Cervidae antlers exploited to manufacture prehistoric tools and hunting implements as a reliable source of ancient DNA.

Antler is one of the primary animal raw materials exploited for technical purposes by the hunter-gatherer groups of the Eurasian Upper Palaeolithic (UP) all over the ecological range of deers, and beyond. It was exhaustively employed to produce one of the most critical tools for the survival of the UP societies: hunting weapons. However, antler implements can be made from diverse deer taxa, with different ecological requirements and ethological behaviours. Identifying the antler's origin at a taxonomic level is thus essential in improving our knowledge of humans' functional, practical and symbolic choices, as well as the human-animal interface during Prehistoric times. Nevertheless, palaeogenetics analyses have focused mainly on bone and teeth, with genetic studies of antler generally focused on modern deer conservation. Here we present the results of the first whole mitochondrial genome ancient DNA (aDNA) analysis by means of in-solution hybridisation capture of antlers from pre-Holocene archaeological contexts. We analysed a set of 50 Palaeolithic and Neolithic (c. 34-8ka) antler and osseous objects from South-Western Europe, Central Europe, South-Western Asia and the Caucasus. We successfully obtained aDNA, allowing us to identify the exploited taxa and demonstrate the archaeological relevance of those finds. Moreover, as most of the antlers were sampled using a minimally-invasive method, further analyses (morphometric, technical, genetic, radiometric and more) remain possible on these objects.

Intellectual Development in Mexican Preterm Children at Risk of Perinatal Brain Damage: A Longitudinal Study.

Preterm birth accounts for about 10% of births worldwide. Studying risk factors for perinatal brain damage is essential, as findings suggest that almost 20% of disabilities are linked to risks in the early stages of development. This research aimed to study longitudinal changes in intelligence from 6 to 8 years of age in a sample of 39 preterm children with a history of risk of brain damage and a control group of 35 children born at term. The Wechsler Intelligence Scale (WISC-IV) was used to measure cognitive ability at six, seven, and eight years old. The results showed that the preterm group obtained significantly lower scores than the control group. The working memory indicator significantly affected the interaction between age and prematurity. We consider it crucial to expand the knowledge we have about the neurocognitive development of premature infants, both in specific cognitive domains and in age ranges, so that the information obtained can help predict the probability of presenting cognitive alterations from early stages. This, therefore, helps in implementing intervention strategies and programs based on scientific evidence, and their design is complemented by clinical experience and empirical and theoretical knowledge of the different professionals involved in infant cognitive intervention.

A time-efficient workflow to purify a library of alanine mutants of surface-exposed residues of the domain III of the envelope protein of dengue virus serotype 1.

Dengue complex is formed by four viral serotypes that cause the disease of the same name. Dengue is the arthropod-borne disease with the highest incidence worldwide. The envelope glycoprotein comprises three structural domains. The domain III (DIII) induces neutralizing antibodies and is involved in the interactions with soluble plasma factors from human host. Recombinant DIII proteins have been used as analytical tools for the characterization of virus-host interactions and have been evaluated as sub-unit vaccines. Here, we report a purification procedure of recombinant DIII protein and seventy-four alanine mutants refolding by size exclusion chromatography that allows obtaining highly homogeneous protein preparations and suitable for efficient purification and folding check. Four positions are identified that significantly affect either the protein expression or folding of recombinant DIIIE1, K310, G304, D330 and P332.

Refractory Status Epilepticus Associated With a Pathogenic Variant in TNFRSF13B.

Febrile infection-related epilepsy syndrome (FIRES) is a rare epileptic syndrome characterized by new-onset refractory status epilepticus preceded by a febrile illness. Limited literature exists regarding the relationship between primary immunodeficiencies and immune-mediated epilepsy, and the relationship between new-onset refractory status epilepticus and common variable immunodeficiency (CVID) is not well-understood. We present a case of a 21-year-old female with a history of recurrent sinus infections, asthma, thrombocytopenia, atrioventricular nodal reentrant tachycardia, and neonatal seizures who presented with fever and new-onset status epilepticus. She was ultimately diagnosed with a heterozygous variant in TNFRSF13B c.311G>A (p.Cys104Tyr), which encodes for a tumor necrosis factor receptor implicated in CVID.

Neuropsychology and Electroencephalography in Rural Children at Neurodevelopmental Risk: A Scoping Review.

Children from rural areas face numerous possibilities of neurodevelopmental conditions that may compromise their well-being and optimal development. Neuropsychology and electroencephalography (EEG) have shown strong agreement in detecting correlations between these two variables and suggest an association with specific environmental and social risk factors. The present scoping review aims to describe studies reporting associations between EEG features and cognitive impairment in children from rural or vulnerable environments and describe the main risk factors influencing EEG abnormalities in these children. The method for this purpose was based on a string-based review from PubMed, EBSCOhost, and Web of Science, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Qualitative and quantitative analyses were conducted from the outcomes that complied with the selected criteria. In total, 2280 records were identified; however, only 26 were eligible: 15 for qualitative and 11 for quantitative analysis. The findings highlight the significant literature on EEG and its relationship with cognitive impairment from studies in children with epilepsy and malnutrition. In general, there is evidence for the advantages of implementing EEG diagnosis and research techniques in children living under risk conditions. Specific associations between particular EEG features and cognitive impairment are described in the reviewed literature in children. Further research is needed to better describe and integrate the state of the art regarding EEG feature extraction.

ERK mediates interferon gamma-induced melanoma cell death.

BACKGROUND: Interferon-gamma (IFNγ) exerts potent growth inhibitory effects on a wide range of cancer cells through unknown signaling pathways. We pursued complementary screening approaches to characterize the growth inhibition pathway. METHODS: We performed chemical genomics and whole genome targeting CRISPR/Cas9 screens using patient-derived melanoma lines to uncover essential nodes in the IFNγ-mediated growth inhibition pathway. We used transcriptomic profiling to identify cell death pathways activated upon IFNγ exposure. Live imaging experiments coupled with apoptosis assays confirmed the involvement of these pathways in IFNγ-mediated cell death. RESULTS: We show that IFNγ signaling activated ERK. Blocking ERK activation rescued IFNγ-mediated apoptosis in 17 of 23 (~ 74%) cell lines representing BRAF, NRAS, NF1 mutant, and triple wild type subtypes of cutaneous melanoma. ERK signaling induced a stress response, ultimately leading to apoptosis through the activity of DR5 and NOXA proteins. CONCLUSIONS: Our results provide a new understanding of the IFNγ growth inhibition pathway, which will be crucial in defining mechanisms of immunotherapy response and resistance.

A short list of high-priority indicators of health system responsiveness for aging: an eDelphi consensus study.

The objective of this article was to provide a consensus-based short list of effective indicators to measure health system responsiveness to the needs of older adults which would be relevant to informing public policy. An e-Delphi study was done with no direct interaction between respondents. Virtual surveys were sent to 141 participants with experience in analysis and monitoring of health indicators, management of health systems, and health care of older adults. A baseline list of 24 previously published indicators was used. The criteria for selection as high priority indicators were: usefulness as a tracer of health system responsiveness and usefulness to inform policy. Consensus was defined as: ≥70% agreement among the participants that the indicator was very high or high priority; plus being benchmarked by ≥50% of respondents as having a higher relative weight than other indicators; plus being in the top 10 in the ranking list. The first round of the process included 38 participants with varied professional backgrounds. Consensus was reached for seven indicators after two rounds. Five indicators were related to distal outcomes (mortality, disability, or healthy life expectancy), one to monitoring functional assessments, and one to poverty levels. Health systems professionals should consider these comprehensive priority indicators in their efforts to provide a better health system for older people.

El objetivo de este artículo es proporcionar una lista breve y consensuada de indicadores eficaces para medir la capacidad de respuesta del sistema de salud al atender las necesidades de las personas mayores que sean pertinentes para fundamentar las políticas públicas. Se realizó un estudio con el uso de eDelphi (el software para el método de Delfos), sin interacción directa entre las personas encuestadas. Se enviaron encuestas virtuales a 141 participantes con experiencia en el análisis y el seguimiento de indicadores de salud, la gestión de sistemas de salud y la atención de salud de las personas mayores. Se utilizó una lista de referencia de 24 indicadores publicada con anterioridad. Los criterios para seleccionar los indicadores de alta prioridad fueron: utilidad como elemento de medición de la capacidad de respuesta de los sistemas de salud y utilidad para fundamentar las políticas. El consenso se definió como lo siguiente: un acuerdo ≥70% entre los participantes de que el indicador era de prioridad muy alta o alta; que ≥50% de los encuestados consideraran que tenía un mayor peso relativo que otros indicadores; y que estuviera entre los diez primeros lugares de la lista. En la primera ronda del proceso intervinieron 38 participantes con distintas competencias profesionales. Después de dos rondas, se llegó a un consenso respecto a siete indicadores. Cinco indicadores estaban relacionados con resultados a largo plazo (mortalidad, discapacidad o esperanza de vida sana), uno con el seguimiento de evaluaciones funcionales y uno con los niveles de pobreza. Los profesionales de los sistemas de salud deberían tener en cuenta estos indicadores prioritarios integrales al adoptar medidas tendientes a proporcionar un mejor sistema de salud para las personas mayores.

Este artigo tem como objetivo fornecer uma breve lista consensual de indicadores efetivos para medir a capacidade de resposta de sistemas de saúde às necessidades das pessoas idosas, relevante para informar políticas públicas. Foi realizado um estudo eDelphi sem interação direta entre os entrevistados. Questionários virtuais foram enviados a 141 participantes com experiência em análise e monitoramento de indicadores de saúde, gestão de sistemas de saúde e atenção à saúde de pessoas idosas, tendo como base uma lista de 24 indicadores publicados anteriormente. Os critérios para seleção como indicadores de alta prioridade foram sua utilidade como marcador da capacidade de resposta do sistema de saúde e utilidade para informar políticas públicas. O consenso foi definido como: ≥70% de concordância entre os participantes de que o indicador tinha prioridade muito alta ou alta; avaliação por ≥50% dos entrevistados de que tinha um peso relativo maior do que outros indicadores; e posicionamento entre os 10 primeiros na lista de classificação. A primeira rodada do processo incluiu 38 participantes com diversos perfis profissionais. Após duas rodadas, chegou-se a um consenso sobre sete indicadores. Cinco estavam relacionados a resultados distais (mortalidade, incapacidade ou expectativa de vida saudável), um ao monitoramento de avaliações funcionais e o último aos níveis de pobreza. Os profissionais de sistemas de saúde devem considerar esses indicadores prioritários abrangentes em seus esforços para oferecer um sistema de saúde melhor para as pessoas idosas.

Ipilimumab with or without nivolumab in PD-1 or PD-L1 blockade refractory metastatic melanoma: a randomized phase 2 trial.

In this randomized phase 2 trial, blockade of cytotoxic T-lymphocyte protein 4 (CTLA-4) with continuation of programmed death protein 1 (PD-1) blockade in patients with metastatic melanoma who had received front-line anti-PD-1 or therapy against programmed cell death 1 ligand 1 and whose tumors progressed was tested in comparison with CTLA-4 blockade alone. Ninety-two eligible patients were randomly assigned in a 3:1 ratio to receive the combination of ipilimumab and nivolumab, or ipilimumab alone. The primary endpoint was progression-free survival. Secondary endpoints included the difference in CD8 T cell infiltrate among responding and nonresponding tumors, objective response rate, overall survival and toxicity. The combination of nivolumab and ipilimumab resulted in a statistically significant improvement in progression-free survival over ipilimumab (hazard ratio = 0.63, 90% confidence interval (CI) = 0.41-0.97, one-sided P = 0.04). Objective response rates were 28% (90% CI = 19-38%) and 9% (90% CI = 2-25%), respectively (one-sided P = 0.05). Grade 3 or higher treatment-related adverse events occurred in 57% and 35% of patients, respectively, which is consistent with the known toxicity profile of these regimens. The change in intratumoral CD8 T cell density observed in the present analysis did not reach statistical significance to support the formal hypothesis tested as a secondary endpoint. In conclusion, primary resistance to PD-1 blockade therapy can be reversed in some patients with the combination of CTLA-4 and PD-1 blockade. Clinicaltrials.gov identifier: NCT03033576 .

A short list of high-priority indicators of health system responsiveness for aging: an eDelphi consensus study

[ABSTRACT]. The objective of this article was to provide a consensus-based short list of effective indicators to measure health system responsiveness to the needs of older adults which would be relevant to informing public policy. An e-Delphi study was done with no direct interaction between respondents. Virtual surveys were sent to 141 participants with experience in analysis and monitoring of health indicators, management of health systems, and health care of older adults. A baseline list of 24 previously published indicators was used. The criteria for selection as high priority indicators were: usefulness as a tracer of health system responsiveness and useful- ness to inform policy. Consensus was defined as: ≥70% agreement among the participants that the indicator was very high or high priority; plus being benchmarked by ≥50% of respondents as having a higher relative weight than other indicators; plus being in the top 10 in the ranking list. The first round of the process included 38 participants with varied professional backgrounds. Consensus was reached for seven indicators after two rounds. Five indicators were related to distal outcomes (mortality, disability, or healthy life expectancy), one to monitoring functional assessments, and one to poverty levels. Health systems professionals should consider these comprehensive priority indicators in their efforts to provide a better health system for older people.

[RESUMEN]. El objetivo de este artículo es proporcionar una lista breve y consensuada de indicadores eficaces para medir la capacidad de respuesta del sistema de salud al atender las necesidades de las personas mayores que sean pertinentes para fundamentar las políticas públicas. Se realizó un estudio con el uso de eDelphi (el software para el método de Delfos), sin interacción directa entre las personas encuestadas. Se enviaron encuestas virtuales a 141 participantes con experiencia en el análisis y el seguimiento de indicadores de salud, la gestión de sistemas de salud y la atención de salud de las personas mayores. Se utilizó una lista de referencia de 24 indicadores publicada con anterioridad. Los criterios para seleccionar los indicadores de alta prioridad fueron: utilidad como elemento de medición de la capacidad de respuesta de los sistemas de salud y utilidad para fundamentar las políticas. El consenso se definió como lo siguiente: un acuerdo ≥70% entre los participantes de que el indicador era de prioridad muy alta o alta; que ≥50% de los encuestados consideraran que tenía un mayor peso relativo que otros indicadores; y que estuviera entre los diez primeros lugares de la lista. En la primera ronda del proceso intervinieron 38 participantes con distintas competencias profesionales. Después de dos rondas, se llegó a un consenso respecto a siete indicadores. Cinco indicadores estaban relacionados con resultados a largo plazo (mortalidad, discapacidad o esperanza de vida sana), uno con el seguimiento de evaluaciones funcionales y uno con los niveles de pobreza. Los profesionales de los sistemas de salud deberían tener en cuenta estos indicadores prioritarios integrales al adoptar medidas tendientes a proporcionar un mejor sistema de salud para las personas mayores.

[RESUMO]. Este artigo tem como objetivo fornecer uma breve lista consensual de indicadores efetivos para medir a capacidade de resposta de sistemas de saúde às necessidades das pessoas idosas, relevante para informar políticas públicas. Foi realizado um estudo eDelphi sem interação direta entre os entrevistados. Questionários virtuais foram enviados a 141 participantes com experiência em análise e monitoramento de indicadores de saúde, gestão de sistemas de saúde e atenção à saúde de pessoas idosas, tendo como base uma lista de 24 indicadores publicados anteriormente. Os critérios para seleção como indicadores de alta prioridade foram sua utilidade como marcador da capacidade de resposta do sistema de saúde e utilidade para infor- mar políticas públicas. O consenso foi definido como: ≥70% de concordância entre os participantes de que o indicador tinha prioridade muito alta ou alta; avaliação por ≥50% dos entrevistados de que tinha um peso relativo maior do que outros indicadores; e posicionamento entre os 10 primeiros na lista de classificação. A primeira rodada do processo incluiu 38 participantes com diversos perfis profissionais. Após duas rodadas, chegou-se a um consenso sobre sete indicadores. Cinco estavam relacionados a resultados distais (mortal- idade, incapacidade ou expectativa de vida saudável), um ao monitoramento de avaliações funcionais e o último aos níveis de pobreza. Os profissionais de sistemas de saúde devem considerar esses indicadores pri- oritários abrangentes em seus esforços para oferecer um sistema de saúde melhor para as pessoas idosas.

Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial.

Importance: Immune dysregulation contributes to poorer outcomes in COVID-19. Objective: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia. Design, Setting, and Participants: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and December 2021. Interventions: Single infusion of abatacept (10 mg/kg; maximum dose, 1000 mg) or infliximab (5 mg/kg) or a 28-day oral course of cenicriviroc (300-mg loading dose followed by 150 mg twice per day). Main Outcomes and Measures: The primary outcome was time to recovery by day 28 evaluated using an 8-point ordinal scale (higher scores indicate better health). Recovery was defined as the first day the participant scored at least 6 on the ordinal scale. Results: Of the 1971 participants randomized across the 3 substudies, the mean (SD) age was 54.8 (14.6) years and 1218 (61.8%) were men. The primary end point of time to recovery from COVID-19 pneumonia was not significantly different for abatacept (recovery rate ratio [RRR], 1.12 [95% CI, 0.98-1.28]; P = .09), cenicriviroc (RRR, 1.01 [95% CI, 0.86-1.18]; P = .94), or infliximab (RRR, 1.12 [95% CI, 0.99-1.28]; P = .08) compared with placebo. All-cause 28-day mortality was 11.0% for abatacept vs 15.1% for placebo (odds ratio [OR], 0.62 [95% CI, 0.41-0.94]), 13.8% for cenicriviroc vs 11.9% for placebo (OR, 1.18 [95% CI 0.72-1.94]), and 10.1% for infliximab vs 14.5% for placebo (OR, 0.59 [95% CI, 0.39-0.90]). Safety outcomes were comparable between active treatment and placebo, including secondary infections, in all 3 substudies. Conclusions and Relevance: Time to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT04593940.

Role of the Hypoxic-Secretome in Seed and Soil Metastatic Preparation.

During tumor growth, the delivery of oxygen to cells is impaired due to aberrant or absent vasculature. This causes an adaptative response that activates the expression of genes that control several essential processes, such as glycolysis, neovascularization, immune suppression, and the cancer stemness phenotype, leading to increased metastasis and resistance to therapy. Hypoxic tumor cells also respond to an altered hypoxic microenvironment by secreting vesicles, factors, cytokines and nucleic acids that modify not only the immediate microenvironment but also organs at distant sites, allowing or facilitating the attachment and growth of tumor cells and contributing to metastasis. Hypoxia induces the release of molecules of different biochemical natures, either secreted or inside extracellular vesicles, and both tumor cells and stromal cells are involved in this process. The mechanisms by which these signals that can modify the premetastatic niche are sent from the primary tumor site include changes in the extracellular matrix, recruitment and activation of different stromal cells and immune or nonimmune cells, metabolic reprogramming, and molecular signaling network rewiring. In this review, we will discuss how hypoxia might alter the premetastatic niche through different signaling molecules.

Survival After Severe COVID-19: Long-Term Outcomes of Patients Admitted to an Intensive Care Unit.

BACKGROUND: Understanding the long-term sequelae of severe COVID-19 remains limited, particularly in the United States. OBJECTIVE: To examine long-term outcomes of patients who required intensive care unit (ICU) admission for severe COVID-19. DESIGN, PATIENTS, AND MAIN MEASURES: This is a prospective cohort study of patients who had severe COVID-19 requiring an ICU admission in a two-hospital academic health system in Southern California. Patients discharged alive between 3/21/2020 and 12/31/2020 were surveyed approximately 6 months after discharge to assess health-related quality of life using Patient-Reported Outcomes Measurement Information System (PROMIS®)-29 v2.1, post-traumatic stress disorder (PTSD) and loneliness scales. A preference-based health utility score (PROPr) was estimated using 7 PROMIS domain scores. Patients were also asked their attitude about receiving aggressive ICU care. KEY RESULTS: Of 275 patients admitted to the ICU for severe COVID-19, 205 (74.5%) were discharged alive and 132 (64%, median age 59, 46% female) completed surveys a median of 182 days post-discharge. Anxiety, depression, fatigue, sleep disturbance, ability to participate in social activities, pain interference, and cognitive function were not significantly different from the U.S. general population, but physical function (44.2, SD 11.0) was worse. PROPr mean score of 0.46 (SD 0.30, range -0.02 to 0.96 [<0 is worse than dead and 1 represents perfect health]) was slightly lower than the U.S. general population, with an even distribution across the continuum. Poor PROPr was associated with chronic medical conditions and receipt of life-sustaining treatments, but not demographics or social vulnerability. PTSD was suspected in 20% and loneliness in 29% of patients. Ninety-eight percent of patients were glad they received life-saving treatment. CONCLUSION: Most patients who survive severe COVID-19 achieve positive outcomes, with health scores similar to the general population at 6 months post-discharge. However, there is marked heterogeneity in outcomes with a substantial minority reporting severely compromised health.

Effects of Socio-Familial Behavior on Sleep Quality Predictive Risk Factors in Individuals under Social Isolation.

Social confinement involves a series of temporary changes in the habits and lifestyles of individuals, severely affecting their regular activities and schedules and substantially modifying socio-familial behavior (SFB) and sleep quality (SQ). There is no literature reporting the effects of SFB changes on SQ during social confinement due to the COVID-19 outbreak. An observational transversal research design, with group comparison and correlation methods, was used to perform the present study. The results were analyzed as follows: (1) An exploratory factor analysis (EFA); (2) A description of the sample was determined by proportions comparisons of sleep habits between the different variables of interest; and (3) A linear regression model was analyzed to explore the predictive association of the negative effects of social isolation during the COVID-19 pandemic on SFB and SQ. In addition to the global SFB score, two SFB factors were identified as predictors affecting the SQ, SF-Habits, and SF-Emotional scores, suggesting a close balance between daily life activities and sleep health during critical social changes. Furthermore, two main risk factors resulted from the regression analysis: economic concerns and increased alcohol consumption. Therefore, the predictive capacity of economic concerns showed statistical significance in anticipating negative sleep quality scores. Overall, this suggests that sleep quality, economic concerns, schedules, and substance use were associated with the self-perception of coping skills, elucidating the importance of fostering habits related to schedules within the home and ensuring that all family members participate.

Mortality and evolution between community and hospital-acquired COVID-AKI.

BACKGROUND: Acute kidney injury (AKI) is associated with poor outcomes in COVID patients. Differences between hospital-acquired (HA-AKI) and community-acquired AKI (CA-AKI) are not well established. METHODS: Prospective, observational cohort study. We included 877 patients hospitalized with COVID diagnosis at two third-level hospitals in Mexico. Primary outcome was all-cause mortality at 28 days compared between COVID patients with CA-AKI and HA-AKI. Secondary outcomes included the need for KRT, and risk factors associated with the development of CA-AKI and HA-AKI. RESULTS: A total of 377 patients (33.7%) developed AKI. CA-AKI occurred in 202 patients (59.9%) and HA-AKI occurred in 135 (40.1%). Patients with CA-AKI had more significant comorbidities, including diabetes (52.4% vs 38.5%), hypertension (58.4% vs 39.2%), CKD (30.1% vs 14.8%), and COPD (5.9% vs 1.4%), than those with HA-AKI. Patients' survival without AKI was 87.1%, with CA-AKI it was 75.4%, and with HA-AKI it was 69.6%, log-rank test p < 0.001. Only age > 60 years (OR 1.12, 95% CI 1.06-1.18, p <0.001), COVID severity (OR 1.09, 95% CI 1.03-1.16, p = 0.002), the need in mechanical lung ventilation (OR 1.67, 95% CI 1.56-1.78, p <0.001), and HA-AKI stage 3 (OR 1.16, 95% CI 1.05-1.29, p = 0.003) had a significant increase in mortality. The presence of CKD (OR 1.48, 95% CI 1.391.56, p < 0.001), serum lymphocytes < 1000 µL (OR 1.03, 95% CI 1.00-1.07, p = 0.03), the need in mechanical lung ventilation (OR 1.06, 95% CI 1.02-1.11, p = 0.003), and CA-AKI stage 3 (OR 1.37, 95% CI 1.29-1.46, p < 0.001) were the only variables associated with a KRT start. CONCLUSIONS: We found that COVID patients who are complicated by CA-AKI have more comorbidities and worse biochemical parameters at the time of hospitalization than HA-AKI patients, but despite these differences, their probability of dying is similar.

Factors Associated With Weight, Length, and BMI Change in Adolescents' Offspring in Their First Year of Life.

Background: Young maternal age is associated with negative outcomes at birth and with offspring's growth. In low- and middle-income countries, adolescents' offspring growth little has been studied. Objective: To determine the association of maternal sociodemographic characteristics with weight, length, and BMI change in adolescents' offspring in their first year of life. Methods: This is a one-year follow-up study that included adolescent mothers and their offspring from 2010 to 2017. The infant anthropometric variables were performed at birth, 3, 6, and 12 months. Maternal health, pregnancy, and social variables were evaluated as well as birth outcomes. Crude, percentage, Z score, and percentile changes of weight, length, and BMI were evaluated from birth to 1-year-old. Statistical analyses were adjusted by maternal chronological age, socioeconomic status, breastfeeding duration, the timing of introduction of complementary feeding, among other variables. Results: We examined 186 dyads (mother-infant). The median maternal age was 15.5 years, and the mean pre-pregnancy BMI was 20. The mean gestational age was 39.1 weeks for infants, birth weight was 3,039 g, and length at birth was 49.5-cm. Maternal chronological age, the timing of introduction of complementary feeding, socioeconomic status, and maternal occupation were associated with offspring's weight gain at 12 months. Length gain was associated with exclusive breastfeeding. Socioeconomic status and occupation were associated with offspring's BMI change. When performing adjusted multivariable analyses, weight and length at birth were associated weight and BMI at 12 months. Conclusions: Weight at birth may negatively predict infant's weight and BMI changes at 12 months, while length at birth may positively predict the changes. Maternal chronological age, socioeconomic level, occupation, and the timing of the introduction of complementary feeding were associated with the weight change. Only exclusive breastfeeding was associated with length Z-score change in adolescents' offspring in their first 12-months of life.

Pragmatic mAb lead molecule engineering from a developability perspective.

As the number of antibody drugs being approved and marketed increases, our knowledge of what makes potential drug candidates a successful product has increased tremendously. One of the critical parameters that have become clear in the field is the importance of mAb "developability." Efforts are being increasingly focused on simultaneously selecting molecules that exhibit both desirable biological potencies and manufacturability attributes. In the current study mutations to improve the developability profile of a problematic antibody that inconsistently precipitates in a batch scale-dependent fashion using a standard platform purification process are described. Initial bioinformatic analysis showed the molecule has no obvious sequence or structural liabilities that might lead it to precipitate. Subsequent analysis of the molecule revealed the presence of two unusual positively charged mutations on the light chain at the interface of VH and VL domains, which were hypothesized to be the primary contributor to molecule precipitation during process development. To investigate this hypothesis, straightforward reversion to the germline of these residues was carried out. The resulting mutants have improved expression titers and recovered stability within a forced precipitation assay, without any change to biological activity. Given the time pressures of drug development in industry, process optimization of the lead molecule was carried out in parallel to the "retrospective" mutagenesis approach. Bespoke process optimization for large-scale manufacturing was successful. However, we propose that such context-dependent sequence liabilities should be included in the arsenal of in silico developability screening early in development; particularly since this specific issue can be efficiently mitigated without the requirement for extensive screening of lead molecule variants.

COVID-19 voluntary social isolation and its effects in sociofamily and children's behavior / Aislamiento social voluntario por COVID-19 y sus efectos en la conducta sociofamiliar e infantil

Abstract Introduction The main prevention strategy for reducing the dispersion of the SARS-CoV-2 has been social distancing. Several investigations began to explore its psychological impact since it began, but there are no data about its effect on social and family behavior. Objectives Were: First, to analyze the reliability of an ad-hoc designed questionnaire to measure sociofamily behavior changes in a sample of parents of children from one to twelve years old. Second, to characterize effects of voluntary social isolation by COVID-19 over sociofamily behavior at a personal level and over children's activities at home. Third, to determine vulnerability predictors for a negative experience by isolation itself. Method An online Questionnaire for Perceptions of Changes in Sociofamily Behavior was applied to 365 Mexican participants. Results Factor analysis showed a reliability of the ad-hoc designed questionnaire for this study. Correlations were found between voluntary social isolation and self-perceived experiences, such as sleep quality, irritability, emotional control, hope about the future, motivation, attention span, and problem solving. Discussion and conclusion The results of this study suggest that family well-being during voluntary social isolation is a complex and multifactorial phenomenon, which addresses specific effects in different domains, especially in sociofamily behavior.

Resumen Introducción La principal estrategia de prevención para frenar la dispersión del SARS-CoV-2 ha sido el distanciamiento social. Varias investigaciones han comenzado a explorar su impacto psicológico, pero no existen datos hasta el momento acerca del efecto en la conducta social y familiar. Objetivos Primero, analizar la confiabilidad de un cuestionario ad-hoc elaborado para medir los cambios sociofamiliares en una muestra de adultos padres de niños de uno a 12 años. Segundo, caracterizar los efectos del aislamiento social voluntario COVID-19 en la conducta sociofamiliar a nivel personal y sobre las actividades infantiles en casa. Tercero, determinar los predictores de vulnerabilidad para presentar una experiencia negativa del aislamiento. Método Se aplicó el Cuestionario de Percepción de Cambios en la Conducta Sociofamiliar en línea a 365 participantes mexicanos. Resultados El análisis factorial mostró que el cuestionario ad-hoc elaborado para este estudio es confiable. Además, los datos mostraron un efecto principal de variables como el nivel socioeconómico, la fuente de ingresos y el estado civil. También, se encontraron correlaciones entre la experiencia personal de aislamiento, como la calidad del sueño, la irritabilidad, el control emocional, las esperanzas sobre el futuro, la motivación, la capacidad de atención y la resolución de problemas. Discusión y conclusión Los resultados de este estudio sugieren que el bienestar familiar durante el aislamiento es un fenómeno complejo y multifactorial, que además revela efectos específicos en la conducta sociofamiliar.

Reflections on the Importance of Community-Partnered Research Strategies for Health Equity in the Era of COVID-19.

OBJECTIVE: In the face of coronavirus disease 2019 (COVID-19) physical distancing mandates, community-engaged research (CER) faces new vulnerabilities in the equitable inclusion of communities within research partnerships aiming to address these very inequities. METHODS: We convened a series of virtual meetings with our CER partnership to discuss the current state of activities and to identify considerations for remote community engagement. We outlined and expanded recommendations through iterative, partnered discussions to inform protections against new CER susceptibilities. RESULTS: This article presents CER recommendations in translational COVID-19 research for health equity, including increasing accessibility for remote engagement, promoting opportunities for bi-directional knowledge exchange, committing to a community-centered workforce, and leveraging novel opportunities within community-academic partnerships. CONCLUSION: Researchers conducting CER face an opportunity to reimagine community engagement remotely for partnered resilience to ensure the voices of the most affected are appropriately and inclusively integrated into all aspects of decision-making within the COVID-19 research, practice, and policymaking continuum.