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Bite force and gape are two important performance metrics of the feeding system, and these metrics are inversely related for a given muscle size because of fundamental constraints in sarcomere length-tension relationships. How these competing performance metrics change in developing primates is largely unknown. Here, we quantified in vivo bite forces and gapes across ontogeny and examined these data in relation to body mass and cranial measurements in captive tufted capuchins, Sapajus spp. Bite force and gape were also compared across geometric and mechanical properties of mechanically challenging foods to investigate relationships between bite force, gape and food accessibility (defined here as the ability to breach shelled nuts). Bite forces at a range of gapes and feeding behavioral data were collected from a cross-sectional ontogenetic series of 20 captive and semi-wild tufted capuchins at the Núcleo de Procriação de Macacos-Prego Research Center in Araçatuba, Brazil. These data were paired with body mass, photogrammetric measures of jaw length and facial width, and food geometric and material properties. Tufted capuchins with larger body masses had absolutely higher in vivo bite forces and gapes, and animals with wider faces had absolutely higher bite forces. Bite forces and gapes were significantly smaller in juveniles compared with subadults and adults. These are the first primate data to empirically demonstrate the gapes at which maximum active bite force is generated and to demonstrate relationships to food accessibility. These data advance our understanding of how primates meet the changing performance demands of the feeding system during development.
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Fuerza de la Mordida , Cráneo , Animales , Estudios Transversales , Conducta Alimentaria/fisiología , Sarcómeros , Fenómenos Biomecánicos , Maxilares/fisiologíaRESUMEN
BACKGROUND AND AIMS: Colorectal endoscopic vacuum therapy (CR EVT) is usually performed using sponges passed through the anus. It may be associated with patient discomfort and displacement of the aspiration tube. METHODS: With the tube-in-tube endoscopic vacuum therapy modification (CR TT-EVT), it is possible to position the aspiration tube in the pelvic cavity through the abdominal wall. In addition, it allows frequent cleaning of the fistula, eliminates the need for programmed device changes, and enables a standardized approach to such a wide variety of fistulas, leaks, and perforations. RESULTS: Here is a technical note on how to perform CR TT-EVT, while we are at the early phase of our case series we have reached 100% of technical success.
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Neoplasias Colorrectales , Terapia de Presión Negativa para Heridas , Humanos , Fuga Anastomótica/etiología , Fuga Anastomótica/cirugía , Endoscopía , Anastomosis QuirúrgicaRESUMEN
Leishmaniasis is a zoonosis caused by protozoan species of the genus Leishmania. It generates different clinical manifestations in humans and animals, and it infects multiple hosts. Leishmania parasites are transmitted by sandfly vectors. The main objective of this systematic review was to identify the host, or reservoir animal species, of Leishmania spp., with the exception of domestic dogs, that were recorded in Brazil. This review included identification of diagnostic methods, and the species of protozoan circulating in the country. For this purpose, a literature search was conducted across index journals. This study covered the period from 2001 to 2021, and 124 studies were selected. Eleven orders possible hosts were identified, including 229 mammalian species. Perissodactyla had the highest number of infected individuals (30.69%, 925/3014), with the highest occurrence in horses. In Brazil, the most commonly infected species were found to be: horses, domestic cats, rodents, and marsupials. Bats, that were infected by one or more protozoan species, were identified as potential reservoirs of Leishmania spp. Molecular tests were the most commonly used diagnostic methods (94 studies). Many studies have detected Leishmania spp. (n = 1422): Leishmania (Leishmania) infantum (n = 705), Leishmania (Viannia) braziliensis (n = 319), and Leishmania (Leishmania) amazonensis (n = 141). Recognizing the species of animals involved in the epidemiology and biological cycle of the protozoan is important, as this allows for the identification of environmental biomarkers, knowledge of Leishmania species can improve the control zoonotic leishmaniasis.
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Reservorios de Enfermedades , Leishmaniasis , Animales , Gatos , Perros , Humanos , Brasil/epidemiología , Reservorios de Enfermedades/parasitología , Leishmaniasis/diagnóstico , Leishmaniasis/epidemiología , Leishmaniasis/parasitología , Leishmaniasis/prevención & control , Leishmania , Zoonosis/epidemiología , Zoonosis/parasitología , Zoonosis/prevención & control , Mamíferos/parasitología , Especificidad del HuéspedRESUMEN
INTRODUCTION AND OBJECTIVES: Espírito Santo state is considered a region with a higher frequency of hepatitis B virus infection. This study characterized demographic, epidemiological, laboratory, virological and clinical aspects of 587 chronic HBV carriers followed up at the University of Espírito Santo Hospital. MATERIALS AND METHODS: Demographic, epidemiological, laboratory and clinical data were extracted from medical records during the entire follow-up period. Classification of the evolutionary phases of chronic hepatitis B was defined as immunotolerant; inactive carrier; chronic active hepatitis HBeAg (+) and HBeAg (-). Characterization of HBV genotypes/subgenotypes was performed by sequencing of overlapping surface antigens and HBV DNA polymerase genes. Phylogenetic relationships were determined using BEAST 1.8.3 software. RESULTS: and Conclusions: Genotypes found were A (132/65.3%) [A1 = 129 (63.9%) and A2 = 3 (1.5%)], D (66/32.7%) [D3 = 56 (27.7%), D4 = 8 (4.0%) and D2 = 2 (1.0%)] and F (4/2.0%) - all F2a. Subgenotypes A1 or D3 were not associated with age, sex, HIV/HCV co-infection, viral load, antiviral usage, HBeAg status or clinical stages of chronic hepatitis B. Mother -to-child-transmission (MTCT) was associated with the subgenotype A1 and intrafamilial transmission with subgenotype D3. Subgenotype A1 was more frequent than D3 among individuals born outside ES compared to those born in ES. CONCLUSIONS: The most predominant clinical phases were HBeAg (-), inactive carrier and chronic active hepatitis HBeAg (-). Subgenotypes A1 and D3 were most frequent and were associated were MTCT and intrafamilial transmission of HBV, respectively.
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Hepatitis B Crónica , Hepatitis B , ADN Viral/genética , Genotipo , Hepatitis B/diagnóstico , Hepatitis B/epidemiología , Antígenos de Superficie de la Hepatitis B/genética , Antígenos e de la Hepatitis B , Virus de la Hepatitis B , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/epidemiología , Humanos , FilogeniaRESUMEN
This study aimed to detect the occurrence of infection by Leishmania spp.in bats from 34 municipalities of Rio Grande do Sul state (RS; southern Brazil) from 2016 to 2021. A total of 109 bats were provided by the Centro Estadual de Vigilância em Saúde of RS, including six species belonged to Molossidae family, six to Vespertilionidae family, and two to Phyllostomidae family. Leishmania spp. was identified using the nested-PCR method by amplifying the SSU rDNA ribosomal subunit gene into four organ pools: (1) the liver, spleen, and lymph node; (2) heart and lungs; (3) skin; and (4) bone marrow of each bat. Three (3/109, 2.7%) animals tested positive for Leishmania spp. The respective PCR-positive organs came from pools 1 and 3. Two bats (Tadarida brasiliensis) were from the municipality of Canoas, and sequences analysis confirms the species identification as Leishmania infantum. In the third bat (Molossus molossus), from Rio Grande, it was not possible to determine the protozoa species, being considered Leishmania spp. Our results indicate that bats can participate in the biological cycle of Leishmania spp. and perform as host, reservoir, and/or source of infection of the protozoa in different areas of RS. More studies will be needed to elucidate the role of these Chiropteras in the circulation of Leishmania spp. This is the first study reporting the occurrence of Leishmania spp. in bats in Rio Grande do Sul state, southern Brazil.
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Quirópteros , Leishmania infantum , Animales , Brasil/epidemiología , Quirópteros/parasitología , ADN Ribosómico/genética , Leishmania infantum/genética , PrevalenciaRESUMEN
The accelerated growth of the automotive supply network has had an immeasurable impact on the environment, especially relating to reusing and disposal of materials. The appropriate management of End-of-Life Vehicles (ELV) has become an imperative item for achieving sustainable development in the field of interest and it is, therefore, a target of special attention from global economies in recent years. Therefore, the present study aims to estimate the future generation of ELVs to assist decision making and mitigate the global impact of this type of waste on the environment. For this, a hybrid forecasting model was used, based on Autoregressive Integrated Moving Average (ARIMA) methodology and on Artificial Neural Networks (ANN), with a set of temporal data extracted from Brazilian sectoral platforms. The results achieved point to a good convergence of the model, indicating better performance than a naive or trivial prediction. The efficiency obtained by the Nash-Sutcliffe coefficient was 98% and the expectation is that for the year 2030, approximately 5.2 million ELVs will be produced in Brazil, of which only 78 thousand units would be effectively recycled, considering the current vehicle recycling rate in the country. Considering the scarcity of information that supports decision-making in waste management in Brazil, this study may also contribute to the proposition of alternatives that favor the proper management of automotive waste, providing a reference for the formulation and implementation of policies related to ELVs in the country.
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Administración de Residuos , Brasil , Predicción , Redes Neurales de la Computación , Reciclaje/métodos , Administración de Residuos/métodosRESUMEN
BACKGROUND: Endoscopic sleeve gastroplasty (ESG) is an option for patients with Class I and II obesity or patients who refuse to undergo a laparoscopic bariatric surgery. The aims of this study are as follows: (1) to demonstrate a short-term outcome after primary ESG and (2) to compare the effectiveness of weight loss between Class I and Class II obesity patients. METHODS: Patients undergoing ESG at four bariatric centers in Brazil between April 1, 2017 and December 31, 2018 were prospectively enrolled in the study (BMI 30.0-39.9 kg/m2). ESG was performed using Overstitch (Apollo Endosurgery, Austin, TX). Descriptive analysis, t test, Chi-square test, and Mann-Whitney test were used to present the results. RESULTS: A total of 233 patients underwent primary ESG. The mean age and BMI of the patients were 41.1 years and 34.7 kg/m2, respectively. Following ESG, the mean percentage of total weight loss (TWL) was 17.1% at 6 months and 19.7% at 12 months. Percentage of excess BMI loss (EBMIL) was 47.3% at 6 months and 54.8% at 12 months after ESG. The mean EBMIL was significantly greater among patients with Class I obesity than those with Class II obesity at 6 (51.1% vs. 43.7%) and 12 months (60.2% vs. 49.2%). One patient experienced bleeding during the procedure that was managed with sclerotherapy. CONCLUSION: Short-term results suggest that ESG is a safe and effective option for patients with Class I and II obesity.
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Endoscopía , Gastroplastia/efectos adversos , Adulto , Cirugía Bariátrica , Índice de Masa Corporal , Brasil , Femenino , Gastroplastia/métodos , Humanos , Masculino , Obesidad/cirugía , Factores de Tiempo , Resultado del Tratamiento , Pérdida de PesoAsunto(s)
Fístula , Fístula Rectal , Humanos , Colgajos Quirúrgicos , Recto/cirugía , Fístula Rectal/cirugía , Resultado del TratamientoRESUMEN
INTRODUCTION: Nonsyndromic primary failure of eruption (PFE) is a rare autosomal dominant disorder of dental eruption with no obvious dental or soft tissue interference. The purposes of this study were to genetically and clinically characterize a family with many members affected by PFE and to describe the natural evolution of the disorder. METHODS: Three generations of a family with 18 members, 10 of them clinically affected by PFE, were evaluated periodically during 20 years of clinical follow-up. PFE was observed in varying degrees of severity in both sexes. Clinical presentation became more severe in adulthood. One patient had spontaneous reeruption of 2 posterior teeth. Cervical root resorptions were observed in 3 members. Genetic analysis showed a deleterious heterozygous mutation in intron 9 of the PTH1R gene (c.639-2A>G) and diagnosed an additional affected member. CONCLUSIONS: The long-term follow-up of PFE cases in this family permitted the following observations: (1) the onset occurred from the preemergence to the postemergence phases, (2) PFE appeared to be closely related to ankylosis, (3) affected teeth maintained the eruptive potential even in adulthood, (4) the earlier the onset the more severe the open bite, and (5) cervical root resorptions occurred in 3 affected members.
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Anquilosis del Diente/genética , Erupción Dental/genética , Adolescente , Adulto , Femenino , Estudios de Seguimiento , Humanos , Intrones , Masculino , Mutación , Extrusión Ortodóncica , Ortodoncia Correctiva , Linaje , Receptor de Hormona Paratiroídea Tipo 1RESUMEN
BACKGROUND: Rift Valley fever virus (RVFV) remains heavily neglected in humans in Mozambique, even though recent outbreaks were reported in neighboring countries in humans and several cases of RVFV in cattle were reported in several districts in Mozambique. FINDINGS: We conducted a cross sectional study during and after severe flooding that occurred in 2013 in Mozambique. Paired acute and convalescent serum samples were tested from febrile patients attending a primary health care unit in a suburban area of Maputo city for the presence of IgG and IgM antibodies against Rift Valley fever virus (RVFV) using enzyme-linked immunosorbent assay (ELISA). Seroconversion of IgG anti-RVFV was observed in 5 % (10/200) of convalescent patients and specific IgM anti-RVFV was detected in one acute patient (0.5 %; 1/200). All sera from acute patient tested negative by real time PCR. CONCLUSION: In conclusion, our results suggest that RVF represent an important but neglected cause of febrile illness following periods of flooding in southern Mozambique.
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Anticuerpos Antivirales/sangre , Fiebre/epidemiología , Fiebre/etiología , Fiebre del Valle del Rift/diagnóstico , Fiebre del Valle del Rift/epidemiología , Virus de la Fiebre del Valle del Rift/inmunología , Pruebas Serológicas , Adulto , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Femenino , Inundaciones , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Masculino , Mozambique/epidemiología , ARN Viral/sangre , Lluvia , Reacción en Cadena en Tiempo Real de la Polimerasa , Virus de la Fiebre del Valle del Rift/genética , Adulto JovenRESUMEN
AIM: To describe the sequential healing of open extraction sockets at which no attempts to obtain a primary closure of the coronal access to the alveolus have been made. MATERIAL AND METHODS: The third mandibular premolar was extracted bilaterally in 12 monkeys, and no sutures were applied to close the wound. The healing after 4, 10, 20, 30, 90 and 180 days was morphometrically studied. RESULTS: After 4 days of healing, a blood clot mainly occupied the extraction sockets, with the presence of an inflammatory cells' infiltrate. A void was confined in the central zones of the coronal and middle regions, in continuity with the entrance of the alveoli. At 10 days, the alveolus was occupied by a provisional matrix, with new bone formation lining the socket bony walls. At 20 days, the amount of woven bone was sensibly increasing. At 30 days, the alveolar socket was mainly occupied by mineralized immature bone at different stages of healing. At 90 and 180 days, the amount of mineralized bone decreased and substituted by trabecular bone and bone marrow. Bundle bone decreased from 95.5% at 4 days to 7.6% at 180 days, of the whole length of the inner alveolar surface. CONCLUSIONS: Modeling processes start from the lateral and apical walls of the alveolus, leading to the closure of the socket with newly formed bone within a month from extraction. Remodeling processes will follow the previous stages, resulting in trabecular and bone marrow formation and in a corticalization of the socket access.
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Alveolo Dental/fisiología , Cicatrización de Heridas/fisiología , Animales , Diente Premolar/cirugía , Cebus , Masculino , Mandíbula/cirugía , Extracción DentalRESUMEN
BACKGROUND: Circumcision is a protective measure against sexually transmitted infections (STIs), reducing the risk of HIV infection. This study reported coverage of male circumcision and assessed the factors associated with male uncircumcision in a peri-urban area in Maputo City, Mozambique. METHODS: This cross-sectional study of the Health Demographic Surveillance System in the Polana Caniço neighborhood investigated the sociodemographic and behavioral factors associated with uncircumcised males aged 15-49 y from October 2019 to June 2021. Data were collected from an HIV risk factors questionnaire and descriptive analyses conducted comparing self-reported male circumcision status by sociodemographic factors and sexual behaviors. The association was assessed via χ2 tests, and a multivariable logistic regression model was constructed. Adjusted ORs and 95% CIs were reported for factors associated with uncircumcised status. RESULTS: Of the 3481 males aged 15-49 y who responded to the questionnaire, 79.5% (2766) self-reported being circumcised. The percentage of uncircumcised men steadily increased with age, ranging from 12.4% (95) among males aged 15-19 y to 34.5% (148) of men aged 40-49 y. Men without education or with primary education, as well as those not practicing Islam, were 3-4 times more likely to be uncircumcised. Uncircumcised men were more likely to self-report an STI and a lack of condom use. CONCLUSIONS: Being uncircumcised was associated with not using condoms and having STIs, highlighting the need to further emphasize combination HIV-prevention programs and regular HIV/STI screening. Targeting males with lower education and across religions can help reach those with lower coverage of this effective prevention intervention.
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Climate change poses severe consequences, particularly in sub-Saharan Africa, where poverty rates may escalate by 2050 without significant climate and development action. The health impacts are diverse, encompassing communicable and non-communicable diseases. Mozambique, a climate-vulnerable nation, has experienced significant natural disasters in the past 42 years, impacting its health system. This study aims to assess Mozambique's health sector's vulnerability and adaptation needs to climate change. Following a methodology proposed by the World Health Organization and the Intergovernmental Panel for Climate Change, a six-step vulnerability and adaptation assessment was conducted to conduct the Health Vulnerability Index (HVI) for Mozambique's regions (n=161). The HVI integrates historical climate, epidemiological, and socio-economic data at the district level, and was computed using exposure, sensitivity, and adaptive capacity dimensions. The results revealed spatial patterns in exposure to climate variables, extreme weather events, and variations in sensitivity and adaptive capacity across the country. The HVI mirrored the exposure findings. Notably, high vulnerability was observed in several districts, while major urban centers displayed lower vulnerability. These findings highlight the country's vulnerability to climate change and underscore the potential for adverse impacts on livelihoods, the economy, and human health. The study provides a foundation for developing strategies and adaptation actions.
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Cambio Climático , Mozambique , Humanos , Poblaciones VulnerablesRESUMEN
Anaplasmosis, transmitted biologically and mechanically, is one of the most prevalent diseases responsible for high production costs worldwide. In this research, the prevalence and risk factors of anaplasmosis in Simmental cattle raised in the Peruvian Amazon were evaluated. 266 blood samples were collected from bovines of different categories such as calves male, calves females, heifers <1.3 years, heifers >1.3 years, steers, bulls, and cows from the districts of Omia and Molinopampa. The enzyme-linked immunosorbent assay (ELISA) technique was used to detect antibodies against Anaplasma marginale. Of the 266 animals sampled, 67% were positive for A. marginale. A higher prevalence was determined in the district of Omia (99.3%), while in the district of Molinopampa, 28.7% was obtained. A prevalence of A. marginale was recorded in females (67.7%) and in males (64.8%) (p > 0.05). There is a significant association of the disease with the category of cattle, verifying the highest prevalence of A. marginale in calves male, heifer >1.3 years, and bull. The multiple correspondence analysis shows that San Mateo, Puma Marca, Mashuyacu, Primavera, and Los Olivos have a higher prevalence of anaplasmosis, associated with altitude of 1701-2000 m, spray baths and paddock rotation. Anaplasmosis is prevalent in Simmental cattle from the Peruvian Amazon, with a higher incidence in Omia and in females, considering May to August the critical months and the altitude less than 2000 meters above sea level.
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OBJECTIVES: Cortical bone geometry is commonly used to investigate biomechanical properties of primate mandibles. However, the ontogeny of these properties is less understood. Here we investigate changes in cortical bone cross-sectional properties throughout capuchin ontogeny and compare captive versus wild, semi-provisioned groups. Tufted capuchins (Sapajus spp.) are known to consume relatively hard/tough foods, while untufted capuchins (Cebus spp.) exploit less mechanically challenging foods. Previous research indicates dietary differences are present early in development and adult Sapajus mandibles can resist higher bending/shear/torsional loads. MATERIALS AND METHODS: This study utilized microCT scans of 22 Cebus and 45 Sapajus from early infancy to adulthood from three sample populations: one captive Cebus, one captive Sapajus, and one semi-provisioned, free-ranging Sapajus. Mandibular cross-sectional properties were calculated at the symphysis, P3, and M1. If the tooth had not erupted, its position within the crypt was used. A series of one-way ANOVAs were performed to assess differences between and within the sample populations. RESULTS: Mandible robusticity increases across ontogeny for all three sample populations. Sapajus were better able to withstand bending and torsional loading even early in ontogeny, but no difference in shear resistance was found. Semi-provisioned, free-ranging Sapajus tend to show increased abilities to resist bending and torsional loading but not shear loading compared to captive Sapajus. DISCUSSION: This study helps advance our understanding of the primate masticatory system development and opens the door for further studies into adaptive plasticity in shaping the masticatory apparatus of capuchins and differences in captive versus free-ranging sample populations.
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Introduction: Chronic anxiety is a statemarked by sustained activation of the masseter muscle, manifesting in both mental and physical strain. This prolonged tension can significantly impact mental wellbeing and cognitive abilities, posing a risk for a range of health complications. This double-blind, randomized, controlled clinical trial investigated the impact of transcutaneous auricular vagus nerve stimulation (TAVNS) on masseter muscle activity, pressure pain threshold (PPT), and anxiety levels in university students with elevated anxiety. Methods: Forty-two participants meeting inclusion criteria were randomly assigned to either active TAVNS or sham TAVNS groups. Various parameters, including masseter muscle electromyographic (EMG) signals, PPT, and Beck Anxiety Inventory (BAI) scores, were assessed before pretreatment, immediately after the intervention week, and 2 weeks follow-up. Results: Active TAVNS significantly reduced both left and right masseter activation during resting mandibular position, persisting for 2 weeks post-intervention. Additionally, TAVNS induced a lasting decrease in both left and right masseter PPT, indicative of altered pain perception. Notably, BAI scores showed a substantial reduction, emphasizing TAVNS as a potential intervention for anxiety, with effects maintained at the 2-week follow-up. Discussion: This study provides comprehensive insights into the multifaceted effects of TAVNS on physiological and psychological aspects associated with anxiety in university students. The promising results underscore TAVNS as a potential neuromodulatory intervention for anxiety-related conditions, warranting further research and clinical exploration. Clinical Trial Registration: https://ensaiosclinicos.gov.br/rg/RBR-4s4kt2r.
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BACKGROUND: Low-and-middle-income countries (LMICs) bear a disproportionate burden of communicable diseases. Social interaction data inform infectious disease models and disease prevention strategies. The variations in demographics and contact patterns across ages, cultures, and locations significantly impact infectious disease dynamics and pathogen transmission. LMICs lack sufficient social interaction data for infectious disease modeling. METHODS: To address this gap, we will collect qualitative and quantitative data from eight study sites (encompassing both rural and urban settings) across Guatemala, India, Pakistan, and Mozambique. We will conduct focus group discussions and cognitive interviews to assess the feasibility and acceptability of our data collection tools at each site. Thematic and rapid analyses will help to identify key themes and categories through coding, guiding the design of quantitative data collection tools (enrollment survey, contact diaries, exit survey, and wearable proximity sensors) and the implementation of study procedures. We will create three age-specific contact matrices (physical, nonphysical, and both) at each study site using data from standardized contact diaries to characterize the patterns of social mixing. Regression analysis will be conducted to identify key drivers of contacts. We will comprehensively profile the frequency, duration, and intensity of infants' interactions with household members using high resolution data from the proximity sensors and calculating infants' proximity score (fraction of time spent by each household member in proximity with the infant, over the total infant contact time) for each household member. DISCUSSION: Our qualitative data yielded insights into the perceptions and acceptability of contact diaries and wearable proximity sensors for collecting social mixing data in LMICs. The quantitative data will allow a more accurate representation of human interactions that lead to the transmission of pathogens through close contact in LMICs. Our findings will provide more appropriate social mixing data for parameterizing mathematical models of LMIC populations. Our study tools could be adapted for other studies.
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Países en Desarrollo , Humanos , Mozambique , Guatemala/epidemiología , Pakistán/epidemiología , India/epidemiología , Grupos Focales , Femenino , Lactante , Interacción Social , Masculino , Enfermedades Transmisibles/epidemiología , Enfermedades Transmisibles/transmisión , Población Rural , Proyectos de InvestigaciónRESUMEN
Cellular senescence affects many physiological and pathological processes and is characterized by durable cell cycle arrest, an inflammatory secretory phenotype and metabolic reprogramming. Here, by using dynamic transcriptome and metabolome profiling in human fibroblasts with different subtypes of senescence, we show that a homoeostatic switch that results in glycerol-3-phosphate (G3P) and phosphoethanolamine (pEtN) accumulation links lipid metabolism to the senescence gene expression programme. Mechanistically, p53-dependent glycerol kinase activation and post-translational inactivation of phosphate cytidylyltransferase 2, ethanolamine regulate this metabolic switch, which promotes triglyceride accumulation in lipid droplets and induces the senescence gene expression programme. Conversely, G3P phosphatase and ethanolamine-phosphate phospho-lyase-based scavenging of G3P and pEtN acts in a senomorphic way by reducing G3P and pEtN accumulation. Collectively, our study ties G3P and pEtN accumulation to controlling lipid droplet biogenesis and phospholipid flux in senescent cells, providing a potential therapeutic avenue for targeting senescence and related pathophysiology.
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Glicerol , Glicerofosfatos , Metabolismo de los Lípidos , Humanos , Glicerol/metabolismo , Etanolaminas , FosfatosRESUMEN
Cellular senescence is a cell fate that prominently impacts physiological and pathophysiological processes. Diverse cellular stresses induce it, and dramatic gene expression changes accompany it. However, determining the interactions comprising the gene regulatory network (GRN) governing senescence remains challenging. Recent advances in signal processing techniques provide opportunities to reconstruct GRNs. Here, we describe a GRN for senescence integrating time-series transcriptome and transcription factor depletion datasets. Specifically, we infer a set of differential equations using the "Sparse Identification of Nonlinear Dynamics" (SINDy) algorithm, discriminate genes with potential hidden regulators, validate the inferred GRN for time-points not included in the training data, and comprehensively benchmark our approach. Our work is a proof of concept for a data-driven GRN reconstruction method, consolidating an iterative, powerful mathematical platform for senescence modeling that can be used to test hypotheses in silico and has the potential for future discoveries of clinical impact.