An acute bout of resistance exercise increases BDNF in hippocampus and restores the long-term memory of insulin-resistant rats.

A sedentary lifestyle, inadequate diet, and obesity are substantial risk factors for Type 2 diabetes mellitus (T2DM) development. A major picture of T2DM is insulin resistance (IR), which causes many impairments in brain physiology, such as increased proinflammatory state and decreased brain-derived neurotrophic factor (BDNF) concentration, hence reducing cognitive function. Physical exercise is a non-pharmacological tool for managing T2DM/IR and its complications. Thus, this study investigated the effects of IR induction and the acute effects of resistance exercise (RE) on memory, neurotrophic, and inflammatory responses in the hippocampus and prefrontal cortex of insulin-resistant rats. IR was induced by a high-fat diet and fructose-rich beverage. Insulin-resistant rats performed acute resistance exercise (IR.RE; vertical ladder climb at 50-100% of the maximum load) or rest (IR.REST; 20 min). Cognitive parameters were assessed by novel object recognition (NOR) tasks, and biochemical analyses were performed to assess BDNF concentrations and inflammatory profile in the hippocampus and prefrontal cortex. Insulin-resistant rats had 20% worse long-term memory (LTM) (p < 0.01) and lower BDNF concentration in the hippocampus (-14.6%; p < 0.05) when compared to non-insulin-resistant rats (CON). An acute bout of RE restored LTM (-9.7% pre vs. post; p > 0.05) and increased BDNF concentration in the hippocampus (9.1%; p < 0.05) of insulin-resistant rats compared to REST. Thus, an acute bout of RE can attenuate the adverse effects of IR on memory and neurotrophic factors in rats, representing a therapeutic tool to alleviate the IR impact on the brain.

Detection of respiratory viruses in primary cholesteatoma tissues.

Cholesteatomas are frequent middle ear benign tumors of unknown etiology. Infectious agents have been considered as possible contributing factors in the pathogenesis of cholesteatomas. Aiming to investigate the presence of respiratory viruses in primary cholesteatoma tissues, 26 formalin-fixed paraffin-embedded primary cholesteatoma tissues obtained from patients seen at the of the Clinical Hospital of the University of São Paulo School of Medicine, in Ribeirão Preto, Brazil were tested by real-time polymerase chain reaction (PCR). Considering the PCR results, 35% of the tissues were positive for human rhinovirus (HRV), 15.3% for human enterovirus (EV), 3.8% for human metapneumovirus (HMPV), and 3.8% for human bocavirus (HBoV). Serial immunohistochemistry for virus antigens and cell surface markers evidenced that the viruses were associated with fibroblasts, dendritic cells, macrophages, B lymphocytes, CD4+ , and CD8+ T lymphocytes. These findings indicate for the first time the presence of active respiratory virus infection in primary cholesteatoma tissues, suggesting that persisting virus infection in the middle could play a role in the pathogenesis and evolution of cholesteatomas.

Cross-Sectional Imaging of Third Molar-Related Abnormalities.

Third molars may be associated with a wide range of pathologic conditions, including mechanical, inflammatory, infectious, cystic, neoplastic, and iatrogenic. Diagnosis of third molar-related conditions can be challenging for radiologists who lack experience in dental imaging. Appropriate imaging evaluation can help practicing radiologists arrive at correct diagnoses, thus improving patient care. This review discusses the imaging findings of various conditions related to third molars, highlighting relevant anatomy and cross-sectional imaging techniques. In addition, key imaging findings of complications of third molar extraction are presented.

Silent Infection of B and CD8+ T Lymphocytes by Influenza A Virus in Children with Tonsillar Hypertrophy.

Influenza A viruses (IAVs) cause more than 2 million annual episodes of seasonal acute respiratory infections (ARI) and approximately 500,000 deaths worldwide. Depending on virus strain and host immune status, acute infections by IAV may reach sites other than the respiratory tract. In the present study, IAV RNA and antigens were searched for in tissues of palatine tonsils and adenoids removed from patients without ARI symptoms. A real-time reverse transcriptase PCR (RT-PCR) screening revealed that 8 tissue samples from 7 patients out of 103 were positive for IAV. Positive samples were subjected to next-generation sequencing (NGS) and 3 of 8 tissues yielded complete IAV pH1N1 genomes, whereas in 5 samples, the PB1 gene was not fully assembled. Phylogenetic analysis placed tonsil-derived IAV in clusters clearly segregated from contemporaneous Brazilian viruses. Flow cytometry of dispersed tissue fragments and serial immunohistochemistry of paraffin-embedded sections of naturally infected biopsies indicated that CD20+ B lymphocytes, CD8+ T lymphocytes, and CD11c+ cells are susceptible to IAV infection. We sought to investigate whether these lymphoid tissues could be sites of viral replication and sources of viable virus particles. MDCK cells were inoculated with tissue lysates, enabling recovery of one IAV isolate confirmed by immunofluorescence, reverse transcriptase quantitative PCR (RT-qPCR), and NGS. The data indicate that lymphoid tissues not only harbor expression of IAV proteins but also contain infectious virus. Asymptomatic long-term infection raises the possibility of IAV shedding from tonsils, which may have an impact on host-to-host transmission.IMPORTANCE Influenza A virus (IAV) infections are important threats to human health worldwide. Although extensively studied, some aspects of virus pathogenesis and tissue tropism remain unclear. Here, by different strategies, we describe the asymptomatic infection of human lymphoid organs by IAV in children. Our results indicate that IAV was not only detected and isolated from human tonsils but displayed unique genetic features in comparison with those of contemporaneous IAVs circulating in Brazil and detected in swabs and nasal washes. Inside the tissue microenvironment, immune cells were shown to be carrying IAV antigens, especially B and T CD8+ lymphocytes. Taken together, these results suggest that human lymphoid tissues can be sites of silent IAV infections with possible impact on virus shedding to the population.

Genotypic characteristics of HIV type 1 based on gp120 hypervariable region 3 of isolates from Southern Brazil.

The aim of this study was to investigate HIV-1 molecular diversity and the epidemiological profile of HIV-1-infected patients from Ribeirão Preto, Brazil. A nested PCR followed by sequencing of a 302-base pair fragment of the env gene (C2-V3 region) was performed in samples from HIV-1-positive patients. A total of 45 sequences were aligned with final manual adjustments. The phylogenetic analyses showed a higher prevalence of HIV-1 subtype B in the studied population (97.8%) with only one sample yielding an F1 subtype. The viral genotyping prediction showed that CCR5 tropism was the most prevalent in the studied cohort. Geno2pheno analysis showed that R5 and CXCR4 prediction were 69% and 31%, respectively. There was no statistical significance, either in viral load or in CD4(+) T cell count when R5 and X4 prediction groups were compared. Moreover, the GPGR tetramer was the most common V3 loop core motif identified in the HIV-1 strains studied (34.1%) followed by GWGR, identified in 18.1% of the samples. The high level of B subtype in this Brazilian population reinforces the nature of the HIV epidemic in Brazil, and corroborates previous data obtained in the Brazilian HIV-infected population.

Molecular dynamics, flexible docking, virtual screening, ADMET predictions, and molecular interaction field studies to design novel potential MAO-B inhibitors.

Monoamine oxidase is a flavoenzyme bound to the mitochondrial outer membranes of the cells, which is responsible for the oxidative deamination of neurotransmitter and dietary amines. It has two distinct isozymic forms, designated MAO-A and MAO-B, each displaying different substrate and inhibitor specificities. They are the well-known targets for antidepressant, Parkinson's disease, and neuroprotective drugs. Elucidation of the x-ray crystallographic structure of MAO-B has opened the way for the molecular modeling studies. In this work we have used molecular modeling, density functional theory with correlation, virtual screening, flexible docking, molecular dynamics, ADMET predictions, and molecular interaction field studies in order to design new molecules with potential higher selectivity and enzymatic inhibitory activity over MAO-B.

Magnetic resonance imaging of the temporal bone in patients with Ménière's disease.

Ménière's disease (MD) is still controversial in several aspects. The vestibular aqueduct, the osseous channel that carries the endolymphatic duct and sac, has previously been studied by tomography and computed tomography, with shortening and narrowing of this structure observed. These findings are apparently correlated to the development of the endolymphatic hydrops present in MD and related to its episodic symptoms. In studying the endolymphatic duct, the key structure in the pathology of this disease, magnetic resonance imaging (MRI) studies of the temporal bone were performed in 12 patients with unilateral MD and in 9 bilateral cases; the results were compared with images obtained from 30 normal ears. The endolymphatic duct appeared to be statistically less visible in MD patients, with no difference between symptomatic and asymptomatic ears in the presence of unilateral disease. No relationship was found between visualization of the endolymphatic duct and time of evolution or response to clinical treatment in these cases. The distance from the posterior semicircular canal to the posterior temporal border was found to be bilaterally reduced in MD. The authors conclude that although the demonstration of endolymphatic hydrops "in vivo" is not yet possible by MRI, some features can be observed that can support a clinical hypothesis of MD.

[Glomus tumors in head and neck: assessment with magnetic resonance]. / Tumores glômicos em cabeça e pescoço: avaliação por ressonância magnética.

Glomus tumors originate from paranglionic tissues. In head and neck, these lesions are mainly found near carotid bifurcation, X nerve, jugular bulb or middle ear. These tumors have a low growing rate and are hypervascularized. Their histology show "nonchromaffin" cells and vascular structures involved by a fibrous matrix. MRI, CT and angiography are imaging methods used in glomus tumor. The author describe four cases of jugulo-timpanic glomus tumors studied by MRI, showing their main findings and the value of this method to detection of these lesions.

Importance of vpr for infection of rhesus monkeys with simian immunodeficiency virus.

The importance of the vpr gene for simian immunodeficiency virus (SIV) replication, persistence, and disease progression was examined by using the infectious pathogenic molecular clone called SIVmac239. The ATG start codon of the vpr gene was converted to TTG by site-specific mutagenesis. The constructed Vpr- mutant virus is identical with the parental SIVmac239/nef-stop virus with the exception of this one nucleotide. These viruses replicated with similar kinetics and to similar extents in rhesus monkey lymphocyte cultures and in the human CEMX174 cell line. Five rhesus monkeys were inoculated with the Vpr- variant of SIVmac239/nef-stop, and two monkeys received SIVmac239/nef-stop as controls. Both controls showed reversion of the TAA stop signal in nef by 2 weeks postinfection, as has been observed previously. Reversion of the TAA stop codon in nef also occurred in the five monkeys that received the Vpr- variant, but reversion was delayed on average to about 4 weeks. Thus, the mutation in vpr appeared to delay the rapidity with which reversion occurred in the nef gene. Reversion of the TTG sequence in vpr to ATG was observed in three of the five test animals. Reversion in vpr was first observed in these three animals 4 to 8 weeks postinfection. No vpr revertants were found over the entire 66 weeks of observation in the other two test animals that received the vpr mutant. Antibodies to vpr developed in those three animals in which reversion of vpr was documented, but antibodies to vpr were not observed in the two animals in which reversion of vpr was not detected. Antibody responses to gag and to whole virus antigens were of similar strength in all seven animals. Both control animals and two of the test animals in which vpr reverted maintained high virus loads and developed progressive disease. Low virus burden and no disease have been observed in the two animals in which vpr did not revert and in the one animal in which vpr reversion was first detected only at 8 weeks. The reversion of vpr in three of the five test animals indicates that there is significant selective pressure for functional forms of vpr in vivo. Furthermore, the results suggest that both vpr and nef are important for maximal SIV replication and persistence in vivo and for disease progression.

[Sexually transmitted agents in gynecology: incidence and importance]. / Agentes sexualmente transmitidos em ginecologia: incidencia e importancia.

PIP: The study comprised the analysis of 77 patients between May 1985 and May 1986 in the emergency clinic of the Gynecological Clinic of the Faculty of Medicine of the University of Sao Paulo. Three different groups constituted the cases: A) 15 women devoid of infectious symptoms, aged 18-52 with an average of 31.5 years; B) 25 patients who were carriers of mucous purulent cervicitis, aged 16-42 with an average age of 27.6 years; and C) 37 carriers of acute salpingitis, aged 16-48 with an average age of 25 years. All patients had been sexually active, and none of them had used any local or systemic anti-infection medication for 30 days preceding the study. Pap smears were carried out in all patients. Laparoscopy indicated light salpingitis in 17 patients, moderate in 12, and grave in 8 patients. Neisseria gonorrhea was isolated from the endocervix of 14 women (37.8%) with acute salpingitis, and from none of the other 2 groups. Chlamydia trachomatis was found in 1 (6.7%), 3 (12%), and 14 (37.8%) patients in the Groups A, B, and C. Ureaplasma urealyticum was identified in 3 (20%), 9 (36%), and 21 (56.8%) in the respective groups. Mycoplasma hominis was isolated in 1 (6.7%), 1 (4%), and 2 (5.4%) patients in the respective groups. Cervical-vaginal cytology in the different groups broke down in this fashion; in Group A, 4 were normal (26.7%) and 11 were infectious (64.7%); in Group B, 3 were normal (12%) and 21 were infectious (84%), while 1 (4%) was suspected of dysplasia; and in Group C, 2 were normal (5.4%) and 31 were infectious (83%), while 4 (10.8%) were suspected of dysplasia. It is well known that colpocytological alterations are intimately related to sexual activity. These alterations may also have to do with cancer of the cervix. In view of the fact that the analyzed groups had been promiscuous, a high percentage of colpocytological alterations could be expected. Indeed, clear increases of inflammatory alterations and cervical displasias were found in the cervicitis and salpingitis groups.^ieng