Viral Load Predicts New World Health Organization Stage 3 and 4 Events in HIV-Infected Children Receiving Highly Active Antiretroviral Therapy, Independent of CD4 T Lymphocyte Value

Background. Many resource-limited countries rely on clinical and immunological monitoring without routine virological monitoring for human immunodeficiency virus (HIV)-infected children receiving highly active antiretroviral therapy (HAART). We assessed whether HIV load had independent predictive value in the presence of immunological and clinical data for the occurrence of new World Health Organization (WHO) stage 3 or 4 events (hereafter, WHO events) among HIV-infected children receiving HAART in Latin America. Methods. The NISDI (Eunice Kennedy Shriver National Institute of Child Health and Human Development International Site Development Initiative) Pediatric Protocol is an observational cohort study designed to describe HIV-related outcomes among infected children. Eligibility criteria for this analysis included perinatal infection, age ! 15 years, and continuous HAART for >= 6 months. Cox proportional hazards modeling was used to assess time to new WHO events as a function of immunological status, viral load, hemoglobin level, and potential confounding variables; laboratory tests repeated during the study were treated as time-varying predictors. Results. The mean duration of follow-up was 2.5 years; new WHO events occurred in 92 (15.8%) of 584 children. In proportional hazards modeling, most recent viral load 15000 copies/mL was associated with a nearly doubled risk of developing a WHO event (adjusted hazard ratio, 1.81; 95% confidence interval, 1.05-3.11; P = 033), even after adjustment for immunological status defined on the basis of CD4 T lymphocyte value, hemoglobin level, age, and body mass index. Conclusions. Routine virological monitoring using the WHO virological failure threshold of 5000 copies/mL adds independent predictive value to immunological and clinical assessments for identification of children receiving HAART who are at risk for significant HIV-related illness. To provide optimal care, periodic virological monitoring should be considered for all settings that provide HAART to children.

Osteoprotegerin/RANKL system imbalance in active polyarticularonset juvenile idiopathic arthritis: a bone damage biomarker?

Objective: To evaluate the importance of receptor activator of nuclear factor kappa B (RANK)/receptor activator of nuclear factor kappa B ligand (RANKL)/osteoprotegerin (OPG) modulation in active polyarticular juvenile idiopathic arthritis (pJIA) patients with and without bone erosions. Methods: Thirty female patients (mean age 11.07 +/- 3.77 years, range 4-17 years) with active pJIA and 30 healthy gender-and age-matched controls were consecutively selected for this study. All involved articulations were assessed by X-ray and examined for the presence of bone erosions. The serum levels of RANKL and OPG were measured using an enzyme-linked immunosorbent assay (ELISA). Results: Patients with active pJIA had higher levels of serum RANKL than controls [2.90 (0.1-37.4) vs. 0.25 (0.1-5.7) pg/mL, p=0.007] and a lower OPG/RANKL ratio [21.25 (1.8-897.6) vs. 347.5 (9-947.8), p=0.005]. However, levels of OPG were comparable in both groups [55.24 (28.34-89.76) vs. 64.42 (30.68-111.28) pg/mL, p=0.255]. Higher levels of serum RANKL and a lower OPG/RANKL ratio were also observed in active pJIA patients with bone erosions compared to controls [3.49 (0.1-37.4) vs. 0.25 (0.1-5.7) pg/mL, p=0.0115 and 14.3 (1.8-897.6) vs. 347.5 (9-947.8), p=0.016]. However, RANKL levels and OPG/RANKL ratio were similar in pJIA patients without bone erosion and controls [1.75 (0.1-10.9) vs. 0.25 (0.1-5.7) pg/mL, p=0.055 and 29.2 (3.3-756.8) vs. 347.5 (9-947.8), p=0.281]. Conclusion: These data suggest that active pJIA with bone erosions is associated with high serum levels of RANKL and a low OPG/RANKL ratio, indicating that these alterations may reflect bone damage in this disease.

Active tuberculosis and Mycobacterium tuberculosis latent infection in patients with HIV/AIDS

Objectives Tuberculosis (TB) remains an important disease associated with HIV infection and AIDS in Brazil, even in a setting of free access to antiretroviral therapy (ART) and TB treatment. In previous studies, isoniazid therapy (IT) for latent infection with Mycobacterium tuberculosis (LIMTb) was found to reduce the risk of TB by 62% in patients with a tuberculin test (TT)> 5 mm. The objectives of this study were to investigate the occurrence of TB, the prevalence of LIMTb and the coverage of the TT and IT, and to estimate the number of missed opportunities to prevent TB in patients with HIV/AIDS. Methods A random sample of patients with HIV/AIDS was selected; data from the medical files were obtained, and a TT was performed in consenting subjects. Results In the 203 subjects included in the study, TB occurrence was 13.3%, LIMTb prevalence was 20% and the coverage of the TT and IT was 59.2 and 55%, respectively. Patients with TB had a lower nadir CD4 cell count, but their CD4 recovery was comparable to that of non-TB patients. Patients with LIMTb always had a higher CD4 cell count. Conclusions By expanding the coverage of the TT and IT to nearly 100%, we could more than double the number of prevented cases of TB. TB prevention programmes must be reinforced to reduce the number of missed opportunities for diagnosis, and IT must be improved to reduce TB among patients with HIV/AIDS. Empowering patients with knowledge about TB, the preventive role of IT and the need for an annual TT may be the best way of lowing rates of TB in patients with HIV/AIDS.

Effect of low-dose combined oral contraceptive on aerobic capacity and anaerobic threshold level in active and sedentary young women

Background: The purpose of this study was to evaluate the effect of long-term use of oral contraceptives (DC) containing 0.20 mg of ethinylestradiol (EE) combined with 0.15 mg of gestodene (GEST) on the peak aerobic capacity and at the anaerobic threshold (AT) level in active and sedentary young women. Study Design: Eighty-eight women (23 +/- 2.1 years old) were divided into four groups active-OC (G1), active-NOC (G2), sedentary-OC (G3) and sedentary-NOC (G4) and were submitted to a continuous ergospirometric incremental test on a cycloergometer with 20 to 25 W min(-1) increments. Data were analyzed by two-way ANOVA with Tukey post hoc test. Level of significance was set at 5%. Results: The OC use effect for the variables relative and absolute oxygen uptake VO(2) mL kg(-1) min(-1); VO(2), L min(-1), respectively), carbon dioxide output (VCO(2), L min(-1)), ventilation (VE, L min(-1)), heart rate (HR, bpm), respiratory exchange ratio (RER) and power output (W) data, as well as the interaction between OC use and exercise effect on the peak of test and at the AT level did not differ significantly between the active groups (G1 and G2) and the sedentary groups (G3 and G4). As to the exercise effect, for all variables studied, it was noted that the active groups presented higher values for the variables VO(2), VCO(2), VE and power output (p<.05) than the sedentary groups. The RER and HR were similar (p>.05) at the peak and at the AT level between G1 vs. G3 and G2 vs. G4. Conclusions: Long-term use of OC containing EE 0.20 mg plus GEST 0.15 mg does not affect aerobic capacity at the peak and at the AT level of exercise tests. (C) 2010 Elsevier Inc. All rights reserved.

Prevalence of trachoma in a population of the upper Rio Negro Basin and risk factors for active disease

Purpose: To determine the prevalence of trachoma in Sao Gabriel da Cachoeira (SGC), the only urban community of the upper Rio Negro Basin of the Amazon state in Brazil, near the Colombian border, and to investigate the risk factors associated with the active forms of the disease. Methods: A total of 1702 people (440 children up to 9 years and 1069 adults aged 15 years and above) were examined. The sample was selected from a probabilistic household sampling procedure based on census data and a previous study of trachoma prevalence in Sao Gabriel da Cachoeira. A two-stage probabilistic household cluster sample was drawn. Household units were randomly selected within each cluster. A variety of socioeconomic and hygiene variables were studied in order to determine the risk factors for active trachoma in a household. Results: The total prevalence of trachoma was 8.9%. Prevalence of active trachoma (TF and/or TI) in children aged 1-9 years was 11.1% and trachomatous trichiasis in adults aged 15 years and above was 0.19%. Trachomatous scarring reached a peak of 22.4% for subjects between 50 to 60 years of age. Corneal opacity occurred in subjects aged 50 years and older with a prevalence of 2.0%. No sex effect was found on the overall prevalence of trachoma in SGC. Risk factors associated with active trachoma were mainly related to poor socioeconomic indicators. Conclusions: Despite the ubiquitous presence of water, the analysis of the risk factors associated with the active forms of the disease supports the idea that a low personal standard of hygiene and not water availability per se, is the key factor associated with trachoma.

Oral lesions and immune reconstitution syndrome in HIV+/AIDS patients receiving highly active antiretroviral therapy. Epidemiological evidence

Objective: To determine whether opportunistic oral infections associated to HIV infection (OOI-HIV) are found in HIV+/AIDS patients with immune reconstitution related to highly active antiretroviral therapy (HAART). Methods. From among 1100 HIV+/AIDS patients (Service of Internal Medicine, Carlos Haya Hospital, Malaga, Spain) subjected to review of the oral cavity between January 1996 and May 2007, we identified those examined in 1996 and which were again examined between 1997 and 2007, and were moreover receiving HAART. The following data were collected: age, gender, form of contagion, antiretroviral therapy at the time of review, number of CD4+ lymphocytes/ml, and viral load (from 1997 onwards). We identified those subjects with an increase in CD4+ lymphocytes/ ml associated to HAART, and classified them as subjects with quantitative evidence of immune reconstitution (QEIR). Among these individuals with QEIR we moreover identified those with undetectable viral loads (QEIR+VL), and differentiated those patients with an increase in CD4+ lymphocytes > 500/ml (QEIRm+VL). In each group we determined the prevalence of OOI-HIV, following the diagnostic recommendations of the EC-Clearinghouse (CDC-Atlanta, USA - WHO). In addition, we analyzed the prevalence of OOI-HIV in the different groups in relation to the duration of HAART. Results. A total of 86 subjects were included (44 females and 42 males; 19 heterosexuals, 34 male homosexuals, and 33 intravenous drug abusers). Forty-two patients showed QEIR: 21 belonged to the QEIR+VL group, and 17 conformed the QEIRm+VL group. The prevalence of OOI-HIV per group was as follows: QEIR = 54.8%; QEIR+VL = 33%; QEIRm+VL = 35%. The most prevalent lesion in all groups was erythematous candidiasis. OOI-HIV increased with the duration of HAART (p=0.008), and were seen to be dependent upon late appearance of the mycotic lesions ( after 24 months under HAART). Conclusions: It is suggested that opportunistic oral infections associated to HIV infection form part of the clinical picture of immune reconstitution inflammatory syndrome, though such infections are of late onset.

Unprecedented oxidation of a biologically active aroylhydrazone chelator catalysed by iron(III): serendipitous identification of diacylhydrazine ligands with high iron chelation efficacy

Ligands of the 2-pyridylcarbaldehyde isonicotinoylhydrazone class show high iron (Fe) sequestering efficacy and have potential as agents for the treatment of Fe overload disease. We have investigated the mechanisms responsible for their high activity. X-ray crystallography studies show that the tridentate chelate 2-pyridylcarbaldehyde isonicotinoylhydrazone undergoes an unexpected oxidation to isonicotinoyl(picolinoyl)hydrazine when complexed with Fe-III. In contrast, in the absence of Fel the parent hydrazone is not oxidized in aerobic aqueous solution. To examine whether the diacylhydrazine could be responsible for the biological effects of 2-pyridylcarbaldehyde isonicotinoylhydrazone, their Fe chelation efficacy was compared. In contrast to its parent hydrazone, the diacylhydrazine showed little Fe chelation activity. Potentiometric titrations suggested that this might be because the diacylhydrazine was charged at physiological pH, hindering its access across membranes to intracellular Fe pools. In contrast, the Fe complex of this diacylhydrazine was charge neutral, which may allow facile movement through membranes. These data allow a model of Fe chelation for this compound to be proposed: the parent aroylhydrazone diffuses through cell membranes to bind Fe and is subsequently oxidized to the diacylhydrazine complex which then diffuses from the cell. Other diacylhydrazine analogues that were charge neutral at physiological pH demonstrated high Fe chelation efficacy. Thus, for this class of ligands, the charge of the chelator appears to be an important factor for determining their ability to access intracellular Fe. The results of this study are significant for understanding the biological activity of 2-pyridylcarbaldehyde isonicotinoylhydrazone and for the design of novel diacylhydrazine chelators for clinical use.

Perceived constraints and social support for active leisure among mothers with young children

Evidence suggests that women who are mothers of young children have lower levels of physical activity than women of similar age who do not have children (Brown, Lee, Mishra, & Bauman, 2000). The purposes of this study were to explore the factors that constrain mothers of young children from being more physically active, and the relationship between physical activity and levels of social support available to the women. The empirical basis for this examination was provided through a study of activity levels and barriers to physical activity experienced by a sample of 543 mothers of young children from differing socioeconomic backgrounds. The data indicate that: (a) more than two-thirds of the mothers were inadequately active in their leisure time for health benefit; (b) while the vast majority of mothers expressed a desire to be more active, they were inhibited in their ability to act out their leisure preferences by a combination of structural (e.g., lack of time, money, energy) and ideological influences (e.g., sense of commitment to others); (c) access to social support (from partners, family, and friends) was seen to place some women in a better position than others to negotiate constraints that inhibit leisure participation; and (d) within groups of varying socioeconomic status (SES) there was wide variation in the amount of time spent each week in active leisure.

Deep and superficial fibers of the lumbar multifidus muscle are differentially active during voluntary arm movements

AB Study Design. A cross-sectional study was conducted. Objective. To determine the activity of the deep and superficial fibers of the lumbar multifidus during voluntary movement of the arm. Summary of Background Data. The multifidus contributes to stability of the lumbar spine. Because the deep and superficial parts of the multifidus are near the center of lumbar joint rotation, the superficial fibers are well suited to control spine orientation, and the deep fibers to control intervertebral movement. However, there currently are limited in vivo data to support this distinction. Methods. Electromyographic activity was recorded in both the deep and superficial multifidus, transversus abdominis, erector spinae, and deltoid using selective intramuscular electrodes and surface electrodes during single and repetitive arm movements. The latency of electromyographic onset in each muscle during single movements and the pattern of electromyographic activity during repetitive movements were compared between muscles. Results. With single arm movements, the onset of electromyography in the erector spinae and superficial multifidus relative to the deltoid was dependent on the direction of movement, but the onset in the deep multifidus and transversus abdominis was not. With repetitive arm movements, peaks in superficial multifidus and erector spinae electromyography occurred only during flexion for most subjects, whereas peaks in deep multifidus electromyography occurred during movement in both directions. Conclusions. The deep and superficial fibers of the multifidus are differentially active during single and repetitive movements of the arm. The data from this study support the hypothesis that the superficial multifidus contributes to the control of spine orientation, and that the deep multifidus has a role in controlling intersegmental motion. (C) 2002 Lippincott Williams & Wilkins, Inc.

Active and passive shoulder range of motion in healthy older people

This study was conducted to determine the effect of increasing age on four shoulder movements and to explore the need for normative data for shoulder range of motion (ROM) in people aged 50 years and older. Forty-one participants were conveniently recruited according to four age categories: 50-59 years, 60-69 years, 70-79 years and 80 years and over. Goniometric measurement of bilateral active and passive ROM for flexion, abduction, internal rotation and external rotation was analysed using paired sample t-tests and compared with the norms of the American Academy of Orthopaedic Surgeons (AAOS) using one sample t-tests. Passive ROM was greater than active ROM for all movements (p

Systematic characterization of mutations in yeast acetohydroxyacid synthase: Interpretation of herbicide-resistance data

Acetohydroxyacid synthase (AHAS, EC 4.1.3.18) catalyses the first step in branched-chain amino acid biosynthesis and is the target for sulfonylurea and imidazolinone herbicides, which act as potent and specific inhibitors. Mutants of the enzyme have been identified that are resistant to particular herbicides. However, the selectivity of these mutants towards various sulfonylureas and imidazolinones has not been determined systematically. Now that the structure of the yeast enzyme is known, both in the absence and presence of a bound herbicide, a detailed understanding of the molecular interactions between the enzyme and its inhibitors becomes possible. Here we construct 10 active mutants of yeast AHAS, purify the enzymes and determine their sensitivity to six sulfonylureas and three imidazolinones. An additional three active mutants were constructed with a view to increasing imidazolinone sensitivity. These three variants were purified and tested for their sensitivity to the imidazolinones only. Substantial differences are observed in the sensitivity of the 13 mutants to the various inhibitors and these differences are interpreted in terms of the structure of the herbicide-binding site on the enzyme.

Active and passive behaviors of soft tissues: Pelvic floor muscles

: A new active-contraction visco-elastic numerical model of the pelvic floor (skeletal) muscle is presented. Our model includes all elements that represent the muscle constitutive behavior, contraction and relaxation. In contrast with the previous models, the activation function can be null. The complete equations are shown and exactly linearized. Small verification and validation tests are performed and the pelvis is modeled using the data from the intra-abdominal pressure tests

Mantle source heterogeneity, magma generation and magmatic evolution at Terceira Island (Azoresarchipelago): Constraints from elemental and isotopic (Sr, Nd, Hf, and Pb) data

This work addresses the present-day (<100 ka) mantle heterogeneity in the Azores region through the study of two active volcanic systems from Terceira Island. Our study shows that mantle heterogeneities are detectable even when "coeval" volcanic systems (Santa Barbara and Fissural) erupted less than 10 km away. These volcanic systems, respectively, reflect the influence of the Terceira and D. Joao de Castro Bank end-members defined by Beier et at (2008) for the Terceira Rift Santa Barbara magmas are interpreted to be the result of mixing between a HIMU-type component, carried to the upper mantle by the Azores plume, and the regional depleted MORB magmas/source. Fissural lavas are characterized by higher Ba/Nb and Nb/U ratios and less radiogenic Pb-206/Pb-204, Nd-143/Nd-144 and Hf-176/Hf-177, requiring the small contribution of delaminated sub-continental lithospheric mantle residing in the upper mantle. Published noble gas data on lavas from both volcanic systems also indicate the presence of a relatively undegassed component, which is interpreted as inherited from a lower mantle reservoir sampled by the ascending Azores plume. As inferred from trace and major elements, melting began in the garnet stability field, while magma extraction occurred within the spinel zone. The intra-volcanic system's chemical heterogeneity is mainly explained by variable proportions of the above-mentioned local end-members and by crystal fractionation processes. (C) 2011 Elsevier By. All rights reserved.

Clinical and functional aspects of work-related musculoskeletal disorders among active workers

OBJECTIVE: To evaluate musculoskeletal disorders among active industrial workers. METHODS: The study was carried out in São Carlos, Southeastern Brazil, in 2005. One hundred and thirty-four female workers were physically evaluated and answered questions about their physical symptoms, filled out a pain scale and gave responses in the Oswestry Disability Questionnaire, and the Work Ability Index questionnaire. The data were analyzed descriptively, and in correlation tests and through applying logistic regression. The outcome was evaluated in relation to the perceptions of pain, symptoms, physical assessment, ability to work and disability. RESULTS: Clinical evaluations and sick leave presented positive correlations with the subjective variables. The Work Ability Index presented a negative correlation with the physical disability index (r=-0.69). Symptoms reported at the time of the assessment presented a good correlation with the results from the pain scale and the clinical findings. Previous sick leave showed an association with disability (OR=1.13; 95% CI:1.08;1.18). CONCLUSION: Symptom reports and pain scales may be useful for assessing current conditions at the time of evaluating individuals with work-related musculoskeletal disorders, as they are easier to apply. In more severe cases of such injuries, clinical and functional evaluations and questionnaires such as those relating to ability to work and disability are preferable. Precise and specific evaluations of these disorders may contribute towards fairer legal and administrative decisions.

Determining the number of clusters in categorical data

Cluster analysis for categorical data has been an active area of research. A well-known problem in this area is the determination of the number of clusters, which is unknown and must be inferred from the data. In order to estimate the number of clusters, one often resorts to information criteria, such as BIC (Bayesian information criterion), MML (minimum message length, proposed by Wallace and Boulton, 1968), and ICL (integrated classification likelihood). In this work, we adopt the approach developed by Figueiredo and Jain (2002) for clustering continuous data. They use an MML criterion to select the number of clusters and a variant of the EM algorithm to estimate the model parameters. This EM variant seamlessly integrates model estimation and selection in a single algorithm. For clustering categorical data, we assume a finite mixture of multinomial distributions and implement a new EM algorithm, following a previous version (Silvestre et al., 2008). Results obtained with synthetic datasets are encouraging. The main advantage of the proposed approach, when compared to the above referred criteria, is the speed of execution, which is especially relevant when dealing with large data sets.