Child and Adolescent Manganese Biomarkers and Adolescent Postural Balance in Marietta CARES Cohort Participants.

BACKGROUND: Manganese (Mn) plays a significant role in both human health and global industries. Epidemiological studies of exposed populations demonstrate a dose-dependent association between Mn and neuromotor effects ranging from subclinical effects to a clinically defined syndrome. However, little is known about the relationship between early life Mn biomarkers and adolescent postural balance. OBJECTIVES: This study investigated the associations between childhood and adolescent Mn biomarkers and adolescent postural balance in participants from the longitudinal Marietta Communities Actively Researching Exposures Study (CARES) cohort. METHODS: Participants were recruited into CARES when they were 7-9 y old, and reenrolled at 13-18 years of age. At both time points, participants provided samples of blood, hair, and toenails that were analyzed for blood Mn and lead (Pb), serum cotinine, hair Mn, and toenail Mn. In adolescence, participants completed a postural balance assessment. Greater sway indicates postural instability (harmful effect), whereas lesser sway indicates postural stability (beneficial effect). Multivariable linear regression models were conducted to investigate the associations between childhood and adolescent Mn biomarkers and adolescent postural balance adjusted for age, sex, height-weight ratio, parent/caregiver intelligence quotient, socioeconomic status, blood Pb, and serum cotinine. RESULTS: CARES participants who completed the adolescent postural balance assessment (n=123) were 98% White and 54% female and had a mean age of 16 y (range: 13-18 y). In both childhood and adolescence, higher Mn biomarker concentrations were significantly associated with greater adolescent sway measures. Supplemental analyses revealed sex-specific associations; higher childhood Mn biomarker concentrations were significantly associated with greater sway in females compared with males. DISCUSSION: This study found childhood and adolescent Mn biomarkers were associated with subclinical neuromotor effects in adolescence. This study demonstrates postural balance as a sensitive measure to assess the association between Mn biomarkers and neuromotor function. https://doi.org/10.1289/EHP13381.

One carbon metabolism and its implication in health and immune functions.

One carbon (1C) metabolism is critical for cellular viability and physiological homeostasis. Starting from its crucial involvement in purine biosynthesis to posttranslational modification of proteins, 1C metabolism contributes significantly to the development and cellular differentiation through methionine and folate cycles that are pivotal for cellular function. Genetic polymorphisms of several genes of these pathways are implicated in disease pathogenesis and drug metabolism. Metabolic products of 1C metabolism have significant roles in epigenetic modifications through DNA and histone protein methylation. Homocysteine is a product that has clinical significance in the diagnosis and prognosis of several critical illnesses, including chronic immune diseases and cancers. Regulation of the function and differentiation of immune cells, including T-cells, B-cells, macrophages, and so forth, are directly influenced by 1C metabolism and thus have direct implications in several immune disease biology. Recent research on therapeutic approaches is targeting nuclear, cytoplasmic, and mitochondrial 1C metabolism to manage and treat metabolic (i.e., type 2 diabetes), neurodegenerative (i.e., Alzheimer's disease), or immune (i.e., rheumatoid arthritis) diseases. 1C metabolism is being explored for therapeutic intervention as a common determinant for a spectrum of immune and metabolic diseases. Identifying the association or correlation between essential metabolic products of this pathway and disease onset or prognosis would further facilitate the clinical monitoring of diseases.

Insufficiencies in sensory systems reweighting is associated with walking impairment severity in chronic stroke: an observational cohort study.

Background: Walking and balance impairment are common sequelae of stroke and significantly impact functional independence, morbidity, and mortality. Adequate postural stability is needed for walking, which requires sufficient integration of sensory information between the visual, somatosensory, and vestibular centers. "Sensory reweighting" describes the normal physiologic response needed to maintain postural stability in the absence of sufficient visual or somatosensory information and is believed to play a critical role in preserving postural stability after stroke. However, the extent to which sensory reweighting successfully maintains postural stability in the chronic stages of stroke and its potential impact on walking function remains understudied. Methods: In this cross-sectional study, fifty-eight community-dwelling ambulatory chronic stroke survivors underwent baseline postural stability testing during quiet stance using the modified Clinical test of Sensory Interaction in Balance (mCTSIB) and assessment of spatiotemporal gait parameters. Results: Seventy-six percent (45/58) of participants showed sufficient sensory reweighting with visual and somatosensory deprivation for maintaining postural stability, albeit with greater postural sway velocity indices than normative data. In contrast, survivors with insufficient reweighting demonstrated markedly slower overground walking speeds, greater spatiotemporal asymmetry, and limited acceleration potential. Conclusion: Adequate sensory system reweighting is essential for chronic stroke survivors' postural stability and walking independence. Greater emphasis should be placed on rehabilitation strategies incorporating multisensory system integration testing and strengthening as part of walking rehabilitation protocols. Given its potential impact on outcomes, walking rehabilitation trials may benefit from incorporating formal postural stability testing in design and group stratification.

Mechanism and recent updates on insulin-related disorders.

Insulin, a small protein with 51 amino acids synthesized by pancreatic ß-cells, is crucial to sustain glucose homeostasis at biochemical and molecular levels. Numerous metabolic dysfunctions are related to insulin-mediated altered glucose homeostasis. One of the significant pathophysiological conditions linked to the insulin associated disorder is diabetes mellitus (DM) (type 1, type 2, and gestational). Insulin resistance (IR) is one of the major underlying causes of metabolic disorders despite its association with several physiological conditions. Metabolic syndrome (MS) is another pathophysiological condition that is associated with IR, hypertension, and obesity. Further, several other pathophysiological disorders/diseases are associated with the insulin malfunctioning, which include polycystic ovary syndrome, neuronal disorders, and cancer. Insulinomas are an uncommon type of pancreatic ß-cell-derived neuroendocrine tumor that makes up 2% of all pancreatic neoplasms. Literature revealed that different biochemical events, molecular signaling pathways, microRNAs, and microbiota act as connecting links between insulin disorder and associated pathophysiology such as DM, insuloma, neurological disorder, MS, and cancer. In this review, we focus on the insulin-related disorders and the underlying mechanisms associated with the pathophysiology.

Unraveling Sodium-Ion Dynamics in Honeycomb-Layered Na2MgxZn2-xTeO6 Solid Electrolytes with Solid-State NMR.

All-solid-state sodium-ion batteries (SIBs) have the potential to offer large-scale, safe, cost-effective, and sustainable energy storage solutions by supplementing the industry-leading lithium-ion batteries. However, for the enhanced bulk properties of SIB components (e.g., solid electrolytes), a comprehensive understanding of their atomic-scale structure and the dynamic behavior of sodium (Na) ions is essential. Here, we utilize a robust multinuclear (23Na, 125Te, 25Mg, and 67Zn) magnetic resonance approach to explore a novel Mg/Zn homogeneously mixed-cation honeycomb-layered oxide Na2MgxZn2-xTeO6 solid solution series. These new intermediate compounds exhibit tailorable bulk Na-ion conductivity (σ) with the highest σ = 0.14 × 10-4 S cm-1 for Na2MgZnTeO6 at room temperature suitable for SIB solid electrolyte applications as observed by powder electrochemical impedance spectroscopy (EIS). A combination of powder X-ray diffraction (XRD), energy-dispersive X-ray (EDX) spectroscopy, and field emission scanning electron microscopy (FESEM) reveals highly crystalline phase-pure compounds in the P6322 space group. We show that the Mg/Zn disorder is random within the honeycomb layers using 125Te nuclear magnetic resonance (NMR) and resolve multiple Na sites using two-dimensional (triple-quantum magic-angle spinning (3QMAS)) 23Na NMR. The medium-range disorder in the honeycomb layer is revealed through the combination of 25Mg and 67Zn NMR, complemented by electronic structure calculations using density functional theory (DFT). Furthermore, we expose very fast local Na-ion hopping processes (hopping rate, 1/τNMR = 0.83 × 109 Hz) by using a laser to achieve variable high-temperature (∼860 K) 23Na NMR, which are sensitive to different Mg/Zn ratios. The Na2MgZnTeO6 with maximum Mg/Zn disorder displays the highest short-range Na-ion dynamics among all of the solid solution members.

Early childhood lead exposure is not reflected in adult bone lead: Results of a sub-cohort of African American women in the Cincinnati lead study.

INTRODUCTION: Pb in bone may serve as a biomarker for cumulative Pb dose over decades. We hypothesized that adult female bone Pb concentrations (BoPb) would be significantly associated with average childhood blood Pb levels (BlPb) in a birth cohort exposed to relatively high levels of Pb from Pb paint residues. METHODS: 94 African American women with a mean age of 32.7 years were recruited from the Cincinnati Lead Study (CLS) cohort. Subjects were born to women residing where there had been a high incidence of childhood Pb poisoning. Biomarkers of Pb exposure were serial BlPb concentrations spanning the prenatal period to approximately 6.5 years of age. BoPb was assessed in the tibia using the McMaster 109Cd K-XRF fourth generation system. Covariates included nutritional variables related to bone health. RESULTS: BlPb concentrations began to rise around 6 months of age and declined at later ages. Study participants were obese with a mean Body Mass Index of 34.4 and suboptimal vitamin D status as indicated by a mean 25-OH-D of 18.5 ng/ml. Average tibia Pb was -2.0 ± 8.6 µgPb/g bone mineral. In multiple linear regression, there was no significant association between BoPb at approximately age 30 and childhood cumulative BlPb(CumBlPb). DISCUSSION: Collectively, BoPb of this group of subjects was not detectable. We suggest that the reason these subjects' BoPb did not reflect their early exposure was that a significantly smaller proportion of Pb body burden resides in bone in young children. As the child grows what Pb there was in bone is diluted and any remaining signal is weak. It has been claimed that BoPb in older children, adolescents, and adults can recapitulate historical exposure to Pb during earlier development; however, in some populations, BoPb at later ages may not be an adequate biomarker to capture childhood exposure to Pb.

Effect of aliovalent bismuth substitution on structure and optical properties of CsSnBr3.

Aliovalent substitution of the B component in ABX3 metal halides has often been proposed to modify the band gap and thus the photovoltaic properties, but details about the resulting structure have remained largely unknown. Here, we examine these effects in Bi-substituted CsSnBr3. Powder X-ray diffraction (XRD) and solid-state 119Sn, 133Cs and 209Bi nuclear magnetic resonance (NMR) spectroscopy were carried out to infer how Bi substitution changes the structure of these compounds. The cubic perovskite structure is preserved upon Bi-substitution, but with disorder in the B site occurring at the atomic level. Bi atoms are randomly distributed as they substitute for Sn atoms with no evidence of Bi segregation. The absorption edge in the optical spectra shifts from 1.8 to 1.2 eV upon Bi-substitution, maintaining a direct band gap according to electronic structure calculations. It is shown that Bi-substitution improves resistance to degradation by inhibiting the oxidation of Sn.

Disorientation effects, circulating small ribonucleic acid, and genetic susceptibility on static postural stability.

Background: Motion Sickness increases risk of performance deficits and safety of flight concerns. The etiology of motion sickness is poorly understood. Here, we attempted to quantify the physiological effects of motion sickness on static balance and determine the genetic predictors associated with these effects. Methods: 16 subjects underwent a disorientation stimulus to induce motion sickness. Motion sickness susceptibility was identified using the Motion Sickness Susceptibility Questionnaire. Postural balance outcomes were measured using two tasks, and small ribonucleic acid profiles were assessed with blood draws before motion sickness stimulus. Differences in postural sway before and after the stimulus as well as effect modification of susceptibility were assessed. A random forest followed by regression tree analysis was constructed for each postural sway variable to determine top genetic and covariate predictors. Findings: Significant differences existed in mean postural balance responses between before and after stimulus. Individuals with longer stimulus survival experienced a greater (but insignificant) perception of sway, even if not displaying increased sway for all conditions. Circulation small ribonucleic acids were differentially expressed between individuals with long and short stimulus survival, many of these microRNA have purported targets in genes related to vestibular disorders. Interpretation: We found motion sickness produces transient motor dysfunction in a healthy military population. Small ribonucleic acids were differentially expressed between subjects with long and short stimulus survival times.

One-pot facile approach to design an efficient macro-porous polymeric matrix to remediate Hg(II)and Pb(II) from aqueous medium and its performance evaluation study by mathematical modelling.

In the present scenario discharge of heavy-metal ions into water bodies is a global threat that is causing serious health hazards even in low concentrations. Thus, in order to remediate the heavy-metal [Hg(II) and Pb(II)] toxicity, an organic-inorganic hybrid functional porous metallo-polymeric network i. e, poly(Zirconyl methacrylate-co-1-vinyl imidazole) (pZrVIm) was fabricated via one-pot facile synthesis approach. The pZrVIm architecture has shown high removal efficiency for Hg(II) and Pb(II) aqueous medium even in extremely low quantities. Advanced instrumental techniques were used to characterize the structural and morphological characteristics of pZrVIm. Different experimental variables i.e., reaction time, pH, initial feed concentration, co-ion effects etc. were explored to examine adsorption behaviour. The maximum adsorption capacities (qmax) of pZrVIm5 were calculated as 168.06 and 162.34 mg g-1 for Hg(II) and Pb(II) respectively by the Langmuir isotherm model. Data from isotherms showed that monolayer adsorption on a homogeneous surface is the rate-limiting stage and followed pseudo-second-order kinetic process. The Artificial Neural Network (ANN) modelling was used to validate kinetics and isotherm data which revealed high accuracy of the model with correlation coefficient values (R = 0.99). Various types of isotherm models such as Langmuir, Freundlich, Dubinin-Radushkevich, Temkin, Redlich-Peterson, Toth and Koble-Corigen have been studied to determine the adsorption phenomena. The pore diffusion model revealed breakthrough time of 91 h and 84 h, Hg(II) and Pb(II) with the feed concentration of 15 mg L-1 respectively. The study revealed that pZrVIm5 has great potential for heavy metal ions remediation for water treatment.

Thin film poly(vinyl alcohol)-polysulfone composite membranes based on recycled polysulfone: salt separation performances.

Poly(vinyl alcohol) (PVA)-coated membranes on polysulfone (Ps) (Memb-Pv) were cross-linked using the dibasic maleic acid. The tailoring of membrane properties (viz. hydrophilicity, permeability) develops through the ester linkage due to cross-linking of PVA and maleic acid (MA). Series of Ps asymmetric membranes were prepared using the successive stages of phase inversion of Ps materials. The recyclability approaches of polysulfone (Ps) pertained. The characteristics and transport properties of all the membranes are evaluated. FTIR-ATR, scanning electron (SEM), and atomic force microscopy (AFM) are used for the structural characterization of the membranes. The salient features of Memb-Pv composite membranes support promising results in desalination. The work aimed to highlight the trade-off between the flux and selectivity of composite membranes' salts (bi-/monovalent) through the recycled Ps matrix. The number of recycling stages influences the salt separation performance. The sulfate rejection differs from Memb-IPv (93.26%) to Memb-IVPv (86.70%) for water-I matrix using 2500 mg/L. The defluoridation potential of the membranes is also convincing. The defluoridation performance of Memb-IPv is 87% for 10 mg/L. A significant dimension is added regarding salt separation performance's dependence on the water matrices' nature. The decrease in fluoride separation is ~ 1-3% for the water-2 matrix as the TDS increases.

Effect of cooling on static postural balance while wearing firefighter's protective clothing in a hot environment.

Objectives. Postural imbalance can result from hyperthermia-mediated muscular fatigue and is a major factor contributing to injuries from falling. The objective of this study was to investigate the effect of exercise-induced hyperthermia and the impact of cooling on postural balance while wearing firefighters' protective clothing (FPC) in a hot environment. Methods. A portable force platform measured postural balance characterized by postural sway patterns using center of pressure metrics. Twelve healthy, physically fit males were recruited to stand on the force platform once with eyes open and once with eyes closed before and after treadmill exercise (40% V˙O2max) inside an environmental chamber under hot and humid conditions (30 °C and 70% relative humidity) while wearing FPC. Subjects participated in two randomly assigned experimental phases: control and cooling intervention. Results. A significant increase in physiological responses and postural balance metrics was observed after exercising in the heat chamber while wearing FPC. Cooling resulted in a significant effect only on postural sway speed after exercise-induced hyperthermia. Conclusions. Hyperthermia can negatively alter postural balance metrics, which may lead to an increased likelihood of falling. The utilization of body cooling reduced the thermal strain but had limited impact on postural balance stability.

Mercurial possibilities: determining site distributions in Cu2HgSnS4 using 63/65Cu, 119Sn, and 199Hg solid-state NMR spectroscopy.

Chalcogenides are an important class of materials that exhibit tailorable optoelectronic properties accessible through chemical modification. For example, the minerals kesterite, stannite, and velikite (Cu2MSnS4, where M = Zn, Cd, or Hg, respectively) are a series of Group 12 transition metal tin sulfides that readily exhibit optical bandgaps spanning the Shockley-Queisser limit; however, achieving consensus on their structure (space group I4̄ vs. I4̄2m) has been difficult. This study explores the average long-range and local structure of Cu2HgSnS4 and evaluates the parallels of M = Zn and Cd sister compounds using complementary X-ray diffraction and solid-state nuclear magnetic resonance (NMR) spectroscopy. The 63/65Cu NMR spectra were acquired at multiple magnetic field strengths (B0 = 7.05, 11.75, and 21.1 T) to assess the unique chemical shift anisotropy and quadrupolar coupling contributions. They reveal two inequivalent sets of Cu sites in Cu2ZnSnS4, in contrast to only one set of sites in Cu2CdSnS4 and Cu2HgSnS4, clarifying structural assignments previously proposed through X-ray diffraction methods. The presence of these Cu sites was further supported by DFT calculations. The 119Sn and 199Hg NMR spectra suggest that an ordering phenomenon takes place in Cu2HgSnS4 when it undergoes annealing treatments. The trend in measured optical band gaps (1.5 eV for Cu2ZnSnS4, 1.2 eV for Cu2CdSnS4, and 0.9 eV for Cu2HgSnS4) was confirmed by electronic structure calculations, which show that the band gap narrows as the difference in electronegativity is diminished and that Hg-S bonds in Cu2HgSnS4 have greater covalent character.

Motion sickness decreases low back function and changes gene expression in military aircrew.

BACKGROUND: Motion sickness and low back disorders are prevalent and debilitating conditions that affect the health, performance, and operational effectiveness of military aircrews. This study explored the effects of a motion sickness stimulus on biomechanical and genetic factors that could potentially be involved in the causal pathways for both disorders. METHODS: Subjects recruited from a military population were exposed to either a mild (n = 12) or aggressive (n = 16) motion sickness stimulus in a Neuro-Otologic Test Center. The independent variable of interest was the motion sickness stimulus exposure (before vs. after), though differences between mild and aggressive stimuli were also assessed. Dependent measures for the study included motion sickness exposure duration, biomechanical variables (postural stability, gait function, low back function, lumbar spine loading), and gene expression. FINDINGS: Seven of twelve subjects experiencing the mild motion sickness stimulus endured the full 30 min in the NOTC, whereas subjects lasted an average of 13.2 (SD 5.0) minutes in the NOTC with the aggressive motion sickness stimulus. Mild motion sickness exposure led to a significant decrease in the postural stability measure of sway area, though the aggressive motion sickness exposure led to a statistically significant increase in sway area. Both stimuli led to decreases in low back function, though the decrease was only statistically significant for the mild protocol. Both stimuli also led to significant changes in gene expression. INTERPRETATION: Motion sickness may alter standing balance, decrease low back function, and lead to changes in the expression of genes with roles in osteogenesis, myogenesis, development of brain lymphatics, inflammation, neuropathic pain, and more. These results may provide preliminary evidence for a link between motion sickness and low back disorders.

Serial Backward Locomotor Treadmill Training Improves Bidirectional Walking Performance in Chronic Stroke.

Background and Research Question: Walking impairment remains a major limitation to functional independence after stroke. Yet, comprehensive and effective strategies to improve walking function after stroke are presently limited. Backward Locomotor Treadmill Training (BLTT) is a promising training approach for improving walking function; however, little is known about its mechanism of effect or the relationship between backward walking training and resulting overground forward walking performance. This study aims to determine the effects of serial BLTT on spatial aspects of backward and forward walking in chronic post-stroke individuals with residual walking impairment. Methods: Thirty-nine adults (>6 months post-stroke) underwent 6 days of BLTT (3 × /week) over 2 weeks. Outcome measures included PRE-POST changes in backward and forward walking speeds, paretic and non-paretic step lengths, and single-support center of pressure distances. To determine the association between BLTT and overground walking, correlation analyses comparing training-related changes in these variables were performed. Results: We report an overall improvement in BLTT and overground walking speeds, bilateral step lengths, and single-support center of pressure distances over six training sessions. Further, there were weak positive associations between PRE-POST changes in BLTT speed, BLTT paretic step length, and overground forward walking speed. Conclusion and Significance: Our findings suggest that individuals with chronic post-stroke walking impairment experience improvements in spatial walking measures during BLTT and overground. Therefore, BLTT may be a potential adjunctive training approach for post-stroke walking rehabilitation.

Backward Locomotor Treadmill Training Differentially Improves Walking Performance across Stroke Walking Impairment Levels.

BACKGROUND: Post-stroke walking impairment is a significant cause of chronic disability worldwide and often leads to loss of life roles for survivors and their caregivers. Walking impairment is traditionally classified into mild (>0.8 m/s), moderate (0.41-0.8 m/s), and severe (≤0.4 m/s), and those categorized as "severe" are more likely to be homebound and at greater risk of falls, fractures, and rehospitalization. In addition, there are minimal effective walking rehabilitation strategies currently available for this subgroup. Backward locomotor treadmill training (BLTT) is a novel and promising training approach that has been demonstrated to be safe and feasible across all levels of impairment; however, its benefits across baseline walking impairment levels (severe (≤0.4 m/s) vs. mild-moderate (>0.4 m/s)) have not been examined. METHODS: Thirty-nine adults (>6 months post-stroke) underwent 6 days of BLTT (3×/week) over 2 weeks. Baseline and PRE to POST changes were measured during treadmill training and overground walking. RESULTS: Individuals with baseline severe walking impairment were at a more significant functional disadvantage across all spatiotemporal walking measures at baseline and demonstrated fewer overall gains post-training. However, contrary to our working hypothesis, both groups experienced comparable increases in cadence, bilateral percent single support times, and step lengths. CONCLUSION: BLTT is well tolerated and beneficial across all walking impairment levels, and baseline walking speed (≤0.4 m/s) should serve as a covariate in the design of future walking rehabilitation trials.

Insights on Epidemiology, Pathogenesis, Diagnosis and Possible Treatment of COVID-19 Infection.

The sudden outbreak of the novel coronavirus infection (COVID-19, SARS-CoV-2 virus) is posing a significant threat by affecting millions of people across the globe showing mild to severe symptoms of pneumonia and acute respiratory distress. The absence of precise information on primary transmission, diagnosis, prognosis, and therapeutics for patients with COVID-19 makes prevention and control tough. In the current scenario, only supportive treatment is available, which in turn possess a biggest challenge for scientists to develop specific drugs and vaccines for COVID-19. Further, India, with the second largest populated country and fluctuating climatic conditions quarterly, has high vulnerability towards COVID-19 infection. Thus, this highlights the importance of a better understanding of the COVID-19 infection, pathology, diagnosis and its treatment. The present review article has been intended to discuss the COVID-19 biology, mechanism of infection in humans with primary effects on pregnancy, the nervous system, diabetes, and cardiovascular disease. The article will also discuss the drug repurposing strategy as an alternative line of treatment and clinical practices recommended by the World Health Organization and other government agencies and represent the COVID-19 scenario with the Indian context.

Experimental validation of high thermoelectric performance in RECuZnP2 predicted by high-throughput DFT calculations.

Accurate density functional theory calculations of the interrelated properties of thermoelectric materials entail high computational cost, especially as crystal structures increase in complexity and size. New methods involving ab initio scattering and transport (AMSET) and compressive sensing lattice dynamics are used to compute the transport properties of quaternary CaAl2Si2-type rare-earth phosphides RECuZnP2 (RE = Pr, Nd, Er), which were identified to be promising thermoelectrics from high-throughput screening of 20 000 disordered compounds. Experimental measurements of the transport properties agree well with the computed values. Compounds with stiff bulk moduli (>80 GPa) and high speeds of sound (>3500 m s-1) such as RECuZnP2 are typically dismissed as thermoelectric materials because they are expected to exhibit high lattice thermal conductivity. However, RECuZnP2 exhibits not only low electrical resistivity, but also low lattice thermal conductivity (∼1 W m-1 K-1). Contrary to prior assumptions, polar-optical phonon scattering was revealed by AMSET to be the primary mechanism limiting the electronic mobility of these compounds, raising questions about existing assumptions of scattering mechanisms in this class of thermoelectric materials. The resulting thermoelectric performance (zT of 0.5 for ErCuZnP2 at 800 K) is among the best observed in phosphides and can likely be improved with further optimization.

Microglia Specific Drug Targeting Using Natural Products for the Regulation of Redox Imbalance in Neurodegeneration.

Microglia, a type of innate immune cell of the brain, regulates neurogenesis, immunological surveillance, redox imbalance, cognitive and behavioral changes under normal and pathological conditions like Alzheimer's, Parkinson's, Multiple sclerosis and traumatic brain injury. Microglia produces a wide variety of cytokines to maintain homeostasis. It also participates in synaptic pruning and regulation of neurons overproduction by phagocytosis of neural precursor cells. The phenotypes of microglia are regulated by the local microenvironment of neurons and astrocytes via interaction with both soluble and membrane-bound mediators. In case of neuron degeneration as observed in acute or chronic neurodegenerative diseases, microglia gets released from the inhibitory effect of neurons and astrocytes, showing activated phenotype either of its dual function. Microglia shows neuroprotective effect by secreting growths factors to heal neurons and clears cell debris through phagocytosis in case of a moderate stimulus. But the same microglia starts releasing pro-inflammatory cytokines like TNF-α, IFN-γ, reactive oxygen species (ROS), and nitric oxide (NO), increasing neuroinflammation and redox imbalance in the brain under chronic signals. Therefore, pharmacological targeting of microglia would be a promising strategy in the regulation of neuroinflammation, redox imbalance and oxidative stress in neurodegenerative diseases. Some studies present potentials of natural products like curcumin, resveratrol, cannabidiol, ginsenosides, flavonoids and sulforaphane to suppress activation of microglia. These natural products have also been proposed as effective therapeutics to regulate the progression of neurodegenerative diseases. The present review article intends to explain the molecular mechanisms and functions of microglia and molecular dynamics of microglia specific genes and proteins like Iba1 and Tmem119 in neurodegeneration. The possible interventions by curcumin, resveratrol, cannabidiol, ginsenosides, flavonoids and sulforaphane on microglia specific protein Iba1 suggest possibility of natural products mediated regulation of microglia phenotypes and its functions to control redox imbalance and neuroinflammation in management of Alzheimer's, Parkinson's and Multiple Sclerosis for microglia-mediated therapeutics.

Probability of hyperthermia in a hot environment while wearing a liquid cooling garment underneath firefighters' protective clothing.

Firefighters' protective clothing (FPC) can limit human thermoregulation due to limited water vapor permeability and insulation. This study investigated the effect of cooling on the physiological responses and probability of hyperthermia in subjects wearing FPC during exercise in a hot environment. Twelve males participated in this study. A maximal graded treadmill exercise test was performed to measure maximal oxygen uptake (V̇O2max) and to assess subjects' capacity to perform the assigned exercise. Exercise included treadmill walking at 40% V̇O2max in warm (30 °C) and humid (70% RH) conditions for 40 min while wearing FPC. Subjects participated in two randomly counterbalanced assigned experimental protocols: control (no cooling) and intervention (cooling). The experimental intervention consisted of a cooling garment infused with cooled water (18 °C) through silastic tubing sewn into the fabric and worn underneath FPC. Each subject served as their own control and, therefore, completed both the control and intervention of the protocol. A logistic regression model was used to analyze the interaction effect of cooling on the probability of progression to hyperthermia (Tc ≥ 38 °C). Subjects' physiological responses increased during exercise in a warm and humid environment. Active cooling decreased (p < 0.05) the thermal stress thereby reducing the probability of hyperthermia while exercising in hot and humid conditions. The results indicate that when cooling was used each subject, on average, was 91% less likely to reach the lower threshold limit of hyperthermia. Exercise in hot environments while wearing FPC results in significant physiological strain, which may lead to hyperthermia. Utilization of a cooling garment reduced physiological strain and the probability of hyperthermia.

Time lost: Factors influencing advanced practice provider's prioritization of sleep.

BACKGROUND: Prescribing patient care providers regularly experience insufficient sleep, putting them at increased risk of committing occupational injuries, accidents, and errors and developing chronic health conditions. OBJECTIVE: Identify antecedents to short sleep (≤6-hours sleep in 24-hour period) in the understudied population of hospital-based Advanced Practice Providers (APPs). METHODS: Using an ethnographic research design, data included APP and key stakeholder interviews, hospital observations, and relevant documents. Interview data were analyzed using modified constant comparative method. RESULTS: Nine APPs were interviewed, revealing four themes: Social/Family Obligations and Value of Connectivity, Community Value of Sleep, Organizational Value of Sleep, and Individual Biology and How the Body Values Sleep. APP decisions to prioritize sleep are based on an interplay of societal, professional, organizational, and personal values. Triangulated data verified results, except regarding how APP sleep deficit can lead to mood disturbances and the lack sleep consideration in patient care error reporting. CONCLUSIONS: Findings demonstrate the importance of consistency in messaging, action, and policy when promoting occupational sleep health among healthcare workers. Implications include instituting worker sleep education, leadership modeling healthy sleep habits, and inclusion of sleep in root cause analyses. Additional consideration includes evaluating the influence of nursing culture on nurse practitioners' sleep habits.