ABSTRACT
Conventionally, women are perceived to feel colder than men, but controlled comparisons are sparse. We measured the response of healthy, lean, young women and men to a range of ambient temperatures typical of the daily environment (17 to 31 °C). The Scholander model of thermoregulation defines the lower critical temperature as threshold of the thermoneutral zone, below which additional heat production is required to defend core body temperature. This parameter can be used to characterize the thermoregulatory phenotypes of endotherms on a spectrum from "arctic" to "tropical." We found that women had a cooler lower critical temperature (mean ± SD: 21.9 ± 1.3 °C vs. 22.9 ± 1.2 °C, P = 0.047), resembling an "arctic" shift compared to men. The more arctic profile of women was predominantly driven by higher insulation associated with more body fat compared to men, countering the lower basal metabolic rate associated with their smaller body size, which typically favors a "tropical" shift. We did not detect sex-based differences in secondary measures of thermoregulation including brown adipose tissue glucose uptake, muscle electrical activity, skin temperatures, cold-induced thermogenesis, or self-reported thermal comfort. In conclusion, the principal contributors to individual differences in human thermoregulation are physical attributes, including body size and composition, which may be partly mediated by sex.
Subject(s)
Body Temperature Regulation , Humans , Female , Male , Body Temperature Regulation/physiology , Adult , Arctic Regions , Young Adult , Adipose Tissue, Brown/physiology , Adipose Tissue, Brown/metabolism , Sex Characteristics , Sex Factors , Body Temperature/physiology , Thermogenesis/physiology , Basal Metabolism/physiologyABSTRACT
INTRODUCTION: Adherence to daily oral antiretroviral therapy (ART) and regular clinic appointments can be challenging for individuals who experience adverse social determinants of health. Long-acting injectable ART administered outside of traditional clinic settings may be a promising solution to adherence barriers, but additional research is needed to assess patients' perspectives. This study assessed perspectives of people living with HIV (PLWH) who had difficulty with adherence to traditional HIV care models and evaluated feasibility and acceptability of receiving a long-acting ART injection at a location outside of a traditional HIV clinic to address barriers to HIV care. METHODS: Qualitative interviews (n = 26) were conducted with PLWH who had experienced barriers to adherence. Participants were referred to the study by staff from Project Trust, a drop in harm reduction and sexually transmitted infection/HIV clinic. The interviews were conducted between May and November 2021. Interviews were recorded, professionally transcribed, coded, and analyzed qualitatively using the integrated-Promoting Action on Research Implementation in Health Services framework. RESULTS: We identified 6 main themes regarding the acceptability of receiving a long-acting injection to treat HIV, and the acceptability and feasibility of receiving injections at an alternative care site. Participants specified that they: (1) have a general understanding about their HIV care and the importance of ART adherence, (2) prefer a long-acting injection over a daily pill regimen, (3) expressed concerns about injection safety and efficacy, (4) had specific logistical aspects around the delivery of long-acting injections, including location of injection administration, that they believed would improve their ability to adhere, (5) have confidence that they can become undetectable and then complete the oral lead-in required to begin receiving the injection, and (6) see potential barriers that remain a concern for successful adherence to long-acting injections. CONCLUSION: To better treat HIV among people who are living with challenging social determinants of health, interventions that include a long-acting injection in a non-traditional care setting may prove to be a promising treatment option.
Subject(s)
Anti-HIV Agents , HIV Infections , Substance-Related Disorders , Humans , HIV , Housing Instability , Anti-Retroviral Agents/therapeutic use , HIV Infections/drug therapy , Substance-Related Disorders/drug therapy , Medication Adherence , Anti-HIV Agents/therapeutic useABSTRACT
The current obesity pandemic results from a physiological imbalance in which energy intake chronically exceeds energy expenditure (EE), and prevention and treatment strategies remain generally ineffective. Approaches designed to increase EE have been informed by decades of experiments in rodent models designed to stimulate adaptive thermogenesis, a long-term increase in metabolism, primarily induced by chronic cold exposure. At the cellular level, thermogenesis is achieved through increased rates of futile cycling, which are observed in several systems, most notably the regulated uncoupling of oxidative phosphorylation from ATP generation by uncoupling protein 1, a tissue-specific protein present in mitochondria of brown adipose tissue (BAT). Physiological activation of BAT and other organ thermogenesis occurs through ß-adrenergic receptors (AR), and considerable effort over the past 5 decades has been directed toward developing AR agonists capable of safely achieving a net negative energy balance while avoiding unwanted cardiovascular side effects. Recent discoveries of other BAT futile cycles based on creatine and succinate have provided additional targets. Complicating the current and developing pharmacological-, cold-, and exercise-based methods to increase EE is the emerging evidence for strong physiological drives toward restoring lost weight over the long term. Future studies will need to address technical challenges such as how to accurately measure individual tissue thermogenesis in humans; how to safely activate BAT and other organ thermogenesis; and how to sustain a negative energy balance over many years of treatment.
Subject(s)
Energy Metabolism , Mitochondria/metabolism , Obesity/therapy , Thermogenesis , Adipose Tissue, Brown/metabolism , Body Weight , Disease Management , Energy Intake/physiology , Humans , Obesity/metabolism , Obesity/physiopathology , Oxidative Phosphorylation , Receptors, Adrenergic, beta/metabolismABSTRACT
PURPOSE: To develop a safe and noninvasive in vivo assay of hepatic propionate oxidative capacity. METHODS: A modified 1-13C-propionate breath test was administered to 57 methylmalonic acidemia (MMA) subjects, including 19 transplant recipients, and 16 healthy volunteers. Isotopomer enrichment (13CO2/12CO2) was measured in exhaled breath after an enteral bolus of sodium-1-13C-propionate, and normalized for CO2 production. 1-13C-propionate oxidation was then correlated with clinical, laboratory, and imaging parameters collected via a dedicated natural history protocol. RESULTS: Lower propionate oxidation was observed in patients with the severe mut0 and cblB subtypes of MMA, but was near normal in those with the cblA and mut- forms of the disorder. Liver transplant recipients demonstrated complete restoration of 1-13C-propionate oxidation to control levels. 1-13C-propionate oxidation correlated with cognitive test result, growth indices, bone mineral density, renal function, and serum biomarkers. Test repeatability was robust in controls and in MMA subjects (mean coefficient of variation 6.9% and 12.8%, respectively), despite widely variable serum methylmalonic acid concentrations in the patients. CONCLUSION: Propionate oxidative capacity, as measured with 1-13C-propionate breath testing, predicts disease severity and clinical outcomes, and could be used to assess the therapeutic effects of liver-targeted genomic therapies for MMA and related disorders of propionate metabolism. TRIAL REGISTRATION: This clinical study is registered in www.clinicaltrials.gov with the ID: NCT00078078. Study URL: http://clinicaltrials.gov/ct2/show/NCT00078078.
Subject(s)
Amino Acid Metabolism, Inborn Errors , Propionates , Amino Acid Metabolism, Inborn Errors/diagnosis , Amino Acid Metabolism, Inborn Errors/genetics , Amino Acid Metabolism, Inborn Errors/therapy , Biomarkers , Breath Tests , Humans , Liver , Methylmalonic AcidABSTRACT
BACKGROUND: It is common practice for healthcare practitioners to swaddle infants in newborn nursery and neonatal intensive care unit settings. Despite the widespread use of this practice, the American Academy of Pediatrics neither bans nor recommends swaddling. To date, there has been no standard protocol developed for either healthcare professionals or parents to establish optimal swaddling techniques in terms of infant arm positioning, infant leg positioning, and tightness of wrap. PURPOSE: To evaluate the variability in swaddling techniques used for infants in the newborn nursery and neonatal intensive care unit. METHODS: Across 2 pediatric hospitals, the swaddling positioning of each open-crib infant in the newborn nursery and neonatal intensive care unit was examined. For each infant, the following data were collected: gender, left and right arm position, left and right leg position, and tightness of wrap. RESULTS: In total, 132 swaddle observations were recorded. There was significant variability in swaddling positioning of arms and legs. The most common combination of arm/leg positioning was "mixed arm positioning" and "both legs flexed" (25.0% of all observations). In 9.1% of cases, tightness of wrap around chest was "tight," and in 30.3% of cases, tightness of wrap around legs was "tight." IMPLICATIONS FOR PRACTICE: There was a large variability in swaddling positioning of both arms and legs. For such a widespread practice, the lack of medical guidelines results in inconsistent, and potentially harmful, positioning. Parents and healthcare professionals would benefit from specific, research-driven guidelines regarding proper swaddling techniques. IMPLICATIONS FOR RESEARCH: Different variations on swaddling should be evaluated for consideration of best practice swaddling.
Subject(s)
Infant Care/methods , Intensive Care Units, Neonatal , Nurseries, Hospital , Patient Positioning/methods , Cross-Sectional Studies , Female , Humans , Infant, Newborn , Male , Nurses, Neonatal , Parents , Practice Patterns, Nurses'ABSTRACT
BACKGROUND: Preterm birth has been linked to increased parental stress, depression, and anxiety. Although the rate of neonatal morbidity and mortality decreases with increasing gestational age, recent research has revealed that there is no threshold age for risk or parental concern. PURPOSE: This study examines parental concern about medical and developmental outcomes of their premature infant. METHODS: Parents of 60 premature infants were surveyed in a follow-up clinic regarding their level of concern about 11 morbidities and their child's gestation-adjusted age; these were compared with the infant's inpatient chart. "Concern scores" were tallied and compared across gestational age groups and knowledge of gestation-adjusted age using Chi-square tests of independence. FINDINGS: Many parents reported concerns about morbidities that were unsupported by their child's diagnoses. Across parents of extremely, very, and moderate-late preterm children, the mean concern scores were 13.9, 15.7, and 19.7, respectively. Overall, 62% of parents incorrectly reported the gestation-adjusted age of their child. Parents who were correct were significantly more likely to correctly anticipate abnormal developmental patterns (70%) and growth patterns (65%) than those who were incorrect (33% and 31%, respectively). IMPLICATIONS FOR RESEARCH: Future research should focus on whether NICU graduate parental stress levels are directly linked to the severity of their child's condition, and how physicians can help decrease NICU graduate parental stress. IMPLICATIONS FOR PRACTICE: Parental anxiety regarding all gestational age neonatal intensive care unit infant outcomes can be decreased by a thorough explanation of gestation-adjusted age and a discussion of expected prematurity-related issues.
Subject(s)
Infant, Premature, Diseases/psychology , Infant, Premature , Parents/psychology , Perception , Female , Humans , Infant, Newborn , Intensive Care, Neonatal , Male , Parent-Child Relations , Premature Birth/psychologyABSTRACT
PURPOSE OF REVIEW: To provide an overview of the literature regarding medical and developmental risks for moderate to late preterm infants (32-36 weeks gestation), with particular attention to the pediatrician's role in care during both inpatient and outpatient periods. RECENT FINDINGS: Although the risks of medical issues and developmental delays decrease with increasing gestational age, research suggests that infants born after 32 weeks' gestation often exhibit significant morbidities associated with prematurity. These infants, often referred to as 'macro preemies', have been found to be at a greater risk for medical complications secondary to immature organ systems including impairments in temperature regulation, respiratory functioning, feeding coordination, bilirubin excretion, glucose control, and infection susceptibility. Recent studies of macro preemies also suggest a higher incidence of significant deficits noted in gross and fine motor skills, speech and communication, and learning and behavior compared to their full-term counterparts. Without careful attention from birth, macro preemie infants could be susceptible to both medical issues and developmental delays. SUMMARY: Physicians should be aware of the research regarding increased medical and developmental risks for all infants born before term in order to provide their patients with comprehensive medical and neurodevelopmental follow-up care.
Subject(s)
Developmental Disabilities/etiology , Hypoglycemia/complications , Hypothermia/complications , Jaundice/complications , Developmental Disabilities/prevention & control , Humans , Incidence , Infant , Infant, Newborn , Infant, Premature , Infant, Premature, Diseases , Physician's Role , Practice Guidelines as Topic , Risk AssessmentABSTRACT
PURPOSE: A major factor limiting the visibility of distant targets is veiling attributed to atmospheric scattering, known commonly as haze. It has been suggested that yellow filters (in this case, the macular pigments, MPs) could selectively absorb this haze, thus extending visual range. This study is an empirical test of the visibility hypothesis. METHODS: Twelve subjects had their full contrast sensitivity function (CSF) (represented by six spatial frequencies) assessed in the presence of two background conditions: simulated blue haze and short wave-deficient light. Contrast sensitivity at the peak of the CSF (7.5 cycles per degree) was measured in the presence of the same two backgrounds as the full CSF, with the addition of a broadband xenon background condition in a separate sample of 25 subjects. RESULTS: Simulated blue haze was found to uniformly reduce the CSF in the 12 subjects for whom the full CSF was assessed. Therefore, only the peak was measured in the larger sample of 25 subjects. Macular pigment density was significantly related to energy at threshold for both the haze and xenon backgrounds but not the short wave-deficient background. Thus, subjects with higher levels of MP could withstand more light before losing sight of the target. CONCLUSIONS: This result is consistent with previous modeling of the visibility hypothesis as well as visual range improvements seen when using an artificial MP filter.
Subject(s)
Contrast Sensitivity/physiology , Environmental Pollution/adverse effects , Macular Pigment/physiology , Vision Disorders/physiopathology , Adolescent , Adult , Area Under Curve , Female , Glare , Humans , Light , Male , Models, Biological , Sensory Thresholds , Vision Disorders/etiology , Visual Acuity/physiology , Young AdultABSTRACT
PURPOSE: Continuing increases in application volume have driven a national dialogue to reform the residency recruitment process. Program signaling allows applicants to express interest in a program at the preinterview stage with the goal of helping programs identify applicants with more genuine interest in their programs. This study explored the relationship between program signals and program and applicant characteristics. METHOD: Participating dermatology, general surgery, and categorical internal medicine (IM) programs and applicants of the 2022 supplemental ERAS application (SuppApp) were included. Data from the SuppApp, the MyERAS Application for Residency Applicants (MyERAS), and the 2020 GME Track Survey were used. Cohen's h was used to determine effect size, and chi-squared was used to determine statistical significance. RESULTS: There was an uneven distribution of signals to programs, with 25% of programs receiving about half of the signals across all 3 specialties. Programs with larger numbers of both residents and applicants received greater numbers of program signals relative to their program density, although this effect was small ( h < 0.50, P < .001). No meaningful differences were seen across genders for any specialty. Only Hispanic applicants in IM sent a higher proportion of signals to programs with more underrepresented in medicine residents than White only applicants (40% vs 26%, h = 0.30, P < .001). Across all specialties, there was a small-to-moderate effect for international medical graduate (IMG) applicants sending a larger proportion of signals to programs with more IMG residents ( h < 0.80, P < .001). CONCLUSIONS: This first-year pilot study (i.e., SuppApp) provided initial evidence that supports the feasibility and fairness of program signals in residency selection. As program signals become more common across specialties, future research should continue to evaluate trends in where applicants send signals, and possible relationships between program and application characteristics.
Subject(s)
Internship and Residency , Humans , Male , Female , Pilot Projects , Surveys and Questionnaires , Motivation , Internal MedicineABSTRACT
Stomach morphology can provide insights into an organism's diet. Gut size or length is typically inversely related to diet quality in most taxa, and has been used to assess diet quality in a variety of systems. However, it requires animal sacrifice and time-consuming dissections. Measures of external morphology associated with diet may be a simpler, more cost-effective solution. At the species level, external measures of the progastric region of the carapace in brachyuran crabs can predict stomach size and diet quality, with some suggestion that this approach may also work to examine individual diet preferences and specialization at the individual level; if so, the size of the progastric region could be used to predict trends in diet quality and consumption for individuals, which would streamline diet studies in crabs. Here, we tested whether external progastric region size predicts internal stomach size across latitude and time of year for individuals of the invasive Asian shore crab Hemigrapsus sanguineus. We found that the width of the progastric region increased at a faster rate with body size than stomach width. In addition, the width of the progastric region followed different trends across sites and over time compared to stomach width. Our results therefore suggest that the progastric region may not be used as a proxy for stomach size variation across individuals.
ABSTRACT
Long-acting injectable (LAI) antiretroviral therapy (ART) has the potential to change the lives of people living with HIV (PLWH). To ensure equitable access to new treatment modalities, we examined the feasibility and acceptability of administering Cabotegravir Rilpivirine Long Acting (CAB/RPV LA) to individuals who experience challenging social determinants of health (SDoH) and struggle with adherence to traditional oral ART. Quantitative and qualitative data were used to assess feasibility of utilizing ART at alternative clinic. Data were collected on individuals eligible to receive CAB/RPV LA at an alternative street-based clinic and on individuals receiving CAB/RPV LA at a traditional HIV clinic. After 6 months, participants were interviewed about their experience. Providers involved in the implementation were also interviewed about their experiences. Only one participant (out of 5) who received CAB/RPV LA at the alternative clinic received consistent treatment, whereas 17 out of 18 participants receiving CAB/RPV LA at the traditional clinic site were adherent. Participants and providers believed that LAI had potential for making treatment adherence easier, but identified several barriers, including discrepancies between patients' desires and their lifestyles, impact of LAI on interactions with the medical system, risk of resistance accompanying sub-optimal adherence, and need for a very high level of resources. While LAI has major potential benefits for high-risk patients, these benefits must be balanced with the complexities of implementation. Despite challenges that impacted study outcomes, improving treatment outcomes for PLWH requires addressing SDoH and substance use.
Subject(s)
Anti-HIV Agents , Feasibility Studies , HIV Infections , Medication Adherence , Rilpivirine , Humans , HIV Infections/drug therapy , Female , Male , Adult , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/therapeutic use , Middle Aged , Medication Adherence/statistics & numerical data , Rilpivirine/administration & dosage , Rilpivirine/therapeutic use , Injections , Delayed-Action Preparations , Qualitative Research , Health Services Accessibility , Social Determinants of Health , Interviews as Topic , Patient Acceptance of Health Care/statistics & numerical data , Pyridones , DiketopiperazinesABSTRACT
Organisms vary in the timing of energy acquisition and use for reproduction. Thus, breeding strategies exist on a continuum, from capital breeding to income breeding. Capital breeders acquire and store energy for breeding before the start of the reproductive season, while income breeders finance reproduction using energy acquired during the reproductive season. Latitude and its associated environmental drivers are expected to heavily influence breeding strategy, potentially leading to latitudinal variation in breeding strategies within a single species. We examined the breeding strategy of the Asian shore crab Hemigrapsus sanguineus at five sites spanning nearly 10° of latitude across its invaded United States range. We hypothesized that the primary breeding strategy of this species would shift from income breeding to capital breeding as latitude increases. We found that though this species' breeding strategy is dominated by capital breeding throughout much of the range, income breeding increases in importance at lower latitudes. This latitudinal pattern is likely heavily influenced by the duration of the foraging and breeding seasons, which also vary with latitude. We also found that reproductive characteristics at the northern and southern edges of the invaded range were consistent with continued range expansion. We suggest that the reproductive flexibility of the Asian shore crab is a key facilitator of its continued invasion success. Our results highlight the influence of latitude on the breeding strategy of a species and emphasize the need for further research regarding the ecological importance and implications of flexibility in breeding strategies within species.
Subject(s)
Brachyura , Animals , Reproduction , Seafood , SeasonsABSTRACT
A distinct adipose tissue distribution pattern was observed in patients with methylmalonyl-CoA mutase deficiency, an inborn error of branched-chain amino acid (BCAA) metabolism, characterized by centripetal obesity with proximal upper and lower extremity fat deposition and paucity of visceral fat, that resembles familial multiple lipomatosis syndrome. To explore brown and white fat physiology in methylmalonic acidemia (MMA), body composition, adipokines, and inflammatory markers were assessed in 46 patients with MMA and 99 matched controls. Fibroblast growth factor 21 levels were associated with acyl-CoA accretion, aberrant methylmalonylation in adipose tissue, and an attenuated inflammatory cytokine profile. In parallel, brown and white fat were examined in a liver-specific transgenic MMA mouse model (Mmut-/- TgINS-Alb-Mmut). The MMA mice exhibited abnormal nonshivering thermogenesis with whitened brown fat and had an ineffective transcriptional response to cold stress. Treatment of the MMA mice with bezafibrates led to clinical improvement with beiging of subcutaneous fat depots, which resembled the distribution seen in the patients. These studies defined what we believe to be a novel lipodystrophy phenotype in patients with defects in the terminal steps of BCAA oxidation and demonstrated that beiging of subcutaneous adipose tissue in MMA could readily be induced with small molecules.
Subject(s)
Amino Acid Metabolism, Inborn Errors , Fibroblast Growth Factors , Lipodystrophy , Animals , Humans , Mice , Amino Acid Metabolism, Inborn Errors/complications , Amino Acid Metabolism, Inborn Errors/genetics , Amino Acid Metabolism, Inborn Errors/metabolism , Mice, TransgenicABSTRACT
PURPOSE: This study examined how applicants interpret the self-reported disadvantaged (SRD) question in the American Medical College Application Service (AMCAS) application. METHOD: Data from 129,262 applicants who applied through AMCAS from 2017 through 2019 were used, including financial and family history, demographic characteristics, and work status and residence. Fifteen applicants from the 2020 and 2021 AMCAS cycles were interviewed about their experiences with the SRD question. RESULTS: Large effects were found for SRD applicants with fee assistance waivers ( h = 0.89), Pell grants ( h = 1.21), state or federal aid ( h = 1.10), and parents with less education ( h = 0.98) and non-SRD applicants with a large proportion of their education paid by family ( d = 1.03). Another large difference was found for reported family income distribution (73% of SRD applicants reporting family income < $50,000 vs 15% of non-SRD applicants). More SRD applicants were Black or Hispanic (26% vs 16% and 5% vs 5%), Deferred Action for Childhood Arrivals recipients (11% vs 2%), born outside the United States (32% vs 16%), and raised in a medically underserved area (60% vs 14%). There was a moderate effect for first-generation to college SRD applicants ( h = 0.61). SRD applicants had lower Medical College Admission Test scores ( d = 0.62) and overall and science grade point averages ( d = 0.50 and 0.49, respectively) but no meaningful differences in acceptance or matriculation rates. The interviews identified 5 themes: (1) unclear disadvantage definition; (2) different perceptions of disadvantage and overcoming challenges or obstacles ; (3) identification as disadvantaged or not; (4) SRD essay content; and (5) concerns about lack of transparency in how the SRD question is used in admissions. CONCLUSIONS: Revising the SRD question by including context, phrasing, and instructions for broader experience categories might be beneficial because of lack of transparency and understanding.
Subject(s)
School Admission Criteria , Schools, Medical , Humans , United States , Child , Self Report , Educational Measurement , College Admission TestABSTRACT
Morphological traits have often been used to predict diet and trophic position of species across many animal groups. Variation in gut size of closely related animals is known to be a good predictor of dietary habits. Species that are more herbivorous or that persist on low-quality diets often have larger stomachs than their carnivorous counterparts. This same pattern exists in crabs and in most species, individuals exhibit external markings on the dorsal side of their carapace that appear to align with the position and size of their gut. We hypothesized that these external markings could be used as an accurate estimate of the crab's cardiac stomach size, allowing an approximation of crab dietary strategies without the need to sacrifice and dissect individual animals. We used literature values for mean diet and standardized external gut size markings taken from crab photographs across 50 species to show that percent herbivory in the diet increases non-linearly across species of brachyuran crab with the external estimate of gut size. We also used data from dissections in four species to show that external gut markings were positively correlated with gut sizes, though the strength of this correlation differed across species. We conclude that when rough approximations of diet quality such as percent herbivory will suffice, measuring external carapace markings in crabs presents a quick, free, non-lethal alternative to dissections. Our results also provide important insights into tradeoffs that occur in crab morphology and have implications for crab evolution.
Subject(s)
Brachyura , Animals , Brachyura/anatomy & histology , Diet , Stomach/anatomy & histology , Feeding Behavior , HerbivoryABSTRACT
The Forkhead box transcription factor FoxO1 regulates metabolic gene expression in mammals. FoxO1 activity is tightly controlled by phosphatidylinositol 3-kinase (PI3K) signaling, resulting in its phosphorylation and nuclear exclusion. We sought here to determine the mechanisms involved in glucose and insulin-stimulated nuclear shuttling of FoxO1 in pancreatic ß cells and its consequences for preproinsulin (Ins1, Ins2) gene expression. Nuclear-localized endogenous FoxO1 translocated to the cytosol in response to elevated glucose (3 versus 16.7 mM) in human islet ß cells. Real-time confocal imaging of nucleo-cytosolic shuttling of a FoxO1-EGFP chimera in primary mouse and clonal MIN6 ß cells revealed a time-dependent glucose-responsive nuclear export, also mimicked by exogenous insulin, and blocked by suppressing insulin secretion. Constitutively active PI3K or protein kinase B/Akt exerted similar effects, while inhibitors of PI3K, but not of glycogen synthase kinase-3 or p70 S6 kinase, blocked nuclear export. FoxO1 overexpression reversed the activation by glucose of pancreatic duodenum homeobox-1 (Pdx1) transcription. Silencing of FoxO1 significantly elevated the expression of mouse Ins2, but not Ins1, mRNA at 3 mM glucose. Putative FoxO1 binding sites were identified in the distal promoter of rodent Ins2 genes and direct binding of FoxO1 to the Ins2 promoter was demonstrated by chromatin immunoprecipitation. A 915-bp glucose-responsive Ins2 promoter was inhibited by constitutively active FoxO1, an effect unaltered by simultaneous overexpression of PDX1. We conclude that nuclear import of FoxO1 contributes to the suppression of Pdx1 and Ins2 gene expression at low glucose, the latter via a previously unsuspected and direct physical interaction with the Ins2 promoter.
Subject(s)
Cell Nucleus/metabolism , Cytosol/metabolism , Forkhead Transcription Factors/metabolism , Gene Expression Regulation/physiology , Insulin-Secreting Cells/metabolism , Insulin/biosynthesis , Response Elements/physiology , Active Transport, Cell Nucleus/drug effects , Active Transport, Cell Nucleus/physiology , Animals , Cell Line , Cell Nucleus/genetics , Forkhead Box Protein O1 , Forkhead Transcription Factors/genetics , Gene Expression Regulation/drug effects , Glucose/metabolism , Glucose/pharmacology , Glycogen Synthase Kinase 3/genetics , Glycogen Synthase Kinase 3/metabolism , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Humans , Insulin/genetics , Mice , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Sweetening Agents/metabolism , Sweetening Agents/pharmacology , Trans-Activators/genetics , Trans-Activators/metabolismABSTRACT
Metabolic rate is a basic individual metric that extends beyond the individual to link the ecology of populations, communities, and ecosystems via its role as a central component of energy budgets. Metabolic rates are often measured indirectly by quantifying respiration under simplified, standard laboratory conditions. This approach limits the application of these measurements to a small range of conditions that commonly do not reflect natural field conditions. We measured metabolic rates of the squareback marsh crab Armases cinereum under field conditions. Previous work highlights that movement of individual A. cinereum, especially females, provides a potential spatial subsidy of energy, as individuals consume foods in salt marshes and then transfer the resulting energy to upland forest ecosystems. We show that metabolic rate increases with size for both males and females and that metabolic rates are influenced by temperature and by whether females are vitellogenic. The metabolic rates that we measured more closely approximate field metabolic rates than standard metabolic rates and demonstrate that individual crabs experience high energy expenditures, reducing the amount of energy that may be transferred as a subsidy between marsh and forest as a result of the daily movements of individual crabs. Our measurements are therefore also a key component for the construction of an energy budget for this species.
ABSTRACT
Rapid warming in the Gulf of Maine may influence the success or invasiveness of the Asian shore crab, Hemigrapsus sanguineus. To better predict the effects of climate change on this invasive species, it is necessary to measure its energy dynamics under a range of conditions. However, previous research has only focused on the metabolism of this intertidal species in water. We sampled adult crabs from three different sites and measured their metabolic rates in the air. We show that metabolic rate increases with body mass and the number of missing limbs, but decreases with the number of regenerating limbs, possibly reflecting the timing of energy allocation to limb regeneration. Importantly, metabolic rates measured here in the air are ~4× higher than metabolic rates previously measured for this species in water. Our results provide baseline measurements of aerial metabolic rates across body sizes, which may be affected by climate change. With a better understanding of respiration in H. sanguineus, we can make more informed predictions about the combined effects of climate change and invasive species on the northeast coasts of North America.
ABSTRACT
PURPOSE: To report the initial safety and effectiveness profile for an anterior shape-changing, modular IOL, Juvene IOL (JIOL), for the treatment of aphakia and presbyopia after removal of the natural crystalline lens due to cataract. SETTING: 2 private practices in Monterrey and Tijuana, Mexico. DESIGN: Exploratory prospective multicenter open-label noncomparative clinical trial. METHODS: A convenience sample of patients aged 50 to 80 years with planned cataract surgery was recruited to undergo unilateral or bilateral implantation with the JIOL. Patients were required to complete an informed consent and be able to dilate to at least 6.0 mm pharmacologically, be in good overall health, and have no significant eye health history to qualify. Visual acuities, defocus curves, and contrast sensitivity were measured for all patients 12 months postoperatively. RESULTS: 51 of 58 eyes completed the 12-month visit. Intraoperative complication rates were extremely low (n = 1; missed base lens tab). The most frequent adverse events (AEs) were prolonged inflammation (N = 6) and cystoid macular edema (N = 4); all AEs were resolved without sequelae by the 12-month visit. The mean monocular logMAR corrected distance visual acuity, distance-corrected intermediate visual acuity, and distance-corrected near visual acuity were 0.01, 0.08, and 0.24, respectively. Defocus testing showed visual acuity > 20/40 from approximately +1.00 through -2.00 diopters. Binocular implantation (n = 16) provided superior performance over monocular implantation. CONCLUSIONS: The JIOL offers a new solution to treat presbyopia, providing clear functional vision performance across a range of distances with an acceptable initial safety profile.