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1.
J Physiol ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38975864

ABSTRACT

Fetal growth restriction (FGR) occurs in 8% of human pregnancies, and the growth restricted newborn is at a greater risk of developing heart disease in later adult life. In sheep, experimental restriction of placental growth (PR) from conception results in FGR, a decrease in cardiomyocyte endowment and an upregulation of pathological hypertrophic signalling in the fetal heart in late gestation. However, there is no change in the expression of markers of cellular proliferation nor in the level of cardiomyocyte apoptosis in the heart of the PR fetus in late gestation. This suggests that FGR arises early in gestation and programs a decrease in cardiomyocyte endowment in early, rather than late, gestation. Here, control and PR fetal sheep were humanely killed at 55 days' gestation (term, 150 days). Fetal body and heart weight were lower in PR compared with control fetuses and there was evidence of sparing of fetal brain growth. While there was no change in the proportion of cardiomyocytes that were proliferating in the early gestation PR heart, there was an increase in measures of apoptosis, and markers of autophagy and pathological hypertrophy in the PR fetal heart. These changes in early gestation highlight that FGR is associated with evidence of early cell death and compensatory hypertrophic responses of cardiomyocytes in the fetal heart. The data suggest that early placental restriction results in a decrease in the pool of proliferative cardiomyocytes in early gestation, which would limit cardiomyocyte endowment in the heart of the PR fetus in late gestation. KEY POINTS: Placental restriction leading to fetal growth restriction (FGR) and chronic fetal hypoxaemia in sheep results in a decrease in cardiomyocyte endowment in late gestation. FGR did not change cardiomyocyte proliferation during early gestation but did result in increased apoptosis and markers of autophagy in the fetal heart, which may result in the decreased endowment of cardiomyocytes observed in late gestation. FGR in early gestation also results in increased hypoxia inducible factor signalling in the fetal heart, which in turn may result in the altered expression of epigenetic regulators, increased expression of insulin-like growth factor 2 and cardiomyocyte hypertrophy during late gestation and after birth.

2.
Am J Surg ; : 115834, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38991911

ABSTRACT

BACKGROUND: Across surgery, marginalized individuals experience worse postoperative outcomes. These disparities stem from the interplay between multiple factors. METHODS: We introduced a novel framework to assess the role of barriers to access and bias in surgical complications (the uChicago Health Inequity Classification System, CHI-CS) in the setting of morbidity and mortality conference and assessed impact through pre and post implementation surveys. RESULTS: Access and bias were related to surgical complications in 14 â€‹% of cases. 97 â€‹% reported enhanced M&M presentations with the grading system, and 47 â€‹% reported a change in decision-making or practice style. Although post-implementation response rate was low, there were improvements in self-reported confidence and comfort in recognizing and discussing these issues. CONCLUSIONS: Implementation of the CHI-CS framework to discuss bias and access to care positively impacted the way providers view, discuss, and process health inequities.

3.
JTCVS Open ; 19: 241-256, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39015442

ABSTRACT

Objectives: The optimal treatment strategy for symptomatic young infants with tetralogy of Fallot (TOF) is unclear. We sought to compare the outcomes of staged repair (SR) (shunt palliation followed by second-stage complete repair) versus primary repair (PR) at 2 institutions that have exclusively adopted each strategy. Methods: We performed propensity score-matched comparison of 143 infants under 4 months of age who underwent shunt palliation at one institution between 1993 and 2021 with 122 infants who underwent PR between 2004 and 2018 at another institution. The primary outcome was mortality. Secondary outcomes were postoperative complications, durations of perioperative support and hospital stays, and reinterventions. Median follow-up was 8.3 years (interquartile range, 8.1-13.4 years). Results: After the initial procedure, hospital mortality (shunt, 2.8% vs PR, 2.5%; P = .86) and 10-year survival (shunt, 95%; 95% confidence interval [CI], 90%-98% vs PR, 90%; 95% CI, 81%-95%; P = .65) were similar. The SR group had a greater risk of early reinterventions but similar rates of late reinterventions. Propensity score matching yielded 57 well-balanced pairs. In the matched cohort, the SR group had similar freedom from reintervention (55%; 95% CI, 39%-68% vs 59%; 95% CI, 43%-71%; P = .85) and greater survival (98%; 95% CI, 88%-99.8% vs 85%; 95% CI, 69%-93%; P = .02) at 10 years, as the result of more noncardiac-related mortalities in the PR group. Conclusions: In symptomatic young infants with TOF operated at 2 institutions with exclusive treatment protocols, the SR strategy was associated with similar cardiac-related mortality and reinterventions as the PR strategy at medium-term follow-up.

4.
J Refract Surg ; 40(6): e371-e380, 2024 May.
Article in English | MEDLINE | ID: mdl-38848054

ABSTRACT

PURPOSE: To report on the prospective evaluation of photorefractive keratectomy (PRK) in experienced ametropic naval aviators that led to the approval of refractive surgery for military pilots. METHODS: This was the first study evaluating refractive surgery in naval aviators. Return to flight status after PRK and clinical outcomes and subjective and objective flight performance were evaluated. RESULTS: A total of 785 U.S. naval aviators were enrolled in the study. Average preoperative refraction was -2.92 ± 1.73 diopters (D) (range: +5.25 to -9.13 D). By 6 months, 85.9% of eyes were within ±0.50 D and 96.4% were within ±1.00 D of emmetropia. 94.4% of eyes achieved 20/20 or better, 74.3% had 20/16 or better, and 45.2% had 20/12.5 or better uncorrected distance visual acuity (UDVA) at 6 months. A total of 78.5% of aviators met return-to-flight criteria by 4 weeks, 83.3% by 8 weeks, and 90.8% by 12 weeks following PRK. All aviators eventually returned to full flight status. Cumulative flight experience included logging more than 48,000 flight hours and 19,500 landings in the 6 months following PRK. Psychometric questionnaire results showed that 78% reported improved ability to detect other aircraft and 92% reported improved ability to land on an aircraft carrier (82% significantly improved) compared to wearing corrective lenses. No one felt their vision was worse in these dynamic environments. All aviators indicated they would undergo the procedure again and would recommend it to a fellow aviator. CONCLUSIONS: This prospective study in U.S. naval aviators determined PRK to be safe and effective in a unique patient population operating in a visually demanding and hazardous environment. The program continues to be enthusiastically supported by aviators and PRK is now allowed in all branches of the military and for National Aeronautics and Space Administration astronauts. [J Refract Surg. 2024;40(6):e371-e380.].


Subject(s)
Lasers, Excimer , Military Personnel , Myopia , Photorefractive Keratectomy , Refraction, Ocular , Visual Acuity , Photorefractive Keratectomy/methods , Humans , Prospective Studies , Visual Acuity/physiology , Adult , Male , United States , Female , Myopia/surgery , Myopia/physiopathology , Lasers, Excimer/therapeutic use , Refraction, Ocular/physiology , Young Adult , Middle Aged , Aerospace Medicine , Treatment Outcome
5.
Device ; 2(5)2024 May 17.
Article in English | MEDLINE | ID: mdl-38911126

ABSTRACT

Diabetic wound healing is uniquely challenging to manage due to chronic inflammation and heightened microbial growth from elevated interstitial glucose. Carbon monoxide (CO), widely acknowledged as a toxic gas, is also known to provide unique therapeutic immune modulating effects. To facilitate delivery of CO, we have designed hyaluronic acid-based CO-gas-entrapping materials (CO-GEMs) for topical and prolonged gas delivery to the wound bed. We demonstrate that CO-GEMs promote the healing response in murine diabetic wound models (full-thickness wounds and pressure ulcers) compared to N2-GEMs and untreated controls.

7.
JTCVS Open ; 18: 156-166, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38690430

ABSTRACT

Objective: The best approach to minimize the observed higher mortality of newborn infants with low birth weight who require congenital heart surgery is unclear. This retrospective study was designed to review outcomes of newborn infants weighing <2000 g who have undergone cardiovascular surgery to identify patient parameters and clinical strategies for care associated with higher survival. Methods: A retrospective chart review of 103 patients who underwent cardiovascular surgery from 2010 to 2021 who were identified as having low birth weight (≤2000 g). Patients who underwent only patent ductus arteriosus ligation or weighing >3500 g at surgery were excluded. Results: Median age was 24 days and weight at the time of surgery was 1920 g. Twenty-six (25%) operative mortalities were recorded. Median follow-up period was 2.7 years. The 1- and 3-year overall Kaplan-Meier survival estimate was 72.4% ± 4.5% and 69.1% ± 4.6%. The 1-year survival of patients who had a weight increase >300 g from birth to surgery was far superior to the survival of those who did not achieve such a weight gain (81.4% ± 5.6% vs 64.0% ± 6.7%; log-rank P = .04). By multivariable Cox-hazard regression analysis, the independent predictor of 1-year mortality was genetic syndrome (hazard ratio, 3.54; 95% CI, 1.67-7.82; P < .001), whereas following a strategy of increasing weight from birth to surgery resulted in lower mortality (hazard ratio, 0.49; 95% CI, 0.24-0.90; P = .02). Conclusions: A strategy of wait and grow for newborn infants with very low birth weight requiring heart surgery results in better survival than immediate surgery provided that the patient's condition allows for this waiting period.

8.
Environ Sci Process Impacts ; 26(5): 942-956, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38690707

ABSTRACT

Small headwater streams can mobilize large amounts of terrestrially derived dissolved organic matter (DOM). While the molecular composition of DOM has important controls on biogeochemical cycles and carbon cycling, how stationary landscape metrics affect DOM composition is poorly understood, particularly in relation to non-stationary effects from hydrological changes across seasons. Here, we apply a combination of Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) and absorbance spectroscopy to characterize stream DOM from 13 diverse watersheds across the central Canadian boreal forests and statistically relate DOM compositional characteristics to landscape topography and hydrological metrics. We found that watershed runoff across different surface physiographies produced DOM with distinctly different chemical compositions related to runoff pH. Specifically, streams in sandy soil watersheds contained more abundant aromatic, nitrogenated and sulfurized fractions of DOM, likely due to a combination of lower soil capacity to absorb DOM than other soil types and high conifer forest coverage that generated acidic litterfall in more sandy watersheds. In contrast, streams with more neutral pH in watersheds with shallow soils had DOM resembling low oxidized phenolic molecules mainly due to increased brush/alder and deciduous vegetation coverage in relatively steeper watersheds. However, as precipitation and flows increased in the fall, the overall water chemistry of streams became more similar as runoff pH increased, the overall chemical diversity of DOM in streams decreased, and stream DOM resembled fresher, lower molecular weight lignin material likely originating from freshly produced leaf litter. Together, our findings show that during hydrologically disconnected periods, pH and landscape characteristics have important controls on the mobilization of aromatic DOM but that many landscape-specific characteristics in the Canadian boreal forest are less influential on DOM processing during wetter conditions where chemically similar, plant-derived DOM signatures are preferentially mobilized. These findings collectively help predict the composition of DOM across diverse watersheds in the Canadian boreal to inform microbial and contaminant biogeochemical processes in downstream ecosystems.


Subject(s)
Environmental Monitoring , Forests , Rivers , Environmental Monitoring/methods , Canada , Rivers/chemistry , Taiga , Humic Substances/analysis
9.
Ecol Appl ; 34(4): e2968, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38562000

ABSTRACT

Understanding how habitat attributes (e.g., patch area and sizes, connectivity) control recruitment and how this is modified by processes operating at larger spatial scales is fundamental to understanding population sustainability and developing successful long-term restoration strategies for marine foundation species-including for globally threatened reef-forming oysters. In two experiments, we assessed the recruitment and energy reserves of oyster recruits onto remnant reefs of the oyster Saccostrea glomerata in estuaries spanning 550 km of coastline in southeastern Australia. In the first experiment, we determined whether recruitment of oysters to settlement plates in three estuaries was correlated with reef attributes within patches (distances to patch edges and surface elevation), whole-patch attributes (shape and size of patches), and landscape attributes (connectivity). We also determined whether environmental factors (e.g., sedimentation and water temperature) explained the differences among recruitment plates. We also tested whether differences in energy reserves of recruits could explain the differences between two of the estuaries (one high- and one low-sedimentation estuary). In the second experiment, across six estuaries (three with nominally high and three with nominally low sedimentation rates), we tested the hypothesis that, at the estuary scale, recruitment and survival were negatively correlated to sedimentation. Overall, total oyster recruitment varied mostly at the scale of estuaries rather than with reef attributes and was negatively correlated with sedimentation. Percentage recruit survival was, however, similar among estuaries, although energy reserves and condition of recruits were lower at a high- compared to a low-sediment estuary. Within each estuary, total oyster recruitment increased with patch area and decreased with increasing tidal height. Our results showed that differences among estuaries have the largest influence on oyster recruitment and recruit health and this may be explained by environmental processes operating at the same scale. While survival was high across all estuaries, growth and reproduction of oysters on remnant reefs may be affected by sublethal effects on the health of recruits in high-sediment estuaries. Thus, restoration programs should consider lethal and sublethal effects of whole-estuary environmental processes when selecting sites and include environmental mitigation actions to maximize recruitment success.


Subject(s)
Ostreidae , Animals , Ostreidae/physiology , Endangered Species , Estuaries , Population Dynamics , Australia
10.
J Econ Entomol ; 117(2): 508-515, 2024 04 12.
Article in English | MEDLINE | ID: mdl-38428947

ABSTRACT

Popillia japonica Newman (Coleoptera: Scarabaeidae) feeding negatively impacts many plant species, including grapes, potentially reducing fruit quality and yield. Chemical control, representing the current grower standard, relies on frequent broadcast applications of broad-spectrum insecticides, with alternative management strategies mostly lacking. Attract-and-kill (A&K) is a behavioral management strategy that combines semiochemical attractants and a killing agent on a substrate. This study assessed the impact of A&K on (i) the number of P. japonica adults and (ii) the percent of P. japonica feeding injury on grape foliage compared to the grower standard in commercial vineyards. This 2-year study was conducted at 3 commercial vineyards with 4 paired plots consisting of a grower standard control and an A&K treatment. The A&K treatment consisted of commercial lures, each placed on outside-edge grapevines, and weekly applications of carbaryl on the plants holding lures. The grower standard received broadcast insecticide applications at the grower's discretion. The A&K treatment experienced similar numbers of P. japonica adults and similar proportions of leaf injury compared to the grower standard. The use of A&K reduced by 96% the crop area treated with insecticides compared to the grower standard. The area treated by A&K was at the edge of the vineyards, where more leaf injury occurred regardless of treatment. A&K is a targeted approach that was effective at managing P. japonica and reducing chemical inputs on a small scale. It has the potential to be scaled up and refined to provide growers with a new management strategy.


Subject(s)
Coleoptera , Insecticides , Vitis , Animals , Insecticides/pharmacology , Farms , Carbaryl , Plants , Plant Leaves
11.
QJM ; 117(6): 476-477, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38498830
12.
Cureus ; 16(2): e53453, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38435161

ABSTRACT

Introduction Diluted Betadine (Purdue Pharma, Stamford, Conn) irrigation following primary total joint arthroplasty (pTJA) may reduce the risk of periprosthetic joint infection (PJI). A recent in vitro study found a minimal inhibitory concentration (MIC) of 0.63% Povidone-iodine (Betadine) for several bacterial isolates. This study reports outcomes of patients undergoing TJA using 0.54% Betadine irrigation compared to a historical cohort using 0.3% Betadine irrigation. Methods A retrospective chart review of patients who underwent pTJA from September 2017 to December 2020. 0.3% Betadine was used in a historical cohort and 0.54% Betadine in the experimental group. Patient demographics, intra-operative data, all-cause revision, and infection data were collected for the three-month post-operative period. Outcome frequencies between groups were compared using Fisher-Exact tests. Results Six hundred sixty-one patients underwent pTJA: 308 total knee arthroplasty (TKA), and 353 total hip arthroplasty (THA). 0.3% Betadine group had seven (3.1%) revisions: five (2.2%) underwent a revision for non-infectious reasons, and two (0.9%) for PJI. 0.54% Betadine group had 11 (2.5%) revisions: nine (2.1%) underwent revision for non-infectious reasons, two (0.4%) for PJI. No significant difference was found for rates of all-cause revision or infection between groups. No adverse intra-operative events occurred with the higher Betadine concentration. Conclusion This study demonstrated no difference in rates of all-cause revision or PJI when using 0.3% Betadine versus 0.54% Betadine for irrigation following pTJA. No adverse intraoperative events occurred with 0.54% Betadine irrigation. Given recent in vitro data supporting increased Betadine MIC, our results showed safety and non-inferiority with respect to three-month post-operative complication rates. Further investigation through a large powered randomized controlled study is needed to determine the optimal Betadine irrigation concentration for PJI prevention is required.

13.
Psychopharmacol Bull ; 54(1): 65-86, 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38449471

ABSTRACT

Purpose of Review: This is a comprehensive review of the literature regarding the use of Solriamfetol for excessive daytime sleepiness. It covers the background and current therapeutic approaches to treating excessive daytime sleepiness, the management of common comorbidities, and the existing evidence investigating the use of Solriamfetol for this purpose. Recent Findings: Excessive daytime sleepiness leads to worse quality of life, a medical sequela and significant economic cost. There are multiple phenotypes of excessive daytime sleepiness depending on the comorbidity making treatment challenging. Due to the complexity of etiology there is not a cure for this ailment. Solriamfetol is a norepinephrine/dopamine dual reuptake antagonist that can be used to manage daytime sleepiness. Solriamfetol was first approved by the FDA in 2018 for use in excessive daytime sleepiness associated with obstructive sleep apnea and narcolepsy. Ongoing literature has proved this drug to be a safe and effective alternative pharmacotherapy. Summary: Recent epidemiological data estimate up to one-third of the general adult population suffers from excessive daytime sleepiness. There is no cure to daytime somnolence and current pharmacotherapeutic regimens have worrisome side effect profiles. Solriamfetol is a new class of drug that offers a safe and effective alternative option for clinical providers treating excessive daytime sleepiness.


Subject(s)
Disorders of Excessive Somnolence , Phenylalanine/analogs & derivatives , Quality of Life , Adult , Humans , Carbamates/therapeutic use , Dopamine Antagonists , Disorders of Excessive Somnolence/drug therapy
14.
Psychopharmacol Bull ; 54(1): 43-64, 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38449475

ABSTRACT

Purpose of Review: This is a comprehensive review of the literature regarding Lemborexant for the treatment of insomnia. It covers the background and management of insomnia and then reviews the body of existing evidence evaluating the use of Lemborexant for this purpose. Recent Findings: Insomnia leads to significant decreased in quality of life and economic burden due to decreased workplace performance and increased health care costs. Insomnia manifests as a single common pathway of hyperarousal due to a highly complex network of interactions between activation of the sympathetic system and the endocrine system. Lemborexant is a dual orexin 1/2 antagonist that blocks cortical arousal and promotes sleep state transition. Lemborexant was approved by the FDA in 2019 for use in insomnia. It belongs to a class of orexin neuropeptide inhibitors that is growing in popular clinical application. Summary: Insomnia is a crippling disorder of the sleep wake cycle that drives significant morbidity and mortality in the United States. It carries a high societal and economic toll due to direct and indirect effects to the healthcare system. Lemborexant is a new addition to the orexin antagonist class of drugs that already includes Almorexant and Suvorexant that has superior pharmacokinetic properties. While Lemborexant does have a mild side effect profile, its clinical safety and efficacy make it a promising insomnia drug of the future.


Subject(s)
Pyridines , Pyrimidines , Sleep Initiation and Maintenance Disorders , Humans , Sleep Initiation and Maintenance Disorders/drug therapy , Orexins , Quality of Life
15.
Clin Case Rep ; 12(3): e8604, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38449895

ABSTRACT

Although endometriosis is a common condition, both extrapelvic endometriosis and endometriosis associated malignancy (EAM) are rare. We describe the first reported case of a patient with Müllerian-type carcinosarcoma arising in gastric endometriosis.

16.
Cell Mol Bioeng ; 17(1): 25-34, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38435791

ABSTRACT

Purpose: Individuals with Down syndrome (DS) are 2000 times more likely to develop a congenital heart defect (CHD) than the typical population Freeman et al. in Am J Med Genet 80:213-217 (1998). The majority of CHDs in individuals with DS characteristically involve the atrioventricular (AV) canal, including the valves and the atrial or ventricular septum. Type VI collagen (COLVI) is the primary structural component in the developing septa and endocardial cushions, with two of the three genes encoding for COLVI located on human chromosome 21 and upregulated in Down syndrome (von Kaisenberg et al. in Obstet Gynecol 91:319-323, 1998; Gittenberger-De Groot et al. in Anatom Rec Part A 275:1109-1116, 2023). Methods: To investigate the effect of COLVI dosage on cardiomyocytes with trisomy 21, induced pluripotent stem cells (iPSC) from individuals with DS and age- and sex-matched controls were differentiated into cardiomyocytes (iPSC-CM) and plated on varying concentrations of COLVI. Results: Real time quantitative PCR showed decreased expression of cardiac-specific genes of DS iPSC-CM lines compared to control iPSC-CM. As expected, DS iPSC-CM had increased expression of genes on chromosome 21, including COL6A1, COL6A2, as well as genes not located on chromosome 21, namely COL6A3, HAS2 and HYAL2. We found that higher concentrations of COLVI result in decreased proliferation and migration of DS iPSC-CM, but not control iPSC-CM. Conclusions: These results suggest that the increased expression of COLVI in DS may result in lower migration-driven elongation of endocardial cushions stemming from lower cell proliferation and migration, possibly contributing to the high incidence of CHD in the DS population. Supplementary Information: The online version contains supplementary material available at 10.1007/s12195-023-00791-x.

17.
J Refract Surg ; 40(3): e173-e181, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38466768

ABSTRACT

PURPOSE: To present the outcomes of the U.S. Navy photorefractive keratectomy (PRK) accessioning study conducted between 2000 and 2005 that helped lead to the acceptance of laser vision correction within the U.S. aviation industry. METHODS: In this prospective masked study, a total of 301 students who had PRK and underwent naval flight training were compared to 4,368 untreated peers. Three training pipelines were compared: propeller/jet transport, jet fighters, and helicopters. The evaluated metrics were flight and academic performance (assessed for the primary and advanced stage of the training as normalized Navy Standard Score [NSS]), as well as the student attrition rate from training. RESULTS: The attrition rate was lower in the PRK group compared to controls (15.9% vs 23.2%; P = .004). In the primary stage of training, students who had PRK outperformed controls in flight training performance in the propeller/jet transport pipeline (average NSS after PRK: 52.4 ± 7.5 vs controls: 50.7 ± 6.4, P = .02), but the flight performance in the jet fighter and helicopter pipelines was comparable between the two groups. Academic performance in the primary stage of training was approximately 7% to 13% higher in students who had PRK for all training pipelines. During the advanced training stage, there was no difference in the flight performance between the groups in any of the presented pipelines. Academic performance was significantly better for students who had PRK in the helicopter pipeline (51.2 ± 11.0 vs 46.7 ± 11.7 P < .001) but comparable between the two groups in the remaining pipelines. CONCLUSIONS: Refractive surgery did not have adverse effects on flight performance metrics. Pilots who had PRK had comparable or better outcomes than their untreated peers. [J Refract Surg. 2024:40(3):e173-e181.].


Subject(s)
Photorefractive Keratectomy , Pilots , Humans , Visual Acuity , Prospective Studies , Students , Lasers, Excimer/therapeutic use , Refraction, Ocular
18.
Sci Adv ; 10(6): eadj5661, 2024 Feb 09.
Article in English | MEDLINE | ID: mdl-38335297

ABSTRACT

Hypoxia-inducible factor pathway genes are linked to adaptation in both human and nonhuman highland species. EPAS1, a notable target of hypoxia adaptation, is associated with relatively lower hemoglobin concentration in Tibetans. We provide evidence for an association between an adaptive EPAS1 variant (rs570553380) and the same phenotype of relatively low hematocrit in Andean highlanders. This Andean-specific missense variant is present at a modest frequency in Andeans and absent in other human populations and vertebrate species except the coelacanth. CRISPR-base-edited human cells with this variant exhibit shifts in hypoxia-regulated gene expression, while metabolomic analyses reveal both genotype and phenotype associations and validation in a lowland population. Although this genocopy of relatively lower hematocrit in Andean highlanders parallels well-replicated findings in Tibetans, it likely involves distinct pathway responses based on a protein-coding versus noncoding variants, respectively. These findings illuminate how unique variants at EPAS1 contribute to the same phenotype in Tibetans and a subset of Andean highlanders despite distinct evolutionary trajectories.


Subject(s)
Adaptation, Physiological , Altitude , Hematocrit , South American People , Humans , Adaptation, Physiological/genetics , Adaptation, Physiological/physiology , East Asian People , Hypoxia/genetics , Hypoxia/metabolism , Mutation, Missense/genetics , South American People/genetics
19.
J Therm Biol ; 119: 103789, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38340464

ABSTRACT

Chill susceptible insects are thought to be injured through different mechanisms depending on the duration and severity of chilling. While chronic chilling causes "indirect" injury through disruption of metabolic and ion homeostasis, acute chilling is suspected to cause "direct" injury, in part through phase transitions of cell membrane lipids. Dietary supplementation of cholesterol can reduce acute chilling injury in Drosophila melanogaster (Shreve et al., 2007), but the generality of this effect and the mechanisms underlying it remain unclear. To better understand how and why cholesterol has this effect, we assessed how a high cholesterol diet and thermal acclimation independently and interactively impact several measures of chill tolerance. Cholesterol supplementation positively affected tolerance to acute chilling in warm-acclimated flies (as reported previously). Conversely, feeding on the high-cholesterol diet negatively affected tolerance to chronic chilling in both cold and warm acclimated flies, as well as tolerance to acute chilling in cold acclimated flies. Cholesterol had no effect on the ability of flies to remain active in the cold or recover movement after a cold stress. Our findings support the idea that dietary cholesterol reduces mechanical injury to membranes caused by direct chilling injury, and that acute and chronic chilling are associated with distinct mechanisms of injury. Feeding on a high-cholesterol diet may interfere with mechanisms involved in cold acclimation, leaving cholesterol augmented flies more susceptible to chilling injury under some conditions.


Subject(s)
Drosophila melanogaster , Drosophila , Animals , Acclimatization , Diet , Homeostasis , Cold Temperature
20.
J Acoust Soc Am ; 155(2): 962-970, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38341729

ABSTRACT

Separating crowd responses from raw acoustic signals at sporting events is challenging because recordings contain complex combinations of acoustic sources, including crowd noise, music, individual voices, and public address (PA) systems. This paper presents a data-driven decomposition of recordings of 30 collegiate sporting events. The decomposition uses machine-learning methods to find three principal spectral shapes that separate various acoustic sources. First, the distributions of recorded one-half-second equivalent continuous sound levels from men's and women's basketball and volleyball games are analyzed with regard to crowd size and venue. Using 24 one-third-octave bands between 50 Hz and 10 kHz, spectrograms from each type of game are then analyzed. Based on principal component analysis, 87.5% of the spectral variation in the signals can be represented with three principal components, regardless of sport, venue, or crowd composition. Using the resulting three-dimensional component coefficient representation, a Gaussian mixture model clustering analysis finds nine different clusters. These clusters separate audibly distinct signals and represent various combinations of acoustic sources, including crowd noise, music, individual voices, and the PA system.

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