Effects of Switching from Stavudine to Raltegravir on Subcutaneous Adipose Tissue in HIV-Infected Patients with HIV/HAART-Associated Lipodystrophy Syndrome (HALS). A Clinical and Molecular Study

HIV-1/HAART-associated lipodystrophy syndrome (HALS) has been associated with exposure to stavudine (d4T) through mitochondrial dysfunction. We performed a 48-week study to assess the effects of switching from d4T to raltegravir (RAL) on metabolic and fat molecular parameters of patients with HALS. Forty-two patients with HALS and a median exposure to d4T > 7 years were switched to RAL and followed for 48 weeks. Fasting metabolic tests, HIV RNA, CD4 cell count, and fat measured by DEXA were obtained at baseline and week 48. mtDNA and gene transcripts for PPAR gamma, adiponectin, cytochrome b, Cox IV, TNF alpha, MCP-1 and CD68 were assessed in paired subcutaneous fat tissue biopsies. Lipid parameters, fasting glucose, insulin, and HOMA-IR did not change significantly. Whole body fat (P = 0.0027) and limb fat mass (P<0.0001) increased from baseline. Trunk/limb fat ratio (P = 0.0022), fat mass ratio (P = 0.0020), fat mass index (P = 0.0011) and percent leg fat normalized to BMI (P<0.0001) improved after 48 weeks. Relative abundance of mtDNA, expression of PPAR gamma, adiponectin, Cyt b, and MCP-1 genes increased, whereas Cox IV, TNF alpha, and CD68 did not change significantly from baseline. Switching from d4T to RAL in patients with HALS is associated with an increase in limb fat mass and an improvement in markers of adipocyte differentiation and mitochondrial function in SAT

Differential effects of dolutegravir, bictegravir and raltegravir in adipokines and inflammation markers on human adipocytes.

Aims: To assess the potential direct effects of the integrase strand-transfer inhibitors (INsTIs) dolutegravir, bictegravir, and raltegravir, drugs used as treatment for people living with human immunodeficiency virus (PLWH), on human adipose cells. Main methods: Drugs were added to the differentiation medium of human Simpson-Golabi-Behmel syndrome (SGBS) adipose cells and morphological adipogenesis was monitored for 10 days. Also, adipocytes were exposed to drugs following differentiation (day 14). The gene expression levels of selected adipogenesis markers, adipocyte metabolism markers, adipokines, and cytokines were determined by quantitative-reverse transcription polymerase-chain reaction. The release of adiponectin and leptin into the culture medium was measured using specific enzyme-linked immunosorbent assay, and release of interleukin-6 and chemokine (CC motif) ligand-2 using Multiplex assays. Key findings: Overall morphological adipogenesis was unaltered by INsTIs. The expression of adipogenesis marker genes (peroxisome proliferator-activated receptor-Ɣ and lipoprotein lipase) was slightly reduced in dolutegravir-treated differentiating adipocytes. Bictegravir repressed gene expression and the release of pro-inflammatory cytokines in differentiating adipocytes. Dolutegravir and raltegravir increased interleukin-6 gene expression, but only dolutegravir increased interleukin-6 release. Dolutegravir repressed adiponectin expression and release in differentiating adipocytes and had a similar but milder effect on leptin. Drug treatment of mature adipocytes reduced adiponectin gene expression in response to dolutegravir. Significance: The INsTIs studied do not have a significant effect on human adipose cell differentiation but exert distinct effects on gene expression and secretion of adipokines and cytokines. These findings will help understand and manage the effects of INsTI-containing treatments on body weight and metabolic dysregulation in PLWH

FGF21 serum levels are related to insulin resistance, metabolic changes and obesity in Mexican people living with HIV (PLWH).

Antiretroviral therapy has significantly improved prognosis in treatment against HIV infection, however, prolonged exposure is associated to cardiovascular diseases, lipodystrophy, type 2 diabetes, insulin resistance, metabolic alteration, as obesity which includes the accumulation of oxidative stress in adipose tissue. FGF21 is a peptide hormone that is known to regulate glucose and lipid metabolism. FGF21 is expressed and secreted primarily in the liver and adipose tissue, promoting oxidation of glucose/fatty acids and insulin sensitivity. Alterations in FGF21 may be associated with the development of insulin resistance, metabolic syndrome and cardiovascular disease. We hypothesized that FGF21 protein levels are associated with metabolic abnormalities, placing special attention to the alterations in relation to the concurrence of overweight/obesity in people living with HIV (PLWH)

The molecular signature of HIV-1-associated Lipomatosis reveals differential involvement of Brown and Beige/Brite Adipocyte cell lineages

Highly active antiretroviral therapy has remarkably improved quality of life of HIV-1-infected patients. However, this treatment has been associated with the so-called lipodystrophic syndrome, which conveys a number of adverse metabolic effects and morphological alterations. Among them, lipoatrophy of subcutaneous fat in certain anatomical areas and hypertrophy of visceral depots are the most common. Less frequently, lipomatous enlargements of subcutaneous fat at distinct anatomic areas occur. Lipomatous adipose tissue in the dorso-cervical area ('buffalo hump') has been associated with a partial white-to-brown phenotype transition and with increased cell proliferation, but, to date, lipomatous enlargements arising in other parts of the body have not been characterized. In order to establish the main molecular events associated with the appearance of lipomatosis in HIV-1 patients, we analyzed biopsies of lipomatous tissue from 'buffalo hump' and from other anatomical areas in patients, in comparison with healthy subcutaneous adipose tissue, using a marker gene expression approach. Both buffalo-hump and non-buffalo-hump lipomatous adipose tissues exhibited similar patterns of non-compromised adipogenesis, unaltered inflammation, non-fibrotic phenotype and proliferative activity. Shorter telomere length, prelamin A accumulation and SA-β-Gal induction, reminiscent of adipocyte senescence, were also common to both types of lipomatous tissues. Buffalo hump biopsies showed expression of marker genes of brown adipose tissue (e.g. UCP1) and, specifically, of 'classical' brown adipocytes (e.g. ZIC1) but not of beige/brite adipocytes. No such brown fat-related gene expression occurred in lipomatous tissues at other anatomical sites. In conclusion, buffalo hump and other subcutaneous adipose tissue enlargements from HIV-1-infected patients share a similar lipomatous character. However, a distorted induction of white-to-'classical brown adipocyte' phenotype appears unique of dorso-cervical lipomatosis. Thus, the insults caused by HIV-1 viral infection and/or antiretroviral therapy leading to lipomatosis are acting in a location- and adipocyte lineage-dependent manner

Recomanacions per a la prevenció de la transmissió vertical del VIH

Transmissió vertical; Transmissió mare-fill; VIHTransmisión vertical; Transmisión madre-hijo; VIHVertical transmission; Mother-son transmission; HIVLa transmissió vertical o mare-fill del virus de la immunodeficiència humana (VIH) és la principal via d’infecció en l’edat pediàtrica. Es pot produir durant la gestació, el part i durant el postpart a través de l’alletament matern. En aquest document s’exposen les recomanacions per a la prevenció de la transmissió vertical del VIH a Catalunya. Parteix de la necessitat d’establir l’estat serològic de la futura mare, tant si ja està embarassada i el desconeix, com si es tracta d’una dona infectada pel VIH que es planteja tenir un fill. Analitza en primer lloc el procediment que cal seguir perquè la gestant conegui el seu estat serològic i també què han de tenir en compte les dones infectades pel VIH abans d’iniciar un embaràs. A continuació s’exposen els controls i tractaments que ha de seguir la gestant infectada, en quines condicions s’ha de desenvolupar el part i a quins controls i procediments s’ha de sotmetre el nadó per protegir-lo de la infecció. Aquest material té l’objectiu de millorar i facilitar la informació necessària en el moment del part, als professionals sanitaris de la xarxa de centres hospitalaris de Catalunya, especialment els pediatres, ginecòlegs, obstetres, infermeres i llevadores, que habitualment estan treballant a la sala de parts i facilitar la presa de decisions en el dia a dia.La transmisión vertical o madre-hijo del virus de la inmunodeficiencia humana (VIH) es la principal vía de infección en la edad pediátrica. Se puede producir durante la gestación, el parto y durante el posparto a través de la lactancia materna. En este documento se exponen las recomendaciones para la prevención de la transmisión vertical del VIH en Cataluña. Parte de la necesidad de establecer el estado serológico de la futura madre, tanto si ya está embarazada y desconoce, como si se trata de una mujer infectada por el VIH que se plantea tener un hijo. Analiza en primer lugar el procedimiento a seguir para que la gestante conozca su estado serológico y también que deben tener en cuenta las mujeres infectadas por el VIH antes de iniciar un embarazo. A continuación se exponen los controles y tratamientos que debe seguir la gestante infectada, en qué condiciones se debe desarrollar el parto y en qué controles y procedimientos se someterá al bebé para protegerlo de la infección. Este material tiene el objetivo de mejorar y facilitar la información necesaria en el momento del parto, a los profesionales sanitarios de la red de centros hospitalarios de Cataluña, especialmente los pediatras, ginecólogos, obstetras, enfermeras y matronas, que habitualmente están trabajando en la sala de partes y facilitar la toma de decisiones en el día a día

Inteligencia emocional como método de prevención del acoso escolar

[spa] Este Trabajo de Fin de Grado (TFG) es una propuesta de iniciación a la investigación educativa basada en el desarrollo de un programa de educación emocional. Este trabajo es una defensa sobre la necesidad urgente de introducir en los aprendizajes escolares la Inteligencia Emocional en la primera etapa de Educación Primaria para prevenir posibles problemas de convivencia escolar posteriormente. Por tanto, este trabajo se inicia con la explicación de dos conceptos muy claves: inteligencia emocional y problemas en la convivencia escolar; para acabar con un Plan de acción Tutorial basado en una serie de actividades que permiten fomentar el desarrollo de la Inteligencia Emocional.[eng] This Grade's End Work (TFG) is an initiation proposal to the educative research based on the development of an emotional education program.This work is a defence on the urgent need of introducing in the school learnings Emotional Intelligence in the first stage of Primary Education to warn possible problems of school coexistence subsequently.Therefore, this work starts one with the two concept explanation very keys:Emotional intelligence and problems in the school coexistence; to end with a Plan of Tutorial action based on a series of activities that allow to promote the Emotional Intelligence development

Una combinación obligada en Silene diversifolia Otth

Peer Reviewe

Response to Combined Antiretroviral Therapy According to Gender and Origin in a Cohort of Naive HIV-Infected Patients: GESIDA-5808 Study

We analyzed differences in response to combined antiretroviral therapy (cART) according to sex and geographic origin in a retrospective comparative study of Spanish-born and immigrant patients initiating cART. The primary endpoint was time to treatment failure (TTF), defined as virological failure, death, opportunistic infection, interruption of cART, or loss to follow-up. Late diagnosis was defined as a CD4+ cell count ≤ 200 cells/mm3 and/or AIDS at initiation of cART. Survival was analyzed using Kaplan-Meier analysis and Cox regression. We followed 1,090 patients, of whom 318 were women (45.6% immigrant women [IW]). At initiation of treatment, women had a higher CD4+ count than men (217 vs 190 cells/mm3), a lower viral load (4.7 vs 5 log), and fewer were late starters (49% vs 59%). The adjusted risk of TTF between women and men was not significantly different (hazard ratio [HR], 1.10; 95% CI, 0.79-1.53). TTF was shorter among IW than Spanish-born women (124 weeks [95% CI, 64-183] vs 151 [95% CI, 127-174]) and loss to follow-up was double that of Spanish-born women (25.5% vs 11.6%). Although response to cART was similar for both sexes, men started treatment later. IW were more frequently lost to follow-up and switched treatment. Measures to improve medical follow-up after initiation of cART should be promoted among this minority group. Response to Combined Antiretroviral Therapy According to Gender and Origin in a Cohort of Naïve HIV-Infected Patients: GESIDA-5808 Study. Available from: https://www.researchgate.net/publication/224971412_Response_to_Combined_Antiretroviral_Therapy_According_to_Gender_and_Origin_in_a_Cohort_of_Naive_HIV-Infected_Patients_GESIDA-5808_Study.2.304 JCR (2012) Q2, 122/261 Pharmacology & pharmacy; Q3, 42/70 Infectious disease