Younger Group Research Articles

Analysis of Persian WhatsApp Messages with Reference to Age, Politeness, and the Speech Act of Request

Abstract This study investigated WhatsApp messages exchanged between two generations of Iranian students and their respective lecturers in light of politeness, age, and the speech act of request. We utilised two sets of data: messages sent by current young students to two young lecturers, and those sent by former middle-aged students to two senior lecturers. Altogether, 100 WhatsApp messages were analysed (50 from each data set) focusing on salutations, body, and closing parts. The findings revealed that politeness is expressed differently across the two age groups: the younger students’ messages featured short and informal expressions and frequent use of emojis while the older group utilised elaborate messages to express politeness through the frequent use of honorifics and other politeness markers. Moreover, the younger group used WhatsApp messages towards their academic goals, such as requesting the postponement of an exam, whereas the older group messages aimed at re-establishing solidarity with their lecturers.

Rib tumors: A ten-year institutional study

Objectives The primary aim of this study was to study the demography and frequency distribution of the various rib tumors. The treatment modality offered and patient outcomes were also recorded wherever available. Material and Methods A ten year data was retrieved from the hospital registry from 2011-2021. Inclusion criteria were all patients with any tumors in the rib. Those patients who did not have a histological diagnosis and those having a chest wall mass and secondary involvement of the ribs were excluded. Results Out of 72 cases of rib tumors, 25 were diagnosed as Ewing Sarcoma, 22 Chondrosarcoma cases, 10 Multiple myeloma/plasmacytoma cases, 9 Osteosarcoma cases, rest 1 case each of Non Hodgkin Lymphoma, Brown tumor, Enchondroma, Osteochondroma, Clear cell sarcoma and metastases. Conclusion In this study the most common primary malignant tumor of the ribs in adults was Chondrosarcoma (41.1%) and in pediatric & young adolescent age group (upto 18yrs) it was Ewing sarcoma (76.1%)

Metabolic Dysfunction-associated Steatotic Liver Disease is Becoming the Leading Driver of the Burden of Cirrhosis in China: Results From the Global Burden of Disease Study 2019.

Cirrhosis and other chronic liver diseases (generally referred to as cirrhosis in this article) are major causes of morbidity and mortality in China. The disease pattern of cirrhosis caused by different etiologies has been changing due to economic development and changes in lifestyle. Prevalence, incidence, disability-adjusted life-years, and mortality data were retrieved from the Global Burden of Disease study, 2019. Estimated annual percentage change was used to quantify the trends in the age-standardized prevalence rate and prevalence number of cirrhosis from 1990 to 2019. We presented the results for five causes of cirrhosis, and for different age and sex groups. Nationwide, we found that the prevalence number of liver cirrhosis increased steadily (from 3025.3×105 to 4279.8×105) from 1990 to 2019. Notably, the age-standardized prevalence rate of cirrhosis caused by metabolic dysfunction-associated steatotic liver disease (MASLD) increased throughout the study period, and MASLD has exceeded the hepatitis B virus and become the leading cause of liver cirrhosis since 1992. The highest prevalence number of MASLD occurred in the young population aged between 15 to 49 years. The prevalence of liver cirrhosis caused by hepatitis B virus decreased, whereas the prevalence of liver cirrhosis caused by MASLD increased. MASLD has become the leading cause of liver cirrhosis in China. The prevalence of liver cirrhosis increased most significantly in the young age group compared with the other age group. Preventive strategies targeting MASLD would be necessary to reduce the disease burden of cirrhosis in China, especially in the young aged generation.

Hypothyroidism in Older Adults: A Concise Review of the Recent Literature

Abstract Introduction Hypothyroidism (HypoT) is a common condition whose prevalence varies according to regional and ethnic factors, dietary iodine, gender, and age. The symptoms of HypoT are generally nonspecific, with considerable overlap with other conditions. These symptoms are not useful for diagnosing HypoT, and a thyroid function test is required for a final diagnosis. Materials and methods We aimed to provide an overview of the recent global literature on HypoT in older adults. A narrative, nonsystematic review of the international literature from a single major medical online database (PubMed) for the past 5 years was performed. The relevant literature was narrated in a concise thematic account. Results Most studies and expert opinions reiterated the benefit of replacement therapy in younger and middle-aged individuals. A good volume of literature also considered the interplay between thyroid hormones and (1) cardiovascular function and risk factors, (2) cognitive function, (3) mental health, and (4) quality of life. Most workers are cognizant of the important difference in normal ranges of thyroid-stimulating hormone (TSH) and the consequent TSH targets in older adults compared to younger age groups. Extra care is recommended for the initiation and titration of thyroid hormone replacement therapy to avoid cardiovascular and skeletal adverse effects of relative overtreatment. Conclusion While clinical benefit is evident in patients under age 65 with overt and subclinical HypoT who are treated with levothyroxine, treatment may be harmful in older adults with subclinical HypoT. The 97th percentile of TSH distribution is 7.5 mIU/L for patients over age 80. Hence, TSH goals should be individualized in older adults to achieve any possible benefit and avoid unnecessary harm.

Loneliness and Expanding Social Ties in Later Life: Motivation, Perceived Success, and Implications for Emotional Health.

Social networks undergo changes in later life, reflecting proactive decreases as well as increases in size, but relatively little is known about the factors that motivate older adults to expand their social ties. Loneliness might be expected to motivate older adults to expand their social ties. Paradoxically, however, studies of younger age groups have linked loneliness to a self-protective reluctance to initiate social contact. The current study investigated whether loneliness fosters or inhibits older adults' efforts to expand their social ties and whether successful efforts are related to gains in emotional health. Loneliness, motivation to expand social ties, and emotional health were assessed in a subset of older participants (N = 375) from the Later Life Study of Social Exchanges. Greater loneliness was associated with less interest, less investment of effort, and less success in making new ties and rekindling dormant ties. Nonetheless, lonelier older adults who expanded their social ties, particularly by rekindling dormant ties, exhibited some gains in emotional health over a 1-year period. Greater attention to the role of loneliness in older adults' motivations for making new ties or rekindling dormant ties will broaden our understanding of social network changes in later life.

Training cadres and establishment of an integrated development post for non-communicable diseases based on a mosque

Introduction: Non-communicable diseases (NCDs) are the highest cause of death due to non-communicable diseases in Indonesia. This condition is certainly very worrying, because the trend of NCDs is increasing followed by a shift in disease patterns, where previously NCDs were experienced by the elderly group, are now starting to threaten younger age groups. Public awareness of NCD risk factors needs to be increased. This requires community participation in PTM (penyakit tidak menular) integrated development activities (Posbindu). Posbindu PTM is an activity for early detection and monitoring of the main risk factors for PTM through community participation. The aim of this activity is cadre training and the establishment of a mesque-based Posbindu PTM. Methods: The method used is Asset Based Community Development (ABCD). The ABCD method is a service method that focuses on the strengths and capacities of local communities. The establishment of the PTM Posbindu was carried out at the Aisyah Abdul Latif Farah Mosque, Namorambe District, Deli Serdang Regency. There were 10 cadres recruited at Posbindu PTM Mosque. Results: The results of the establishment of the mask-based PTM Posbindu are expected to be able to detect PTM risk factors as early as possible and reduce the number of PTM congregants at mosques in particular and society in general. Conclusion: The socialization and formation of the mosque-based Posbindu PTM received positive support from the Deli Serdang Health Service and the Aisyah Abdul Latif Farah Mosque.

Evaluation of Philadelphia-negative myeloproliferative neoplasms in Erbil Iraq; analysis of JAK 2, CALR, and MPL mutations

Introduction: The prevalence of Janus kinase 2 V617F, Jak 2-Exon12, calreticulin (CALR) gene mutations and myeloproliferative leukemia mutations in myeloproliferative neoplasms (MPNs) without BCR-ABL1 gene fusion rearrangement in Iraq remains unknown due to inadequate data. Objectives: The aim of this study was to ascertain the prevalence of these mutations and assess the clinical characteristics of polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) in Erbil, Iraq. Patients and Methods: In this cross-sectional study, 80 patients were evaluated for the presence of JAK 2 V617, CALR, and MPL mutations. Specific primers were utilized to amplify MPNs-associated mutations (JAK 2 V617F, Jak 2 -Exon12, CALR, and MPL) using DNA extracted from whole blood. Results: The presence of the JAK 2 V617F mutation was identified in 96% of patients diagnosed with PV and 35% of patients diagnosed with ET. Additionally, JAK 2 exon 12 was detected in 4% of PV patients. CALR mutation was identified in 65% of ET patients. No detection of MPL mutation was observed. A higher prevalence of the CALR mutation was observed in younger age groups, whereas the JAK 2 V617F mutation was predominantly found in older age groups. Conclusion: The incorporation of genetic tests for JAK 2 V617F, JAK 2 exon 12, MPL exon 10, and CALR exon 9 significantly improves the diagnostic effectiveness for BCR ABL1-gene fusion negative MPNs.

Trends in SARS-CoV-2 Cycle Threshold Values in Bosnia and Herzegovina-A Retrospective Study.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which led to the COVID-19 pandemic, has significantly impacted global public health. The proper diagnosis of SARS-CoV-2 infection is essential for the effective control and management of the disease. This study investigated the SARS-CoV-2 infection using RT-qPCR tests from laboratories in Bosnia and Herzegovina. We performed a retrospective study of demographic data and Ct values from 170,828 RT-qPCR tests from April 2020 to April 2023, representing 9.3% of total national testing. Samples were collected from 83,413 individuals across different age groups. Of all tests, 33.4% were positive for SARS-CoV-2, with Ct values and positivity rates varying across demographics and epidemic waves. The distribution was skewed towards older age groups, although lower positivity rates were observed in younger age groups. Ct values, indicative of viral load, ranged from 12.5 to 38. Lower Ct values correlated with higher positive case numbers, while higher Ct values signaled outbreak resolution. Additionally, Ct values decreased during epidemic waves but increased with the dominance of certain variants. Ct value-distribution has changed over time, particularly after the introduction of SARS-CoV-2 variants of interest/concern. Established Ct value trends might, therefore, be used as an early indicator and additional tool for informed decisions by public health authorities in SARS-CoV-2 and future prospective pandemics. Moreover, they should not be overlooked in future epidemiological events.

Age-related differences in fluctuations in insulin resistance evaluated with HOMA-IR and triglyceride and glucose-based indices during the menstrual cycle, as determined using the NHANES cross-sectional dataset

ObjectivesTo determine how age affects insulin resistance during the menstrual cycle and insulin resistance-associated indices: the Triglyceride-glucose and Triglyceride-glucose-BMI indexes. MethodsThis prospective observational study used fasting plasma glucose, fasting insulin, triglycerides, body mass index (BMI), and days since the start of the menstrual period collected from the NHANES dataset (1999–2006). Insulin resistance was determined using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). The participants were categorized as young (16–34 years) or older (>35 years). Rhythmicity during the menstrual cycle was analyzed using the Cosinor and Cosinor2 packages for R. Main outcome measuresCosine fit curves for insulin resistance during the menstrual cycle and age-associated effects on rhythmicity. ResultsUsing 1256 participants, rhythmicity was observed for fasting insulin and HOMA-IR (p < 0.05) but not for fasting plasma glucose, the Triglyceride-glucose index, or the Triglyceride-glucose-BMI index. Significant amplitudes for fasting insulin and HOMA-IR were observed when age was considered. Acrophases for fasting insulin and HOMA-IR were significant only for the younger group, and the differences between these groups were significant, suggesting that the changes in scores for insulin resistance for the younger and older groups occur at different times of their menstrual cycle. ConclusionsInsulin resistance does fluctuate during the menstrual cycle, and it is at a maximum at different times for younger and older women. Since these results are unadjusted, this study is preliminary and further investigation is required.

The association of initial and changes in serum A-FABP level with the development and improvement of pre-sarcopenia.

Several cross-sectional studies have reported the association between serum adipocyte fatty acid binding protein (A-FABP) level and pre-sarcopenia. However, data on the impacts of serum A-FABP level and its changes over time on the development and improvement of pre-sarcopenia are scarce. This longitudinal cohort study included 1496 adults (41.2% men; median age, 58 [53-63] years) in 2013-2014 and was followed up to 2015-2016. Participants underwent serum A-FABP level measurements at baseline and follow-up visit. Visceral fat area (VFA) was measured using magnetic resonance imaging. Skeletal muscle mass (SMM) was estimated by bioelectrical impedance analysis and converted to skeletal muscle index (SMI). Pre-sarcopenia was defined as SMI < 1 standard deviation of the sex-specific mean for the young reference group. During an average follow-up period of 2.1 years, baseline serum A-FABP level was positively associated with the incidence of pre-sarcopenia (standardized by weight: risk ratio [RR] 3.22, 95% confidence interval [CI] 1.96-5.38; standardized by VFA: RR 2.11, 95%CI 1.29-3.51) and negatively associated with the improvement of pre-sarcopenia (standardized by weight: RR 0.66, 95%CI 0.45-0.97; standardized by VFA: RR 0.71, 95%CI 0.54-0.94), regardless of whether SMM was standardized by weight or VFA. Moreover, changes in serum A-FABP level provided additional information on the incidence and improvement of pre-sarcopenia, independent of baseline serum A-FABP level (all P < 0.05). Baseline serum A-FABP level and its changes were positively associated with the incidence, and negatively associated with the improvement of pre-sarcopenia.

Age Influence on Total Ankle Arthroplasty Outcomes: A Systematic Review

Total ankle arthroplasty has gained popularity as advancing technology has resulted in higher survivorship and lower complication rates. In the past, total ankle replacement candidates have been reserved for patients greater than 50 years old with low physical demands and minimal deformity. However, with newer designs, surgeons have begun to expand their patient inclusion criteria. The purpose of this study was to analyze current literature comparing patient outcomes among total ankle replacement patients over and under age 50. A systematic review of the literature was performed comparing the impact of age to total ankle replacement outcomes. 159 articles were reviewed. Seven studies met our inclusion criteria and therefore were included in the synthesis. No statistically significant difference in outcomes was determined for the younger and older age groups in regard to reoperation, complications, and implant survivorship (p = .412, .955, .155, respectively). However, the statistical model is underpowered given the limited number of studies. While the findings of this study infer that total ankle replacement outcomes are not significantly different among older and younger age groups, further research in this area is needed.

SARS-CoV-2 co-detection with other respiratory pathogens-descriptive epidemiological study

BackgroundCo-detection of respiratory pathogens with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is poorly understood. This descriptive epidemiological study aimed to determine the effect of the interaction of different respiratory pathogens on clinical variables. MethodsWe retrospectively reviewed the results of comprehensive multiplex polymerase chain reaction (PCR) testing from November 2020 to March 2023 to estimate respiratory pathogen co-detection rates in Shinjuku, Tokyo. We evaluated the interactions of respiratory pathogens, particularly SARS-CoV-2, between observed and expected co-detection. We estimated the trend of co-detection with SARS-CoV-2 in terms of age and sex and applied a multiple logistic regression model adjusted for age, testing period, and sex to identify influencing factors between co-detection and single detection for each pathogen. ResultsAmong 57,746 patients who underwent multiplex PCR testing, 10,516 (18.2%) had positive for at least one of the 22 pathogens. Additionally, 881 (1.5%) patients were confirmed to have a co-detection. SARS-CoV-2 exhibited negative interactions with adenovirus, coronavirus, human metapneumovirus, parainfluenza virus, respiratory syncytial virus, and rhino/enterovirus. SARS-CoV-2 co-detection with other pathogens occurred most frequently in patients of the youngest age group (0–4 years). A multiple logistic regression model indicated that younger age was the most influential factor for SARS-CoV-2 co-detection with other respiratory pathogens. ConclusionThe study highlights the prevalence of SARS-CoV-2 co-detection with other respiratory pathogens in younger age groups, necessitating further exploration of the clinical implications and severity of SARS-CoV-2 co-detection.

Quantifying upper lip height difference between two young male and female populations by direct surface measurement: Implications for gender-affirming upper lip shortening surgery

The female upper lip is shorter than its male counterpart. We have recently described a precise direct surface measurement technique of the philtral height. In this study we aim to quantify the difference in philtral height using this same measuring technique between two groups of young male and female Lebanese subjects. The mean philtral height obtained in the young male group was 15.7 ± 1.7 mm. By comparing this result to the previously described mean philtral height of 14.3 ± 1.9 mm in the young female group, we obtained a mean difference of 1.3 ± 1.8 mm between the two groups. This result confirms and quantifies by direct surface measurement the gender difference in upper lip height and should be considered when planning a gender-affirming upper lip shortening surgery.

Association of race and ethnicity with the development of cystic fibrosis-related diabetes

BackgroundCF-related diabetes (CFRD) is a common, life-expectancy limiting complication of CF. While Black race and Hispanic ethnicity in youth-onset type 1 and type 2 diabetes are well-recognized risk factors for worse diabetes complications, the potential for racial/ethnic disparities in CFRD has received limited attention. MethodsWe conducted a retrospective cohort study utilizing the CF Foundation Patient Registry from 2010 to 2019 to determine the prevalence and incidence of CFRD by race/ethnicity. Three age cohorts were identified at baseline in 2010 (11–20y, 21–30y, and 31–40y). Logistic regression and Cox regression stratified by age group were used to determine the prevalence and incidence, respectively, among Hispanic, non-Hispanic Blacks (NHB), and non-Hispanic whites (NHW) after adjustment for relevant confounders, including demographics, socioeconomic status, clinical factors, and chronic medication use. ResultsAmong 14,660 registry participants, 510 were NHB and 890 Hispanic. NHB associated with higher odds of CFRD baseline prevalence in all age cohorts (11–20y: OR 2.53 (95 % CI: 1.88–3.41, P < 0.05), 21–30y: OR 1.80 (1.25–2.59, P < 0.05), and 31–40y: OR 1.93 (1.00–3.73, P < 0.05)) relative to NHW. In the 11–20y cohort, the hazard of new-onset CFRD was 40 % higher in NHB (HR 1.40 (1.09–1.8, P < 0.05)) and 19 % higher in Hispanics (HR 1.19 (1.01–1.41, P < 0.05)). ConclusionNHB had a higher prevalence of CFRD across all age groups, with NHB and Hispanics showing higher incidence of CFRD in the youngest group. Multicenter studies performed in diverse CF populations are warranted to identify modifiable factors influencing earlier CFRD development in minoritized groups and their potential contribution to diabetes complication disparities.

Influence of Age on Outcomes of Endovascular Treatment in Posterior versus Anterior Circulation Stroke: A Comparative Analysis in a Nationwide Registry.

It is unknown whether the influence of age on clinical outcomes post endovascular treatment (EVT) is similar in posterior circulation stroke (PCS) compared to anterior circulation stroke (ACS). Data were extracted from the ETIS registry, a nationwide prospective, multicenter, observational registry for stroke EVT procedures in France. We included patients treated with EVT for PCS or ACS between January 2015 - August 2023. The relationship between patient age and clinical outcome variables was studied using regression analysis. Good clinical outcome was defined as modified Rankin scale score ≤2 at 90 days. The study included 935 patients with PCS and 11427 patients with ACS. There were no significant differences between PCS and ACS in the influence of age on the likelihood of good clinical outcome. The influence of age on the likelihood of mortality was significantly different. Mortality was higher for PCS between 30-85 years, without significant differences in younger or older patients. Elderly patients (≥80 years) with PCS had similar rates of good clinical outcome and mortality compared to patients with ACS from the same age group. In this comparative analysis assessing the impact of age on EVT outcomes in posterior versus anterior circulation stroke, differences were observed in middle aged patients, whereas outcomes tended to converge in young and elderly age groups. Elderly PCS patients had similar outcomes as ACS patients from the same age group.

Antimicrobial Susceptibility and Genomic Profiles of Multidrug-Resistant Staphylococcus aureus from Nasopharynx of Asymptomatic Children in Dhaka, Bangladesh.

Children carrying Staphylococcus aureus in their nasopharynx are at a higher risk of contracting systemic infection. Due to lack of sufficient information regarding such carriage, this study was conducted to explore the prevalence, antibiotic susceptibility, and genomic profiles of S. aureus isolated from nasopharyngeal samples of 163 randomly selected asymptomatic Bangladeshi children aged from 5-<15 years. Antibiotic susceptibility pattern and genomic analysis of the samples were conducted using standard microbiological methods and genomic tools. The carriage was confirmed in 44 (27%) children who were mostly well nourished without respiratory symptoms in the last 3 months. Higher carriage was observed among the younger age group (5-<10 years) who completed vaccines for pneumonia (p = 0.002) and influenza (p = 0.004). Among the isolates, 84.1% were multidrug-resistant and 47.5% (n = 40) were methicillin-resistant S. aureus (MRSA). All the isolates (100%) were resistant to cefixime with higher resistance to ampicillin (95.5%) and penicillin (90.9%). Among the three investigated isolates, two were ST80 (ID-1 and ID-52) and one was a novel strain (ID-19) with the presence of aph-Stph, blaI, blaZ, dha1, fosB, lmrS, mepA, norA, and tet38 genes. The current research demonstrates a high incidence of multidrug-resistant S. aureus and reports the first instance of ST80 in asymptomatic children in Bangladesh.

Gaussianity Evaluation of HD-sEMG Signals with Aging and Sex During Low and Moderate Isometric Contractions of the Biceps Brachii

IntroductionAging is associated with muscle decline, which alters both functional and anatomical properties of the neuromuscular system. These modifications can be reflected in high-density surface electromyography (HD-sEMG) signals. This study examines how age and sex impact the shape of the amplitude Probability Density Function (PDF) of HD-sEMG signals. Materials and MethodsMonopolar HD-sEMG signals were collected from the Biceps Brachii in a cohort of 17 individuals: 10 women (mean age: 22.9 ± 3.6 years) and 7 men (mean age: 24.4 ± 2.5 years) in the younger group, and 10 women (mean age: 69.8 ± 4.8 years) and 7 men (mean age: 72.8 ± 2.7 years) in the elderly group. The recordings were conducted during an elbow flexion at both 20% and 40% maximum voluntary contraction. The signal amplitude was evaluated using root means square amplitude (RMSA) and the PDF shape of each HD-sEMG signal was assessed through skewness, excess Kurtosis, and robust functional statistics. These shape distance metrics evaluate the departure from Gaussianity related to muscle aging. a) We conducted a comparison study of the HD-sEMG PDF shapes between younger and elderly individuals. b) Evaluating differences between men and women. c) Considering monopolar and Laplacian electrode configurations that are sensitive to different muscle regions. ResultsA) The HD-sEMG PDFs of elderly subjects demonstrated a lower departure from Gaussianity than their younger counterparts. B) Women exhibited lower RMSA values than men, and, on average, a lower departure from Gaussianity whatever the age and contraction level C) Trends of departure from Gaussianity with contraction level, seems to be influenced by the electrode configuration. In fact, a decrease in Gaussianity departure is observed with monopolar recordings where an increase is observed with Laplacian one, clearly indicating different muscle region assessment. DiscussionThe findings highlight the influence of factors such aging, sex, contraction level and electrode montage on the shape of the HD-sEMG PDF, emphasizing the significance of using this descriptor for monitoring and better assessment of muscle aging.

Articular Cartilage Damage in the Patellofemoral Compartment at ACL Reconstruction Predicts Poor Postoperative Subjective Outcomes in Patients Age 40 and Older.

The purpose of this study was to investigate factors that influence clinical outcomes after anterior cruciate ligament (ACL) reconstruction in patients aged ≥40 years. We studied 264 patients aged ≥40 and 154 patients aged ≤20 years who underwent ACL reconstruction at several surgical centers. A logistic regression analysis was conducted to identify factors that influenced the Knee Injury and Osteoarthritis Outcome Score (KOOS) at 1 year post-ACL reconstruction. In the older patient group, cartilage damage in the patellofemoral compartment at surgery was a significant risk factor for poor postoperative KOOS subscores (pain, activities of daily living [ADL], sports, and quality of life [QOL]). Articular cartilage damage in the lateral compartment also significantly influenced one of the postoperative KOOS subscores (symptoms). In the younger patient group, articular cartilage damage in any compartments did not influence the postoperative KOOS subscores; only two preoperative KOOS subscores (symptoms and QOL) significantly influenced their postoperative KOOS subscores. We concluded that the articular cartilage damage in the patellofemoral compartment at ACL reconstruction predicts poor KOOS subscores at the 1-year follow-up in patients aged ≥40 years. STUDY DESIGN: Cohort study (Prevalence); Level of evidence, 2.

Clinical Outcomes of Electroconvulsive Therapy (ECT) for Depression in Older Old People Relative to Other Age Groups Across the Adult Life Span: A CARE Network Study.

Electroconvulsive therapy (ECT) is a commonly used treatment for severe psychiatric illness in older adults, including in the 'older old' population aged 80years and above. However, there can sometimes be a reluctance to treat the 80+ year old age group with ECT due to medical comorbidities, frailty, and concerns about cognition. This multi-site, longitudinal Australian study aimed to investigate the effectiveness and safety of ECT in older old people compared with younger age groups. Data from 310 people receiving ECT for depression at three participating hospitals was collected in a naturalistic setting, between 2015 and 2022. Clinical ratings were conducted pre-ECT and end-acute ECT using the Montgomery-Åsberg Depression Rating Scale (MADRS). Cognitive outcomes were assessed using the Montreal Cognitive Assessment (MoCA). Older old adults demonstrated a significant reduction MADRS scores at post-treatment. They were more likely to meet remission criteria compared with the younger age groups. Older old adults were also less likely to show clinically significant cognitive decline post-ECT, and were more likely to show clinically significant cognitive improvement post-ECT compared with younger age groups. ECT is highly effective in treating severe psychiatric illness in older old adults. Relative to the younger age groups, the older old group were more likely to remit with ECT and a greater proportion showed cognitive improvement post-ECT. These findings suggest that ECT should be considered as a valuable and safe treatment option for older old individuals with depression.

Biologic and Clinical Analysis of Childhood Gamma Delta T-ALL Identifies LMO2/STAG2 Rearrangements as Extremely High Risk.

Acute lymphoblastic leukemia expressing the gamma delta T-cell receptor (γδ T-ALL) is a poorly understood disease. We studied 200 children with γδ T-ALL from 13 clinical study groups to understand the clinical and genetic features of this disease. We found age and genetic drivers were significantly associated with outcome. γδ T-ALL diagnosed in children under 3 years of age was extremely high-risk and enriched for genetic alterations that result in both LMO2 activation and STAG2 inactivation. Mechanistically, using patient samples and isogenic cell lines, we show that inactivation of STAG2 profoundly perturbs chromatin organization by altering enhancer-promoter looping, resulting in deregulation of gene expression associated with T-cell differentiation. High-throughput drug screening identified a vulnerability in DNA repair pathways arising from STAG2 inactivation, which can be targeted by poly(ADP-ribose) polymerase inhibition. These data provide a diagnostic framework for classification and risk stratification of pediatric γδ T-ALL. Significance: Patients with acute lymphoblastic leukemia expressing the gamma delta T-cell receptor under 3 years old or measurable residual disease ≥1% at end of induction showed dismal outcomes and should be classified as having high-risk disease. The STAG2/LMO2 subtype was enriched in this very young age group. STAG2 inactivation may perturb chromatin conformation and cell differentiation and confer vulnerability to poly(ADP-ribose) polymerase inhibition.