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Aims Past research suggests that people report a greater desire to consume alcohol when they experience social threat—or threats to their social selves, such as social exclusion. Nevertheless, experimental research on the role of social threat in alcohol consumption is limited. The present study examined the causal relationship between social threat and wine consumption. Methods Undergraduate students (N = 83; Mage = 21.8 years old, SDage = 1.62 years old; 72.3% women; 61.4% Latinx/Hispanic) participated in a study under the pretense that they were in a focus group gauging students’ opinions of a bar being constructed at their university. During the study, participants and two confederate researchers completed a group activity in which they selected design elements for the bar. Participants were randomly assigned to one of two conditions. In the social threat condition, confederates rejected participants’ design choices and socially excluded them during a follow-up task. In the social acceptance condition, confederates supported participants’ choices and did not socially exclude them. All participants then completed a wine taste test. Results Contrary to predictions, an independent-samples t-test revealed that participants who experienced social threat consumed significantly less wine than those who were socially accepted, t(81) = −2.22, P = 0.03, d = −0.49. Furthermore, a linear regression test revealed that this effect persisted even when controlling for typical alcohol-consumption behavior, b = 56.09, t = −2.50, P = 0.02, d = −0.61. Conclusion The relationship between social threat and alcohol consumption may be more nuanced than anticipated. Discussion centers around two potential moderators including positive affect and identity.

Aim Phenomena within the psychosis continuum that varies in frequency/duration/intensity have been increasingly identified. Different terms describe these phenomena, however there is no standardization within the terminology. This review evaluated the definitions and assessment tools of seven terms - (i) 'psychotic experiences'; (ii) 'psychotic-like experiences'; (iii) 'psychotic-like symptoms'; (iv) 'attenuated psychotic symptoms'; (v) 'prodromal psychotic symptoms'; (vi) 'psychotic symptomatology'; and (vii) 'psychotic symptoms'. Methods EMBASE, MEDLINE, and CINAHL were searched during February-March 2019. Inclusion criteria included 1989-2019, full text, human, and English. Papers with no explicit definition or assessment tool, duplicates, conference abstracts, systematic reviews, meta-analyses, or no access were excluded. Results A total of 2238 papers were identified and of these, 627 were included. Definitions and assessment tools varied, but some trends were found. Psychotic experiences and psychotic-like experiences were transient and mild, found in the general population and those at-risk. Psychotic-like symptoms were subthreshold and among at-risk populations and non-psychotic mental disorders. Attenuated psychotic symptoms were subthreshold but associated with distress, risk, and help-seeking. Prodromal psychotic symptoms referred to the prodrome of psychotic disorders. Psychotic symptomatology included delusions and hallucinations within psychotic disorders. Psychotic symptoms was the broadest term, encompassing a range of populations but most commonly involving hallucinations, delusions, thought disorder, and disorganization. Discussion A model for conceptualizing the required terms is proposed and future directions needed to advance this field of research are discussed.

Osteoarthritis (OA) is a leading cause of chronic disability. It is a progressive disease, involving pathological changes to the entire joint, resulting in joint pain, stiffness, swelling, and loss of mobility. There is currently no disease-modifying pharmaceutical treatment for OA, and the treatments that do exist suffer from significant side effects. An increasing understanding of the molecular pathways involved in OA is leading to many potential drug targets. However, both current and new therapies can benefit from a targeted approach that delivers drugs selectively to joints at therapeutic concentrations, while limiting systemic exposure to the drugs. Delivery systems including hydrogels, liposomes, and various types of particles have been explored for intra-articular drug delivery. This review will describe progress over the past several years in the development of polymer-based particles for OA treatment, as well as their in vitro, in vivo, and clinical evaluation. Systems based on biopolymers such as polysaccharides and polypeptides, as well as synthetic polyesters, poly(ester amide)s, thermoresponsive polymers, poly(vinyl alcohol), amphiphilic polymers, and dendrimers will be described. We will discuss the role of particle size, biodegradability, and mechanical properties in the behavior of the particles in the joint, and the challenges to be addressed in future research.

BackgroundThe large volume and suboptimal image quality of portable chest X-rays (CXRs) as a result of the COVID-19 pandemic could post significant challenges for radiologists and frontline physicians. Deep-learning artificial intelligent (AI) methods have the potential to help improve diagnostic efficiency and accuracy for reading portable CXRs.PurposeThe study aimed at developing an AI imaging analysis tool to classify COVID-19 lung infection based on portable CXRs.Materials and methodsPublic datasets of COVID-19 (N = 130), bacterial pneumonia (N = 145), non-COVID-19 viral pneumonia (N = 145), and normal (N = 138) CXRs were analyzed. Texture and morphological features were extracted. Five supervised machine-learning AI algorithms were used to classify COVID-19 from other conditions. Two-class and multi-class classification were performed. Statistical analysis was done using unpaired two-tailedttests with unequal variance between groups. Performance of classification models used the receiver-operating characteristic (ROC) curve analysis.ResultsFor the two-class classification, the accuracy, sensitivity and specificity were, respectively, 100%, 100%, and 100% for COVID-19 vs normal; 96.34%, 95.35% and 97.44% for COVID-19 vs bacterial pneumonia; and 97.56%, 97.44% and 97.67% for COVID-19 vs non-COVID-19 viral pneumonia. For the multi-class classification, the combined accuracy and AUC were 79.52% and 0.87, respectively.ConclusionAI classification of texture and morphological features of portable CXRs accurately distinguishes COVID-19 lung infection in patients in multi-class datasets. Deep-learning methods have the potential to improve diagnostic efficiency and accuracy for portable CXRs.

Certain migrant groups have been identified as being at increased risk of developing a psychotic disorder, but there is limited research on the outcomes for migrants who develop a first episode of psychosis (FEP). We investigated symptomatic outcomes (remission and relapse rates), functional outcomes (occupational status and relationships) and service utilization (hospital admission and engagement).Young people, aged between 15 and 24, who presented with FEP to the Early Psychosis Prevention and Intervention Centre (EPPIC) at Orygen between 01.01.11 and 31.12.16 were included. Place of birth was recorded at the time of presentation. To determine remission, symptoms were scored at three-month intervals using the short-form Scale for the Assessment of Positive Symptoms.A total of 1220 young people presented with FEP over the six-year period (mean age = 19.6 ± 2.8). Of these, 58.1% were male and 24.0% were first-generation migrants. While there was no difference in overall rates of admission after presentation, migrants were more likely to have an involuntary admission after presentation (31.4% vs. 24.6%, aHR = 1.54, 95% CI [1.19, 2.01]) and this risk was greatest for African migrants (HR = 1.98, 95% C.I. [1.37, 2.86]. The rates of remission and relapse were similar in migrants and those born in Australia and there was no difference in functional outcomes, such as employment rates at follow-up.The outcomes for migrants who experience FEP appear to be largely similar to those for the Australian-born population. Our finding that a greater rate of involuntary admission for migrants at presentation supports existing literature and needs further exploration to improve clinical care.

The existence of an implicit living microscopic world, composed primarily of bacteria, has been known for centuries. The exact mechanisms that govern the contribution of bacteria to human health and disease have only recently become the subject of intense research efforts. Within this very evident shift in paradigms, the rational design of probiotic formulations has led to the creation of an industry that seeks to progress the engineering of probiotic bacteria that produce metabolites that may enhance human host health and prevent disease. The promotion of probiotics is often made in the absence of quality scientific and clinically plausible data. The latest incursions into the probiotic market of claims have posited the amelioration of oxidative stress via potent antioxidant attributes or limiting the administration of probiotics to those species that do not produce D-Lactic acid (i.e., claims that D-Lactic acid acidosis is linked to chronic health conditions) or are strain-specific (shaping an industry point of difference) for appraising a therapeutic effect. Evidence-based research should guide clinical practice, as there is no place in science and medicine that supports unsubstantiated claims. Extravagant industry based notions continue to fuel the imprimatur of distrust and skepticism that is leveled by scientists and clinicians at an industry that is already rife with scientific and medical distrust and questionable views on probiotics. Ignoring scientifically discordant data, when sorting through research innovations and false leads relevant to the actions of probiotics, drives researcher discomfit and keeps the bar low, impeding the progress of knowledge. Biologically plausible posits are obligatory in any research effort; companies formulating probiotics often exhibit a lack of analytical understanding that then fuels questionable investigations failing to build on research capacity.

Clinical Practice Guidelines are succinct evidence-based recommendations and in psychiatry, exist to advise on psychotropic prescribing to effectively treat mental health conditions whilst minimising medication adverse effects. Implementation of psychiatric guidelines have, in the past, demonstrated little and transient impact on clinical practice. How effective prescribing guidelines are in aligning practice with evidence currently is unknown and this systematic review aimed to investigate said efficacy. Literature searches were performed on MEDLINE, EMBASE, and CINAHL up to September 2019 and articles were selected by two reviewers independently with discrepancies resolved by a third reviewer. The review identified 18 eligible articles pertaining to the following conditions: depressive disorders, psychotic disorders, post-traumatic stress disorder, anxiety disorders, bipolar affective disorder, attention deficit/hyperactivity disorder, borderline personality disorder, and opiate addiction with depression guidelines being the most frequently evaluated. Seven studies revealed guidelines effected no change in psychotropic prescribing. The remaining studies illustrated that even when practice was changed, the effect was generally small, emphasising the need to change guideline development and implementation, taking into account obstacles or opportunities specific to psychotropic pharmacotherapy.

The sodium hydrogen exchanger isoform one (NHE1) plays a critical role coordinating asymmetric events at the leading edge of migrating cells and is regulated by a number of phosphorylation events influencing both the ion transport and cytoskeletal anchoring required for directed migration. Lysophosphatidic acid (LPA) activation of RhoA kinase (Rock) and the Ras-ERK growth factor pathway induces cytoskeletal reorganization, activates NHE1 and induces an increase in cell motility. We report that both Rock I and II stoichiometrically phosphorylate NHE1 at threonine 653 in vitro using mass spectrometry and reconstituted kinase assays. In fibroblasts expressing NHE1 alanine mutants for either Rock (T653A) or ribosomal S6 kinase (Rsk; S703A) we show that each site is partially responsible for the LPA-induced increase in transport activity while NHE1 phosphorylation by either Rock or Rsk at their respective site is sufficient for LPA stimulated stress fiber formation and migration. Furthermore, mutation of either T653 or S703 leads to a higher basal pH level and a significantly higher proliferation rate. Our results identify the direct phosphorylation of NHE1 by Rock and suggest that both RhoA and Ras pathways mediate NHE1-dependent ion transport and migration in fibroblasts.

In recent years, librarians in various sectors have been moving forward a conversation on the distinct information needs and information-seeking behavior of our lesbian, gay, bisexual, trans, and queer (LGBTQ) patrons and how well the profession recognizes and meets those needs. Health sciences librarianship has been slower than other areas of the profession in creating an evidence base covering the needs of its LGBTQ patrons, with, until recently, only very limited literature on this subject. LGBTQ health sciences librarianship is now starting to attract new interest, with librarians working together to bring this emerging specialization to the attention of the broader professional community. In this paper, the authors report on a dedicated panel discussion that took place at the 2016 joint annual meeting of the Medical Library Association and Canadian Health Libraries Association/Association des bibliothèques de la santé du Canada in Toronto, Ontario, Canada; discuss subsequent reflections; and highlight the emerging role for health sciences librarians in providing culturally competent services to the LGBTQ population. Recommendations are also provided for establishing a tool kit for LGBTQ health sciences librarianship from which librarians can draw. We conclude by highlighting the importance of critically reflective practice in health sciences librarianship in the context of LGBTQ health information.

Management of vascular trauma has evolved tremendously since the turn of the 20(th) century. The lessons from each major military conflict over the past 100 years have refined our understanding of how to care for soldiers and civilians with vascular injuries. The recent wars in Iraq and Afghanistan have likewise improved our strategy for treating victims of vascular trauma. Understanding the principles that guide management of vascular injuries will result in preservation of life and limb.

We report the identification and characterization of mouse matriptase-2 (m-matriptase-2), an 811-amino-acid protein composed of an N-terminal cytoplasmic domain, a membrane-spanning domain, two CUB (complement protein subcomponents C1r/C1s, urchin embryonic growth factor and bone morphogenetic protein 1) domains, three LDLR (low-density-lipoprotein receptor class A) domains and a C-terminal serine-protease domain. All m-matriptase-2 protein domain boundaries corresponded with intron/exon junctions of the encoding gene, which spans approx. 29 kb and comprises 18 exons. Matriptase-2 is highly conserved in human, mouse and rat, with the rat matriptase-2 gene (r-maltriptase-2) predicted to encode transmembrane and soluble isoforms. Western-blot analysis indicated that m-matriptase-2 migrates close to its theoretical molecular mass of 91 kDa, and immunofluorescence analysis was consistent with the proposed surface membrane localization of this protein. Reverse-transcription PCR and in-situ-hybridization analysis indicated that m-matriptase-2 expression overlaps with the distribution of mouse hepsin (m-hepsin, a cell-surface serine protease identified in hepatoma cells) in adult tissues and during embryonic development. In adult tissues both are expressed at highest levels in liver, kidney and uterus. During embryogenesis m-matriptase-2 expression peaked between days 12.5 and 15.5. m-hepsin expression was biphasic, with peaks at day 7.5 to 8.5 and again between days 12.5 and 15.5. In situ hybridization of embryonic tissues indicated abundant expression of both m-matriptase-2 and m-hepsin in the developing liver and at lower levels in developing pharyngo–tympanic tubes. While m-hepsin was detected in the residual embryonic yolk sac and with lower intensity in lung, heart, gastrointestinal tract, developing kidney tubules and epithelium of the oral cavity, m-matriptase-2 was absent in these tissues, but strongly expressed within the nasal cavity by olfactory epithelial cells. Mechanistic insight into the potential role of this new transmembrane serine protease is provided by its novel expression profile in embryonic and adult mouse.

We propose a multi-atlas labeling method for subcortical structures and cerebral vascular territories in brain CT images. Each atlas image is registered to the query image by a non-rigid registration and the deformation is then applied to the labeling of the atlas image to obtain the labeling of the query image. Four label fusion strategies (single atlas, most similar atlas, major voting, and STAPLE) were compared. Image similarity values in non-rigid registration were calculated and used to select and rank atlases. Major voting fusion strategy gave the best accuracy, with DSC (Dice similarity coefficient) around 0.85 ± 0.03 for caudate, putamen, and thalamus. The experimental results also show that fusing more atlases does not necessarily yield higher accuracy and we should be able to improve accuracy and decrease computation cost at the same time by selecting a preferred set with the minimum number of atlases.

Objective To test the relative effects of a clinician versus non-clinician delivered goal setting intervention to assist patients presenting with Intermittent Allergic Rhinitis (IAR) in community pharmacies. Methods A 10-day mixed-method, parallel group repeated measures study was conducted in Sydney. Clinicians (pharmacists) and non-clinicians (pharmacy assistants) recruited patients suffering IAR. Intervention group pharmacy staff delivered a brief structured goal setting intervention to support IAR patient self-management whilst the control group delivered standard care. Results One hundred and fifty participants (N = 77 intervention; N = 73 control) were recruited at 20 community pharmacies. Both groups significantly improved on all outcome measures when assisted by either clinicians or non-clinicians. The intervention group patients supported by non-clinicians made significant improvements in self-efficacy and quality of life compared to the control group supported by non-clinicians. Strategies devised to control IAR triggers reflected practical actions whereas adherence and dose information strategies addressed IAR symptoms. Adherence did not impact significantly on self-reported symptom severity. Conclusion Both clinicians and non-clinicians can deliver this service. There is a need for a detailed and practical approach to assist patients towards a goal-directed and autonomous management of IAR. Practice implications With training non-clinicians can support patients with IAR, reducing the time constraints and workload for clinicians.

Conventional cancer therapies are based on preferential killing of tumor cells by DNA damage. Previous work showed that, for certain cell types, loss of integrin-mediated adhesion decreased the apoptotic response to DNA damage because of decreased p53 levels after detachment from the extracellular matrix. Integrin ligation restored p53 and sensitivity to DNA damage. In this study, we show that c-Abl mediates a second pathway by which adhesion to extracellular matrix regulates cell killing by chemotherapeutic agents 5-arabinofuranosylcytosine, cisplatin, and camptothecin. Activation of c-Abl tyrosine kinase by DNA damage requires cell adhesion. Abl-dependent stabilization of p73, a p53-related proapoptotic transcription factor, is also adhesion-dependent. Sensitivity to the Abl inhibitor STI571 suggests differential utilization of the p53 and c-Abl/p73 pathways by different tumor cell lines. These data suggest that killing of p53-negative tumor cells by chemotherapy would be enhanced by integrin ligation to activate the alternative c-Abl/p73 pathway.

Hepatitis C virus (HCV) is remarkably efficient in establishing persistent infection, possibly mediated by an impaired immune response to HCV infection. There is compelling evidence that HCV can infect immune cells, such as macrophages, B cells, and T cells. It has been previously reported that HCV core, the first protein expressed during the early phase of viral infection, contains the immunomodulatory function of suppressing host immune responses. This altered function of immune cells caused by HCV infection may explain the ineffective immune response to HCV. To further characterize the immunomodulatory role of HCV core in vivo, we generated transgenic (TG) mice by directing the expression of core protein to T lymphocytes by using the CD2 promoter. T-lymphocyte responses, including the production of gamma interferon and interleukin-2, were significantly diminished in these mice compared to their non-TG littermates. The inhibition of T-lymphocyte responsiveness may be due to the increased susceptibility of peripheral T lymphocytes to Fas-mediated apoptosis. Surprisingly, significant lymphocyte infiltration was observed in the portal tracts of livers isolated from core TG mice, associated with increasing serum alanine aminotransferase levels. Moreover, no intrahepatic lymphocytes or liver damage was found in non-TG littermates and core TG mice bred to Fas-deficientlprmice. These results suggest that HCV core drives liver injury by increasing Fas-mediated apoptosis and liver infiltration of peripheral T cells.

p53 mediates apoptosis of cells after DNA damage including tumor cells after radiation or chemotherapy. Survival of isolated cancer cells after therapy leads to recurrence of therapy-resistant tumors. We now show that for some melanoma, sarcoma, or fibroblastic cell types that survive without integrin-mediated adhesion, apoptosis in response to DNA damage requires cell adhesion. This effect correlates with rapid changes in levels of p14/p19 Arf and its downstream component, p53. Killing of nonadherent cells is increased by treatment with antiintegrin antibodies or by increasing levels of p53 or Arf. Consistent with low p53 levels, suspended cells show chromosomal instability after irradiation. Thus, loss of normal adhesion in susceptible tumor cells during genotoxic stress may play a role in therapy resistance and promote survival of cells with aberrant DNA.

Complement proteins are involved in early innate immune responses against pathogens and play a role in clearing circulating viral Ags from the blood of infected hosts. We have previously demonstrated that hepatitis C virus (HCV) core, the first protein to be expressed and circulating in the blood of infected individuals, inhibited human T cell proliferative response through interaction with the complement receptor, globular domain of C1q receptor (gC1qR). To investigate the mechanisms of HCV core/gC1qR-induced inhibition of T cell proliferation, we examined the effect of core protein on the early events in T cell activation. We found that HCV core inhibited phosphorylation of extracellular signal-regulated kinase (ERK) and mitogen-activated ERK kinase (MEK). HCV core-induced impairment of ERK/MEK mitogen-activated protein kinase resulted in the inhibition of IL-2 and IL-2Rα gene transcription, which led to the inhibition of IL-2 production and high-affinity IL-2R expression. Importantly, the ability of anti-gC1qR Ab treatment to reverse HCV core-induced inhibition of ERK/MEK phosphorylation reveals that the interaction between HCV core and gC1qR is linked to the interference of ERK/MEK mitogen-activated protein kinase activation. These results imply that HCV core-induced blockage of intracellular events in T cell activation by a complement-dependent regulatory pathway may play a critical role in the establishment of HCV persistence during the acute phase of viral infection.