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BACKGROUND: Young adults have historically high levels of cannabis use at a time which coincides with emotional and cognitive development. Age of regular onset of cannabis use and sex at birth are hypothesized to influence the relationship between cannabis use and cognition. Here we investigated past 6-month cannabis use in relation to emotional and executive functioning. We further considered age of onset and sex in subgroup analyses. METHOD: Young adults (N = 225; ages 16-22) completed a substance use interview and cognitive battery, including the Emotional Word-Emotional Face Stroop and NIH toolbox executive functioning tasks. Linear regressions examined relationships between past 6-month cannabis use episodes and performance. Subgroup analyses investigated whether age of onset or sex impacted relationships. RESULTS: After correcting for multiple comparisons, greater past 6-month cannabis use episodes were related to poorer Emotional Stroop Congruent Accuracy (p = .0004, FDR-p = .002) and List Sorting Working Memory (p = .02, FDR-p = .10) performance. Younger age of regular use onset marginally related to lower Emotional Stroop Congruent Accuracy performance (p = .03, FDR-p = .13). There were no cannabis use by sex interactions on cognition. CONCLUSIONS: Consistent with prior findings, results suggest small reductions in cannabis-related performance in processing speed during emotional Stroop and working memory tasks. Age of onset was modestly related to Stroop performance, but not sex. Longitudinal studies which detail patterns of cannabis and other substance use are needed to better assess brain-behavior relationships and other factors (e.g., age of onset of regular use, sex) which could influence cannabis-related impairments in cognitive functioning.

OBJECTIVE: This study aimed to investigate the prevalence of autism spectrum disorder and its possible correlations with clinical characteristics in patients with infantile epileptic spasms syndrome in a single center in Brazil. METHODS: This retrospective cross-sectional study examined 53 children with the diagnosis of infantile epileptic spasms syndrome prior to an autism spectrum disorder assessment. Participants were divided into two groups based on the presence or absence of autism spectrum disorder. Available variables (sex, medications, median age at onset of infantile epileptic spasms syndrome, and presence of comorbidities) were compared using Mann-Whitney U or chi-square tests. RESULTS: Among the included patients, 12 (23 %) were diagnosed with autism spectrum disorder, corresponding to a relative risk of 0.29 (95 % confidence interval 0.174-0.492). The age at the first seizure ranged from 3 to 15 months, with a mean of 6.65 months. This age significantly differed between participants with autism spectrum disorder (10.58 months) and those without (5.43 months), p

ImportanceEarly-onset colorectal cancer (EOCRC), defined as a diagnosis at younger than age 50 years, is increasing, and so-called red flag signs and symptoms among these individuals are often missed, leading to diagnostic delays. Improved recognition of presenting signs and symptoms associated with EOCRC could facilitate more timely diagnosis and impact clinical outcomes.ObjectiveTo report the frequency of presenting red flag signs and symptoms among individuals with EOCRC, to examine their association with EOCRC risk, and to measure variation in time to diagnosis from sign or symptom presentation.Data sourcesPubMed/MEDLINE, Embase, CINAHL, and Web of Science were searched from database inception through May 2023.Study selectionStudies that reported on sign and symptom presentation or time from sign and symptom presentation to diagnosis for patients younger than age 50 years diagnosed with nonhereditary CRC were included.Data extraction and synthesisData extraction and quality assessment were performed independently in duplicate for all included studies using Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines. Joanna Briggs Institute Critical Appraisal tools were used to measure risk of bias. Data on frequency of signs and symptoms were pooled using a random-effects model.Main outcomes and measuresOutcomes of interest were pooled proportions of signs and symptoms in patients with EOCRC, estimates for association of signs and symptoms with EOCRC risk, and time from sign or symptom presentation to EOCRC diagnosis.ResultsOf the 12 859 unique articles initially retrieved, 81 studies with 24 908 126 patients younger than 50 years were included. The most common presenting signs and symptoms, reported by 78 included studies, were hematochezia (pooled prevalence, 45% [95% CI, 40%-50%]), abdominal pain (pooled prevalence, 40% [95% CI, 35%-45%]), and altered bowel habits (pooled prevalence, 27% [95% CI, 22%-33%]). Hematochezia (estimate range, 5.2-54.0), abdominal pain (estimate range, 1.3-6.0), and anemia (estimate range, 2.1-10.8) were associated with higher EOCRC likelihood. Time from signs and symptoms presentation to EOCRC diagnosis was a mean (range) of 6.4 (1.8-13.7) months (23 studies) and a median (range) of 4 (2.0-8.7) months (16 studies).Conclusions and relevanceIn this systematic review and meta-analysis of patients with EOCRC, nearly half of individuals presented with hematochezia and abdominal pain and one-quarter with altered bowel habits. Hematochezia was associated with at least 5-fold increased EOCRC risk. Delays in diagnosis of 4 to 6 months were common. These findings highlight the need to identify concerning EOCRC signs and symptoms and complete timely diagnostic workup, particularly for individuals without an alternative diagnosis or sign or symptom resolution.

Purpose: The current study queries the American Academy of Ophthalmology (AAO) Intelligent Research in Sight (IRIS) registry for data on the epidemiology, work-up, and management patterns of autoimmune orbital inflammation. Methods: Analysis and description of patient data from the IRIS registry between 2013 and 2019 reviewing patients with autoimmune or idiopathic orbital inflammation with filters based on International Classification of Disease (ICD) and Current Procedural Terminology (CPT) codes. Patients with thyroid eye disease, orbital cellulitis, and orbital abscess were excluded. Main Outcome Measures: Demographic descriptions included gender, age, geographic region, and treatment. Sub-analysis was performed by assessing rates of imaging, biopsy, lab work-up, and diagnostic categories. Results: In a final cohort of 20,584 patients, the mean age of onset of orbital inflammation was 51.7 years; 67% female; and 63% Caucasian, 21% unknown, 12% Black, 2.6% Asian, and 1.5% other. Only 49 had imaging, 78 had laboratory work-up, and 1,411 had biopsy codes. Treatment results showed 166 patients receiving antibiotics, 224 patients receiving steroids, and 35 patients receiving both. Conclusions: This study assessed the epidemiology, diagnostic patterns, and treatment patterns for orbital inflammation through the AAO IRIS registry. Practise patterns suggest a relatively low overall rate of imaging and laboratory studies compared to biopsies, although this certainly under-represents the actual number of imaging and laboratory studies and exemplifies the inherent imprecision of using a large database. However, the methodology of this study provides a framework of approaching the IRIS registry for oculoplastic research. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the gradual death of motor neurons in the brain and spinal cord, leading to fatal paralysis. Socioeconomic status (SES) is a measure of an individual's shared economic and social status, which has been shown to have an association with health outcomes. Understanding the impact of SES on health conditions is crucial, as it can influence and be influenced by health-related variables. The role of socioeconomic status in influencing the risk and progression of ALS has not been established, and understanding the various factors that impact ALS is important in developing strategies for treatment and prevention. To investigate this relationship, we recruited 413 participants with definite, probable, or possible ALS according to the El Escorial criteria, from three tertiary centers in London, Sheffield, and Birmingham. Logistic regression was used to examine the association between case-control status, socioeconomic criteria, and ALS risk. Linear regression was used to examine the association between age of onset and socioeconomic variables. Two sensitivity analyses were performed, one using an alternative occupational classifier, and the other using Mendelian Randomization analysis to examine association. There was no significant relationship between any variables and ALS risk. We found an inverse relationship between mean lifetime salary and age of ALS onset (Beta = −0.157, p = 0.011), but no effect of education or occupation on the age of onset. The finding was confirmed in both sensitivity analyses and in Mendelian Randomization. We find that a higher salary is associated with a younger age of ALS onset taking into account sex, occupation, years of education, and clinical presentation. [ABSTRACT FROM AUTHOR]

Purpose: Breast cancer (BC) incidence is increasing globally. Age-specific BC incidence trend analyses are lacking for women under age 50 in Canada. In this study, we evaluate the incidence trends in breast cancer in women under age 50 in Canada and compare them with corresponding trends among women 50 to 54. Methods: BC case counts were obtained from the National Cancer Incidence Reporting System (1984-1991) and the Canadian Cancer Registry (1992-2019) both housed at Statistics Canada. Population data were also obtained from Statistics Canada. Annual female BC age-specific incidence rates from 1984 to 2019 were derived for the following age groups: 20 to 29, 30 to 39, 40 to 49, 40 to 44, 45 to 49, and 50 to 54. Changes in trends in age-specific BC incidence rates, if any, and annual percent changes (APCs) for each identified trend, were determined using JoinPoint. Results: Statistically significant increasing trends in BC incidence rates were noted for almost all age groups: since 2001 for 20 to 29 (APC = 3.06%, P <.001); since 2009 for 30 to 39 (APC = 1.25%, P =.007); since 1984 for both 40 to 49 (APC = 0.26%, P <.001) and 40 to 44 (APC = 0.19%, P =.011), increased since 2015 for 40 to 49 (APC = 0.77%, P =.047); and since 2005 for 50 to 54 (APC = 0.38%, P =.022). Among women 45 to 49 there was a non-significant increase since 2005 (APC = 0.24, P =.058). Statistically significant average annualized increases in BC incidence rates were observed for each age group studied. Conclusions: Examining age-specific incidence rates formed a more complete picture of BC time trends with significant increasing trends in the incidence of BC among women in their 20s, 30s, 40s, and early 50s. A greater awareness regarding the increasing number of cases of BC in women younger than 50 is critical to allow for earlier diagnosis with its resultant reduced mortality and morbidity. [ABSTRACT FROM AUTHOR]

Childhood glaucoma is a heterogeneous group of ocular disorders defined by an age of onset from birth to 18 years. These vision‐threatening disorders require early diagnosis, timely treatment, and lifelong management to maintain vision and minimise irreversible blindness. The genetics of childhood glaucoma is complex with both phenotypic and genetic heterogeneity. The purpose of this review is to summarise the different types of childhood glaucoma and their genetic architecture to aid in the genetic counselling process with patients and their families. We provide an overview of associated syndromes and discuss implications for genetic counselling, including genetic testing strategies, cascade genetic testing, and reproductive options. [ABSTRACT FROM AUTHOR]

Calcinosis is a sequela of Juvenile Dermatomyositis (JDM) with significant morbidity. A retrospective study observing risk factors for JDM calcinosis, including a possible association between higher intensity of subcutaneous and myofascial edema in initial magnetic resonance imaging (MRI) and development of calcinosis was performed at a tertiary pediatric medical center. Data from the past 20 years on JDM patients with MRIs at the time of JDM diagnosis were obtained. MRIs were individually evaluated by two pediatric musculoskeletal radiologists who blindly graded the intensity of edema on a 0–4 Likert scale. Clinical data and edema scores were compared between patients who developed calcinosis and who did not. Forty-three patients (14 with calcinosis and 29 without calcinosis) were identified. The calcinosis group contained more racial and ethnic minorities, younger ages of JDM onset and longer time to reach JDM diagnosis. Muscle enzyme levels at JDM diagnosis were lower in the calcinosis group, especially Creatinine Kinase (CK) (p = 0.047) and Alanine Aminotransferase (ALT) (p = 0.015). The median score for edema in both groups was 3 (p = 0.39) with an inter-rater reliability of 95%. There was no association between increased subcutaneous and myofascial edema in MRIs at the time of JDM diagnosis and development of calcinosis. Earlier age of JDM onset, racial and ethnic minority, and delay in JDM diagnosis could be risks for developing calcinosis. The calcinosis group presented with lower muscle enzyme levels at the time of JDM diagnosis, especially CK and ALT with statistical significance. This could reflect delay in diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Nutrition is largely affected in bipolar disorder (BD), however, there is a lack of understanding on the relationship between dietary categories, BD, and the prevalence of metabolic syndrome. The objective of this study is to examine dietary trends in BD and it is hypothesized that diets with increased consumption of seafood and high-fiber carbohydrates will be correlated to improved patient outcomes, and a lower frequency of metabolic syndrome. This retrospective cohort study includes two French cohorts. The primary cohort, FACE-BD, includes 268 stable BD patients. The second cohort, I-GIVE, includes healthy controls, both stable and acute BD and schizophrenia patients. Four dietary categories were assessed: meat, seafood, low-fiber and high-fiber carbohydrates. Dietary data from two food frequency questionnaires were normalized using min-max scaling and assessed using various statistical analyses. In our primary cohort, the increased high-fiber carbohydrate consumption was correlated to lower prevalence of metabolic syndrome and improved mood. Low-fiber carbohydrate consumption is associated with higher BMI, while higher seafood consumption was correlated to improved mood and delayed age of onset. Results were not replicated in our secondary cohort. Limitations: Our populations were small and two different dietary questionnaires were used; thus, results were used to examine similarities in trends. Overall, various dietary trends were associated with metabolic syndrome, BMI, lactate, mood and age of onset. Improving our understanding of nutrition in BD can provide mechanistic insight, clinically relevant nutritional guidelines for precision medicine and ultimately improve the quality of lives for those with BD. • Food frequency questionnaires evaluated in 2 French cohorts of Bipolar patients. • Various statistical analyses utilized to assess dietary trends in bipolar disorder. • Seafood consumption was associated with mood and age of disease onset. • High fiber carbohydrates consumption decreases prevalence of metabolic syndrome. • Low-fiber carbohydrate consumption was associated with higher Body Mass Index. [ABSTRACT FROM AUTHOR]

Alexander disease (ALXDRD) is a rare neurodegenerative disorder of astrocytes resulting from pathogenic variants in the GFAP gene. The genotype-phenotype correlation remains elusive due to the variable expressivity of clinical manifestations. In an attempt to clarify the effects of GFAP variants in ALXDRD, numerous studies were collected and analyzed. In particular, we systematically searched for GFAP variants associated with ALXDRD and collected information on the location within the gene and protein, prediction of deleteriousness/pathogenicity, occurrence, sex and country of origin of patients, DNA source, genetic testing, and clinical signs. To identify possible associations, statistical analyses and meta-analyses were applied, thus revealing a higher than expected percentage of adult patients with ALXDRD. Furthermore, substitution of Arginine, the most frequently altered residue among the 550 predominantly missense causative GFAP variants collected, were mostly de novo and more prevalent in early-onset forms of ALXDRD. The effect of defective splicing in modifying the impact of GFAP variants on the age of onset of ALXDRD was also postulated after evaluating the distribution of the corresponding deleterious predictive values. In conclusion, not only previously unrecognized genotype-phenotype correlations were revealed in ALXDRD, but also subtle mechanisms could explain the variable manifestations of the ALXDRD clinical phenotype. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to characterize the phenotype and genotype of patients with Yao syndrome (YAOS), with focus on comparing to prior cohorts, identifying novel features, and describing treatment observations. Methods: A retrospective medical records review of patients with YAOS seen at Mayo Clinic was conducted to characterize clinical features, NOD2 genotypes, and therapeutic trials and responses. Results: Twenty-two patients diagnosed with YAOS were included. Eighteen patients (81.8%) were female and twenty (90.9%) were White. Mean age at symptom onset was 24.0 ± 14.8 years. Common clinical manifestations included fever (81.8% of patients), rash (95.5%), chronic gastrointestinal symptoms (100%), arthralgia/arthritis (95.5%), and sicca symptoms (68.2%). NOD2 genotypes as single variants included IVS8 + 158 in 14 patients (63.6%), R702W in 8 patients (36.4%), 1007fs in 4 (18.2%), and one patient had only a previously unreported rare variant. Eight patients (36.4%) had compound (two or more) NOD2 variants. Potential comorbidities of YAOS observed in this cohort included gastrointestinal dysmotility, autonomic dysfunction, and mast cell activation-like symptoms. Glucocorticoid responsiveness was observed in 15 of 20 patients exposed (75%). Eleven patients (50.0%) received IL-1 inhibitor therapy, and one patient (4.5%) received IL-6 inhibitor therapy with adequate disease control. Conclusion: Our findings substantiate the occurrence of fevers, arthralgia/ arthritis, rash, chronic gastrointestinal symptoms, and sicca-like symptoms described previously in patients with YAOS. Novel clinical features and one NOD2 variant not previously described were identified. Glucocorticoids, biologic IL-1 inhibitors, and IL-6 receptor inhibitors appeared to be effective for treatment of patients with YAOS. [ABSTRACT FROM AUTHOR]

From adolescence, women become more likely to experience fear dysregulation. Oral contraceptives (OCs) can modulate the brain regions involved in fear processes. OCs are generally used for years and often initiated during adolescence, a sensitive period where certain brain regions involved in the fear circuitry are still undergoing important reorganization. It remains unknown whether OC use during adolescence may induce long‐lasting changes in the fear circuitry. This study aimed to examine whether age of onset moderated the relationship between duration of use and fear‐related brain structures. We collected structural MRI data in 98 healthy adult women (61 current users, 37 past users) and extracted grey matter volumes (GMV) and cortical thickness (CT) of key regions of the fear circuitry. Non‐linear multiple regressions revealed interaction effects between age of onset and quadratic duration of use on GMV of the right hippocampus and right ventromedial prefrontal cortex (vmPFC). Among women who initiated OCs earlier in adolescence, a short duration of use was associated with smaller hippocampal GMV and thicker vmPFC compared to a longer duration of use. For both GMV and CT of the right vmPFC, women with an early OC onset had more grey matter at a short duration of use than those with a later onset. Our results suggest that OC use earlier in adolescence may induce lasting effects on structural correlates of fear learning and its regulation. These findings support further investigation into the timing of OC use to better comprehend how OCs could disrupt normal brain development processes. [ABSTRACT FROM AUTHOR]

ABSTRACT Characterising the spatial and temporal distribution of the S‐N‐trending rift in southern Tibet is crucial for elucidating the dynamics of E‐W extension within the Tibetan Plateau since the Miocene. The Kung Co–Tangra Yumco rift, located in the central part of the rift system, was initiated at the peak of rifting development. While the initiation of rifting has been ascertained through low‐temperature thermochronology, direct timing constraints remain absent for the Gangga Graben in the southernmost region. Utilising the quartz electron spin resonance (ESR) dating technique, we ascertained the onset age of the eastern boundary fault of the Gangga Graben to be 12.00 ± 1.80 Ma, with an accelerated activity phase at 9.17 ± 1.19 Ma, and an activity age for the western boundary fault at 2.22 ± 0.24 Ma. U‐series dating conducted on the western boundary disclosed a time span of 20–13 ka for hot spring fissure activity. Seismic evidence, inclusive of those from the Gongdapu Horst, indicates persistent activity of the Gangga Graben since the Pleistocene. Comparative analysis of age data from the Kung Co–Tangra Yumco rift suggests that it commenced almost synchronously along its strike at ~14.5–12 Ma. Considering the rifts trending from west to east in southern Tibet and the genetic mechanism of leucogranite, we propose an E‐W extension mechanism in southern Tibet. At ~26–14 Ma, the lithosphere experienced weakened delamination and asthenosphere upwelling, leading to a series of magmatic activities and onset of E‐W extension in southern Tibet. At ~17–7 Ma, as the basal shearing of the underthrusting Indian Plate increased, it marked the peak phase of rifting in southern Tibet. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion X‐linked dystonia‐parkinsonism (XDP), a neurodegenerative movement disorder endemic to the Philippines, is primarily investigated in patients from Panay Island and the Greater Manila area. However, individuals residing in geographically distant regions may exhibit different clinical or genetic characteristics compared to those documented in earlier reports.The aim was to investigate the relationship of XDP clinical features in a Mindanao cohort with modifiers of age at onset (AAO) variability and utilization of a previously reported AAO model.We investigated clinical and genetic features in 27 XDP patients from southern Mindanao. In all patients, we genotyped the 4 polymorphisms linked to AAO.The XDP‐relevant hexanucleotide repeat number significantly correlated with AAO in the 27 patients and explained about 68% of AAO variability. There is no statistical difference between the predicted and actual AAO.The AAO model may provide reliable predictions by employing the effect of XDP genetic modifiers of AAO variability. [ABSTRACT FROM AUTHOR]

Objective: Late-onset systemic lupus erythematosus (LoSLE) is known to possess characteristics different from those of early-onset SLE (EoSLE), thereby making their diagnosis difficult. This study aimed to assess the characteristic features of LoSLE in Japan, a model country with a super-aged society. Methods: Data were obtained from the Lupus Registry of Nationwide Institutions, which includes a multicenter cohort of patients with SLE in Japan who satisfied the 1997 American College of Rheumatology revised classification criteria for SLE. Data were compared between patients with LoSLE (≥50 years old at onset) and EoSLE (<50 years old at onset). To identify factors associated with LoSLE, binary logistic regression was used for the multivariate analysis, and missing values were complemented by multiple imputations. We also conducted a sub-analysis for patients diagnosed within 5 years of onset. Results: Out of 929 enrolled patients, 34 were excluded owing to a lack of data regarding onset age. Among the 895 remaining patients, 100 had LoSLE, whereas 795 had EoSLE. The male-to-female ratio was significantly higher in the LoSLE group than in the EoSLE group (0.32 vs 0.11, p < 0.001). With respect to SLEDAI components at onset, patients with LoSLE exhibited a higher frequency of myositis (11.9% vs 3.75%, p = 0.031), lower frequency of skin rash (33.3% vs 67.7%, p < 0.001), and lower frequency of alopecia (7.32% vs 24.7%, p = 0.012). No significant differences in overall disease activity at onset were observed between the two groups. Regarding medical history, immunosuppressants were more commonly used in EoSLE. A multivariate analysis revealed that a higher male proportion and a lower proportion of new rash at onset were independent characteristic features of LoSLE. We also identified late onset as an independent risk factor for a high SDI score at enrollment and replicated the result in a sub-analysis for the population with a shorter time since onset. Conclusions: We clarified that LoSLE was characterized by a higher male proportion, a lower frequency of skin rash and a tendency to organ damage. Now that the world is faced with aging, our results may be helpful at diagnosis of LoSLE. [ABSTRACT FROM AUTHOR]

Suicidal thoughts and behaviors often emerge in a predictable sequence, with suicidal ideation (SI) preceding planning, and planning preceding actions. Few studies, however, have considered the timing and duration of non-suicidal self-injury (NSSI) in these transitions. Accordingly, this study examined: 1) the developmental sequencing of NSSI, SI and suicide attempts, and 2) whether age of onset or duration predict transitions from NSSI to other SITB, and from SI to NSSI. 704 first-year students from a mid-sized Canadian university (Sample 1) and 2095 adults from an online research volunteer panel (Sample 2) completed the Self-Injurious Thoughts and Behaviors Interview self-report, which assessed the presence, age of onset, and recency of SITB. NSSI and SI typically onset before age 15, while suicide planning and attempt usually began at or after age 15. Transition from NSSI to SI was likeliest in the first year after NSSI onset. Transition from NSSI to suicide attempt was likeliest in the second and third year after NSSI onset in Sample 1, and up to four years after NSSI onset in Sample 2. Early (before age 13) and late (after age 16) onsets of NSSI predicted higher odds of transitioning from NSSI to SI or attempt. Transition from SI to NSSI was likeliest in the first two years after SI onset and when SI began before age 13. The first year after NSSI or SI onset are critical for transitions to other SITB. Targeted prevention and monitoring should be considered for people who recently initiated NSSI. • NSSI and suicidal ideation (SI) typically begin within 1–2 years of each other • Transition from NSSI to SI was likeliest in the first year after NSSI onset • Transition risk from NSSI to attempt persisted for 3+ years after NSSI onset • NSSI onset before age 13 or after 16 predicted transitioning to SI or attempt • Onset of SI before age 13 predicted transition to NSSI [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionsWhile substantial research has focused on systemic immunomodulatory therapy for ocular cicatricial pemphigoid (OCP), limited data exist on managing associated ocular surface disease (OSD). This study evaluates treatments for OCP-related OSD at our institution.We conducted a retrospective analysis of patients diagnosed with cicatrizing conjunctivitis at the University of Colorado Hospital from January 1, 2013, to October 31, 2023. Patients with cicatrizing conjunctivitis due to non-OCP conditions were excluded, and disease severity was classified using the Foster Staging System.Our review included 30 patients with OCP, all with at least six months of follow-up. The mean age of symptom onset (n = 19) was 62.2 years (SD = 16.4), while the mean age at diagnosis (n = 28) was 65.1 years (SD = 12.7). The most common OSD treatments at the last visit were preservative-free artificial tears (87%), topical corticosteroids (43%), autologous serum eye drops (40%), topical antibiotics (30%), and topical immunomodulators (23%). All patients used at least one treatment, with 83.3% on prescription therapies. Patients averaged 3.33 (SD: 1.4) treatments, with 1.7 (SD: 1.2) being prescriptions. Topical immunomodulators had the highest discontinuation rate at 73.1% (n = 19/26). Autologous serum eye drops and topical corticosteroids were the least discontinued treatments. Number of total treatments, prescriptions, and procedures sharply increased at stage three OCP.The number of treatments and procedures increased with OCP severity, indicating that advanced OCP often necessitated more intensive OSD management. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory disease with significant impact upon quality of life. Generic quality‐of‐life measures suffer from decreased face validity and content validity, leading to the development of disease‐specific quality‐of‐life measures such as the Hidradenitis Suppurativa Quality of Life (HiSQOL) outcome measure. The aim of this study was to validate the use of the HiSQOL in the Australian population and evaluate the quality‐of‐life impact in HS patients in Australia.A total of 301 patients were recruited and consented to be involved in this study. All participants were invited to complete the HiSQOL questionnaire along with basic demographic and disease information, the DLQI and HADS anxiety and depression scale. Participants were then asked to repeat the questionnaires 14 days later to assess test–retest reliability.The mean HiSQOL score was 46.5 out of a possible total score of 76 (SD = 24.2) indicating a very large impact on quality of life. Based upon the published validity bands this corresponds to a very large impact on quality of life. Validation statistics indicated a high degree of internal consistency (Cronbach's alpha = 0.956) with expected levels of convergent validity and excellent test–retest reliability (p = 0.95). Multiple regression analysis indicated individuals with a younger age of onset and positive family history had significantly greater quality‐of‐life impact as measured by the HiSQOL.The HiSQOL is a valid, reliable measure for assessing the quality‐of‐life impact of HS. Significant factors influencing quality of life include age of onset and family history. Longitudinal measurements will enable evaluation of the impact of therapy upon QOL in the Australian context. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aims Methods Results Conclusion Rosacea is more common in women and Caucasians, leading to little research on rosacea in Asian men. Additionally, there is limited research on the patients across different age groups.The aim of this study is to analyze and compare the characteristics of male patients of rosacea among different age groups.A retrospective analysis was conducted on 215 male patients with rosacea, investigating their characteristics, clinical symptoms, exacerbating factors, complications, psychological status, and treatment, as well as exploring factors influencing the early onset of male rosacea.The patients were divided into three age groups (≤ 30 years, 31–44 years, and ≥ 45 years), with the study revealing an average age of 38.59 ± 13.13 years among the patients. The most common subtype of rosacea in men was erythematotelangiectatic rosacea (ETR), followed by phymatous rosacea (PhR). The main reported features included persistent erythema (87.4%) and telangiectasia (71.2%), predominantly affecting the nose (58.6%) and cheeks (56.3%). Twenty‐six percent of patients reported concurrent skin diseases, with 14.0% reporting systemic diseases. Significant differences were observed among different age groups regarding family history, clinical features, lesion distribution, symptom severity, aggravating factors, presence of systemic diseases, and treatment preferences. Subjective skin typing, Fitzpatrick phototype, and positive family history were identified as factors influencing the age of onset of rosacea in men.Male patients with rosacea exhibit distinct clinical characteristics, with a greater prevalence of nasal involvement and nasal lesions among male patients. Clinical features vary among different age groups, with patients aged ≥ 45 experiencing more complex and severe symptoms. Patients aged ≤ 30 may be more influenced by genetic factors and have higher treatment expectations. [ABSTRACT FROM AUTHOR]

The present longitudinal study examined a large sample of individuals with PIMD/Polyhandicap to: (i) describe the evolution over time of the health status in terms of severity, (ii) identify the potential predictors of health status change. This study used the data of the French national EVAL-PLH cohort. Inclusion criteria were: individuals with PIMD/Polyhandicap; age > 3 years at the time of inclusion; age at onset of cerebral lesion younger than 3 years old. The definition of the change in health status over the 5-year period was derived from the Polyhandicap Severity Scale. Among the 875 individuals included in 2015–2016, 492 (56.2%) individuals were assessed in 2020–2021. According to the definition, 68.8% (n = 309), 64.7% (n = 310), and 80.2% (n = 368) of the individuals presented with a worsened or stable severity status based on the global score, the abilities score, and the comorbidities score, respectively. Compared with the individuals with a non-worsened health status (global score), the individuals with a stable or worsened health status were more likely to receive care in specialized rehabilitation centres, more likely to have an antenatal or progressive aetiology, and more likely to have a higher dependency level. The current study provides a robust perspective of the worsened health among persons with PIMD/Polyhandicap over time. [ABSTRACT FROM AUTHOR]

Objective: Previous studies assessing factors associated with drug‐resistant epilepsy (DRE) were constrained by their amalgamation of all epilepsy syndromes in their analyses and the absence of uniform criteria for defining DRE. Our objective was to identify predictors of DRE among the four primary childhood epilepsy syndrome groups within a cohort of children with new onset seizures, using the International League Against Epilepsy (ILAE) definition of DRE and the recent classification of epilepsies. Methods: This is a prospective study of 676 children with new onset seizures initiated on antiseizure medication. Patients were monitored for the occurrence of DRE according to the ILAE criteria and were categorized into one of four epilepsy groups: self‐limited focal epilepsies (SeLFEs), genetic generalized epilepsies (GGEs), developmental epileptic encephalopathies (DEEs), and focal epilepsies. Cox regression analysis was performed to identify predictors of DRE within each epilepsy group. Results: Overall, 29.3% of children were classified as having DRE, with the highest incidence observed among children diagnosed with DEEs (77.7%), followed by focal epilepsies (31.5%). Across the entire cohort, predictors of DRE included the presence of an epileptogenic lesion, a higher pretreatment number of seizures, experiencing multiple seizure types, presence and severity of intellectual and developmental delay, myoclonus, and younger age at epilepsy onset. Within the GGEs, only a younger age at seizure onset and experiencing multiple seizure types predicted DRE. Among focal epilepsies, predictors of DRE included the presence of an epileptogenic lesion, experiencing multiple seizure types, and having a greater number of pretreatment seizures. Within the DEEs, predictors of DRE were the occurrence of tonic seizures. Predictors of DRE within SeLFEs could not be identified. Significance: This study indicates that different epilepsy syndromes are associated with distinct predictors of drug resistance. Anticipation of drug resistance within various groups is feasible using accessible clinical variables throughout the disease course. [ABSTRACT FROM AUTHOR]

The incidence of colorectal cancer (CRC) among individuals younger than age 50 (early-onset CRC [EOCRC]) has substantially increased, and yet the etiology and molecular mechanisms underlying this alarming rise remain unclear. We compared tumor-associated T-cell repertoires between EOCRC and average-onset CRC (AOCRC) to uncover potentially unique immune microenvironment-related features by age of onset. Our discovery cohort included 242 patients who underwent surgical resection at Cleveland Clinic from 2000 to 2020. EOCRC was defined as younger than age 50 years at diagnosis (N = 126) and AOCRC as 60 years of age or older (N = 116). T-cell receptor (TCR) abundance and clonality were measured by immunosequencing of tumors. Logistic regression models were used to evaluate the associations between TCR repertoire features and age of onset, adjusting for sex, race, tumor location, and stage. Findings were replicated in 152 EOCRC and 1984 AOCRC cases from the Molecular Epidemiology of Colorectal Cancer Study. EOCRC tumors had significantly higher TCR diversity compared with AOCRC tumors in the discovery cohort (odds ratio [OR] = 0.44, 95% confidence interval [CI] = 0.32 to 0.61, P  < .0001). This association was also observed in the replication cohort (OR = 0.74, 95% CI = 0.62 to 0.89, P  = .0013). No significant differences in TCR abundance were observed between EOCRC and AOCRC in either cohort. Higher TCR diversity, suggesting a more diverse intratumoral T-cell response, is more frequently observed in EOCRC than AOCRC. Further studies are warranted to investigate the role of T-cell diversity and the adaptive immune response more broadly in the etiology and outcomes of EOCRC. [ABSTRACT FROM AUTHOR]

The Hippo signalling pathway is a conserved kinase cascade that orchestrates diverse cellular processes, such as proliferation, apoptosis, lineage commitment and stemness. With the onset of society ages, research on skeletal aging‐mechanics‐bone homeostasis has exploded. In recent years, aging and mechanical force in the skeletal system have gained groundbreaking research progress. Under the regulation of mechanics and aging, the Hippo signalling pathway has a crucial role in the development and homeostasis of bone. We synthesize the current knowledge on the role of the Hippo signalling pathway, particularly its downstream effectors yes‐associated protein (YAP) and transcriptional co‐activator with PDZ‐binding motif (TAZ), in bone homeostasis. We discuss the regulation of the lineage specification and function of different skeletal cell types by the Hippo signalling pathway. The interactions of the Hippo signalling pathway with other pathways, such as Wnt, transforming growth factor beta and nuclear factor kappa‐B, are also mentioned because of their importance for modulating bone homeostasis. Furthermore, YAP/TAZ have been extensively studied as mechanotransducers. Due to space limitations, we focus on reviewing how mechanical forces and aging influence cell fate, communications and homeostasis through a dysregulated Hippo signalling pathway. [ABSTRACT FROM AUTHOR]

Purpose: The treatment of mental disorders has shifted from inpatient wards to community-based settings in recent years, but some patients may still have to be admitted to inpatient wards, sometimes involuntarily. It is important to maintain the length of hospital stay (LoS) as short as possible while still providing adequate care. The present study aimed to explore the factors associated with the LoS in involuntarily admitted psychiatric patients. Methods: A ten-year retrospective chart review of 332 patients admitted involuntarily to the inpatient psychiatric ward of the General University Hospital of Ioannina, Northwestern Greece, between 2008 and 2017 was conducted. Results: The mean LoS was 23.8 (SD = 33.7) days and was relatively stable over the years. Longer-stay hospitalization was associated with schizophrenia-spectrum disorder diagnosis, previous hospitalizations and the use of mechanical restraint, whereas patients in residential care experienced significantly longer LoS (52.6 days) than those living with a caregiver (23.5 days) or alone (19.4 days). Older age at disease onset was associated with shorter LoS, whereas no statistically significant differences were observed with regard to gender. Conclusion: While some of our findings were in line with recent findings from other countries, others could not be replicated. It seems that multiple factors influence LoS and the identification of these factors could help clinicians and policy makers to design more targeted and cost-effective interventions. The optimization of LoS in involuntary admissions could improve patients' outcomes and lead to more efficient use of resources. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusionTo apply the multistep model of pathogenesis in amyotrophic lateral sclerosis (ALS) to data from a multiethnic Malaysian registry.Clinical data, including age at symptom onset, was collected from 289 patients who presented to our multidisciplinary clinic from 2016 until 2024. A least squares linear regression model was constructed from the logarithm of approximated incidence and the logarithm of age. Population incidence was approximated by adjusting the absolute numbers of patients in 5 year groups by the size of the general population in the respective age group.A linear relationship between log of incidence versus log of age was observed, with a slope of 4.57 (95% CI, 3.3–5.8) and an r2 value of 0.93, suggesting a 6-step process.Progression toward symptom onset in Malaysian ALS patients appears consistent with a multistep model of disease as observed in other cohorts. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) heritability is estimated to be around 70–80%. Yet, much of it remains to be explained. Studying transmission patterns may help in understanding other factors contributing to the development of AD. Objective: In this study, we aimed to search for evidence of autosomal recessive or X- and Y-linked inheritance of risk factors in a large cohort of Portuguese AD patients. Methods: We collected family history from patients with AD and cognitively healthy controls over 75 years of age. We compared the proportions of maternal and paternal history in male and female patients and controls (to search for evidence of X-linked and Y-linked inherited risk factors). We compared the risk of developing AD depending on parents' birthplace (same vs. different), as a proxy of remote consanguinity. We performed linear regressions to study the association of these variables with different endophenotypes. Results: We included 3090 participants, 2183 cognitively healthy controls and 907 patients with AD. Men whose mother had dementia have increased odds of developing AD comparing to women whose mother had dementia. In female patients with a CSF biomarker-supported diagnosis of AD, paternal history of dementia is associated with increased CSF phosphorylated Tau levels. People whose parents are from the same town have higher risk of dementia. In multivariate analysis, this proxy is associated with a lower age of onset and higher CSF phosphorylated tau. Conclusions: Our study gives evidence supporting an increased risk of developing AD associated with an X-linked inheritance pattern and remote consanguinity. [ABSTRACT FROM AUTHOR]

Progressive inflammation of one hemisphere characterises Rasmussen's encephalitis (RE), but contralesional epileptiform activity has been repeatedly reported. We aimed to quantify contralesional epileptiform activity in RE and uncover its functional and structural underpinnings. We retrospectively ascertained people with RE treated between 2000 and 2018 at a tertiary centre (Centre 1) and reviewed all available EEG datasets. The temporal occurrence of preoperative contralesional epileptiform activity (interictal/ictal) was evaluated using mixed-effects logistic regression. Cases with/without contralesional epileptiform activity were compared for cognition, inflammation (ipsilesional brain biopsies), and MRI (cortical and fixel-based morphometry). EEG findings were validated in a second cohort treated at another tertiary centre (Centre 2) between 1995 and 2020. We included 127 people with RE and 687 EEG samples. Preoperatively, contralesional epileptiform activity was seen in 30/68 (44%, Centre 1) and 8/59 (14%, Centre 2). In both cohorts, this activity was associated with younger onset age (OR = 0.9; 95% CI 0.83–0.97; P = 0.006). At centre 1, contralesional epileptiform activity was associated with contralesional MRI alterations, lower intelligence (OR = 5.19; 95% CI 1.28–21.08; P = 0.021), and impaired verbal memory (OR = 10.29; 95% CI 1.97–53.85; P = 0.006). After hemispherotomy, 11/17 (65%, Centre 1) and 28/37 (76%, Centre 2) were seizure-free. Contralesional epileptiform activity was persistent postoperatively in 6/12 (50%, Centre 1) and 2/34 (6%, Centre 2). Preoperative contralesional epileptiform activity reduced the chance of postoperative seizure freedom in both cohorts (OR = 0.69; 95% CI 0.50–0.95; P = 0.029). Our findings question the concept of strict unilaterality of RE and provide the evidence of contralesional epileptiform activity as a possible EEG predictor for persisting postoperative seizures. [ABSTRACT FROM AUTHOR]

Background: Epidemiological studies on multisystem atrophy (MSA) are scarce. Our aim has been to analyse 10-year incidence, point prevalence, survival, and the time to diagnosis of MSA in Navarre, a northern Spanish region. Methods: This is a population-based observational retrospective study, from 2012 to 2021, which covered the population of Navarre (followed until 31 December 2021). Data from various sources of health information were reviewed in order to identify all potential diagnoses of MSA, that were validated from medical records. Patients were included if they fulfilled the new Movement Disorder Society criteria. Results: We observed a crude average annual incidence rate (IR) of 0.49/100,000 person-years, with the highest occurring in the age group of 60–69 years. No significant IR differences by sex or subtype were observed. Point prevalence in December 2021 was 2.43/100,000 inhabitants. Joinpoint analysis for global incidence and prevalence experienced stable annual rates during the whole period, showing an upward trend for prevalence without a statistically significant slop. The median age at symptom onset was 65 years (range 47–76). The median time to diagnosis was 36 months, without statistically significant differences between sex, age at diagnosis or subtypes. Median time of survival from clinical onset was 7 years. Age of onset above 70 years and autonomic onset were associated with reduced survival. Conclusions: This is the first population-based epidemiological study on MSA in Spain. It provides detailed incidence and prevalence data for MSA that may be useful for appropriate management of health resources. [ABSTRACT FROM AUTHOR]

Oocytes play a crucial role in transmitting maternal mitochondrial DNA (mtDNA), essential for the continuation of species. However, the effects of mitochondrial reactive oxygen species (ROS) on mammalian oocyte maturation and mtDNA maintenance remain unclear. We investigated this by conditionally knocking out the Sod2 gene in primordial follicles, elevating mitochondrial matrix ROS levels from early oocyte stages. Our data indicates that reproductive aging in Sod2 conditional knockout females begins at 6 months, with oxidative stress impairing oocyte quality, particularly affecting OXPHOS complex II and mtDNA-encoded mRNA levels. Despite unchanged mtDNA mutation load, mtDNA copy numbers exhibited significant variations. Strikingly, reducing mtDNA copy numbers by reducing mtSSB protein, crucial for mtDNA replication, accelerated reproductive aging onset to three months, underscoring the critical role of mtDNA copy number maintenance under oxidative stress conditions. This research provides new insights into the relationship among mitochondrial ROS, mtDNA, and reproductive aging, offering potential strategies for delaying aging-related fertility decline. Elevating mitochondrial ROS induces female reproductive aging without increasing maternal mtDNA mutation load where deducing mtDNA copy numbers accelerates this phenomenon, highlighting the importance of maintaining mtDNA quantity under oxidative stress. [ABSTRACT FROM AUTHOR]

Introduction/Objectives: Optic nerve sheath (ONS) enhancement using magnetic resonance imaging of the orbits was observed in patients with giant cell arteritis (GCA). We previously showed that ONS diameter (ONSD) by bedside ultrasound is increased in patient with active GCA. This study aims to assess whether ONSD decreases with clinical remission in patients with GCA. Methods: A prospective cohort study was conducted from June 2022 to January 2023. Patients who had an optic nerve ultrasound at GCA diagnosis as part of a previous crosssectional study were eligible. Optic nerve ultrasound was performed by the same investigator at diagnosis and month 3. ONSD (includes the optic nerve and its sheath) and optic nerve diameter (OND) were measured. Descriptive statistics for baseline characteristics and paired sample t-test were performed to assess the mean difference in OND and ONSD between diagnosis and month 3. Results: Nine patients with GCA were included. The median age at disease onset was 79 years (interquartile range (IQR) of 79–82 years), and 7 patients were males. All patients were in clinical remission at month 3 on prednisone (median dose of 15 mg/day, IQR of 10–25 mg). The mean ONSD was lower at month 3 (3.76 mm) compared to baseline (5.98 mm), with a paired mean difference of 2.22 mm (95% CI 1.41–3.03 mm, p < 0.001). As anticipated, OND measurements did not vary between diagnosis and month 3. Conclusion: ONSD on ultrasound improves after 3 months of therapy in patients with GCA. A longer prospective study is required to determine if ONSD is useful to assess disease activity in GCA. Key Points • ONS ultrasound can identify patients with active GCA. • The ONSD on ultrasound is dynamic and improved after 3 months of GCA therapy. • ONS ultrasound may be useful to monitor disease activity in GCA. [ABSTRACT FROM AUTHOR]

Background: Temporal lobe epilepsy associated with hippocampal sclerosis (TLE-HS) is a surgically treatable epileptic syndrome. While the core of pre-surgical evaluations rely on video-EEG, recent studies question the necessity of recorded seizures denying a possible role of ictal EEG in surgical decision. This study aims to retrospectively assess the prognostic value of EEG ictal patterns in TLE-HS, in order to identify which patients need further investigations before offering surgery. Methods: We included TLE-HS patients who underwent surgery with at least one captured seizure during non-invasive pre-surgical video-EEG recordings. They were classified in "mesial" and "lateral/mixed", according to the ictal EEG patterns, defined by the frequency of the discharge (mesial ≥ 5 Hz, lateral < 5 Hz). Seizure outcome was assessed by Engel's Class. Statistical analyses were performed to evaluate associations between EEG patterns and post-surgical outcomes. Results: Sixty-nine exhibited a mesial pattern, forty- two displayed lateral/mixed patterns. Mesial pattern group had a significantly higher rate of postsurgical seizure freedom (82.7% vs. 28.6%). Gender, age of onset, age at surgery, duration of epilepsy, seizure frequency, and lateralization did not influence the outcome. Mesial pattern significantly correlated with favorable outcomes (p < 0.001), suggesting its potential predictive value. Conclusion: This retrospective study proposes ictal EEG patterns as possible predictors of postoperative prognosis in TLE-HS. A mesial pattern correlates with better outcomes, indicating a potentially more circumscribed epileptogenic zone. Patients with lateral/mixed patterns may benefit from additional investigations to delineate the epileptogenic zone. Further studies are warranted to validate and extend these findings. [ABSTRACT FROM AUTHOR]

The escalating worldwide prevalence of Crohn's disease (CD) among children and adolescents, coupled with a trend toward earlier onset, presents significant challenges for healthcare systems. Moreover, the chronicity of this condition imposes substantial individual burdens. Consequently, the principal objective of CD treatment revolves around rapid inducing remission. This study scrutinizes the impact of age, gender, initial disease localization, and therapy on the duration to achieve disease activity amelioration. Data from the Saxon Pediatric IBD Registry in Germany were analyzed over a period of 15 years. In addition to descriptive methods, logistic and linear regression analyses were conducted to identify correlations. Furthermore, survival analyses and Cox regressions were utilized to identify factors influencing the time to improvement in disease activity. These effects were expressed as Hazard Ratios (HR) with 95% confidence intervals. Data on the clinical course of 338 children and adolescents with CD were available in the registry. The analyses showed a significant correlation between a young age of onset and the severity of disease activity. It was evident that treatment with anti-TNF (Infliximab) was associated with a more favorable prognosis in terms of the time required for improvement in disease activity. Similarly, favorable outcomes were observed with the combination therapies of infliximab with enteral nutrition therapy and Infliximab with immunosuppressants. Conclusion: Our analysis of data from the Saxon Pediatric IBD Registry revealed that the timeframe for improvement of disease activity in pediatric Crohn's disease is influenced by several factors. Specifically, patient age, treatment modality, and initial site of inflammation were found to be significant factors. The study provides important findings that underline the need for individualized treatment. [ABSTRACT FROM AUTHOR]

There is an imbalance between goal-directed and habitual-learning system in patients with obsessive-compulsive disorder (OCD). At present, the relationship between cognitive behavior therapy (CBT) as a first-line therapy and goal-directed and habitual-learning disorder is still unclear. We attempted to discuss the effect of CBT treatment in patients with OCD, using abnormalities in goal-directed and habitual-learning-related brain regions at baseline as predictive factors. A total of 71 subjects, including 35 OCD patients and 36 healthy controls, were recruited. The OCD patients underwent 8 weeks of CBT. These patients were divided into two groups based on treatment response (N responders = 18, N nonresponders = 17). Further subgroup analysis was conducted based on disease duration (N short = 17, N long = 18) and age of onset (N early = 14, N late = 21). We collected resting-state ROI-ROI functional connectivity data and apply repeated-measures linear mixed-effects models to investigate the differences of different subgroups. CBT led to symptom improvement in OCD patients, with varying degrees of effectiveness across subgroups. The orbitofrontal cortex (OFC) and insula, key regions for goal-directed behavior and habitual-learning, respectively, showed significant impacts on CBT efficacy in subgroups with different disease durations and ages of onset. The findings suggest that the goal-directed system may influence the efficacy of CBT through goal selection, maintenance, and emotion regulation. Furthermore, we found that disease duration and age of onset may affect treatment outcomes by modulating functional connectivity between goal-directed and habitual-learning brain regions. • The study examines how CBT affects OCD patients and brain function related to learning patterns. • The research uncovers diverse responses to CBT based on disease duration and age of onset. • The findings emphasize the role of the goal-directed system in influencing CBT's effectiveness. [ABSTRACT FROM AUTHOR]

Copyright of Journal of China Medical University is the property of Journal of China Medical University Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of West China Journal of Stomatology is the property of Sichuan University, West China College of Stomatology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective Methods Results Interpretation To assess the prevalence, timing, and functional impact of neuropsychiatric symptoms in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and to assess whether these neuropsychiatric symptoms are associated with magnetic resonance imaging (MRI) features of the patients.Our study included a total of 78 patients with CADASIL. To assess neuropsychiatric symptoms, we evaluated the caregivers using the Neuropsychiatric Inventory (NPI). Patients were considered to have an irritability, depression, apathy, aggression, or anxiety disorder if they scored ≥1 in the NPI. Subsequently, we conducted a more detailed assessment of irritability, depression, apathy, aggression, and anxiety. Multivariate logistic regression was employed to analyze the relationships between neuropsychiatric symptoms and clinical/MRI features in the patients.Overall, 57.69% of patients with CADASIL experienced neuropsychiatric symptoms. Among these symptoms, irritability was the most prevalent (52.56%), followed by depression (19.23%), apathy (17.95%), aggression (7.69%), and anxiety (6.41%). The mean age of onset for irritability was the youngest, followed by anxiety, apathy, aggression, and depression. Among patients with both stroke/TIA and neuropsychiatric symptoms, 31.03% reported experiencing neuropsychiatric symptoms prior to stroke/TIA. Furthermore, both irritability and apathy had a negative impact on the patients' daily functioning. Additionally, there was a correlation between the presence of neuropsychiatric symptoms and the patients' MRI lesion burden.Our study has discovered that neuropsychiatric symptoms are highly prevalent in patients with CADASIL and may occur before cerebrovascular events, suggesting that neuropsychiatric symptoms of CADASIL deserve more attention and earlier exploration. [ABSTRACT FROM AUTHOR]

Background: Hereditary angioedema with normal C1-inhibitor function (HAE nC1-INH) and idiopathic angioedema of unknown etiology (AE-UNK) are rare conditions that cause recurrent subcutaneous and submucosal swelling. The characteristics and clinical outcomes of patients with these conditions in Canada have not been studied. Methods: The aim of this study was to extract real-world evidence from the electronic health records of patients with HAE nC1-INH or AE-UNK who were managed in selected practices of Canadian HAE-treating specialist physicians between 01-Jan-2012 and 01-Jan-2022, to examine case numbers, treatment, clinical outcomes, and healthcare utilization. Results: Of 60 patients (37 with HAE nC1-INH, 23 with AE-UNK), median (range) age at symptom onset was 21.5 (5.0–57.0) and 23.0 (10.0–54.0) years, respectively. Time to diagnosis from onset of symptoms was 7.0 (0.0–43.0) and 2.0 (− 10.0 to 50.0) years. Significant differences were observed in terms of the predominant triggers for angioedema attacks between patients with HAE nC1-INH and AE-UNK: stress (65% vs. 26%, p = 0.007) and estrogen therapy (35% vs. 9%, p = 0.031). Before diagnosis, most patients received antihistamines (50% of HAE nC1-INH and 61% of AE-UNK patients). Post-diagnosis, 73% and 74% of HAE nC1-INH and AE-UNK patients received long-term prophylaxis (LTP), with the most common LTP treatments being subcutaneous pdC1-INH (43% of HAE nC1-INH patients and 39% of AE-UNK patients) and tranexamic acid (41% of HAE nC1-INH patients and 35% of AE-UNK patients). Of patients with HAE nC1-INH, and patients with AE-UNK, 22% and 13%, respectively, were taking more than one LTP treatment concurrently. Before HAE treatment initiation, significantly fewer patients with AE-UNK compared to patients with HAE nC1-INH had angioedema attacks affecting their extremities (13% vs. 38%, p = 0.045) and GI system (22% vs. 57%, p = 0.015). In the three months following treatment initiation, patients with AE-UNK experienced significantly fewer angioedema attacks compared to patients with HAE nC1-INH (median 2.0 attacks [0.0–48.0] vs. 6.0 attacks [0.0–60.0], p = 0.044). Additionally, fewer patients with AE-UNK compared to HAE nC1-INH experienced attacks affecting their GI system (26% vs. 57%, p = 0.032). Attack duration and frequency significantly decreased for patients with HAE nC1-INH from a median of 1.00 day (range: 0.00–7.00) to 0.29 day (range: 0.02–4.00; p = 0.001) and from 10.50 attacks (range: 0.00–90.00) to 6.00 attacks (range: 0.00–60.00; p = 0.004) in the three months following HAE treatment initiation. Conclusions: Using Canadian real-world evidence, these data demonstrate differing clinical trajectories between patients with HAE nC1-INH and AE-UNK, including diagnostic delays, varied attack characteristics, treatment responses and healthcare utilization. Despite treatment response, many patients still experienced frequent angioedema attacks. These results suggest an unmet need for treatment guidelines and therapies specifically for patients with HAE nC1-INH and AE-UNK and better understanding of the pathophysiology accounting for the reported differences between the two. [ABSTRACT FROM AUTHOR]

Childhood and adolescent overweight and obesity are one of the most serious public health challenges of the 21st century. A range of genetic, family, and environmental factors, and health behaviors are associated with childhood obesity. Developing models to predict childhood obesity requires careful examination of how these factors contribute to the emergence of childhood obesity. This paper has employed Multiple Linear Regression (MLR), Random Forest (RF), Decision Tree (DT), and K-Nearest Neighbour (KNN) models to predict the age at the onset of childhood obesity in Saudi Arabia (S.A.) and to identify the significant factors associated with it. De-identified data from Arar and Riyadh regions of S.A. were used to develop the prediction models and to compare their performance using multi-prediction accuracy measures. The average age at the onset of obesity is 10.8 years with no significant difference between boys and girls. The most common age group for onset is (5-15) years. RF model with the R2 = 0.98, the root mean square error = 0.44, and mean absolute error = 0.28 outperformed other models followed by MLR, DT, and KNN. The age at the onset of obesity was linked to several demographic, medical, and lifestyle factors including height and weight, parents' education level and income, consanguineous marriage, family history, autism, gestational age, nutrition in the first 6 months, birth weight, sleep hours, and lack of physical activities. The results can assist in reducing the childhood obesity epidemic in Saudi Arabia by identifying and managing high-risk individuals and providing better preventive care. Furthermore, the study findings can assist in predicting and preventing childhood obesity in other populations. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion To study the changes in incidence, age at onset and severity of visual impairment (VI) due to retinitis pigmentosa (RP) in the Years 1980–2019, and the incidence and age at diagnosis of hereditary retinal dystrophy (HRD) diagnoses coded by ICD10 H35.5 in the Years 1998–2019 in Finland.A total of 1606 persons with VI due to RP registered by the Finnish Register of Visual Impairment and total of 4291 HRD diagnoses registered by the Care Register of the Finnish Institute for Health and Welfare were included. VI was classified according to the Finnish national definitions derived from the WHO definitions. The significance of the changes in incidence and age at onset were tested with statistical tests (Kruskal–Wallis, Mann–Whitney U and Cochran‐Armitage). Two‐tailed p‐value below 0.05 was considered significant.The incidence of VI due to RP has decreased from 0.96/100 000 in the 1980s to 0.55/100 000 in the 2010s (p 0.004). The age at onset of VI has increased from 41.6 to 50.3 years. The severity of VI has not changed. The incidence of HRD diagnoses has decreased from 3.66/100 000 in the 2000s to 2.86/100 000 in the 2010s (p 0.024). The age at diagnosis has risen in male patients from 42.1 to 44.5 years (p 0.024).The VI caused by RP in Finland has decreased. It develops at an older age than in the past. We hypothesize that this trend may be attributed to informed decisions by visually impaired persons to refrain from having offspring to prevent the transmission of hereditary mutations. The severity of VI due to RP has remained relatively unchanged. The incidence of HRD diagnoses has decreased, and the diagnosis occurs at an older age among men. [ABSTRACT FROM AUTHOR]

Background: The association between cytokines in peripheral blood and clinical symptoms of multiple system atrophy (MSA) has been explored in only a few studies with small sample size, and the results were obviously controversial. Otherwise, no studies have explored the diagnostic value of serum cytokines in MSA. Methods: Serum cytokines, including interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-a), were measured in 125 MSA patients and 98 healthy controls (HCs). Correlations of these serum cytokines with clinical variables were analyzed in MSA patients. Diagnostic value of cytokines for MSA was plotted by receiver operating curves. Results: No significant differences were found in sex and age between the MSA group and the HCs. TNF-a in MSA patients were significantly higher than those in HCs (area under the curve (AUC) 0.768), while IL-6 and IL-8 were not. Only Hamilton Anxiety Scale (HAMA) has a positive correlation between with TNF-a in MSA patients with age and age at onset as covariates. Serum IL-6 was associated with HAMA, Hamilton Depression Scale (HAMD), the Unified MSA Rating Scale I (UMSARS I) scores, the UMSARS IV and the Instrumental Activity of Daily Living scores. However, IL-8 was not associated with all clinical variables in MSA patients. Regression analysis showed that HAMA and age at onset were significantly associated with TNF-a, and only HAMA was mild related with IL-6 levels in MSA patients. Conclusion: Serum TNF-a and IL-6 levels in MSA patients may be associated with anxiety symptom; however, only TNF-a was shown to be a useful tool in distinguishing between MSA and HCs. [ABSTRACT FROM AUTHOR]

Background/Objectives: Determining the outcome of epilepsy is crucial for making proactive and timely treatment decisions and for counseling patients. Recent research efforts have focused on using various imaging techniques and EEG for prognostication; however, there is insufficient evidence regarding the role of blood parameters. Our study aimed to investigate the additional prognostic value of routine blood parameters in predicting epilepsy outcomes. Methods: We analyzed data from 1782 patients who underwent routine blood tests within 90 days of their first visit and had a minimum follow-up duration of three years. The etiological types were structural (35.1%), genetic (14.2%), immune (4.7%), infectious (2.9%), and unknown (42.6%). The outcome was defined as the presence of seizures in the last year. Results: Initially, a multivariate analysis was conducted based on clinical variables, MRI data, and EEG data. This analysis revealed that sex, age of onset, referred cases, epileptiform discharge, structural etiology, and the number of antiseizure medications were related to the outcome, with an area under the curve (AUC) of 0.705. Among the blood parameters, fibrinogen, bilirubin, uric acid, and aPTT were significant, with AUCs of 0.602, 0.597, 0.455, and 0.549, respectively. Including these blood parameters in the analysis slightly improved the AUC to 0.710. Conclusions: Some blood parameters were found to be related to the final outcome, potentially paving the way to understanding the mechanisms of epileptogenesis and drug resistance. [ABSTRACT FROM AUTHOR]

Multiple endocrine neoplasia (MEN) syndromes are part of a spectrum of clinically well-defined tumor syndromes ultimately characterized by histologically similar tumors arising in patients and families with mutations in one of the following four genes: MEN1, RET, CDKN1B, and MAX. The high level of genetic and phenotypic heterogeneity has been linked to phenocopies and modifying genes, as well as unknown mechanisms that might be investigated in the future based on preclinical and translational considerations. MEN1, also known as Wermer's syndrome (OMIM *131100), is an autosomal dominant syndrome codifying for the most frequent MEN syndrome showing high penetrance due to mutations in the MEN1 gene; nevertheless, clinical manifestations vary among patients in terms of tumor localization, age of onset, and clinical aggressiveness/severity, even within the same families. This has been linked to the effect of modifying genes, as described in the review. MEN 2-2b-4 and 5 also show remarkable clinical heterogeneity. The traditional view of genetically predisposing monogenic or multifactorial disorders is no longer valid, and mandates a change in scientific focus. Phenotypes are indeed rarely consistent across genetic backgrounds and environments. In the future, understanding factors and genetic variants that control cellular functions and the expression of disease genes should provide insights into fundamental disease processes, providing implications for counseling and therapeutic and prophylactic possibilities. [ABSTRACT FROM AUTHOR]

Background: Though an association between cluster headache (CH) and smoking has been postulated, data from the Middle East region is scarce. Aim of work: To study the relationship between smoking and CH clinical characteristics and responsiveness to therapy in Egypt. Methodology: This was a prospective cohort hospital-based study conducted on patients with episodic and chronic CH in a tertiary headache clinic in Egypt during the period between 2019 and 2023. Patients were consecutively recruited at the time of their presentation and were followed up for two weeks after initiation of prophylactic treatment and steroids (as transitional therapy). Results: Of 172 patients with CH recruited, 144 (83.7%) were smokers. Twenty-eight patients (16.3%) had chronic CH. The mean age was 42.08 ± 10.93 (20–66) years, and 131 (76.2%) were males. Smokers had a significantly higher median number of cluster bouts in the past five years (3.0 (IQR2.0–4.0) versus 2.0 (IQR 1.0–2.0)) and worse HIT-6 scores [51.0 (44.0–59.75) versus 41.0 (38.0–41.75)] than non-smokers (p < 0.001). The number of cluster bouts in the past five years was positively correlated with the smoking index (r = 0.249 (p = 0.006) and the smoking duration (in years) (r = 0.392 (p < 0.001)). HIT-6 scores were significantly correlated with the age at smoking onset (r=-0.190, = 0.023), smoking index (r = 0.519, p < 0.001), smoking duration (r = 0.611, p < 0.001), and number of cigarettes consumed per day (r = 0.392, p < 0.001). Conclusion: Smoking is significantly correlated with the daily frequency of CH attacks, the frequency of CH bouts in the past five years, and the HIT-6 scores among our cohort. [ABSTRACT FROM AUTHOR]

Background: Young-onset AD (YOAD) typically occurs before the age of 65 and affects less than 6% of all people diagnosed with AD. There is a lack of research on differences between decision-making capacity and awareness according to age at onset of dementia. Objective: We investigated the relationship between decision-making capacity and awareness domains in people with young- (YOAD) and late-onset Alzheimer's disease (LOAD). Methods: A cross-sectional study included 169 consecutively selected people with AD and their caregivers (124 people with LOAD and 45 people with YOAD). Results: People with YOAD were more cognitively impaired, but more aware of their cognitive deficits and health condition, with moderate effect sizes. All people with AD presented deficits in the domains of decision-making capacity, with more impairment in understanding. There was a relationship between understanding and awareness domains, such that awareness was particularly important for decision-making capacity in the YOAD group. Conclusions: Better awareness involved better understanding in the YOAD group. Clinically, our findings shed light on the need to consider the differences in the domains of awareness and their relationship with other clinical aspects such as decision-making capacity according to age at onset of AD. Furthermore, our data can suggest hypotheses for larger and more robust prospective studies. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusions Despite considerable heritability, previous smaller genome‐wide association studies (GWASs) have not identified any robust genetic risk factors for isolated dystonia.The objective of this study was to perform a large‐scale GWAS in a well‐characterized, multicenter sample of >6000 individuals to identify genetic risk factors for isolated dystonia.Array‐based GWASs were performed on autosomes for 4303 dystonia participants and 2362 healthy control subjects of European ancestry with subgroup analysis based on age at onset, affected body regions, and a newly developed clinical score. Another 736 individuals were used for validation.This GWAS identified no common genome‐wide significant loci that could be replicated despite sufficient power to detect meaningful effects. Power analyses imply that the effects of individual variants are likely very small.Moderate single‐nucleotide polymorphism–based heritability indicates that common variants do not contribute to isolated dystonia in this cohort. Sequence‐based GWASs (eg, by whole‐genome sequencing) might help to better understand the genetic basis. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aims Methods Results Conclusion Periorbital hyperpigmentation (POH) is a common cosmetic problem with a negative impact on the patient's self‐confidence, leading to a decrease in the quality of life. Current treatments include topical agents and mesotherapy, but research remains limited.Due to the undesirable effect of the available treatments, the present study was designed to compare the effectiveness of platelet‐rich plasma (PRP) injection and intradermal injection of tranexamic acid plus vitamin C mesotherapy as a therapeutic method to treat POH.Patients received an intradermal injection of PRP randomly on one side and an intradermal injection of tranexamic acid + vitamin C on the other side of their face, for three sessions with an interval of 3 weeks. Digital photography was taken, and data were assessed based on physician global assessment (PGA) and patient satisfaction.Eighteen patients were studied. Among all, 12 patients had a positive family history, 2 had asthma, and 4 had a history of atopic dermatitis. Even though patient satisfaction was higher in the PRP group than in mesotherapy, it was not statistically significant. Both groups showed similar rates of improvement. However, improvement rates did not significantly differ based on various factors including gender, skin type, family history, or medical history. Age and the age of disease onset also did not significantly affect the improvement rates.Both methods revealed successful results in the reduction of POH. Comparing the efficacy of these two methods showed that both treatments had similar improvements. [ABSTRACT FROM AUTHOR]

Age at first onset of depression as a clinical factor affecting cognitive improvement in late life depression was investigated. This is a secondary analysis of an eight-week randomized controlled trial involving 452 elderly patients treated by vortioxetine, duloxetine or placebo (1:1:1). Patients were subcategorized into early-onset (LLD-EO) and late-onset (LLD-LO) groups divided by onset age of 50. Cognitive performance was assessed by composite score of Digit Symbol Substitution Test (DSST) and the Rey Auditory Verbal Learning Test (RAVLT) tasks, while depressive symptoms were assessed by Montgomery–Åsberg Depression Rating Scale (MADRS). Vortioxetine and duloxetine exhibited advantages versus placebo in improving cognitive performance in the LLD-LO group, yet not in the LLD-EO group after eight weeks. Patients in the LLD-EO group showed overall advantage to placebo in depressive symptoms before endpoint (week 8) of treatment, while patients in the LLO-LO group showed no advantage until endpoint. Path analysis suggested a direct effect of vortioxetine (B = 0.656, p =.036) and duloxetine (B = 0.726, p =.028) on improving cognition in the LLD-LO group, yet in all-patients treated set both medications improved cognition indirectly through changes of depressive symptoms. Reliability of clinical history could raise caution as it was collected by subjective recall of patients. Age at first onset might affect cognitive improvement as well as change in depressive symptoms and its mediation towards cognitive improvement in late life depression treated with vortioxetine and duloxetine. • Vortioxetine and Duloxetine improved cognitive performance of elderly depressed patients with first onset after 50. • Patients with first depressive onset before 50 showed earlier symptomatic change than those with first onset after 50. • Vortioxetine and duloxetine showed direct treatment effect on improving cognition in patients with first episode after 50. [ABSTRACT FROM AUTHOR]

Multiple genes might interact to determine the age at onset of bipolar disorder. We investigated gene-gene interactions related to age at onset of bipolar disorder in the Korean population, using genome-wide association study (GWAS) data. The study population consisted of 303 patients with bipolar disorder. First, the top 1000 significant single-nucleotide polymorphisms (SNPs) associated with age at onset of bipolar disorder were selected through single SNP analysis by simple linear regression. Subsequently, the QMDR method was used to find gene-gene interactions. The best 10 SNPs from simple regression were located in chromosome 1, 2, 3, 10, 11, 14, 19, and 21. Only five SNPs were found in several genes, such as FOXN3 , KIAA1217 , OPCML , CAMSAP2 , and PTPRS. On QMDR analyses, five pairs of SNPs showed significant interactions with a CVC exceeding 1/5 in a two-locus model. The best interaction was found for the pair of rs60830549 and rs12952733 (CVC = 1/5, P < 1E−07). In three-locus models, four combinations of SNPs showed significant associations with age at onset, with a CVC of >1/5. The best three-locus combination was rs60830549, rs12952733, and rs12952733 (CVC = 2/5, P < 1E−6). The SNPs showing significant interactions were located in the KIAA1217 , RBFOX3 , SDK2 , CYP19A1 , NTM , SMYD3 , and RBFOX1 genes. Our analysis confirmed genetic interactions influencing the age of onset for bipolar disorder and identified several potential candidate genes. Further exploration of the functions of these promising genes, which may have multiple roles within the neuronal network, is necessary. • Genetic interactions are crucial for the sub-phenotype of psychiatric disorder. • Age at onset of bipolar disorder was influenced by gene-gene interactions. • The SNPs showing significant interactions were located in the KIAA1217 , RBFOX3 , SDK2 , CYP19A1 , NTM , SMYD3 , and RBFOX1 genes. [ABSTRACT FROM AUTHOR]

Introduction: Large genome-wide association studies (GWASs) using case-control study designs have now identified tens of loci associated with ischemic stroke (IS). As a complement to these studies, we performed GWAS in a case-only design to identify loci influencing the age at onset (AAO) of ischemic stroke. Methods: Analyses were conducted in a discovery cohort of 10,857 ischemic stroke cases using a linear regression framework. We meta-analyzed all SNPs with p-value <1 x 10-5 in a sexcombined or sex-stratified analysis using summary data from two additional replication cohorts. Results: In the women-only meta-analysis, we detected significant evidence for the association of AAO with rs429358, an exonic variant in apolipoprotein E (APOE) that encodes for the APOE-Є4 allele. Each copy of the rs429358:T>C allele was associated with a 1.29-year earlier stroke AAO (meta p-value = 2.48 x 10-11). This APOE variant has previously been associated with increased mortality and ischemic stroke AAO. We hypothesized that the association with AAO may reflect a survival bias attributable to an age-related decrease in mortality among APOE-Є4 carriers and have no association to stroke AAO per se. A simulation study showed that a variant associated with overall mortality might indeed be detected with an AAO analysis. A variant with a 2-fold increase in mortality risk would lead to an observed effect of AAO that is comparable to what we found. Discussion: In conclusion, we detected a robust association of the APOE locus with stroke AAO and provided simulations to suggest that this association may be unrelated to ischemic stroke per se but related to a general survival bias. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic, immune-mediated inflammatory skin disease associated with a polygenic mode of inheritance. There are few studies that explore the association of a psoriasis Polygenic Risk Score (PRS) with patient clinical characteristics, and to our knowledge there are no studies examining psoriasis PRS associations across different ethnicities. In this study, we used a multi-racial psoriasis cohort to investigate PRS associations with clinical phenotypes including age of onset, psoriatic arthritis, other comorbidities, psoriasis body location, psoriasis subtype, environmental triggers, and response to therapies. We collected patient data and Affymetrix genome-wide SNP data from a cohort of 607 psoriasis patients and calculated an 88-loci PRS (PRS-ALL), also partitioned between genetic loci within the HLA region (PRS-HLA; 11 SNPS) and loci outside the HLA region (PRS-NoHLA; 77 SNPS). We used t-test and logistic regression to analyze the association of PRS with clinical phenotypes. We found that PRS-HLA and PRS-noHLA had differing effects on psoriasis age of onset, psoriatic arthritis, psoriasis located on the ears, genitals, nails, soles of feet, skin folds, and palms, skin injury as an environmental trigger, cardiovascular comorbidities, and response to phototherapy. In some cases these PRS associations were ethnicity specific. Overall, these results show that the genetic basis for clinical manifestations of psoriasis are driven by distinct HLA and non-HLA effects, and that these PRS associations can be dependent on ethnicity. [ABSTRACT FROM AUTHOR]