Adjunctive Dexamethasone for Tuberculous Meningitis in HIV-Positive Adults.

BACKGROUND: Adjunctive glucocorticoids are widely used to treat human immunodeficiency virus (HIV)-associated tuberculous meningitis despite limited data supporting their safety and efficacy. METHODS: We conducted a double-blind, randomized, placebo-controlled trial involving HIV-positive adults (≥18 years of age) with tuberculous meningitis in Vietnam and Indonesia. Participants were randomly assigned to receive a 6-to-8-week tapering course of either dexamethasone or placebo in addition to 12 months of antituberculosis chemotherapy. The primary end point was death from any cause during the 12 months after randomization. RESULTS: A total of 520 adults were randomly assigned to receive either dexamethasone (263 participants) or placebo (257 participants). The median age was 36 years; 255 of 520 participants (49.0%) had never received antiretroviral therapy, and 251 of 484 participants (51.9%) with available data had a baseline CD4 count of 50 cells per cubic millimeter or less. Six participants withdrew from the trial, and five were lost to follow-up. During the 12 months of follow-up, death occurred in 116 of 263 participants (44.1%) in the dexamethasone group and in 126 of 257 participants (49.0%) in the placebo group (hazard ratio, 0.85; 95% confidence interval, 0.66 to 1.10; P = 0.22). Prespecified analyses did not reveal a subgroup that clearly benefited from dexamethasone. The incidence of secondary end-point events, including cases of immune reconstitution inflammatory syndrome during the first 6 months, was similar in the two trial groups. The numbers of participants with at least one serious adverse event were similar in the dexamethasone group (192 of 263 participants [73.0%]) and the placebo group (194 of 257 participants [75.5%]) (P = 0.52). CONCLUSIONS: Among HIV-positive adults with tuberculous meningitis, adjunctive dexamethasone, as compared with placebo, did not confer a benefit with respect to survival or any secondary end point. (Funded by the Wellcome Trust; ACT HIV ClinicalTrials.gov number, NCT03092817.).

Adjustment of optical absorption in phosphorene through electron-phonon coupling and an electric field.

This study investigates the optical absorption of monolayer phosphorene, focusing on its response to the electron-phonon coupling (EPC) and an electric field. Using a tight-binding Hamiltonian model based on the Barisic-Labbe-Friedel-Su-Schrieffer-Heeger model and the Kubo formula, we calculate the electronic band structure and optical absorption characteristics. The anisotropic dispersion of carriers along armchair and zigzag directions leads to distinct optical responses. Positive and negative EPC effects increase and decrease hopping parameters, respectively, enlarging and reducing/closing the band gap. Moreover, both EPCs cause an admixture of blue and red shift spectrum along the armchair direction, while a red (blue) shift spectrum is observed for positive (negative) EPC along the zigzag direction. Incorporating electric field effects in the EPC increases band gaps for both positive and negative EPC activities, resulting in shifted optical peaks along both directions.

Characterization and Investigation of Risk Factors for Late-Relapsing Hepatitis After Yellow Fever.

BACKGROUND: Late-relapsing hepatitis after yellow fever (LHep-YF) during the convalescent phase of the disease has been described during recent yellow fever (YF) outbreaks in Brazil. LHep-YF is marked by a rebound in liver enzymes and nonspecific clinical manifestations around 46-60 days after YF symptom onset. METHODS: Here we have characterized the clinical course and risk factors for LHep-YF using data from a representative cohort of patients who survived YF in Brazil, 2017-2018. A total of 221 YF-positive patients were discharged from the infectious disease reference hospital in Minas Gerais and were followed up at 30, 45, and 60 days post-symptom onset. RESULTS: From 46 to 60 days post-symptom onset, 16% of YF patients (n = 36/221) exhibited a rebound of aminotransferases (aspartate aminotransferase or alanine aminotransferase >500 IU/L), alkaline phosphatase, and total bilirubin levels. Other etiologies of liver inflammation such as infectious hepatitis, autoimmune hepatitis, and metabolic liver disease were ruled out. Jaundice, fatigue, headache, and low platelet levels were associated with LHep-YF. Demographic factors, clinical manifestations, laboratory tests, ultrasound findings, and viral load during the acute phase of YF were not associated with the occurrence of LHep-YF. CONCLUSIONS: These findings provide new data on the clinical course of Late-relapsing hepatitis during the convalescent phase of YF and highlight the need for extended patient follow-up after acute YF.

Mercury in multimedia system of Itacaiúnas Basin, Brazilian Amazon: An integrated approach to understand its distribution, origin, and ecological risk.

This study presents the first integrated study on total Hg (THg) level in surface soil (SS), bottom soil (BS), stream sediments (SD), lake sediments (LS), stream water (SW), and lake water (LW) of Itacaiúnas River Watershed (IRW), Brazil to investigate the source and distribution of Hg in different environmental media considering contrasts of geological domains and sub-basins and its potential ecological and human risk. Hg content in most of the soils and sediments were above the upper crustal average values (56 µg/kg), however, when compared to the legal limits set by the Resolution CONAMA (Conselho Nacional de Meio Ambiente: soil 500 µg/kg; sediment 486 µg/kg), only 1 soil sample from Parauapebas sub-basin and 4 sediment samples from Violão Lake exceeded the limit. None of the SW and LW samples (<0.2 µg/L; CONAMA limit for Class II freshwater) are markedly contaminated by Hg. The SS and BS show similar contents and spatial distribution of Hg with higher contents being registered mostly in the Itacaiúnas and Parauapebas sub-basins, which are closely correlated with SD. This suggests that Hg levels are largely of geogenic origin and anthropogenic effect is highly limited. Principal Component Analysis (PCA) results show that Hg is strongly associated with total organic carbon (TOC), loss on ignition (LOI), and SO3, indicating organic matter as the main factor controlling the distribution of Hg and this is the major cause of accentuated Hg enrichment in lake sediments. The ecological risk index revealed a low pollution risk for most of the solid samples, except 11% LS and <1.5% SS and SD samples, which registered moderate risk. Health risk assessment indicated no adverse non-carcinogenic health effect on either adults and children in terms of Hg contamination. This information will be useful for Hg risk assessment in the Carajás region and future environmental research in this direction in the Amazonia.

Docking and Electronic Structure of Rutin, Myricetin, and Baicalein Targeting 3CLpro.

Understanding the role of 3CLpro protease for SARS-CoV-2 replication and knowing the potential of flavonoid molecules like rutin, myricetin, and baicalein against 3CLpro justify an investigation into their inhibition. This study investigates possible bonds and reactivity descriptors of rutin, myricetin, and baicalein through conformational and electronic properties. Density functional theory was used to determine possible interactions. Analyses were carried out through the molecular electrostatic potential, electron localization function, Fukui function descriptors based on frontier orbitals, and non-covalent interactions. A docking study was performed using a resolution of 1.55 Å for 3CLpro to analyze the interactions of rutin, myricetin, and baicalein. Scores of structures showed that rutin is the best ligand, followed by myricetin and baicalein. Docking studies showed that baicalein and rutin can establish effective interactions with residues of the catalytic dyad (Cys145 and His41), but just rutin forms a hydrogen bond. Myricetin, in turn, could not establish an effective interaction with Cys145. Baicalein interaction arose with active residues such as Arg188, Val186, Gln189, and Gln192. Interactions of rutin and myricetin with Arg188 and Gln189 were also found. A critical interaction was observed only for rutin with the hydroxyls of ring A with His41, and also for Cys145 with rings B and C, which is probably related to the highest score of rutin.

Bedtime smart device usage and accelerometer-measured sleep outcomes in children and adolescents.

PURPOSE: We analyzed the association between bedtime smart device usage habits and accelerometer-measured sleep outcomes (total sleeping time, sleep efficiency, and wake after sleep onset) in Hong Kong children and adolescents aged 8-14. METHODS: A total of 467 students in Hong Kong participated in this study from 2016 to 2017. They self-reported their bedtime smart device usage habits. The primary caregiver of each participant was also invited to complete a self-administered questionnaire about the family's social-economic status and bedtime smart device usage habits. An ActiGraph GT3X accelerometer was used to assess participants' 7-day sleep outcomes. RESULTS: The mean age of the participants was 10.3 (SD 1.9), and 54% were girls. Among the participants, 27% (n = 139) used a smart device before sleep, and 33% (n = 170) kept the smart device on before sleep. In total, 27% (n = 128) placed the smart device within reach before sleep, 23% (n = 107) would wake up when notifications were received, and 25% (n = 117) immediately checked the device after being awakened by a notification. Multiple regression controlling for age, sex, socio-economic status, and other confounders showed that those who woke up after receiving a notification had a statistically longer sleeping time (19.7 min, 95% CI: 0.3, 39.1, p = 0.046), lower sleep efficiency (- 0.71%, 95% CI - 1.40, - 0.02, p = 0.04), and a longer wake after sleep onset (2.6 min, 95% CI: 0.1, 5.1, p = 0.045) than those who did not. Nonetheless, all primary caregivers' bedtime smart device habits were insignificantly associated with all sleep outcomes of their children. CONCLUSION: Those who woke up after receiving smart device notifications had lower sleep efficiency and longer wake after sleep onset than those who did not, and they compensated for their sleep loss by lengthening their total sleep time.

Antioxidant and anti-inflammatory activity of curcumin transdermal gel in an IL-10 knockout mouse model of inflammatory bowel disease.

Inflammatory bowel diseases are a group of inflammatory disorders of the gastrointestinal tract. Their prevalence is still low in Brazil, but the incidence is increasing annually. A variety of compounds present in Curcuma longa L., particularly curcumin, have been shown to reduce oxidative stress and aid in the prevention of associated diseases. This study aimed to assess the effect of curcumin transdermal gel on oxidative stress and intestinal inflammation in IL-10 knockout mice. Female mice were divided into four groups: a control group (C0) treated with vehicle and three experimental groups treated with transdermal gel containing 50 (C50), 75 (C75), and 100 (C100) mg curcumin kg-1 body weight. Colon malondialdehyde concentrations were lower in C50 and C75 groups. C100 treatment led to reduced catalase activity in the small intestine, whereas C50, C75, and C100 treatments resulted in decreased catalase activity in the colon. In contrast, superoxide dismutase activity increased in the small intestine of C50 and C75 mice and decreased in the colon of C50, C75, and C100 mice. Glutathione S-transferase activity increased in the small intestine and decreased in the colon of C75 animals. These findings suggest that curcumin transdermal gel exerts a protective effect against oxidative stress.

Green Extraction of Annatto Seed Oily Extract and Its Use as a Pharmaceutical Material for the Production of Lipid Nanoparticles.

This work developd nanomaterials formulated from annatto seed oily extract (ASE), myristic acid (tetradecanoic acid), and their fatty acid esters. The annatto seed oily extract was obtained using only soybean oil (ASE + SO) and Brazil nut oil (ASE + BNO). The UV/VIS analysis of the oily extracts showed three characteristic peaks of the bixin molecule at 430, 456 and 486 nm. The lipid nanoparticles obtained using myristic acid and ASE + BNO or only BNO showed better results than the oil soybean extract, i.e., the particle size was <200 nm, PDI value was in the range of 0.2−0.3, and had no visual physical instability as they kept stable for 28 days at 4 °C. Lipid nanoemulsions were also produced with esters of myristic acid and ASE + BNO. These fatty acid esters significantly influenced the particle size of nanoemulsions. For instance, methyl tetradecanoate led to the smallest particle size nanoemulsions (124 nm), homogeneous size distribution, and high physical stability under 4 and 32 °C for 28 days. This work demonstrates that the chemical composition of vegetable oils and myristic acid esters, the storage temperature, the chain length of fatty acid esters (FAE), and their use as co-lipids improve the physical stability of lipid nanoemulsions and nanoparticles from annatto seed oily extract.

Long-term impact of early initiation of enzyme replacement therapy in 34 MPS VI patients: A resurvey study.

Patients with mucopolysaccharidosis type VI (MPS VI) present with a wide range of disease severity and clinical manifestations, with significant functional impairment and shortened lifespan. Enzyme replacement therapy (ERT) with galsulfase has been shown to improve clinical and biochemical parameters including patient survival, quality of life and growth. The present study is a resurvey of 34 Brazilian MPS VI patients with rapidly progressive disease (classical phenotype) who initiated ERT with galsulfase under five years of age and had been on ERT until data collection in 2019, with few exceptions (n = 4 patients who died before 2019). Anthropometric measures, urinary glycosaminoglycans, and data regarding cardiac, orthopedic, neurologic, sleep apnea, hearing and ophthalmologic outcomes were filled in by specialists. Pubertal development, clinical complications, hospitalizations, and surgeries were also assessed. In this resurvey study, treatment with galsulfase has shown to be safe and well tolerated in MPS VI patients who initiated ERT under the age of 5 years and who have been undergoing ERT for approximately 10 years. Mortality rate suggests that early initiation of ERT may have a positive impact on patients' survival, improving but not preventing disease progression and death. MPS VI patients on ERT also showed improved growth velocity and the pubertal development was normal in all surviving patients. Follow-up data on pneumonia and hospitalization suggest that early ERT may have a protective effect against major respiratory complications. Cardiac valve disease progressed since their prior evaluation and spinal cord compression was observed in a large number of patients, suggesting that these disease complications were not modified by ERT.

Virological failure and HIV drug resistance among adults living with HIV on second-line antiretroviral therapy in the Asia-Pacific.

OBJECTIVES: To assess second-line antiretroviral therapy (ART) virological failure and HIV drug resistance-associated mutations (RAMs), in support of third-line regimen planning in Asia. METHODS: Adults > 18 years of age on second-line ART for ≥ 6 months were eligible. Cross-sectional data on HIV viral load (VL) and genotypic resistance testing were collected or testing was conducted between July 2015 and May 2017 at 12 Asia-Pacific sites. Virological failure (VF) was defined as VL > 1000 copies/mL with a second VL > 1000 copies/mL within 3-6 months. FASTA files were submitted to Stanford University HIV Drug Resistance Database and RAMs were compared against the IAS-USA 2019 mutations list. VF risk factors were analysed using logistic regression. RESULTS: Of 1378 patients, 74% were male and 70% acquired HIV through heterosexual exposure. At second-line switch, median [interquartile range (IQR)] age was 37 (32-42) years and median (IQR) CD4 count was 103 (43.5-229.5) cells/µL; 93% received regimens with boosted protease inhibitors (PIs). Median duration on second line was 3 years. Among 101 patients (7%) with VF, CD4 count > 200 cells/µL at switch [odds ratio (OR) = 0.36, 95% confidence interval (CI): 0.17-0.77 vs. CD4 ≤ 50) and HIV exposure through male-male sex (OR = 0.32, 95% CI: 0.17-0.64 vs. heterosexual) or injecting drug use (OR = 0.24, 95% CI: 0.12-0.49) were associated with reduced VF. Of 41 (41%) patients with resistance data, 80% had at least one RAM to nonnucleoside reverse transcriptase inhibitors (NNRTIs), 63% to NRTIs, and 35% to PIs. Of those with PI RAMs, 71% had two or more. CONCLUSIONS: There were low proportions with VF and significant RAMs in our cohort, reflecting the durability of current second-line regimens.

Association of body mass index with immune recovery, virological failure and cardiovascular disease risk among people living with HIV.

OBJECTIVES: We conducted a longitudinal cohort analysis to evaluate the association of pre-treatment body mass index (BMI) with CD4 recovery, virological failure (VF) and cardiovascular risk disease (CVD) markers among people living with HIV (PLHIV). METHODS: Participants who were enrolled between January 2003 and March 2019 in a regional Asia HIV cohort with weight and height measurements prior to antiretroviral therapy (ART) initiation were included. Factors associated with mean CD4 increase were analysed using repeated-measures linear regression. Time to first VF after 6 months on ART and time to first development of CVD risk markers were analysed using Cox regression models. Sensitivity analyses were done adjusting for Asian BMI thresholds. RESULTS: Of 4993 PLHIV (66% male), 62% had pre-treatment BMI in the normal range (18.5-25.0 kg/m2 ), while 26%, 10% and 2% were underweight (< 18.5 kg/m2 ), overweight (25-30 kg/m2) and obese (> 30 kg/m2 ), respectively. Both higher baseline and time-updated BMI were associated with larger CD4 gains compared with normal BMI. After adjusting for Asian BMI thresholds, higher baseline BMIs of 23-27.5 and > 27.5 kg/m2 were associated with larger CD4 increases of 15.6 cells/µL [95% confidence interval (CI): 2.9-28.3] and 28.8 cells/µL (95% CI: 6.6-50.9), respectively, compared with normal BMI (18.5-23 kg/m2 ). PLHIV with BMIs of 25-30 and > 30 kg/m2 were 1.27 times (95% CI: 1.10-1.47) and 1.61 times (95% CI: 1.13-2.24) more likely to develop CVD risk factors. No relationship between pre-treatment BMI and VF was observed. CONCLUSIONS: High pre-treatment BMI was associated with better immune reconstitution and CVD risk factor development in an Asian PLHIV cohort.

Early mortality after late initiation of antiretroviral therapy in the TREAT Asia HIV Observational Database (TAHOD) of the International Epidemiologic Databases to Evaluate AIDS (IeDEA) Asia-Pacific.

OBJECTIVES: Early mortality among those still initiating antiretroviral therapy (ART) with advanced stages of HIV infection in resource-limited settings remains high despite recommendations for universal HIV treatment. We investigated risk factors associated with early mortality in people living with HIV (PLHIV) starting ART at low CD4 levels in the Asia-Pacific. METHODS: PLHIV enrolled in the Therapeutics, Research, Education and AIDS Training in Asia (TREAT Asia) HIV Observational Database (TAHOD) who initiated ART with a CD4 count < 100 cells/µL between 2003 and 2018 were included in the study. Early mortality was defined as death within 1 year of ART initiation. PLHIV in follow-up for > 1 year were censored at 12 months. Competing risk regression was used to analyse risk factors with loss to follow-up as a competing risk. RESULTS: A total of 1813 PLHIV were included in the study, of whom 74% were male. With 73 (4%) deaths, the overall first-year mortality rate was 4.27 per 100 person-years (PY). Thirty-eight deaths (52%) were AIDS-related, 10 (14%) were immune reconstituted inflammatory syndrome (IRIS)-related, 13 (18%) were non-AIDS-related and 12 (16%) had an unknown cause. Risk factors included having a body mass index (BMI) < 18.5 [sub-hazard ratio (SHR) 2.91; 95% confidence interval (CI) 1.60-5.32] compared to BMI 18.5-24.9, and alanine aminotransferase (ALT) ≥ 5 times its upper limit of normal (ULN) (SHR 6.14; 95% CI 1.62-23.20) compared to ALT < 5 times its ULN. A higher CD4 count (51-100 cells/µL: SHR 0.28; 95% CI 0.14-0.55; and > 100 cells/µL: SHR 0.12; 95% CI 0.05-0.26) was associated with reduced hazard for mortality compared to CD4 count ≤ 25 cells/µL. CONCLUSIONS: Fifty-two per cent of early deaths were AIDS-related. Efforts to initiate ART at CD4 counts > 50 cell/µL are associated with improved short-term survival rates, even in those with late stages of HIV disease.

Physical activity intervention improved the number and functionality of endothelial progenitor cells in low birth weight children.

BACKGROUND AND AIMS: The purpose of this study was to investigate whether an intervention with physical activity (PA) would promote positive effects on the angiogenic factors, mobilization, and functionality of circulating endothelial progenitor cells (EPCs) in children with low birth weight (LBW). METHODS AND RESULTS: Thirty-five children participated in a 10-week PA program (intensity: 75-85% of heart rate reserve, frequency: four times/week, and duration: 45 min). Before and after the PA program, we evaluated anthropometric parameters, blood pressure levels, biochemical profile, number of EPCs, number of EPC colony forming units, and plasma levels of vascular endothelial growth factor-A (VEGF-A), nitric oxide (NO), and matrix metalloproteinases (MMPs) 2 and 9. We found a significant main effect of the PA program on waist circumference (ηp2 = 0.489), cardiorespiratory fitness (ηp2 = 0.463), and MMP-9 (ηp2 = 0.582). Birth weight or the PA program produced significant independent effects on systolic blood pressure (birth weight: ηp2 = 0.431; PA program: ηp2 = 0.615) and EPC colony forming units (birth weight: ηp2 = 0.541; PA program: ηp2 = 0.698) with no significant interactions. The combination of birth weight and the PA program produced a significant interaction effect on the number of circulating EPCs (ηp2 = 0.123), NO (ηp2 = 0.258), and VEGF-A (ηp2 = 0.175). The variation in the number of EPCs from baseline to 10 weeks of the PA program correlated positively with the change in NO (P = 0.002) and VEGF-A (P = 0.004). CONCLUSIONS: A 10-week PA program attenuates the adverse effect of LBW on the number and functionality of EPCs; this effect occurs through an improvement in circulating levels of NO and VEGF-A. CLINICAL TRIALS: https://www.clinicaltrials.gov. Unique Identifier: NCT02982967. Date: December/2016.

Diabetes, mortality and glucose monitoring rates in the TREAT Asia HIV Observational Database Low Intensity Transfer (TAHOD-LITE) study.

OBJECTIVES: Diabetes is a growing cause of morbidity and mortality in people living with HIV (PLHIV) receiving antiretroviral therapy (ART). We investigated the association between fasting plasma glucose (FPG) levels and mortality, and factors associated with FPG monitoring rates in Asia. METHODS: Patients from the Therapeutics Research, Education, and AIDS Training in Asia (TREAT Asia) HIV Observational Database Low Intensity Transfer (TAHOD-LITE) cohort were included in the present study if they had initiated ART. Competing risk and Poisson regression were used to analyse the association between FPG and mortality, and assess risk factors for FPG monitoring rates, respectively. FPG was categorized as diabetes (FPG ≥ 7.0 mmol/L), prediabetes (FPG 5.6-6.9 mmol/L) and normal FPG (FPG < 5.6 mmol/L). RESULTS: In total, 33 232 patients were included in the analysis. Throughout follow-up, 59% had no FPG test available. The incidence rate for diabetes was 13.7 per 1000 person-years in the 4649 patients with normal FPG at ART initiation. Prediabetes [sub-hazard ratio (sHR) 1.32; 95% confidence interval (CI) 1.07-1.64] and diabetes (sHR 1.90; 95% CI 1.52-2.38) were associated with mortality compared to those with normal FPG. FPG monitoring increased from 0.34 to 0.78 tests per person-year from 2012 to 2016 (P < 0.001). Male sex [incidence rate ratio (IRR) 1.08; 95% CI 1.03-1.12], age > 50 years (IRR 1.14; 95% CI 1.09-1.19) compared to ≤ 40 years, and CD4 count ≥ 500 cells/µL (IRR 1.04; 95% CI 1.00-1.09) compared to < 200 cells/µL were associated with increased FPG monitoring. CONCLUSIONS: Diabetes and prediabetes were associated with mortality. FPG monitoring increased over time; however, less than half of our cohort had been tested. Greater resources should be allocated to FPG monitoring for early diabetic treatment and intervention and to optimize survival.

Long-term loss to follow-up in the TREAT Asia HIV Observational Database (TAHOD).

OBJECTIVES: With earlier antiretroviral therapy (ART) initiation, time spent in HIV care is expected to increase. We aimed to investigate loss to follow-up (LTFU) in Asian patients who remained in care 5 years after ART initiation. METHODS: Long-term LTFU was defined as LTFU occurring after 5 years on ART. LTFU was defined as (1) patients not seen in the previous 12 months; and (2) patients not seen in the previous 6 months. Factors associated with LTFU were analysed using competing risk regression. RESULTS: Under the 12-month definition, the LTFU rate was 2.0 per 100 person-years (PY) [95% confidence interval (CI) 1.8-2.2 among 4889 patients included in the study. LTFU was associated with age > 50 years [sub-hazard ratio (SHR) 1.64; 95% CI 1.17-2.31] compared with 31-40 years, viral load ≥ 1000 copies/mL (SHR 1.86; 95% CI 1.16-2.97) compared with viral load < 1000 copies/mL, and hepatitis C coinfection (SHR 1.48; 95% CI 1.06-2.05). LTFU was less likely to occur in females, in individuals with higher CD4 counts, in those with self-reported adherence ≥ 95%, and in those living in high-income countries. The 6-month LTFU definition produced an incidence rate of 3.2 per 100 PY (95% CI 2.9-3.4 and had similar associations but with greater risks of LTFU for ART initiation in later years (2006-2009: SHR 2.38; 95% CI 1.93-2.94; and 2010-2011: SHR 4.26; 95% CI 3.17-5.73) compared with 2003-2005. CONCLUSIONS: The long-term LTFU rate in our cohort was low, with older age being associated with LTFU. The increased risk of LTFU with later years of ART initiation in the 6-month analysis, but not the 12-month analysis, implies that there was a possible move towards longer HIV clinic scheduling in Asia.

Cardiovascular disease-related mortality and factors associated with cardiovascular events in the TREAT Asia HIV Observational Database (TAHOD).

OBJECTIVES: With aging of the HIV-positive population, cardiovascular disease (CVD) increasingly contributes to morbidity and mortality. We investigated CVD-related and other causes of death (CODs) and factors associated with CVD in a multi-country Asian HIV-positive cohort. METHODS: Patient data from 2003-2017 were obtained from the Therapeutics, Research, Education and AIDS Training in Asia (TREAT Asia) HIV Observational Database (TAHOD). We included patients on antiretroviral therapy (ART) with > 1 day of follow-up. Cumulative incidences were plotted for CVD-related, AIDS-related, non-AIDS-related, and unknown CODs, and any CVD (i.e. fatal and nonfatal). Competing risk regression was used to assess risk factors of any CVD. RESULTS: Of 8069 patients with a median follow-up of 7.3 years [interquartile range (IQR) 4.4-10.7 years], 378 patients died [incidence rate (IR) 6.2 per 1000 person-years (PY)], and this total included 22 CVD-related deaths (IR 0.36 per 1000 PY). Factors significantly associated with any CVD event (IR 2.2 per 1000 PY) were older age [sub-hazard ratio (sHR) 2.21; 95% confidence interval (CI) 1.36-3.58 for age 41-50 years; sHR 5.52; 95% CI 3.43-8.91 for ≥ 51 years, compared with < 40 years], high blood pressure (sHR 1.62; 95% CI 1.04-2.52), high total cholesterol (sHR 1.89; 95% CI 1.27-2.82), high triglycerides (sHR 1.55; 95% CI 1.02-2.37) and high body mass index (BMI) (sHR 1.66; 95% CI 1.12-2.46). CVD crude IRs were lower in the later ART initiation period and in lower middle- and upper middle-income countries. CONCLUSIONS: The development of fatal and nonfatal CVD events in our cohort was associated with older age, and treatable risk factors such as high blood pressure, triglycerides, total cholesterol and BMI. Lower CVD event rates in middle-income countries may indicate under-diagnosis of CVD in Asian-Pacific resource-limited settings.

Diversity of RH and transfusion support in Brazilian sickle cell disease patients with unexplained Rh antibodies.

BACKGROUND: Genetic diversity in the RH genes among sickle cell disease (SCD) patients is well described but not yet extensively explored in populations of racially diverse origin. Transfusion support is complicated in patients who develop unexpected Rh antibodies. Our goal was to describe RH variation in a large cohort of Brazilian SCD patients exhibiting unexpected Rh antibodies (antibodies against RH antigens to which the patient is phenotypically positive) and to evaluate the impact of using the patient's RH genotype to guide transfusion support. STUDY DESIGN AND METHODS: Patients within the Recipient Epidemiology and Evaluation Donor Study (REDS)-III Brazil SCD cohort with unexpected Rh antibodies were selected for study. RHD and RHCE exons and flanking introns were sequenced by targeted next-generation sequencing. RESULTS: Fifty-four patients with 64 unexplained Rh antibodies were studied. The majority could not be definitively classified as auto- or alloantibodies using serologic methods. The most common altered RH were RHD*DIIIa and RHD*DAR (RHD locus) and RHCE*ce48C, RHCE*ce733G, and RHCE*ceS (RHCE locus). In 53.1% of the cases (34/64), patients demonstrated only conventional alleles encoding the target antigen: five of 12 anti-D (41.7%), 10 of 12 anti-C (83.3%), 18 of 38 anti-e (47.4%), and one of one anti-E (100%). CONCLUSION: RHD variation in this SCD cohort differs from that reported for African Americans, with increased prevalence of RHD*DAR and underrepresentation of the DAU cluster. Many unexplained Rh antibodies were found in patients with conventional RH allele(s) only. RH genotyping was useful to guide transfusion to determine which patients could potentially benefit from receiving RH genotyped donor units.

Polyamidoxime chain length drives emergent metal-binding phenomena.

Emergence is complex behavior arising from the interactions of many simple constituents that do not display such behavior independently. Polyamidoxime (PAO) uranium adsorbents show such phenomena, as recent works articulate that the polymer binds uranium differently than the monomeric constituents. In order to investigate the origins of this emergent uranium-binding behavior, we synthesized a series of amidoxime polymers with low polydispersity and small molecules with lengths ranging from 1 to 125 repeat units. Following immersion in a uranyl-containing solution, the local, intermediate, and macroscopic structures were investigated by X-ray absorption fine structure (XAFS) spectroscopy, small angle neutron scattering (SANS), and dynamic light scattering (DLS). Fits of the extended XAFS (EXAFS) region revealed a progressive change in uranium coordination environment as a function of polymer molecular weight, identifying chain length as a driving force in emergent metal binding and resolving the controversy over how amidoxime adsorbents bind uranium.

Synthesis of Ni-SiO2/C Supported Platinum Catalysts for Improved Electrochemical Activity Towards Ethanol Oxidation.

A series of Pt/Ni-SiO2/C catalysts with different mass proportions of Ni-SiO2/C (0:100, 30:70, 50:50, 70:30 and 100:0) were prepared and studied towards ethanol electrochemical oxidation in acid medium. The support silica particles were initially synthesized via sol-gel and then modified with NiCl2. The Ni deposited on the silica surface plays a role promoting nucleation sites for the reduction of platinum. Pt was further chemically reduced onto Ni-SiO2 using formic acid and loaded onto carbon Vulcan XC-72 R. The Pt/Ni-SiO2/C catalysts were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, temperature-programmed reduction, X-ray photoelectron spectroscopy, transmission electron microscopy and inductively coupled plasma-optical emission spectroscopy. The physical characterizations reveal the formation of oxide-metal composite and strong interaction between Pt and the Ni-SiO2 composite. The Pt/Ni-SiO2/C catalyst with meso/macroporous structure exhibits higher electrocatalytic activity towards ethanol oxidation and better stability, after 48 h of electrolysis, than a commercial Pt/C catalyst. These improved features could be due to presence of Ni-SiO2 composite that promotes corrosion resistance of the support and prevents the aggregation of Pt nanoparticles and their detachment from the support. The low poisoning of the Pt/Ni-SiO2/C catalyst is probably due to the enhanced oxygen content on the composite surface. The high electrocatalytic activity and enhanced electrochemical stability of the Pt/Ni-SiO2/C catalyst make it promising for further fuel cell applications.

Psychometric Properties of the Behavioral Pain Scale in Traumatic Brain Injury.

BACKGROUND: Pain assessment of patients with traumatic brain injury is a challenge because they are unable to self-report their pain experience. AIMS: To investigate the psychometric properties of validity, reliability, and responsiveness of the Brazilian version of the Behavioral Pain Scale (BPS-Br) in patients with traumatic brain injury. METHODS: This was an observational, cross-sectional, repeated-measure and analytical study. This study was developed at the medical and surgical ICUs in a high-complexity public hospital at Aracaju, Sergipe, Brazil. Thirty-seven adult patients with moderate or severe TBI were included. This study was completed with 444 independent observations, a pairwise comparison, and was performed simultaneously before, during, and after eye cleaning and endotracheal suctioning of 37 adult patients with moderate to severe traumatic brain injury. RESULTS: The BPS-Br had good internal consistency (.7 ≤ α ≤ .9), good discriminant validity (p < .001), moderate to excellent reliability based on inter-rater agreement (intraclass correlation coefficient = 0.66-1.00; κ = 0.5-1.0), and high responsiveness (0.7-1.7). The upper limbs subscale had the highest score during the nociceptive procedure (1.8 ± 0.9). Deep sedation affected the increase of grading during painful procedures (p < .001). CONCLUSIONS: Our results suggest the BPS-Br is a useful tool for clinical practice to evaluate the pain experienced by patients with traumatic brain injury. Further studies of different samples are needed to evaluate the benefits of systematic pain assessment of critically ill patients.