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Background Osteoarthritis (OA) is a prevalent, chronic joint condition that commonly affects the knee and hip causing pain, impaired function, and reduced quality of life. As there is no cure, the main goal of treatment is to alleviate symptoms via ongoing self-management predominantly consisting of exercise and weight loss (if indicated). However, many people with OA do not feel adequately informed about their condition and management options to self-manage effectively. Patient education is recommended by all OA Clinical Practice Guidelines to support appropriate self-management, but little is known about the optimal delivery method and content. Massive Open Online Courses (MOOCs) are free, interactive, e-learning courses. They have been used to deliver patient education in other chronic health conditions but have not been used in OA. Methods A two-arm parallel-design, assessor- and participant-blinded superiority randomised controlled trial. People with persistent knee/hip pain consistent with a clinical diagnosis of knee/hip OA (n = 120) are being recruited from the Australia-wide community. Participants are randomly allocated into one of two groups i) electronic information pamphlet (control group) or ii) MOOC (experimental group). Those allocated to the control group receive access to an electronic pamphlet about OA and its recommended management, currently available from a reputable consumer organisation. Those allocated to the MOOC receive access to a 4-week 4-module interactive consumer-facing e-Learning course about OA and its recommended management. Course design was informed by behaviour theory and learning science, and consumer preferences. The two primary outcomes are OA knowledge and pain self-efficacy with a primary endpoint of 5 weeks and a secondary endpoint of 13 weeks. Secondary outcomes include measures of fear of movement, exercise self-efficacy, illness perceptions, OA management and health professional care seeking intentions, physical activity levels, and actual use of physical activity/exercise and weight loss, pain medication, and health professional care seeking to manage joint symptoms. Clinical outcomes and process measures are also collected. Discussion Findings will determine whether a comprehensive consumer-facing MOOC improves OA knowledge and confidence to self-manage joint pain compared to a currently available electronic OA information pamphlet. Trial registration Prospectively registered (Australian New Zealand Clinical Trials Registry ID: ACTRN12622001490763).

A deep learning model (LCP CNN) for the stratification of indeterminate pulmonary nodules (IPNs) demonstrated better discrimination than commonly used clinical prediction models. However, the LCP CNN score is based on a single timepoint that ignores longitudinal information when prior imaging studies are available. Clinically, IPNs are often followed over time and temporal trends in nodule size or morphology inform management. In this study we investigated whether the change in LCP CNN scores over time was different between benign and malignant nodules. This study used a prospective-specimen collection, retrospective-blinded-evaluation (PRoBE) design. Subjects with incidentally or screening detected IPNs 6–30 mm in diameter with at least 3 consecutive CT scans prior to diagnosis (slice thickness ≤ 1.5 mm) with the same nodule present were included. Disease outcome was adjudicated by biopsy-proven malignancy, biopsy-proven benign disease and absence of growth on at least 2-year imaging follow-up. Lung nodules were analyzed using the Optellum LCP CNN model. Investigators performing image analysis were blinded to all clinical data. The LCP CNN score was determined for 48 benign and 32 malignant nodules. There was no significant difference in the initial LCP CNN score between benign and malignant nodules. Overall, the LCP CNN scores of benign nodules remained relatively stable over time while that of malignant nodules continued to increase over time. The difference in these two trends was statistically significant. We also developed a joint model that incorporates longitudinal LCP CNN scores to predict future probability of cancer. Malignant and benign nodules appear to have distinctive trends in LCP CNN score over time. This suggests that longitudinal modeling may improve radiomic prediction of lung cancer over current models. Additional studies are needed to validate these early findings.

Purpose of review There is increasing recognition that virtual tools, enabled by the internet and telecommunications technology, can increase access to health care. We review evidence about the clinical effectiveness and acceptability of telephone-delivered and videoconferencing clinician consultations, websites and internet-delivered programs, and SMS and mobile applications in enabling the management of people with knee osteoarthritis (OA). We discuss barriers to using virtual tools and suggest strategies to facilitate implementation in clinical settings. Recent findings An increasing number of systematic reviews, meta-analyses, and clinical trials provide evidence showing the effectiveness of virtual tools for improving knee OA management. Qualitative research shows that virtual tools increase patient access to knee OA care, are generally acceptable and convenient for patients, but can be associated with barriers to use from patient and clinician perspectives. Summary Virtual tools offer new opportunities to enable people with knee OA to manage their condition and receive care that may otherwise be difficult or not possible to access. Telephone calls and videoconferencing can be used for real-time synchronous consultations between clinicians and patients, increasing the geographic reach of health services. Websites and internet-based programs can be used to educate patients about their condition, as well as deliver exercise, weight management, and psychological interventions. Mobile apps can monitor and track OA symptoms, exercise, and physical activity, while SMS can facilitate positive behaviour changes for self-management over the long-term when sustained clinician contact may not be possible.

Background Chronic hip pain is common and disabling and is largely due to osteoarthritis (OA). Self-management is recommended by international OA clinical guidelines yet there are few effective treatment options. Footwear has been suggested as a self-management approach, given that foot motion influences hip forces. Currently, guidelines advocate ‘stable supportive’ shoes for people with OA, however this is based solely on expert opinion given no research has investigated whether these shoes are effective at reducing symptoms in people with OA-related chronic hip pain. Therefore, this randomized controlled trial (RCT) aims to determine if stable supportive footwear reduces hip pain during walking compared to flat flexible footwear in people with chronic hip pain consistent with OA. Methods This trial is a 6-month, participant- and assessor-blinded, pragmatic, comparative effectiveness, superiority RCT conducted in Melbourne, Australia. We are recruiting 120 participants aged over 45 years with chronic hip pain consistent with OA from the community. Following baseline assessment, participants are randomized to receive either i) stable supportive shoes or ii) flat flexible shoes. Participants are permitted to choose two different pairs of shoes in their allocated group from a range of options that match prespecified shoe classification criteria. They are advised to wear either pair of study shoes daily for a minimum of 6 hours each day for 6 months. The primary outcome is the 6-month change in average hip pain on walking in the last week. Secondary outcomes include changes in other measures of hip pain, symptoms, function in daily living and sports and recreation, hip-related quality of life, pain at other sites, adverse events, and physical activity. Other measures include co-intervention use, adherence, shoe comfort, descriptive characteristics, footwear characteristics, and objective foot measures. Discussion This RCT will determine whether stable supportive shoes reduce hip pain during walking more than flat flexible shoes in people with chronic hip pain. Outcomes will help to inform footwear recommendations in international clinical guidelines for OA-related chronic hip pain, which to date have been based solely on expert opinion because of an absence of RCTs. Trial registration Australian New Zealand Clinical Trials Registry reference: ACTRN12621001532897.

Ineffective antibody-mediated responses are a key characteristic of chronic viral infection. However, our understanding of the intrinsic mechanisms that drive this dysregulation are unclear. Here, we identify that targeting the epigenetic modifier BMI-1 in mice improves humoral responses to chronic lymphocytic choriomeningitis virus. BMI-1 was upregulated by germinal center B cells in chronic viral infection, correlating with changes to the accessible chromatin landscape, compared to acute infection. B cell-intrinsic deletion of Bmi1 accelerated viral clearance, reduced splenomegaly and restored splenic architecture. Deletion of Bmi1 restored c-Myc expression in B cells, concomitant with improved quality of antibody and coupled with reduced antibody-secreting cell numbers. Specifically, BMI-1-deficiency induced antibody with increased neutralizing capacity and enhanced antibody-dependent effector function. Using a small molecule inhibitor to murine BMI-1, we could deplete antibody-secreting cells and prohibit detrimental immune complex formation in vivo. This study defines BMI-1 as a crucial immune modifier that controls antibody-mediated responses in chronic infection.

Background Borderline personality disorder (BPD) pathology is common among patients with substance use disorders (SUDs) and associated with a variety of negative outcomes, including worse SUD outcomes. One particularly relevant outcome with links to substance use problems that is likely to be elevated among SUD patients with BPD symptoms is ineffective conflict resolution strategies in romantic relationships. However, no research to date has examined the relation of BPD pathology to strategies for managing conflict in romantic relationships among patients with SUDs, or the factors that may increase the use of ineffective strategies within this population. Thus, this study examined the relations of BPD symptoms to ineffective responses to romantic relationship conflict surrounding substance use among residential patients with SUDs, as well as the explanatory roles of fear of compassion from and for others in these relations. Methods Patients in a community-based correctional SUD residential treatment facility (N = 93) completed questionnaires, including a measure of BPD symptoms, fear of compassion from and for others, and strategies for responding to conflict surrounding substance use in romantic relationships. Results Fear of compassion from others accounted for significant variance in the relations of BPD symptoms to the ineffective conflict resolution strategies of reactivity, domination, and submission, whereas fear of compassion for others only accounted for significant variance in the relation between BPD symptoms and the strategy of separation (which is not always ineffective). Conclusions Together, findings suggest that it is fear of compassion from others (vs. fear of compassion for others) that explains the relation between BPD symptoms and ineffective responses to romantic relationship conflict surrounding substance use among SUD patients. Findings highlight the potential utility of interventions aimed at reducing fears of compassion and increasing comfort with and tolerance of compassion from both others and oneself among SUD patients with BPD symptoms in order to strengthen relationships and reduce risk for relapse.

Background Patellofemoral pain is highly prevalent across the lifespan, and a significant proportion of people report unfavourable outcomes years after diagnosis. Previous research has implicated patellofemoral joint loading during gait in patellofemoral pain and its sequelae, patellofemoral osteoarthritis. Biomechanical foot-based interventions (e.g., footwear, insoles, orthotics, taping or bracing) can alter patellofemoral joint loads by reducing motions at the foot that increase compression between the patella and underlying femur via coupling mechanisms, making them a promising treatment option. This systematic review will summarise the evidence about the effect of biomechanical foot-based interventions on patellofemoral joint loads during gait in adults with and without patellofemoral pain and osteoarthritis. Methods MEDLINE (Ovid), the Cumulative Index to Nursing and Allied Health Literature CINAHL, The Cochrane Central Register of Controlled Trials (CENTRAL), SPORTdiscus (EBSCO) and Embase (Ovid) will be searched. Our search strategy will include terms related to ‘patellofemoral joint’, ‘loads’ and ‘biomechanical foot-based interventions’. We will include studies published in the English language that assess the effect of biomechanical foot-based interventions on patellofemoral joint loads, quantified by patellofemoral joint pressure, patellofemoral joint reaction force and/or knee flexion moment. Two reviewers will independently screen titles and abstracts, complete full-text reviews, and extract data from included studies. Two reviewers will assess study quality using the Revised Cochrane Risk of Bias (RoB 2) tool or the Cochrane Risk Of Bias In Non-Randomized Studies – of Interventions (ROBINS-I) tool. We will provide a synthesis of the included studies’ characteristics and results. If three or more studies are sufficiently similar in population and intervention, we will pool the data to conduct a meta-analysis and report findings as standardised mean differences with 95% confidence intervals. If a meta-analysis cannot be performed, we will conduct a narrative synthesis of the results and produce forest plots for individual studies. Discussion This protocol outlines the methods of a systematic review that will determine the effect of biomechanical foot-based interventions on patellofemoral joint loads. Our findings will inform clinical practice by identifying biomechanical foot-based interventions that reduce or increase patellofemoral joint loads, which may aid the treatment of adults with patellofemoral pain and osteoarthritis. Trial registration Registered with PROSPERO on the 4th of May 2022 (CRD42022315207).

PURPOSE: The precise timing of insemination after oocyte retrieval is sometimes challenging. In this study, we have assessed the effect of the variation in insemination timing on reproductive outcome for both conventional insemination (CI) and intracytoplasmic sperm injection (ICSI) cycles. METHODS: A single-center retrospective cohort data analysis was performed on 6559 patients (9575 oocyte retrievals) from January 2017 to July 2019. The main outcome measured was live birth rates. Secondary outcomes included fertilization rate per all oocytes retrieved, blastocyst utilization, clinical pregnancy, and miscarriage rates. The time interval between oocyte retrieval and insemination was analyzed in eight categories: 0 (0– 6.5 h, any detrimental effects are moderate on fertilization but do not affect blastocyst usage and birth rates. TRIAL REGISTRATION: Institutional Review Board Approval from the Beth Israel Deaconess Medical Centre [IRB Protocol #: 2015P000122]. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10815-021-02299-7.

Oriented short hemp fibre mats were produced using dynamic sheet forming (DSF) incorporating cellulose nanocrystals (CNCs) to improve their integrity. The CNCs were found to act as a binder and improve mechanical strength of the mats as well as the strength of polypropylene matrix composites produced with the mats. Improved thermal stability was also obtained for composites by using CNC treatment of fibre mats.

SIVmac239 infection of macaques is a favored model of human HIV infection. However, the SIVmac239 envelope (Env) trimer structure, glycan occupancy, and the targets and ability of neutralizing antibodies (nAbs) to protect against SIVmac239 remain unknown. Here, we report the isolation of SIVmac239 nAbs that recognize a glycan hole and the V1/V4 loop. A high-resolution structure of a SIVmac239 Env trimer-nAb complex shows many similarities to HIV and SIVcpz Envs, but with distinct V4 features and an extended V1 loop. Moreover, SIVmac239 Env has a higher glycan shield density than HIV Env that may contribute to poor or delayed nAb responses in SIVmac239-infected macaques. Passive transfer of a nAb protects macaques from repeated intravenous SIVmac239 challenge at serum titers comparable to those described for protection of humans against HIV infection. Our results provide structural insights for vaccine design and shed light on antibody-mediated protection in the SIV model.

Hepatic cell lines serve as economical and reproducible alternatives for primary human hepatocytes. However, the utility of hepatic cell lines to examine bile acid homeostasis and cholestatic toxicity is limited due to abnormal expression and function of bile acid-metabolizing enzymes, transporters, and the absence of canalicular formation. We discovered that culturing HuH-7 human hepatoma cells with dexamethasone (DEX) and 0.5% dimethyl sulfoxide (DMSO) for two weeks, with Matrigel overlay after one week, resulted in a shorter and improved differentiation process. These culture conditions increased the expression and function of the major bile acid uptake and efflux transporters, sodium taurocholate co-transporting polypeptide (NTCP) and the bile salt export pump (BSEP), respectively, in two-week cultures of HuH-7 cells. This in vitro model was further characterized for expression and function of bile acid-metabolizing enzymes, transporters, and cellular bile acids. Differentiated HuH-7 cells displayed a marked shift in bile acid composition and induction of cytochrome P450 (CYP) 7A1, CYP8B1, CYP3A4, and bile acid-CoA: amino acid N-acyltransferase (BAAT) mRNAs compared to control. Inhibition of taurocholate uptake and excretion after a 24-h treatment with prototypical cholestatic drugs suggests that differentiated HuH-7 cells are a suitable model to examine cholestatic hepatotoxicity.

Background Patient organisations may be an under-utilised resource in follow-up of patients requiring long-term exercise as part of their disease management. The purpose of this study was to explore the feasibility of a web-based exercise program delivered by a patient organisation to patients with hip and/or knee osteoarthritis (OA). Methods In this pre–post feasibility study, patients aged 40–80 years with hip and/or knee OA were recruited from Diakonhjemmet Hospital. The 12-week intervention was delivered through a patient organisation’s digital platform. Feasibility was evaluated by proportion of eligible patients enrolled, proportion of enrolled patients who provided valid accelerometer data at baseline, and proportion completing the cardiorespiratory exercise test according to protocol at baseline and completed follow-up assessments. Patient acceptability was evaluated for website usability, satisfaction with the initial exercise level and comprehensibility of the exercise program. Change in clinical outcomes were assessed for physical activity, cardiorespiratory fitness and patient-reported variables. Results In total, 49 eligible patients were identified and 35 were enrolled. Thirty (86%) of these attended baseline assessments and provided valid accelerometer data and 18 (51%) completed the maximal cardiorespiratory exercise test according to protocol. Twenty-two (63%) patients completed the follow-up questionnaire, and they rated the website usability as ‘acceptable’ [median 77.5 out of 100 (IQR 56.9, 85.6)], 19 (86%) reported that the initial exercise level was ‘just right’ and 18 (82%) that the exercise program was ‘very easy’ or ’quite easy’ to comprehend. Improvement in both moderate to vigorous physical activity (mean change 16.4 min/day; 95% CI 6.9 to 25.9) and cardiorespiratory fitness, VO2peak (mean change 1.83 ml/kg/min; 95% CI 0.29 to 3.36) were found in a subgroup of 8 patients completing these tests. Across all patient-reported outcomes 24–52% of the patients had a meaningful improvement (n = 22). Conclusion A web-based exercise program delivered by a patient organisation was found to be feasible and acceptable in patients with hip and/or knee OA. Trial registration ClinicalTrials.gov, NCT04084834 (registered 10 September 2019). The Regional Committee for Medical and Health Research Ethics south-east, 2018/2198. URL: Prosjekt #632074 - Aktiv med web-basert støtte. - Cristin (registered 7 June 2019).

Extant research indicates a robust association between anxiety and nonsuicidal self-injury (NSSI). However, research identifying factors that may account for this relation is lacking. Mindfulness is one candidate construct that may account for the relation of anxiety to NSSI. The objective of the present study was to examine the indirect relation of anxiety to recurrent NSSI and NSSI versatility (i.e., the number of different NSSI methods used) through overall and specific facets of mindfulness while controlling for participant sex and depression symptoms. Undergraduates (N = 339; Female = 76.4%), of whom approximately 14% reported recurrent NSSI behavior, completed the Deliberate Self-Harm Inventory, Depression Anxiety Stress Scales-21, and Five Facet Mindfulness Questionnaire. Four path-analytic regression analyses were conducted. Results revealed significant positive indirect relations of anxiety to recurrent NSSI and NSSI versatility through low total mindfulness, [95% CIs [0.001, 0.024] and [0.001, 0.008], respectively. Examination of mindfulness facets indicated significant positive indirect relations of anxiety to recurrent NSSI and NSSI versatility through nonjudging only, 95% CIs [0.001, 0.033] and [0.0001, 0.012], respectively. Mindfulness partially accounts for NSSI behavior among individuals struggling with anxiety.

In this essay, Kim Niewolny, current President of AFHVS, responds to the 2020 AFHVS Presidential Address given by Molly Anderson. Niewolny is encouraged by Anderson’s message of moving “beyond the boundaries” by focusing our gaze on the insurmountable un-sustainability of the globalized food system. Anderson recommends three ways forward to address current challenges. Niewolny argues that building solidarity with social justice movements and engendering anti-racist praxis take precedence. This work includes but is not limited to dismantling the predominance of neoliberal-fueled technocratic productivism in agricultural science and policy while firmly centering civil society collective action and human rights frameworks as our guiding imaginary for racial, gender, environmental, and climate justice possibilities for sustainable food systems praxis. She concludes by exploring the epistemic assertion to push beyond our professional and political imaginaries to build a more fair, just, and humanizing food system.

Dietary emulsifier consumption promotes systemic low-grade inflammation, metabolic deregulation, and possibly an anxiety-like phenotype. The latter finding suggests that dietary emulsifiers impact brain areas that modulate stress responses. The goal of the current study was to test whether emulsifier consumption is associated with changes in gene expression in the amygdala and the paraventricular nucleus of the hypothalamus (PVN), two brain areas that are involved in behavioral and neuroendocrine responses to stress. Using RNA-Seq, we compared groups consuming either carboxymethylcellulose or polysorbate 80 for 12-weeks. A total of 243 genes were differentially expressed in the amygdala and PVN of emulsifier-treated mice compared to controls. There was minimal overlap of differentially expressed genes in CMC- and P80-treated animals, suggesting that each emulsifier acts via distinct molecular mechanisms to produce an anxiety-like phenotype. Furthermore, gene ontology and pathway analysis revealed that various stress, metabolic, and immune terms and pathways were altered by emulsifiers. These findings are the first to demonstrate that emulsifier consumption changes gene expression in brain regions that are critical for stress responding, providing possible molecular mechanisms that may underly the previously observed anxiety-like phenotype.

Background Hip osteoarthritis (OA) is a leading cause of musculoskeletal pain. Exercise is a core recommended treatment. Most evidence is based on muscle-strengthening exercise, but aerobic physical activity has potential to enhance clinical benefits. The primary aim of this study is to test the hypothesis that adding aerobic physical activity to a muscle strengthening exercise leads to significantly greater reduction in hip pain and improvements in physical function, compared to a lower-limb muscle strengthening exercise program alone at 3 months. Methods This is a superiority, 2-group, parallel randomised controlled trial including 196 people with symptomatic hip OA from the community. Following baseline assessment, participants are randomly allocated to receive either i) aerobic physical activity and muscle strengthening exercise or; ii) muscle strengthening exercise only. Participants in both groups receive 9 consultations with a physiotherapist over 3 months. Both groups receive a progressive muscle strengthening exercise program in addition to advice about OA management. The aerobic physical activity plan includes a prescription of moderate intensity aerobic physical activity with a goal of attaining 150 min per week. Primary outcomes are self-reported hip pain assessed on an 11-point numeric rating scale (0 = ‘no pain’ and 10 = ‘worst pain possible’) and self-reported physical function (Western Ontario and McMaster Universities Osteoarthritis Index physical function subscale) at 3 months. Secondary outcomes include other measures of self-reported pain (assessed at 0, 3, 9 months), self-reported physical function (assessed at 0, 3, 9 months), performance-based physical function (assessed at 0, 3 months), joint stiffness (assessed at 0, 3, 9 months), quality of life (assessed at 0, 3, 9 months), muscle strength (assessed at 0, 3 months), and cardiorespiratory fitness (assessed at 0, 3 months). Other measures include adverse events, co-interventions, and adherence. Measures of body composition, serum inflammatory biomarkers, quantitative sensory measures, anxiety, depression, fear of movement and self-efficacy are included to explore causal mechanisms. Discussion Findings will assist to provide an evidence-based recommendation regarding the additional effect of aerobic physical activity to lower-limb muscle strengthening on hip OA pain and physical function. Trial registration Australian New Zealand Clinical Trials Registry reference: ACTRN 12619001297112. Registered 20th September 2019.

Deliberate self-harm (DSH) is a widespread transdiagnostic health problem with increasing prevalence among adolescences, and young adults. It is therefore essential to effectively chart the epidemiology of DSH, as well as to assess the efficacy of interventions designed to modify this behavior. The aim was to translate and analyze the psychometric properties of the Norwegian versions of two instruments designed to assess DSH: the Deliberate Self-harm Inventory (DSHI) and the Inventory of Statements About Self-Injury (ISAS), as well as to assess the prevalence of DSH within a nonclinical Norwegian adult population. Of the 402 participants who completed a questionnaire packet comprising the DSHI, ISAS, general questions about DSH, and other related measures, 30.6% reported some form of DSH. Those with a history of DSH reported greater difficulties with emotion regulation than those without. Participants with and without a history of DSH did not differ in unrelated constructs, including social desirability. The frequency of specific DSH behaviors was in accordance with previous research, with cutting being the most frequent. The factor structure of DSH functions in the Norwegian ISAS was generally comparable to the factor structure of the English version. Overall, results indicate that: a) the Norwegian versions of the DSHI and ISAS behave as expected and in accordance with prior research in other languages and other populations, and b) both the DSHI and ISAS have high internal consistency and adequate construct, convergent, and discriminant validity, and may be applied to evaluate DSH in adult Norwegian populations.

Adolescents from rural, resource poor regions of the United States have disproportionately higher rates of drug and alcohol misuse, which may lead to increased sexual risk behaviors. Adolescents living in both urban and rural areas are major users of smartphones as a source for health information. Yet, the quality and accuracy of some Internet sites tend to be unreliable. The purpose of this study was to explore the perceptions and attitudes of adolescents from a rural region in the southeastern United States regarding health and social concerns to inform the development of a risk reduction application for smartphone use. This study used a qualitative descriptive design guided by the Theory of Triadic Influence. The research team was composed of community partners, faculty, and students from a mid-Atlantic university. Forty-nine adolescents (18 boys and 31 girls) participated in one of five mixed-gender focus groups; they were predominantly Black and Latino, with a mean age of 13.8. Content and thematic analysis led to three interrelated themes: Family as Nexus, Unlevel Playing Field, and Threats to Safety and Security. Structural (racism and bullying) and proximal (neighborhood, family and peers) determinants of health were congruent with other recent reports. Snapchat and Instagram were the most popular social media platforms used. Using a contextual approach, we analyzed the daily experiences of ethnic minority adolescents to inform the development of a risk reduction mobile health application. Community-academic partnerships with engaged youth can assist in smartphone application development and beta testing.

Those caring for someone diagnosed with a neurodevelopmental disorder are at risk of experiencing depression and anxiety. However, limited research has examined risk and predictive factors associated with internalizing symptomatology in caregivers from ethnic and culturally diverse backgrounds. We aimed to identify predictive factors for internalizing symptomatology. Using standardized scales, anxiety and depression levels were measured in a predominantly Latinx sample along with their endorsed levels of familism, perceived social, and support affiliate stigma. Multivariate regression analyses were used to test the hypotheses that familism, perceived social support, and affiliate stigma are associated with self-reported depression and anxiety symptoms, separately. The results indicated a significant effect of perceived social support and affiliate stigma on depression and anxiety symptoms, but no such effect of familism. Findings indicate that higher perceived social support scores predicted lower rates of anxiety and depression in caregivers. Conversely, higher affiliate stigma scores predicted higher rates of anxiety and depression. Results provide important clinical implications when working with Latinx families and caregivers of a family member diagnosed with a neurodevelopmental disorder.

Approximately 20-30% of human lung adenocarcinomas (LUAD) harbor loss-of-function (LOF) mutations in Kelch-like ECH Associated-Protein 1 (KEAP1), which lead to hyperactivation of the nuclear factor, erythroid 2-like 2 (NRF2) antioxidant pathway and correlate with poor prognosis(1-3). We previously showed that Keap1 mutation accelerates KRAS-driven LUAD and produces a marked dependency on glutaminolysis(4). To extend the investigation of genetic dependencies in the context of Keap1 mutation, we performed a druggable genome CRISPR-Cas9 screen in Keap1-mutant cells. This analysis uncovered a profound Keap1 mutant-specific dependency on solute carrier family 33 member 1 (Slc33a1), an endomembrane-associated protein with roles in autophagy regulation(5), as well as a series of functionally-related genes implicated in the unfolded protein response. Targeted genetic and biochemical experiments using mouse and human Keap1-mutant tumor lines, as well as preclinical genetically-engineered mouse models (GEMMs) of LUAD, validate Slc33a1 as a robust Keap1-mutant-specific dependency. Furthermore, unbiased genome-wide CRISPR screening identified additional genes related to Slc33a1 dependency. Overall, our study provides a strong rationale for stratification of patients harboring KEAP1-mutant or NRF2-hyperactivated tumors as likely responders to targeted SLC33A1 inhibition and underscores the value of integrating functional genetic approaches with GEMMs to identify and validate genotype-specific therapeutic targets.

With several different CAR T cell therapies under advanced phases of clinical trials, and the first FDA-approved CAR treatments in 2017 (Yescarta and Kymriah), CAR T cell therapy has become one of the most promising therapies for the treatment of certain types of cancer. This success has bred an opportunity to optimize the production of CAR T cells for easier patient access. CAR T cell therapy is a rather expensive and personalized process that requires expensive measures to collect cells from patients, engineer those cells, and re-infuse the cells into the patient with adequate quality controls at each phase. With this in mind, significant attempts at creating a "universal" CAR T cell are underway in order to create an "off-the-shelf" product that would reduce the expense and time required for traditional CAR T cell treatment. The primary obstacle facing this endeavor is avoiding graft-versus-host disease that accompanies allogeneic transplants between genetically dissimilar individuals. With the advent of CRISPR and TALEN technology, editing the genome of allogeneic cells has become very possible, and several groups have provided initial data analyzing the effects of CAR T cells that have been edited to avoid host rejection and avoid endogenous TCR alloreactivity. These engineered cells not only have to avoid GVHD but also have to retain their anti-tumor efficacy in vivo. Here, we expand on the recent efforts and strides that have been made in the design and testing of universal allogeneic CAR T cells.

The main objective of this study was to produce aligned hemp fibre mats from high strength hemp fibres using dynamic sheet forming (DSF). Alkali treatment of hemp fibre was carried out at ambient and high temperature to separate fibres. Single fibre tensile testing was used to assess the tensile properties of the fibres. It was found that the highest tensile properties were exhibited by high temperature treated fibre, whereas the tensile properties exhibited by ambient temperature treated fibre were lower than for untreated fibre. It was also found that fibre granulated after high temperature treatment, was better separated than that granulated before high temperature treatment. This well-separated fibre could successfully be formed into mats using DSF. The orientation of the formed mat was analysed using ImageJ (NIH, USA) software by which the potential of DSF to produce aligned hemp fibre mat was supported. The tensile properties of composite reinforced by these aligned hemp fibre mats were assessed.

Background Hip osteoarthritis (OA) is a leading cause of musculoskeletal pain. Exercise is a core recommended treatment. Despite some clinical guidelines also recommending weight loss for hip OA, there is no evidence from randomised controlled trials (RCT) to substantiate these recommendations. This superiority, 2-group, parallel RCT will compare a combined diet and exercise program to an exercise only program, over 6 months. Methods One hundred people with symptomatic and radiographic hip OA will be recruited from the community. Following baseline assessment, participants will be randomly allocated to either, i) diet and exercise or; ii) exercise only. Participants in the diet and exercise group will have six consultations with a dietitian and five consultations with a physiotherapist via videoconferencing over 6 months. The exercise only group will have five consultations with a physiotherapist via videoconferencing over 6 months. The exercise program for both groups will include prescription of strengthening exercise and a physical activity plan, advice about OA management and additional educational resources. The diet intervention includes prescription of a ketogenic very low-calorie diet with meal replacements and educational resources to support weight loss and healthy eating. Primary outcome is self-reported hip pain via an 11-point numeric rating scale (0 = ‘no pain’ and 10 = ‘worst pain possible’) at 6 months. Secondary outcomes include self-reported body weight (at 0, 6 and 12 months) and body mass index (at 0, 6 and 12 months), visceral fat (measured using dual energy x-ray absorptiometry at 0 and 6 months), pain, physical function, quality of life (all measured using subscales of the Hip Osteoarthritis Outcome Scale at 0, 6 and 12 months), and change in pain and physical activity (measured using 7-point global rating of change Likert scale at 6 and 12 months). Additional measures include adherence, adverse events and cost-effectiveness. Discussion This study will determine whether a diet intervention in addition to exercise provides greater hip pain-relief, compared to exercise alone. Findings will assist clinicians in providing evidence-based advice regarding the effect of a dietary intervention on hip OA pain. Trial registration ClinicalTrials.gov . Identifier: NCT04825483. Registered 31st March 2021.

BackgroundDespite well-established benefits of physical activity for knee osteoarthritis (OA), nine of ten people with knee OA are inactive. People with knee OA who are inactive often believe that physical activity is dangerous, fearing that it will further damage their joint(s). Such unhelpful beliefs can negatively influence physical activity levels. We aim to evaluate the clinical- and cost-effectiveness of integrating physiotherapist-delivered pain science education (PSE), an evidence-based conceptual change intervention targeting unhelpful pain beliefs by increasing pain knowledge, with an individualised walking, strengthening, and general education program.MethodsTwo-arm, parallel-design, multicentre randomised controlled trial involving 198 people aged ≥50 years with painful knee OA who do not meet physical activity guideline recommendations or walk regularly for exercise. Both groups receive an individualised physiotherapist-led walking, strengthening, and OA/activity education program via 4x weekly in-person treatment sessions, followed by 4 weeks of at-home activities (weekly check-in via telehealth), with follow-up sessions at 3 months (telehealth) and 5 and 9 months (in-person). The EPIPHA-KNEE group also receives contemporary PSE about OA/pain and activity, embedded into all aspects of the intervention. Outcomes are assessed at baseline, 12 weeks, 6 and 12 months. Primary outcomes are physical activity level (step count; wrist-based accelerometry) and self-reported knee symptoms (WOMAC Total score) at 12 months. Secondary outcomes are quality of life, pain intensity, global rating of change, self-efficacy, pain catastrophising, depression, anxiety, stress, fear of movement, knee awareness, OA/activity conceptualisation, and self-regulated learning ability. Additional measures include adherence, adverse events, blinding success, COVID-19 impact on activity, intention to exercise, treatment expectancy/perceived credibility, implicit movement/environmental bias, implicit motor imagery, two-point discrimination, and pain sensitivity to activity. Cost-utility analysis of the EPIPHA-KNEE intervention will be undertaken, in addition to evaluation of cost-effectiveness in the context of primary trial outcomes.DiscussionWe will determine whether the integration of PSE into an individualised OA education, walking, and strengthening program is more effective than receiving the individualised program alone. Findings will inform the development and implementation of future delivery of PSE as part of best practice for people with knee OA.Trial registrationAustralian New Zealand Clinical Trials Registry:ACTRN12620001041943(13/10/2020).

We present evidence from diverse disciplines and populations to identify the current and emerging role of genomics in prevention from both medical and public health perspectives as well as key challenges and potential untoward consequences of increasing the role of genomics in these endeavors. We begin by comparing screening in healthy populations (newborn screening), with testing in symptomatic populations, which may incidentally identify secondary findings and at-risk relatives. Emerging evidence suggests that variants in genes subject to the reporting of secondary findings are more common than expected in patients who otherwise would not meet the criteria for testing and population testing for variants in these genes may more precisely identify discrete populations to target for various prevention strategies starting in childhood. Conversely, despite its theoretical promise, recent studies attempting to demonstrate benefits of next-generation sequencing for newborn screening have instead demonstrated numerous barriers and pitfalls to this approach. We also examine the special cases of pharmacogenomics and polygenic risk scores as examples of ways genomics can contribute to prevention amongst a broader population than that affected by rare Mendelian disease. We conclude with unresolved questions which will benefit from future investigations of the role of genomics in disease prevention.

The first presidential debate of 2016 was historic along a number of dimensions, including the first woman general election candidate and the first general election candidate in history with no political or military experience. Given the presence of the first woman nominee of a major party, along with dramatic gender differences in support for the candidates, we focus on the role of gender in shaping people’s emotional responses to candidate messaging during the debate. Through the use of a controlled experiment, we measure changes in attitudes after exposure to the debate. In addition, we utilize facial expression software to explore real-time reaction to the candidates during the debate. Leveraging data generated during the debate by the facial expression software and as well as responses to pretest and post-test questionnaires, we find that men and women respond differently to candidates’ messaging during the debate and these emotional responses influence post-debate evaluations.

Although researchers have identified a number of factors that may motivate individuals to engage in nonsuicidal self-injury (NSSI), few studies have examined whether motives for NSSI differ as a function of psychiatric diagnosis. Therefore, the goal of the present study was to examine motives for lifetime NSSI among individuals with a history of psychiatric disorders associated with elevated rates of NSSI: depressive disorders and posttraumatic stress disorder (PTSD). Young adults (N = 139) with a history of NSSI completed several diagnostic interviews and questionnaires, including a measure of lifetime NSSI motives. Results demonstrated that participants with (vs. without) a lifetime depressive disorder reported significantly lower levels of interpersonal influence motives for NSSI, and participants with (vs. without) lifetime PTSD reported significantly higher levels of emotional relief and feeling generation motives. Further, results revealed a significant interaction between lifetime depressive disorders and PTSD for interpersonal communication motives; specifically, whereas participants with lifetime diagnoses of both a depressive disorder and PTSD did not differ significantly in reported interpersonal communication motives from participants with neither diagnosis, those with lifetime PTSD but without a lifetime depressive disorder reported significantly higher levels of interpersonal communication motives than those without either diagnosis. Results suggest that a history of depression and PTSD (alone and in combination) may be associated with different motives for NSSI.

Objective: Pharmacokinetic (PK) data to guide cefazolin dosing in premature infants is virtually non-existent. Therefore, we aimed to characterize cefazolin PK in infants aged ≤32 weeks of gestation at birth. Study Design: We conducted a prospective, open-label PK and safety study of cefazolin in infants ≤32 weeks gestation from a University Medical Center. We administered intravenous cefazolin and collected both timed and scavenged blood samples. We analyzed data using non-linear mixed effect modeling and simulated several dosage regimens to achieve target concentrations against methicillin-susceptible Staphylococcus aureus. Results: We analyzed 40 samples from 9 infants and observed that premature infants had lower clearance and greater volume of distribution for cefazolin compared to older children. The median (range) individual Bayesian estimates were 0.03 L/h/kg (0.01-0.08) for clearance and 0.39 L/kg (0.31-0.52) for volume. Conclusion: Simulations suggested reduced cefazolin dosing based on postmenstrual age achieve target concentrations and potentially reduce unnecessary exposure.

The main objective of this study was to assess the effect of stearic acid vapour treatment on hemp fibre mats produced using dynamic sheet forming, and the potential use of these treated mats as reinforcement in polypropylene matrix composites. Stearic acid was successfully applied through vapour treatment, appearing to form a layer on fibre surfaces. It was found that the presence of stearic acid increased hydrophobicity and thermal stability of fibre mats. It was also found to increase thermal stability of polypropylene matrix composites as well as their strength.

The benefit of using alkali-treated hemp fibre as the reinforcement for rotationally moulded polyethylene composites was evaluated in this research. Untreated and alkali-treated hemp fibre were characterised using different techniques such as scanning electron microscopy (SEM), thermal analysis, and Fourier transform infrared spectroscopy (FT-IR). These techniques showed that the alkali treatment removed non-cellulosic components from hemp fibres, which improved their separation and thermal resistance. Composites with alkali-treated fibre resisted the exposure to elevated temperatures for prolonged periods (characteristic of the rotational moulding process) with no apparent signs of thermal degradation, unlike when untreated fibre was used. The effect of using maleic anhydride grafted polyethylene (MAPE) as a coupling agent was also investigated. The addition of 3 wt% MAPE improved the properties tensile strength and Young's modulus of composites with treated hemp fibre, which was attributed to better fibre-matrix adhesion. Different fibre contents were assessed in this research to produce rotationally moulded composites; a poor fibre distribution was observed above 5 wt% fibre content, which resulted in low tensile strength and Young's modulus.

Background The aim of this study is to determine whether Hypoxanthine Guanine Phosphoribosyltransferase (HPRT) could be used as a biomarker for the diagnosis and treatment of B cell malignancies. With 4.3% of all new cancers diagnosed as Non-Hodgkin lymphoma, finding new biomarkers for the treatment of B cell cancers is an ongoing pursuit. HPRT is a nucleotide salvage pathway enzyme responsible for the synthesis of guanine and inosine throughout the cell cycle. Methods Raji cells were used for this analysis due to their high HPRT internal expression. Internal expression was evaluated utilizing western blotting and RNA sequencing. Surface localization was analyzed using flow cytometry, confocal microscopy, and membrane biotinylation. To determine the source of HPRT surface expression, a CRISPR knockdown of HPRT was generated and confirmed using western blotting. To determine clinical significance, patient blood samples were collected and analyzed for HPRT surface localization. Results We found surface localization of HPRT on both Raji cancer cells and in 77% of the malignant ALL samples analyzed and observed no significant expression in healthy cells. Surface expression was confirmed in Raji cells with confocal microscopy, where a direct overlap between HPRT specific antibodies and a membrane-specific dye was observed. HPRT was also detected in biotinylated membranes of Raji cells. Upon HPRT knockdown in Raji cells, we found a significant reduction in surface expression, which shows that the HPRT found on the surface originates from the cells themselves. Finally, we found that cells that had elevated levels of HPRT had a direct correlation to XRCC2, BRCA1, PIK3CA, MSH2, MSH6, WDYHV1, AK7, and BLMH expression and an inverse correlation to PRKD2, PTGS2, TCF7L2, CDH1, IL6R, MC1R, AMPD1, TLR6, and BAK1 expression. Of the 17 genes with significant correlation, 9 are involved in cellular proliferation and DNA synthesis, regulation, and repair. Conclusions As a surface biomarker that is found on malignant cells and not on healthy cells, HPRT could be used as a surface antigen for targeted immunotherapy. In addition, the gene correlations show that HPRT may have an additional role in regulation of cancer proliferation that has not been previously discovered.

Although trauma-focused cognitive behavior therapy (TF-CBT) is the frontline treatment for post-traumatic stress disorder (PTSD), up to one-half of patients are treatment nonresponders. To understand treatment nonresponse, it is important to understand the neural mechanisms of TF-CBT. Here, we used whole-brain intrinsic functional connectivity analysis to identify neural connectomic signatures of treatment outcome. In total, 36 PTSD patients and 36 healthy individuals underwent functional MRI at pre-treatment baseline. Patients then underwent nine sessions of TF-CBT and completed clinical and follow-up MRIs. We used an established large-scale brain network atlas to parcellate the brain into 343 brain regions. Pairwise intrinsic task-free functional connectivity was calculated and used to identify pre-treatment connectomic features that were correlated with reduction of PTSD severity from pretreatment to post treatment. We formed a composite metric of intrinsic connections associated with therapeutic outcome, and then interrogated this composite metric to determine if it distinguished PTSD treatment responders and nonresponders from healthy control status and changed post treatment. Lower pre-treatment connectivity for the cingulo-opercular, salience, default mode, dorsal attention, and frontoparietal executive control brain networks was associated with treatment improvement. Treatment responders had lower while nonresponders had significantly greater connectivity than controls at pretreatment. With therapy, connectivity significantly increased for responders and decreased for nonresponders, while controls remain unchanged over this time period. We provide evidence that the intrinsic functional architecture of the brain, specifically connectivity within and between brain networks associated with external vigilance, self-awareness, and cognitive control, may characterize a positive response to TF-CBT for PTSD.

Background Thymidine kinase 1 (TK1) is a pyrimidine salvage pathway enzyme that is up-regulated in malignant tissues and elevated in the serum of cancer patients. While TK1 has been well established as a tumor biomarker, little has been done to explore its potential as a tumor target. Recently, we reported the membrane expression of TK1 on malignant cells, but not on normal cells. This study explores the possible use of monoclonal antibodies for the targeting of membrane associated TK1 in lung, breast, colon and prostate cancer cells. Methods We generated and evaluated a panel of monoclonal antibodies against six different epitopes exposed in the tetrameric form of TK1. Antibodies were developed with hybridoma technology and validated with Western blot, siRNA TK1 knockdown, enzyme-linked immunosorbent assay (ELISA) and flow cytometry. The therapeutic potential of the antibodies was evaluated in vitro in antibody-dependent cell-mediated-cytotoxicity (ADCC) experiments. Results Binding of the antibodies to TK1 was confirmed by Western blot in purified recombinant protein, cancer serum, and cell lysate. After a TK1 knockdown was performed, a reduction of TK1 expression was observed with five antibodies. Using indirect ELISA, we identified 3B2E11, 9C10, 7H2, 3B4, 8G2 among the most sensitive antibodies (LOD = 10.73–66.9 pg/ml). Surface expression of TK1 on the membrane of various cancer cell lines was analyzed with flow cytometry. Antibodies 8G2, 3B4, 7HD and 5F7G11 detected TK1 on the membrane of various cancer cell lines, including lung, prostate, colon and breast. No significant binding was detected on normal lymphocytes. Increased cytolysis of lung (~ 70%. p = 0.0001), breast (~ 70%, p = 0.0461) and colon (~ 50% p = 0.0216) cancer cells by effector cells was observed when anti-TK1 antibodies were added during ADCC experiments. Conclusions The antibodies developed showed potential to be used to detect and target TK1 on the membrane of various tumor cells. The targeting of TK1 in malignant cells using monoclonal antibodies may be a feasible approach for the elimination of high TK1 expressing tumor cells.

Background Structural features of lateral tibiofemoral (TF) joint osteoarthritis (OA) occur in up to half of all people with knee OA, and co-existing lateral TF OA is associated with worse knee pain in people with mixed compartmental knee OA. Clinical guidelines for management of knee OA advocate advice about appropriate footwear, yet there is no research evaluating which types of footwear are best for managing pain associated with lateral TF OA. Biomechanical evidence suggests that “motion-control” footwear, which possess midsoles that are stiffer medially compared to laterally, may shift load away from the lateral compartment of the knee and thus may reduce knee pain associated with lateral TF OA. The primary aim of this study is to compare the effects of motion-control shoes to neutral shoes on knee pain in people with predominantly lateral TF OA. Methods This will be an assessor- and participant-blinded, two-arm, comparative effectiveness randomized controlled trial (RCT) conducted in Melbourne, Australia. We will recruit a minimum of 92 people with painful lateral TF OA from the community. Participants will be randomly allocated to receive either motion-control shoes or neutral shoes and will be instructed to wear their allocated shoes for a minimum of 6 h per day for 6 months. The primary outcome is change in self-reported knee pain on walking, measured using a numerical rating scale, assessed at baseline and 6 months. Secondary outcomes include other measures of knee pain, physical function, quality of life, participant-perceived change in pain and function, and physical activity levels. Discussion This study will compare the efficacy of motion-control shoes to neutral shoes for people with painful lateral TF OA. Findings will be the first to provide evidence of the effects of footwear on knee pain in this important subgroup of people with knee OA and allow clinicians to provide accurate advice about the most appropriate footwear for managing pain associated with lateral TF OA. Trial registration This trial has been prospectively registered by the Australian New Zealand Clinical Trials Registry on 15/11/2018 (reference: ACTRN12618001864213).

Osteonecrosis of the femoral head (ONFH) is a multi-factorial disease with relatively unknown aetiology and unclear pathogenetic mechanism. Left untreated, the natural history of the disease is progressive collapse of the femoral head and destruction of the joint with substantial pain and disability. The disease primarily affects younger individuals, in whom many surgeons will typically prefer to delay performing total hip arthroplasty (THA). Therefore, increasing attention has been given to a wide variety of femoral head-preserving procedures. The use of non-vascularized bone grafting (NVBG) to treat ONFH has mainly been advocated for pre-collapse and select, early post-collapse lesions. Currently, multiple studies reported on various non-vascularized bone grafting techniques of treating ONFH. Clinical outcomes have varied widely, with success rates reported between 55 and 87% in the short- to mid-term, with long-term results lacking. Due to the current paucity of studies, in this review we aimed to discuss (1) indications, (2) techniques, and (3) outcomes of non-vascularized bone grafting used to treat osteonecrosis of the femoral head.

Risk factors for melanoma, the deadliest form of skin cancer, include lifetime sun exposure and a history of sunburns. However, a minority of adolescents report consistent engagement in sun protective behaviors. The few sun protection interventions that have targeted adolescents have had little effect on behavior change, which suggests that a better understanding of the issue, especially from the adolescents' perspective, is needed. Although efforts to qualitatively examine adolescent sun protection have been carried out in a handful of countries, no studies to date have focused on U.S. adolescents. We conducted focus groups with 44 6th-8th grade students in Colorado to explore their sun protection knowledge, attitudes and behaviors. Results supported previous findings that adolescents do not engage in regular skin protection but have experienced the negative consequences of sun exposure (e.g., severe sun burns, and blistering). In addition, participants demonstrated limited and sometimes inaccurate knowledge about the long-term risks of sun exposure, as well as effective methods of sun protection. Barriers to engaging in sun protective behaviors included a desire to tan, inconvenience, and physical discomfort. Facilitators included peer and family encouragement, previous experience with sunburns and/or skin cancer, and knowledge of potential consequences. These findings provide valuable insights that can inform future intervention and research related to sun protection among U.S. adolescents.

Emotion regulation deficits have been implicated in anxiety and depressive disorders, and these internalising disorders are more prevalent in women than men. Few electrophysiological studies have investigated sex differences in emotional reactivity and emotion regulation controlling for menstrual phase. Event-related potentials (ERPs) were recorded from 28 early follicular women, 29 midluteal women, and 27 men who completed an emotion regulation task. A novel finding of increased N2 amplitude during suppression was found for midluteal women compared with men. These findings suggest midluteal women may be significantly less able to suppress cortical processing of negative stimuli compared to men. This ERP finding was complemented by behavioral ratings data which revealed that while both early follicular and midluteal women reported more distress than men, midluteal women also reported greater effort when suppressing their responses than men. P1 and N1 components were increased in midluteal women compared to men regardless of instructional set, suggesting greater early attentional processing. No sex or menstrual phase differences were apparent in P3 or LPP. This study underscores the importance of considering menstrual phase when examining sex differences in the cortical processing of emotion regulation and demonstrates that midluteal women may have deficits in down-regulating their neural and behavioural responses.

The objective of this study was to determine the effect of alcohol consumption on outcomes among women undergoing in vitro fertilization (IVF). This study is a retrospective cohort study. This study was performed in a private academically affiliated IVF center. Patients included women presenting for their first IVF cycle from July 2004 through October 2012. Women completed self-administered questionnaires before their first IVF cycle, which included report of usual alcohol consumption. Women were categorized as non-drinkers, social drinkers, or daily drinkers, as well as by the number of drinks consumed per week. Competing risks analysis was used to calculate the cumulative incidence of live birth after 6 cycles stratified by alcohol consumption. Main outcome measures included spontaneous abortion, clinical pregnancy, and live birth following IVF. There were 591 (27.7%) non-drinkers, 1466 (68.7%) social drinkers, and 77 (3.6%) daily drinkers (total n = 2134). In the first cycle, compared to non-drinkers, daily drinkers had a twofold increased risk of spontaneous abortion (adjusted risk ratio [aRR] 2.2; 95% confidence interval [CI] 1.1–4.5) among all cycle starts, and while their risk of live birth was 30% lower (aRR 0.7; 95% CI 0.4–1.3), the sample size was small, and it was not significantly lower. By the end of 6 cycles, social drinkers and daily drinkers did not differ from non-drinkers in their cumulative incidence of live birth (56.1, 50.6, and 52.1%, respectively; both P ≥ 0.28). There was a trend towards lower risk of live birth among daily drinkers. Daily drinkers had an increased risk of spontaneous abortion in the first cycle, but the number of daily drinkers was small.

The purpose of the study was to examine the association between serum progesterone levels on the day of hCG administration and birth weight among singleton live births after fresh embryo transfer. This study was conducted as a retrospective cohort database analysis on patients who underwent IVF treatment cycles from January 2004 to April 2012. The study was performed at a University affiliated private infertility practice. All cycles that had achieved a singleton live birth after fresh embryo transfer and for which progesterone was measured on the day of hCG administration were examined. Generalized linear models were used to calculate mean birth weight and z-scores. We analyzed 817 fresh IVF embryo transfers in which birth weight, gestational age, and progesterone (ng/mL) level on day of hCG administration were documented. While there was a decrease in birth weight as progesterone quartile [≤0.54; >0.54 to ≤0.81; >0.81 to ≤1.17; >1.17 ng/mL] increased, the difference in mean birth weights among the four quartiles was not statistically significant (p = 0.11) after adjusting for maternal age and peak estradiol levels. When dichotomizing based on a serum progesterone considered clinically elevated, cycles with progesterone >2.0 ng/mL had a significantly lower mean singleton birth weight (2860 g (95% CI 2642 g, 3079 g)) compared to cycles with progesterone ≤2.0 ng/mL (3167 g (95% CI 3122 g, 3211 g) p = 0.007)) after adjusting for maternal age and estradiol. We demonstrated that caution should be exercised when performing fresh embryo transfers with elevated progesterone levels and in particular with levels (>2.0 ng/mL) as this may lead to lower birth weight.

Adherence to antiretroviral therapy (ART) is associated with positive health outcomes among HIV+ patients. However, non-adherence remains high. Though factors that account for non-adherence remain unclear, social support has been consistently associated with ART adherence. As such, identifying malleable factors that hinder patients' ability to form supportive relationships may have consequence for improving ART adherence. Emotional avoidance (EA) may be one such factor given that it has been linked to difficulties in social situations. The present study examined relations among EA, the patient-provider relationship, other sources of social support, and ART adherence within a sample of HIV+ ART-prescribed patients. High EA was related to poor adherence and patient-provider relationships. EA was indirectly related to poor adherence through poorer patient-provider interactions. The indirect relation of EA to ART adherence through other sources of social support was not significant. Implications for developing targeted behavioral interventions focused on improving ART adherence are discussed.

The combination of single-cell RNA-seq and in vivo CRISPR–Cas9 screens reveal a new circuit that directs germinal center B cells toward a memory B cell phenotype during viral infection.

The original version of this article unfortunately contained a mistake.