Five-year follow-up of children with perinatal HIV-1 infection receiving early highly active antiretroviral therapy

<p>Abstract</p> <p>Background</p> <p>Early highly active antiretroviral therapy (HAART), started within the first months of age, has been proven to be the optimal strategy to prevent immunological and clinical deterioration in perinatally HIV-infected children. Nevertheless, data about long-term follow-up of early treated children are lacking.</p> <p>Methods</p> <p>We report data from 40 perinatally HIV-infected-children receiving early HAART, with a median follow-up period of 5.96 years (interquartile range [IQR]:4.21–7.62). Children were enrolled at birth in the Italian Register for HIV Infection in Children. Comparison with 91 infected children born in the same period, followed-up from birth, and receiving deferred treatment was also provided.</p> <p>Results</p> <p>Nineteen children (47.5%) were still receiving their first HAART regimen at last follow-up. In the remaining children the first regimen was discontinued, after a median period of 3.77 years (IQR: 1.71–5.71) because of viral failure (8 cases), liver toxicity (1 case), structured therapy interruption (3 cases), or simplification/switch to a PI-sparing regimen (9 cases). Thirty-nine (97.5%) children showed CD4⁺T-lymphocyte values>25%, and undetectable viral load was reached in 31 (77.5%) children at last visit. Early treated children displayed significantly lower viral load than not-early treated children, until 6 years of age, and higher median CD4⁺T-lymphocyte percentages until 4 years of age. Twenty-seven (29.7%) not-early treated vs. 0/40 early treated children were in clinical category C at last follow-up (P < 0.0001).</p> <p>Conclusion</p> <p>Our findings suggest that clinical, virologic and immunological advantages from early-HAART are long-lasting. Recommendations indicating the long-term management of early treated children are needed.</p

Predicting needlestick and sharps injuries in nursing students: Development of the SNNIP scale

© 2020 The Authors. Nursing Open published by John Wiley & Sons Ltd. Aim: To develop an instrument to investigate knowledge and predictive factors of needlestick and sharps injuries (NSIs) in nursing students during clinical placements. Design: Instrument development and cross-sectional study for psychometric testing. Methods: A self-administered instrument including demographic data, injury epidemiology and predictive factors of NSIs was developed between October 2018–January 2019. Content validity was assessed by a panel of experts. The instrument's factor structure and discriminant validity were explored using principal components analysis. The STROBE guidelines were followed. Results: Evidence of content validity was found (S-CVI 0.75; I-CVI 0.50–1.00). A three-factor structure was shown by exploratory factor analysis. Of the 238 participants, 39% had been injured at least once, of which 67.3% in the second year. Higher perceptions of “personal exposure” (4.06, SD 3.78) were reported by third-year students. Higher scores for “perceived benefits” of preventive behaviours (13.6, SD 1.46) were reported by second-year students

Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

Schizophrenia and bipolar disorder are two distinct diagnoses that share symptomology. Understanding the genetic factors contributing to the shared and disorder-specific symptoms will be crucial for improving diagnosis and treatment. In genetic data consisting of 53,555 cases (20,129 bipolar disorder [BD], 33,426 schizophrenia [SCZ]) and 54,065 controls, we identified 114 genome-wide significant loci implicating synaptic and neuronal pathways shared between disorders. Comparing SCZ to BD (23,585 SCZ, 15,270 BD) identified four genomic regions including one with disorder-independent causal variants and potassium ion response genes as contributing to differences in biology between the disorders. Polygenic risk score (PRS) analyses identified several significant correlations within case-only phenotypes including SCZ PRS with psychotic features and age of onset in BD. For the first time, we discover specific loci that distinguish between BD and SCZ and identify polygenic components underlying multiple symptom dimensions. These results point to the utility of genetics to inform symptomology and potential treatment

Endocrine disruption in the sub Antarctic fish Patagonotothen tessellata (Perciformes, Notothenidae) from Beagle Channel associated to anthropogenic impact

Situated in the sub-Antarctic region, Beagle Channel represents a unique marine ecosystem due to the connection between the Pacific and the Atlantic Oceans, and its proximity to the Antarctic Peninsula. Ushuaia city, the biggest settlement on the channel, exerts an increasing anthropogenic pressure by discharges of urban and industrial effluents. In the present work, we use Patagonotothen tessellata, one of the most abundant and widespread species in the channel, as a bioindicator species in order to evidence anthropic impact from Ushuaia Bay and surrounding areas. We first analyzed and characterized real time gene expression of androgen receptor, estrogen receptor and different forms of vitellogenin (VTG), under laboratory conditions. This was achieved by induction with estradiol of P. tessellata males. Then, the selected genes were used as biomarkers for an environmental biomonitoring study. Morphometric indices and circulating sex steroids (estradiol and testosterone) were also quantified in male fish collected from different sites. The qPCR analysis showed that vtgAb form is more inducible than vtgAa or vtgC forms after estrogen induction. The field survey revealed the up-regulation of vtgAb and the androgen receptor in fish from sites with higher anthropogenic influence. Sex steroids followed seasonal variations according to their reproductive cycle, with higher levels of estradiol and testosterone in winter and summer seasons. The use of biomarkers such as gene expression of VTG demonstrates that fish from Ushuaia Bay are likely to be exposed to endocrine disrupting compounds. To our knowledge, this research is the first attempt to assess the endocrine disruption associated to anthropic impact in a widespread fish of the Beagle Channel and contributes to a better understanding of the reproductive physiology of sub Antarctic ichthyofauna.Fil: Ferreira, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Biodiversidad y Biología Experimental y Aplicada. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biodiversidad y Biología Experimental y Aplicada; ArgentinaFil: Lo Nostro, Fabiana Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Biodiversidad y Biología Experimental y Aplicada. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biodiversidad y Biología Experimental y Aplicada; ArgentinaFil: Fernandez, Daniel Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; Argentina. Universidad Nacional de Tierra del Fuego, Antártida e Islas del Atlántico Sur. Instituto de Ciencias Polares, Ambientales y Recursos Naturales; ArgentinaFil: Genovese, Griselda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Biodiversidad y Biología Experimental y Aplicada. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biodiversidad y Biología Experimental y Aplicada; Argentin

Ultrasound-guided biopsy of the testis: indications and results

Ultrasound examination of the testis is the imaging modality of choice for the evaluation of intratesticular focal lesions. In spite of its high sensibility, eco-Doppler-elastography is lacking of specificity in discrimination between benign and malign lesions, not always allowing us to make a definitive diagnosis of malignancy. When a diagnostic doubt persists, for such lesions that are indeterminate at clinical and radiological evaluation, it is possible to recur to ultrasound-guided testicular needle biopsy. This paper describes the main application scenarios of testicular fine-needle aspiration under ultrasound guidance and the experience in our institute

Inhibition of the nuclear factor-kappaB activation with pyrrolidine dithiocarbamate attenuating inflammation and oxidative stress after experimental spinal cord trauma in rats

The nuclear factor-kappaB (NF-kappaB) is a transcription factor that plays a pivotal role in the induction of genes involved in physiological processes and in the response to inflammation. The authors of recent studies have demonstrated that NF-kappaB and oxidative stress contribute to secondary injury after impact-induced spinal cord injury (SCI) in the rat. Dithiocarbamates are antioxidants that are potent inhibitors of NF-kappaB. The authors postulated that pyrrolidine dithiocarbamate (PDTC) would attenuate NF-kappaB-related inflammatory and oxidative events that occur after SCI. METHODS: Spinal cord injury was induced by the application of vascular clips (force of 50 g) to the dura mater after a four-level T5-8 laminectomy. The authors investigated the effects of PDTC (30 mg/kg administered 30 minutes before SCI and 6 hours after SCI) on the development of the inflammatory response associated with SCI in rats. Levels of myeloperoxidase activity were measured as an indicator of polymorphonuclear infiltration; malondialdehyde levels in the spinal cord tissue were determined as an indicator of lipid peroxidation. The following studies were performed: immunohistochemical analysis to assess levels of inducible nitric oxide synthase (iNOS), nitrotyrosine formation, poly([adenosine diphosphate]-ribose) polymerase (PARP) activity; Western blot analysis to determine cytoplasmic levels of inhibitory-kappaB-alpha (IkappaB-alpha); and electrophoretic mobility-shift assay to measure the level of DNA/NF-kappaB binding. The PDTC treatment exerted potent antiinflammatory effects with significant reduction of polymorphonuclear cell infiltration, lipid peroxidation, and iNOS activity. Furthermore, administration of PDTC reduced immunohistochemical evidence of formation of nitrotyrosine and PARP activation in the spinal cord section obtained in the SCI-treated rats. Additionally, PDTC treatment significantly prevented the activation of NF-kappaB (electrophoretic mobility-shift assay and immunoblot analysis). CONCLUSIONS: Overall, the results clearly demonstrate that PDTC-related prevention of the activation of NF-kappaB reduces the development of some secondary injury events after SCI. Therefore, inhibition of NF-kappaB may represent a novel approach in the treatment of SCIs