Surface engineering for stable electrocatalysis.

In recent decades, significant progress has been achieved in rational developments of electrocatalysts through constructing novel atomistic structures and modulating catalytic surface topography, realizing substantial enhancement in electrocatalytic activities. Numerous advanced catalysts were developed for electrochemical energy conversion, exhibiting low overpotential, high intrinsic activity, and selectivity. Yet, maintaining the high catalytic performance under working conditions with high polarization and vigorous microkinetics that induce intensive degradation of surface nanostructures presents a significant challenge for commercial applications. Recently, advanced operando and computational techniques have provided comprehensive mechanistic insights into the degradation of surficial functional structures. Additionally, various innovative strategies have been devised and proven effective in sustaining electrocatalytic activity under harsh operating conditions. This review aims to discuss the most recent understanding of the degradation microkinetics of catalysts across an entire range of anodic to cathodic polarizations, encompassing processes such as oxygen evolution and reduction, hydrogen reduction, and carbon dioxide reduction. Subsequently, innovative strategies adopted to stabilize the materials' structure and activity are highlighted with an in-depth discussion of the underlying rationale. Finally, we present conclusions and perspectives regarding future research and development. By identifying the research gaps, this review aims to inspire further exploration of surface degradation mechanisms and rational design of durable electrocatalysts, ultimately contributing to the large-scale utilization of electroconversion technologies.

Effects of heat and personal protective equipment on thermal strain in healthcare workers: part B-application of wearable sensors to observe heat strain among healthcare workers under controlled conditions.

PURPOSE: As climate change accelerates, healthcare workers (HCW) are expected to be more frequently exposed to heat at work. Heat stress can be exacerbated by physical activity and unfavorable working requirements, such as wearing personal protective equipment (PPE). Thus, understanding its potential negative effects on HCW´s health and working performance is becoming crucial. Using wearable sensors, this study investigated the physiological effects of heat stress due to HCW-related activities. METHODS: Eighteen participants performed four experimental sessions in a controlled climatic environment following a standardized protocol. The conditions were (a) 22 °C, (b) 22 °C and PPE, (c) 27 °C and (d) 27 °C and PPE. An ear sensor (body temperature, heart rate) and a skin sensor (skin temperature) were used to record the participants´ physiological parameters. RESULTS: Heat and PPE had a significant effect on the measured physiological parameters. When wearing PPE, the median participants' body temperature was 0.1 °C higher compared to not wearing PPE. At 27 °C, the median body temperature was 0.5 °C higher than at 22 °C. For median skin temperature, wearing PPE resulted in a 0.4 °C increase and higher temperatures in a 1.0 °C increase. An increase in median heart rate was also observed for PPE (+ 2/min) and heat (+ 3/min). CONCLUSION: Long-term health and productivity risks can be further aggravated by the predicted temperature rise due to climate change. Further physiological studies with a well-designed intervention are needed to strengthen the evidence for developing comprehensive policies to protect workers in the healthcare sector.

Pregnancy and birth outcomes among young women living with perinatally acquired HIV in Thailand and Vietnam.

We conducted a retrospective cohort study of pregnancy and infant outcomes in 670 adolescents and young adult women with perinatally acquired HIV (AYAPHIV), aged 15-24 years, in Thailand and Vietnam. Between January 2013 and December 2018, there were 52 pregnancies, for an incidence of 2.49 (95% CI 1.90-3.27) per 100 person-years. The median age at pregnancy was 17.7 years (IQR 16.8-18.9). Pregnant AYAPHIV had been on cART for a lifetime median of 9.8 years (IQR 7.3-12.4). At the time of conception, the median CD4 was 521 cells/mm3 (IQR 213-760), and 76% had HIV RNA ≤400 copies/ml. Of the 51 pregnancies with available outcomes, 90% resulted in live singleton births at a median gestational age of 38 weeks (IQR 37-39); 77% of mothers (n = 27/35) had HIV RNA ≤400 copies/ml at delivery. Among infants with available data, 50% (n = 21/42) were male and 29% (n = 12/42) were reported to be low birthweight (<2,500gm); none (n = 0/41) were breastfed. One infant was diagnosed with HIV. Our findings emphasize that efforts to strengthen reproductive health education, including contraception, pregnancy-related psychosocial support services, and prevention of vertical HIV transmission interventions, in our region are needed for adolescents with perinatally acquired HIV as they transition to young adults.

Disclosure of HIV status and associated clinical outcomes of children and adolescents living with HIV in Asia.

Disclosure of HIV status is an important part of pediatric care. We studied disclosure and clinical outcomes in a multi-country Asian cohort of children and adolescents with HIV. Those 6-19 years of age who initiated combination antiretroviral therapy (cART) between 2008 and 2018, and who had at least one follow-up clinic visit were included. Data up to December 2019 were analyzed. Cox and competing risk regression analyses were used to assess the effect of disclosure on disease progression (WHO clinical stage 3 or 4), loss to follow-up (LTFU; > 12 months), and death. Of 1913 children and adolescents (48% female; median [IQR] age 11.5 [9.2-14.7] years at last clinic visit), 795 (42%) were disclosed to about their HIV status at a median age of 12.9 years (IQR: 11.8-14.1). During follow-up, 207 (11%) experienced disease progression, 75 (3.9%) were LTFU, and 59 (3.1%) died. There were lower hazards of disease progression (adjusted hazard ratio [aHR] 0.43 [0.28-0.66]) and death (aHR 0.36 [0.17-0.79]) for those disclosed to compared with those who were not. Disclosure and its appropriate implementation should be promoted in pediatric HIV clinics in resource-limited settings.

Combined Therapeutic Plasma Exchange and Continuous Renal Replacement Therapy in Children With Dengue-Associated Acute Liver Failure and Shock Syndrome: Single-Center Cohort From Vietnam.

OBJECTIVES: Pediatric acute liver failure (PALF) is a fatal complication in patients with severe dengue. To date, clinical data on the combination of therapeutic plasma exchange (TPE) and continuous renal replacement therapy (CRRT) for managing dengue-associated PALF concomitant with shock syndrome are limited. DESIGN: Retrospective cohort study (January 2013 to June 2022). PATIENTS: Thirty-four children. SETTING: PICU of tertiary Children's Hospital No. 2 in Vietnam. INTERVENTIONS: We assessed a before-versus-after practice change at our center of using combined TPE and CRRT (2018 to 2022) versus CRRT alone (2013 to 2017) in managing children with dengue-associated acute liver failure and shock syndrome. Clinical and laboratory data were reviewed from PICU admission, before and 24 h after CRRT and TPE treatments. The main study outcomes were 28-day in-hospital mortality, hemodynamics, clinical hepatoencephalopathy, and liver function normalization. MEASUREMENTS AND MAIN RESULTS: A total of 34 children with a median age of 10 years (interquartile range: 7-11 yr) underwent standard-volume TPE and/or CRRT treatments. Combined TPE and CRRT ( n = 19), versus CRRT alone ( n = 15), was associated with lower proportion of mortality 7 of 19 (37%) versus 13 of 15 (87%), difference 50% (95% CI, 22-78; p < 0.01). Use of combined TPE and CRRT was associated with substantial advancements in clinical hepatoencephalopathy, liver transaminases, coagulation profiles, and blood lactate and ammonia levels (all p values < 0.001). CONCLUSIONS: In our experience of children with dengue-associated PALF and shock syndrome, combined use of TPE and CRRT, versus CRRT alone, is associated with better outcomes. Such combination intervention was associated with normalization of liver function, neurological status, and biochemistry. In our center we continue to use combined TPE and CRRT rather than CRRT alone.

Dementia care practices among community healthcare workers in Vietnam: a qualitative descriptive study.

BACKGROUND: Vietnam is one of the most rapidly aging countries in the world and the likelihood that someone may have dementia rises dramatically as the population ages. Although caring for persons living with dementia is important, little is known about the circumstances under which community healthcare professionals in Vietnam provide dementia care. This study aimed to describe the practice of caring for persons with dementia among community healthcare professionals in Vietnam. METHODS: This qualitative descriptive study was conducted with 23 community healthcare professionals recruited from 10 primary healthcare centers, representing 10 of 24 districts in Ho Chi Minh City, Vietnam. Participants were physicians (n = 11), physician's assistants (n = 8) and community nurses (n = 4). Data were collected through in-depth face-to-face semi-structured interviews. Interview data were audio recorded, transcribed verbatim, and analyzed using content analysis. RESULTS: The mean age of the 23 participants was 44.6 ± 8.8 years; most were female (n = 16, 69.6%); and the mean time of working in the field of dementia care was 15.9 ± 8.4 years. Analysis of the interview data revealed five categories, which informed how care was provided: 1) Knowledge about dementia and its prevalence among older adults; 2) Identification of dementia in Vietnam; 3) Lack of attention to early diagnosis of dementia and difficulty in providing continuous care; 4) Dependence on family members for prompt and continuous care; and 5) challenges to providing dementia care. Despite having knowledge about dementia, some healthcare professionals incorrectly viewed dementia as an inevitable part of the ageing process. Participants reported that their limited training and practical experience in caring for persons with dementia caused a lack of confidence in dementia care. CONCLUSIONS: The quality of care provided to persons living with dementia was negatively impacted by the limited training of healthcare personnel. The diagnosis, treatment, and provision of supportive services to persons living with dementia and their families are substantial challenges for the Vietnamese healthcare system. It is crucial to initiate and cultivate dementia care education programs aimed at expanding curricula for physicians, physicians' assistants, and nurses.

Identification, Management, and Outcomes of Combination Antiretroviral Treatment Failure in Adolescents With Perinatal Human Immunodeficiency Virus Infection in Asia.

BACKGROUND: Combination antiretroviral therapy (cART) failure is a major threat to human immunodeficiency virus (HIV) programs, with implications for individual- and population-level outcomes. Adolescents with perinatally acquired HIV infection (PHIVA) should be a focus for treatment failure given their poorer outcomes compared to children and adults. METHODS: Data (2014-2018) from a regional cohort of Asian PHIVA who received at least 6 months of continuous cART were analyzed. Treatment failure was defined according to World Health Organization criteria. Descriptive analyses were used to report treatment failure and subsequent management and evaluate postfailure CD4 count and viral load trends. Kaplan-Meier survival analyses were used to compare the cumulative incidence of death and loss to follow-up (LTFU) by treatment failure status. RESULTS: A total 3196 PHIVA were included in the analysis with a median follow-up period of 3.0 years, of whom 230 (7.2%) had experienced 292 treatment failure events (161 virologic, 128 immunologic, 11 clinical) at a rate of 3.78 per 100 person-years. Of the 292 treatment failure events, 31 (10.6%) had a subsequent cART switch within 6 months, which resulted in better immunologic and virologic outcomes compared to those who did not switch cART. The 5-year cumulative incidence of death and LTFU following treatment failure was 18.5% compared to 10.1% without treatment failure. CONCLUSIONS: Improved implementation of virologic monitoring is required to realize the benefits of virologic determination of cART failure. There is a need to address issues related to accessibility to subsequent cART regimens, poor adherence limiting scope to switch regimens, and the role of antiretroviral resistance testing.

The value of first-line chemotherapy and targeted therapy in the treatment of breast cancer.

OBJECTIVE: To investigate the value (survival benefit and cost) of first-line chemotherapy and targeted therapy in breast cancer at a population level. METHODS: Based on guideline recommendations, a model of optimal utilisation was constructed for first-line chemotherapy and targeted therapy in breast cancer, calculating the survival benefit and average cost of all regimens recommended for each treatment indication at 5 years and at 10 years. RESULTS: Survival benefits from chemotherapy and targeted therapy differ markedly depending on the treatment indications. The cost per life-year gained at 5 years is $38,044 for stages I and II, $33,749 for stage III and $ 151,668 for patients presenting with stage IV breast cancer. The cost per life-year gained at 10 years is $ 13,587 for early breast cancer. The most expensive chemotherapy indication in breast cancer is the treatment of metastatic HER2-positive breast cancer costing $330,978 per LYG for a survival benefit of 11% at 5 years falling to zero survival benefit at 10 years. CONCLUSION: There are large differences in value between the different indications for first-course chemotherapy and targeted therapy in the treatment of breast cancer that should be considered when pricing cancer drugs.

Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial.

BACKGROUND: The PORTEC-3 trial investigated the benefit of combined adjuvant chemotherapy and radiotherapy versus pelvic radiotherapy alone for women with high-risk endometrial cancer. We updated the analysis to investigate patterns of recurrence and did a post-hoc survival analysis. METHODS: In the multicentre randomised phase 3 PORTEC-3 trial, women with high-risk endometrial cancer were eligible if they had International Federation of Gynaecology and Obstetrics (FIGO) 2009 stage I, endometrioid grade 3 cancer with deep myometrial invasion or lymphovascular space invasion, or both; stage II or III disease; or stage I-III disease with serous or clear cell histology; were aged 18 years and older; and had a WHO performance status of 0-2. Participants were randomly assigned (1:1) to receive radiotherapy alone (48·6 Gy in 1·8 Gy fractions given on 5 days per week) or chemoradiotherapy (two cycles of cisplatin 50 mg/m2 given intravenously during radiotherapy, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2 given intravenously), by use of a biased coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage, and histological type. The co-primary endpoints were overall survival and failure-free survival. Secondary endpoints of vaginal, pelvic, and distant recurrence were analysed according to the first site of recurrence. Survival endpoints were analysed by intention-to-treat, and adjusted for stratification factors. Competing risk methods were used for failure-free survival and recurrence. We did a post-hoc analysis to analyse patterns of recurrence with 1 additional year of follow-up. The study was closed on Dec 20, 2013; follow-up is ongoing. This study is registered with ISRCTN, number ISRCTN14387080, and ClinicalTrials.gov, number NCT00411138. FINDINGS: Between Nov 23, 2006, and Dec 20, 2013, 686 women were enrolled, of whom 660 were eligible and evaluable (330 in the chemoradiotherapy group, and 330 in the radiotherapy-alone group). At a median follow-up of 72·6 months (IQR 59·9-85·6), 5-year overall survival was 81·4% (95% CI 77·2-85·8) with chemoradiotherapy versus 76·1% (71·6-80·9) with radiotherapy alone (adjusted hazard ratio [HR] 0·70 [95% CI 0·51-0·97], p=0·034), and 5-year failure-free survival was 76·5% (95% CI 71·5-80·7) versus 69·1% (63·8-73·8; HR 0·70 [0·52-0·94], p=0·016). Distant metastases were the first site of recurrence in most patients with a relapse, occurring in 78 of 330 women (5-year probability 21·4%; 95% CI 17·3-26·3) in the chemoradiotherapy group versus 98 of 330 (5-year probability 29·1%; 24·4-34·3) in the radiotherapy-alone group (HR 0·74 [95% CI 0·55-0·99]; p=0·047). Isolated vaginal recurrence was the first site of recurrence in one patient (0·3%; 95% CI 0·0-2·1) in both groups (HR 0·99 [95% CI 0·06-15·90]; p=0·99), and isolated pelvic recurrence was the first site of recurrence in three women (0·9% [95% CI 0·3-2·8]) in the chemoradiotherapy group versus four (0·9% [95% CI 0·3-2·8]) in the radiotherapy-alone group (HR 0·75 [95% CI 0·17-3·33]; p=0·71). At 5 years, only one grade 4 adverse event (ileus or obstruction) was reported (in the chemoradiotherapy group). At 5 years, reported grade 3 adverse events did not differ significantly between the two groups, occurring in 16 (8%) of 201 women in the chemoradiotherapy group versus ten (5%) of 187 in the radiotherapy-alone group (p=0·24). The most common grade 3 adverse event was hypertension (in four [2%] women in both groups). At 5 years, grade 2 or worse adverse events were reported in 76 (38%) of 201 women in the chemoradiotherapy group versus 43 (23%) of 187 in the radiotherapy-alone group (p=0·002). Sensory neuropathy persisted more often after chemoradiotherapy than after radiotherapy alone, with 5-year rates of grade 2 or worse neuropathy of 6% (13 of 201 women) versus 0% (0 of 187). No treatment-related deaths were reported. INTERPRETATION: This updated analysis shows significantly improved overall survival and failure-free survival with chemoradiotherapy versus radiotherapy alone. This treatment schedule should be discussed and recommended, especially for women with stage III or serous cancers, or both, as part of shared decision making between doctors and patients. Follow-up is ongoing to evaluate long-term survival. FUNDING: Dutch Cancer Society, Cancer Research UK, National Health and Medical Research Council, Project Grant, Cancer Australia Grant, Italian Medicines Agency, and the Canadian Cancer Society Research Institute.

Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial.

BACKGROUND: Although women with endometrial cancer generally have a favourable prognosis, those with high-risk disease features are at increased risk of recurrence. The PORTEC-3 trial was initiated to investigate the benefit of adjuvant chemotherapy during and after radiotherapy (chemoradiotherapy) versus pelvic radiotherapy alone for women with high-risk endometrial cancer. METHODS: PORTEC-3 was an open-label, international, randomised, phase 3 trial involving 103 centres in six clinical trials collaborating in the Gynaecological Cancer Intergroup. Eligible women had high-risk endometrial cancer with FIGO 2009 stage I, endometrioid-type grade 3 with deep myometrial invasion or lymph-vascular space invasion (or both), endometrioid-type stage II or III, or stage I to III with serous or clear cell histology. Women were randomly assigned (1:1) to receive radiotherapy alone (48·6 Gy in 1·8 Gy fractions given on 5 days per week) or radiotherapy and chemotherapy (consisting of two cycles of cisplatin 50 mg/m2 given during radiotherapy, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2) using a biased-coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage of cancer, and histological type. The co-primary endpoints were overall survival and failure-free survival. We used the Kaplan-Meier method, log-rank test, and Cox regression analysis for final analysis by intention to treat and adjusted for stratification factors. The study was closed on Dec 20, 2013, after achieving complete accrual; follow-up is ongoing. PORTEC-3 is registered with ISRCTN, number ISRCTN14387080, and ClinicalTrials.gov, number NCT00411138. RESULTS: 686 women were enrolled between Nov 23, 2006, and Dec 20, 2013. 660 eligible patients were included in the final analysis, of whom 330 were assigned to chemoradiotherapy and 330 were assigned to radiotherapy. Median follow-up was 60·2 months (IQR 48·1-73·1). 5-year overall survival was 81·8% (95% CI 77·5-86·2) with chemoradiotherapy versus 76·7% (72·1-81·6) with radiotherapy (adjusted hazard ratio [HR] 0·76, 95% CI 0·54-1·06; p=0·11); 5-year failure-free survival was 75·5% (95% CI 70·3-79·9) versus 68·6% (63·1-73·4; HR 0·71, 95% CI 0·53-0·95; p=0·022). Grade 3 or worse adverse events during treatment occurred in 198 (60%) of 330 who received chemoradiotherapy versus 41 (12%) of 330 patients who received radiotherapy (p<0·0001). Neuropathy (grade 2 or worse) persisted significantly more often after chemoradiotherapy than after radiotherapy (20 [8%] women vs one [1%] at 3 years; p<0·0001). Most deaths were due to endometrial cancer; in four patients (two in each group), the cause of death was uncertain. One death in the radiotherapy group was due to either disease progression or late treatment complications; three deaths (two in the chemoradiotherapy group and one in the radiotherapy group) were due to either intercurrent disease or late treatment-related toxicity. INTERPRETATION: Adjuvant chemotherapy given during and after radiotherapy for high-risk endometrial cancer did not improve 5-year overall survival, although it did increase failure-free survival. Women with high-risk endometrial cancer should be individually counselled about this combined treatment. Continued follow-up is needed to evaluate long-term survival. FUNDING: Dutch Cancer Society, Cancer Research UK, National Health and Medical Research Council Project Grant and Cancer Australia, L'Agenzia Italiana del Farmaco, and Canadian Cancer Society Research Institute.

Effects of siRNA-dependent knock-down of cardiolipin synthase and tafazzin on mitochondria and proliferation of glioma cells.

The mitochondrial phospholipid cardiolipin (CL) has been implicated with mitochondrial morphology, function, and cell proliferation. Changes in CL are often paralleled by changes in the lipid environment of mitochondria that may contribute to mitochondrial function and proliferation. This study aimed to separate the effects of CL content and CL composition from cellular free fatty acid distribution on bioenergetics and proliferation in C6 glioma cells. To this end, cardiolipin synthase and the CL remodelling enzyme, tafazzin, were knocked-down by siRNA in C6 cells. After 72 h of cultivation, we analysed CL composition by means of LC/MS/MS, distribution of cellular fatty acids by means of gas chromatography, and determined oxygen consumption and proliferation. Knock-down of cardiolipin synthase affected the cellular CL content in the presence of linoleic acid (LA) in the culture medium. Knock-down of tafazzin had no consequence with respect to the pattern of cellular fatty acids but caused a decrease in cell proliferation. It significantly changed the distribution of molecular CL species, increased CL content, decreased oxygen consumption, and decreased cell proliferation when cultured in the presence of linoleic acid (LA). The addition of linoleic acid to the culture medium caused significant changes in the pattern of cellular fatty acids and the composition of molecular CL species. These data suggest that tafazzin is required for efficient bioenergetics and for proliferation of glioma cells. Supplementation of fatty acids can be a powerful tool to direct specific changes in these parameters.

Early Height and Weight Changes in Children Using Cotrimoxazole Prophylaxis With Antiretroviral Therapy.

BACKGROUND: The growth benefits of cotrimoxazole during early antiretroviral therapy (ART) are not well characterized. METHODS: Individuals enrolled in the Therapeutics Research, Education, and AIDS Training in Asia Pediatric HIV Observational Database were included if they started ART at ages 1 month-14 years and had both height and weight measurements available at ART initiation (baseline). Generalized estimating equations were used to identify factors associated with change in height-for-age z-score (HAZ), follow-up HAZ ≥ -2, change in weight-for-age z-score (WAZ), and follow-up WAZ ≥ -2. RESULTS: A total of 3217 children were eligible for analysis. The adjusted mean change in HAZ among cotrimoxazole and non-cotrimoxazole users did not differ significantly over the first 24 months of ART. In children who were stunted (HAZ < -2) at baseline, cotrimoxazole use was not associated with a follow-up HAZ ≥ -2. The adjusted mean change in WAZ among children with a baseline CD4 percentage (CD4%) >25% became significantly different between cotrimoxazole and non-cotrimoxazole users after 6 months of ART and remained significant after 24 months (overall P < .01). Similar changes in WAZ were observed in those with a baseline CD4% between 10% and 24% (overall P < .01). Cotrimoxazole use was not associated with a significant difference in follow-up WAZ in children with a baseline CD4% <10%. In those underweight (WAZ < -2) at baseline, cotrimoxazole use was associated with a follow-up WAZ ≥ -2 (adjusted odds ratio, 1.70 vs not using cotrimoxazole [95% confidence interval, 1.28-2.25], P < .01). This association was driven by children with a baseline CD4% ≥10%. CONCLUSIONS: Cotrimoxazole use is associated with benefits to WAZ but not HAZ during early ART in Asian children.

A continuous coupled spectrophotometric assay for debranching enzyme activity using reducing end-specific α-glucosidase.

A novel continuous spectrophotometric assay to measure the activity of the debranching enzyme and α-amylase has been developed. The assay mixture comprises the debranching enzyme (GlgX from Escherichia coli) or α-amylase (PPA from porcine pancreas), a reducing end-specific α-glucosidase (MalZ), maltodextrin-branched ß-cyclodextrin (Glcn-ß-CD) as the substrate, and the glucose oxidase/peroxidase system (GOPOD). Due to its high reducing end specificity, the branch chains of the substrates are not hydrolyzed by MalZ. After hydrolysis by GlgX or PPA, the released maltodextrins are immediately hydrolyzed into glucose from the reducing end by MalZ, whose concentration is continuously measured by GOPOD at 510 nm in a thermostat spectrophotometer. The kinetic constants determined for GlgX (Km = 0.66 ± 0.02 mM and kcat = 76.7 ± 1.5 s(-1)) are within a reasonable range compared with those measured using high-performance anion-exchange chromatography (HPAEC). The assay procedure is convenient and sensitive, and it requires lower concentrations of enzymes and substrate compared with dinitrosalicylic acid (DNS) and HPAEC analysis.

Development and evaluation of a non-ribosomal random PCR and next-generation sequencing based assay for detection and sequencing of hand, foot and mouth disease pathogens.

BACKGROUND: Hand, foot and mouth disease (HFMD) has become a major public health problem across the Asia-Pacific region, and is commonly caused by enterovirus A71 (EV-A71) and coxsackievirus A6 (CV-A6), CV-A10 and CV-A16. Generating pathogen whole-genome sequences is essential for understanding their evolutionary biology. The frequent replacements among EV serotypes and a limited numbers of available whole-genome sequences hinder the development of overlapping PCRs for whole-genome sequencing. We developed and evaluated a non-ribosomal random PCR (rPCR) and next-generation sequencing based assay for sequence-independent whole-genome amplification and sequencing of HFMD pathogens. A total of 16 EV-A71/CV-A6/CV-A10/CV-A16 PCR positive rectal/throat swabs (Cp values: 20.9-33.3) were used for assay evaluation. RESULTS: Our assay evidently outperformed the conventional rPCR in terms of the total number of EV-A71 reads and the percentage of EV-A71 reads: 2.6 % (1275/50,000 reads) vs. 0.1 % (31/50,000) and 6 % (3008/50,000) vs. 0.9 % (433/50,000) for two samples with Cp values of 30 and 26, respectively. Additionally the assay could generate genome sequences with the percentages of coverage of 94-100 % of 4 different enterovirus serotypes in 73 % of the tested samples, representing the first whole-genome sequences of CV-A6/10/16 from Vietnam, and could assign correctly serotyping results in 100 % of 24 tested specimens. In all but three the obtained consensuses of two replicates from the same sample were 100 % identical, suggesting that our assay is highly reproducible. CONCLUSIONS: In conclusion, we have successfully developed a non-ribosomal rPCR and next-generation sequencing based assay for sensitive detection and direct whole-genome sequencing of HFMD pathogens from clinical samples.

Therapeutic Drug Monitoring of Lopinavir in HIV-Infected Children on Second-Line Antiretroviral Therapy in Asia.

BACKGROUND: Failure rates of second-line boosted protease inhibitor antiretroviral therapy regimens in children rise over time. Therapeutic drug monitoring can contribute to assessments of adherence. The authors assessed the performance characteristics of the US DHHS-recommended lopinavir (LPV) concentration of 1.0 mg/L for predicting virologic failure (VF) and intermediate- to high-level LPV resistance in Asian children. METHODS: LPV concentration, HIV RNA level, and adherence data from study participants in Thailand, Vietnam, and Indonesia receiving second-line LPV-based ART and followed for ≥24 weeks were analyzed. RESULTS: A total of 223 children at a median age of 10.4 (interquartile range, 7.9-13.4) years were enrolled, and 61% of them were male. Their mean CD4 was 842 ± 438 cells per cubic millimeter, and the median LPV duration was 2.5 (interquartile range, 1.3-4.2) years. Five of 84 (6%) and 18 of 139 (13%) children had LPV trough and random concentrations <1.0 mg/L at study week 24. Using either of these trough or random LPV concentrations, a cutoff at 1.0 mg/L gave an area under the receiver operating characteristics curve of 0.69 in predicting VF with sensitivity of 44% (95% CI 23-66) and specificity of 94% (95% CI 89-97). Seven of 21 with VF and resistance results available had ≥1 major protease inhibitor mutation. Multivariate logistic regression found LPV concentrations <1.0 mg/L (odds ratio, 6.47; 95% CI 2.15-19.50, P = 0.001) and CD4 ≤20% (odds ratio, 2.83; 95% CI 1.01-7.89, P = 0.05) were independently associated with HIV RNA >1000 copies per milliliter. No factors predicted major LPV resistance mutations. CONCLUSIONS: The authors support that the DHHS target LPV concentration of <1.0 mg/L is predictive of VF, but not of the presence of major LPV mutations.

Assessment of subjective well-being of healthcare workers in response to heat and personal protective equipment under controlled conditions using a standardized protocol.

BACKGROUND: Due to climate change, the increasing frequency of hot summer days and heat waves can result in occupational heat strain, especially in non-air-conditioned workplaces. Healthcare workers (HCW) engaged in patient care are particularly affected, as they are additionally exposed to physical stress. The use of personal protective equipment (PPE) can aggravate heat strain in HCW. This study aimed to examine the subjective well-being of HCW when exposed to heat and PPE under controlled conditions. METHODS: This study was designed as a randomized crossover trial. Participants performed standardized healthcare tasks in a climatic chamber for approximately 3.5 h at different indoor temperatures (22 °C and 27 °C) and varied working conditions (with or without PPE). The effects on participants' subjective well-being, encompassing thermal, physiological and psychological stress were assessed using a customized questionnaire. RESULTS: Heat had a greater effect than PPE on thermal, physical and psychological stress. Conversely, PPE had a greater effect on physical demand and effort. For the majority of outcomes, combined exposure to heat and PPE resulted in the highest perceived discomfort. Furthermore, the participants reported increased sweating and other discomforts when working at elevated temperatures or with PPE. CONCLUSIONS: In this study, heat and PPE, but particularly the combination of both factors, were identified as unfavorable working environments. Although the trials were conducted in a controlled environment, the outcomes provide valuable information about the effect of heat and PPE on HCW in a real-life setting. Furthermore, the design used in this study can be beneficial in evaluating the effect of mitigation strategies.

Subnanometric Osmium Clusters Confined on Palladium Metallenes for Enhanced Hydrogen Evolution and Oxygen Reduction Catalysis.

Highly efficient, cost-effective, and durable electrocatalysts, capable of accelerating sluggish reaction kinetics and attaining high performance, are essential for developing sustainable energy technologies but remain a great challenge. Here, we leverage a facile heterostructure design strategy to construct atomically thin Os@Pd metallenes, with atomic-scale Os nanoclusters of varying geometries confined on the surface layer of the Pd lattice, which exhibit excellent bifunctional properties for catalyzing both hydrogen evolution (HER) and oxygen reduction reactions (ORR). Importantly, Os5%@Pd metallenes manifest a low η10 overpotential of only 11 mV in 1.0 M KOH electrolyte (HER) as well as a highly positive E1/2 potential of 0.92 V in 0.1 M KOH (ORR), along with superior mass activities and electrochemical durability. Theoretical investigations reveal that the strong electron redistribution between Os and Pd elements renders a precise fine-tuning of respective d-band centers, thereby guiding adsorption of hydrogen and oxygen intermediates with an appropriate binding energy for the optimal HER and ORR.

Dorsoradial capsulodesis for trapeziometacarpal joint instability.

We describe an alternative method for treating chronic trapeziometacarpal (TM) joint instability after acute injury or chronic repetitive use of the thumb by performing a dorsoradial capsulodesis procedure. The procedure is done by imbricating the redundant TM joint dorsoradial ligament and capsule after reducing the joint by pronating the thumb. The dorsoradial capsulodesis is a reasonable reconstructive option for chronic TM joint instability and subluxation.

Cosmetic rhinoplasty: revision rates revisited.

BACKGROUND: Cosmetic rhinoplasty has great potential to change a patient's appearance. It also carries the very real risk of patient dissatisfaction and request for revision. Although there have been many published patient series studying various aspects of rhinoplasty, questions remain regarding revision rates, as well as risk factors for complications, dissatisfaction, and revision. OBJECTIVES: The authors investigate the rate of cosmetic rhinoplasty revision at a plastic surgery group practice and identify risk factors for revision. METHODS: Medical records were retrospectively reviewed for all patients who presented to a single multisurgeon practice for primary rhinoplasty, septorhinoplasty, and revision rhinoplasty between 1998 and 2008. Patient demographics, preoperative complaints, preoperative physical examination findings, detailed operative data, and postoperative outcomes were abstracted from the charts. Complication rates, revision rates, and postoperative patient satisfaction were calculated and analyzed for identifiable risk factors. RESULTS: Of 369 consecutive cosmetic rhinoplasties performed during the study period, 279 (72.7%) were conducted with an open approach. The overall complication, dissatisfaction, and revision rates were 7.9%, 15.4%, and 9.8%, respectively. Postoperatively, most patients (87%) were identified by their surgeons as having had successful anatomical correction of their nasal deformity. History of previous nasal operation or facial fracture, lack of anatomical correction, and occurrence of postoperative complications were associated with both revision and dissatisfaction (P < .05). Failure to address the nasal tip at the time of primary rhinoplasty was associated with a higher level of dissatisfaction. CONCLUSIONS: Cosmetic rhinoplasty is one of the most challenging procedures in plastic surgery; however, these data indicate that a high level of patient satisfaction is attainable within a plastic surgery group practice if certain factors are considered. Specifically, surgeons should be aware of risk factors that are potentially associated with dissatisfaction and revision. LEVEL OF EVIDENCE: 4.