.04% (n=1) in E. coli. CTX-M-3, CTX-M-14, SHV-5-like ESBLs, and CMY-2 were detected alone or in combination in 21, 6, 11, and 2, respectively, of the 28 armA-positive isolates. CTX-M-14 was detected in six of the seven rmtB-positive isolates. Fingerprinting of conjugative plasmids revealed the dissemination of closely related plasmids containing both armA and bla(CTX-M-3). PFGE suggests that armA and rmtB spread by both horizontal transfer and clonal spread. This is the first report of the emergence of 16S rRNA methylases in Enterobacteriaceae in Taiwan. The spread of the multidrug-resistant isolates producing both ESBLs and 16S rRNA methylases may become a clinical problem.


Polyphasic insights into the microbiomes of the Takamatsuzuka Tumulus and Kitora Tumulus.
Microbial outbreaks and related biodeterioration problems have affected the 1300-year-old multicolor (polychrome) mural paintings of the special historic sites Takamatsuzuka Tumulus (TT) and Kitora Tumulus (KT). Those of TT are designated as a national treasure. The microbiomes of these tumuli, both located in Asuka village, Nara, Japan, are critically reviewed as the central subject of this report. Using culture-dependent methods (conventional isolation and cultivation), we conducted polyphasic studies of the these microbial communities and identified the major microbial colonizers (Fusarium spp., Trichoderma spp., Penicillium spp., dark Acremonium spp., novel Candida yeast spp., Bacillus spp., Ochrobactrum spp., Stenotrophomonas tumulicola, and a few actinobacterial genera) and noteworthy microbial members (Kendrickiella phycomyces, Cephalotrichum verrucisporum (≡Doratomyces verrucisporus), Sagenomella striatispora, Sagenomella griseoviridis, two novel Cladophialophora spp., Burgoa anomala, one novel species Prototheca tumulicola, five novel Gluconacetobacter spp., three novel Bordetella spp., and one novel genus and species Krasilnikoviella muralis) involved in the biodeterioration of mural paintings, plaster walls, and stone chamber interiors. In addition, we generated microbial community data from TT and KT samples using culture-independent methods (molecular biological methods, including PCR-DGGE, clone libraries, and pyrosequence analysis). These data are comprehensively presented, in contrast to those derived from culture-dependent methods. Furthermore, the microbial communities detected using both methods are analytically compared, and, as a result, the complementary roles of these methods and approaches are highlighted. In related contexts, knowledge of similar biodeterioration problems affecting other prehistoric cave paintings, mainly at Lascaux in France and Altamira in Spain, are referred to and commented upon. Based on substrate preferences (or ecological grouping) and mapping (plotting detection sites of isolates), we speculate on the possible origins and invasion routes whereby the major microbial colonizers invaded the TT stone chamber interior. Finally, concluding remarks, lessons, and future perspectives based on our microbiological surveys of these ancient tumuli, and similar treasures outside of Japan, are briefly presented. A list of the microbial taxa that have been identified and fully or briefly described by us as known and novel taxa for TT and KT isolates since 2008 is presented in Supplementary Materials.


Comparison of Hospital Readmission After Total Hip and Total Knee Arthroplasty vs Spinal Surgery After Implementation of the Hospital Readmissions Reduction Program.
The Hospital Readmissions Reduction Program (HRRP) was recently expanded to penalize excessive readmissions after total hip arthroplasty (THA) and total knee arthroplasty (TKA). These are the first surgical procedures to be included in the HRRP. To determine whether the HRRP was associated with a greater decrease in readmissions after targeted procedures (THA and TKA) compared with similar nontargeted procedures (lumbar spine fusion and laminectomy). A retrospective cohort study was conducted of patients 50 years or older among all payers in the Nationwide Readmissions Database who underwent THA, TKA, lumbar spine fusion, or laminectomy between January 1, 2010, and September 30, 2015. Multivariable logistic regression and interrupted time-series models were used to calculate and compare 30-day readmission trends in 3 periods associated with the HRRP: preimplementation (January 2010-September 2012), implementation (October 2012-September 2014), and penalty (October 2014-September 2015). Statistical analysis was performed from January 1, 2010, to September 30, 2015. Announcement and implementation of the HRRP. Readmission within 30 days after hospitalization for THA, TKA, lumbar spine fusion, or laminectomy surgery. The study included 6 687 077 (58.3% women and 41.7% men; mean age, 66.7 years; 95% CI, 66.7-66.8 years) weighted hospitalizations for THA, TKA, lumbar spine fusion, and laminectomy surgery: 4 765 466 hospitalizations for targeted conditions and 1 921 611 for nontargeted conditions. After passage of the Patient Protection and Affordable Care Act, the risk-adjusted rates of readmission after all procedures decreased in a similar fashion. Implementation of the HRRP was associated with a 0.018% per month decrease in the rate of readmission (95% CI, -0.025% to -0.010%) after targeted procedures, which was not observed after nontargeted procedures (slope per month, -0.003%; 95% CI, -0.016% to 0.010%). Penalties were not associated with a greater decrease in readmission for either targeted or nontargeted procedures. These results appear to be consistent with hospitals responding to the future possibility of penalties by reducing readmissions after surgical procedures targeted by the HRRP.


The effect of clinical simulation assessment on stress and anxiety measures in emergency care students.
Clinical simulation has become widespread as a training and assessment tool across a range of health professions, including emergency care. As with any form of assessment, simulations may be associated with stress and anxiety ("distress") which may have a negative effect on student performance if demands required by the simulation outweigh the available resources. This study aimed to assess the effect of participation by students in an emergency care simulation on an objective measure of stress and a subjective measure of anxiety. Heart rate variability (HRV) and scores from a validated state anxiety instrument (the State-Trait Anxiety Inventory) were assessed in 36 emergency medical care students participating in scheduled simulation assessments. Data recorded during a resting control period were used for comparison. HRV variables showed changes in the simulation assessment group suggesting decreased variability and parasympathetic withdrawal, however these were not significantly different to control. Heart rate in the simulation assessment group increased significantly (73.5/min vs. 107.3/min, p < 0.001). State anxiety scores increased significantly both before (33.5 vs. 49.1, p < 0.001) and after (33.5 vs. 60, p < 0.001) the simulation assessment, compared to control. No linear relationship was found between any HRV variables and anxiety scores. Participating in an emergency care simulation assessment significantly elevated levels of anxiety in a group of 36 students, however an objective measure of stress did not identify changes significantly different to those at rest, with the exception of heart rate. The high levels of anxiety documented before and after simulation assessments may have a negative effect on performance and require further investigation.


Treatment of unawareness of deficits in patients with acquired brain injury: a systematic review.
To review and evaluate the effectiveness and methodological quality of available treatment methods for unawareness of deficits after acquired brain injury (ABI). Systematic literature search for treatment studies for unawareness of deficits after ABI. Information concerning study content and reported effectiveness was extracted. Quality of the study reports and methods were evaluated. A total of 471 articles were identified; 25 met inclusion criteria. 16 were uncontrolled or single-case studies. Nine were of higher quality: 2 randomized controlled trials, 5 single case experimental designs, 1 single-case design with pre- and posttreatment measurement, and 1 quasi-experimental controlled design. Overall, interventions consisted of multiple components including education and multimodal feedback on performance. Five of the 9 high-quality studies reported a positive effect of the intervention on unawareness in patients with some knowledge of their impairments. Effect sizes ranged from questionable to large. Patients with ABI may improve their awareness of their disabilities and possibly attain a level at which they personally experience problems when they occur. At present, because of lack of evidence, no recommendation can be made for treatment approaches for persons with severe impairment of self-awareness in the chronic phase of ABI. We recommended developing and evaluating theory-driven interventions specifically focused on disentangling the components of treatment that are successful in improving awareness. High-quality intervention studies are urgently needed using controlled designs (eg, single-case experimental designs, randomized controlled trials) based on a theoretic perspective with a detailed description of the content of the intervention and suitable outcome measures.


Vestibular Stimulus and Perceived Roll Tilt During Coordinated Turns in Aircraft and Gondola Centrifuge.
One disorienting movement pattern, common during flight, is the entering of a coordinated turn. While the otoliths persistently sense upright head position, the change in roll attitude constitutes a semicircular canal stimulus. This sensory conflict also arises during acceleration in a swing-out gondola centrifuge. From a vestibular viewpoint there are, however, certain differences between the two stimulus situations; the aim of the present study was to elucidate whether these differences are reflected in the perceived roll attitude. Eight nonpilots were tested in a centrifuge (four runs) and during flight (two turns). The subjective visual horizontal (SVH) was measured using an adjustable luminous line in darkness. The centrifuge was accelerated from stationary to 1.56 G (roll 50°) within 7 s; the duration of the G plateau was 5 min. With the aircraft, turns with approximately 1.4 G (45°) were entered within 15 s and lasted for 5 min. Tilt perception (TP) was defined as the ratio of SVH/real roll tilt; initial and final values were calculated for each centrifugation/turn. In both systems there was a sensation of tilt that declined with time. The initial TP was (mean ± SD): 0.40 ± 0.27 (centrifuge) and 0.37 ± 0.30 (flight). The final TP was 0.20 ± 0.26 and 0.17 ± 0.19, respectively. Both initial and final TP correlated between the two conditions. The physical roll tilt is under-estimated to a similar degree in the centrifuge and aircraft. Also the correspondence at the individual level suggests that the vestibular dilemma of coordinated flight can be recreated in a lifelike manner using a gondola centrifuge.


100 YEARS OF INSULIN: Towards improved precision and a new classification of diabetes mellitus.
Type 2 diabetes (T2D) is one of the fastest increasing diseases worldwide. Although it is defined by a single metabolite, glucose, it is increasingly recognized as a highly heterogeneous disease with varying clinical manifestations. Identification of different subtypes at an early stage of disease when complications might still be prevented could hopefully allow for more personalized medicine. An important step toward precision medicine would be to target the right resources to the right patients, thereby improving patient health and reducing health costs for the society. More well-defined disease populations also offer increased power in experimental, genetic and clinical studies. In a recent study, we used six clinical variables (glutamate decarboxylase autoantibodies, age at onset of diabetes, glycated hemoglobin, BMI and simple measures of insulin resistance and insulin secretion (so called HOMA estimates) to cluster adult-onset diabetes patients into five subgroups. These subgroups have been robustly reproduced in several populations worldwide and are associated with different risks of diabetic complications and responses to treatment. Importantly, the group with severe insulin-deficient diabetes had increased risk of retinopathy and neuropathy, whereas the severe insulin-resistant diabetes group has the highest risk for diabetic kidney disease (DKD) and fatty liver. This emphasizes the key role of insulin resistance in the pathogenesis of DKD and fatty liver in T2D. In conclusion, this novel subclassification, breaking down T2D in clinically meaningful subgroups, provides the prerequisite framework for expanded personalized medicine in diabetes beyond what is already available for monogenic and to some extent type 1 diabetes.


Occurrence and fate of pesticides in four contrasting agricultural settings in the United States.
Occurrence and fate of 45 pesticides and 40 pesticide degradates were investigated in four contrasting agricultural settings--in Maryland, Nebraska, California, and Washington. Primary crops included corn at all sites, soybeans in Maryland, orchards in California and Washington, and vineyards in Washington. Pesticides and pesticide degradates detected in water samples from all four areas were predominantly from two classes of herbicides--triazines and chloroacetanilides; insecticides and fungicides were not present in the shallow ground water. In most samples, pesticide degradates greatly exceeded the concentrations of parent pesticide. In samples from Nebraska, the parent pesticide atrazine [6-chloro-N-ethyl-N'-(1-methylethyl)-1,3,5-triazine-2,4-diamine] was about the same concentration as the degradate, but in samples from Maryland and California atrazine concentrations were substantially smaller than its degradate. Simazine [6-chloro-N,N'-diethyl-1,3,5-triazine-2,4-diamine], the second most detected triazine, was detected in ground water from Maryland, California, and Washington. Metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl)acetamide] rarely was detected without its degradates, and when they were detected in the same sample metolachlor always had smaller concentrations. The Root-Zone Water-Quality Model was used to examine the occurrence and fate of metolachlor at the Maryland site. Simulations accurately predicted which metolachlor degradate would be predominant in the unsaturated zone. In analyses of relations among redox indicators and pesticide variance, apparent age, concentrations of dissolved oxygen, and excess nitrogen gas (from denitrification) were important indicators of the presence and concentration of pesticides in these ground water systems.


Persist or Produce: A Community Trade-Off Tuned by Species Evenness.
Understanding the effects of biodiversity on community persistence and productivity is key to managing both natural and production systems. Because rare species face greater danger of extinction, species evenness, a measure of how similar abundances are across species in a community, is seen as a key component of biodiversity. However, previous studies have failed to find a consistent association of species evenness with species survival and biomass production. Here we provide a theoretical framework for the relationship among these three elements. We demonstrate that the lack of consistent outcomes is not an idiosyncratic artifact of different studies but can be unified under one common framework. Applying a niche theory approach, we confirm that under demographic stochasticity evenness is a general indicator of the risk of future species extinctions in a community, in accordance with the majority of empirical studies. In contrast, evenness cannot be used as a direct indicator of the level of biomass production in a community. When a single species dominates, as expressed by the constraints imposed by the population dynamics, biomass production depends on the niche position of the dominating species and can increase or decrease with evenness. We demonstrate that high species evenness and an intermediate level of biomass production is the configuration that maximizes the average species survival probability in response to demographic stochasticity.


A numerical method to predict the effects of frequency-dependent attenuation and dispersion on speed of sound estimates in cancellous bone.
Many studies have demonstrated that time-domain speed-of-sound (SOS) measurements in calcaneus are predictive of osteoporotic fracture risk. However, there is a lack of standardization for this measurement. Consequently, different investigators using different measurement systems and analysis algorithms obtain disparate quantitative values for calcaneal SOS, impairing and often precluding meaningful comparison and/or pooling of measurements. A numerical method has been developed to model the effects of frequency-dependent attenuation and dispersion on transit-time-based SOS estimates. The numerical technique is based on a previously developed linear system analytic model for Gaussian pulses propagating through linearly attenuating, weakly dispersive media. The numerical approach is somewhat more general in that it can be used to predict the effects of arbitrary pulse shapes and dispersion relationships. The numerical technique, however, utilizes several additional assumptions (compared with the analytic model) which would be required for the practical task of correcting existing clinical databases. These include a single dispersion relationship for all calcaneus samples, a simple linear model relating phase velocity to broadband ultrasonic attenuation, and a constant calcaneal thickness. Measurements on a polycarbonate plate and 30 human calcaneus samples were in good quantitative agreement with numerical predictions. In addition, the numerical approach predicts that in cancellous bone, frequency-dependent attenuation tends to be a greater contributor to variations in transit-time-based SOS estimates than dispersion. This approach may be used to adjust previously acquired individual measurements so that SOS data recorded with different devices using different algorithms may be compared in a meaningful fashion.


Psoriasis: Keratinocytes or Immune Cells - Which Is the Trigger?
Psoriasis is a common, chronic inflammatory skin disorder, which can significantly impact quality of life. Despite major breakthroughs in our understanding of the pathogenesis of psoriasis, the chronological order of the underlying mechanisms leading to the development of psoriatic plaques remains to be completely understood. Although psoriasis is classically perceived as a T-cell disease, it is now well recognized that T lymphocytes do not function in exclusivity. This theory is supported by evidence from transgenic murine models that develop marked psoriasiform disease. In addition, immune cells and cytokines regulate both early and late events involved in the pathogenesis of psoriasis. Key Messages: Psoriasis is a complex disease - a dynamic interplay between immune cells, keratinocytes, and various other skin-resident cells, such as endothelial and immune cells. The contribution of each cell type is crucial in the initiation and maintenance phases of psoriatic alterations.


Cis-regulation downstream of cell type specification: a single compact element controls the complex expression of the CyIIa gene in sea urchin embryos.
CyIIa, a cytoskeletal actin gene of Strongylocentrotus purpuratus, is expressed specifically though transiently in the embryonic skeletogenic and secondary mesenchyme and, later in development, is permanently activated in the hindgut and midgut. CyIIa transcription follows, and is therefore downstream of, the initial specification of these embryonic domains. A detailed functional analysis of the cis-regulatory system governing the rate and the location of CyIIa expression during development was carried out using GFP expression constructs. About 4.4 kb of CyIIa sequence including a leader intron were examined for cis-regulatory function. Distal elements scattered over several kb account for 60% of the quantitative output of the expression construct and a strong amplifier of expression is located within the leader intron. However, the complex spatial pattern of CyIIa expression is completely reproduced by a compact upstream regulatory element <450 bp in length. We found no evidence anywhere in the 4.4 kb sequence examined for negative regulators required to repress ectopic expression. The specific site that mediates CyIIa expression in the midgut in late embryos and larvae was identified. This site is the same as that necessary and sufficient for midgut expression of the Endo16 gene late in development, and was shown to bind the same transcription factor. Except for some temporal and quantitative features, the S. purpuratus expression construct is expressed accurately and specifically in the same diverse cell types when introduced into embryos of Lytechinus pictus, which belongs to a different echinoid order. No ectopic expression was observed, in contrast to the result of a similar interspecific gene transfer experiment carried out earlier on a different cytoskeletal actin gene that is expressed much earlier in development. Presentation of the set of transcription factors that activate CyIIa in the differentiated cells in which it is expressed is apparently a conserved feature of these cell types.


Intrapelvic migration of a Kirschner wire.
Intrapelvic migration of a Kirschner wire, used in the treatment of hip fracture, is rare. We report a case of intrapelvic migration of a Kirschner wire 10 years after its placement. Even though the patient was asymptomatic, we proceeded to remove the migrated wire using laparoscopic techniques. Given the increasing number of hip operations being performed, and given that intrapelvic foreign bodies can result in serious or fatal complications, it is important to keep this problem in mind in patients who have had previous hip surgery.


[The neurological manifestations of blast trauma to the brain].
The article describes mechanisms of cerebral injuries and clinical symptomatology of light and medium trauma. It is stressed that a certain succession in medical and diagnostical measures must be observed, as well as physicians of several medical specialties must participate in the treatment of such cases. There is a description of morphological picture of cerebrum in this type of trauma. The article also shows pathogenetical and clinical differences between burst and mechanical brain injuries.


Year-round reproduction and induced spawning of Chinese amphioxus, Branchiostoma belcheri, in laboratory.
Amphioxus is a best candidate for studying the evolutionary and developmental mechanisms of vertebrates, because of its vertebrate-like but much simpler morphology, embryonic development and genome structure. Producing live amphioxus embryos throughout the year is an ideal for comparative evolution and developmental studies. However, all amphioxus species have distinct breeding seasons in the wild and laboratory. We recently found that Chinese amphioxus B. belcheri could reproduce repeatedly beyond its natural breeding season when reared under proper conditions. In this study, we were able to extend further and produce embryos throughout the year from October 2011 to October 2012. We found all examined animals had spawned repeatedly during the examined period. In addition, both lancelets B. belcheri and B. japonicum could be induced to spawn by heat-shock method, although the induced spawning efficiency was not as high as that observed in the European lancelet. In general, we have succeeded in producing B. belcheri embryos almost daily throughout the year. This advancement will provide essential embryonic material for evolutionary and developmental studies, and have great implications for the cultivation and spawning induction of other amphioxus species.


Implant-retained auricular prostheses: an assessment of implant success and prosthetic complications.
The aims of this study were to evaluate the success rates and peri-implant soft tissue responses of auricular implants, to assess prosthetic complications, and to calculate the survival rate of silicone auricular prostheses. Twenty-nine extraoral implants were placed in 10 patients with 11 auricular defects. Implant failure was defined as clinically detectable implant mobility, and a 5-point scale was used to record the health of peri-implant soft tissues. Prosthetic complications were assessed, and the survival rate of silicone auricular prostheses was calculated using Kaplan-Meier analysis. The implant success rate was 100%. A few soft tissue problems were noted. The overall cumulative survival rate for the first prostheses of the patients was 70% after 18 months. The mean survival time was 17 months. Extraoral implants had a very high success rate in the mastoid region. Prosthetic assessment indicated that although experience with wearing prostheses reduces retention degradation, discoloration and reduced quality of fit at the prosthesis edge over time remain the major problems in maxillofacial prosthetics.


[Effect of hypothermia and anti-angina preparations with malonate-like action on myocardial glycolysis and oxidative phosphorylation].
It has been discovered that hypothermia under 20 degrees C produces no effect on the reactions of anaerobic glycolysis and lactate level in the rat and dog myocardium during ischemia and anoxia. At the same time hypothermia reduces 8-10-fold the rate of free and conjugated mitochondrial respiration, which is similar to the malonate-like action of a number of antianginal drugs. Based on the fact that hypothermia protects the tissues from ischemic lesions it is concluded that inhibition of mitochondrial respiration with the drugs having a malonate-like action or with other mechanisms is to also protect the myocardium at early times of acute ischemia.


State-of-the-art magnetic resonance imaging of the kidneys and upper urinary tract.
State-of-the-art magnetic resonance imaging (MRI) is an excellent examination in several clinical contexts of interest to endourologists. First, it offers a one-stop imaging examination of prospective renal donors, obviating the need for arteriography and conventional excretory urography. Second, it reliably depicts urinary tract obstruction and can usually distinguish acute from chronic obstruction, although it is not as sensitive as helical CT in detecting small, nonobstructing stones. Third, it is an excellent examination for characterizing renal masses, especially complex cystic masses, and for surgical planning. Because MRI does not use ionizing radiation and because gadolinium contrast agents are essentially non-nephrotoxic, MRI is especially useful in children, women of childbearing age, and patients with renal insufficiency or renal allografts. Future developments will likely include MR "fluoroscopy," which will provide real-time imaging guidance for interventional procedures in the urinary tract.


HIV-1 Rev protein specifies the viral RNA export pathway by suppressing TAP/NXF1 recruitment.
Nuclear RNA export pathways in eukaryotes are often linked to the fate of a given RNA. Therefore, the choice of export pathway should be well-controlled to avoid an unfavorable effect on gene expression. Although some RNAs could be exported by more than one pathway, little is known about how the choice is regulated. This issue is highlighted when the human immunodeficiency virus type 1 (HIV-1) Rev protein induces the export of singly spliced and unspliced HIV-1 transcripts. How these RNAs are exported is not well understood because such transcripts should have the possibility of utilizing CRM1-dependent export via Rev or cellular TAP/NXF1-dependent export via the transcription/export (TREX) complex, or both. Here we found that Rev suppressed TAP/NXF1-dependent export of model RNA substrates that recapitulated viral transcripts. In this effect, Rev interacted with the cap-binding complex and inhibited the recruitment of the TREX complex. Thus, Rev controls the identity of the factor occupying the cap-proximal region that determines the RNA export pathway. This ribonucleoprotein remodeling activity of Rev may favor viral gene expression.


Transcervical Carotid Stent Placement in the Setting of a Hostile Neck and a Type III Aortic Arch.
Previous radical neck dissection and neck irradiation pose considerable operative risks in patients requiring carotid endarterectomy for symptomatic carotid disease. Carotid stenting is an acceptable alternative for these patients but carries a higher risk of cerebrovascular accidents especially in patients with type III aortic arch anatomy. Herein, we present a technically challenging case of a patient with an irradiated neck and a history of radical neck dissection who presented with a symptomatic high-grade left internal carotid artery stenosis in the setting of a type III aortic arch. He was treated via a hybrid approach for carotid artery stenting.


Dried plums and their products: composition and health effects--an updated review.
This paper describes composition of dried plums and their products (prune juice and dried plum powder) with special attention to possibly bioactive compounds. Dried plums contain significant amounts of sorbitol, quinic acid, chlorogenic acids, vitamin K1, boron, copper, and potassium. Synergistic action of these and other compounds, which are also present in dried plums in less conspicuous amounts, may have beneficial health effects when dried plums are regularly consumed. Snacking on dried plums may increase satiety and reduce the subsequent intake of food, helping to control obesity, diabetes, and related cardiovascular diseases. Despite their sweet taste, dried plums do not cause large postprandial rise in blood glucose and insulin. Direct effects in the gastrointestinal tract include prevention of constipation and possibly colon cancer. The characteristic phenolic compounds and their metabolites may also act as antibacterial agents in both gastrointestinal and urinary tracts. The indirect salutary effects on bone turnover are supported by numerous laboratory studies with animals and cell cultures. Further investigation of phenolic compounds in dried plums, particularly of high molecular weight polymers, their metabolism and biological actions, alone and in synergy with other dried plum constituents, is necessary to elucidate the observed health effects and to indicate other benefits.


An Emerging Role of Extracellular Traps in Chronic Rhinosinusitis.
Chronic rhinosinusitis (CRS) is a complicated, heterogeneous disease likely caused by inflammatory and infectious factors. There is clear evidence that innate immune cells, including neutrophils and eosinophils, play a significant role in CRS. Multiple immune cells, including neutrophils and eosinophils, have been shown to release chromatin and granular proteins into the extracellular space in response to triggering extracellular traps (ETs). The formation of ETs remains controversial due to their critical function during pathogen clearance while being associated with harmful inflammatory illnesses. This article summarizes recent research on neutrophil extracellular traps (NETs) and eosinophil extracellular traps (EETs) and their possible significance in the pathophysiology of CRS. A novel type of programmed cell death called ETosis, which releases ETs, has been proposed by recent study. Significantly more NETs are presented in nasal polyps, and its granule proteins LL-37 induce NETs production in CRS with nasal polyps (CRSwNP) patients. Similar to NETs, developed in the tissue of nasal polyps, primarily in subepithelial regions with epithelial barrier defects, and are associated with linked to elevated tissue levels of IL-5 and S. aureus colonization. This article provides a comprehensive overview of NETs and EETs, as well as an in-depth understanding of the functions of these ETs in CRS.


Changes in Cannabis Use Risk Behaviors during the First and Second COVID-19 Lockdown in Israel: A Short-term 2-wave Longitudinal Study.
The COVID-19 pandemic, and stringent lockdown measures implemented to curb transmission, might be related to increased cannabis use risk behaviors. This rapid response short-term longitudinal study investigated predictors of increased cannabis use risk behaviors and their association with severity of cannabis dependence during 2 separate COVID-19 lockdown periods. Analyses were based on data from 116 monthly cannabis users who responded to 2 survey waves, corresponding to the first and the second lockdown periods in Israel. Multinomial regressions predicted risk of increased cannabis use, solitary use, and morning use during 1 or both of the lockdown periods as a function of sociodemographic factors and coping motives. Robust regression analyses assessed whether changes in cannabis use risk behaviors predicted severity of cannabis dependence at wave 2. A substantial proportion reported increased cannabis use, solitary use, and use before noon during both lockdown periods. Coping motives were related to reported increases in cannabis use and more frequent use before noon at 1 and both lockdown periods. Respondents who reported increases in cannabis use and use before noon at both lockdown periods, but not those who reported increases at only 1 lockdown period, had more severity of cannabis dependence at wave 2. The COVID-19 pandemic is likely to have ongoing and long-term effects on the health of the population, including those related to increased cannabis use risk behaviors. Continued monitoring of individual differences and long-term changes in cannabis use is needed to assess consequences of lockdown restrictions.


Polylinker-encoded peptides can confer toxicity to recombinant proteins produced in Escherichia coli.
Three DNA segments encoding fragments of the p60 capsid protein of rabbit haemorrhagic disease virus (RHDV) have been cloned and expressed in Escherichia coli. The cDNAs were placed under the control of the T7 promoter in a pET-derived expression vector designed to produce C-terminal histidine tail fusions. By using different cloning strategies, cell toxicity exhibited by some of the expressed products was dramatically affected, coincident with minor modifications in the carboxy terminus sequences of the recombinant proteins. In particular, the presence of a nonhydrophobic peptide encoded by polylinker sequences promotes cell death and a reduced yield after induction of gene expression, whereas a histidine tail has no detectable effect. These data point out the critical role that needless peptide tails, accidentally introduced into recombinant proteins by nonrelevant DNA stretches, can have on protein expression and final yield of a production process.