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Background: A primary barrier to curing HIV is the HIV reservoir. The leading infectious cause of death worldwide for people living with HIV is tuberculosis (TB), but we do not know how TB impacts the HIV reservoir. Methods: Participants in identification and validation cohorts were selected from previously enrolled studies at Groupe Haïtien d'Étude du Sarcome de Kaposi et des Infections Opportunistes (GHESKIO) in Port au Prince, Haiti. Intact and non-intact proviral DNA were quantified using droplet digital PCR of peripheral blood mononuclear cell (PBMC)-derived CD4+ T cells. Kruskal-Wallis tests were used to compare medians with tobit regression for censoring. Results: In the identification cohort, we found that people living with HIV with a history of active pulmonary TB (n=19) had higher levels of intact provirus than people living with HIV without a history of active TB (n=47) (median 762; IQR, 183-1173 vs 117; IQR, 24-279 intact provirus per million CD4, respectively; P=0.0001). This difference also was seen in the validation cohort (n=31), (median 102; IQR, 0-737 vs 0; IQR, 0-24.5 intact provirus per million CD4, P=0.03) for TB vs no-TB history groups, respectively. The frequencies of CD4+ T cells with any detectable proviral fragment was directly proportional to the levels of interleukin-1 beta (r=0.524, P= 0.0025) and interleukin-2 (r=0.622, P=0.0002). Conclusions: People living with HIV with a history of active pulmonary TB have more HIV pro-virus in their circulating CD4+ T cells, even years after TB cure. We need to characterize which CD4+ T cells are harboring intact provirus to consider the impact of T cell-targeting HIV cure interventions for people living in TB-endemic areas.
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Coronavirus disease 2019 (COVID-19) might impact disease progression in people living with HIV (PLWH), including those on effective combination antiretroviral therapy (cART). These individuals often experience chronic conditions characterized by proviral latency or low-level viral replication in CD4+ memory T cells and tissue macrophages. Pro-inflammatory cytokines, such as TNF-α, IL-1ß, IL-6, and IFN-γ, can reactivate provirus expression in both primary cells and cell lines. These cytokines are often elevated in individuals infected with SARS-CoV-2, the virus causing COVID-19. However, it is still unknown whether SARS-CoV-2 can modulate HIV reactivation in infected cells. Here, we report that exposure of the chronically HIV-1-infected myeloid cell line U1 to two different SARS-CoV-2 viral isolates (ancestral and BA.5) reversed its latent state after 24 h. We also observed that SARS-CoV-2 exposure of human primary monocyte-derived macrophages (MDM) initially drove their polarization towards an M1 phenotype, which shifted towards M2 over time. This effect was associated with soluble factors released during the initial M1 polarization phase that reactivated HIV production in U1 cells, like MDM stimulated with the TLR agonist resiquimod. Our study suggests that SARS-CoV-2-induced systemic inflammation and interaction with macrophages could influence proviral HIV-1 latency in myeloid cells in PLWH.
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COVID-19 , Citocinas , Infecciones por VIH , VIH-1 , Macrófagos , Células Mieloides , SARS-CoV-2 , Latencia del Virus , Humanos , SARS-CoV-2/fisiología , VIH-1/fisiología , COVID-19/virología , COVID-19/inmunología , Macrófagos/virología , Macrófagos/inmunología , Células Mieloides/virología , Citocinas/metabolismo , Infecciones por VIH/virología , Infecciones por VIH/inmunología , Infecciones por VIH/tratamiento farmacológico , Línea Celular , Efecto Espectador , Activación Viral , Replicación Viral/efectos de los fármacos , Linfocitos T CD4-Positivos/virología , Linfocitos T CD4-Positivos/inmunologíaRESUMEN
BACKGROUND: This study explored the correlation between pancreatic islet α cell function, as reflected by the plasma glucagon levels, and Diabetic Peripheral Neuropathy (DPN) in patients with Type 2 Diabetes Mellitus (T2DM). METHODS: A total of 358 patients with T2DM were retrospectively enrolled in this study and divided into the Non-DPN (NDPN) group (n = 220) and the DPN group (n = 138). All patients underwent an oral glucose tolerance test to detect levels of blood glucose, insulin and glucagon, and the Area Under the Curve (AUC) for Glucagon (AUCglu) was used to estimate the overall glucagon level. The Peripheral Nerve Conduction Velocity (PNCV), Amplitude (PNCA) and Latency (PNCL) were obtained with electromyography, and their Z scores were calculated. RESULTS: There were significant differences regarding the age, disease duration, serum levels of alanine aminotransferase, aspartate aminotransferase, urea nitrogen, high-density lipoprotein, and 2h-C peptide between these two groups (p < 0.05). The NDPN group had higher glucagon levels at 30, 60 and 120 min and AUCglu (p < 0.05). The Z-scores of PNCV and PNCA showed an increasing trend (p < 0.05), while the Z-score of PNCL showed a decreasing trend (p < 0.05). The glucagon levels were positively correlated with PNCV and PNCA, but negatively correlated with PNCL, with Gluca30min having the strongest correlation (p < 0.05). Gluca30min was independently related to PNCV, PNCL, PNCA and DPN, respectively (p < 0.05). The function of pancreatic α islet cells, as reflected by the plasma glucagon level, is closely related to the occurrence of DPN in T2DM patients. CONCLUSION: Gluca30min may be a potentially valuable independent predictor for the occurrence of DPN.
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Glucemia , Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Glucagón , Prueba de Tolerancia a la Glucosa , Conducción Nerviosa , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/fisiopatología , Masculino , Persona de Mediana Edad , Femenino , Neuropatías Diabéticas/sangre , Neuropatías Diabéticas/fisiopatología , Neuropatías Diabéticas/etiología , Glucagón/sangre , Estudios Retrospectivos , Glucemia/análisis , Conducción Nerviosa/fisiología , Anciano , Adulto , Electromiografía , Células Secretoras de Glucagón , Insulina/sangre , Área Bajo la Curva , Factores de Tiempo , Valores de ReferenciaRESUMEN
Two unusual phorbol esters, namely 20-deoxyphorbol-3,4,12-triacetate-13-phenylacetate (1) and phorbol-3,4,12,13-tetraacetate-20-phenylacetate (2) plus ingol-3,8,12-triacetate-7-phenylacetate (3) were isolated from the latex of Euphorbia umbellata and identified by HRESIMS and 2D NMR. Compound 1 is herein described for the first time. Assignment of the phenylacetyl group at C-7 in compound 3 was suggested by the HMBC and NOESY spectra obtained in pyridine-d5. In addition to the latex and its distinct terpenoid fractions, the isolated compounds were tested as latent reversal agents against HIV-1-infected J-Lat cells, with reference to phorbol-12-myristate-13-acetate and ingenol-B. Compound 2 reverted 75-80% the viral latency on the GFP-positive cells, resulting EC50 3.70 µg/mL (SI 6.7), while 1 induced 34-40% reactivation at the same concentration range (4-20 µg/mL). The ingol derivative 3 was ineffective. Phorbol esters were confirmed as effective constituents in the latex since the fraction containing them was 2.4-fold more active than the lyophilised latex at the lowest concentration assayed.
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Due to a common mode of transmission through infected human blood, hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection is relatively prevalent. In alignment with this, HCV co-infection is associated with an increased size of the HIV reservoir in highly active antiretroviral therapy (HAART)-treated individuals. Hence, it is crucial to comprehend the physiological mechanisms governing the latency and reactivation of HIV in reservoirs. Consequently, our study delves into the interplay between HCV/HIV co-infection in liver cells and its impact on the modulation of HIV latency. We utilized the latently infected monocytic cell line (U1) and the latently infected T-cell line (J-Lat) and found that mediators produced by the infection of hepatic stellate cells and hepatocytes with HIV and HCV, respectively, were incapable of inducing latency reversal under the studied conditions. This may favor the maintenance of the HIV reservoir size among latently infected mononuclear cells in the liver. Further investigations are essential to elucidate the role of the interaction between liver cells in regulating HIV latency and/or reactivation, providing a physiologically relevant model for comprehending reservoir microenvironments in vivo.
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ABSTRACT Objective: To investigate the association between sleep duration, nocturnal awakenings, and sleep latency with body mass index (BMI) at six and 12 months of age. Methods: 179 children from a birth cohort were enrolled. At six and 12 months of age, anthropometric data were obtained using standardized techniques and infants' mothers answered the Brief Infant Sleep Questionnaire for sleep data. The association of BMI with the independent variables (sleep duration, latency, and nocturnal awakenings) was assessed by linear regression models. Analyses were adjusted for potential confounders and a p-value<0.05 was adopted to define statistical significance. Results: For each additional hour of sleep duration, BMI was reduced by 0.15 kg/m² (95% confidence interval [CI] -0.28; -0.01; p=0.03) and each additional minute of sleep latency increased BMI by 0.01 kg/m² (95%CI -0.00; 0.03; p=0.02). These associations were independent of gestational age, child sex, birth weight, duration of exclusive breastfeeding, smoking during pregnancy, and mother's BMI, education, and marital status. Nocturnal awakenings showed no association with the outcome. Conclusions: Our findings suggest that sleep duration and sleep latency time are associated with BMI in the first year of life. Insights into the influence of sleep early in life on weight status may be helpful to complement future nutritional recommendations and prevent and treat obesity.
RESUMO Objetivo: Investigar a associação entre duração do sono, despertares noturnos e latência do sono com o índice de massa corporal (IMC) aos seis e 12 meses de idade. Métodos: foram incluídas 179 crianças de uma coorte de nascimentos. Aos seis e 12 meses de idade, dados antropométricos foram obtidos por meio de técnicas padronizadas e as mães dos lactentes responderam ao Brief Infant Sleep Questionnaire para dados do sono. A associação do IMC com as variáveis independentes (duração do sono, latência e despertares noturnos) foi avaliada por modelos de regressão linear. As análises foram ajustadas para potenciais fatores de confusão e o p-valor<0,05 foi adotado para definir a significância estatística. Resultados: Para cada hora adicional de duração do sono, o IMC foi reduzido em 0,15 kg/m² (intervalo de confiança [IC]95% -0,28; -0,01; p=0,03) e cada minuto adicional no tempo de latência resultou em aumento de 0,01 kg/m² (IC95% -0,00; 0,03; p=0,02) no IMC. Essas associações foram independentes da idade gestacional, sexo da criança, peso ao nascer, duração do aleitamento materno exclusivo, tabagismo durante a gravidez e IMC, escolaridade e estado civil da mãe. Os despertares noturnos não apresentaram associação com o desfecho. Conclusões: Nossos achados sugerem que a duração e a latência do sono estão associadas ao IMC no primeiro ano de vida. Informações sobre a influência do sono no início da vida sobre o status do peso podem ser úteis para complementar futuras recomendações nutricionais e prevenir e tratar a obesidade.
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Abstract Background: This study explored the correlation between pancreatic islet α cell function, as reflected by the plasma glucagon levels, and Diabetic Peripheral Neuropathy (DPN) in patients with Type 2 Diabetes Mellitus (T2DM). Methods: A total of 358 patients with T2DM were retrospectively enrolled in this study and divided into the Non-DPN (NDPN) group (n = 220) and the DPN group (n = 138). All patients underwent an oral glucose tolerance test to detect levels of blood glucose, insulin and glucagon, and the Area Under the Curve (AUC) for Glucagon (AUCglu) was used to estimate the overall glucagon level. The Peripheral Nerve Conduction Velocity (PNCV), Amplitude (PNCA) and Latency (PNCL) were obtained with electromyography, and their Z scores were calculated. Results: There were significant differences regarding the age, disease duration, serum levels of alanine aminotransferase, aspartate aminotransferase, urea nitrogen, high-density lipoprotein, and 2h-C peptide between these two groups (p < 0.05). The NDPN group had higher glucagon levels at 30, 60 and 120 min and AUCglu (p < 0.05). The Z-scores of PNCV and PNCA showed an increasing trend (p < 0.05), while the Z-score of PNCL showed a decreasing trend (p < 0.05). The glucagon levels were positively correlated with PNCV and PNCA, but negatively correlated with PNCL, with Gluca30min having the strongest correlation (p < 0.05). Gluca30min was independently related to PNCV, PNCL, PNCA and DPN, respectively (p < 0.05). The function of pancreatic α islet cells, as reflected by the plasma glucagon level, is closely related to the occurrence of DPN in T2DM patients. Conclusion: Gluca30min may be a potentially valuable independent predictor for the occurrence of DPN.
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Despite being considered fragile and fastidious, Campylobacter jejuni is the most prevalent cause of foodborne bacterial gastroenteritis, and chicken meat is considered the main vehicle of transmission to humans. This agent can survive adverse conditions in the form of biofilms, but extreme stress (nutritional, oxidative and thermal) promotes the acquisition of a state called viable but not culturable (VBNC). The emergence of this pathogen worldwide and the recent international requirements in its control instigated us to qualitatively and quantitatively estimate the time required for the acquisition of the VBNC form in 27 strains of C. jejuni, characterize morphological aspects, determine its adaptive and invasive potential and perform comparative metabolomic evaluation. Extreme stress promoted the complete acquisition of the VBNC form in a mean time of 26 days. Starting from an average initial count of 7.8 log CFU/mL, the first four days determined the greatest average reduction of the culturable form of 3.2 log CFU/mL. The scanning and transmission image analyses showed a transition from the typical viable form (VT) to the VBNC form, with initial acquisition of the straight rod shape, followed by loss of the flagella and subdivision into two to 11 imperfect cocci arranged in a chain and rich in cellular content, until their individual release. RT-PCR identified the presence of ciaB and p19 transcripts in the 27 cultivable C. jejuni strains, a character maintained in the VBNC form only for p19 and in 59.3% (16/27) of the VBNC strains for the ciaB gene. The average inoculation of 1.8 log CFU/mL of C. jejuni VBNC into primary chicken embryo hepatocyte cells promoted the occurrence of apoptosis processes significantly after 24 hours of contact by one of the strains tested. In C. jejuni VBNC, we detected higher expression of metabolites linked to protective and adaptation mechanisms and of volatile organic precursor compounds indicative of metabolism interruption. The oscillations in the time of acquisition of the VBNC form together with the presence of transcripts for ciaB and p19, the identification of cell lysis and metabolites that ensure the maintenance of the pathogen alert to the fact that C. jejuni VBNC remains virulent and adapted to stress, which makes evident the potential danger of this latent form, which is not detectable by official methodologies.
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Infecciones por Campylobacter , Campylobacter jejuni , Embrión de Pollo , Animales , Humanos , Campylobacter jejuni/genética , Infecciones por Campylobacter/microbiología , Biopelículas , Adaptación Fisiológica , MetabolómicaRESUMEN
Introducción: La calidad del sueño tiene efectos en la salud física y mental, su alteración en estudiantes universitarios dificulta los procesos de memoria, concentración y capacidad de aprendizaje. En Colombia los estudios de sueño se centran principalmente en estudiantes de medicina y enfermería, y muy pocos identifican su relación con la carga académica. Objetivo: Describir los cambios en la calidad del sueño durante un semestre académico y acorde al ciclo de formación en universitarios de una facultad de salud y rehabilitación de Cali, Colombia. Materiales y métodos: Estudio descriptivo, prospectivo mediante la aplicación del Índice de calidad del sueño de Pittsburgh al inicio y cierre del semestre a 241 estudiantes de Fisioterapia, Nutrición y Terapia ocupacional. Resultados: La mayoría de participantes eran mujeres, de 20 años o menos y de estratos socioeconómicos medio y bajo. Al inicio del semestre el 76,35% de estudiantes dormían 7 horas o más y al final se redujo al 49,79%. Al inicio del estudio el 24,90% presentaban mala calidad del sueño y al final la cifra ascendió a 54,36%. Conclusiones: Se presentó un incremento significativo de mala calidad del sueño al final del semestre académico, siendo mayor el cambio en los estudiantes del ciclo profesional.
Introduction: Sleep quality affects physical and mental health and its alteration in university students hinders memory processes, concentration, and learning capacity. In Colombia, studies on sleep patterns focus mainly on medical and nursing students and few of them identify its relationship with academic load. Objective: To describe sleep quality changes during an academic semester and according to education cycles in university students from a health and rehabilitation program in Cali, Colombia. Materials and methods: Descriptive prospective study, which applied the Pittsburg Sleep Quality Index at the beginning and end of the semester to 241 Physiotherapy, Nutrition, and Occupational Therapy students. Results: Most participants were women, aged 20 years old or younger, and belonged to medium to low socioeconomic strata. At the beginning of the semester, 76.35% of students were able to sleep 7 hours or more and at the end this population decreased to 49.79%. At the beginning of the study, 24.9% displayed poor sleep quality, whereas this group increased to 54.36% at the end. Conclusions: There was a significant increase in poor sleep quality at the end of the academic semester, the change being greater in students from the professional cycle.
Introdução: A qualidade do sono tem efeitos na saúde física e mental, sua alteração em estudantes universitários dificulta os processos de memória, concentração e capacidade do aprendizagem. Na Colômbia, os estudos do sono se concentram basicamente em estudantes de medicina e enfermería, e poucos identificam sua relação com a carga acadêmica. Objetivo: Descrever as alterações na qualidade do sono durante um semestre letivo de acordo com o ciclo de formação em estudantes universitários de uma escola de saúde e reabilitação em Cali, Colômbia. Materiais e métodos: Estudo descritivo, prospectivo por meio da aplicação do Índice de Qualidade do Sono de Pittsburgh no início e final do semestre em 241 alunos de Fisioterapia, Nutrição e Terapia Ocupacional. Resultados: A maioria dos participantes foram mulheres, com idade igual ou inferior a 20 anos e de estratos socioeconômicos médio e baixo. No início do semestre, 76,35% dos alunos dormiam 7 horas ou mais, e no final diminuiu para 49,79%. No início do estudo, 24,90% tinham má qualidade do sono e no final o número subiu para 54,36%. Conclusões: Houve um aumento significativo da má qualidade do sono no final do semestre letivo, sendo a alteração maior nos estudantes do ciclo profissional.
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Humanos , Sueño , Personas , Trastornos del Sueño-Vigilia , Estudiantes , Estudiantes del Área de la Salud , Latencia del Sueño , Calidad del SueñoRESUMEN
In this paper we consider a SEIRD epidemic model for a population composed by two groups of individuals with asymmetric interaction. Given an approximate solution for the two-group model, we estimate the error of this approximation to the unknown solution to the second group based on the known error that the approximation has with respect to the solution to the first group. We also study the final size of the epidemic for each group. We illustrate our results with the spread of the coronavirus disease 2019 (COVID-19) pandemic in the New York County (USA) for the initial stage of the contamination, and in the cities of Petrolina and Juazeiro (Brazil).
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COVID-19 , Humanos , COVID-19/epidemiología , Pandemias , Ciudades , Brasil/epidemiologíaRESUMEN
La prueba de latencia múltiple del sueño nos permite evaluar objetivamente las variaciones normales y patológicas en la somnolencia y el estado de alerta. Es una prueba que evalúa qué tan rápido una persona se duerme en condiciones estandarizadas que facilitan el sueño, y se repite a intervalos de 2 horas durante todo el día. Es el estándar para documentar el inicio del sueño REM (SOREMP), que es un síntoma de narcolepsia y en la somnolencia idiopática podría ser útil. Su uso está ampliamente descrito en adultos, pero la prueba no es tan común en niños. En esta revisión, se analizan los valores en adultos y niños, y su utilidad, a partir de la historia de la prueba.
The multiple sleep latency test allows us to objectively assess normal and pathological variations in sleepiness and alertness. It is a test that assesses how quickly a person falls asleep under standardized conditions that facilitate sleep and is repeated at 2-h intervals throughout the day. is the standard for documenting sleep onset REM (SOREMP), which is a symptom of Narcolepsy and idiopathic sleepiness could be useful. Its use is widely described in adults, but the test is not so common in children. In this review, we analyze the values in adults and children, and their usefulness, based on from the history of the test.
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Humanos , Masculino , Femenino , Niño , Adolescente , Latencia del Sueño/fisiología , Somnolencia , Narcolepsia/fisiopatologíaRESUMEN
BACKGROUND: We assessed the incidence and risk factors for first detection and redetection with the same human papillomavirus (HPV) genotype, and prevalence of cytological lesions during HPV redetections. METHODS: The Ludwig-McGill cohort study followed women aged 18-60 years from São Paulo, Brazil in 1993-1997 for up to 10 years. Women provided cervical samples for cytology testing and HPV DNA testing at each visit. A redetection was defined as a recurring genotype-specific HPV positive result after 1 or more intervening negative visits. Predictors of genotype-specific redetection were assessed using adjusted hazard ratios (aHR) with Cox regression modeling. RESULTS: In total, 2184 women contributed 2368 incident HPV genotype-specific first detections and 308 genotype-specific redetections over a median follow-up of 6.5 years. The cumulative incidence of redetection with the same genotype was 6.6% at 1 year and 14.8% at 5 years after the loss of positivity of the first detection. Neither age (aHR 0.90; 95% confidence interval [CI], .54-1.47 for ≥45 years vs < 25 years) nor new sexual partner acquisition (aHR 0.98; 95% CI, .70-1.35) were statistically associated with genotype-specific redetection. High-grade squamous intraepithelial lesion prevalence was similar during first HPV detections (2.9%) and redetection (3.2%). CONCLUSIONS: Our findings suggest many HPV redetections were likely reactivations of latent recurring infections.
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Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Adulto , Femenino , Humanos , Brasil/epidemiología , Estudios de Cohortes , Virus del Papiloma Humano , Recurrencia Local de Neoplasia/complicaciones , Papillomaviridae/genética , Factores de Riesgo , Adolescente , Adulto Joven , Persona de Mediana EdadRESUMEN
Many bacteria have the ability to survive in challenging environments; however, they cannot all grow on standard culture media, a phenomenon known as the viable but non-culturable (VBNC) state. Bacteria commonly enter the VBNC state under nutrient-poor environments or under stressful conditions. This review explores the concept of the VBNC state, providing insights into the beneficial bacteria known to employ this strategy. The investigation covers different chemical and physical factors that can induce the latency state, cell features, and gene expression observed in cells in the VBNC state. The review also covers the significance and applications of beneficial bacteria, methods of evaluating bacterial viability, the ability of bacteria to persist in environments associated with higher organisms, and the factors that facilitate the return to the culturable state. Knowledge about beneficial bacteria capable of entering the VBNC state remains limited; however, beneficial bacteria in this state could face adverse environmental conditions and return to a culturable state when the conditions become suitable and continue to exert their beneficial effects. Likewise, this unique feature positions them as potential candidates for healthcare applications, such as the use of probiotic bacteria to enhance human health, applications in industrial microbiology for the production of prebiotics and functional foods, and in the beer and wine industry. Moreover, their use in formulations to increase crop yields and for bacterial bioremediation offers an alternative pathway to harness their beneficial attributes.
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In mammals, ivermectin acts as a GABAA receptor agonist and stimulates GABA release. Previous studies showed that ivermectin (IVM) reduces sexual performance, impairing the latency to the first mount and intromission. These parameters are usually considered motivational parameters of sexual behavior. However, IVM increases GABAergic activity leading to motor incoordination. Thus, it is reasonable to propose that IVM affects sexual performance via motor incoordination pathways. The present study analyzed ultrasonic vocalization in rats to verify whether IVM impairs sexual behavior via motivational mechanisms or motor impairment. Because sexual experience attenuates the impairment of motor performance, rats with sexual experience were also studied. Sexually naive and experienced rats were administered a therapeutic IVM dose and saline. The rats were exposed to receptive females, and the latency to the first mount was evaluated, followed by the 50-kHz USV test. IVM treatment in naïve rats increased the latency to first to mount relative to Saline naïve rats, while no differences were observed between saline and experienced rats. In naïve-IVM rats, a reduced frequency and total calls and increased mean time of calls occur relative to SAL-naïve rats. Experienced IVM rats did not show differences in the frequency, mean, and maximal calls close to Saline experienced rats. However, an increase in the total calls and the dominant frequency of calls were observed in IVM-experienced rats compared to Saline experienced rats. A negative and positive correlation occurred between the latency to the first mount and USVs in groups with and without ivermectin exposure. Hence, we propose that ivermectin increased the sexual motivation of rats exposed to a female in estrous based in USVs despite an increased latency to the first mount that occurred. The increased latency to the first mount resulted from motor incoordination, as previously observed and proposed by our group.(AU)
Em mamíferos, a ivermectina (IVM) atua como agonista do receptor GABAA e estimula a liberação de GABA. Estudos anteriores mostraram que a IVM reduz o desempenho sexual, prejudicando a latência para a primeira monta e intromissão. Esses parâmetros são geralmente considerados parâmetros motivacionais do comportamento sexual. Por outro lado, a IVM aumenta a atividade GABAérgica levando à incoordenação motora. Assim, é possível que a IVM afete o desempenho sexual devido a um impedimento motor. O presente estudo analisou a vocalização ultrassônica em ratos para verificar se a IVM prejudica o comportamento sexual via mecanismos motivacionais ou comprometimento motor. Uma vez que a experiência sexual atenua o comprometimento do desempenho motor, também foram estudados ratos com experiência sexual. Ratos sexualmente inexperientes e experientes foram administrados com uma dose terapêutica de IVM ou solução salina IVM. Os ratos foram expostos a fêmeas receptivas e foi avaliada a latência para a primeira monta, seguida do teste de vocalização ultrassônica (USV) de 50 kHz. O tratamento com IVM em ratos inexperientes aumentou a latência para a primeira monta em relação a ratos inexperientes tratados com solução salina, enquanto não foram observadas diferenças entre ratos experientes tratados com IVM e solução salina. Em ratos inexperientes tratados com IVM ocorreu redução da frequência e total de USVs, bem como aumento do tempo médio de USVs em relação aos ratos sem experiência. Ratos experientes tratados com IVM não mostraram diferenças na frequência, média e máxima das USVs em relação aos ratos experientes tratados com solução salina; no entanto, observou-se aumento no total de USVs e na frequência dominante de USVS em ratos experientes tratados com IVM comparados aos experientes tratados com solução salina. Observou-se correlação negativa e positiva entre a latência para a primeira monta e USVs nos grupos sem e com experiência tratados com IVM, respectivamente. Assim, propomos que a IVM aumentou a motivação sexual de ratos expostos a uma fêmea em estro com base em USVs, apesar de apresentar aumento na latência para a primeira monta. O aumento da latência para a primeira monta foi atribuída à incoordenação motora, conforme observado anteriormente e proposto por nosso grupo.(AU)
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Animales , Femenino , Ratas/fisiología , Conducta Sexual Animal/efectos de los fármacos , Ivermectina/farmacología , Vocalización Animal/efectos de los fármacosRESUMEN
Tactile internet applications allow robotic devices to be remotely controlled over a communication medium with an unnoticeable time delay. In bilateral communication, the acceptable round trip latency is usually 1 ms up to 10 ms, depending on the application requirements. The communication network is estimated to generate 70% of the total latency, and master and slave devices produce the remaining 30%. Thus, this paper proposes a strategy to reduce 30% of the total latency produced by such devices. The strategy is to use FPGAs to minimize the execution time of device-associated algorithms. With this in mind, this work presents a new hardware reference model for modules that implement nonlinear positioning and force calculations and a tactile system formed by two robotic manipulators. In addition to presenting the implementation details, simulations and experimental tests are performed in order to validate the hardware proposed model. Results associated with the FPGA sampling rate, throughput, latency, and post-synthesis occupancy area are analyzed.
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Robótica , Tacto , Algoritmos , Computadores , InternetRESUMEN
Herpesviruses are double-stranded DNA viruses occurring at a high prevalence in the human population and are responsible for a wide array of clinical manifestations and diseases, from mild to severe. These viruses are classified in three subfamilies (Alpha-, Beta- and Gammaherpesvirinae), with eight members currently known to infect humans. Importantly, all herpesviruses can establish lifelong latent infections with symptomatic or asymptomatic lytic reactivations. Accumulating evidence suggest that chemical modifications of viral RNA and DNA during the lytic and latent phases of the infections caused by these viruses, are likely to play relevant roles in key aspects of the life cycle of these viruses by modulating and regulating their replication, establishment of latency and evasion of the host antiviral response. Here, we review and discuss current evidence regarding epitranscriptomic and epigenetic modifications of herpesviruses and how these can influence their life cycles. While epitranscriptomic modifications such as m6A are the most studied to date and relate to positive effects over the replication of herpesviruses, epigenetic modifications of the viral genome are generally associated with defense mechanisms of the host cells to suppress viral gene transcription. However, herpesviruses can modulate these modifications to their own benefit to persist in the host, undergo latency and sporadically reactivate.
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SUMMARY OBJECTIVE: The aim of this study was to evaluate the quality of life of patients with lifelong and acquired premature ejaculation and to examine its relationship with depression and anxiety. METHODS: Between February 2017 and January 2018, a total of 175 patients with premature ejaculation and 132 control men who applied to the urology department of the training and research hospital with the complaint of Premature Ejaculation were included. Patients were divided into three groups according to International Society for Sexual Medicine (ISSM) criteria as follows: Group 1, lifelong premature ejaculation; Group 2, acquired premature ejaculation, and Group 3, control group without premature ejaculation. A detailed medical history of patients was obtained and physical examinations were performed. Intravaginal ejaculation latency time (IELT) was recorded and patients were administered International Erectile Function Index-5 (IIEF-5), Premature Ejaculation Diagnostic Tool (PEDT), Sexual Health Inventory for Men (SHIM), Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI)-1 and STAI-2, and Short Form-36 (SF-36). RESULTS: The mean mental component score (MCS) of the SF-36 was 51.65±6.57 in the lifelong premature ejaculation group, 49.33±8.65 in the acquired premature ejaculation group, and 61.12±11.09 in the control group (p<0.0001). The mean physical component score (PCS) was 50.99±7.43 in the lifelong premature ejaculation group, 48.32±11.58 in the acquired premature ejaculation group, and 55.17±8.10 in the control group (p<0.0001). Quality of life of premature ejaculation patients as assessed by SF-36 was lower in the subscales of physical functioning, general health perception, vitality, and role limitations due to emotional functioning, compared to the control group. CONCLUSIONS: Lifelong and acquired premature ejaculation patients deteriorate their quality of life: the deterioration in these patients' quality of life also negatively affects their depression and anxiety states.
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Abstract Introduction: Galvanic vestibular evoked myogenic potentials evaluate vestibular nerve responses using electric stimulation by records collected from the sternocleidomastoid muscle. A normal vestibular evoked myogenic potential response consists of the first positive, P1, and negative, N1, peaks. The response can be affected by factors such as age and gender and is also consequential in the diagnosis of pathologies. Objectives: The present study was performed to obtain normative data on healthy adults, to help in diagnosis by establishing clinical norms as well as to investigate changing test parameters with age in galvanic vestibular evoked myogenic potentials. Methods: A total of 100 healthy participants were included in the study. Galvanic vestibular evoked myogenic potential (current 3 mA, duration 1ms) was performed randomly on both ears of each participant. The participants between the ages of 18-65 (mean age 39.7 ± 13.9) were divided into 5 groups according to their ages. Normative data of galvanic vestibular evoked myogenic potentials parameters were calculated in groups and in total, and age-related changes were examined. Results: The galvanic vestibular evoked myogenic potential waveform was elicited from all participants (200 ears). The latency of P1 and N1 was 7.82 ± 3.29ms and 22.06 ± 3.95 ms, respectively. The P1-N1 amplitude value was 66.64 ± 24.5 μV. The percentage of vestibular asymmetry was 16.29 ±11.99%. The latencies of P1 and N1 and P1-N1 amplitude values demonstrated significant differences among different age groups (p < 0.01). Conclusions: The results of this study show that as age increased, latencies were prolonged, and amplitudes gradually decreased. The normative data aids in the diagnosis of retrolabyrinthine lesions and the increase in the clinical use of galvanic vestibular evoked myogenic potentials.
Resumo Introdução: Os potenciais evocados miogênicos vestibulares galvânicos avaliam as respostas do nervo vestibular com estimulação elétrica por meio de registros coletados do músculo esternocleidomastóideo. Uma resposta normal de potenciais evocados miogênicos vestibulares consiste nos primeiros picos positivo, P1, e negativo, N1. A resposta pode ser afetada por fatores como idade e sexo e também tem importância no diagnóstico de doenças. Objetivos: Obter dados normativos em adultos saudáveis, para ajudar no diagnóstico através do estabelecimento de normas clínicas, e investigar a alteração dos parâmetros de teste com a idade em potenciais evocados miogênicos vestibulares galvânicos. Método: Foram incluídos no estudo 100 participantes saudáveis. O potencial evocado miogênico vestibular galvânico (corrente 3mA, duração 1ms) foi realizado de forma aleatória nas duas orelhas de cada participante. Os participantes entre 18 e 65 anos (média de 39,7 ±13,9) foram divididos em 5 grupos de acordo com a idade. Os dados normativos dos parâmetros dos potenciais evocados miogênicos vestibulares galvânicos foram calculados nos grupos e no total e as alterações relacionadas à idade foram examinadas. Resultados: A forma de onda do potencial evocado miogênico vestibular galvânico foi obtida de todos os participantes (200 orelhas). A latência de P1 e N1 foi de 7,82±3,29ms e 22,06 ±3,95 ms, respectivamente. O valor da amplitude P1-N1 foi de 66,64 ±24,5 μV. O percentual de assimetria vestibular foi de 16,29± 11,99%. Os valores das latências de P1 e N1 e da amplitude P1-N1 mostraram diferenças significantes entre os diferentes grupos etários (p < 0,01). Conclusão: Os resultados deste estudo mostram que à medida que a idade aumentou as latências foram prolongadas e as amplitudes diminuíram gradualmente. Os dados normativos auxiliam no diagnóstico de lesões retrolabirínticas e na disseminação do uso clínico dos potenciais evocados miogênicos vestibulares galvânicos.
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Many drugs have been evaluated to reactivate HIV-1 from cellular reservoirs, but the off-target effects of these latency reversal agents (LRA) remain poorly defined. Transposable elements (TEs) are reactivated during HIV-1 infection, but studies of potential off-target drug effects on TE expression have been limited. We analyzed the differential expression of TEs induced by canonical and non-canonical NF-κB signaling. We evaluated the effect of PKC agonists (Bryostatin and Ingenol B) on the expression of TEs in memory CD4+ T cells. Ingenol B induced 38 differentially expressed TEs (17 HERV (45%) and 21 L1 (55%)). Interestingly, TE expression in effector memory CD4+ T cells was more affected by Bryostatin compared to other memory T-cell subsets, with 121 (107 upregulated and 14 downregulated) differentially expressed (DE) TEs. Of these, 31% (n = 37) were HERVs, and 69% (n = 84) were LINE-1 (L1). AZD5582 induced 753 DE TEs (406 HERV (54%) and 347 L1 (46%)). Together, our findings show that canonical and non-canonical NF-κB signaling activation leads to retroelement expressions as an off-target effect. Furthermore, our data highlights the importance of exploring the interaction between LRAs and the expression of retroelements in the context of HIV-1 eradication strategies.