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Non-communicable diseases (NCD) such as CVD and type 2 diabetes mellitus are major contributors to the burden of disease. NCD are largely driven by modifiable lifestyle factors including poor diet and insufficient physical activity, and consequently, prevention is a public health priority. Although diet and physical activity levels can be improved via lifestyle interventions, long-term adherence to such interventions remains low, which limits their effectiveness. Thus, it is critical to identify the underlying mechanisms that challenge uptake and adherence to such interventions. The current commentary discusses an important, but underexplored, psychological driver of poor adherence to lifestyle interventions, namely, future discounting, which describes the tendency to prefer smaller, short-term rewards over larger, long-term rewards. For example, in the nutrition domain, future discounting refers to valuing the immediate reward of excessive intake of energy-dense, nutrient-poor, discretionary foods high in salt, sugar, and saturated fat, and insufficient intake of low-energy, nutrient-dense, whole foods such as vegetables. Prominent theoretical models propose that excessive future discounting is a major contributor to the development of unhealthy lifestyle behaviours. Furthermore, a vast body of evidence suggests that future discounting plays a key role in risk of NCD. Thus, the evidence to date supports the idea that future discounting is an important multi-behaviour target for supporting lifestyle behaviour change; however, this approach has been largely neglected in preventive health efforts. Furthermore, this commentary discusses promising techniques (e.g. Episodic Future Thinking) for disrupting future discounting to promote improved adherence to lifestyle interventions aimed at reducing NCD risk.

To determine the epidemiology of human parainfluenza virus in homeless shelters during the COVID-19 pandemic, we analyzed data and sequences from respiratory specimens collected in 23 shelters in Washington, USA, during 2019-2021. Two clusters in children were genetically similar by shelter of origin. Shelter-specific interventions are needed to reduce these infections.

The global Coronavirus disease 2019 (COVID-19) pandemic has resulted in public health, political, scientific and private sector response at an unprecedented scale. However, this shift in focus has caused widespread disruption to global health services and has the potential to reverse gains made in efforts to control malaria. If health systems are not able to maintain malaria control interventions while managing the response to the COVID-19 pandemic, malaria cases will increase, thereby placing even more strain on already overtaxed systems. Using a Narrative Review Approach, this commentary explores the impact of COVID-19 on progress made with malaria control and prevention strategies in Africa; and discusses possible mitigation steps to aid community resilience building, through proactive planning and implementation of integrated, inclusive and sustainable strategies to re-shift the focus to attain the malaria elimination goals. We propose strengthening community partnerships, where academia and communities should collaborate and these knowledge-sharing strategies be implemented in order for awareness and interventions to become more networked, inclusive, resilient and effective. Communities should be viewed as 'thought partners', who challenge conventional strategies and aid in developing innovative approaches to community resilience building.

Dominant mutations in ubiquitously expressed mitofusin 2 gene (MFN2) cause Charcot-Marie-Tooth type 2A (CMT2A; OMIM 609260), an inherited sensory-motor neuropathy that affects peripheral nerve axons. Mitofusin 2 protein has been found to take part in mitochondrial fusion, mitochondria–endoplasmic reticulum tethering, mitochondrial trafficking along axons, mitochondrial quality control and various types of cancer, in which MFN2 has been indicated as a tumor suppressor gene. Discordant data on the mitochondrial altered phenotypes in patient-derived fibroblasts harboring MFN2 mutations and in animal models have been reported. We addressed some of these issues by focusing on mitochondria behavior during autophagy and mitophagy in fibroblasts derived from a CMT2AMFN2 patient with an MFN2650G > T/C217F mutation in the GTPase domain. This study investigated mitochondrial dynamics, respiratory capacity and autophagy/mitophagy, to tackle the multifaceted MFN2 contribution to CMT2A pathogenesis. We found that MFN2 mutated fibroblasts showed impairment of mitochondrial morphology, bioenergetics capacity, and impairment of the early stages of autophagy, but not mitophagy. Unexpectedly, transcriptomic analysis of mutated fibroblasts highlighted marked differentially expressed pathways related to cell population proliferation and extracellular matrix organization. We consistently found the activation of mTORC2/AKT signaling and accelerated proliferation in the CMT2AMFN2 fibroblasts. In conclusion, our evidence indicates that MFN2 mutation can positively drive cell proliferation in CMT2AMFN2 fibroblasts.

Background Rhinovirus (RV) is a common cause of respiratory illness in all people, including those experiencing homelessness. RV epidemiology in homeless shelters is unknown. Methods We analyzed data from a cross-sectional homeless shelter study in King County, Washington, October 2019–May 2021. Shelter residents or guardians aged ≥3 months reporting acute respiratory illness completed questionnaires and submitted nasal swabs. After 1 April 2020, enrollment expanded to residents and staff regardless of symptoms. Samples were tested by multiplex RT-PCR for respiratory viruses. A subset of RV-positive samples was sequenced. Results There were 1066 RV-positive samples with RV present every month of the study period. RV was the most common virus before and during the coronavirus disease 2019 (COVID-19) pandemic (43% and 77% of virus-positive samples, respectively). Participants from family shelters had the highest prevalence of RV. Among 131 sequenced samples, 33 RV serotypes were identified with each serotype detected for ≤4 months. Conclusions RV infections persisted through community mitigation measures and were most prevalent in shelters housing families. Sequencing showed a diversity of circulating RV serotypes, each detected over short periods of time. Community-based surveillance in congregate settings is important to characterize respiratory viral infections during and after the COVID-19 pandemic. Clinical Trials Registration NCT04141917.

Homeless shelter residents and staff may be at higher risk of SARS-CoV-2 infection. However, SARS-CoV-2 infection estimates in this population have been reliant on cross-sectional or outbreak investigation data. We conducted routine surveillance and outbreak testing in 23 homeless shelters in King County, Washington to estimate the occurrence of laboratory-confirmed SARS-CoV-2 infection and risk factors during 1/1/2020-5/31/2021. Symptom surveys and nasal swabs were collected for SARS-CoV-2 testing by RT-PCR for residents aged 3 months and older and staff. We collected 12,915 specimens from 2,930 unique participants. We identified 4.74 (95% CI 4.00-5.58) SARS-CoV-2 infections per 100 individuals (residents: 4.96, 95% CI 4.12-5.91; staff: 3.86, 95% CI 2.43-5.79). Most infections were asymptomatic at time of detection (74%) and detected during routine surveillance (73%). Outbreak testing yielded higher test positivity compared to routine surveillance (2.7% vs. 0.9%). Among those infected, residents were less likely to report symptoms than staff. Participants who were vaccinated against seasonal influenza and were current smokers had lower odds of having an infection detected. Active surveillance that includes SARS-CoV-2 testing of all persons is essential in ascertaining the true burden of SARS-CoV-2 infections among residents and staff of congregate settings.

BigNeuron is an open community bench-testing platform with the goal of setting open standards for accurate and fast automatic neuron tracing. We gathered a diverse set of image volumes across several species that is representative of the data obtained in many neuroscience laboratories interested in neuron tracing. Here, we report generated gold standard manual annotations for a subset of the available imaging datasets and quantified tracing quality for 35 automatic tracing algorithms. The goal of generating such a hand-curated diverse dataset is to advance the development of tracing algorithms and enable generalizable benchmarking. Together with image quality features, we pooled the data in an interactive web application that enables users and developers to perform principal component analysis, t-distributed stochastic neighbor embedding, correlation and clustering, visualization of imaging and tracing data, and benchmarking of automatic tracing algorithms in user-defined data subsets. The image quality metrics explain most of the variance in the data, followed by neuromorphological features related to neuron size. We observed that diverse algorithms can provide complementary information to obtain accurate results and developed a method to iteratively combine methods and generate consensus reconstructions. The consensus trees obtained provide estimates of the neuron structure ground truth that typically outperform single algorithms in noisy datasets. However, specific algorithms may outperform the consensus tree strategy in specific imaging conditions. Finally, to aid users in predicting the most accurate automatic tracing results without manual annotations for comparison, we used support vector machine regression to predict reconstruction quality given an image volume and a set of automatic tracings. This resource describes a collection of neurons from a variety of light microscopy-based datasets, which can serve as a gold standard for testing automated tracing algorithms, as shown by comparison of the performance of 35 algorithms.

Introduction Little is known about COVID-19 vaccination intent among people experiencing homelessness. This study assesses surveyed COVID-19 vaccination intent among adult homeless shelter residents and staff and identifies factors associated with vaccine deliberation (responded “undecided”) and reluctance (responded “no”), including time trends. Methods From 11/1/2020–2/28/21, we conducted repeated cross-sectional surveys at nine shelters in King County, WA as part of ongoing community-based SARS-CoV-2 surveillance. We used a multinomial model to identify characteristics associated with vaccine deliberation and reluctance. Results A total of 969 unique staff (n=297) and residents (n=672) participated and provided 3,966 survey responses. Among residents, 53.7% (n=361) were vaccine accepting, 28.1% reluctant, 17.6% deliberative, and 0.6% already vaccinated, whereas among staff 56.2% were vaccine accepting, 14.1% were reluctant, 16.5% were deliberative, and 13.1% already vaccinated at their last survey. We observed higher odds of vaccine deliberation or reluctance among Black/African American individuals, those who did not receive a seasonal influenza vaccine, and those with lower educational attainment. There was no significant trend towards vaccine acceptance. Conclusions Strong disparities in vaccine intent based on race, education, and prior vaccine history were observed. Increased vaccine intent over the study period was not detected. An intersectional, person-centered approach to addressing health inequities by public health authorities planning vaccination campaigns in shelters is recommended.

Dendritic morphology underlies the source and processing of neuronal signal inputs. Morphology can be broadly described by two types of geometric characteristics. The first is dendrogram topology, defined by the length and frequency of the arbor branches; the second is spatial embedding, mainly determined by branch angles and tortuosity. We have previously demonstrated that microtubules and actin filaments are associated with arbor elongation and branching, fully constraining dendrogram topology. Here we relate the local distribution of these two primary cytoskeletal components with dendritic spatial embedding. We first reconstruct and analyze 167 sensory neurons from theDrosophilalarva encompassing multiple cell classes and genotypes. We observe that branches with higher microtubule concentration are overall straighter and tend to deviate less from the direction of their parent branch. F-actin displays a similar effect on the angular deviation from the parent branch direction, but its influence on branch tortuosity varies by class and genotype. We then create a computational model of dendritic morphology purely constrained by the cytoskeletal composition imaged from real neurons. The model quantitatively captures both spatial embedding and dendrogram topology across all tested neuron groups. These results suggest a common developmental mechanism regulating diverse morphologies, where the local cytoskeletal distribution can fully specify the overall emergent geometry of dendritic arbors.

Dendrites are the primary points of sensory or synaptic inputs to a neuron and play an essential role in synaptic integration and neural function. Despite the functional importance of dendrites, relatively less is known about the underlying mechanisms regulating cell-type specific dendritic patterning. Herein, we have dissected functional roles of a previously uncharacterized gene,CG3995, in cell-type specific dendritic development inDrosophila melanogaster.CG3995, which we have namedbedwarfed(bdwf), encodes a zinc-finger BED-type protein which is required for proportional growth and branching of dendritic arbors, exhibits nucleocytoplasmic expression, and functions in both transcriptional and translational cellular pathways. At the transcriptional level, we demonstrate a reciprocal regulatory relationship between Bdwf and the homeodomain transcription factor (TF) Cut. We show that Cut positively regulates Bdwf expression and that Bdwf acts as a downstream effector of Cut-mediated dendritic development, whereas overexpression of Bdwf negatively regulates Cut expression in multidendritic sensory neurons. Proteomic analyses revealed that Bdwf interacts with ribosomal proteins and disruption of these proteins produced phenotypically similar dendritic hypotrophy defects as observed inbdwfmutant neurons. We further demonstrate that Bdwf and its ribosomal protein interactors are required for normal microtubule and F-actin cytoskeletal architecture. Finally, our findings reveal that Bdwf is required to promote protein translation and ribosome trafficking along the dendritic arbor. Taken together, these results provide new insights into the complex, combinatorial and multi-functional roles of transcription factors (TFs) in directing diversification of cell-type specific dendritic development.

Individual sensory neurons can be tuned to many stimuli, each driving unique, stimulus-relevant behaviors, and the ability of multimodal nociceptor neurons to discriminate between potentially harmful and innocuous stimuli is broadly important for organismal survival. Moreover, disruptions in the capacity to differentiate between noxious and innocuous stimuli can result in neuropathic pain. Drosophila larval class III (CIII) neurons are peripheral noxious cold nociceptors and innocuous touch mechanosensors; high levels of activation drive cold-evoked contraction (CT) behavior, while low levels of activation result in a suite of touch-associated behaviors. However, it is unknown what molecular factors underlie CIII multimodality. Here, we show that the TMEM16/anoctamins subdued and white walker (wwk; CG15270) are required for cold-evoked CT, but not for touch-associated behavior, indicating a conserved role for anoctamins in nociception. We also evidence that CIII neurons make use of atypical depolarizing chloride currents to encode cold, and that overexpression of ncc69—a fly homologue of NKCC1—results in phenotypes consistent with neuropathic sensitization, including behavioral sensitization and neuronal hyperexcitability, making Drosophila CIII neurons a candidate system for future studies of the basic mechanisms underlying neuropathic pain.

IntroductionAlthough SARS-CoV-2 vaccines were first approved under Emergency Use Authorization by the FDA in late 2020 for adults, approval for young children 6 months to < 5 years of age did not occur until 2022. Understanding real world vaccine effectiveness in the setting of emerging variants is critical. The primary goal of this study is to evaluate SARS-CoV-2 vaccine effectiveness (VE) against infection among children aged >6 months and adults aged MethodsCASCADIA is a four-year community-based prospective study of SARS-CoV-2 VE among adult and pediatric populations aged 6 months to 49 years in Oregon and Washington. At enrollment and regular intervals, participants complete a sociodemographic questionnaire. Individuals provide a blood sample at enrollment and annually thereafter, with additional, optional blood draws after infection and vaccination. Participants complete weekly self-collection of anterior nasal swabs and symptom questionnaires. Swabs are tested for SARS-CoV-2 and other respiratory pathogens by RT-PCR, with results of selected pathogens returned to participants; nasal swabs with SARS-CoV-2 detected will undergo whole genome sequencing. Participants who report symptoms outside of their weekly swab collection and symptom survey are asked to collect an additional swab. Participants who test positive for SARS-CoV-2 undergo serial swab collection every three days for three weeks. Serum samples are tested for SARS-CoV-2 antibody by binding and neutralization assays.AnalysisCox regression models will be used to estimate the hazard ratio associated with SARS-CoV-2 vaccination among the pediatric and adult population, controlling for demographic factors and potential confounders, including clustering within households.Ethics and disseminationAll study materials including the protocol, consent forms, participant communication and recruitment materials, and data collection instruments were approved by the Kaiser Permanente Northwest (KPNW) Institutional Review Board, the IRB of record for the study.Strengths/LimitationsCASCADIA will include a large sample of children and adults that will contribute to estimation of vaccine effectiveness.The study will generate a data repository that can be used to address many research questions, such as duration of SARS-CoV-2 serologic results, post-acute sequelae of COVID-19, and re-infection rates.Retention and compliance may be challenging given the four-year duration of the study.Annual blood collection for assessment of humoral immunity may be a potential deterrent for participation, particularly among younger children.

Background It is estimated that 1.4 million people identify as transgender and over 700,000 people identify as non-binary in the United States, many of whom face significant health disparities impacting health care access. Although previous studies have reported greater vaccine uptake in women compared to men, national-level estimates of influenza vaccine uptake among transgender and non-binary people are unknown. This study aims to characterize differences in influenza vaccination by gender identity and examine associations between vaccination status and state-based gender equality policies. Methods We used cross-sectional data from adults aged 18 and older who participated in the 2015-2019 United States Behavioral Risk Factors Surveillance System surveys. Weighted prevalence differences (PDs) and associated confidence intervals (CIs) of being unvaccinated against influenza by self-reported gender identity were estimated using generalized linear regression models. We identified state policies on gender identity (Figure 1) as a potential effect modifier a priori and assessed through stratification. Figure 1.U.S. states implementing the SOGI module in Behavioral Risk Factors Surveillance System between 2015-2019, classified as having restrictive versus protective policies on gender equality (N = 38) Results A total of 1,016,012 individuals met the inclusion criteria. Compared to cisgender women (unvaccinated prevalence=57.3%), the prevalence of being unvaccinated was significantly higher among cisgender men (64.4%; PD=7.0 per 100, 95% CI: 6.7-7.4), transgender women (65.4%; PD=8.1 per 100, 95% CI: 4.0-12.2), transgender men (64.6%; PD=7.3 per 100, 95% CI: 2.7-11.8), and non-binary individuals (64.6%; PD=7.2 per 100, 95% CI: 1.3-13.2). This pattern was similar among individuals living in protective states with more favorable gender-related policies compared to restrictive states with less favorable policies (Figure 2). Figure 2.Weighted prevalence of U.S. adults unvaccinated against influenza by gender identity, Behavioral Risk Factors Surveillance System, 2015-2019 Conclusion Our results provide evidence of a disparity in influenza vaccine uptake by gender identity. To improve vaccine uptake among transgender and non-binary individuals, future research should focus on identifying barriers to and facilitators of vaccination by gender identity. These findings could be used to inform policies and public health interventions to improve vaccine uptake co-designed and implemented in partnership with the transgender and non-binary communities. Disclosures All Authors: No reported disclosures.

Background COVID-19 vaccines are important to mitigate severe disease in congregate settings, yet uptake remains lower among people experiencing homelessness (PEH) than in the general population. This study aimed to explain changes in COVID-19 vaccination intent over time and identify modifiable factors to improve vaccine acceptance among PEH. Methods We utilized the Health Belief Model and 3Cs Model of Vaccine Hesitancy to develop a conceptual framework to explore factors that may influence COVID-19 vaccination intent among PEH. Between July 27 - October 15, 2021, we conducted semi-structured interviews (SSIs) and focus group discussions (FGDs) across six homeless shelters in Seattle-King County, Washington. Residents and staff aged 18 years and older were recruited through purposive sampling for SSIs and convenience sampling for FGDs. We captured retrospective information about perceptions of and intent to receive COVID-19 vaccines between March 2020 - August 2021. Thematic analysis was conducted using Dedoose. Results We conducted 31 SSIs (25 residents and six staff) and eight FGDs with 43 residents. Participants reported that too much contradictory and changing information about COVID-19 vaccines led to confusion. Information deemed trustworthy (i.e., objective, honest, professional, and recommended by others) contributed to individual’s knowledge and in some cases changed their vaccination intent. Despite intention to vaccinate, participants reported barriers to COVID-19 vaccine access including availability, eligibility, appointments, and timeliness. While many intended to get vaccinated on their own, others were motivated by incentives and requirements. Participants presented recommendations to improve COVID-19 information content and dissemination, access, and incentives in shelter settings (Table 1). Table 1.Recommendations for Interventions to Increase COVID-19 Vaccine Uptake in Shelter Settings Conclusion COVID-19 vaccination strategies that are rooted in the voices and experiences of PEH are presented and can inform improved vaccine implementation among key stakeholders. Future research should test recommended strategies to determine feasibility and effectiveness in shelter settings. Disclosures Helen Y. Chu, MD, MPH, Cepheid: Reagents|Ellume: Advisor/Consultant|Gates Ventures: Grant/Research Support|Merck: Advisor/Consultant|Pfizer: Advisor/Consultant.

Background Human parainfluenza viruses (HPIV) cause respiratory illness in individuals of all ages. However, HPIV epidemiology data in people experiencing homelessness (PEH) are limited. Methods We analyzed cross-sectional data from a clinical trial and SARS-CoV-2 surveillance study in 23 homeless shelters in King County, Washington from October 2019-May 2021. Questionnaires and nasal swab specimens were obtained from eligible participants at enrollment. Between October 2019-March 31, 2020, participants included those aged > 3 months with acute respiratory illness. Monthly shelter surveillance was also conducted where participants were recruited regardless of symptoms. With the community spread of SARS-CoV-2, the study design transitioned from a clinical trial to a SARS-CoV-2 surveillance study which expanded enrollment eligibility to include participants with or without symptoms from April 1, 2020, onward. Participants were not followed longitudinally but were permitted to enroll multiple times during the study period. Specimens were tested for HPIV 1-4 and other respiratory viruses using RT-PCR. Results Among 14,464 specimens, 32 were HPIV-positive from 29 participants (median age 9 years, range 0.3-64 years; 45% female; 28% Black; 10% with chronic conditions) of which 59% were children. Family shelters had the highest percentage of HPIV infections (Table). HPIV was detected every month before the community spread of SARS-CoV-2. All HPIV-positive samples in May 2021 came from a single family shelter (Figure). Only 67% of HPIV-positive participants had symptoms with runny nose, cough and sore throat the most commonly reported. HPIV co-detection with other respiratory viruses occurred in 19% of HPIV-positive specimens; Rhinovirus co-detection (16%) was the most common. Human Parainfluenza Encounters by Shelter Type Before and After April 1, 2020 Human Parainfluenza Positive Samples by Shelter Type Among Unique Participants Conclusion HPIV affected PEH of all ages with most cases in shelters with children. Coinciding with community-wide SARS-CoV-2 mitigation efforts, the number of HPIV infections were reduced. However, a cluster of HPIV infections still occurred within one family shelter. Shelter-specific public health measures including non-pharmaceutical interventions used during the COVID-19 pandemic may reduce HPIV infections among residents. Disclosures Janet A. Englund, MD, AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Helen Y. Chu, MD, MPH, Cepheid: Reagents|Ellume: Advisor/Consultant|Gates Ventures: Grant/Research Support|Merck: Advisor/Consultant|Pfizer: Advisor/Consultant.

Uncovering molecular mechanisms regulating dendritic diversification is essential to understanding the formation and modulation of functional neural circuitry. Transcription factors play critical roles in promoting dendritic diversity and here, we identify PP2A phosphatase function as a downstream effector of Cut-mediated transcriptional regulation of dendrite development. Mutant analyses of the PP2A catalytic subunit (mts) or the scaffolding subunit (PP2A-29B) reveal cell-type specific regulatory effects with the PP2A complex required to promote dendritic growth and branching in Drosophila Class IV (CIV) multidendritic (md) neurons, whereas in Class I (CI) md neurons, PP2A functions in restricting dendritic arborization. Cytoskeletal analyses reveal requirements for Mts in regulating microtubule stability/polarity and F-actin organization/dynamics. In CIV neurons, mts knockdown leads to reductions in dendritic localization of organelles including mitochondria and satellite Golgi outposts, while CI neurons show increased Golgi outpost trafficking along the dendritic arbor. Further, mts mutant neurons exhibit defects in neuronal polarity/compartmentalization. Finally, genetic interaction analyses suggest β-tubulin subunit 85D is a common PP2A target in CI and CIV neurons, while FoxO is a putative target in CI neurons.

Background Globally, an urgent need exists to expand access to HIV prevention among adolescent girls and young women (AGYW), but the need is particularly acute in sub-Saharan Africa. Oral pre-exposure prophylaxis (PrEP) offers an effective HIV prevention method. In many countries, however, accessing PrEP necessitates that AGYW visit their local health clinic, where they may face access challenges. Some countries have implemented youth-friendly services to reduce certain challenges in local health clinics, but barriers to access persist, including clinic stigma. However, evidence of clinic stigma toward AGYW, particularly with respect to PrEP service delivery, is still limited. This mixed methods study explores stigma toward AGYW seeking clinic services, in particular PrEP, from the perspective of both clinic staff (clinical and nonclinical) and AGYW who seek services at clinic sites in Tshwane province, South Africa. Methods Six focus group discussions were conducted with AGYW (43 total participants) and four with clinic staff (42 total participants) and triangulated with survey data with AGYW (n = 449) and clinic staff (n = 130). Thematic analysis was applied to the qualitative data and descriptive statistics were conducted with the survey data. Results Four common themes emerged across the qualitative and quantitative data and with both AGYW and clinic staff, although with varying degrees of resonance between these two groups. These themes included (1) clinic manifestations of stigma toward AGYW, (2) concerns about providing PrEP services for AGYW, (3) healthcare providers’ identity as mothers, and (4) privacy and breaches of confidentiality. An additional theme identified mainly in the AGYW data pertained to stigma and access to healthcare. Conclusion Evidence is needed to inform strategies for addressing clinic stigma toward AGYW, with the goal of removing barriers to PrEP services for this group. While awareness has increased and progress has been achieved around the provision of comprehensive, youth-friendly sexual and reproductive health services, these programs need to be adapted for the specific concerns of young people seeking PrEP services. Our findings point to the four key areas noted above where programs seeking to address stigma toward AGYW in clinics can tailor their programming.

Children’s vegetable intake remains inadequate and school canteens may provide opportunities to address this public health concern. This study aimed to determine the effectiveness of an 8-week multi-strategy behavioral intervention that included vegetable provisioning and online menu architecture on vegetable sales in primary school canteens. A randomized controlled trial was undertaken in 16 Australian primary schools (n = 4302 students). The control arm kept their regular canteen menu. The primary outcome was vegetable sales measured by assessing vegetable content (in grams) from all menu items and using canteen sales (ordered online and over-the-counter) to calculate vegetable sales (in grams/week) at baseline (3 weeks) and during intervention implementation (8 weeks). Secondary outcomes were vegetable sales in subcategories, intervention acceptability among canteen managers and vegetable waste (four schools). Linear mixed model analysis showed that from baseline to follow-up, the intervention group had significantly higher weekly vegetable sales overall compared with the control group (2707 g/week, 95% CI 1276 to 4137 g/week; p < 0.001), with increased vegetable sales in the subcategories of burgers, hot foods and snacks, but not in sandwiches and pasta/rice dishes. The intervention did not lead to more vegetable waste, nor to a decrease in canteen revenue. The canteen managers found the intervention easy to implement and felt children responded favorably to three of the seven strategies. In conclusion, a multi-strategy behavioral canteen intervention increased vegetable sales amongst primary school students.

Low-temperature, metastable electrochromism has been used as a tool to assign pigments in Photosystem I (PS I) from Thermosynechococcus vulcanus and both the white light and far-red light (FRL) forms of Chroococcidiopsis thermalis. We find that a minimum of seven pigments is required to satisfactorily model the electrochromism of PS I. Using our model, we provide a short list of candidates for the chlorophyll f pigment in FRL C. thermalis that absorbs at 756 nm, whose identity, to date, has proven to be controversial. Specifically, we propose the linker pigments A40 and B39 and two antenna pigments A26 and B24 as defined by crystal structure 1JB0. The pros and cons of these assignments are discussed, and we propose further experiments to better understand the functioning of FRL C. thermalis.

Objective:To prioritise and refine a set of evidence-informed statements into advice messages to promote vegetable liking in early childhood, and to determine applicability for dissemination of advice to relevant audiences.Design:A nominal group technique (NGT) workshop and a Delphi survey were conducted to prioritise and achieve consensus (≥70 % agreement) on thirty evidence-informed maternal (perinatal and lactation stage), infant (complementary feeding stage) and early years (family diet stage) vegetable-related advice messages. Messages were validated via triangulation analysis against the strength of evidence from an Umbrella review of strategies to increase children’s vegetable liking, and gaps in advice from a Desktop review of vegetable feeding advice.Setting:Australia.Participants:A purposeful sample of key stakeholders (NGT workshop, n 8 experts; Delphi survey, n 23 end users).Results:Participant consensus identified the most highly ranked priority messages associated with the strategies of: ‘in-utero exposure’ (perinatal and lactation, n 56 points) and ‘vegetable variety’ (complementary feeding, n 97 points; family diet, n 139 points). Triangulation revealed two strategies (‘repeated exposure’ and ‘variety’) and their associated advice messages suitable for policy and practice, twelve for research and four for food industry.Conclusions:Supported by national and state feeding guideline documents and resources, the advice messages relating to ‘repeated exposure’ and ‘variety’ to increase vegetable liking can be communicated to families and caregivers by healthcare practitioners. The food industry provides a vehicle for advice promotion and product development. Further research, where stronger evidence is needed, could further inform strategies for policy and practice, and food industry application.

Background: Many children worldwide do not eat recommended amounts of vegetables. Disliking vegetables is a key factor associated with low intake. Objective: This umbrella review synthesized systematic reviews to determine the effectiveness of sensory and behavioral strategies to facilitate liking of vegetables (primary outcome) in young children up to 5 y of age, as key predictors of vegetable intake (secondary outcome). Methods: Nine databases were searched up to May 2019 (updated in September 2020). Two reviewers independently conducted study screening and selection, data extraction, and assessment of methodological quality using AMSTAR 2 (A MeaSurement Tool to Assess systematic Reviews). Eleven reviews (n = 1 rated strong quality, n = 4 moderate quality, n = 6 low/critically low quality)examining 85 primary studies met the review criteria: systematic reviews and meta-analyses of primary studies (any quantitative design) that examined sensory or behavioral strategies on vegetable liking or intake (outcomes reported separately for children ≤5y). Strategy effectiveness was synthesized into 3 categories based on evidence strength: 1) promising (large and consistent body of moderate quality evidence), 2) emerging (small to moderate body of mixed consistency and quality evidence), and 3) limited (small body of limited consistency and quality evidence). Results: Promising evidence was identified for repeated exposure to a single or a variety of vegetables. Emerging evidence was identified for several strategies that increase familiarity with vegetable flavors(e.g., via exposure in utero and through breast milk, and a “vegetable first” approach to complementary feeding) and/or willingness to try vegetables (e.g., via parental role modeling, nonfood rewards, and vegetable-based story books). Conclusions: Current evidence supports incorporation of tailored advice into guideline documents for parents and carers to repeatedly expose their children to a variety of vegetables to increase vegetable intake. Ongoing robust research on strategies to facilitate children’s liking of vegetables is warranted to strengthen the evidence base underpinning advice for parents and health professionals Refereed/Peer-reviewed

Introduction During a pandemic, there are many situations in which the first available vaccines may not have as high effectiveness as vaccines that are still under development or vaccines that are not yet ready for distribution, raising the question of whether it is better to go with what is available now or wait. Methods In 2020, the team developed a computational model that represents the U.S. population, COVID-19 coronavirus spread, and vaccines with different possible efficacies (to prevent infection or to reduce severe disease) and vaccination timings to estimate the clinical and economic value of vaccination. Results Except for a limited number of situations, mainly early on in a pandemic and for a vaccine that prevents infection, when an initial vaccine is available, waiting for a vaccine with a higher efficacy results in additional hospitalizations and costs over the course of the pandemic. For example, if a vaccine with a 50% efficacy in preventing infection becomes available when 10% of the population has already been infected, waiting until 40% of the population are infected for a vaccine with 80% efficacy in preventing infection results in 15.6 million additional cases and 1.5 million additional hospitalizations, costing $20.6 billion more in direct medical costs and $12.4 billion more in productivity losses. Conclusions This study shows that there are relatively few situations in which it is worth foregoing the first COVID-19 vaccine available in favor of a vaccine that becomes available later on in the pandemic even if the latter vaccine has a substantially higher efficacy.

Calcium (Ca2+) plays a pivotal role in modulating neuronal-mediated responses to multimodal sensory stimuli. Recent studies in Drosophila reveal class III (CIII) multidendritic (md) sensory neurons function as multimodal sensors regulating distinct behavioral responses to innocuous mechanical and nociceptive thermal stimuli. Functional analyses indicate that CIII-mediated multimodal behavioral output is dependent upon activation levels with stimulus-evoked Ca2+ displaying relatively low vs. high intracellular levels in response to gentle touch vs. noxious cold, respectively. However, the mechanistic bases underlying modality-specific differential Ca2+ responses in CIII neurons remain incompletely understood. We hypothesized that noxious cold-evoked high intracellular Ca2+ responses in CIII neurons may rely upon Ca2+-induced Ca2+ release (CICR) mechanisms involving transient receptor potential (TRP) channels and/or metabotropic G-protein coupled receptor (GPCR) activation to promote cold nociceptive behaviors. GABAB receptor mutants and CIII-specific knockdown resulted in impaired noxious cold-evoked behaviors. Gαq and Phospholipase C signaling are likewise required for noxious cold sensing. Additionally, ER localized Ca2+ channels including the Ryanodine receptor (RyR) and Inositol trisphosphate receptor (IP3R) are required for cold nociceptive behaviors. GPCR mediated signaling, through GABAB-R2 and IP3R, is not required in CIII neurons for innocuous touch evoked behaviors. However, CICR via RyR is required in CIII neurons for innocuous touch-evoked behaviors. Disruptions in GABAB-R2, IP3R and RyR in CIII neurons leads to significantly lower levels of cold-evoked Ca2+ responses indicating GPCR and CICR signaling mechanisms function in regulating Ca2+ release. CIII neurons exhibit bipartite cold-evoked firing patterns, where CIII neurons burst during rapid temperature change and tonically fire during steady state cold temperatures. GABAB-R2 knockdown in CIII neurons resulted in disorganized firing patterns during cold exposure. Upon ryanodine pharmacological application, CIII neurons exhibit increased bursting activity and with CIII specific RyR knockdown, there is an increase in cold-evoked tonic firing and decrease in bursting. Lastly, our previous studies implicated the TRPP channel Pkd2 in cold nociception, and here, we show that Pkd2 and IP3R genetically interact in regulating cold-evoked behavior. Collectively, these analyses support novel, modality-specific roles for metabotropic GABAergic signaling and CICR mechanisms in regulating intracellular Ca2+ levels and cold-evoked behavioral output from multimodal CIII neurons.

Coding noxious cold signals, such as the magnitude and rate of temperature change, play essential roles in the survival of organisms. We combined electrophysiological and computational neuroscience methods to investigate the neural dynamics of Drosophila larva cold-sensing Class III (CIII) neurons. In response to a fast temperature change (–2 to –6°C/s) from room temperature to noxious cold, the CIII neurons exhibited a pronounced peak of a spiking rate with subsequent relaxation to a steady-state spiking. The magnitude of the peak was higher for a higher rate of temperature decrease, while slow temperature decrease (–0.1°C/s) evoked no distinct peak of the spiking rate. The rate of the steady-state spiking depended on the magnitude of the final temperature and was higher at lower temperatures. For each neuron, we characterized this dependence by estimating the temperature of the half activation of the spiking rate by curve fitting neuron’s spiking rate responses to a Boltzmann function. We found that neurons had a temperature of the half activation distributed over a wide temperature range. We also found that CIII neurons responded to decrease rather than increase in temperature. There was a significant difference in spiking activity between fast and slow returns from noxious cold to room temperature: The CIII neurons usually stopped activity abruptly in the case of the fast return and continued spiking for some time in the case of the slow return. We developed a biophysical model of CIII neurons using a generalized description of transient receptor potential (TRP) current kinetics with temperature-dependent activation and Ca2+-dependent inactivation. This model recapitulated the key features of the spiking rate responses found in experiments and suggested mechanisms explaining the transient and steady-state activity of the CIII neurons at different cold temperatures and rates of their decrease and increase. We conclude that CIII neurons encode at least three types of cold sensory information: the rate of temperature decrease by a peak of the firing rate, the magnitude of cold temperature by the rate of steady spiking activity, and direction of temperature change by spiking activity augmentation or suppression corresponding to temperature decrease and increase, respectively.

Previous reviews have established that workplace wellbeing initiatives are effective at promoting wellbeing, but less is known about which intervention characteristics or “active ingredients” underpin this effectiveness (i.e., behavior change techniques [BCTs]). This review aims to illuminate the connections between the types of BCTs and the level of intervention intensity with intervention effectiveness. A systematic search for peer-reviewed studies evaluating a workplace wellbeing initiative was undertaken across five databases: Medline, Scopus, PsycInfo, and CINAHL (Ovid Emcare). Eligible studies included those that evaluated the effect of a workplace wellbeing initiative on participants’ physical wellbeing (e.g., physical activity and quality of life) and psychological wellbeing (e.g., mental health and stress), were published between 2009 and September 2019, and utilized a comparator (e.g., control group or prepost change). Studies were screened in independent duplicate to minimize bias. Effect sizes were calculated. Following removal of duplicates, 1,541 studies were identified and screened for eligibility. Of these, 23 studies reporting 28 comparisons were deemed to meet eligibility criteria. Just over 50% of these studies reported evidence of either a strong or moderate effect across a physical and a psychological outcome, providing a positive indication that workplace wellbeing programs can promote physical and psychological wellbeing in workers. Interventions tended to employ multiple BCTs (mean range 8.1–9.4), however, no discernible patterns between the types or numbers of BCTs employed and intervention effectiveness was found. Further experimental work is required that compares and contrasts workplace wellbeing initiatives to enable a better understanding of how to develop and implement highly effective programs.

Objectives:Consumption is driven by children’s sensory acceptance, but little is known about the sensory characteristics of vegetables that children commonly eat. A greater understanding could help design more effective interventions to help raise intakes, thus realising beneficial health effects. This study sought to: (1) Understand the vegetable consumption patterns in children, with and without potatoes, using the Australian and WHO definitions. (2) Describe the sensory characteristics of vegetables consumed by children by age group, level of intake and variety. (3) Determine the vegetable preferences of children, by age group, level of intake and variety.Design:Analysis of National Nutrition Survey data, combining reported vegetable intake with sensory characteristics described by a trained panel.Setting:AustraliaParticipants:A nationally representative sample of Australian children and adolescents aged 2–17·9 years (n 2812).Results:While consumption increased in older age groups, variety remained constant. Greater variety, however, was associated with higher vegetable consumption. Potato intake increased with consumption, contributing over one-third of total vegetable intake for highest vegetable consumption and for older age groups. Children favoured relatively sweet vegetables and reported lower consumption of bitter vegetables. There were no differences in the sensory properties of vegetables consumed by children in different age groups. After potatoes, carrots, sweetcorn, mixtures, fruiting and cruciferous types were preferred vegetables.Conclusion:Children tend to prefer vegetables with sensory characteristics consistent with innate taste preferences (sweet and low bitterness). Increasing exposure to a variety of vegetables may help increase the persistently low vegetable consumption patterns of children.

The starfish Tethyaster subinermis is documented from the south-western parts of British waters, with one specimen caught by trawl at 48° 27.5’N, 009° 35.3’W (208–250 m depth) in 2001 and a further two specimens caught by trawl at 48° 28.32’N, 009° 33.23’W (189–217 m depth) in 2020., Autori iznose novi nalaz morske zvijezdače Tethyaster subinermis iz jugozapadnih dijelova britanskih voda, s jednim primjerkom ulovljenim koćom na 48 ° 27,5 ‘N, 009 ° 35,3’ W (dubine 208–250 m) 2001. godine i dva primjerka koja su ulovljena povlačnom mrežom na 48 ° 28,32’N, 009 ° 33,23’W (dubina 189–217 m) u 2020. godini.

Rare genetic diseases preponderantly affect the nervous system causing neurodegeneration to neurodevelopmental disorders. This is the case for both Menkes and Wilson disease, arising from mutations in ATP7A and ATP7B, respectively. The ATP7A and ATP7B proteins localize to the Golgi and regulate copper homeostasis. We demonstrate genetic and biochemical interactions between ATP7 paralogs with the conserved oligomeric Golgi (COG) complex, a Golgi apparatus vesicular tether. Disruption ofDrosophilacopper homeostasis by ATP7 tissue-specific transgenic expression caused alterations in epidermis, aminergic, sensory, and motor neurons. Prominent among neuronal phenotypes was a decreased mitochondrial content at synapses, a phenotype that paralleled with alterations of synaptic morphology, transmission, and plasticity. These neuronal and synaptic phenotypes caused by transgenic expression of ATP7 were rescued by downregulation of COG complex subunits. We conclude that the integrity of Golgi-dependent copper homeostasis mechanisms, requiring ATP7 and COG, are necessary to maintain mitochondria functional integrity and localization to synapses.SIGNIFICANCE STATEMENTMenkes and Wilson disease affect copper homeostasis and characteristically afflict the nervous system. However, their molecular neuropathology mechanisms remain mostly unexplored. We demonstrate that copper homeostasis in neurons is maintained by two factors that localize to the Golgi apparatus, ATP7 and the conserved oligomeric Golgi (COG) complex. Disruption of these mechanisms affect mitochondrial function and localization to synapses as well as neurotransmission and synaptic plasticity. These findings suggest communication between the Golgi apparatus and mitochondria through homeostatically controlled cellular copper levels and copper-dependent enzymatic activities in both organelles.

In the United States, the market for “hard” (alcoholic) ciders is growing rapidly, with over $1 billion USD in sales in 2018. These ciders present a broad range of sensory profiles, especially for ...