SARS-CoV-2 Mpro oligomerization as a potential target for therapy.

The main protease (Mpro) of SARS-CoV-2 is critical in the virus's replication cycle, facilitating the maturation of polyproteins into functional units. Due to its conservation across taxa, Mpro is a promising target for broad-spectrum antiviral drugs. Targeting Mpro with small molecule inhibitors, such as nirmatrelvir combined with ritonavir (Paxlovid™), which the FDA has approved for post-exposure treatment and prophylaxis, can effectively interrupt the replication process of the virus. A key aspect of Mpro's function is its ability to form a functional dimer. However, the mechanics of dimerization and its influence on proteolytic activity remain less understood. In this study, we utilized biochemical, structural, and molecular modelling approaches to explore Mpro dimerization. We evaluated critical residues, specifically Arg4 and Arg298, that are essential for dimerization. Our results show that changes in the oligomerization state of Mpro directly affect its enzymatic activity and dimerization propensity. We discovered a synergistic relationship influencing dimer formation, involving both intra- and intermolecular interactions. These findings highlight the potential for developing allosteric inhibitors targeting Mpro, offering promising new directions for therapeutic strategies.

Functional screening in human HSPCs identifies optimized protein-based enhancers of Homology Directed Repair.

Homology Directed Repair (HDR) enables precise genome editing, but the implementation of HDR-based therapies is hindered by limited efficiency in comparison to methods that exploit alternative DNA repair routes, such as Non-Homologous End Joining (NHEJ). In this study, we develop a functional, pooled screening platform to identify protein-based reagents that improve HDR in human hematopoietic stem and progenitor cells (HSPCs). We leverage this screening platform to explore sequence diversity at the binding interface of the NHEJ inhibitor i53 and its target, 53BP1, identifying optimized variants that enable new intermolecular bonds and robustly increase HDR. We show that these variants specifically reduce insertion-deletion outcomes without increasing off-target editing, synergize with a DNAPK inhibitor molecule, and can be applied at manufacturing scale to increase the fraction of cells bearing repaired alleles. This screening platform can enable the discovery of future gene editing reagents that improve HDR outcomes.

Impact of Initiating a GLP1 Agonist and/or SGLT2 Inhibitor Therapy on De-Escalation and Discontinuation of Insulin and Diabetes Control When Managed by an Interprofessional Collaborative Team.

BACKGROUND: An FQHC in Denver, Colorado developed and implemented an interprofessional care model to collaboratively manage type 2 diabetes mellitus (T2DM). Utilizing the 340B program, the team protocolized ADA Guidelines to promote the early adoption of first-line medications, glucagon-like peptide1 receptor agonists (GLP1 RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) to improve patient outcomes. OBJECTIVES: To assess the impact of interprofessional collaborative management versus standard care on early initiation of a SGLT2i and/or GLP1 RA as first-line therapies to enhance (1) deprescribing of insulin, (2) reducing overbasalization of insulin through insulin de-escalation, and (3) effectively lowering A1C levels in adult primary care patients with T2DM. METHODS: This was a retrospective chart review of adult patients with T2DM who were initiated on a GLP1 RA and/or a SGLT2i. To determine the effects of initiating GLP1 RA and/or SGLT2i therapy on insulin usage and glycemic control, the total daily dose (TDD) of insulin before initiation was compared with the most recent TDD post-initiation to evaluate deprescribing. To determine the impact on overbasalization, pre-initiation and post-initiation insulin doses were evaluated. The effectiveness of GLP1 RA and/or SGLT2i in lowering A1C levels was determined by comparing the A1C prior to initiation with the A1C postinitiation. To evaluate the influence of interprofessional collaborative care on insulin deprescribing, overbasalization, and diabetes control, relevant measures were compared between patients receiving collaborative care versus standard care. RESULTS: Of the 60 total patients treated with insulin, 46.6% were deprescribed insulin, with a majority in the interprofessional collaborative group (93.1%) compared to standard care (6.9%). A total of 78.3% of patients benefited from a reduction in A1C following the initiation of a GLP1 RA and/or SGLT2i. The greatest A1C reduction was -2.9% in the group receiving metformin in addition to a GLP1 RA and a SGLT2i. Patients who received interprofessional collaborative care had an average A1c reduction of -2.9% compared to-1.1% with standard care. CONCLUSION: Most patients initially overbasalized on insulin experienced a reduction in overbasalization after initiating GLP1 RA and/or SGLT2i. There was a notable A1C reduction, de-escalation, and deprescribing of insulin in patients receiving interprofessional collaborative care.

The preventive effects of broccoli bioactives against cancer: Evidence from a validated rat glioma model.

The aggressive and incurable diffuse gliomas constitute 80% of malignant brain tumors, and patients succumb to recurrent surgeries and drug resistance. Epidemiological research indicates that substantial consumption of fruits and vegetables diminishes the risk of developing this tumor type. Broccoli consumption has shown beneficial effects in both cancer and neurodegenerative diseases. These effects are partially attributed to the isothiocyanate sulforaphane (SFN), which can regulate the Keap1/Nrf2/ARE signaling pathway, stimulate detoxifying enzymes, and activate cellular antioxidant defense processes. This study employs a C6 rat glioma model to assess the chemoprotective potential of aqueous extracts from broccoli seeds, sprouts, and inflorescences, all rich in SFN, and pure SFN as positive control. The findings reveal that administering a dose of 100 mg/kg of broccoli sprout aqueous extract and 0.1 mg/kg of SFN to animals for 30 days before introducing 1 × 104 cells effectively halts tumor growth and progression. This study underscores the significance of exploring foods abundant in bioactive compounds, such as derivatives of broccoli, for potential preventive integration into daily diets. Using broccoli sprouts as a natural defense against cancer development might seem idealistic, yet this investigation establishes that administering this extract proves to be a valuable approach in designing strategies for glioma prevention. Although the findings stem from a rat glioma model, they offer promising insights for subsequent preclinical and clinical research endeavors.

Daytime-Restricted Feeding Ameliorates Oxidative Stress by Increasing NRF2 Transcriptional Factor in the Rat Hippocampus in the Pilocarpine-Induced Acute Seizure Model.

Seizure-mediated oxidative stress is a crucial mechanism in the pathophysiology of epilepsy. This study evaluated the antioxidant effects of daytime-restricted feeding (DRF) and the role of the Nrf2 signaling pathway in a lithium-pilocarpine model seizure model that induces status epilepticus (SE). We performed a lipoperoxidation assay and dihydroethidium fluorescence to measure oxidative stress markers in the hippocampus (malondialdehyde and reactive oxygen species). The protein content of Nrf2 and its downstream protein SOD2 was evaluated using Western blotting. The cellular distribution of the Nrf2 and SOD2 proteins in the pyramidal cell layer of both the CA1 and CA3 hippocampal subfields and astrocytes (GFAP marker) were quantified using immunofluorescence and immunohistochemistry, respectively. Our results indicate that DRF reduced the malondialdehyde levels and the production of reactive oxygen species. Furthermore, a significant increase in Nrf2 and SOD2 protein content was observed in animals subjected to restrictive diet. In addition, DRF increased the relative intensity of the Nrf2 fluorescence in the perinuclear and nuclear compartments of pyramidal neurons in the CA1 subfield. Nrf2 immunoreactivity and the astrocyte marker GFAP also increased their colocalization under DRF conditions. Additionally, SOD2 immunoreactivity was increased in CA1 pyramidal neurons but not in the CA3 region. Our findings suggest that DRF partially prevents oxidative stress by increasing the Nrf2 transcriptional factor and the SOD2 enzyme during the development of SE.

Blistering and aggressive paniculite cutaneous T-cell lymphoma.

BACKGROUND: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is characterized by atypical T-cells expressing the α/ß T-cell receptor in the subcutaneous fat. Although it is usually indolent, some cases can show an aggressive course. It is usually a disease of the middle-aged, but can rarely affect children. CASE REPORT: We describe the case of a 12-year-old male, previously healthy, who presented a dermatosis disseminated to the four segments consisting of vesicles, blisters, erythematous and hematonecrotic plaques, atrophic scars, associated with edema. The biopsy confirmed limited cutaneous panniculitic T-cell lymphoma with extensive epidermal necrosis. CONCLUSIONS: We report the case of a SPTCL in a child. Although rare in this age group, the diagnosis should be considered in children who present similar conditions and who do not respond to treatment. Diagnosis is made on clinical suspicion and confirmed by histology. We discuss the challenges in its management and how timely diagnosis influences patient survival.

INTRODUCCIÓN: El linfoma de células T tipo paniculitis subcutánea (LCCTP) se caracteriza por la presencia de linfocitos T atípicos que expresan el receptor de células T α/ß en el tejido celular subcutáneo. Aunque generalmente es indolente, algunos casos presentan un curso agresivo. Es mayormente una enfermedad de la mediana edad, rara vez afecta a los niños. CASO CLÍNICO: Se describe el caso de un paciente de sexo masculino de 12 años de edad, previamente sano que presentó una dermatosis diseminada a los cuatro segmentos constituida por vesículas, ampollas, placas eritematocostrosas y hematonecróticas, además de atróficas, asociadas con edema. La biopsia confirmó linfoma cutáneo de células T paniculítico con extensa necrosis epidérmica. CONCLUSIONES: Reportamos el caso de un LCCTP en un paciente pediátrico. Aunque es raro en este grupo de edad, se debe considerar en los niños que presentan cuadros similares y que no responden a tratamiento. El diagnóstico se realiza por sospecha clínica y se confirma por histología. Se discuten los desafíos en su manejo y cómo el diagnóstico oportuno influye en la sobrevida del paciente.

HIV treatment cascade in regions of Peru with the highest HIV prevalence.

OBJECTIVES: To describe the HIV treatment cascade and care continuum in regions of highest HIV prevalence in Peru. METHODS: An observational longitudinal study was carried out in 14 tertiary hospitals in Peru. These are the main hospitals that administer antiretroviral treatment (ART) in the regions that represent approximately 95% of reports of HIV/AIDS cases in Peru in 2013. We included individuals older than 18 years newly diagnosed with HIV from 1 January 2011 to 31 December 2012. Medical records were reviewed until 2015. RESULTS: A total of 2119 people living with HIV (PLHIV) were identified in the selected health facilities (mean age = 35.26 years, 78% male). 97.25% [1845/1897; 95% confidence interval (CI): 96.4-97.9%] of the patients attended the consultation at least once during the follow-up, but only 64.84% (885/1365; 95% CI: 62.2-67.4%) attended within a month after the diagnosis. After starting ART, 74.63% (95% CI: 71.9-77.2%) of PLHIV remained in healthcare. Regardless of the time after diagnosis, 88.40% (1837/2078; 95% CI: 86.9-89.7%) of PLHIV started ART during the observation time. However, 78.68% (95% CI: 76.8-80.4%) did so during the first post-treatment year and only 28.88% (95% CI: 27.9-31.9%) after 1 month. After starting treatment, it was observed that 51.60% (95% CI: 49.2-54%) of PLHIV reached viral suppression during the follow-up period. CONCLUSIONS: Further analysis and improvements in the definition of indicators are required to achieve conclusive results; however, these data will give us a general understanding of the progress of Peruvian health policies in achieving the goal established by the WHO.

Linfoma cutáneo de células T paniculítico, ampolloso y agresivo / Blistering and aggressive paniculite cutaneous T-cell lymphoma

Resumen Introducción: El linfoma de células T tipo paniculitis subcutánea (LCCTP) se caracteriza por la presencia de linfocitos T atípicos que expresan el receptor de células T α/β en el tejido celular subcutáneo. Aunque generalmente es indolente, algunos casos presentan un curso agresivo. Es mayormente una enfermedad de la mediana edad, rara vez afecta a los niños. Caso clínico: Se describe el caso de un paciente de sexo masculino de 12 años de edad, previamente sano que presentó una dermatosis diseminada a los cuatro segmentos constituida por vesículas, ampollas, placas eritematocostrosas y hematonecróticas, además de atróficas, asociadas con edema. La biopsia confirmó linfoma cutáneo de células T paniculítico con extensa necrosis epidérmica. Conclusiones: Reportamos el caso de un LCCTP en un paciente pediátrico. Aunque es raro en este grupo de edad, se debe considerar en los niños que presentan cuadros similares y que no responden a tratamiento. El diagnóstico se realiza por sospecha clínica y se confirma por histología. Se discuten los desafíos en su manejo y cómo el diagnóstico oportuno influye en la sobrevida del paciente.

Abstract Background: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is characterized by atypical T-cells expressing the α/β T-cell receptor in the subcutaneous fat. Although it is usually indolent, some cases can show an aggressive course. It is usually a disease of the middle-aged, but can rarely affect children. Case report: We describe the case of a 12-year-old male, previously healthy, who presented a dermatosis disseminated to the four segments consisting of vesicles, blisters, erythematous and hematonecrotic plaques, atrophic scars, associated with edema. The biopsy confirmed limited cutaneous panniculitic T-cell lymphoma with extensive epidermal necrosis. Conclusions: We report the case of a SPTCL in a child. Although rare in this age group, the diagnosis should be considered in children who present similar conditions and who do not respond to treatment. Diagnosis is made on clinical suspicion and confirmed by histology. We discuss the challenges in its management and how timely diagnosis influences patient survival.

Antiviral activity of natural phenolic compounds in complex at an allosteric site of SARS-CoV-2 papain-like protease.

SARS-CoV-2 papain-like protease (PLpro) covers multiple functions. Beside the cysteine-protease activity, facilitating cleavage of the viral polypeptide chain, PLpro has the additional and vital function of removing ubiquitin and ISG15 (Interferon-stimulated gene 15) from host-cell proteins to support coronaviruses in evading the host's innate immune responses. We identified three phenolic compounds bound to PLpro, preventing essential molecular interactions to ISG15 by screening a natural compound library. The compounds identified by X-ray screening and complexed to PLpro demonstrate clear inhibition of PLpro in a deISGylation activity assay. Two compounds exhibit distinct antiviral activity in Vero cell line assays and one inhibited a cytopathic effect in non-cytotoxic concentration ranges. In the context of increasing PLpro mutations in the evolving new variants of SARS-CoV-2, the natural compounds we identified may also reinstate the antiviral immune response processes of the host that are down-regulated in COVID-19 infections.

Biophysical Screening Pipeline for Cryo-EM Grid Preparation of Membrane Proteins.

Successful sample preparation is the foundation to any structural biology technique. Membrane proteins are of particular interest as these are important targets for drug design, but also notoriously difficult to work with. For electron cryo-microscopy (cryo-EM), the biophysical characterization of sample purity, homogeneity, and integrity as well as biochemical activity is the prerequisite for the preparation of good quality cryo-EM grids as these factors impact the result of the computational reconstruction. Here, we present a quality control pipeline prior to single particle cryo-EM grid preparation using a combination of biophysical techniques to address the integrity, purity, and oligomeric states of membrane proteins and its complexes to enable reproducible conditions for sample vitrification. Differential scanning fluorimetry following the intrinsic protein fluorescence (nDSF) is used for optimizing buffer and detergent conditions, whereas mass photometry and dynamic light scattering are used to assess aggregation behavior, reconstitution efficiency, and oligomerization. The data collected on nDSF and mass photometry instruments can be analyzed with web servers publicly available at spc.embl-hamburg.de. Case studies to optimize conditions prior to cryo-EM sample preparation of membrane proteins present an example quality assessment to corroborate the usefulness of our pipeline.

Aberrant Connection Formation and Glia Involvement in the Progression of Pharmacoresistant Mesial Temporal Lobe Epilepsy.

Epilepsy is the most common chronic neurological disease, affecting approximately 65 million people worldwide, with mesial temporal lobe epilepsy (mTLE) being the most common type, characterized by the presence of focal seizures that begin in the hippocampus, and subsequently generalize to structures such as the cerebral cortex. It is estimated that approximately 40% of patients with mTLE develop drug resistance (DR), whose pathophysiological mechanisms remain unclear. The neuronal network hypothesis is one attempt to understand the mechanisms underlying resistance to antiepileptic drugs (AEDs), since recurrent seizure activity generates excitotoxic damage and activation of neuronal death and survival pathways that, in turn, promote the formation of aberrant neuronal networks. This review addresses the mechanisms that are activated, perhaps as compensatory mechanisms in response to the neurological damage caused by epileptic seizures, but that affect the formation of aberrant connections that allow the establishment of inappropriate circuits. On the other hand, glia seems to have a relevant role in post-seizure plasticity, thus supporting the hypothesis of the neuronal network in drug-resistant epilepsy, which has been proposed for ELT.

Hipercolesterolemia familiar descripción de un caso en una familia de Armenia - Quindío (Colombia)

Introducción: La Hipercolesterolemia familiar (HF) es una enfermedad genética de carácter autosómico dominante, poco frecuente, generada por la mutación en el cromosoma 19. Es la primera causa de enfermedad cardiovascular prematura. Las mutaciones patogénicas que generan la HF se relacionan con el receptor de LDL (LDLr), la apolipoproteina B-100 (Apo- B100) y la proteína convertasa subtilisina / kexina tipo 9 (PCSK9), que produce elevación del colesterol y alteración de la vía del LDLr en el 80 % de los casos diagnosticados de HF (5). Presentamos un reporte de caso de cuatro pacientes que pertenecen a la misma familia, quienes presentan mutaciones patogénicas de diferente compromiso a nivel cardiovascular y sistémico que ha afectado de manera negativa su cotidianidad. El objetivo de este trabajo es realizar una correlación del hipercolesterolemia familiar de tipo genético a partir de la literatura, con respecto a la serie de casos presentada, y evaluar el impacto que este genera en los servicios de salud, en la vida del paciente y su familia. Discusión: El reporte de caso que presentamos se fundamenta en la sospecha de HF según los criterios de Holanda. En estos pacientes se reconoce mutación del gen LDLr que se relaciona con HF. Sin embargo, no ha sido ampliamente estudiada. Chmara realizó en Polonia por primera vez un estudio en el que reportó la variante ac 11G>T. En Colombia, el estudio de López encontró tres mutaciones, identificadas como variante a c.11G > A, n c.416A > G y c.1187G > A (8). Conclusión: La HF en nuestro medio es poco frecuente y con gran impacto social, en la mayoría de los casos genera síntomas clínicos y aumento del riesgo cardiovascular desde una edad temprana. Es importante resaltar el diagnóstico oportuno y el conocimiento por parte del personal de salud para generar una calidad de vida adecuada a los pacientes y evitar que aumente el riesgo cardiovascular.

Introduction: Familial hypercholesterolemia (FH) is a rare autosomal dominant genetic disease caused by a chromosome 19 mutation. It is the main cause of premature cardiovascular disease. Pathogenic mutations which cause FH are related to the LDL receptor (LDLr), B-100 apolipoprotein (Apo-B100) and type 9 subtilisin/kexin convertase protein (PCSK9), causing blood cholesterol increase and impairment of the LDLr pathway in up to 80% of patients diagnosed with FH. We present the case of 4 patients belonging to the same family and who present pathogenic mutations leading to diverse kinds of cardiovascular and systemic disease. Discussion: The case report we are presenting is based on the suspicion of FH according to the dutch criteria. These patients had the LDLr gene mutation related to FH. However, this mutation has not been thoroughly studied. The ac 11G>T variant was reported for the first time in Poland by Chmara. In Colombia, Lopez found 3 mutations identified as variant a c.11G > A, variant n c.416A > G and variant c.1187G > A. Conclusion: FH is rare in Colombia. Early diagnosis and healthcare worker awareness must be highlighted to improve the quality of life and decrease the cardiovascular risk of patients.

Don't take the context out of the picture: Contextually shaped parents' and children's obesogenic behaviors in a marginalized area of Mexico City.

Santa Fe Gully zone is a marginalized area of Mexico City where nearly 39% of children live with either overweight or obesity. Despite the extensive research on obesogenic behaviors, studies frequently overlook the contexts where such behaviors occur. This qualitative study described individual and familial obesogenic behaviors among children with obesity from Santa Fe Gully, and explained how these behaviors might be contextually shaped. We used a grounded theory approach to investigate the process of development/maintenance of obesity in our sample. Fifteen participants (seven 10-year-olds with overweight or obesity and their parents) participated in nine art-based focus groups, and parents completed individual semi-structured interviews. Data were analyzed using a structured thematic content analysis. Results showed children's weight status was part of their identity, providing children with a familial 'fitting' sense while increasing psychosocial difficulties, leading to emotional overeating as a coping strategy. Parents' use of controlling and low-structured parenting practices reinforced children's emotional overeating and failed to regulate children's dietary and physical activity behaviors. Some low-structured parenting practices were guilt-motivated or fostered by socioeconomic and cultural factors (e.g., limited food access, unhealthy food exposure, community unsafety). Future interventions in Santa Fe Gully aimed at modifying obesogenic behaviors should incorporate systemic and ecological approaches to help participants navigate through contextual obstacles, as their behaviors should be analized considering the context where they occur.

Prevention of Chemotherapy-Induced Peripheral Neuropathy With PRESIONA, a Therapeutic Exercise and Blood Flow Restriction Program: A Randomized Controlled Study Protocol.

OBJECTIVE: This trial will analyze the acute and cumulative effects of a tailored program called PRESIONA that combines therapeutic exercise and blood flow restriction to prevent chemotherapy-induced peripheral neuropathy (CIPN) in individuals with early breast cancer undergoing neoadjuvant chemotherapy. METHODS: PRESIONA will be a physical therapist-led multimodal exercise program that uses blood flow restriction during low-load aerobic and strength exercises. For the acute study, only 1 session will be performed 1 day before the first taxane cycle, in which 72 women will be assessed before intervention and 24 hours post intervention. For the cumulative study, PRESIONA will consist of 24 to 36 sessions for 12 weeks following an undulatory prescription. At least 80 women will be randomized to the experimental group or control group. Feasibility will be quantified based on the participant recruitment to acceptance ratio; dropout, retention, and adherence rates; participant satisfaction; tolerance; and program security. In the efficacy study, the main outcomes will be CIPN symptoms assessed with a participant-reported questionnaire (EORTC QLQ-CIPN20). In addition, to determine the impact on other participant-reported health and sensorimotor and physical outcomes, the proportion of completed scheduled chemotherapy sessions will be examined at baseline (t0), after anthracycline completion (t1), after intervention (t2), and at the 2-month (t3) and 1-year follow-ups (t4). CONCLUSION: The proposed innovative approach of this study could have a far-reaching impact on therapeutic options, and the physical therapist role could be essential in the oncology unit to improve quality of life in individuals with cancer and reduce side effects of cancer and its treatments. IMPACT: Physical therapists in the health care system could be essential to achieve the planned doses of chemotherapy to improve survival and decrease the side effects of individuals with breast cancer. The prevention of CIPN would have an impact on the quality of life in these individuals, and this protocol potentially could provide an action guide that could be implemented in any health care system.

Conductas promotoras de salud en personas con diabetes mellitus II durante pandemia por COVID 19 / Health-promoting behaviors in people with diabetes mellitus II during the COVID 19 pandemic / Condutas promotoras de saúde eM pessoas com diabetes mellitus II durante pandemia por COVID 19

Objetivo: Identificar las conductas promotoras de salud de personas que padecen diabetes mellitus II en tiempos de pandemia. Materiales y métodos: Investigación cualitativa con diseño fenomenológico. Se realizó una entrevista semiestructurada a 12 personas mayores de edad, con diagnóstico de diabetes mellitus 2, residentes en la ciudad de Armenia- Quindío, quienes asistieron a controles de su patología por lo menos tres veces cada año, entre 2020 y 2021. La técnica de muestreo utilizada fue por saturación de categorías. Resultados: A partir del discurso de los participantes que padecen diabetes mellitus, se describen las con-ductas promotoras de salud, las cuales se agruparon en las siguientes categorías: Conductas y conocimientos adquiridos; efectos originados por las conductas; y, barreras para generar conductas promotoras de salud en tiempos de pandemia. De la información, emergió la cate-goría denominada "Necesidades de cuidado a la salud mental". Conclusiones: Es necesario repensar las prácticas de cuidado, de atención y de educación en salud a las personas que padecen diabetes. Por tanto, es importante realizar un abordaje holístico que garantice una atención integral de la salud y una educación emancipadora; es decir, que el conocimiento y las conductas adquiridas sean capaces de transformar la realidad vivida por cada persona.

Objective: To identify the health-promoting behaviors of people suffering from diabetes mel-litus II in times of pandemic. Materials and methods: qualitative research with a phenom-enological design. Semi-structured interview was conducted with 12 people of legal age, diagnosed with diabetes mellitus 2, residing in the city of Armenia-Quindío and who attended the controls for their pathology at least three times a year, from 2019 to 2020.The sampling technique used was saturation of categories. Results: from the discourse of the participants who live with diabetes mellitus, the health-promoting behaviors are described, which were grouped into the following categories: Acquired behaviors and knowledge; effects caused by behaviors and; Barriers to generating health-promoting behaviors in times of pandemic. From the information, the category called "Mental health care needs" emerged. Conclusions:It is necessary to rethink the practices of care, attention and health education for people who live with chronic diseases, intuiting to carry out a holistic approach that guarantees compre-hensive health care and emancipatory education, through in which the knowledge and behaviors acquired are capable of transforming the lived reality of each person

Objetivo: Identificar os comportamentos promotores de saúde de pessoas com diabetes mellitus II em tempos de pandemia. Materiais e métodos: Pesquisa qualitativa com delineamento fenom-enológico, foi realizada entrevista semiestruturada com 12 pessoas maiores de idade, diagnosti-cadas com diabetes mellitus 2, residentes na cidade de Armênia- Quindío e que frequentaram aos controles de sua patologia pelo menos três vezes ao ano, de 2019 a 2020. A técnica de amostr-agem utilizada foi a saturação de categorias. Resultados: a partir do discurso dos participantes que convivem com o diabetes mellitus, descrevem-se os comportamentos promotores da saúde, os quais foram agrupados nas seguintes categorias: Comportamentos e conhecimentos adquiri-dos; efeitos causados por comportamentos e; Barreiras para gerar comportamentos promotores de saúde em tempos de pandemia. A partir das informações, emergiu a categoria denominada "Necessidades de cuidados em saúde mental". Conclusões: É necessário repensar as práticas de cuidado, atenção e educação em saúde para as pessoas que convivem com doenças crônicas, com a finalidade de realizar uma abordagem holística que garanta uma atenção integral à saúde e educação emancipatória, por meio da qual os conhecimentos e comportamentos adquiridos sejam capaz de transformar a realidade vivida de cada pessoa

Homicidios de niñas, niños y adolescentes en el sureste de México, entre 2000 y 2017 / Homicides in children and adolescents in Southeast Mexico, between 2000 and 2017

Resumen Introducción: México atraviesa por un contexto de violencia creciente que incluye el aumento de homicidios y feminicidios a lo largo del territorio nacional. Los estudios existentes presentan vacíos de corte regional y de grupos de edad, en particular, el de 0 a 17 años. El objetivo de este artículo es describir el impacto de la mortalidad por homicidios sobre la población de 0 a 17 años en el sureste mexicano, una de las regiones más sacrificadas en materia de derechos humanos y bienestar social. Metodología: mediante las estadísticas de mortalidad general del Instituto Nacional de Estadística y Geografía, se calcularon las tasas brutas de mortalidad y las tasas específicas por sexo y grupos de edad correspondientes al período 2000-2017. Se estimó el promedio de Años de Vida Perdidos. El tipo de estudio es descriptivo y analiza el efecto de los homicidios en la tendencia de la mortalidad y la esperanza de vida. Resultados: los resultados mostraron que el más alto porcentaje de homicidios lo obtuvieron los hombres de todos los grupos etarios. En términos del promedio de AVP, las mujeres adolescentes del conjunto de 12 a 17 años evidenciaron los mayores incrementos. Conclusiones: las tasas de mortalidad por homicidio se comportaron heterogéneamente; resalta la vigencia y aumento de ataques letales contra niñas, niños y, especialmente, adolescentes.

Abstract Introduction: Mexico is currently facing a context of raising violence that includes the increase of homicides and feminicides in the nation-wide territory. The existent studies present certain gaps regarding regional and age groups information. In particular, those gaps are relevant for population from 0 to 17 years old. That is why this article aims to describe the mortality impacts by means of homicides among that age group in Southeast Mexico. This region is one of the most abandoned in terms of Human Rights and Social Well-Being. Methodology: The article uses the general mortality statistics of the National Institute of Statistics and Geography to calculate the gross mortality rates as well as the specific rates by age and sex groups from 2000 to 2017. Likewise, the average years of life lost are calculated. The study is descriptive and analyzes the impact of homicides within the trend of mortality and life expectancy. Results: A main result shows to the highest percentage of homicides occur among men. However, in terms of the average number of YLL and for the age group 12 to 17 years the largest increases occur among adolescent women. Conclusions: The Southeast region of Mexico presents heterogeneous behavior in homicide mortality rates for the age group 0 to 17 years, highlights the validity and increase of lethal violence against girls, boys and particularly adolescents.

Cyclohexyl-α maltoside as a highly efficient tool for membrane protein studies.

Membrane proteins (MPs) constitute a large fraction of the proteome, but exhibit physicochemical characteristics that impose challenges for successful sample production crucial for subsequent biophysical studies. In particular, MPs have to be extracted from the membranes in a stable form. Reconstitution into detergent micelles represents the most common procedure in recovering MPs for subsequent analysis. n-dodecyl-ß-D-maltoside (DDM) remains one of the most popular conventional detergents used in production of MPs. Here we characterize the novel DDM analogue 4-trans-(4-trans-propylcyclohexyl)-cyclohexyl α-maltoside (t-PCCαM), possessing a substantially lower critical micelle concentration (CMC) than the parental compound that represents an attractive feature when handling MPs. Using three different types of MPs of human and prokaryotic origin, i.e., a channel, a primary and a secondary active transporter, expressed in yeast and bacterial host systems, respectively, we investigate the performance of t-PCCαM in solubilization and affinity purification together with its capacity to preserve native fold and activity. Strikingly, t-PCCαM displays favorable behavior in extracting and stabilizing the three selected targets. Importantly, t-PCCαM promoted extraction of properly folded protein, enhanced thermostability and provided negatively-stained electron microscopy samples of promising quality. All-in-all, t-PCCαM emerges as competitive surfactant applicable to a broad portfolio of challenging MPs for downstream structure-function analysis.

Pediatric Emergency Medicine ECHO (Extension for Community Health Care Outcomes): Cultivating Connections to Improve Pediatric Emergency Care.

BACKGROUND: An Extension for Community Health Care Outcomes (ECHO) provides the opportunity for specialists at academic medical centers (AMCs) and frontline community generalists to engage in bidirectional learning. Specialists provide generalists with the current best evidence, and generalists share the local challenges applying this evidence to their practice. All ECHO participants strategize how to navigate these challenges together. Pediatric emergency medicine (PEM) may benefit from this knowledge translation strategy because most children seek emergency care from generalists in community emergency departments (CEDs) where variations in care between the AMC and the CED have been reported. METHODS: Our objective was to use ECHO to cultivate a PEM community of practice that facilitated knowledge translation and generated future CED pediatric improvement initiatives. As such, we developed, implemented, and evaluated a PEM ECHO. We conducted general and targeted needs assessments to inform our curriculum and formatted the sessions to generate bidirectional learning. A postparticipation evaluation collected self-reported perceptions about knowledge translation, planned provider practice changes, and perceptions of the formation of a community of practice. Additionally, we solicited information on the implementation of any pediatric improvement activities attributed to the PEM ECHO. RESULTS: Thirteen 1-hour sessions covered the chosen PEM topics. Participants represented diverse CEDs, with varied experience and roles in caring for children. All respondents (13/13) appreciated the ECHO learning format, reported improved PEM knowledge, and perceived the cultivation of a community of practice. Nine (85%) individuals attributed implementation of new pediatric improvement activities to the PEM ECHO. CONCLUSIONS: Our PEM ECHO was associated with improved perceptions of PEM knowledge, cultivated a community of practice, and facilitated the implementation of CED pediatric improvement activities. The PEM ECHO's bidirectional learning format generated new initiatives and partnerships aiming to improve the emergency care of children.

Concurrent validity of five prediction equations to evaluate fat percentage in a sports group expected to yield high performance from Medellín, Colombia. / Validez concurrente de cinco ecuaciones de predicción para evaluar el porcentaje de grasa en un grupo de deportistas con expectativas de alto rendimiento de Medellín, Colombia

INTRODUCTION: No equations to predict the body composition of athletes from Medellín expected to have high performance have been constructed and, thus, decisions regarding their training and nutrition plans lack support. OBJECTIVE: To calculate the concurrent validity of five prediction equations for fat percentage in a group of athletes from Medellín, Colombia, expected to yield high performance. MATERIALS AND METHODS: We conducted a cross-sectional analysis to validate diagnostic tests using secondary-source data of athletes under the age of 18 who were part of the "Medellín Team". The gold standard was dual-energy X-ray densitometry (DEXA). We analyzed the Slaughter, Durnin and Rahaman, Lohman, and Johnston prediction equations, as well as the five-component model. We used the intraclass correlation coefficient to assess the consistency of the methods and the Bland-Altman plot to calculate the average bias and agreement limits of each of the equations. RESULTS: We included 101 athletes (50,5 % of them women). The median age was 14,8 years (IR: 13,0 - 16,0). The concurrent validity was "good/excellent" for the Johnston and the Durnin and Rahaman equations and the five-components model. The Lohman equation overestimated the fat percentage in 12,7 points. All of the equations showed broad agreement limits. CONCLUSIONS: The Durnin and Rahaman and the Johnston equations, as well as the fivecomponent model, can be used to predict the FP in the study population as they showed a "good/excellent" concurrent validity and a low average bias. The equations analyzed have low accuracy, which hinders their use to diagnose the individual fat percentage within this population.

Introducción. La falta de ecuaciones de predicción de la composición corporal de deportistas con expectativas de alto rendimiento en Medellín dificulta la toma de decisiones para su entrenamiento y nutrición. Objetivo. Calcular la validez concurrente de cinco ecuaciones de predicción del porcentaje de grasa en un grupo de deportistas con expectativas de alto rendimiento en Medellín, Colombia. Materiales y métodos. Se hizo un estudio trasversal de validación de pruebas diagnósticas con datos de una fuente secundaria de deportistas menores de 18 años pertenecientes al "Team Medellín". La densitometría dual de rayos X (DEXA) fue la prueba de referencia. Se analizaron las ecuaciones de predicción de Slaughter, de Durnin y Rahaman, de Lohman y de Johnston, así como el modelo de cinco componentes. Para evaluar la concordancia entre los métodos se utilizó el coeficiente de correlación intraclase y se hicieron análisis de Bland y Altman para calcular el sesgo promedio y los límites de acuerdo de cada una de las ecuaciones. Resultados. Participaron 101 deportistas (50,5 % de ellos mujeres) con una mediana de edad de 14,8 años (RI: 13,0-16,0). La validez concurrente fue "buena-excelente" para las ecuaciones de Johnston, Durnin y Rahaman y el modelo de cinco componentes. La ecuación de Lohman sobreestimó el porcentaje de grasa en 12,7 puntos porcentuales, pero todas mostraron límites de acuerdo amplios. Conclusiones. En la población del estudio se pueden utilizar las ecuaciones de Durnin y Rahaman, la de Johnston y el modelo de cinco componentes para predecir el porcentaje de grasa, pues su validez concurrente fue "buena-excelente" y el sesgo promedio fue bajo. Las ecuaciones que se estudiaron tienen poca precisión, lo que dificulta utilizarlas para el diagnóstico individual del porcentaje de grasa en dicha población.

Concurrent validity of five prediction equations to evaluate fat percentage in a sports group expected to yield high performance from Medellín, Colombia / Validez concurrente de cinco ecuaciones de predicción para evaluar el porcentaje de grasa en un grupo de deportistas con expectativas de alto rendimiento de Medellín, Colombia

Abstract | Introduction: No equations to predict the body composition of athletes from Medellín expected to have high performance have been constructed and, thus, decisions regarding their training and nutrition plans lack support. Objective: To calculate the concurrent validity of five prediction equations for fat percentage in a group of athletes from Medellín, Colombia, expected to yield high performance. Materials and methods: We conducted a cross-sectional analysis to validate diagnostic tests using secondary-source data of athletes under the age of 18 who were part of the "Medellín Team'.' The gold standard was dual-energy X-ray densitometry (DEXA). We analyzed the Slaughter, Durnin and Rahaman, Lohman, and Johnston prediction equations, as well as the five-component model. We used the intraclass correlation coefficient to assess the consistency of the methods and the Bland-Altman plot to calculate the average bias and agreement limits of each of the equations. Results: We included 101 athletes (50,5 % of them women). The median age was 14,8 years (IR: 13,0 - 16,0). The concurrent validity was "good/excellent" for the Johnston and the Durnin and Rahaman equations and the five-components model. The Lohman equation overestimated the fat percentage in 12,7 points. All of the equations showed broad agreement limits. Conclusions: The Durnin and Rahaman and the Johnston equations, as well as the five-component model, can be used to predict the FP in the study population as they showed a "good/excellent" concurrent validity and a low average bias. The equations analyzed have low accuracy, which hinders their use to diagnose the individual fat percentage within this population.

Resumen | Introducción. La falta de ecuaciones de predicción de la composición corporal de deportistas con expectativas de alto rendimiento en Medellín dificulta la toma de decisiones para su entrenamiento y nutrición. Objetivo. Calcular la validez concurrente de cinco ecuaciones de predicción del porcentaje de grasa en un grupo de deportistas con expectativas de alto rendimiento en Medellín, Colombia. Materiales y métodos. Se hizo un estudio trasversal de validación de pruebas diagnósticas con datos de una fuente secundaria de deportistas menores de 18 años pertenecientes al "Team Medellín". La densitometría dual de rayos X (DEXA) fue la prueba de referencia. Se analizaron las ecuaciones de predicción de Slaughter, de Durnin y Rahaman, de Lohman y de Johnston, así como el modelo de cinco componentes. Para evaluar la concordancia entre los métodos se utilizó el coeficiente de correlación intraclase y se hicieron análisis de Bland y Altman para calcular el sesgo promedio y los límites de acuerdo de cada una de las ecuaciones. Resultados. Participaron 101 deportistas (50,5 % de ellos mujeres) con una mediana de edad de 14,8 años (RI: 13,0-16,0). La validez concurrente fue "buena-excelente" para las ecuaciones de Johnston, Durnin y Rahaman y el modelo de cinco componentes. La ecuación de Lohman sobreestimó el porcentaje de grasa en 12,7 puntos porcentuales, pero todas mostraron límites de acuerdo amplios. Conclusiones. En la población del estudio se pueden utilizar las ecuaciones de Durnin y Rahaman, la de Johnston y el modelo de cinco componentes para predecir el porcentaje de grasa, pues su validez concurrente fue "buena-excelente" y el sesgo promedio fue bajo. Las ecuaciones que se estudiaron tienen poca precisión, lo que dificulta utilizarlas para el diagnóstico individual del porcentaje de grasa en dicha población.