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1.
J Matern Fetal Neonatal Med ; 37(1): 2407038, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39322428

ABSTRACT

OBJECTIVE: Maternal hemoglobin A1c (HbA1c) has been suggested to be a predictor of left ventricular hypertrophy (LVH) in the offspring of mothers with pre-gestational diabetes mellitus, although there is little data supporting this contention. We aimed to assess the relationship between maternal HbA1c and postnatal LVH. METHODS: We performed a retrospective cohort study of infants born to mothers with pre-gestational diabetes mellitus from 2015 to 2021 at our institution. The primary predictor was maternal HbA1c; neonatal left ventricular mass (LVM) z-score was the primary outcome; LVM z-score was considered as both a continuous variable and a binary variable by dichotomizing at 4 to define LVH. Additionally, we used linear regression to determine the relationship between maternal HbA1c and LVM z-score. RESULTS: There were 116 infants who met inclusion (50% female). Mean maternal HbA1c was generally higher in infants with LVH compared to those without LVH (8.2% with LVH vs. 7.2% without LVH [p = 0.009] in the second trimester, and 7.8% vs. 7.0% [p = 0.025] in the third trimester; no significant difference for first trimester). A greater percentage of infants with LVH were intubated (36% vs. 6%, p < 0.001) and had longer average days of hospitalization (9 vs. 5, p = 0.044). Second and third trimester HbA1c was weakly associated with LVM z-score (R2 = 0.063, p < 0.001 and R2 = 0.068, p < 0.001, respectively); first trimester HbA1c was not significantly predictive of LVM z-score. CONCLUSION: Second and third trimester HbA1c is modestly predictive of LVH in infants born to mothers with pre-gestational diabetes mellitus.


Subject(s)
Glycated Hemoglobin , Hypertrophy, Left Ventricular , Humans , Female , Pregnancy , Glycated Hemoglobin/analysis , Retrospective Studies , Infant, Newborn , Hypertrophy, Left Ventricular/blood , Adult , Pregnancy in Diabetics/blood , Male
2.
Spectrochim Acta A Mol Biomol Spectrosc ; 325: 125142, 2024 Sep 14.
Article in English | MEDLINE | ID: mdl-39299078

ABSTRACT

This study investigates the effect of a natural dye extracted from common poppy (Papaver rhoeas) waste flowers on the optical properties of chitosan (CS) films. The extraction of natural dyes from waste flowers can be considered a new field for research in green chemistry. CS films are flexible and biodegradable but have low optical activity and band gap, limiting their applications in optical devices. The doped CS polymer with different concentrations of Papaver rhoeas dye exhibited enhanced optical properties. Also, 30 % glycerol was added as a plasticizer to omit film brittleness. The FTIR examinations is helpful to propose a mechanism that explains the interaction of the dye with the host polymer. The UV-vis spectroscopic examination establish that the optical characteristics of the films can be modified by adjusting the dye concentration. Furthermore, optical absorption properties are described using the Tauc non-direct transition model, revealing an approximate optical band gap of 1.64 eV. This band gap defines the energy required for electron transitions, elucidating the material's electronic characteristics. The extinction coefficient (k) and refractive index (n) of the CS-doped films' shows a dispersion behavior at visible regions of EM radiation. The Wemple-DiDomenico single oscillator model was used to investigate the n dispersion and determine the oscillator energy equivalent to the optical band gap. Additionally, calculations have been performed on optical dielectric properties and optical conductivity. The Urbach energy was measured and used to detect the structure of the films. The findings underscore the potential applications of these natural dye-doped CS films in eco-friendly materials and optical devices.

3.
PLoS One ; 19(8): e0297374, 2024.
Article in English | MEDLINE | ID: mdl-39137172

ABSTRACT

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) represents an important but limited treatment for patients with severe COVID-19. We assessed the effects of an educational intervention on a person's ECMO care preference and examined whether patients and providers had similar ECMO preferences. METHODS: In the Video+Survey group, patients watched an educational video about ECMO's purpose, benefits, and risks followed by an assessment of ECMO knowledge and care preferences in seven scenarios varying by hypothetical patient age, function, and comorbidities. Patients in the Survey Only group and providers didn't watch the video. Logistic regression was used to estimate the probability of agreement for each ECMO scenario between the two patient groups and then between all patients and providers. RESULTS: Video+Survey patients were more likely (64% vs. 17%; p = 0.02) to correctly answer all ECMO knowledge questions than Survey Only patients. Patients in both groups agreed that ECMO should be considered across all hypothetical scenarios, with predicted agreement above 65%. In adjusted analyses, patients and providers had similar predicted agreement for ECMO consideration across six of the seven scenarios, but patients showed greater preference (84% vs. 41%, p = 0.003) for the scenario of a functionally dependent 65-year-old with comorbidities than providers. DISCUSSION AND CONCLUSIONS: An educational video increased a person's ECMO knowledge but did not change their ECMO preferences. Clinicians were less likely than patients to recommend ECMO for older adults, so advanced care planning discussion between patients and providers about treatment options in critically ill patients with COVID-19 is critical.


Subject(s)
COVID-19 , Extracorporeal Membrane Oxygenation , Patient Education as Topic , Patient Preference , Humans , COVID-19/therapy , COVID-19/epidemiology , Male , Female , Middle Aged , Adult , Patient Education as Topic/methods , Aged , Surveys and Questionnaires , SARS-CoV-2 , Health Personnel/psychology , Health Knowledge, Attitudes, Practice
4.
RSC Adv ; 14(36): 26362-26387, 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39165793

ABSTRACT

The current study employed a novel approach to design polymer composites with modified structural and declined optical band gaps. The results obtained in the present work for polymer composites can be considered an original method to make a new field for research based on green chemistry. Natural dyes extracted from green tea were mixed with hydrated zinc acetate (Zn(CH3COO)2·2H2O) to produce a metal complex. FTIR results comprehensively established the formation of the Zn-metal complex. The interaction among various components of PVA : Zn-metal complex composite was investigated using FTIR spectroscopy. The non-existence of anion bands of acetate in the Zn-metal complex spectrum confirms the formation of the Zn-metal complex. XRD analysis reveals that the Zn-metal complex improves the amorphous phase of the PVA-based composites. The absorption edge of the doped films shifted towards the lower photon energies. Optical dielectric properties were used to determine N/m*, ε ∞, τ, µ opt, ω p, and ρ opt; the W-D model was used to calculate E d, E o and n o parameters. The optical dielectric loss parameter was used to determine the optical band gap while the Tauc model was employed to identify various types of electron transitions. The optical energy band gap was 6.05 eV for clean PVA while it decreased to 1 eV for PVA inserted with the Zn-metal complex. The increase in Urbach energy from 0.26 eV to 0.45 eV is an evidence of the boost of amorphous phases in PVA : Zn-metal complex composites. The nonlinear refractive index and the first-order and second-order nonlinear optical susceptibilities were determined. The value of E o obtained from the W-D model closely matches the optical energy band gap obtained from the Tauc model, which indicates the precision of the analysis in the present study. The increase in SELF and VELF in the composite films establishes that new energy states assigned to the added Zn-metal complex amplify the probability of light-matter interaction.

5.
Antimicrob Agents Chemother ; 68(8): e0022024, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-38975753

ABSTRACT

Data guiding the duration and route of streptococcal bloodstream infection (BSI) treatment are lacking. We conducted a retrospective cohort study of adults hospitalized with uncomplicated streptococcal BSI in a large integrated healthcare system from 2013 to 2020. The exposures of interest were antibiotic duration (5-10 days vs. 11-15 days) and antibiotic route (oral switch vs. entirely intravenous). The primary outcome was a composite 90-day outcome comprised of all-cause mortality, recurrent streptococcal BSI, or readmission. We performed non-inferiority analyses for each exposure. Separate multivariable Cox proportional hazards regression models were constructed for each exposure. The antibiotic duration analysis included 1,407 patients (5-10 days, n = 246; 11-15 days, n = 1,161). We found that 5-10-day courses were non-inferior to 11-15-day courses (P = 0.047). The antibiotic route analysis included 1,461 patients (oral switch, n = 1,112; entirely intravenous, n = 349). Oral step-down therapy did not meet the criteria for non-inferiority (P = 0.06). In the adjusted models, no significant difference was found in the primary outcome rate by antibiotic duration or antibiotic route at discharge. We found that 5-10-day courses were non-inferior to longer courses, and thus may be a safe and effective treatment option in the treatment of uncomplicated streptococcal bacteremia. Randomized controlled trials are needed to confirm the equivalent outcomes with shorter regimens and to definitively determine the optimal antibiotic route on discharge.


Subject(s)
Anti-Bacterial Agents , Bacteremia , Streptococcal Infections , Humans , Anti-Bacterial Agents/therapeutic use , Streptococcal Infections/drug therapy , Streptococcal Infections/microbiology , Retrospective Studies , Male , Female , Middle Aged , Bacteremia/drug therapy , Bacteremia/microbiology , Adult , Aged , Administration, Intravenous , Administration, Oral , Proportional Hazards Models , Patient Readmission/statistics & numerical data
6.
Biochemistry ; 63(13): 1663-1673, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38885634

ABSTRACT

The mono(2-hydroxyethyl) terephthalate hydrolase (MHETase) from Ideonella sakaiensis carries out the second step in the enzymatic depolymerization of poly(ethylene terephthalate) (PET) plastic into the monomers terephthalic acid (TPA) and ethylene glycol (EG). Despite its potential industrial and environmental applications, poor recombinant expression of MHETase has been an obstacle to its industrial application. To overcome this barrier, we developed an assay allowing for the medium-throughput quantification of MHETase activity in cell lysates and whole-cell suspensions, which allowed us to screen a library of engineered variants. Using consensus design, we generated several improved variants that exhibit over 10-fold greater whole-cell activity than wild-type (WT) MHETase. This is revealed to be largely due to increased soluble expression, which biochemical and structural analysis indicates is due to improved protein folding.


Subject(s)
Burkholderiales , Burkholderiales/enzymology , Burkholderiales/genetics , Burkholderiales/metabolism , Phthalic Acids/metabolism , Phthalic Acids/chemistry , Hydrolases/metabolism , Hydrolases/genetics , Hydrolases/chemistry , Solubility , Polyethylene Terephthalates/metabolism , Polyethylene Terephthalates/chemistry , Recombinant Proteins/metabolism , Recombinant Proteins/genetics , Recombinant Proteins/chemistry , Protein Engineering/methods , Protein Folding , Escherichia coli/genetics , Escherichia coli/metabolism , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/chemistry , Models, Molecular
7.
Mol Metab ; 85: 101931, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38796310

ABSTRACT

OBJECTIVE: Simultaneous activation of ß2- and ß3-adrenoceptors (ARs) improves whole-body metabolism via beneficial effects in skeletal muscle and brown adipose tissue (BAT). Nevertheless, high-efficacy agonists simultaneously targeting these receptors whilst limiting activation of ß1-ARs - and thus inducing cardiovascular complications - are currently non-existent. Therefore, we here developed and evaluated the therapeutic potential of a novel ß2-and ß3-AR, named ATR-127, for the treatment of obesity and its associated metabolic perturbations in preclinical models. METHODS: In the developmental phase, we assessed the impact of ATR-127's on cAMP accumulation in relation to the non-selective ß-AR agonist isoprenaline across various rodent ß-AR subtypes, including neonatal rat cardiomyocytes. Following these experiments, L6 muscle cells were stimulated with ATR-127 to assess the impact on GLUT4-mediated glucose uptake and intramyocellular cAMP accumulation. Additionally, in vitro, and in vivo assessments are conducted to measure ATR-127's effects on BAT glucose uptake and thermogenesis. Finally, diet-induced obese mice were treated with 5 mg/kg ATR-127 for 21 days to investigate the effects on glucose homeostasis, body weight, fat mass, skeletal muscle glucose uptake, BAT thermogenesis and hepatic steatosis. RESULTS: Exposure of L6 muscle cells to ATR-127 robustly enhanced GLUT4-mediated glucose uptake despite low intramyocellular cAMP accumulation. Similarly, ATR-127 markedly increased BAT glucose uptake and thermogenesis both in vitro and in vivo. Prolonged treatment of diet-induced obese mice with ATR-127 dramatically improved glucose homeostasis, an effect accompanied by decreases in body weight and fat mass. These effects were paralleled by an enhanced skeletal muscle glucose uptake, BAT thermogenesis, and improvements in hepatic steatosis. CONCLUSIONS: Our results demonstrate that ATR-127 is a highly effective, novel ß2- and ß3-ARs agonist holding great therapeutic promise for the treatment of obesity and its comorbidities, whilst potentially limiting cardiovascular complications. As such, the therapeutic effects of ATR-127 should be investigated in more detail in clinical studies.


Subject(s)
Adipose Tissue, Brown , Mice, Inbred C57BL , Muscle, Skeletal , Animals , Adipose Tissue, Brown/metabolism , Adipose Tissue, Brown/drug effects , Mice , Muscle, Skeletal/metabolism , Muscle, Skeletal/drug effects , Male , Rats , Obesity/metabolism , Obesity/drug therapy , Fatty Liver/metabolism , Fatty Liver/drug therapy , Thermogenesis/drug effects , Adrenergic Agonists/pharmacology
8.
Am J Obstet Gynecol MFM ; 6(6): 101374, 2024 06.
Article in English | MEDLINE | ID: mdl-38583712

ABSTRACT

BACKGROUND: Respiratory distress syndrome is strongly associated with prematurity, including late preterm births. Respiratory distress syndrome has been shown to be associated with certain neonatal morbidities and mortality, but these associations are not well described among late preterm births. OBJECTIVE: We sought to determine the association between respiratory distress syndrome and adverse neonatal outcomes among late preterm (34-36 weeks) born singleton neonates. STUDY DESIGN: This is a retrospective cohort study using California's linked vital statistics and patient discharge data (2008-2019). We included singleton, nonanomalous births with a gestational age of 34-36 weeks. Outcomes of interest were interventricular hemorrhage, necrotizing enterocolitis, retinopathy of prematurity, neonatal sepsis, length of hospital stay, neonatal death, and infant death. Chi-square and multivariable Poisson regression analyses were used to examine the association of respiratory distress syndrome with outcomes at each gestational age. Adjusted risk ratio and 95% confidence interval values were estimated. RESULTS: A total of 242,827 births were included, of which 11,312 (4.7%) had respiratory distress syndrome. We found that among neonates with respiratory distress syndrome, necrotizing enterocolitis was higher at 35 weeks (adjusted risk ratio, 3.97 [95% confidence interval, 1.88-8.41]) and 36 weeks (adjusted risk ratio, 4.53 [95% confidence interval, 1.45-14.13]). Intraventricular hemorrhage, retinopathy of prematurity, neonatal sepsis, and length of hospital stay were significantly higher at 34-36 weeks of gestation in neonates with respiratory distress syndrome. Neonatal death was significantly higher among neonates with respiratory distress syndrome at 35 weeks (adjusted risk ratio, 3.04 [95% confidence interval, 1.58-5.85]) and 36 weeks (adjusted risk ratio, 3.25; 95% confidence interval, 1.59-6.68). In addition, infant death was significantly higher at 35 weeks (adjusted risk ratio, 2.27 [95% confidence interval, 1.43-3.61]) and 36 weeks (adjusted risk ratio, 2.60 [95% confidence interval, 1.58-4.28]). CONCLUSION: We found that respiratory distress syndrome was associated with intraventricular hemorrhage, retinopathy of prematurity, and sepsis at 34-36 weeks of gestation, whereas respiratory distress syndrome was associated with neonatal death, infant death, and necrotizing enterocolitis at 35 and 36 weeks. Clinicians should keep these outcomes in mind when making decisions about delivery timing, the potential benefits of antenatal steroids in pregnancies in the late preterm period, and the management of respiratory distress syndrome in late preterm neonates.


Subject(s)
Enterocolitis, Necrotizing , Gestational Age , Infant, Premature , Respiratory Distress Syndrome, Newborn , Retinopathy of Prematurity , Humans , Female , Infant, Newborn , Retrospective Studies , Respiratory Distress Syndrome, Newborn/epidemiology , Enterocolitis, Necrotizing/epidemiology , Enterocolitis, Necrotizing/mortality , Male , Pregnancy , Retinopathy of Prematurity/epidemiology , Retinopathy of Prematurity/diagnosis , California/epidemiology , Length of Stay/statistics & numerical data , Infant , Adult , Premature Birth/epidemiology , Infant Mortality/trends , Neonatal Sepsis/epidemiology , Neonatal Sepsis/mortality , Neonatal Sepsis/diagnosis , Cerebral Intraventricular Hemorrhage/epidemiology , Perinatal Death , Infant, Premature, Diseases/epidemiology , Infant, Premature, Diseases/mortality
9.
J Pharm Bioallied Sci ; 16(Suppl 1): S537-S539, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38595400

ABSTRACT

Background: Orthodontic treatment is commonly used to correct misaligned teeth and improve dental aesthetics and function. Archwires play a crucial role in this treatment by exerting forces on teeth, prompting them to shift into desired positions. Materials and Methods: For this experimental study, 60 participants requiring orthodontic treatment were selected and divided into three groups: Group A, treated with stainless steel archwires; Group B, treated with nickel-titanium archwires; and Group C, treated with beta-titanium archwires. Standardized orthodontic procedures were followed for all participants. The rate of tooth movement was measured over a period of 6 months using digital models and a calibrated measurement technique. Results: The study revealed notable differences in the rate of orthodontic tooth movement among the three groups. Group B (nickel-titanium archwires) demonstrated the highest mean rate of tooth movement, with an average of 1.5 mm per month. Group A (stainless steel archwires) exhibited a mean rate of 1.2 mm per month, while Group C (beta-titanium archwires) showed the lowest mean rate at 0.9 mm per month. Conclusion: In conclusion, this study highlights the varying efficacy of different archwire materials in accelerating orthodontic tooth movement. Nickel-titanium archwires exhibited the highest rate of tooth movement compared to stainless steel and beta-titanium archwires.

10.
J Pharm Bioallied Sci ; 16(Suppl 1): S534-S536, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38595637

ABSTRACT

This study investigates the effectiveness of nanoparticles in preventing the formation of biofilms on orthodontic brackets. Biofilm formation is a common concern during orthodontic treatment, as it can lead to oral health issues. Materials and Methods: The study utilized a randomized controlled trial design. The participants were divided into two groups: the experimental group and the control group. The experimental group received orthodontic brackets coated with nanoparticles, while the control group received regular brackets. The patients' oral hygiene was monitored, and plaque index scores were recorded at specific intervals. Results: The results of this study demonstrated a significant difference in biofilm formation between the two groups. The experimental group, which had orthodontic brackets with nanoparticle coatings, exhibited a lower plaque index compared to the control group. The mean plaque index score difference was statistically significant (P < 0.05), indicating that the nanoparticles effectively reduced biofilm formation on orthodontic brackets. Conclusion: In conclusion, the findings of this clinical study suggest that the utilization of nanoparticles as coatings for orthodontic brackets can be an effective approach to prevent biofilm formation.

11.
Stem Cells Transl Med ; 13(5): 448-453, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38521608

ABSTRACT

BACKGROUND: Cord blood units (CBUs) that are ineligible for licensure due to incomplete compliance with FDA recommendations may be used for hematopoietic stem cell transplantation under urgent medical need and an Investigational Drug Application. The largest reason for CBU donor ineligibility is Zika virus (ZIKV) risk. The study's objective was to analyze the impact of current FDA recommendations for ZIKA risk on a large public cord blood bank and propose updated recommendations. METHODS: We performed a retrospective analysis of Carolinas Cord Blood Bank (CCBB), an FDA licensed public CBB, using data from January 1, 2016 to November 21, 2023 and compared FDA recommendations for transfusion transmitted infections (TTI) for blood products and relevant communicable disease agents or diseases for human cell, tissue, or cellular or tissue-based products (HCT/Ps). RESULTS: CCBB: 9057 (84.3% licensed) CBUs were banked. 984/1682 (58.5%) of unlicensed CBUs had ZIKV risk. 22.0% of CBUs with ZIKV risk were from Hispanic parents, compared to 16.1% of all units. 31 of IND CBUs (11 due to ZIKV risk without reported ZIKV transmission) were safely infused. FDA Guidance: HCT/P ZIKV, HIV, and vCJD recommendations have not been updated since 2018 in contrast to FDA removal of ZIKV as a relevant TTI in 2021 and updating HIV and vCJD guidance related to TTI in 2023 and 2022, respectively. DISCUSSION: The FDA should consider new data to revise the HCT/P donor eligibility recommendations, which will increase the number of eligible HCT/P donors, and potentially improve access to therapies for a more diverse patient population.


Subject(s)
Blood Banks , Fetal Blood , United States Food and Drug Administration , Zika Virus Infection , Humans , United States , Zika Virus Infection/transmission , Fetal Blood/virology , Blood Banks/standards , Zika Virus , Retrospective Studies , Female , Male
12.
Sci Rep ; 14(1): 6383, 2024 Mar 16.
Article in English | MEDLINE | ID: mdl-38493250

ABSTRACT

The relentless pursuit of miniaturization and performance enhancement in electronic devices has led to a fundamental challenge in the field of circuit design and simulation-how to accurately account for the inherent stochastic nature of certain devices. While conventional deterministic models have served as indispensable tools for circuit designers, they fall short when it comes to capturing the subtle yet critical variability exhibited by many electronic components. In this paper, we present an innovative approach that transcends the limitations of traditional modeling techniques by harnessing the power of machine learning, specifically Mixture Density Networks (MDNs), to faithfully represent and simulate the stochastic behavior of electronic devices. We demonstrate our approach to model heater cryotrons, where the model is able to capture the stochastic switching dynamics observed in the experiment. Our model shows 0.82% mean absolute error for switching probability. This paper marks a significant step forward in the quest for accurate and versatile compact models, poised to drive innovation in the realm of electronic circuits.

13.
Proc Natl Acad Sci U S A ; 121(9): e2214160121, 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38377206

ABSTRACT

Gossip, the exchange of personal information about absent third parties, is ubiquitous in human societies. However, the evolution of gossip remains a puzzle. The current article proposes an evolutionary cycle of gossip and uses an agent-based evolutionary game-theoretic model to assess it. We argue that the evolution of gossip is the joint consequence of its reputation dissemination and selfishness deterrence functions. Specifically, the dissemination of information about individuals' reputations leads more individuals to condition their behavior on others' reputations. This induces individuals to behave more cooperatively toward gossipers in order to improve their reputations. As a result, gossiping has an evolutionary advantage that leads to its proliferation. The evolution of gossip further facilitates these two functions of gossip and sustains the evolutionary cycle.


Subject(s)
Communication , Cooperative Behavior , Humans , Biological Evolution
14.
Pharmacol Res Perspect ; 12(1): e1176, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38332691

ABSTRACT

Truncation of the C-terminal tail of the ß2 -AR, transfection of ßARKct or over-expression of a kinase-dead GRK mutant reduces isoprenaline-stimulated glucose uptake, indicating that GRK is important for this response. We explored whether phosphorylation of the ß2 -AR by GRK2 has a role in glucose uptake or if this response is related to the role of GRK2 as a scaffolding protein. CHO-GLUT4myc cells expressing wild-type and mutant ß2 -ARs were generated and receptor affinity for [3 H]-CGP12177A and density of binding sites determined together with the affinity of isoprenaline and BRL37344. Following receptor activation by ß2 -AR agonists, cAMP accumulation, GLUT4 translocation, [3 H]-2-deoxyglucose uptake, and ß2 -AR internalization were measured. Bioluminescence resonance energy transfer was used to investigate interactions between ß2 -AR and ß-arrestin2 or between ß2 -AR and GRK2. Glucose uptake after siRNA knockdown or GRK inhibitors was measured in response to ß2 -AR agonists. BRL37344 was a poor partial agonist for cAMP generation but displayed similar potency and efficacy to isoprenaline for glucose uptake and GLUT4 translocation. These responses to ß2 -AR agonists occurred in CHO-GLUT4myc cells expressing ß2 -ARs lacking GRK or GRK/PKA phosphorylation sites as well as in cells expressing the wild-type ß2 -AR. However, ß2 -ARs lacking phosphorylation sites failed to recruit ß-arrestin2 and did not internalize. GRK2 knock-down or GRK2 inhibitors decreased isoprenaline-stimulated glucose uptake in rat L6 skeletal muscle cells. Thus, GRK phosphorylation of the ß2 -AR is not associated with isoprenaline- or BRL37344-stimulated glucose uptake. However, GRKs acting as scaffold proteins are important for glucose uptake as GRK2 knock-down or GRK2 inhibition reduces isoprenaline-stimulated glucose uptake.


Subject(s)
G-Protein-Coupled Receptor Kinases , Glucose , Rats , Animals , Isoproterenol/pharmacology , Glucose/metabolism , Receptors, G-Protein-Coupled , Receptors, Adrenergic
15.
Expert Opin Investig Drugs ; 33(3): 183-190, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38372052

ABSTRACT

INTRODUCTION: Type 2 diabetes (T2D) is metabolic disorder associated with a decrease in insulin activity and/or secretion from the ß-cells of the pancreas, leading to elevated circulating glucose. Current management practices for T2D are complex with varying long-term effectiveness. Agonism of the G protein-coupled receptor GPR119 has received a lot of recent interest as a potential T2D therapeutic. AREAS COVERED: This article reviews studies focused on GPR119 agonism in animal models of T2D and in patients with T2D. EXPERT OPINION: GPR119 agonists in vitro and in vivo can potentially regulate incretin hormone release from the gut, then pancreatic insulin release which regulates blood glucose concentrations. However, the success in controlling glucose homeostasis in rodent models of T2D and obesity, failed to translate to early-stage clinical trials in patients with T2D. However, in more recent studies, acute and chronic dosing with the GPR119 agonist DS-8500a had increased efficacy, although this compound was discontinued for further development. New trials on GPR119 agonists are needed, however it may be that the future of GPR119 agonists lie in the development of combination therapy with other T2D therapeutics.


Subject(s)
Diabetes Mellitus, Type 2 , Animals , Humans , Diabetes Mellitus, Type 2/drug therapy , Glucose/metabolism , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Incretins , Insulin/metabolism , Receptors, G-Protein-Coupled/agonists
17.
AJP Rep ; 13(4): e61-e64, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37937268

ABSTRACT

Congenital sodium diarrhea (CSD) is a rare, life-threatening condition characterized by intractable diarrhea, hyponatremia, and metabolic acidosis. It presents similarly to other congenital disorders and, therefore, is often misdiagnosed and mistreated. We present a case of CSD that presented with dilated loops of bowel and polyhydramnios at 18 weeks and was thought to be a congenital bowel obstruction. The patient was therefore managed surgically after birth with a diverting ileostomy, however was later found to have elevated stool sodium levels and metabolic derangements consistent with CSD. Our case demonstrates the need for high index of suspicion for congenital diarrheal disorders to prevent unnecessary surgery and a delay in appropriate medical management of this rare condition.

19.
J Appl Physiol (1985) ; 135(6): 1300-1311, 2023 12 01.
Article in English | MEDLINE | ID: mdl-37883101

ABSTRACT

Slow heart rate recovery following exercise may be influenced by persistent sympathoexcitation. This study examined 1) the effect of muscle metaboreflex activation (MMA) on heart rate recovery following dynamic exercise; and 2) whether the effect of MMA on heart rate recovery is reversible by reducing sympathoexcitation [baroreflex activation via phenylephrine (PE)] in canines. Twenty-two young adults completed control and MMA protocols during cycle ergometry at 110% ventilatory threshold with 5 min recovery. Heart rate recovery kinetics [tau (τ), amplitude, end-exercise, and end-recovery heart rate] and root mean square of successive differences (RMSSD) were measured. Five chronically instrumented canines completed control, MMA (50%-60% imposed reduction in hindlimb blood flow), and MMA with end-exercise PE infusion (MMA + PE) protocols during moderate exercise (6.4 km·h-1) and 3 min recovery. Heart rate recovery kinetics and MAP were measured. MAP increased during MMA versus control in canines (P < 0.001). Heart rate recovery τ was slower during MMA versus control in humans (17% slower; P = 0.011) and canines (150% slower; P = 0.002). Heart rate recovery τ was faster during MMA + PE versus MMA (40% faster; P = 0.034) and was similar to control in canines (P = 0.426). Amplitude, end-exercise, and end-recovery heart rate were similar between conditions in humans (all P ≥ 0.122) and in canines (all P ≥ 0.084). MMA decreased RMSSD in early recovery (P = 0.004). MMA-induced sympathoexcitation slows heart rate recovery and this effect is markedly attenuated with PE. Therefore, elevated sympathoexcitation via MMA impairs heart rate recovery and inhibition of this stimulus normalizes, in part, heart rate recovery.NEW & NOTEWORTHY Augmented sympathoexcitation, via muscle metaboreflex activation, functionally slows heart rate recovery in both young healthy adults and chronically instrumented canines. Furthermore, elevated sympathoexcitation corresponded with lower parasympathetic activity, as assessed by heart rate variability, during the first 3 min of recovery. Finally, sympathoinhibition, via phenylephrine infusion, normalizes heart rate recovery during muscle metaboreflex activation.


Subject(s)
Arterial Pressure , Reflex , Young Adult , Humans , Animals , Dogs , Heart Rate/physiology , Reflex/physiology , Arterial Pressure/physiology , Cardiac Output/physiology , Muscle, Skeletal/physiology , Phenylephrine , Blood Pressure
20.
J Clin Psychiatry ; 84(5)2023 08 28.
Article in English | MEDLINE | ID: mdl-37656181

ABSTRACT

Objective: While sexually and gender diverse (SGD) people have higher odds of alcohol use disorder (AUD) compared to heterosexual and cisgender people, AUD treatment access and use disparities are not well characterized. The purpose of this study is to assess differences in AUD treatment among SGD versus non-SGD populations.Methods: A retrospective cohort study was performed using data from a federally qualified health center electronic health record system in Boston, Massachusetts. Patients were 18 years or older with an International Classification of Diseases (ICD)-9 or ICD-10 AUD diagnosis and any clinic visit from January 2013 until June 2021 (N = 3,607). Treatment for AUD was identified using binary variables for medication prescription orders and visits for AUD.Results: Among patients identifying as lesbian/gay, 6.9% had an AUD diagnosis, as compared to 2.6% of patients identifying as straight/heterosexual (P < .001). The prevalence of AUD was higher in the gender diverse group as compared to the cisgender group (5.5% vs 4.4%, P < .001). There were no significant differences in receipt of a prescription for injectable naltrexone, acamprosate, or disulfiram between SGD and non-SGD patients. For oral naltrexone, 16.1% of sexually diverse patients received a prescription, as compared to 9.8% of straight/heterosexual patients (P < .001). For visits, both the straight/heterosexual cohort and the cisgender cohorts had the lowest proportion of AUD-related pharmacotherapy and individual psychotherapy visits, as compared to SGD cohorts.Conclusions: SGD patients had higher proportions of AUD diagnosis and AUD care utilization through behavioral health as compared to non-SGD patients.


Subject(s)
Alcoholism , Female , United States , Humans , Alcoholism/diagnosis , Alcoholism/drug therapy , Alcoholism/epidemiology , Naltrexone/therapeutic use , Retrospective Studies , United States Department of Veterans Affairs , Acamprosate/therapeutic use
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