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The practice of storing and dispensing medications by providers at an inner city neighborhood health center that serves predominantly ethnic minority clients was terminated due to accreditation regulations. This practice promoted adherence since many clients did not want to receive medications by mail at home due to confidentiality concerns or were unwilling to present to their local pharmacy due to fear of discrimination related to HIV status. The purpose of this paper is to describe an alternative means to access HIV medications in a safe and supportive environment for clients confronted with cultural and social barriers through a unique collaboration between an HIV specialty care program and HIV specialty pharmacy. [ABSTRACT FROM AUTHOR]

Several biomarkers have been evaluated as predictors of severity or in directing the treatment of COVID-19, however there are no conclusive results. In this study, we evaluated serum levels of cytokines, chemokines, and cell growth factors in association with the pathobiology of mild to moderate SARS-CoV-2 infection. Serum levels of SARS-CoV-2 infected patients (n = 113) and flu symptoms individuals negative for SARS-CoV-2 (n = 58), tested by the RT-qPCR test-nasal swab were compared to healthy controls (n = 53). Results showed that the proinflammatory cytokines IL-1β, MCP-3, TNF-α, and G-CSF were increased in symptomatic patients and the cytokines IL-6 and IL-10 were associated with patients positive for SARS-CoV-2 when compared to healthy controls. Symptoms associated with COVID-19 were fever, anosmia, ageusia, and myalgia. For patients without SARS-CoV-2 infection, their major symptom was sore throat. The pathobiology of mild to moderate SARS-CoV-2 infection was associated with increasing proinflammatory cytokines and a pleiotropic IL-6 and anti-inflammatory IL-10 cytokines compared to healthy controls. Thus, knowledge about the pathophysiology and the involvement of biomarkers in the mild to moderate profile of the disease should be evaluated. Monitoring these biomarkers in patients with mild to moderate disease can help establish adequate treatment and prevention strategies for long-term COVID-19., (© 2023 Wiley Periodicals LLC.)

Diffuse leptomeningeal glioneuronal tumors (DLGNTs) are rare central nervous system tumors of childhood that were recently described as a new entity. DLGNTs usually manifest with symptoms related to increased intracranial pressure or spinal cord compression. The classic radiological feature is a widespread leptomeningeal enhancement that may involve the entire neuroaxis. Microscopic examination demonstrates oligodendroglial-like cells that are positive for OLIG2, MAP2, and S100 and negative for IDH-1. Anaplastic features occur in some cases. Molecularly, DLGNTs are characterized by chromosome arm 1p deletion and alteration of a mitogen-activated protein kinase (MAPK) pathway gene, most commonly BRAF-KIAA1549 fusion. There is no established grading system for these tumors, which may have an indolent or aggressive behavior. Treatment usually involves chemotherapy and radiation therapy., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This article aims to discuss the use of Social Reproduction, proposed by Juan Samaja, in the analysis of living and health conditions in a context of an sustanaible development reserve in the Brazilian Amazon. This study uses a comprehensive approach to Social Reproduction processes that comprise the network of hierarchically organized structures using the analysis of social interactions of narrated and observable events, applied to the data matrix. The Ecological Reproduction of life in the riverside forest is negatively expressed in bio-communal life, as the strategic actions provided by the Political, Economic and Cultural Reproductions, that is, the environmental policy actions, do not value the local way of life. The deficient access to social goods and services, including health care, from the Political and Techno-Economic Reproductions, has an impact on the material basis of the Bio-Communal Reproduction, whose outcome is high frequency of disease complaints and workplace accidents, such as infectious gastroenteritis, malaria, tuberculosis, leprosy, and poisoning by venomous animals. Ensuring access to social goods and services, in particular health care, is essential for improving resilience to the forest adversities. In conclusion, the social reproduction data matrix helped understand the processes of Social Reproduction that are part of the hierarchically organized structures, whose interactions shaped the living and health conditions of the riverside population analyzed in this study.

We adopted the reverse-transcriptase-loop-mediated isothermal amplification (RT-LAMP) to detect severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) in patient samples. Two primer sets for genes N and Orf1ab were designed to detect SARS-CoV-2, and one primer set was designed to detect the human gene Actin. We collected prospective 138 nasopharyngeal swabs, 70 oropharyngeal swabs, 69 salivae, and 68 mouth saline wash samples from patients suspected to have severe acute respiratory syndrome (SARS) caused by SARS-CoV-2 to test the RT-LAMP in comparison with the gold standard technique reverse-transcription quantitative polymerase chain reaction  (RT-qPCR). The accuracy of diagnosis using both primers, N5 and Orf9, was evaluated. Sensitivity and specificity for diagnosis were 96% (95% confidence interval [CI]: 87-99) and 85% (95% CI: 76-91) in 138 samples, respectively. Accurate diagnosis results were obtained only in nasopharyngeal swabs processed via extraction kit. Accurate and rapid diagnosis could aid coronavirus disease 2019 (COVID-19) pandemic management by identifying, isolating, and treating patients rapidly., (© 2022 Wiley Periodicals LLC.)

Purpose: Pineal anlage tumors (PAT) are extremely rare malignant tumors in the pediatric population considered to be a variant of pineoblastomas. These tumors are characterized by a combination of neuroectodermal and heterologous ectomesenchymal components. PAT can be clinically aggressive and has a propensity to cerebrospinal fluid (CSF) dissemination. So far, only 13 cases of these tumors have been reported in the literature., Case Article: In this article, we report the case of an anlage tumor in a 3-year-old girl with a rapidly aggressive course., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The aim of this study was to determine the effect of lipodystrophy on self-esteem and adherence to antiretroviral therapy (ART) in people living with HIV (PLHIV). A cross-sectional and comparative study was carried out in an infection clinic, with 125 patients with lipodystrophy and 125 without lipodystrophy. Sociodemographic, clinical and epidemiological data were collected, using the Rosenberg Self-Esteem Scale and Assessment of Adherence to Antiretroviral Treatment Questionnaire (CEAT-VIH). Descriptive statistics and univariate and multivariate logistic regression analysis were used. Of the total sample, 57.2% had unsatisfactory self-esteem and 57.6% adequate adherence to ART. Self-esteem was lower in PLHIV with lipodystrophy (66.4%). PLHIV with monthly income less than or equal to two minimum wages ( P < 0.001) and those with lipodystrophy had more unsatisfactory self-esteem ( P < 0.001). Catholics had better self-esteem ( P = 0.012), when compared to those without religion. Patients with monthly income less than or equal to two minimum wages ( P = 0.021) and people with unsatisfactory self-esteem had more inadequate adherence to ART ( P = 0.001). Catholics had better adherence to antiretrovirals ( P = 0.007). In conclusion, lipodystrophy and low income negatively affect the self-esteem of PLHIV. Low income and unsatisfactory self-esteem make adherence to ART difficult. Religion is a protective factor for satisfactory self-esteem and adherence to antiretrovirals.

Abstract: The aim of this study was to determine the prevalence of sleep disorders and associated factors in people living with HIV (PLWH). This was a cross-sectional study with a sample of 385 participants followed-up on an outpatient basis in Fortaleza, Ceará, Brazil. Interviews were conducted using the Sociodemographic, Epidemiological and Clinical Form for PLWH and the Pittsburgh Sleep Quality Index. Descriptive statistics and univariate and multivariate logistic regression analysis were performed, and the odds ratio (OR) and 95% confidence interval (95% CI) were calculated, considering p < .05 as statistically significant. The prevalence of sleep disorders was 43.38%. Having children ( p = .0054; OR = 1.91; 95% CI = 1.21-3.01), less than 8 years of education ( p = .0013; OR = 2.11; 95% CI = 1.34-3.34), and not engaging in regular physical exercise ( p = .0001; OR = 2.61; 95% CI = 1.61-4.23) were factors associated with the occurrence of sleep disorders. It was concluded that almost half of the sample had sleep disorders, especially those with children, low level education, and sedentary habits. These data point to the need for increased guidance on sleep hygiene, in addition to the practice of regular physical exercise for this population., (Copyright © 2022 Association of Nurses in AIDS Care.)

Introduction: Coffee has been inversely associated with Parkinson's disease (PD) in many studies, and caffeine is the leading candidate to mediate this effect. Mate ( Ilex paraguariensis , IP), a caffeinated beverage rich in antioxidants consumed in South America, was also inversely associated with PD in one study from Argentina. Other varieties of IP infusion, such as chimarrão , were never studied in PD. Chimarrão is a common caffeinated beverage consumed in Brazil made with the leaves and stems of IP. Methods: A case-control study was conducted to evaluate the relationship between chimarrão ingestion and PD in southern Brazil. All subjects answered a questionnaire about the frequency of chimarrão and coffee intake. A multiple regression analysis adjusted for age and sex was performed to assess the association between PD and chimarrão consumption. Results: We included 200 PD patients and 200 healthy controls. High consumption of chimarrão was inversely associated with PD (OR = 0.44, 95% CI = 0.24-0.81, P = 0.008). High consumption of coffee was also inversely associated with PD, as expected. Chimarrão remained associated when adjusted for coffee consumption, smoking history, and age (OR 0.46, 95% CI = 0.25-0.86, P = 0.014). These two exposures showed an additive effect. Conclusion: Chimarrão consumption was inversely associated with PD, even after adjusting for coffee intake, suggesting a possible protective role. IP's effect can be mediated by caffeine and through its antioxidant components. Chimarrão has a lower concentration of caffeine compared with coffee and has numerous substances with antioxidative effects that may be important to PD protection. Further studies are needed to test this hypothesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Medeiros, Schumacher-Schuh, Altmann and Rieder.)

Objectives: The present coronavirus disease (COVID-19) pandemic has ushered in an unprecedented era of quality control that has necessitated advanced safety precautions and the need to ensure the adequate protection of healthcare professionals (HCPs). Endoscopy units, endoscopists, and other HCP may be at a significant risk for transmission of the virus. Given the immense burden on the healthcare system and surge in the number of patients with COVID-19, well-designed protocols and recommendations are needed. We aimed to systematically characterize our approach to endoscopic procedures in a quaternary university hospital setting and provide summary protocol recommendations., Method: This descriptive study details a COVID-19-specific protocol designed to minimize infection risks to patients and healthcare workers in the endoscopy unit., Results: Our institution, located in São Paulo, Brazil, includes a 900-bed hospital, with a 200-bed-specific intensive care unit exclusively designed for patients with moderate and severe COVID-19. We highlighted recommendations for infection prevention and control during endoscopic procedures, including appropriate triage and screening, outpatient management and procedural recommendations, role and usage of personal protective equipment (PPE), and role and procedural logistics involving COVID-19-positive patients. We also detailed hospital protocols for reprocessing endoscopes and cleaning rooms and also provided recommendations to minimize severe acute respiratory syndrome coronavirus 2 transmission., Conclusion: This COVID-19-specific administrative and clinical protocol can be replicated or adapted in multiple institutions and endoscopy units worldwide. Furthermore, the recommendations and summary protocol may improve patient and HCP safety in these trying times.

Despite emerging evidence that disruption in circadian rhythms may contribute to the pathophysiology of psychiatric disorders, there is a significant knowledge gap on the rhythmicity of psychological symptoms. Here, we aimed at investigating the rhythmicity of mood symptoms in individuals at risk for psychiatric disorders. 391 Brazilian and 317 Spanish participants completed the Self-Reporting Questionnaire-20 for non-psychotic mental disorders; the Mood Rhythm Instrument was used to assess rhythmicity of mood symptoms and the Munich ChronoType Questionnaire to assess sleep patterns. We found that the rhythmicity of specific mood-related symptoms and behaviors, particularly pessimism and motivation to exercise, were associated with being at risk for psychiatric disorders, even after controlling for sleep timing, sleep deficit, and season of data collection. We also found that the peak of some mood symptoms and behaviors were different between individuals at high vs. low risk for psychiatric disorders, with specific differences between countries. These results are consistent with previous research showing that circadian misalignment is associated with higher risk for mental health conditions. These findings also suggest that lifestyle changes preventing circadian misalignment might be useful to reduce the risk of psychiatric disorders, where cultural differences must be taken into account.

Objective: To evaluate women's care during home visits for the "First Comprehensive Care Week"., Method: A cross-sectional study was carried out in a specialized service in Recife, Pernambuco, Brazil. A total of 190 women who had recently given birth enrolled at the Family Health Strategy answered the questionnaire between September and December 2013 to verify the association between home visits and the investigated variables. This association was verified using the chi-square test with a confidence level of 95%., Results: Most of the women were 29 years old or under (68.5%), with high gestational risk (59.5%), and primiparous (46.9%). On the first week after hospital discharge, 42.1% received a home visit. An association was detected between local pre-natal care and a home visit on the first week (p = 0.049). The participation of the nurses during the visits was associated with better performance for breast and abdomen examinations (p = 0.000) and investigations on emotional conditions (p = 0.029)., Conclusions: These findings stress the need to establish a routine home visit plan to solve the issues of women with high-risk pregnancies after labour.

Objective We seek to comprehensively assess stillbirths in Brazil, to compare the Brazilian findings with global trends and to identify the limitations of the fetal death record system. Method We studied fetal deaths in Brazil between 1996 and 2012 within the following five regions of the country: the North, Northeast, Southeast, South, and Central-West, through an analysis of data obtained from the Unified Health System's (SUS) Informatics Department. The rates of stillbirth in Brazil and in these regions were calculated in relation to the maternal and gestational age and education, birth weight, type of pregnancy, delivery type, weight ranges and cause of death. Results There were 579,661 recorded fetal deaths and a decrease of 22.9 % in the stillbirth rate. In 2012, the overall rate was 10.0/1000 births; the North and Northeast regions had the highest rates (10.3 and 12.1, respectively) and the South region had the lowest rate (7.7/1000 births). Two-thirds of the deaths occurred in pregnancies of 28 or more weeks. Low education was an important risk factor, with rates of 24.3/1000 birth in women with no formal education and 4.7/1000 birth in women with 12 or more years of study in 2012. More than 40 % of the causes of deaths were nonspecific. Conclusions Despite the gradual decline in stillbirth rates, Brazil still has stillbirth rates that are nearly two times higher than those found in developed countries. There are inequalities between country regions portrayed by the significant variation in mortality rates specified by cause.

This study aimed to evaluate the relationship between the cardiometabolic profile, vitamin D status and BsmI polymorphism of the VDR gene in non-institutionalized elderly subjects. A cross-sectional study was conducted with a random and representative sample of 142 elderly subjects selected by cluster and recruited from a municipal assistance program. Clinical, nutritional, biochemical and inflammatory profiles, oxidative stress and genotyping for the BsmI polymorphism were evaluated. Participants had mean age of 69.9 (7.0) years, BMI of 28.3 (4.4) kg/m(2) and 80.3% were women. The prevalence of a 25-hydroxyvitamin D [25(OH)D] status <75nmol/L was 40.8%. A vitamin D level<75nmol/L was found to be associated with gender and fish consumption. The INSUF/DEF group [25(OH)D<75nmol/L] showed higher fasting blood glucose MDA values when compared to the SUF group [25(OH)D≥75nmol/L]; this relationship was maintained only for women in the analysis by sex. The BsmI polymorphism showed allelic frequencies in the SUF group of B 49% and b 51% and in the INSUF/DEF group B 38% and b 62%. The frequency of bb homozygosity was significantly associated with lower serum total cholesterol and LDL cholesterol concentrations compared to Bb, both in the general population and in the SUF group. Among individuals with bb, the INSUF/DEF group showed higher levels of triglycerides and VLDL cholesterol. Blood glucose levels and oxidative stress were increased in elderly subjects with 25(OH)D<75nmol/L. The presence of the bb genotype with adequate vitamin D status resulted in lower total and LDL cholesterol, but the benefit was lost when vitamin D insufficiency or deficiency was present., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To describe the initial steps in the development and validation of a new self-reported instrument designed to assess daily rhythms of mood symptoms, namely, the Mood Rhythm Instrument., Methods: A multidisciplinary group of experts took part in systematic meetings to plan the construction of the instrument. Clarity of items, their relevance to evaluation of mood states, and the consistency of findings in relation to the available evidence on the biological basis of mood disorders were investigated. The internal consistency of the questionnaire was evaluated through Cronbach's alpha., Results: All of the items proposed in a first version were well rated in terms of clarity. The items more frequently rated as "rhythmic" were related to the somatic symptoms of mood. Their peaks in 24 hours were more frequent in the morning. The items associated with affective symptoms of mood were rated as less rhythmic, and their peak in 24 hours occurred more frequently in the afternoon and evening. Males and females behaved more similarly with respect to somatic than behavioral-affective items. The second version of the Mood Rhythm Instrument had a Cronbach's alpha of 0.73., Conclusion: The proposed Mood Rhythm Instrument may be able to detect individual rhythms of cognitive and behavioral measures associated with mood states. Validation in larger samples and against objective measures of rhythms, such as actigraphy, is warranted.

Parkinson's disease (PD) is characterized by progressive motor impairment attributed to progressive loss of dopaminergic neurons in the substantia nigra (SN) pars compacta. In addition to an accumulation of iron, there is also an increased production of reactive oxygen/nitrogen species (ROS/RNS) and inflammatory markers. These observations suggest that iron dyshomeostasis may be playing a key role in neurodegeneration. However, the mechanisms underlying this metal-associated oxidative stress and neuronal damage have not been fully elucidated. To determine peripheral levels of iron, ferritin, and transferrin in PD patients and its possible relation with oxidative/nitrosative parameters, whilst attempting to identify a profile of peripheral biomarkers in this neurological condition. Forty PD patients and 46 controls were recruited to compare serum levels of iron, ferritin, transferrin, oxidative stress markers (superoxide dismutase (SOD), catalase (CAT), nitrosative stress marker (NOx), thiobarbituric acid reactive substances (TBARS), non-protein thiols (NPSH), advanced oxidation protein products (AOPP), ferric reducing ability of plasma (FRAP) and vitamin C) as well as inflammatory markers (NTPDases, ecto-5'-nucleotidase, adenosine deaminase (ADA), ischemic-modified albumin (IMA) and myeloperoxidase). Iron levels were lower in PD patients, whereas there was no difference in ferritin and transferrin. Oxidative stress (TBARS and AOPP) and inflammatory markers (NTPDases, IMA, and myeloperoxidase) were significantly higher in PD, while antioxidants FRAP, vitamin C, and non-protein thiols were significantly lower in PD. The enzymes SOD, CAT, and ecto-5'-nucleotidase were not different among the groups, although NOx and ADA levels were significantly higher in the controls. Our data corroborate the idea that ROS/RNS production and neuroinflammation may dysregulate iron homeostasis and collaborate to reduce the periphery levels of this ion, contributing to alterations observed in the pathophysiology of PD.

A study on magnetoelectric phenomena in the barium titanate-barium hexaferrite (BaTiO3-BaFe12O19) composite system, using high resolution techniques including switching spectroscopy piezoresponse force microscopy (SSPFM) and spatially resolved confocal Raman microscopy (CRM), is presented. It is found that both the local piezoelectric coefficient and polarization switching parameters change on the application of an external magnetic field. The latter effect is rationalized by the influence of magnetostrictive stress on the domain dynamics. Processing of the Raman spectral data using principal component analysis (PCA) and self-modelling curve resolution (SMCR) allowed us to achieve high resolution phase distribution maps along with separation of average and localized spectral components. A significant effect of the magnetic field on the Raman spectra of the BaTiO3 phase has been revealed. The observed changes are comparable with the classical pressure dependent studies on BaTiO3, confirming the strain mediated character of the magnetoelectric coupling in the studied composites.

Levodopa is the most effective symptomatic therapy for Parkinson's disease, but its chronic use could lead to chronic adverse outcomes, such as motor fluctuations, dyskinesia and visual hallucinations. HOMER1 is a protein with pivotal function in glutamate transmission, which has been related to the pathogenesis of these complications. This study investigates whether polymorphisms in the HOMER1 gene promoter region are associated with the occurrence of the chronic complications of levodopa therapy. A total of 205 patients with idiopathic Parkinson's disease were investigated. Patients were genotyped for rs4704559, rs10942891 and rs4704560 by allelic discrimination with Taqman assays. The rs4704559 G allele was associated with a lower prevalence of dyskinesia (prevalence ratio (PR)=0.615, 95% confidence interval (CI) 0.426-0.887, P=0.009) and visual hallucinations (PR=0.515, 95% CI 0.295-0.899, P=0.020). Our data suggest that HOMER1 rs4704559 G allele has a protective role for the development of levodopa adverse effects.

Objective: To perform a critical comparison between the Brazilian national essential medicines list (Rename, 2012) with the list of essential medicines for children (LEMC, 2011) of the World Health Organization (WHO), regarding the differences among drugs and formulations listed for children., Methods: The LEMC drugs were classified into four categories: 1) absent in Rename; 2) included in Rename but without any formulation suitable for children; 3) listed in Rename only in some formulations; 4) present in Rename in all formulations. The missing formulations were analyzed by therapeutic group. Alternatives present in Rename were searched., Results: From the 261 drugs of interest on the LEMC, 30.3% are absent from Rename, 11.1% are in Rename but without any pediatric formulation, and 32.2% are present in some but not all formulations listed in LEMC. Considering all formulations items listed in the LEMC (n = 577), 349 are missing from Rename, of these 19.6% due to their strength, and 18.5% due to the the dosage form. Useful formulations specific for neonatal care, respiratory tract, central nervous system, and anti-infectives, among other groups, are missing., Conclusion: The lack of age-appropriate formulations of essential medicines for children in Brazil includes important therapeutic groups and indispensable drugs for severe clinical conditions. Some of these products exist in the Brazilian pharmaceutical market, but not in public facilities; others could be produced by national laboratories with commercial interest or stimulated by a specific governmental policy, as in other countries., (Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

Orthodontic appliances for skeletal anchorage are becoming increasingly more common in clinical practice. Similarly, different terms such as mini-implants, microimplants, and miniscrews have been used. There is a wide array of appliances currently on the market, in different designs and sizes, diameters, degree of titanium purity, and surface treatment. These appliances have been used for a variety of indications, including tooth retraction, intrusion, and traction. This study aimed to report the clinical case of a 19-year-old patient with a fractured mandible and to propose a novel use of mini-implants: the perioperative placement of mini-implants as anchors for maxillomandibular fixation steel wire ligatures. We concluded that this appliance provides an effective maxillomandibular fixation in patients with mandibular fracture, with little increase in the cost of surgery.

Polysubstance use has been posited to be a significant contributor to excess burden of HIV disease among men who have sex with men (MSM). The current study investigated polysubstance use and sexual risk among men who utilize Massachusetts Department of Public Health (MDPH) van services (such as HIV, chlamydia, gonorrhea, or syphilis testing; Hepatitis A and B vaccinations) at venues targeting MSM. Participants (n = 214) completed a one-time, cross-sectional survey via an audio computer-assisted self-interview (ACASI) in English or Spanish between June 2007 and September 2007. Fifteen percent of the overall sample did not know their HIV status; 11% reported polysubstance use (concurrent use of three or more: poppers, ecstasy, GHB, cocaine, crystal methamphetamine, Viagra) during sex in the 12 months prior to study enrollment. Polysubstance users were more likely to be HIV infected (odds ratio [OR] = 4.62; p = 0.03) and to have a history of one or more sexually transmitted diseases (STDs; OR = 4.74; p = 0.03) relative to participants who did not report polysubstance use during sex. After controlling for covariates of age, race/ethnicity, education level, insurance status, sexual orientation, STD history, HIV status, and depression, multivariable logistic regression analyses revealed that polysubstance users were 9 times more likely to have reported unprotected anal (insertive or receptive) sex in the 12 months prior to study enrollment (adjusted OR = 9.53; p = 0.007) compared to nonpolysubstance-using MSM. Polysubstance users lacked access to care (21% were uninsured) and the overwhelming majority (96%) were first time users of mobile health van services. Accessible outreach services for MSM such as mobile van services need to include drug screening and interventions that triage men into treatment programs; year-round availability of van services is warranted.

Highly-potent antiretroviral therapy is necessary to avoid viral replication in HIV patients; however, it can favor the appearance of resistance mutations. The mutations 41L, 67N, 70R, 210W, 215Y/F, 219E/Q, 44D and 118I are defined as nucleoside analogous mutations (NAMs), because they affect the efficacy of all nucleoside reverse transcriptase inhibitors (NRTI). The mutation most frequently associated with non-nucleoside reverse transcriptase inhibitors (NNRTIs) is 103N. 33W/F, 82A/F/L/T, 84V and 90M are called protease inhibitor resistance-associated mutations (PRAM), because they are associated with resistance to several protease inhibitors (PI). This study evaluated the development of resistance mutations and examine the susceptibility of HIV with these mutations to antiretrovirals in HIV-1 patients who have failed one or more therapy regimes. Analyses were made of 101 genotypic tests of patients with therapeutic failure to 2 or 3-drug regimens with NRTI, NNRTI or PI. We used the Stanford database to define the susceptibility profile of the viruses. The samples were divided into three treatment-failure groups: first (F), second (S) and multi-failure (MF) to antiretroviral regimens, and we correlated these groups with resistance profiles and principal mutations. There was a significant increase in resistance mutations V82A/F/L/T, I84V, L90M, M41L, K70R, L210W, T215Y/F and K219Q/E in MF. We also found significantly higher resistance to zidovudine, didanosine, stavudine and abacavir in MF. There was no increase in resistance to tenofovir (p=0.28) and lopinavir (p=0.079) in MF. A high degree of resistance to NNRTIs was observed in all groups. Increased resistance mutations will affect future therapeutic options for HIV patients in Brazil because it results in a significant increase in resistance to antiretroviral drugs.

Genotype testing for HIV-1 drug resistance is useful for selecting antiretroviral drug regimens for patients experiencing therapeutic failure, but the optimal means for interpreting the test results is unknown because many HIV-1 protease and reverse transcriptase (RT) mutations contribute to drug resistance. This study identified common combinations of resistance mutations related to antiretroviral resistance profiles. From April 2002 to March 2004, 101 protease and RT sequences were determined for HIV-1 isolates from patients who were failing antiretroviral therapy. The resistance profile was evaluated using the Stanford Database program. Male patients predominated (76.2%), the median age was 38 years, the average CD4 count was 279.21 cells/mm(3) and the average viral load was 4.49 log. In relation to protease inhibitors (IP) 31 mutation patterns were detected, 49 mutation patterns were detected in Nucleoside RT Inhibitors (NRTI), and 17 patterns were found in the Non Nucleoside RT Inhibitors (NNRTI). K65R was detected in 5.9% of the isolates. The most frequent mutations were: L90M, M184V and K103N related to PI's, NRTI's and NNRTI's, respectively. The best antiretroviral susceptibility was found to be Lopinavir in the PI class and Tenofovir in the NRTI class. The top six mutation patterns accounted for 49% of the resistance to PI's, for 38.5% of NRTI resistance, and the top two mutation patterns accounted for 40.9% of resistance to NNRTI's.

Primary Objective: To assess factors that may influence functional gain of patients with chronic sequelae of stroke., Research Design: Prospective study of 290 stroke patients consecutively admitted to a rehabilitation setting., Methods and Procedures: Functional Independence Measure Scale (FIM) was used to assess functional capacity. Functional improvement registered during hospitalization (FIM-gain score) was compared to demographic data, stroke sub-type, vascular risk factors, motor deficit, visual hemineglect, aphasia, level of response and sphincter control. FIM-gain score was classified as high-gain (=22) and low-gain (<22)., Main Outcomes and Results: Two hundred and fifty-two patients who had no prior rehabilitation and were capable of completing the rehabilitation programme were studied (average age 58.4+/-13.9 years; 42.9% women). The mean time from stroke onset to admission was 271.5 days. Average FIM score at admission was 58.8 and at discharge was 81.6. Average FIM Gain was 23.6. The 38% patients admitted later than 6 months after stroke had an average FIM Gain of 19 vs 26 for patients admitted prior to 6 months. Significant predictors of functional improvement were time from stroke onset, age, sitting balance and level of responsiveness., Conclusion: The functional improvement scores in persons with stroke beginning a rehabilitation programme at a later stage are 73% of the scores obtained by patients beginning treatment in the first 6 months. FIM score improvement can be predicted by time since stroke onset, age, sitting balance and level of responsiveness.

Post-secretory metabolism is an important event in the overall homeostasis of regulatory peptides and the enzymes involved in these processes may be suitable targets for pharmacological intervention. Some examples are reviewed here. Peptide YY and neuropeptide Y, both members of the pancreatic polypeptide family, can be processed by dipeptidyl peptidase IV to their (3-36) fragments by removal of the N-terminal Tyr-Pro dipeptide, which generates a metabolite of different receptor selectivity. Aminopeptidase P and endopeptidase-24.11 also metabolize these peptides and the relative levels of these three cell-surface enzymes may regulate their interconversion between receptor-selective forms and inactive metabolites.

The thiol activated endo-oligopeptidases A and B were studied in the soluble fraction of human hypothalamus and various endocrine glands. For the identification, characterization and purification of the enzymes, Z-Gly-Pro-NH-Np and bradykinin were used as substrates. Endo-oligopeptidase B showed a molecular mass ranging from 55.5 to 65.5 kDa and isoelectric point from 4.7 to 4.95. Its activity in tissues was highest in the testis, with intermediate levels in the thyroid, neurohypophysis, adenohypophysis and hypothalamus and the lowest activity in the pineal gland. Endo-oligopeptidase A, 467-fold purified by immunoaffinity chromatography, exhibited a molecular mass of 65.5 kDa in the adenohypophysis but 58.5 kDa in other tissues. The isoelectric point ranged from 5.22 to 5.50. High endo-oligopeptidase A activity was observed in the adenohypophysis, testis and hypothalamus with lesser activity in the neurohypophysis and thyroid and the lowest in the pineal gland. Endo-oligopeptidase A cleaved the bonds Phe-Ser of bradykinin, Met-Arg of BAM-12P and Arg-Arg of neurotensin as described for rabbit brain and heart and bovine brain enzymes. This work shows that endo-oligopeptidase A also hydrolysed the bonds Tyr-Gly of LH-releasing hormone, Pro-Phe of angiotensin I and Tyr-Ile of angiotensin II.

Rat alpha- and alpha-CGRP are substrates for endopeptidase 24.11 in vitro. Cleavage of both peptides occurs at several points, including an unusual substrate recognition site to the amino side of ala36. In alpha-CGRP this resulted in the early formation of val32-gly-ser-glu35, a sequence previously reported to be a component of the eosinophil chemotactic factor of anaphylaxis (ECF-A). The biological activity of this peptide fragment was confirmed by bioassay. Chemotactic activity in other hydrolysis fragments of both alpha- and beta-CGRP was observed. Both alpha- and beta-CGRP could thus serve as precursors to different eosinophil chemotactic peptide fragments. A novel function of endopeptidase 24.11 may be to modify rather than to terminate the biological activity of CGRP peptides.

The sequence of rat alpha-calcitonin gene-related peptide (CGRP-alpha) contains the tetrapeptide eosinophil granulocyte chemotactic factor Val32-Gly-Ser-Glu35. Peptide fragments formed following hydrolysis of rat CGRP-alpha in vitro by endopeptidase-24.11 were identified. The tetrapeptide fragment was generated following cleavage at a substrate recognition site unusual for this enzyme (-Glu-Ala-). Chemotactic activity of rat CGRP-alpha was increased following hydrolysis. Furthermore, rat CGRP-beta, which lacks the tetrapeptide sequence and is completely devoid of chemotactic activity, displayed low but measurable activity after hydrolysis. Val-Gly-Ser-Glu was identified as the principle fragment with chemotactic activity in rat CGRP-alpha. The results show that the chemotactic activity of the neuropeptide rat CGRP-alpha towards eosinophil polymorphonuclear leukocytes is increased following its hydrolysis in vitro by endopeptidase 24.11 through the formation of a previously identified eosinophil chemotactic tetrapeptide.