Age-related Physiological Changes Research Articles

The peculiarities of setting goals in geriatric rehabilitation

Aim. To determine the peculiarities of setting SMART goals in geriatric rehabilitation. Materials and methods. Materials of scientific publications and international guidelines on the organization of rehabilitation; methods of data analysis, systematization and generalization were used. Results. Age-related physiological changes in the body of older people combined with their own life experience and individual personality qualities require special approaches to setting goals in geriatric rehabilitation. When setting goals in geriatric rehabilitation, certain problems may arise: patients may feel that their opinion is not sufficiently taken into account, and difficulties in understanding what exactly they expect from the rehabilitation process; specialists may have doubts about the ability of older patients to formulate realistic goals; not all patients seek an active role in the goal-setting process. To solve these problems, members of the multidisciplinary team can use certain tools: the use of language that is understandable for the patient in discussions; determination of the patient’s role in setting goals; achievement of a balance between the patient’s wishes and capabilities; demarcation of goals to better achieve them. Directly, the process of setting goals can be presented as a process consisting of three stages: introduction, goal setting, summary and clarification of goals. The authors consider in detail the actions that must be performed by members of the multidisciplinary team at each stage. The use of a three-step algorithm for forming goals can help specialists better interact with the patient and better form the goals of the rehabilitation cycle. Conclusions. The article highlights the problems that arise when setting goals in geriatric rehabilitation; tools for solving these problems and a three-stage goal formation algorithm, which allows increasing the efficiency of interaction with the patient to achieve the SMART goals set have been proposed.

Cancer Care in Elderly Patients; A Record Based Retrospective Analysis of Clinical Profile and Overview of Treatment

Background and Objective: Cancer can develop at any age, but the incidence of cancer rises dramatically at a later stage in life. Cancer management in older people can be complex. Comorbidity and Physiologic age-related changes can affect how and when cancer is diagnosed, whether or not treatment is offered and the individual tolerance to anticancer therapy. This retrospective study aimed to assess the clinical profiles of elderly cancer patient to optimize cancer care. Materials and Methods: This retrospective study comprised cancer patients attended our oncology department between 2018 to 2022 who were above the age ≥65 years. All the information regarding the type of cancer, performance status, intent of treatment, treatment completion and follow up status at 3 years were documented and analyzed. Results: A total of 230 patients were included in the study. The common malignancies were Carcinoma Head and Neck and Lung Cancer followed by Esophagus and Colorectal malignancies. Most of the patients presented with Performance Status of 1 (57.8%). The intent of therapy was curative in 49.1% and Palliative in 30.1% patients. At median follow up 36 months 15% of treated patients were on regular follow-up and they were alive without disease. Conclusion: Head and Neck Cancer was the most common cancer seen in our study. Elderly patients with cancer presented with good performance status, hence Elderly Cancer patients deserve same opportunity as younger patients for treatment and survival options.

Cancer Care in Elderly Patients; A Record Based Retrospective Analysis of Clinical Profile and Overview of Treatment

Background and Objective: Cancer can develop at any age, but the incidence of cancer rises dramatically at a later stage in life. Cancer management in older people can be complex. Comorbidity and Physiologic age-related changes can affect how and when cancer is diagnosed, whether or not treatment is offered and the individual tolerance to anticancer therapy. This retrospective study aimed to assess the clinical profiles of elderly cancer patient to optimize cancer care. Materials and Methods: This retrospective study comprised cancer patients attended our oncology department between 2018 to 2022 who were above the age ≥65 years. All the information regarding the type of cancer, performance status, intent of treatment, treatment completion and follow up status at 3 years were documented and analyzed. Results: A total of 230 patients were included in the study. The common malignancies were Carcinoma Head and Neck and Lung Cancer followed by Esophagus and Colorectal malignancies. Most of the patients presented with Performance Status of 1 (57.8%). The intent of therapy was curative in 49.1% and Palliative in 30.1% patients. At median follow up 36 months 15% of treated patients were on regular follow-up and they were alive without disease. Conclusion: Head and Neck Cancer was the most common cancer seen in our study. Elderly patients with cancer presented with good performance status, hence Elderly Cancer patients deserve same opportunity as younger patients for treatment and survival options.

Strength Simulator Codes for Different Age Groups Considering Physiological Processes of Adaptation in Conditions of Strength Fitness

Topicality. Determination of optimal load parameters in fitness, based on age-related physiological features and adaptive changes of the neuromuscular system, is one of the most debated issues among leading scientists in this field. The research purpose was to develop models of code combinations for strength training of different age groups, considering physiological processes of human body adaptation to a stressful physical stimulus in the conditions of strength fitness. Methods. A comparative analysis of the research results on the effectiveness of using the optimal combination between the parameters of an external physical stimulus and the physiological features of the human body adaptive reactions has been used over the research. The results. It was established that in the process of developing code combinations for different age groups` strength training, the nature of the physiological reactions of their neuromuscular system to a stressful stimulus depend on the features of the load regime and the structure of the exercise program. For adolescence, considering the peculiarities of the physiological process of adaptation, it is used of moderate-intensity activity in combination with a complex of isolation exercises that promotes the processes of intra-muscular and inter-muscular coordination. For youth, in the process of developing code combinations aimed at the development of the main types of strength, the entire range of load modes is actively used. Particular attention is paid to stimuli that contribute to increasing the number of active (FF) motor units. In adulthood, especially in the second period, the content of code combinations to increase strength capabilities changes significantly. In the vast majority, this applies to the parameters of the intensity of load modes, the use of which will selectively affect the hypertrophy of a certain type of muscle fibers within intermuscular coordination. For the elderly, in the process of developing code combinations for strength training, priority is given to the selective activity of agonists during moderate-intensity isolated exercises. Findings. Strength Simulator codes considering physiological processes of the neuromuscular system adaptation to a stressful physical stimulus, is one of the innovative mechanisms for improving the training program of different age groups in the conditions of strength fitness.

Value of preclinical systematic reviews and meta-analyses in pediatric research.

Similar to systematic reviews (SRs) in clinical fields, preclinical SRs address a specific research area, furnishing information on current knowledge, possible gaps, and potential methodological flaws of study design, conduct, and report. One of the main goals of preclinical SRs is to identify aspiring treatment strategies and evaluate if currently available data is solid enough to translate to clinical trials or highlight the gaps, thus justifying the need for new studies. It is imperative to rigorously follow the methodological standards that are widely available. These include registration of the protocol and adherence to guidelines for assessing the risk of bias, study quality, and certainty of evidence. A special consideration should be made for pediatric SRs, clinical and preclinical, due to the unique characteristics of this age group. These include rationale for intervention and comparison of primary and secondary outcomes. Outcomes measured should acknowledge age-related physiological changes and maturational processes of different organ systems. It is crucial to choose the age of the animals appropriately and its possible correspondence for specific pediatric age groups. The findings of well-conducted SRs of preclinical studies have the potential to provide a reliable evidence synthesis to guide the design of future preclinical and clinical studies. IMPACT: This narrative review highlights the importance of rigorous design, conduct and reporting of preclinical primary studies and systematic reviews. A special consideration should be made for pediatric systematic reviews of preclinical studies, due to the unique characteristics of this age group.

Outcomes in Older Inpatients with Hyperkalemia: A Follow-up Observational Study

Abstract Objectives: Hyperkalemia is a common electrolyte disturbance encountered in hospitalized older patients secondary to age-related physiological changes in the kidneys, multiple comorbidities, and the burden of multiple medication usage. Metabolic acidosis, rhabdomyolysis, and tumor lysis syndrome cause the shift of potassium into the extracellular space. This contributes to hyperkalemia. This study aims to determine the outcomes in patients with hyperkalemia admitted to a tertiary care center and to list the factors contributing to the development of hyperkalemia in these patients. Methods: This was a prospective observational study conducted among older inpatients (≥60 years of age) admitted to the geriatric and medical wards in a tertiary care hospital. The patients with hyperkalemia were followed up till discharge or death. Results: Among the 225 study participants who presented with hyperkalemia, the mortality rate was found to be 22.2%. In the multivariate analysis, older people aged more than 70 years (P = 0.007) and those who were male had a significantly higher mortality (P = 0.009). The use of angiotensin-converting enzyme inhibitors (ACEIs) (P = 0.049) and beta-blockers (P = 0.02) was significantly associated with the development of hyperkalemia. Conclusions: ACEIs and beta-blockers increased the risk of developing hyperkalemia in the study population. Hyperkalemia was found to be associated with an increase in mortality, especially in the very old (>70 years) and in males.

A thermoregulation model based on the physical and physiological characteristics of Chinese elderly

Given the increasing aging population and rising living standards in China, developing an accurate and straightforward thermoregulation model for the elderly has become increasingly essential. To address this need, an existing one-segment four-node thermoregulation model for the young was selected as the base model. This study developed the base model considering age-related physical and physiological changes to predict mean skin temperatures of the elderly. Measured data for model optimization were collected from 24 representative healthy Chinese elderly individuals (average age: 67 years). The subjects underwent temperature step changes between neutral and warm conditions with a temperature range of 25–34 °C. The model's demographic representation was first validated by comparing the subjects' physical characteristics with Chinese census data. Secondly, sensitivity analysis was performed to investigate the influences of passive system parameters on skin and core temperatures, and adjustments were implemented using measurement or literature data specific to the Chinese elderly. Thirdly, the active system was modified by resetting the body temperature set points. The active parameters to control thermoregulation activities were further optimized using the TPE (Tree-structured Parzen Estimator) hyperparameter tuning method. The model's accuracy was further verified using independent experimental data for a temperature range of 18–34 °C for Chinese elderly. By comprehensively considering age-induced thermal response changes, the proposed model has potential applications in designing and optimizing thermal management systems in buildings, as well as informing energy-efficient strategies tailored to the specific needs of the Chinese elderly population.

State of the art in pediatric nanomedicines.

In recent years, the continuous development of innovative nanopharmaceuticals is expanding their biomedical and clinical applications. Nanomedicines are being revolutionized to circumvent the limitations of unbound therapeutic agents as well as overcome barriers posed by biological interfaces at the cellular, organ, system, and microenvironment levels. In many ways, the use of nanoconfigured delivery systems has eased challenges associated with patient differences, and in our opinion, this forms the foundation for their potential usefulness in developing innovative medicines and diagnostics for special patient populations. Here, we present a comprehensive review of nanomedicines specifically designed and evaluated for disease management in the pediatric population. Typically, the pediatric population has distinguishing needs relative to those of adults majorly because of their constantly growing bodies and age-related physiological changes, which often need specialized drug formulation interventions to provide desirable therapeutic effects and outcomes. Besides, child-centric drug carriers have unique delivery routes, dosing flexibility, organoleptic properties (e.g., taste, flavor), and caregiver requirements that are often not met by traditional formulations and can impact adherence to therapy. Engineering pediatric medicines as nanoconfigured structures can potentially resolve these limitations stemming from traditional drug carriers because of their unique capabilities. Consequently, researchers from different specialties relentlessly and creatively investigate the usefulness of nanomedicines for pediatric disease management as extensively captured in this compilation. Some examples of nanomedicines covered include nanoparticles, liposomes, and nanomicelles for cancer; solid lipid and lipid-based nanostructured carriers for hypertension; self-nanoemulsifying lipid-based systems and niosomes for infections; and nanocapsules for asthma pharmacotherapy.

Protocolo diagnóstico y terapéutico de la enfermedad péptica en el anciano

The incidence of peptic ulcer is decreasing in the general population. On the contrary, hospitalization and mortality rates for gastrointestinal ulcers remain high in older patients. The factors that may explain this epidemiological feature in older adults are age-related physiological changes, the high prevalence of H. pylori infection, and increasing prescribing of gastroduodenal-damaging drugs such as NSAIDs or antiplatelet therapy. The main goals of peptic ulcer treatment in the older adult population are to reduce recurrence of the disease and prevent complications. The general approach to an older adult patient should include a comprehensive geriatric assessment. The treatments available for peptic ulcer are based primarily on suppression of gastric acid with antisecretory drugs and the eradication of H. pylori infection. Treatment with PPI antisecretory agents has a favorable tolerability profile in older adult patients; however, their use must be rational and it is necessary to respect the treatment indications.

Age-Related Orthostatic Hypotension: A Comprehensive Analysis of Prevalence, Mechanisms, and Management in the Geriatric Population.

Geriatric patients frequently encounter orthostatic hypotension (OH), a multifaceted condition characterized by a significant drop in blood pressure upon assuming an upright position. As the elderly population is particularly susceptible to OH, our review endeavors to comprehensively explore the complex nature of this condition and various factors contributing to its development. We investigate the impact of comorbidities, polypharmacy, age-related physiological changes, and autonomic dysfunction in the pathogenesis of OH. Geriatric patients with OH are faced with an elevated risk of falls, syncope, a decline in their overall quality of life, and hence increased mortality. These implications require careful consideration, necessitating a thorough examination of therapeutic strategies. We evaluate various pharmaceutical and nonpharmacological therapies, delving into the effectiveness and safety of each approach in managing OH within geriatric populations. We explore the role of pharmacotherapy in alleviating symptoms and mitigating OH-related complications, as well as the potential benefits of volume expansion techniques to augment blood volume and stabilize blood pressure. We place particular emphasis on the significance of lifestyle changes and nonpharmacological interventions in enhancing OH management among the elderly. These interventions encompass dietary modifications, regular physical activity, and postural training, all tailored to the unique needs of the individual patient. To optimize outcomes and ensure patient safety, we underscore the importance of individualized treatment plans that take into account the geriatric patient's overall health status, existing comorbidities, and potential interactions with other medications. This review aims to improve clinical practice and patient outcomes by advocating for early detection, properly tailored management, and targeted interventions to address OH in the elderly population. By raising awareness of OH's prevalence and complexities among healthcare professionals, we hope to foster a comprehensive understanding of OH and contribute to the overall wellness and quality of life of this vulnerable demographic.

Tuberculosis in the elderly population

ABSTRACT Tuberculosis (TB) is a significant public health challenge, with the elderly population being particularly affected in certain regions. Around 17.5% of TB cases in France, in 2019, occurred in individuals over 65 years old. Aging leads to decreased lung function and structural changes that predispose the elderly to TB infection. Immunosenescence, comorbidities, malnutrition, and communal living situations increase TB risk in the elderly. TB symptoms in the elderly are often nonspecific and overlap with other conditions, complicating diagnosis. Radiological presentations may differ from younger patients, and the elderly may struggle to produce sputum for testing. Elderly patients may experience varying tolerances to TB medications, and age-related physiological changes and comorbidities influence treatment tolerance and outcomes. Careful management of drug interactions is crucial. Elderly TB patients, especially those who are frail or dependent, are at higher risk for infection and complications. Adherence to treatment is critical, often necessitating directly observed therapy and nutritional support.

Age and sex-related variations in murine laryngeal microbiota.

The larynx undergoes significant age and sex-related changes in structure and function across the lifespan. Emerging evidence suggests that laryngeal microbiota influences immunological processes. Thus, there is a critical need to delineate microbial mechanisms that may underlie laryngeal physiological and immunological changes. As a first step, the present study explored potential age and sex-related changes in the laryngeal microbiota across the lifespan in a murine model. We compared laryngeal microbial profiles of mice across the lifespan (adolescents, young adults, older adults and elderly) to determine age and sex-related microbial variation on 16s rRNA gene sequencing. Measures of alpha diversity and beta diversity were obtained, along with differentially abundant taxa across age groups and biological sexes. There was relative stability of the laryngeal microbiota within each age group and no significant bacterial compositional shift in the laryngeal microbiome across the lifespan. There was an abundance of short-chain fatty acid producing bacteria in the adolescent group, unique to the laryngeal microbiota; taxonomic changes in the elderly resembled that of the aged gut microbiome. There were no significant changes in the laryngeal microbiota relating to biological sex. This is the first study to report age and sex-related variation in laryngeal microbiota. This data lays the groundwork for defining how age-related microbial mechanisms may govern laryngeal health and disease. Bacterial compositional changes, as a result of environmental or systemic stimuli, may not only be indicative of laryngeal-specific metabolic and immunoregulatory processes, but may precede structural and functional age-related changes in laryngeal physiology.

Guidance to Improve Prehospital Trauma Triage Decisions for Geriatric Patients: A Review of the Literature

Major trauma has become a major issue in older people. Prehospital assessment of older trauma patients is not clearly defined, with reported high rates of undertriage. There are several factors that potentially impact upon appropriate prehospital assessment and decision-making for older trauma patients: (a) the presentation of trauma in this population including mechanism, location, and pattern of injury; (b) unique factors with older adults including age-related anatomical and physiological changes, comorbidities, and medication use; (c) distance to trauma centers; and (d) paramedics’ subjective judgments. These factors may have contributed to suboptimal assessment and triage decisions and, hence, increased undertriage rates for this population in prehospital care. This paper aims to provide guidance for paramedics to appropriately assess and accurately triage these patients through applying adjusted physiological criteria specifically for older trauma patients and considering the assessment of mechanism of injury, age cutoffs, comorbidities, and anticoagulants as a method of triage. It also highlights and provides recommendations about other important aspects to optimize prehospital trauma triage decisions for older patients including the integration of frailty assessment in prehospital care and shared decision-making.

Microgravity effects and aging physiology: similar changes or common mechanisms?

Despite the use of preventive measures (including intense physical activity), cosmonauts and astronauts develop muscle atony and atrophy, insufficiency of the cardiovascular system, osteopenia, etc. All these changes, reminiscent of age-related physiological changes, occur in a healthy person in microgravity quite quickly - within a few months. Adaptation to the absence of gravity leads to the symptoms of aging, which are compensated after returning to Earth. The prospect of interplanetary flights raises the question of gravity thresholds, below which the main physiological systems will lose their functional potential, similar to aging, and affect life expectancy. An important role in the aging process belongs to the body’s cellular reserve - progenitor cells, which are involved in physiological remodeling and regenerative/reparative processes of all physiological systems. With age, progenitor cell count and the regenerative potential decreases. Moreover, their paracrine spectrum becomes pro-inflammatory during replicative senescence, disrupting tissue homeostasis. Mesenchymal stem/stromal cells (MSCs) are mechanosensitive, and therefore the absence of a gravitational stimulus causes serious changes in their functional status. The review compares the cellular effects of microgravity and changes developing in senescent cells, including stromal precursors.

Analysis of Drug Management Ability on the Elderly in the East Surabaya Using MedMaIDE™

The elderly are at the highest risk for drug-related problems caused by age-related physiological changes, multiple chronic illnesses, polypharmacy, and poor drug management. This study aims to analyze the ability of elderly regarding drug management. This study used an observational research method with an elderly population in the East Surabaya area. The research instrument used was MedMaIDETM (Medication Management Instrument for Deficiencies in the Elderly), which can be used to measure ability in medication management in the elderly community who are undergoing self-medication with at least one medication. Sampling was carried out using a non-random sampling method with a purposive sampling technique. The number of respondents obtained in this study were 100 elderly who live in the East Surabaya area. The inclusion criteria for research respondents were: (1) willing to be a respondent; (2) domiciled in the East Surabaya area; (3) aged ≥ 60 years; (4) able to communicate in Indonesian; and (5) consuming at least one medicine. The variable studied was drug management skills in the elderly which includes knowledge of the medications aspect, knowledge on how to take the medication aspect, and knowledge on how to obtain the medication. The average MedMAIDE scores of respondents in the three domains with a total average value of 1.18 and a standard deviation of 0.10, meanings each elderly at least had one deficiency out of 13 maximun score of deficiencies. There were 70 respondents out of 100 respondents who had limitations in drug management with one deficiency score as the smallest score and the largest total deficiency score being 7. Meanwhile, 30 other respondents had a no deficiency. The most difficult tasks were identified the problems after taking the medication, fill a glass with water, sip enough water to swallow medication and identify if a refill exists on a prescription. The ability of elderly people in the East Surabaya area to manage their medicines was good. The elderly were able to recognize the drugs used, use the drugs correctly, and comply with drug administration.

Prediction of pediatric dose of tirzepatide from the reference adult dose using physiologically based pharmacokinetic modelling

Tirzepatide is an emerging hypoglycemic agent that has been increasing used in adults, yet its pharmacokinetic (PK) behavior and dosing regimen in pediatric population remain unclear. This study aimed to employ the physiologically based pharmacokinetic (PBPK) model to predict changes of tirzepatide exposure in pediatric population and to provide recommendations for its dose adjustments. A PBPK model of tirzepatide in adults was developed and verified by comparing the simulated plasma exposure with the observed data using PK-Sim&MoBi software. This model was then extrapolated to three specific age subgroups, i.e., children (10–12 years), early adolescents (12–15 years), and adolescents (15–18 years). Each subgroup included healthy and obese population, respectively. All known age-related physiological changes were incorporated into the pediatric model. To identify an appropriate dosing regimen that yielded PK parameters which were comparable to those in adults, the PK parameters for each aforementioned subgroup were predicted at pediatric doses corresponding to 87.5%, 75%, 62.5%, and 50% of the adult reference dose. According to the results of simulation, dose adjustments of tirzepatide are necessary for the individuals aged 10–12 years, as well as those aged 12–15 years with healthy body weights. In conclusion, the adult PBPK model of tirzepatide was successfully developed and validated for the first time, and the extrapolated pediatric model could be used to predict pediatric dosing regimen of tirzepatide, which will provide invaluable references for the design of future clinical trials and its rational use in the pediatric population.

THU157 Epigenetic Regulation Of Genes Involved In The Signaling Cascade Of The GH Axis - IGF1 And Insulin. Implication In Children Postnatal Growth

Abstract Disclosure: L. Zoff: None. F. Garcia: None. G. Aschettino: None. G. Veneruzzo: None. M.C. Mattone: None. N. Perez Garrido: None. M. Juanes: None. N.I. Saraco: None. C. Alonso: None. G. Guercio: None. A. Belgorosky: None. M.S. Baquedano: None. Growth is influenced by genetic, nutritional, environmental, and hormonal factors, but it proceeds in a predictable pattern characterized by a constant growth deceleration between childhood and adolescence. This growth deceleration is coordinated in tissues and organs in order to maintain body proportions. Growth hormone (GH)/ insulin-like growth factor type 1 (IGF1) axis and insulin are crucial stimulators of growth, cell proliferation and metabolism. However, their levels do not change with age in a pattern that would explain the prepubertal decline in growth rate. DNA methylation represents a fundamental epigenetic mark that is associated with transcriptional repression during development. We hypothesize that the postnatal growth pattern could be orchestrated by epigenetic mechanisms. In order to analyze age related physiological changes, we evaluated promoter methylation in the GHR, IGF1R and INSR genes in peripheral blood from 40 healthy children of both sexes (females (F) n=21 and males (M) n=19), between 3 and 15 years old by using targeted deep-amplicon bisulfite sequencing on a MiSeq system. Sequencing libraries of 4 promoter CpG rich regions for GHR, 3 for IGF1R and 5 for INSR (104, 103 and 141 CpG sites, respectively) were analyzed for mean methylation values of all CpG sites using amplikyzer2 software. The results would suggest a sexual dimorphism in the epigenetic regulation of GH, IGF1 and insulin receptors gene expression. A significant negative correlation between GHR methylation and age was observed in both sexes (Multiple Spearman correlation, p<0.05), but in different GHR promoter regions. Specifically, a decrease in themethylation levels with age were detected in CpG-8, CpG+183 and CpG+243 in F; and in CpG+343, CpG+346, CpG+385, CpG+391, CpG+407 and CpG+487 in M. In contrast, in the IGF1R promoter region, a positive correlation was observed exclusively in F, between mean methylation levels and age in CpG-51, CpG-43, CpG-41, CpG-23, CpG-17, CpG-15, CpG-13, CpG-11, and CpG-9, p<0.05. Male-specific positive correlation between INSR promotermethylation values and age were found in CpG-768, CpG+10, CpG+31, CpG+87, CpG+95, CpG+163, CpG+199, CpG+206, CpG+238, CpG+700, CpG+815 and CpG+900, p<0.05.Taking together, our findings are in agreement with the hypothesis that age-associated DNA promoter methylation changes could be involved in the physiological growth pattern. Finally, the observed sexual dimorphism suggests age- and sex-dependent regulatory mechanisms for normal growth. Presentation: Thursday, June 15, 2023

Morphofunctional Changes in Brain and Peripheral Blood in Adult and Aged Wistar Rats with AlCl3-Induced Neurodegeneration.

the general lifespan has been prolonged greatly during the past century, and the incidence of age-associated diseases, including neurodegenerative ones, has increased as well. However, modelling of age-related pathologies is mostly conducted on adult rodents. We studied morphofunctional changes in the brain and peripheral blood of adult Wistar rats in comparison with old Wistar rats to determine age-related physiological changes and differences in adaptive reactions to AlCl3 exposure. the work was performed on adult and old male Wistar rats. The animals consumed a 100 mg/kg solution of AlCl3 each day for 60 days. Morphological changes of neurons and microglia, mRNA expression levels of pro-inflammatory and anti-inflammatory cytokines, microglia activation markers, amyloid-related proteins, and hallmarks of cellular senescence, monocyte, and lymphocyte subpopulations in the peripheral blood were examined. old rats showed increasing hyperchromic neurons in the hippocampus; activation of microglia; upregulation of pro-inflammatory cytokines and cellular senescence markers; downregulation of anti-inflammatory cytokines; and Hif-1a and a decrease in B-cells and monocyte in peripheral blood. compared to young animals, aged rats respond to aluminum exposure with a severe decline of most cells' function and irreversible neuronal loss. Regarding all reported data, neurodegeneration modelling and investigating of factors capable of accelerating or preventing it should be performed in experimental work on aged animals.

An mRNA Profiling Study of Vaginal Swabs from Pre- and Postmenopausal Women.

Body fluid identification by means of mRNA profiling provides valuable supplementary information in forensic investigations. In particular, the detection of vaginal mucosa mRNA markers is highly relevant in sexual assault cases. Although the vagina undergoes characteristic age-related physiological changes over a lifetime, few studies have evaluated the efficacy of vaginal mRNA markers in women of different ages. In this multicentric study, a 19-plex mRNA profiling assay including vaginal-specific markers (CYP2B7P1, MUC4, MYOZ1) was tested in a collection of 6-20-month-old vaginal swabs obtained from pre- (n = 84) and postmenopausal (n = 55) female volunteer donors. Overall, participating laboratories were able to correctly identify ~85% of samples as vaginal mucosa by mRNA profiling. The assay's success rate did not differ between the two age groups and was not affected by the time interval between swab collection and RNA analysis. MYOZ1 resulted a less sensitive vaginal marker compared to MUC4 and CYP2B7P1. A significant relative increase in the contribution to the total amplification signal was observed for MUC4, compared to CYP2B7P1 and MYOZ1, in postmenopausal women. Observation of other body fluids and tissues different from vaginal mucosa was also evaluated in connection to information on previous sexual activity and menstrual cycle phase at the time of sampling.

Serum neurofilament light chain reference database for individual application in paediatric care: a retrospective modelling and validation study

Neurological conditions represent an important driver of paediatric disability burden worldwide. Measurement of serum neurofilament light chain (sNfL) concentrations, a specific marker of neuroaxonal injury, has the potential to contribute to the management of children with such conditions. In this context, the European Medicines Agency recently declared age-adjusted reference values for sNfL a top research priority. We aimed to establish an age-adjusted sNfL reference range database in a population of healthy children and adolescents, and to validate this database in paediatric patients with neurological conditions to affirm its clinical applicability. To generate a paediatric sNfL reference dataset, sNfL values were measured in a population of healthy children and adolescents (aged 0-22 years) from two large cohorts in Europe (the Coronavirus Antibodies in Kids from Bavaria study, Germany) and North America (a US Network of Paediatric Multiple Sclerosis Centers paediatric case-control cohort). Children with active or previous COVID-19 infection or SARS-CoV-2 antibody positivity at the time of sampling, or a history of primary systemic or neurological conditions were excluded. Linear models were used to restrospectively study the effect of age and weight on sNfL concentrations. We modelled the distribution of sNfL concentrations as a function of age-related physiological changes to derive reference percentile and Z score values via a generalised additive model for location, scale, and shape. The clinical utility of the new reference dataset was assessed in children and adolescents (aged 1-19 years) with neurological diseases (epilepsy, traumatic brain injury, bacterial CNS infections, paediatric-onset multiple sclerosis, and myelin oligodendrocyte glycoprotein antibody-associated disease) from the paediatric neuroimmunology clinic at the University of California San Francisco (San Francisco, CA, USA) and the Children's Hospital of the University of Regensburg (Regensburg, Germany). Samples from 2667 healthy children and adolescents (1336 [50·1%] girls and 1331 [49·9%] boys; median age 8·0 years [IQR 4·0-12·0]) were used to generate the reference database covering neonatal age to adolescence (target age range 0-20 years). In the healthy population, sNfL concentrations decreased with age by an estimated 6·8% per year until age 10·3 years (estimated multiplicative effect per 1 year increase 0·93 [95% CI 0·93-0·94], p<0·0001) and was mostly stable thereafter up to age 22 years (1·00 [0·52-1·94], p>0·99). Independent of age, the magnitude of the effect of weight on sNfL concentrations was marginal. Samples from 220 children with neurological conditions (134 [60·9%] girls and 86 [39·1%] boys; median age 14·7 years [IQR 10·8-16·5]) were used to validate the clinical utility of the reference Z scores. In this population, age-adjusted sNfL Z scores were higher than in the reference population of healthy children and adolescents (p<0·0001) with higher effect size metrics (Cohen's d=1·56) compared with the application of raw sNfL concentrations (d=1·28). The established normative sNfL values in children and adolescents provide a foundation for the clinical application of sNfL in the paediatric population. Compared with absolute sNfL values, the use of sNfL Z score was associated with higher effect size metrics and allowed for more accurate estimation of the extent of ongoing neuroaxonal damage in individual patients. Swiss National Science Foundation, US National Institutes of Health, and the National Multiple Sclerosis Society.