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The Atlantic Forest Biome (AFB) creates an ideal environment for the proliferation of vector mosquitoes, such as Haemagogus and Sabethes species, which transmit the Yellow Fever virus (YFV) to both human and non-human primates (NHP) (particularly Alouatta sp. and Callithrix sp.). From 2016 to 2020, 748 fatal cases of YF in humans and 1,763 in NHPs were reported in this biome, following several years free from the disease. This underscores the imminent risk posed by the YFV. In this study, we examined the spatiotemporal distribution patterns of YF cases in both NHPs and humans across the entire AFB during the outbreak period, using a generalized linear mixed regression model (GLMM) at the municipal level. Our analysis examined factors associated with the spread of YFV, including environmental characteristics, climate conditions, human vaccination coverage, and the presence of two additional YFV-affected NHP species. The occurrence of epizootics has been directly associated with natural forest formations and the presence of species within the Callithrix genus. Additionally, epizootics have been shown to be directly associated with human prevalence. Furthermore, human prevalence showed an inverse correlation with urban areas, temporary croplands, and savannah and grassland areas. Further analyses using Moran's Index to incorporate the neighborhoods of municipalities with cases in each studied host revealed additional variables, such as altitude, which showed a positive correlation. Additionally, the occurrence of the disease in both hosts exhibited a spatio-temporal distribution pattern. To effectively mitigate the spread of the virus, it is necessary to proactively expand vaccination coverage, refine NHP surveillance strategies, and enhance entomological surveillance in both natural and modified environments.
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Bosques , Mosquitos Vectores , Fiebre Amarilla , Virus de la Fiebre Amarilla , Fiebre Amarilla/epidemiología , Fiebre Amarilla/transmisión , Animales , Humanos , Brasil/epidemiología , Mosquitos Vectores/virología , Clima , Brotes de Enfermedades , EcosistemaRESUMEN
Neoadjuvant pembrolizumab plus chemotherapy (P + CT) has emerged as a standard of care for stage II-III triple-negative breast cancer (TNBC). However, the best anthracycline-cyclophosphamide (AC) schedule remains to be determined. While the KEYNOTE-522 regimen employs AC every 3 weeks (q3w AC), previous studies have shown overall survival benefits of dose-dense regimens for early-stage breast cancer. The Neo-Real study (GBECAM-0123) is a real-world data effort evaluating patients with TNBC treated with neoadjuvant P + CT in ten cancer centers since July 2020. The objective of this analysis was to evaluate the effectiveness and safety of dose-dense AC (ddAC) versus q3w AC. Among 333 patients included until November 2023, 311 completed neoadjuvant therapy and 279 underwent surgery with pathology reports available; ddAC was used in 58.2% and q3w AC in 41.8% of the cases. Most patients (69.1%) had stage II TNBC. A pCR was observed in 65.4% with ddAC and 58.7% with q3w AC (P = 0.260), while RCB 0-1 occurred in 82.4% and 73.5%, respectively (P = 0.115). Patients with stage III disease had a numerically higher pCR with ddAC (59% vs 40%, P = 0.155), while pCR rates were similar regardless of AC regimen in stage II disease (66.6% vs 64.5%; P = 0.760). While no significant disparities in drug discontinuation was noted, ddAC showed a trend towards higher rates of grade ≥3 AE (40.5% vs. 30.7%, P = 0.092). The Neo-Real study could not rule out a difference between ddAC and q3w AC during neoadjuvant P + CT. The observation of a potentially higher pCR with ddAC in stage III disease warrants further investigation.
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PURPOSE: Most patients with cancer will be hospitalized throughout the disease course. However, most evidence on the causes and outcomes of these hospitalizations comes from administrative data or small retrospective studies from high-income countries. METHODS: This study is a retrospective cohort of patients with solid tumors hospitalized from February 1, 2021, to December 31, 2021, in a tertiary cancer center in São Paulo, Brazil. We collected data on cancer diagnosis, symptoms at admission, hospitalization diagnosis, and survival clinical outcomes during in-hospital stay (in-hospital mortality) and after discharge (readmission rates and overall survival [OS]). Progressive disease (PD) diagnosis during admission was retrieved from manual chart review if explicitly stated by the attending physician. We modeled in-hospital mortality and postdischarge OS with logistic regression and Cox proportional hazards models, respectively. RESULTS: A total of 3,726 unique unplanned admissions were identified. The most common symptoms at admission were pain (40.6%), nausea (16.8%), and dyspnea (16.1%). PD (34.0%), infection (31.1%), and cancer pain (13.4%) were the most frequent reasons for admission. The in-hospital mortality rate was 18.9%. Patients with PD had a high in-hospital mortality rate across all tumor groups and higher odds of in-hospital death (odds ratio, 3.5 [95% CI, 3.0 to 4.2]). The 7-, 30-, and 90-day readmission rates were 11.9%, 33.5%, and 54%, respectively. The postdischarge median OS (mOS) was 12.6 months (95% CI, 11.6 to 13.7). Poorer postdischarge survival was observed among patients with PD (mOS, 5 months v 18 months; P < .001; hazard ratio, 2.4 [95% CI, 2.1 to 2.6]). CONCLUSION: PD is a common diagnosis during unplanned hospitalizations and is associated with higher in-hospital mortality rates and poorer OS after discharge. Oncologists should be aware of the prognostic implications of PD during admission and align goals of care with their patients.
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Mortalidad Hospitalaria , Hospitalización , Neoplasias , Humanos , Neoplasias/mortalidad , Neoplasias/terapia , Neoplasias/epidemiología , Brasil/epidemiología , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Hospitalización/estadística & datos numéricos , Progresión de la Enfermedad , Adulto , Readmisión del Paciente/estadística & datos numéricosRESUMEN
Herpesviruses are significant pathogens of ruminants. In water buffaloes (Bubalus bubalis), however, herpesviruses have not been thoroughly studied. Although bubaline alphaherpesvirus 1 (BuAHV1) and bovine alphaherpesvirus 1 (BoAHV1) have already been recovered from water buffaloes, to date, no reports on the occurrence of bovine alphaherpesvirus 5 (BoAHV5) in these animals have been published. Therefore, the aim of this study was to search for BuAHV1, BoAHV1, and BoAHV5 in palatine tonsils of apparently healthy water buffaloes from the Pará state, Northern Brazil. Tissue samples of tonsils (n = 293) were screened by a nested PCR (nPCR) targeting a region of UL44 (gC coding gene), followed by sequencing, to detect and differentiate between the viral types. Viral genome segments were detected in 18 out of 293 (6.1%) of the palatine tonsil samples. Two animals carried genomes of BoAHV1 only, eleven animals carried BoAHV5 genomes only, and four animals carried BuAHV1 only. Another animal had both BoAHV1 and BoAHV5 genomes in its tonsils. No infectious virus could be recovered from any of the samples. The BuAHV1 sequences identified here were more closely related to BuAHV1 genomes identified in India. Phylogenetic analyses suggested a closer relationship between the recovered BoAHV5 and BuAHV1 genomes. Therefore, evidence is provided here to confirm that not only BoAHV1 and BuAHV1, but also BoAHV5, can infect water buffaloes. This report highlights (i) the first detection of BoAHV5 in water buffaloes and (ii) the occurrence of coinfections with BoAHV1 and BoAHV5 in that species. Such findings and the similarity of BoAHV5 to Indian herpesvirus genomes suggest that the origin of type 5 may be linked to recombinations between bovine and bubaline herpesviruses within bubalines, since the scenario for generation of recombinants in buffaloes is potentially present.
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Alphaherpesvirinae , Búfalos , Infecciones por Herpesviridae , Tonsila Palatina , Animales , Bovinos , Alphaherpesvirinae/genética , Alphaherpesvirinae/aislamiento & purificación , Alphaherpesvirinae/clasificación , Brasil , ADN Viral/genética , Genoma Viral , Infecciones por Herpesviridae/veterinaria , Infecciones por Herpesviridae/virología , Tonsila Palatina/virología , Filogenia , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADNRESUMEN
A Collapsible Light Trap (CLT) for collecting insects, particularly aquatic insects, is described here. CLT is a modified Pennsylvania Light Trap with the advantage of being collapsible and lightweight to be carried in a small backpack and very easy to set up in the field. CLT is equipped with LED light strip wrapped around a PVC tube and can be connected to a regular 12 V / 7 Ah battery, running for more than 48 uninterrupted hours. Complete CLT weighs 0.8-1.0 kg, depending on the metal used, and the battery weighs around 2 kg, being easily transportable to more remote collecting areas. Over the years, CLTs have been used for collecting and describing the diversity of aquatic insects from Brazil, particularly caddisflies. Depending on the locality, only one trap for one night can collect over a thousand insect specimens and more than 200 individuals of caddisflies.
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Insectos , Animales , Insectos/clasificación , Brasil , Luz , Diseño de EquipoRESUMEN
Low-pass whole genome sequencing (LP-WGS) has been applied as alternative method to detect copy number variants (CNVs) in the clinical setting. Compared with chromosomal microarray analysis (CMA), the sequencing-based approach provides a similar resolution of CNV detection at a lower cost. In this study, we assessed the efficiency and reliability of LP-WGS as a more affordable alternative to CMA. A total of 1363 patients with unexplained neurodevelopmental delay/intellectual disability, autism spectrum disorders, and/or multiple congenital anomalies were enrolled. Those patients were referred from 15 nonprofit organizations and university centers located in different states in Brazil. The analysis of LP-WGS at 1x coverage (>50kb) revealed a positive testing result in 22% of the cases (304/1363), in which 219 and 85 correspond to pathogenic/likely pathogenic (P/LP) CNVs and variants of uncertain significance (VUS), respectively. The 16% (219/1363) diagnostic yield observed in our cohort is comparable to the 15%-20% reported for CMA in the literature. The use of commercial software, as demonstrated in this study, simplifies the implementation of the test in clinical settings. Particularly for countries like Brazil, where the cost of CMA presents a substantial barrier to most of the population, LP-WGS emerges as a cost-effective alternative for investigating copy number changes in cytogenetics.
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Variaciones en el Número de Copia de ADN , Secuenciación Completa del Genoma , Humanos , Variaciones en el Número de Copia de ADN/genética , Secuenciación Completa del Genoma/economía , Secuenciación Completa del Genoma/métodos , Brasil , Masculino , Femenino , Niño , Discapacidad Intelectual/genética , Discapacidad Intelectual/diagnóstico , Análisis Costo-Beneficio , Análisis por Micromatrices/economía , Análisis por Micromatrices/métodos , Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/diagnóstico , Preescolar , Anomalías Múltiples/genética , Anomalías Múltiples/diagnóstico , Países en Desarrollo , Adolescente , Trastornos del Neurodesarrollo/genética , Trastornos del Neurodesarrollo/diagnóstico , Pruebas Genéticas/economía , Pruebas Genéticas/métodosRESUMEN
Detection of Salmonella sp. is important for the broiler chicken production chain because it is one microorganisms involved in food-borne diseases. Thus, this study performed the optimization of a technique of Loop-mediated isothermal DNA amplification (LAMP) through the 3MTM Molecular Detection Assay 2: Salmonella (MDS®), in accordance with Ordinance number 126 of the Ministry of Agriculture, for the detection of Salmonella sp. in drag swab. The methodology followed ISO 16140-2: 2016, with the analysis naturally contaminated drag swab samples collected from broiler aviaries and artificially contaminated with salmonella ATCCs. Of the 300 samples processed in protocol A (pre-enrichment tetrathionate broth (TT)), 45 were positive for Salmonella sp., 242 negative, one false-positive, and 12 false-negative, while of the 300 samples analyzed in protocol B (pre-enrichment brain-heart infusion broth (BHI)), 40 were positive, 256 negative, one false-positive, and three false-negative. The result for protocol A was a sensitivity of 79%, specificity of 99.6%, Positive Predictive Value (PPV) of 98%, and Negative Predictive Value (NPV) of 95%; and for protocol B, 93% sensitivity, 99.6% specificity, 98% PPV, and 99% NPV. Both protocols were associated with the reference method (p>0.05), concluding that the MDS® can be used for the qualitative detection of Salmonella sp.
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Pollos , Técnicas de Amplificación de Ácido Nucleico , Salmonella , Sensibilidad y Especificidad , Salmonella/aislamiento & purificación , Salmonella/genética , Animales , Técnicas de Amplificación de Ácido Nucleico/métodos , Pollos/microbiología , Técnicas de Diagnóstico Molecular/métodos , Salmonelosis Animal/diagnóstico , Salmonelosis Animal/microbiología , ADN Bacteriano/análisis , Reproducibilidad de los ResultadosRESUMEN
Slaughterhouse inspections play a crucial role in the sanitary control of zoonoses and foodborne diseases. This study aimed to identify and analyze the frequencies of lymph node diseases in cattle slaughtered for human consumption, using the samples sent to the anatomic pathology service of the Federal Laboratory for Agricultural Defense (Laboratório Federal de Defesa Agropecuária), Minas Gerais, Brazil, from January 2015 to September 2022. In total, 2000 lymph node samples were analyzed, and additional information was individually retrieved. Lesions were most frequently identified in thoracic lymph nodes. Bacterial isolation and quantitative polymerase chain reaction (qPCR) were performed using samples suspected of tuberculosis. Tuberculosis cases accounted for 89.3% of the samples. Histopathology was more sensitive than other ancillary tests for diagnosing tuberculosis. Paraffin-embedded tissues from lymphoma cases were subjected to immunophenotyping using anti-CD3 and anti-CD79a immunohistochemistry. Frozen and/or paraffin-embedded tissues from lymphoma cases were used to identify the enzootic bovine leukosis (EBL) retrovirus through qPCR. Other diagnoses included primary (T- and B-cell lymphoma) and metastatic neoplasms (squamous cell carcinoma, pulmonary adenocarcinoma, undifferentiated carcinoma, undifferentiated adenocarcinoma, undifferentiated sarcoma, undifferentiated round cell tumor, mesothelioma, hepatic carcinoid, meningioma, and seminoma), actinogranulomas (pyogranulomatous lymphadenitis [actinobacillosis and actinomycosis]), idiopathic lymphadenitis (neutrophilic and/or histiocytic, granulomatous, and suppurative), and miscellaneous nonspecific lymphadenopathies (depletion/lymphoid atrophy, lymphangiectasia, erythrocyte drainage, parasitic eosinophilic lymphadenitis, follicular hyperplasia, and toxic granulomatous lymphadenitis). The combination of histopathology with complementary techniques is important for successful diagnosis, especially in complex cases of high epidemiological, economic, and zoosanitary importance, such as tuberculosis and EBL.
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This systematic review and meta-analysis aimed to assess the effects of pre and intraoperative lidocaine infusion on short-term recovery quality after laparoscopic bariatric surgeries. In the search across MEDLINE, Embase, and Cochrane databases, we considered randomized controlled trials comparing intravenous lidocaine vs placebo (saline) for patients with obesity undergoing laparoscopic bariatric surgery. Seven studies (640 patients) were included. The lidocaine group had a significantly higher recovery quality score, a lower morphine consumption, and a notably reduced rate of nausea and vomiting compared with the placebo group. Additionally, Lidocaine infusion was associated with a shorter hospital stay, while no significant difference was observed in the time to bowel function recovery between both groups. In conclusion, lidocaine infusion before and during laparoscopic bariatric surgery contributes to an enhanced quality of recovery.
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Anestésicos Locales , Cirugía Bariátrica , Laparoscopía , Tiempo de Internación , Lidocaína , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Anestésicos Locales/administración & dosificación , Anestésicos Locales/uso terapéutico , Infusiones Intravenosas , Tiempo de Internación/estadística & datos numéricos , Lidocaína/administración & dosificación , Lidocaína/uso terapéutico , Obesidad Mórbida/cirugía , Dolor Postoperatorio/tratamiento farmacológico , Náusea y Vómito Posoperatorios/prevención & control , Recuperación de la Función/efectos de los fármacos , Resultado del TratamientoRESUMEN
To date, the presence of pulmonary organs in the fossil record is extremely rare. Among extant vertebrates, lungs are described in actinopterygian polypterids and in all sarcopterygians, including coelacanths and lungfish. However, vasculature of pulmonary arteries has never been accurately identified neither in fossil nor extant coelacanths due to the paucity of fossil preservation of pulmonary organs and limitations of invasive studies in extant specimens. Here we present the first description of the pulmonary vasculature in both fossil and extant actinistian, a non-tetrapod sarcopterygian clade, contributing to a more in-depth discussion on the morphology of these structures and on the possible homology between vertebrate air-filled organs (lungs of sarcopterygians, lungs of actinopterygians, and gas bladders of actinopterygians).
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Evolución Biológica , Peces , Fósiles , Arteria Pulmonar , Animales , Arteria Pulmonar/anatomía & histología , Peces/anatomía & histología , Vertebrados/anatomía & histología , Pulmón/irrigación sanguínea , FilogeniaRESUMEN
BACKGROUND: Anabolic androgenic steroids (AAS) are traditionally used for the treatment/control of various diseases; however, they are being used for non-therapeutic and indiscriminate purposes to enhance sports performance and physical appearance. This study aimed to assess the prevalence and associated factors of AAS use among professional CrossFit® competitors. METHODS: We conducted an observational cross-sectional survey in which an anonymous questionnaire was applied to professional CrossFit® athletes. RESULTS: The prevalence of AAS usage was 33.3%. Most users were male (74.2%), aged between 30 and 39 years (51.6%), with completed higher education (83.9%), and had been training for more than 5 years (77.4%); the primary motivation for AAS use was performance enhancement (77.4%). Individuals who were older (p < 0.05) and more experienced in competitions (p < 0.01) are more likely to use AAS. Testosterone was the most employed AAS (71.0%); CrossFit® athletes typically used an average of 2 different AAS. The majority of users had notably sought advice from a physician (74.2%), and AAS were acquired from either drugstores (80.6%) or through illicit channels (29.0%). Moreover, 61.3% of AAS users reported experiencing adverse effects. CONCLUSIONS: Our results demonstrated a higher prevalence of AAS users among professional competitors in CrossFit® compared to the general population; older age and greater experience in official competitions were decisive factors for a greater inclination toward AAS use. A significant percentage of athletes seek drugs through illegal channels. Despite the majority of users experiencing adverse effects, athletes report satisfaction with use, believing that the benefits still outweigh the drawbacks.
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Anabolizantes , Atletas , Doping en los Deportes , Motivación , Humanos , Masculino , Adulto , Femenino , Estudios Transversales , Atletas/psicología , Atletas/estadística & datos numéricos , Anabolizantes/efectos adversos , Doping en los Deportes/psicología , Doping en los Deportes/estadística & datos numéricos , Adulto Joven , Congéneres de la Testosterona/efectos adversos , Persona de Mediana Edad , Encuestas y Cuestionarios , Prevalencia , Esteroides Anabólicos AndrogénicosRESUMEN
Recent studies have found increased cardiovascular mortality risk in patients with type 1 diabetes when compared to normoglycemic people, even when they were kept under good glycemic control. However, the mechanisms underlying this condition have yet to be fully understood. Using streptozotocin (STZ)-induced diabetic rats, we evaluated the effects of insulin replacement therapy on cardiac, autonomic, inflammatory, and oxidative stress parameters. Daily treatment with insulin administrated subcutaneously in the STZ-diabetic rats showed a reduction in hyperglycemia (>250 mg/dL) to normalized values. The insulin treatment was effective in preventing alterations in cardiac morphometry and systolic function but had no impact on diastolic function. Also, the treatment was not able to prevent the impairment of baroreflex-tachycardic response and systolic arterial pressure variability (SAP-V). A correlation was found between improvement of these autonomic parameters and higher levels of IL-10 and lower levels of oxidized glutathione. Our findings show that insulin treatment was not able to prevent diastolic, baroreflex, and SAP-V dysfunction, suggesting an outstanding cardiovascular risk, even after obtaining a good glycemic control in STZ-induced diabetic rats. This study shed light on a relatively large population of diabetic patients in need of other therapies to be used in combination with insulin treatment and thus more effectively manage cardiovascular risk.
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Many actinopterygian fish groups, including fossil and extant polypteriforms and lepisosteiforms, fossil halecomorphs, and some basal teleosts, have stout bony scales covered by layers of ganoin-an enamel layer ornamented with minute tubercles. Ganoid scales preserve well as disarticulated remains and notably constitute most of the fossil record for polypteriform in both South America and Africa. Based on two variables (tubercle size and distance between tubercles), some authors reported that the ganoin tubercle ornamentation in these scales is constant within a species and differs between species and allows distinguishing species or at least groups of species. However, despite its promising potential for assessing polypteriform paleodiversity, this tool has remained unused, probably because the variables are not well defined, and intraspecific variation does not seem to have been considered. To address this gap, we aimed to test the intraspecific and intra-individual variation in the ornamentation of ganoid scales in the type species Polypterus bichir. We propose three different parameters to describe the tubercle ornamentation: the distance between contiguous tubercles centers, their density, and their relative spatial organization. With these parameters, we investigate the variation in ganoin ornamentation among four specimens and across different regions of the body. Our results show that the distribution of the tubercles is highly variable within a same species, regardless of the body region, and sometimes even between different sectors of a same scale. Moreover, the variation observed in P. bichir overlaps with the distribution described in the literature for several extant and fossil species. Thus far, the ornamentation of ganoid scales is not a reliable diagnostical feature for polypterids.
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Escamas de Animales , Animales , Escamas de Animales/anatomía & histología , Peces/anatomía & histología , Peces/clasificación , Especificidad de la EspecieAsunto(s)
Antiasmáticos , Asma , Humanos , Asma/terapia , Asma/tratamiento farmacológico , Antiasmáticos/uso terapéuticoRESUMEN
BACKGROUND: Seafood consumers are widely exposed to diclofenac due to the high contamination levels often present in aquatic organisms. It is a potential risk to public health due its endocrine disruptor properties. Limited information is available about diclofenac behavior after food digestion to enable a more realistic scenario of consumer exposure. This study aimed to evaluate cooking effects on diclofenac levels, and determine diclofenac bioaccessibility by an in vitro digestion assay, using commercial fish species (seabass and white mullet) as models. The production of the main metabolite 4'-hydroxydiclofenac was also investigated. Fish hamburgers were spiked at two levels (150 and 1000 ng g-1) and submitted to three culinary treatments (roasting, steaming and grilling). RESULTS: The loss of water seems to increase the diclofenac levels after cooking, except in seabass with higher levels. The high bioaccessibility of diclofenac (59.1-98.3%) observed in both fish species indicates that consumers' intestines are more susceptible to absorption, which can be worrisome depending on the level of contamination. Contamination levels did not affect the diclofenac bioaccessibility in both species. Seabass, the fattest species, exhibited a higher bioaccessibility of diclofenac compared to white mullet. Overall, cooking decreased diclofenac bioaccessibility by up to 40% in seabass and 25% in white mullet. The main metabolite 4'-hydroxydiclofenac was not detected after cooking or digestion. CONCLUSION: Thus, consumption of cooked fish, preferentially grilled seabass and steamed or baked white mullet are more advisable. This study highlights the importance to consider bioaccessibility and cooking in hazard characterization studies. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
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Culinaria , Diclofenaco , Digestión , Contaminación de Alimentos , Alimentos Marinos , Diclofenaco/metabolismo , Diclofenaco/química , Animales , Contaminación de Alimentos/análisis , Alimentos Marinos/análisis , Peces/metabolismo , Lubina/metabolismo , Humanos , Contaminantes Químicos del Agua/metabolismo , Contaminantes Químicos del Agua/química , Smegmamorpha/metabolismo , Modelos BiológicosRESUMEN
To assess the influence of physical training on neuronal activation and hypothalamic expression of vasopressin and oxytocin in spontaneously hypertensive rats (SHR), untrained and trained normotensive rats and SHR were submitted to running until fatigue while internal body and tail temperatures were recorded. Hypothalamic c-Fos expression was evaluated in thermoregulatory centers such as the median preoptic nucleus (MnPO), medial preoptic nucleus (mPOA), paraventricular nucleus of the hypothalamus (PVN), and supraoptic nucleus (SON). The PVN and the SON were also investigated for vasopressin and oxytocin expressions. Although exercise training improved the workload performed by the animals, it was reduced in SHR and followed by increased internal body temperature due to tail vasodilation deficit. Physical training enhanced c-Fos expression in the MnPO, mPOA, and PVN of both strains, and these responses were attenuated in SHR. Vasopressin immunoreactivity in the PVN was also increased by physical training to a lesser extent in SHR. The already-reduced oxytocin expression in the PVN of SHR was increased in response to physical training. Within the SON, neuronal activation and the expressions of vasopressin and oxytocin were reduced by hypertension and unaffected by physical training. The data indicate that physical training counterbalances in part the negative effect of hypertension on hypothalamic neuronal activation elicited by exercise, as well as on the expression of vasopressin and oxytocin. These hypertension features seem to negatively influence the workload performed by SHR due to the hyperthermia derived from the inability of physical training to improve heat dissipation through skin vasodilation.
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Hipertensión , Carrera , Ratas , Animales , Ratas Endogámicas SHR , Oxitocina/metabolismo , Oxitocina/farmacología , Hipotálamo/metabolismo , Núcleo Hipotalámico Paraventricular/metabolismo , Vasopresinas/metabolismo , Hipertensión/metabolismo , FatigaRESUMEN
INTRODUCTION: Next generation sequencing technology has greatly reduced the cost and time required for sequencing a genome. An approach that is rapidly being adopted as an alternative method for CNV analysis is the low-pass whole genome sequencing (LP-WGS). Here, we evaluated the performance of LP-WGS to detect copy number variants (CNVs) in clinical cytogenetics. MATERIALS AND METHODS: DNA samples with known CNVs detected by chromosomal microarray analyses (CMA) were selected for comparison and used as positive controls; our panel included 44 DNA samples (12 prenatal and 32 postnatal), comprising a total of 55 chromosome imbalances. The selected cases were chosen to provide a wide range of clinically relevant CNVs, the vast majority being associated with intellectual disability or recognizable syndromes. The chromosome imbalances ranged in size from 75 kb to 90.3 Mb, including aneuploidies and two cases of mosaicism. RESULTS: All CNVs were successfully detected by LP-WGS, showing a high level of consistency and robust performance of the sequencing method. Notably, the size of chromosome imbalances detected by CMA and LP-WGS were compatible between the two different platforms, which indicates that the resolution and sensitivity of the LP-WGS approach are at least similar to those provided by CMA. DISCUSSION: Our data show the potential use of LP-WGS to detect CNVs in clinical diagnosis and confirm the method as an alternative for chromosome imbalances detection. The diagnostic effectiveness and feasibility of LP-WGS, in this technical validation study, were evidenced by a clinically representative dataset of CNVs that allowed a systematic assessment of the detection power and the accuracy of the sequencing approach. Further, since the software used in this study is commercially available, the method can easily be tested and implemented in a routine diagnostic setting.
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Aneuploidia , Variaciones en el Número de Copia de ADN , Embarazo , Femenino , Humanos , Análisis Costo-Beneficio , Secuenciación Completa del Genoma/métodos , ADNRESUMEN
This paper analyzes the role of the diffusion coefficient in the movement of analytes that can reversibly react with a selector given a product in the presence of drift. The problem mimics the movement of enantiomers in a capillary electrophoresis experiment. As is well known, the signal in the capillary must be sharp enough to make a good determination of the effective mobility of the analytes being analyzed. The essence of the technique is based on fast interconversion rates. Therefore, the effective diffusion coefficient must be negligible during the experiment. In the present work, an exact expression for both the apparent mobility and the diffusion coefficient is obtained. This is done by writing the rate equations governing the process and solving them using the generating function technique. The effective mobility coincides with the Wren and Rowe equation, whereas the diffusion coefficient allows us to determine the values of the parameters to be taken into account so that this quantity is minimal or close to zero. On the other hand, the numerical solution of the kinetic equations and Monte Carlo simulations allow us to follow the signal in the capillary and to determine its space-time evolution.