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This paper shares insights from an international community of educators who have been using social media as a virtual space for a scholarly reading group: #edureading. The collection of educator narratives presented in this paper show how social networks on Twitter and Flipgrid were used as inclusive environments for teacher-led professional development. This paper is both a report of research involving five practitioners inquiring into their collective experience, and an exercise in building the scholarly capacity of the #edureading group. The accessibility of the social media platforms, as well as the collaborative, inquiry-based approach to scholarly reading, emerge as key themes in the educator narratives. The findings of this research emphasise that professional learning occurring in virtual spaces is open to social mediation using the norms of social networks, rather than the norms of workplaces, jurisdictions or education sectors, and that this can lead to a greater sense of empowerment for educators.

Abstract Background Human induced pluripotent stem cell (iPSC)-derived peripheral sensory neurons present a valuable tool to model human diseases and are a source for applications in drug discovery and regenerative medicine. Clinically, peripheral sensory neuropathies can result in maladies ranging from a complete loss of pain to severe painful neuropathic disorders. Sensory neurons are located in the dorsal root ganglion and are comprised of functionally diverse neuronal types. Low efficiency, reproducibility concerns, variations arising due to genetic factors and time needed to generate functionally mature neuronal populations from iPSCs remain key challenges to study human nociception in vitro. Here, we report a detailed functional characterization of iPSC-derived sensory neurons with an accelerated differentiation protocol (“Anatomic” protocol) compared to the most commonly used small molecule approach (“Chambers” protocol). Anatomic’s commercially available RealDRG™ were further characterized for both functional and expression phenotyping of key nociceptor markers. Methods Multiple iPSC clones derived from different reprogramming methods, genetics, age, and somatic cell sources were used to generate sensory neurons. Manual patch clamp was used to functionally characterize both control and patient-derived neurons. High throughput techniques were further used to demonstrate that RealDRGs™ derived from the Anatomic protocol are amenable to high throughput technologies for disease modelling. Results The Anatomic protocol rendered a purer culture without the use of mitomycin C to suppress non-neuronal outgrowth, while Chambers differentiations yielded a mix of cell types. Chambers protocol results in predominantly tonic firing when compared to Anatomic protocol. Patient-derived nociceptors displayed higher frequency firing compared to control subject with both, Chambers and Anatomic differentiation approaches, underlining their potential use for clinical phenotyping as a disease-in-a-dish model. RealDRG™ sensory neurons show heterogeneity of nociceptive markers indicating that the cells may be useful as a humanized model system for translational studies. Conclusions We validated the efficiency of two differentiation protocols and their potential application for functional assessment and thus understanding the disease mechanisms from patients suffering from pain disorders. We propose that both differentiation methods can be further exploited for understanding mechanisms and development of novel treatments in pain disorders.

Post-menopausal persons living with HIV (PWH) report elevated levels of psychological stress and monocyte activation compared to persons living without HIV (PWOH). Resting state functional connectivity (rsFC) of mesolimbic brain regions underpinning stress and emotion regulation are susceptible to inflammatory insult. Although psychological stress is elevated, rsFC reduced, and CD16+ monocytes overexpressed in the brains of PWH, it is unclear whether the relationships amongst these variables differ compared to PWOH.An ethnically diverse sample of postmenopausal women, 24 PWH and 30 PWOH provided self-report mood surveys and provided peripheral blood specimens to quantify LPS-stimulated CD16+/− expression of TNF-α via flow cytometric analysis. An anatomical and resting state functional MRI scan were used to derive time-series metrics of connectivity between the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAcc) as well as the amygdala.A positive association was observed between levels of perceived stress and CD16+/− TNF-α in both LPS-stimulated and unstimulated cells. PLWH showed lower connectivity between mPFC and NAcc. In turn, lower rsFC between these regions predicted greater psychological stress and proportion of CD16−, but not CD16+, cells expression of TNF-α.Neuroimmune effects of monocyte inflammation on the functional connectivity of mesolimbic regions critical for discrimination of uncertainty-safety and reward signals were observed in an ethnically diverse sample of postmenopausal women living with and without HIV. PWH showed lower mPFC-NAcc functional connectivity, which in turn was associated with greater perceived stress.

The aim of the article is to discuss the flipped learning-FL method. The research problem focuses on finding answers to the following questions: which scientific theories provide the theoretical framework for this method? Why is FL a teaching approach for the 21st century? The research method is a critical literature review. An analysis through the lens of constructivism and B. Bloom’s Taxonomy of Educational Objectives reveals that the method develops higher-order thinking skills and learner’s autonomy. The approach places educators in the role of facilitators and guides, shifting the learners to the centre of the educational process. In addition, the method can be successfully applied to bilingual as well as distance education.

Background: Low back pain (LBP) has been shown to have various biological, psychological, and social factors that affect prognosis. However, it is unclear how personality may influence self-reported outcome measures and therapeutic alliance (TA). Methods: Eysenck’s personality inventory was used to assess personality, while the numeric pain rating scale (NPRS), Oswestry Disability Index (ODI), Tampa Scale of Kinesiophobia (TSK), Global Rating of Change (GROC), and the Working Alliance Inventory (WAI) measured patient progress and relationship strength. All outcome measures were formulated in a single survey that both the therapist and patient completed electronically. Results: Sixty-seven patients with LBP and twenty-two licensed physical therapists participated. For personality measures, there was a significant positive correlation between neuroticism and GROC (rho = 0.295, p = 0.015) and a significant negative correlation between extraversion and WAI (rho = −0.243, p = 0.048). Significant correlations were found between ODI and TSK (rho = 0.462, p ≤ 0.001) and between ODI and GROC (rho = −0.416, p ≤ 0.001). A significant negative correlation was found between TSK and GROC (rho = −0.301, p = 0.013). Conclusions: Patients with higher levels of disability seemed to report higher levels of kinesiophobia and less overall improvement in physical therapy. Patients classified as neurotic reported higher levels of improvement while extraverted patients demonstrated a weaker therapeutic alliance with their therapist.

Objectives of the research: This article presents a diagnosis of the learned helplessness experienced by secondary-school students learning English remotely during the 2021 lockdown due to the COVID-19 pandemic. The objectives are to (1) show the level of learned helplessness of secondary-school students learning English, (2) investigate the relationship between foreign language learning strategies and the learned helplessness of secondary-school students, and (3) determine the relationship between the level of learned helplessness and the use of private tutoring by secondary-school students. Research methods: The study was conducted via a written diagnostic survey. It also employed the School Helplessness Scale by B. Ciżkowicz (2009) and the Strategy Inventory for Language Learning (SILL) by R. Oxford (1990). A short description of the context of the issue: The aim of the text is to answer the following research questions: What is the level of learned helplessness of secondary-school students? Is there a relationship between foreign language learning strategies and the learned helplessness of secondary-school students? Does the use of private tutoring differentiate the level of learned helplessness of secondary-school students? Research findings: The results demonstrate a significant negative correlation between learned helplessness and the use of memory, cognitive, metacognitive, affective, and social strategies. The average score of learned helplessness was 2.54, which indicates that the respondents usually felt the symptoms of it. An analysis of the results for the three deficits revealed that the motivational deficit made the greatest contribution to learned helplessness. The students who had hired a private tutor in English had a lower level of learned helplessness and cognitive deficit. Conclusions and/or recommendations: The research findings lead to several recommendations for educational practice in the context of foreign language learning: using new, effective pedagogical approaches to keep learners motivated—including elements of strategy training or social and emotional learning (SEL)—arranging remedial teaching, and promoting teachers’ professional development.

BackgroundDeep phenotyping of Parkinson’s disease (PD) is essential to investigate this fastest-growing neurodegenerative disorder. Since 2015, over 800 individuals with PD and atypical parkinsonism along with more than 800 control subjects have been recruited in the frame of the observational, monocentric, nation-wide, longitudinal-prospective Luxembourg Parkinson’s study.ObjectiveTo profile the baseline dataset and to explore risk factors, comorbidities and clinical profiles associated with PD, atypical parkinsonism and controls.MethodsEpidemiological and clinical characteristics of all 1,648 participants divided in disease and control groups were investigated. Then, a cross-sectional group comparison was performed between the three largest groups: PD, progressive supranuclear palsy (PSP) and controls. Subsequently, multiple linear and logistic regression models were fitted adjusting for confounders.ResultsThe mean (SD) age at onset (AAO) of PD was 62.3 (11.8) years with 15% early onset (AAO 50 years, 2.80 (2.62) years, 62.7% and 53.3 (19.5). The highest frequency of hyposmia was detected in PD followed by PSP and controls (72.9%; 53.2%; 14.7%), challenging the use of hyposmia as discriminating feature in PD vs. PSP. Alcohol abstinence was significantly higher in PD than controls (17.6 vs. 12.9%, p = 0.003).ConclusionLuxembourg Parkinson’s study constitutes a valuable resource to strengthen the understanding of complex traits in the aforementioned neurodegenerative disorders. It corroborated several previously observed clinical profiles, and provided insight on frequency of hyposmia in PSP and dietary habits, such as alcohol abstinence in PD.Clinical trial registration: clinicaltrials.gov, NCT05266872.

Abstract Background The resurgence of HIV outbreaks and rising prevalence among people who inject drugs (PWID) remain exigent obstacles to Ending the HIV Epidemic in the USA. Adapting a low threshold, comprehensive treatment model for PWID with HIV can leverage syringe services programs (SSPs) to increase availability and accessibility of antiretrovirals (ART), medications for opioid use disorder (MOUD), and hepatitis C cure. We developed Tele-Harm Reduction, a telehealth-enhanced, harm reduction intervention delivered within an SSP venue. Methods The T-SHARP trial is an open-label, multi-site, randomized controlled superiority trial with two parallel treatment arms. Participants (n=240) recruited from SSPs in Miami, Ft. Lauderdale, and Tampa, Florida, who are PWID with uncontrolled HIV (i.e., HIV RNA>200) will be randomized to Tele-Harm Reduction or off-site linkage to HIV care. The primary objective is to compare the efficacy of Tele-Harm Reduction for initiation of ART at SSPs vs. off-site linkage to an HIV clinic with respect to viral suppression across follow-up (suppression at 3, 6, and 12 months post randomization). Participants with HIV RNA

Purpose: This paper explores the features of pracademic practice within online spaces where pracademics, academics and teachers interact. Design/methodology/approach: This paper uses autoethnographic case studies to showcase the boundary-spanning thinking of two pracademics, one a practicing teacher, the other an early career researcher, to provide an overview of how pracademics are engaging with research and the profession online in Australia, in 2021. Findings: The paper describes five key features that are central to the development of pracademic practice. They are rigour and depth, discussion beyond immediate cultural context, accessibility, knowledge creation and collaboration. Research limitations/implications: This paper is focused on the teacher and early career researcher perspectives on pracademia, due to the extant literature focusing on the well-established academic perspective primarily. It focuses on fora within the Twitter social media platform and the #edureading group specifically. The authors propose that the use of Twitter fora, as those outlined, provides a legitimate form of professional development, and does contribute to the development of pracademics. Originality/value: This piece itself is an output of pracademia; through the writing of this paper, the authors show that pracademia is possible through teacher and researcher collaboration. The focus on online spaces, pracademic teachers and a coverage of what's occurring provide a new agenda for further research and consideration.

Introduction BedMed-Frail explores risks and benefits of switching antihypertensives from morning to bedtime in a frail population at greater risk of hypotensive adverse effects.Methods and analysis Design: Prospective parallel randomised, open-label, blinded end-point trial.Participants: Hypertensive continuing care residents, in either long-term care or supportive living, who are free from glaucoma, and using ≥1 once daily antihypertensive.Setting: 16 volunteer continuing care facilities in Alberta, Canada, with eligible residents identified using electronic health claims data.Intervention: All non-opted out eligible residents are randomised centrally by the provincial health data steward to bedtime versus usual care (typically morning) administration of once daily antihypertensives. Timing changes are made (maximum one change per week) by usual care facility pharmacists.Follow-up: Via linked governmental healthcare databases tracking hospital, continuing care and community medical services.Primary outcome: Composite of all-cause death, or hospitalisation for myocardial infarction/acute-coronary syndrome, stroke, or congestive heart failure.Secondary outcomes: Each primary outcome element on its own, all-cause unplanned hospitalisation or emergency department visit, non-vertebral fracture and, as assessed roughly 135 days postrandomisation, fall in the last 30 days, deteriorated cognition, urinary incontinence, decubitus skin ulceration, inappropriate or disruptive behaviour a minimum of 4 days per week, and receipt of antipsychotic medication or physical restraints in the last 7 days.Process outcome: Proportion of blood pressure medication doses taken at bedtime (broken down monthly).Primary outcome analysis: Cox-Proportional Hazards Survival Analysis.Sample size: The trial will continue until a projected 368 primary outcome events have occurred.Current status: Enrolment is ongoing with 642 randomisations to date (75% female, mean age 88 years).Ethics and dissemination BedMed-Frail has ethical approval from the University of Alberta Health Ethics Review Board (Pro00086129) and will publish results in a peer-reviewed journal.Trial registration number NCT04054648.

Background: Personality type plays a key role in how individuals respond to a variety of stimuli; however, it is unclear if there is a significant influence on pain perception. While pain is associated with many conditions, chronic low back pain (cLBP) is one of the most prevalent and debilitating problems in modern society. Treating this condition can be a challenge and clinicians must understand all factors that can influence pain perception. Purpose: The present study investigated the relationship between personality type and pain experience in patients experiencing cLBP. Methods: One hundred twenty-four participants completed the Eysenck Personality Inventory (EPI), which identifies two major components of the human personality, neuroticism, and extraversion. Participants also completed the Oswestry Disability Index (ODI), the Tampa Scale for Kinesiophobia (TSK), the Numeric Pain Rating Scale (NPRS), and the Pain Catastrophizing Scale (PCS). The association between pain and personality was determined with a Spearman Rank Correlation Coefficient. A hierarchical cluster analysis with Ward’s clustering method examined for subgroups of individuals based on these variables. Results: The neuroticism score (EPI-N) was found to have a statistically significant relationship with all pain outcome measures. This suggests that people exhibiting a neurotic personality type are likely to have more fear of movement (p = 0.001), greater catastrophizing behavior (p < 0.001), higher self-reported levels of disability (p < 0.001), and higher overall reported levels of pain (p = 0.046) than those with other, more stable personality types. Three clusters were derived with varying levels of pain-related factors and personality. Conclusions: Personality type appears to have an influence on many of the attributes associated with cLBP and may be a useful determinate in both prognosis and interventions.

Objectives We sought to validate, or refute, the common belief that bedtime diuretics are poorly tolerated due to nocturia.Design Prespecified prospective cohort analysis embedded within the randomised BedMed trial, in which hypertensive participants are randomised to morning versus bedtime antihypertensive administration.Setting 352 community family practices across 4 Canadian provinces between March 2017 and September 2020.Participants 552 hypertensive patients (65.6 years old, 57.4% female) already established on a single once-daily morning antihypertensive and randomised to switch that antihypertensive to bedtime. Of these, 203 used diuretics (27.1% thiazide alone, 70.0% thiazide/non-diuretic combinations) and 349 used non-diuretics.Intervention Switching the established antihypertensive from morning to bedtime, and comparing the experience of diuretic and non-diuretic users.Primary and secondary outcome measures Primary outcome: Adherence to bedtime allocation time at 6 months (defined as the willingness to continue with bedtime use, not an assessment of missed doses). Secondary 6-month outcomes: (1) nocturia considered to be a major burden and (2) increase in overnight urinations/week. All outcomes were self-reported and additionally collected at 6 weeks.Results At 6 months: Adherence to bedtime allocation time was lower in diuretic users than non-diuretic users (77.3% vs 89.8%; difference 12.6%; 95% CI 5.8% to 19.8%; p

# Background Up to 67% of adults experience shoulder pain in their lifetime. Numerous factors are related to the etiology of shoulder pain, one of which is thought to be scapular dyskinesis (SD). Given the prevalence of SD among the asymptomatic population a concern is that the condition is being medicalized (clinical findings suggested to require treatment but is ultimately a normal finding). Therefore, the purpose of this systematic review was to investigate the prevalence of SD among both symptomatic and asymptomatic populations. # Methods A systematic review of the literature up to July of 2021. Relevant studies identified from PubMed, EMBASE, Cochrane and CINAHL were screened utilizing the following inclusion and exclusion criteria; inclusion: (a) individuals being assessed as having SD, including reliability and validity studies (b) subjects aged 18 or older; (c) sport and non-sport participants; (d) no date restriction; (e) symptomatic, asymptomatic, or both populations; (f) all study designs except case reports. Studies were excluded if: (a) they were not published in the English language; (b) they were a case report design; (c) the presence of SD was part of the studies inclusion criteria; (d) data were not present distinguishing the number of subjects with or without SD; (e) they did not define participants as having or not having SD. Methodological quality of the studies was assessed utilizing the Joanna Briggs Institute checklist. # Results The search resulted in 11,619 after duplicates were removed with 34 studies ultimately retained for analysis after three were removed due to low quality. A total of 2,365 individuals were studied. Within the studies for the symptomatic athletic and general orthopedic population there were 81% and 57% individuals with SD, respectively, and a total of 60% among both symptomatic groups (sport and general orthopedic population). Within the studies for the asymptomatic athletic and general population there were 42% and 59% individuals with SD, respectively, and a total of 48% among both asymptomatic groups (sport and general orthopedic population). # Limitation A strict inclusion and exclusion criteria was used to identify studies that provided the appropriate data for the purpose of this study. There was a lack of consistency for measuring SD across studies. # Conclusion A considerable number of individuals with shoulder symptoms do not present with SD. More revealing is the number of asymptomatic individuals who do present with SD, suggesting that SD may be a normal finding among nearly half of the asymptomatic population. # Level of Evidence 2a

Neuropathic and nociplastic pain are major causes of pain and involve brain areas such as the central nucleus of the amygdala (CeA). Within the CeA, neurons expressing protein kinase c-delta (PKCδ) or somatostatin (SST) have opposing roles in pain-like modulation. In this manuscript, we describe our progress towards developing a 3-D computational model of PKCδ and SST neurons in the CeA and the use of this model to explore the pharmacological targeting of these two neural populations in modulating nociception. Our 3-D model expands upon our existing 2-D computational framework by including a realistic 3-D spatial representation of the CeA and its subnuclei and a network of directed links that preserves morphological properties of PKCδ and SST neurons. The model consists of 13,000 neurons with cell-type specific properties and behaviors estimated from laboratory data. During each model time step, neuron firing rates are updated based on an external stimulus, inhibitory signals are transmitted between neurons via the network, and a measure of nociceptive output from the CeA is calculated as the difference in firing rates of pro-nociceptive PKCδ neurons and anti-nociceptive SST neurons. Model simulations were conducted to explore differences in output for three different spatial distributions of PKCδ and SST neurons. Our results show that the localization of these neuron populations within CeA subnuclei is a key parameter in identifying spatial and cell-type pharmacological targets for pain.

BACKGROUND:Objective adherence metrics for tenofovir (TFV) disoproxil fumarate/emtricitabine(FTC)-based PrEP were critical for interpretation of efficacy in PrEP clinical trials, and there is increasing interest in using drug levels to tailor interventions for reengagement and adherence. Point-of-care immunoassays (POC) for TFV, which examine short-term adherence, are in development. However the ability of poor short-term and long-term adherence to predict future PrEP non-retention is unknown. SETTING:Secondary data analysis of a large, prospective multi-site U.S. PrEP demonstration project METHODS:: An adjusted Cox-proportional hazards model examined the relationship of dried blood spot (DBS) levels of FTC-triphosphate (FTC-TP) or TFV-diphosphate (TFV-DP), measures of short-term and long-term PrEP adherence, respectively, with future study non-retention. RESULTS:Overall, 294 individuals (median age 33 years) contributed drug levels within the U.S. PrEP demonstration project. By study end, 27% were lost to follow-up, 25% had at least one undetectable FTC-TP level indicating poor short-term adherence, and 29% had a drug level indicating sub-optimal long-term adherence (TFV-DP

Background: Hepatic tumors with complex vascular supply or poor relative perfusion are prone to decreased rates of objective response. This is compounded in the setting of Yttrium-90 (Y90) transarterial radioembolization (TARE), which is minimally embolic and flow-dependent, relying on high threshold dose for complete response. Objective: We describe our experience with intrahepatic flow diversion (FD) prior to TARE of hepatocellular carcinoma (HCC) with challenging vascular supply. Materials and methods: Between April 2014 and January 2020, 886 cases of coinciding MAA or TARE and bland embolization or temporary occlusion were identified. Intraprocedural embolizations performed for more routine purposes were excluded. FD was performed by bland embolization or temporary occlusion of vessels supplying non-malignant parenchyma in cases where flow was not preferential to target tumor. Lesion characteristics, vascular supply, treatment approach, angiography, and adverse events (AEs) were reviewed. Radiographic response was assessed using mRECIST criteria. Results: 22 cases of FD of focal HCC were identified. Embolics included calibrated microspheres (n ​= ​11), microcoils (n ​= ​4), gelfoam (n ​= ​3), temporary balloon occlusion (n ​= ​2) and temporary deployment of a microvascular plug (n ​= ​1). Post-treatment SPECT-CT dosimetry coverage was concordant with target lesions in all cases. Mean follow-up was 16.7 months (1.4–45 ​mos). Tumor-specific response per mRECIST was 41% complete response, 50% objective response, and 59% disease control rate. No major adverse events or grade 3/4 hepatotoxicity were reported. Conclusion: Our findings suggest that FD prior to TARE is safe and potentially effective in treating HCC with complex vascular supply or poor tumor perfusion.

In an attempt to control the spread of COVID-19 in Australia in 2020 state and territory governments mandated the closing of schools for all but vulnerable children and the children of frontline workers in various parts of Australia for various lengths of time. In what follows, five English teachers from across Australia reflect on the everyday experience of teaching during lockdown. Using the framework of 'who' and 'what' stories (Cavarero, 2000), these narratives explore the individual and contextual experience of the everyday work of teaching remotely, while also contributing to the collective story of English teaching during a global pandemic. The narratives raise questions about teachers' identity and development as well as broader questions about subject English.

Introduction: Learned helplessness is a condition that arises as a result of a person’s belief that they are unable to control events. Having no sense of control over unpleasant experiences, a person learns that there is no relationship between the actions they take and their results. This condition is accompanied by changes in behaviour. These include cognitive, motivational and emotional deficits. Research Aim: The objectives of the study described in this article are to assess the learned helplessness of eighth grade primary school students in three examination subjects: Polish, mathematics and English, and to show the relationship between the gender of the respondents and the perceived level of helplessness. Method: The study used the diagnostic survey method, and the research technique applied was a questionnaire. In order to measure the level of learned helplessness, the School Helplessness Scale (SBS) by Ciżkowicz (2009) was used. The survey was conducted between late March and early April of the 2020/21 school year. It covered 502 eighth grade primary school students learning remotely. Results: The study shows that the highest average level of helplessness was recorded in mathematics, slightly lower in Polish, and lowest in English. Girls have a higher sense of helplessness than boys in mathematics and English. The motivational deficit makes the greatest contribution to the feeling of helplessness. Conclusion: The results indicate the need to implement a number of activities in the areas of psychological and pedagogical support at school. It is important that this support covers not only students, but also teachers and parents. Students should receive pedagogical and psychological help in the area of emotional education and constructive thinking. Teachers and parents should understand the essence of the phenomenon, know its causes and be able to recognise the first symptoms of helplessness.

Abstract Background Opioid use is escalating in North America and comes with a multitude of health consequences, including HIV and hepatitis C virus (HCV) outbreaks among persons who inject drugs (PWID). HIV pre-exposure prophylaxis (PrEP) and HCV treatment regimens have transformative potential to address these co-occurring epidemics. Evaluation of innovative multi-modal approaches, integrating harm reduction, opioid agonist therapy (OAT), PrEP, and HCV treatment is required. The aim of this study is to assess the effectiveness of an on-site integrated care model where delivery of PrEP and HCV treatment for PWID takes places at syringe service programs (SSP) and OAT programs compared with referring PWID to clinical services in the community through a patient navigation model and to examine how structural factors interact with HIV prevention adherence and HCV treatment outcomes. Methods The Miami-Montreal Hepatitis C and Pre-Exposure Prophylaxis trial (M2HepPrEP) is an open-label, multi-site, multi-center, randomized, controlled, superiority trial with two parallel treatment arms. A total of 500 persons who injected drugs in the prior 6 months and are eligible for PrEP will be recruited in OAT clinics and SSP in Miami, FL, and Montréal, Québec. Participants will be randomized to either on-site care, with adherence counseling, or referral to off-site clinics assisted by a patient navigator. PrEP will be offered to all participants and HCV treatment to those HCV-infected. Co-primary endpoints will be (1) adherence to pre-exposure prophylaxis medication at 6 months post-randomization and (2) HCV sustained virological response (SVR) 12 weeks post-treatment completion among participants who were randomized within the HCV stratum. Up to 100 participants will be invited to participate in a semi-structured interview regarding perceptions of adherence barriers and facilitators, after their 6-month assessment. A simulation model-based cost-effectiveness analysis will be performed to determine the comparative value of the strategies being evaluated. Discussion The results of this study have the potential to demonstrate the effectiveness and cost-effectiveness of offering PrEP and HCV treatment in healthcare venues frequently attended by PWID. Testing the intervention in two urban centers with high disease burden among PWID, but with different healthcare system dynamics, will increase generalizability of findings. Trial registration Clinicaltrials.gov NCT03981445 . Trial registry name: Integrated HIV Prevention and HCV Care for PWID (M2HepPrEP). Registration date: June 10, 201.

A doença de Lyme é pouco diagnosticada, apesar de frequente no mundo. Apresenta potencial zoonótico e os cães são considerados sentinelas da doença. Este trabalho tem como finalidade relatar um caso de um animal da raça Poodle atendido em uma clínica veterinária particular em Ribeirão Pires - SP, positivo para a presença de anticorpos de Borrelia burgdorferi confirmados através de sorologia pelo método Dot-Blot e teste rápido. O animal estava realizando exames pré-cirúrgicos para retirada de um tumor em região anal, não apresentava alterações no exame físico, sendo a trombocitopenia única desordem observada. O diagnóstico é fechado através da sorologia juntamente com a clínica/ histórico do animal, mas na maioria dos casos é um achado clínico. Como a borreliose, outro nome para doença de Lyme, tem sinais inespecíficos e de grande importância para a saúde pública, é essencial que seja incluída como diagnóstico diferencial de demais doenças com sintomas semelhantes, embora a mesma já foi relatada associada a Erliquiose, Anaplasmose e entre outras hemoparasitoses transmitidas através do carrapato. Este trabalho tem caráter informativo e de educação sanitária e epidemiológica, dando oportunidade aos leitores conhecerem mais profundamente a doença e seus riscos à saúde pública.

Eco-labels are an instrument for enabling informed food choices and supporting a demand-sided change towards an urgently needed sustainable food system. Lately, novel eco-labels that depict a product’s environmental life cycle assessment on a multi-level scale are being tested across Europe’s retailers. This study elicits consumers’ preferences and willingness to pay (WTP) for a multi-level eco-label. A Discrete Choice Experiment was conducted; a representative sample (n = 536) for the Austrian population was targeted via an online survey. Individual partworth utilities were estimated by means of the Hierarchical Bayes. The results show higher WTP for a positively evaluated multi-level label, revealing consumers’ perceived benefits of colorful multi-level labels over binary black-and-white designs. Even a negatively evaluated multi-level label was associated with a higher WTP compared to one with no label, pointing towards the limited effectiveness of eco-labels. Respondents’ preferences for eco-labels were independent from their subjective eco-label knowledge, health consciousness, and environmental concern. The attribute “protein source” was most important, and preference for an animal-based protein source (beef) was strongly correlated with consumers’ meat attachment, implying that a shift towards more sustainable protein sources is challenging, and sustainability labels have only a small impact on the meat product choice of average consumers.

BackgroundPrognostic variables for assessing people with whiplash associated disorder (WAD) following a motor vehicle collision (MVC) have been evaluated in numerous studies. However, there is minimal evidence assessing how these variables may differ between males and females.Question/purpose1) To assess if the sex of a person interacts with known prognostic variables within the development of chronic WAD. 2) To determine if commonly used outcome measures used in the assessment of chronic WAD differ between sexes.MethodsThe study was a secondary analysis of an observational study with an inception cohort immediately following an MVC in an emergency department in Chicago, IL, USA. Ninety-seven adults aged 18 to 60 (mean 34.7 years old; 74% female) participated in the study. The primary outcome was long-term disability as determined by Neck Disability Index (NDI) scores at 52-weeks post-MVC. Data was collected at baseline (less than 1-week), 2, 12, 52-weeks post MVC. Hierarchal linear regression was used to determine significance (ΔF-score, p < 0.05) and R2 for each of the variables. The primary variables of interest were sex of the participant, age, baseline scores on the numeric pain rating scale (NPRS) and NDI and created interaction terms for sex x z-baseline NPRS and sex x z-NDI.ResultsFrom analysis 1, both NDI (R2 = 8.7%, p < 0.01) and NPRS (R2 = 5.7%, p = 0.02) collected at baseline predicted significant variance in NDI score at 52-weeks. The interaction term of sex x z-NPRS was also significant (R2 = 3.8%, p = 0.04). In analysis 2 the regression models when disaggregated by sex showed that baseline NDI was the significant predictor of 52-week outcome in males (R2 = 22.4%, p = 0.02) while it was the NPRS as the significant predictor in females (R2 = 10.5%, p < 0.01).

BackgroundHIV preexposure prophylaxis (PrEP) using daily oral tenofovir-disoproxil-fumarate/emtricitabine (TDF/FTC) is effective for preventing HIV acquisition, but concerns remain about its potential kidney toxicity. This study examined kidney function in individuals using PrEP in real-world clinical settings.SettingDemonstration project in 2 sexually transmitted infection clinics and a community health center.MethodsWe evaluated kidney function among men who have sex with men and transgender women taking tenofovir-disoproxil-fumarate/emtricitabine PrEP for up to 48 weeks. Serum creatinine and urine dipstick for protein were obtained at 12-week intervals. Kidney function was estimated using creatinine clearance (CrCl) (Cockcroft-Gault) and estimated glomerular filtration rate (eGFR) (CKD-EPI).ResultsFrom October 2012 to January 2014, we enrolled 557 participants (median age 33). Mean creatinine increased from baseline to week 12 by 0.03 mg/dL (4.6%) (P < 0.0001); mean CrCl decreased by 4.8 mL/min (3.0%) (P < 0.0001). These changes remained stable through week 48 (P = 0.81, P = 0.71 respectively). There were 75/478 (15.7%) participants who developed worsening proteinuria at week 12 compared with baseline (P < 0.0001), and this percent remained stable through week 48 (P = 0.73). Twenty-five participants (5.1%) developed new-onset eGFR

Nitrogen (N) is the major limiting nutrient for phytoplankton growth and productivity in large parts of the world's oceans. Differential preferences for specific N substrates may be important in controlling phytoplankton community composition. To date, there is limited information on how specific N substrates influence the composition of naturally occurring microbial communities. We investigated the effect of nitrate ((Formula presented.)), ammonium ((Formula presented.)), and urea on microbial and phytoplankton community composition (cell abundances and 16S rRNA gene profiling) and functioning (photosynthetic activity, carbon fixation rates) in the oligotrophic waters of the North Pacific Ocean. All N substrates tested significantly stimulated phytoplankton growth and productivity. Urea resulted in the greatest (>300%) increases in chlorophyll a (

Personality type can influence pain perception and prognosis. Therefore, it is important for clinicians to consider personality factors that may influence outcomes and understand personality inventories to garner a better understanding of how an individual may perceive pain. This paper explores different elements that contribute to low back pain (LBP) and evaluates a personality inventory reported in the medical literature. Understanding how to evaluate personality type as well as how to approach clinical interactions based on personality may help to provide context for the unique needs of individual patients when developing a plan of care to treat LBP.

Celem badania jest ukazanie związku pomiędzy strategiami uczenia się a czynnikami środowiskowymi. Próbę badawczą stanowiło 371 uczniów uczących się języka angielskiego w liceach ogólnokształcących w województwie kujawsko-pomorskim, a do zebrania materiału wykorzystano kwestionariusz ankiety Inwentarz Strategii Uczenia się Języka (wersja 7.0) autorstwa R. Oxford. Badanie pokazuje, że istnieje związek pomiędzy zachowaniem strategicznym uczniów a znajomością języka obcego i wykształceniem ich rodziców. Wnioski mogą zainteresować teoretyków edukacji, nauczycieli oraz rodziców.

ObjectiveThe US preexposure prophylaxis (PrEP) Demonstration Project (U.S. Demo) evaluated MSM on PrEP postmarketing and found low seroconversion rates. The objective of this study is to examine hair levels as an adherence measure to PrEP.DesignUsing an 'opt-in' design, participants of PrEP Demo were invited to enroll into a substudy where hair was collected quarterly.MethodsTenofovir concentrations were measured in hair by liquid chromatography/tandem mass spectrometry. Hair levels consistent with ≥4 doses/week (protective in other studies) defined adequate adherence. Mixed effects multivariate logistic regression models examined factors associated with ≥4 doses/week. Separate mixed effects models evaluated the relationship between hair PrEP levels and changes in creatinine clearance (CrCl) over time.ResultsOverall, 58% of U.S. Demo participants enrolled into this opt-in study; reasons for nonparticipation included insufficient hair (61%) and concerns about hairstyle (27%). Hair and dried blood spots levels consistent with ≥4 doses/week were highly concordant (84%). Hair levels showed adequate adherence in 87% of 875 person-visits (among 280 participants). Factors associated with adequate adherence in multivariate models were amphetamine use [adjusted odds ratio (aOR) 2.59 (0.97-6.9, P 0.06)], condomless receptive anal sex [aOR 2.28 (1.19-4.40, P 0.01)], and stable housing [aOR 2.63 (1.03-6.67), P 0.04]. Hair levels of tenofovir showed a monotonic relationship with decline in CrCl (P 0.01 for trend).ConclusionIn this substudy of the U.S. PrEP demonstration project, hair and dried blood spots levels were highly concordant and hair concentrations demonstrated adequate adherence 87% of the time, with stable housing and high-risk behavior associated with higher adherence. Daily PrEP drug taking is associated with modest declines in CrCl.

AbstractMorphine is a well-characterized and effective analgesic commonly used to provide pain relief to patients suffering from both acute and chronic pain conditions. Despite its widespread use and effectiveness, one of the major drawbacks of morphine is its relatively short half-life of approximately 4 h. This short half-life often necessitates multiple administrations of the drug each day, which may contribute to both dependence and tolerance to morphine. Here, we tested the analgesic properties of a new polymer form of morphine known as PolyMorphine. This polymer has monomeric units of morphine incorporated into a poly(anhydride-ester) backbone that has been shown to hydrolyze into free morphine in vitro. Using an animal model of chronic pain, the spared nerve injury surgery, we showed that PolyMorphine is able to block spared nerve injury-induced hypersensitivity in mice for up to 24-h post-administration. Free morphine was shown to only block spared nerve injury-induced hypersensitivity for up to 2-h post-injection. PolyMorphine was also shown to act through the mu opioid receptor due to the ability of naloxone (a mu opioid receptor antagonist) to block PolyMorphine-induced analgesia in spared nerve injury animals pretreated with PolyMorphine. Additionally, we observed that PolyMorphine causes similar locomotor and constipation side effects as free morphine. Finally, we investigated if PolyMorphine had any effects in a non-evoked pain assay, conditioned place preference. Pretreatment of spared nerve injury mice with PolyMorphine blocked the development of conditioned place preference for 2-methyl-6-(phenylethynyl)pyridine (MPEP), a short-lasting mGluR5 antagonist with analgesic-like properties. Free morphine does not block the development of preference for MPEP, suggesting that PolyMorphine has longer lasting analgesic effects compared to free morphine. Together, these data show that PolyMorphine has the potential to provide analgesia for significantly longer than free morphine while likely working through the same receptor.

Abstract Background The regulation and control of pressure stimuli is useful for many studies of pain and nociception especially those in the visceral pain field. In many in vivo experiments, distinct air and liquid stimuli at varying pressures are delivered to hollow organs such as the bladder, vagina, and colon. These stimuli are coupled with behavioral, molecular, or physiological read-outs of the response to the stimulus. Care must be taken to deliver precise timed stimuli during experimentation. For example, stimuli signals can be used online to precisely time-lock the stimulus with a physiological output. Such precision requires the development of specialized hardware to control the stimulus (e.g., air) while providing a precise read-out of pressure and stimulus signal markers. Methods In this study, we designed a timed pressure regulator [termed visceral pressure stimulator (VPS)] to control air flow, measure pressure (in mmHg), and send stimuli markers to online software. The device was built using a simple circuit and primarily off-the-shelf parts. A separate custom inline analog-to-digital pressure converter was used to validate the real pressure output of the VPS. Results Using commercial physiological software (Spike2, CED), we were able to measure mouse bladder pressure continuously during delivery of unique air stimulus trials in a mouse while simultaneously recording an electromyogram (EMG) of the overlying abdominal muscles. Conclusions This device will be useful for those who need to (1) deliver distinct pressure stimuli while (2) measuring the pressure in real-time and (3) monitoring stimulus on–off using physiological software.

People living with HIV (PLHIV) are at a higher risk of having cerebrocardiovascular diseases (CVD) compared to HIV negative (HIVneg) individuals. The mechanisms underlying this elevated risk remains elusive. We hypothesize that HIV infection results in modified microRNA (miR) content in plasma extracellular vesicles (EVs), which modulates the functionality of vascular repairing cells, i.e., endothelial colony-forming cells (ECFCs) in humans or lineage negative bone marrow cells (lin− BMCs) in mice, and vascular wall cells. PLHIV (N = 74) have increased atherosclerosis and fewer ECFCs than HIVneg individuals (N = 23). Plasma from PLHIV was fractionated into EVs (HIVposEVs) and plasma depleted of EVs (HIV PLdepEVs). HIVposEVs, but not HIV PLdepEVs or HIVnegEVs (EVs from HIVneg individuals), increased atherosclerosis in apoE−/− mice, which was accompanied by elevated senescence and impaired functionality of arterial cells and lin− BMCs. Small RNA-seq identified EV-miRs overrepresented in HIVposEVs, including let-7b-5p. MSC (mesenchymal stromal cell)-derived tailored EVs (TEVs) loaded with the antagomir for let-7b-5p (miRZip-let-7b) counteracted, while TEVs loaded with let-7b-5p recapitulated the effects of HIVposEVs in vivo. Lin− BMCs overexpressing Hmga2 (a let-7b-5p target gene) lacking the 3′UTR and as such is resistant to miR-mediated regulation showed protection against HIVposEVs-induced changes in lin− BMCs in vitro. Our data provide a mechanism to explain, at least in part, the increased CVD risk seen in PLHIV.

Marine cyanobacteria are a rich source of bio-active metabolites that have been utilized as leads for drug discovery and pharmacological tools for basic science research. Here, we describe the re-isolation of a well-known metabolite, barbamide, from Curaçao on three different occasions and the characterization of barbamide’s biological interactions with targets of the mammalian nervous system. Barbamide was originally discovered as a molluscicidal agent from a filamentous marine cyanobacterium. In our hands, we found little evidence of toxicity against mammalian cell cultures. However, barbamide showed several affinities when screened for binding affinity for a panel of 45 receptors and transporters known to be involved in nociception and sensory neuron activity. We found high levels of binding affinity for the dopamine transporter, the kappa opioid receptor, and the sigma receptors (sigma-1 and sigma-2 also known as transmembrane protein 97; TMEM97). We tested barbamide in vitro in isolated sensory neurons from female mice to explore its functional impact on calcium flux in these cells. Barbamide by itself had no observable impact on calcium flux. However, barbamide enhanced the effect of the TRPV1 agonist capsaicin and enhanced store-operated calcium entry (SOCE) responses after depletion of intracellular calcium. Overall, these results demonstrate the biological potential of barbamide at sensory neurons with implications for future drug development projects surrounding this molecule.

Synthetic biologists often co-opt heterologous parts to affect new functions in living cells, yet such an approach has rarely been extended to structural components of the ribosome. Here, the authors describe generalizable methods to express ribosomes from divergent microbes in E. coli and maximize their function.

AbstractIntroduction Hospitalizations for severe injection-related infections (SIRI), such as endocarditis, osteomyelitis, and skin and soft tissue infections (SSTI) are increasingly common. People who inject drugs (PWID) experiencing SIRIs often receive inadequate substance use disorder (SUD) treatment and lack of access to harm reduction services. This translates into lengthy hospitalizations with high rates of patient-directed discharge, readmissions, and post-hospitalization mortality. The purpose of this study was to describe the development of an integrated “SIRI Team” and its initial barriers and facilitators to success.Materials and methods The Jackson SIRI Team was developed to improve both hospital and patient-level outcomes for individuals hospitalized with SIRIs at Jackson Memorial Hospital, a 1550-bed public hospital in Miami, Florida, United States. The SIRI Team provides integrated infectious disease and SUD treatment across the healthcare system starting from the inpatient setting and continuing for 90-days post-hospital discharge. The team uses a harm reduction approach, provides care coordination, focuses on access to medications for opioid use disorder (MOUD), and utilizes a variety of infection and addiction treatment modalities to suit each individual patient.Results Over the initial 8-months of the SIRI Team, 21 patients were treated with 20 surviving until discharge. Infections included osteomyelitis, endocarditis, bacteraemia/fungemia, SSTIs, and septic arthritis. All patients had OUD and 95% used stimulants. All patients were discharged on MOUD and 95% completed their prescribed antibiotic course. At 90-days post-discharge, 25% had been readmitted and 70% reported taking MOUD.Conclusions A model of integrated infectious disease and SUD care for the treatment of SIRIs has the potential to improve infection and addiction outcomes. Providing attentive, patient-centered care, using a harm reduction approach can facilitate engagement of this marginalized population with the healthcare system.KEY MESSAGESIntegrated infectious disease and addiction treatment is a novel approach to treating severe injection-related infections.Harm reduction should be applied to treating patients with severe injection-related infections with a goal of facilitating antibiotic completion, remission from substance use disorder, and reducing hospital readmissions.

ImportanceSeveral randomized clinical trials have demonstrated the efficacy of preexposure prophylaxis (PrEP) in preventing human immunodeficiency virus (HIV) acquisition. Little is known about adherence to the regimen, sexual practices, and overall effectiveness when PrEP is implemented in clinics that treat sexually transmitted infections (STIs) and community-based clinics serving men who have sex with men (MSM).ObjectiveTo assess PrEP adherence, sexual behaviors, and the incidence of STIs and HIV infection in a cohort of MSM and transgender women initiating PrEP in the United States.Design, setting, and participantsDemonstration project conducted from October 1, 2012, through February 10, 2015 (last date of follow-up), among 557 MSM and transgender women in 2 STI clinics in San Francisco, California, and Miami, Florida, and a community health center in Washington, DC. Data were analyzed from December 18, 2014, through August 8, 2015.InterventionsA combination of daily, oral tenofovir disoproxil fumarate and emtricitabine was provided free of charge for 48 weeks. All participants received HIV testing, brief client-centered counseling, and clinical monitoring.Main outcomes and measuresConcentrations of tenofovir diphosphate in dried blood spot samples, self-reported numbers of anal sex partners and episodes of condomless receptive anal sex, and incidence of STI and HIV acquisition.ResultsOverall, 557 participants initiated PrEP, and 437 of these (78.5%) were retained through 48 weeks. Based on the findings from the 294 participants who underwent measurement of tenofovir diphosphate levels, 80.0% to 85.6% had protective levels (consistent with ≥4 doses/wk) at follow-up visits. African American participants (56.8% of visits; P = .003) and those from the Miami site (65.1% of visits; P

# Background Range of motion (ROM) impairments of the overhead athletes' shoulder are commonly addressed through mobility-based treatments, however, adaptations from humeral torsion (HT) are not amenable to such interventions. A clinical measurement to quantify HT has been proposed, however, the validity is not conclusive. # Purpose The primary aim of this study is to determine the intrarater reliability and standard error of measurement (SEM) of the biceps forearm angle (BFA) measurement. The secondary aim of this study is to investigate the convergent validity of the BFA compared to diagnostic ultrasound. # Study Design Cross Sectional Reliability and Validity Study # Methods HT measurements, utilizing diagnostic ultrasound, were compared to BFA in 74 shoulders (37 subjects) over two sessions. Each measurement was performed three times and a third investigator recorded measures to ensure blinding. Reliability was investigated using utilizing an intraclass correlation coefficient (ICC 3,k) # Results Intrarater reliability values were 0.923 and 0.849 for diagnostic ultrasound and BFA methods respectively. Convergent validity was *r* = 0.566. The standard error of measurement for diagnostic ultrasound and BFA was 3° and 5°, respectively. The 95% limits of agreement between the two measurement methods were -24.80° and 19.80° with a mean difference of -2.50° indicating that on average the diagnostic ultrasound measurement was lower than that of the BFA method. # Conclusion The BFA is a reliable clinical method for quantifying HT, however, demonstrates moderate to poor convergent validity when compared to diagnostic ultrasound. # Level of Evidence 2b

Objective Indices of cardiovascular disease (CVD) risk, vascular endothelial dilation, arterial stiffness and endothelial repair were examined in persons with HIV (PWH) on an antiretroviral therapy (ART) that included abacavir (ABC+) in comparison with PWH on ART without abacavir (ABC-), and with HIV seronegative (HIV-) individuals. Approach The 115 participants (63% men), aged 30–50 years, did not have CVD, metabolic, endocrine, or chronic renal conditions. PWH were on stable ART for six-months or more. Vascular assessments included flow-mediated dilation (FMD), aortic, radial and femoral arterial stiffness (cAIx, crPWV, cfPWV), and thigh and calf arterial compliance (Vmax50). Endothelial repair was indexed by endothelial progenitor cell colony forming units (EPC-CFU). Traditional CVD risk measures included blood pressure, central adiposity, lipids, insulin resistance (HOMA-IR), CRP and ASCVD score. Analyses controlled for demographics (age, sex, education), medications (antihypertensive, statin/fibrate, antipsychotic), and substance abuse (ASSIST). Results No group differences were observed in central adiposity, HOMA-IR, CRP, or ASCVD risk score. However, the ABC- group displayed greater dyslipidemia. The ABC+ group displayed no difference on FMD, cAIx, cfPWV or calf Vmax50 compared with other groups. When CD4 count and viral load were controlled, no additional differences between the ABC+ and ABC- groups emerged. Analyses of crPWV and thigh Vmax50 suggested supported by a trend toward lower EPC-CFU in the HIV+ groups than the HIV- group. Conclusions Findings indicate that ABC treatment of 30–50 year-old PWH on stable ART is not likely to contribute in a robust way to higher CVD risk.