RESUMEN
BACKGROUND: Studies show that healthcare-associated infections (HAIs) represent a crucial issue in healthcare and can lead to substantial economic impacts in intensive care units (ICUs). AIM: To estimate direct costs associated with the most significant HAIs in 50 teaching hospitals in Brazil, affiliated to the unified health system (Sistema Único de Saúde: SUS). METHODS: A Monte Carlo simulation model was designed to estimate the direct costs of HAIs; first, epidemiologic and economic parameters were established for each HAI based on a cohort of 949 critical patients (800 without HAI and 149 with); second, simulation based on three Brazilian prevalence scenarios of HAIs in ICU patients (29.1%, 51.2%, and 61.6%) was used; and third, the annual direct costs of HAIs in 50 university hospitals were simulated. FINDINGS: Patients with HAIs had 16 additional days in the ICU, along with an extra direct cost of US$13.892, compared to those without HAIs. In one hypothetical scenario without HAI, the direct annual cost of hospital care for 26,649 inpatients in adult ICUs of 50 hospitals was US$112,924,421. There was an increase of approximately US$56 million in a scenario with 29.1%, and an increase of US$147 million in a scenario with 61.6%. The impact on the direct cost became significant starting at a 10% prevalence of HAIs, where US$2,824,817 is added for each 1% increase in prevalence. CONCLUSION: This analysis provides robust and updated estimates showing that HAI places a significant financial burden on the Brazilian healthcare system and contributes to a longer stay for inpatients.
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Infección Hospitalaria , Adulto , Brasil/epidemiología , Infección Hospitalaria/epidemiología , Atención a la Salud , Hospitales Universitarios , Humanos , Unidades de Cuidados Intensivos , Tiempo de InternaciónRESUMEN
Overfishing is a key stressor in many coral reefs, affecting their function and ecosystem services. In the Gulf of California, 50 years of artisanal and recreational fishing have removed most of the largest and most vulnerable fish species, the Espiritu Santo Archipelago (ESA) is a marine protected area (MPA) where artisanal and recreational fishing are allowed in most of the natural reefs, while the artificial reefs (wrecks) are fully protected. An important question under such circumstances is whether artificial reefs can serve as surrogate habitats for the natural reefs. To address this question, we characterized the fish community (species richness, abundance, differences in taxonomic structure) and analyzed the obtained data by multivariate ordination and similarity analysis. The highest species richness was found in the artificial reefs, with total of 83 species, of which 21 species were exclusive. Contrary to the species richness, the total fish abundance was 20% higher at the natural reefs. The fish assemblages of the artificial reefs differ significantly from those of the natural reefs. The natural reefs of the ESA are dominated by few fish species from families of lower trophic levels. In contrast, the studied shipwrecks provide refuge to commercially important fish species (such as Snappers, Triggerfish, Jacks, and Groupers) including threatened species. The different fish compositions on the natural and artificial reefs is likely to be the outcome of differential fishing pressure. The non-fished areas (wrecks) of the ESA may represent a good strategy for reef restoration, enhanced fishing grounds (via spillover) and fishing management. However, the fish community structure of the artificial reefs differs from natural rocky reefs of the ESA, and therefore, should not be considered as surrogate habitats for natural reefs. The results point out the need to reassess the management effectiveness of the natural reefs of the ESA.
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Conservación de los Recursos Naturales , Ecosistema , Animales , Arrecifes de Coral , Explotaciones Pesqueras , Peces , Alimentos MarinosRESUMEN
Not available.
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Síndrome de Fatiga Crónica/terapia , Fatiga/terapia , Estimulación Transcraneal de Corriente Directa/métodos , Adulto , Enfermedad Crónica , Femenino , Humanos , Atrapamiento del Tendón/diagnóstico , Puntos DisparadoresRESUMEN
PURPOSE: The small bites surgical technique supported by the STITCH trial has been touted as a strategy for preventing early laparotomy dehiscence through greater force distribution at the suture-tissue interface. However, this hernia prevention strategy requires an alteration in the standard closure technique that has not been widely adopted in the USA. This study seeks to determine whether incorporating a mid-weight polypropylene mesh material into a hollow-bore surgical suture material will effectively increase the force distribution at the suture-tissue interface and potentially help prevent early laparotomy dehiscence in an ex vivo model. METHODS: A cyclic stress ball-burst model was used to compare suturable mesh (0 DuraMesh™) to conventional suture. After midline laparotomy, 28 porcine abdominal wall specimens were closed with either 0 DuraMesh™ or #1 polydioxanone double-loop suture. A custom 3D-printed ball-burst test apparatus was used to fatigue the repair on a MTS Bionix Load Frame. The tissue was repetitively stressed at a physiological force of 15-120 N cycled at a rate of 0.25 Hz for a total of 1000 repetitions, followed by a load to failure, and the maximal force was recorded. RESULTS: The mean maximal force at suture pull-through was significantly higher (p < 0.0095) in the 0 DuraMesh suture group (mean: 850.1 N) compared to the 1 PDS group (mean: 714.7 N). CONCLUSION: This ex vivo study suggests that using rational suture design to improve force distribution at the suture-tissue interface may be a viable strategy for preventing the suture pull-through that drives incisional hernia.
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Técnicas de Cierre de Herida Abdominal , Hernia/prevención & control , Laparotomía , Dehiscencia de la Herida Operatoria/prevención & control , Técnicas de Sutura , Suturas , Pared Abdominal/fisiopatología , Pared Abdominal/cirugía , Técnicas de Cierre de Herida Abdominal/instrumentación , Animales , Materiales Biocompatibles , Fenómenos Biomecánicos , Hernia/etiología , Hernia/fisiopatología , Hernia Abdominal/etiología , Hernia Abdominal/prevención & control , Hernia Incisional/etiología , Hernia Incisional/fisiopatología , Hernia Incisional/prevención & control , Laparotomía/efectos adversos , Laparotomía/métodos , Polipropilenos , Falla de Prótesis , Estrés Mecánico , Mallas Quirúrgicas , Dehiscencia de la Herida Operatoria/etiología , Dehiscencia de la Herida Operatoria/fisiopatología , PorcinosRESUMEN
Abamectin (ABA) toxicity in fish, amphibian and mammals was already proven, but its effect on birds is almost unknown. Thus, the aim of our study is to assess the impact of exposure to water with ABA for 40â¯days at predicted environmentally relevant concentrations on the behavior of female Japanese quails (Coturnix coturnix japonica). The three following experimental groups (nâ¯=â¯10 each) were set: "control", quails exposed to drinking water, without ABA, "EC1x" and "EC1000x" (0.31â¯mg a.i./L and 310.0 a.i./L, respectively; via commercial formulation Kraft® 36EC). The open field test showed anxiolytic response in birds exposed to ABA. These birds did not show locomotor changes or aggressive behavior in the aggressiveness test. Quails exposed to the pesticide did not react to the introduction of an object in the experimental box during the object recognition test, and it suggested perception deficit due to ABA. Moreover, these birds did not recognize the cat (Felix catus) and the vocalization of a hawk (Rupornis magnirostris) as potential predatory threats. These responses also suggest anti-predatory behavior deficit due to the pesticide. Thus, our study is pioneer in showing that water with ABA, at tested concentrations, influences the behavior of C. coturnix japonica, as well as in highlighting the potential impacts of this pesticide on this group of birds.
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Conducta Animal/efectos de los fármacos , Coturnix/fisiología , Ivermectina/análogos & derivados , Plaguicidas/toxicidad , Animales , Gatos , Femenino , Ivermectina/toxicidadAsunto(s)
Circulación Asistida/instrumentación , Circulación Asistida/normas , Oxigenación por Membrana Extracorpórea/instrumentación , Oxigenación por Membrana Extracorpórea/normas , Corazón Auxiliar , Circulación Asistida/métodos , Brasil , Oxigenación por Membrana Extracorpórea/métodos , Insuficiencia Cardíaca/terapia , Humanos , Factores de Riesgo , Sociedades MédicasRESUMEN
PURPOSE: Monitored anesthesia care with intravenous sedation (MAC/IV), recently proposed as a good choice for hernia repair, has faster recovery and better patient satisfaction than general anesthesia; however the possibility of oversedation and respiratory distress is a widespread concern. There is a paucity of the literature examining umbilical hernia repairs (UHR) and optimal anesthesia choice, despite its importance in determining clinical outcomes. METHODS: A retrospective analysis of anesthesia type in UHR was performed in the National Surgical Quality Improvement Program 2005-2013 database. General anesthesia and MAC/IV groups were propensity-score-matched (PSM) to reduce treatment selection bias. Surgical complications, medical complications, and post-operative hospital stays exceeding 1 day were the primary outcomes of interest. Pre-operative characteristics and post-operative outcomes were compared between the two anesthesia groups using univariate and multivariate statistics. RESULTS: PSM removed all observed differences between the two groups (p > 0.05 for all tracked pre-operative characteristics). MAC/IV cases required fewer post-operative hospital stays exceeding 1 day (3.5 vs 6.3 %, p < 0.001). Univariate analysis showed that overall complication rate did not differ (1.7 vs 1.8 %, p = 0.569), however MAC/IV cases resulted in fewer incidences of septic shock (<0.1 vs 0.1 %, p = 0.016). After multivariate logistic regression, MAC/IV was revealed to yield significantly lower chances of overall medical complications (OR = 0.654, p = 0.046). CONCLUSION AND RELEVANCE: UHR under MAC/IV causes fewer medical complications and reduces post-operative hospital stays compared to general anesthesia. The implications for surgeons and patients are broad, including improved surgical safety, cost-effective care, and patient satisfaction.
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Anestesia General , Sedación Consciente , Hernia Umbilical/cirugía , Herniorrafia , Monitoreo Intraoperatorio , Administración Intravenosa , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Puntaje de Propensión , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
We aimed to evaluate knowledge of first aid among new undergraduates and whether it is affected by their chosen course. A questionnaire was developed to assess knowledge of how to activate the Mobile Emergency Attendance Service - MEAS (Serviço de Atendimento Móvel de Urgência; SAMU), recognize a pre-hospital emergency situation and the first aid required for cardiac arrest. The students were also asked about enrolling in a first aid course. Responses were received from 1038 of 1365 (76.04%) new undergraduates. The questionnaires were completed in a 2-week period 1 month after the beginning of classes. Of the 1038 respondents (59.5% studying biological sciences, 11.6% physical sciences, and 28.6% humanities), 58.5% knew how to activate the MEAS/SAMU (54.3% non-biological vs 61.4% biological, P=0.02), with an odds ratio (OR)=1.39 (95%CI=1.07-1.81) regardless of age, sex, origin, having a previous degree or having a relative with cardiac disease. The majority could distinguish emergency from non-emergency situations. When faced with a possible cardiac arrest, 17.7% of the students would perform chest compressions (15.5% non-biological vs 19.1% biological first-year university students, P=0.16) and 65.2% would enroll in a first aid course (51.1% non-biological vs 74.7% biological, P<0.01), with an OR=2.61 (95%CI=1.98-3.44) adjusted for the same confounders. Even though a high percentage of the students recognized emergency situations, a significant proportion did not know the MEAS/SAMU number and only a minority had sufficient basic life support skills to help with cardiac arrest. A significant proportion would not enroll in a first aid course. Biological first-year university students were more prone to enroll in a basic life support course.
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Adolescente , Femenino , Humanos , Masculino , Adulto Joven , Sistemas de Comunicación entre Servicios de Urgencia , Primeros Auxilios , Alfabetización en Salud/estadística & datos numéricos , Cuidados para Prolongación de la Vida/clasificación , Estudiantes , Universidades , Brasil , Educación de Postgrado/clasificación , Alfabetización Informacional , Modelos Logísticos , Factores Sexuales , Encuestas y CuestionariosRESUMEN
We aimed to evaluate knowledge of first aid among new undergraduates and whether it is affected by their chosen course. A questionnaire was developed to assess knowledge of how to activate the Mobile Emergency Attendance Service - MEAS (Serviço de Atendimento Móvel de Urgência; SAMU), recognize a pre-hospital emergency situation and the first aid required for cardiac arrest. The students were also asked about enrolling in a first aid course. Responses were received from 1038 of 1365 (76.04%) new undergraduates. The questionnaires were completed in a 2-week period 1 month after the beginning of classes. Of the 1038 respondents (59.5% studying biological sciences, 11.6% physical sciences, and 28.6% humanities), 58.5% knew how to activate the MEAS/SAMU (54.3% non-biological vs 61.4% biological, P=0.02), with an odds ratio (OR)=1.39 (95%CI=1.07-1.81) regardless of age, sex, origin, having a previous degree or having a relative with cardiac disease. The majority could distinguish emergency from non-emergency situations. When faced with a possible cardiac arrest, 17.7% of the students would perform chest compressions (15.5% non-biological vs 19.1% biological first-year university students, P=0.16) and 65.2% would enroll in a first aid course (51.1% non-biological vs 74.7% biological, P<0.01), with an OR=2.61 (95%CI=1.98-3.44) adjusted for the same confounders. Even though a high percentage of the students recognized emergency situations, a significant proportion did not know the MEAS/SAMU number and only a minority had sufficient basic life support skills to help with cardiac arrest. A significant proportion would not enroll in a first aid course. Biological first-year university students were more prone to enroll in a basic life support course.
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Sistemas de Comunicación entre Servicios de Urgencia , Primeros Auxilios , Alfabetización en Salud/estadística & datos numéricos , Cuidados para Prolongación de la Vida/clasificación , Estudiantes , Universidades , Adolescente , Brasil , Educación de Postgrado/clasificación , Femenino , Humanos , Alfabetización Informacional , Modelos Logísticos , Masculino , Factores Sexuales , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Ecdysteroid titers, developmental landmarks and the presence of prominent amplifying regions (DNA puffs) have been compared during late larval to pupal development in four groups of Rhynchosciara americana larvae and in R. americana and Rhynchosciara milleri. Three prominent DNA puffs (B2, C3 and C8) expand and regress sequentially on the rising phase of the 20-hydroxyecdysone (20E) titer in R. americana as a firm, cellular cocoon is being constructed. A sharp rise in 20E coincides with the regression of these puffs. The shape of the 20E curve is similar in R. milleri, a species that does not construct a massive cocoon, but the behavior of certain DNA puffs and their temporal relationship to the curve differs. Regions corresponding to B2 and C3 can be identified in R. milleri by banding pattern similarity with R. americana chromosomes and, in the case of B2, by hybridization to an R. americana probe. A B2 puff appears in R. milleri as the 20E titer rises but remains small in all gland regions. A puff similar to the R. americana C3 puff occurs in posterior gland cells of R. milleri (C3(Rm)) after the B2 puff, but this site did not hybridize to R. americana C3 probes. C3(Rm) incorporated (3)H-thymidine above background, but showed less post-puff DNA accumulation than C3 of R. americana. R. americana C8 probes hybridized to a more distal region of the R. milleri C chromosome that did not appear to amplify or form a large puff. These differences can be related to developmental differences, in particular differences in cocoon construction between the two species.
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Dípteros/genética , Proteínas y Péptidos Salivales/genética , Animales , Cromosomas , Dípteros/metabolismo , Ecdisteroides/metabolismo , Femenino , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Larva/genética , Masculino , Proteínas y Péptidos Salivales/metabolismo , Especificidad de la EspecieRESUMEN
Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder caused by a polyglutamine expansion in the amino-terminal region of the huntingtin protein (htt), leading to motor dysfunction, cognitive decline, psychiatric alterations, and death. The metabotropic glutamate receptor 5 (mGluR5) has been implicated in HD and we have recently demonstrated that mGluR5 positive allosteric modulators (PAMs) are neuroprotective in vitro. In the present study we demonstrate that the mGluR5 PAM, CDPPB, is a potent neuroprotective drug, in vitro and in vivo, capable of delaying HD-related symptoms. The HD mouse model, BACHD, exhibits many HD features, including neuronal cell loss, htt aggregates, motor incoordination and memory impairment. However, chronic treatment of BACHD mice with CDPPB 1.5 mg/kg s.c. for 18 weeks increased the activation of cell signaling pathways important for neuronal survival, including increased AKT and ERK1/2 phosphorylation and augmented the BDNF mRNA expression. CDPPB chronic treatment was also able to prevent the neuronal cell loss that takes place in the striatum of BACHD mice and decrease htt aggregate formation. Moreover, CDPPB chronic treatment was efficient to partially ameliorate motor incoordination and to rescue the memory deficit exhibited by BACHD mice. Importantly, no toxic effects or stereotypical behavior were observed upon CDPPB chronic treatment. Thus, CDPPB is a potential drug to treat HD, preventing neuronal cell loss and htt aggregate formation and delaying HD symptoms.
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Benzamidas/uso terapéutico , Enfermedad de Huntington/tratamiento farmacológico , Enfermedad de Huntington/patología , Enfermedad de Huntington/fisiopatología , Neuronas/efectos de los fármacos , Pirazoles/uso terapéutico , Factores de Edad , Animales , Muerte Celular/efectos de los fármacos , Células Cultivadas , Cuerpo Estriado/citología , Modelos Animales de Enfermedad , Embrión de Mamíferos , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Ácido Glutámico/farmacología , Humanos , Proteína Huntingtina , Enfermedad de Huntington/genética , Ratones , Ratones Transgénicos , Mitocondrias/patología , Actividad Motora/efectos de los fármacos , Actividad Motora/genética , Proteínas del Tejido Nervioso/metabolismo , Neuronas/patología , Reconocimiento en Psicología/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Sinapsis/patología , Sinapsis/ultraestructuraRESUMEN
The objective of this study was to evaluate the efficiency of two doses of PGF associated or not to hCG on the associated reproductive parameters in dairy goats. A total of 29 goats received two doses of 30µg d-cloprostenol latero-vulvar at a 10 day intervals (Day 1 and Day 10). The does were allocated according to body weight and body condition score into two treatments, to receive hCG (250IU) or saline at estrus onset. After the second dose of PGF, estrus was monitored and ultrasound exams were performed twice daily. All does were inseminated 16h after estrus onset. Blood collection was performed every day for progesterone assay. The use of hCG at estrus onset did not affect any studied parameter and therefore the data were pooled. Estrous response rate was similar (P>0.05) after the first (75.9%, 22/29) and the second dose of PGF (79.3%, 23/29). The interval between the administration of PGF and estrus onset was greater (P<0.05) after Day 1 (75.8±53.9h) than Day 10 (47.7±10.1 h). Estrus duration was superior (P < 0.05) after Day 1 (35.4±15.9h) to Day 10 (26.8±15.0h). Ovulation rate was 79.3% (23/29) after the second dose of PGF. No differences (P>0.05) between both experimental groups were detected in the following parameters, averaging: the interval from the second dose administration to the ovulation (86.6±11.4h), interval from estrus to ovulation (39.9±12.3 h), diameter of largest follicle (7.2±1.4) and number of ovulations (1.8±0.6). At Day 1, 52.4% (11/21) of does presented progesterone concentrations <1ng/mL. At Day 10, 100% of the animals presented concentrations >1ng/mL. The results of the present study indicate that estrus can be efficiently synchronized in dairy goats with the use of two doses of PGF at a 10 day interval. Further research should be done evaluating hCG use in different doses or moments of administration.
O objetivo deste estudo foi avaliar a eficiência do uso de duas doses de PGF associadas ou não à administração de hCG no início do estro sobre os parâmetros reprodutivos de cabras leiteiras. Um total de 29 cabras receberam duas doses de 30 µg d-cloprostenol pela via latero-vulvar com 10 dias de intervalo (Dia 1 e Dia 10). As cabras foram alocadas para receberem o hCG (250 IU) ou salina i.m. no momento em que o estro foi detectado. Depois da realização da segunda dose de PGF, o estro foi monitorado e exames ultrassonográficos foram realizados duas vezes ao dia. Todas as fêmeas foram inseminadas 16 h após o inicio do estro. Amostras de sangue foram coletadas diariamente para determinação das concentrações plasmáticas de progesterona. O uso do hCG no momento do início do estro não afetou os parâmetros estudados e, portanto, os dados serão apresentados agrupados. A taxa de manifestação de estro foi similar (P > 0,05) na primeira (75,9% - 22/29) ou na segunda dose de PGF (79,3% - 23/29). O intervalo entre a administração de PGF e o início do estro foi maior (P < 0,05) no Dia 1 (75,8±53,9 h) que no Dia 10 (47,7±10,1 h). Duração do estro também diferiu (P < 0,05) 35,4±15,9 (Dia 1) vs 26,8±15, 0 h (Dia 10). A taxa de ovulação foi 79,3% (23/29) após a segunda dose PGF. Não foi encontrada diferença (P>0,05) entre os grupos experimentais quanto aos parâmetros reprodutivos: intervalo entre a aplicação da segunda dose e a ovulação (86,6±11,4h), intervalo do estro a ocorrência da ovulação (39,9±12,3h), diâmetro do maior folículo (7,2±1,4) e número de ovulações (1,8±0,6). No Dia 1, 52,4% (11/21) apresentavam concentrações de progesterona < 1 ng/mL. No Dia 10, 100% dos animais apresentavam concentrações >1ng/mL. O presente estudo permite concluir que o estro pode ser eficientemente sincronizado em cabras leiteiras com duas doses de PGF intervaladas em 10 dias. Novas pesquisas devem se realizadas para avaliar diferentes doses e momentos de utilização do hCG.
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Animales , Inseminación Artificial , Ovulación/fisiología , Conducta Sexual Animal , Sincronización del Estro/fisiología , CabrasRESUMEN
OBJECTIVE: To evaluate the relationship between birth weight and rapid weight gain in infancy and markers of overweight/obesity in childhood, using different cutoff values for rapid weight gain. SUBJECTS/METHODS: Cross-sectional study involving 98 5-year old pre-school Brazilian children. Rapid weight gain was considered as weight gain in standard deviation score (SDS) above +0.67, +1 and +2 in relation to birth weight, at any time during the first 2 years of life. The nutritional status of the children was determined by anthropometry and electrical bioimpedance. Multiple linear regression analysis was used, considering fat mass percentage, body mass index (BMI), waist and neck circumferences as outcomes. RESULTS: Birth weight, rapid weight gain (assessed by different cutoff values) and maternal obesity were positively associated with increased fat mass percentage, BMI, waist and neck circumferences. Different cutoff values of rapid weight gain did not change the positive associations between rapid weight gain and fat mass percentage (>+0.67 SDS, P=0.007; >+1 SDS, P=0.007; >+2 SDS, P=0.01), BMI (>+0.67 SDS, P=0.002; >+1 SDS, P=0.007; >+2 SDS, P<0.001), waist circumference (>+0.67 SDS, P=0.002; >+1 SDS, P=0.002; >+2 SDS, P<0.001) and neck circumference (>+0.67 SDS, P=0.01; >+1 SDS, P=0.03; >+2 SDS, P<0.001). CONCLUSIONS: The use of different cutoff values for the definition of rapid weight gain did not interfere in the associations between birth weight and rapid weight gain with fat mass percentage, BMI, waist and neck circumferences. Children with the highest birth weight, those who undergo rapid weight gain in infancy and whose mothers were obese, seemed to be more at risk for overweight/obesity.
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Antropometría/métodos , Peso al Nacer , Composición Corporal , Estado Nutricional , Obesidad Infantil/etiología , Aumento de Peso , Tejido Adiposo , Adolescente , Adulto , Índice de Masa Corporal , Brasil , Preescolar , Estudios Transversales , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Cuello , Sobrepeso , Valores de Referencia , Factores de Riesgo , Circunferencia de la Cintura , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a polyglutamine expansion in the huntingtin protein. We have previously demonstrated that the cell signalling of the metabotropic glutamate receptor 5 (mGluR5) is altered in a mouse model of HD. Although mGluR5-dependent protective pathways are more activated in HD neurons, intracellular Ca²âº release is also more pronounced, which could contribute to excitotoxicity. In the present study, we aim to investigate whether mGluR5 positive allosteric modulators (PAMs) could activate protective pathways without triggering high levels of Ca²âº release and be neuroprotective in HD. EXPERIMENTAL APPROACH: We performed a neuronal cell death assay to determine which drugs are neuroprotective, Western blot and Ca²âº release experiments to investigate the molecular mechanisms involved in this neuroprotection, and object recognition task to determine whether the tested drugs could ameliorate HD memory deficit. KEY RESULTS: We find that mGluR5 PAMs can protect striatal neurons from the excitotoxic neuronal cell death promoted by elevated concentrations of glutamate and NMDA. mGluR5 PAMs are capable of activating Akt without triggering increased intracellular Ca²âº concentration ([Ca²âº]i ); and Akt blockage leads to loss of PAM-mediated neuroprotection. Importantly, PAMs' potential as drugs that may be used to treat neurodegenerative diseases is highlighted by the neuroprotection exerted by mGluR5 PAMs on striatal neurons from a mouse model of HD, BACHD. Moreover, mGluR5 PAMs can activate neuroprotective pathways more robustly in BACHD mice and ameliorate HD memory deficit. CONCLUSIONS AND IMPLICATIONS: mGluR5 PAMs are potential drugs that may be used to treat neurodegenerative diseases, especially HD.
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Enfermedad de Huntington/tratamiento farmacológico , Trastornos de la Memoria/prevención & control , Proteínas del Tejido Nervioso/agonistas , Fármacos Neuroprotectores/uso terapéutico , Nootrópicos/uso terapéutico , Receptor del Glutamato Metabotropico 5/agonistas , Regulación Alostérica/efectos de los fármacos , Animales , Conducta Animal/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Células Cultivadas , Cuerpo Estriado/citología , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Embrión de Mamíferos/citología , Activación Enzimática/efectos de los fármacos , Proteína Huntingtina , Enfermedad de Huntington/metabolismo , Enfermedad de Huntington/fisiopatología , Trastornos de la Memoria/etiología , Ratones , Ratones Endogámicos , Ratones Transgénicos , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Neuronas/citología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Fármacos Neuroprotectores/efectos adversos , Fármacos Neuroprotectores/farmacología , Nootrópicos/efectos adversos , Nootrópicos/farmacología , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fosforilación/efectos de los fármacos , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/agonistas , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptor del Glutamato Metabotropico 5/metabolismoRESUMEN
PURPOSE: Several works correlate the synthesis of IL-17 and IL-22 with tumoral progression. However, there are no studies of these cytokines on cervical cancer. The authors studied the concentration of IL-17 and IL-22 on serum obtained from patients with different grades of squamous intraepithelial lesions (SILs) and invasive cervical carcinoma. MATERIALS AND METHODS: Eighty-one women were enrolled in this study, including 23 in the healthy control (with no history of infection or lesions), 11 with low-grade squamous intraepithelial lesion (LSIL), 36 with high-grade squamous intraepithelial lesion (HSIL), and 11 who were diagnosed anatomo-pathologically with invasive carcinoma. Levels of the IL-17 and IL-22 cytokines were measured in the serum obtained from these patients using the enzyme-linked immunoabsorbent assay (ELISA) method. RESULTS: IL-17 and IL-22 displayed a similar pattern of results, with an increase in the serum level of LSIL patients, when compared with serum from HSIL patients (respectively, mean- pg/ml: 22.50 vs 12.20, and 168.2 vs 61.48, p < 0.05). CONCLUSION: Concentrations of IL-17 and IL-22 in the peripheral blood of patients with LSIL were increased compared to HSIL patients.
Asunto(s)
Interleucina-17/sangre , Interleucinas/sangre , Displasia del Cuello del Útero/inmunología , Neoplasias del Cuello Uterino/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Interleucina-22RESUMEN
The CD44 family belongs to a larger group of hyaluronic acid-binding proteins and plays important roles in oocyte maturation, fertilization and preimplantational embryo development. We analyzed the CD44 receptor in sheep oocytes and embryos. Immature oocytes (N = 66) were obtained from a local abattoir; mature oocytes (N = 35) and embryos (N = 41) were obtained by laparotomy from adult hair ewes submitted to ovarian stimulation treatment. The CD44 mRNA was detected by hemi-nested PCR, after reverse transcription, while proteins were located by indirect immunofluorescence, using anti-human CD44 monoclonal antibody. Human lymphocytes and immature bovine oocytes were used as positive and negative controls, respectively. Assessment of the oocyte nuclear stages as well as classification of the embryonic development stage were made with Hoechst 33342 staining. Indirect immunofluorescence detected CD44 expression on the surface of mature oocytes and embryos; immature oocytes did not take up the stain. These findings were supported by the RT-PCR data, which showed no mRNA templates for CD44, even after two consecutive amplifications, in material from immature oocytes and cumulus cells. The CD44 amplicons were detected after a second hemi-nested PCR in mature oocytes and embryos. The finding of CD44 in mature oocytes and preimplantational embryos could reflect the expression profile of hyaluronic acid during terminal folliculogenesis and preimplantational embryo development in sheep.
Asunto(s)
Blastocisto , Receptores de Hialuranos/inmunología , Oocitos/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Secuencia de Bases , Cartilla de ADN , Femenino , Receptores de Hialuranos/genética , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , OvinosRESUMEN
The aim of this study was to verify the efficacy of reusing intravaginal progesterone (P4) devices on the reproductive parameters in Santa Inês ewes. Females received intravaginal P4 devices for their first, second or third use for five days plus 300 IU eCG IM and 5mg dinoprost laterovulvar 24h before device removal. Blood was collected at different moments. Transrectal ultrasonography was performed from device removal to ovulation. Part of the ewes were submitted to artificial insemination by laparoscopy (IAL - n=55) with fresh semen, whereas the rest were bred by fertile rams (n=41). On the initial 18 h, ewes that received devices for the first time showed higher P4 concentrations (5.1±1.8 vs 3.5±1.4 vs 2.4±1.1 - P<0.05). However, after the first 48h no difference was observed among all treatments and P4 supraluteal concentrations were detected in all ewes upon device removal. Estrous response, interval from device removal to estrus, rate of ovulating animals, number of ovulations, time from device removal to ovulation and average conception rates after IAL or natural mating were similar among all 3 groups. Intravaginal progesterone devices can be used up to three times without altering reproductive parameters in Santa Inês ewes.
Avaliou-se a eficácia da reutilização de dispositivos intravaginais de progesterona (P4) sobre características reprodutivas em ovelhas Santa Inês. As fêmeas receberam dispositivos intravaginais contendo P4 para o seu primeiro, segundo ou terceiro uso por cinco dias, associado a 300 UI eCG IM e 5mg dinoprost laterovulvar 24h antes da remoção dos dispositivos. Ultrassonografia transretal foi realizada da remoção dos dispositivos até a ovulação. Parte das ovelhas foi submetida à inseminação artificial laparoscópica (IAL- n=55) com sêmen a fresco, enquanto outra parte foi acasalada por machos férteis (n=41). Nas 18 h iniciais, as ovelhas que receberam dispositivos pela primeira vez apresentaram maior concentração de P4 (5.1±1.8 vs 3.5±1.4 vs 2.4±1.1 - P<0.05). Entretanto, após as primeiras 48h nenhuma diferença foi observada entre os tratamentos quanto as concentrações circulantes de progesterona. Foram encontradas concentrações de progesterona supraluteais em todas as ovelhas na retirada dos dispositivos. Estro, intervalo da retirada ao estro, taxa de animais que ovularam, número de ovulações, momento da retirada à ovulação e taxa média de concepção após IAL ou monta natural foram similares entre os tratamentos. Dispositivos intravaginais de progesterona podem ser usados até três vezes sem alterar as características reprodutivas de ovelhas Santa Inês.
RESUMEN
This study reported the effects of prostaglandin (PGF2a) administration 10 days apart on reproductive parameters of cyclic artificial inseminated (AI) nulliparous Alpine (n=9) and Saanen (n=9) goats. Animals received two doses of 22.5mg PGF2a 10 days apart. After 1st and 2nd PGF2a administrations, estrus was monitored at 12 h intervals, with a buck teaser. Plasma progesterone concentration (ng/mL) was determined from blood sampled on day 0 (1st PGF2a) and the following 5, 10 (2nd PGF2a), 15, 20, 25 and 30 days. After the onset of the second estrus, females were transrectally (5 MHz probe) scanned at 4 hour intervals until at least 8h after ovulation. Pregnancy was checked through transrectal ultrasound on days 20, 25, 30, 35 and 90 after insemination. All parameters studied did not differ between breeds (P>0.05). Estrous response and interval to estrus, respectively, after 1st (78.9% and 50.6±17.2h) and 2nd PGF2a (88.9% and 50.0±14.8h) administration did not differ (P>0.05). Overall animals ovulating (100.0%), interval to ovulation after 2nd PGF2a (64.5±19.5h) and after estrous onset (18.0±9.1h), ovulation rate (1.3±0.5), diameter of ovulatory follicle (8.1±1.1mm) were recorded. Embryo loss occurred before day 30 of pregnancy. Estrus can be efficiently synchronized in nulliparous Alpine and Saanen goats with two doses of prostaglandin 10 days apart.
Relataram-se os efeitos da aplicação de prostaglandina sobre características reprodutivas de cabras leiteiras nulíparas cíclicas. Cabras Alpinas (n=9) e Saanen (n=9) receberam duas doses de 22,5mg PGF2a com 10 dias de intervalo. A progesterona plasmática (ng/mL) foi determinada a partir de amostras de sangue coletadas nos dias 0 (primeira dose), 5, 10 (segunda dose), 15, 20, 25 e 30. Após início do segundo estro, as fêmeas foram monitoradas por ultrassonografia transretal a cada quatro horas até oito horas após a ovulação. A gestação foi verificada por ultrassonografia transretal nos dias 20, 25, 30, 35 e 90 após a segunda dose. As características estudadas foram semelhantes entre as raças (P>0,05). Animais em estro e o intervalo parto-estro de, respectivamente, 78,9% e 50,6±17,2h e 88,9% e 50,0±14,8h após a primeira e segunda administrações de prostaglandina, não diferiram (P>0,05). Todas as cabras ovularam e registraram-se valores do intervalo parto-ovulação após a segunda aplicação de prostaglandina de 64,5±19,5h e após início do estro de 18,0±9,1h, a taxa de ovulação de 1,3±0,5 e diâmetro do folículo ovulatório de 8,1±1,1mm. Perda embrionária ocorreu antes de 30 dias de gestação. O estro pode ser eficientemente sincronizado em cabras leiteiras núliparas com duas doses de prostaglandina intervaladas de 10 dias.