RESUMEN
The SARS-CoV-2 virus spreading across the world has led to surges of COVID-19 illness, hospitalizations, and death. The complex and multifaceted pathophysiology of life-threatening COVID-19 illness including viral mediated organ damage, cytokine storm, and thrombosis warrants early interventions to address all components of the devastating illness. In countries where therapeutic nihilism is prevalent, patients endure escalating symptoms and without early treatment can succumb to delayed in-hospital care and death. Prompt early initiation of sequenced multidrug therapy (SMDT) is a widely and currently available solution to stem the tide of hospitalizations and death. A multipronged therapeutic approach includes 1) adjuvant nutraceuticals, 2) combination intracellular anti-infective therapy, 3) inhaled/oral corticosteroids, 4) antiplatelet agents/anticoagulants, 5) supportive care including supplemental oxygen, monitoring, and telemedicine. Randomized trials of individual, novel oral therapies have not delivered tools for physicians to combat the pandemic in practice. No single therapeutic option thus far has been entirely effective and therefore a combination is required at this time. An urgent immediate pivot from single drug to SMDT regimens should be employed as a critical strategy to deal with the large numbers of acute COVID-19 patients with the aim of reducing the intensity and duration of symptoms and avoiding hospitalization and death.
Asunto(s)
Tratamiento Farmacológico de COVID-19 , Leprostáticos/uso terapéutico , Pandemias , SARS-CoV-2 , Telemedicina/métodos , COVID-19/epidemiología , Quimioterapia Combinada , HumanosRESUMEN
Weather factors are widely studied for their effects on indicating dengue incidence trends. However, these studies have been limited due to the complex epidemiology of dengue, which involves dynamic interplay of multiple factors such as herd immunity within a population, distinct serotypes of the virus, environmental factors and intervention programs. In this study, we investigate the impact of weather factors on dengue in Singapore, considering the disease epidemiology and profile of virus serotypes. A Poisson regression combined with Distributed Lag Non-linear Model (DLNM) was used to evaluate and compare the impact of weekly Absolute Humidity (AH) and other weather factors (mean temperature, minimum temperature, maximum temperature, rainfall, relative humidity and wind speed) on dengue incidence from 2001 to 2009. The same analysis was also performed on three sub-periods, defined by predominant circulating serotypes. The performance of DLNM regression models were then evaluated through the Akaike's Information Criterion. From the correlation and DLNM regression modeling analyses of the studied period, AH was found to be a better predictor for modeling dengue incidence than the other unique weather variables. Whilst mean temperature (MeanT) also showed significant correlation with dengue incidence, the relationship between AH or MeanT and dengue incidence, however, varied in the three sub-periods. Our results showed that AH had a more stable impact on dengue incidence than temperature when virological factors were taken into consideration. AH appeared to be the most consistent factor in modeling dengue incidence in Singapore. Considering the changes in dominant serotypes, the improvements in vector control programs and the inconsistent weather patterns observed in the sub-periods, the impact of weather on dengue is modulated by these other factors. Future studies on the impact of climate change on dengue need to take all the other contributing factors into consideration in order to make meaningful public policy recommendations.
Asunto(s)
Dengue/epidemiología , Modelos Estadísticos , Dengue/transmisión , Humanos , Humedad , Incidencia , Singapur/epidemiología , TemperaturaRESUMEN
Globalization has led to a rapid influx of female workers from Asian countries with high prevalence of HIV to Singapore, with many entering the entertainment industry. We assessed the prevalence of sexual services, condom use, and self-initiated screening for sexually transmitted infections (STIs) and associated variables among foreign female entertainment workers in Singapore. A cross-sectional survey of 317 female entertainment workers, using mystery clients, was conducted on a two-stage proportional cluster sample of 93 entertainment establishments stratified by geographical zone in Singapore. We found a high prevalence (71 %) of sexual services in entertainment establishments with 53 % of the female entertainment workers reporting selling sex. Consistent condom use for sex with paying clients in a usual week in the past 3 months was low, ranging from 37.9 % for oral sex, 46.9 % for anal sex, to 51.9 % for vaginal sex. On multivariate logistic regression, consistent condom use for vaginal sex with clients showed a significant independent association with the entertainment worker's behavior of asking clients to use condoms and a borderline association with entertainment worker being a Chinese national. Less than half (48.9 %) of the sex workers had ever been screened for STIs either locally or in their home country. The only independent factor significantly associated with STI screening was having to support one's family. In summary, a high percentage of foreign female entertainment workers in Singapore reported selling sex. Condom use and STI screening were low among them. Access to STI screening, treatment, and education services should be enhanced for foreign female entertainment workers in Singapore.
Asunto(s)
Condones/estadística & datos numéricos , Emigrantes e Inmigrantes , Trabajo Sexual/estadística & datos numéricos , Trabajadores Sexuales , Enfermedades de Transmisión Sexual/diagnóstico , Población Urbana , Adulto , Estudios Transversales , Femenino , Humanos , Modelos Logísticos , Tamizaje Masivo/estadística & datos numéricos , Persona de Mediana Edad , Prevalencia , Asunción de Riesgos , Trabajo Sexual/etnología , Conducta Sexual/estadística & datos numéricos , Enfermedades de Transmisión Sexual/etnología , Singapur , Adulto JovenRESUMEN
Blast injury to the brain is one of the major causes of death and can also significantly affect cognition and physical and psychological skills in survivors of blast. The complex mechanisms via which blast injury causes impairment of cognition and other symptoms are poorly understood. In this study, we investigated the effects of varying degrees of primary blast overpressure (BOP; 80 and 200 kPa) on the pathophysiological and magnetic resonance imaging (MRI) changes and neurocognitive performance as assessed by the monkey Cambridge Neuropsychological Test Automated Battery (mCANTAB) in non-human primates (NHP). The study aimed to examine the effects of neurobehavioral and histopathological changes in NHP. MRI and histopathology revealed ultrastructural changes in the brain, notably in the Purkinje neurons in the cerebellum and pyramidal neurons in the hippocampus, which were most vulnerable to the blast. The results correlated well with the behavioral changes and changes in motor coordination and working memory of the affected monkeys. In addition, there was white matter damage affecting myelinated axons, astrocytic hypertrophy, and increased aquaporin-4 (AQP-4) expression in astrocytes, suggesting cerebral edema. Increased apoptosis appeared to involve astrocytes and oligodendrocytes in the animals following blast exposure. The small sample size could have contributed to the non-significant outcome in cognitive performance post-blast and limited quantitative analyses. Nevertheless, the study has provided initial descriptive changes for establishing a primary BOP threshold for brain injury to serve as a useful platform for future investigations that aim to estimate brain injury potential and set safe limits of exposure.
Asunto(s)
Traumatismos por Explosión/patología , Traumatismos por Explosión/fisiopatología , Lesiones Encefálicas/patología , Lesiones Encefálicas/fisiopatología , Encéfalo/patología , Cognición/fisiología , Animales , Traumatismos por Explosión/psicología , Encéfalo/fisiología , Encéfalo/fisiopatología , Lesiones Encefálicas/psicología , Trastornos del Conocimiento/patología , Trastornos del Conocimiento/fisiopatología , Trastornos del Conocimiento/psicología , Modelos Animales de Enfermedad , Macaca fascicularis , MasculinoRESUMEN
Paraoxonase 1 (PON1) is a cardioprotective enzyme associated with high-density lipoprotein (HDL). We tested the hypothesis that vitamin C protects HDL and PON1 from deleterious effects of hypochlorous acid, a proinflammatory oxidant. In our experiments, HDL (from human plasma) or diluted human plasma was incubated with hypochlorite in either the absence (control) or presence of vitamin C before measuring chemical modification and PON1 activities. Vitamin C minimized chemical modification of HDL, as assessed by lysine modification and accumulation of chloramines. In the absence of vitamin C, chloramines accumulated to 114 +/- 4 micromol/L in HDL incubated with a 200-fold molar excess of hypochlorite; but addition of vitamin C (200 micromol/L) limited formation to 36 +/- 6 micromol/L (P < .001). In plasma exposed to hypochlorite, IC(50) values of 1.2 +/- 0.1, 9.5 +/- 1.0, and 5.0 +/- 0.6 mmol/L were determined for PON1's phosphotriesterase, arylesterase, and (physiologic) lactonase activities, respectively. Vitamin C lessened this inhibitory effect of hypochlorite on PON1 activities. In plasma supplemented with vitamin C (400 micromol/L), PON1 phosphotriesterase activity was 72% +/- 17% of normal after incubation with hypochlorite (2 mmol/L), compared with 42% +/- 6% for unsupplemented plasma (P < .05). Similar effects were seen for other PON1 activities. In some experiments, vitamin C also appeared to reverse hypochlorite-mediated loss of PON1 phosphotriesterase activity; but this effect was not observed for the other PON1 activities. In conclusion, vitamin C attenuated hypochlorite-mediated loss of PON1 activity in vitro and may, therefore, preserve cardioprotective properties of HDL during inflammation.
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Antioxidantes/farmacología , Arildialquilfosfatasa/sangre , Ácido Ascórbico/farmacología , Ácido Hipocloroso/farmacología , Lipoproteínas HDL/metabolismo , Ácido Ascórbico/sangre , Hidrolasas de Éster Carboxílico/sangre , Hidrolasas de Éster Carboxílico/metabolismo , Enfermedades Cardiovasculares/prevención & control , Humanos , Lipoproteínas LDL/metabolismo , Hidrolasas de Triéster Fosfórico/sangreRESUMEN
This study aims to investigate the therapeutic potential of adult bone marrow stromal cells (BMSCs). Exposed to a cocktail of induction medium, some BMSCs could differentiate into cell types with phenotypes of neural lineages in vitro. These cells expressed neural markers nestin, GFAP, 68-kDa neurofilament and beta-tubulin III as detected by immunohistochemistry and RT-PCR. Fluorescence-labeled cells were injected intravenously at 72 h after traumatic brain injury. Transplanted cells survived and migrated to the ipsilateral cerebral cortex at different time points after injection. They were immunopositive for neuronal marker MAP-2, oligodendrocyte marker CNPase, astrocytic maker GFAP or microglial marker OX-42 in vivo. In rats receiving BMSC transplants, there were significant improvements in motor and neurological functions when compared with the control groups. Hence, the therapeutic potential of BMSCs for traumatic brain injury is further amplified.
Asunto(s)
Células de la Médula Ósea/citología , Trasplante de Médula Ósea , Lesiones Encefálicas/terapia , 2',3'-Nucleótido Cíclico Fosfodiesterasas/metabolismo , Animales , Lesiones Encefálicas/patología , Lesiones Encefálicas/fisiopatología , Diferenciación Celular , Movimiento Celular , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Proteína Ácida Fibrilar de la Glía/metabolismo , Inmunohistoquímica , Proteínas de Filamentos Intermediarios/metabolismo , Masculino , Proteínas del Tejido Nervioso/metabolismo , Nestina , Neuronas/metabolismo , Neuronas/patología , Especificidad de Órganos , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células del Estroma/trasplante , Tubulina (Proteína)/metabolismoRESUMEN
PURPOSE: To develop a high-performance liquid chromatography (HPLC) method with photodiode-array ultraviolet detection for the simultaneous determination of vitamin C, vitamin E and beta-carotene. METHODS: Following liquid-phase extraction from the human plasma samples, these three vitamins were successfully separated on the LiChrospher 100 RP-18 column (125 x 4 mm I.D.; particle size, 5 microm) at a flow-rate of 1.2 ml/min, with a mobile phase of methanol-acetonitrile-tetrahydrofuran (75: 20: 5, v/v/v). RESULTS: The limits of quantitation were 100, 0.25 and 0.25 microg/ml for vitamin C, vitamin E and beta-carotene respectively. The method is linear over the studied range of 0.25 to 5 g/ml for vitamin E and beta-carotene and 100 to 5000 microg/ml for vitamin C. The extraction recoveries were greater than 83% for these three vitamins. The within day and between-day precision of the analysis did not exceed 15.3 and 16.2%, respectively. CONCLUSION: A suitable method to determine the concentration of vitamin C, vitamin E and beta-carotene following oral administration of antioxidant supplement capsules to a healthy Chinese volunteer.
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Antioxidantes/análisis , Ácido Ascórbico/sangre , Vitamina E/sangre , beta Caroteno/sangre , Adulto , Cromatografía Líquida de Alta Presión/instrumentación , Cromatografía Líquida de Alta Presión/métodos , Humanos , Masculino , Fotoquímica/instrumentación , Análisis de Regresión , Reproducibilidad de los Resultados , Espectrofotometría UltravioletaRESUMEN
Several studies have shown that the angiotensin-converting enzyme (ACE) I allele is associated with enhanced physical performance. We investigated whether this phenomenon is observed in a cohort of 67 Chinese men in Singapore. Angiotensin-converting enzyme ID polymorphism was typed with PCR method and maximal oxygen uptake (VO(2max)) of the DD, ID, and II genotypes was compared. Analysis of covariance revealed that VO(2max) was significantly higher (p<0.05) for the DD genotype (57.86 +/- 3.5 ml.kg.(-1)min(-1)) versus the ID (50.58 +/- 1.80 ml.kg.(-1)min(-1)) or II (50.48 +/- 1.58 ml.kg.(-1) min(-1)) genotype. Our findings suggest that the ACE DD genotype in young adult Chinese males is associated with higher levels of VO(2max).