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Trimethoprim-sulfamethoxazole (TMP-SMX) is widely used for Pneumocystis carinii pneumonia prophylaxis in human immunodeficiency virus (HIV)—infected patients, but little is known about the effects of this practice on the emergence of TMP-SMX—resistant bacteria. A serial cross-sectional study of resistance to TMP-SMX among all clinical isolates of Staphylococcus aureus and 7 genera of Enterobacteriaceae was performed at San Francisco General Hospital. Resistance among all isolates was <5.5% from 1979 to 1986 but then markedly increased, reaching 20.4% in 1995. This was most prominent in HIV-infected patients: resistance increased from 6.3% in 1988 to 53% in 1995. The largest increases in resistance were in Escherichia coli (24% in 1988 to 74% in 1995) and S. aureus (0% to 48%) obtained from HIV-infected patients. A rapid increase in the use of prophylactic TMP-SMX in HIV disease was also observed during this time in San Francisco and is likely responsible for the increase in TMP-SMX resistance.

Abstract Rationale: Mycobacterium avium complex pulmonary disease (MAC-PD) is associated with substantial morbidity, and standard daily multidrug therapy is difficult to tolerate. Objectives To characterize response to a three-times-weekly (TIW) regimen of clarithromycin, ethambutol, and rifampin. Methods A 1-yr prospective noncomparative trial of TIW treatment was conducted during 2000–2003 in 17 U.S. cities. Participants were 91 HIV-negative adults, diagnosed with moderate to severe MAC-PD, who originally participated in a trial of an inhaled IFN-γ treatment. Improvement in sputum culture, high-resolution computed tomography (HRCT), and symptoms were assessed. Results Treatment response rates (and median response times) were 44% (2 mo or longer) for culture, 60% (5.5–11.5 mo) for HRCT, and 53% (8.5 mo) for symptoms. Having noncavitary, compared with cavitary, disease increased culture response by 4.0 times (95% confidence interval [CI], 1.7–9.2) and HRCT response by 4.9 times (95% CI, 1.9–13.0). Culture response was 1.5 times (95% CI, 1.1–2.2) higher for older subjects and 2.2 times (95% CI, 1.0–4.7) higher for previously untreated subjects. Being smear-negative increased culture response by 2.3 times (95% CI, 1.1–5.2) but decreased HRCT response by 4.4 times (95% CI, 1.7–11.5). Increasing ethambutol use by 5 mo increased culture response by 1.5 times (95% CI, 1.0–2.1) but decreased symptom response. Not having chronic obstructive pulmonary disease, bronchiectasis, or poor lung function increased symptom response by 1.9 to 3.9 times. Conclusions TIW therapy was less effective for MAC-PD patients with cavitary disease and a history of chronic obstructive pulmonary disease, bronchiectasis, or previous treatment for MAC-PD. Further research is needed to study the long-term outcomes of TIW treatment.

Objective. This study examines the sex-specific associations of plasma concentrations of iron, copper, and zinc with cognitive function in older community-dwelling adults.Design: Cross-sectional study.Setting: 1988–92 follow-up clinic visit.Participants: 602 men and 849 women (average age=75 ±8 years) who were community-dwelling and not clinically demented.Measurements: Blood samples were assayed for trace elements and 12 cognitive function tests were administered. Sex-specific analyses were adjusted for age, education, alcohol consumption, smoking, exercise, and estrogen use in women.Results. Men and women differed significantly in education and alcohol intake (p's<0.001), concentrations of plasma iron, copper and zinc (p's<0.001) and scores on 11 of 12 cognitive function tests (p=0.04 to <0.001). Regression analyses showed significant inverted U-shaped associations in men;both low and high iron levels were associated with poor performance on total and long-term recall and Serial 7's (p's=0.018, 0.042 and 0.004, respectively) compared to intermediate concentrations. In women, iron and copper concentrations had inverse linear associations with Buschke total, long and short-term recall and Blessed scores (p's<0.05). Zinc was positively associated with performance on Blessed Items (p=0.008). Analyses comparing cognitive function using categorically defined mineral concentrations yielded similar sex specific results.Conclusion. Optimal trace element concentrations may exist for optimal cognitive function in older adults, and these levels may differ by sex and cognitive function domain.

A mother's prepregnancy obesity has been suggested as a risk factor for having offspring with an obdominal wall defect. We evaluated this hypothesis among 104 cases of gastroschisis-a severe birth defect of the abdominal wall most prevalent in infants of young women-and 220 controls with no defect. Using Quetelet's index (QI = weight in kg/height in m2) as a measure of body mass, we found a higher risk of gastroschisis (odds ratio (OR) = 3.2; 95% confidence interval (CI) = 1.4-7.3) for underweight mothers $({\\rm QI}\\ <18.1\\ {\\rm kg}/{\\rm m}^{2})$ and a lower risk (OR = 0.2; 0.05-0.9) for overweight mothers $({\\rm QI}\\ >28.3\\ {\\rm kg}/{\\rm m}^{2})$ as compared with mothers of normal weight. As QI was correlated to height, with the correlation varying according to mother's ethnicity and age, we adjusted for these factors in the analysis; the adjusted values approximated the unadjusted values. Evaluation of QI as a continuous variable showed that, for every unit increase in QI, the risk for gastroschisis decreased by about 11%. Sociodemographic, pregnancy, and nutrient factors did not confound the association. These results suggest that low prepregnancy body mass rather than obesity is a risk factor for gastroschisis.

Enterovirus-A71 (EV-A71) is a common cause of hand-foot-and-mouth disease (HFMD) and, rarely, causes severe neurological disease. This study aimed to elucidate the epidemiological and genetic characteristics and virulence of EV-A71 strains isolated from children diagnosed with HFMD. Rectal and throat swabs were collected from 488 children with HFMD in Hanoi, Vietnam, in 2015–2016. From 391 EV-positive patients, 15 EVs, including coxsackievirus A6 (CV-A6; 47.1%) and EV-A71 (32.5%, n = 127), were identified. Of the 127 EV-A71 strains, 117 (92.1%) were the B5 subgenotype and 10 (7.9%) were the C4 subgenotype. A whole-genome analysis of EV-A71 strains showed that seven of the eight C4a strains isolated in 2016 formed a new lineage, including two possible recombinants between EV-A71 C4 and CV-A8. The proportion of inpatients among C4-infected children was higher than among B5-infected children (80.0% vs. 27.4%; P = 0.002). The virulence of EV-A71 strains was examined in human scavenger receptor class B2 (hSCARB2)-transgenic mice, and EV-A71 C4 strains exhibited higher mortality than B5 strains (80.0% vs. 30.0%, P = 0.0001). Thus, a new EV-A71 C4a-lineage, including two possible recombinants between EV-A71 C4 and CV-A8, appeared in 2016 in Vietnam. The EV-A71 C4 subgenotype may be more virulent than the B5 subgenotype.

Marine pollution by various debris is rising in the context of increasing urbanization, industrialization and worldwide trade. Here, we review marine macro-litter with focus on sources, abundance, distribution, and impact on aquatic wildlife, human health, and the economy. We observe that about 75–80% of marine litter originates from land-based sources, including poorly managed landfills and improper disposal. Macro-litter ingestion by marine life is of growing concern, in particular concerning the presence of plastics and associated pollutants, e.g., bisphenol A and phthalates, in fishes. These pollutants are accumulated and transferred to human via seafood. Marine plastic pollution induces a substantial rise of economic costs due to the decline of ecosystem services. Mitigation of marine plastic pollution should be done by following the ten Rs principles of refuse, rethink, reduce, re-use, repair, refurbish, remanufacture, repurpose, recycle, and recover.

Background. Dengue is the most common arboviral infection of humans. There are currently no specific treatments for dengue. Balapiravir is a prodrug of a nucleoside analogue (called R1479) and an inhibitor of hepatitis C virus replication in vivo. Methods. We conducted in vitro experiments to determine the potency of balapiravir against dengue viruses and then an exploratory, dose-escalating, randomized placebo-controlled trial in adult male patients with dengue with <48 hours of fever. Results. The clinical and laboratory adverse event profile in patients receiving balapiravir at doses of 1500 mg (n = 10) or 3000 mg (n = 22) orally for 5 days was similar to that of patients receiving placebo (n = 32), indicating balapiravir was well tolerated. However, twice daily assessment of viremia and daily assessment of NS1 antigenemia indicated balapiravir did not measurably alter the kinetics of these virological markers, nor did it reduce the fever clearance time. The kinetics of plasma cytokine concentrations and the whole blood transcriptional profile were also not attenuated by balapiravir treatment. Conclusions. Although this trial, the first of its kind in dengue, does not support balapiravir as a candidate drug, it does establish a framework for antiviral treatment trials in dengue and provides the field with a clinically evaluated benchmark molecule. Clinical Trials Registration. NCT01096576.

Increased data availability has prompted the creation of clinical decision support systems. These systems utilise clinical information to enhance health care provision, both to predict the likelihood of specific clinical outcomes or evaluate the risk of further complications. However, their adoption remains low due to concerns regarding the quality of recommendations, and a lack of clarity on how results are best obtained and presented. We used autoencoders capable of reducing the dimensionality of complex datasets in order to produce a 2D representation denoted as latent space to support understanding of complex clinical data. In this output, meaningful representations of individual patient profiles are spatially mapped in an unsupervised manner according to their input clinical parameters. This technique was then applied to a large real-world clinical dataset of over 12,000 patients with an illness compatible with dengue infection in Ho Chi Minh City, Vietnam between 1999 and 2021. Dengue is a systemic viral disease which exerts significant health and economic burden worldwide, and up to 5% of hospitalised patients develop life-threatening complications. The latent space produced by the selected autoencoder aligns with established clinical characteristics exhibited by patients with dengue infection, as well as features of disease progression. Similar clinical phenotypes are represented close to each other in the latent space and clustered according to outcomes broadly described by the World Health Organisation dengue guidelines. Balancing distance metrics and density metrics produced results covering most of the latent space, and improved visualisation whilst preserving utility, with similar patients grouped closer together. In this case, this balance is achieved by using the sigmoid activation function and one hidden layer with three neurons, in addition to the latent dimension layer, which produces the output (Pearson, 0.840; Spearman, 0.830; Procrustes, 0.301; GMM 0.321). This study demonstrates that when adequately configured, autoencoders can produce two-dimensional representations of a complex dataset that conserve the distance relationship between points. The output visualisation groups patients with clinically relevant features closely together and inherently supports user interpretability. Work is underway to incorporate these findings into an electronic clinical decision support system to guide individual patient management.