Compromised heat loss leads to a delayed ice slurry induced reduction in heat storage.

Compromised heat loss due to limited convection and evaporation can increase thermal strain. We aimed to determine the effectiveness of ice slurry ingestion to reduce thermal strain following hyperthermia in a state of compromised heat loss. Twelve healthy males (age: 25 ± 4y) underwent hot water immersion to elevate rectal temperature (Trec) by 1.82 ± 0.08°C on four occasions. In the subsequent 60-min of seated recovery, participants ingested either 6.8 g·kg-1 of ice slurry (-0.6°C) or control drink (37°C) in ambient conditions (21 ± 1°C, 39 ± 10% relative humidity), wearing either t-shirt and shorts (2 trials: ICE and CON) or a whole-body sweat suit (2 trials: ICE-SS and CON-SS). Trec and mean skin temperature (Tsk) were recorded and a two-compartment thermometry model of heat storage was calculated. Heat storage was lower in ICE compared with CON at 20-40min (p ≤ 0.044, d ≥ 0.88) and for ICE-SS compared with CON-SS at 40-60 min (p ≤ 0.012, d ≥ 0.93). Trec was lower in ICE compared with CON from 30-60min (p ≤ 0.034, d ≥ 0.65), with a trend for a reduced Trec in ICE-SS compared with CON-SS at 40min (p = 0.079, d = 0.60). A greater Tsk was found in ICE-SS and CON-SS compared with ICE and CON (p < 0.001, d ≥ 3.37). A trend for a lower Tsk for ICE compared with CON was found at 20-40min (p ≤ 0.099, d ≥ 0.53), no differences were found for ICE-SS vs CON-SS (p ≥ 0.554, d ≤ 0.43). Ice slurry ingestion can effectively reduce heat storage when heat loss through convection and evaporation is compromised, relevant to those wearing personal protective equipment or those with compromised sweat loss. Compromised heat loss delays the reduction in heat storage, possibly related to ice slurry ingestion not lowering Tsk.

Differential impact of perfluorooctanoic acid and fluorotelomer ethoxylates on placental metabolism in mice.

Poly- and perfluoroalkyl substances (PFAS) are a group of compounds with uses in industry and many consumer products. Concerns about the potential health effects of these compounds resulted in regulation by the Stockholm Convention on the use of three of the most common PFAS, including perfluorooctanoic acid (PFOA). Thousands of PFAS remain in production that are unregulated and for which their toxicity is unknown. Our group recently identified a new class of PFAS, fluorotelomer ethoxylates (FTEOs), in indoor dust and industrial wastewater. In this study, we investigated the effect of PFAS on placental metabolism by exposing healthy, pregnant CD-1 mice to PFOA or FTEOs at one of three concentrations (0 ng/L (controls), 5 ng/L, 100 ng/L) (n = 7-8/group). While PFOA is banned and PFOA concentrations in human blood are decreasing, we hypothesize that FTEOs will cause adverse pregnancy outcomes similar to PFOA, the compounds they were meant to replace. Placental tissue samples were collected at embryonic day 17.5 and 1H solid-state magic angle spinning nuclear magnetic resonance spectroscopy was used to determine the relative concentration of placental metabolites (n = 18-20/group). At the highest concentration, the relative concentrations of glucose and threonine were increased and the relative concentration of creatine was decreased in the PFOA-exposed placentas compared to controls (p < 0.05). In contrast, the relative concentrations of asparagine and lysine were decreased and the relative concentration of creatine was increased in the FTEOs-exposed placentas compared to controls (p < 0.05). Partial least squares - discriminant analysis showed the FTEOs-exposed and control groups were significantly separated (p < 0.005) and pathway analysis found four biochemical pathways were perturbed following PFOA exposure, while one pathway was altered following FTEOs exposure. Maternal exposure to PFOA and FTEOs had a significant impact on the placental metabolome, with the effect depending on the pollutant. This work motivates further studies to determine exposure levels and evaluate associations with adverse outcomes in human pregnancies.

RTN2 deficiency results in an autosomal recessive distal motor neuropathy with lower limb spasticity.

Heterozygous RTN2 variants have been previously identified in a limited cohort of families affected by autosomal dominant spastic paraplegia (SPG12-OMIM:604805) with a variable age of onset. Nevertheless, the definitive validity of SPG12 remains to be confidently confirmed due to the scarcity of supporting evidence. In this study, we identified and validated seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven consanguineous families with distal hereditary motor neuropathy (dHMN) using exome, genome and Sanger sequencing coupled with deep-phenotyping. All affected individuals (seven males and seven females, aged 9-50 years) exhibited weakness in the distal upper and lower limbs, lower limb spasticity and hyperreflexia, with onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography. Despite a slowly progressive disease course, all patients remained ambulatory over a mean disease duration of 19.71 ± 13.70 years. Characterization of Caenorhabditis elegans RTN2 homologous loss-of-function variants demonstrated morphological and behavioural differences compared with the parental strain. Treatment of the mutant with an endoplasmic/sarcoplasmic reticulum Ca2+ reuptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences, suggesting a potential therapeutic benefit for RTN2-disorder. Despite RTN2 being an endoplasmic reticulum (ER)-resident membrane shaping protein, our analysis of patient fibroblast cells did not find significant alterations in ER structure or the response to ER stress. Our findings delineate a distinct form of autosomal recessive dHMN with pyramidal features associated with RTN2 deficiency. This phenotype shares similarities with SIGMAR1-related dHMN and Silver-like syndromes, providing valuable insights into the clinical spectrum and potential therapeutic strategies for RTN2-related dHMN.

Whole genome sequencing and genotyping Klebsiella pneumoniae multi-drug resistant hospital isolates from Western Kenya.

Objectives: Klebsiella pneumoniae are a frequent cause of nosocomial infections worldwide. Sequence type 147 (ST147) has been reported as a major circulating high-risk lineage in many countries, and appears to be a formidable platform for the dissemination of antimicrobial resistance (AMR) determinants. However, the distribution of this pathogen in Western African hospitals has been scarcely studied. The main objective of this work was to perform whole genome sequencing of K. pneumoniae isolates from a referral hospital in Kakamega (Kenya) for genotyping and identification of AMR and virulence determinants. Methods: In total, 15 K. pneumoniae isolates showing a broad spectrum antimicrobial resistance were selected for whole genome sequencing by Illumina HiSeq 2500 platform. Results: ST147 was the dominant lineage among the highly-resistant K. pneumoniae isolates that we sequenced. ST147 was associated with both community- and the hospital-acquired infections, and with different infection sites, whereas other STs were predominantly uropathogens. Multiple antibiotic resistance and virulence determinants were detected in the genomes including extended-spectrum ß-lactamases (ESBL) and carbapenemases. Many of these genes were plasmid-borne. Conclusions: Our data suggest that the evolutionary success of ST147 may be linked with the acquisition of broad host-range plasmids, and their propensity to accrue AMR and virulence determinants. Although ST147 is a dominant lineage in many countries worldwide, it has not been previously reported as prevalent in Africa. Our data suggest an influx of new nosocomial pathogens with new virulence genes into African hospitals from other continents.

Maternal exposure to polyethylene micro- and nanoplastics impairs umbilical blood flow but not fetal growth in pregnant mice.

While microplastics have been recently detected in human blood and the placenta, their impact on human health is not well understood. Using a mouse model of environmental exposure during pregnancy, our group has previously reported that exposure to polystyrene micro- and nanoplastics throughout gestation results in fetal growth restriction. While polystyrene is environmentally relevant, polyethylene is the most widely produced plastic and amongst the most commonly detected microplastic in drinking water and human blood. In this study, we investigated the effect of maternal exposure to polyethylene micro- and nanoplastics on fetal growth and placental function. Healthy, pregnant CD-1 dams were divided into three groups: 106 ng/L of 740-4990 nm polyethylene with surfactant in drinking water (n = 12), surfactant alone in drinking water (n = 12) or regular filtered drinking water (n = 11). At embryonic day 17.5, high-frequency ultrasound was used to investigate the placental and fetal hemodynamic responses following exposure. While maternal exposure to polyethylene did not impact fetal growth, there was a significant effect on placental function with a 43% increase in umbilical artery blood flow in the polyethylene group compared to controls (p < 0.01). These results suggest polyethylene has the potential to cause adverse pregnancy outcomes through abnormal placental function.

Rectal and gastrointestinal temperature differ during passive heating and subsequent recovery.

We aimed to compare rectal temperature (Trec) and gastro-intestinal temperature (TGI) during passive heating and subsequent recovery with and without ice slurry ingestion. Twelve males (age: 25 ± 4 years, body mass index: 25.7 ± 2.5 kg m-2) were immersed in hot water on two occasions (Trec elevation: 1.82 ± 0.08°C). In the subsequent 60-min recovery in ambient conditions, participants ingested either 6.8 g kg-1 of ice slurry (-0.6°C, ICE) or control drink (37°C, CON). During passive heating, Trec was lower than TGI (P < 0.001), in the recovery, Trec was higher than TGI (P < 0.001). During passive heating, mean bias and 95%LoA (Limits of Agreement) were -0.10(±0.25)°C and -0.12(±0.36)°C for CON and ICE, respectively. In the recovery, mean bias and 95%LoA were 0.30(±0.60)°C and 0.42(±0.63)°C for CON and ICE, respectively. Trec and TGI differed during both heating and recovery, and less favourable agreement between Trec and TGI was found in the recovery from passive heating with or without ice slurry ingestion.

Stair-Fall Risk Parameters in a Controlled Gait Laboratory Environment and Real (Domestic) Houses: A Prospective Study in Faller and Non-Faller Groups.

BACKGROUND: Falling on stairs is a major health hazard for older people. Risk factors for stair falls have been identified, but these are mostly examined in controlled biomechanics/gait laboratory environments, on experimental stairs with a given set of step dimensions. It remains unknown whether the conclusions drawn from these controlled environments would apply to the negotiation of other domestic staircases with different dimensions in real houses where people live. OBJECTIVES: The aim of this paper is to investigate whether selected biomechanical stepping behavior determined through stair gait parameters such as foot clearance, foot contact length and cadence are maintained when the staircase dimensions are different in real houses. METHODS: Twenty-five older adults (>65 years) walked on a custom-made seven-step laboratory staircase. Older adults were classified into two groups (fallers and non-fallers) based on recent fall history. Among the 25 participants, 13 people had at least one fall, trip, or slip in the last six months and they were assigned to the fallers group; 12 people did not experience any fall in the last six months, so they were assigned to the non-fallers group. In addition, these participants walked on the stairs in three different real exemplar houses wearing a novel instrumented shoe sensor system that could measure the above stair gait parameters. MATLAB was used to extract fall risk parameters from the collected data. One-way ANOVA was used to compare fall risk parameters on the different staircases. In addition, the laboratory-based fall risk parameters were compared to those derived from the real house stairs. RESULTS: There was a significant difference in selected stair-fall biomechanical risk factors among the house and laboratory staircases. The fall risk group comparisons suggest that high-risk fallers implemented a biomechanically riskier strategy that could increase overall falling risk. CONCLUSIONS: The significant differences due to the main effects of the fallers and non-fallers groups were obtained. For example, when ascending, the fallers group had less foot clearance on the entry (p = 0.016) and middle steps (p = 0.003); in addition, they had more foot clearance variability on the entry steps (p = 0.003). This suggests that the fallers group in this present study did not adopt more conservative stepping strategies during stair ascent compared to low-risk older adults. By showing less foot clearance and more variability in foot clearance, the risk for a trip would be increased.

A Novel Smart Shoe Instrumented with Sensors for Quantifying Foot Placement and Clearance during Stair Negotiation.

Trips and slips are significant causal perturbations leading to falls on stairs, especially in older people. The risk of a trip caused by a toe or heel catch on the step edge increases when clearance is small and variable between steps. The risk of a slip increases if the proportion of the foot area in contact with the step is reduced and variable between steps. To assess fall risk, these measurements are typically taken in a gait lab using motion-capture optoelectronic systems. The aim of this work was to develop a novel smart shoe equipped with sensors to measure foot placement and foot clearance on stairs in real homes. To validate the smart shoe as a tool for estimating stair fall risk, twenty-five older adults' sensor-based measurements were compared against foot placement and clearance measurements taken in an experimental staircase in the lab using correlations and Bland-Altman agreement techniques. The results showed that there was a good agreement and a strong positive linear correlation for foot placement (r = 0.878, p < 0.000) and foot clearance (r = 0.967, p < 0.000) between sensor and motion analysis, offering promise for advancing the current prototype into a measurement tool for fall risk in real-life staircases.

The world´s microbiology laboratories can be a global microbial sensor network / Los laboratorios de microbiología del mundo pueden convertirse en una red de detección microbiana

The microbes that infect us spread in global and local epidemics, and the resistance genes that block their treatment spread within and between them. All we can know about where they are to track and contain them comes from the only places that can see them, the world´s microbiology laboratories, but most report each patient´s microbe only to that patient´s caregiver. Sensors, ranging from instruments to birdwatchers, are now being linked in electronic networks to monitor and interpret algorithmically in real-time ocean currents, atmospheric carbon, supply-chain inventory, bird migration, etc. To so link the world´s microbiology laboratories as exquisite sensors in a truly lifesaving real-time network their data must be accessed and fully subtyped. Microbiology laboratories put individual reports into inaccessible paper or mutually incompatible electronic reporting systems, but those from more than 2,200 laboratories in more than 108 countries worldwide are now accessed and translated into compatible WHONET files. These increasingly web-based files could initiate a global microbial sensor network. Unused microbiology laboratory byproduct data, now from drug susceptibility and biochemical testing but increasingly from new technologies (genotyping, MALDI-TOF, etc.), can be reused to subtype microbes of each genus/species into sub-groupings that are discriminated and traced with greater sensitivity. Ongoing statistical delineation of subtypes from global sensor network data will improve detection of movement into any patient of a microbe or resistance gene from another patient, medical center or country. Growing data on clinical manifestations and global distributions of subtypes can automate comments for patient´s reports, select microbes to genotype and alert responders.

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Vigilancia de la resistencia bacteriana a los antibióticos en Venezuela / Surveillance of bacterial resistance to antibiotics in Venezuela

Los resultados presentados ponen de manifiesto las cifras de resistencia a los antibióticos en cepas bacterianas aisladas recientemente en hospitales venezolanos. La necesidad de modificaciones a los esquemas tradicionales de tratamiento quedó de manifiesto. Problemas recientes parecen ser la resistencia en gonococco, la sensibilidad disminuida a la pinicilina en neumococo, la resistencia creciente a cefalosporinas de tercera generación en bacilos Gram negativos y el incremento de resistencia a las nuevas quinolonas. El sistema de vigilancia presentado ha funcionado y representa una valiosa ayuda para la selección empírica de antibióticos. Igualmente, permite detectar precozmente cambios de patrón y, gracias a los programas existentes de computación, permite inferir mecanismos especificos de resistencia. Intentar correlacionar estos resultados con patrones de uso de antibióticos escapa del propósito del presente trabajo. Sin embargo, las cifras presentadas invitan el uso juicioso y ponderado de los mismos

Hepatitis fulminante en la Sierra Nevada: una forma de superinfección del virus delta con el virus de la hepatitis B / Fulminant hepatitis in La Sierra Nevada: a type of Delta superinfection with hepatitis B virus

Durante septiembre de 1980 a octubre de 1983, se realizó un estudio seroepidemiológico para hepatitis A y B, en 258 personas en una ciudad (Santa Marta) población de 250.000 y tres pequeños municipios (Santa Rosalía, Julio Zawady y Aracataca), poblaciones de 768.800 y 5.000 habitantes respectivamente. La presencia de hepatitis A se encontró en un 77 a 93 por ciento (IgG Hepatitis A). Hbs Ag o Anti-Hbs Ag en 30.5 por ciento de la población en dos municipios (Santa Rosalía y Julio Zawady), en 2,5 por ciento en el municipio de Aracataca y 48.5 por ciento en la ciudad de Santa Marta. La presencia del agente Delta (Anti-Delta en el suero) se determinó también en estas mismas poblaciones, encontrándose ausente en la ciudad y uno de los municipios (Aracataca), en contraste con una prevalencia de 13,7 por ciento y 22 por ciento en Julio Zawady y Santa Rosalía (P:0.0001). Se escluyeron por historia clínica, antecedentes de drogadicción, transfusiones, o prácticas homosexuales, como mecanismos de transmisión de los virus B y delta. En veinte pacientes con diagnóstico histopatológico de hepatitis fulminante y en quienes se descartaron otras etiologías se demostró la presencia serológica de los virus de la hepatitis B y Delta. De estos veinte, diez provenían de Julio Zawady y los otros diez de Santa Rosalía. La evolución clínica de esta enfermedad fue indistinguible de otras causas de falla hepática aguda. La mortalidad de estas formas fulminantes de hepatitis alcanzaron hasta un 65 por ciento. Los corticoides no modificaron el curso de esta enfermedad. La población joven mostró mayor compromiso y peor diagnóstico (P: 0.033). La hepatitis fulminante de la Sierra Nevada de Santa Marta es el resultado de la superinfección con el virus Delta sobre la infección virus B. La aparición simultánea de casos intrafamiliares sugiere una relación importante entre los grupos comprometidos, aunque la forma exacta de transmisión permanece aún desconocida