Metabolic reprogramming during Candida albicans planktonic-biofilm transition is modulated by the transcription factors Zcf15 and Zcf26.

Candida albicans is a commensal of the human microbiota that can form biofilms on implanted medical devices. These biofilms are tolerant to antifungals and to the host immune system. To identify novel genes modulating C. albicans biofilm formation, we performed a large-scale screen with 2,454 C. albicans doxycycline-dependent overexpression strains and identified 16 genes whose overexpression significantly hampered biofilm formation. Among those, overexpression of the ZCF15 and ZCF26 paralogs that encode transcription factors and have orthologs only in biofilm-forming species of the Candida clade, caused impaired biofilm formation both in vitro and in vivo. Interestingly, overexpression of ZCF15 impeded biofilm formation without any defect in hyphal growth. Transcript profiling, transcription factor binding, and phenotypic microarray analyses conducted upon overexpression of ZCF15 and ZCF26 demonstrated their role in reprogramming cellular metabolism by regulating central metabolism including glyoxylate and tricarboxylic acid cycle genes. Taken together, this study has identified a new set of biofilm regulators, including ZCF15 and ZCF26, that appear to control biofilm development through their specific role in metabolic remodeling.

Life expectancy among Native Americans during the COVID-19 pandemic: estimates, uncertainty, and obstacles.

Few reliable estimates have been available for assessing the impact of the COVID-19 pandemic on mortality among Native Americans. Using deidentified publicly available data on deaths and populations by age, we estimated life expectancy for the years 2019-2022 for single-race non-Hispanic Native Americans. Life expectancy in 2022 was 67.8 years, 2.3 years higher than in 2021 but a huge 4-year loss from 2019. Although our life expectancy estimates for 2022 varied under different assumptions about racial/ethnic classification and age misreporting errors, all estimates were lower than the average for middle-income countries. Estimates of losses and gains in life expectancy were consistent across assumptions. Large reductions in COVID-19 death rates between 2021 and 2022 were largely offset by increases in rates of death from unintentional injuries (particularly drug overdoses), chronic liver disease, diabetes, and heart disease, underscoring the difficulties facing Native Americans in achieving reductions in mortality, let alone returning to levels of mortality prior to the pandemic. Serious data problems have persisted for many years, but the scarcity and inadequacy of estimates during the pandemic have underscored the urgent need for timely and accurate demographic data on the Native American population.

Integrating support persons into maternity care and associations with quality of care: a postpartum survey of mothers and support persons in Kenya.

BACKGROUND: Despite research that has shown that the presence of support persons during maternity care is associated with more respectful care, support persons are frequently excluded due to facility practices or negative attitudes of providers. Little quantitative research has examined how integrating support persons in maternity care has implications for the quality of care received by women, a potential pathway for improving maternal and neonatal health outcomes. This study aimed to investigate how integrating support persons in maternity care is associated with multiple dimensions of the quality of maternity care. METHODS: We used facility-based cross-sectional survey data from women (n = 1,138) who gave birth at six high-volume facilities in Nairobi and Kiambu counties in Kenya and their support persons (n = 606) present during the immediate postpartum period. Integration was measured by the Person-Centered Integration of Support Persons (PC-ISP) items. We investigated quality of care outcomes including person-centered care outcomes (i.e., Person-Centered Maternity Care (PCMC) and Satisfaction with care) and clinical outcomes (i.e., Implementation of WHO-recommended clinical practices). We used fractional regression with robust standard errors to estimate associations between PC-ISP and care outcomes. RESULTS: Compared to low integration, high integration (≥four woman-reported PC-ISP experiences vs. <4) was associated with multiple dimensions of quality care: 3.71%-point (95% CI: 2.95%, 4.46%) higher PCMC scores, 2.76%-point higher (95% CI: 1.86%, 3.65%) satisfaction with care scores, and 4.43%-point (95% CI: 3.52%, 5.34%) higher key clinical practices, controlling for covariates. PC-ISP indicators related to communication with providers showed stronger associations with quality of care compared to other PC-ISP sub-constructs. Some support person-reported PC-ISP experiences were positively associated with women's satisfaction and key practices. CONCLUSIONS: Integrating support persons, as key advocates for women, is important for respectful maternity care. Practices to better integrate support persons, especially improving communication between support persons with providers, can potentially improve the person-centered and clinical quality of maternity care in Kenya and other low-resource settings.

Social Isolation, Brain Food Cue Processing, Eating Behaviors, and Mental Health Symptoms.

Importance: Perceived social isolation is associated with negative health outcomes, including increased risk for altered eating behaviors, obesity, and psychological symptoms. However, the underlying neural mechanisms of these pathways are unknown. Objective: To investigate the association of perceived social isolation with brain reactivity to food cues, altered eating behaviors, obesity, and mental health symptoms. Design, Setting, and Participants: This cross-sectional, single-center study recruited healthy, premenopausal female participants from the Los Angeles, California, community from September 7, 2021, through February 27, 2023. Exposure: Participants underwent functional magnetic resonance imaging while performing a food cue viewing task. Main Outcomes and Measures: The main outcomes included brain reactivity to food cues, body composition, self-reported eating behaviors (food cravings, reward-based eating, food addiction, and maladaptive eating behaviors), and mental health symptoms (anxiety, depression, positive and negative affect, and psychological resilience). Results: The study included 93 participants (mean [SD] age, 25.38 [7.07] years). Participants with higher perceived social isolation reported higher fat mass percentage, lower diet quality, increased maladaptive eating behaviors (cravings, reward-based eating, uncontrolled eating, and food addiction), and poor mental health (anxiety, depression, and psychological resilience). In whole-brain comparisons, the higher social isolation group showed altered brain reactivity to food cues in regions of the default mode, executive control, and visual attention networks. Isolation-related neural changes in response to sweet foods correlated with various altered eating behaviors and psychological symptoms. These altered brain responses mediated the connection between social isolation and maladaptive eating behaviors (ß for indirect effect, 0.111; 95% CI, 0.013-0.210; P = .03), increased body fat composition (ß, -0.141; 95% CI, -0.260 to -0.021; P = .02), and diminished positive affect (ß, -0.089; 95% CI, -0.188 to 0.011; P = .09). Conclusions and Relevance: These findings suggest that social isolation is associated with altered neural reactivity to food cues within specific brain regions responsible for processing internal appetite-related states and compromised executive control and attentional bias and motivation toward external food cues. These neural responses toward specific foods were associated with an increased risk for higher body fat composition, worsened maladaptive eating behaviors, and compromised mental health. These findings underscore the need for holistic mind-body-directed interventions that may mitigate the adverse health consequences of social isolation.

Prospective study of the link between overweight/obesity and diabetes incidence among Mexican older adults: 2001-2012 / Estudio prospectivo de la asociación entre sobrepeso/obesidad e incidencia de diabetes en adultos mayores en México: 2001 -2012

Objective. To prospectively assess the relationship between overweight/obesity and incidence of type 2 diabetes mellitus (T2DM) among Mexicans aged 50+, assessing effects of age, genetic predisposition, education, physical activity, and place of residence. Materials and methods. The Mexican Health and Aging Study (MHAS) was used to prospectively follow respondents free of diabetes in 2001 who became diabetic by 2012. Multivariate random effects logistic regression was used to assess covariates effects on the incidence of T2DM. Results. Obese or overweight individuals at baseline (2001) were about 3 and 2 times, respectively, significantly more likely to become diabetic by 2012. Genetic predisposition increases the risk of diabetes by about three times compared to those with no family history of diabetes. Conclusion. Overweight/obesity and genetic predisposition are the primary drivers of diabetes incidence among Mexican older adults. Reducing body weight and having access to health care may amel iorate the disease burden of T2DM.

Objetivo. Cuantificar prospectivamente la relación entre sobrepeso/obesidad e incidencia de diabetes entre mexicanos mayores de 50 años mediante la medición de los efectos de la edad, predisposición genética, educación, actividad física y lugar de residencia. Material y métodos. Se utilizó el Estudio Nacional de Salud y Envejecimiento en México (Enasem) para seguir a adultos mayores sin diabetes en 2001 y que se convirtieron en diabéticos en 2012. Se utilizó el modelo de regresión logística de efectos aleatorios para cuantificar el efecto de covariables en la incidencia de diabetes. Resultados. Quienes tenían obesidad y sobrepeso en 2001 fueron 3 y 2 veces más propensos a adquirir diabetes en 2012, respectivamente. La predisposición genética aumentó tres veces el riesgo de padecer diabetes en comparación con aquéllos sin historia familiar de diabetes. Conclusiones. Sobrepeso, obesidad y predisposición genética son causantes de diabetes en adultos mayores mexicanos. Reducción de peso y acceso a atención de salud podrían reducir las consecuencias que tiene la diabetes.

Contribution of socioeconomic factors and health care access to the awareness and treatment of diabetes and hypertension among older Mexican adults / Contribución de los factores socioeconómicos y de acceso a servicios médicos en el autorreporte y el tratamiento de diabetes e hipertensión en adultos mayores en México

Objective. To estimate changes in self-report and treatment of diabetes and hypertension between 2001 and 2012 among Mexican aged 50-80, assessing the contribution of education and health insurance coverage. Materials and methods. The Mexican Health and Aging Study was used to estimate associations of education and insurance on prevalence and treatment of diabetes and hypertension in 2001 and 2012. Multivariate decomposition was used to assess the contribution of changes in the composition of covariates vs. their "effects" on changes in prevalence and treatment over time. Results. Increases in the prevalence/diagnosis and treatment during the period are largely attributable to the expansion of health insurance. Its effects on diagnosis/prevalence and treatment have also increased over time. Conclusions. The expansion of Seguro Popular likely improved screening and treatment. More research is needed to assess if these have translated into better control and a lower burden of disease.

Objetivo. Estimar cambios en el autorreporte y en el tratamiento de diabetes e hipertensión en adultos de entre 50 y 80 años en México, en 2001 y 2012, y explicarlos en función de los sufridos en cuanto a composición educativa y de cobertura/derechohabiencia en servicios de salud. Material y métodos. Se utilizó la Encuesta Nacional de Salud y Envejecimiento en México y técnicas de descomposición multivariada. Resultados. El incremento en la prevalencia/ diagnóstico y tratamiento durante el periodo se debe en gran medida al aumento en la cobertura de servicios de salud. Los "efectos" de la cobertura también se incrementaron de forma importante. Conclusiones. La expansión del Seguro Popular probablemente tuvo un papel importante en la detección y tratamiento de la diabetes e hipertensión. Investigaciones futuras discernirán si dicha expansión se ha traducido en un mejor control y una menor carga de morbilidad.

Adult obesity, disease and longevity in Mexico / Obesidad, enfermedad y longevidad en adultos mexicanos

Objective. To obtain estimates of the effects of overweight and obesity on the incidence of type 2 diabetes (T2D) and adult mortality. Materials and methods. We use three waves (2000, 2002, 2012) of the Mexican Health and Aging Survey (MHAS).We employ parametric hazard models to estimate mortality and conventional logistic models to estimate incidence of T2D. Results. Obesity and overweight have a strong effect on the incidence of T2D;this, combined with the large impact of diabetes on adult mortality, generates increases in mortality that translate into losses of 2 to 3 years of life expectancy at age 50. Conclusions. If increasing trends in obesity in Mexico continue as in the past, progress in adult survival may be slowed down considerably and the incidence of T2D will continue to increase.

Objetivo. Estimar los efectos de sobrepeso y obesidad en edad adulta en la incidencia de diabetes tipo 2 y en la mortalidad. Material y métodos. Se emplearon tres paneles (2000, 2002, 2012) de la Encuesta Nacional de Salud y Envejecimiento en México (Enasem), junto a modelos de sobrevivencia y logísticos convencionales para estimar la mortalidad y la incidencia de diabetes, respectivamente. Resultados. El sobrepeso y la obesidad tienen un impacto poderoso en la incidencia de diabetes tipo 2, lo que en combinación con el incremento del riesgo de mortalidad asociado con la diabetes de tipo 2, se traduce en pérdidas de 2 a 3 años de vida a la edad de 50 años. Conclusiones. Si la tasa de crecimiento de la prevalencia de sobrepeso y obesidad en edad adulta mantiene el ritmo que ha tenido recientemente, las mejoras en sobrevivencia adulta se verán comprometidas y la incidencia de diabetes tipo 2 continuará en aumento.

Estudio mediante tomografía axial computarizada de haz cónico de la morfología de los conductos radiculares de primeros molares permanentes en una muestra de la población nicaragüense / Study, using cone beam computed tomography, of the root canal system morphology of permanent first molars in Nicaraguan population

El conocimiento de la morfología del sistema de conductos radiculares y sus posibles variaciones, es fundamental para poder realizar un tratamiento endodóntico con mayor predictibilidad y una mayor tasa de éxito. El presente estudio, se elaboró con la finalidad de conocer la morfología del sistema de conductos en primeros molares permanentes superiores e inferiores, en Nicaragua, tomando como muestra 60 molares extraídos. Objetivo: Determinar mediante el uso de CBCT, la morfología radicular de primeros molares permanentes. Material y métodos: Se realizaron dos grupos, 30 primeros mola-res superiores y 30 primeros molares inferiores, montados sobre una placa de acrílico. Se realizó un CBCT previo de la anatomía radicular, haciendo cortes por cada milímetro de la raíz, obteniendo un total de 15 cortes por diente, los cuales fueron analizados detenidamente, observando la morfología interna del sistema de conductos, siguiendo la clasificación de Vertucci. 1Resultados: Según la clasificación de Vertucci, la morfología radicular más frecuente en molares superiores fue la tipo I (40%), en molares inferiores fue la tipo IV en raíces mesiales (36.7%) y tipo I en raíces distales (66.7%). Los primeros molares superiores pre-sentaron 3 raíces en el 100% de las muestras, y 4 conductos en el 43.3% de las muestras, mientras los primeros molares inferiores presentaron 2 raíces en el 93.3% de las muestras y 3 conductos en el 43.3% de las muestras

The knowledge of the root canal system morphology and its possible variations is fundamental to be able to perform an endodontic treatment with greater predictability as well as a higher success rate. The present study was elaborated with the purpose to know the morphology of the canal system in upper and lower permanent first molars, in Nicaragua, taking as sample 60 extracted molars. Objective: To determine, through the use of CBCT, the root morphology of permanent, superior and inferior first molars. Material and methods: Two groups, 30 first upper molars and 30 lower first molars, were mounted on an acrylic plate. The CBCT was performed on the roots, making cuts for each millimeter, in total obtaining 15 cuts, which were analyzed carefully and observing the internal morphology of the root canal system was observed, following the Vertucci classification. 1Results: According to the Vertucci classification, the most frequent root morphology in upper molars was type I (40%), in lower molars it was type IV in mesial roots (36.7%) and type I in distal roots (66.7%). The first upper molars had 3 roots in 100% of the samples, and 4 canals in 43.3% of the samples, while the lower first molars had 2 roots in 93.3% of the samples and 3 canals in 43.3% of the samples

Effects of a DNA vaccine in an animal model of Alternaria alternata sensitivity

La sensibilidad al hongo Alternaria se asocia con la persistencia y gravedad del asma. Las opciones terapéuticasactuales para el tratamiento de la inflamación de las vías aéreas inducida por Alternaria son limitadas.En este estudio se han utilizado ratas Brown Norway para estudiar la eficacia de una vacuna de ADN administradapor vía aérea para atenuar la respuesta al alérgeno mayor de Alternaria rAlt a 2. Comparados conlos animales sensibilizados sin tratar, o con los animales que recibieron una vacuna de ADN con un marcode lectura incorrecto, los animales tratados con una vacuna ADN con un marco de lectura correcto mostraronuna atenuación en los títulos de anticuerpos específicos IgE frente a rAlt a 2, un aumento en IgG2b (unarespuesta Th1), una reducción en la liberación espontánea de IL-13 por suspensiones celulares de nóduloslinfáticos peribronquiales y una atenuación en la diminución en la capacidad pulmonar total 72 h despuésde la administración del alérgeno. El examen histopatológico de los tejidos pulmonares reveló una inflamaciónpulmonar reducida tras la administración del alérgeno en los animales tratados con ADN comparadoscon los animales sensibilizados sin tratamiento. Se concluye que una vacuna de ADN administrada por víaaérea ejerce una influencia significativa sobre las alteraciones inmunológicas, fisiológicas pulmonares ehistológicas inducidas por el alérgeno mayor de Alternaria rAlt a 2 en animales sensibilizados(AU)

Sensitivity to the fungus Alternaria is associated with asthma persistence and severity. Current therapeuticoptions for treating Alternaria-induced airway inflammation are limited. In this study, Brown Norway ratsare used to study the effectiveness of a DNA-based vaccine delivered to the airway in attenuating theresponse to a major Alternaria allergen, rAlt a 2. Compared to untreated sensitized animals, or animalsreceiving an “out-of-frame” DNA-based vaccine, animals treated with “in-frame” DNA vaccine showed anattenuation in specific IgE antibody titers to rAlt a 2, an increase in IgG2b (a Th1 response), a reduction inspontaneous IL-13 release by peribronchial lymph node cell suspensions, and an attenuation in thedecrease in total lung capacity 72 h post-allergen challenge. Further, histopathologic examination of thelung tissues revealed reduced pulmonary inflammation post-allergen challenge in the DNA-vaccine-treatedcompared to sensitized, untreated animals. We conclude that a DNA-based vaccine delivered to the airwaysignificantly influences the immunologic, pulmonary physiologic, and histological alterations induced bychallenge with a major Alternaria allergen, rAlt a 2, in sensitized animals(AU)