OBJECTIVE:In POWER 1 and POWER 2, darunavir (TMC114) with low-dose ritonavir (darunavir/r) demonstrated greater efficacy versus control protease inhibitors (PIs). To examine the efficacy and safety ...of the selected darunavir/r dose further, additional patients were analyzed.
METHODS:Treatment-experienced HIV-1-infected patients received darunavir/r at a dose of 600/100 mg twice daily plus an optimized background regimen. The primary intent-to-treat analysis was the proportion of patients with an HIV-1 RNA reduction ≥1 log10 at week 24.
RESULTS:Three hundred twenty-seven patients were treated; the baseline mean HIV-1 RNA was 4.6 log10 copies/mL, and the median CD4 count was 115 cells/mm (median primary PI mutations = 3, PI resistance-associated mutations = 9). Two hundred forty-six patients reached week 24 by the cutoff date and were included in the efficacy analysis65% and 40% achieved HIV-1 RNA reductions of ≥1 log10 and <50 copies/mL, respectively, at week 24. The mean CD4 count increase was 80 cells/mm. The most common adverse events (AEs) were diarrhea (14%), nasopharyngitis (11%), and nausea (10%). Nine (3%) patients discontinued treatment because of AEs or HIV-1-related events. Six treatment-unrelated deaths (2%) were reported.
CONCLUSIONS:These results corroborate POWER 1 and POWER 2. In this larger set of treatment-experienced patients, darunavir/r at a dose of 600/100 mg twice daily provided substantial virologic and immunologic responses and was generally safe and well tolerated.
The cryopreservation of jaguar semen must be improved to produce high-quality biobanking doses. Until now, the rare studies of semen freezing in the species have only evaluated glycerol, always with ...a significant reduction in sperm quality in thawed semen. The purpose of this study was to assess the efficacy of three cryoprotectants, dimethylsulfoxide (DMSO), glycerol (GLY), and methanol (MET), in the cryopreservation of jaguar semen in an LDL-based extender, as well as the effect of thawing temperature on dosage quality. Five mature males with a history of reproduction were used. On the males, an infrared thermal image (IRT) was captured, the spicules and testes were analyzed, and the CASA system was used to evaluate the quality of fresh and thawed sperm. The superficial IRT was 4.6 ± 1.2 °C cooler than the anal sphincter, and the semen measured between 27.3 and 28.7 °C shortly after exiting the urethra. The total motility of fresh sperm was 55.3 ± 22.6%, and progressive motility was 36.3 ± 18%. The total motility of thawed sperm was 5.28 ± 2.51%, 4.49 ± %2.49, and 0.51 ± 0.62% for DMSO, GLY, and MET, respectively. DMSO and GLY performed better than MET, and there was no difference in thawing temperature (37°C 30 s vs. 50°C 12 s). All animals exhibit a considerable level of morphological changes in sperm. Low amounts of total and progressive motility were found in the thawed sperm. Males with a high level of sperm morphological changes were found to be fertile, but the lone male with normospermia was infertile. Thus, we contest the applicability of the commonly used morphological classification for bovines to felid species.
One Conservation concept in practice Luczinski, Thiago Cavalheri; Jorge-Neto, Pedro Nacib; Ribeiro, Rafaella Martins ...
Theriogenology Wild (Online),
2023, 2023-00-00, 2023-01-01, Letnik:
2
Journal Article
Recenzirano
Odprti dostop
The One Conservation is an integrative process for biodiversity conservation. This communication describes how this integrated method, involving many institutions, resulted in the birth of a jaguar ...cub that should be reintroduced to the wild, thereby contributing to the species' long-term survival. Each parent was saved from the wilderness. While the sire was saved as a cub, the dam was rescued after the devastating Pantanal wildfires that killed over 16.9 million vertebrates. Rescues, treatments, and ex situ care involved a large number of specialists and institutions. We report the ex situ reproduction of the only pair of Jaguars under reproductive age from the Pantanal biome. The One Conservation approach made the good outcome possible, which brought together numerous people and organizations.
Here we review how immune activation and insulin resistance contribute to the metabolic alterations observed in HIV-infected patients, and how these alterations increase the risk of developing CVD. ...The introduction and evolution of antiretroviral drugs over the past 25 years has completely changed the clinical prognosis of HIV-infected patients. The deaths of these individuals are now related to atherosclerotic CVDs, rather than from the viral infection itself. However, HIV infection, cART, and intestinal microbiota are associated with immune activation and insulin resistance, which can lead to the development of a variety of diseases and disorders, especially with regards to CVDs. The increase in LPS and proinflammatory cytokines circulating levels and intracellular mechanisms activate serine kinases, resulting in insulin receptor substrate-1 (IRS-1) serine phosphorylation and consequently a down regulation in insulin signaling. While lifestyle modifications and pharmaceutical interventions can be employed to treat these altered metabolic functions, the mechanisms involved in the development of these chronic complications remain largely unresolved. The elucidation and understanding of these mechanisms will give rise to new classes of drugs that will further improve the quality of life of HIV-infected patients, over the age of 50.
Um importante meio de estudar escoamentos bifásicos é através do uso de softwares de fluido dinâmica computacional (Computational Fluid Dynamics, CFD) técnica que abrange a área de fenômenos de ...transporte e matemática computacional. Contudo, para garantir que tal análise seja isenta de erros de discretização, é necessário realizar um estudo de convergência de malha. Este trabalho utiliza o método GCI proposto pela ASME para testar a convergência de três diferentes malhas em escoamento gás-líquido, obtendo resultados apropriados para a malha intermediária e a mais refinada, com GCI médio 2,03%.
Background Staphylococcus aureus nasal carriage in HIV patients remains incompletely characterized. The aim of the present study was to describe epidemiologic and molecular features of S. aureus ...nasal colonization in HIV outpatients. Methods HIV outpatients with no history of hospitalization within the previous 2 years were screened for S aureus nasal colonization. Three samples were collected from each patient, and the risk factors for colonization were assessed. Nasal carriage was classified as persistent colonization, transient colonization, or no colonization. Persistent colonization was subdivided into simple (same DNA profile) or multiple (different DNA profiles) using pulsed-field gel electrophoresis (PFGE) for genotyping the strains of S. aureus. Results A total of 111 patients were evaluated, of which 70 (63.1%) had at least 1 positive culture for S aureus. Patients in clinical stages of AIDS were more likely to be colonized than non-AIDS patients ( P = .02). Among the patients with S aureus nasal carriage, 25.2% were transient carriers and 39.4% were persistent carriers. PFGE analysis showed that the persistent colonization was simple in 24 patients and multiple in 17 patients. Conclusion The HIV patients had a high rate of S. aureus nasal colonization. The most common characteristic of colonization was simple persistent colonization showing the same genomic profile.
In HIV patients using HAART insulin resistance is a central pathophysiological condition that can contribute to the development of diabetes and cardiovascular complications. To examine the role of ...adipocyte hormones and LPS in insulin resistance in HIV patients, we investigated the role of adiponectin, leptin, visfatin and LPS levels in the insulin resistance of HIV-infected patients treated with HAART.
This study included 67 HIV positive individuals on HAART and ten healthy controls. All participants performed plasma or serum levels of glucose; insulin; lipids, visfatin, leptin, adiponectin, and LPS. The homeostasis model assessment (HOMA-IR), was used to estimate insulin resistance.
The levels of visfatin, leptin and adiponectin were similar between controls and HIV patients. However, circulating levels of LPS were higher in HIV patients on HAART than in controls. There was a positive correlation between LPS and TG (r = 0.49, p = 0.0001), between LPS and TG/HDL (r = 0.50, p = 0.0001), between LPS and insulin (r = 0.52, p = 0.0003), and between LPS and HOMA-IR (r = 0.52, p = 0.0005), in HIV patients.
Our results showed a clear correlation between plasma LPS and markers of insulin resistance, suggesting a relationship between LPS levels and metabolic alterations, particularly affecting lipids and insulin resistance in HIV patients.
Maraviroc is a first-in-class chemokine coreceptor type-5 (CCR5) antagonist with demonstrated immunovirologic activity in treatment-experienced (TE) patients with CCR5 (R5)-tropic HIV-1; however, ...experience in regimens containing newer antiretroviral agents is limited. The primary objective of this 96-week open-label, noncomparative, multicenter Phase 3b study (NCT00478231) was to assess the safety of maraviroc in combination with optimized background therapy (OBT), which could include recently introduced agents such as darunavir and raltegravir in TE patients in Brazil with R5 HIV-1 and limited therapeutic options. Immunovirologic activity was a secondary endpoint. Of 638 patients screened, 206 were treated and 125 completed the study. Approximately 70% were male; the mean age was 43.2 years. Most patients (65.0%) received an OBT combination of protease inhibitor plus nucleoside reverse transcriptase inhibitor. Adverse event (AE) and treatment-related AE incidence was 91.3% and 36.9%, respectively. The most common AEs were diarrhea, nasopharyngitis, and headache. Serious AEs and treatment-related serious AEs occurred in 16.5% and 4.4% of patients. Only eight patients (3.9%) discontinued due to AEs. Few AIDS-defining events were observed (4.9%). The proportion of patients with viral load <400 copies/ml increased from 2.4% at baseline to 43.9% at week 8, remaining >40% until week 48. At the end of treatment, 26.7% of patients had a viral load <400 copies/ml. Median CD4(+) cell count increased throughout the study; the mean change from baseline to end of treatment was 174.1 cells/μl. In conclusion, maraviroc, combined with different agents from multiple classes, was well tolerated in highly TE patients. Maraviroc plus OBT was associated with an immunovirologic response in this population.
PDF
