Software and equations using segmental measures to estimate height in children and adolescents with cerebral palsy considering the level of gross motor function.

BACKGROUND & AIMS: In children with Cerebral palsy (CP) bone deformities create a difficulty in the collection of height measures by direct methods. Body segments are an alternative to study for anthropometric evaluation in children with CP. Motor compromise affects growth in these children. To our knowledge, no equations have been developed to estimate height that consider the level of involvement of children with CP. The aim was to develop equations to estimate height using segmental measures for children with cerebral palsy (CP). METHODS: This was a cross-sectional study. The sample consisted of children and adolescents with CP of both sexes from 2 to 19 years old from five cities in Argentina. Children whose height and knee-heel height (KH) could be measured were included. Height, KH, and clinical covariables were collected. Linear regression models with height as the dependent variable and KH as predictors adjusted for significant covariates were developed and compared for R2, adjusted R2, and the root mean square of the error. RESULTS: 242 children and adolescents (mean age 9 ± 4 years) with a confirmed diagnosis of CP were included. The interaction between height and other variables such KH, sex, GMFCS, and age was analyzed. Two equations were developed to estimate height according to GMFCS level (GMFCS Level I-III: H = 1.5 × KH(cm) + 2.28 × age(years) + 51; GMFCS Level IV-V: H = 2.13 × KH (cm)+ 0.91 × age(years) + 37). The concordance correlation coefficient between estimated and observed height was 0.95 (95%CI [0.94; 0.96]). CONCLUSION: Height in children and adolescents with CP can be predicted using KH, GMFCS, and age. The equations and software can estimate height when this cannot be obtained directly.

Developmental metformin exposure does not rescue physiological impairments derived from early exposure to altered maternal metabolic state in offspring mice.

OBJECTIVE: The incidence of gestational diabetes mellitus (GDM) and metabolic disorders during pregnancy are increasing globally. This has resulted in increased use of therapeutic interventions such as metformin to aid in glycemic control during pregnancy. Even though metformin can cross the placental barrier, its impact on offspring brain development remains poorly understood. As metformin promotes AMPK signaling, which plays a key role in axonal growth during development, we hypothesized that it may have an impact on hypothalamic signaling and the formation of neuronal projections in the hypothalamus, the key regulator of energy homeostasis. We further hypothesized that this is dependent on the metabolic and nutritional status of the mother at the time of metformin intervention. Using mouse models of maternal overnutrition, we aimed to assess the effects of metformin exposure on offspring physiology and hypothalamic neuronal circuits during key periods of development. METHODS: Female C57BL/6N mice received either a control diet or a high-fat diet (HFD) during pregnancy and lactation periods. A subset of dams was fed a HFD exclusively during the lactation. Anti-diabetic treatments were given during the first postnatal weeks. Body weights of male and female offspring were monitored daily until weaning. Circulating metabolic factors and molecular changes in the hypothalamus were assessed at postnatal day 16 using ELISA and Western Blot, respectively. Hypothalamic innervation was assessed by immunostaining at postnatal days 16 and 21. RESULTS: We identified alterations in weight gain and circulating hormones in male and female offspring induced by anti-diabetic treatment during the early postnatal period, which were critically dependent on the maternal metabolic state. Furthermore, hypothalamic agouti-related peptide (AgRP) and proopiomelanocortin (POMC) neuronal innervation outcomes in response to anti-diabetic treatment were also modulated by maternal metabolic state. We also identified sex-specific changes in hypothalamic AMPK signaling in response to metformin exposure. CONCLUSION: We demonstrate a unique interaction between anti-diabetic treatment and maternal metabolic state, resulting in sex-specific effects on offspring brain development and physiological outcomes. Overall, based on our findings, no positive effect of metformin intervention was observed in the offspring, despite ameliorating effects on maternal metabolic outcomes. In fact, the metabolic state of the mother drives the most dramatic differences in offspring physiology and metformin had no rescuing effect. Our results therefore highlight the need for a deeper understanding of how maternal metabolic state (excessive weight gain versus stable weight during GDM treatment) affects the developing offspring. Further, these results emphasize that the interventions to treat alterations in maternal metabolism during pregnancy need to be reassessed from the perspective of the offspring physiology.

Temporal dynamics of muscle mitochondrial uncoupling-induced integrated stress response and ferroptosis defense.

Mitochondria play multifaceted roles in cellular function, and impairments across domains of mitochondrial biology are known to promote cellular integrated stress response (ISR) pathways as well as systemic metabolic adaptations. However, the temporal dynamics of specific mitochondrial ISR related to physiological variations in tissue-specific energy demands remains unknown. Here, we conducted a comprehensive 24-hour muscle and plasma profiling of male and female mice with ectopic mitochondrial respiratory uncoupling in skeletal muscle (mUcp1-transgenic, TG). TG mice are characterized by increased muscle ISR, elevated oxidative stress defense, and increased secretion of FGF21 and GDF15 as ISR-induced myokines. We observed a temporal signature of both cell-autonomous and systemic ISR in the context of endocrine myokine signaling and cellular redox balance, but not of ferroptotic signature which was also increased in TG muscle. We show a progressive increase of muscle ISR on transcriptional level during the active phase (night time), with a subsequent peak in circulating FGF21 and GDF15 in the early resting phase. Moreover, we found highest levels of muscle oxidative defense (GPX and NQO1 activity) between the late active to early resting phase, which could aim to counteract excessive iron-dependent lipid peroxidation and ferroptosis in muscle of TG mice. These findings highlight the temporal dynamics of cell-autonomous and endocrine ISR signaling under skeletal muscle mitochondrial uncoupling, emphasizing the importance of considering such dissociation in translational strategies and sample collection for diagnostic biomarker analysis.

Maternal dietary components in the development of gestational diabetes mellitus: a systematic review of observational studies to timely promotion of health.

BACKGROUND: There is ample evidence that considers diet as an important factor in the prevention of gestational diabetes mellitus (GDM). The aim of this review is to synthesise the existing evidence on the relationship between GDM and maternal dietary components. METHODS: We performed a systematic bibliographic search in Medline, Latin American and Caribbean Health Sciences Literature (Lilacs) and the Latin American Nutrition Archive (ALAN) of regional and local literature, limiting the searches to observational studies published between 2016 and 2022. Search terms related to nutrients, foods, dietary patterns and the relationship to GDM risk were used. The review included 44 articles, 12 of which were from America. The articles considered different topics about maternal dietary components as follows: 14 are about nutrient intake, 8 about food intake, 4 combined nutrient and food analysis and 18 about dietary patterns. RESULTS: Iron, processed meat and a low carbohydrate diet were positively associated with GDM. Antioxidant nutrients, folic acid, fruits, vegetables, legumes and eggs were negatively associated with GDM. Generally, western dietary patterns increase GDM risk, and prudent dietary patterns or plant-based diets decrease the risk. CONCLUSIONS: Diet is considered one of the causes of GDM. However, there is no homogeneity in how people eat nor in how researchers assess diet in different contextual conditions of the world.

Mitochondrial stress-induced GFRAL signaling controls diurnal food intake and anxiety-like behavior.

Growth differentiation factor 15 (GDF15) is a mitochondrial stress-induced cytokine that modulates energy balance in an endocrine manner. However, the importance of its brainstem-restricted receptor GDNF family receptor alpha-like (GFRAL) to mediate endocrine GDF15 signaling to the brain upon mitochondrial dysfunction is still unknown. Using a mouse model with muscle-specific mitochondrial dysfunction, we here show that GFRAL is required for activation of systemic energy metabolism via daytime-restricted anorexia but not responsible for muscle wasting. We further find that muscle mitochondrial stress response involves a GFRAL-dependent induction of hypothalamic corticotropin-releasing hormone, without elevated corticosterone levels. Finally, we identify that GFRAL signaling governs an anxiety-like behavior in male mice with muscle mitochondrial dysfunction, with females showing a less robust GFRAL-dependent anxiety-like phenotype. Together, we here provide novel evidence of a mitochondrial stress-induced muscle-brain crosstalk via the GDF15-GFRAL axis to modulate food intake and anxiogenic behavior.

Regulation of diurnal energy balance by mitokines.

The mammalian system of energy balance regulation is intrinsically rhythmic with diurnal oscillations of behavioral and metabolic traits according to the 24 h day/night cycle, driven by cellular circadian clocks and synchronized by environmental or internal cues such as metabolites and hormones associated with feeding rhythms. Mitochondria are crucial organelles for cellular energy generation and their biology is largely under the control of the circadian system. Whether mitochondrial status might also feed-back on the circadian system, possibly via mitokines that are induced by mitochondrial stress as endocrine-acting molecules, remains poorly understood. Here, we describe our current understanding of the diurnal regulation of systemic energy balance, with focus on fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15), two well-known endocrine-acting metabolic mediators. FGF21 shows a diurnal oscillation and directly affects the output of the brain master clock. Moreover, recent data demonstrated that mitochondrial stress-induced GDF15 promotes a day-time restricted anorexia and systemic metabolic remodeling as shown in UCP1-transgenic mice, where both FGF21 and GDF15 are induced as myomitokines. In this mouse model of slightly uncoupled skeletal muscle mitochondria GDF15 proved responsible for an increased metabolic flexibility and a number of beneficial metabolic adaptations. However, the molecular mechanisms underlying energy balance regulation by mitokines are just starting to emerge, and more data on diurnal patterns in mouse and man are required. This will open new perspectives into the diurnal nature of mitokines and action both in health and disease.

Alimentación y riesgo de depresión en mujeres embarazadas de la ciudad de Córdoba / Diet and risk of depression in pregnant women in the city of Córdoba

La deficiencia de micro y macronutrientes puede tener efectos en el embarazo, entre ellos la depresión materna. El objetivo fue analizar el consumo de Ácidos Grasos Poliinsaturados (AGPI) omega-3(ω-3) y omega-6(ω-6) y Vitamina D (VD) y el riesgo de depresión en mujeres embarazadas atendidas en centros de salud públicos y privados de la ciudad de Córdoba entre noviembre 2021-agosto 2022. Se realizó un estudio observacional, correlacional, transversal. Se aplicó un cuestionario sobre datos sociodemográficos y de salud perinatal. Se realizó una encuesta de consumo alimentario habitual y respondieron un cuestionario "Escala de Depresión Perinatal de Edimburgo" (EDPE) para evaluar el riesgo de depresión durante el embarazo (DDE). Los datos alimentarios fueron procesados en el software Nutrio V2. Se realizó un análisis para describir la distribución del riesgo de DDE y caracterizar la ingesta de alimentos-nutrientes. Se desarrollaron modelos de regresión logística de respuesta binomial (presenta riesgo/no presenta) para valorar su asociación con la ingesta de AGPI y VD ajustando por posibles confundentes (variables sociodemográficas y de salud). Los análisis estadísticos se realizaron en Stata V15. El 25% presentó riesgo de DDE. El 83% y 86% no cumple con las recomendaciones establecidas para AGPI ω-3 y VD respectivamente. El 96% cubrió la recomendación de ω-6. Se encontraron diferencias significativas en la ingesta AGPI ω-6 entre las mujeres con y sin riesgo de DDE (57.6 vs 26.7; p=0.006). Se observa un consumo bajo de AGPI ω-3, que sumado al consumo elevado de AGPI ω-6 profundiza el disbalance entre estos nutrientes. Se encontraron diferencias en el consumo de AGPI entre mujeres con y sin riesgo de DDE, no obstante, los resultados no evidencian una asociación significativa. Resulta necesario profundizar el estudio de la alimentación como fenómeno potencialmente modificable que podría contribuir a mejorar la salud materno-infantil.

Muscle-derived GDF15 drives diurnal anorexia and systemic metabolic remodeling during mitochondrial stress.

Mitochondrial dysfunction promotes metabolic stress responses in a cell-autonomous as well as organismal manner. The wasting hormone growth differentiation factor 15 (GDF15) is recognized as a biomarker of mitochondrial disorders, but its pathophysiological function remains elusive. To test the hypothesis that GDF15 is fundamental to the metabolic stress response during mitochondrial dysfunction, we investigated transgenic mice (Ucp1-TG) with compromised muscle-specific mitochondrial OXPHOS capacity via respiratory uncoupling. Ucp1-TG mice show a skeletal muscle-specific induction and diurnal variation of GDF15 as a myokine. Remarkably, genetic loss of GDF15 in Ucp1-TG mice does not affect muscle wasting or transcriptional cell-autonomous stress response but promotes a progressive increase in body fat mass. Furthermore, muscle mitochondrial stress-induced systemic metabolic flexibility, insulin sensitivity, and white adipose tissue browning are fully abolished in the absence of GDF15. Mechanistically, we uncovered a GDF15-dependent daytime-restricted anorexia, whereas GDF15 is unable to suppress food intake at night. Altogether, our evidence suggests a novel diurnal action and key pathophysiological role of mitochondrial stress-induced GDF15 in the regulation of systemic energy metabolism.

Role of GDF15 in active lifestyle induced metabolic adaptations and acute exercise response in mice.

Physical activity is an important contributor to muscle adaptation and metabolic health. Growth differentiation factor 15 (GDF15) is established as cellular and nutritional stress-induced cytokine but its physiological role in response to active lifestyle or acute exercise is unknown. Here, we investigated the metabolic phenotype and circulating GDF15 levels in lean and obese male C57Bl/6J mice with long-term voluntary wheel running (VWR) intervention. Additionally, treadmill running capacity and exercise-induced muscle gene expression was examined in GDF15-ablated mice. Active lifestyle mimic via VWR improved treadmill running performance and, in obese mice, also metabolic phenotype. The post-exercise induction of skeletal muscle transcriptional stress markers was reduced by VWR. Skeletal muscle GDF15 gene expression was very low and only transiently increased post-exercise in sedentary but not in active mice. Plasma GDF15 levels were only marginally affected by chronic or acute exercise. In obese mice, VWR reduced GDF15 gene expression in different tissues but did not reverse elevated plasma GDF15. Genetic ablation of GDF15 had no effect on exercise performance but augmented the post exercise expression of transcriptional exercise stress markers (Atf3, Atf6, and Xbp1s) in skeletal muscle. We conclude that skeletal muscle does not contribute to circulating GDF15 in mice, but muscle GDF15 might play a protective role in the exercise stress response.

Understanding the effect of ventilation, intermittent pumping and seasonality in hydrogen sulfide and methane concentrations in a coastal sewerage system.

Gas pollutants emitted during wastewater transport contribute to atmospheric pollution, aggravated risks for utility workers, infrastructure corrosion, and odour nuisance. Field studies have shown that is difficult to effectively obtain reliable correlations between in-sewer air movement and gas pollutant concentrations. This study aimed at investigating the influence of different ventilation and operating conditions in H2S and CH4 horizontal and vertical movement in a section of a gravity sewer, downstream of a pumping station. Relevant liquid and gas phase quality parameters were monitored, and significant H2S concentrations were measured (with lower contents of CH4). Results evidenced that headspace temperature and ventilation played a key effect when analysing H2S and CH4 dynamics. Setups with a similar content of sulfide and chemical oxygen demand resulted in different H2S and CH4 headspace concentrations. It was also observed that an increase in ventilation resulted in a decrease of average headspace relative humidity of over 70%, with clear implications in corrosion potential estimates. Another interesting observation was that the wastewater drag induced by intermittent pumping, in absence of ingassing, originated pressure differences of up to 0.2 Pa m-1 between studied manholes. This differential originated a wave pattern of gas moving upstream and downstream, thus resulting in several gas peaks per pumping event, at the same sections. In addition, in confined setups, full mixing was not observed along the manholes.

Systematic pharmacological screens uncover novel pathways involved in cerebral cavernous malformations.

Cerebral cavernous malformations (CCMs) are vascular lesions in the central nervous system causing strokes and seizures which currently can only be treated through neurosurgery. The disease arises through changes in the regulatory networks of endothelial cells that must be comprehensively understood to develop alternative, non-invasive pharmacological therapies. Here, we present the results of several unbiased small-molecule suppression screens in which we applied a total of 5,268 unique substances to CCM mutant worm, zebrafish, mouse, or human endothelial cells. We used a systems biology-based target prediction tool to integrate the results with the whole-transcriptome profile of zebrafish CCM2 mutants, revealing signaling pathways relevant to the disease and potential targets for small-molecule-based therapies. We found indirubin-3-monoxime to alleviate the lesion burden in murine preclinical models of CCM2 and CCM3 and suppress the loss-of-CCM phenotypes in human endothelial cells. Our multi-organism-based approach reveals new components of the CCM regulatory network and foreshadows novel small-molecule-based therapeutic applications for suppressing this devastating disease in patients.

Neuronal Chemosensation and Osmotic Stress Response Converge in the Regulation of aqp-8 in C. elegans.

Aquaporins occupy an essential role in sustaining the salt/water balance in various cells types and tissues. Here, we present new insights into aqp-8 expression and regulation in Caenorhabditis elegans. We show, that upon exposure to osmotic stress, aqp-8 exhibits a distinct expression pattern within the excretory cell compared to other C. elegans aquaporins expressed. This expression is correlated to the osmolarity of the surrounding medium and can be activated physiologically by osmotic stress or genetically in mutants with constitutively active osmotic stress response. In addition, we found aqp-8 expression to be constitutively active in the TRPV channel mutant osm-9(ok1677). In a genome-wide RNAi screen we identified additional regulators of aqp-8. Many of these regulators are connected to chemosensation by the amphid neurons, e.g., odr-10 and gpa-6, and act as suppressors of aqp-8 expression. We postulate from our results, that aqp-8 plays an important role in sustaining the salt/water balance during a secondary response to hyper-osmotic stress. Upon its activation aqp-8 promotes vesicle docking to the lumen of the excretory cell and thereby enhances the ability to secrete water and transport osmotic active substances or waste products caused by protein damage. In summary, aqp-8 expression and function is tightly regulated by a network consisting of the osmotic stress response, neuronal chemosensation as well as the response to protein damage. These new insights in maintaining the salt/water balance in C. elegans will help to reveal the complex homeostasis network preserved throughout species.

Fatores associados ao nível de atividade física entre idosos asilares / Factors associated with level of physical activity among institutionalized elderly

Este estudo teve como objetivo analisar os fatores associados ao nível de atividade física em idosos asilares. Trata-se de um estudo transversal, de caráter descritivo, realizado com 16 idosos de uma instituição asilar no município de Jequié-BA. Na coleta de dados,realizou-se uma entrevista sobre informações sociodemográficas,sendo aplicado questionário sobre perfil do estado de saúde e nível de atividade física. Utilizaram-se procedimentos da estatística descritiva, através de medidas de tendência central, (média e mediana) e de dispersão (desvio-padrão), para variáveis numéricas e frequência simples, para variáveis categóricas. Calculou-se o nível de atividade física (NAF) segundo características sociodemográficas e estado de saúde. Nos resultados, observou-se que, 12,5% dos idosos foram classificados como ativos fisicamente e 87,5%, como inativos fisicamente. Indivíduos com idade mais avançada (com80 ou mais) (14,3%), do sexo masculino (16,7%), com estado civil solteiro/separado (25,0%), não alfabetizado (14,3%) e de raça/cor branca (25,0%) apresentaram maior frequência de atividade física habitual. Um maior nível de independência (15,4%), percepção positiva da qualidade de vida (20,0%) e do estado de saúde (20,0%)e maior risco coronariano (20,0%) foram verificados nos indivíduos ativos fisicamente. O conhecimento sobre os fatores associados ao nível de atividade física habitual favorece o melhor direcionamento dos programas de atenção à saúde dos idosos residentes em instituições de longa permanência. Faz-se necessário a realização de outros estudos no intuito de compreender melhor esta associação.

This study aimed to analyze the factors associated with physical activity in elderly nursing homes. This is a descriptive cross-sectional study, which was conducted with 16 individuals from a nursing home in Jequié-BA. To collect data, the following instruments were used: a questionnaire applied in the form of individual interviews with information sociodemographic profile of health status and physical activity level. We used descriptive statistics procedures to trace the profile of elderly subjects according to sociodemographic characteristics and health status. Physical activity level (PAL) was calculated according to sociodemographic characteristics and health status. The results showed that 12.5% of the elderly were classified as physically active and 87.5% as physically inactive. Individuals with more advanced age (80 or older) (14.3%), male (16.7%), with being single / separated(25.0%), illiterate (14.3%) and race / white (25.0%) had higher frequency of physical activity. A higher level of independence (15.4%),positive perceptions of quality of life (20.0%) and health (20.0%) and higher coronary risk (20.0%) were found for active individuals physically. Knowledge about the factors associated with level of habitual physical activity promotes improved targeting of programs for healthcare to elderly residents in long-stay institutions. It is necessary to conduct further studies in order to better understand this association.

Fatores associados ao nível de atividade física entre idosos asilares / Factors associated with level of physical activity among institutionalized elderly

Este estudo teve como objetivo analisar os fatores associados ao nível de atividade física em idosos asilares. Trata-se de um estudo transversal, de caráter descritivo, realizado com 16 idosos de uma instituição asilar no município de Jequié-BA. Na coleta de dados,realizou-se uma entrevista sobre informações sociodemográficas,sendo aplicado questionário sobre perfil do estado de saúde e nível de atividade física. Utilizaram-se procedimentos da estatística descritiva, através de medidas de tendência central, (média e mediana) e de dispersão (desvio-padrão), para variáveis numéricas e frequência simples, para variáveis categóricas. Calculou-se o nível de atividade física (NAF) segundo características sociodemográficas e estado de saúde. Nos resultados, observou-se que, 12,5% dos idosos foram classificados como ativos fisicamente e 87,5%, como inativos fisicamente. Indivíduos com idade mais avançada (com80 ou mais) (14,3%), do sexo masculino (16,7%), com estado civil solteiro/separado (25,0%), não alfabetizado (14,3%) e de raça/cor branca (25,0%) apresentaram maior frequência de atividade física habitual. Um maior nível de independência (15,4%), percepção positiva da qualidade de vida (20,0%) e do estado de saúde (20,0%)e maior risco coronariano (20,0%) foram verificados nos indivíduos ativos fisicamente. O conhecimento sobre os fatores associados ao nível de atividade física habitual favorece o melhor direcionamento dos programas de atenção à saúde dos idosos residentes em instituições de longa permanência. Faz-se necessário a realização de outros estudos no intuito de compreender melhor esta associação.(AU)

This study aimed to analyze the factors associated with physical activity in elderly nursing homes. This is a descriptive cross-sectional study, which was conducted with 16 individuals from a nursing home in Jequié-BA. To collect data, the following instruments were used: a questionnaire applied in the form of individual interviews with information sociodemographic profile of health status and physical activity level. We used descriptive statistics procedures to trace the profile of elderly subjects according to sociodemographic characteristics and health status. Physical activity level (PAL) was calculated according to sociodemographic characteristics and health status. The results showed that 12.5% of the elderly were classified as physically active and 87.5% as physically inactive. Individuals with more advanced age (80 or older) (14.3%), male (16.7%), with being single / separated(25.0%), illiterate (14.3%) and race / white (25.0%) had higher frequency of physical activity. A higher level of independence (15.4%),positive perceptions of quality of life (20.0%) and health (20.0%) and higher coronary risk (20.0%) were found for active individuals physically. Knowledge about the factors associated with level of habitual physical activity promotes improved targeting of programs for healthcare to elderly residents in long-stay institutions. It is necessary to conduct further studies in order to better understand this association.(AU)

Seronegative infection and AIDS caused by an A2 subsubtype HIV-1.

The study of true seronegative HIV-1 infections may have important implications for the diagnosis and prevention of HIV-1 infection. The case of an AIDS patient with persistently negative HIV serology is described. Genetic and phylogenetic analysis indicated that she was infected with A2 subsubtype HIV-1 transmitted by her seropositive and asymptomatic sexual partner. The clinical and serological discordant results suggest the presence of an immunological deficiency that prevents the formation of HIV-1-specific antibodies.