Dynamic assessment of human sperm DNA damage III: the effect of sperm freezing techniques.

Among the currently available strategies for sperm freezing, vitrification may be considered as the leading alternative to conventional cryopreservation. Nevertheless, a direct comparison of both techniques with respect to the iatrogenic sperm DNA damage has not been performed yet. As such, this study was focused to assess the static and dynamic behavior of human sperm DNA damage following thawing of cryopreserved or vitrified spermatozoa. Semen samples were obtained from fifty donors with a normal spermiogram, and divided into four aliquots. The first aliquot represented the neat sample. In the second aliquot the seminal plasma was discarded, and the resulting sperm pellet was resuspended in PBS. The third fraction was used for slow freezing and the fourth fraction was subjected to vitrification. Each set of samples was incubated at 37 °C for 24 h and sperm DNA damage (SDF) was assessed using the chromatin-dispersion test following 0 h, 2 h, 4 h and 24 h of incubation. When comparing the rate of DNA fragmentation (r-SDF) at 2 h, significant differences were observed between the PBS group, cryopreserved (p .000) or vitrified semen (p .015). Furthermore, the sperm longevity comparison using Kaplan-Meier survival curves revealed significant differences between cryopreservation and vitrification (p .000). Our data suggest that exposure of spermatozoa to low temperatures, independently of the chosen freezing protocol, leads to a higher susceptibility of sperm DNA towards damage. This damage is nevertheless lower following vitrification in comparison to traditional cryopreservation. As vitrification leads to a smaller proportion of spermatozoa with DNA damage, we may recommend its use in reproductive techniques which rely on a longer sperm survival, such as artificial insemination.

Stepwise Tikhonov Regularisation: Application to the Prediction of HIV-1 Drug Resistance.

This paper focuses on constructing genotypic predictors for antiretroviral drug susceptibility of HIV. To this end, a method to recover the largest elements of an unknown vector in a least squares problem is developed. The proposed method introduces two novel ideas. The first idea is a novel forward stepwise selection procedure based on the magnitude of the estimates of the candidate variables. To implement this newly introduced procedure, we revise Tikhonov regularisation from a sparse representations' perspective. This analysis leads us to the second novel idea in the paper, which is the development of a new method to recover the largest elements of the unknown vector in the least squares problem. The method implements a sequence of Tikhonov regularisation problems which aim to recover the largest of the remaining elements of the unknown vector. Additionally, we derive sufficient conditions that ensure the recovery of the largest elements of the unknown vector. We perform numerical studies using simulated data and data from the Stanford HIV resistance database. The performance of the proposed method is compared against a state-of-the-art method.

A systematic follow-up protocol achieving a low hemodialysis graft thrombosis rate.

INTRODUCTION: Graft is an alternative to native arteriovenous fistula to ensure permanent vascular access in hemodialysis patients. The most common complication is significant stenosis, which frequently causes thrombosis and graft loss. Periodic monitoring and surveillance with elective correction of stenotic lesions can prolong graft survival. OBJECTIVE: To describe the effect of early diagnosis of significant stenosis on the rate of thrombosis and graft patency. METHODS: Retrospective, observational study of a cohort of 86 prevalent patients undergoing hemodialysis with a graft as their vascular access. We applied a systematic follow-up protocol of 115 grafts based on various screening methods of monitoring (clinical monitoring, pre-pump arterial pressure, dynamic venous pressure, percentage of recirculation, and dose of dialysis) in conjunction with surveillance (normalized intra-access venous pressure and access flow). The annual rates of thrombosis, and primary, primary-assisted, and secondary patency were assessed. RESULTS: The incidence of significant stenosis and thrombosis was 57.4% (65/115) and 39.0% (45/115), respectively. Of all screening procedures, normalized intra-access venous pressure was the best predictor of significant stenosis (hazards ratio, 7.71; 95% confidence interval, 3.06-19.46). The annual rate of thrombosis fluctuated from 0 to 0.26 thromboses/patient/year, with an average rate of 0.14 thromboses/patient/year. Primary, primary-assisted, and secondary patency were 74%/79%/82%, 50%/60%/66%, and 23%/35%/37% at 1, 2, and 5 years, respectively. CONCLUSION: The implementation of a systematic graft follow-up protocol combined with monitoring and surveillance enabled early diagnosis and elective correction of significant stenosis, prolonged graft patency, and a low thrombosis rate.

Aspirin for Primary Prevention of Cardiovascular Disease and Renal Disease Progression in Chronic Kidney Disease Patients: a Multicenter Randomized Clinical Trial (AASER Study).

BACKGROUND: Patients with chronic kidney disease (CKD) are at high risk for developing cardiovascular events. However, limited evidence is available regarding the use of aspirin in CKD patients to decrease cardiovascular risk and to slow renal disease progression. STUDY DESIGN: Prospective, multicenter, open-label randomized controlled trial. SETTING AND PARTICIPANTS: One hundred eleven patients with estimated glomerular filtration rate (eGFR) 15-60 ml/min/1.73 m2 without previous cardiovascular events. INTERVENTION: Aspirin treatment (100 mg/day) (n = 50) or usual therapy (n = 61). Mean follow-up time was 64.8 ± 16.4 months. OUTCOMES: The primary endpoint was composed of cardiovascular death, acute coronary syndrome (nonfatal MI, coronary revascularization, or unstable angina pectoris), cerebrovascular disease, heart failure, or nonfatal peripheral arterial disease. Secondary endpoints were fatal and nonfatal coronary events, renal events (defined as doubling of serum creatinine, ≥ 50% decrease in eGFR, or renal replacement therapy), and bleeding episodes. RESULTS: During follow-up, 17 and 5 participants suffered from a primary endpoint in the control and aspirin groups, respectively. Aspirin did not significantly reduce primary composite endpoint (HR, 0.396 (0.146-1.076), p = 0.069. Eight patients suffered from a fatal or nonfatal coronary event in the control group compared to no patients in the aspirin group. Aspirin significantly reduced the risk of coronary events (log-rank, 5.997; p = 0.014). Seventeen patients in the control group reached the renal outcome in comparison with 3 patients in the aspirin group. Aspirin treatment decreased renal disease progression in a model adjusted for age, baseline kidney function, and diabetes mellitus (HR, 0.272; 95% CI, 0.077-0.955; p = 0.043) but did not when adjusted for albuminuria. No differences were found in minor bleeding episodes between groups and no major bleeding was registered. LIMITATIONS: Small sample size and open-label trial. CONCLUSIONS: Long-term treatment with low-dose aspirin did not reduce the composite primary endpoint; however, there were reductions in secondary endpoints with fewer coronary events and renal outcomes. ClinicalTrials.gov Identifier: NCT01709994.

Rituximab treatment of adult patients with steroid-resistant focal segmental glomerulosclerosis.

BACKGROUND AND OBJECTIVES: Isolated case reports have shown a beneficial effect of rituximab on pediatric patients with primary FSGS, but there is no information about rituximab treatment of FSGS in adults. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: All patients who had biopsy-proven FSGS and were treated with rituximab in Spain were identified, independent of their positive or negative response, among the nephrology departments that belong to the Spanish Group for the Study of Glomerular Diseases (GLOSEN). Their characteristics and outcome after rituximab treatment were studied. RESULTS: Eight patients were identified. Rituximab failed to improve nephrotic syndrome in five of eight patients, who continued to show massive proteinuria and exhibited a rapidly deteriorating renal function in two cases. Among the remaining three patients, two of them showed an improvement of renal function and a remarkable proteinuria reduction and one experienced a beneficial but transitory effect after rituximab. There were no differences in clinical or laboratory characteristics or in the CD20 B lymphocyte count after rituximab between these three patients and the five who had a negative response. The only difference was in the regimen of rituximab administration: Whereas the five patients with a negative response received only four weekly consecutive infusions of 375 mg/m(2), the three remaining patients received additional doses of rituximab. CONCLUSIONS: Only a minority (three of eight) of patients in our series of adult patients with FSGS showed a positive influence of rituximab. More studies are necessary to characterize further the optimal dosages and the mechanisms of action of rituximab in FSGS.

Estudio epidemiológico-molecular de un brote de tuberculosis en el hospital psiquiátrico de La Habana / Epidemiological-molecular study of a tuberculosis outbreak in the Psychiatric Hospital of Havana City

El incremento de la tuberculosis en Cuba en los últimos años ha estado parcialmente relacionado con la ocurrencia de brotes institucionales, confirmado por el análisis del polimorfismo de los fragmentos de restricción. En este trabajo se estudió, por métodos epidemiológicos convencionales y moleculares, el aumento de casos de tuberculosis diagnosticados en 1995-1998 entre los pacientes en el Hospital Psiquiátrico de La Habana para conocer su posible carácter epidémico. Se observó que la mayoría de los pacientes pertenecían a salas localizadas en un área bien definida de la institución. Tenían un patrón de restricción idéntico 11 de las 14 cepas analizadas. Los hallazgos moleculares y convencionales permitieron confirmar el carácter de brote y definir el caso índice y la posible vía de transmisión. Se reafirmó el valor de las técnicas moleculares como instrumento valioso en la epidemiología de la tuberculosis y su contribución al control epidemiológico local de esta enfermedad

Estudio epidemiológico-molecular de un brote de tuberculosis en el hospital psiquiátrico de La Habana / Epidemiological-molecular study of a tuberculosis outbreak in the Psychiatric Hospital of Havana City

El incremento de la tuberculosis en Cuba en los últimos años ha estado parcialmente relacionado con la ocurrencia de brotes institucionales, confirmado por el análisis del polimorfismo de los fragmentos de restricción. En este trabajo se estudió, por métodos epidemiológicos convencionales y moleculares, el aumento de casos de tuberculosis diagnosticados en 1995-1998 entre los pacientes en el Hospital Psiquiátrico de La Habana para conocer su posible carácter epidémico. Se observó que la mayoría de los pacientes pertenecían a salas localizadas en un área bien definida de la institución. Tenían un patrón de restricción idéntico 11 de las 14 cepas analizadas. Los hallazgos moleculares y convencionales permitieron confirmar el carácter de brote y definir el caso índice y la posible vía de transmisión. Se reafirmó el valor de las técnicas moleculares como instrumento valioso en la epidemiología de la tuberculosis y su contribución al control epidemiológico local de esta enfermedad(AU)

Prevención de accidentes en escolares / Accident and prevention in students

En la búsqueda de contribuir con la prevención de accidentes escolares, se realizó un estudio en la Unidad Escuela Nacional "Rafael Napoleón Baute", Petare Municipio Sucre, Estado Miranda, durante el año 1986. A través de una entrevista personal se obtuvieron datos sobre edad, sexo grado de escolaridad, habilidad para reconocer el significado de un accidente, número de accidentes ocurridos, sitio de ocurrencia, probable agente causal, tratamiento recibido, cumplimiento de normas para prevenir accidentes y normas consideradas importantes por los niños para evitar accidentes en el ambiente escolar. Un análisis descriptivo a través de porcentajes representados en cuadros y gráficos estadísticos determinó que un 24,39 por ciento de la muestra presentó un accidente durante los períodos escolares 1993-1994 y 1994-1995, el patio de la escuela fue el lugar de mayor frecuencia en la producción de accidentes y las riñas o peleas el agente causal más frecuente. Se ofrecen normas para la prevención de accidentes en el ambiente escolar basadas en las respuestas dadas por los niños según las situaciones de mayor riesgo