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2.
J Am Heart Assoc ; 13(20): e036557, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-39392155

ABSTRACT

BACKGROUND: Among patients diagnosed with high blood pressure (BP), initial dual therapy has been recommended for patients with high pretreatment systolic BP (≥160 mm Hg) since 2003, and first-line ß-blocker use without a compelling condition has fallen out of favor in US guidelines. METHODS AND RESULTS: This serial cross-sectional study of national Veterans Health Administration data included adult Veterans with incident hypertension initiating antihypertensive medication between January 1, 2000, and December 31, 2019. We assessed annual trends in initial regimens dispensed (index date: first antihypertensive dispense date) by number of classes and unique class combinations used overall and by pretreatment systolic BP (<140, 140 to <160, and ≥160 mm Hg), as well as trends in subgroups (age, sex, race and ethnicity, and comorbidities warranting ß-blocker use). Among 2 832 684 eligible Veterans (average age 61 years, 95% men, 65% non-Hispanic White, and 8% with cardiovascular disease), from 2000-2004 to 2015-2019, initial monotherapy increased across all pretreatment systolic BP levels (<140 mm Hg: 62.1% to 66.4%; 140 to <160 mm Hg: 70.7% to 76.8%; ≥160 mm Hg: 64.2% to 69.7%). Initiation of dual therapy decreased across all pretreatment systolic BP levels (<140 mm Hg: 25.0% to 24.2%; 140 to <160 mm Hg: 20.4% to 17.6%; ≥160 mm Hg: 22.7% to 22.0%). Among 2 521 696 Veterans (89% of overall) without a ß-blocker-indicated condition in 2015 to 2019, 20% initiated a ß-blocker, most commonly as monotherapy. CONCLUSIONS: More than half of US Veterans diagnosed with hypertension with a pretreatment systolic BP ≥160 mm Hg were started on antihypertensive monotherapy. There are disparities between guideline-recommended first-line treatments and the actual regimens initiated for newly diagnosed Veterans with hypertension.


Subject(s)
Antihypertensive Agents , Blood Pressure , Hypertension , Practice Patterns, Physicians' , Veterans , Humans , Antihypertensive Agents/therapeutic use , Hypertension/drug therapy , Hypertension/epidemiology , Male , Female , Middle Aged , United States/epidemiology , Cross-Sectional Studies , Aged , Practice Patterns, Physicians'/trends , Practice Patterns, Physicians'/statistics & numerical data , Blood Pressure/drug effects , Veterans/statistics & numerical data , Drug Prescriptions/statistics & numerical data , Adrenergic beta-Antagonists/therapeutic use , Drug Therapy, Combination , United States Department of Veterans Affairs/trends
3.
Emerg Radiol ; 2024 Oct 14.
Article in English | MEDLINE | ID: mdl-39400643

ABSTRACT

PURPOSE: Previous studies have demonstrated that radiologists and other providers perceive maging to be higher than they actually are. Thus, pregnant patients were less likely to receive ionizing radiation procedures. While it is imperative to minimize fetal radiation exposure, clinicians must remember that diagnostic studies should not be avoided due to fear of radiation, particularly if the imaging study can significantly impact patient care. Although guidelines do exist regarding how best to image pregnant patients, many providers are unaware of these guidelines and thus lack confidence when making imaging decisions for pregnant patients. This study aimed to gather information about current education, confidence in, and knowledge about emergency imaging of pregnant women among radiology, emergency medicine, and OB/GYN providers. METHODS: We created and distributed an anonymous survey to radiology, emergency medicine, and OB/GYN providers to evaluate their knowledge and confidence in imaging pregnant patients in the emergent setting. This study included a questionnaire with the intent of knowing the correct answers among physicians primarily across the United States (along with some international participation). We conducted subgroup analyses, comparing variables by specialty, radiology subspecialty, and training levels. Based on the survey results, we subsequently developed educational training videos. RESULTS: 108 radiologists, of which 32 self-identified as emergency radiologists, ten emergency medicine providers and six OB/GYN clinicians completed the survey. The overall correct response rate was 68.5%, though performance across questions was highly variable. Within our 18-question survey, four questions had a correct response rate under 50%, while five questions had correct response rates over 90%. Most responding physicians identified themselves as either "fairly" (58/124, 47%) or "very" (51/124, 41%) confident. Amongst specialties, there were differences in performance concerning the knowledge assessment (p = 0.049), with the strongest performance from radiologists. There were no differences in knowledge by training level (p = 0.4), though confidence levels differed significantly between attending physicians and trainees (p < 0.001). CONCLUSION: This study highlights deficiencies in knowledge to support appropriate decision-making surrounding the imaging of pregnant patients. Our results indicate the need for improved physician education and dissemination of standardized clinical guidelines.

5.
Proc Natl Acad Sci U S A ; 121(39): e2400503121, 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39298487

ABSTRACT

Most eukaryotes have one nucleus and nuclear genome per cell. Ciliates have instead evolved distinct nuclei that coexist in each cell: a silent germline vs. transcriptionally active somatic nuclei. In the best-studied model species, both nuclei can divide asexually, but only germline nuclei undergo meiosis and karyogamy during sex. Thereafter, thousands of DNA segments, called internally eliminated sequences (IESs), are excised from copies of the germline genomes to produce the streamlined somatic genome. In Loxodes, however, somatic nuclei cannot divide but instead develop from germline copies even during asexual cell division, which would incur a huge overhead cost if genome editing was required. Here, we purified and sequenced both genomes in Loxodes magnus to see whether their nondividing somatic nuclei are associated with differences in genome architecture. Unlike in other ciliates studied to date, we did not find canonical germline-limited IESs, implying Loxodes does not extensively edit its genomes. Instead, both genomes appear large and equivalent, replete with retrotransposons and repetitive sequences, unlike the compact, gene-rich somatic genomes of other ciliates. Two other hallmarks of nuclear development in ciliates-domesticated DDE-family transposases and editing-associated small RNAs-were also not found. Thus, among the ciliates, Loxodes genomes most resemble those of conventional eukaryotes. Nonetheless, base modifications, histone marks, and nucleosome positioning of vegetative Loxodes nuclei are consistent with functional differentiation between actively transcribed somatic vs. inactive germline nuclei. Given their phylogenetic position, it is likely that editing was present in the ancestral ciliate but secondarily lost in the Loxodes lineage.


Subject(s)
Cell Nucleus , Ciliophora , Cell Nucleus/genetics , Cell Nucleus/metabolism , Ciliophora/genetics , Genome, Protozoan , DNA, Protozoan/genetics
6.
Clin Nutr ; 43(10): 2430-2437, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39305753

ABSTRACT

BACKGROUND & AIMS: Body shape expressed as the trunk-to-leg volume ratio is associated with diabetes and mortality due to the associations between higher adiposity and lower lean mass with Metabolic Syndrome (MetS) risk. Reduced appendicular muscle mass is associated with malnutrition risk and age-related frailty, and is a risk factor for poor treatment outcomes related to MetS and other clinical conditions (e.g.; cancer). These measures are traditionally assessed by dual-energy X-ray absorptiometry (DXA), which can be difficult to access in clinical settings. The Shape Up! Adults trial (SUA) demonstrated the accuracy and precision of 3-dimensional optical imaging (3DO) for body composition as compared to DXA and other criterion measures. Here we assessed whether trunk-to-leg volume estimates derived from 3DO are associated with MetS risk in a similar way as when measured by DXA. We further explored if estimations of appendicular lean mass (ALM) could be made using 3DO to further improve the accessibility of measuring this important frailty and disease risk factor. METHODS: SUA recruited participants across sex, age (18-40, 40-60, >60 years), BMI (under, normal, overweight, obese), and race/ethnicity (non-Hispanic [NH] Black, NH White, Hispanic, Asian, Native Hawaiian/Pacific Islander) categories. Each participant had whole-body DXA and 3DO scans, and measures of cardiovascular health. The 3DO measures of trunk and leg volumes were calibrated to DXA to express equivalent trunk-to-leg volume ratios. We expressed each blood measure and overall MetS risk in quartile gradations of trunk-to-leg volume previously defined by National Health and Nutrition Examination Survey (NHANES). Finally, we utilized 3DO measures to estimate DXA ALM using ten-fold cross-validation of the entire dataset. RESULTS: Participants were 502 (273 female) adults, mean age = 46.0 ± 16.5y, BMI = 27.6 ± 7.1 kg/m2 and a mean DXA trunk-to-leg volume ratio of 1.47 ± 0.22 (females: 1.43 ± 0.23; males: 1.52 ± 0.20). After adjustments for age and sex, each standard deviation increase in trunk-to-leg volume by 3DO was associated with a 3.3 (95% odds ratio [OR] = 2.4-4.2) times greater risk of MetS, with individuals in the highest quartile of trunk-to-leg at 27.4 (95% CI: 9.0-53.1) times greater risk of MetS compared to the lowest quartile. Risks of elevated blood biomarkers as related to high 3DO trunk-to-leg volume ratios were similar to previously published comparisons using DXA trunk-to-leg volume ratios. Estimated ALM by 3DO was correlated to DXA (r2 = 0.96, root mean square error = 1.5 kg) using ten-fold cross-validation. CONCLUSION: Using thresholds of trunk-to-leg associated with MetS developed on a sample of US-representative adults, trunk-to-leg ratio by 3DO after adjustments for offsets showed significant associations to blood parameters and MetS risk. 3DO scans provide a precise and accurate estimation of ALM across the range of body sizes included in the study sample. The development of these additional measures improves the clinical utility of 3DO for the assessment of MetS risk as well as the identification of low muscle mass associated with poor cardiometabolic and functional health.


Subject(s)
Absorptiometry, Photon , Body Composition , Leg , Humans , Male , Female , Adult , Middle Aged , Absorptiometry, Photon/methods , Young Adult , Metabolic Syndrome , Imaging, Three-Dimensional/methods , Adolescent , Risk Factors , Torso/diagnostic imaging , Risk Assessment , Aged , Optical Imaging/methods , Body Mass Index
7.
Psychophysiology ; : e14694, 2024 Sep 28.
Article in English | MEDLINE | ID: mdl-39342443

ABSTRACT

Error monitoring is essential for detecting errors and may facilitate behavioral adjustments that can reduce or prevent future errors. At times, error monitoring must occur while individuals are engaged in other, cognitively demanding tasks that might consume processing resources necessary for error monitoring. Here, we set out to determine whether concurrent working memory (WM) load interferes with error monitoring, as measured using event-related potentials, the error-related negativity (Ne/ERN), and error positivity (Pe). Fifty-four participants (n = 33 female) completed an arrowhead flanker task, with trials presented under low (2 letter) or high (6 letter) WM load. Participants were required to hold letter strings in memory and to recall these letters at the end of a set of flanker trials. Results showed that WM load reduced the Pe but did not affect the Ne/ERN. Therefore, WM load appeared to attenuate later, more elaborated stages of error processing, though initial error detection was unaffected. Additionally, high WM load slowed reaction times overall, but did not lead to a significant increase in errors. As such, slower responses may have helped participants maintain comparable accuracy for low-load versus high-load trials. Overall, results indicate that WM load interferes with the evaluation of error significance, which could interfere with behavioral adaptations over time.

8.
Front Radiol ; 4: 1332535, 2024.
Article in English | MEDLINE | ID: mdl-39301168

ABSTRACT

Recent advancements in artificial intelligence (AI) and machine learning offer numerous opportunities in musculoskeletal radiology to potentially bolster diagnostic accuracy, workflow efficiency, and predictive modeling. AI tools have the capability to assist radiologists in many tasks ranging from image segmentation, lesion detection, and more. In bone and soft tissue tumor imaging, radiomics and deep learning show promise for malignancy stratification, grading, prognostication, and treatment planning. However, challenges such as standardization, data integration, and ethical concerns regarding patient data need to be addressed ahead of clinical translation. In the realm of musculoskeletal oncology, AI also faces obstacles in robust algorithm development due to limited disease incidence. While many initiatives aim to develop multitasking AI systems, multidisciplinary collaboration is crucial for successful AI integration into clinical practice. Robust approaches addressing challenges and embodying ethical practices are warranted to fully realize AI's potential for enhancing diagnostic accuracy and advancing patient care.

9.
Hypertension ; 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39229724

ABSTRACT

BACKGROUND: Antihypertensive medication use patterns have likely been influenced by changing costs and accessibility over the past 3 decades. This study examines the relationships between patent exclusivity loss, medication costs, and national health policies on antihypertensive medication use. METHODS: Using 1996 to 2021 Medical Expenditure Panel Survey data of US adults with hypertension taking at least 1 antihypertensive medication, we conducted a cross-sectional analysis. We explored the associations between patent exclusivity loss, per-pill costs, and Medicare Part D enactment on medication use over time, focusing on the most commonly used medications (lisinopril, amlodipine, losartan, hydrochlorothiazide, and metoprolol). RESULTS: The unweighted sample comprised 50 095 US adults (mean age, 62 years; 53% female). The survey-weighted number of adults taking antihypertensive medications increased from 22 million (95% CIs, 20-23 million) to 55 million (95% CI, 51-60 million) between 1996 and 2021. Loss of patent exclusivity led to increased medication fills, notably for lisinopril, amlodipine, and losartan, which all exhibited within-class dominance. However, per-pill cost decreases coinciding with Medicare Part D did not increase the number of individuals treated or the use of specific antihypertensive medications or classes. CONCLUSIONS: The increase in antihypertensive medication use over the past decades highlights the significant impact of loss of patent exclusivity on the uptake in the use of specific medications. These findings underscore the complexity of factors influencing medication use, beyond cost reductions alone, and suggest that policies need to consider multiple facets to effectively improve antihypertensive medication accessibility and utilization.

10.
J Neurochem ; 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39233365

ABSTRACT

Fear-related psychopathologies, such as post-traumatic stress disorder, are linked to dysfunction in neural circuits that govern fear memory and arousal. The lateral hypothalamus (LH) and zona incerta (ZI) regulate fear, but our understanding of the precise neural circuits and cell types involved remains limited. Here, we examined the role of relaxin family peptide receptor 3 (RXFP3) expressing cells in the LH/ZI in conditioned fear expression and general arousal in male RXFP3-Cre mice. We found that LH/ZI RXFP3+ (LH/ZIRXFP3) cells projected strongly to fear learning, stress, and arousal centres, notably, the periaqueductal grey, lateral habenula, and nucleus reuniens. These cells do not express hypocretin/orexin or melanin-concentrating hormone but display putative efferent connectivity with LH hypocretin/orexin+ neurons and dopaminergic A13 cells. Following Pavlovian fear conditioning, chemogenetically activating LH/ZIRXFP3 cells reduced fear expression (freezing) overall but also induced jumping behaviour and increased locomotor activity. Therefore, the decreased freezing was more likely to reflect enhanced arousal rather than reduced fear. Indeed, stimulating these cells produced distinct patterns of coactivation between several motor, stress, and arousal regions, as measured by Fos expression. These results suggest that activating LH/ZIRXFP3 cells generates brain-wide activation patterns that augment behavioural arousal.

13.
World Neurosurg ; 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39270786

ABSTRACT

BACKGROUND: This study assessed neurological outcomes and variables associated with favorable outcomes in aSAH patients with low functional status (Glasgow Coma Scale [GCS] score ≤8) on postbleed day 7 (PBD7). METHODS: A retrospective analysis was conducted of all patients in the Barrow Ruptured Aneurysm Trial (January 1, 2014-July 31, 2019) treated for a ruptured aneurysm and who had a GCS score ≤8 on PBD7. The primary outcome was a favorable neurological outcome (modified Rankin Scale score ≤2) at last follow-up. RESULTS: Of 312 patients, 63 had low GCS scores at PBD7. These patients had a significantly greater proportion of poor Hunt and Hess scale grades (≥4) (44/63 [70%] vs 49/249 [19.7%], P < 0.001) and poor Fisher grades (grade=4) (58/63 [92%] vs 174/249 [69.9%], P < 0.001) compared to patients who did not have low GCS scores on PBD7, but no differences were found in age, sex, anterior location, aneurysm size, or type of treatment. Of the 63 patients, 7 (11%) experienced a favorable neurological outcome. On univariate analysis, none of the physical examination reflexes predicted a favorable neurological outcome. The middle cerebral artery aneurysm territory was the only significant predictor of a favorable neurological outcome by multivariate analysis (odds ratio, 10.8; 95% confidence interval, 1.16-100], P = 0.04). CONCLUSIONS: This study yielded no significant physical examination findings that predict a favorable outcome in patients with GCS score ≤8 on PBD7. This finding may inform the decision of whether to prolong hospital management or arrange for end-of-life care.

14.
J Biomech Eng ; 146(12)2024 Dec 01.
Article in English | MEDLINE | ID: mdl-39152721

ABSTRACT

Fatigue failure in biological soft tissues plays a critical role in the etiology of chronic soft tissue injuries and diseases such as osteoarthritis (OA). Understanding failure mechanisms is hindered by the decades-long timescales over which damage takes place. Analyzing the factors contributing to fatigue failure requires the help of validated computational models developed for soft tissues. This study presents a framework for fatigue failure of fibrous biological tissues based on reaction kinetics, where the composition of intact and fatigued material regions can evolve via degradation and breakage over time, in response to energy-based fatigue and damage criteria. Using reactive constrained mixture theory, material region mass fractions are governed by the axiom of mass balance. Progression of fatigue is controlled by an energy-based reaction rate, with user-selected probability functions defining the damage propensity of intact and fatigued material regions. Verification of this reactive theory, which is implemented in the open-source FEBio finite element software, is provided in this study. Validation is also demonstrated against experimental data, showing that predicted damage can be linked to results from biochemical assays. The framework is also applied to study fatigue failure during frictional contact of cartilage. Simulating previous experiments suggests that frictional effects slightly increase fatigue progression, but the main driver is cyclic compressive contact loading. This study demonstrated the ability of theoretical models to complement and extend experimental findings, advancing our understanding of the time progression of fatigue in biological tissues.


Subject(s)
Finite Element Analysis , Models, Biological , Cartilage , Stress, Mechanical , Biomechanical Phenomena , Friction , Animals , Cartilage, Articular/physiopathology
15.
Clin Nutr ESPEN ; 63: 540-550, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39047869

ABSTRACT

BACKGROUND & AIMS: Bioelectrical impedance analysis (BIA) for body composition estimation is increasingly used in clinical and field settings to guide nutrition and training programs. Due to variations among BIA devices and the proprietary prediction equations used, studies have recommended the use of raw measures of resistance (R) and reactance (Xc) within population-specific equations to predict body composition. OBJECTIVE: We compared raw measures from three BIA devices to assess inter-device variation and the impact of differences on body composition estimations. METHODS: Raw R, Xc, impedance (Z) parameters were measured on a calibrated phantom and athletes using tetrapolar supine (BIASUP4), octapolar supine (BIASUP8), and octapolar standing (BIASTA8) devices. Measures of R and Xc were compared across devices and graphed using BIA vector analysis (BIVA) and raw parameters were entered into recommended athlete-specific equations for predicting fat-free mass (FFM) and appendicular lean soft tissue (ALST). Whole-body FFM and regional ALST were compared across devices and to a criterion five-compartment (5C) model and dual energy X-ray absorptiometry for ALST. RESULTS: Data from 73 (23.2 ± 4.8 y) athletes were included in the analyses. Technical differences were observed between Z (range 12.2-50.1Ω) measures on the calibrated phantom. Differences in whole-body impedance were apparent due to posture (technological) and electrode placement (biological) factors. This resulted in raw measures for all three devices showing greater dehydration on BIVA compared to published norms for athletes using a separate BIA device. Compared to the 5C FFM, significant differences (p < 0.05) were observed on all three equations for BIASUP8 and BIASTA8, with constant error (CE) from -2.7 to -4.6 kg; no difference was observed for BIASUP4 or when device-specific algorithms were used. Published equations resulted in differences as large as 8.8 kg FFM among BIA devices. For ALST, even after a correction in the error of the published empirical equation, all three devices showed significant (p < 0.01) CE from -1.6 to -2.9 kg. CONCLUSIONS: Raw bioimpedance measurements differ among devices due to technical, technological, and biological factors, limiting interchangeability of data across BIA systems. Professionals should be aware of these factors when purchasing systems, comparing data to published reference ranges, or when applying published empirical body composition prediction equations.


Subject(s)
Absorptiometry, Photon , Body Composition , Electric Impedance , Humans , Adult , Male , Young Adult , Female , Athletes , Reproducibility of Results
16.
Cell ; 187(18): 4964-4980.e21, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39059380

ABSTRACT

The highly conserved and essential Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) has emerged as the leading target for vaccines against the disease-causing blood stage of malaria. However, the features of the human vaccine-induced antibody response that confer highly potent inhibition of malaria parasite invasion into red blood cells are not well defined. Here, we characterize 236 human IgG monoclonal antibodies, derived from 15 donors, induced by the most advanced PfRH5 vaccine. We define the antigenic landscape of this molecule and establish that epitope specificity, antibody association rate, and intra-PfRH5 antibody interactions are key determinants of functional anti-parasitic potency. In addition, we identify a germline IgG gene combination that results in an exceptionally potent class of antibody and demonstrate its prophylactic potential to protect against P. falciparum parasite challenge in vivo. This comprehensive dataset provides a framework to guide rational design of next-generation vaccines and prophylactic antibodies to protect against blood-stage malaria.


Subject(s)
Antibodies, Monoclonal , Antibodies, Protozoan , Antigens, Protozoan , Immunoglobulin G , Malaria Vaccines , Malaria, Falciparum , Plasmodium falciparum , Protozoan Proteins , Animals , Humans , Mice , Antibodies, Monoclonal/immunology , Antibodies, Protozoan/immunology , Antigens, Protozoan/immunology , Carrier Proteins/immunology , Epitopes/immunology , Erythrocytes/parasitology , Erythrocytes/immunology , Immunoglobulin G/immunology , Malaria Vaccines/immunology , Malaria, Falciparum/immunology , Malaria, Falciparum/prevention & control , Malaria, Falciparum/parasitology , Plasmodium falciparum/immunology , Protozoan Proteins/immunology
17.
Cell ; 187(18): 4981-4995.e14, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39059381

ABSTRACT

Plasmodium falciparum reticulocyte-binding protein homolog 5 (RH5) is the most advanced blood-stage malaria vaccine candidate and is being evaluated for efficacy in endemic regions, emphasizing the need to study the underlying antibody response to RH5 during natural infection, which could augment or counteract responses to vaccination. Here, we found that RH5-reactive B cells were rare, and circulating immunoglobulin G (IgG) responses to RH5 were short-lived in malaria-exposed Malian individuals, despite repeated infections over multiple years. RH5-specific monoclonal antibodies isolated from eight malaria-exposed individuals mostly targeted non-neutralizing epitopes, in contrast to antibodies isolated from five RH5-vaccinated, malaria-naive UK individuals. However, MAD8-151 and MAD8-502, isolated from two malaria-exposed Malian individuals, were among the most potent neutralizers out of 186 antibodies from both cohorts and targeted the same epitopes as the most potent vaccine-induced antibodies. These results suggest that natural malaria infection may boost RH5-vaccine-induced responses and provide a clear strategy for the development of next-generation RH5 vaccines.


Subject(s)
Antibodies, Neutralizing , Antibodies, Protozoan , Antigens, Protozoan , Malaria Vaccines , Malaria, Falciparum , Plasmodium falciparum , Humans , Antibodies, Neutralizing/immunology , Plasmodium falciparum/immunology , Malaria, Falciparum/immunology , Malaria, Falciparum/prevention & control , Malaria, Falciparum/parasitology , Malaria Vaccines/immunology , Antibodies, Protozoan/immunology , Antigens, Protozoan/immunology , Immunoglobulin G/immunology , Immunoglobulin G/blood , Protozoan Proteins/immunology , Antibodies, Monoclonal/immunology , Adult , B-Lymphocytes/immunology , Epitopes/immunology , Female , Mali , Carrier Proteins/immunology , Male , Adolescent
18.
Eval Health Prof ; : 1632787241263372, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39030071

ABSTRACT

We examined the psychometric properties of the Physical Activity, Nutrition, and Technology (PANT) survey, developed by researchers to track weight management behaviors among youth. Data from 2,039 middle school students (M age = 12.4, SD = .5; 51.4% girls) were analyzed to explore and then confirm the factor structure of the PANT survey. We also examined the bivariate associations between the PANT survey, body mass index (BMI), and the Progressive Aerobic Cardiorespiratory Endurance Run (PACER). Results suggest that the PANT survey is comprised of two factors-Physical Activity and Healthy Choices-each with adequate internal consistency (α = .79 and 0.86, respectively). The Physical Activity subscale appears to be significantly associated with both z-BMI (r = -0.10, p < .001) and the PACER (r = 0.33, p < .001) in the anticipated directions, but the criterion validity of the Healthy Choices subscale is less clear. We discuss these findings and explore future directions for developing meaningful self-report wellness behavior scales for youth.

19.
Sci Rep ; 14(1): 16487, 2024 07 17.
Article in English | MEDLINE | ID: mdl-39019902

ABSTRACT

Cerebral dopamine neurotrophic factor (CDNF) and its close structural relative, mesencephalic astrocyte-derived neurotrophic factor (MANF), are proteins with neurotrophic properties. CDNF protects and restores the function of dopamine (DA) neurons in rodent and non-human primate (NHP) toxin models of Parkinson's disease (PD) and therefore shows promise as a drug candidate for disease-modifying treatment of PD. Moreover, CDNF was found to be safe and to have some therapeutic effects on PD patients in phase 1/2 clinical trials. However, the mechanism underlying the neurotrophic activity of CDNF is unknown. In this study, we delivered human CDNF (hCDNF) to the brain using an adeno-associated viral (AAV) vector and demonstrated the neurotrophic effect of AAV-hCDNF in an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. AAV-hCDNF resulted in the expression of hCDNF in the striatum (STR) and substantia nigra (SN), and no toxic effects on the nigrostriatal pathway were observed. Intrastriatal injection of AAV-hCDNF reduced motor impairment and partially alleviated gait dysfunction in the acute MPTP mouse model. In addition, gene therapy with AAV-hCDNF had significant neuroprotective effects on the nigrostriatal pathway and decreased the levels of interleukin 1beta (IL-1ß) and complement 3 (C3) in glial cells in the acute MPTP mouse model. Moreover, AAV-hCDNF reduced C/EBP homologous protein (CHOP) and glucose regulatory protein 78 (GRP78) expression in astroglia. These results suggest that the neuroprotective effects of CDNF may be mediated at least in part through the regulation of neuroinflammation and the UPR pathway in a mouse MPTP model of PD in vivo.


Subject(s)
Dependovirus , Disease Models, Animal , Dopaminergic Neurons , Endoplasmic Reticulum Chaperone BiP , Endoplasmic Reticulum Stress , Genetic Vectors , Nerve Growth Factors , Animals , Dopaminergic Neurons/metabolism , Dependovirus/genetics , Mice , Humans , Nerve Growth Factors/metabolism , Nerve Growth Factors/genetics , Genetic Vectors/administration & dosage , Genetic Vectors/genetics , Gene Transfer Techniques , Male , Parkinson Disease/therapy , Parkinson Disease/metabolism , Parkinson Disease/genetics , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine , Inflammation/metabolism , Genetic Therapy/methods , Mice, Inbred C57BL , Corpus Striatum/metabolism , MPTP Poisoning/therapy , MPTP Poisoning/metabolism , Substantia Nigra/metabolism
20.
Am J Otolaryngol ; 45(5): 104391, 2024.
Article in English | MEDLINE | ID: mdl-39053311

ABSTRACT

OBJECTIVE: Upper airway stimulation effectively treats patients with obstructive sleep apnea, especially among those with low long-term compliance with continuous positive airway pressure. Traditional methods to implant the hypoglossal nerve stimulator involve retraction of the digastric tendon to identify the nerve and improve exposure for stimulator implantation. Transient submental pain and discomfort are known side effects of the procedure. Placement without retraction provides an alternative approach to minimize postoperative pain. This study compares post-operative pain outcomes of patients in whom the digastric tendon was and was not retracted. METHODS: Retrospective chart review of patients who received the hypoglossal nerve stimulation implant at a single institution between 2017 and 2021. A combination of descriptive and qualitative data, including age, gender, comorbidities, and postoperative symptoms are analyzed to characterize patient outcomes resulting from this intraoperative technique. The categorical and continuous variables were analyzed using chi-squared tests and independent t-tests, respectively. RESULTS: Patients report overall satisfaction after implantation and titration. A total of 108 patients underwent HGNS implantation between September 2017 and January 2021 using the aforementioned techniques. 1.69 % of patients experienced postoperative submental pain as compared to 18.37 % prior to the change in technique (p < 0.01). CONCLUSION: Avoidance of digastric tendon retraction in the implantation of the stimulating lead is a safe and effective technique that reduces postoperative pain and discomfort. Our institution has demonstrated an alternative technique for hypoglossal stimulator implantation which improves perioperative outcomes. LAY SUMMARY: Upper airway stimulation is an effective treatment for obstructive sleep apnea. During surgery, the digastric tendon is often moved to identify the nerve and improve access. This study shows that avoiding digastric tendon movement safely reduces postoperative pain and discomfort. LEVEL OF EVIDENCE: III.


Subject(s)
Electric Stimulation Therapy , Hypoglossal Nerve , Pain, Postoperative , Sleep Apnea, Obstructive , Humans , Hypoglossal Nerve/surgery , Female , Male , Middle Aged , Retrospective Studies , Sleep Apnea, Obstructive/therapy , Sleep Apnea, Obstructive/surgery , Electric Stimulation Therapy/methods , Pain, Postoperative/prevention & control , Pain, Postoperative/etiology , Treatment Outcome , Aged , Tendons/surgery , Adult , Patient Satisfaction
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