High-performance liquid chromatography (HPLC) as a means of assessing the presence of uric acid in archeological human remains: Challenges and future directions.

OBJECTIVES: This research aimed to replicate the Swinson, D., Snaith, J., Buckberry, J., & Brickley, M. (2010). High performance liquid chromatography (HPLC) in the investigation of gout in paleopathology. International Journal of Osteoarchaeology, 20, 135-143. https://doi.org/10.1002/oa.1009 method for detecting uric acid in archeological human remains to investigate gout in past populations and to improve the original High Performance Liquid Chromatography-ultraviolet (HPLC-UV) method by using HPLC-mass spectrometry (HPLC-MS), a more sensitive, compound-specific detection method. MATERIALS AND METHODS: We used reference samples of uric acid to create a dilution series to assess the limits of quantification and detection. Samples from individuals with and without gout lesions were taken from foot bones and ribs from the English cemeteries of Tanyard, Hickleton, Gloucester, and Lincoln. RESULTS: We could not replicate the results of Swinson and colleagues using HPLC-UV. Tests using a dilution series of uric acid showed HPLC-MS was approximately 100× more sensitive than HPLC-UV, with the additional benefit of being compound specific. A newly developed hydrophilic interaction chromatography (HILIC) method improved retention characteristics. Fourteen samples from eight individuals, five with skeletal lesions consistent with gout, were analyzed with the final method. None showed evidence of uric acid despite the newly developed method's improved sensitivity and specificity. DISCUSSION: The lack of detectable uric acid extracted from these samples suggests that (1) urate crystals were not present in any of the bone samples, regardless of gout status; (2) urate crystals did not survive these specific archeological conditions; or (3) the concentration of uric acid in our bone extracts was low, and thus larger samples would be required.

Biological sex does not independently influence time-dependent changes in core temperature and sweating of children exercising in uncompensable heat stress.

PURPOSE: To investigate the influence of biological sex, independent of differences in aerobic fitness and body fatness, on the change in gastro-intestinal temperature (∆Tgi) and whole-body sweat rate (WBSR) of children exercising under uncompensable heat stress. METHODS: Seventeen boys (mean±SD; 13.7±1.3 years) and 18 girls (13.7±1.4) years) walked for 45 min at a fixed rate of metabolic heat production per kg body mass (8 W·kg-1) in 40°C and 30% relative humidity. Sex and V̇O2peak were entered into a Bayesian hierarchical general additive model (HGAM) for Tgi. Sex, V̇O2peak and the evaporative requirement for heat balance (Ereq) were entered into a Bayesian hierarchical linear regression for WBSR. For 26 (12 M, 14 F) of the 35 children with measured body composition, body fat percentage was entered in a separate HGAM and hierarchical linear regression for Tgi and WBSR respectively. RESULTS: Conditional on sex-specific mean V̇O2peak, ∆Tgi was 1.00°C [90% credible intervals: 0.84, 1.16] for boys and 1.17°C [1.01, 1.33] for girls, with a difference of 0.17°C [-0.39, 0.06]. When sex differences in V̇O2peak were accounted for, the difference in ∆Tgi between boys and girls was 0.01°C [-0.25, 0.22]. The difference in WBSR between boys and girls was 0.03 L·h-1 [-0.02, 0.07], when isolated from differences in Ereq. The difference in ∆Tgi between boys and girls was -0.10°C [-0.38, 0.17] when sex differences in body fat (%) were accounted for. CONCLUSION: Biological sex did not independently influence the ∆Tgi and WBSR of children exercising under uncompensable heat stress.

Plant trait and vegetation data along a 1314 m elevation gradient with fire history in Puna grasslands, Perú.

Alpine grassland vegetation supports globally important biodiversity and ecosystems that are increasingly threatened by climate warming and other environmental changes. Trait-based approaches can support understanding of vegetation responses to global change drivers and consequences for ecosystem functioning. In six sites along a 1314 m elevational gradient in Puna grasslands in the Peruvian Andes, we collected datasets on vascular plant composition, plant functional traits, biomass, ecosystem fluxes, and climate data over three years. The data were collected in the wet and dry season and from plots with different fire histories. We selected traits associated with plant resource use, growth, and life history strategies (leaf area, leaf dry/wet mass, leaf thickness, specific leaf area, leaf dry matter content, leaf C, N, P content, C and N isotopes). The trait dataset contains 3,665 plant records from 145 taxa, 54,036 trait measurements (increasing the trait data coverage of the regional flora by 420%) covering 14 traits and 121 plant taxa (ca. 40% of which have no previous publicly available trait data) across 33 families.

Influence of Biological Sex and Fitness on Core Temperature Change and Sweating in Children Exercising in Warm Conditions.

PURPOSE: This study aimed to investigate the associations of biological sex and aerobic fitness (i.e., V̇O 2peak ) on the change in gastrointestinal temperature (∆ Tgi ) and whole-body sweat rate (WBSR) of children exercising in warm conditions. METHODS: Thirty-eight children (17 boys, mean ± SD = 13.7 ± 1.2 yr; 21 girls, 13.6 ± 1.8 yr) walked for 45 min at a fixed rate of metabolic heat production (8 W·kg -1 ) in 30°C and 40% relative humidity. Biological sex and relative V̇O 2peak were entered as predictors into a Bayesian hierarchical generalized additive model for Tgi . For a subsample of 13 girls with measured body composition, body fat percent was entered into a separate hierarchical generalized additive model for Tgi . Sex, V̇O 2peak , and the evaporative requirement for heat balance ( Ereq ) were entered into a Bayesian hierarchical linear regression for WBSR. RESULTS: The mean ∆ Tgi for boys was 0.71°C (90% credible interval = 0.60-0.82) and for girls 0.78°C (0.68-0.88). A predicted 20 mL·kg -1 ·min -1 higher V̇O 2peak resulted in a 0.19°C (-0.03 to 0.43) and 0.24°C (0.07-0.40) lower ∆ Tgi in boys and girls, respectively. A predicted ~13% lower body fat in the subsample of girls resulted in a 0.15°C (-0.12 to 0.45) lower ∆ Tgi . When Ereq was standardized to the grand mean, the difference in WBSR between boys and girls was -0.00 L·h -1 (-0.06 to 0.06), and a 20-mL·kg -1 ·min -1 higher predicted V̇O 2peak resulted in a mean difference in WBSR of -0.07 L·h -1 (-0.15 to 0.00). CONCLUSIONS: Biological sex did not independently influence ∆ Tgi and WBSR in children. However, a higher predicted V̇O 2peak resulted in a lower ∆ Tgi of children, which was not associated with a greater WBSR, but may be related to differences in body fat percent between high and low fitness individuals.

Quantifying Exercise Heat Acclimatisation in Athletes and Military Personnel: A Systematic Review and Meta-analysis.

BACKGROUND: Athletes and military personnel are often expected to compete and work in hot and/or humid environments, where decrements in performance and an increased risk of exertional heat illness are prevalent. A physiological strategy for reducing the adverse effects of heat stress is to acclimatise to the heat. OBJECTIVE: The aim of this systematic review was to quantify the effects of relocating to a hotter climate to undergo heat acclimatisation in athletes and military personnel. ELIGIBILITY CRITERIA: Studies investigating the effects of heat acclimatisation in non-acclimatised athletes and military personnel via relocation to a hot climate for < 6 weeks were included. DATA SOURCES: MEDLINE, SPORTDiscus, CINAHL Plus with Full Text and Scopus were searched from inception to June 2022. RISK OF BIAS: A modified version of the McMaster critical review form was utilised independently by two authors to assess the risk of bias. DATA SYNTHESIS: A Bayesian multi-level meta-analysis was conducted on five outcome measures, including resting core temperature and heart rate, the change in core temperature and heart rate during a heat response test and sweat rate. Wet-bulb globe temperature (WBGT), daily training duration and protocol length were used as predictor variables. Along with posterior means and 90% credible intervals (CrI), the probability of direction (Pd) was calculated. RESULTS: Eighteen articles from twelve independent studies were included. Fourteen articles (nine studies) provided data for the meta-analyses. Whilst accounting for WBGT, daily training duration and protocol length, population estimates indicated a reduction in resting core temperature and heart rate of - 0.19 °C [90% CrI: - 0.41 to 0.05, Pd = 91%] and - 6 beats·min-1 [90% CrI: - 16 to 5, Pd = 83%], respectively. Furthermore, the rise in core temperature and heart rate during a heat response test were attenuated by - 0.24 °C [90% CrI: - 0.67 to 0.20, Pd = 85%] and - 7 beats·min-1 [90% CrI: - 18 to 4, Pd = 87%]. Changes in sweat rate were conflicting (0.01 L·h-1 [90% CrI: - 0.38 to 0.40, Pd = 53%]), primarily due to two studies demonstrating a reduction in sweat rate following heat acclimatisation. CONCLUSIONS: Data from athletes and military personnel relocating to a hotter climate were consistent with a reduction in resting core temperature and heart rate, in addition to an attenuated rise in core temperature and heart rate during an exercise-based heat response test. An increase in sweat rate is also attainable, with the extent of these adaptations dependent on WBGT, daily training duration and protocol length. PROSPERO REGISTRATION: CRD42022337761.

Physical activity intervention improves executive function and language development during early childhood: The active early learning cluster randomized controlled trial.

This study aimed to determine the effects of the Active Early Learning (AEL) childcare center-based physical activity intervention on early childhood executive function and expressive vocabulary via a randomized controlled trial. Three-hundred-and-fourteen preschool children (134 girls) aged 3-5 years from 15 childcare centers were randomly assigned to the intervention (8 centers; n = 170 children) or control group (7 centers, n = 144 children) in May 2019. Participants were mostly Australian (85%) and from slightly higher areas of socio-economic status than the Australian average. There was an AEL intervention effect on inhibition (ß = 0.5, p = .033, d = 0.29) and expressive vocabulary (ß = 1.97, p = .001, d = 0.24). Integration of the AEL physical activity intervention into the daily childcare routine was effective in enhancing children's executive function and expressive language development.

Plant traits and associated data from a warming experiment, a seabird colony, and along elevation in Svalbard.

The Arctic is warming at a rate four times the global average, while also being exposed to other global environmental changes, resulting in widespread vegetation and ecosystem change. Integrating functional trait-based approaches with multi-level vegetation, ecosystem, and landscape data enables a holistic understanding of the drivers and consequences of these changes. In two High Arctic study systems near Longyearbyen, Svalbard, a 20-year ITEX warming experiment and elevational gradients with and without nutrient input from nesting seabirds, we collected data on vegetation composition and structure, plant functional traits, ecosystem fluxes, multispectral remote sensing, and microclimate. The dataset contains 1,962 plant records and 16,160 trait measurements from 34 vascular plant taxa, for 9 of which these are the first published trait data. By integrating these comprehensive data, we bridge knowledge gaps and expand trait data coverage, including on intraspecific trait variation. These data can offer insights into ecosystem functioning and provide baselines to assess climate and environmental change impacts. Such knowledge is crucial for effective conservation and management in these vulnerable regions.

Reversible conformational switching of a photo-responsive ortho-azobenzene/2,6-pyridyldicarboxamide heterofoldamer.

We report on a convenient synthetic route to rapidly access a new photo-responsive ortho-azobenzene/2,6-pyridyldicarboxamide heterofoldamer. The adoption of a stable helical conformation has been established for this scaffold in both the solid state and in solution using single crystal X-ray diffraction and circular dichroism (CD) spectroscopy respectively. Reversible control over the stimuli-driven structural re-ordering of the supramolecular scaffold, from a stable helical conformation under non-irradiative conditions, to a less well-ordered state under irradiative conditions, has been identified. The robust nature of the responsive, conformational, molecular switching behaviour has been determined using UV/Vis, 1H NMR and CD spectroscopy. Minimal loss in the efficiency of the stimuli-driven, structural re-ordering processes of the foldamer scaffold is observed, even upon multiple cyclic treatments with irradiative/non-irradiative conditions.

Supramolecular chemistry enables vat photopolymerization 3D printing of novel water-soluble tablets.

Vat photopolymerization has garnered interest from pharmaceutical researchers for the fabrication of personalised medicines, especially for drugs that require high precision dosing or are heat labile. However, the 3D printed structures created thus far have been insoluble, limiting printable dosage forms to sustained-release systems or drug-eluting medical devices which do not require dissolution of the printed matrix. Resins that produce water-soluble structures will enable more versatile drug release profiles and expand potential applications. To achieve this, instead of employing cross-linking chemistry to fabricate matrices, supramolecular chemistry may be used to impart dynamic interaction between polymer chains. In this study, water-soluble drug-loaded printlets (3D printed tablets) are fabricated via digital light processing (DLP) 3DP for the first time. Six formulations with varying ratios of an electrolyte acrylate monomer, [2-(acryloyloxy)ethyl]trimethylammonium chloride (TMAEA), and a co-monomer, 1-vinyl-2-pyrrolidone (NVP), were prepared to produce paracetamol-loaded printlets. 1H NMR spectroscopy analysis confirmed the integration of TMAEA and NVP in the polymer, and residual TMAEA monomers were found to be present only in trace amounts (0.71 - 1.37 %w/w). The apparent molecular mass of the photopolymerised polymer was found to exceed 300,000 Da with hydrodynamic radii of 15 - 20 nm, estimated based on 1H DOSY NMR measurements The loaded paracetamol was completely released from the printlets between 45 minutes to 5 hours. In vivo single-dose acute toxicity studies in rats suggest that the printlets did not cause any tissue damage. The findings reported in this study represent a significant step towards the adoption of vat photopolymerization-based 3DP to produce personalised medicines.

Hammett correlation in competition experiments in dissociation of ionised substituted benzophenones and dibenzylideneacetones.

A convenient method of applying competition experiments to devise a Hammett correlation in the dissociation by α-cleavage of 17 ionised 3- and 4-substituted benzophenones, YC6H4COC6H5 [Y=F, Cl, Br, CH3, CH3O, NH2, CF3, OH, NO2, CN and N(CH3)2] is reported and discussed. The results given by this approach, which rely on the relative abundance of [M-C6H5]+ and [M-C6H4Y]+ ions in the electron ionisation spectra of the substituted benzophenones, are compared with those obtained by previous methods. Various refinements of the method are considered, including reducing the ionising electron energy, making allowance for the relative abundance of ions such as C6H5+ and C6H4Y+, which may be formed to some extent by secondary fragmentation, and using substituent constants other than the standard σ constants. The reaction constant, ρ, of 1.08, which is in good agreement with that deduced previously, is consistent with a considerable reduction in electron density (corresponding to an increase in positive charge) at the carbon of the carbonyl group during fragmentation. This method has been successfully extended to the corresponding cleavage of 12 ionised substituted dibenzylideneacetones, YC6H4CH=CHCOCH=CHC6H5 (Y=F, Cl, CH3, OCH3, CF3, and NO2), which may fragment to form either a substituted cinnamoyl cation, [YC6H4CH=CHCO]+, or the cinnamoyl cation, [C6H5CH=CHCO]+. The derived ρ value of 0.76 indicates that the substituent, Y, influences the stability of the cinnamoyl cation somewhat less strongly than it does the analogous benzoyl cation.

Proximity effects in the electron ionisation mass spectra of substituted cinnamamides.

The electron ionisation mass spectra of an extensive set of 53 ionised monosubstituted and disubstituted cinnamamides [XC6H4CH=CHCONH2, X = H, F, Cl, Br, I, CH3, CH3O, CF3, NO2, CH3CH2, (CH3)2CH and (CH3)3C; and XYC6H3CH=CHCONH2, X = Y = Cl; and X, Y = F, Cl or Br] are reported and discussed. Particular attention is paid to the significance of loss of the substituent, X, from the 2-position, via a rearrangement that is sometimes known as a proximity effect, which has been reported for a range of radical-cations, but is shown in this work to be especially important for ionised cinnamamides. When X is in the 2-position of the aromatic ring, [M - X]+ is formed to a far greater extent than [M - H]+; in contrast, when X is in the 3-position or 4-position, [M - H]+ is generally much more important than [M - X]+. Parallel trends are found in the spectra of XYC6H3CH=CHCONH2: the signal for [M - X]+ dominates that for [M - Y]+ when X is in the 2-position and Y in the 4-position or 5-position, irrespective of the nature of X and Y. Further insight is obtained by studying the competition between expulsion of X· and alternative fragmentations that may be described as simple cleavages. Loss of ·NH2 results in the formation of a substituted cinnamoyl cation, [XC6H4CH=CHCO]+ or [XYC6H3CH=CHCO]+; this process competes far less effectively with the proximity effect when X is in the 2-position than when it is in the 3-position or 4-position. Additional information has been obtained by investigating the competition between formation of [M - H]+ by the proximity effect and loss of CH3· by cleavage of a 4-alkyl group to give a benzylic cation, [R1R2CC6H4CH=CHCONH2]+ (R1, R2 = H, CH3).

Close to open-Factors that hinder and promote open science in ecology research and education.

The Open Science (OS) movement is rapidly gaining traction among policy-makers, research funders, scientific journals and individual scientists. Despite these tendencies, the pace of implementing OS throughout the scientific process and across the scientific community remains slow. Thus, a better understanding of the conditions that affect OS engagement, and in particular, of how practitioners learn, use, conduct and share research openly can guide those seeking to implement OS more broadly. We surveyed participants at an OS workshop hosted by the Living Norway Ecological Data Network in 2020 to learn how they perceived OS and its importance in their research, supervision and teaching. Further, we wanted to know what OS practices they had encountered in their education and what they saw as hindering or helping their engagement with OS. The survey contained scaled-response and open-ended questions, allowing for a mixed-methods approach. We obtained survey responses from 60 out of 128 workshop participants (47%). Responses indicated that usage and sharing of open data and code, as well as open access publication, were the most frequent OS practices. Only a minority of respondents reported having encountered OS in their formal education. A majority also viewed OS as less important in their teaching than in their research and supervisory roles. The respondents' suggestions for what would facilitate greater OS engagement in the future included knowledge, guidelines, and resources, but also social and structural support. These are aspects that could be strengthened by promoting explicit implementation of OS practices in higher education and by nurturing a more inclusive and equitable OS culture. We argue that incorporating OS in teaching and learning of science can yield substantial benefits to the research community, student learning, and ultimately, to the wider societal objectives of science and higher education.

The role of plant functional groups mediating climate impacts on carbon and biodiversity of alpine grasslands.

Plant removal experiments allow assessment of the role of biotic interactions among species or functional groups in community assembly and ecosystem functioning. When replicated along climate gradients, they can assess changes in interactions among species or functional groups with climate. Across twelve sites in the Vestland Climate Grid (VCG) spanning 4 °C in growing season temperature and 2000 mm in mean annual precipitation across boreal and alpine regions of Western Norway, we conducted a fully factorial plant functional group removal experiment (graminoids, forbs, bryophytes). Over six years, we recorded biomass removed, soil microclimate, plant community composition and structure, seedling recruitment, ecosystem carbon fluxes, and reflectance in 384 experimental and control plots. The dataset consists of 5,412 biomass records, 360 species-level biomass records, 1,084,970 soil temperature records, 4,771 soil moisture records, 17,181 plant records covering 206 taxa, 16,656 seedling records, 3,696 ecosystem carbon flux measurements, and 1,244 reflectance measurements. The data can be combined with longer-term climate data and plant population, community, ecosystem, and functional trait data collected within the VCG.

Zirconium-Based MOFs and Their Biodegradable Polymer Composites for Controlled and Sustainable Delivery of Herbicides.

Adsorption and controlled release of agrochemicals has been studied widely using different nanomaterials and a variety of formulations. However, the potential for application of high surface-area metal-organic frameworks (MOFs) for the controlled release of agrochemicals has not been thoroughly explored. Herein, we report controlled and sustainable release of a widely used herbicide (2-methyl-4-chlorophenoxyacetic acid, MCPA) via incorporation in a range of zirconium-based MOFs and their biodegradable polymer composites. Three Zr-based MOFs, viz., UiO-66, UiO-66-NH2, and UiO-67 were loaded with MCPA either postsynthetically or in situ during synthesis of the MOFs. The MCPA-loaded MOFs were then incorporated into a biodegradable polycaprolactone (PCL) composite membrane. All three MOFs and their PCL composites were thoroughly characterized using FT-IR, TGA, SEM, PXRD, BET, and mass spectrometry. Release of MCPA from each of these MOFs and their PCL composites was then studied in both distilled water and in ethanol for up to 72 h using HPLC. The best performance for MCPA release was observed for the postsynthetically loaded MOFs, with PS-MCPA@UiO-66-NH2 showing the highest MCPA concentrations in ethanol and water of 0.056 and 0.037 mg/mL, respectively. Enhanced release of MCPA was observed in distilled water when the MOFs were incorporated in PCL. The concentrations of herbicides in the release studies provide us with a range of inhibitory concentrations that can be utilized depending on the crop, making this class of composite materials a promising new route for future agricultural applications.

The effect of a 6-month physical literacy intervention on preschool children's gross and fine motor skill: The Active Early Learning randomised controlled trial.

OBJECTIVES: The Active Early Learning intervention was designed to support childcare educators to imbed physical literacy promoting activities into the daily childcare curriculum. The objective of this study was to determine whether this physical literacy intervention had any influence on motor skill development. DESIGN: 22-week stratified cluster randomised controlled trial. METHODS: Fifteen childcare centres (8 intervention, 7 control centres; 314 children, 180 boys, 4.3y ±â€¯0.4) participated in the study. Six motor skills were assessed: object control (ball drop/catch and bean bag throw accuracy), locomotor control (10 m shuttle run), stability (one-leg balance and tiptoe walking on a line), and fine motor control (coin manipulation). Intervention effects were evaluated using linear mixed models adjusted for age, sex, socio-economic status, and centre clustering. RESULTS: There was evidence for an intervention effect on fine motor control (-0.47 s, CI [-0.93 to -0.02], p = .041) and the ball drop/catch task (0.68, CI [0.01-1.35], p = .046), but not for locomotor control, stability, or throw accuracy. CONCLUSIONS: Improvements in children's gross and fine motor skills can be achieved with a physical literacy intervention delivered by childcare educators. However, broad enhancement of motor skills cannot be assumed by simply introducing more physical literacy promoting activities into the daily routine, and specific motor skill instruction seems warranted in childcare settings.

Influence of sex and biological maturation on the sudomotor response to exercise-heat stress: are girls disadvantaged?

Both adult females and children have been reported to have a lower sweating capacity and thus reduced evaporative heat loss potential that may increase their susceptibility to exertional hyperthermia in the heat. Compared with males, females have a lower maximal sweat rate and thus a theoretically lower maximum skin wettedness due to a lower sweat output per gland. Similarly, children have been suggested to be disadvantaged in high ambient temperatures due to a lower sweat production and therefore reduced evaporative capacity, despite modifications of heat transfer due to physical attributes and possible evaporative efficiency. The reported reductions in the sudomotor activity of females and children suggest a lower sweating capacity in girls. However, because of the complexities of isolating sex and maturation from the confounding effects of morphological differences (e.g., body surface area-to-mass ratio) and metabolic heat production, limited evidence exists supporting whether children, and, more specifically, girls are at a thermoregulatory disadvantage. Furthermore, a limited number of child-adult comparison studies involve females and very few studies have directly compared regional and whole body sudomotor activity between boys and girls. This minireview highlights the exercise-induced sudomotor response of females and children, summarizes previous research investigating the sudomotor response to exercise in girls, and suggests important areas for further research.

Seasonal Heat Acclimatisation in Healthy Adults: A Systematic Review.

BACKGROUND: Physiological heat adaptations can be induced following various protocols that use either artificially controlled (i.e. acclimation) or naturally occurring (i.e. acclimatisation) environments. During the summer months in seasonal climates, adequate exposure to outdoor environmental heat stress should lead to transient seasonal heat acclimatisation. OBJECTIVES: The aim of the systematic review was to assess the available literature and characterise seasonal heat acclimatisation during the summer months and identify key factors that influence the magnitude of adaptation. ELIGIBILITY CRITERIA: English language, full-text articles that assessed seasonal heat acclimatisation on the same sample of healthy adults a minimum of 3 months apart were included. DATA SOURCES: Studies were identified using first- and second-order search terms in the databases MEDLINE, SPORTDiscus, CINAHL Plus with Full Text, Scopus and Cochrane, with the last search taking place on 15 July 2021. RISK OF BIAS: Studies were independently assessed by two authors for the risk of bias using a modified version of the McMaster critical review form. DATA EXTRACTION: Data for the following outcome variables were extracted: participant age, sex, body mass, height, body fat percentage, maximal oxygen uptake, time spent exercising outdoors (i.e. intensity, duration, environmental conditions), heat response test (i.e. protocol, time between tests), core temperature, skin temperature, heart rate, whole-body sweat loss, whole-body and local sweat rate, sweat sodium concentration, skin blood flow and plasma volume changes. RESULTS: Twenty-nine studies were included in this systematic review, including 561 participants across eight countries with a mean summer daytime wet-bulb globe temperature (WBGT) of 24.9 °C (range: 19.5-29.8 °C). Two studies reported a reduction in resting core temperature (0.16 °C; p < 0.05), 11 reported an increased sweat rate (range: 0.03-0.53 L·h-1; p < 0.05), two observed a reduced heart rate during a heat response test (range: 3-8 beats·min-1; p < 0.05), and six noted a reduced sweat sodium concentration (range: - 22 to - 59%; p < 0.05) following summer. The adaptations were associated with a mean summer WBGT of 25.2 °C (range: 19.6-28.7 °C). LIMITATIONS: The available studies primarily focussed on healthy male adults and demonstrated large differences in the reporting of factors that influence the development of seasonal heat acclimatisation, namely, exposure time and duration, exercise task and environmental conditions. CONCLUSIONS: Seasonal heat acclimatisation is induced across various climates in healthy adults. The magnitude of adaptation is dependent on a combination of environmental and physical activity characteristics. Providing environmental conditions are conducive to adaptation, the duration and intensity of outdoor physical activity, along with the timing of exposures, can influence seasonal heat acclimatisation. Future research should ensure the documentation of these factors to allow for a better characterisation of seasonal heat acclimatisation. PROSPERO REGISTRATION: CRD42020201883.

Rational Development of a Carrier-Free Dry Powder Inhalation Formulation for Respiratory Viral Infections via Quality by Design: A Drug-Drug Cocrystal of Favipiravir and Theophylline.

Formulating pharmaceutical cocrystals as inhalable dosage forms represents a unique niche in effective management of respiratory infections. Favipiravir, a broad-spectrum antiviral drug with potential pharmacological activity against SARS-CoV-2, exhibits a low aqueous solubility. An ultra-high oral dose is essential, causing low patient compliance. This study reports a Quality-by-Design (QbD)-guided development of a carrier-free inhalable dry powder formulation containing a 1:1 favipiravir-theophylline (FAV-THP) cocrystal via spray drying, which may provide an alternative treatment strategy for individuals with concomitant influenza infections and chronic obstructive pulmonary disease/asthma. The cocrystal formation was confirmed by single crystal X-ray diffraction, powder X-ray diffraction, and the construction of a temperature-composition phase diagram. A three-factor, two-level, full factorial design was employed to produce the optimized formulation and study the impact of critical processing parameters on the resulting median mass aerodynamic diameter (MMAD), fine particle fraction (FPF), and crystallinity of the spray-dried FAV-THP cocrystal. In general, a lower solute concentration and feed pump rate resulted in a smaller MMAD with a higher FPF. The optimized formulation (F1) demonstrated an MMAD of 2.93 µm and an FPF of 79.3%, suitable for deep lung delivery with no in vitro cytotoxicity observed in A549 cells.

Antioxidant Supplementation Protects Elite Athlete Muscle Integrity During Submaximal Training.

PURPOSE: To determine (1) the effect of a 40-minute steady-state run on muscle membrane integrity of elite athletes as reflected by serum creatine kinase (CK), (2) whether antioxidant supplementation (AS) with vitamins E and C has a protective effect, and (3) if a minimal blood concentration of vitamin E or C is required for any such protection. METHODS: Fifteen elite-level endurance athletes (V˙O2max=71.5±1.2 mL·kg-1 min-1) were randomly assigned to 6 weeks AS (1000 IU·d-1 natural vitamin E and 1000 mg·d-1 vitamin C) or placebo. Using a double-blind crossover design and 4-week washout period, each treatment was followed by a 40-minute steady-state run at 3 mM blood lactate. Blood samples before and 0 and 24 hours after the run were assayed for serum and red cell α-tocopherol (α-TOH), serum ascorbate, and CK. RESULTS: The AS produced a 2.5-fold, well-correlated (r = .84) increase in serum and red cell α-TOH (P < .001) that attenuated the increase in postrun CK (P = .01). There was no change in serum ascorbate with AS and no relationship with CK (P > .1). Curvilinear regression revealed some evidence that a critical level of serum α-TOH in the vicinity of 12 mg·L-1 was required to attenuate CK efflux, a level only achieved with AS. CONCLUSION: The muscle membrane integrity of elite-level athletes is compromised even during steady-state running of moderate intensity and duration. The AS provided a protective effect, with evidence that a serum α-TOH concentration of around 12 mg·L-1 is required.