Monthly intravenous methylprednisolone in relapsing-remitting multiple sclerosis - reduction of enhancing lesions, T2 lesion volume and plasma prolactin concentrations

BACKGROUND: Intravenous methylprednisolone (IV-MP) is an established treatment for multiple sclerosis (MS) relapses, accompanied by rapid, though transient reduction of gadolinium enhancing (Gd+) lesions on brain MRI. Intermittent IV-MP, alone or with immunomodulators, has been suggested but insufficiently studied as a strategy to prevent relapses. METHODS: In an open, single-cross-over study, nine patients with relapsing-remitting MS (RR-MS) underwent cranial Gd-MRI once monthly for twelve months. From month six on, they received a single i.v.-infusion of 500 mg methylprednisolone (and oral tapering for three days) after the MRI. Primary outcome measure was the mean number of Gd+ lesions during treatment vs. baseline periods; T2 lesion volume and monthly plasma concentrations of cortisol, ACTH and prolactin were secondary outcome measures. Safety was assessed clinically, by routine laboratory and bone mineral density measurements. Soluble immune parameters (sTNF-RI, sTNF-RII, IL1-ra and sVCAM-1) and neuroendocrine tests (ACTH test, combined dexamethasone/CRH test) were additionally analyzed. RESULTS: Comparing treatment to baseline periods, the number of Gd+ lesions/scan was reduced in eight of the nine patients, by a median of 43.8% (p = 0.013, Wilcoxon). In comparison, a pooled dataset of 83 untreated RR-MS patients from several studies, selected by the same clinical and MRI criteria, showed a non-significant decrease by a median of 14% (p = 0.32). T2 lesion volume decreased by 21% during treatment (p = 0.001). Monthly plasma prolactin showed a parallel decline (p = 0.027), with significant cross-correlation with the number of Gd+ lesions. Other hormones and immune system variables were unchanged, as were ACTH test and dexamethasone-CRH test. Treatment was well tolerated; routine laboratory and bone mineral density were unchanged. CONCLUSION: Monthly IV-MP reduces inflammatory activity and T2 lesion volume in RR-MS

Effectiveness of Non-nucleoside Reverse-Transcriptase Inhibitor-Based Antiretroviral Therapy in Women Previously Exposed to a Single Intrapartum Dose of Nevirapine: A Multi-country, Prospective Cohort Study

In a comparative cohort study, Jeffrey Stringer and colleagues investigate the risk of ART failure in women who received single-dose nevirapine for PMTCT, and assess the duration of increased risk

Couple-oriented prenatal HIV counseling for HIV primary prevention: an acceptability study

<p>Abstract</p> <p>Background</p> <p>A large proportion of the 2.5 million new adult HIV infections that occurred worldwide in 2007 were in stable couples. Feasible and acceptable strategies to improve HIV prevention in a conjugal context are scarce. In the preparatory phase of the ANRS 12127 Prenahtest multi-site HIV prevention trial, we assessed the acceptability of couple-oriented post-test HIV counseling (COC) and men's involvement within prenatal care services, among pregnant women, male partners and health care workers in Cameroon, Dominican Republic, Georgia and India.</p> <p>Methods</p> <p>Quantitative and qualitative research methods were used: direct observations of health services; in-depth interviews with women, men and health care workers; monitoring of the COC intervention and exit interviews with COC participants.</p> <p>Results</p> <p>In-depth interviews conducted with 92 key informants across the four sites indicated that men rarely participated in antenatal care (ANC) services, mainly because these are traditionally and programmatically a woman's domain. However men's involvement was reported to be acceptable and needed in order to improve ANC and HIV prevention services. COC was considered by the respondents to be a feasible and acceptable strategy to actively encourage men to participate in prenatal HIV counseling and testing and overall in reproductive health services.</p> <p>Conclusions</p> <p>One of the keys to men's involvement within prenatal HIV counseling and testing is the better understanding of couple relationships, attitudes and communication patterns between men and women, in terms of HIV and sexual and reproductive health; this conjugal context should be taken into account in the provision of quality prenatal HIV counseling, which aims at integrated PMTCT and primary prevention of HIV.</p

Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases

Prenatal HIV counselling as an opportunity to reach men ? : conjugal relationships and gender norms in the context of the prenahtest ANRS 12127 trial

In the context of the worldwide initiative towards the elimination of mother-to-child transmission of HIV (MTCT), renewed efforts are being made to increase the availability of prenatal HIV testing. These could be seized as an opportunity to increase the overall coverage of HIV testing and to improve the involvement of men in PMTCT. Within the Prenahtest ANRS 12127 trial conducted in Cameroon, Dominican Republic, Georgia and India, a couple-oriented HIV counselling (COC) intervention was delivered to pregnant women, to help them discuss sexual risks and HIV prevention with their male partner, and bring him to HIV testing during prenatal care. Based on in-depth interviews and on published scientific literature, we describe couple relationships and gender roles in the four study sites and explore how these may have enabled or constrained the success of the COC intervention. Three elements were identified as facilitating men’s involvement in prenatal HIV counselling and testing: the implication of a health worker as a third and professional voice between husband and wife; the appeal to men’s responsibility as fathers for the baby to be born; and a “male-friendly” organisation of prenatal services. Men can be involved in PMTCT and prenatal HIV counselling and testing when services are adapted to both gender norms and cultural contexts

Análisis económico de un modelo educativo de seguridad humana en los Bateyes del Suroeste de la República Dominicana

Objetivos: realizar un análisis económico para evaluar los costos de una intervención educativa, utilizando los principios de un modelo de seguridad humana en Bateyes del suroeste de la República Dominicana. Métodos: se consideraron cuatro recursos de intervención, incluyendo la capacitación del personal, los incentivos mensuales, la supervisión de las actividades de campo y el costo total asociado al tratamiento anual de la diarrea aguda. El gasto se comparó entre el programa estándar de atención (Batey Control) y la intervención con el modelo de seguridad humana (Batey Caso). Resultados: el ahorro del costo total anual para el Ministerio de Salud de República Dominicana asociado con la reducción de la incidencia de episodios de diarrea aguda fue de US$252,399. Si se extrapolan a los 300 Bateyes de República Dominicana, se podría ahorrar aproximadamente US$75 millones en prevención de enfermedades infecciosas. Conclusiones: el modelo de seguridad humana luce ser un método eficaz para mejorar el conocimiento sobre la prevención de enfermedades y aumentar el empoderamiento de la comunidad para la movilización de recursos. Aplicada a otros entornos, la intervención podría tener una incidencia beneficiosa en las poblaciones de refugiados e indocumentados bajo el impacto de la violencia estructural