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.).

Spatial Analysis of Drug-Susceptible and Multidrug-Resistant Cases of Tuberculosis, Ho Chi Minh City, Vietnam, 2020-2023.

We characterized the spatial distribution of drug-susceptible (DS) and multidrug-resistant (MDR) tuberculosis (TB) cases in Ho Chi Minh City, Vietnam, a major metropolis in southeastern Asia, and explored demographic and socioeconomic factors associated with local TB burden. Hot spots of DS and MDR TB incidence were observed in the central parts of Ho Chi Minh City, and substantial heterogeneity was observed across wards. Positive spatial autocorrelation was observed for both DS TB and MDR TB. Ward-level TB incidence was associated with HIV prevalence and the male proportion of the population. No ward-level demographic and socioeconomic indicators were associated with MDR TB case count relative to total TB case count. Our findings might inform spatially targeted TB control strategies and provide insights for generating hypotheses about the nature of the relationship between DS and MDR TB in Ho Chi Minh City and the wider southeastern region of Asia.

Observation of magnet-induced star-like radiation of a plasma created from cancer cells in a laser trap.

We present a new phenomenon resulting from the interaction of magnetic beads with cancer cells in a laser trap formed on a slide containing a depression 16.5 mm in diameter and 0.78 mm of maximum depth. This phenomenon includes the apparent formation and expansion of a dark bubble that attracts and incinerates surrounding matter when it explodes, which leads to a plasma emitting intense radiation that has the appearance of a star on a microscopic scale. We have observed the star-like phenomenon for more than 4 years, and the intensity depends on the laser's power. Measuring the laser power of the dark bubble shows the entrapment of electromagnetic energy as it expands.

Bone marrow adipose tissue is associated with fracture history in anorexia nervosa.

Although bone mineral density (BMD) is decreased and fracture risk increased in anorexia nervosa, BMD does not predict fracture history in this disorder. We assessed BMD, bone microarchitecture, and bone marrow adipose tissue (BMAT) in women with anorexia nervosa and found that only BMAT was associated with fracture history. INTRODUCTION: Anorexia nervosa (AN) is a psychiatric disorder characterized by low body weight, low BMD, and increased risk of fracture. Although BMD is reduced and fracture risk elevated, BMD as assessed by DXA does not distinguish between individuals with versus those without prior history of fracture in AN. Despite having decreased peripheral adipose tissue stores, individuals with AN have enhanced bone marrow adipose tissue (BMAT), which is inversely associated with BMD. Whether increased BMAT is associated with fracture in AN is not known. METHODS: We conducted a cross-sectional study in 62 premenopausal women, including 34 with AN and 28 normal-weight women of similar age. Fracture history was collected during patient interviews and BMD measured by DXA, BMAT by 1H-MRS, and parameters of bone microarchitecture by HR-pQCT. RESULTS: Sixteen women (47.1%) with AN reported prior history of fracture compared to 11 normal-weight women (39.3%, p = 0.54). In the entire group and also the subset of women with AN, there were no significant differences in BMD or parameters of bone microarchitecture in women with prior fracture versus those without. In contrast, women with AN with prior fracture had greater BMAT at the spine and femur compared to those without (p = 0.01 for both). CONCLUSION: In contrast to BMD and parameters of bone microarchitecture, BMAT is able to distinguish between women with AN with prior fracture compared to those without. Prospective studies will be necessary to understand BMAT's potential pathophysiologic role in the increased fracture risk in AN.

Strong-field molecular ionization beyond the single active electron approximation.

This work explores quantitative limits to the single-active electron approximation, often used to deal with strong-field ionization and subsequent attosecond dynamics. Using a time-dependent, multiconfiguration approach, specifically the time-dependent configuration interaction method, we solve the time-dependent Schrödinger equation for the two-electron dihydrogen molecule with the possibility of tuning at will the electron-electron interaction by an adiabatic switch-on/switch-off function. We focus on signals of the single ionization of H2 under a strong near-infrared, four-cycle, linearly polarized laser pulse of varying intensity and within a vibrationally frozen molecular model. The observables we address are post-pulse total ionization probability profiles as a function of the laser peak intensity. Three values of the internuclear distance R taken as a parameter are considered, R = Req = 1.4 a.u. for the equilibrium geometry of the molecule, R = 5.0 a.u. for an elongated molecule, and R = 10.2 a.u. for a dissociating molecule. The most striking observation is the non-monotonous behavior of the ionization probability profiles at intermediate elongation distances with an instance of enhanced ionization and one of partial ionization quenching. We give an interpretation of this in terms of a resonance-enhanced-multiphoton ionization mechanism with interfering overlapping resonances resulting from excited electronic states.

Using the health beliefs model to explore children's attitudes and beliefs on air pollution.

OBJECTIVES: Traffic-related air pollution (TRAP) negatively impacts children's health. Self-protective measures are available, but population uptake is variable. It is essential to understand human beliefs and behaviours related to air pollution in order to understand the lack of self-protection in communities. As a prelude to undertaking a comprehensive assessment of children's attitudes and beliefs on the health effects of TRAP exposure, we sought to develop and validate an appropriate instrument. STUDY DESIGN: This study used exploratory sequential mixed methods. METHODS: This instrument, based on the constructs of the health belief model (HBM), aimed to determine factors predicting wearing a mask to protect against TRAP exposure. An initial literature-based questionnaire was modified using in-depth interviews, focus group discussions, and a quantitative survey pilot. This study included 121 school students and nine professional experts in Vietnam. The questionnaire was tested for content validity, agreement, test-retest reliability, and internal consistency. RESULTS: The concordance of questionnaire items between two repeated assessments ranged from 47.2% to 78.3%, intraclass correlation coefficients ranged from 0.16 to 0.87 and Cronbach's internal reliability coefficient for the instrument was 0.60. CONCLUSION: The self-administered instrument, based on the HBM, is suitable to understand health attitudes and beliefs related to self-protective behaviours to reduce TRAP exposure.

Sources of Multidrug Resistance in Patients With Previous Isoniazid-Resistant Tuberculosis Identified Using Whole Genome Sequencing: A Longitudinal Cohort Study.

BACKGROUND: Meta-analysis of patients with isoniazid-resistant tuberculosis (TB) given standard first-line anti-TB treatment indicated an increased risk of multidrug-resistant TB (MDR-TB) emerging (8%), compared to drug-sensitive TB (0.3%). Here we use whole genome sequencing (WGS) to investigate whether treatment of patients with preexisting isoniazid-resistant disease with first-line anti-TB therapy risks selecting for rifampicin resistance, and hence MDR-TB. METHODS: Patients with isoniazid-resistant pulmonary TB were recruited and followed up for 24 months. Drug susceptibility testing was performed by microscopic observation drug susceptibility assay, mycobacterial growth indicator tube, and by WGS on isolates at first presentation and in the case of re-presentation. Where MDR-TB was diagnosed, WGS was used to determine the genomic relatedness between initial and subsequent isolates. De novo emergence of MDR-TB was assumed where the genomic distance was 5 or fewer single-nucleotide polymorphisms (SNPs), whereas reinfection with a different MDR-TB strain was assumed where the distance was 10 or more SNPs. RESULTS: Two hundred thirty-nine patients with isoniazid-resistant pulmonary TB were recruited. Fourteen (14/239 [5.9%]) patients were diagnosed with a second episode of TB that was multidrug resistant. Six (6/239 [2.5%]) were identified as having evolved MDR-TB de novo and 6 as having been reinfected with a different strain. In 2 cases, the genomic distance was between 5 and 10 SNPs and therefore indeterminate. CONCLUSIONS: In isoniazid-resistant TB, de novo emergence and reinfection of MDR-TB strains equally contributed to MDR development. Early diagnosis and optimal treatment of isoniazid-resistant TB are urgently needed to avert the de novo emergence of MDR-TB during treatment.

Intensified Antituberculosis Therapy in Adults with Tuberculous Meningitis.

BACKGROUND: Tuberculous meningitis is often lethal. Early antituberculosis treatment and adjunctive treatment with glucocorticoids improve survival, but nearly one third of patients with the condition still die. We hypothesized that intensified antituberculosis treatment would enhance the killing of intracerebral Mycobacterium tuberculosis organisms and decrease the rate of death among patients. METHODS: We performed a randomized, double-blind, placebo-controlled trial involving human immunodeficiency virus (HIV)-infected adults and HIV-uninfected adults with a clinical diagnosis of tuberculous meningitis who were admitted to one of two Vietnamese hospitals. We compared a standard, 9-month antituberculosis regimen (which included 10 mg of rifampin per kilogram of body weight per day) with an intensified regimen that included higher-dose rifampin (15 mg per kilogram per day) and levofloxacin (20 mg per kilogram per day) for the first 8 weeks of treatment. The primary outcome was death by 9 months after randomization. RESULTS: A total of 817 patients (349 of whom were HIV-infected) were enrolled; 409 were randomly assigned to receive the standard regimen, and 408 were assigned to receive intensified treatment. During the 9 months of follow-up, 113 patients in the intensified-treatment group and 114 patients in the standard-treatment group died (hazard ratio, 0.94; 95% confidence interval, 0.73 to 1.22; P=0.66). There was no evidence of a significant differential effect of intensified treatment in the overall population or in any of the subgroups, with the possible exception of patients infected with isoniazid-resistant M. tuberculosis. There were also no significant differences in secondary outcomes between the treatment groups. The overall number of adverse events leading to treatment interruption did not differ significantly between the treatment groups (64 events in the standard-treatment group and 95 events in the intensified-treatment group, P=0.08). CONCLUSIONS: Intensified antituberculosis treatment was not associated with a higher rate of survival among patients with tuberculous meningitis than standard treatment. (Funded by the Wellcome Trust and the Li Ka Shing Foundation; Current Controlled Trials number, ISRCTN61649292.).

Twelve-day medium pumping into tubular cell-laden scaffold using a lab-made PDMS connector.

In the current study, a method is proposed to supply culture medium into a two-layered cell-laden tubular scaffold in order to enhance cell proliferation, confluence, and viability. The two-layered cell-laden tubular scaffold was made of calcium-alginate mixed with fibroblast cells (NIH/3T3) using a lab-made double- coaxial laminar-flow generator. Afterwards, the tubular scaffold was connected to a syringe pump system using a polydimethylsiloxane (PDMS) micro-connector for long-term cell culture. Three medium pumping conditions were applied and compared: a heart-beat-mimicking pumping (20 µL/s, 1 s period, and 50 % pulse width), a continuous pumping (20 µL/s) and a non-pumping. Non-leaky connections between the tubular scaffolds and the micro-connector outlet were sustained for 13.5 ± 0.83 d in heartbeat-mimicking pumping and 11.8 ± 0.33 d in continuous pumping condition, due to the elasticity of the tubular scaffolds. Importantly, the two pumping conditions resulted in more cell proliferation, confluence, and viability than the non-pumping condition. Furthermore, analysis of newly-produced type-I collagen matrix indicated that the cells under the two pumping conditions formed a tissue-like structure. The proposed technique could further be applied to vascular co-culturing for vascular engineered tissue.

Autism-associated Dyrk1a truncation mutants impair neuronal dendritic and spine growth and interfere with postnatal cortical development.

Autism is a prevailing neurodevelopmental disorder with a large genetic/genomic component. Recently, the dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A (DYRK1A) gene was implicated as a risk factor for autism spectrum disorder (ASD). We identified five DYRK1A variants in ASD patients and found that the dose of DYRK1A protein has a crucial role in various aspects of postnatal neural development. Dyrk1a loss of function and gain of function led to defects in dendritic growth, dendritic spine development and radial migration during cortical development. Importantly, two autism-associated truncations, R205X and E239X, were shown to be Dyrk1a loss-of-function mutants. Studies of the truncated Dyrk1a mutants may provide new insights into the role of Dyrk1a in brain development, as well as the role of Dyrk1a loss of function in the pathophysiology of autism.

Progress towards rabies control and elimination in Vietnam.

Rabies is a fatal viral disease that causes an estimated 59,000 human deaths each year. The majority of these deaths occur in developing countries in Asia. Canine rabies is endemic to Vietnam, which is, however, moving towards the disease's elimination. Many countries, such as Vietnam, have invested tremendous resources in controlling rabies, highlighting the goal of regional and global elimination of this neglected disease. In Vietnam, rabies is recognised as one of five high-priority, zoonotic diseases by the Ministry of Health and the Ministry of Agriculture and Rural Development. Investment by the government and by international partners for rabies prevention and control has played a substantial role in reducing human rabies deaths from 404 cases in 1992 to 74 cases in 2017. The catalyst for this effort was the Prime Minister's creation of the National Rabies Program in 1996, which led to increased support and resources for rabies prevention and control. Interventions carried out since then include the expansion of post-exposure prophylaxis centres throughout the country, the introduction or revision of key legislation and guidelines, and improved multisectoral One Health collaboration. In addition, support from international partners, such as the World Organisation for Animal Health (OIE), the World Health Organization (WHO), the Food and Agriculture Organization of the United Nations (FAO), and the Centers for Disease Control and Prevention (CDC), has helped to increase awareness, manage dog populations more effectively, and improve Vietnam's surveillance and diagnostic capabilities. To pursue the goal of eliminating dog-mediated rabies in Vietnam, political commitment is crucial. Resources must be made available to enforce the regulations and guidelines that will enable Vietnam to achieve greater canine rabies vaccination coverage. In this paper, the authors provide an overview of the animal and human health systems in Vietnam, as well as past, current and future directions of rabies prevention and control.

La rage est une maladie virale à l'issue mortelle faisant chaque année un nombre estimé de 59 000 victimes humaines. La plupart de ces décès surviennent dans les pays en développement d'Asie. Au Vietnam, la rage canine est endémique mais le pays poursuit activement l'objectif d'éliminer la rage de son territoire. À l'instar du Vietnam, plusieurs pays ont investi des ressources colossales pour contrôler la rage, renforçant ainsi la dimension régionale et mondiale de l'objectif d'élimination de cette maladie négligée. Au Vietnam, la rage figure parmi les cinq zoonoses hautement prioritaires prises en compte par le ministère de la Santé et le ministère de l'Agriculture et du développement rural. Les investissements consacrés à la prévention et au contrôle de la rage par le gouvernement et ses partenaires internationaux ont joué un rôle déterminant dans la réduction du nombre de décès humains dus à la rage, qui est passé de 404 cas en 1992 à 74 cas en 2017. L'élément catalyseur de cet effort a été la création en 1996 du Programme national de lutte contre la rage par le premier ministre de l'époque, ce qui a permis de renforcer les ressources et le soutien dédiés à la prévention et à la lutte contre la rage. Depuis lors, les interventions ont porté sur la création de centres de prophylaxie post-exposition sur tout le territoire, l'introduction ou la révision de la législation et des lignes directrices applicables et l'amélioration de la collaboration Une seule santé. En outre, le soutien de partenaires internationaux tels que l'Organisation mondiale de la santé animale (OIE), l'Organisation mondiale de la santé (OMS), l'Organisation des Nations Unies pour l'alimentation et l'agriculture (FAO) et les Centres pour le contrôle et la prévention des maladies (CDC, États-Unis d'Amérique) a abouti à une meilleure sensibilisation, à une gestion plus efficace des populations de chiens et à un renforcement des capacités de surveillance et de diagnostic au Vietnam. Un engagement politique fort est indispensable pour réussir à éliminer totalement la rage transmise par les chiens au Vietnam. Des ressources doivent être rendues disponibles afin de mettre en oeuvre la réglementation et les lignes directrices pertinentes et d'augmenter ainsi la couverture vaccinale de la population canine du pays. Les auteurs décrivent les systèmes de santé animale et publique du Vietnam ainsi que les orientations passées, actuelles et futures de la prévention et du contrôle de la rage dans le pays.

La rabia es una enfermedad vírica fatal, que según las estimaciones mata a 59 000 personas al año, mayoritariamente en países en desarrollo asiáticos. La rabia canina es endémica en el Vietnam, país que no obstante avanza ahora hacia la eliminación de la enfermedad. Como el Vietnam, muchos países han invertido cantidades colosales de recursos en la lucha antirrábica, subrayando con ello su compromiso con el objetivo de eliminar esta enfermedad desatendida a escala regional y mundial. El Ministerio de Salud y el Ministerio de Agricultura y Desarrollo Rural del Vietnam tienen catalogada la rabia como una de las cinco enfermedades zoonóticas que revisten máxima prioridad. Las inversiones en prevención y control de la rabia realizadas por el gobierno y por asociados internacionales han ayudado sensiblemente a reducir el número de personas muertas por la rabia, que ha pasado de 404 casos en 1992 a 74 en 2017. El catalizador de este esfuerzo fue la creación en 1996, por iniciativa del Primer Ministro, del Programa Nacional contra la Rabia, que se tradujo en un aumento del apoyo y los recursos destinados a prevenir y combatir la enfermedad. Entre otras intervenciones, desde entonces se ha multiplicado en todo el país el número de centros donde se dispensa profilaxis tras la exposición, se han promulgado o revisado leyes, decretos y directrices fundamentales y se ha mejorado la colaboración multisectorial en clave de Una sola salud. Además, el respaldo de asociados internacionales como la Organización Mundial de Sanidad Animal (OIE), la Organización Mundial de la Salud (OMS), la Organización de las Naciones Unidas para la Alimentación y la Agricultura (FAO) o los Centros para el Control y la Prevención de Enfermedades (CDC) de los Estados Unidos ha ayudado a generar una mayor conciencia del problema, a gestionar más eficazmente las poblaciones de perros y a dotar al país de mejores medios de vigilancia y diagnóstico. Para hacer realidad el objetivo de eliminar del Vietnam la rabia transmitida por perros, la voluntad política es un factor clave, pues hay que poner sobre la mesa los recursos necesarios para aplicar los reglamentos y normas que permitirán al país ampliar la cobertura de vacunación canina antirrábica. Tras trazar una panorámica de los sistemas sanitario y zoosanitario del Vietnam, los autores describen el rumbo pasado, presente y futuro de las labores de prevención y control de la rabia en el país.

Prediction of Zika-confirmed cases in Brazil and Colombia using Google Trends.

Zika virus infection in humans has been linked to severe neurological sequels and foetal malformations. The rapidly evolving epidemics and serious complications made the frequent updates of Zika virus mandatory. Web search query has emerged as a low-cost real-time surveillance system to anticipate infectious diseases' outbreaks. Hence, we developed a prediction model that could predict Zika-confirmed cases based on Zika search volume in Google Trends. We extracted weekly confirmed Zika cases of two epidemic countries, Brazil and Colombia. We got the weekly Zika search volume in the two countries from Google Trends. We used standard time-series regression (TSR) to predict the weekly confirmed Zika cases based on the Zika search volume (Zika query). The basis TSR model - using 1-week lag of Zika query and using 1-week lag of Zika cases as a control for autocorrelation - was the best for predicting Zika cases in Brazil and Colombia because it balanced the performance of the model and the advance time in the prediction. Our results showed that we could use Google search queries to predict Zika cases 1 week earlier before the outbreak. These findings are important to help healthcare authorities evaluate the outbreak and take necessary precautions.

Virulent bacteriophage of Edwardsiella ictaluri isolated from kidney and liver of striped catfish Pangasianodon hypophthalmus in Vietnam.

Striped catfish Pangasianodon hypophthalmus farmed in the Mekong Delta, Vietnam, represents an important contribution to Vietnamese aquaculture exports. However, these fish are affected by frequent disease outbreaks across the entire region. One of the most common infections involves white spots in the internal organs, caused by the bacterium Edwardsiella ictaluri. In this study, a virulent phage specific to E. ictaluri, designated MK7, was isolated from striped catfish kidney and liver samples and characterized. Morphological analysis indicates probable placement in the family Myoviridae with a 65 nm icosahedral head and a 147 %%CONV_ERR%% 19 nm tail. A double-stranded DNA genome of approximately 34 kb was predicted by restriction fragment analysis following digestion with SmaI. The adsorption affinity (ka) of the MK7 phage was estimated as 1.6 %%CONV_ERR%% 10-8 ml CFU-1 min-1, and according to a 1-step growth curve, its latent period and burst size were ~45 min and ~55 phage particles per infected host cell, respectively. Of the 17 bacterial strains tested, MK7 only infected E. ictaluri, although other species of Edwardsiella were not tested. E. ictaluri was also challenged in vitro, in both broth and water from a striped catfish pond and was inactivated by MK7 for 15 h in broth and 51 h in pond water. Thus, initial characterization of phage MK7 indicates its potential utility as a biotherapeutic agent against E. ictaluri infection in striped catfish. This is the first report of a lytic phage specific to an important striped catfish pathogen.

Vascularized Heterodigital Island Flap for Fingertip and Dorsal Finger Reconstruction.

A heterodigital vascularized island flap can functionally restore large soft tissue defects to the injured fingertip in a single stage. It is optimally used for digits of unequal length so that the donor fingertip is not violated, and the skin island is best taken from the less dominant side of the donor finger. Because it is a transposition flap with a proximal axis of rotation, its transposition arc can also reach the dorsum of an adjacent digit. This article describes how the heterodigital arterialized flap preserves the donor finger digital nerve and distal pulp, thus reducing donor site morbidity. Indications, method of flap elevation, and flap design will be reviewed to optimize case selection, minimize donor site morbidity, and enhance safety of flap elevation and transposition.

Rates and risk factors for recurrent pneumonia in patients hospitalized with community-acquired pneumonia: population-based prospective cohort study with 5 years of follow-up.

BACKGROUND: The rates and risk factors for developing recurrent pneumonia following hospitalization with community-acquired pneumonia (CAP) are poorly understood. METHODS: We examined a population-based cohort of patients with CAP who survived hospital admission and who were free of pneumonia for at least 3 months. We collected clinical, functional, and medication-related information and pneumonia severity index (PSI). Using linked databases we followed patients for 5 years and captured any clinical episode of pneumonia 90 days or more post-discharge. We used Cox proportional hazards models (adjusted for age, sex, PSI, functional status, medications) to determine rates and independent correlates of recurrent pneumonia. RESULTS: The final cohort included 2709 inpatients; 43% were 75 years or older, 34% were not fully independent, and 56% had severe pneumonia. Over 5 years of follow-up, 245 (9%; 95% confidence interval [CI], 8%-10%) patients developed recurrent pneumonia, and 156 (64%) of these episodes required hospitalization. Rate of recurrence was 3.0/100 person-years and median time to recurrence was 317 days (interquartile range, 177-569); 32 (13%) patients had 2 or more recurrences. In multivariable analyses only age >75 years (adjusted P = .047) and less than fully independent functional status (12% recurrence rate with impaired functional status vs 7% for fully independent; adjusted hazard ratio, 1.7; 95% CI, 1.3-2.2; P < .001) were significantly associated with recurrent pneumonia. CONCLUSIONS: One of 11 patients who survived CAP hospitalization had recurrent pneumonia over 5 years and those with impaired functional status were at particularly high risk. Recurrent pneumonia is common and more attention to preventive strategies at discharge and closer follow-up over the long-term seem warranted.

Effect of natural organic matter on iron uptake by the freshwater cyanobacterium Microcystis aeruginosa.

The mode of Fe uptake by the cyanobacterium Microcystis aeruginosa cultured in Fraquil* (pH 8) containing Suwannee River fulvic acid (SRFA) was examined using short-term radiolabeled (55)Fe uptake assays and a kinetic model that describes extracellular Fe transformations. Both Fe(II) and Fe(III) uptake rates decreased substantially with increasing SRFA concentration as the availability of unchelated Fe decreased due to complexation by SRFA. Fe uptake rates under illuminated conditions were comparable to or slightly higher than those observed in the dark at the same Fe:SRFA concentration ratio, in contrast to results for systems containing ethylenediaminetetraacetic acid where Fe uptake rates were much greater under illumination than in the dark. The limited effect of light principally resulted from the relatively high rates of thermal dissociation and dark reduction of Fe(III) bound to SRFA and complexation of photogenerated Fe(II) by SRFA. Our findings imply that Fe uptake by M. aeruginosa at a fixed total Fe concentration of 200 nM is close to saturation when fulvic acid is present at concentrations near those typically found in natural waters (< ∼5 mg·L(-1)), with cellular growth likely to be limited by Fe availability only when natural organic matter is present at very high concentrations (>25 mg·L(-1)).

Impact of sitting at work on musculoskeletal complaints of German workers - results from the study on mental health at work (S-MGA).

INTRODUCTION: Sedentary behavior (including prolonged sitting) is a form of physical inactivity that has a negative impact on health, possibly including musculoskeletal complaints (MSCs). The purpose of this study was to determine the extent to which time spent sitting at work is associated with the one-year prevalence of MSCs in the neck, shoulder, upper back/thoracic spine, and lower back among workers from the Study of Mental Health in the Workplace (S-MGA). In addition, the study also examined whether leisure time, physical activity, and sex modify the relationship between occupational sitting and MSCs. METHODS: For this analysis, we used the S-MGA, a 5-year prospective study in Germany. The S-MGA is a nationwide representative employee cohort study with a baseline survey in 2012 and a follow-up survey in 2017. Sitting at work was measured using a question asked at baseline. The Nordic Musculoskeletal Questionnaire was used to determine the one-year prevalence of MSCs in the neck, shoulder, upper back, and lower back pain (yes/no). The assessment of MSCs was only conducted at the 2017 follow-up. Adjusted Poisson regression models were used to determine the association of baseline level of weekly hours spent sitting at work with MSCs during follow-up. In addition to unadjusted models, models were adjusted for demographic (age, sex, body mass index and occupational skill level), occupational (heavy lifting at work), psychological disorders and lifestyle factors (smoking status and leisure time physical activity), as well as preexisting musculoskeletal conditions reported at baseline. To examine whether the relationship between sitting time and pain was modified by sex and leisure time physical activity, the models were stratified for both these variables. RESULTS: Among the participants analyzed (n = 2,082), 49.8% were male, while 50.2% were female, and more than 60% of the study population spent over half of their working hours in a sitting position. Exposure to increased sitting at work reported at baseline was not consistently associated with 12-month prevalence of MSCs in the upper body at follow-up. However, differences in the association between occupational sitting and MSCs were dependent on the intensity of leisure time physical activity. Prevalence ratios (PRs) indicated an increased prevalence of MSC in the neck (PR = 1.46; 95% CI = 1.18-1.80) and shoulder (PR = 1.30; 95% CI = 1.03-1.64) in workers without leisure time physical activity who spent 25 to < 35 weekly working hours sitting. DISCUSSION: These findings suggest that leisure time physical activity interacts with the relationship between sitting at work and MSCs. The relationship between sitting at work and musculoskeletal pain needs further investigation, but we found indications that leisure time physical activity may counter the effects of sitting at work.

Characterization of plasma cytokines in an infant population cohort of challenge-proven food allergy.

BACKGROUND: Sensitization to food allergens indicates the production of food-specific IgE; however, sensitization is not a definite indicator of allergic reaction upon ingestion (N Engl J Med, 344, 2001, 30: J Allergy Clin Immunol, 120, 2007, 491). Currently, food challenge is the best approach to identify the presence or absence of allergy. While 95% positive predictive values (PPVs) thresholds for sIgE can assist with identifying increased likelihood of allergy among those who are sensitized, there are no specific biological markers that differentiate between allergic and sensitized individuals. OBJECTIVES: To determine whether plasma serum cytokine profiles predict (i) sensitization to peanut and egg and (ii) food allergy among sensitized infants. METHODS: Peanut-sensitized (PT) and egg-sensitized 14-month-old infants and nonsensitized controls enrolled in HealthNuts, a population-based study of food allergy, underwent an oral food challenge (OFC). Blood was collected within 1 h after OFC. Serum levels of Th1, Th2 and regulatory cytokines were determined in allergic (n = 79), sensitized (n = 40) and nonsensitized, nonallergic (n = 37) infants by multiplex assay. RESULTS: Food-sensitized infants had significantly higher plasma IL-4, IL-13, IL-12p70 and lower IL-10 levels compared to nonsensitized infants. IL-10 and IL-6 levels were significantly higher in sensitized compared with allergic infants. Egg-allergic infants had significantly higher IL-13 and IL-12p70 levels compared to peanut-allergic (PA) infants. CONCLUSION: Levels of Th2-related cytokines in plasma are higher in food-sensitized infants, irrespective of clinical food allergy status. In contrast, IL-10 levels appear to predict food allergy among sensitized infants. Differences in IL-13 and IL-12p70 between egg- and peanut-allergic infants could help explain the different resolution rates of the allergies.

Computer controlled expansion of equine cord blood mesenchymal stromal cells on microcarriers in 3 L vertical-wheel® bioreactors.

Mesenchymal stromal cells (MSCs) are an ideal cell source for allogenic cell therapy due to their immunomodulatory and differentiation properties. Equine MSCs (eMSCs) have been found to be a promising treatment for equine joint injuries including meniscal injuries, cartilage degradation, and osteoarthritis. Although the use of eMSCs has shown efficacy in preliminary studies, challenges associated with biomanufacturing remain. To achieve the required cell numbers for clinical application, bioreactor-based processes are required. Initial studies have shown that eMSCs can be cultivated in microcarrier-based, stirred suspension bioreactor culture at the laboratory 0.1 L scale using a Vertical-Wheel® (VW) bioreactor. However, investigations regarding scale up of these processes to the required biomanufacturing scales are required. This study investigated the scale-up of a equine cord blood MSC (eCB-MSC) bioprocess in VW bioreactors at three scales. This included scale-up from the 0.1-0.5 L bioreactor, scale-up from static culture to the 3 L computer-controlled bioreactor, and scale-up into the 3 L computer-controlled bioreactor using a mock clinical trial process. Results from the various scale-up experiments demonstrated similar cell expansion at the various tested scales. The 3 L computer-controlled system resulted in a final cell densities of 1.5 × 105 cells/cm2 on average, achieving 1.5 × 109 harvested cells. Biological testing of the cells showed that cell phenotype and functionality were maintained after scale-up. These findings demonstrate the scalability of an eCB-MSC bioprocess using microcarriers in VW bioreactors to achieve clinically relevant cell numbers, a critical step to translate MSC treatments from research to clinical applications. This study also represents the first known published study expanding any cell type in the 3 L VW bioreactor.

On Fusogenicity of Positively Charged Phased-Separated Lipid Vesicles: Experiments and Computational Simulations.

This paper studies the fusogenicity of cationic liposomes in relation to their surface distribution of cationic lipids and utilizes membrane phase separation to control this surface distribution. It is found that concentrating the cationic lipids into small surface patches on liposomes, through phase-separation, can enhance liposome's fusogenicity. Further concentrating these lipids into smaller patches on the surface of liposomes led to an increased level of fusogenicity. These experimental findings are supported by numerical simulations using a mathematical model for phase-separated charged liposomes. Findings of this study may be used for design and development of highly fusogenic liposomes with minimal level of toxicity.