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Background and Objectives Methods Results Conclusion Coronary artery calcification (CAC) is a frequent additional finding on lung cancer screening (LCS) low‐dose computed tomography (LDCT). Cardiovascular disease (CVD) is a major cause of death in LCS participants. We aimed to describe prevalence of incidental CAC detected on LDCT in LCS participants without prior history of coronary artery disease (CAD), evaluate their CVD risk and describe subsequent investigation and management.Prospective observational nested cohort study including all participants enrolled at a single Australian site of the International Lung Screen Trial. Baseline LDCTs were reviewed for CAC, and subsequent information collected regarding cardiovascular health. 5‐year CVD risk was calculated using the AusCVD risk calculator.55% (226/408) of participants had CAC on LDCT and no prior history of CAD, including 23% with moderate–severe CAC. Mean age of participants with CAC was 65 years, 68% were male. 53% were currently smoking. Majority were high risk (51%) or intermediate risk (32%) of a cardiovascular event in 5 years. 21% of participants were re‐stratified to a higher CVD risk group when CAC detected on LCS was incorporated. Only 10% of participants with CAC received lifestyle advice (only 3% currently smoking received smoking cessation advice). 80% of participants at high‐risk did not meet guideline recommendations, with 47% of this group remaining without cholesterol lowering therapy.LCS with LDCT offers the potential to identify and communicate CVD risk in this population. This may improve health outcomes for high‐risk LCS participants and further personalize management once screening results are known. [ABSTRACT FROM AUTHOR]

Introduction: Subsequent osteoporotic vertebral fractures (SOVF) are a serious complication of osteoporosis that can lead to spinal deformity, chronic pain and disability. Several risk factors have been previously identified for developing SOVF. However, there are conflicting reports regarding the association between sarcopenia and multiple vertebral compression fractures. As such, the goal of this study was to investigate whether sarcopenia is an independent risk factor of SOVF. Methods: This was a retrospective case–control study of elderly patients who underwent percutaneous vertebral augmentation (PVA) due to a new osteoporotic vertebral compression fracture (OVCF). Collected data included: age, sex, BMI, steroid treatment, fracture level and type, presence of kyphosis at the level of the fracture and bone mineral density (BMD). Identification of SVOFs was based on clinical notes and imaging corroborating the presence of a new fracture. Sarcopenia was measured using the normalized psoas muscle total cross-sectional area (nCSA) at the L4 level. Results: Eighty-nine patients that underwent PVA were followed for a minimum of 24 months. Average age was 80.2 ± 7.1 years; 58 were female (65.2%) and 31 male (34.8%). Psoas muscle nCSA was significantly associated with age (p = 0.031) but not with gender (p = 0.129), corticosteroid treatment (p = 0.349), local kyphosis (p = 0.715), or BMD (p = 0.724). Sarcopenia was significantly associated with SOVF (p = 0.039) after controlling for age and gender. Conclusions: Psoas muscle nCSA can be used as a standalone diagnostic tool of sarcopenia in patients undergoing PVA. In patients undergoing PVA for OVCF, sarcopenia is an independent risk factor for SOVF. [ABSTRACT FROM AUTHOR]

Purpose. Inferior alveolar nerve (IAN) can be subjected to iatrogenic injury during implant surgical procedures. The purpose of this retrospective study was to identify the buccolingual orientation of IAN in posterior mandible as adjunct information for implant planning and to estimate ethnicity-, sex-, and side-related variations in Malaysian population. Material and Methods. A total of 121 CBCT images were viewed with eXamVision software. The buccolingual position of IAN was identified in the posterior region. Buccal bone width (B), canal thickness (C), and lingual bone width (L) were measured at the horizontal canal levels. Kruskal–Wallis H test and Friedman test were used to analyze the buccolingual position. One-way ANOVA was performed to evaluate the variations in B, C, and L values. Results. Overall, most of the IANs were located on the lingual sides of the second molar regions (left: 71.9%; right: 71.1%) and at the centers of the first molar regions (left: 57.9%; right: 47.10%) and exited through the mental foramen before the second premolar regions. There was statistically significant difference in the buccolingual position of the IAN between the sexes in the left second premolar regions (P = 0.03). There was variation in B between the sexes in the left first molar regions (P = 0.01). Statistically significant differences in C and L were also found between different ethnic groups (P = 0.04). Between both sides, there were variations in C in the first molar regions (P < 0.001) and the second molar regions (P = 0.03). Conclusion. From the second molar to the second premolar, the buccal bone width decreased while the lingual bone width increased. There were variations between ethnicities, sexes, and sides among Malaysians. [ABSTRACT FROM AUTHOR]

Background: With the challenges that aging populations pose to health care, interventions that facilitate alleviation of age-related morbidities are imperative. A prominent risk factor for developing age-related morbidities is immunosenescence, characterized by increased chronic low-grade inflammation, resulting in T-cell exhaustion and senescence. Contact with nature and associated physical activities have been shown to boost immunity in older adults and may be promoted in the form of horticultural therapy (HT). We aimed to examine the effects of HT on immunosenescence.Method: We conducted a randomized controlled trial with 59 older adults assigned to either the HT intervention or waitlist control group. Older adults in the HT intervention group underwent HT intervention program over 6 months. Venous blood was drawn at baseline and at the third and sixth month from the commencement of this study. For participants who attended all 3 blood collection time points (HT: n = 22; waitlist: n = 24), flow cytometry analysis was performed on whole blood samples to evaluate the kinetics of lymphocyte subsets over the intervention period, revealing the composition of CD4+ and CD8+ subsets expressing exhaustion markers-CD57, CTLA4, and KLRG1. Enzyme-linked immunosorbent assays were employed to measure changes in plasma IL-6 levels.Results: HT is associated with increased numbers of naive CD8+ T cells and fewer CTLA4-expressing terminally differentiated effector CD4+ and CD8+ memory T cells re-expressing CD45RA (TEMRA). Furthermore, IL-6 levels were reduced during HT, and the frequencies of naive and TEMRA CD8+ T cells were found to be associated with IL-6 levels.Conclusion: HT is associated with a reduction in the levels of biomarkers that measure the extent of T-cell exhaustion and inflammaging in older adults. The positive effects of HT on T-cell exhaustion were associated with the reduction of IL-6 levels. [ABSTRACT FROM AUTHOR]

Vertebral compression fractures (VCFs) are a common cause of back pain and disability and are usually osteoporotic in nature. Therapy aims to adequately control pain and allow early mobilisation and return of function while preventing additional fractures. A proportion of patients do not achieve adequate pain relief using conservative measures alone. Unwanted adverse effects from medications may also ensue. Vertebroplasty represents an alternative treatment option for VCFs. Patients with acute VCFs (≤6 weeks old) may gain the most benefit from vertebroplasty as healed fractures are not as amenable to cement injection. High-quality studies have reported conflicting results regarding the use of vertebroplasty in the treatment of acute VCFs. Despite high-quality evidence, varying study designs and heterogenous patient cohorts make interpretation of this data difficult. Only one sham-controlled randomised controlled trial (RCT) has evaluated vertebroplasty exclusively in patients with acute VCFs, reporting favourable results. Pooled data from RCTs also suggest vertebroplasty to be safe. This article provides a concise and critical review of the current literature regarding vertebroplasty for the treatment of acute VCFs. [ABSTRACT FROM AUTHOR]

Physical inactivity is one of the leading contributors to worldwide morbidity and mortality. The elderly are particularly susceptible since the features of physical inactivity overlap with the outcomes of natural aging - including the propensity to develop cardiovascular diseases, cancer, diabetes mellitus, sarcopenia and cognitive impairment. The age-dependent loss of immune function, or immunosenescence, refers to the progressive depletion of primary immune resources and is linked to the development of many of these conditions. Immunosenescence is primarily driven by chronic immune activation and physical activity interventions have demonstrated the potential to reduce the risk of complications in the elderly by modulating inflammation and augmenting the immune system. Since poor vaccination outcome is a hallmark of immunosenescence, the assessment of vaccine efficacy provides a window to study the immunological effects of regular physical activity. Using an accelerator-based study, we demonstrate in a Singaporean Chinese cohort that elderly women (n=56) who walk more after vaccination display greater post-vaccination expansion of monocytes and plasmablasts in peripheral blood. Active elderly female participants also demonstrated lower baseline levels of IP-10 and Eotaxin, and the upregulation of genes associated with monocyte/macrophage phagocytosis. We further describe postive correlations between the monocyte response and the post-vaccination H1N1 HAI titres of participants. Finally, active elderly women reveal a higher induction of antibodies against Flu B in their 18-month second vaccination follow-up. Altogether, our data are consistent with better immunological outcomes in those who are more physically active and highlight the pertinent contribution of monocyte activity. [ABSTRACT FROM AUTHOR]

The hydroxycinnamates (HCAs) ferulate and p-coumarate are among the most abundant constituents of lignin and their degradation by bacteria is an essential step in the remineralization of vascular plant material. Here, we investigate the catabolism of these two HCAs by the marine bacterium, Sagittula stellata E-37, a member of the roseobacter lineage with lignolytic potential. Bacterial degradation of HCAs is often initiated by the activity of a hydroxycinnamoyl-CoA synthase. Genome analysis of S. stellata revealed the presence of two feruloyl-CoA (fcs) synthase homologs, an unusual occurrence amongst characterized HCA degraders. In order to elucidate the role of these homologs in HCA catabolism, fcs1 and fcs2 were disrupted using insertional mutagenesis, yielding both single and double fcs mutants. Growth on p-coumarate was abolished in the fcs double mutant, whereas maximum cell yield on ferulate was only 2% of wildtype. Interestingly, the single mutants demonstrated opposing phenotypes: the fcs1 mutant showed impaired growth (extended lag and ~60% of wildtype rate) on p-coumarate and the fcs2 mutant showed impaired growth (extended lag and ~20% of wildtype rate) on ferulate, pointing to distinct, but overlapping roles of the encoded fcs homologs with fcs1 primarily dedicated to p coumarate utilization and fcs2 playing a dominant role in ferulate utilization. Finally, a TRAP family transporter was found to be required for growth on both HCAs. These findings provide evidence for functional redundancy in the degradation of HCAs in S. stellata E-37 and offer important insight into the genetic complexity of aromatic compound degradation in bacteria. [ABSTRACT FROM AUTHOR]

Antarctic subice environments are diverse, underexplored microbial habitats. Here, we describe the ecophysiology and annotated genome of a Marinobacter strain isolated from a cold, saline, iron-rich subglacial outflow of the Taylor Glacier, Antarctica. This strain (BF04_ CF4) grows fastest at neutral pH (range 6-10), is psychrophilic (range: 0°C-20°C), moderately halophilic (range: 0.8%-15% NaCl) and hosts genes encoding potential low temperature and high salt adaptations. The predicted proteome suggests it utilizes fewer charged amino acids than a mesophilic Marinobacter strain. BF04_ CF4 has increased concentrations of membrane unsaturated fatty acids including palmitoleic (33%) and oleic (27.5%) acids that may help maintain cell membrane fluidity at low temperatures. The genome encodes proteins for compatible solute biosynthesis and transport, which are known to be important for growth in saline environments. Physiological verification of predicted metabolic functions demonstrate BF04 CF4 is capable of denitrification and may facilitate iron oxidation. Our data indicate that strain BF04_ CF4 represents a new Marinobacter species, Marinobacter gelidimuriae sp. nov., that appears well suited for the subglacial environment it was isolated from. Marinobacter species have been isolated from other cold, saline environments in the McMurdo Dry Valleys and permanently cold environments globally suggesting that this lineage is cosmopolitan and ecologically relevant in icy brines. [ABSTRACT FROM AUTHOR]

Variations of the anterior cerebral artery-anterior communicating artery complex are commonly identified in aneurysm surgery. An infraoptic course of the anterior cerebral artery is exceedingly rare. Robison first described this anomaly from an anatomic dissection in 1959. A unilateral anomalous infraoptic anterior cerebral artery is more common than anomalies of bilateral infraoptic anterior cerebral arteries. We present the case of an unruptured aneurysm at the anterior communicating artery in a patient with bilateral infraoptic anterior cerebral arteries, identified by computed tomography angiography and verified during surgery. Implications for aneurysm formation and surgical treatment are discussed. [ABSTRACT FROM AUTHOR]

Dementia is a burgeoning global problem. Novel magnetic resonance imaging (MRI) metrics beyond volumetry may bring new insight and aid clinical trial evaluation of interventions early in the Alzheimer's disease course to complement existing imaging and clinical metrics. To determine whether: (i) normalized regional sodium-MRI values (Na-SI) are better predictors of neurocognitive status than volumetry (ii) cerebral amyloid PET status improves modelling. Nondemented older adult (>60 years) volunteers of known Alzheimer's Disease Assessment Scale (ADAS-Cog11), Mini-Mental State Examination (MMSE) and Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neurocognitive test scores, ApolipoproteinE (APOE) e4 +/- cerebral amyloid PET status were prospectively recruited for 3T sodium-MRI brain scans. Left and right hippocampal, entorhinal and precuneus volumes and Na-SI (using the proportional intensity scaling normalization method with field inhomogeneity and partial volume corrections) were obtained after segmentation and co-registration of 3D-T1-weighted proton images. Descriptive statistics, correlation and best-subset regression analyses were performed. In our 76 nondemented participants (mean(standard deviation) age 75(5) years; woman 47(62%); cognitively unimpaired 54/76(71%), mildly cognitively impaired 22/76(29%)), left hippocampal Na-SI, not volume, was preferentially in the best models for predicting MMSE (Odds Ratio (OR) = 0.19(Confidence Interval (CI) = 0.07,0.53), P -value = 0.001) and ADAS-Cog11 (Beta(B) = 1.2(CI = 0.28,2.1), P -value = 0.01) scores. In the entorhinal analysis, right entorhinal Na-SI, not volume, was preferentially selected in the best model for predicting ADAS-Cog11 (B = 0.94(CI = 0.11,1.8), P -value = 0.03). While right entorhinal Na-SI and volume were both selected for MMSE modelling (Na-SI OR = 0.23(CI = 0.09,0.6), P -value = 0.003; volume OR = 2.6(CI = 1.0,6.6), P -value = 0.04), independently, Na-SI explained more of the variance (Na-SI R 2 = 10.3; volume R 2 = 7.5). No imaging variable was selected in the best CERAD models. Adding cerebral amyloid status improved model fit (Akaike Information Criterion increased 2.0 for all models, P -value < 0.001-0.045). Regional Na-SI were more predictive of MMSE and ADAS-Cog11 scores in our nondemented older adult cohort than volume, hippocampal more robust than entorhinal region of interest. Positive amyloid status slightly further improved model fit., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Diverse gut microorganisms present in humans and mice are essential for the prevention of microbial pathogen colonization. However, antibiotic-induced dysbiosis of the gut microbiome reduces microbial diversity and allows C. difficile to colonize the intestine. The Oligo Mouse Microbiota 19.1 (OMM19.1) is a synthetic community that consists of bacteria that are taxonomically and functionally designed to mimic the specific pathogen-free (SPF) mouse gut microbiota. Here, we examined the susceptibility of OMM19.1 colonized mice to C. difficile infection at a range of infectious doses (10 3 , 10 5 , and 10 7 spores) without prior antibiotic treatment. We found that mice colonized with OMM19.1 were susceptible to C. difficile infection regardless of the dose. The clinical scores increased with increasing C. difficile dosage. Infection with C. difficile was correlated with a significant increase in Ligilactobacillus murinus and Escherichia coli , while the abundance of Bacteroides caecimuris, Akkermansia muciniphila, Extibacter muris, and Turicimonas muris significantly decreased following C. difficile infection. Our results demonstrate that the OMM19.1 community requires additional bacteria to enable colonization resistance.

Vancomycin-resistant enterococci (VRE) pose a serious threat to public health because of their limited treatment options. Therefore, there is an increasing need to identify novel targets to develop new drugs. Here, we examined the roles of the universal PTS components, PtsI and PtsH, in Enterococcus faecium to determine their roles in carbon metabolism, biofilm formation, stress response, and the ability to compete in the gastrointestinal tract. Clean deletion of ptsHI resulted in a significant reduction in the ability to import and metabolize simple sugars, attenuated growth rate, reduced biofilm formation, and decreased competitive fitness both in vitro and in vivo . However, no significant difference in stress survival was observed when compared with the wild type. These results suggest that targeting universal or specific PTS may provide a novel treatment strategy by reducing the fitness of E. faecium ., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of FEMS.)

Background: Although copy number variations (CNVs) are infrequent, each anomaly is unique, and multiple CNVs can appear simultaneously. Growing evidence suggests that CNVs contribute to a wide range of diseases. When CNVs are detected, assessment of their clinical significance requires a thorough literature review. This process can be extremely time-consuming and may delay disease diagnosis. Therefore, we have developed CNV Extraction, Transformation, and Loading Artificial Intelligence (CNV-ETLAI), an innovative tool that allows experts to classify and interpret CNVs accurately and efficiently., Methods: We combined text, table, and image processing algorithms to develop an artificial intelligence platform that automatically extracts, transforms, and organizes CNV information into a database. To validate CNV-ETLAI, we compared its performance to ground truth datasets labeled by a human expert. In addition, we analyzed the CNV data, which was collected using CNV-ETLAI via a crowdsourcing approach., Results: In comparison to a human expert, CNV-ETLAI improved CNV detection accuracy by 4% and performed the analysis 60 times faster. This performance can improve even further with upscaling of the CNV-ETLAI database as usage increases. 5,800 CNVs from 2,313 journal articles were collected. Total CNV frequency for the whole chromosome was highest for chromosome X, whereas CNV frequency per 1 Mb of genomic length was highest for chromosome 22., Conclusions: We have developed, tested, and shared CNV-ETLAI for research and clinical purposes (https://lmic.mgh.harvard.edu/CNV-ETLAI). Use of CNV-ETLAI is expected to ease and accelerate diagnostic classification and interpretation of CNVs., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Considered a serious threat by the Centers for Disease Control and Prevention, multidrug-resistant Enterococcus faecium is an increasing cause of hospital-acquired infection. Here, we provide details on a single-plasmid CRISPR-Cas12a system for generating clean deletions and insertions. Single manipulations were carried out in under 2 weeks, with successful deletions/insertions present in >80% of the clones tested. Using this method, we generated three individual clean deletion mutations in the acpH , treA , and lacL genes and inserted codon-optimized unaG , enabling green fluorescent protein (GFP)-like fluorescence under the control of the trehalase operon. The use of in vivo recombination for plasmid construction kept costs to a minimum. IMPORTANCE Enterococcus faecium is increasingly associated with hard-to-treat antibiotic-resistant infections. The ability to generate clean genomic alterations is the first step in generating a complete mechanistic understanding of how E. faecium acquires pathogenic traits and causes disease. Here, we show that CRISPR-Cas12a can be used to quickly (under 2 weeks) and cheaply delete or insert genes into the E. faecium genome. This substantial improvement over current methods should speed up research on this important opportunistic pathogen.

We conducted a randomized controlled trial to examine choral singing's effect on cognitive decline in aging. Older Singaporeans who were at high risk of future dementia were recruited: 47 were assigned to choral singing intervention (CSI) and 46 were assigned to health education program (HEP). Participants attended weekly one-hour choral singing or weekly one-hour health education for two years. Change in cognitive function was measured by a composite cognitive test score (CCTS) derived from raw scores of neuropsychological tests; biomarkers included brain magnetic resonance imaging, oxidative damage and immunosenescence. The average age of the participants were 70 years and 73/93 (78.5%) were female. The change of CCTS from baseline to 24 months was 0.05 among participants in the CSI group and -0.1 among participants in the HEP group. The between-group difference (0.15, p =0.042) became smaller (0.12, p =0.09) after adjusting for baseline CCTS. No between-group differences on biomarkers were observed. Our data support the role of choral singing in improving cognitive health in aging. The beneficial effect is at least comparable than that of health education in preventing cognitive decline in a community of elderly people. Biological mechanisms underlying the observed efficacy should be further studied.