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Beckwith-Wiedemann spectrum (BWSp) is caused by genetic and epigenetic alterations on chromosome 11 that regulate cell growth and division. Considering the diverse phenotypic landscape in BWSp, the characterization of the CDKN1C molecular subtype remains relatively limited. Here, we investigate the role of CDKN1C in the broader BWSp phenotype. Notably, patients with CDKN1C variants appear to exhibit a different tumor risk than other BWSp molecular subtypes. We performed a comprehensive literature review using the search term "CDKN1C Beckwith" to identify 113 cases of patients with molecularly confirmed CDKN1C-BWSp. We then assessed the genotype and phenotype in a novel cohort of patients with CDKN1C-BWSp enrolled in the BWS Research Registry. Cardinal and suggestive features were evaluated for all patients reported, and tumor risk was established based on available reports. The most common phenotypes included macroglossia, omphalocele, and ear creases/pits. Tumor types reported from the literature included neuroblastoma, acute lymphocytic leukemia, superficial spreading melanoma, and intratubular germ cell neoplasia. Overall, this study identifies unique features associated with CDKN1C variants in BWSp, enabling more accurate clinical management. The absence of Wilms tumor and hepatoblastoma suggests that screening for these tumors may not be necessary, while the neuroblastoma risk warrants appropriate screening recommendations., (© 2024 The Author(s). American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

The Wiedemann-Beckwith syndrome (WBS) was first described in 1963 as a group of anomalies involving primarily macrosomia, macroglossia, and omphalocele. Histologic studies of WBS show nesidioblastosis of the pancreas, adrenocortical cytomegaly, and persistent metanephric blastema of the kidney. Multiple lines of evidence indicate that the human 11p15.5 region is the locus of abnormality in WBS. Insulin-like growth factor II (IGF-2) frequently has been considered a candidate gene, and expression of IGF-2 is known to be significantly delayed in fetal skeletal muscle of double-muscle (DM) cattle. Other candidate genes recently have been proposed for WBS. A number of recessive alleles in the bovine myostatin gene (GDF8, mapped to bovine chromosome 2 and apparently orthologous to the human 2q22 region) have been shown to be responsible for DM. Recently the first human case of deficient GDF8 function has been reported, confirming the importance of this gene. Bovine IGF-2 has been sequenced and localized to chromosome 25. The primary purpose of this study was to compare and contrast histologic findings in DM and WBS. Immunohistochemical staining confirms changes similar to nesidioblastosis in the pancreas. Other dysplastic changes of a cystic nature are seen in the adrenal. The renal histology of DM fetuses did not appear significantly different than controls. [ABSTRACT FROM AUTHOR]

High-sensitivity C-reactive protein (hs-CRP) is a widely used clinical biomarker of systemic inflammation, implicated in many chronic conditions, including type 1 diabetes (T1D). Despite the increasing emphasis on dietary intake as a modifiable risk factor for systemic inflammation, the association of hs-CRP with fruit and vegetable consumption is relatively underexplored in T1D. To address this gap, we investigated the longitudinal associations of dietary pattern-derived fruit and vegetable scores with hs-CRP in adults with and without T1D. Additionally, we examined the impact of berry consumption as a distinct food group. Data were collected in the Coronary Artery Calcification in Type 1 Diabetes study over two visits that were three years apart. At each visit, participants completed a food frequency questionnaire, and hs-CRP was measured using a particle-enhanced immunonephelometric assay. Mixed effect models were used to examine the three-year association of fruit and vegetable scores with hs-CRP. Adjusted models found a significant inverse association between blueberry intake and hs-CRP in the nondiabetic (non-DM) group. Dietary Approaches to Stop Hypertension- and Alternative Healthy Eating Index-derived vegetable scores were also inversely associated with hs-CRP in the non-DM group (all p-values ≤ 0.05). Conversely, no significant associations were observed in the T1D group. In conclusion, dietary pattern-derived vegetable scores are inversely associated with hs-CRP in non-DM adults. Nonetheless, in T1D, chronic hyperglycemia and related metabolic abnormalities may override the cardioprotective features of these food groups at habitually consumed servings. [ABSTRACT FROM AUTHOR]

Beckwith-Wiedemann Spectrum (BWSp) is an overgrowth and cancer predisposition disorder characterized by a wide spectrum of phenotypic manifestations including macroglossia, abdominal wall defects, neonatal hypoglycemia, and predisposition to embryonal tumors. In 1981, Best and Hoekstra reported four patients with BWSp in a single family which suggested autosomal dominant inheritance, but standard clinical testing for BWSp was not available during this time. Meticulous phenotyping of this family has occurred over the past 40 years of follow-up with additional family members being identified and samples collected for genetic testing. Genetic testing revealed a pathogenic mutation in CDKN1C, consistent with the most common cause of familial BWSp. CDKN1C mutations account for just 5% of sporadic cases of BWSp. Here, we report the variable presentation of BWSp across the individuals affected by the CDKN1C mutation and other extended family members spanning multiple generations, all examined by the same physician. Additional phenotypes thought to be atypical in patients with BWSp were reported which included cardiac abnormalities. The incidence of tumors was documented in extended family members and included rhabdomyosarcoma, astrocytoma, and thyroid carcinoma, which have previously been reported in patients with BWSp. These observations suggest that in addition to the inheritance of the CDKN1C variant, there are modifying factors in this family driving the phenotypic spectrum observed. Alternative theories are suggested to explain the etiology of clinical variability including diffused mosaicism, anticipation, and the presence of additional variants tracking in the family. This study highlights the necessity of long-term follow-up in patients with BWSp and consideration of individual familial characteristics in the context of phenotype and/or (epi)genotype associations., (© 2022 Wiley Periodicals LLC.)

Background: Sleep-related disorders have been associated with cognitive decline and neurodegeneration. American Indians are at increased risk for dementia. Here, we aim to characterize, for the first time, the associations between sleep characteristics and subsequent cognitive performance in a sample of aging American Indians. Methods: We performed analyses on data collected in two ancillary studies from the Strong Heart Study, which occurred approximately 10 years apart with an overlapping sample of 160 American Indians (mean age at follow-up 73.1, standard deviation 5.6; 69.3% female and 80% with high school completion). Sleep measures were derived by polysomnography and self-reported questionnaires, including sleep timing and duration, sleep latency, sleep stages, indices of sleep-disordered breathing, and self-report assessments of poor sleep and daytime sleepiness. Cognitive assessment included measures of general cognition, processing speed, episodic verbal learning, short and long-delay recall, recognition, and phonemic fluency. We performed correlation analyses between sleep and cognitive measures. For correlated variables, we conducted separate linear regressions. We analyzed the degree to which cognitive impairment, defined as more than 1.5 standard deviations below the average Modified Mini Mental State Test score, is predicted by sleep characteristics. All regression analyses were adjusted for age, sex, years of education, body mass index, study site, depressive symptoms score, difference in age from baseline to follow-up, alcohol use, and presence of APOE e4 allele. Results: We found that objective sleep characteristics measured by polysomnography, but not subjective sleep characteristics, were associated with cognitive performance approximately 10 years later. Longer sleep latency was associated with worse phonemic fluency (β = -0.069, p = 0.019) and increased likelihood of being classified in the cognitive impairment group later in life (odds ratio 1.037, p = 0.004). Longer duration with oxygen saturation < 90% was associated with better immediate verbal memory, and higher oxygen saturation with worse total learning, short and long-delay recall, and processing speed. Conclusion: In a sample of American Indians, sleep characteristics in midlife were correlated with cognitive performance a decade later. Sleep disorders may be modifiable risk factors for cognitive impairment and dementia later in life, and suitable candidates for interventions aimed at preventing neurodegenerative disease development and progression. [ABSTRACT FROM AUTHOR]

Dyslipidemia caused by abnormal lipid profiles significantly increases the risk of cardiovascular disease (CVD) in individuals with diabetes. Effective management necessitates a comprehensive approach that encompasses lifestyle modifications and pharmacological intervention. Lifestyle adjustments such as adopting a healthy diet and engaging in regular physical activity play a crucial role in managing dyslipidemia. Avoiding foods high in saturated fat, trans fat, and cholesterol, while incorporating high-fiber foods and omega-3 fatty acids, helps regulate lipid profiles. Regular exercise increases high-density lipoprotein (HDL) cholesterol levels, promotes weight loss, and aids in managing dyslipidemia. While behavioral changes are beneficial, pharmacological treatments are pivotal. Statins are the cornerstone for managing dyslipidemia in diabetic patients, regardless of standard lipid levels, due to their ability to lower low-density lipoprotein (LDL) cholesterol levels. Additional lipid-lowering agents such as ezetimibe, bile acid sequestrants, and PCSK9 inhibitors may complement treatment strategies to improve lipid profiles. The advancements include new formulations of antidiabetic medications that demonstrate favorable effects on lipid parameters in diabetic patients. Sodiumglucose co-transporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) not only provide cardiovascular benefits but also aid in lowering lipid levels. SGLT-2 inhibitors reduce LDL cholesterol and triglyceride levels, while GLP-1 RAs primarily target triglycerides and LDL cholesterol levels. [ABSTRACT FROM AUTHOR]

Previous studies provided evidence for the importance of cardiac structure abnormalities, in particular greater left ventricular (LV) mass, for brain aging, but longitudinal studies are lacking to date. We included 926 individuals (median age 48 years; 53% women) from the TREND cohort of the Study of Health in Pomerania (SHIP) without reduced ejection fraction or a history of myocardial infarction. LV mass index (LVMI) was determined by echocardiography at baseline. Brain morphometric measurements were derived from magnetic resonance images at baseline and 7‐year follow‐up. Direct effects of baseline LVMI on brain morphometry at follow‐up were estimated using linear regression models with adjustment for baseline brain morphometry. At baseline, median LVMI was 40 g/m2.7 and 241 individuals (26%) met the criterion of LV hypertrophy. After correction for multiple testing, baseline LVMI was directly associated with reduced global cortical thickness and increased cortical brain age at follow‐up independent from hypertension and blood pressure. Exposure‐outcome relations were nonlinear and significantly stronger in the upper half of the exposure distribution. Specifically, an increase in baseline LVMI from the 50% quantile to the 95% quantile was associated additional 2.7 years (95% confidence interval = [1.5 years, 3.8 years]) of cortical brain age at follow‐up. Additional regional analyses yielded bilateral effects on multiple frontal cortical regions. Our findings highlight the role of cardiac structure in brain aging. LVMI constitutes an easily measurable marker that might help to identify persons at risk for cognitive impairment and dementia. [ABSTRACT FROM AUTHOR]

The complex anatomy of the aortic root is of great importance for many surgical and transcatheter cardiac procedures. Therefore, the aim of this study was to provide a comprehensive morphological description of the nondiseased aortic root. We morphometrically examined 200 autopsied human adult hearts (22.0% females, 47.9 ± 17.7 years). A meticulous macroscopic analysis of aortic root anatomy was performed. The largest cross-section area of the aortic root was observed in coaptation center plane (653.9 ± 196.5 mm 2 ), followed by tubular plane (427.7 ± 168.0 mm 2 ) and basal ring (362.7 ± 159.1 mm 2 ) (p < 0.001). The right coronary sinus was the largest (area: 234.3 ± 85.0 mm 2 ), followed by noncoronary sinus (218.7 ± 74.8 mm 2 ) and left coronary sinus (201.2 ± 78.08 mm 2 ). The noncoronary sinus was the deepest, followed by right and left coronary sinus (16.4 ± 3.2 vs. 15.9 ± 3.1 vs. 14.9 ± 2.9 mm, p < 0.001). In 68.5% of hearts, the coaptation center was located near the aortic geometric center. The left coronary ostium was located 15.6 ± 3.8 mm above sinus bottom (within the sinus in 91.5% and above sinutubular junction in 8.5%), while for right coronary ostium, it was 16.2 ± 3.5 mm above (83.5% within sinus and 16.5% above). In general, males exhibited larger aortic valve dimensions than females. A multiple forward stepwise regression model showed that anthropometric variables might predict the size of coaptation center plane (age, sex, and heart weight; R 2  = 31.8%), tubular plane (age and sex; R 2  = 25.6%), and basal ring (age and sex; R 2  = 16.9%). In conclusion, this study presents a comprehensive analysis of aortic-root morphometry and provides a platform for further research into the intricate interplay between structure and function of the aortic root., (© 2024 The Authors. Clinical Anatomy published by Wiley Periodicals LLC on behalf of American Association of Clinical Anatomists and British Association of Clinical Anatomists.)

The European Commission asked EFSA to update its 2009 risk assessment on arsenic in food carrying out a hazard assessment of inorganic arsenic (iAs) and using the revised exposure assessment issued by EFSA in 2021. Epidemiological studies show that the chronic intake of iAs via diet and/or drinking water is associated with increased risk of several adverse outcomes including cancers of the skin, bladder and lung. The CONTAM Panel used the benchmark dose lower confidence limit based on a benchmark response (BMR) of 5% (relative increase of the background incidence after adjustment for confounders, BMDL05) of 0.06 μg iAs/kg bw per day obtained from a study on skin cancer as a Reference Point (RP). Inorganic As is a genotoxic carcinogen with additional epigenetic effects and the CONTAM Panel applied a margin of exposure (MOE) approach for the risk characterisation. In adults, the MOEs are low (range between 2 and 0.4 for mean consumers and between 0.9 and 0.2 at the 95th percentile exposure, respectively) and as such raise a health concern despite the uncertainties. [ABSTRACT FROM AUTHOR]

Diabetes, a group of metabolic disorders characterized by dysregulation of oxidative stress and elevated blood glucose levels. It has been studied with emphasis on malondialdehyde (MDA) and glutathione (GSH) levels as biomarkers of lipid peroxidation and antioxidant activity in the serum of type II Diabetes examines patients. The study involved the analysis of 105 serum samples from 75 type II diabetes patients and 30 healthy individuals. MDA and GSH levels served as measures of oxidative stress and antioxidant activity, respectively. In addition, lipid profiles were examined, which include measurements such as total cholesterol (Total C), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). The results showed significantly increased MDA, total cholesterol, triglycerides and glucose levels in the diabetic group compared to controls. In contrast, GSH and HDL levels were significantly lower in diabetics. In the type 2 diabetes patient group, a correlation between glucose levels and MDA concentration was observed, while no other significant associations were found between lipid profile parameters, glucose levels and MDA or GSH levels. Studies show the complex connection between diabetes and the increase in free radicals and the corresponding decrease in antioxidant synthesis. This dynamic interaction is an important factor in the development of oxidative stress. [ABSTRACT FROM AUTHOR]

Our previous study showed that sodium arsenite (200 mg/L) affected the nervous system and induced motor neuron development via the Sonic hedgehog pathway in zebrafish larvae. To gain more insight into the effects of arsenite on other signaling pathways, including apoptosis, we have performed quantitative polymerase chain reaction array‐based gene expression analyses. The 96‐well array plates contained primers for 84 genes representing 10 signaling pathways that regulate several biological functions, including apoptosis. We exposed eggs at 5 h postfertilization until the 72 h postfertilization larval stage to 200 mg/L sodium arsenite. In the Janus kinase/signal transducers and activators of transcription, nuclear factor κ‐light‐chain‐enhancer of activated B cells, and Wingless/Int‐1 signaling pathways, the expression of only one gene in each pathway was significantly altered. The expression of multiple genes was altered in the p53 and oxidative stress pathways. Sodium arsenite induced excessive apoptosis in the larvae. This compelled us to analyze specific genes in the p53 pathway, including cdkn1a, gadd45aa, and gadd45ba. Our data suggest that the p53 pathway is likely responsible for sodium arsenite‐induced apoptosis. In addition, sodium arsenite significantly reduced global DNA methylation in the zebrafish larvae, which may indicate that epigenetic factors could be dysregulated after arsenic exposure. Together, these data elucidate potential mechanisms of arsenic toxicity that could improve understanding of arsenic's effects on human health. Gene expression analysis for multiple genes (a total of 84) in zebrafish embryos exposed to inorganic arsenic (sodium arsenite) showed altered expression of specific genes related to p53, oxidative stress, JAK/STAT, NF‐kB, and Wnt signaling pathways. Sodium arsenite upregulated expression of genes in the p53 signaling pathways (cdkn1a, gadd45aa, and gadd45ba) that play proapoptotic roles and induced apoptosis. Sodium arsenite significantly reduced global DNA methylation. These data reveal potential mechanisms of arsenic toxicity. [ABSTRACT FROM AUTHOR]

Background: Ectodermal dysplasias are inherited disorders, which are characterized by congenital defects in two or more ectodermal structures such as skin, sweat glands, hair, nails, teeth, and mucous membranes. Method: Here, we describe a new observation of significant oligodontia in a female patient with the EDA gene variant c.742‐2A>G. Results: The results strongly suggest that the EDA gene variant c.742‐2A>G is pathogenic. The oligodontia in the proband was exceptionally severe. Conclusion: We demonstrate that the very rare splice acceptor variant EDA c.742‐2A>G is associated with severe oligodontia even in females. Our study points that this variant is pathogenic. An early identification of this variant is crucial for planning adequate treatment and follow‐up in time by a multidisciplinary team. [ABSTRACT FROM AUTHOR]

Background: An integral part of clinical practice is decision‐making. Yet there is widespread acceptance that there is evidence of cognitive bias within clinical practice among nurses and physicians. However, how cognitive bias among emergency nurses and physicians' decision‐making influences patient outcomes remains unclear. Aim: The aim of this review was to systematically synthesise research exploring the emergency nurses' and physicians' cognitive bias in decision‐making and its influence on patient outcomes. Methods: This scoping review was guided by the PRISMA Extension for Scoping Reviews. The databases searched included CINAHL, MEDLINE, Web of Science and PubMed. No date limits were applied. The Patterns, Advances, Gaps, Evidence for practice and Research recommendation (PAGER) framework was used to guide the discussion. Results: The review included 18 articles, consisting of 10 primary studies (nine quantitative and one qualitative) and eight literature reviews. Of the 18 articles, nine investigated physicians, five articles examined nurses, and four both physicians and nurses with sample sizes ranging from 13 to 3547. Six primary studies were cross‐sectional and five used hypothetical scenarios, and one real‐world assessment. Three were experimental studies. Twenty‐nine cognitive biases were identified with Implicit bias (n = 12) most frequently explored, followed by outcome bias (n = 4). Results were inconclusive regarding the influence of biases on treatment decisions and patient outcomes. Four key themes were identified; (i) cognitive biases among emergency clinicians; (ii) measurement of cognitive bias; (iii) influence of cognitive bias on clinical decision‐making; and (iv) association between emergency clinicians' cognitive bias and patient outcomes. Conclusions: This review identified that cognitive biases were present among emergency nurses and physicians during clinical decision‐making, but it remains unclear how cognitive bias influences patient outcomes. Further research examining emergency clinicians' cognitive bias is required. Relevance to Clinical Practice: Awareness of emergency clinicians' own cognitive biases may result to the provision of equity in care. No Patient or Public Contribution in this review: We intend to disseminate the results through publication in a peer‐reviewed journals and conference presentations. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is the seventh leading cause of death in the United States and the leading cause of death in the U.S. American Indian/Alaskan Natives (AI/ANs), who comprise only 2% of the total population. The AI/AN population has a high prevalence of DM in adults aged 20 years or older and is developing DM at a younger age than the general U.S. population. DM is a major risk factor for cardiovascular disease (CVD), and mortality from CVD is higher in AI/ANs than the general population, as is the prevalence of stroke and 1-year poststroke mortality for both genders when compared to non-Hispanic whites. A genome-wide scan found a number of chromosome linkages in the AI/AN population that suggest that genetic factors may contribute to their high risk of DM and CVD. Importantly, studies also suggest that in addition to race/ethnicity, cultural norms and historic conditions play important roles in the prevalence of DM and CVD in this population. Therefore, multiple factors should be taken into consideration when establishing prevention programs to decrease the prevalence of obesity, diabetes, and CVD incidence among adults and children in the AI/AN population. Prevention programs should focus on behavioral risk factors and lifestyle changes like encouraging smoking cessation, healthy diet, and increased physical activity while taking into consideration cultural, economic, and geographic factors. [ABSTRACT FROM AUTHOR]

Background: TGFB3 variants cause Loeys–Dietz syndrome type 5, a syndromic form of thoracic aortic aneurysm and dissection. The exact disease phenotype is hard to delineate because of few identified cases and highly variable clinical representation. Methodology: We provide the results of a haplotype analysis and a medical record review of clinical features of 27 individuals from 5 different families, originating from the Campine region in Flanders, carrying the NM_003239.5(TGFB3): c.787G>C p.(Asp263His) likely pathogenic variant, dbSNP:rs796051886, ClinVar: 203492. The Asp263 residue is essential for integrin binding to the Arg-Gly-Asp (RGD) motif of the TGFβ3-cytokine. Results: The haplotype analysis revealed a shared haplotype of minimum 1.92 Mb and maximum 4.14 Mb, suggesting a common founder originating >400 years ago. Variable clinical features included connective tissue manifestations, non-aneurysmal cardiovascular problems such as hypertrophic cardiomyopathy, bicuspid aortic valve, mitral valve disease, and septal defects. Remarkably, only in 4 out of the 27 variant-harboring individuals, significant aortic involvement was observed. In one family, a 31-year-old male presented with type A dissection. In another family, the male proband (65 years) underwent a Bentall procedure because of bicuspid aortic valve insufficiency combined with sinus of Valsalva of 50 mm, while an 80-year-old male relative had an aortic diameter of 43 mm. In a third family, the father of the proband (75 years) presented with ascending aortic aneurysm (44 mm). Conclusion: The low penetrance (15%) of aortic aneurysm/dissection suggests that haploinsufficiency alone by the TGFB3 variant may not result in aneurysm development but that additional factors are required to provoke the aneurysm phenotype. [ABSTRACT FROM AUTHOR]

Aim: To investigate individual susceptibility to periodontitis by conducting an epigenome‐wide association study using peripheral blood. Materials and Methods: We included 1077 African American and 457 European American participants of the Atherosclerosis Risk in Communities (ARIC) study who had completed a dental examination or reported being edentulous at Visit 4 and had available data on DNA methylation from Visit 2 or 3. DNA methylation levels were compared by periodontal disease severity and edentulism through discovery analyses and subsequent testing of individual CpGs. Results: Our discovery analysis replicated findings from a previous study reporting a region in gene ZFP57 (6p22.1) that was significantly hypomethylated in severe periodontal disease compared with no/mild periodontal disease in European American participants. Higher methylation levels in a separate region in an unknown gene (located in Chr10: 743,992‐744,958) was associated with significantly higher odds of edentulism compared with no/mild periodontal disease in African American participants. In subsequent CpG testing, four CpGs in a region previously associated with periodontitis located within HOXA4 were significantly hypermethylated in severe periodontal disease compared with no/mild periodontal disease in African American participants (odds ratio per 1 SD increase in methylation level: cg11015251: 1.28 (1.02, 1.61); cg14359292: 1.24 (1.01, 1.54); cg07317062: 1.30 (1.05, 1.61); cg08657492: 1.25 (1.01, 1.55)). Conclusions: Our study highlights epigenetic variations in ZPF57 and HOXA4 that are significantly and reproducibly associated with periodontitis. Future studies should evaluate gene regulatory mechanisms in the candidate regions of these loci. [ABSTRACT FROM AUTHOR]

The Food Resource Equity and Sustainability for Health ("FRESH") study is an Indigenous-led intervention to increase vegetable and fruit intake among Native American children. As part of this study, we developed a hybrid (online and in-person) food sovereignty and nutrition education curriculum for the parents of these children. This 16-week curriculum was developed to promote household- and community-level healthy eating and food sovereignty practices to parents of preschool-aged children residing in Osage Nation, Oklahoma. A total of 81 parent/caregivers participated in the curriculum component of the FRESH study, with a median age of 34 years (range: 23–54 years). Most study participants were female (88.9%) and less than half (45.7%) had an annual household income of more than US$50,000. Most were married or had a significant other (76.5%) and worked full-time (65.4%). The median total number of children in the home <18 years of age was three (range: 1–8). Participation among the 94 parents was 56% during the first week and was 12% in the final week. Having some college or technical training (vs. having a college degree) and having an annual household income of US$20,000–US$50,000 (vs. more than US$50,000) were associated with fewer sessions attended (p = 0.004 and 0.02, respectively) Being married (vs. not) was associated with higher attendance (p <.0001). Participation in a hybrid food sovereignty and nutrition education curriculum for parents was generally low, but income, education, and marital status were associated with curriculum participation. Our research adds to the literature by describing the development and implementation of this curriculum and recommendations for future research incorporating Indigenous approaches to health. [ABSTRACT FROM AUTHOR]

Telomerase preserves genomic integrity by maintaining and protecting the telomeres. Seminal findings from 1985 revealed the canonical role of telomerase and motivated investigations into potential therapeutic strategies to combat one of the hallmarks of ageing—telomere attrition. Since then, the field of telomere biology has rapidly expanded, with telomerase serving essential roles in cancer and cell development through its canonical function. However, telomerase also exerts critical extra‐telomeric functions through its protein (telomerase reverse transcriptase, TERT) and RNA components (telomerase RNA component, TERC). Telomerase re‐activation or ectopic expression promotes survival and permits unlimited proliferation in tumours and healthy non‐malignant cells. TERT gene therapies improve health and lifespan in ageing mice and mouse models of age‐related diseases. The extra‐telomeric functions of telomerase are critical to ageing. These include protection against oxidative stress, orchestration of chromatin modifications and transcription, and regulation of angiogenesis and metabolism (e.g. mitochondrial function and glucose control). Given these biological functions are key adaptations to endurance training and the recent meta‐analytical findings that indicate exercise up‐regulates TERT and telomerase, a comprehensive discussion on the implications of the canonical and extra‐telomeric roles of telomerase is warranted. This review highlights the therapeutic benefits of telomerase‐based treatments for idiopathic and chronic diseases that are linked to ageing. Discussion on the canonical and extra‐telomeric roles of telomerase are presented, followed by a detailed summary of the evidence on how exercise influences telomerase. Finally, the potential cell signalling underpinning the exercise‐induced modulation of telomerase are discussed with directions for future research. [ABSTRACT FROM AUTHOR]

Aquatic organisms such as fish can accumulate high concentrations of arsenic (As), which has toxic effects on fish. However, whether the intestinal flora are involved in As damage to fish intestinal tissues and the underlying process are unclear. Common carp (Cyprinus carpio) were exposed to As (2.83 mg/L) in water for 30 days, and blood, muscle, intestine, and intestine samples were collected. Intestinal pathological sections were observed, and the lipopolysaccharide (LPS) levels in serum and the levels of As accumulation and tight junction-related factors in intestinal tissues were measured. The gut microbiota was analysed by 16S rRNA sequencing. The results showed that As treatment decreased the abundance of microbiota, increased the number of harmful bacteria, and decreased the number of beneficial bacteria in the intestine. In our experiment, the top 30 harmful and beneficial bacteria with the highest relative abundance were identified. Among the top 30 harmful and beneficial bacteria, As treatment resulted in a significant (P < 0.05) increase in harmful bacteria (such as Fusobacteriota, Bacteroidota (LPS-producing bacteria), Verrucomicrobiota, Bacteroides, Aeromonas, and Stenotrophomonas) and a significant (P < 0.05) decrease in beneficial bacteria (such as Actinobacteriota, Planctomycetota, Firmicutes, Reyranella, Akkermansia, and Pseudorhodobacter), which further demonstrated that As affects the abundance of intestinal flora. In addition, As exposure increased the LPS level in serum and the abundance of Bacteroidota (LPS-producing bacteria) in the intestine. Bacteroidota exhibits the six highest relative abundance at the phylum level, which indicates that LPS produced by Bacteroidota can increase the LPS level in serum. Additionally, the protein and gene levels of the tight junction markers ZO-1 and occludin in the intestine were reduced by As treatment, which further indicated that As exposure impaired the structural integrity of the intestine. In conclusion, the results obtained in our study indicate that the intestinal flora, LPS, and tight junctions participate in the impairment of the structural integrity of the common carp intestine resulting from As exposure. [ABSTRACT FROM AUTHOR]

Non-syndromic tooth agenesis (NSTA) is one of the most common dental developmental malformations affected by genetic factors predominantly. Among all 36 candidate genes reported in NSTA individuals, EDA, EDAR, and EDARADD play essential roles in ectodermal organ development. As members of the EDA/EDAR/NF-κB signaling pathway, mutations in these genes have been implicated in the pathogenesis of NSTA, as well as hypohidrotic ectodermal dysplasia (HED), a rare genetic disorder that affects multiple ectodermal structures, including teeth. This review provides an overview of the current knowledge on the genetic basis of NSTA, with a focus on the pathogenic effects of the EDA/EDAR/NF-κB signaling pathway and the role of EDA, EDAR, and EDARADD mutations in developmental tooth defects. We also discuss the phenotypic overlap and genetic differences between NSTA and HED. Ultimately, this review highlights the importance of genetic analysis in diagnosing and managing NSTA and related ectodermal disorders, and the need for ongoing research to improve our understanding of these conditions. [ABSTRACT FROM AUTHOR]

Background and Purpose: Cognitive, affective, and physical symptoms and alterations in their function are seen across chronic illnesses. Data suggest that environmental, psychological, and physiological factors contribute to symptom experience, potentially through loss of telomeres (telomere attrition), structures at the ends of chromosomes. Telomere length is affected by many factors including environmental (e.g., exercise, diet, smoking) and physiological (e.g., response to stress), as well as from oxidative damage and inflammation that occurs in many disease processes. Moreover, telomere attrition is associated with chronic disease (cancer, cardiovascular disease, Alzheimer's disease) and predicts higher morbidity and mortality rates. However, findings are inconsistent among telomere roles and relationships with health outcomes. This article aims to synthesize the current state-of-the-science of telomeres and their relationship with cognitive, affective, and physical function and symptoms. Method: A comprehensive literature search was performed in two databases: CINAHL and PUBMED. A total of 33 articles published between 2000 and 2022 were included in the final analysis. Results: Telomere attrition is associated with various changes in cognitive, affective, and physical function and symptoms. However, findings are inconsistent. Interventional studies (e.g., meditation and exercise) may affect telomere attrition, potentially impacting health outcomes. Conclusion: Nursing research and practice are at the forefront of furthering the understanding of telomeres and their relationships with cognitive, affective, and physical function and symptoms. Future interventions targeting modifiable risk factors may be developed to improve health outcomes across populations. [ABSTRACT FROM AUTHOR]

NaAsO 2 is known as a harmful pollutant all over the world, and many chronic heart diseases can be attributed to its prolonged exposure in NaAsO 2 -contaminated water. Therefore, considering the anti-inflammatory and antioxidant effects of betaine (BET), in this study, our team investigated the cardioprotective effects of this phytochemical agent on sodium arsenite (NaAsO 2 )-induced cardiotoxicity. Forty male mice were randomly divided into 4 groups: (I) Control; (II) BET (500 mg/kg); (III) NaAsO 2 (50 ppm); and (IV) NaAsO 2  + BET. NaAsO 2 was given to the animals for 8 weeks, but BET was given in the last two weeks. After decapitation, inflammatory factors and biochemical parameters were measured, and Western blot analyses were performed. BET decrease the activity level of alanine aspartate aminotransferase, creatine kinase MB, thiobarbituric acid reactive substances level, inflammatory factors (tumor necrosis factor-α) content, and nuclear factor kappa B expression. Furthermore, BET increased cardiac total thiol and activity levels of catalase, superoxide dismutase, and glutathione peroxidase and nuclear factor erythroid-2 expression. Hence, the administration of BET ameliorated the deleterious effects stemming from the imbalance of oxidative and antioxidant pathways and histopathological alterations observed in NaAsO 2 -intoxicated mice, thereby attenuating oxidative stress-induced damage and inflammation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Diabetes-related dyslipidemia is a multifaceted, complicated disorder characterized by an abnormal lipid profile in individuals with diabetes. The incidence of different types of dyslipidemia, however, was not a focus of prior investigations. The patients were characterized into three categories of dyslipidemia. Different patterns of dyslipidemia were combined into single dyslipidemia (7 patterns), mixed dyslipidemia (16 patterns), and triple dyslipidemia (4 patterns)., Methods: In this cross-sectional study, 586 people suffering from type 2 diabetes mellitus (T2DM) were included. We assessed the serum lipid profile and used log (TG/HDL-C) to determine the atherogenic index of plasma (AIP). Dyslipidemia was examined as a categorical variable, and the findings were presented as percentages and numbers. To compare categorical variables, we either utilized Fisher exact tests or Chi square tests., Results: The study comprised of 586 T2DM patients, with 310 (52.9%) women and 276 (47.1%) men. Women have significantly higher hypertension (33.6%) as compared to men (23.2%). 18.94% (111) of patients were having coronary artery disease (CAD) history consisting of 12.28% (72) females and 6.66% (39) males, a difference which is statistically significant. 98.12% of total individuals had as a minimum of one lipid abnormality. 4.61% (27) of study subjects were having isolated dyslipidemia and 93.51% (548) had dual or triple pattern of dyslipidemia (mixed dyslipidemia). High AIP >0.24 (94.8%) was the most predominant trend of dyslipidemia. The dual combination of AIP (>0.24) and HDL (<50 mg/dL in Females and <40 mg/dL in Males) was found to be the most common pattern of mixed dyslipidemia (68.08%). The most prevalent trend of isolated dyslipidemia was found to be high AIP (>0.24), In patients with CAD history. Among the mixed dyslipidemia, the common pattern of dyslipidemia (71.17%) was the dual combination of high AIP (>0.24) and low HDL (<50 mg/dL women and <40 mg/dL males). The triple combination of TG (≥200 mg/dL) and HDL (<40 and <50 mg/dL) and LDL (≥100 mg/dL) was only found in females., Conclusion: In conclusion, dyslipidemia is highly prevalent in T2DM patients, with mixed dyslipidemia being the most common type observed in the community of Kashmir valley, India. High AIP was the most prevalent pattern in the current investigation., (© 2023 Wiley Periodicals LLC.)

Arsenic exposure is correlated with atherosclerosis in epidemiological studies and in animal models. We have previously shown that arsenic exposure enhanced the atherosclerotic plaque size, increased the plaque lipid content, and decreased the plaque smooth muscle cell and collagen contents in the apolipoprotein E knockout (apoE−/−) mice. However, the percentage of plaque-resident macrophages, the primary drivers of atherosclerosis remained unchanged. Therefore, we hypothesized that although arsenic does not change the quantity of macrophages, it alters the macrophage transcriptome towards a proatherogenic state. To test this hypothesis, we used bone marrow-derived macrophages, polarized them to either interferon-γ (IFN-ɣ) stimulated, proinflammatory or interleukin-4 (IL-4) stimulated, alternatively activated macrophages in the presence or absence of 0.67 µM (50 ppb) arsenic and performed RNA sequencing. Arsenic exposure altered the gene expression of the macrophages in a subtype-specific manner. Most differentially expressed genes (88%) were altered specifically in either IFN-ɣ- or IL-4-stimulated macrophages, whereas in the remaining 12% of genes that changed in both cell types, did so in opposite directions. In IL-4-stimulated macrophages, arsenic significantly downregulated the genes involved in cholesterol biosynthesis and the chemokines CCL17/CCL22, whereas in IFN-ɣ-stimulated macrophages, the genes associated with the liver X receptor (LXR) pathway were downregulated by arsenic. Using a bone marrow transplant experiment, we validated that the deletion of LXRα from the hematopoietic compartment rescued arsenic-enhanced atherosclerosis in the apoE−/− mouse model. Together, these data suggest that arsenic modulates subtype-specific transcriptomic changes in macrophages and further emphasize the need to define macrophage heterogeneity in atherosclerotic plaques in order to evaluate the proatherogenic role of arsenic. [ABSTRACT FROM AUTHOR]

Small drinking water systems in the United States often suffer from repeated Safe Drinking Water Act water quality violations that necessitate upgrades to the existing centralized systems to achieve compliance. Community water systems (CWSs) need to evaluate the tradeoffs between public health, environmental and economic impacts when choosing these system improvements. This study developed the input and output components of a triple‐bottom‐line methodology to compare two alternatives: (1) installing a centralized treatment upgrade or (2) a point‐of‐use/point‐of‐entry device over a 30‐year period, using a health exposure assessment specific contaminants, life cycle analysis of environmental impacts improvement, and life cycle costing to account for the useful life of components and the number of households served by a CWS. We present recommendations and considerations for future usage of the triple‐bottom‐line approach methodology. [ABSTRACT FROM AUTHOR]

Arsenic is a heavy metal with atomic number 33, which lies in the fourth period and fifteenth group of the periodic table. Arsenic cycle occurs in the nature where it gets converted form one form to other. The preponderance of arsenic is ubiquitous and its presence can be seen in air, water and land. It is a medicine as well as a poison. It affects all the biota hence playing an important role in the ecosystem. Anthropogenic activities have let to the rise of its toxic level in the environment through it is also release naturally. This article reviews about the occurrence of arsenic, in ecosystem with reference to natural and human activities. Its toxic effects on the living beings and cheaper methods for fighting this trouble maker. [ABSTRACT FROM AUTHOR]

The vascular endothelium is not only the semipermeable membrane that separates tissue from blood but also an organ that regulates inflammation, vascular tone, blood clotting, angiogenesis and synthesis of connective tissue proteins. It is susceptible to the direct cytotoxic action of numerous xenobiotics and to the acute hypoxia that accompanies acute poisoning. This damage is superimposed on the preformed state of the vascular endothelium, which, in turn, depends on many humoral factors. The probability that an exogenous toxicant will cause life‐threatening dysfunction of the vascular endothelium, thereby complicating the course of acute poisoning, increases with an increase in the content of endogenous substances in the blood that disrupt endothelial function. These include ammonia, bacterial endotoxin, indoxyl sulfate, para‐cresyl sulfate, trimethylamine N‐oxide, asymmetric dimethylarginine, glucose, homocysteine, low‐density and very‐low‐density lipoproteins, free fatty acids and products of intravascular haemolysis. Some other endogenous substances (albumin, haptoglobin, haemopexin, biliverdin, bilirubin, tetrahydrobiopterin) or food‐derived compounds (ascorbic acid, rutin, omega‐3 polyunsaturated fatty acids, etc.) reduce the risk of lethal vascular endothelial dysfunction. The individual variability of the content of these substances in the blood contributes to the stochasticity of the complications of acute poisoning and is a promising target for the risk reduction measures. Another feasible option may be the repositioning of drugs that affect the function of the vascular endothelium while being currently used for other indications. The vascular endothelium is damaged by the direct cytotoxic action of numerous xenobiotic chemicals and (or) acute hypoxia. This damage is superimposed on the initial state of vascular endothelium, which, in turn, depends on many endogenous humoral factors. Vascular endothelium dysfunction increases the acute poisoning complications risk. Approach to the prevention of acute poisoning complications is considered. [ABSTRACT FROM AUTHOR]

Individual variation in telomere length is predictive of health and mortality risk across a range of species. However, the relative influence of environmental and genetic variation on individual telomere length in wild populations remains poorly understood. Heritability of telomere length has primarily been calculated using parent–offspring regression which can be confounded by shared environments. To control for confounding variables, quantitative genetic "animal models" can be used, but few studies have applied animal models in wild populations. Furthermore, parental age at conception may also influence offspring telomere length, but most studies have been cross‐sectional. We investigated within‐ and between‐parental age at conception effects and heritability of telomere length in the Seychelles warbler using measures from birds caught over 20 years and a multigenerational pedigree. We found a weak negative within‐paternal age at conception effect (as fathers aged, their offspring had shorter telomeres) and a weak positive between‐maternal age at conception effect (females that survived to older ages had offspring with longer telomeres). Animal models provided evidence that heritability and evolvability of telomere length were low in this population, and that variation in telomere length was not driven by early‐life effects of hatch period or parental identities. Quantitative polymerase chain reaction plate had a large influence on telomere length variation and not accounting for it in the models would have underestimated heritability. Our study illustrates the need to include and account for technical variation in order to accurately estimate heritability, as well as other environmental effects, on telomere length in natural populations. [ABSTRACT FROM AUTHOR]

Most individuals with intellectual disability (ID) lack the motivation and willingness to do exercise on their own. The purpose of this study was to apply the response-stimulation strategy to encourage three overweight students with ID to engage in walking/running. This was a preliminary study to implement the strategy by using a dance pad combined with a LEGO® Train. The LEGO® Train was used as the stimulation to motivate the participants and a dance pad was used to detect the participants' walking/running activity in order to trigger the LEGO® Train. This study adopted a multiple probe design across participants, including one baseline phase and two intervention phases. The experimental results show that the three participants performed a greater number of walking/running steps during the intervention phases, compared to the baseline phase. The findings demonstrate that a dance pad combined with the LEGO® Train was a feasible motivator to increase the participants' willingness to perform walking/running on their own. [ABSTRACT FROM AUTHOR]

The purpose of this integrative review is to explore and synthesize literature about the relationship between perceived social support and cardiac vagal modulation, measured by heart rate variability (HRV), during phases of an acute stress response to assess this potential relationship underlying the stress-buffering effects of perceived social support. A systematic search of seven databases was conducted, including MEDLINE, CINAHL, PsychINFO, Embase, ProQuest, medRxiv, and clinicaltrials.gov. Eight studies met the inclusion criteria and were systematically synthesized. A quality appraisal was completed for each included study. Majority of studies focused on time and frequency domain measures of HRV thought to reflect parasympathetic modulation of heart rate and identified them as positively associated with perceived social support during rest, stress induction, and recovery from an acute stressor. Results highlight the importance for nurses and other health care professionals to assess patients' perceived social support, as increased perceived social support may contribute to an adaptive stress response. [ABSTRACT FROM AUTHOR]

Platelets express the transmembrane chemokine SR-PSOX/CXCL16, proteolytic cleavage of which generates the sCXCL16 soluble-(s) chemokine. The sCXCL16 engages CXCR6 on platelets to synergistically propagate degranulation, aggregation and thrombotic response. Currently, we have investigated the pro-thrombotic and prognostic association of platelet CXCL16–CXCR6 axis in CAD-(n = 240; CCS n = 62; ACS n = 178) patients. Platelet surface-associated-CXCL16 and CXCR6 surface expression ascertained by flow cytometry correlated significantly with platelet activation markers (CD62P denoting degranulation and PAC-1 binding denoting α2bβ3-integrin activation). Higher platelet CXCL16 surface association (1st quartile vs. 2nd–4th quartiles) corresponded to significantly elevated collagen-induced platelet aggregation assessed by whole blood impedance aggregometry. Platelet-CXCL16 and CXCR6 expression did not alter with dyslipidemia, triglyceride, total cholesterol, or LDL levels, but higher (>median) plasma HDL levels corresponded with decreased platelet-CXCL16 and CXCR6. Although platelet-CXCL16 and CXCR6 expression did not change significantly with or correlate with troponin I levels, they corresponded with higher Creatine Kinase-(CK) activity and progressively deteriorating left ventricular ejection fraction (LVEF) at admission. Elevated-(4th quartile) platelet-CXCL16 (p = 0.023) and CXCR6 (p = 0.030) measured at admission were significantly associated with a worse prognosis. However, after Cox-PH regression analysis, only platelet-CXCL16 was ascertained as an independent predictor for all-cause of mortality. Therefore, the platelet CXCL16–CXCR6 axis may influence thrombotic propensity and prognosis in CAD patients. [ABSTRACT FROM AUTHOR]

Globally, there is a growing acknowledgment of Indigenous Peoples' rights to control data related to their communities. This is seen in the development of Indigenous Data Governance standards. As health data collection increases, it's crucial to apply these standards in research involving Indigenous communities. Our study, therefore, aims to systematically review research using routinely collected health data of Indigenous Peoples, understanding the Indigenous Data Governance approaches and the associated advantages and challenges. We searched electronic databases for studies from 2013 to 2022, resulting in 85 selected articles. Of these, 65 (77%) involved Indigenous Peoples in the research, and 60 (71%) were authored by Indigenous individuals or organisations. While most studies (93%) provided ethical approval details, only 18 (21%) described Indigenous guiding principles, 35 (41%) reported on data sovereignty, and 28 (33%) addressed consent. This highlights the increasing focus on Indigenous Data Governance in utilising health data. Leveraging existing data sources in line with Indigenous data governance principles is vital for better understanding Indigenous health outcomes., (© 2024. The Author(s).)

The serum level of C-reactive protein (CRP) is a significant independent risk factor for Coronavirus disease 2019 (COVID-19). A link was found between serum CRP and genetic diversity within the CRP gene in earlier research. This study examined whether CRP rs1205 and rs1800947 polymorphisms were associated with COVID-19 mortality among various severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) variants. We genotyped CRP rs1205 and rs1800947 polymorphisms in 2023 deceased and 2307 recovered patients using the polymerase chain reaction-restriction fragment length polymorphism method. There was a significant difference between the recovered and the deceased patients in terms of the minor allele frequency of CRP rs1205 T and rs1800947 G. In all three variants, COVID-19 mortality rates were associated with CRP rs1800947 GG genotype. Furthermore, CRP rs1205 CC and rs1800947 GG genotypes showed higher CRP levels. It was found that the G-T haplotype was prevalent in all SARS-CoV-2 variants. The C-C and C-T haplotypes were statistically significant in Delta and Omicron BA.5 variants, respectively. In conclusion, polymorphisms within the CRP gene may relate to serum CRP levels and mortality among COVID-19 patients. In order to verify the utility of CRP polymorphism correlation in predicting COVID-19 mortality, a replication of these results is needed., (© 2024. The Author(s).)