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The Journals of Gerontology. Series A,... Oct 2023The Health, Aging, and Body Composition Study is a longitudinal cohort study that started just over 25 years ago. This ground-breaking study tested specific hypotheses... (Review)
Review
BACKGROUND
The Health, Aging, and Body Composition Study is a longitudinal cohort study that started just over 25 years ago. This ground-breaking study tested specific hypotheses about the importance of weight, body composition, and weight-related health conditions for incident functional limitation in older adults.
METHODS
Narrative review with analysis of ancillary studies, career awards, publications, and citations.
RESULTS
Key findings of the study demonstrated the importance of body composition as a whole, both fat and lean mass, in the disablement pathway. The quality of the muscle in terms of its strength and its composition was found to be a critical feature in defining sarcopenia. Dietary patterns and especially protein intake, social factors, and cognition were found to be critical elements for functional limitation and disability. The study is highly cited and its assessments have been widely adopted in both observational studies and clinical trials. Its impact continues as a platform for collaboration and career development.
CONCLUSIONS
The Health ABC provides a knowledge base for the prevention of disability and promotion of mobility in older adults.
Topics: Humans; Aged; Longitudinal Studies; Aging; Sarcopenia; Body Composition; Cohort Studies
PubMed: 37431156
DOI: 10.1093/gerona/glad167 -
Current Opinion in Structural Biology Oct 2023Members of the primase-polymerase (Prim-Pol) superfamily are found in all domains of life and play diverse roles in genome stability, including primer synthesis during... (Review)
Review
Members of the primase-polymerase (Prim-Pol) superfamily are found in all domains of life and play diverse roles in genome stability, including primer synthesis during DNA replication, lesion repair and damage tolerance. This review focuses primarily on Prim-Pol members capable of de novo primer synthesis that have experimentally derived structural models available. We discuss the mechanism of DNA primer synthesis initiation by Prim-Pol catalytic domains, based on recent structural and functional studies. We also describe a general model for primer initiation that also includes the ancillary domains/subunits, which stimulate the initiation of primer synthesis.
Topics: DNA Primase; DNA Replication; Catalytic Domain
PubMed: 37459807
DOI: 10.1016/j.sbi.2023.102652 -
Respiratory Investigation Nov 2023Bronchoscopes are continuously improving. Increasingly, thinner bronchoscopes with larger working channels and better imaging quality are becoming available for clinical... (Review)
Review
Bronchoscopes are continuously improving. Increasingly, thinner bronchoscopes with larger working channels and better imaging quality are becoming available for clinical use. Concurrently, useful ancillary devices have been developed, such as radial probe endobronchial ultrasound (rEBUS) and navigation devices. Randomized studies have demonstrated the diagnostic superiority of ultrathin bronchoscopy over thin bronchoscopy under rEBUS and virtual bronchoscopic navigation guidance for small, peripheral pulmonary lesions. Furthermore, biopsy needles and cryoprobes have been miniaturized and adapted to the working channel of the new ultrathin bronchoscopes. Multi-modality and multi-instrumental ultrathin bronchoscopy using such new technologies has facilitated high diagnostic yields.
Topics: Humans; Bronchoscopy; Lung Neoplasms; Bronchoscopes; Biopsy, Needle; Endosonography
PubMed: 37708637
DOI: 10.1016/j.resinv.2023.07.008 -
BMJ Open Jul 2023Prevention of cardiovascular disease (CVD) is of key importance in reducing morbidity, disability and mortality worldwide. Observational studies suggest that digital... (Randomized Controlled Trial)
Randomized Controlled Trial
Rationale and design of the CV-PREVITAL study: an Italian multiple cohort randomised controlled trial investigating innovative digital strategies in primary cardiovascular prevention.
INTRODUCTION
Prevention of cardiovascular disease (CVD) is of key importance in reducing morbidity, disability and mortality worldwide. Observational studies suggest that digital health interventions can be an effective strategy to reduce cardiovascular (CV) risk. However, evidence from large randomised clinical trials is lacking.
METHODS AND ANALYSIS
The CV-PREVITAL study is a multicentre, prospective, randomised, controlled, open-label interventional trial designed to compare the effectiveness of an educational and motivational mobile health (mHealth) intervention versus usual care in reducing CV risk. The intervention aims at improving diet, physical activity, sleep quality, psycho-behavioural aspects, as well as promoting smoking cessation and adherence to pharmacological treatment for CV risk factors. The trial aims to enrol approximately 80 000 subjects without overt CVDs referring to general practitioners' offices, community pharmacies or clinics of Scientific Institute for Research, Hospitalization and Health Care (Italian acronym IRCCS) affiliated with the Italian Cardiology Network. All participants are evaluated at baseline and after 12 months to assess the effectiveness of the intervention on short-term endpoints, namely improvement in CV risk score and reduction of major CV risk factors. Beyond the funded life of the study, a long-term (7 years) follow-up is also planned to assess the effectiveness of the intervention on the incidence of major adverse CV events. A series of ancillary studies designed to evaluate the effect of the mHealth intervention on additional risk biomarkers are also performed.
ETHICS AND DISSEMINATION
This study received ethics approval from the ethics committee of the coordinating centre (Monzino Cardiology Center; R1256/20-CCM 1319) and from all other relevant IRBs and ethics committees. Findings are disseminated through scientific meetings and peer-reviewed journals and via social media. Partners are informed about the study's course and findings through regular meetings.
TRIAL REGISTRATION NUMBER
NCT05339841.
Topics: Humans; Prospective Studies; Cardiovascular Diseases; Diet; Exercise
PubMed: 37451717
DOI: 10.1136/bmjopen-2023-072040 -
JAMA Internal Medicine Jul 2024Current US physical activity (PA) guidelines prescribe moderate to vigorous PA (MVPA) time of at least 150 minutes per week for health. An analogous step-based... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Current US physical activity (PA) guidelines prescribe moderate to vigorous PA (MVPA) time of at least 150 minutes per week for health. An analogous step-based recommendation has not been issued due to insufficient evidence.
OBJECTIVE
To examine the associations of MVPA time and step counts with all-cause mortality and cardiovascular disease (CVD).
DESIGN, SETTING, AND PARTICIPANTS
This cohort study analyzed data from an ongoing follow-up study of surviving participants of the Women's Health Study, a randomized clinical trial conducted from 1992 to 2004 in the US to evaluate use of low-dose aspirin and vitamin E for preventing cancer and CVD. Participants were 62 years or older who were free from CVD and cancer, completed annual questionnaires, and agreed to measure their PA with an accelerometer as part of a 2011-2015 ancillary study. Participants were followed up through December 31, 2022.
EXPOSURES
Time spent in MVPA and step counts, measured with an accelerometer for 7 consecutive days.
MAIN OUTCOMES AND MEASURES
The associations of MVPA time and step counts with all-cause mortality and CVD (composite of myocardial infarction, stroke, and CVD mortality) adjusted for confounders. Cox proportional hazards regression models, restricted mean survival time differences, and area under the receiver operating characteristic curve (AUC) were used to evaluate the associations.
RESULTS
A total of 14 399 women (mean [SD] age, 71.8 [5.6] years) were included. The median (IQR) MVPA time and step counts were 62 (20-149) minutes per week and 5183 (3691-7001) steps per day, respectively. During a median (IQR) follow-up of 9.0 (8.0-9.9) years, the hazard ratios (HR) per SD for all-cause mortality were 0.82 (95% CI, 0.75-0.90) for MVPA time and 0.74 (95% CI, 0.69-0.80) for step counts. Greater MVPA time and step counts (top 3 quartiles vs bottom quartile) were associated with a longer period free from death: 2.22 (95% CI, 1.58-2.85) months and 2.36 (95% CI, 1.73-2.99) months at 9 years follow-up, respectively. The AUCs for all-cause mortality from MVPA time and step counts were similar: 0.55 (95% CI, 0.52-0.57) for both metrics. Similar associations of these 2 metrics with CVD were observed.
CONCLUSION AND RELEVANCE
Results of this study suggest that among females 62 years or older, MVPA time and step counts were qualitatively similar in their associations with all-cause mortality and CVD. Step count-based goals should be considered for future guidelines along with time-based goals, allowing for the accommodation of personal preferences.
Topics: Humans; Female; Exercise; Cardiovascular Diseases; Middle Aged; Aged; Time Factors; Accelerometry; Follow-Up Studies; United States; Cohort Studies; Women's Health; Cause of Death
PubMed: 38767892
DOI: 10.1001/jamainternmed.2024.0892 -
Asian Journal of Neurosurgery Sep 2023We report 30 cases of nonmeningothelial dural-based lesions encountered during a 3-year study period. We retrospectively reviewed pathology records of patients...
We report 30 cases of nonmeningothelial dural-based lesions encountered during a 3-year study period. We retrospectively reviewed pathology records of patients operated for extra-axial, dural-based lesions during the years 2016 to 2018 and included nonmeningothelial lesions as a part of this study. Among the 3,243 neurosurgical specimens for histopathologic examination, only 30 (0.93%) were "nonmeningothelial dural-based lesions." Six (20%) patients were in the pediatric age group. Pathologic assessment identified 13 cases of solitary fibrous tumor/hemangiopericytoma (43.3%) and 7 cases of Ewing's sarcoma/primitive neuroectodermal tumor (23.3%). Two cases (6.7%) were of metastasis. Other lesions included a single case each of non-Hodgkin's lymphoma, undifferentiated sarcoma, solitary plasmacytoma, and granulocytic sarcoma. Nonneoplastic lesions included two cases each of Rosai-Dorfman disease and nonspecific inflammatory lesions. Nonmeningothelial dural-based lesions being rare, thorough examination of morphological features is a must by the pathologist, to arrive at the accurate diagnosis. Ancillary tests, if required, should be employed in the context of the morphologic picture.
PubMed: 38152510
DOI: 10.1055/s-0043-1771315 -
JAMA Network Open Nov 2023Repeated transfusions in preterm neonates with anemia of prematurity replace fetal hemoglobin (HbF) with adult Hb (HbA), which has a low oxygen affinity. The reduction... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Repeated transfusions in preterm neonates with anemia of prematurity replace fetal hemoglobin (HbF) with adult Hb (HbA), which has a low oxygen affinity. The reduction of HbF is associated with a higher incidence of retinopathy of prematurity (ROP).
OBJECTIVE
To assess whether HbF and HbA are differently associated with cerebral tissue oxygenation in preterm neonates.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study was a single-center, pilot study on cerebral oxygenation kinetics in preterm neonates with a gestational age between 24.0 weeks and 27.9 weeks who were admitted to the neonatal intensive care unit of Policlinico Universitario A. Gemelli IRCCS from December 27, 2021, to May 15, 2023. This study was ancillary to the ongoing, double-blind, multicenter Umbilical or Adult Donor Red Blood Cells in Extremely Low Gestational Age Neonates and Retinopathy of Prematurity (BORN) randomized clinical trial. The BORN trial outcome was ROP severity in neonates randomized to receive standard packed red blood cell (PRBC) transfusions obtained from RBCs of adult donors (A-RBCs) or from cord blood (CB-RBCs). According to standard procedures at the institute's neonatal intensive care unit, patients concurrently received continuous cerebral near-infrared spectroscopy (NIRS) monitoring. This cohort study was not prespecified in the trial protocol.
EXPOSURE
Transfusion with A-RBCs or CB-RBCs.
MAIN OUTCOMES AND MEASURES
The main outcome was the kinetics of cerebral regional oxygen saturation (crSO2) and cerebral fraction of tissue oxygen extraction (cFTOE) associated with A-RBC or CB-RBC transfusions. Cerebral NIRS monitoring was performed by neonatologists and nurses, who were blinded to the PRBC type. The NIRS monitoring was conducted starting with the blood product order, during transfusion, and for the subsequent 24 hours after transfusion completion. The mean treatment effects of A-RBCs or CB-RBCs were quantified using a linear mixed model for repeated measures.
RESULTS
Of 23 randomized neonates, 17 (11 male [64.7%]; median gestational age at birth, 25.6 weeks [IQR, 25.3-26.1 weeks]) with a median birth weight of 840 g (IQR, 580-900 g) were included in the study; NIRS was evaluated for 42 transfusion episodes, of which 22 were A-RBCs and 20 were CB-RBCs. Globally considering all posttransfusion time points, the overall crSO2 covariate-adjusted mean after CB-RBC transfusions was 5.27% lower (95% CI, 1.20%-9.34%; P = .01) than that after A-RBC transfusions, while the cFTOE after CB-RBC transfusions was 6.18% higher (95% CI, 1.66%-10.69%; P = .009) than that after A-RBCs.
CONCLUSIONS AND RELEVANCE
The findings of this cohort study suggest that A-RBC transfusions may be associated with more oxygen delivery to cerebral tissues of preterm neonates than transfusions from CB-RBCs. This finding may explain the previously observed association between low HbF and high ROP risk. It also suggests that use of CB to meet the RBC transfusion needs of neonates with a gestational age of less than 28 weeks may protect cerebral tissues from overexposure to oxygen.
Topics: Adult; Humans; Infant; Infant, Newborn; Male; Cohort Studies; Erythrocyte Transfusion; Fetal Blood; Oxygen; Pilot Projects; Retinopathy of Prematurity; Female
PubMed: 37934499
DOI: 10.1001/jamanetworkopen.2023.41643 -
Nutrients Aug 2023The POUNDS Lost trial is a 2-year clinical trial testing the effects of dietary interventions on weight loss. This study included 811 adults with overweight or obesity... (Review)
Review
The POUNDS Lost trial is a 2-year clinical trial testing the effects of dietary interventions on weight loss. This study included 811 adults with overweight or obesity who were randomized to one of four diets that contained either 15% or 25% protein and 20% or 40% fat in a 2 × 2 factorial design. By 2 years, participants on average lost from 2.9 to 3.6 kg in body weight in the four intervention arms, while no significant difference was observed across the intervention arms. In POUNDS Lost, we performed a series of ancillary studies to detect intrinsic factors particular to genomic, epigenomic, and metabolomic markers that may modulate changes in weight and other cardiometabolic traits in response to the weight-loss dietary interventions. Genomic variants identified from genome-wide association studies (GWASs) on obesity, type 2 diabetes, glucose and lipid metabolisms, gut microbiome, and dietary intakes have been found to interact with dietary macronutrients (fat, protein, and carbohydrates) in relation to weight loss and changes of body composition and cardiometabolic traits. In addition, we recently investigated epigenomic modifications, particularly blood DNA methylation and circulating microRNAs (miRNAs). We reported DNA methylation levels at , , , and were related to weight loss or changes of glucose, lipids, and blood pressure; we also reported thrifty miRNA expression as a significant epigenomic marker related to changes in insulin sensitivity and adiposity. Our studies have also highlighted the importance of temporal changes in novel metabolomic signatures for gut microbiota, bile acids, and amino acids as predictors for achievement of successful weight loss outcomes. Moreover, our studies indicate that biochemical, behavioral, and psychosocial factors such as physical activity, sleep disturbance, and appetite may also modulate metabolic changes during dietary interventions. This review summarized our major findings in the POUNDS Lost trial, which provided preliminary evidence supporting the development of precision diet interventions for obesity management.
Topics: Adult; Humans; Diabetes Mellitus, Type 2; Genome-Wide Association Study; Diet; Obesity; Cardiovascular Diseases; Randomized Controlled Trials as Topic
PubMed: 37630855
DOI: 10.3390/nu15163665 -
Journal of Neuro-ophthalmology : the... Dec 2023Susac syndrome is a vasculopathy, resulting in the classic triad of branch retinal artery occlusion (BRAO), inner ear ischemia, and brain ischemia. In this retrospective...
BACKGROUND
Susac syndrome is a vasculopathy, resulting in the classic triad of branch retinal artery occlusion (BRAO), inner ear ischemia, and brain ischemia. In this retrospective chart review, we characterize fluorescein angiography (FA) findings and other ancillary studies in Susac syndrome, including the appearance of persistent disease activity and the occurrence of new subclinical disease on FA.
METHODS
This multicenter, retrospective case series was institutional review board-approved and included patients with the complete triad of Susac syndrome evaluated with FA, contrasted MRI of the brain, and audiometry from 2010 to 2020. The medical records were reviewed for these ancillary tests, along with demographics, symptoms, visual acuity, visual field defects, and findings on fundoscopy. Clinical relapse was defined as any objective evidence of disease activity during the follow-up period after initial induction of clinical quiescence. The main outcome measure was the sensitivity of ancillary testing, including FA, MRI, and audiometry, to detect relapse.
RESULTS
Twenty of the 31 (64%) patients had the complete triad of brain, retinal, and vestibulocochlear involvement from Susac syndrome and were included. Median age at diagnosis was 43.5 years (range 21-63), and 14 (70%) were women. Hearing loss occurred in 20 (100%), encephalopathy in 13 (65%), vertigo in 15 (75%), and headaches in 19 (95%) throughout the course of follow-up. Median visual acuity at both onset and final visit was 20/20 in both eyes. Seventeen (85%) had BRAO at baseline, and 10 (50%) experienced subsequent BRAO during follow-up. FA revealed nonspecific leakage from previous arteriolar damage in 20 (100%), including in patients who were otherwise in remission. Of the 11 episodes of disease activity in which all testing modalities were performed, visual field testing/fundoscopy was abnormal in 4 (36.4%), MRI brain in 2 (18.2%), audiogram in 8 (72.7%), and FA in 9 (81.8%).
CONCLUSIONS
New leakage on FA is the most sensitive marker of active disease. Persistent leakage represents previous damage, whereas new areas of leakage suggest ongoing disease activity that requires consideration of modifying immunosuppressive therapy.
Topics: Humans; Female; Young Adult; Adult; Middle Aged; Male; Susac Syndrome; Fluorescein Angiography; Retrospective Studies; Retinal Artery Occlusion; Magnetic Resonance Imaging; Retina; Recurrence
PubMed: 37075250
DOI: 10.1097/WNO.0000000000001826