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1.
Nutrients ; 16(11)2024 May 31.
Article En | MEDLINE | ID: mdl-38892651

The consumption of protein-rich foods stimulates satiety more than other macronutrient-rich foods; however, the underlying mechanisms-of-action are not well-characterized. The objective of this study was to identify the direct and indirect effects of postprandial amino acid (AA) responses on satiety. Seventeen women (mean ± SEM, age: 33 ± 1 year; BMI: 27.8 ± 0.1 kg/m2) consumed a eucaloric, plant-based diet containing two servings of lean beef/day (i.e., 7.5 oz (207 g)) for 7 days. During day 6, the participants completed a 12 h controlled-feeding, clinical testing day including repeated satiety questionnaires and blood sampling to assess pre- and postprandial plasma AAs, PYY, and GLP-1. Regression and mediation analyses were completed to assess AA predictors and hormonal mediators. Total plasma AAs explained 41.1% of the variance in perceived daily fullness (p < 0.001), 61.0% in PYY (p < 0.001), and 66.1% in GLP-1 (p < 0.001) concentrations, respectively. Several individual AAs significantly predicted fluctuations in daily fullness, PYY, and GLP-1. In completing mediation analyses, the effect of plasma leucine on daily fullness was fully mediated by circulating PYY concentrations (indirect effect = B: 0.09 [Boot 95% CI: 0.032, 0.17]) as no leucine-fullness direct effect was observed. No other mediators were identified. Although a number of circulating AAs predict satiety, leucine was found to do so through changes in PYY concentrations in middle-aged women.


Amino Acids , Overweight , Peptide YY , Postprandial Period , Red Meat , Satiation , Humans , Female , Adult , Amino Acids/blood , Peptide YY/blood , Satiation/drug effects , Overweight/blood , Glucagon-Like Peptide 1/blood , Biomarkers/blood , Meals , Animals , Cattle , Satiety Response/drug effects
2.
Cell Biosci ; 14(1): 74, 2024 Jun 07.
Article En | MEDLINE | ID: mdl-38849850

BACKGROUND: The glycolytic enzyme alpha-enolase is a known biomarker of many cancers and involved in tumorigenic functions unrelated to its key role in glycolysis. Here, we show that expression of alpha-enolase correlates with subcellular localisation and tumorigenic status in the MCF10 triple negative breast cancer isogenic tumour progression model, where non-tumour cells show diffuse nucleocytoplasmic localisation of alpha-enolase, whereas tumorigenic cells show a predominantly cytoplasmic localisation. Alpha-enolase nucleocytoplasmic localisation may be regulated by tumour cell-specific phosphorylation at S419, previously reported in pancreatic cancer. RESULTS: Here we show ENO1 phosphorylation can also be observed in triple negative breast cancer patient samples and MCF10 tumour progression cell models. Furthermore, prevention of alpha-enolase-S419 phosphorylation by point mutation or a casein kinase-1 specific inhibitor D4476, induced tumour-specific nuclear accumulation of alpha-enolase, implicating S419 phosphorylation and casein kinase-1 in regulating subcellular localisation in tumour cell-specific fashion. Strikingly, alpha-enolase nuclear accumulation was induced in tumour cells by treatment with the specific exportin-1-mediated nuclear export inhibitor Leptomycin B. This suggests that S419 phosphorylation in tumour cells regulates alpha-enolase subcellular localisation by inducing its exportin-1-mediated nuclear export. Finally, as a first step to analyse the functional consequences of increased cytoplasmic alpha-enolase in tumour cells, we determined the alpha-enolase interactome in the absence/presence of D4476 treatment, with results suggesting clear differences with respect to interaction with cytoskeleton regulating proteins. CONCLUSIONS: The results suggest for the first time that tumour-specific S419 phosphorylation may contribute integrally to alpha-enolase cytoplasmic localisation, to facilitate alpha-enolase's role in modulating cytoskeletal organisation in triple negative breast cancer. This new information may be used for development of triple negative breast cancer specific therapeutics that target alpha-enolase.

3.
Expert Rev Clin Immunol ; 20(7): 695-702, 2024 Jul.
Article En | MEDLINE | ID: mdl-38879876

INTRODUCTION: Vitiligo is a chronic, autoimmune condition characterized by skin depigmentation caused by inflammatory-mediated melanocyte degradation. Treatment of vitiligo is challenging due to the chronic nature of the condition. Ruxolitinib cream 1.5% was recently approved by the Food and Drug Administration (FDA) as a Janus kinase 1 and 2 inhibitor for use in nonsegmental vitiligo for those 12 years and older. AREAS COVERED: The purpose of this review is to describe the role of ruxolitinib in treating nonsegmental vitiligo.We searched PubMed using search terms nonsegmental vitiligo, jak inhibitor, and ruxolitinib. Clinicaltrials.gov was used to identify clinical trial data including efficacy, pharmacodynamics, pharmacokinetics, safety, and tolerability. EXPERT OPINION: In both phase II and phase III (TRuE-V1 and TRuE-V2) trials, ruxolitinib cream 1.5% improved repigmentation with minimal adverse effects. Topical ruxolitinib is a much needed new vitiligo treatment option.  Real life efficacy may not match that seen in clinical trials if the hurdle of poor adherence to topical treatment is not surmounted.


Nitriles , Pyrazoles , Pyrimidines , Vitiligo , Humans , Vitiligo/drug therapy , Pyrimidines/therapeutic use , Pyrazoles/therapeutic use , Skin Pigmentation/drug effects , Janus Kinase 1/antagonists & inhibitors , Skin Cream/therapeutic use , Janus Kinase 2/antagonists & inhibitors , Janus Kinase Inhibitors/therapeutic use
4.
J Cell Biol ; 223(9)2024 Sep 02.
Article En | MEDLINE | ID: mdl-38787349

Cell processes require precise regulation of actin polymerization that is mediated by plus-end regulatory proteins. Detailed mechanisms that explain plus-end dynamics involve regulators with opposing roles, including factors that enhance assembly, e.g., the formin mDia1, and others that stop growth (capping protein, CP). We explore IQGAP1's roles in regulating actin filament plus-ends and the consequences of perturbing its activity in cells. We confirm that IQGAP1 pauses elongation and interacts with plus ends through two residues (C756 and C781). We directly visualize the dynamic interplay between IQGAP1 and mDia1, revealing that IQGAP1 displaces the formin to influence actin assembly. Using four-color TIRF, we show that IQGAP1's displacement activity extends to formin-CP "decision complexes," promoting end-binding protein turnover at plus-ends. Loss of IQGAP1 or its plus-end activities disrupts morphology and migration, emphasizing its essential role. These results reveal a new role for IQGAP1 in promoting protein turnover on filament ends and provide new insights into how plus-end actin assembly is regulated in cells.


Actin Capping Proteins , Actin Cytoskeleton , Formins , ras GTPase-Activating Proteins , Animals , Humans , Actin Capping Proteins/metabolism , Actin Capping Proteins/genetics , Actin Cytoskeleton/metabolism , Actins/metabolism , Cell Movement , Formins/metabolism , HeLa Cells , Protein Binding , ras GTPase-Activating Proteins/metabolism , ras GTPase-Activating Proteins/genetics , Mice , NIH 3T3 Cells
5.
Pharmaceuticals (Basel) ; 17(5)2024 May 15.
Article En | MEDLINE | ID: mdl-38794207

Even slight structural differences between phytocannabinoid isomers are usually enough to cause a change in their biological properties. In this study, we used in vitro CB1 agonism/antagonism assays to compare the receptor binding functionality of THCV (tetrahydrocannabivarin) and HHC (hexahydrocannabinol) isomers and applied molecular docking to provide an explanation for the difference in the activities. No CB1 agonism was observed for ∆9- and ∆8-THCV. Instead, both isomers antagonized CP 55940, with ∆9-THCV being approximately two times more potent than the ∆8 counterpart (IC50 = 52.4 nM and 119.6 nM for ∆9- and ∆8-THCV, respectively). Docking simulations found two binding poses for THCV isomers, one very similar to ∆9-THC and one newly discovered pose involving the occupation of side pocket 1 of the CB1 receptor by the alkyl chain of the ligand. We suggested the latter as a potential antagonist pose. In addition, our results established 9R-HHC and 9S-HHC among partial agonists of the CB1 receptor. The 9R-HHC (EC50 = 53.4 nM) isomer was a significantly more potent agonist than 9S (EC50 = 624.3 nM). ∆9-THC and 9R-HHC showed comparable binding poses inside the receptor pocket, whereas 9S-HHC adopted a new and different binding posture that can explain its weak agonist activity.

6.
ACS Omega ; 9(20): 22203-22212, 2024 May 21.
Article En | MEDLINE | ID: mdl-38799302

Organic ionic plastic crystals (OIPCs) have attracted attention as novel organic solid electrolyte materials, but their insufficient mechanical strength and ionic conductivity have prevented their application. In this study, a lithium salt, lithium bis(fluorosulfonyl)amide (LiFSA), and an inorganic solid electrolyte, Li7La3Zr2O12 (LLZO), were added to an OIPC, N,N-diethylpyrrolidinium bis(fluorosulfonyl)amide ([C2epyr][FSA]). The fabricated organic-inorganic hybrid solid electrolytes were evaluated thermally, mechanically, and electrochemically to reveal which factors affect the properties of the electrolytes. All samples showed excellent thermal stability regardless of LiFSA or LLZO concentration, and they were found to be highly plastic and ion-conductive solids at a wide range of temperatures. It was also revealed that the addition of LLZO raised the nanoindentation stiffness (HIT) of the [C2epyr][FSA]/LiFSA composites. The ionic conductivity of the hybrid electrolytes was higher than that of the pristine OIPC, reaching a value of 2.1 × 10-4 S cm-1 at 25 °C upon addition of appropriate amounts of LiFSA and LLZO. Overall, samples with higher LiFSA concentration and moderate LLZO concentration exhibited higher ionic conductivity. Cyclic voltammetry results showed that the [C2epyr][FSA]/LiFSA/LLZO composites were lithium-ion conductors. These findings indicate that by optimizing the concentrations of lithium salt and LLZO, it would be possible to realize their applications as solid electrolytes.

7.
Am J Surg ; 2024 May 18.
Article En | MEDLINE | ID: mdl-38789322

BACKGROUND: Fascial plane blocks (FPBs) are widely used for abdominal surgery with the assumption that liposomal bupivacaine (LB) is more effective than standard bupivacaine (SB). METHODS: This was a single-institution retrospective cohort study of patients administered FPBs with LB or SB â€‹+ â€‹admixtures (dexamethasone/dexmedetomidine) for open abdominal cancer surgery. Propensity score matching generated a 2:1 (LB:SB) matched cohort. Opioid use (mg oral morphine equivalents, OME) and severe pain (≥3 pain scores ≥7 in a 24-h period) were compared. RESULTS: Opioid use was >150 â€‹mg OME in 19.9 â€‹% (29/146) LB and 16.4 â€‹% (12/73) SB patients (p â€‹= â€‹0.586). Severe pain was experienced by 44 â€‹% (64/146) LB and 53 â€‹% (39/73) SB patients (p â€‹= â€‹0.198). On multivariable analysis, SB vs LB choice was not associated with high opioid volume >150 â€‹mg or severe pain. CONCLUSIONS: FPBs with standard bupivacaine were not associated with higher 72-h opioid use or more severe pain compared to liposomal bupivacaine.

8.
ACS Earth Space Chem ; 8(5): 957-964, 2024 May 16.
Article En | MEDLINE | ID: mdl-38774358

With its large size, dense atmosphere, methane-based hydrological-like cycle, and diverse surface features, the Saturnian moon Titan is one of the most unique of the outer Solar System satellites. Study of the photochemically produced molecules in Titan's atmosphere is critical in order to understand the mechanics of the atmosphere and, by extension, the interactions between atmosphere, surface, and subsurface water ocean. One example is propyne vapor, a photochemically produced species in Titan's upper atmosphere expected to condense in Titan's stratosphere at lower altitudes. Propyne may also be a trace species in Titan's stratospheric co-condensed ice clouds detected by the Cassini Composite InfraRed Spectrometer. Bulk structural characterization of propyne ice is currently incomplete and is lacking in published laboratory Raman spectra and X-ray diffraction data. Here, we present a laboratory characterization of propyne ice, including the first published X-ray diffraction and Raman spectroscopy results for propyne ice.

9.
JCI Insight ; 9(10)2024 Apr 23.
Article En | MEDLINE | ID: mdl-38652535

BACKGROUNDPersistent cough and dyspnea are prominent features of postacute sequelae of SARS-CoV-2 (also termed "long COVID"); however, physiologic measures and clinical features associated with these pulmonary symptoms remain poorly defined. Using longitudinal pulmonary function testing (PFT) and CT imaging, this study aimed to identify the characteristics and determinants of pulmonary long COVID.METHODSThis single-center retrospective study included 1,097 patients with clinically defined long COVID characterized by persistent pulmonary symptoms (dyspnea, cough, and chest discomfort) lasting for 1 or more months after resolution of primary COVID infection.RESULTSAfter exclusion, a total of 929 patients with post-COVID pulmonary symptoms and PFTs were stratified as diffusion impairment and pulmonary restriction, as measured by percentage predicted diffusion capacity for carbon monoxide (DLCO) and total lung capacity (TLC). Longitudinal evaluation revealed diffusion impairment (DLCO ≤ 80%) and pulmonary restriction (TLC ≤ 80%) in 51% of the cohort overall (n = 479). In multivariable modeling regression analysis, invasive mechanical ventilation during primary infection conferred the greatest increased odds of developing pulmonary long COVID with diffusion impairment and restriction (adjusted odds ratio [aOR] = 9.89, 95% CI 3.62-26.9]). Finally, a subanalysis of CT imaging identified radiographic evidence of fibrosis in this patient population.CONCLUSIONLongitudinal PFTs revealed persistent diffusion-impaired restriction as a key feature of pulmonary long COVID. These results emphasize the importance of incorporating PFTs into routine clinical practice for evaluation of long COVID patients with prolonged pulmonary symptoms. Subsequent clinical trials should leverage combined symptomatic and quantitative PFT measurements for more targeted enrollment of pulmonary long COVID patients.FUNDINGNational Institute of Allergy and Infectious Diseases (AI156898, K08AI129705), National Heart, Lung, and Blood Institute (HL153113, OTA21-015E, HL149944), and the COVID-19 Urgent Research Response Fund at the University of Alabama at Birmingham.


COVID-19 , Lung , Post-Acute COVID-19 Syndrome , Respiratory Function Tests , SARS-CoV-2 , Humans , COVID-19/complications , COVID-19/epidemiology , Male , Female , Middle Aged , Retrospective Studies , Aged , Lung/diagnostic imaging , Lung/physiopathology , Tomography, X-Ray Computed , Dyspnea/physiopathology , Dyspnea/etiology , Cough/physiopathology
10.
Blood Adv ; 2024 Apr 12.
Article En | MEDLINE | ID: mdl-38608257

Clonal hematopoiesis (CH) is an age-associated phenomenon leading to increased risk of both hematologic malignancy and non-malignant organ dysfunction. Increasingly available genetic testing has made incidental discovery of CH clinically common, yet evidence-based guidelines and effective management strategies to prevent adverse CH health outcomes are lacking. To address this gap, the prospective CHIVE registry and biorepository was created to identify and monitor individuals at risk, support multidisciplinary CH clinics, and to refine standards of practice for CH risk mitigation. Data from the first 181 patients enrolled in this registry recapitulate the molecular epidemiology of CH from biobank scale retrospective studies, with DNMT3A, TET2, ASXL1, and TP53 as the most commonly mutated genes. CH patients had higher rates of end organ dysfunction, in particular chronic kidney disease (p=0.001). Among patients with CH, variant allele frequency was independently associated with presence of cytopenias (p=0.008) and progression to hematologic malignancy (p=0.010), while other common high-risk CH clone features were not clear. Notably, accumulation of multiple distinct high-risk clone features was also associated with cytopenias (p=0.013) and hematologic malignancy progression (p=0.004), supporting a recently published CH risk score. Surprisingly, ~30% of patients enrolled in CHIVE from CH clinics were adjudicated as not having CHIP, highlighting the need for molecular standards and purpose-built assays in this field. Maintenance of this well-annotated cohort and continued expansion of CHIVE to multiple institutions is underway and will be critical to understand how to thoughtfully care for this patient population.

11.
MethodsX ; 12: 102693, 2024 Jun.
Article En | MEDLINE | ID: mdl-38633417

Dust is a sink for many semi-volatile compounds including flame retardants of the organophosphate ester (OPE) and brominated flame-retardant (BFR) classes. Given the large amount of time that we spend indoors, our exposure to these compounds via dust is of significant interest. Here, we present a novel microextraction approach to determine quantitative levels of selected OPEs and BFRs sampled from residential air filters from HVAC systems using a small volume of solvent. Dust samples (25 mg) is extracted with 1 mL of hexane/acetone (50/50, v/v). Upon solvent extraction of these HVAC dust samples, the analytes (TCPP, TDCPP, TPHP, T24DtBPP, TBBPA, and TriBBPA) were quantified via gas chromatography-mass spectrometry (GC/MS) or liquid chromatography-mass spectrometry (LC/MS). The methods for extracting these compounds from HVAC dust samples are detailed here with extensive method validation data to demonstrate accuracy and precision of these methods. •Dust is a sink for many semi-volatile compounds, including novel or emerging indoor pollutants like the organophosphate ester flame retardant T24DtBPP.•Here, a small amount of dust (25 mg) is extracted with a small volume of solvent (1 mL hexane and acetone) prior to analysis via chromatographic separation and mass spectrometric detection.

12.
Neurol Clin Pract ; 14(3): e200294, 2024 Jun.
Article En | MEDLINE | ID: mdl-38682006

Background and Objectives: This cross-sectional observational study retrospectively examined clinical data collected from adolescents and young adults (AYAs) seeking care in a specialty headache clinic. We characterized participants' headache characteristics and psychological functioning and examined the association between self-reported anxiety and depressive symptoms and headache frequency, severity, and disability. Methods: During their clinic visit, AYAs (M age = 18.36; range = 14-32, 79.5% female) completed an intake questionnaire and reported about their headache characteristics (i.e., frequency, severity, and duration of symptoms in months), mental health history (i.e., previous diagnosis of an anxiety or depressive disorder), and utilization of emergency department (ED) services for migraine. AYAs also completed psychometrically validated screening tools for anxiety and depressive symptoms (i.e., the GAD-7 and PHQ-9). We computed descriptive statistics and examined associations among scores on psychological measures and headache characteristics, including migraine-related disability. We also tested whether individuals with clinically elevated GAD-7 and PHQ-9 scores had higher levels of disability relative to those with fewer/subclinical levels of anxiety and depressive symptoms. Results: Participants (N = 283) reported more than 19 headache days per month on average, with more than 90% describing their average headache intensity as moderate or severe. Nearly half of AYAs reported severe headache-related disability. Approximately one-quarter of AYAs reported a previous diagnosis anxiety or depressive disorder diagnosis, and more than one-third scored above clinical cutoffs on the PHQ-9 and GAD-7. Higher scores on both psychological screening instruments were associated with greater headache frequency. More than 10% of patients endorsed current suicidal ideation; this was not related to headache-related disability. Participants reported a high degree of ED utilization for headache; these rates were unrelated to endorsement of psychological comorbidities. Discussion: In this sample of AYAs, headache characteristics were generally unrelated to scores on measures on psychological functioning. However, the observed rates of clinically elevated anxiety/depressive symptoms and suicidality in this sample of AYAs underscore the importance of screening for psychological comorbidities in neurology clinics that serve this age group, irrespective of self-reported disability. Results also emphasize the need to expand access to behavioral health services for AYAs with headache disorders and the importance of incorporating a biopsychosocial perspective to the transition of health care from pediatrics to adult neurology practice.

13.
PLoS One ; 19(4): e0299126, 2024.
Article En | MEDLINE | ID: mdl-38683806

Currently available pain assessment scales focus on pain-related symptoms and limitations imposed by pain. Validated assessment tools that measure how pain is regulated by those who live well with pain are missing. This study seeks to fill this gap by describing the development and preliminary validation of the Biobehavior Life Regulation (BLR) scale. The BLR scale assesses engagement, social relatedness, and self-growth in the presence of chronic pain and the unpredictability of chronic pain. Sources for items included survivor strategies, patient experiences, existing scales, and unpredictable pain research. Review for suitability yielded 52 items. Validation measures were identified for engagement, social relatedness, self-growth, and unpredictability of pain. The study sample (n = 202) represented patients treated in the Phoenix VA Health Care System (n = 112) and two community clinics (n = 90). Demographic characteristics included average age of 52.5, heterogeneous in ethnicity and race at the VA, mainly Non-Hispanic White at the community clinics, 14 years of education, and pain duration of 18 years for the VA and 15.4 years for community clinics. Exploratory factor analysis using Oblimin rotation in the VA sample (n = 112) yielded a two-factor solution that accounted for 48.23% of the total variance. Confirmatory factor analysis (CFA) in the same sample showed high correlations among items in Factor 1, indicating redundancy and the need to further reduce items. The final CFA indicated a 2-factor solution with adequate fit to the data. The 2-factor CFA was replicated in Sample 2 from the community clinics (n = 90) with similarly adequate fit to the data. Factor 1, Pain Regulation, covered 8 items of engagement, social relatedness, and self-growth while Factor 2, Pain Unpredictability, covered 6 items related to the experience of unpredictable pain. Construct validity showed moderate to higher Pearson correlations between BLR subscales and relevant well-established constructs that were consistent across VA and community samples. The BLR scale assesses adaptive regulation strategies in unpredictable pain as a potential tool for evaluating regulation resources and pain unpredictability.


Chronic Pain , Pain Measurement , Humans , Chronic Pain/psychology , Chronic Pain/diagnosis , Male , Middle Aged , Female , Pain Measurement/methods , Adult , Aged , Psychometrics/methods , Surveys and Questionnaires , Quality of Life , Factor Analysis, Statistical
14.
MicroPubl Biol ; 20242024.
Article En | MEDLINE | ID: mdl-38665313

Freshwater red algae are important primary producers, widely distributed, contributing significantly to nutrient cycling in aquatic ecosystems. Recent studies have focused on identifying the effect of different environmental conditions such as light on the gene expression in photosynthesis pathways. However, obtaining the necessary RNA quantity and quality for sequencing from these algae has been challenging. Although RNA extractions have been optimized for model organisms, RNA extraction for non-model organisms, such as gelatinous (polysaccharide-rich) red algae, requires considerable troubleshooting. The common freshwater red alga, Batrachospermum gelatinosum , was used to test protocols. The extraction efficiency of various sample disruption methods in combination with seven RNA extraction kits was compared. Using a 2-minute disruption procedure with a modification of TRIzol ™ Plus RNA Purification Kit (PureLink ™ RNA Mini Kit + Trizol ™ ) protocol resulted in significantly higher RIN scores (p < 0.05) and high RNA concentration, compared to other methods. The fine-tuned protocol yielded quality RNA (RIN>7) in high concentrations for subsequent sequencing.

16.
Meat Sci ; 213: 109498, 2024 Jul.
Article En | MEDLINE | ID: mdl-38520828

This study was conducted to evaluate the effects of relative humidity (RH) on moisture loss and flavor in dry-aged beef. Sixteen strip loins were assigned to one of the four aging treatments: vacuum (WET), dry-aging at 50% RH, dry-aging at 70% RH, or dry-aging at 85% RH and aged for 42 days at 2 °C. Loins were evaluated for evaporation loss, trim loss, tenderness, sensory, and microbiological characteristics. Results show that lower RH results in accelerated moisture loss during the first 3 days of the aging process without significantly affecting the total amount of moisture loss. Pseudomonadales dominated the aerobically dry-aged loins while Enterobacteriales was the most abundant in the wet-aged samples. Dry-aged samples had increased content of free amino acids in the cooked meat juice compared to the wet-aged counterpart. Dry aging at 50% RH tended to associate with more desirable flavor notes.


Food Handling , Humidity , Red Meat , Taste , Animals , Cattle , Red Meat/analysis , Red Meat/microbiology , Food Handling/methods , Humans , Amino Acids/analysis , Vacuum , Water/analysis , Food Microbiology
17.
Am J Physiol Renal Physiol ; 326(5): F802-F813, 2024 May 01.
Article En | MEDLINE | ID: mdl-38545652

Men are likely at greater risk for heat-induced acute kidney injury compared with women, possibly due to differences in vascular control. We tested the hypothesis that the renal vasoconstrictor and vasodilator responses will be greater in younger women compared with men during passive heat stress. Twenty-five healthy adults [12 women (early follicular phase) and 13 men] completed two experimental visits, heat stress or normothermic time-control, assigned in a block-randomized crossover design. During heat stress, participants wore a water-perfused suit perfused with 50°C water. Core temperature was increased by ∼0.8°C in the first hour before commencing a 2-min cold pressor test (CPT). Core temperature remained clamped and at 1-h post-CPT, subjects ingested a whey protein shake (1.2 g of protein/kg body wt), and measurements were taken pre-, 75 min, and 150 min post-protein. Beat-to-beat blood pressure (Penaz method) was measured and segmental artery vascular resistance (VR, Doppler ultrasound) was calculated as segmental artery blood velocity ÷ mean arterial pressure. CPT-induced increases in segmental artery VR did not differ between trials (trial effect: P = 0.142) nor between men (heat stress: 1.5 ± 1.0 mmHg/cm/s, normothermia: 1.4 ± 1.0 mmHg/cm/s) and women (heat stress: 1.4 ± 1.2 mmHg/cm/s, normothermia: 2.1 ± 1.1 mmHg/cm/s) (group effect: P = 0.429). Reductions in segmental artery VR following oral protein loading did not differ between trials (trial effect: P = 0.080) nor between men (heat stress: -0.6 ± 0.8 mmHg/cm/s, normothermia: -0.6 ± 0.6 mmHg/cm/s) and women (heat stress: -0.5 ± 0.5 mmHg/cm/s, normothermia: -1.1 ± 0.6 mmHg/cm/s) (group effect: P = 0.204). Renal vasoconstrictor responses to the cold pressor test and vasodilator responses following an oral protein load during heat stress or normothermia do not differ between younger men and younger women in the early follicular phase of the menstrual cycle.NEW & NOTEWORTHY The mechanisms underlying greater heat-induced acute kidney injury risk in men versus women remain unknown. This study examined renal vascular control, including both vasodilatory (oral protein load) and vasoconstrictor (cold presser test) responses, during normothermia and heat stress and compared these responses between men and women. The results indicated that in both conditions neither renal vasodilatory nor vasoconstrictor responses differ between younger men and younger women.


Heat-Shock Response , Vasodilation , Humans , Female , Male , Adult , Young Adult , Heat-Shock Response/physiology , Cross-Over Studies , Sex Factors , Vascular Resistance , Kidney/blood supply , Vasoconstriction , Renal Circulation , Renal Artery , Heat Stress Disorders/physiopathology , Blood Pressure/physiology , Age Factors
18.
Sci Adv ; 10(12): eadl0849, 2024 Mar 22.
Article En | MEDLINE | ID: mdl-38517965

Icy moons like Enceladus, and perhaps Europa, emit material sourced from their subsurface oceans into space via plumes of ice grains and gas. Both moons are prime targets for astrobiology investigations. Cassini measurements revealed a large compositional diversity of emitted ice grains with only 1 to 4% of Enceladus's plume ice grains containing organic material in high concentrations. Here, we report experiments simulating mass spectra of ice grains containing one bacterial cell, or fractions thereof, as encountered by advanced instruments on board future space missions to Enceladus or Europa, such as the SUrface Dust Analyzer onboard NASA's upcoming Europa Clipper mission at flyby speeds of 4 to 6 kilometers per second. Mass spectral signals characteristic of the bacteria are shown to be clearly identifiable by future missions, even if an ice grain contains much less than one cell. Our results demonstrate the advantage of analyses of individual ice grains compared to a diluted bulk sample in a heterogeneous plume.


Extraterrestrial Environment , Jupiter , Ice , Exobiology/methods , Oceans and Seas
19.
R Soc Open Sci ; 11(3): 231368, 2024 Mar.
Article En | MEDLINE | ID: mdl-38545612

Killer whales (Orcinus orca) are currently recognized as a single ecologically and morphologically diverse, globally distributed species. Multiple morphotypes or ecotypes have been described, often associated with feeding specialization, and several studies have suggested taxonomic revision to include multiple subspecies or species in the genus. We review the ecological, morphological and genetic data for the well-studied 'resident' and Bigg's (aka 'transient') ecotypes in the eastern North Pacific and use quantitative taxonomic guidelines and standards to determine whether the taxonomic status of these killer whale ecotypes should be revised. Our review and new analyses indicate that species-level status is justified in both cases, and we conclude that eastern North Pacific Bigg's killer whales should be recognized as Orcinus rectipinnus (Cope in Scammon, 1869) and resident killer whales should be recognized as Orcinus ater (Cope in Scammon, 1869).

20.
Article En | MEDLINE | ID: mdl-38493959

OBJECTIVE: Peripheral regional anesthesia is proposed to enhance recovery. We sought to evaluate the efficacy of bilateral continuous erector spinae plane blocks (B-ESpB) for postoperative analgesia and the impact on recovery in children undergoing cardiac surgery. METHODS: Patients aged 2 through 17 years undergoing cardiac surgery in the enhanced recovery after cardiac surgery program were prospectively enrolled to receive B-ESpB at the end of the procedure, with continuous infusions via catheters postoperatively. Participants wore an activity monitor until discharge. B-ESpB patients were retrospectively matched with control patients in the enhanced recovery after cardiac surgery program. Outcomes of the matched clusters were compared using exact conditional logistic regression and generalized linear modeling. RESULTS: Forty patients receiving B-ESpB were matched to 78 controls. There were no major complications from the B-ESpB or infusions, and operating room time was longer by a median of 31 minutes. While blocks were infusing, patients with B-ESpB received fewer opioids in oral morphine equivalents than controls at 24 hours (0.60 ± 0.06 vs 0.78 ± 0.04 mg/kg; P = .02) and 48 hours (1.13 ± 0.08 vs 1.35 ± 0.06 mg/kg; P = .04), respectively. Both groups had low median pain scores per 12-hour period. There was no difference in early mobilization, length of stay, or complications. CONCLUSIONS: B-ESpBs are safe in children undergoing cardiac surgery. When performed as part of a multimodal pain strategy in an enhanced recovery after cardiac surgery program, pediatric patients with B-ESpB experience good pain control and require fewer opioids in the first 48 hours.

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