Molecular analysis of the virulence attenuation process in Junín virus vaccine genealogy

The Junín virus strain Candid#1 was developed as a live attenuated vaccine for Argentine hemorrhagic fever. In this article, we report sequence information of the L and S RNAs of Junín virus Candid#1 and XJ#44 strains, and show the comparisons with the XJ13 wild-type strain and with other Junín virus strains, like Romero, IV4454 and MC2 strains, and other closely and distantly related arenaviruses. Comparisons of the nucleotide and amino acid sequences of all genes of three strains from the same vaccine genealogy, revealed different point mutations that could be associated with the attenuated phenotype. A 91% of the mutations found are consistent with a hypothesis of progressive attenuation of virulence from XJ13 to XJ#44 and to Candid#1; 39% of mutations were observed in XJ#44 and conserved in Candid#1, while another 52% of the mutations appeared only in Candid#1 strain. The remaining 9% corresponded to reverse mutations in the L gene. In summary, the present work shows a set of mutations that could be related to the virulence attenuation phenomenon. This information will serve as a starting point to study this biological phenomenon, provided that a reverse genetics system for Junín virus is developed to allow the generation of infectious virions with specific mutations.     

Hearing loss in people with HIV/AIDS and associated factors: an integrative review

The current scientific literature reports on the incidence of hearing impairments due to HIV/AIDS, and the hearing changes can occur due to damage to the outer, middle or inner ear. Thus, it is important to study how these changes occur, the hearing loss and their associations with the HIV/AIDS infection.ObjectiveTo identify the factors related to hearing loss in people with HIV/AIDS in the global scientific literature.MethodStudy carried out an Integrative Review of the Literature. The key words used were: hearing loss, hearing disorders and deafness, separately associated to the keyword HIV on PUBMED, ScIELO, LILACS and ISI databases. We used complete original papers, of free access, in English, Spanish, French and Portuguese. Thirteen quantitative studies from 1994-2010 were selected.ConclusionWe did not find any strong direct association between anti-retroviral therapy and hearing loss; however, there are indications of hearing loss in the population studied, and their associations and causes need to be better investigated.     

Sequence analysis of HIV-1 isolates from Guinea-Bissau: selection of vaccine epitopes relevant in both West African and European countries

For a CD8 epitope-based vaccine to match different geographic locations, the targeted epitopes for cytotoxic T-lymphocytes (CTLs) must be present in the local circulating HIV-1 strains. Secondly, the vaccine epitopes should match the host population HLA types. We characterized two new HIV-1 isolates from Guinea-Bissau. Also, we have identified 15 subdominant CD8 epitopes representing common HLA super-types theoretically covering most HLA alleles in any population. Herein we demonstrate that the selected vaccine epitopes are well conserved and simultaneously present in sequences from West Africa and Denmark. Use of the selected epitopes will likely ensure ≥10 immune targets in the majority of candidates for experimental therapeutic vaccination in both geographic regions. Our results warrant testing of the selected vaccine epitopes in both geographic locations.     

Maxillofacial fractures sustained by unmounted equestrians

Facial injuries caused by horses are relatively common among riding enthusiasts, but little is known about the nature of maxillofacial fractures sustained by those not mounted. We collected data on patients’ characteristics, fractures sites, mechanisms of injury, and treatment of these fractures from the departmental records of the oral and maxillofacial unit at Christchurch Hospital, New Zealand between 1996 and 2008. Of 49 patients with equine-related facial fractures, 35 (mean (SD) age 35.8 (16.7) years) had sustained their injuries while unmounted (71%). Most of the fractures occurred in women (66%), of whom 39% were aged between 16 and 30 years. There was an increasing trend in the incidence of these fractures over much of the 13-year period. Most injuries were caused by kicks (69%), followed by head-butts (26%), and trampling (6%). The zygoma was the most common fracture site (63%), followed by the mandible (34%), and orbital floor (31%). Surgical intervention was required in 60% of cases.     

Estimating the extent of underreporting of mortality among HIV-infected individuals in Rio de Janeiro, Brazil

Non-HIV-related causes of death have been increasing after the introduction of highly active antiretroviral therapy. Underlying and contributing causes of death were assessed in respect to the presence/absence of HIV/AIDS among HIV-infected/AIDS patients in Rio de Janeiro, Brazil. Demographic variables (age, gender, ethnicity, and schooling) and CD4?cell counts closest to death were assessed through logistic regression models comparing those who did not have with those who had HIV/AIDS mentioned on the death certificate. The linkage with the two cohorts identified 1249 records, of which 370 (29.6%) did not have HIV/AIDS listed on any field of the death certificate [77 (20.8%) attributed to undefined and 72 (19.5%) to external causes]. After excluding external causes, 25.3% still did not have HIV/AIDS listed on the death certificate. Multiple logistic regression analysis showed that age >40 years (OR?=?2.09; 95%CI?=?1.49-2.93; p?相似文献   

Hyperandrogenic syndrome in a postmenopausal woman: a case report

Hyperandrogenic syndromes include diseases that manifest through an increased biological activity of androgens and that can originate from neoplastic or functional diseases. Androgen-secreting ovarian tumors represent about 1% of ovarian neoplasias. Steroid cell tumors are among the more rare types which account for less than 0.1% of all ovarian tumors. They are usually benign, of small dimensions and unilateral. We report here a rare case of a unilateral steroid cell tumor. A 60-year-old woman was seen after four months of evolution of hirsutism, clitoris hypertrophy and elevation of serum estradiol levels. Her total testosterone and 17-OH-progesterone levels were also increased.     

Public knowledge, beliefs and attitudes towards patients with schizophrenia: Buenos Aires

Objective

The purpose of our study was to assess the knowledge, social distance and perception of social discrimination towards persons with schizophrenia in the general adult population of Buenos Aires, Argentina.

Methods

One thousand two-hundred fifty-four persons were surveyed at different neighborhoods of the city of Buenos Aires. Their knowledge about schizophrenia, personal social distance and perception of social discrimination were assessed with several questions. Afterwards, a scale for each one of these measures was built.

Results

Almost half of the general population believed that patients with schizophrenia suffer from split personality and that most of them are dangerous and violent. Knowledge about schizophrenia in the general population was moderate and it was associated with age and education. Almost 80% of the population had less than one-third of the maximum possible social distance score, but their perception of social discrimination was high. Social distance was greater in the elderly. Knowledge was correlated weakly with social distance. Respondents directly related with patients suffering from schizophrenia were more knowledgeable about the illness, but had the same social distance and perception of social discrimination than the rest of the general population.

Conclusions

The persons surveyed felt their own attitudes are more favorable to people with schizophrenia than ??most other people??s?? attitudes. The elderly should be specifically addressed in specially designed anti-stigma campaigns.     

Evidence for Metabolic Hypothalamo-Amygdala Dysfunction in Narcolepsy

Study Objectives:

Proton resonance spectroscopy (¹H-MRS) allows noninvasive chemical tissue analysis in the living brain. As neuronal loss and gliosis have been described in narcolepsy, metabolites of primary interest are N-acetylaspartate (NAA), a marker of neuronal integrity and myo-Inositol (mI), a glial marker and second messenger involved in the regulation of intracellular calcium. One ¹H-MRS study in narcolepsy found no metabolic changes in the pontomedullary junction. Another study showed a reduction in NAA/creatine-phosphocreatine (Cr) in the hypothalamus of narcolepsy patients with cataplexy. We aimed to test for metabolic changes in specific brain areas, “regions of interest,” thought to be involved in emotional processing, sleep regulation and pathophysiology of narcolepsy: hypothalamus, pontomesencephalic junction and both amygdalae.

Design:

We performed ¹H-MRS using a 3T Philips Achieva whole body MR scanner. Single-voxel proton MR spectra were acquired and quantified with LCModel to determine metabolite concentration ratios.

Setting:

The participants in the study were recruited at the outpatient clinic for sleep medicine, Department of Neurology and magnetic resonance spectroscopy was performed at the MRI facility, University Hospital Zurich.

Participants:

¹H-MRS was performed in fourteen narcolepsy patients with cataplexy, CSF hypocretin deficiency (10/10) and HLA-DQB1*0602 positivity (14/14) and 14 age, gender and body mass index matched controls. Patients were treatment naïve or off therapy for at least 14 days before scanning.

Measurements and Results:

No differences were observed in the regions of interest for (total NAA)/Cr ratios. Myo-Inositol (mI)/Cr was significantly lower in the right amygdala of the patients, compared to controls (P < 0.042). Significant negative correlations only in the patients group were found between (total NAA)/Cr in hypothalamus and mI/Cr in the right amygdala (r = −0.89, P < 0.001), between mI/Cr in hypothalamus and (total NAA)/Cr in the right amygdala (r = −63, P < 0.05) and between mI/Cr in the left amygdala and total NAA)/Cr in the pontomesencephalic junction (r = −0.69, P < 0.05).

Conclusion:

Our findings suggest amygdala involvement and possible hypothalamo-amygdala dysfunction in narcolepsy.

Citation:

Poryazova R; Werth E; Khatami R; Dydak U; Meier D; Boesiger P; Bassetti CL. Evidence for metabolic hypothalamo-amygdala dysfunction in narcolepsy. SLEEP 2009;32(5):607-613.