Effects of forest age and season on soil microbial communities in Chinese fir plantations.

Understanding changes in the distribution patterns and diversity of soil microbial communities from the perspectives of age-related changes, seasonal variations, and the interaction between the two factors can facilitate the management of plantations. In Chinese fir plantations, we collected soils from different depths in over-mature forests, mature forests, near-mature forests, middle-aged forests, and young forests in summer, autumn, and winter in China's subtropical regions. As the forests developed, bacterial and fungal communities' diversity changed, reached a minimum value at near-mature forests, and then increased in mature forests or over-mature forests. Near-mature forests had the lowest topological properties. The Shannon index of microbial communities varied with seasonal changes (P < 0.05). Bacterial and fungal community composition at genus level was more closely related to temperature indicators (including daily average temperature, daily maximum temperature, and daily minimum temperature) (P < 0.01, 0.5554 < R2 <0.8185) than daily average precipitation (P > 0.05, 0.0321 < R2 <0.6773). Bacteria were clustered by season and fungi were clustered by forest age. We suggested that extending the tree cultivation time of plantations could promote microbial community recovery. In addition, we found some species worthy of attention, including Bacteroidetes in autumn in over-mature forests, and Firmicutes in summer in young forests.IMPORTANCEChinese fir [Cunninghamia lanceolata (Lamb.) Hook] is an important fast-growing species with the largest artificial forest area in China, with the outstanding problems of low quality in soil. Soil microorganisms play a crucial role in soil fertility by decomposing organic matter, optimizing soil structure, and releasing essential nutrients for plant growth. In order to maintain healthy soil quality and prevent nutrient depletion and land degradation, it is crucial to understand the changes of soil microbial composition and diversity. Our study determined to reveal the change of soil microbial community from stand age, season, and the interaction between the two aspects, which is helpful to understand how interannual changes in different years and seasonal changes in one year affect soil fertility restoration and sustainable forest plantation management. It is a meaningful exploration of soil microbial communities and provides new information for further research.

A new model of human lymphopoiesis across development and aging.

Over the past decade our research has implemented a multimodal approach to human lymphopoiesis, combining clonal-scale mapping of lymphoid developmental architecture with the monitoring of dynamic changes in the pattern of lymphocyte generation across ontogeny. We propose that lymphopoiesis stems from founder populations of CD127/interleukin (IL)7R- or CD127/IL7R+ early lymphoid progenitors (ELPs) polarized respectively toward the T-natural killer (NK)/innate lymphoid cell (ILC) or B lineages, arising from newly characterized CD117lo multi-lymphoid progenitors (MLPs). Recent data on the lifelong lymphocyte dynamics of healthy donors suggest that, after birth, lymphopoiesis may become increasingly oriented toward the production of B lymphocytes. Stemming from this, we posit that there are three major developmental transitions, the first occurring during the neonatal period, the next at puberty, and the last during aging.

Psychometric Properties and Measurement Invariance of the Awareness of Age-Related Change Short Form in Older Adult Samples from Taiwan and Germany.

BACKGROUND AND OBJECTIVES: This study examined the psychometric properties and measurement invariance of the 10-item Awareness of Age-Related Change Short Form (AARC-SF) questionnaire in a Chinese-speaking sample of older adults in Taiwan. RESEARCH DESIGN AND METHODS: Data from 292 participants (Mage = 77.64 years) in the Healthy Aging Longitudinal Study in Taiwan (HALST) cohort were used for Study 1, whereas data from young-old adult samples in Germany were used for Study 2. RESULTS: Study 1 showed that the AARC-SF had satisfactory reliability and validity for assessing adults' AARC in Taiwan. Analyses confirmed the two-factor structure of AARC-gains and AARC-losses. Study 2 demonstrated strong measurement invariance across men and women, whereas direct comparisons of the item scores between young-old adults and old-old adults need to be made with caution. Non-invariance of loadings indicated that certain items were more closely linked to AARC-gains and AARC-losses in Taiwan than in Germany. Non-invariance of intercepts suggested potential biases in comparing item scores between Taiwanese and German older adults. DISCUSSION AND IMPLICATIONS: The AARC-SF emerged as a reliable and valid instrument for capturing positive and negative subjective aging experiences among Taiwanese older adults. However, it is noteworthy that some items on the AARC-SF may solicit different responses from individuals of different ages and different countries of origin, requiring caution with age group and cross-cultural comparisons.

Age-Related Characteristics of Resting-State Electroencephalographic Signals and the Corresponding Analytic Approaches: A Review.

The study of the effects of aging on neural activity in the human brain has attracted considerable attention in neurophysiological, neuropsychiatric, and neurocognitive research, as it is directly linked to an understanding of the neural mechanisms underlying the disruption of the brain structures and functions that lead to age-related pathological disorders. Electroencephalographic (EEG) signals recorded during resting-state conditions have been widely used because of the significant advantage of non-invasive signal acquisition with higher temporal resolution. These advantages include the capability of a variety of linear and nonlinear signal analyses and state-of-the-art machine-learning and deep-learning techniques. Advances in artificial intelligence (AI) can not only reveal the neural mechanisms underlying aging but also enable the assessment of brain age reliably by means of the age-related characteristics of EEG signals. This paper reviews the literature on the age-related features, available analytic methods, large-scale resting-state EEG databases, interpretations of the resulting findings, and recent advances in age-related AI models.

Maize multi-omics reveal leaf water status controlling of differential transcriptomes, proteomes and hormones as mechanisms of age-dependent osmotic stress response in leaves.

Drought-induced osmotic stress severely affects the growth and yield of maize. However, the mechanisms underlying the different responses of young and old maize leaves to osmotic stress remain unclear. To gain a systematic understanding of age-related stress responses, we compared osmotic-stress-induced changes in maize leaves of different ages using multi-omics approaches. After short-term osmotic stress, old leaves suffered more severe water deficits than young leaves. The adjustments of transcriptomes, proteomes, and hormones in response to osmotic stress were more dynamic in old leaves. Metabolic activities, stress signaling pathways, and hormones (especially abscisic acid) responded to osmotic stress in an age-dependent manner. We identified multiple functional clusters of genes and proteins with potential roles in stress adaptation. Old leaves significantly accumulated stress proteins such as dehydrin, aquaporin, and chaperones to cope with osmotic stress, accompanied by senescence-like cellular events, whereas young leaves exhibited an effective water conservation strategy mainly by hydrolyzing transitory starch and increasing proline production. The stress responses of individual leaves are primarily determined by their intracellular water status, resulting in differential transcriptomes, proteomes, and hormones. This study extends our understanding of the mechanisms underlying plant responses to osmotic stress.

Age-related changes in reading performance in normally sighted Arabic-speaking adults.

CLINICAL RELEVANCE: Reading performance is important for evaluating near vision and predicting and prescribing near-vision correction. There is a significant gap in the literature on Arabic reading performance and its associated effects. BACKGROUND: Normative data from control participants serve as the baseline for future studies involving groups with specific characteristics. This study aimed to assess baseline measures of Arabic reading performance. METHODS: In total, 428 normally sighted adults aged 19-83 years read the Balsam Alabdulkader - Leat chart to measure their reading performance. The participants were divided into five age groups. The outcome measures were the maximum reading speed in standard-length words per minute, critical print size, reading acuity, and reading accessibility index. RESULTS: The average reading performance measures were as follows: 171 ± 27 standard-length words per minute for maximum reading speed, 0.01 logarithm of the minimum angle of resolution for critical print size, -0.17 logarithm of the minimum angle of resolution for reading acuity, and 1.02 for the accessibility index. There were significant differences among the age groups, indicating a dependency on age and showing a plateau for the young adult group and a decline with age. The accessibility index had an almost perfect correlation with maximum reading speed and a weak but significant relationship with reading acuity and critical print size. CONCLUSION: Arabic exhibits an age-dependent trend in reading speed. However, owing to differences in orthography, visual demands, and reading strategies, the magnitude of the decrease and increase differs, potentially accounting for the variations between languages, especially when compared to English. This study serves as a foundation for future studies on Arabic reading performance. Future studies should examine the reading performance in patients with low vision, study the effects of common diseases on reading ability, evaluate the effectiveness of reading devices, and assess improvements in vision rehabilitation.

In Vitro Osteogenesis Study of Shell Nacre Cement with Older and Young Donor Bone Marrow Mesenchymal Stem/Stromal Cells.

Bone void-filling cements are one of the preferred materials for managing irregular bone voids, particularly in the geriatric population who undergo many orthopedic surgeries. However, bone marrow mesenchymal stem/stromal cells (BM-MSCs) of older-age donors often exhibit reduced osteogenic capacity. Hence, it is crucial to evaluate candidate bone substitute materials with BM-MSCs from the geriatric population to determine the true osteogenic potential, thus simulating the clinical situation. With this concept, we investigated the osteogenic potential of shell nacre cement (SNC), a bone void-filling cement based on shell nacre powder and ladder-structured siloxane methacrylate, using older donor BM-MSCs (age > 55 years) and young donor BM-MSCs (age < 30 years). Direct and indirect cytotoxicity studies conducted with human BM-MSCs confirmed the non-cytotoxic nature of SNC. The standard colony-forming unit-fibroblast (CFU-F) assay and population doubling (PD) time assays revealed a significant reduction in the proliferation potential (p < 0.0001, p < 0.05) in older donor BM-MSCs compared to young donor BM-MSCs. Correspondingly, older donor BM-MSCs contained higher proportions of senescent, ß-galactosidase (SA-ß gal)-positive cells (nearly 2-fold, p < 0.001). In contrast, the proliferation capacity of older donor BM-MSCs, measured as the area density of CellTrackerTM green positive cells, was similar to that of young donor BM-MSCs following a 7-day culture on SNC. Furthermore, after 14 days of osteoinduction on SNC, scanning electron microscopy with energy-dispersive spectroscopy (SEM-EDS) showed that the amount of calcium and phosphorus deposited by young and older donor BM-MSCs on SNC was comparable. A similar trend was observed in the expression of the osteogenesis-related genes BMP2, RUNX2, ALP, COL1A1, OMD and SPARC. Overall, the results of this study indicated that SNC would be a promising candidate for managing bone voids in all age groups.

Microphysiological systems for human aging research.

Recent advances in microphysiological systems (MPS), also known as organs-on-a-chip (OoC), enable the recapitulation of more complex organ and tissue functions on a smaller scale in vitro. MPS therefore provide the potential to better understand human diseases and physiology. To date, numerous MPS platforms have been developed for various tissues and organs, including the heart, liver, kidney, blood vessels, muscle, and adipose tissue. However, only a few studies have explored using MPS platforms to unravel the effects of aging on human physiology and the pathogenesis of age-related diseases. Age is one of the risk factors for many diseases, and enormous interest has been devoted to aging research. As such, a human MPS aging model could provide a more predictive tool to understand the molecular and cellular mechanisms underlying human aging and age-related diseases. These models can also be used to evaluate preclinical drugs for age-related diseases and translate them into clinical settings. Here, we provide a review on the application of MPS in aging research. First, we offer an overview of the molecular, cellular, and physiological changes with age in several tissues or organs. Next, we discuss previous aging models and the current state of MPS for studying human aging and age-related conditions. Lastly, we address the limitations of current MPS and present future directions on the potential of MPS platforms for human aging research.

CSF and venous blood flow from childhood to adulthood studied by real-time phase-contrast MRI.

PURPOSE: In vivo measurements of CSF and venous flow using real-time phase-contrast (RT-PC) MRI facilitate new insights into the dynamics and physiology of both fluid systems. In clinical practice, however, use of RT-PC MRI is still limited. Because many forms of hydrocephalus manifest in infancy and childhood, it is a prerequisite to investigate normal flow parameters during this period to assess pathologies of CSF circulation. This study aims to establish reference values of CSF and venous flow in healthy subjects using RT-PC MRI and to determine their age dependency. METHODS: RT-PC MRI was performed in 44 healthy volunteers (20 females, age 5-40 years). CSF flow was quantified at the aqueduct (Aqd), cervical (C3) and lumbar (L3) spinal levels. Venous flow measurements comprised epidural veins, internal jugular veins and inferior vena cava. Parameters analyzed were peak velocity, net flow, pulsatility, and area of region of interest (ROI). STATISTICAL TESTS: linear regression, student's t-test and analysis of variance (ANOVA). RESULTS: In adults volunteers, no significant changes in flow parameters were observed. In contrast, pediatric subjects exhibited a significant age-dependent decrease of CSF net flow and pulsatility in Aqd, C3 and L3. Several venous flow parameters decreased significantly over age at C3 and changed more variably at L3. CONCLUSION: Flow parameters varies depending on anatomical location and age. We established changes of brain and spinal fluid dynamics over an age range from 5-40 years. The application of RT-PC MRI in clinical care may improve our understanding of CSF flow pathology in individual patients.

Age-related decline of various cognitive functions in well-experienced male rats treated with the putative anti-aging compound (2R)-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine ((-)BPAP).

Aging-associated cognitive disorders lack proper medication. To meet this need translation-wise, modification of the animal models is also required. In the present study, effect of the putative anti-aging compound (2R)-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine ((-)BPAP, a deprenyl derivative) on age-related cognitive decline was investigated in experienced, aged Long-Evans rats. During their lifetime, animals had acquired knowledge in various cognitive assays. Their performance in these tests was then parallel followed from the age of 27 months until their death meanwhile half of them were treated with BPAP. Cognitive performance in various tasks showed different sensitivities/resistances to age-related impairment. Pot jumping performance (motor skill-learning) started to impair first, at 21 months of age, followed by decreasing performance in five-choice serial reaction time task (attention) at 26 months. Navigation performance in Morris water maze (spatial learning) started to decline at 31 months. Performance in a cooperation task (social cognition) started to decline the latest, at 34 months. Our findings suggest that in this process, the primary factor was the level of motivation to be engaged with the task and not losing the acquired knowledge. The average lifespan of the tested rat population was 36 months. BPAP could not improve the cognitive performance; neither could it prolong lifespan. A possible reason might be that dietary restriction and lifelong cognitive engagement had beneficial effects on cognitive capabilities and lifespan creating a "ceiling effect" for further improvement. The results confirmed that experienced animals provide a translationally relevant model to study age-related cognitive decline and measure the effect of putative anti-aging compounds.

Cellular Senescence in Human Skin Aging: Leveraging Senotherapeutics.

BACKGROUND: As the largest organ in the human body, the skin is continuously exposed to intrinsic and extrinsic stimuli that impact its functionality and morphology with aging. Skin aging entails dysregulation of skin cells and loss, fragmentation, or fragility of extracellular matrix fibers that are manifested macroscopically by wrinkling, laxity, and pigmentary abnormalities. Age-related skin changes are the focus of many surgical and nonsurgical treatments aimed at improving overall skin appearance and health. SUMMARY: As a hallmark of aging, cellular senescence, an essentially irreversible cell cycle arrest with apoptosis resistance and a secretory phenotype, manifests across skin layers by affecting epidermal and dermal cells. Knowledge of skin-specific senescent cells, such as melanocytes (epidermal aging) and fibroblasts (dermal aging), will promote our understanding of age-related skin changes and how to optimize patient outcomes in esthetic procedures. KEY MESSAGES: This review provides an overview of skin aging in the context of cellular senescence and discusses senolytic intervention strategies to selectively target skin senescent cells that contribute to premature skin aging.

Predicting chronological age based on age-related osteophyte development in the superior and inferior vertebral centrum margins of T12-L5.

The purpose of this study was to determine the relationship between vertebral margins at individual vertebral levels between T12-L5 vertebra and chronological age and develop predictive models. Three hundred and nineteen CT scans from a medical imaging database in North America were randomly selected. Three superior and inferior vertebral margin sites were scored based on observable age-related changes. All individual vertebral margin site scores significantly correlated with age at death with Pearson r values ranging from 0.47 to 0.77. Totaling the individual vertebral margin site scores for L1-L5 improved Pearson r to 0.92. All resulting predictive models were significant, and the best models predicted age at death within 10 years 70%-76% of the time for males, females, and combined male and females. In conclusion, this study produced accurate and reliable models to predict age at death using age-related changes in the spine for a North American population.

Targeting Cartilage miR-195/497 Cluster for Osteoarthritis Treatment Regulates the Circadian Clock.

INTRODUCTION: Osteoarthritis (OA) is the most prevalent and debilitating joint disease without an effective therapeutic option. Multiple risk factors for OA have been identified, including abnormal chondrocyte miRNA secretion and circadian rhythms disruption, both of which have been found to cause progressive damage and loss of articular cartilage. Environmental disruption of circadian rhythms in mice predisposes animals to cartilage injury and OA. METHODS: The role of miR-195/497 cluster during OA progression was verified by mouse OA model with intra-articular injection of Agomir and Antagomir. We performed micro-CT analysis, Osteoarthritis Research Society International scores, and histological analysis in mouse knee joints. RNA sequencing was performed on the mouse cartilage cell line to explore the molecular mechanism of the miR-195/497 cluster and proteins in signaling pathway were evaluated using Western blot. Senescence-associated phenotypes were detected by Western blot, senescence ß-galactosidase staining, and immunofluorescence. RESULTS: This study demonstrated that miR-195/497-5p expression is disrupted in OA with senescent chondrocytes. In addition, miR-195/497-5p influenced the circadian rhythm of mice chondrocytes by modulating the expression of the Per2 protein, resulting in the gradual degradation of articular cartilage. We found that the miR-195/497 cluster targets DUSP3 expression. The deletion of the miR-195/497 cluster increased the level of DUSP3 expression and decreased the levels of phosphorylated ERK 1/2 and CREB. Per2 transcription is upregulated by stimulating CREB and ERK 1/2 phosphorylation. CONCLUSION: Our findings identify a regulatory mechanism connecting chondrocyte miR-195/497-5p to cartilage maintenance and repair and imply that circadian rhythm disturbances affected by miR-195/497-5p are risk factors for age-related joint diseases such as OA.

A Nonsystematic Review of the Features of Pharmacotherapy in the Elderly at the Stage of Taking Medications.

The human body is subservient to the age-related changes that affect not only the outer appearance but also organs and tissues. They also concern the processes of pharmacokinetics and dynamics. This means that the absorption, distribution, and metabolism of drugs used by an elderly patient will be slowed down. Therefore, it becomes necessary to prescribe a special dosing regimen for older people. An actual problem is also that, with age, many patients require more drugs than young people. This increases the risk of side effects because many drugs are difficult to combine with each other. Pharmacy of our time is a science that is constantly developing and modernizing, which allows changing therapy for the better: prescribing drugs in smaller quantities, with a smaller range of adverse reactions and a better effect. The aim of the work is to analyze the impact and relationship of older age on the pharmacotherapy of patients, as well as the risks of drug-induced diseases. To carry out this work, such research methods as analysis, synthesis, comparative analysis, classification, analogy, abstraction, induction, and generalization were used. The features of the stages of pharmacokinetics and pharmacodynamics in the elderly were considered; we studied the data of clinical studies and literature in geriatrics; and the effects of a combination or increase in the dosage of drugs have been noted. After the collection of research data and the analysis, it turned out that it is real and necessary to avoid the negative consequences of pharmacotherapy in elderly and senile patients. Considering the natural age-related changes in the condition and functioning of organs and systems, constantly monitoring the effectiveness of drugs and undesirable reactions of the body to them, adjusting treatment protocols will have a favorable result and help optimize pharmacotherapy for the elderly and reduce the risk of side effects and diseases caused by medications.

[Transcription Factor NRF2 in Endothelial Functions].

The transcription factor NRF2 is a major regulator of cell antioxidant defense. NRF2 is activated by various stimuli, such as oxidants and electrophiles, to induce transcription of a number of genes whose products are involved in xenobiotic metabolism and contribute to the reduction of oxidative stress. NRF2 is one of the key transcription factors that ensure the endothelial cell function. The endothelium is a cell layer that lines the lumens of blood vessels and performs various homeostatic functions, controlling migration of leukocytes, regulating thrombosis and vascular tone, and playing a role in angiogenesis. Endothelial dysfunction is often accompanied by inflammation and oxidative stress, which may lead to cell aging and cell death by apoptosis, necrosis, or ferroptosis. Endothelial dysfunction contributes to the development of diabetes and common cardiovascular disorders, such as hypertension and atherosclerosis. Many pathophysiological processes in the endothelium, including senile changes, are associated with decreased NRF2 activity, leading to inflammatory activation and decreasing activity of the cell antioxidant defense systems. Activation of the NRF2 signaling pathway generally contributes to the resolution of inflammation and oxidative stress. The review focuses on the role that NRF2 plays in basic functions of the endothelium in normal and pathological conditions. Advantages and disadvantages of NRF2 activation as a way to prevent and treat cardiovascular diseases are discussed additionally.

Age-Related Changes in Hepatic Lipid Metabolism and Abdominal Adipose Deposition in Yellow-Feathered Broilers Aged from 1 to 56 Days.

The objective of this study was to evaluate the age-related changes in hepatic lipid metabolism, adipocyte hyperplasia, hypertrophy, and lipid metabolism in the abdominal adipose tissue of yellow-feathered broilers. Blood, liver, and abdominal adipose samples were collected on days 1, 7, 14, 21, 28, 35, 42, 49, and 56. Body, liver, and abdominal weight increased (p < 0.05) with age-related changes. The triacylglycerol content peaked on day 14, and total cholesterol content peaked on day 56. The adipocyte diameter and area peaked on day 56, and total DNA content peaked on day 7. The age-related changes in hepatic lipogenesis-related gene (ChREBP, SREBP-1c, ACC, FAS, SCD1) expression mainly occurred during days 1 to 21, hepatic lipolysis-related gene (CPT1, LPL, ApoB) expression mainly occurred during days 1 to 14, and abdominal adipose-deposition-related gene (PPARα, CPT1, LPL, PPARγ, C/EBPß) expression occurred during days 1 to 14. These results demonstrated a dynamic pattern of hepatic lipid metabolism and abdominal adipose deposition in yellow-feathered broilers, which provides practical strategies to regulate hepatic lipid metabolism and reduce abdominal adipose deposition in yellow-feathered broilers.

The Anatomic Variability of the Lateral Ventricles of the Human Brain Depending on Age and Sex.

The evaluation of the different parameters of the brain ventricles is used in the diagnostics of age-related degenerative diseases of the central nervous system, as well as psychiatric disorders. The purpose of this study was to obtain data about the normal morphologic parameters of the lateral ventricles of the human brain and their relations with age and sex to establish a solid background for the diagnostics of any pathologic changes. Computed tomography (CT) studies of 108 healthy individuals aged from 17 to 86 (mean age: 46.87 ± 17.31) were selected for the study. The width of the different portions of the lateral ventricles was measured, and its relations with age and gender were assessed. The study has demonstrated a statistically significant dependence of the width of the different portions of the lateral ventricles on age. There was no statistically significant difference in this parameter identified between male and female groups. The width of the different portions of the lateral ventricles of the brain increases with age. Parameters are similar in males and females.

The Correlation between Retinal and Choroidal Thickness with Age-Related White Matter Hyperintensities in Progressive Supranuclear Palsy.

Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease. Recently, several retinal layers in PSP compared to healthy controls. were found to be thinner. However, no studies evaluating the correlation between retinal layers and cerebral white matter changes, nor eventual choroidal changes in PSP, have been conducted so far. The goals of the present study were to explore potential differences in choroidal structure between PSP and healthy controls, and to describe the relationship between retinal layers' thickness and volume, using spectral-domain optical coherence tomography (SD-OCT) and age-related white matter change scores (ARWMC) using magnetic resonance imaging (MRI) of the brain. Choroidal structures of 26 PSP patients and 26 healthy controls using standard SD-OCT with an enhanced depth imaging (EDI) approach were analyzed; then, retinal the structures of 16 of these PSP patients using standard SD-OCT were examined; finally, the same patients underwent brain MRI, and their cerebral white matter changes were calculated. Non-statistically significant differences between PSP patients' and healthy controls' choroidal structure were found. On the contrary, PSP patients' inner retinal layers (INR), retinal pigmented epithelium (RPE) and all retinal layers' thicknesses in the macular region were found to be significantly correlated with ARWMC, independently from age and axial length (AL). PSP patients' neurological alterations go hand in hand with retinal ones, independently from age and axial length. Our results suggest a mutual relationship between cerebral and retinal structure pathological alterations. On the other hand, no significant differences in the choroidal evaluation compared to healthy controls have been found.

High morbidity and mortality in children with untreated congenital deficiency of leptin or its receptor.

The long-term clinical outcomes of severe obesity due to leptin signaling deficiency are unknown. We carry out a retrospective cross-sectional investigation of a large cohort of children with leptin (LEP), LEP receptor (LEPR), or melanocortin 4 receptor (MC4R) deficiency (n = 145) to evaluate the progression of the disease. The affected individuals undergo physical, clinical, and metabolic evaluations. We report a very high mortality in children with LEP (26%) or LEPR deficiency (9%), mainly due to severe pulmonary and gastrointestinal infections. In addition, 40% of surviving children with LEP or LEPR deficiency experience life-threatening episodes of lung or gastrointestinal infections. Although precision drugs are currently available for LEP and LEPR deficiencies, as yet, they are not accessible in Pakistan. An appreciation of the severe impact of LEP or LEPR deficiency on morbidity and early mortality, educational attainment, and the attendant stigmatization should spur efforts to deliver the available life-saving drugs to these children as a matter of urgency.

Subjective Cognitive Decline and Frailty Trajectories and Influencing Factors in Japanese Community-Dwelling Older Adults: A Longitudinal Study.

We studied frailty and subjective cognitive decline (SCD) trajectories in older Japanese adults and evaluated the influence of various factors on these trajectories. We analyzed data from 1157 non-demented adults aged 70 and above from 2013 to 2019. Frailty was assessed using the self-administered Kihon Checklist (KCL), a Japanese frailty index. SCD was evaluated using the questionnaire of the Subjective Memory Complaints scale. Through group-based joint trajectory models, we discerned three frailty trajectories: non-progressive (n = 775), moderate progressive (n = 312), and rapid progressive (n = 70); and three SCD trajectories: non-progressive (n = 302), moderate progressive (n = 625), and rapid progressive (n = 230). Individuals in the rapid progressive SCD trajectory had a 32.2% probability of also being in the rapid progressive frailty trajectory. In contrast, those in the non-progressive SCD trajectory had zero probability of being in the rapid progressive frailty trajectory. Both the rapid progressive frailty and SCD groups combined had a higher incidence of depressive symptoms and slow gait speed. Our results have found that frailty and SCD share a similar trajectory in Japanese older adults. Additionally, rapid progressive frailty and SCD were associated with the highest risk of depressive symptoms and slow gait speed. Thus, interventions targeting both frailty and cognitive decline should prioritize mental health enhancement and gait speed improvement.