Long-term Efficacy And Safety Of Tenofovir Disoproxil Fumarate In Hiv-1-infected Adolescents Failing Antiretroviral Therapy: The Final Results Of Study Gs-us-104-0321.

Reports of long-term tenofovir disoproxil fumarate (TDF) treatment in HIV-infected adolescents are limited. We present final results from the open-label (OL) TDF extension following the randomized, placebo (PBO)-controlled, double-blind phase of GS-US-104-0321 (Study 321). HIV-infected 12- to 17-year-olds treated with TDF 300 mg or PBO with an optimized background regimen (OBR) for 24-48 weeks subsequently received OL TDF plus OBR in a single arm study extension. HIV-1 RNA and safety, including bone mineral density (BMD), was assessed in all TDF recipients. Eighty-one subjects received TDF (median duration 96 weeks). No subject died or discontinued OL TDF for safety/tolerability. At week 144, proportions with HIV-1 RNA <50 copies/mL were 30.4% (7 of 23 subjects with baseline HIV-1 RNA >1000 c/mL initially randomized to TDF), 41.7% (5 of 12 subjects with HIV-1 RNA <1000 c/mL who switched PBO to TDF) and 0% (0 of 2 subjects failed randomized PBO plus OBR with HIV-1 RNA >1000 c/mL and switched PBO to TDF). Viral resistance to TDF occurred in 1 subject. At week 144, median decrease in estimated glomerular filtration rate was 38.1 mL/min/1.73 m (n = 25). Increases in median spine (+12.70%, n = 26) and total body less head BMD (+4.32%, n = 26) and height-age adjusted Z-scores (n = 21; +0.457 for spine, +0.152 for total body less head) were observed at week 144. Five of 81 subjects (6%) had persistent >4% BMD decreases from baseline. Some subjects had virologic responses to TDF plus OBR, and TDF resistance was rare. TDF was well tolerated and can be considered for treatment of HIV-infected adolescents.

Long-term Decline Of The Amazon Carbon Sink.

Atmospheric carbon dioxide records indicate that the land surface has acted as a strong global carbon sink over recent decades, with a substantial fraction of this sink probably located in the tropics, particularly in the Amazon. Nevertheless, it is unclear how the terrestrial carbon sink will evolve as climate and atmospheric composition continue to change. Here we analyse the historical evolution of the biomass dynamics of the Amazon rainforest over three decades using a distributed network of 321 plots. While this analysis confirms that Amazon forests have acted as a long-term net biomass sink, we find a long-term decreasing trend of carbon accumulation. Rates of net increase in above-ground biomass declined by one-third during the past decade compared to the 1990s. This is a consequence of growth rate increases levelling off recently, while biomass mortality persistently increased throughout, leading to a shortening of carbon residence times. Potential drivers for the mortality increase include greater climate variability, and feedbacks of faster growth on mortality, resulting in shortened tree longevity. The observed decline of the Amazon sink diverges markedly from the recent increase in terrestrial carbon uptake at the global scale, and is contrary to expectations based on models.

Antitumor Activity Of Irradiated Riboflavin On Human Renal Carcinoma Cell Line 786-o.

Riboflavin (vitamin B2) is a precursor for coenzymes involved in energy production, biosynthesis, detoxification, and electron scavenging. Previously, we demonstrated that irradiated riboflavin (IR) has potential antitumoral effects against human leukemia cells (HL60), human prostate cancer cells (PC3), and mouse melanoma cells (B16F10) through a common mechanism that leads to apoptosis. Hence, we here investigated the effect of IR on 786-O cells, a known model cell line for clear cell renal cell carcinoma (CCRCC), which is characterized by high-risk metastasis and chemotherapy resistance. IR also induced cell death in 786-O cells by apoptosis, which was not prevented by antioxidant agents. IR treatment was characterized by downregulation of Fas ligand (TNF superfamily, member 6)/Fas (TNF receptor superfamily member 6) (FasL/Fas) and tumor necrosis factor receptor superfamily, member 1a (TNFR1)/TNFRSF1A-associated via death domain (TRADD)/TNF receptor-associated factor 2 (TRAF) signaling pathways (the extrinsic apoptosis pathway), while the intrinsic apoptotic pathway was upregulated, as observed by an elevated Bcl-2 associated x protein/B-cell CLL/lymphoma 2 (Bax/Bcl-2) ratio, reduced cellular inhibitor of apoptosis 1 (c-IAP1) expression, and increased expression of apoptosis-inducing factor (AIF). The observed cell death was caspase-dependent as proven by caspase 3 activation and poly(ADP-ribose) polymerase-1 (PARP) cleavage. IR-induced cell death was also associated with downregulation of v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homologue (avian)/protein serine/threonine kinase B/extracellular signal-regulated protein kinase 1/2 (Src/AKT/ERK1/2) pathway and activation of p38 MAP kinase (p38) and Jun-amino-terminal kinase (JNK). Interestingly, IR treatment leads to inhibition of matrix metalloproteinase-2 (MMP-2) activity and reduced expression of renal cancer aggressiveness markers caveolin-1, low molecular weight phosphotyrosine protein phosphatase (LMWPTP), and kinase insert domain receptor (a type III receptor tyrosine kinase) (VEGFR-2). Together, these results show the potential of IR for treating cancer.

Long-term follow-up of an 8-year-old boy with insulinoma as the first manifestation of a familial form of multiple endocrine neoplasia type 1

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant hereditary cancer syndrome characterized mostly by parathyroid, enteropancreatic, and anterior pituitary tumors. We present a case of an 8-year-old boy referred because of hypoglycemic attacks. His diagnosis was pancreatic insulinoma. Paternal grandmother died due to repeated gastroduodenal ulcerations and a paternal aunt presented similar manifestations. At a first evaluation, the father presented only gastric ulceration but subsequently developed hyperparathyroidism and lung carcinoid tumor. During almost 15 years of follow-up, three brothers and the index case presented hyperparathyroidism and hyperprolactinemia. Molecular study showed a G to A substitution in intron 4, at nine nucleotides upstream of the splicing acceptor site, causing a splicing mutation. All affected members of the family have the same mutation. Paternal grandmother and aunt were not studied and the mother does not carry any mutation. MEN1 is a rare condition that requires permanent medical assistance. Early clinical and genetic identification of affected individuals is essential for their own surveillance and also for genetic counseling.

A Escola Superior de Educação Fisica de Muzambinho no contexto da Educação Fisica brasileira

Universidade Estadual de Campinas . Faculdade de Educação Física

Shelf-life of a 2.5% sodium hypochlorite solution as determined by arrhenius equation

Accelerated stability tests are indicated to assess, within a short time, the degree of chemical degradation that may affect an active substance, either alone or in a formula, under normal storage conditions. This method is based on increased stress conditions to accelerate the rate of chemical degradation. Based on the equation of the straight line obtained as a function of the reaction order (at 50 and 70 ºC) and using Arrhenius equation, the speed of the reaction was calculated for the temperature of 20 ºC (normal storage conditions). This model of accelerated stability test makes it possible to predict the chemical stability of any active substance at any given moment, as long as the method to quantify the chemical substance is available. As an example of the applicability of Arrhenius equation in accelerated stability tests, a 2.5% sodium hypochlorite solution was analyzed due to its chemical instability. Iodometric titration was used to quantify free residual chlorine in the solutions. Based on data obtained keeping this solution at 50 and 70 ºC, using Arrhenius equation and considering 2.0% of free residual chlorine as the minimum acceptable threshold, the shelf-life was equal to 166 days at 20 ºC. This model, however, makes it possible to calculate shelf-life at any other given temperature.

Proposta educacional on-line sobre úlcera por pressão para alunos e profissionais de enfermagem

OBJETIVOS: Desenvolver uma proposta educacional on-line sobre o tema úlcera por pressão para alunos e profissionais de enfermagem. MÉTODOS: Pesquisa aplicada, de produção tecnológica, composta pelas etapas de concepção/ planejamento e desenvolvimento, caracterizadas por um conjunto de procedimentos, documentação, digitalização de informações e de imagens. Foram utilizados recursos computacionais didáticos interativos como: o Cybertutor e o Homem Virtual. RESULTADOS: Desenvolvimento de uma proposta educacional virtual sobre úlcera por pressão (UP) dividida em módulos de aprendizagem, contendo lista de discussão, estudos de casos e recursos didáticos, tais como fotos e o Homem Virtual. CONCLUSÕES: Utilizou-se de novas tecnologias educacionais, com a finalidade de promover o aprendizado sobre UP a estudantes de graduação de enfermagem e possibilitar a educação continuada de enfermeiros, uma vez que as UP representam um desafio aos profissionais da saúde e aos serviços de saúde.

Long-term social recognition memory in adult male rats: factor analysis of the social and non-social behaviors

A modified version of the intruder-resident paradigm was used to investigate if social recognition memory lasts at least 24 h. One hundred and forty-six adult male Wistar rats were used. Independent groups of rats were exposed to an intruder for 0.083, 0.5, 2, 24, or 168 h and tested 24 h after the first encounter with the familiar or a different conspecific. Factor analysis was employed to identify associations between behaviors and treatments. Resident rats exhibited a 24-h social recognition memory, as indicated by a 3- to 5-fold decrease in social behaviors in the second encounter with the same conspecific compared to those observed for a different conspecific, when the duration of the first encounter was 2 h or longer. It was possible to distinguish between two different categories of social behaviors and their expression depended on the duration of the first encounter. Sniffing the anogenital area (49.9% of the social behaviors), sniffing the body (17.9%), sniffing the head (3%), and following the conspecific (3.1%), exhibited mostly by resident rats, characterized social investigation and revealed long-term social recognition memory. However, dominance (23.8%) and mild aggression (2.3%), exhibited by both resident and intruders, characterized social agonistic behaviors and were not affected by memory. Differently, sniffing the environment (76.8% of the non-social behaviors) and rearing (14.3%), both exhibited mostly by adult intruder rats, characterized non-social behaviors. Together, these results show that social recognition memory in rats may last at least 24 h after a 2-h or longer exposure to the conspecific.

VUV spectral line emission measurements in the TCABR tokamak

The study of tokamak plasma light emissions in the vacuum ultraviolet (VUV) region is an important subject since many impurity spectral emissions are present in this region. These spectral emissions can be used to determine the plasma ion temperature and density from different species and spatial positions inside plasma according to their temperatures. We have analyzed VUV spectra from 500 Å to 3200 Å wavelength in the TCABR tokamak plasma including higher diffraction order emissions. There have been identified 37 first diffraction order emissions, resulting in 28 second diffraction order, 24 third diffraction order, and 7 fourth diffraction order lines. The emissions are from impurity species such as OII, OIII, OIV, OV, OVI, OVII, CII, CIII, CIV, NIII, NIV, and NV. All the spectra beyond 1900 Å are from higher diffraction order emissions, and possess much better spectral resolution. Each strong and isolated spectral line, as well as its higher diffraction order emissions suitable for plasma diagnostic is identified and discussed. Finally, an example of ion temperature determination using different diffraction order is presented.

On-line identification of minor flavones from sugarcane juice by LC/UV/MS and post-column derivatization

This work describes the on-line characterization of minor flavones from sugarcane (Saccharum officinarum) juice by high-performance liquid chromatography coupled to diode array UV detection and mass spectrometry (LC/UV/MS) using atmospheric pressure chemical ionization-collision-induced dissociation (APCI-CID-MS/MS) and post-column derivatization using UV shift reagents. HPLC-UV analysis with shift reagents provided information about the substitution pattern in the flavonoid skeleton and, combined with MS data, these techniques allowed for the on-line identification of five "garapa" flavones: luteolin-8-C-glucosyl-7-O-glucuronide; tricin-7-O-neohesperoside-4'-O-rhamnoside; tricin-7-O-methylglucuronate-4'-O-rhamnoside; tricin-7-O-methylglucuronide; swertisin, while four other compounds were partially identified as glycosylflavones. Only swertisin (7-O-methylapigenin-6-C-glucoside) was reported previously in sugarcane molasses.

A new species of Trichogenes from the rio Itapemirim drainage, southeastern Brazil, with comments on the monophyly of the genus (Siluriformes: Trichomycteridae)

A new species of the formerly monotypic genus Trichogenes is described from a high-altitude stream of the rio Itapemirim system, an isolated Atlantic drainage in the State of Espírito Santo, southeastern Brazil. Trichogenes claviger, new species, differs from all other trichomycterids by the sexually dimorphic posterior process of the opercle, much elongated in males; the terminal mouth; the deeply bifurcated anterior neural spines and the presence of a large anterodorsal claw-like process on the neural arches of the anterior four free vertebrae. The new species also differs from its only congener, T. longipinnis, by a number of additional traits, including the the lack of branched anal-fin rays in specimens of any size; the broader than long posterior nostril; the deeper head (head depth 72.9-86.6% HL); the presence of a fine dark line along the base of the anal fin; the lack of dark spots on cheeks; the shape of the interopercle; the presence of odontodes on a bony expansion on the posterodorsal margin of the interopercle; the fewer vertebrae (35); the absence of an antorbital; and the fewer pleural ribs (eight). Small juveniles of the new species are also strikingly different from those of all other Trichomycteridae, including T. longipinnis, having a very large lateral eye, an upturned mouth, and compressed head. Trichogenes claviger occurs in shaded sectors of a blackwater sluggish stream with sandy substrate and patchy accumulations of vegetable debris, a habitat markedly different from the rocky torrential environment known for T. longipinnis. A comparison of the internal anatomy of the two species provides the basis for a hypothesis of a monophyletic Trichogenes. Data from the new species further support a sister-group relationship between Trichogeninae and Copionodontinae, as well as the position of that clade as sister group to all remaining Trichomycteridae.

Description of a new species of the genus Leporinus Spix (Characiformes: Anostomidae) from the rio Araguaia, Brazil, with comments on the taxonomy and distribution of L. parae and L. lacustris

A new species of the genus Leporinus is described from the rio Araguaia, in Mato Grosso and Goiás states, Brazil. The new species has the dental formula 4/3, a unique feature within the genus; all other species of Leporinus have dental formulae 3/3, 3/4 or 4/4. In addition, the new species can also be distinguished by the following combination of characters: 36 to 37 scales in the lateral line, 4/4.5 or 4/5 series of scales in the transversal line, 16 circumpeduncular scale series, anal fin surpassing base of lower caudal-fin rays and three blotches along the lateral line. The new species shares with L. parae and L. lacustris a rather deep body, terminal mouth, long anal fin, three small dark blotches on the lateral line, the latter two, particularly the last one, usually fading, and preference for lentic habitats. Comments on the taxonomy and distribution of the species L. parae and L. lacustris are provided.

Genetic trend estimates of meat quality traits in a male broiler line

The present research was conducted to estimate the genetic trends for meat quality traits in a male broiler line. The traits analyzed were initial pH, pH at 6 h after slaughter, final pH, initial range of falling pH, final range of falling pH, lightness, redness, yellowness, weep loss, drip loss, shrink loss, and shear force. The number of observations varied between 618 and 2125 for each trait. Genetic values were obtained by restricted maximum likelihood, and the numerator relationship matrix had 107,154 animals. The genetic trends were estimated by regression of the broiler average genetic values with respect to unit of time (generations), and the average genetic trend was estimated by regression coefficients. Generally, for the traits analyzed, small genetic trends were obtained, except for drip loss and shear force, which were higher. The small magnitude of the trends found could be a consequence of the absence of selection for meat quality traits in the line analyzed. The estimates of genetic trends obtained were an indication of an improvement in the meat quality traits in the line analyzed, except for drip loss.

Long Terminal Repeat Sequence Analysis of HTLV-2 Molecular Variants Identified in Southern Brazil

In Brazil, human T-lymphotropic virus type 2 (HTLV-2) is endemic in Amerindians and epidemic in intravenous drug users (IDUs). The long terminal repeat (LTR) is the most divergent genomic region of HTLV-2, therefore useful to characterize subtypes. Nucleotide sequence and restriction fragment length polymorphism (RFLP) analysis of LTR genomic segments of fourteen HTLV-2 strains isolated from HIV-infected patients of Londrina, Southern Brazil, were carried out. Molecular analysis disclosed that all HTLV-2 strains belonged to 2a subtype, and RFLP detected the presence of the a4, a5, and a6 subgroups according to Switzer's nomenclature. RFLP correlated with nucleotide sequence, and phylogenetic analysis clustered HTLV-2 sequences of IDUs into subgroups a5 and a6. HTLV-2 sequences from individuals of sexual risk factor clustered into the a4 subgroup. These results extend the knowledge of the genetic diversity of HTLV-2 circulating in Brazil and provide insights into HTLV-2 transmission and virus movement in this geographic area.