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Upon infection of its host cell, human immunodeficiency virus (HIV) establishes a quiescent and non-productive state capable of spontaneous reactivation. Diverse cell types harboring the provirus form a latent reservoir, constituting a major obstacle to curing HIV. Here, we investigate the effects of latency reversal agents (LRAs) in an HIV-infected THP-1 monocyte cell line in vitro. We demonstrate that leading drug treatments synergize activation of the HIV long terminal repeat (LTR) promoter. We establish a latency model in THP-1 monocytes using a replication incompetent HIV reporter vector with functional Tat, and show that chromatin modifiers synergize with a potent transcriptional activator to enhance HIV reactivation, similar to T-cells. Furthermore, leading reactivation cocktails are shown to differentially affect latency reactivation and surface expression of chemokine receptor type 4 (CXCR4), leading to altered host cell migration. This study investigates the effect of chromatin-modifying LRA treatments on HIV latent reactivation and cell migration in monocytes. As previously reported in T-cells, epigenetic mechanisms in monocytes contribute to controlling the relationship between latent reactivation and cell migration. Ultimately, advanced “Shock and Kill” therapy needs to successfully target and account for all host cell types represented in a complex and composite latency milieu.

Building on our previous works that compared the efficacy of terpolymers vs. ternary blends in improving the performance of bulk heterojunction organic solar cells, the final piece of this series of studies focuses on comparing terpolymer and ternary blends constructed with two polymers with structurally similar backbones (monoCNTAZ and FTAZ) yet markedly different open circuit voltage (Voc) values. Terpolymers and ternary blends of five different ratios were studied and the results demonstrate that while the overall performance of both the systems is similar, the ternary blends exhibit higher short circuit current (Jsc) values, while the terpolymers exhibit higher Voc values. Investigation of the charge transfer state using low-energy external quantum efficiency (EQE) indicates that the ternary blends are governed by a parallel-like mechanism, while the terpolymer does not follow this mechanism. The key morphological difference between the systems, as elucidated by resonance soft X-ray scattering (RSoXS), is the slightly smaller size (∼60 nm) of domains in the ternary blends compared to that of the terpolymer (∼80 nm), which may affect exciton harvesting in the terpolymer system and lead to lower Jsc values. In addition, a lower driving force for the formation of charge transfer (CT) state is also likely to contribute to the lower Jsc values in the terpolymer system. All together, the data show that structurally similar (perhaps even miscible) polymers still exhibit key differences in performance when paired in terpolymers vs. ternary blends and allow us to further illuminate the underlying mechanisms of such complex systems.

Abstract Background Synovial sarcoma is a rare malignant soft tissue tumor originating mainly in the extremities and usually related to the joint capsule, tendon sheath, or synovial capsule. Only a few cases of synovial sarcoma arising in the abdomen, particularly the omentum, have been reported. We presented a case of omental synovial sarcoma and reviewed 7 cases of this disease. Case presentation A 37-year-old man presented to the hospital with abdominal pain and distension for 2 months. A computed tomography scan revealed a massive heterogeneous low attenuation mass with amorphous solid components between the stomach and colon with suspected hemoperitoneum. The patient underwent surgery, and the pathological result demonstrated a greater omentum biphasic synovial sarcoma. Chemotherapy was administered with a good response. He has no signs of recurrence during 3 years of follow-up. Among 7 cases of omental synovial sarcoma, the mean age was 42, ranging from 16 to 66 years old with predominantly female (71.4%), tumor size from 9.5 cm to 20 cm. Biphasic synovial sarcoma accounted for 50%. The recurrence rate within one year is high (57.1%). Conclusions Primary omental synovial sarcoma is uncommon and presents with nonspecific clinical symptoms, often leading to potential misdiagnosis with other conditions before surgery. They occur predominantly in females, mainly middle-aged, with a large mass size before presentation. Due to the high recurrence and mortality rate, it needs to be recognized at the early stage.

Abstract Background Systemic lupus erythematosus (SLE) is an autoimmune disease with protean manifestations. There is little understanding of why some organs are specifically impacted in patients and the mechanisms of disease persistence remain unclear. While much work has been done characterizing the DNA methylation status in SLE, there is less information on histone modifications, a more dynamic epigenetic feature. This study identifies two histone marks of activation and the binding of p300 genome-wide in three cell types and three clinical subsets to better understand cell-specific effects and differences across clinical subsets. Results We examined 20 patients with SLE and 8 controls and found that individual chromatin marks varied considerably across T cells, B cells, and monocytes. When pathways were examined, there was far more concordance with conservation of TNF, IL-2/STAT5, and KRAS pathways across multiple cell types and ChIP data sets. Patients with cutaneous lupus and lupus nephritis generally had less dramatically altered chromatin than the general SLE group. Signals also demonstrated significant overlap with GWAS signals in a manner that did not implicate one cell type more than the others. Conclusions The pathways identified by altered histone modifications and p300 binding are pathways known to be important from RNA expression studies and recognized pathogenic mechanisms of disease. NFκB and classical inflammatory pathways were strongly associated with increased peak heights across all cell types but were the highest-ranking pathway for all three antibodies in monocytes according to fgsea analysis. IL-6 Jak/STAT3 signaling was the most significant pathway association in T cells marked by H3K27ac change. Therefore, each cell type experiences the disease process distinctly although in all cases there was a strong theme of classical inflammatory pathways. Importantly, this NFκB pathway, so strongly implicated in the patients with generalized SLE, was much less impacted in monocytes when cutaneous lupus was compared to the general SLE cohort and also less impacted in lupus nephritis compared to general SLE. These studies define important cell type differences and emphasize the breadth of the inflammatory effects in SLE.

Abstract Hematological malignancies are associated with an increased risk of complications during SARS-CoV-2 infections. Primary series or monovalent booster vaccines reduce disease severity, hospitalization, and death among multiple myeloma patients. We characterized virus-neutralizing and spike-binding antibody profiles following monovalent (WA1) or bivalent (WA1/BA.5) SARS-CoV-2 booster vaccination in MM patients. Bivalent vaccination improved the breadth of binding antibodies but not neutralization activity against contemporary variants. Hybrid immunity and immune imprinting impact vaccine-elicited immunity.

Abstract Objective Limb girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous autosomal conditions with some degree of phenotypic homogeneity. LGMD is defined as having onset >2 years of age with progressive proximal weakness, elevated serum creatine kinase levels and dystrophic features on muscle biopsy. Advances in massively parallel sequencing have led to a surge in genes linked to LGMD. Methods The ClinGen Muscular Dystrophies and Myopathies gene curation expert panel (MDM GCEP, formerly Limb Girdle Muscular Dystrophy GCEP) convened to evaluate the strength of evidence supporting gene–disease relationships (GDR) using the ClinGen gene–disease clinical validity framework to evaluate 31 genes implicated in LGMD. Results The GDR was exclusively LGMD for 17 genes, whereas an additional 14 genes were related to a broader phenotype encompassing congenital weakness. Four genes (CAPN3, COL6A1, COL6A2, and COL6A3) were split into two separate disease entities, based on each displaying both dominant and recessive inheritance patterns, resulting in curation of 35 GDRs. Of these, 30 (86%) were classified as definitive, 4 (11%) as moderate, and 1 (3%) as limited. Two genes, POMGNT1 and DAG1, though definitively related to myopathy, currently have insufficient evidence to support a relationship specifically with LGMD. Interpretation The expert‐reviewed assertions on the clinical validity of genes implicated in LGMDs form an invaluable resource for clinicians and molecular geneticists. We encourage the global neuromuscular community to publish case‐level data that help clarify disputed or novel LGMD associations.

In this manuscript, two professors sought to reflect on personal discoveries from their recent research collaboration examining the relationship between strengths-based teaching and students’ self-efficacy. The findings of their study indicated that educators in higher education institutions who employ a strengths-based teaching approach that focuses on students’ capabilities, opportunities, and possibilities while creating a growth mindset, resiliency, and agency can improve students’ self-efficacy. As educators, we regularly engage in reflective practice to enhance and improve our teaching strategies. Through reflection, we were able to examine the revelations from our research and explore how we could effectively implement these practices in our teaching to highlight our students’ strengths and help them build a foundation for lifelong learning and improved self-efficacy.

This article will explore outcomes for care experienced young people in education and will examine and dissect the current statistics for care experienced students. Furthermore, this article will identify various support mechanisms which could be implemented and embedded within further and higher education settings and will discuss how staff members can gain an awareness and understanding of supporting our care experienced population.

Film tourism has gained significant notoriety in recent years, emerging as a prominent phenomenon to promote destinations, attract visitors, and stimulate economic and social development. Despite the popularity of Portugal as a filming destination, the extent to which film tourism in Portugal is planned for and managed is currently unknown. Thus, this research examines the current provision and implementation of strategies to plan for and manage film tourism at a national and regional level in Portugal through a quantitative content analysis approach to existing tourism planning and management plans and strategies in Portugal. Findings revealed an overwhelming lack of planning provision for film tourism at national and regional levels. Although some regions appear to promote film tourism, no transparent efforts are being made to plan for or manage its development or impacts sustainably. As such, there is a need for a more strategic and sustainable approach to planning for and managing film tourism at regional and local levels. This could ensure that destinations harness, in the long-term, the multifaceted benefits that can be derived from film tourism while also ensuring that the negative implications of film tourism activities are minimised or mitigated to preserve the sustainability and competitiveness of the film tourism industry.

Abstract In this work, we investigate thick brane models with a single three-form field. We find novel solutions for thick braneworlds where only three-forms exist and interact gravitationally in the bulk, both with and without matter fields. We use an additional scalar field as proxy for the matter fields. As an initial study, we consider the results here in contrast to the single scalar field thick braneworld case. The properties of the specific three-form parameterisation limits the freedom we have to choose the form of the warp factor, leading to a closed system of equations with nontrivial yet unstable solutions. The stability of the gravitational sector for thick brane three-forms is investigated and the models are shown to be unstable against small perturbations of the metric, further indicating that three-forms cannot exist stably in thick braneworld settings.

Aim: In this study, ultrastructural, chemical, and histological analyses of extracted deciduous teeth were performed to analyze the effect of two different types of glass ionomer cements used in association with selective caries removal in deep lesions of deciduous teeth. Methods: A clinical, ex vivo, longitudinal study was conducted. A total of 19 deciduous molars from 9 volunteer patients were used. The teeth were randomly restored with one of two types of glass ionomer cement following the selective caries removal technique. The groups were divided into a control group, which used Fuji IX (GC- Europe, Leuven, Belgium), and a test group, which used Maxxion R (FGM- Joinville, Santa Catarina, Brazil). After exfoliation, the teeth were stored at 4°C and subjected to scanning electron microscopy (SEM), optical microscopy (OM), and energy dispersive spectrometry (EDS). Results: EDS analysis revealed that calcium (Ca) and phosphorus (P) were present in 100% of the specimens in both the control and test groups. Fluoride was found in 60% of the control group specimens and 63% of the test group specimens. OM images showed areas of mineralized dentin in both treatment groups. Conclusions: Selective caries removal for deep lesions in deciduous teeth was shown to be a safe therapeutic protocol, demonstrating signs of dentin mineralization and control of disease progression.

Salmonella spp. are important foodborne pathogens often associated with infectious outbreaks caused by consuming contaminated food. Although these microorganisms are widely distributed in several animal production chains, there are few records of their occurrence in aquaculture. This study aimed to evaluate the presence and antimicrobial resistance of Salmonella spp. isolated from fish farms. Samples were collected from three fish farms, covering water, fish, and epilithic biofilm. Salmonella isolates were identified by PCR, and serotyping was performed using the slide agglutination method, according to the Kaufman-White system. Susceptibility to antimicrobial agents was assessed using the Kirby and Bauer disk diffusion method. The presence of class 1 and 2 integrons was determined by PCR. Ninety samples were examined, of which 13 (14.44%) were positive for S. enterica, of which 5 strains were isolated from lagoon water, 3 from fish, and 5 from epilithic biofilm. Among the samples, the serotypes S. Minnesota, S. Panamá, and S. Anatum were identified. Antimicrobial resistance rates were highest for sulfonamides (92.30%), trimethoprim (84.61%), tetracycline (46.15%), and streptomycin (46.15%). Multiple antibiotic resistance was confirmed in 84.61% of the isolates, with 100% presenting integron class 1 and 7.69% integron class 2. This study demonstrated a high prevalence of multiresistant bacteria in fish farms, which reinforces public health concerns due to the use of antibiotics and the risk associated with food from farmed freshwater fish. Given these results, the need for new external research into control and prevention strategies for Salmonella spp. is evident. in aquaculture, as well as greater regulation in fish production chains.

O artigo apresenta resultados de uma pesquisa qualitativa que teve como objetivo identificar e analisar os usos que estudantes universitários cegos fazem de tecnologias digitais e da tecnologia assistiva em suas atividades de estudo e na elaboração de suas estratégias para aprendizagem. A partir de um questionário enviado para núcleos de acessibilidade de 6 universidades do Rio de Janeiro e região metropolitana, chegou-se a 14 estudantes que se disponibilizaram a participar da pesquisa por meio de entrevista semiestruturada. A entrevista buscou compreender o acesso e o percurso de estudantes cegos no ensino superior, com foco nas estratégias de aprendizagem adotadas por eles para minimizar barreiras atitudinais, técnicas e pedagógicas que dificultam seus processos de aprendizagem. Como resultado, destaca-se a fundamental relevância das tecnologias assistiva e digitais na aquisição dos conteúdos curriculares por estudantes cegos, impactando a permanência no curso, o desempenho acadêmico e sua trajetória no ensino superior. A análise descreve como as técnicas e práticas desenvolvidas pelos participantes da pesquisa para os estudos estão ligadas ao uso dessas tecnologias e a grande relevância da aprendizagem por pares e da tutoria no acesso a materiais de estudo e, principalmente, na realização de tarefas acadêmicas. Constata-se que as estratégias de aprendizagem desses estudantes são potencializadas pelo letramento digital.

The Eastern Cape Province is a drought-prone area and it had been impacted by water service delivery problems for several decades. At the same time, there have been widespread instances of the need to supply water from alternative potable sources as to meet the drinking water demand of the population. Further to this point, there is an ongoing need to collect and evaluate water quality data from drought-affected areas in the Eastern Cape. In the current study, the authors seek to achieve two aims. Firstly, there is a need to conduct an investigation of the potable water quality from the local municipalities in the Eastern Cape where such investigations have not been common recently. Secondly, the authors seek to conduct an investigation into the carbon footprint of provision of alternative bottled water into a local municipality in the Eastern Cape Province of South Africa. Turbidity, pH and presence/levels of faecal contamination of drinking water were measured. In addition, the carbon footprint of the supply of bottled water was estimated for road transport of 5 litre bottles. Results indicate that microbial water quality is a problem and there is finite, but significant carbon dioxide emissions due to supply of alternative water sources. There is significant carbon footprint of the shipping of bottled water into the Eastern Cape Province, should the municipal water supply break down completely. The study results point to the need to monitor and treat the alternative sources of potable water in the study area. This is necessary protect human health and environment.

O processo de assistência à saúde da criança torna-se progressivamente integral quando há ênfase no crescimento, desenvolvimento e na qualidade de vida desta, de modo que a participação dos cuidadores é imprescindível. A massagem é um recurso terapêutico de baixo custo capaz de produzir uma série de efeitos benéficos para a saúde da criança. O objetivo deste artigo é compreender os benefícios da aplicação da Shantala para os envolvidos e descobrir se é possível repassá-la a cuidadores em diferentes contextos sociais. Trata-se de uma revisão bibliográfica nos periódicos da LILACS, PubMed e SciELO a partir do descritor em saúde: “Shantala”. Com a pesquisa foram encontrados 34 artigos. Após a leitura na íntegra, 10 artigos seguiram para análise completa e inferências dos resultados. Verificou-se que a Shantala proporciona numerosas vantagens ao desenvolvimento físico, motor, fisiológico e emocional da criança. Há melhora na interação social e uma maior vinculação do cuidador, mesmo nos casos dos pais mais ausentes ou portadores de transtornos emocionais menores, gerando uma noção de cuidado e proteção com a criança que recebe a massagem. As questões sociais e o grau de escolaridade não interferem no aprendizado e aplicação da técnica.

Objetivo: verificar na produção científica quais as publicações existentes sobre a assistência de enfermagem não farmacológica à puérpera. Métodos: Trata-se de uma revisão integrativa, com coleta de dados no mês de outubro de 2021, nas bases de dados eletrônicos: LILACS, SciELO, Pubmed e BDENF. Como questão norteadora: Quais as publicações existentes sobre a assistência de enfermagem não farmacológica à puérpera? Empregaram-se os termos de busca combinados: ‘Cuidados de Enfermagem’, ‘Período Pós-Parto’, ‘Terapias Complementares’, ‘Enfermagem Obstétrica’ resultando em 29 artigos, sendo destes 11 elegíveis. Resultados: Os resultados expressam maioria dos estudos selecionados realizados em países asiáticos (54,55%) com destaque para Coréia do sul e Turquia, publicados em 2013 (18,50%) e os descritivos foram os mais prevalentes (36,4%). Duas categorias emergiram. I- Uso de terapias complementares na assistência de enfermagem puerperal; II- Avaliação do uso de terapias alternativas na assistência de enfermagem puerperal. Conclusões: Portanto, os achados deste estudo identificaram estudos sobre medidas e intervenções alternativas/complementares que se distanciam da assistência no modelo convencional, atuando de forma coadjuvante no âmbito da assistência de enfermagem no puerpério.

Objective: To assess the relationship between celiac disease and the prevalence of dental caries in children and adolescents and also evaluate if dental enamel defects in celiac children predispose to dental caries. Material and Methods: Searches were performed in the following databases: PubMed, Scopus, Cochrane Library, Latin American and Caribbean Literature on Health Sciences, and OpenGrey. The risk of bias was assessed using the Newcastle-Ottawa Scale. DMFT/dmft and DMFS/dmfs data of observational studies that compared the prevalence of caries between children and adolescents with celiac disease and healthy individuals. Meta-analysis was performed using a random effects model. Heterogeneity between studies was estimated using Cochran’s Q test, and inconsistency was measured using I2 statistics. Results: Of the 121 studies retrieved, 17 were selected, and 12 were included in the meta-analysis. The prevalence of caries in the primary dentition (dmft) did not differ between celiac patients and controls [SMD = -0.35; 95% CI (-0.83; 0.13); p = 0,15; I2 = 89%]. There was also no difference in the prevalence of caries in permanent teeth (DMFT) between groups [SMD = -0.44; 95% CI (-1.02; 0.14); p = 0.14; I2 = 95%]. Conclusion: Celiac disease is not a determinant factor in the development of dental caries in children and adolescents compared to the control group.

Background: Evidence for the effectiveness of crisis helplines is limited by inappropriate and inconsistent outcome measurement. The aim of this study was to develop a core outcome set that reflects the most relevant and important outcomes to help-seekers accessing a crisis helpline via any delivery mode (e.g., phone, SMS text, online chat). Method: We used a three-panel Delphi method to compare and integrate the views of three expert groups: people with lived experience of accessing crisis helplines (n = 32), researchers with experience assessing crisis helpline outcomes (n = 25), and crisis helpline supporters (n = 58). Across two online survey rounds (89 % retention rate), participants rated the importance of 33 potential outcomes for help-seekers accessing a crisis helpline. Participants also provided open-text comments and suggestions. Outcomes that reached consensus (≥75 % agreement) by at least two panels were included in the core outcome set. Results: Ten outcomes met the criteria for inclusion in the core outcome set. In order of importance, these were: distress, feeling heard, suicide risk, connectedness/support, hopelessness, overwhelm, non-suicidal self-injury risk, service experience, helplessness, and next steps. Limitations: Participants self-selected and were mainly from English-speaking countries. Conclusions: We recommend future outcome and evaluation studies minimally measure and report the 10 outcomes identified in this study. Assessing an agreed set of meaningful outcomes will improve comparability and facilitate a deeper understanding of crisis helpline effectiveness. More work is needed to determine how best to assess these outcomes in the crisis helpline context.

Abstract Background Chronic lung disease is a common and complex condition. Pulmonary rehabilitation programmes—either hospital‐based or in the community are recommended in evidence‐based clinical practice guidelines. Aim To explore the experience of older people with chronic lung disease involved in a peer support community‐based exercise maintenance programme. Design and Method Participants were a part of the Lungs in Action programme run in a local community leisure centre through Lung Foundation Australia. All the programme participants (n = 25) were invited by an independent person through email and/or letter to participate in the study and provided with a participant information and consent form. Participants who returned consent forms were scheduled for group interviews. Participants were recruited over a 2‐week period between 30 August and 13 September 2022. We conducted qualitative group interviews using a semi‐structured interview guide to explore the experiences of older people living with chronic lung disease. Data were analysed using reflexive thematic analysis. Results A total of 14 participants (eight female and six male) aged between 64 and 86 years were interviewed. Three themes emerged from the data: motivation, authentic social engagement, and sustainable achievement. Motivation stemmed from the participants' perceived health benefits, and from the trainers' motivation and encouragement. Participants discussed how sharing experiences created an environment of trust and understanding, fun and friendship. Social engagement and creating authentic relationships were key aspects raised by participants. Feeling more confident in themselves and being able to accomplish physical tasks, making activities of daily living more manageable featured highly in participants' responses. Discussion and Conclusion Community‐based peer support exercise groups enable environments for people with chronic lung disease to maintain physical fitness, and to connect with others to form friendships and have fun.

Abstract Although macrophages contribute to cancer cell dissemination, immune evasion, and metastatic outgrowth, they have also been reported to coordinate tumor-specific immune responses. We therefore hypothesized that macrophage polarization could be modulated therapeutically to prevent metastasis. Here, we show that macrophages respond to β-glucan (odetiglucan) treatment by inhibiting liver metastasis. β-glucan activated liver-resident macrophages (Kupffer cells), suppressed cancer cell proliferation, and invoked productive T cell-mediated responses against liver metastasis in pancreatic cancer mouse models. Although excluded from metastatic lesions, Kupffer cells were critical for the anti-metastatic activity of β-glucan, which also required T cells. Furthermore, β-glucan drove T cell activation and macrophage re-polarization in liver metastases in mice and humans and sensitized metastatic lesions to anti-PD1 therapy. These findings demonstrate the significance of macrophage function in metastasis and identify Kupffer cells as a potential therapeutic target against pancreatic cancer metastasis to the liver.

Cerebrocardiovascular diseases are a major global public health concern, significantly impacting morbidity, mortality, and posing substantial socio-economic challenges. In Cabo Verde, non-communicable diseases have become the leading causes of morbidity and mortality. This study aimed to estimate the prevalence of risk factors for cerebrocardiovascular diseases and their association with cardiac electrical alterations in adults on Santiago Island, Cabo Verde. A cross-sectional population-based study using simple random sampling was conducted on individuals over 18 years of age. The sample size of 599 was based on Santiago Island’s 2021 population projection. Data collection occurred in October and November 2021, involving questionnaires on risk factors and cerebrocardiovascular diseases; blood pressure assessments; and capillary blood glucose measurements. The sample was predominantly female, with the 18–27 age group being the largest. Key risk factors included physical inactivity (65.1%), BMI ≥ 25 kg/m2 (42.6%), hypertension (32.6%), and family history of cerebrocardiovascular diseases (19.9%). Other factors were alcoholism (14.4%), hypercholesterolemia (8.3%), smoking (7.3%), diabetes (4.5%), and hypertriglyceridemia (1.3%). Notably, 9.3% had no risk factors, 27.5% had one, 36.2% had two, and 26.9% had three or more. There is a high prevalence of risk factors for cerebrocardiovascular diseases on Santiago Island, particularly among females.

Abstract Background Sedentary lifestyle and unhealthy diet combined with overweight are risk factors for type 2 diabetes (T2D). Lifestyle interventions with weight-loss are effective in T2D-prevention, but unsuccessful completion and chronic stress may hinder efficacy. Determinants of chronic stress and premature cessation at the start of the 3-year PREVIEW study were examined. Methods Baseline Quality of Life (QoL), social support, primary care utilization, and mood were examined as predictors of intervention cessation and chronic stress for participants aged 25 to 70 with prediabetes (n = 2,220). Moderating effects of sex and socio-economic status (SES) and independence of predictor variables of BMI were tested. Results Participants with children, women, and higher SES quitted intervention earlier than those without children, lower SES, and men. Lower QoL, lack of family support, and primary care utilization were associated with cessation. Lower QoL and higher mood disturbances were associated with chronic stress. Predictor variables were independent (p ≤ .001) from BMI, but moderated by sex and SES. Conclusions Policy-based strategy in public health should consider how preventive interventions may better accommodate different individual states and life situations, which could influence intervention completion. Intervention designs should enable in-built flexibility in delivery enabling response to individual needs. Trial registration ClinicalTrials.gov Identifier: NCT01777893.

Abstract Pharmacogenomics has the potential to inform drug dosing and selection, reduce adverse events, and improve medication efficacy; however, provider knowledge of pharmacogenomic testing varies across provider types and specialties. Given that many actionable pharmacogenomic genes are implicated in cardiovascular medication response variability, this study aimed to evaluate cardiology providers' knowledge and attitudes on implementing clinical pharmacogenomic testing. Sixty‐one providers responded to an online survey, including pharmacists (46%), physicians (31%), genetic counselors (15%), and nurses (8%). Most respondents (94%) reported previous genetics education; however, only 52% felt their genetics education prepared them to order a clinical pharmacogenomic test. In addition, most respondents (66%) were familiar with pharmacogenomics, with genetic counselors being most likely to be familiar (p

Conclusions: Any new technology to support crisis supporters needs to be carefully codesigned with the workforce to ensure effective implementation and avoid any potential or perceived negative impacts on help-seekers.

Dental caries remains the most prevalent chronic disease globally, and its management should adhere to the principles of minimal intervention dentistry. This study reports a series of successful cases involving the selective removal of carious tissue in permanent molars, with follow-up periods of up to 21 years. Six permanent molars with severe and deep carious lesions were treated with selective caries removal and restored with high-viscosity glass ionomer cement. Clinical examination revealed that the teeth were free from pain and sensitivity. Follow-up assessments were conducted at 7 and 21 years posttreatment. Treatment success was defined by the absence of clinical and radiographic signs, symptoms of pulp alterations, and lesion arrest. Successful minimally invasive approaches were observed with selective removal of carious tissue and maintenance of pulp vitality for up to 21 years.

Abstract Purkinje cell (PC) loss occurs at an early age in patients and animal models of Niemann-Pick Type C (NPC), a lysosomal storage disease caused by mutations in the Npc1 or Npc2 genes. Although degeneration of PCs occurs early in NPC, little is known about how NPC1 deficiency affects the postnatal development of PCs. Using the Npc1 nmf164 mouse model, we found that NPC1 deficiency significantly affected the postnatal development of PC dendrites and synapses. The developing dendrites of Npc1 nmf164 PCs were significantly deficient in mitochondria and lysosomes. Furthermore, anabolic (mTORC1) and catabolic (TFEB) signaling pathways were not only perturbed but simultaneously activated in NPC1-deficient PCs, suggesting a loss of metabolic balance. We also found that mice with conditional heterozygous deletion of the Phosphatase and Tensin Homolog Deleted on Chromosome 10 gene (Pten-cHet), an inhibitor of mTORC1, showed similar early dendritic alterations in PCs to those found in Npc1-deficient mice. However, in contrast to Npc1 nmf164 mice, Pten-cHet mice exhibited the overactivation of the mTORC1 pathway but with a strong inhibition of TFEB signaling, along with no dendritic mitochondrial reductions by the end of their postnatal development. Our data suggest that disruption of the lysosomal-metabolic signaling in PCs causes dendritic and synaptic developmental deficits that precede and promote their early degeneration in NPC.

In eukaryotes, EPSINs are Epsin N-terminal Homology (ENTH) domain-containing proteins that serve as monomeric clathrin adaptors at the plasma membrane (PM) or the trans-Golgi Network (TGN)/early endosomes (EE). The model plant Arabidopsis thaliana encodes for seven ENTH proteins, of which so far, only AtEPSIN1 (AtEPS1) and MODIFIED TRANSPORT TO THE VACUOLE1 (AtMTV1) localize to the TGN/EE and contribute to cargo trafficking to both the cell surface and the vacuole. However, relatively little is known about role(s) of any plant EPSIN in governing physiological responses. We have recently shown that AtEPS1 is a positive modulator of plant immune signaling and pattern-triggered immunity against flagellated Pseudomonas syringae pv. tomato (Pto) DC3000 bacteria. In eps1 mutants, impaired immune responses correlate with reduced accumulation of the receptor FLAGELLIN SENSING2 (AtFLS2) and the convergent immune co-receptor BRASSINOSTEROID INSENTIVE1-ASSOCIATED RECEPTOR KINASE1 (AtBAK1) in the PM. Here, we report that in contrast to AtEPS1, the TGN/EE-localized AtMTV1 did not contribute significantly to immunity against pathogenic Pto DC3000 bacteria. We also compared the amino acid sequences, peptide motif structures and in silico tertiary structures of the ENTH domains of AtEPS1 and AtMTV1 in more detail. We conclude that despite sharing the classical tertiary alpha helical ENTH-domain structure and clathrin-binding motifs, the overall low amino acid identity and differences in peptide motifs may explain their role(s) in trafficking of some of the same as well as distinct cargo components to their site of function, with the latter potentially contributing to differences in physiological responses.

STEM higher education in the U.S. has long been an uninviting space for minoritized individuals, particularly women, persons of color, and international students and scholars. In recent years, the contemporary realities of a global pandemic, sociopolitical divides, and heightened racial tensions, along with elevated levels of mental illness and emotional distress among college students, have intensified the need for an undergraduate STEM education culture and climate that recognizes and values the humanity of our students. The purpose of this article is to advance a more humanized undergraduate STEM education and to provide a framework to guide efforts toward achieving that vision. We argue that humanizing approaches recognize and value the complexity of individuals and the cultural capital that they bring to their education, and that this is particularly important for empowering minoritized students who are subordinated in status in STEM higher education. A STEM education that centers students’ humanity gives rise to equity and promotes human well-being and flourishing alongside knowledge acquisition and skill development. We then offer a guiding framework for conceptualizing the broader ecosystem in which undergraduate STEM students are embedded, and use it to outline the individual and collective roles that different stakeholders in the ecosystem can play in humanizing STEM education.

Summary: As SARS-CoV-2 becomes endemic, it is critical to understand immunity following early-life infection. We evaluated humoral responses to SARS-CoV-2 in 23 infants/young children. Antibody responses to SARS-CoV-2 spike antigens peaked approximately 30 days after infection and were maintained up to 500 days with little apparent decay. While the magnitude of humoral responses was similar to an adult cohort recovered from mild/moderate COVID-19, both binding and neutralization titers to WT SARS-CoV-2 were more durable in infants/young children, with spike and RBD IgG antibody half-life nearly 4X as long as in adults. IgG subtype analysis revealed that while IgG1 formed the majority of the response in both groups, IgG3 was more common in adults and IgG2 in infants/young children. These findings raise important questions regarding differential regulation of humoral immunity in infants/young children and adults and could have broad implications for the timing of vaccination and booster strategies in this age group.