Single-cell epigenetic, transcriptional, and protein profiling of latent and active HIV-1 reservoir revealed that IKZF3 promotes HIV-1 persistence.

Understanding how HIV-1-infected cells proliferate and persist is key to HIV-1 eradication, but the heterogeneity and rarity of HIV-1-infected cells hamper mechanistic interrogations. Here, we used single-cell DOGMA-seq to simultaneously capture transcription factor accessibility, transcriptome, surface proteins, HIV-1 DNA, and HIV-1 RNA in memory CD4+ T cells from six people living with HIV-1 during viremia and after suppressive antiretroviral therapy. We identified increased transcription factor accessibility in latent HIV-1-infected cells (RORC) and transcriptionally active HIV-1-infected cells (interferon regulatory transcription factor [IRF] and activator protein 1 [AP-1]). A proliferation program (IKZF3, IL21, BIRC5, and MKI67 co-expression) promoted the survival of transcriptionally active HIV-1-infected cells. Both latent and transcriptionally active HIV-1-infected cells had increased IKZF3 (Aiolos) expression. Distinct epigenetic programs drove the heterogeneous cellular states of HIV-1-infected cells: IRF:activation, Eomes:cytotoxic effector differentiation, AP-1:migration, and cell death. Our study revealed the single-cell epigenetic, transcriptional, and protein states of latent and transcriptionally active HIV-1-infected cells and cellular programs promoting HIV-1 persistence.

Single-cell multiomics reveals persistence of HIV-1 in expanded cytotoxic T cell clones.

Understanding the drivers and markers of clonally expanding HIV-1-infected CD4+ T cells is essential for HIV-1 eradication. We used single-cell ECCITE-seq, which captures surface protein expression, cellular transcriptome, HIV-1 RNA, and TCR sequences within the same single cell to track clonal expansion dynamics in longitudinally archived samples from six HIV-1-infected individuals (during viremia and after suppressive antiretroviral therapy) and two uninfected individuals, in unstimulated conditions and after CMV and HIV-1 antigen stimulation. Despite antiretroviral therapy, persistent antigen and TNF responses shaped T cell clonal expansion. HIV-1 resided in Th1-polarized, antigen-responding T cells expressing BCL2 and SERPINB9 that may resist cell death. HIV-1 RNA+ T cell clones were larger in clone size, established during viremia, persistent after viral suppression, and enriched in GZMB+ cytotoxic effector memory Th1 cells. Targeting HIV-1-infected cytotoxic CD4+ T cells and drivers of clonal expansion provides another direction for HIV-1 eradication.

Viral Load Dynamics in Plasma and Semen When Antiretroviral Therapy Is Initiated During Early HIV-1 Infection.

We assessed human immunodeficiency virus (HIV) load in plasma and semen during primary HIV infection using serial samples of semen and plasma during the first 24 weeks after diagnosis in untreated participants and those who started antiretroviral therapy (ART) immediately at diagnosis. In the absence of treatment, semen viral load was >1000 copies/mL in almost all specimens (83%) collected 2-10 weeks after the estimated date of HIV acquisition and remained >1000 copies/mL in 35% of untreated participants at the last observed time point. Thus, in the absence of ART, semen viral load remained at a level consistent with transmissibility throughout primary infection.

Clinical and Immunologic Outcomes After Immediate or Deferred Antiretroviral Therapy Initiation During Primary Human Immunodeficiency Virus Infection: The Sabes Randomized Clinical Study.

BACKGROUND: In addition to demonstrated public health benefits on reducing transmission, it remains unclear how early antiretroviral therapy (ART) must be started after acquisition of human immunodeficiency virus (HIV) to maximize individual benefits. METHODS: We conducted an open-label randomized clinical study in Lima, Peru among adult men who have sex with men and transgender women with acute (HIV-antibody negative/HIV-1 RNA positive) or recent (confirmed negative HIV-antibody or RNA test within 3 months) HIV infection, who were randomized to start ART immediately versus defer by 24 weeks. We evaluated outcomes by treatment arm and immunologic markers by days since estimated date of detectible infection (EDDI). RESULTS: Of 216 participants, 105 were assigned to immediate arm and 111 to deferred arm (median age 26.8 years, 37% with acute HIV). The incidence of non-ART-related adverse events was lower in immediate versus deferred arm (83 vs 123/100 person-years, IRR 0.67 (95% confidence interval [CI] .47, .95; P = .02), the difference dominated by fewer infections in those treated immediately. After 24 weeks of ART, between-group differences in CD4/CD8 cell ratio lessened (P = .09 overall), but differences between those initiating ART ≤ 30 days from EDDI (median 1.03, interquartile range [IQR] 0.84, 1.37), and those initiating > 90 days (0.88, IQR 0.61, 1.11) remained, P = .02. Principal components analysis of 20 immune biomarkers demonstrated distinct patterns between those starting ART > 90 days from EDDI versus those starting within 30 or 90 days (both P < .001). CONCLUSIONS: To our knowledge, this is the only evaluation of randomized ART initiation during primary HIV and provides evidence to explicitly consider acute HIV in World Health Organization recommendations for universal ART. CLINICAL TRIALS REGISTRATION: NCT01815580.

Sexual Behavior and Sexually Transmitted Infection Outcomes Among Men Who Have Sex With Men and Transgender Women Participating in a Study of the Timing of Antiretroviral Therapy in Lima, Peru.

BACKGROUND: We assessed sexual behavior and incidence of sexually transmitted infections (STIs) among men who have sex with men and transgender women participating in Sabes, a study of an expanded treatment as prevention strategy focused on early diagnosis and treatment of HIV infection in Lima, Peru (2013-2017). METHODS: Sabes participants were tested monthly for HIV to identify acute or early infections, and HIV-positive participants were randomized to receive antiretroviral therapy immediately (immediate arm) or after 24 weeks (deferred arm) during a 48-week follow-up period. Sexual behavior was assessed at randomization (baseline) and every 12 weeks thereafter. Participants were tested for urethral and rectal chlamydia and gonorrhea and for syphilis at baseline, 12, 24, and 48 weeks. We describe patterns of sexual behavior during the 48-week follow-up period and compare sexual behavior and STI incidence between study arms. RESULTS: After randomization, 207 HIV-positive participants completed questionnaires and STI testing at 2 or more visits. After HIV diagnosis, participants in both arms reported increases in condom use with main and casual partners and decreased drug and alcohol use before or during anal sex. We observed no between-arm differences in sexual behavior. Deferred arm participants had higher incidence of chlamydia (incidence rate ratio, 2.33; 95% confidence interval, 1.14-4.77) but not gonorrhea or syphilis. CONCLUSIONS: Despite reported increases in condom use, the overall high incidence of STIs reflects some ongoing condomless sex among HIV-positive men who have sex with men and transgender women, highlighting the importance of regular STI screening and counseling to support consistent condom use among HIV-positive individuals at risk for STIs.

Control of the dual reactivity (iminium-dienamine) of ß-arylmethyl α,ß-unsaturated aldehydes in organocatalytic 1,3-dipolar cycloadditions with N-benzoyl C,N-cyclic azomethine imines.

1,3-Dipolar cycloadditions of C,N-cyclic azomethine imines with α,ß-unsaturated aldehydes can be performed with complete control of the regio-, exo-, and enantioselectivity under aminocatalytic conditions. The so far never studied competence of the iminium-dienamine reactivity inherent to ß-alkyl α,ß-unsaturated aldehydes was studied, which was possible by allowing achievement of complete control of the chemoselectivity in reactions of the ß-arylmethyl derivatives with azomethine imines by using different additives and organocatalysts, whose role has been rationalized by DFT calculations and chemical proofs. Thus, it has been possible to selectively obtain the pyrazolidines resulting from both the attack to the C2-C3 (via iminium) and the C3-C4 (via dienamine) bonds at the starting enals, which can be used as precursors of interesting tetrahydroisoquinolinic compounds.

Copper(I)-catalyzed formal carboboration of alkynes: synthesis of tri- and tetrasubstituted vinylboronates.

The first copper-catalyzed formal carboboration of alkynes, in which a C-B bond and a C-C bond are created in a single catalytic cycle, is presented. The reaction proceeds with high regioselectivity and syn-stereoselectivity to form tri- and tetrasubstituted vinylboronic esters from commercially available bis(pinacolato)diboron. A subsequent cross-coupling reaction gives access to highly substituted alkenes.

Dynamic immune markers predict HIV acquisition and augment associations with sociobehavioral factors for HIV exposure.

Prior studies attempting to link biomarkers of immune activation with risk of acquiring HIV have relied on cross sectional samples, most without proximity to HIV acquisition. We created a nested case-control study within the Sabes study in Peru, and assessed a panel of plasma immune biomarkers at enrollment and longitudinally, including within a month of diagnosis of primary HIV or matched timepoint in controls. We used machine learning to select biomarkers and sociobehavioral covariates predictive of HIV acquisition. Most biomarkers were indistinguishable between cases and controls one month before HIV diagnosis. However, levels differed between cases and controls at study entry, months to years earlier. Dynamic changes in IL-2, IL-7, IL-10, IP-10 and IL-12, rather than absolute levels, jointly predicted HIV risk when added to traditional risk factors, and there was modest effect modification of biomarkers on association between sociobehavioral risk factors and HIV acquisition.

Long-term effects of early antiretroviral initiation on HIV reservoir markers: a longitudinal analysis of the MERLIN clinical study.

BACKGROUND: Early antiretroviral therapy (ART) initiation (ie, within 3 months of infection) limits establishment of the HIV reservoir. However, the effect of early ART initiation on the long-term dynamics of the pool of infected cells remains unclear. METHODS: In this longitudinal analysis, we included cisgender men who have sex with men (MSM) and transgender women (aged 18-54 years) at high risk for HIV infection, enrolled in the ongoing longitudinal MERLIN study in Peru between Oct 28, 2014, and Nov 8, 2018. Participants were eligible if they had been infected with HIV less than 90 days before enrolment, and if they had cryopreserved peripheral blood mononuclear cell (PBMC) samples. Participants were stratified into three groups on the basis of whether they initiated ART at 30 days or less (acute group), at 31-90 days (early group), or more than 24 weeks (deferred group) after the estimated date of detectable infection. PBMC samples were collected before ART initiation and longitudinally for up to 4 years on ART. The main outcomes were to establish the size of the HIV reservoir before ART initiation and to assess the effect of the timing of ART initiation on the decay of the HIV reservoir over 4 years follow-up. We quantified viral load, and isolated CD4 cells to quantify total HIV DNA, integrated HIV DNA and 2-long terminal repeat circles. Longitudinal analysis of active and inducible HIV reservoirs were measured by quantifying the frequency of CD4 cells producing multiply-spliced HIV RNA ex vivo and after in-vitro stimulation with a tat/rev induced limiting dilution assay (TILDA). A mixed-effects model from the time of ART initiation was used to measure longitudinal decays in viral loads and each HIV reservoir measure in each of the three groups. FINDINGS: We included 56 participants in this analysis, all of whom were MSM: 15 were in the acute group, 19 were in the early group, and 22 were in the deferred group. Participants in all three groups had similar levels of all HIV reservoir markers before ART initiation. All participants, including those in the acute group, had a pool of transcriptionally silent HIV-infected cells before ART initiation, as indicated by a substantial increase in TILDA measures upon stimulation. Longitudinal analysis over 4 years of ART revealed a biphasic decay of all HIV persistence markers, with a rapid initial decline followed by a slower decay in all participants. During the first-phase decay, the half-lives of both total and integrated HIV DNA and TILDA measures were significantly shorter in the acute group than in the early and deferred groups. During the second-phase decay, HIV reservoir markers continued to decline only in participants in the acute group. INTERPRETATION: Participants who initiated ART within 30 days or less of HIV infection showed a steeper and more sustained decay in HIV reservoir measures, suggesting long-term benefit of acute ART initiation on reservoir clearance. FUNDING: The US National Institutes of Health and the Canadian Institutes for Health Research.

Long-term effects of early antiretroviral initiation on HIV reservoir markers: a longitudinal analysis of the MERLIN clinical study.

BACKGROUND: Early antiretroviral therapy (ART) initiation (ie, within 3 months of infection) limits establishment of the HIV reservoir. However, the effect of early ART initiation on the long-term dynamics of the pool of infected cells remains unclear. METHODS: In this longitudinal analysis, we included cisgender men who have sex with men (MSM) and transgender women (aged 18-54 years) at high risk for HIV infection, enrolled in the ongoing longitudinal MERLIN study in Peru between Oct 28, 2014, and Nov 8, 2018. Participants were eligible if they had been infected with HIV less than 90 days before enrolment, and if they had cryopreserved peripheral blood mononuclear cell (PBMC) samples. Participants were stratified into three groups on the basis of whether they initiated ART at 30 days or less (acute group), at 31-90 days (early group), or more than 24 weeks (deferred group) after the estimated date of detectable infection. PBMC samples were collected before ART initiation and longitudinally for up to 4 years on ART. The main outcomes were to establish the size of the HIV reservoir before ART initiation and to assess the effect of the timing of ART initiation on the decay of the HIV reservoir over 4 years follow-up. We quantified viral load, and isolated CD4 cells to quantify total HIV DNA, integrated HIV DNA and 2-long terminal repeat circles. Longitudinal analysis of active and inducible HIV reservoirs were measured by quantifying the frequency of CD4 cells producing multiply-spliced HIV RNA ex vivo and after in-vitro stimulation with a tat/rev induced limiting dilution assay (TILDA). A mixed-effects model from the time of ART initiation was used to measure longitudinal decays in viral loads and each HIV reservoir measure in each of the three groups. FINDINGS: We included 56 participants in this analysis, all of whom were MSM: 15 were in the acute group, 19 were in the early group, and 22 were in the deferred group. Participants in all three groups had similar levels of all HIV reservoir markers before ART initiation. All participants, including those in the acute group, had a pool of transcriptionally silent HIV-infected cells before ART initiation, as indicated by a substantial increase in TILDA measures upon stimulation. Longitudinal analysis over 4 years of ART revealed a biphasic decay of all HIV persistence markers, with a rapid initial decline followed by a slower decay in all participants. During the first-phase decay, the half-lives of both total and integrated HIV DNA and TILDA measures were significantly shorter in the acute group than in the early and deferred groups. During the second-phase decay, HIV reservoir markers continued to decline only in participants in the acute group. INTERPRETATION: Participants who initiated ART within 30 days or less of HIV infection showed a steeper and more sustained decay in HIV reservoir measures, suggesting long-term benefit of acute ART initiation on reservoir clearance. FUNDING: The US National Institutes of Health and the Canadian Institutes for Health Research.

[Clinical guide for diagnosis, treatment and prevention of overweight and obesity in children]. / Guía clínica para el diagnóstico, tratamiento y prevención del sobrepeso y la obesidad en pediatría.

The prevalence of overweight has significantly increased thorough the world and Mexico is not an exception considering that the National Survey of Nutrition (1999) showed that 19.5% of scholar children in Mexico have overweight and other survey from Mexico City (ENURBAL, 2002) have shown that 17% in the same range of age are obese. Therefore, this clinical guide pretends to be an instrument for supporting the professionals of health for the diagnosis, treatment and prevention of obesity in children using the levels of medical attention. It is known that the treatment is difficult and it requires a full multidisciplinary team of professionals and that the key of prevention is the modification of the sedentary lifestyle and the decrease of energy intake. This guide was elaborated by pediatricians working in nutrition in public and university institutions, family and general physicians and pediatricians with private practice.

MIPO con placa helicoidal en fractura de húmero

Introducción: Las fracturas humerales diafisarias multifragmentarias con extensión proximal son patrones infrecuentes de lesión causados principalmente por trauma de alta energía. La forma anatómica del húmero, la presencia de la tuberosidad deltoidea y la proximidad del nervio radial al surco radial representan retos a tratar, por ello se recomiendan incisiones mínimamente invasivas y la estabilización de la fractura con placa proximal humeral internal locking system. Objetivo: Demostrar la eficacia de la técnica minimally invasive plate osteosynthesis con el moldeamiento helicoidal de la placa proximal humeral internal locking system. Presentación del caso: Paciente de 29 años que sufrió accidente de tránsito y presentó fractura diafisaria multifragmentaria extendida al húmero proximal. Se trató con la técnica minimally invasive plate osteosynthesis y placa helicoidal proximal humeral internal locking system. Alcanzó la consolidación completa y rápida recuperación funcional. Conclusiones: La técnica minimally invasive plate osteosynthesis con placa helicoidal proximal humeral internal locking system es una opción quirúrgica eficaz y segura para las fracturas humerales diafisarias multifragmentarias con extensión proximal, ya que preserva la inserción muscular deltoidea, mejora el contacto placa hueso con riesgo mínimo de lesión neurológica axilar y radial, favorece la curación ósea y mejora el resultado funcional.

Introduction: Multifragmentary diaphyseal humeral fractures with proximal extension are infrequent patterns of injury caused mainly by high-energy trauma. The anatomical shape of the humerus, the presence of the deltoid tuberosity and the proximity of the radial nerve to the radial groove represent challenges to be treated, therefore minimally invasive incisions and fracture stabilization with the proximal humeral internal locking system plate are recommended. Objective: To establish the efficacy of the minimally invasive plate osteosynthesis technique with helical molding of the proximal humeral plate internal locking system. Case report: We report the case of a 29-year-old patient who suffered a traffic accident and had a multifragmentary diaphyseal fracture extended to the proximal humerus. He was treated with the minimally invasive plate osteosynthesis technique and the humeral proximal helical plate internal locking system. He achieved complete consolidation and rapid functional recovery. Conclusions: The minimally invasive plate osteosynthesis technique with the humeral proximal helical plate internal locking system is an effective and safe surgical option for multifragmentary diaphyseal humeral fractures with proximal extension, since it preserves the deltoid muscle insertion, improves bone-plate contact with minimal risk of fracture. Axillary and radial neurological injury, promotes bone healing and improves functional outcome.

Fracturas por epilepsia en el hospital Víctor Lazarte Echegaray / Epilepsy Fractures at Víctor Lazarte Echegaray Hospital

Introducción: Las convulsiones pueden producir una tensión muscular significativa capaz de fracturar el hueso. Se halló que el aumento significativo en la incidencia de fracturas se encuentra dentro del grupo de edad entre 45 a 64 años, lo que demuestra que los epilépticos no solo son más vulnerables a las fracturas, sino que tienen un comienzo de fractura más precoz. Las medidas de prevención comprenden suplementos de calcio, vitamina D, densitometría ósea y tratamiento con bifosfonatos, que deben reforzarse en pacientes con epilepsia que tienen riesgo de osteoporosis. Objetivo: Presentar casos de fracturas extracapsular e intracapsular de la cadera por convulsiones epilépticas, atendidos en el hospital Víctor Lazarte Echegaray, Trujillo, Perú, en el periodo comprendido entre 2013 y 2019. Presentación de los casos: Se reporta dos casos de fractura de cadera por convulsiones epilépticas, uno con fractura del acetábulo e iliaco izquierdo y otro a nivel del cuello femoral y subtrocantérica. Conclusiones: Las personas con convulsiones epilépticas poseen un mayor peligro de fracturas, por consiguiente se recomienda a los médicos que maximicen su conciencia sobre las fracturas relacionadas a convulsiones, en especial a pacientes con dolor postictal, debido a que los síntomas pueden ser inespecíficos y una mala interpretación puede impedir la rehabilitación(AU)

Introduction: Seizures can produce significant muscle tension capable of fracturing the bone. The significant increase in the incidence of fractures was found to be within the age group between 45 and 64 years, which shows that epileptics are not only more vulnerable to fractures, but also have earlier fracture onset. Prevention measures include calcium supplements, vitamin D, bone densitometry, and bisphosphonate treatment that should be reinforced in patients with epilepsy who are at risk for osteoporosis. Objective: To present cases of hip fractures due to epileptic seizures, treated at Víctor Lazarte Echegaray Hospital, Trujillo, Peru, from 2013 to 2019. Case report: Cases of hip fracture due to epileptic seizures have been reported, one with fracture of the acetabulum and left iliac and another at the level of the femoral and subtrochanteric neck. Conclusions: Individuals with epileptic seizures have greater risk of fractures, it is recommended that physicians maximize their awareness of seizure-related fractures, especially in patients with postictal pain, since the symptoms can be nonspecific and misinterpretation can prevent rehabilitation(AU)

Fisioterapia de rehabilitación y pinzamiento femoroacetabular / Rehabilitation Physiotherapy and Femoroacetabular Impingement

Introducción: Durante los últimos 20 años el tratamiento del pinzamiento acetabular ha sido quirúrgico, sin embargo, se ha propuesto el manejo conservador y la aplicación de protocolos de fisioterapia individualizada como tratamiento para el pinzamiento femoroacetabular, lo cual es fundamental para reestablecer la función de la articulación. Objetivo: Comparar los resultados entre la fisioterapia de rehabilitación del pinzamiento femoroacetabular y el tratamiento quirúrgico. Métodos: El artículo se dividió en conceptos para facilitar la revisión bibliográfica de los últimos 5 años en la base de datos de Pubmed con el sistema MeSH, Embase, Cochrane Library, Medline y BVS. Se utilizaron las siguientes palabras clave en el buscador, combinadas con el operador AND: femoroacetabular impingement, fhysiotherapy AND femoroacetabular impingement, femoroacetabular impingement treatment, Non-operative Management of Femoroacetabular Impingement. Análisis y síntesis de la información: Se incluyeron en la revisión todos los metaanálisis, ensayos clínicos aleatorizados y controlados, estudios prospectivos y artículos de revisión que comparan el tratamiento quirúrgico versus la fisiopterapia de rehabilitación en el tratamiento del síndrome de pinzamiento femoroacetabular, así como los que proponen la fisioterapia como opción de tratamiento inicial para el pinzamiento femoroacetabular, con la finalidad de evidenciar el grado de beneficio que tiene el manejo con fisioterapia en comparación con el quirúrgico. Conclusiones: La fisioterapia de rehabilitación ofrece un efecto beneficioso para el mejoramiento de la sintomatología, lo que permite, la disminución del dolor de cadera, además de restablecer la función y fuerza de la articulación(AU)

Introduction: During the last 20 years the treatment of acetabular impingement has been surgical; however, conservative management and the application of individualized physiotherapy protocols have been proposed as treatment for femoroacetabular impingement. This is essential to re-establish joint function. Objective: To compare the results between rehabilitation physiotherapy of femoroacetabular impingement and surgical treatment. Methods: The article was divided into concepts to facilitate the bibliographic review of the last 5 years in the Pubmed database with the MeSH system, Embase, Cochrane Library, Medline and BVS. The keywords used in the search engine, combined with the AND operator were femoroacetabular impingement, fhysiotherapy AND femoroacetabular impingement, femoroacetabular impingement treatment, Non-operative Management of Femoroacetabular Impingement. Analysis and synthesis of the information: All meta-analyzes, randomized and controlled clinical trials, prospective studies and review articles comparing surgical treatment versus rehabilitation physiotherapy in the treatment of femoroacetabular impingement syndrome were included in the review, as well as those that propose physiotherapy as an initial treatment option for femoroacetabular impingement, in order to demonstrate the degree of benefit that physiotherapy management has compared to surgery. Conclusions: Rehabilitation physiotherapy offers a beneficial effect for the improvement of symptoms, which allows the reduction of hip pain, in addition to restoring the function and strength of the joint(AU)

Terapia con células madre en la osteonecrosis de la cabeza femoral / Stem Cell Therapy in Osteonecrosis of the Femoral Head

RESUMEN Objetivos: Describir el efecto terapéutico del uso de células madre en el manejo de la osteonecrosis de la cabeza femoral. Métodos: Se realizó una búsqueda en las distintas bases de datos como Pubmed/MEDLINE, BVS y Cochrane de los últimos 10 años, incluyéndose estudios relevantes de metaanálisis, ensayos clínicos y revisiones. Además, se revisó la página electrónica oficial de la Organización Mundial de la Salud para referencias adicionales. Las palabras de búsqueda fueron: "("Stem Cells" OR "Stem Cell Transplantation"[Mesh] OR "Mesenchymal Stem Cell Transplantation"[Mesh] OR Hematopoietic Stem Cell Transplantation"[Mesh] OR Cell-and Tissue-Based Therapy"[Mesh] "Multipotent Stem Cells"[Mesh] OR "Embryonic Stem Cells"[Mesh]) AND ("Osteonecrosis"[Mesh] OR "Femur Head Necrosis"[Mesh] "osteonecrosis of the femoral head" OR "Femoral head"). Incluimos un total de 7 estudios. 2 metaanálisis, 2 artículos de revisión, 2 ensayos clínicos controlados y aleatorizados y un estudio de evidencia. Resultados: Todos los estudios evidenciaron que la terapia con células madre en el manejo de la osteonecrosis de la cabeza femoral es segura y efectiva. El tratamiento combinado de descompresión central más implantación de células madre mostró mayor efectividad. Conclusiones: La terapia con células madre es una opción terapéutica para tratar la osteonecrosis de la cabeza femoral, sobre todo en etapas tempranas. La combinación de descompresión central más la infiltración de células madre en la zona necrótica produce mejoría de la sintomatología y contiene el progreso de la enfermedad(AU)

ABSTRACT Objectives: To describe the therapeutic effect of the stem cell use in managing osteonecrosis of the femoral head. Methods: A search was carried out in the different databases as Pubmed / MEDLINE, BVS and Cochrane for the last 10 years, including relevant meta-analysis studies, clinical trials and reviews. In addition, the official website of the World Health Organization was checked for additional references. The search words were: "(" Stem Cells "OR" Stem Cell Transplantation "[Mesh] OR" Mesenchymal Stem Cell Transplantation "[Mesh] OR Hematopoietic Stem Cell Transplantation" [Mesh] OR Cell-and Tissue-Based Therapy "[ Mesh] "Multipotent Stem Cells" [Mesh] OR "Embryonic Stem Cells" [Mesh]) AND ("Osteonecrosis" [Mesh] OR "Femur Head Necrosis" [Mesh] "osteonecrosis of the femoral head" OR "Femoral head"). We include a total of 7 studies, 2 meta-analyzes, 2 review articles, 2 controlled and randomized clinical trials, and one evidence study. Findings: All the studies showed that stem cell therapy in managing osteonecrosis of the femoral head is safe and effective. The combined treatment of central decompression plus stem cell implantation showed greater effectiveness. Conclusions: Stem cell therapy is a therapeutic option to treat osteonecrosis of the femoral head, especially in the early stages. The combination of central decompression plus the infiltration of stem cells in the necrotic area produces an improvement in the symptoms and contains the progress of the disease(AU)

Adicción a internet y calidad de sueño en estudiantes de medicina de una Universidad peruana, 2016 / Internet addiction and sleep quality in medical students from a Peruvian university, 2016

RESUMEN Introducción: El internet se ha convertido en una herramienta prácticamente indispensable de la vida diaria. No obstante, existen casos en los que su uso excesivo empieza a generar cierta dependencia en los usuarios, y provoca así el trastorno conocido como adicción a internet. Objetivo: Evaluar la adicción a internet y la calidad de sueño en estudiantes de Medicina de una universidad peruana e identificar las variables relacionadas a su presencia. Material y Métodos: Estudio transversal analítico que incluyó alumnos de Ciencias Básicas de la Facultad de Medicina Humana escogidos mediante un muestreo estratificado aleatorio. Para la medición de las variables principales se usaron dos instrumentos, el Índice de Calidad de Sueño de Pittsburgh (PSQI) y el Test de Adicción a Internet (AI). Para evaluar la asociación entre las variables de estudio calculamos las razones de prevalencias crudas (RPc) y ajustadas (RPa), consideramos como significativo un valor p < 0,05. Resultados: Se encuestó un total de 297 estudiantes. La media de edad fue 18,7 ± 1,7 años y el 55,6 % fue de sexo femenino. El porcentaje de mala calidad de sueño y adicción a internet fue de 72,4 % y 10,4 %, respectivamente. En el modelo ajustado encontramos que estar cursando el tercer año de la carrera fue un factor protector para la mala calidad de sueño (RPa: 0,59; IC 95 %: 0,36-0,97) y los factores asociados a padecerla fueron ser un usuario problemático (RPa: 1,51; IC 95 %: 1,01-2,23) o con adicción a internet (RPa: 1,71; IC 95 %: 1,01-2,90). Conclusiones: La adicción a internet y la mala calidad de sueño son problemas de salud mental frecuentes en los estudiantes de medicina y están relacionadas entre sí.

ABSTRACT Introduction: The internet has become a practically indispensable tool of daily life. However, there are cases in which its inadequate use begins to generate some dependence on users, causing the disorder known as Internet addiction. Objective: To evaluate the association between internet addiction and sleep quality in medical students from a Peruvian university. Material and Methods: We conducted a cross-sectional analytical study in Basic Sciences medical students. We selected the participants using a random stratified sampling method. For the measurement of the main variables, two instruments were used: The Pittsburg Sleep Quality Index (PSQI) and the Internet Addiction Test (AI). To evaluate the association between the study variables, we calculated the crude (cPR) and adjusted prevalence ratios (aPR), considering a p value <0.05 significant. Results: We surveyed a total of 297 medical students. The mean age was 18.7 ± 1.7 years and 55,6 % was female. The prevalence of poor sleep quality and Internet addiction was 72,4 % and 10,4 %, respectively. In the adjusted model we found that being in the third year of the medical studies was a protective factor for poor sleep quality (aPR: 0.59, 95 % CI: 0.36-0.97) and the factors associated with having this condition were being a problematic user (aPR: 1.51, 95 % CI: 1.01-2.23) or having Internet addiction (aPR: 1.71, 95 % CI: 1.01-2.90). Conclusions: We found an association between internet addiction and poor sleep quality in medical students. Higher Education Centers should conduct periodic psychometric evaluations and propose strategies and interventions for the mental health of their students.

Enantioselective aza-Henry reactions of cyclic α-carbonyl ketimines under bifunctional catalysis.

The aza-Henry reaction of nitroalkanes with the C=N group of 2-aryl-3H-indol-3-ones catalyzed by thiourea-chincona derivatives takes place with good yield and high ee's.