Individual and poly-substance use and condomless sex among HIV-uninfected adults reporting heterosexual sex in a multi-site cohort.

BACKGROUND: We analyzed the association between substance use (SU) and condomless sex (CS) among HIV-negative adults reporting heterosexual sex in the Seek, Test, Treat, and Retain (STTR) consortium. We describe the impact of SU as well as person/partner and context-related factors on CS, identifying combinations of factors that indicate the highest likelihood of CS. METHODS: We analyzed data from four US-based STTR studies to examine the effect of SU on CS using two SU exposures: 1) recent SU (within 3 months) and 2) SU before/during sex. Behavioral data were collected via 1:1 or self-administered computerized interviews. Adjusted individual-study, multivariable relative risk regression was used to examine the relationship between CS and SU. We also examined interactions with type of sex and partner HIV status. Pooled effect estimates were calculated using traditional fixed-effects meta-analysis. We analyzed data for recent SU (n = 6781; 82% men, median age = 33 years) and SU before/during sex (n = 2915; 69% men, median age = 40 years). RESULTS: For both exposure classifications, any SU other than cannabis increased the likelihood of CS relative to non-SU (8-16%, p-values< 0.001). In the recent SU group, however, polysubstance use did not increase the likelihood of CS compared to single-substance use. Cannabis use did not increase the likelihood of CS, regardless of frequency of use. Type of sex was associated with CS; those reporting vaginal and anal sex had a higher likelihood of CS compared to vaginal sex only for both exposure classifications (18-21%, p < 0.001). Recent SU increased likelihood of CS among those reporting vaginal sex only (9-10%, p < 0.001); results were similar for those reporting vaginal and anal sex (5-8%, p < 0.01). SU before/during sex increased the likelihood of CS among those reporting vaginal sex only (20%; p < 0.001) and among those reporting vaginal and anal sex (7%; p = 0.002). Single- and poly-SU before/during sex increased the likelihood of CS for those with exclusively HIV-negative partners (7-8%, p ≤ 0.02), and for those reporting HIV-negative and HIV-status unknown partners (9-13%, p ≤ 0.03). CONCLUSION: Except for cannabis, any SU increased the likelihood of CS. CS was associated with having perceived HIV-negative partners and with having had both anal/vaginal sex.

Pharmacological and toxicological effects of Ruta chalepensis L. on experimentally induced seizures and electroencephalographic spectral power in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Ruta chalepensis L. (Rutaceae) is used in traditional medicine to treat a wide variety of disorders such as rheumatism, fever, mental disorders, dropsy, neuralgia, menstrual problems, anxiety, and epilepsy. AIM OF THE STUDY: To evaluate and compare the anticonvulsant properties of an aqueous extract and ethyl acetate (AcOEt) fraction of R. chalepensis on pentylenetetrazole (PTZ)-induced seizures and maximal electroshock (MES) test in mice, by analyzing behavior and electroencephalogram (EEG), as well as GABAA receptors involvement. METHODS: The effect of an acute administration of different dosage of the aqueous extract (300 or 500 mg/kg) or AcOEt fraction (100, 300, 500 or 1000 mg/kg) of R. chalepensis was explored on two different models of acute seizure induction in mice, the PTZ and maximal electroshock (MES) tests. Behavioral and electrographic effects were quantified. Additionally, the possible involvement of the GABAA receptors was explored in the presence of picrotoxin (a non-competitive antagonist of the GABAA receptor). RESULTS: AcOEt fraction of R. chalepensis was more efficient than aqueous extract to reduce the incidence of tonic-clonic seizures and mortality in a significant and dose-dependent manner in both the PTZ and MES tests. This anticonvulsant effect was not abolished in the presence of picrotoxin. The EEG spectral power analysis revealed that aqueous extract decreased alpha and beta power, while AcOEt fraction decreased alpha and gamma power confirming previous findings of its depressant effect in the central nervous system. It is important to mention that the highest dosage of the AcOEt (1000 mg/kg) produced a severe suppression or isoelectric EEG activity (EEG flattening), recognized as a comatose state, suggesting a neurotoxic effect at this dosage. CONCLUSION: Our data reinforce that depressant and anticonvulsant effects of R. chalepensis depend in part on the presence of constituents from medium polarity. We also found that anticonvulsant effect is not mediated by GABAA receptors. In addition, cautious is emphasized when high doses of this natural product are used in traditional medicine since it might produce neurotoxic effects.

[Maternal complications in preeclamptic patients with hyperuricemia managed in Intensive Care Unit]. / Complicaciones maternas en pacientes con preeclampsia e hiperuricemia tratadas en la unidad de cuidados intensivos.

BACKGROUND: Hyperuricemia is a factor related to a higher frequency of complications in patients with preeclampsia. OBJECTIVES: To determine maternal complications in preeclamptic patients with hyperuricemia managed in the intensive care unit of a high-specialty hospital. MATERIAL AND METHODS: Cross-sectional study. Clinical files of 127 preeclamptic patients with criteria of severe disease were reviewed. Maternal complications were studied only in patients with hyperuricemia defined as a serum uric acid (UA) level > 4 mg/dL upon admission. Descriptive statistics were used. RESULTS: Frequency of patients with hyperuricemia was 88.1% (112 cases). Median value of UA was 6.6 ± 1.5 mg/dL (range 4.6-12.4), maternal age 28.1 ± 5.98 years, parity 2 and gestational age 32.9 ± 3.7 weeks. Cesarean section was performed in 98.21%. Frequency of maternal complications was 50% (56 cases): HELLP syndrome 40.1% (45 cases), acute renal injury 6.2% (7 cases), abruptio placentae 1 .7% (2 cases), hemorrhage due to uterine atony 0.8% (1 case) and acute pulmonary edema 0.8% (1 case). There were no cases of multiorgan failure syndrome and maternal mortality was 0%. None of the patients experienced worsening of their condition. CONCLUSIONS: There was an elevated frequency of patients with hyperuricemia and maternal complications. Reported complications were different from those reported in previous studies. All patients were successfully intervened with the administered medical treatment and may be a reflection of the beneficial effect of intensive care treatment.

A review of the impact of oxidative stress and some antioxidant therapies on renal damage.

An increase in the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) leads to complications during chronic kidney disease (CKD). This increase essentially derives from the impairment of natural antioxidant systems of the organism. The resulting oxidative stress produces damage to kidney tissue, especially by affecting nephrons and more generally by disrupting the function and structure of the glomerulus and interstitial tubule. This leads to a rapid decline in the condition of the patient and finally renal failure. Possible causes of kidney tissue damage are explored, as are different therapies, especially those related to the administration of antioxidants.

Dysfunctional cortical inhibition in adult ADHD: neural correlates in auditory event-related potentials.

In recent times, the relevance of an accurate diagnosis of attention-deficit/hyperactivity disorder (ADHD) in adults has been the focus of several studies. No longer considered a pathology exclusive to children and adolescents, and taking into account its social implications, developing enhanced support tools for the current diagnostic procedure becomes a priority. Here we present a method for the objective assessment of ADHD in adults using chirp-evoked, paired auditory late responses (ALRs) combined with a two-dimensional ALR denoising scheme to extract correlates of intracortical inhibition. Our method allows for an effective single-sweep denoising, thus requiring less trials to obtain recognizable physiological features, useful as pointers of cortical impairment. Results allow an optimized diagnosis, reduction of data loss and acquisition time; moreover, they do not account exclusively for critical elements within clinical evaluations, but also allow studying the pathophysiology of the condition by providing objective information regarding impaired cortical functions.

Brachytherapy versus radical hysterectomy after external beam chemoradiation with gemcitabine plus cisplatin: a randomized, phase III study in IB2-IIB cervical cancer patients.

BACKGROUND: The aim of the present study was to demonstrate that radical hysterectomy (RH) leads to improved survival outcomes in FIGO stage IB2-IIB cervical cancer when compared with standard brachytherapy (BCT) after identical external beam chemoradiation (EBRT-CT). PATIENTS AND METHODS: EBRT-CT treatment consisted of six courses of cisplatin at 40 mg/m² and gemcitabine at 125 mg/m² per week concurrent with 50.4 Gy of radiation. In the BCT arm, EBRT-CT was followed by BCT to reach a point A dose of 85 Gy, whereas in the experimental arm, a type III RH with bilateral pelvic lymph node dissection and para-aortic lymph node sampling (RH) was carried out within 4-6 weeks after EBRT-CT. RESULTS: Between May 2004 and June 2009, 211 patients were enrolled (BCT, 100 and RH, 111). At a median follow-up time of 36 months (3-80), progression-free survival (PFS) and overall survival (OS) rates were similar in both the arms. PFS rates were 74.8% and 71.7% in the BCT and RH arms [HR 0.6516 (95% confidence interval (CI) 0.3504-1.2116)], P = 0.186. OS rates were 76.3% in the BCT versus 74.5% in the surgical arm [HR 0.6981 (95% CI 0.3106-1.3439)], P = 0.236. No differences were observed in the pattern of local and systemic failures. CONCLUSIONS: This study failed to demonstrate that RH after EBRT-CT is superior to standard BCT.

Tityus zulianus and Tityus discrepans venoms induced massive autonomic stimulation in mice

Venezuelan scorpion envenomation is a public health problem produced by Tityus discrepans (TD) and Tityus zulianus (TZ) species. Patients-envenomend by TD developed gastrointestinal and pacreatic disorders and scorpion accidents involving TZ are associated with high mortality rate, which showed cardiopulmonary clinical disorders may be associated to the high levels of plasma catecholamines levels. This distinctive clinical output seems to be associated to a toxin repertoire diversity, which has been previously demonstrated. Trying to mimic the human-envenomation, some toxinological studies have been performed using TD and TZ venoms in several biomedels such as mice and anesthetized rams. The purpose of this study was to evaluate, in vivo using biomodels (mice), the role of autonomic nervous system (sympathetic) stimulation producing some of the clinical signs, via the catecholamines release, on the patho-physiology of the TZ and TD induced envenomation. Thus, a clinical signs here reported during a period of 1 hr, after a single intra-peritoneal injection of sub-lethal doses of TZ or TD venom, which are related with diarrhea, diaphoresis, intense salivation, dehydratation, dyspnea and spasticity in hind limbs. However, these animals did not exhibit vomiting, which is the most frequent human-envenomed TD patients. All animals inoculated with (TD or TZ) venoms develped diarrhea being more pronounced in TD group. Diaphoresis, sialorrhea and dehydratation were mainly observed in TD group. Dyspnea and the hind limb spasticity were only developed in TZ mice. These clinical manifestations (diarrhea, sialorrhea, dehydratation and intense salivation) are related to an activation of autonomic nervous system, via an intense release of their related neurotransmitters. Thus, autonomic stimulation (sympathetic) was evaluated following the catecholamine (Nor-Epinephrine) (NE) plasma levels in a function of envenomation time. We found a significant increments at 1 hr,...

El escorpionismo en Venezuela es un problema actual de salud pública producido por las especies de Tityus discrepans (TD) y Tityus zulianus (TZ). Los pacientes que presentan escorpionismo producido por TD desarrollan trastornos gastrointestinales y pancreáticos mientras que los afectados por TZ presentan una alta mortalidad y muestran una sintomatología relacionada a desordenes cardiopulmonares, los cuales parecen estar asociados a niveles elevados de las catecolaminas plasmáticas. Esta clínica diferente parece estar asociada a una composición distinta de toxinas de dichos venenos, lo cual ha sido previamente demostrado. En un intento de mimetizar o reproducir el escorpionismo en humanos se han realizado estudios toxinológicos con los venenos de TZ y TD utilizando varios biomodelos como son ratones y carneros anestesiados. El propósito de este trabajo fue evaluar, “in vivo” usando un Biomodelo (ratones), el papel de la estimulación del sistema nervioso autónomo (simpático) para producir algunos signos clínicos, vía la liberación de catecolaminas, en la fisiopatología del escorpionismo producido por TZ y TD. Así, los signos clínicos aquí descritos y observados durante 1 hr., después de la inyección de una dosis sub-letal de los venenos de TZ y TD, fueron la presencia de diarrea, diaforesis, salivación intensa, deshidratación, disnea y parálisis en las extremidades posteriores. Sin embargo, estos animales no presentaron vómitos, el cual es uno de los signos más frecuentemente observado en los pacientes con accidentes escorpiónicos por TD. Todos los animales inyectados con los venenos de TD y TZ presentaron diarrea especialmente en grupo TD. La disnea y la parálisis en los miembros posteriores fueron sólo observadas en el grupo de ratones inyectados con TZ. Las manifestaciones clínicas como son diarrea, diaforesis y la salivación intensa están asociadas a una activación del sistema nervioso autónomo...

[Immunohistochemical expression of progesterone receptor in relationship with histological grade and risk of relapses in intracranial meningiomas]. / Expresión inmunohistoquímica del receptor de progesterona en relación con el grado histológico y riesgo de recidivas en meningiomas intracraneanos.

INTRODUCTION: Meningiomas are frequent primary neoplasms of the central nervous system, usually benign and susceptible to healing through surgery. The histological grade of the WHO and the extension of the initial surgical resection are determining prognostic factors in these tumors. Nevertheless, a recurrence rate close to 20 % in benign meningiomas completely diseccated arises the need of considering new prognostic factors. METHODS: A total of 93 cases were selected for the immunohistochemical study of the progesterone receptor (PR) in relation to the histological grade and the risk of recurrencies in meningiomas. RESULTS: Though the immunohistochemical labelling index (LI) of the PR decreased with the progression of the histological grade (means of 27.37 % for grade I, 17.89% for grade II, and 13.50% for grade III), such correlation was not statistically significant and the cut off estimated in 20% was not satisfactory to discriminate among benign meningiomas (grade I) and non benign (grades II-III) due to its poor sensitivity (56.10%) and positive predictive value (56.10 %). The comparison of the LI of the PR among non recurrent meningiomas (36.35 %) and recurrent (22.10%) was neither statistically significant, but permitted to establish a useful cut off of 40% (LI >40% in 13/23 non recurrent tumors and <40% in 19/23 recurrent tumors) with a sensitivity of 82.61% and a positive predictive value of 65.52%. CONCLUSION: The LI of the PR is apparently not related to the histological grade of the meningiomas, but is significantly smaller in recurrent meningiomas. A meningioma with a LI of the PR less than 40 % suggests the risk of recurrences.

Expresión inmunohistoquímica del receptor de progesterone en relación con el grado histológico y riesgo de recidivas en meningiomas intracraneanos / Immunohistochemical expression of progesterone receptor in relationship with histological grade and risk of relapses in intracranial meningiomas

Introducción. Los meningiomas son neoplasias primarias frecuentes del sistema nervioso central, usualmente benignos y susceptibles de curación mediante cirugía. El grado histológico de la OMS y la extensión de la resección quirúrgica inicial son factores pronósticos determinantes en estos tumores. Sin embargo, una tasa de recidiva cercana al 20% en meningiomas benignos totalmente resecados plantea la necesidad de considerar nuevos factores pronósticos. Métodos. Un total de 93 casos fueron seleccionados para el estudio inmunohistoquímico del receptor de progesterona (RP) en relación con el grado histológico y riesgo de recidivas en los meningiomas. Resultados. Aunque el índice de marcaje inmunohistoquímico (IM) del RP disminuyó con la progresión del grado histológico (promedios de 27,37% para el grado I, 17,89% para el II y 13,50% para el III), tal correlación no fue estadísticamente significativa y el punto de corte estimado en 20% no resultó satisfactorio para discriminar entre meningiomas benignos (grado I) y no benignos (grados II-III) dada su pobre sensibilidad (56,10 %) y valor predictivo positivo (56,10%). La comparación del IM del RP entre meningiomas no recidivantes (36,35 %) y recidivantes (22,10%) tampoco resultó estadísticamente significativa, pero permitió establecer un punto de corte útil de 40% (IM¡Ý40% en 13/23 tumores no recidivantes y <40% en 19/23 tumores recidivantes) con una sensibilidad de 82,61% y un valor predictivo positivo de 65,52%. Conclusiones. El IM del RP no guarda relación aparente con el grado histológico de los meningiomas, pero resulta significativamente menor en tumores recidivantes. Ante un meningioma dado, un IM del RP menor de 40% sugiere la posibilidad de un riesgo mayor para desarrollar recidivas (AU)

Introduction: Meningiomas are frequent primary neoplasms of the central nervous system, usually benign and susceptible to healing through surgery. The histological grade of the WHO and the extension of the initial surgical resection are determining prognostic factors in these tumors. Nevertheless, a recurrence rate close to 20 % in benign meningiomas completely diseccated arises the need of considering new prognostic factors. Methods: A total of 93 cases were selected for the immunohistochemical study of the progesterone receptor (PR) in relation to the histological grade and the risk of recurrencies in meningiomas. Results: Though the immunohistochemical labelling index (LI) of the PR decreased with the progression of the histological grade (means of 27.37 % for grade I, 17.89% for grade II, and 13.50% for grade III), such correlation was not statistically significant and the cut off estimated in 20% was not satisfactory to discriminate among benign meningiomas (grade I) and non benign (grades II-III) due to its poor sensitivity (56.10%) and positive predictive value (56.10 %). The comparison of the LI of the PR among non recurrent meningiomas (36.35 %) and recurrent (22.10%) was neither statistically significant, but permitted to establish a useful cut off of 40% (LI >40% in 13/23 non recurrent tumors and <40% in 19/23 recurrent tumors) with a sensitivity of 82.61% and a positive predictive value of 65.52%. Conclusion: The LI of the PR is apparently not related to the histological grade of the meningiomas, but is significantly smaller in recurrent meningiomas. A meningioma with a LI of the PR less than 40 % suggests the risk of recurrences (AU)

Evaluación del test rápido ontrak teststik para detectar cocaína y marihuana en muestras de orina / Ontrak teststik rapid test evaluation for the detecting cocaine and marijuana in urine samples

Este estudio tiene como objetivo evaluar la validez del test rápido TesTsitk para detectar cocaína y marihuna en muestras de orina, comparándolo con el método de inmunoflurescencia polarizada (FPIA-TDx) y el inmunoenzimático heterogéneo (ELISA), en vista de sus próxima introducción en el mercado venezolano. Se recolectaron 69 muestras de orina en las cuales se realizaron 58 determinaciones para marihuana y 61 para cocaína. Este test es sensible a concentraciones de droga iguales o cercanas a los valores de cut-off (300 ng/mL para cocaína y 50 ng/mL para la marihuana) establecidos por el Instituto Nacional de Drogas de Abuso (NIDA). De acuerdo a los resultados obtenidos no se observaron variaciones significativas entre el teststik y los otros métodos, lo que nos permite concluir que el teststik es un test confiable que se puede aplicar cuando se requiera de un resultado rápido

Serotonin turnover rate, [3H]paroxetine binding sites, and 5-HT1A receptors in the hippocampus of rats subchronically treated with clonazepam.

Selective central benzodiazepine agonists, such as clonazepam, are known to modify serotonin and 5-hydroxyindoleacetic content in the brain. In order to further study the effect of this benzodiazepine on serotonin turnover rate, rats received clonazepam, 10 mg/kg for 10 days, and the concentrations of serotonin and 5-hydroxyindoleacetic acid were determined in the hippocampus after inhibition of monoamineoxidase with pargyline. The results indicate a reduction in the turnover rate of the monoamine. In addition, the systemic administration of clonazepam produced a decrease in the Bmax of [3H]DPAT binding to 5-HT1A sites in the hippocampus. By contrast, this effect was not observed if clonazepam was delivered into the dorsal raphe nucleus by osmotic minipumps. The binding of [3H]paroxetine to 5-HT reuptake sites was increased by the treatment with clonazepam. The present observations indicate that clonazepam produces a reduction of serotonin turnover rate in the hippocampus of the rat concomitant with a down-regulation of 5-HT1A binding sites, probably by an effect at the forebrain projections. There is also an up-regulation of the serotonin transporter, which might contribute to a reduction in the synaptic availability of serotonin during clonazepam treatment.

Modulation of 5HT1A receptors in the hippocampus and the raphe area of rats treated with clonazepam.

1. Clonazepam is one of the most potent benzodiazepines known to decrease the activity of the central serotonergic systems. The acute and subchronic administration of clonazepam reduced serotonin (5HT) turnover rate in the hippocampus of the rat, as determined by the ratio of the monoamine and its metabolite, 5-hydroxyindoleacetic acid. 2. The modulation of 5HT binding sites and 5HT1A receptors by the administration of clonazepam for various periods of time were studied in the hippocampus and the raphe area by experiments with radioligands. 3. The density of [3H]5HT recognition sites increased in the hippocampus of clonazepam-treated rats in a dose- and time-dependent manner. This increase was impaired by the simultaneous administration of the 5HT agonist 5-methoxy-N,N-dimethyltryptamine. The affinity of this binding did not significantly change. This observation might indicate an increase in some of the 5HT receptors or an increase of the uptake site. 4. The binding parameters for [3H]DPAT, Bmax and Kd, decreased in the hippocampus but not in the raphe area of clonazepam-treated rats. It seems that the presynaptic reduction in 5HT function, resulting in the decrease of its availability at the synaptic space, modifies the corresponding 5HT recognition sites. 5. These changes could be related to the anxyolitic activity or the withdrawal symptoms of benzodiazepines.