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Many people living with dementia and unpaid carers experience inequalities in care related to challenges in receiving a correct diagnosis, care and support. Whilst complexities of the evidence are well recognised including barriers in receiving a diagnosis or post-diagnostic care, no coherent model has captured the far-reaching types and levels of inequalities to date. Building on the established Dahlgren & Whitehead Rainbow model of health determinants, this paper introduces the new Dementia Inequalities model. The Dementia Inequalities model, similar to the original general rainbow model, categorises determinants of health and well-being in dementia into three layers: (1) Individual; (2) Social and community networks; and (3) Society and infrastructure. Each layer comprises of general determinants, which have been identified in the original model but also may be different in dementia, such as age (specifically referring to young- versus late-onset dementia) and ethnicity, as well as new dementia-specific determinants, such as rare dementia subtype, having an unpaid carer, and knowledge about dementia in the health and social care workforce. Each layer and its individual determinants are discussed referring to existing research and evidence syntheses in the field, arguing for the need of this new model. A total of 48 people with lived, caring, and professional experiences of dementia have been consulted in the process of the development of this model. The Dementia Inequalities model provides a coherent, evidence-based overview of inequalities in dementia diagnosis and care and can be used in health and social care, as well as in commissioning of care services, to support people living with dementia and their unpaid carers better and try and create more equity in diagnosis and care. [ABSTRACT FROM AUTHOR]

The complex process of aging leads to a gradual deterioration in the function of cells, tissues, and the entire organism, thereby increasing the risk of disease and death. Nicotinamide N-methyltransferase (NNMT) has attracted attention as a potential target for combating aging and its related pathologies. Studies have shown that NNMT activity increases over time, which is closely associated with the onset and progression of age-related diseases. NNMT uses S-adenosylmethionine (SAM) as a methyl donor to facilitate the methylation of nicotinamide (NAM), converting NAM into S-adenosyl-L-homocysteine (SAH) and methylnicotinamide (MNA). This enzymatic action depletes NAM, a precursor of nicotinamide adenine dinucleotide (NAD+), and generates SAH, a precursor of homocysteine (Hcy). The reduction in the NAD+ levels and the increase in the Hcy levels are considered important factors in the aging process and age-related diseases. The efficacy of RNA interference (RNAi) therapies and small-molecule inhibitors targeting NNMT demonstrates the potential of NNMT as a therapeutic target. Despite these advances, the exact mechanisms by which NNMT influences aging and age-related diseases remain unclear, and there is a lack of clinical trials involving NNMT inhibitors and RNAi drugs. Therefore, more in-depth research is needed to elucidate the precise functions of NNMT in aging and promote the development of targeted pharmaceutical interventions. This paper aims to explore the specific role of NNMT in aging, and to evaluate its potential as a therapeutic target. [ABSTRACT FROM AUTHOR]

The glymphatic system is cerebrospinal fluid–brain tissue fluid exchange flow mediated by aquaporin‐4 (AQP4) on the end feet of astrocytes for a system, which is capable of rapidly removing brain metabolites and thus maintaining brain homeostasis, and is known as the central immune system. Dysfunction of the glymphatic system causes accumulation of misfolded and highly phosphorylated proteins (amyloid‐β and Tau proteins), which destabilizes the proteins, and the body's neuroinflammatory factors are altered causing aging of the immune system and leading to neurodegenerative diseases. Damage to the glymphatic system and aging share common manifestations, as well as unstudied biological mechanisms that are also linked, such as mitochondria, oxidative stress, chronic inflammation, and sleep. In this paper, we first summarize the structure, function, and research methods of the glymphatic system and the relationship between the glymphatic system and the peripheral immune system, and second, sort out and summarize the factors of the glymphatic system in removing metabolites and resolving aging‐related diseases and factors affecting aging, to explore its related biological mechanisms, and moreover, to provide a new way of thinking for treating or intervening aging‐related diseases. [ABSTRACT FROM AUTHOR]

Chagas disease, discovered over a century ago, continues to pose a global health challenge, affecting millions mainly in Latin America. This historical review with commentary outlines the disease's discovery, its evolution into a global concern due to migration, and highlights significant advances in diagnostics and treatment strategies. Despite these advancements, the paper discusses ongoing challenges in eradication, including vector control, congenital transmission, the disease's asymptomatic nature, and socioeconomic barriers to effective management. It calls for a multidisciplinary approach, enhanced diagnostics, improved treatment accessibility, and sustained vector control efforts. The review emphasizes the importance of global collaboration and increased funding to reduce Chagas disease's impact. [ABSTRACT FROM AUTHOR]

Osteoporosis is a disease characterized by loss of bone mass, where bones become fragile and more likely to fracture. Bone density begins to decrease at age 50, and a state of osteoporosis is defined by loss of more than 25%. Cellular senescence is a permanent arrest of normal cell cycle, while maintaining cell viability. The number of senescent cells increase with age. Since osteoporosis is an aging disease, it is natural to consider the question to what extend senescent cells induce bone density loss and osteoporosis. In this paper we use a mathematical model to address this question. We determine the percent of bone loss for men and women during age 50 to 100 years, and the results depend on the rate η of net formation of senescent cell, with η = 1 being the average rate. In the case η = 1, the model simulations are in agreement with empirical data. We also consider senolytic drugs, like fisetin and quercetin, that selectively eliminate senescent cells, and assess their efficacy in terms of reducing bone loss. For example, at η = 1, with estrogen hormonal therapy and early treatment with fisetin, bone density loss for women by age 75 is 23.4% (below osteoporosis), while with no treatment with fisetin it is 25.8% (osteoporosis); without even a treatment with estrogen hormonal therapy, bone loss of 25.3% occurs already at age 65. [ABSTRACT FROM AUTHOR]

DNA methylation indicates the individual's aging, so-called Epigenetic clocks, which will improve the research and diagnosis of aging diseases by investigating the correlation between methylation loci and human aging. Although this discovery has inspired many researchers to develop traditional computational methods to quantify the correlation and predict the chronological age, the performance bottleneck delayed access to the practical application. Since artificial intelligence technology brought great opportunities in research, we proposed a perceptron model integrating a channel attention mechanism named PerSEClock. The model was trained on 24,516 CpG loci that can utilize the samples from all types of methylation identification platforms and tested on 15 independent datasets against seven methylation-based age prediction methods. PerSEClock demonstrated the ability to assign varying weights to different CpG loci. This feature allows the model to enhance the weight of age-related loci while reducing the weight of irrelevant loci. [ABSTRACT FROM AUTHOR]

The rising prevalence of paediatric type 2 diabetes (T2D) is concerning, particularly with limited medical intervention despite evidence of accelerated disease progression. This study of a Barts Health NHS Trust cohort from 2008 to 2022 aims to elucidate the incidence, clinical outcomes, and complications associated with paediatric T2D. A retrospective analysis utilising electronic and paper records identified 40 patients with T2D. The incidence doubled from 2.6/year in 2008–2013 to 5.4/year in 2014–2018. Sixty-eight percent exhibited co-morbidities, notably learning disabilities. At diagnosis, the mean BMI was 32.4 ± 6.71 kg/m2, with no gender-based disparity and no significant change over a two-year follow-up. The initial HbA1c was 75.2 ± 21.0 mmol/mol, decreasing to 55.0 ± 17.4 mmol/mol after three months (p = 0.001) and then rising to 63.0 ± 25.5 mmol/mol at one year (p = 0.07). While 22/37 patients achieved HbA1c < 48 mmol/mol, only 9 maintained this for a year. Several metabolic and cardiovascular complications were observed at diagnosis and follow-up, with no significant change in frequency. In 2022, 15 patients transitioned to adult services. HbA1c at transition was 74.7 ± 27.6 mmol/mol, showing no change one year post-transition (71.9 ± 26.9 mmol/mol, p = 0.34). This study highlights substantial therapeutic failure, with current management falling short in achieving a sustained reduction in BMI or HbA1c. Novel treatment approaches are needed to improve clinical outcomes and address the high burden of co-morbidities and complications. [ABSTRACT FROM AUTHOR]

Background: The relationship between periodontitis and cardiovascular disease (CVD) has been extensively studied, but the role of biological aging in this relationship remains poorly understood. This study is dedicated to investigating the effect of periodontitis on the incidence of CVD and to elucidating the potential mediating role of biological aging. Furthermore, this study will seek to elucidate the causal association between periodontitis, CVD, and biological aging. Methods: We included 3269 participants from the National Health and Nutrition Examination Survey (2009–2014) with diagnostic information on periodontitis and composite CVD events. Biological aging was evaluated by utilizing both the Klemera–Doubal method's calculated biological age (KDMAge) and phenotypic age (PhenoAge). Logistic regression, restricted cubic spline (RCS) analysis, and subgroup analysis were used for data analysis. Mediation analysis was employed to explore the mediating role of biological aging. Subsequently, Mendelian randomization (MR) analyses were performed using genome-wide association study databases to explore potential causal relationships between periodontitis, CVD, and biological aging. Results: Periodontitis was associated with a higher risk of CVD. Participants with periodontitis were found to have increased levels of biological aging, and elevated levels of biological aging were associated with increased CVD risk. Mediation analyses showed a partial mediating effect of biological aging (PhenoAge: 44.6%; KDMAge: 22.9%) between periodontitis and CVD risk. MR analysis showed that periodontitis played a causal role in increasing the risk of small vessel stroke, while myocardial infarction was found to increase the risk of periodontitis. In addition, reverse MR analysis showed that phenotypic aging can increase the risk of periodontitis, and there is a two-way causal relationship between CVD and biological aging. Conclusions: Periodontitis is associated with an increased CVD risk, partially mediated by biological aging, with a complex causal interrelationship. Targeted interventions for periodontal health may slow the biological aging processes and reduce CVD risk. [ABSTRACT FROM AUTHOR]

Reducing spillover of zoonotic pathogens is an appealing approach to preventing human disease and minimizing the risk of future epidemics and pandemics. Although the immediate human health benefit of reducing spillover is clear, over time, spillover reduction could lead to counterintuitive negative consequences for human health. Here, we use mathematical models and computer simulations to explore the conditions under which unanticipated consequences of spillover reduction can occur in systems where the severity of disease increases with age at infection. Our results demonstrate that, because the average age at infection increases as spillover is reduced, programs that reduce spillover can actually increase population-level disease burden if the clinical severity of infection increases sufficiently rapidly with age. If, however, immunity wanes over time and reinfection is possible, our results reveal that negative health impacts of spillover reduction become substantially less likely. When our model is parameterized using published data on Lassa virus in West Africa, it predicts that negative health outcomes are possible, but likely to be restricted to a small subset of populations where spillover is unusually intense. Together, our results suggest that adverse consequences of spillover reduction programs are unlikely but that the public health gains observed immediately after spillover reduction may fade over time as the age structure of immunity gradually re-equilibrates to a reduced force of infection. Author summary: Many pathogens, such as rabies, coronaviruses, and hantaviruses primarily circulate within wild animals but can infect humans when the opportunity arises. This pervasive challenge to public health has motivated the development of new methods designed to reduce the frequency of these spillover events. Although reducing spillover infection of humans appears to be an obvious win for public health, it is conceivable that altering historical patterns of spillover could change the age structure of human immunity in a way that undermines human health. Using mathematical and computational models we evaluate the conditions required for these counterintuitive impacts to occur. Our analyses demonstrate that reducing spillover from wild animals will generally improve public health and that negative outcomes can occur in only rare and unusual circumstances. Although negative impacts of spillover reduction are likely to be rare, our results show that the public health benefits of spillover reduction may fade over time unless a near total elimination of spillover can be achieved. [ABSTRACT FROM AUTHOR]

Background: Viral respiratory infections may precipitate type 1 diabetes (T1D). A possible association between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, and the incidence of T1D is being determined. This study was carried out using Portuguese registries, aiming at examining temporal trends between COVID-19 and T1D. Methods: Hospital data, comparing the incidence before and during the COVID-19 pandemic, from children and young adults diagnosed with new-onset T1D, was acquired beginning in 2017 and until the end of 2022. Data was obtained from nine different Portuguese hospital units. The impact of the COVID-19 pandemic, beginning in March 2020, was assessed comparing the annual numbers of new-onset T1D cases. The annual median levels of glucose, glycated hemoglobin (HbA1c) and fasting C-peptide at T1D diagnosis were compared. The annual number of diabetic ketoacidosis (DKA) episodes among new T1D cases was also assessed at two centers. Results: In total, data from 574 newly diagnosed T1D patients was analyzed, including 530 (92.3%) children. The mean ages for child and adult patients were 9.1 (SD 4.4) and 32.8 (SD 13.6) years, respectively. 57.8% (331/573) were male, one patient had unknown sex. The overall median (25–75 percentiles) levels of glucose, HbA1c and fasting C-peptide at diagnosis were 454 mg/dL (356–568), 11.8% (10.1–13.4) and 0.50 µg/L (0.30–0.79), respectively. DKA at T1D diagnosis was present in 48.4% (76/157). For eight centers with complete 2018 to 2021 data (all calendar months), no overall significant increase in T1D cases was observed during the COVID-19 pandemic, i.e. 90 cases in 2018, 90 cases in 2019, 112 in 2020 and 100 in 2021 (P for trend = 0.36). Two of the centers, Faro (CHUA) and Dona Estefânia (CHULC) hospitals, did however see an increase in T1D from 2019 to 2020. No significant changes in glucose (P = 0.32), HbA1c (P = 0.68), fasting C-peptide (P = 0.20) or DKA frequency (P = 0.68) at the time of T1D diagnosis were observed over the entire study period. Conclusion: The T1D incidence did not increase significantly, when comparing the years before and during the COVID-19 pandemic, nor did key metabolic parameters or number of DKA episodes change. [ABSTRACT FROM AUTHOR]

Evaluating stroke campaigns and associated behavioural changes is crucial to assess intervention effectiveness and inform future strategies. We aimed to evaluate patient's and bystanders' foreknowledge of stroke signs and symptoms and their response at stroke onset. We interviewed stroke patients using a validated questionnaire or their bystanders if the stroke patient had disabling stroke. The questionnaire was administered to 165 participants, 142 (86.1%) stroke patients and 23 (13.9%) bystanders. The mean age was 52.6 (SD = 11.7), and male–female ratio was 7:1. Among the participants, 33 (20.1%) had foreknowledge of stroke signs, and of these, 27 (16.5%) were aware of the stroke campaign in Qatar. The behavioural responses at stroke onset included; activating Emergency Medical Services (EMS) (n = 55, 33.3%), calling friends/relatives (n = 69, 41.8%), driving to hospital (n = 33, 20%), waiting for improvement in condition (n = 21, 12.7%). There was no association of ethnicity, marital status, or campaign awareness with EMS activation. Despite limited community awareness of stroke signs and campaign, help-seeking behaviour through EMS activation was generally high, underscoring the need for focused educational efforts and public health interventions. [ABSTRACT FROM AUTHOR]

Objective: The study aimed to investigate the clinical characteristics of patients with multi-canal benign paroxysmal positional vertigo (MC-BPPV). Methods: We performed a retrospective analysis of 927 patients with BPPV who were admitted to our hospital between January 1, 2016 and December 31, 2019. The clinical data of all patients were collected. The Dix-Hallpike, straight head-hanging, and supine Roll tests were performed in all patients. The nystagmus was recorded using videonystagmography. The clinical characteristics of patients with MC-BPPV and single canal BPPV (SC-BPPV) was analyzed and compared. Results: Among 927 patients included, 49 (5.29%) patients had MC-BPPV, 878 (94.71%) patients had SC-BPPV. There were significant differences in the male to female ratio (1:3.90 vs 1:1.81, P <.05), mean age (62.47±12.51 vs 59.04±13.72, P <.05), as well as the ratio of cupulolithiasis to canalithiasis (1:1.45 vs 1:4.78, P <.01) between patients with MC-BPPV and SC-BPPV. The frequency of involvement of PC, HC, and AC were involved for 66 (67.35%), 23 (23.47%), and 9 (9.18%) times, respectively, in patients with MC-BPPV, which were involved in 581 (66.17%), 281 (32.0%), and 16 (1.82%) patients, respectively, in patients with SC-BPPV. No significant difference was found in the frequency of involvement of PC and HC between patients with MC-BPPV and SC-BPPV, while there was significant difference in the frequency of AC involvement between 2 groups (P <.01). Ipsilateral PC-HC-BPPV (n = 18) and bilateral PC-BPPV (n=19) were the most common among patients with MC-BPPV. Twenty-six (53.06%) patients had ipsilateral MC-BPPV, 23 (46.94%) had bilateral MC-BPPV. Of the 26 patients with ipsilateral MC-BPPV, 7 patients combined with unilateral peripheral vestibular disorder. Conclusion: Patients with MC-BPPV had a significantly older mean age at disease onset and a higher proportion of females compared with patients with SC-BPPV. Cupulolithiasis was more common in MC-BPPV. AC involvement was also much more common in MC-BPPV than in SC-BPPV. [ABSTRACT FROM AUTHOR]

Both diabetes mellitus (DM) and hypertension (HTN) have been on the rise in recent decades all over the world more remarkably in developing countries like India. We intend to measure the prevalence of DM and HTN in the Indian population and to compare the trends and various correlates of these diseases in NFHS (National Family Health Survey)-4 and 5. Data of NFHS-4 and 5 were accessed from dhs program website. All statistical analyses were done in SAS (version 9.4). Mixed effects survey logistic regression models were used for estimating odds ratio (OR).p-values <0.05 were considered significant.1,637,762 individual case entries were evaluated. Both the diseases showed an increasing trend as per the advancing age in both sexes. The highest prevalence of DM is seen in the age group of 45–49 years (7.8%) in females and > 50 years (11.9%) in males as per NFHS-5. Similarly, the highest prevalence of HTN was seen in the age group of45–49 years (31.2%) in females and > 50 years (41.4%) in males as per NFHS-5. The OR (95% CI) of prevalence of DM, HTN and both the diseases in age group >50 years was 14.46 (13.14–15.7), 16.65 (15.78–17.6), 79.5 (64.76–97.73) respectively when compared to reference age group15-19 years. Highest odds for having both DM, HTN concurrently was in age >50 years with aOR(95% CI) 65.32 (52.26–72.63) in NFHS 4 and 35.57 (97.47–45.53) in NFHS 5.Rise in prevalence of DM, HTN and concurrent presence is noted with an apparent increase in cases. [ABSTRACT FROM AUTHOR]

Objective: To translate Amyotrophic Lateral Sclerosis-Specific Quality of Life-Short Form (ALSSQOL-SF) and test its reliability and validity, so that explore feasibility in Chinese mainland and make up the gap of specific tools for measuring quality of life of patients with ALS. Methods: This was a cross-sectional design. The Brislin translation model was used to translate ALSSQOL-SF, and the Chinese version of ALSSQOL-SF (C-ALSSQOL-SF) was revised through cultural adaptation and pre-test. The convenience sampling method was used to investigate 138 patients with ALS in Tianjin to test the reliability and validity of the C-ALSSQOL-SF. Results: The C-ALSSQOL-SF included 20 items, covering 6 dimensions: physical symptoms, bulbar function, negative emotion, interaction with people and the environment, religiosity and intimacy. The scale-level content validity index (S-CVI) of C-ALSSQOL-SF was 0.964, and the item-level content validity index (I-CVI) was between 0.857 to 1.000. The results of Confirmatory Factor Analysis (CFA) showed that CMIN/DF = 1.161, RMSEA = 0.034, GFI = 0.892, IFI = 0.976, TLI = 0.969, CFI = 0.975, and the 6-factor model fitted well. The scores of C-ALSSQOL-SF and WHOQOL-BREF were positively correlated (r = 0.745). The Cronbach's α coefficient of the scale was 0.85, the Cronbach's α coefficient of each dimension was between 0.59 to 0.86, and the split-half reliability was 0.78. Conclusion: The Chinese version of ALSSQOL-SF has good reliability and validity, and can be used as a tool to evaluate the quality of life of patients with ALS in Chinese mainland. [ABSTRACT FROM AUTHOR]

A ~3-kb deletion-type DNA copy number variation (CNV, esv3587290) located at intron 7 of the VANGL1 gene (1p13.1, MIM*610132) has been proposed as a genetic factor in lupus nephritis (LN) development in adult systemic lupus erythematosus (SLE) patients across European-descent populations, but its replication in other ethnicities has been inconsistent and its association with LN in childhood-onset SLE (cSLE) remains unknown. Here, we performed an exploratory association study in a sample of 66 unrelated cSLE Mexican patients (11 males, 55 females; ages 7.8 to 18.6 years). Two stratified groups were compared: cSLE patients with (N = 39) or without (N = 27) LN, as diagnosed by renal biopsy (N = 17), proteinuria (N = 33), urinary protein–creatinine ratio > 0.2 (N = 34), and erythrocyturia and/or granular casts in urinary sediment (N = 16). For esv3587290 CNV genotyping, we performed an end-point PCR assay with breakpoint confirmation using Sanger sequencing. We also determined the allelic frequencies of the esv3587290 CNV in 181 deidentified ethnically matched individuals (reference group). The obtained genotypes were tested for Hardy–Weinberg equilibrium using the χ2 test. Associations between LN and esv3587290 CNV were tested by calculating the odds ratio (OR) and using Pearson's χ2 tests, with a 95% confidence interval and p ≤ 0.05. The esv3587290 CNV allele (OR 0.108, 95% CI 0.034–0.33, p = 0.0003) and the heterozygous genotype (OR 0.04, 95% CI 0.119–0.9811, p = 0.002) showed a significant protective effect against LN development. Finally, we characterized the precise breakpoint of the esv3587290 CNV to be NG_016548.1(NM_138959.3):c.1314+1339_1315-897del in our population. This report supports the notion that a broad genetic heterogeneity underlies the susceptibility for developing LN. [ABSTRACT FROM AUTHOR]

Since October 2022, alerts have spread from several countries about the increase in invasive group A streptococcal (iGAS) and scarlet fever cases affecting young children. We aim to analyze the epidemiology of GAS infections in the last 12 years in our hospital and identify the clinical features of invasive cases observed in 2023. We conducted a retrospective study enrolling children and adolescents hospitalized at our pediatric clinic from January to December 2023 for a definitive diagnosis of iGAS infection. Clinical, laboratory, and imaging data were collected and analyzed. Comparing 2016 and 2023, we observed a similar number of GAS infections (65 vs. 60 cases). Five children with iGAS infection were hospitalized between March and April 2023. The median age was five years. At admission, all patients showed tachycardia disproportionate to their body temperature. Vomiting was a recurrent symptom (80%). Laboratory tests mostly showed lymphopenia, hyponatremia, and high inflammatory markers. The number of pediatric iGAS cases significantly increased in 2023. Clinical (pre-school-aged children with high fever, unexplained tachycardia, and vomiting) and laboratory parameters (high procalcitonin levels, hyponatremia, and lymphopenia) could help identify and suspect a potential iGAS infection. [ABSTRACT FROM AUTHOR]

Introduction: Women and those with younger onset Parkinson's Disease (YOPD) are typically diagnosed later and face unique situations and challenges. This essay aims to raise awareness of the difficulties in diagnosing YOPD and the need for a personalised approach to care for women with YOPD. Methods: Two professional women with YOPD (academic physiotherapist and practicing dentist) and a female neurologist (clinician academic) came together to write a narrative essay on their personal experience and perspectives in relation to women and YOPD. Results: The essay outlines how the experience of diagnosis is likened to a complex puzzle box with many interlocking components that are hidden and difficult to solve. The concerns of the women about their identity, work, family and the future, with most supports targeting those that are older and retired are outlined. Conclusion: It is concluded that YOPD is a complex puzzle to solve, but can be done by understanding all the intricate interlocking components of the puzzle and combined with greater awareness could lead to earlier diagnosis and the delivery of successful person‐centred care. Patient or Public Contribution: People with lived experience were involved in the essay conception and writing. [ABSTRACT FROM AUTHOR]

The extraocular muscles (EOMs) possess unique characteristics that set them apart from other skeletal muscles. These muscles, responsible for eye movements, exhibit remarkable resistance to various muscular dystrophies and aging, presenting a significant contrast to the vulnerability of skeletal muscles to these conditions. In this review, we delve into the cellular and molecular underpinnings of the distinct properties of EOMs. We explore their structural complexity, highlighting differences in fiber types, innervation patterns, and developmental origins. Notably, EOM fibers express a diverse array of myosin heavy-chain isoforms, retaining embryonic forms into adulthood. Moreover, their motor innervation is characterized by a high ratio of nerve fibers to muscle fibers and the presence of unique neuromuscular junctions. These features contribute to the specialized functions of EOMs, including rapid and precise eye movements. Understanding the mechanisms behind the resilience of EOMs to disease and aging may offer insights into potential therapeutic strategies for treating muscular dystrophies and myopathies affecting other skeletal muscles. [ABSTRACT FROM AUTHOR]

Dynamic changes in genomic DNA methylation patterns govern the epigenetic developmental programs and accompany the organism's aging. Epigenetic clock (eAge) algorithms utilize DNA methylation to estimate the age and risk factors for diseases as well as analyze the impact of various interventions. High-throughput bisulfite sequencing methods, such as reduced-representation bisulfite sequencing (RRBS) or whole genome bisulfite sequencing (WGBS), provide an opportunity to identify the genomic regions of disordered or heterogeneous DNA methylation, which might be associated with cell-type heterogeneity, DNA methylation erosion, and allele-specific methylation. We systematically evaluated the applicability of five scores assessing the variability of methylation patterns by evaluating within-sample heterogeneity (WSH) to construct human blood epigenetic clock models using RRBS data. The best performance was demonstrated by the model based on a metric designed to assess DNA methylation erosion with an MAE of 3.686 years. We also trained a prediction model that uses the average methylation level over genomic regions. Although this region-based model was relatively more efficient than the WSH-based model, the latter required the analysis of just a few short genomic regions and, therefore, could be a useful tool to design a reduced epigenetic clock that is analyzed by targeted next-generation sequencing. [ABSTRACT FROM AUTHOR]

Simple Summary: Newly diagnosed type 2 diabetes mellitus is associated with a higher risk of cancer, possibly in young individuals with diabetes. While the incidence of cancer is mildly decreasing in the background population, it does not decrease in patients with type 2 diabetes. In non-diabetic persons, certain types of cancer also occur in young age, while the 60–69-year-old group dominates for cancer cases in patients with type 2 diabetes. The majority of the new cancer cases is recognized within 6 months after the diagnosis of diabetes. This may call for increased cancer surveillance in patients with newly diagnosed type 2 diabetes mellitus. (1) Background: Patients with type 2 diabetes mellitus (T2DM) are at higher risk of cancer but how these two diseases associate is still debated. The goal of this study was the assessment of the overall incidence of cancer among patients with newly diagnosed T2DM in Hungary. (2) Methods: A nationwide, retrospective, longitudinal study was performed using a Hungarian database. After exclusion of cases of age < 18 years, with gestational diabetes, with polycystic ovary syndrome, and with type 1 and prevalent type 2 diabetes mellitus, the incident T2DM (approx. 50,000 cases yearly) and for comparison, the diabetes-free Hungarian adult population (approx. 7,000,000 cases yearly) was included in the study. The primary endpoints were the overall and site-specific incidence and annual percentage change of the incidence of cancer in both populations. (3) Results: The overall incidence of cancer in patients amounted to 29.4/1000 and 6.6/1000 with or without T2DM, respectively, and the OR (95%CI) of cancer of the T2DM group was 4.32 (4.14–4.53), p < 0.0001. The risk of having cancer was age dependent. The incidence of cancer was declining in the non-diabetic but was unchanged in the T2DM population. The average lag time of diagnosing cancer after the detection of T2DM was 3.86 months. (4) Conclusions: Incident T2DM is associated with a significantly higher overall risk of incident cancer, with a reverse correlation of age. Newly registered T2DM patients were suggested to be screened for cancer within 6 months. [ABSTRACT FROM AUTHOR]

Objective. Microvascular complications increase the risk of cardiovascular disease and premature death in adults with type 1 diabetes. We examined the association between microvascular complications during adolescence, including cardiac autonomic nerve dysfunction and subsequent mortality. Research Design and Methods. We undertook data linkage with the Australian National Death Index in a cohort of 409 adolescents (diagnosed between 1973 and 1993), 48% male, median age at final complications assessment 17.4 years (interquartile range: 16.0–18.9), followed longitudinally for median 22.3 years (21.0–23.4) from diagnosis. Generalized estimating equations (GEE) were used to examine associations between mortality and adolescent complications. Mortality risk was calculated as standardized mortality ratio (SMR). Results. At final adolescent visit, 20% had CAN abnormality, 30% abnormal pupillary response, 20% albuminuria, 40% early elevation of albumin excretion rate (AER) and 45% retinopathy. Data linkage 8–13 years later showed 14 were deceased (3% of cohort), 57% male, median age 28.3 years (24.8–32.9). Acute or chronic diabetes complications accounted for 25% of deaths. In multivariable GEE, elevated AER (OR 4.54, 1.23–16.80, p = 0.030), pupillary abnormality (OR 4.27, 1.20–15.22, p = 0.023), systolic blood pressure SDS (OR 2.17, 1.26–3.74, p = 0.005) and CAN (OR 4.65, 1.03–21.0, p = 0.045) predicted mortality. HbA1c was not significant. SMR was 2.5 (1.4–4.2) and was higher in females (SMR 3.5, 1.3–7.8) but not in males (SMR 2.1, 0.9–4.0). Conclusion. Mortality in young adults with type 1 diabetes is predicted by subclinical markers of autonomic neuropathy and elevated AER during adolescence, but not glycemia. Mortality was over twice that of the background population in females but not in males. [ABSTRACT FROM AUTHOR]

Aging is the primary risk factor for cognitive decline, impacting multiple cognitive domains and significantly elevating the risk of conditions such as mild cognitive impairment and dementia. In addition to aging, several diseases contribute to cognitive decline. Alzheimer's disease, a progressive neurodegenerative disorder, leads to the loss of neurons and synapses in the brain, resulting in a profound decline in cognitive abilities and functional capacity. Several studies provide compelling evidence that modifiable lifestyle factors play a crucial role in influencing cognitive health. Adopting healthier behaviors has been shown to significantly reduce the risk of cognitive decline. Genetic factors also play a crucial role in cognitive decline, with several genes being identified that influence the risk of developing conditions like Alzheimer's disease and other dementias. Long-term use of opioids and cocaine is also associated with cognitive decline, affecting functions such as memory and executive processes. Understanding the factors contributing to cognitive decline in aging and disease is essential for developing strategies to mitigate its impact. The drugs available to treat patients with cognitive decline due to advanced aging and drug abuse are also summarized. [ABSTRACT FROM AUTHOR]

Aim: The study was aimed to find out the efficacy of a stool color card (SCC) in differentiating biliary atresia (BA) from non-BA in resource-limited countries. Background: stool color screening system was introduced in 2004 which lead to marked improvement in sensitivity of detecting BA. Methods: This cross-sectional observational study was conducted from January, 2019 through July, 2022 on purposively sampled infants who developed jaundice before three months of age, had direct bilirubin of > 20 % of total with pale stool and dark urine. Results: 144 cases (male, 96) were included in the study and their mean age at admission was 87.3±37.2 days and mean age at onset of jaundice was 6.1±7.7 days. BA was confirmed in 106 (73.6%) cases and 38 (26.4%) children were in non-BA group. Frequency of persistent pale stool between BA and non- BA were 88 vs 8 (83.0 % Vs 21.0 %) which was highly significant (p=0.000). Mean difference of total and direct serum bilirubin, median alanine transferase and alkaline phosphatase were not statistically significant between two groups. Median of serum gamma glutamyl transpeptidase (GGT) in BA was 570 U/L and in non-BA it was 138.0 U/L which was statistically significant (p=0.000). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of SCC were 83%, 78.9%, 91.7%, 62.5% and 81.9% respectively. Conclusion: SCC has good sensitivity to diagnose BA but failed to prove better specificity to rely simply on it. SCC may be used as early screening tool for prompt referral to appropriate medical care centers for final evaluation of BA. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to compare two groups of celiac patients: the first one, in which diagnosis was based on a "biopsy sparing" approach according to the 2012 ESPGHAN criteria, and the second one, based on the biopsy approach like the one of the 1991 Revised Criteria, in order to find relevant difference for sex, M/F ratio, age at diagnosis, clinical features at the onset, presence and prevalence of concomitant autoimmune disorders. Methods: Our study involves 61 patients having the Celiac Disease (CD) onset from February 2013 to February 2020. The 32 patients who received diagnosis according "biopsy sparing" criteria were enrolled in group (1) The 29 patients who received diagnosis by duodenal biopsy were enrolled in group (2) Prevalence of comorbidities was analysed through chi-square test. Results: In group 1 the prevalence of comorbidities such as Insulin-Dependent Diabetes Mellitus (IDDM) and thyroiditis was of 53%, while in group 2 it was only of 24%. Analysing the IDDM prevalence between the two groups we found a relevant difference. At the same time, the prevalence of thyroiditis was also significantly different. In group 1, male patients, in particular, would seem to have a higher incidence of CD related autoimmune disorders. Conclusions: An increased prevalence of IDDM, thyroiditis and juvenile idiopathic arthritis (JIA) in the first group would show that the "biopsy sparing" approach could expose patients to a greater length of disease activity that might be responsible for the onset of such comorbidities. Further studies should be carried out on more numerous samples of patients in order to confirm or not these data. [ABSTRACT FROM AUTHOR]

Introduction: Preconception care (PCC) is an important window to target maternal morbidity and mortality, especially for women with chronic diseases. However, little is known about knowledge and attitudes towards preconception care among women with chronic disease. Therefore, this study aimed to assess knowledge and attitude towards preconception care and associated factors among women of reproductive age with chronic disease in Amhara region referral hospitals, Ethiopia, 2022. Method: A multicenter cross-sectional study was conducted in Amhara region referral hospitals from April 15 to June 1, 2022. A total 828 women of reproductive age with chronic disease in four referral hospitals were selected using a stratified and systematic random sampling technique. Data was collected by using a structured interviewer-administered questionnaire and chart review. Bivariate and multivariable logistic regression analyses were carried out. An Adjusted Odds Ratio (AOR) with 95% Confidence Interval (CI) was computed to see the strength of association between outcome and independent variables. P-value < 0.05 was considered as statistically significant. Results: This study found that 55.6% of respondents had a good knowledge of preconception care, and 50.2% had a good attitude towards PCC. Formal education (AOR: 1.997, 95% CI: 1.247, 3.196), primiparity (AOR: 2.589, 95% CI: 1.132, 5.921), preconception counseling (AOR: 3.404, 95% CI: 2.170, 5.340), duration of disease ≥ 5 years (AOR: 6.495, 95% CI: 4.091, 10.310) were significantly associated with knowledge of PCC. Older age (≥ 35years) (AOR: 2.143, 95% CI: 1.058, 4.339), secondary education and above (AOR: 2.427, 95% CI: 1.421, 4.146), history of modern family planning use (AOR: 2.853 95% CI: 1.866, 4.362), preconception counseling (AOR: 2.209, 95% CI: 1.429, 3.414) and good knowledge of PCC (AOR: 20.629, 95% CI: 12.425, 34.249) were significantly associated with attitude towards PCC. Conclusions: Women's knowledge and attitude towards preconception care were found to be low. Important measures include promoting secondary education and carrying out awareness campaigns, incorporating preconception counseling into routine medical follow-up care, and encouraging the use of modern family planning methods. [ABSTRACT FROM AUTHOR]

The blood-brain barrier (BBB) is pivotal in maintaining neuronal physiology within the brain. This review delves into the alterations of the BBB specifically in the context of geriatric epilepsy. We examine how age-related changes in the BBB contribute to the pathogenesis of epilepsy in the elderly and present significant challenges in pharmacotherapy. Subsequently, we evaluate recent advancements in drug delivery methods targeting the BBB, as well as alternative approaches that could bypass the BBB's restrictive nature. We particularly highlight the use of neurotropic viruses and various synthetic nanoparticles that have been investigated for delivering a range of antiepileptic drugs. Additionally, the advantage and limitation of these diverse delivery methods are discussed. Finally, we analyze the potential efficacy of different drug delivery approaches in the treatment of geriatric epilepsy, aiming to provide insights into more effective management of this condition in the elderly population. [ABSTRACT FROM AUTHOR]

The gradual aging of the global population has led to a surge in age-related diseases, which seriously threaten human health. Researchers are dedicated to understanding and coping with the complexities of aging, constantly uncovering the substances and mechanism related to aging like chronic low-grade inflammation. The NOD-like receptor protein 3 (NLRP3), a key regulator of the innate immune response, recognizes molecular patterns associated with pathogens and injury, initiating an intrinsic inflammatory immune response. Dysfunctional NLRP3 is linked to the onset of related diseases, particularly in the context of aging. Therefore, a profound comprehension of the regulatory mechanisms of the NLRP3 inflammasome in aging-related diseases holds the potential to enhance treatment strategies for these conditions. In this article, we review the significance of the NLRP3 inflammasome in the initiation and progression of diverse aging-related diseases. Furthermore, we explore preventive and therapeutic strategies for aging and related diseases by manipulating the NLRP3 inflammasome, along with its upstream and downstream mechanisms. [ABSTRACT FROM AUTHOR]

Background: Childhood myopia represents a global concern with increasing prevalence in recent decades. Lifestyle factors significantly impact myopia. Aim: To evaluate lifestyle factors in myopic children from a metropolitan area in Europe. Methods: This was a descriptive study including myopic subjects aged 4–18 years. Patient demographic and clinical data were collected, including cycloplegic refraction in spherical equivalent refraction (SER) and axial length (AL). In addition, a questionnaire on lifestyle factors was conducted between September 2022 and April 2023. Results: A total of 321 myopic children were included, aged 10.72 ± 3.05 years, of whom 51.4% were boys, with SER −2.25 ± 1.9 D and AL 24.54 ± 0.98 mm. The mean age of myopia onset was 7.69 ± 3.05 years. A total of 59.8% had family history of myopia. Those children who had <2 h/day of screen time (on weekdays) presented SER −2 ± 1.91 D, compared to those who had >2 h/day, SER: −2.50 ±1.88 D (p = 0.009). Children who spent <2 h/day doing near work after school were less myopic compared to those who spent >2 h/day (SER: −1.75 ± 1.83 vs. SER: −2.75 ± 1.82, respectively, p = 0.03). However, no significant association was observed between SER and AL and time spent outdoors nor between SER and AL and academic performance (p > 0.05). Conclusions: Screen time and near-work time appear to be lifestyle factors related to myopia. [ABSTRACT FROM AUTHOR]

Background: The impact of the COVID-19 pandemic on the incidence rate of childhood type 1 diabetes (T1D) is controversial. Our aim was to analyze the incidence of new-onset T1D among children aged 0–17 before and during the COVID-19 pandemic in Israel. Methods: Data obtained from the national T1D registry for children aged 0–17 were analyzed for the pre-pandemic (1997–2019) and pandemic (2020–2022) periods. In the pre-pandemic period, 7246 children with newly diagnosed T1D were compared with 1490 children diagnosed during the pandemic period. Results: T1D incidence significantly increased in the 0–17 age group from a mean of 12.9/105 (pre-pandemic) to 17.7/105 and 16.7/105 during the first two years of the pandemic (2020 and 2021, respectively) (p = 0.0001). Stratifying by age group (0–4, 5–9, 10–14, and 15–17) revealed a significant increase in the 5–9, 10–14, and 15–17 groups, both in 2020 (p = 0.0001) and in 2021 (p = 0.0001). The incidence rate in the 0–4 age group showed no change in the first year of the pandemic (2020) (p = 0.4). However, in the second year of the pandemic (2021), there was a significant increase from 6.3/105 in the pre-pandemic period to 9.1/105 (p = 0.001). Anti-COVID-19 vaccination in 2022 led to a significant decrease in the incidence rates in the 10–14 and 15–17 age groups (p = 0.03 and p = 0.02, respectively). Conclusion: The COVID-19 pandemic was associated with a significant increase in the incidence of new-onset T1D in prepubertal and pubertal children. Anti-COVID-19 vaccination decreased the incidence rate significantly only in pubertal children. [ABSTRACT FROM AUTHOR]

Background: The effects of subthalamic nucleus deep brain stimulation (STNDBS) on the cognition and mood of patients with PD are still not uniformly concluded, and young-onset Parkinson's disease (YOPD) is even less explored. Objective: To observe the effectiveness of STN-DBS on the cognition and mood of YOPD patients. Methods: A total of 27 subjects, with a mean age at onset of 39.48 ± 6.24 and age at surgery for STN-DBS of 48.44 ± 4.85, were followed up preoperatively and for 2 years postoperatively. Using the Unified Parkinson disease rating scale (UPDRS), H&Y(Hoehn and Yahr stage), 39-Item Parkinson's Disease Questionnaire (PDQ-39), Mini-mental state examination (MMSE), Montreal Cognitive Assessment (MoCA), Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) to assess motor, cognition, and mood. Results: At the 2-year follow-up after STN-DBS, YOPD patients showed significant improvements in motor and quality of life (UPDRS III: p < 0.001, PDQ-39: p < 0.001); overall cognition was not significantly different from preoperative (MMSE: p = 0.275, MoCA: p = 0.913), although language function was significantly impaired compared to preoperative (MMSE: p = 0.004, MoCA: p = 0.009); depression and anxiety symptoms also improved significantly (HAMD: p < 0.001, HAMA: p < 0.001) and the depression score correlated significantly with motor (preoperative: r = 0.493, p = 0.009), disease duration (preoperative: r = 0.519, p = 0.006; postoperative: r = 0.406, p = 0.036) and H&Y (preoperative: r = 0.430, p = 0.025; postoperative: r = 0.387, p = 0.046); total anxiety scores were also significantly correlated with motor (preoperative: r = 0.553, p = 0.003; postoperative: r = 0.444, p = 0.020), disease duration (preoperative: r = 0.417, p = 0.031), PDQ-39 (preoperative: r = 0.464, p = 0.015) and H&Y (preoperative: r = 0.440, p = 0.022; postoperative: r = 0.526, p = 0.005). Conclusion: STN-DBS is a safe and effective treatment for YOPD. The mood improved significantly, and overall cognition was not impaired, were only verbal fluency decreased but did not affect the improvement in quality of life. [ABSTRACT FROM AUTHOR]

Eosinophilic esophagitis (EoE) is a chronic, progressive, type 2 inflammatory disease with increasing global prevalence. An eosinophil-predominant inflammation that permeates the epithelium and deeper esophageal layers characterizes the disease. Several cytokines, mainly derived from inflammatory T-helper 2 (Th2) cells and epithelial cells, are involved in perpetuating inflammatory responses by increasing surface permeability and promoting tissue remodeling characterized by epithelial–mesenchymal transition (EMT) and collagen deposition. This leads to esophageal strictures and narrow caliber esophagi, which are proportional a patient's age and untreated disease length. Pathophysiological mechanisms leading to EoE have been described in recent years, and transforming growth factor beta (TGF)-beta have been involved in fibrotic phenomena in EoE. However, evidence on the dependence of these phenomena on TGF-beta is scarce and contradictory. This review provides state-of-the art knowledge on intimate mechanisms of esophageal fibrosis in EoE and its clinical consequences. [ABSTRACT FROM AUTHOR]

Background: Slower paces of aging are related to lower risk of developing diseases and premature death. Therefore, the greatest challenge of modern societies is to ensure that the increase in lifespan is accompanied by an increase in health span. To better understand the differences in human lifespan, new insight concerning the relationship between lifespan and the age of onset of diseases, and the ability to avoid them is needed. We aimed to comprehensively study, at a population-wide level, the sex-specific disease patterns associated with human lifespan. Methods: Observational data from the SIDIAP database of a cohort of 482,058 individuals that died in Catalonia (Spain) at ages over 50 years old between the 1st of January 2006 and the 30th of June 2022 were included. The time to the onset of the first disease in multiple organ systems, the prevalence of escapers, the percentage of life free of disease, and their relationship with lifespan were evaluated considering sex-specific traits. Results: In the study cohort, 50.4% of the participants were women and the mean lifespan was 83 years. The results show novel relationships between the age of onset of disease, health span, and lifespan. The key findings include: Firstly, the onset of both single and multisystem diseases is progressively delayed as lifespan increases. Secondly, the prevalence of escapers is lower in lifespans around life expectancy. Thirdly, the number of disease-free systems decreases until individuals reach lifespans around 87–88 years old, at which point it starts to increase. Furthermore, long-lived women are less susceptible to multisystem diseases. The associations between health span and lifespan are system-dependent, and disease onset and the percentage of life spent free of disease at the time of death contribute to explaining lifespan variability. Lastly, the study highlights significant system-specific disparities between women and men. Conclusions: Health interventions focused on delaying aging and age-related diseases should be the most effective in increasing not only lifespan but also health span. The findings of this research highlight the relevance of Electronic Health Records in studying the aging process and open up new possibilities in age-related disease prevention that should assist primary care professionals in devising individualized care and treatment plans. [ABSTRACT FROM AUTHOR]

Objective: The significance of the onset of seizure based on the medical and social aspects of epilepsy. The aim of this study was to investigate the age of seizure onset based on the specific characteristics of each age of seizure onset in many epilepsy syndromes to make an appropriate diagnosis. Methods: The age at epilepsy was retrospectively studied in 155 women aged between 16 and 45 years with a verified diagnosis of epilepsy. The epidemiological method revealed the age at epilepsy onset, and females were divided into three groups: pre-puberty (10-11 years old), puberty (10-18 years old), and postpuberty (18+ years old). A correlation study of the frequency of onset with the periods of formation and function of the female reproductive tract was conducted. Results: A statistically significant quantitative predominance of females with epilepsy onset during puberty (p<0.001) was identified. Statistically valid was the prevalence of epilepsy onset in the combined age range of 12 to16 (p<0.001). A direct link between menarche and epilepsy onset was detected in the general cohort in 13% of females, which is among the risk factors for catamenial seizure onset. Conclusion: Epilepsy onset in females of reproductive age dominates during childhood development. In more than half of the cases, the epilepsy onset occurs in the puberty period. Epilepsy onset most often occurs between the ages of 12 and 16. Seizure onset occurs at the ages of 12-16 years during menstrual bleeding and ovulatory cycle development due to the proconvulsive effects of estrogens. [ABSTRACT FROM AUTHOR]

(1) Background: Neonatal early-onset sepsis (EOS) is associated with important mortality and morbidity. The aims of this study were to evaluate the association between serum and hematological biomarkers with early onset neonatal sepsis in a cohort of patients with prolonged rupture of membranes (PROM) and to calculate their diagnostic accuracy. (2) Methods: A retrospective cohort study was conducted on 1355 newborns with PROM admitted between January 2017 and March 2020, who were divided into two groups: group A, with PROM ≥ 18 h, and group B, with ROM < 18 h. Both groups were further split into subgroups: proven sepsis, presumed sepsis, and no sepsis. Descriptive statistics, analysis of variance (ANOVA) and a Random Effects Generalized Least Squares (GLS) regression were used to evaluate the data. (3) Results: The statistically significant predictors of neonatal sepsis were the high white blood cell count from the first (p = 0.005) and third day (p = 0.028), and high C-reactive protein (CRP) values from the first day (p = 0.004). Procalcitonin (area under the curve—AUC = 0.78) and CRP (AUC = 0.76) measured on the first day had the best predictive performance for early-onset neonatal sepsis. (4) Conclusions: Our results outline the feasibility of using procalcitonin and CRP measured on the first day taken individually in order to increase the detection rate of early-onset neonatal sepsis, in the absence of positive blood culture. [ABSTRACT FROM AUTHOR]

This document is an editorial published in the journal Frontiers in Cell & Developmental Biology. It discusses the use of multi-omics studies to understand aging and age-related diseases. The editorial highlights the importance of studying aging mechanisms and identifying biomarkers for these diseases. It also provides examples of studies that have used genomic, transcriptomic, metabolomic, and proteomic data to identify potential biomarkers for aging and age-related diseases such as cancer and Alzheimer's disease. The editorial emphasizes the potential therapeutic benefits of these insights and the opportunities provided by multi-omics methods in understanding the molecular alterations of aging. [Extracted from the article]

This editorial titled "Cytoskeletal alterations in aging and disease" explores the role of the cytoskeleton in neuronal development and maintenance, specifically focusing on microtubules, actin, and intermediate filaments. The dysfunction of these components can contribute to neurodegenerative diseases like Alzheimer's and Charcot-Marie-Tooth disease. The editorial highlights the importance of posttranslational modifications and microtubule-associated proteins in regulating the cytoskeleton and their potential implications for neurodegenerative disorders. The authors stress the need for further research to understand the molecular mechanisms behind these cytoskeletal alterations and their impact on aging and disease. The document includes references to scientific articles on microtubules and their role in neurodegenerative diseases, as well as information about grants and conflicts of interest related to the research. [Extracted from the article]