Association of metabolic dysregulation with volumetric brain magnetic resonance imaging and cognitive markers of subclinical brain aging in middle-aged adults: the Framingham Offspring Study.

ObjectiveDiabetic and prediabtic states, including insulin resistance, fasting hyperglycemia, and hyperinsulinemia, are associated with metabolic dysregulation. These components have been individually linked to increased risks of cognitive decline and Alzheimer's disease. We aimed to comprehensively relate all of the components of metabolic dysregulation to cognitive function and brain magnetic resonance imaging (MRI) in middle-aged adults.Research design and methodsFramingham Offspring participants who underwent volumetric MRI and detailed cognitive testing and were free of clinical stroke and dementia during examination 7 (1998-2001) constituted our study sample (n = 2,439; 1,311 women; age 61 ± 9 years). We related diabetes, homeostasis model assessment of insulin resistance (HOMA-IR), fasting insulin, and glycohemoglobin levels to cross-sectional MRI measures of total cerebral brain volume (TCBV) and hippocampal volume and to verbal and visuospatial memory and executive function. We serially adjusted for age, sex, and education alone (model A), additionally for other vascular risk factors (model B), and finally, with the inclusion of apolipoprotein E-ε4, plasma homocysteine, C-reactive protein, and interleukin-6 (model C).ResultsWe observed an inverse association between all indices of metabolic dysfunction and TCBV in all models (P < 0.030). The observed difference in TCBV between participants with and without diabetes was equivalent to approximately 6 years of chronologic aging. Diabetes and elevated glycohemoglobin, HOMA-IR, and fasting insulin were related to poorer executive function scores (P < 0.038), whereas only HOMA-IR and fasting insulin were inversely related to visuospatial memory (P < 0.007).ConclusionsMetabolic dysregulation, especially insulin resistance, was associated with lower brain volumes and executive function in a large, relatively healthy, middle-aged, community-based cohort

Impact of Surface Type on Single-Leg Jumping and Landing Mechanics using EMG, Kinematics, and Ground Reaction Force

Previous studies have found that athletes who need to jump in their sport often have asymmetry in their landing, resulting in a higher load on one leg. This can cause acute and chronic injuries to the knee such as ACL injuries, ligament injuries, stress fractures, and arthritis. PURPOSE: This project aims to measure the ground reaction force (GRF) of repetitive jumping of a single-leg on difference surfaces, identify key muscles and activation patterns, and understand the biomechanical kinematics of the jump sequence. By analyzing these aspects of repetitive jumping, and investigating the correlations and mutual influence, the effects of single-leg jumping and landing on firm surface versus sand can be determined. METHODS: Fifteen participants (7 male, 8 female) were taken through a 5-minute warm up on a cycle ergometer followed by familiarization jump trials. Afterwards, EMG sensors were placed on seven muscles of the dominant leg: gluteus maximus (GLUT), rectus femoris (RF), biceps femoris (BF), vastus lateralis (VS), vastus medialis (VM), gastrocnemius (GAST), and tibialis anterior (TA). Next, 7 retroreflective markers were placed on the lower body to measure joint kinematics. Video capture was recorded at 120fps in the frontal and sagittal plane. Participants were randomly assigned to start trials on a firm surface or on 10cm of sand. Using a force platform, participants were asked to jump five times on their dominant leg with a five second break in between each jump. The surface that participants started on was alternated, with a three-minute break in between each trial, ultimately completing two sand trials and two firm trials each. RESULTS: Significant differences were found in the muscle activation of the VL and BF between sand and firm surfaces (p \u3c 0.05). The peak vertical force and internal rotation moment during a jump were significantly lower on the sand surface (p \u3c 0.001). Average and maximum angular acceleration of the knee in the frontal plane was significantly lower on the sand surface (p \u3c 0.05). CONCLUSION: These findings reveal that sand provides a lower total impact, and higher muscle activation environment for training compared to a firm surface. Clinicians can use these findings to better inform treatment protocols regarding stabilization during the landing phase of a jump

The Women Making Their Mark in Modern Scottish Medical History

Introduction: Women in medicine and surgery are a recent phenomenon. The aim of this study was to review the modern history of pioneering women in medicine and surgery in Scotland.Methods: A variety of sources were searched including Google, PubMed, and the Royal College of Surgeons of Edinburgh publications to source the material for this paper.Results: Despite over five centuries of Scottish universities offering medical degrees, women have only had the right to study medicine for 150 years. However, the lives of women pioneers who either circumnavigated or surmounted this inequality, namely, “James Barry” and Sophia Jex-Blake, are briefly told.Conclusion: Doctors today owe a debt to those who pushed the boundaries, challenged the unfair rules and tackled institutional gender inequality in medicine. Reading about their lives and work is uplifting

Association of Metabolic Dysregulation With Volumetric Brain Magnetic Resonance Imaging and Cognitive Markers of Subclinical Brain Aging in Middle-Aged Adults

Objective: Diabetic and prediabtic states, including insulin resistance, fasting hyperglycemia, and hyperinsulinemia, are associated with metabolic dysregulation. These components have been individually linked to increased risks of cognitive decline and Alzheimer’s disease. We aimed to comprehensively relate all of the components of metabolic dysregulation to cognitive function and brain magnetic resonance imaging (MRI) in middle-aged adults. Research Design and Methods: Framingham Offspring participants who underwent volumetric MRI and detailed cognitive testing and were free of clinical stroke and dementia during examination 7 (1998–2001) constituted our study sample (n = 2,439; 1,311 women; age 61 ± 9 years). We related diabetes, homeostasis model assessment of insulin resistance (HOMA-IR), fasting insulin, and glycohemoglobin levels to cross-sectional MRI measures of total cerebral brain volume (TCBV) and hippocampal volume and to verbal and visuospatial memory and executive function. We serially adjusted for age, sex, and education alone (model A), additionally for other vascular risk factors (model B), and finally, with the inclusion of apolipoprotein E-ε4, plasma homocysteine, C-reactive protein, and interleukin-6 (model C). Results: We observed an inverse association between all indices of metabolic dysfunction and TCBV in all models (P < 0.030). The observed difference in TCBV between participants with and without diabetes was equivalent to approximately 6 years of chronologic aging. Diabetes and elevated glycohemoglobin, HOMA-IR, and fasting insulin were related to poorer executive function scores (P < 0.038), whereas only HOMA-IR and fasting insulin were inversely related to visuospatial memory (P < 0.007). Conclusions: Metabolic dysregulation, especially insulin resistance, was associated with lower brain volumes and executive function in a large, relatively healthy, middle-aged, community-based cohort

Antioxidant responses and lipid peroxidation in gills and erythrocytes of fish (Rhabdosarga sarba) upon exposure to Chattonella marina and hydrogen peroxide : implications on the cause of fish kills

Author Posting. © Elsevier B.V., 2006. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Journal of Experimental Marine Biology and Ecology 336 (2006): 230-241, doi:10.1016/j.jembe.2006.05.013.Chattonella marina, a red tide or harmful algal bloom species, has caused mass fish kills and serious economic loss worldwide, and yet its toxic actions remain highly controversial. Previous studies have shown that this species is able to produce reactive oxygen species (ROS), and therefore postulated that ROS are the causative agents of fish kills. The present study investigates antioxidant responses and lipid peroxidation in gills and erythrocytes of fish (Rhabdosarga sarba) upon exposure to C. marina, compared with responses exposed to equivalent and higher levels of ROS exposure. Even though C. marina can produce a high level of ROS, gills and erythrocytes of sea bream exposed to C. marina for 1 to 6 h showed neither significant induction of antioxidant enzymes nor lipid peroxidation. Antioxidant responses and oxidative damage did not occur as fish mortality began to occur, yet could be induced upon exposure to artificially supplied ROS levels an order of magnitude higher. The result of this study implies that ROS produced by C. marina is not the principal cause of fish kills.This study was supported by a CERG grant (CityU 1109/03M / No. 9040864) of the University Grants Committee, Hong Kong SAR government. Support for Don Anderson was also provided by the U.S. National Science Foundation through grant no. OCE-0136861

Predicting temporary threshold shifts in a bottlenose dolphin (Tursiops truncatus) : the effects of noise level and duration

Author Posting. © Acoustical Society of America, 2009. This article is posted here by permission of Acoustical Society of America for personal use, not for redistribution. The definitive version was published in Journal of the Acoustical Society of America 125 (2009): 1816-1826, doi:10.1121/1.3068456.Noise levels in the ocean are increasing and are expected to affect marine mammals. To examine the auditory effects of noise on odontocetes, a bottlenose dolphin (Tursiops truncatus) was exposed to octave-band noise (4–8 kHz) of varying durations (<2–30 min) and sound pressures (130–178 dB re 1 µPa). Temporary threshold shift (TTS) occurrence was quantified in an effort to (i) determine the sound exposure levels (SELs) (dB re 1 µPa2 s) that induce TTS and (ii) develop a model to predict TTS onset. Hearing thresholds were measured using auditory evoked potentials. If SEL was kept constant, significant shifts were induced by longer duration exposures but not for shorter exposures. Higher SELs were required to induce shifts in shorter duration exposures. The results did not support an equal-energy model to predict TTS onset. Rather, a logarithmic algorithm, which increased in sound energy as exposure duration decreased, was a better predictor of TTS. Recovery to baseline hearing thresholds was also logarithmic (approximately −1.8 dB/doubling of time) but indicated variability including faster recovery rates after greater shifts and longer recoveries necessary after longer duration exposures. The data reflected the complexity of TTS in mammals that should be taken into account when predicting odontocete TTS.This work was funded by the Office of Naval Research Grant No. 00014-098-1-687 to P.E.N. and the support of Bob Gisiner and Mardi Hasting is noted. Additional support came from SeaSpace to T.A.M

Improving Behavioral Healthcare Access Disparities by Training Providers in Disadvantaged Communities - Evidence of Strategy Effectiveness.

BACKGROUND: Inadequate access to behavioral health services disproportionately impacts marginalized populations who live in disadvantaged areas. To reduce this gap, programs dedicated to optimizing behavioral health education and training must focus their efforts to enroll providers who practice in these disadvantaged areas. OBJECTIVE: The Train New Trainers (TNT) fellowship program aims to enhance behavioral health knowledge, skills, and attitudes of primary care providers (PCPs) who deliver care in disadvantaged communities. We evaluate the effectiveness of the TNT recruitment strategy and the use of scholarships for targeting and recruiting PCPs who practice in disadvantaged communities. DESIGN: Observational study. PARTICIPANTS: TNT fellows from 2016 to 2023. MAIN MEASURES: State/federal classifications of medically underserved counties were used to establish scholarship criteria. Area Deprivation Index (ADI) was utilized to provide criterion validity for the use of state/federal criteria in the recruitment strategy, and to evaluate the effectiveness of the program in successfully recruiting PCPs practicing in disadvantaged communities. KEY RESULTS: Practice location data were available for 347 fellows, 88.8% of whom received scholarships. Of the 347 practices, 300 (86.5%) primarily served communities meeting at least one state or federal criterion for medical shortage areas and/or underserved areas. According to ADI scores, 32.3% of practices served areas classified in the highest ADI (ADI decile 9 or 10), with a progressive increase in the proportion of fellows practicing in underserved areas each year; in 2023, 89.9% of practices met federal shortage criteria and 40.5% served areas with the highest deciles of ADI. CONCLUSIONS: The TNT program strategy for recruiting PCPs from high medical need geographical areas is associated with bringing primary care psychiatry education to areas considered underserved and disadvantaged. Equipping PCPs practicing in underserved areas with enhanced knowledge and skills in behavioral medicine has the potential to significantly improve the existing access gap in disadvantaged communities

Adverse obstetric outcomes after breast cancer diagnosis : an observational database study in Germany

Background/Objectives: Breast cancer may negatively affect later pregnancy and childbirth. We aimed to analyze the impact of previous breast cancer on obstetric outcomes in postdiagnosis pregnancies. Methods: Insurance claims data in Southern Germany were used to identify breast cancer (BC) survivors with at least one subsequent delivery after cancer diagnosis between 2010 and 2020. In total, 74 BC survivors were compared to 222 age-matched controls with frequency matching on their age at their postdiagnosis delivery. Results: Endocrine therapy was associated with a significantly lower probability of birth compared to BC survivors without endocrine therapy (HR 0.36; 95% CI 0.18–0.53; p < 0.0001). The risks of preterm birth, low birth weight (LBW), gestational diabetes, hypertensive disorders, and cesarean section were not significantly increased among BC survivors compared to healthy controls. BC survivors were at an increased risk for a small-for-gestational-age (SGA) fetus (OR 3.24; 95% CI 1.17–8.97, p = 0.03). Delivery in less than 2 years after diagnosis increased the risk for SGA (OR 5.73; 95% CI 1.37–24.02, p = 0.03) and LBW (OR 4.57; 95% CI 1.32–15.87, p = 0.02). Conclusions: Our findings are encouraging regarding the risks of preterm delivery, gestational diabetes, hypertensive disorders, and cesarean section to women who consider pregnancy after BC. Delivery in less than 2 years after diagnosis was associated with an increased risk for SGA and LBW

Association of Pediatric Buccal Epigenetic Age Acceleration With Adverse Neonatal Brain Growth and Neurodevelopmental Outcomes Among Children Born Very Preterm With a Neonatal Infection.

IMPORTANCE: Very preterm neonates (24-32 weeks\u27 gestation) remain at a higher risk of morbidity and neurodevelopmental adversity throughout their lifespan. Because the extent of prematurity alone does not fully explain the risk of adverse neonatal brain growth or neurodevelopmental outcomes, there is a need for neonatal biomarkers to help estimate these risks in this population. OBJECTIVES: To characterize the pediatric buccal epigenetic (PedBE) clock-a recently developed tool to measure biological aging-among very preterm neonates and to assess its association with the extent of prematurity, neonatal comorbidities, neonatal brain growth, and neurodevelopmental outcomes at 18 months of age. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study was conducted in 2 neonatal intensive care units of 2 hospitals in Toronto, Ontario, Canada. A total of 35 very preterm neonates (24-32 weeks\u27 gestation) were recruited in 2017 and 2018, and neuroimaging was performed and buccal swab samples were acquired at 2 time points: the first in early life (median postmenstrual age, 32.9 weeks [IQR, 32.0-35.0 weeks]) and the second at term-equivalent age (TEA) at a median postmenstrual age of 43.0 weeks (IQR, 41.0-46.0 weeks). Follow-ups for neurodevelopmental assessments were completed in 2019 and 2020. All neonates in this cohort had at least 1 infection because they were originally enrolled to assess the association of neonatal infection with neurodevelopment. Neonates with congenital malformations, genetic syndromes, or congenital TORCH (toxoplasmosis, rubella, cytomegalovirus, herpes and other agents) infection were excluded. EXPOSURES: The extent of prematurity was measured by gestational age at birth and PedBE age difference. PedBE age was computed using DNA methylation obtained from 94 age-informative CpG (cytosine-phosphate-guanosine) sites. PedBE age difference (weeks) was calculated by subtracting PedBE age at each time point from the corresponding postmenstrual age. MAIN OUTCOMES AND MEASURES: Total cerebral volumes and cerebral growth during the neonatal intensive care unit period were obtained from magnetic resonance imaging scans at 2 time points: approximately the first 2 weeks of life and at TEA. Bayley Scales of Infant and Toddler Development, Third Edition, were used to assess neurodevelopmental outcomes at 18 months. RESULTS: Among 35 very preterm neonates (21 boys [60.0%]; median gestational age, 27.0 weeks [IQR, 25.9-29.9 weeks]; 23 [65.7%] born extremely preterm [\u3c28 \u3eweeks\u27 gestation]), extremely preterm neonates had an accelerated PedBE age compared with neonates born at a later gestational age (β = 9.0; 95% CI, 2.7-15.3; P = .01). An accelerated PedBE age was also associated with smaller cerebral volumes (β = -5356.8; 95% CI, -6899.3 to -2961.7; P = .01) and slower cerebral growth (β = -2651.5; 95% CI, -5301.2 to -1164.1; P = .04); these associations remained significant after adjusting for clinical neonatal factors. These findings were significant at TEA but not earlier in life. Similarly, an accelerated PedBE age at TEA was associated with lower cognitive (β = -0.4; 95% CI, -0.8 to -0.03; P = .04) and language (β = -0.6; 95% CI, -1.1 to -0.06; P = .02) scores at 18 months. CONCLUSIONS AND RELEVANCE: This cohort study of very preterm neonates suggests that biological aging may be associated with impaired brain growth and neurodevelopmental outcomes. The associations between epigenetic aging and adverse neonatal brain health warrant further attention

Increased epigenetic age in normal breast tissue from luminal breast cancer patients

BACKGROUND: Age is one of the most important risk factors for developing breast cancer. However, age-related changes in normal breast tissue that potentially lead to breast cancer are incompletely understood. Quantifying tissue-level DNA methylation can contribute to understanding these processes. We hypothesized that occurrence of breast cancer should be associated with an acceleration of epigenetic aging in normal breast tissue. RESULTS: Ninety-six normal breast tissue samples were obtained from 88 subjects (breast cancer = 35 subjects/40 samples, unaffected = 53 subjects/53 samples). Normal tissue samples from breast cancer patients were obtained from distant non-tumor sites of primary mastectomy specimens, while samples from unaffected women were obtained from the Komen Tissue Bank (n = 25) and from non-cancer-related breast surgery specimens (n = 28). Patients were further stratified into four cohorts: age < 50 years with and without breast cancer and age ≥ 50 with and without breast cancer. The Illumina HumanMethylation450k BeadChip microarray was used to generate methylation profiles from extracted DNA samples. Data was analyzed using the "Epigenetic Clock," a published biomarker of aging based on a defined set of 353 CpGs in the human genome. The resulting age estimate, DNA methylation age, was related to chronological age and to breast cancer status. The DNAmAge of normal breast tissue was strongly correlated with chronological age (r = 0.712, p < 0.001). Compared to unaffected peers, breast cancer patients exhibited significant age acceleration in their normal breast tissue (p = 0.002). Multivariate analysis revealed that epigenetic age acceleration in the normal breast tissue of subjects with cancer remained significant after adjusting for clinical and demographic variables. Additionally, smoking was found to be positively correlated with epigenetic aging in normal breast tissue (p = 0.012). CONCLUSIONS: Women with luminal breast cancer exhibit significant epigenetic age acceleration in normal adjacent breast tissue, which is consistent with an analogous finding in malignant breast tissue. Smoking is also associated with epigenetic age acceleration in normal breast tissue. Further studies are needed to determine whether epigenetic age acceleration in normal breast tissue is predictive of incident breast cancer and whether this mediates the risk of chronological age on breast cancer risk