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ProblemOur nation faces an urgent need for more primary care (PC) physicians, yet interest in PC careers is dwindling. Students from underrepresented in medicine (UIM) backgrounds are more likely to choose PC and practice in underserved areas yet their representation has declined. Accelerated PC programs have the potential to address workforce needs, lower educational debt, and diversify the physician workforce to advance health equity.ApproachWith support from Kaiser Permanente Northern California (KPNC) and the American Medical Association's Accelerating Change in Medical Education initiative, University of California School of Medicine (UC Davis) implemented the Accelerated Competency-based Education in Primary Care (ACE-PC) program - a six-year pathway from medical school to residency for students committed to health equity and careers in family medicine or PC-internal medicine. ACE-PC accepts 6-10 students per year using the same holistic admissions process as the 4-year MD program with an additional panel interview that includes affiliated residency program faculty from UC Davis and KPNC. The undergraduate curriculum features: PC continuity clinic with a single preceptor throughout medical school; a 9-month longitudinal integrated clerkship; supportive PC faculty and culture; markedly reduced student debt with full-tuition scholarships; weekly PC didactics; and clinical rotations in affiliated residency programs with the opportunity to match into specific ACE-PC residency tracks.OutcomesSince 2014, 70 students have matriculated to ACE-PC, 71% from UIM groups, 64% are first-generation college students. Of the graduates, 48% have entered residency in family medicine and 52% in PC-internal medicine. In 2020, the first graduates entered the PC workforce; all are practicing in California, including 66% at federally qualified health centers, key providers of underserved care.

Digestion of waste feedstocks by larvae of the black soldier fly Hermetia illucens (Diptera: Stratiomyidae) (BSF) results in proteins for animal feed and organic fertilizer with a reduced environmental footprint, but it can still have negative environmental effects through greenhouse gas (GHG) and ammonia (NH3) emissions. Both biomass conversion by BSF larvae and associated GHG and NH3 emissions can depend on substrate properties that may be optimized through microbial inoculation pre-treatments, such as bokashi fermentation. Here, we quantified the effects of bokashi fermentation of brewery's spent grains on BSF rearing metrics and associated GHG and NH3 emissions at benchtop scale. We found that bokashi fermentation increased larval biomass by 40% and shortened development time by over two days on average, compared with unfermented spent grains. In line with increased larval growth, CO2 emissions in BSF larvae treatments were 31.0 and 79.0% higher in the bokashi fermented spent grains and Gainesville substrates, respectively, compared to the unfermented spent grains. Adding BSF larvae to the spent grains increased cumulative N2O emissions up to 64.0 mg N2O kg substratedry-1 but there were essentially no N2O emissions when larvae were added to fermented spent grains. Bokashi fermentation also reduced NH3 fluxes from the volatilization of substrate nitrogen in the BSF larvae treatment by 83.7-85.8% during days 7 and 9, possibly by increasing N assimilation by larvae or by reducing the transformation of substrate NH4+ to NH3. Therefore, bokashi fermentation may be applied to improve performance of BSF larvae on a common industrial waste stream and reduce associated emissions.

Abstract Many cancer patients do not benefit from PD-L1/PD-1 blockade immunotherapies. PD-1 and LAG-3 co-upregulation in T-cells is one of the major mechanisms of resistance by establishing a highly dysfunctional state in T-cells. To identify shared features associated to PD-1/LAG-3 dysfunctionality in human cancers and T-cells, multiomic expression profiles were obtained for all TCGA cancers immune infiltrates. A PD-1/LAG-3 dysfunctional signature was found which regulated immune, metabolic, genetic, and epigenetic pathways, but especially a reinforced negative regulation of the TCR signalosome. These results were validated in T-cell lines with constitutively active PD-1, LAG-3 pathways and their combination. A differential analysis of the proteome of PD-1/LAG-3 T-cells showed a specific enrichment in ubiquitin ligases participating in E3 ubiquitination pathways. PD-1/LAG-3 co-blockade inhibited CBL-B expression, while the use of a bispecific drug in clinical development also repressed C-CBL expression, which reverted T-cell dysfunctionality in lung cancer patients resistant to PD-L1/PD-1 blockade. The combination of CBL-B-specific small molecule inhibitors with anti-PD-1/anti-LAG-3 immunotherapies demonstrated notable therapeutic efficacy in models of lung cancer refractory to immunotherapies, overcoming PD-1/LAG-3 mediated resistance.

Objetivos: demostrar el efecto de la infusión de adrenalina en relación con la noradrenalina con el propósito de prevenir la hipotensión materna post anestesia intradural. Métodos: estudio prospectivo, longitudinal, analítico y doble ciego con enfoque cuantitativo. Población de 114, muestra de 46 pacientes dividido en 2 agrupaciones. grupo A (noradrenalina) y grupo B (adrenalina) a dosis de 0,02 mcg/kg/min. Medición de variables continuas se sacó media y aplicación de prueba de normalidad de Shapiro- Wilk. Se aplicó T de student para las medias y U de Mann – Whitney para las medianas. En variables nominales se sacó frecuencia. Resultados: la media de la edad entre 32 a 33 años de ambas agrupaciones, con latido cardiaco significativo en T3 y T4 para el grupo B, valor p 0,045 y 0,000. Sin cambios importantes en la tensión arterial ni en las puntuaciones del APGAR. Los efectos secundarios son la presencia de cefalea posiblemente relacionado con uso de oxitocina. 18 y 16 pacientes no presentaron hipotensión con chi cuadrado de 0,89. Volumen total de cristaloides de 650 ml a 700 ml tanto en el grupo A y B. El costo referencial fue de 0,9 bolivianos. Conclusiones: la adrenalina es un vasopresor sugerente, sin alteraciones en los latidos cardíacos maternos, pero con un mayor control que la noradrenalina, y con una acción similar en la tensión arterial media en ambas agrupaciones.

Abstract Background Continuous glucose monitoring can improve glycemic control for hospitalized patients with diabetes, according to current evidence. However, there is a lack of consensus-established recommendations for the management of hospitalized patients with diabetes using flash continuous glucose monitoring system (fCGM) in Latin America. Therefore, this expert consensus exercise aimed to establish guidelines on the implementation of fCGM in the management of hospitalized patients with diabetes in Latin America. Methods The modified Delphi method was applied on a panel of nine specialists, establishing consensus at 80%. A twenty-two-question instrument was developed to establish recommendations on the use of fCGM in hospitalized patients living with diabetes. Results Based on consensus, experts recommend the use of fCGM in hospitalized patients with diabetes starting at admission or whenever hyperglycemia (> 180 mg/dl) is confirmed and continue monitoring throughout the entire hospital stay. The recommended frequency of fCGM scans varies depending on the patient's age and diabetes type: ten scans per day for pediatric patients with type 1 and 2 diabetes, adult patients with type 1 diabetes and pregnant patients, and seven scans for adult patients with type 2 diabetes. Different hospital services can benefit from fCGM, including the emergency room, internal medicine departments, intensive care units, surgery rooms, and surgery wards. Conclusions The use of fCGM is recommended for patients with diabetes starting at the time of admission in hospitals in Latin America, whenever the necessary resources (devices, education, personnel) are available.

Abstract Effective blood glucose management is crucial for people with diabetes to avoid acute complications. Predicting extreme values accurately and in a timely manner is of vital importance to them. People with diabetes are particularly concerned about suffering a hypoglycemia (low value) event and, moreover, that the event will be prolonged in time. It is crucial to predict hyperglycemia (high value) and hypoglycemia events that may cause health damages in the short term and potential permanent damages in the long term. This paper describes our research on predicting hypoglycemia events at 30, 60, 90, and 120 minutes using machine learning methods. We propose using structured Grammatical Evolution and dynamic structured Grammatical Evolution to produce interpretable mathematical expressions that predict a hypoglycemia event. Our proposal generates white-box models induced by a grammar based on if-then-else conditions using blood glucose, heart rate, number of steps, and burned calories as the inputs for the machine learning technique. We apply these techniques to create three types of models: individualized, cluster, and population-based. They all are then compared with the predictions of eleven machine learning techniques. We apply these techniques to a dataset of 24 real patients of the Hospital Universitario Principe de Asturias, Madrid, Spain. The resulting models, presented as if-then-else statements that incorporate numeric, relational, and logical operations between variables and constants, are inherently interpretable. The True Positive Rate and True Negative Rate metrics are above 0.90 for 30-minute predictions, 0.80 for 60 min, and 0.70 for 90 min and 120 min for the three types of models. Individualized models exhibit the best metrics, while cluster and population-based models perform similarly. Structured and dynamic structured grammatical evolution techniques perform similarly for all forecasting horizons. Regarding the comparison of different machine learning techniques, on the shorter forecasting horizons, our proposals have a high probability of winning, a probability that diminishes on the longer time horizons. Structured grammatical evolution provides advanced forecasting models that facilitate model explanation, modification, and retesting, offering flexibility for refining solutions post-creation and a deeper understanding of blood glucose behavior. These models have been integrated into the glUCModel application, designed to serve people with diabetes.

Abstract Over the last quarter century, increasing honey bee colony losses motivated standardized large-scale surveys of managed honey bees (Apis mellifera), particularly in Europe and the United States. Here we present the first large-scale standardized survey of colony losses of managed honey bees and stingless bees across Latin America. Overall, 1736 beekeepers and 165 meliponiculturists participated in the 2-year survey (2016–2017 and 2017–2018). On average, 30.4% of honey bee colonies and 39.6% of stingless bee colonies were lost per year across the region. Summer losses were higher than winter losses in stingless bees (30.9% and 22.2%, respectively) but not in honey bees (18.8% and 20.6%, respectively). Colony loss increased with operation size during the summer in both honey bees and stingless bees and decreased with operation size during the winter in stingless bees. Furthermore, losses differed significantly between countries and across years for both beekeepers and meliponiculturists. Overall, winter losses of honey bee colonies in Latin America (20.6%) position this region between Europe (12.5%) and the United States (40.4%). These results highlight the magnitude of bee colony losses occurring in the region and suggest difficulties in maintaining overall colony health and economic survival for beekeepers and meliponiculturists.

Introdução: Citomegalovírus (CMV) é um evento frequente no transplante alogênico de células hematopoéticas (Alo-TCH), cuja primo infecção ocorre, em geral, no período da infância. A imunossupressão aumenta o risco de reativação e está associada a alta morbidade e mortalidade nessa população. Esse estudo tem por objetivo avaliar se a reativação de CMV na população pediátrica apresenta comportamento semelhante a reativação na população adulta submetida a Alo-TCH. Métodos: Estudo de coorte prospectivo em indivíduos submetidos a TCH em uma única instituição entre 2013 e 2024. Pacientes foram testados por PCR quantitativo de CMV (Taqman Sistem – artus CMV Qiagen) no plasma para detecção de DNAemia (limite de detecção 31 UI/mL). A testagem iniciou na primeira semana pós transplante. Pacientes menores de 18 anos foram classificados como pediátricos. Os dados foram analisados usando SPSS 21 e a significância estatística definida foi p < 0.05. Foram usados testes Qui-Quadrado, Mann Whitney e Pearson, considerando as características das variáveis. Kaplan-Meier foi usado para avaliação de incidência. O estudo foi aprovado pelo Comitê de Ética em Pesquisa Institucional. Resultados: Foram realizados 287 TCH alogênico, dos quais 40 (14%) pacientes pediátricos e 247 adultos. As medianas de idade dos pediátricos e adultos foram de 9 (1‒16) e 46 (18‒75) anos, respectivamente. A mediana do tempo de follow-up da coorte foi de 335 dias. As principais indicações para o Alo-TCH nos pediátricos foram LLA (42% × 17%; p < 0,01), anemia aplástica (20% × 4%; p < 0,01) e LMA (17,5 × 41%; p < 0,01) em comparação com os adultos. Em relação ao TCH, o tipo de doador e a fonte entre pediátricos e adultos foram respectivamente: doadores não aparentados (NAP) 45% x 23% e haploidênticos (Haplo) 40% × 34% (p < 0,01), com predomínio da fonte de medula óssea 70% × 39% (p < 0,01). Até o D+180, 19 pediátricos e 94, adultos tiveram reativação por CMV. A incidência de reativação por CMV até o D+100 e até o D+180 ocorreu em 49% x 35% e 52% x 42% (p = 0,12) respectivamente entre pediátricos e adultos. A mediana de dias pós TCH para reativação foi de D+23 × D+35 dias (p = NS), e 58% × 40% das reativações aconteceram até o D+30 (p = NS), entre pediátricos e adultos. As medianas da carga viral inicial e a de pico foram 73 × 162 UI/mL (p < 0,01) e 487 × 4180 UI/mL (p < 0,01), respectivamente. O tempo entre a primeira carga viral positiva e o clareamento foi de 28 × 38 dias (p = NS). Comparando as características de casos de reativação em pediatria versus adultos, houve diferença quanto a doença de base LLA (42% x 18), AA (26% x 6%) e LMA (26% × 40%) (p < 0,05); tipo de doador (NAP e Haplo foram 47% × 28% e 37% × 29%; p = 0,08) e fonte de células utilizada (medula óssea: 77% × 66%; p = 0,05). Conclusão: Comparando as duas populações, observou-se que o TCH pediátrico mais frequentemente foi realizado com doadores alternativos comparando com adultos. Houve uma incidência de reativação de CMV ao redor de 50% até o D+180, porém a diferença na incidência de CMV entre a população pediátrica e a adulta não foi estatisticamente significativa. 50% das reativações em pediatria ocorreram até o D+30. No entanto, a cinética viral indicou que as cargas virais iniciais e de pico foram significativamente menores nos pediátricos, porém sem diferença significativa no clareamento viral. A população pediátrica apresentou alta reativação de CMV, com reativações precoces em uma coorte com alta frequência de doadores alternativos.

Introdução: O programa de Transplante de Medula Óssea do Hospital Universitário da UFRJ completa 30 anos em 2024. Neste período, passamos por diversas fases e ajustes neste programa. O conhecimento das curvas de sobrevida atingidas poderão guiar as melhorias futuras. Neste trabalho, escolhemos atualizar as curvas de sobrevida dos pacientes com mieloma múltiplo e linfomas, as maiores indicações de Transplante Autólogo de Células-Tronco hematopoéticas (TACTH). Objetivo: Analisar a sobrevida global dos pacientes submetidos ao TACTH no Hospital Universitário da UFRJ no tempo entre 2014 e 2023, comparando casos de linfoma e mieloma. Além disso, comparamos as recaídas pós transplante e o tempo para realizar o procedimento. Material e métodos: Coletamos informações dos nossos pacientes submetidos ao TATCH, por meio do prontuário eletrônico do Hospital. Reunimos esses dados em uma tabela de Excel para posterior cálculo de medianas da sobrevida global, do tempo para infusão e da recaída pós transplante. Nossa coorte tem 153 pacientes (88 homens e 65 mulheres), sendo 69 com diagnóstico de linfomas (38 linfoma de Hodgkin), 83 de mielomas e 1 de amiloidose. Resultados: Análise dos pacientes com linfoma: A mediana da Sobrevida Global (SG) foi 4,4 anos (1,1‒12,7a) a partir do diagnóstico inicial; a SG mediana após o TACTH foi de 1,9 anos (0,03‒9,4a); o tempo mediano entre o diagnóstico e o TACTH foi de cerca de 2,0 anos (0,5‒9,6a). No período analisado, ocorreram 29 recidivas e 28 óbitos. Análise dos pacientes com mieloma múltiplo: A SG mediana foi 5,4 anos (0,9‒13,0a) a partir do diagnóstico inicial; a SG mediana após o TACTH foi de 3,5 anos (0,1‒11,0a); o tempo mediano entre o diagnóstico e o TACTH foi de cerca de 1,7 anos (0,5‒8,7a). No período analisado, ocorreram 31 recidivas e 32 óbitos. O status de doença não pode ser observado em um número de pacientes que foram seguir acompanhamento nos centros de tratamento original. Discussão: Nos pacientes que foram transplantados por linfoma, a SG após o TACTH é bem menor do que a reportada para linfoma de Hodgkin (Sirohi et al, Ann Oncol. 2008 Jul;19(7):1312-1319), porém está em linha com a reportada para linfomas agressivos (Van Den Neste et al. Bone Marrow Transplantation (2017) 52, 216–221). Já nos pacientes com mieloma, o tempo para transplante é maior do que o desejado e resulta em uma sobrevida mediana após o TACTH menor do que o esperado. Conclusão: Esta análise permitirá ajustes no nosso programa de TACTH, particularmente nos pacientes com mieloma. Esperamos trazer os dados do linfoma separados por subtipo para o HEMO 2024.

Archivo histórico de Kipus: Revista Andina de Letras y Estudios Culturales, 2002 y 2003.

Unlike conventional CD4+ T cells, which are phenotypically and functionally plastic, invariant NKT (iNKT) cells generally exist in a terminally differentiated state. Naïve CD4+ T cells can acquire alternative epigenetic states in response to different cues, but it remains unclear whether peripheral iNKT cells are epigenetically stable or malleable. Repetitive encounters of liver-resident iNKT cells (LiNKTs) with alpha-galactosylceramide (αGalCer)/CD1d-coated nanoparticles (NPs) can trigger their differentiation into a LiNKT cell subset expressing a T regulatory type 1 (TR1)-like (LiNKTR1) transcriptional signature. Here we dissect the epigenetic underpinnings of the LiNKT-LiNKTR1 conversion as compared to those underlying the peptide-major histocompatibility complex (pMHC)-NP-induced T-follicular helper (TFH)-to-TR1 transdifferentiation process. We show that gene upregulation during the LINKT-to-LiNKTR1 cell conversion is associated with demethylation of gene bodies, inter-genic regions, promoters and distal gene regulatory elements, in the absence of major changes in chromatin exposure or deposition of expression-promoting histone marks. In contrast, the naïve CD4+ T cell-to-TFH differentiation process involves extensive remodeling of the chromatin and the acquisition of a broad repertoire of epigenetic modifications that are then largely inherited by TFH cell-derived TR1 cell progeny. These observations indicate that LiNKT cells are epigenetically malleable and particularly susceptible to gene de-methylation.

IntroductionThis study is based on the paradigm of collaborative law and the current absence of instruments that evaluate the lawyer-client relationship as a function of the needs of the family system. The objective was to construct and validate an instrument, conceptualizing the lawyer-client relationship as a helping relationship.MethodTwo groups of experts and 239 parents (58% mothers and 42% fathers), users of Family Visitation Centers, participated in the study. The content, construct, and criterion validity of the instrument, as well as its invariance for both parents, were analyzed.ResultsThe resulting 12-item instrument has been shown to have a two-dimensional structure, invariant for both parents, with high psychometric solidity.DiscussionThe LCR scale seems to be a valuable and effective measure for use in a legal context, with important correlations with the parents’ psychological well-being, leading to a promising and relevant instrument for the holistic approach to the divorce process.

This dataset provides a collection of Continuous Glucose Monitoring (CGM) data, insulin dose administration, meal ingestion counted in carbohydrate grams, steps, calories burned, heart rate, and sleep quality and quantity assessment ac- quired from 25 people with type 1 diabetes mellitus (T1DM). CGM data was acquired by FreeStyle Libre 2 CGMs, and Fitbit Ionic smartwatches were used to obtain steps, calories, heart rate, and sleep data for at least 14 days. This dataset could be utilized to obtain glucose prediction models, hypoglycemia and hyperglycemia prediction models, and research on the relationships among sleep, CGM values, and the rest of the mentioned variables. This dataset could be used directly from the preprocessed version or customized from raw data. The data set has been used previously with different machine learning algorithms to predict glucose values, hypo, and hyperglycemia and to analyze influences among the features and the quality and quantity of sleep in people with T1DM.