Evaluation of internal markers in digestibility estimation for sheep and goats.

The objective of this study was to compare the indirect methods of obtaining digestibility with the direct method of total fecal collection to estimate the apparent digestibility of nutrients in sheep and goats supplemented with non-protein nitrogen. Five goats and five sheep with no defined racial pattern were used, distributed in two 5 × 5 Latin squares, with split plots, considering the diets as plots and the apparent digestibility determination methodologies as subplots. The diets were composed of buffelgrass hay and the addition, via ruminal infusion, of increasing amounts of nitrogen supplementation in order to gradually raise the CP level of the basal diet in intervals of 2% points, that is, + 2, +4, + 6 and + 8%. Samples of the feeds offered, and the leftovers were collected daily during the five days of collection to determine the nutrient intake, as well as the total collection of feces to determine the apparent digestibility of the nutrients. The amount of fecal dry matter excreted was estimated by the concentration of Indigestible Acid Detergent Fiber (ADFi), Indigestible Neutral Detergent Fiber (NDFi), Indigestible Dry Matter at 244 h (DMi 244 h) and Indigestible Dry Matter at 264 h (DMi 264 h). Among the evaluated markers, DMi 264 h had the lowest accuracy in estimating fecal excretion and nutrient digestibility. For the goat species, the markers ADFi and DMi 244 h proved to be able to adequately predict fecal excretion and digestibility indices, while NDFi stood out for both species. Among the evaluated markers, NDFi is the one that most accurately estimates the nutrient digestibility of the diet for goats and sheep.

Main drivers of dragonflies and damselflies (Insecta; Odonata) metacommunities in streams inside protected areas in the Brazilian Amazon.

The evaluation of environmental and spatial influence in freshwater systems is crucial for the conservation of aquatic diversity. So, we evaluated communities of Odonata in streams inside and outside sustainable use areas in the Brazilian western Amazon. We predicted that these streams would differ regarding habitat integrity and species α and ß diversity. We also predict that environmental and spatial variables will be important for both suborders, but with more substantial effects on Zygoptera species, considering their nature of forest-specialist. The study was conducted in 35 streams, 19 inside and 16 outside sustainable use areas. The streams outside presented high species richness, abundance, and number of exclusive forest-specialist species from Zygoptera and higher scores of habitat integrity. In contrast, one sustainable use area presented the lowest values of these metrics. Besides, we found that environmental and spatial variables were significantly associated to Zygoptera species composition, but not with Anisoptera, which can be explained by their cosmopolitan nature. Our results indicated that an interplay between environmental and spatial processes determines the structure of the metacommunities of Zygoptera. The less effective dispersal rates and narrow ecological tolerance of Zygoptera species make them more influenced by local conditions and dispersal limitation, and more sensible to habitat modifications. We highlight the importance of improving the local management of the sustainable use areas by environmental agencies, mainly on areas that are losing their capacity to maintain the aquatic fauna, and implementation of social policies toward traditional people.

Targeting the lipid kinase PIKfyve upregulates surface expression of MHC class I to augment cancer immunotherapy.

Despite the remarkable clinical success of immunotherapies in a subset of cancer patients, many fail to respond to treatment and exhibit resistance. Here, we found that genetic or pharmacologic inhibition of the lipid kinase PIKfyve, a regulator of autophagic flux and lysosomal biogenesis, upregulated surface expression of major histocompatibility complex class I (MHC-I) in cancer cells via impairing autophagic flux, resulting in enhanced cancer cell killing mediated by CD8+ T cells. Genetic depletion or pharmacologic inhibition of PIKfyve elevated tumor-specific MHC-I surface expression, increased intratumoral functional CD8+ T cells, and slowed tumor progression in multiple syngeneic mouse models. Importantly, enhanced antitumor responses by Pikfyve-depletion were CD8+ T cell- and MHC-I-dependent, as CD8+ T cell depletion or B2m knockout rescued tumor growth. Furthermore, PIKfyve inhibition improved response to immune checkpoint blockade (ICB), adoptive cell therapy, and a therapeutic vaccine. High expression of PIKFYVE was also predictive of poor response to ICB and prognostic of poor survival in ICB-treated cohorts. Collectively, our findings show that targeting PIKfyve enhances immunotherapies by elevating surface expression of MHC-I in cancer cells, and PIKfyve inhibitors have potential as agents to increase immunotherapy response in cancer patients.

Study of Melipona quadrifasciata brain under operant learning using proteomic and phosphoproteomic analysis.

Learning to anticipate events based on the predictive relationship between an action and an outcome (operant conditioning) is a form of associative learning shared by humans and most of other living beings, including invertebrates. Several behavioral studies on the mechanisms of operant conditioning have included Melipona quadrifasciata, a honey bee that is easily manipulated due to lack of sting. In this work, brain proteomes of Melipona bees trained using operant conditioning and untrained (control) bees were compared by two-dimensional gel electrophoresis analysis within pI range of 3-10 and 4-7; in order to find proteins specifically related to this type of associative learning.One protein was detected with differential protein abundance in the brains of trained bees, when compared to not trained ones, through computational gel imaging and statistical analysis. This protein was identified by peptide mass fingerprinting and MS/MS peptide fragmentation using a MALDI-TOF/TOF mass spectrometer as one isoform of arginine kinase monomer, apparently dephosphorylated. Brain protein maps were obtained by 2-DE (Two-dimensional gel electrophoresis) from a total proteins and phosphoproteins extract of the bee Melipona quadrifasciata. One isoform of arginine kinase, probably a dephosphorylated isoform, was significantly more abundant in the brain of trained bees using operant conditioning. Arginine kinase has been reported as an important enzyme of the energy releasing process in the visual system of the bee, but it may carry out additional and unexpected functions in the bee brain for learning process.

Biochemical responses of the mussel Perna perna after exposure to environmental concentrations of the UV filter Benzophenone-3.

Personal care products, such as UV filters, are frequently present in aquatic ecosystems, but studies on their impact on marine organisms are still scarce. Here we addressed the effects of benzophenone-3 (BP-3) on the antioxidant status of Perna perna mussels exposed to concentrations of 0.1 and 3 µg.L-1 for 72 h and 7 days. Glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), glucose-6-phosphate dehydrogenase (G6PDH) activity and lipoperoxidation (MDA) were evaluated in the gills. A significant reduction (p < 0.05) in the activity of G6PDH and GPx was observed after exposure for 7 days to 0.1 µg.L-1. However, no significant differences were observed in GST activity and MDA levels, independently of the exposure time. Principal component analysis (PCA) showed an association of BP-3 highest concentration with GR and MDA at 72 h and only with GR at 7 days of exposure. Similarly, the integrated biomarker response (IBR) demonstrated GR and MDA alterations. In conclusion, environmentally relevant concentrations of BP-3 altered antioxidant and auxiliary enzymes, which could cause long-term damage to P.perna mussels. The need to implement more efficient techniques in wastewater treatment systems is pointed out, especially in summer, when UV filters are used more frequently and abundantly.

Human land-uses homogenize stream assemblages and reduce animal biomass production.

Human land-use change is a major threat to natural ecosystems worldwide. Nonetheless, the effects of human land-uses on the structure of plant and animal assemblages and their functional characteristics need to be better understood. Furthermore, the pathways by which human land uses affect ecosystem functions, such as biomass production, still need to be clarified. We compiled a unique dataset of fish, arthropod and macrophyte assemblages from 61 stream ecosystems in two Neotropical biomes: Amazonian rainforest and Uruguayan grasslands. We then tested how the cover of agriculture, pasture, urbanization and afforestation affected the taxonomic richness and functional diversity of those three species assemblages, and the consequences of these effects for animal biomass production. Single trait categories and functional diversity were evaluated, combining recruitment and life-history, resource and habitat-use, and body size. The effects of intensive human land-uses on taxonomic and functional diversities were as strong as other drivers known to affect biodiversity, such as local climate and environmental factors. In both biomes, the taxonomic richness and functional diversity of animal and macrophyte assemblages decreased with increasing cover of agriculture, pasture, and urbanization. Human land-uses were associated with functional homogenization of both animal and macrophyte assemblages. Human land-uses reduced animal biomass through direct and indirect pathways mediated by declines in taxonomic and functional diversities. Our findings indicate that converting natural ecosystems to supply human demands results in species loss and trait homogenization across multiple biotic assemblages, ultimately reducing animal biomass production in streams.

Changes in Stage at Presentation among Lung and Breast Cancer Patients During the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic altered access to healthcare by decreasing the number of patients able to receive preventative care and cancer screening. We hypothesized that, given these changes in access to care, radiologic screening for breast and lung cancer would be decreased, and patients with these cancers would consequently present at later stages of their disease. STUDY DESIGN: This is a retrospective cross-sectional study of 2017 to September 2021 UMass Memorial Tumor Registry data for adult breast and lung cancer patients. Changes in stage at presentation of breast and lung cancer during the COVID-19 pandemic were measured, defined as before and during COVID-19. RESULTS: There were no statistically significant changes in the overall stage of presentation before or during the COVID-19 pandemic for either breast or lung cancer patients. Analysis of case presentation and stage during periods of COVID-19 surges that occurred during the time of this study compared with prepandemic data demonstrated a statistically significant decrease in overall presentation of breast cancer patients in the first surge, with no other statistically significant changes in breast cancer presentation. A nonstatistically significant decrease in lung cancer presentation was seen during the initial surge of COVID-19. There was also a statistically significant increase in early-stage presentation of lung cancer during the second and third COVID-19 surges. CONCLUSIONS: In the 2 years after the COVID-19 pandemic, we were not able to demonstrate stage migration at presentation of breast and lung cancer patients to later stages despite decreases in overall presentation during the initial 2 years of the COVID pandemic. An increase in early-stage lung cancer during the second and third surges is interesting and could be related to increased chest imaging for COVID pneumonia.

Carcass traits and meat quality of goats fed with cactus pear (Opuntia ficus-indica Mill) silage subjected to an intermittent water supply.

The effect of different proportions of cactus pear (Opuntia ficus-indica Mill) silage (CPS) and intermittent water supply (IWS) to crossbreed goats' diets on carcass traits and meat quality were evaluated. The IWS caused a reduction (p = 0.03) in the percentage of leg fat in the animals. The rib eye area, carcass weight, and physical-chemical characteristics were not affected (p > 0.05) by the CPS or IWS. The IWS reduced (p = 0.04) the elongase enzyme activity. The CPS inclusion in the diet reduced C22:0 (p = 0.01), some branched-chain fatty acid (BCFA), C20:1 (p = 0.03), c13-C18:1 (p = 0.01) fatty acids. Therefore, in situations of water scarcity, an intermittent water supply of up to 48 h and diets with up to 42% cactus pear silage, can be adopted in goat feedlot, without affecting carcass traits and meat quality.

Edentulism and number of medications are associated with nutritional status in older adults: a population-based cross-sectional study / Edentuslimo e número de medicações estão associados com estado nutricional em idosos: um estudo transversal de base populacional

ABSTRACT Objective: This study evaluated the nutritional status and associated factors among older adults of a southern Brazilian city. Methods: A cross-sectional home-based study, with a probabilistic sample per cluster, was carried out with 282 older adults aged ≥60 years in the city of Veranópolis, Brazil. Through a structured questionnaire, socioeconomic, general and behavioral health aspects were assessed. Nutritional status was assessed using the Mini Nutritional Assessment (MAN®) instrument, categorizing the sample into eutrophic or nutritional risk (risk of malnutrition + malnourished). Oral health was assessed by counting teeth and the use of and need for dental prosthesis. Two independent multivariate models were constructed, using number of daily medication and polypharmacy (≥2 daily medications). Logistic regression was used to verify associations. Results: The prevalence of nutritional risk was 14.5% (N=41). In the final multivariate analysis, users of ≥6 daily medications demonstrated a greater odds ratio (OR) of being at nutritional risk when compared to those who did not use medication daily (OR: 12.16; 95% confidence interval [95%CI]: 1.47 - 100.82). Non-edentulous older adults had 67.7% (p = 0.006) lower OR for nutritional risk when compared to edentulous. Conclusion: The prevalence of nutritional risk was low among this sample, and it was associated with edentulism and number of daily medications.

RESUMO Objetivo: Esse estudo avaliou o estado nutricional e fatores associados em idosos de uma cidade do Sul do Brasil. Métodos: Um estudo transversal de base populacional, com amostragem probabilística por cluster, foi realizado com 282 idosos com idade ≥60 anos na cidade de Veranópolis, Brasil. Por meio de um questionário estruturado, aspectos socioeconômicos, comportamentais e de saúde geral foram aferidos. Estado nutricional foi verificado usando a Mini Avaliação Nutricional (MAN), categorizando a amostra em eutróficos e risco nutricional (risco de desnutrição + desnutridos). Saúde bucal foi verificada pela contagem dos dentes e uso e necessidade de prótese dentária. Dois modelos multivariados independentes foram construídos, utilizando o número de medicações diárias e polifarmácia (≥2 medicamentos por dia). Regressão logística foi utilizada para verificar as associações. Resultados: A prevalência de risco nutricional foi de 14,5% (N=41). Na análise multivariada final, usuários de ≥6 medicamentos por dia demonstraram uma maior razão de chance (RC) de terem risco nutricional quando comparados com aqueles que não utilizaram medicamento diariamente (RC: 12,164; intervalo de confiança de 95% [IC95%]: 1,468 - 100,821). Idosos não edêntulos tiveram 67,7% (p=0,006) menor RC para risco nutricional quando comparados com não edêntulos. Conclusão: A prevalência de risco nutricional foi baixa nessa amostral, ela foi associada com edentulismo e número diário de medicações.

[PRION+] States Are Associated with Specific Histone H3 Post-Translational Modification Changes.

Prions are proteins able to take on alternative conformations and propagate them in a self-templating process. In Saccharomyces cerevisiae, prions enable heritable responses to environmental conditions through bet-hedging mechanisms. Hence, [PRION+] states may serve as an atypical form of epigenetic control, producing heritable phenotypic change via protein folding. However, the connections between prion states and the epigenome remain unknown. Do [PRION+] states link to canonical epigenetic channels, such as histone post-translational modifications? Here, we map out the histone H3 modification landscape in the context of the [SWI+] and [PIN+] prion states. [SWI+] is propagated by Swi1, a subunit of the SWI/SNF chromatin remodeling complex, while [PIN+] is propagated by Rnq1, a protein of unknown function. We find [SWI+] yeast display decreases in the levels of H3K36me2 and H3K56ac compared to [swi-] yeast. In contrast, decreases in H3K4me3, H3K36me2, H3K36me3 and H3K79me3 are connected to the [PIN+] state. Curing of the prion state by treatment with guanidine hydrochloride restored histone PTM to [prion-] state levels. We find histone PTMs in the [PRION+] state do not match those in loss-of-function models. Our findings shed light into the link between prion states and histone modifications, revealing novel insight into prion function in yeast.

Green Synthesis of Silver Nanoparticles for Preparation of Gelatin Films with Antimicrobial Activity.

Silver nanoparticles were successfully synthesized using Thuja orientalis aqueous extract and AgNO3 as a precursor. UV-Vis showed a distinct absorption peak at 424 nm attributed to silver nanoparticles due to their surface plasmon resonance. Atomic absorption analysis reflected an increase in the concentration of nanoparticles in relation to the progress of the synthesis, obtaining a peak concentration value of 15.7 mg/L at 50 min. The FTIR spectra revealed the characteristic functional groups of phytomolecules involved in the silver-ion binding process, such as R-O-H (3335 cm-1) O=C-OH (2314 cm-1) and C-C=C (1450 cm-1). At 50 min, zeta potential showed the stability of the nanoparticles with the value of -21.73 mV. TEM micrographs revealed the formation of spherical nanoparticles with an average size of about 85.77 nm. Furthermore, films incorporated with nanoparticles exhibited a Tg from 66.42 °C to 73.71 °C and Tm at 103.31 °C. Films from the G22 formulation presented excellent antibacterial properties inhibiting the growth of Staphylococcus aureus. Thuja orientalis aqueous extract could be a low-cost, eco-friendly, and efficient reducing and capping agent for the synthesis of nanometric-sized Ag particles. Gelatin films with nanoparticles are expected to have high potential as an active food packaging system.

Impact of FGFR2 gene fusions on survival of patients with intrahepatic cholangiocarcinoma following curative intent resection.

BACKGROUND: Intrahepatic Cholangiocarcinoma (iCCA) is an aggressive cancer with diverse mutational profiles. An important molecular subtype is fibroblast growth factor receptor 2 (FGFR2) fusion. The effect of FGFR2 fusions on prognosis is unknown. Our aim was to assess the outcomes in resected CCA patients in relation to FGFR2 status. METHODS: Surgically treated CCA patients from a single institution were retrospectively reviewed between 2008 and 2014. FGFR rearrangements were detected by fluorescence in situ hybridization (FISH). Data included patient demographics, tumor pathology, disease-free survival (DFS) and overall survival (OS). RESULTS: Ninety-five patients underwent surgical resection for iCCA. Twelve (13%) of these were found to have FGFR2 fusion, none of which were treated with FGFR targeted therapy. Patients with FGFR2 fusions were found to have a longer 5-year (83 vs. 32%, p = 0.01) and 10-year (46 vs. 22%, p = 0.04) OS. Five and 10-year DFS was also increased (68 vs. 33% p = 0.04) and (68 vs. 25 %, p = 0.02,). FGFR2 fusion status was the strongest independent factor associated with improved OS (HR 0.23, 0.09-0.62, p=0.003) and DFS (HR 0.18, 0.05-0.67, p=0.01). CONCLUSION: Patients with CCA FGFR2 fusion have improved OS and DFS following surgical resection.

COVID-19 and automation in a developing economy: Evidence from Chile.

This paper analyzes the Covid-19 pandemic impact of the global process of automation on employment in a developing economy. This is particularly interesting because developing economies characteristics, such as having larger informal sectors and weaker social safety nets, shapes the impact of automation on labor markets. We show that occupations with a higher risk of automation exhibit the most significant employment contraction. More specifically, we find that one standard deviation higher in sectoral share of employment in occupations at risk of automation (OaRA) implied around 7% less employment on average between the last quarter of 2019 and the first quarter of 2021. The effect on informal employees is three times more in comparison to formal employees, and the estimation for self-employed workers is not statistically significant. We also find that employees in sector with relatively low compared to high wages, both vis-à-vis the US, exhibit a 20% smaller reaction on employment due to the pandemic restrictions. We do not find robust evidence showing that the employment contraction has been larger among female workers or in jobs with higher at-work physical proximity, but we do find a positive relationship related to the capacity of working remotely.

Effects of voluntary contraction on the soleus H-reflex of different amplitudes in healthy young adults and in the elderly.

A number of H-reflex studies used a moderate steady voluntary contraction in an attempt to keep the motoneuron pool excitability relatively constant. However, it is not clear whether the voluntary muscle activation itself represents a confounding factor for the elderly, as a few ongoing mechanisms of reflex modulation might be compromised. Further, it is well-known that the amount of either inhibition or facilitation from a given conditioning depends on the size of the test H-reflex. The present study aimed at evaluating the effects of voluntary contraction over a wide range of reflex amplitudes. A significant reflex facilitation during an isometric voluntary contraction of the soleus muscle (15% of the maximal voluntary isometric contraction-MVC) was found for both young adults and the elderly (p < 0.05), regardless of their test reflex amplitudes (considering the ascending limb of the H-reflex recruitment curve-RC). No significant difference was detected in the level of reflex facilitation between groups for all the amplitude parameters extracted from the RC. Simulations with a computational model of the motoneuron pool driven by stationary descending commands yielded qualitatively similar amount of reflex facilitation, as compared to human experiments. Both the experimental and modeling results suggest that possible age-related differences in spinal cord mechanisms do not significantly influence the reflex modulation during a moderate voluntary muscle activation. Therefore, a background voluntary contraction of the ankle extensors (e.g., similar to the one necessary to maintain upright stance) can be used in experiments designed to compare the RCs of both populations. Finally, in an attempt to elucidate the controversy around changes in the direct motor response (M-wave) during contraction, the maximum M-wave (Mmax) was compared between groups and conditions. It was found that the Mmax significantly increases (p < 0.05) during contraction and decreases (p < 0.05) with age arguably due to muscle fiber shortening and motoneuron loss, respectively.

Response of aquatic insects to an environmental gradient in Amazonian streams.

The increasing land use in the Amazon region has resulted in the widespread substitution of forest areas with pasture and bauxite mining. These land uses reduce the forest cover of streams and modify their characteristics, reducing the diversity of aquatic insect assemblages. In the present study, we aimed to identify the threshold of the assemblages of the larvae of insects of the orders Ephemeroptera, Plecoptera, and Trichoptera (collectively known as EPT), and adults of the order Odonata, along an environmental gradient of land use and land cover (LULC). We sampled 30 streams along an environmental gradient determined by the proportion of forest, pasture, and bauxite mining observed within the catchment of each stream. We identified 12 taxa associated with forest (nine positively and three negatively) and four negatively associated with pasture. However, no taxa were associated explicitly with the bauxite mining gradient. As forest is converted to pasture, the abundance and frequency of occurrence of the taxa sensitive to pasture are reduced, reflecting their environmental sensitivity and their potential as sentinels of preserved streams. The identification of the thresholds of the EPT and odonates taxa allowed us to determine which of these organisms are positively or negatively associated with the environmental gradient of LULC in Amazonian streams. We hope that the results of the present study can be applied in future biomonitoring programs, particularly for monitoring the response of aquatic insects to the degradation of streams.

Percutaneous treatments of primary aneurysmal bone cysts: systematic review and meta-analysis.

PURPOSE: To systematically review the literature to determine recurrence rates of percutaneous treatments for primary aneurysmal bone cysts (ABC). METHODS: Search strategies were performed in the following databases: PubMed, SCIELO, LILACS and BVS, using terms in English, Spanish and Portuguese (PROSPERO Registration Number: CRD42020170340). Longitudinal studies, either observational or clinical trials, with at least five patients and with a mean of 18 months of follow-up were included. Studies had to use any type of percutaneous treatments and report the recurrence rates of primary ABC treatment. Studies selection, data extraction and risk of bias assessment were performed independently by two researchers. A global meta-analysis was carried out to assess the proportion of recurrence. Studies were categorized into two subgroups: selective arterial embolization and sclerotherapy. RESULTS: Thirteen studies were included in the present study. The average success rate of percutaneous treatments for ABC was 91.11%, with a total of 37 lesions recurrences in the 416 patients. The sex ratio was 1:1. The subgroup of sclerotherapies presented a lower proportion of recurrence. The proportion of recurrence in the subgroup of selective arterial embolization was 19% (95%IC 12.11-27.54) and that of sclerotherapies was 6% (95%IC 3.65-9.19). CONCLUSIONS: Both percutaneous treatments for ABC are effective, showing a lower rate of recurrence. Sclerotherapy treatments seem to be promising, but further clinical trials must be conducted with a longer follow-up.

Spineless cactus use management on microbiological quality, performance, and nutritional disorders in sheep.

The physically effective neutral detergent fiber content alone has not been able to explain the appearance of diarrhea in ruminants fed diets with large volumes of spineless cactus, so the proliferation of enterobacteria in spineless cactus may be associated with cases of diarrhea in sheep. In the in vitro test, used two varieties of spineless cactus, both of which were chopped to particles of 4 and 2 cm2. For the in vivo test, 15 lambs were allocated to three treatment groups, namely, spineless cactus crushed and immediately supplied to the animals; spineless cactus crushed 8 h before supply; and silage of spineless cactus. The variables evaluated were dry matter intake, weight gain, fecal score, hemogram, and fecal colony count. In the in vitro test, higher Enterobacteriaceae and lactic acid bacteria counts were found both at 12 h and 24 h when the spineless cactus was crushed to 2 cm2 in both varieties. The sheep fed the spineless cactus crushed 8 h prior to supply showed the highest Enterobacteriaceae count in the feces (8.48 CFU/g), compared to animals fed silage of spineless cactus (4.95 CFU/g). It can thus be concluded that the management of spineless cactus influences the development of total and fecal coliforms, especially when it is chopped to 2 cm2 and exposed to the environment for periods longer than 7 h, and that the bacterial population can be controlled by administering the spineless cactus in the form of silage.

Circadian Structural Plasticity Drives Remodeling of E Cell Output.

Behavioral outputs arise as a result of highly regulated yet flexible communication among neurons. The Drosophila circadian network includes 150 neurons that dictate the temporal organization of locomotor activity; under light-dark (LD) conditions, flies display a robust bimodal pattern. The pigment-dispersing factor (PDF)-positive small ventral lateral neurons (sLNv) have been linked to the generation of the morning activity peak (the "M cells"), whereas the Cryptochrome (CRY)-positive dorsal lateral neurons (LNds) and the PDF-negative sLNv are necessary for the evening activity peak (the "E cells") [1, 2]. While each group directly controls locomotor output pathways [3], an interplay between them along with a third dorsal cluster (the DN1ps) is necessary for the correct timing of each peak and for adjusting behavior to changes in the environment [4-7]. M cells set the phase of roughly half of the circadian neurons (including the E cells) through PDF [5, 8-10]. Here, we show the existence of synaptic input provided by the evening oscillator onto the M cells. Both structural and functional approaches revealed that E-to-M cell connectivity changes across the day, with higher excitatory input taking place before the day-to-night transition. We identified two different neurotransmitters, acetylcholine and glutamate, released by E cells that are relevant for robust circadian output. Indeed, we show that acetylcholine is responsible for the excitatory input from E cells to M cells, which show preferential responsiveness to acetylcholine during the evening. Our findings provide evidence of an excitatory feedback between circadian clusters and unveil an important plastic remodeling of the E cells' synaptic connections.

Factores de riesgo para obesidad en población femenina del Istmo de Tehuantepec, Oaxaca, México / Risk factors for obesity in the female population of the Isthmus of Tehuantepec, Oaxaca, Mexico

Resumen Justificación y objetivo: La identificación de los factores de riesgo asociados a la obesidad contribuye a implementar estrategias para la modificación de conductas y estilos de vida saludables. En la región del Istmo de Oaxaca, México, no hay registros sobre dicho fenómeno. El presente estudio determina los niveles de obesidad y su relación con factores de riesgo entre la población femenina residente en las localidades de Santa María Xadani y Juchitán de Zaragoza. Métodos: A través de un estudio transversal, se encuestó a 355 mujeres para documentar información sociodemográfica, antecedentes de salud, hábitos de alimentación y ejercicio. Mediante una exploración física se midió la masa corporal y altura para el cálculo del índice de masa corporal, y así se estableció el nivel de obesidad de acuerdo con la Norma Oficial Mexicana NOM-043-SSA2-2012. La información se analizó mediante estadística descriptiva y regresión logística. Resultados: El 38,6 % de las mujeres presentaba sobrepeso y en el 39,2 % se encontró en algún nivel de obesidad. Los factores de riesgo encontrados fueron la procedencia rural, el hábito de cenar, los antecedentes familiares de enfermedades crónico - degenerativas y el sedentarismo, que representaron un riesgo de 1,6; 1,6; 1,8 y 1,9 veces más a desarrollar algún nivel de obesidad, respectivamente. Conclusiones: La prevalencia de sobrepeso y obesidad entre las mujeres fue alta (77,8 %). Se identificaron cuatro factores de riesgo para el desarrollo de obesidad. Es necesario implementar estrategias integrales de atención a la problemática en la población estudiada, en particular, en la infantil.

Abstract Background and aim: The identification of risk factors associated with obesity helps to implement strategies for the modification of healthy behaviors and lifestyles. In the isthmus region of Oaxaca, Mexico, there are no records of this phenomenon. The present study determines the levels of obesity and the relationship with risk factors among the female population that resides in the towns of Santa Maria Xadani and Juchitan de Zaragoza. Methods: Through a cross-sectional study, 355 women were surveyed to document sociodemographic information, health history, and eating habits and exercise. Through a physical examination, body mass and height were measured for the calculation of the body mass index, and thus the level of obesity was established according to the Official Mexican Standard NOM-043-SSA2-2012. The information was analyzed using descriptive statistic and logistic regression. Results: 38,6% of women are overweight and in 39,2% some level of obesity was found. The risk factors identified were rural origin, the habit of dinning, family history o cfhronic degenerative diseases and sedentary lifestyle, which represent a risk of 1,6; 1,6; 1,8 and 1,9 times more to develop some level of obesity, respectively. Conclusions: The prevalence of overweight and obesity among women was high (77,8%). Four risk factors for the development of obesity were identified. It is necessary to implement strategies for attention to the problem in the population studied, particularly in children.

Hemodynamic and clinical effects of selexipag in children with pulmonary hypertension.

Selexipag is an oral prostacyclin receptor agonist; it was recently approved for use in adults with pulmonary arterial hypertension. The safety and efficacy of selexipag has not yet been determined in the pediatric population. We describe short-term hemodynamic and clinical data with selexipag therapy in four pediatric patients with pulmonary hypertension. We reviewed clinical, echocardiographic, and hemodynamic data. One patient was transitioned from subcutaneous treprostinil to selexipag, and in three patients, selexipag was added as a third agent. Drug dosing was attained empirically based on patient body size. A follow-up catheterization was performed 12-18 months after initiation of selexipag therapy. All four patients tolerated selexipag well, without significant side effects. One patient transitioned successfully from subcutaneous treprostinil to selexipag. None of the four patients had clinical deterioration. In three patients who were able to perform a 6-minute walk test, pre and post selexipag distances were 350 and 400, 409 and 390, and 300 and 360 m, respectively. Echocardiograms showed no significant changes. Catheterization showed a variable change in pulmonary vascular resistance (small decrease in three patients and increase in one patient). Brain natriuretic peptide levels before and after selexipag in the four patients were 38 and 49, 33 and 54, 29 and 25, and 12 and 14 pg/mL, respectively. Selexipag use for 16-28 months was safe in four pediatric patients; none of them had clinical deterioration. Larger number of patients and longer follow-up intervals are necessary before further recommendations can be made.