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Context: Excessive hip adduction and internal rotation are abnormal movements that may lead to the onset and progression of patellofemoral pain. Previous studies have reported that lower dynamic frontal plane hip joint stiffness in the gait of women is associated with the magnitude of hip adduction and internal rotation angles. However, the factors contributing to the lack of dynamic frontal plane hip joint stiffness in the gait of young women are unclear. This study aims to investigate the factors affecting dynamic frontal plane hip joint stiffness during the weight-acceptance phase of the gait of healthy young women. Design: Cross-sectional study. Methods: This study included 30 healthy women between the ages of 18 and 30 years. The pelvic width/femur length ratio was calculated by dividing the pelvic width by the femur length. Data on hip kinematics and kinetics and activation of the gluteus maximus and medius, tensor fasciae latae, and adductor longus muscles during gait were collected using a motion capture system, force plates, and surface electromyography. Stepwise multiple regression analysis was conducted to determine the extent to which each independent factor affected dynamic frontal plane hip joint stiffness. Results: In healthy young women, decreased dynamic frontal plane hip joint stiffness was associated with decreased muscle activity of the gluteus maximus during the gait, as well as greater pelvic width/femur length ratio. Conclusions: Women with a relatively great pelvic width relative to femur length may have more difficulty in producing dynamic frontal plane hip joint stiffness. However, increasing the muscle activity of the gluteus maximus may contribute to increased dynamic frontal plane hip joint stiffness. [ABSTRACT FROM AUTHOR]

Introduction Objectives Materials and methods Results Discussion and conclusion Several robust epidemiological studies suggest that men are often engaged in sexual relationships with younger women with a variable, age‐dependent age difference. However, the ageing process determines a significant worsening of the andrological status, which favors the onset of erectile dysfunction and hypogonadism.To analyze the effects of differences in age between the partners [delta (Δ) age (M − F)] on patients referring to the Andrology Unit of Careggi University Hospital for male sexual dysfunction.A monocentre cohort of 4055 male subjects was evaluated by SIEDY structured interview. The cross‐sectional analysis assessed the psychobiological and relational correlates. The rate of forthcoming major cardiovascular events (MACE) was investigated in the longitudinal analysis. All the models have been adjusted for age, education, lifestyle, and chronic disease score.∆ age (M–F) shows a stepwise increase, according to the increasing age bands of the male partner. ∆ age (M–F) was associated with a greater number of children, at the cost of more conflictual relationships within the family. The phenotype of these relationships is characterized by the report of a partner with a higher sexual desire and a higher ability to reach climax. Men seeking a younger partner show more often a histrionic personality (p = 0.023) and higher testosterone levels (p = 0.032). However, having a younger partner doesn't improve the ability to obtain a full erection. Kaplan–Maier analysis of a longitudinal subgroup of patients followed longitudinally (N = 1402) for 4.3 ± 2,59 years, showed that patients in the fourth quartile had a higher rate of forthcoming MACE versus those in the first quartile (p = 0.005).In subjects with sexual dysfunctions (as in the general population) age‐different relationships increase as a function of male ageing. A greater Δ age (M–F) is associated with specific men and relationship features and a higher risk of MACE. [ABSTRACT FROM AUTHOR]

Background: Childhood-onset systemic lupus erythematosus (c-SLE) is a multifaceted autoimmune disorder predominantly affecting the musculoskeletal (MSK) system. This investigation delineated the spectrum and sequelae of MSK involvement in c-SLE patients. Methods: This retrospective analysis included SLE patients aged ≤ 18 years treated at a tertiary center between 2009 and 2019. Data were extracted from electronic health records. Results: The cohort comprised 321 SLE patients (mean age 13.2 ± 2.5 years, 91.3% female). MSK manifestations were observed in 134 (41.7%) individuals, with joint pain universally present, followed by joint swelling in 32.1% and morning stiffness in 9.7%. Arthritis was documented in 52 (38.8%) patients, whereas 82 (61.2%) had arthralgia. Symmetrical joint involvement was observed in 96 (71.7%) subjects. The knees, wrists, and fingers were most commonly affected, with incidences of 43.3%, 40.3%, and 33.6%, respectively. Neither erosive arthritis nor Jaccoud's arthropathy was detected. MSK symptoms were significantly correlated with older age at diagnosis, the presence of non-scarring alopecia, neuropsychiatric manifestations, and elevated SLE disease activity index scores at diagnosis. Over a median follow-up of 53.6 months (IQR 26.1–84.6), five patients developed septic arthritis or osteomyelitis, and avascular necrosis was identified in 16 (4.9%) patients. Conclusions: Nearly half of c-SLE patients demonstrated MSK manifestations, chiefly characterized by symmetrical involvement of both large and small joints without evidence of erosive arthritis or Jaccoud's arthropathy. Avascular necrosis is a critical concern and warrants close monitoring. [ABSTRACT FROM AUTHOR]

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]

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]

Age-related neurodegenerative diseases, like Alzheimer's disease (AD), are challenging diseases for those affected with no cure and limited treatment options. Functional, human derived brain tissues that represent the diverse genetic background and cellular subtypes contributing to sporadic AD (sAD) are limited. Human stem cell derived brain organoids recapitulate some features of human brain cytoarchitecture and AD-like pathology, providing a tool for illuminating the relationship between AD pathology and neural cell dysregulation leading to cognitive decline. In this review, we explore current strategies for implementing brain organoids in the study of AD as well as the challenges associated with investigating age-related brain diseases using organoid models. [ABSTRACT FROM AUTHOR]

Background: To assess the association between various systemic lupus erythematosus (SLE) disease manifestations, SLE disease activity index 2000 (SLEDAI-2K), systemic lupus international collaborating clinics/American College of Rheumatology Damage Index (SLICC/ACR- SDI) and serum levels of Slit2 in SLE patients. Results: The mean age of SLE patients was 31.12 ± 8.68 years while the age at onset was 26.05 ± 7.60 years. Female: male was 9 vs 1. The mean serum levels of Slit2 in SLE patients were significantly higher than the controls (0.55 ± 0.25 vs 0.42 ± 0.15) (P = 0.013). There was no significant difference in Slit2 levels between patients with active vs inactive SLE (P = 0.353) or between patients with and without lupus nephritis (P = 0.900). An insignificant difference in Slit2 levels was found among SLE patients using SDI (P = 0.982). No significant correlations were observed between the serum Slit2 and SLE patients' demographics, laboratory data, SLEDAI-2K, and SDI except for a positive correlation with platelets and a negative correlation with serum albumin. ROC curve analysis showed that at a cutoff value of 0.44, the area under the curve was 0.677 (95% CI 0.538–0.816, P = 0.013) with a sensitivity of 74%, specificity of 56%, and accuracy of 68%. Conclusion: While we observed elevated serum Slit2 levels in SLE patients, there was no significant correlation observed between serum Slit2 levels and SLE clinical manifestations, disease activity, or damage index. Trial registration: NCT05105217. Registered 3 November 2021 [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]

The average lifespan of humans has been increasing, resulting in a rapidly rising percentage of older individuals and high morbidity of aging-associated diseases, especially cardiovascular diseases (CVDs). Diverse intracellular and extracellular factors that interrupt homeostatic functions in the endoplasmic reticulum (ER) induce ER stress. Cells employ a dynamic signaling pathway of unfolded protein response (UPR) to buffer ER stress. Recent studies have demonstrated that ER stress triggers various cellular processes associated with aging and many agingassociated diseases, including CVDs. Autophagy is a conserved process involving lysosomal degradation and recycling of cytoplasmic components, proteins, organelles, and pathogens that invade the cytoplasm. Autophagy is vital for combating the adverse influence of aging on the heart. The present report summarizes recent studies on the mechanism of ER stress and autophagy and their overlap in aging and on CVD pathogenesis in the context of aging. It also discusses possible therapeutic interventions targeting ER stress and autophagy that might delay aging and prevent or treat CVDs. [ABSTRACT FROM AUTHOR]

Background: Arginine vasopressin deficiency (AVP-D) can occur due to various conditions, so clarifying its cause is important for deciding treatment strategy. Although several cases of AVP-D following coronavirus disease 2019(COVID-19) infection or COVID-19 vaccination have been reported, the diagnosis of the underlying disease has not been reported in most cases. Case presentation: A 75-year-old woman who presented with polydipsia and polyuria 9 weeks after contracting COVID-19 and 5 weeks after receiving the SARS-CoV-2 vaccination, leading to the final diagnosis of AVP-D 8 months after the first appearance of symptoms. Interestingly, pituitary magnetic resonance imaging (MRI) still revealed stalk enlargement frequently observed in patients with SARS-CoV-2 vaccination-induced AVP-D. Although this finding could not rule out any malignancies, we additionally measured anti-rabphilin-3A antibodies, a known marker for lymphocytic infundibulo-neurohypophysitis (LINH), and found that the results were positive, strongly suggesting LINH as the cause of this disease. Thus, we avoided pituitary biopsy. At the follow-up MRI conducted 12 months after the initial consultation, enlargement of the pituitary stalk was still observed. Conclusion: We experienced a case with LINH probably induced by SARS-CoV-2 vaccination. In SARS-CoV-2 vaccination-related LINH, unlike typical LINH, there is a possibility of persistent pituitary stalk enlargement on MRI images for an extended period, posing challenges in differential diagnosis from other conditions. Pituitary stalk enlargement and positive anti-rabphilin-3A antibodies may help in the diagnosis of AVP-D induced by SARS-CoV-2 vaccination. [ABSTRACT FROM AUTHOR]

Aging is characterized by a progressive decline in physiological function and underlies several disabilities, including the increased sensitivity of cells and tissues to undergo pathological oxidative stress. In recent years, efforts have been made to better understand the relationship between age and oxidative stress and further develop therapeutic strategies to minimize the impact of both events on age‐related diseases. In this work, we review the impact of the oxidant and antioxidant systems during aging and disease development and discuss the crosstalk of oxidative stress and other aging processes, with a focus on studies conducted in elderly populations. [ABSTRACT FROM AUTHOR]

The increasing prevalence of myopia worldwide presents a significant public health challenge. A key strategy to combat myopia is with early detection and prediction in children as such examination allows for effective intervention using readily accessible imaging technique. To this end, we introduced DeepMyopia, an artificial intelligence (AI)-enabled decision support system to detect and predict myopia onset and facilitate targeted interventions for children at risk using routine retinal fundus images. Based on deep learning architecture, DeepMyopia had been trained and internally validated on a large cohort of retinal fundus images (n = 1,638,315) and then externally tested on datasets from seven sites in China (n = 22,060). Our results demonstrated robustness of DeepMyopia, with AUCs of 0.908, 0.813, and 0.810 for 1-, 2-, and 3-year myopia onset prediction with the internal test set, and AUCs of 0.796, 0.808, and 0.767 with the external test set. DeepMyopia also effectively stratified children into low- and high-risk groups (p < 0.001) in both test sets. In an emulated randomized controlled trial (eRCT) on the Shanghai outdoor cohort (n = 3303) where DeepMyopia showed effectiveness in myopia prevention compared to NonCyc-based model, with an adjusted relative reduction (ARR) of −17.8%, 95% CI: −29.4%, −6.4%. DeepMyopia-assisted interventions attained quality-adjusted life years (QALYs) of 0.75 (95% CI: 0.53, 1.04) per person and avoided blindness years of 13.54 (95% CI: 9.57, 18.83) per 1 million persons compared to natural lifestyle with no active intervention. Our findings demonstrated DeepMyopia as a reliable and efficient AI-based decision support system for intervention guidance for children. [ABSTRACT FROM AUTHOR]

Objectives: A low handgrip strength (HGS) is a significant risk factor for multiple diseases. However, most relevant studies investigate the complications of a low HGS, while the risk potential of causative factors of low HGS remain poorly characterized. Methods: We investigated the potentials of quality of life, depression, dyslipidaemia, diabetes mellitus, cancer, Alzheimer's disease, stroke, frailty, and difficulties performing daily activities in predicting low HGS (≤ 27 kg for men, ≤ 16 kg for women) in European older adults aged 50 or above from 15 countries (n = 42,183). All data was collected from four successive waves of survey of health, ageing, and retirement in Europe (SHARE) conducted between 2013 and 2020. Logistic models are applied, and estimated effects are presented as odds ratios and probabilities. Results: Collectively, 3016 participants (men; n = 1395; 7.38%, women; n = 1621, 6.97%) developed low HGS during the 6.5 years study period. After adjusting for covariables, we identified an advancing age (1.6–48.1% points higher risk of low HGS), male gender (1.0%-point higher risk of low HGS), lower quality of life (1.6%-point higher), and stroke (1.5%-points) as significant risk factors for low HGS. We also found a dose-dependent association of Euro-D depression scores with the risk of low HGS, as the higher scores were associated with between 0.6- and 2.3%-points higher risk of developing low HGS than participants without depression. Among physical performance indicators, difficulty climbing stairs (2.0%-points higher low HGS risk) or rising from a chair (0.7%-points) were significantly associated with developing low HGS. Lastly, frailty (0.9%-points higher risk of low HGS) and the fear of falling down (1.6%-points higher risk) also increased the risk of developing low HGS. Conclusion: Altogether, we report several risk factors for developing low HGS. Our observations may help evaluating and monitoring high-risk population for developing low HGS in pre-clinical settings. [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]

Background: Pregabalin, approved for various medical conditions, has shown increasing misuse potential globally. However, limited research exists on pregabalin dependence in India. This study aimed to investigate the prevalence and characteristics of pregabalin dependence among individuals seeking substance use disorder (SUD) treatment in North India. Methods: A cross-sectional, analytical study was conducted on patients enrolled between August 2022 and July 2023 at an academic institution-based addiction treatment center. Case records of patients with pregabalin dependence were retrieved and compared with controls with opioid dependence but no history of pregabalin use. Results: Among 3766 registered patients, 135 had pregabalin dependence (prevalence: 3.58 per 100 registered patients). Pregabalin-dependent patients were male, with a median usage duration of eight months and a median daily dose of 1200 mg. Most had concurrent opioid dependence, primarily heroin, used via the injection route. The odds of pregabalin dependence among those with opioid dependence were significantly higher than those with other substance dependence (OR 1.44, 95% CI 1.13-1.85). Reasons for pregabalin use included opioid craving reduction, sedation, and euphoria. Patients with pregabalin dependence were more likely to have lower socioeconomic status (P < 0.0001) and urban residence (P = 0.032), an earlier age of substance use initiation (P = 0.02) and treatment seeking (P < 0.0001), and a higher co-occurrence of psychiatric disorders (P = 0.007) and less occurrence of alcohol dependence (P = 0.03). Conclusion: Findings underscore the need for heightened awareness, screening, and intervention efforts targeting pregabalin misuse within SUD treatment. Further research should focus on longitudinal studies to elucidate pregabalin dependence's trajectory. [ABSTRACT FROM AUTHOR]

Schizophrenia (SCZ) and schizoaffective disorder (SHZ) are psychiatric disorders commonly identified in individuals in their late adolescence or early adulthood. Comorbidities are common, though a concurrent diagnosis of leukemia, one of the most frequently occurring cancers of adolescence, has not yet been described in such cases. This case study outlines the clinical presentation, course, and treatment response of two 17-year-old male adolescents whose psychotic disorders complicated their leukemia treatment. The first patient was diagnosed with leukemia and subsequently with SCZ while undergoing leukemia treatment. The second patient was diagnosed with SHZ prior to the onset of leukemia. The case study will follow the methodology of Robert E. Stake (Abma & Stake, 2014), as the two cases share a leukemia diagnosis and the reported mental health impact connected with cancer-directed treatment. Early identification and treatment are critical for both psychotic disorders and cancers, often impacting the long-term prognosis. However, when co-occurring, their interplay can present unique challenges to care. [ABSTRACT FROM AUTHOR]

The short-term use of glucocorticoids (GCs) in combination with methotrexate was recommended for the initial treatment of rheumatoid arthritis by the European League Against Rheumatism. A randomized controlled trial (GLORIA) showed that treatment of older patients with low-dose GCs in combination with disease-modifying anti-rheumatic drugs was more efficacious than disease-modifying anti-rheumatic drugs plus placebo in terms of disease activity control and prevention of joint destruction. Glucocorticoid-related adverse events were likely to increase relative to placebo, with no increase in serious adverse events and fractures over 2 years. Observational studies showed an increased risk of serious infections, cardiovascular events, and fractures associated with long-term continuation of GCs in older patients, but the adverse events may be associated not only with GC toxicity but also with poor disease control of rheumatoid arthritis. In the GLORIA study, low-dose GCs during 2 years could be tapered off safely, but many patients had a flare of disease activity after discontinuation of GCs. In the two representative large Japanese registries (IORRA and NinJa), the proportion of patients using GCs and non-tumor necrosis factor inhibitors increased with increasing age at disease onset, with a decreasing trend in methotrexate use. The proportion of patients in remission with GC treatment also increased with increasing age at onset. These suggested that it is not easy to discontinue GCs in older patients. If GCs cannot be terminated in the short term, it may be acceptable to use GCs to control disease activity for up to 2 years. [ABSTRACT FROM AUTHOR]

Autophagy impairment in Huntington disease (HD) has been reported for almost two decades. However, the molecular mechanisms underlying this phenomenon are still unclear. This is partially because it is challenging to model the impact of the disease‐causing mutation, aging, as well as the selective vulnerability of neurons in a single model. Recently developed direct neuronal reprogramming that allows researchers to induce neurons‐of‐interest retaining biological aging information made it possible to establish HD cellular models to study more relevant age‐ and disease‐related molecular changes in neurons. We here summarized the findings from a few latest studies utilizing directly reprogrammed HD neurons and discussed the new insights they brought to the understanding of the age‐ and disease‐related autophagy impairment in HD. [ABSTRACT FROM AUTHOR]

Objective Familial aggregation of systemic autoimmune diseases is frequently reported, but little is known about how fathers and mothers differentially contribute to the development of autoimmune diseases in their offspring. This study aimed to investigate the impact of maternal and paternal autoimmunity on the risk of offspring rheumatic diseases. Methods We constructed a nationwide population-based cohort using data from the Maternal and Child Health Database and the Taiwan National Health Insurance Research Data (NHIRD) from 2004 to 2019. The outcome was presence of an autoimmune disease in the offspring. Inverse probability of treatment–weighted Cox models were used to estimate adjusted hazard ratios (aHRs) and 95% CIs for autoimmune diseases. Results Babies born to a father or mother with an autoimmune disease had, respectively, 1.22 times and 1.38 times the risk of developing an autoimmune disease compared with their counterparts with no parental autoimmune diseases. Maternal autoimmunity substantially contributed to the risk of SLE (aHR = 5.46, 95% CI: 5.28–5.66), and paternal autoimmunity contributed to the risk of JIA (aHR = 1.76, 95% CI: 1.71–1.81) and of type 1 diabetes mellitus (aHR = 1.59, 95% CI: 1.39–1.81) in their offspring. The contributions of mothers to the risk of development of SLE (aHR = 8.55, 95% CI: 8.10–9.02) and inflammatory myopathy (aHR = 2.08, 95% CI: 1.72–2.51) in their offspring were exacerbated in boys. Babies of two parents with an autoimmune disease showed a 1.39-fold risk of developing an autoimmune disease. The maternal contribution effect was stronger for preterm births than for full-term births. Conclusion This study demonstrated broadly how autoimmune diseases pass from parents to infants of both genders and separately quantified the maternal and paternal contributions to disease. [ABSTRACT FROM AUTHOR]

Objective To estimate mortality and survival rates of SLE in a contemporary, population-based setting and assess potential influences by time, sex, ethnicity, classification criteria and age at diagnosis. Methods We assessed mortality and survival in the Nor-SLE cohort, which includes all chart review–confirmed SLE cases resident in Southeast Norway (population 2.9 million) 1999–2017. Study end was at death, emigration or 1 October 2022. We defined juvenile SLE by age <16 years at diagnosis. For standardized mortality rate (SMR) estimates, we applied 15 population controls per case, all matched for age, sex, residency and ethnicity. We analysed survival by Kaplan–Meier and risk factors by Cox regression. Results The Nor-SLE cohort included 1558 SLE cases, of whom 749 were incident and met the 2019 EULAR and ACR (2019-EA) classification criteria. SMR was increased to 1.8 (95% CI 1.6–2.2) in incident adult-onset SLE but did not differ between females and males. Survival rates at 5, 10, 15 and 20 years were lower in incident adult-onset SLE than in matched controls. In multivariable analysis, LN associated with decreased survival, while sex did not. Separate, long-term mortality analyses in the total Nor-SLE cohort showed that SMR peaked at 7.2 (95% CI 3.3–14) in juvenile-onset SLE (n  = 93) and fell gradually by increasing age at SLE diagnosis. Conclusion This study shows persistence of a mortality gap between adult-onset SLE and controls at population level and provides indications of worryingly high mortality in juvenile-onset SLE. [ABSTRACT FROM AUTHOR]

Background Educational inequalities in major depressive disorder (MDD) pose a major challenge. Tackling this issue requires evidence on the long-term impact of intervening on modifiable factors, for example lifestyle and psychosocial factors. For this reason, we aimed to simulate the development of educational inequalities in MDD across the life course, and to estimate the potential impact of intervening on modifiable factors. Methods We used data from the prospective Dutch Lifelines Cohort Study to estimate the required input for a continuous-time microsimulation. The microsimulation allowed us to project the development of educational inequalities in MDD between ages 18 and 65, and to assess the potential benefit of intervening on quality of social contacts, health literacy and smoking. Results On average, an additional 19.1% of individuals with low education will ever experience MDD between ages 18 and 65 compared with those with high education. Additionally, individuals with low education generally will develop MDD 0.9 years earlier and spend 1.2 years more with MDD, than individuals with high education. Improving the quality of social contacts in individuals with low education produced the largest effect; it would reduce the inequalities in the prevalence, onset and duration of MDD by an average of 18.4%, 18.3% and 28.6%, respectively. Conclusions Intervening on modifiable factors, particularly quality of social contacts, in individuals with low education could help reduce the estimated educational inequalities in MDD over the life course. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the gap between adaptive functioning and cognitive functioning, especially verbal and nonverbal intelligence quotient (IQ) in Chinese children with ASD. We systematically explored cognitive functioning, ASD severity, early signs of developmental abnormalities, and socioeconomic factors as mediating factors of adaptive functioning. We enrolled 151 children (age: 2.5?6 years) with ASD and categorized them into one group with IQ ≥ 70 and another with IQ < 70. The two groups were calibrated for age, age at diagnosis, and IQ, and the relationship of adaptive skills with vocabulary acquisition index (VAI) and nonverbal index (NVI) were separately analyzed. Results show that the gap between IQ and adaptive functioning was significant in children with ASD having IQ ≥ 70, with both VAI and NVI showing statistically significant differences (all P < 0.001). VAI correlated positively with scores for overall adaptive skills and specific domains, whereas NVI had no significant correlations with adaptive skill scores. Age of first walking unaided had an independent positive correlation (all P < 0.05) with scores of adaptive skills and specific domains. IQ-adaptive functioning gap is significant in children with ASD having IQ ≥ 70, suggesting that defining "high-functioning autism" merely on the basis of IQ is not appropriate. Verbal IQ and early signs of motor development are specific and possible predictors of adaptive functioning in children with ASD, respectively. [ABSTRACT FROM AUTHOR]

Postacute symptoms are not uncommon after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with pre-Omicron variants. How the Omicron variant and coronavirus disease 2019 (COVID-19) booster vaccination influence the risk of postacute symptoms is less clear. We analyzed data from a nationwide Danish questionnaire study, EFTER-COVID, comprising 36 109 individuals aged ≥15 years who were tested between July 2021 and January 2022, to evaluate the associations of the Omicron variant and COVID-19 booster vaccination with postacute symptoms and new-onset general health problems 4 months after infection with SARS-CoV-2. Risk differences (RDs) were estimated by comparing Omicron cases with controls, comparing Omicron cases with Delta cases, and comparing Omicron cases vaccinated with 3 doses with those vaccinated with 2 doses, adjusting for age, sex, body mass index, self-reported chronic diseases, Charlson comorbidity index, health-care occupation, and vaccination status. Four months after testing for SARS-CoV-2 during the Omicron period, cases experienced substantial postacute symptoms and new-onset health problems in comparison with controls; the largest RD was observed for memory issues (RD = 7.4%; 95% CI, 6.4-8.3). However, risks were generally lower than those in the Delta period, particularly for dysosmia (RD = –15.0%; 95% CI, −17.0 to −13.2) and dysgeusia (RD = –11.2%; 95% CI, −13.2 to −9.5). Booster vaccination was associated with fewer postacute symptoms and new-onset health problems 4 months after Omicron infection as compared with 2 doses of COVID-19 vaccine. [ABSTRACT FROM AUTHOR]

The association between cardiometabolic risk factors and cognitive function has been well documented, but the underlying mechanisms are not fully understood. This longitudinal study aimed to investigate the potential mediating role of DNA methylation in this association. We conducted the analyses in 3 708 participants (mean [standard deviation { SD }] age: 67.3 [9.5], women: 57.9%) from the Health and Retirement Study who were assessed in the 2014–2020 waves, had Infinium Methylation EPIC BeadChip methylation assays from the 2016 Venous Blood Study, and had cognitive assessment between 2016 and 2020. Causal mediation analyses were used to test the mediation role of DNA methylation in the associations between cardiometabolic risk factors and cognition, adjusting for demographic, socioeconomic, and lifestyle factors. Hypertension (−0.061 in composite cognitive z -score; 95% confidence interval [CI: −0.119, −0.004]) and diabetes (−0.134; 95% CI: [−0.198, −0.071]) were significantly associated with worse cognitive function while abnormal body weight and hypercholesterolemia were not. An increased number of cardiometabolic risk factors was associated with worse cognitive function (p  = .002). DNA methylation significantly mediated the association of hypertension (mediated effect on composite cognitive z -score: −0.023; 95% CI: −0.033, −0.014), diabetes (−0.022; 95% CI: −0.032, −0.014), and obesity (−0.021; 95% CI: −0.033, −0.011) with cognitive function, whereas the mediation effect was not observed for having hypercholesterolemia. The estimated proportions mediated were 37.4% for hypertension and 16.7% for diabetes. DNA methylation may be an important mediator linking cardiometabolic risk factors to worse cognition and might even provide a potential target for dementia prevention. [ABSTRACT FROM AUTHOR]

Objectives: Mental health triage services are the first contact for people wanting support for their mental health and provide access to public mental health services in Victoria, Australia. People living with young-onset dementia and their families may contact triage services seeking assistance for behaviour changes and pathways to care as there are few alternative services available. Methods: The authors reviewed the minimum triage dataset from one of the largest mental health services in Victoria, Australia from 2018 to 2021 investigating reasons for referral for people with young-onset dementia. Results: Of the 1766 referrals for 'dementia', 145 were for young-onset dementia. Of these, 69% were referred for behaviour changes. About half of the referrals for behaviour changes were triaged as 'advice only'. One-third of referrals were from general practitioners. Conclusions: The availability of dementia-specific support services that could provide advice on dementia as well as advice for behaviour changes related to the disease could potentially ease the burden of phone calls received by mental health triage services. What is known about the topic? Young-onset dementia refers to a dementia with onset at less than 65 years of age. People with young-onset dementia may contact mental health services for support but the reasons for contact are unknown. What does this paper add? The reasons for contacting one Victorian mental health service included behaviour changes such as agitation or aggression and psychotic symptoms (74%) and general advice, including about dementia pathways (14%). General practitioners made up one-third of referral sources. What are the implications for practitioners? Victorian mental health services are generally overloaded and complex. There is a need to promote alternative dementia support organisations in order to provide an alternative contact for people affected by young-onset dementia. [ABSTRACT FROM AUTHOR]

Objectives: Individuals living with young-onset dementia fall through the gaps of adult and geriatric services. Given that non-cognitive symptoms of dementia in younger people are often psychiatric and behavioural in nature, these people may contact mental health services. There is sparse information investigating the frequency of people with young-onset dementia who contact mental health triage in Victoria. Methods: Triage data were obtained from the Victorian Agency for Health Information. The data contained demographics for people registered with Victorian mental health services. Consumers who had an International Classification for Diseases code for dementia and were aged less than 65 years were identified as people with young-onset dementia. Using information of the frequency of people with young-onset dementia who were registered with each area-based mental health service, population census statistics were used to make estimates of the frequency of young-onset dementia. Results: Of the 6172 people who had a dementia diagnosis, 1020 of them were aged less than 65 years and had young-onset dementia. There were proportionally more men who had young-onset dementia compared to women. There were more people with young-onset dementia registered to rural mental health services compared to metropolitan services. Conclusion: Findings provide important information for service planning in Victoria. Recommendations include upskilling and education for the assessment of dementia for those clinicians who work in mental health services, particularly in rural regions. What is known about the topic? Young-onset dementia refers to a dementia with onset at an age less than 65 years. Accessing age-appropriate services for these people is difficult as they fall through the gaps of adult and aged services due to their age. What does this paper add? Due to the behavioural and psychiatric manifestations related to young-onset dementia, data is provided about mental health service involvement for these people. What are the implications for practitioners? There is a need to upskill mental health clinicians, especially in rural areas, as younger people with dementia are accessing these services. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study described disease characteristics and long-term outcomes in patients diagnosed with very early onset inflammatory bowel disease (VEOIBD) (diagnosed before 6 years of age) and infantile-IBD (before 2 years). METHODS: Cases from 21 centers worldwide diagnosed with VEOIBD (2008-2018), with minimum 2 years of follow-up, were retrospectively reviewed. RESULTS: The cohort included 243 patients (52% males, median follow-up of 5.8 [range 2-18] years, including 69 [28%]) with infantile-IBD. IBD subtypes included Crohn's disease (CD), ulcerative colitis (UC), or IBD-unclassified (IBDU) in 30%, 59%, and 11%, respectively. Among patients with CD, 94% had colonic involvement, and among patients with UC/IBDU, 75% had pancolitis. Patients with infantile-IBD presented with higher rates of IBDU, lower hemoglobin and albumin levels, and higher C-reactive protein, and had lower response rates to first-induction therapy and corticosteroids therapy (P < .05 for all). Colectomy and diversion surgeries were performed in 11% and 4%, respectively, with no significant differences between age groups. Corticosteroid-free remission rates were 74% and 78% after 3 and 5 years, respectively, and 86% at end of follow-up. Genetic testing was performed in 96 (40%) patients. Among tested population, 15 (16%) were identified with monogenic disease. This group demonstrated lower response rates to induction therapies, higher rates of surgical intervention, and higher rates of major infections (P < .05 for all). CONCLUSIONS: Patients with VEOIBD, including infantile-IBD, exhibit low rate of complications and surgical interventions at the long term. Patients with monogenic IBD are at risk for more severe disease course. [ABSTRACT FROM AUTHOR]

To systematically review the prevalence, risk factors and timing of onset of hip displacement in children with a post-neonatal (PNN) brain injury with regards to hip surveillance recommendations. A search of PubMed, MEDLINE, Embase, CINAHL and Web of Science was conducted on 22nd February 2022. Studies were included if they reported presence of, and risk factors for, hip displacement in children with PNN brain injury. Data was extracted on patient characteristics, and analyzed in terms of risk factors of interest and timing of development of hip displacement. Six studies met the inclusion criteria (n = 408 participants). All were cohort studies: five retrospective and one prospective. Rates of hip displacement ranged from 1% to 100%, and were higher in children with diffuse brain injury at an early age, who were non-ambulant and had spastic quadriplegia. Hip displacement and hip dislocation were first identified at one and three months respectively following PNN brain injury. Evidence on hip displacement in children with PNN brain injury is sparse and low quality. Children who remain non-ambulant after diffuse PNN brain injury before five years of age appear most at risk of developing progressive hip displacement and earlier hip surveillance is recommended. As for children with cerebral palsy (CP), children with a post-neonatal (PNN) brain injury who are non-ambulant are most at risk of progressive hip displacement. Children with a diffuse brain injury before five years of age appear to be at greater risk. Hip displacement can occur very early and progress rapidly following PNN brain injury. [ABSTRACT FROM AUTHOR]

Melanoma is a highly malignant and drug-resistant disease that imposes a substantial economic burden on the world. There are many studies linking trace elements to diverse types of cancers, including melanoma. This review elucidates the relationship between trace elements exposure and melanoma. It was identified that copper, manganese, selenium, zinc, iron, and many other trace elements were associated with melanoma in humans. In terms of epidemiology, different elements have different correlations with melanoma. These trace elements affect the occurrence and development of melanoma through various mechanisms, such as oxidative stress and the MAPK pathway. The literature on the role of trace elements in the pathogenesis and treatment of melanoma depicts promising prospects for this field. [ABSTRACT FROM AUTHOR]

Little is known about family mental illness and substance use disorder (SUD). This case-control study explored the relationship between family (parents and/or siblings) mental health problems (FMHP) and lifetime substance use disorder (SUD), considering a gender perspective. A sample of 387 patients (n = 306 men, 79.1%; n = 81 women, 20.9%) was recruited from the Proyecto Hombre Navarra (Spain) addiction treatment program. Patients with (80 men; 24 women) and without (226 men; 57 women) FMHP were compared, taking sex into account. The prevalence of FMHP was 26.9%, without significant differences between men (n = 80; 26.1%) and women (n = 24; 29.6%). Men with FMHP reported higher severity in family/social and psychiatric areas than those without FMHP. Women with FMHP reported a higher severity in the psychiatric area and a higher prevalence of anxiety problems, suicidal attempts, previous psychopharmacological treatments, and physical abuse than women without FMHP. FMHP is highly prevalent in patients with SUD. They are associated with lifetime psychopathological problems, mainly in men. Further specific research is needed to evaluate this issue to develop specific treatments tailored to the needs of patients with FMHP. [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]

Simple Summary: The PELICan hypothesis speaks to the role of perinatal and early life stressors (including malnutrition) in the causation of young-onset cancers. To date, there is no evidence correlating perinatal malnutrition and the risk of young-onset cancer. The Great Famine of China was a significant event in human history. The present study compared the incidence of young-onset cancers in individuals born during and just after the famine to those born prior to the famine. Perinatal exposure to famine, especially in females, was associated with a higher risk of young-onset cancer. This was particularly evident for young-onset genitourinary cancers. Background/Objectives: Perinatal exposure to malnutrition has been hypothesised to influence the development of young-onset cancer (≤50 years of age). This study aimed to determine if perinatal malnutrition in individuals exposed to the Great Famine of China increased their risk of developing young-onset cancer compared to other individuals born prior to the famine. Subjects/Methods: This cross-sectional study involved 7272 participants from the China Health and Nutrition Survey who were classified into four groups based on birth year: participants born between 1953 and 1955 (before the famine) were designated as the pre-famine group (unexposed); the remainder formed perinatal exposure groups comprised of those exposed during the famine (1959–1961), those exposed in the early post-famine period (1962–1964), and those exposed in the late post-famine period (1965–1967). Multivariable adjusted log-binomial regression models were used to calculate the RR and 95% CI of young-onset cancer (including genitourinary cancer) across four groups. Results: Perinatal exposure to early post-famine (RR 2.08; 95%CI 1.04, 4.34; p = 0.043) and the female sex (RR 15.6, 95%CI 4.54, 60.3; p < 0.001) were noted to have a significantly increased risk of young-onset cancer. In addition, the early (RR 13.8; 95%CI 2.68, 253; p = 0.012) and late post-famine (RR 12.3; 95%CI 2.16, 231; p = 0.020) cohorts demonstrated a significantly increased risk of young-onset genitourinary cancer. The latter was accompanied by an increased risk of hypertension (RR 3.30; 95%CI 1.28, 7.87; p = 0.009). Conclusions: Perinatal exposure to famine, especially in females, was associated with a higher risk of young-onset cancer. This was particularly evident for young-onset genitourinary cancers. These findings highlight the potential long-term impact of perinatal malnutrition on young-onset carcinogenesis. [ABSTRACT FROM AUTHOR]

The article discusses the "Metabaging Cycle," which connects metabolic disorders and chronic diseases of aging. It explains how metabolic dysregulation, inflammation, and conditions like obesity, muscle atrophy, neurodegenerative diseases, osteoporosis, arthritis, and cancer are interconnected. The article emphasizes the need to understand these mechanisms for better human health and healthy aging, but acknowledges that more research is needed. It suggests interventions like improving diet, increasing physical activity, managing weight, and using pharmacological therapies to prevent and treat these chronic diseases. The document also provides a list of scientific articles on topics like cognitive impairment, gut microbiota, pregnancy, metabolic abnormalities, neuroinflammation, insulin signaling, muscle metabolism, obesity, and cancer, which can be helpful for library patrons researching these specific areas. [Extracted from the article]

Background: FMF (Familial Mediterranean Fever) is the most prevalent autoinflammatory disease. It arises due to mutations in the pyrin-encoding MEFV gene. Prolidase, an enzyme culpable of splitting the bonds of proline-containing dipeptides, is essential for matrix remodeling, collagen turnover, and cell proliferation. It has a crucial role in inflammation. Aim: To compare serum levels of prolidase between FMF children during the attack-free periods and healthy children and to correlate it with different FMF disease criteria and inflammatory marker, also to investigate if it can serve as a marker for subclinical inflammation. Results: Forty-one children diagnosed with FMF and 41 sex and age-matched apparently healthy children as a control group were included in this study, serum prolidase was measured by ELISA. The mean ± SD serum level of prolidase among FMF patients was 0.6 ± 0.2 mU/ml × 104, while among the control group, it was 1.3 ± 1.4 mU/ml × 104, a statistically significant difference existed between both groups, p value = 0.001. The level of serum prolidase was not correlated with FMF severity score, inflammatory markers, and other FMF disease criteria. Conclusion: Serum prolidase level was lower among FMF patients during the attack-free period than in the healthy control group, it was not correlated with disease severity and was not predictive of the presence of subclinical inflammation. Further studies are needed to highlight the role of serum prolidase in FMF children. [ABSTRACT FROM AUTHOR]

Motor neuron disease (MND) is an uncommon but invariably fatal condition, with a median survival of 24-48 months from symptom onset. Although there is no cure at the moment, early diagnosis is crucial to enable timely access to multidisciplinary care, and enrolment in clinical trials utilising investigational therapies. Unfortunately, diagnostic delays remain common, and the average delay between symptom onset and diagnosis is 12 months. Large numbers of specialist referrals have been suggested as a key contributor to diagnostic delays. We conducted a retrospective review of the medical records of patients diagnosed with MND in Lancashire and South Cumbria, to investigate whether large numbers of specialty referrals are a common occurrence in MND. Our review identified that 35% of patients with MND were seen by two or more specialties before being referred to neurology. This rose to 49% when patients with bulbar onset disease were considered. 9% of cases saw three or more specialists. There was a statistically significant correlation between the number of specialist referrals and delays in neurology referral. We hope our findings will increase awareness of the importance of early neurology referral in the diagnosis of MND and promote the use of the MND Red Flag tool as a means of identifying patients in need of prompt neurological evaluation. [ABSTRACT FROM AUTHOR]

We investigated the substance-specific and cross-substance risk associated with early onset (before age 15) of drunkenness and cannabis use in the subsequent development of alcohol (AUD) and cannabis use disorder (CUD) in Mexican American young adults. Survival analyses employed Cox proportional hazards models for AUD and CUD, separately. In cross-risk analyses, we modeled estimates for those participants reporting lifetime use of both substances. Early onset of drunkenness and early onset of cannabis use were associated with shorter time to AUD and CUD, respectively, even after accounting for psychiatric disorders. While there were no cross-risk associations, adjusting for psychiatric disorders and early onset cannabis use attenuated the association of early drunkenness with AUD. [ABSTRACT FROM AUTHOR]

Introduction: the selective IL-17 inhibitor secukinumab has demonstrated efficacy and safety in the treatment of moderate–severe psoriasis in recent years. Objective: evaluate effectiveness and drug survival (DS) of secukinumab in patients with psoriasis for up to 5 years. Methods: This is a retrospective study on a monocentric cohort of patients with psoriasis on secukinumab evaluating the achievement of PASI100, PASI90, and PASI ≤ 3 and DS analysis up to 260 weeks. DS multivariate analysis was carried out considering sex, age, age of onset of the disease, obesity, cardiovascular comorbidities, diabetes, involvement of difficult-to-treat sites, psoriatic arthritis, treatment-naïve status, and mean baseline PASI. Results: At baseline, we evaluated 255 patients on secukinumab. PASI100 was reached by 41.7% and 70.6% of patients at weeks 16 and 260, respectively. PASI90 showed a similar trend with 46.5% of patients achieving it at week 16 and 88.2% at week 260. Non-obese patients showed a faster response than patients with obesity in achieving PASI100, PASI90, and PASI ≤ 3, with significant differences at 28 weeks [55% vs. 40% (p = 0.033), 64% vs. 49% (p = 0.038), and 76% vs. 62% (p = 0.036), respectively]. The estimated DS for secukinumab was 84.3% at 12 and 48% at 60 months. Obesity and smoking habits were associated with a higher risk of discontinuation in multivariate models (HR 1.6 CI 1.05–2.45, p = 0.028; HR 1.48 CI 1.01–2.17, p = 0.043, respectively). Conclusions: Secukinumab showed effectiveness for up to 5 years of treatment, with a high DS and achievement of PASI100, PASI90, and PASI < 3 at these time points. Only obesity reduced the response and maintenance of DS. [ABSTRACT FROM AUTHOR]

Simple Summary: Identification of germline pathogenic variants in breast cancer patients holds significant importance for accurate risk assessment and therapeutic interventions. However, research focusing on very young breast cancer patients remains limited. Our objective was to describe the prevalence, gene, and variant spectra alongside clinicopathological characteristics and outcomes of women diagnosed with breast cancer ≤30 years. Our observations revealed that one in three patients carried predisposing variants distributed in eight established breast cancer genes. Predominantly, causative variants implicated loss-of-function of BRCA1, TP53, and BRCA2, with TP53 emerging as the second most frequently mutated gene within this cohort. While carrier status did not impact event-free survival, carriers who underwent neoadjuvant chemotherapy exhibited improved prognostic outcomes. Our data underscore the substantial proportion of patients with hereditary predisposition, advocate for the inclusion of TP53 genetic testing, and suggest possible benefits of neoadjuvant chemotherapy in this very young group of breast cancer patients. Early-onset breast cancer constitutes a major criterion for genetic testing referral. Nevertheless, studies focusing on breast cancer patients (≤30 years) are limited. We investigated the contribution and spectrum of known breast-cancer-associated genes in 267 Greek women with breast cancer ≤30 years while monitoring their clinicopathological characteristics and outcomes. In this cohort, a significant proportion (39.7%) carried germline pathogenic variants (PVs) distributed in 8 genes. The majority, namely 36.7%, involved BRCA1, TP53, and BRCA2. PVs in BRCA1 were the most prevalent (28.1%), followed by TP53 (4.5%) and BRCA2 (4.1%) PVs. The contribution of PVs in CHEK2, ATM, PALB2, PTEN, and RAD51C was limited to 3%. In the patient group ≤26 years, TP53 PVs were significantly higher compared to the group 26–30 years (p = 0.0023). A total of 74.8% of TP53 carriers did not report a family history of cancer. Carriers of PVs receiving neoadjuvant chemotherapy showed an improved event-free survival (p < 0.0001) compared to non-carriers. Overall, many women with early-onset breast cancer carry clinically actionable variants, mainly in the BRCA1/2 and TP53 genes. The inclusion of timely testing of TP53 in these patients provides essential information for appropriate clinical management. This is important for countries where reimbursement involves the cost of genetic analysis of BRCA1/2 only. [ABSTRACT FROM AUTHOR]

Background: Preterm birth and low birthweight (LBW) might be associated with reduced physical fitness, although evidence remains inconclusive. Objective: To examine the influence of preterm birth and LBW on physical fitness, as well as to assess whether variables such as gestational age, birthweight, or age at assessment moderate these effects. Methods: PubMed, Scopus, and PsycINFO were systematically searched from inception to 7 December 2023 for case–control and cohort studies analyzing the association between preterm birth or LBW (or gestational age or birthweight as continuous variables) with at least one physical fitness-related outcome (i.e., cardiorespiratory fitness (CRF), muscle strength, flexibility, speed, agility). Random-effects meta-analysis and meta-regression models were used to estimate the pooled effect size, as well as to examine potential associations between the magnitude of the effect and gestational age, birthweight, or age at assessment. Results: Fifty-two studies (n = 920,603 participants, average age ranging from 4.7 to 34.4 years) were included. Preterm birth was associated with reduced CRF (standardized mean difference (SMD) = −0.38, 95% confidence interval (CI) = −0.51 to −0.25) and muscle strength (SMD = −0.44, 95% CI = −0.79 to −0.08). LBW was associated with reduced CRF (SMD = −0.40, 95% CI = −0.64 to −0.17), muscle strength (SMD = −0.18, 95% CI = −0.24 to −0.13), flexibility (SMD = −0.11, 95% CI = −0.22 to −0.01), and agility (SMD = −0.99, 95% CI = −1.91 to −0.07). Meta-regression analyses showed that a lower gestational age or birthweight were associated with larger reductions in physical fitness, whereas no consistent association was found for the age at assessment. Conclusion: Both preterm birth and LBW seem associated with reduced physical fitness regardless of age, with larger reductions overall observed in individuals with lower gestational age or birthweight. These findings might support the implementation of preventive strategies (e.g., fitness monitoring and physical exercise interventions) in these populations through the life course. PROSPERO registration: CRD42021231845. [ABSTRACT FROM AUTHOR]

Aim: We sought to explore the experiences and perceptions of the quality of life of adolescents with pediatric‐onset multiple sclerosis and assess their readiness for academic, employment and/or health care‐related transitions. Background: Adolescents with pediatric‐onset multiple sclerosis face unique challenges in managing a chronic illness while navigating future scholastic, social and occupational goals. We conducted a qualitative study with in‐depth, semi‐structured interviews from July 2017 to March 2019. Adolescents with pediatric‐onset multiple sclerosis were recruited from a pediatric neurology subspeciality practice until reaching data saturation. A total of 17 interviews were completed via telephone with participants ages 15 through 26. Results: Through content analysis of the interviews, we identified five major themes: (1) receiving a new diagnosis; (2) adapting to life with pediatric‐onset multiple sclerosis; (3) evaluating education/career transition preparedness; (4) adjusting within family life and establishing support systems; and (5) assessing current medical services and preparedness for adult medical care. Conclusions: Autonomy in health care management, adequate control of physical symptoms and sufficient family support impacted perceptions of quality of life. Implementing a dedicated transition visit, including the parent(s) of those with pediatric‐onset multiple sclerosis, early in adolescence may provide an avenue for appropriate anticipatory guidance regarding available services, independent medical management and continuity of care. [ABSTRACT FROM AUTHOR]

The two most frequent early-onset restrictive food intake disorders are early-onset anorexia nervosa (EOAN) and avoidant/restrictive food intake disorders (ARFID). Although the core symptoms of EOAN (i.e., fear of gaining weight and disturbed body image) are not present in ARFID, these symptoms are difficult to assess during the initial phase of hospitalisation. Our aim was to identify restrictive food intake disorder subtypes in children using latent class analysis (LCA) based on the information available at admission to hospital, and to determine the agreement between the subtypes identified using LCA and the final diagnosis: EOAN or ARFID. We retrospectively included 97 children under 13 years old with severe eating disorders (DSM-5) at their first hospitalisation in a specialised French paediatric unit. LCA was based on clinical information, growth chart analyses and socio-demographic parameters available at admission. We then compared the probabilities of latent class membership with the diagnosis (EOAN or ARFID) made at the end of the hospitalisation. The most parsimonious LCA model was a 2-class solution. Children diagnosed with EOAN at the end of hospitalisation had a 100% probability of belonging to class 1 while children diagnosed with ARFID had an 8% probability of belonging to class 1 based on parameters available at admission. Our results indicate that clinical and socio-demographic characteristics other than the core symptoms of EOAN may be discriminating for a differential diagnosis. [ABSTRACT FROM AUTHOR]

Objectives: Coronavirus disease 2019 pandemic caused many changes in the social behaviors of individuals and the provision of health systems. Many studies revealed reductions in the number of diagnoses and delays in diagnosis time during the pandemic. This study aimed to evaluate the effect of the pandemic on the time to diagnosis of major diseases of pediatric pulmonology. Materials and Methods: Newly diagnosed patients with cystic fibrosis (CF), childhood interstitial lung disease (chILD), tuberculosis (TB), and primary ciliary dyskinesia (PCD) were grouped into pandemic (group 1) and 2 consecutive pre-pandemic periods divided into equal intervals (groups 2 and 3). For each disease group, the time to diagnosis was compared between the specified periods. Results: A total number of patients were 171 in this study. In the CF group, there was no statistically difference in time to diagnosis between periods. In the chILD group, there was a statistically significant difference in time to diagnosis (P = .036) between groups (group 1: 2 months, group 2: 4 months and group 3: 10.5 months) that was not originated from pandemic period. In TB group there was no statistically significant difference between groups. In the PCD group, the impact of the pandemic on the time to diagnosis could not be clarified because the time interval to diagnosis (minimum: 2 years, maximum: 16 years) exceeded the studied periods (21 months). Conclusion: In our study, no effect found between the pandemic and age at diagnosis or time to diagnosis in patients with PCD, chILD, CF, and TB at our center. [ABSTRACT FROM AUTHOR]

Childhood-onset systemic lupus erythematosus (cSLE) is a chronic autoimmune disease with a multisystemic involvement diagnosed during childhood. The disease is marked by the production of autoantibodies targeting self-antigens, often before symptoms emerge. The presentation, clinical course, and outcome vary significantly among patients with cSLE. The onset of cSLE can be at any age during childhood while a diagnosis of cSLE before the age of 5 years is rare and raises a suspicion of monogenic lupus. Childhood-onset systemic lupus erythematosus affects various organs and systems, most frequently presenting with mucocutaneous, musculoskeletal, renal, and neuropsychiatric manifestations. Multiple disease flares can be seen during the disease course. Childhood-onset systemic lupus erythematosus causes significant morbidity and mortality. Children and adolescents with cSLE show higher disease activity and damage, and more aggressive immunosuppressive treatments are needed compared to adultonset SLE. Early diagnosis can be difficult due to the insidious onset with nonspecific symptoms. Disease activity and damage measures aim to ensure an accurate evaluation of disease status. A multidisciplinary approach and individualized disease management are important. Disease management is complex including the control of disease activity, the reduction of flares and damage, and a limitation of drug toxicity while improving the health-related quality of life in patients with cSLE. [ABSTRACT FROM AUTHOR]

Objectives To explore the status of reproductive health and related factors in female patients with systemic sclerosis (SSc). Methods A cross-sectional study was conducted among female patients from the Chinese Organization for Scleroderma through a questionnaire. Data on the status of reproductive health including fertility condition and menstrual status were obtained. The clinical and laboratory data of SSc were collected. For patients with pregnancies after disease onset, each pregnancy was matched with a healthy control. Associations between clinical characteristics and the status of reproductive health were analysed. Results A total of 342 female patients with SSc were included, and 31.8% (108/342, 95% CI 26.9%–36.7%) of them presented problems with reproductive health. Compared with the national data, the menopausal age of patients with disease onset before menopause was earlier (45.2 ± 6.1 vs 48.2 ± 4.4, P  < 0.001). Age of disease onset (P  = 0.018) and digital ulcer (P  = 0.020) had statistically significant effects on menopausal age. Although the infertility rate of patients was not increased, the rate of spontaneous abortions was higher compared with the national data (9/74, 12.2% vs 4.3%, P  < 0.001). Compared with the healthy control group, the rate of premature infants (12/55, 21.8% vs 7/110, 6.4%, P  = 0.003), low birth weight infants (15/55, 27.3% vs 6/110, 5.5%, P  < 0.001), and cesarean section (27/55, 49.1% vs 21/110, 19.1%, P  < 0.001) increased significantly. Conclusion The impairment of reproductive health is common and in many quarters in patients with SSc. Further action should be taken to improve reproductive health in patients with SSc, especially in maternal care. [ABSTRACT FROM AUTHOR]

Aim: To describe the childhood experiences of patients with polio from the acute phase of the disease during post‐war Finland in the 1950s and 1960s. Design: Qualitative empirical study based on self‐reported history of nursing rooted in the past, a history of experiences. Methodology: Interview materials were gathered in the form of themes (45) and written interviews (4) (29 September 2018 to 30 June 2019). Data were analysed by reflexive thematic analysis to highlight hidden and latent experiences. This approach generated the study's main theme, themes and subthemes. Results: The main theme, 'shattered childhood', generated from the study results and was then divided into two themes, both of which were influenced in part by the loss of a familiar childhood, the changed environment, the breakdown of the body and the absence of control. Through their childhood memories, polio survivors described their broken childhoods using the following themes: 'betrayal by their bodies' and 'isolation'. In the narratives, the theme 'betrayal by one's own body' was generated by the following subthemes: 'suddenness of the affliction', 'paralysis' and 'being moved to the hospital'. The 'isolation' theme developed from the subthemes 'isolation from the body and surroundings' and 'emotional and social loneliness'. Conclusion: Polio survivors' experiences during the acute stage of the disease were traumatic and demonstrated children's inferior nursing position in Finland in the 1950s and 1960s. Impact: The study increases our understanding of the history of caring for children and families who were affected and disabled by polio and the importance of their experiences in society and healthcare settings. Patient or Public Contribution: The authors collaborated with the Finnish Polio Association to recruit study participants and plan the study. Patients with polio during childhood underwent interviews, and their experiences formulated the data, which were analysed and the basis of the results. Reporting Method: Consolidated criteria for reporting qualitative research (COREQ), a 32‐item checklist for interviews and focus groups, have been used as a reporting and checklist tool. All authors have agreed on the final version and the use of the COREQ criteria, relationship with participants, theoretical framework, setting, data collection and data analysis and report. [ABSTRACT FROM AUTHOR]

Senescence and epigenetic alterations are two important hallmarks of cellular aging. During aging, cells subjected to stress undergo many cycles of damage and repair before finally entering either apoptosis or senescence, a permanent state of cell cycle arrest. The first biomarkers of senescence to be identified were increased ß‐galactosidase activity and induction of p16INK4a. Another feature of senescent cells is the senescence‐associated secretory phenotype (SASP), a complex secretome containing more than 80 pro‐inflammatory factors including metalloproteinases, growth factors, chemokines and cytokines. The secretome is regulated through a dynamic process involving a self‐amplifying autocrine feedback loop and activation of the immune system. Senescent cells play positive and negative roles depending on the composition of their SASP and may participate in various processes including wound healing and tumour suppression, as well as cell regeneration, embryogenesis, tumorigenesis, inflammation and finally aging. The SASP is also a biomarker of age, biological aging and age‐related diseases. Recent advances in anti‐age research have shown that senescence can be now prevented or delayed by clearing the senescent cells or mitigating the effects of SASP factors, which can be achieved by a healthy lifestyle (exercise and diet), and senolytics and senomorphics, respectively. An alternative is tissue rejuvenation, which can be achieved by stimulating aged stem cells and reprogramming deprogrammed aged cells. These non‐clinical findings will open up new avenues of clinical research into the development of treatments capable of preventing or treating age‐related pathologies in humans. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of cranial deformities, including nonsynostotic plagiocephaly, has been increasing, especially since the “Back to Sleep” campaign. Treatment of these deformities can use a cranial remolding orthosis or helmet. However, inconsistencies in results of studies of cranial remolding orthoses have made it increasingly more difficult for providers to accurately make recommendations for individuals with nonsynostotic plagiocephaly. Therefore, the purpose of this study was to assess the effectiveness of cranial remolding orthoses effective in treating nonsynostotic plagiocephaly by reducing cranial vault asymmetry (CVA) and to assess whether age and severity impact length and success of treatment. Materials and Methods: A retrospective analysis of patient files from September 2019–September 2020 was conducted. Paired samples of initial average and discharge average CVA measures and severity ratings were compared. Regression analyses were used to assess the relationship between all factors and severity rating at discharge. Results: A total of 106 infants (73 male, 33 female) were included in final analyses. Results indicated a significant difference between initial and discharge CVA and severity rating as a result of cranial remolding orthosis treatment. It was found that CVA at initial evaluation significantly predicted CVA at discharge (β = 0.73, P = 0.000) and severity at discharge (β = 0.52, P = 0.000), but all other variables were not significant predictors. Conclusions: The cranial remolding orthosis is an effective treatment in the correction of nonsynostotic plagiocephaly when used by a certified practitioner. In addition, this study found that treatment led to significant improvement regardless of age or initial severity. [ABSTRACT FROM AUTHOR]

Background: Autism has been considered a 'male‐dominant' condition. However, recent research suggests that autistic females are underdiagnosed, misdiagnosed, and later diagnosed. Females may also have different and more nuanced behavioral profiles. To examine diagnosis rates of females, we used 20 years of state‐wide data to characterize historical trends in the diagnosis of autism in females to determine whether the proportion of females diagnosed with autism has changed over time. Methods: Data were drawn from 10,247 participants (males = 8,319, females = 1928) who received an autism diagnosis between 2000 and 2021 from state‐wide autism centers associated with the University of North Carolina TEACCH Autism Program. Results: The rates of females diagnosed with autism increased at a greater rate compared with males. Age of diagnosis remained consistently higher for females. Late diagnosis (defined as 13+) increased over time across both males and females, however, was more commonly associated with females, particularly those with co‐occurring intellectual disability. Conclusions: Our results indicate that the proportion of females diagnosed with autism has increased steadily over a 20‐year period, which likely reflects greater societal knowledge of how autism may manifest differentially in females. [ABSTRACT FROM AUTHOR]