The role of exosomes in adult neurogenesis:implications for neurodegenerative diseases

Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exosomes exert biological function by transporting factors between different cells and by regulating biological pathways in recipient cells.As an important form of intercellular communication,exosomes are increasingly being investigated due to their ability to transfer bioactive molecules such as lipids,proteins,mRNAs,and microRNAs between cells,and because they can regulate physiological and pathological processes in the central nervous system.Adult neurogenesis is a multistage process by which new neurons are generated and migrate to be integrated into existing neuronal circuits.In the adult brain,neurogenesis is mainly localized in two specialized niches:the subventricular zone adjacent to the lateral ventricles and the subgranular zone of the dentate gyrus.An increasing body of evidence indicates that adult neurogenesis is tightly controlled by environmental conditions with the niches.In recent studies,exosomes released from different sources of cells were shown to play an active role in regulating neurogenesis both in vitro and in vivo,thereby participating in the progression of neurodegenerative disorders in patients and in various disease models.Here,we provide a state-of-the-art synopsis of existing research that aimed to identify the diverse components of exosome cargoes and elucidate the therapeutic potential of exosomal contents in the regulation of neurogenesis in several neurodegenerative diseases.We emphasize that exosomal cargoes could serve as a potential biomarker to monitor functional neurogenesis in adults.In addition,exosomes can also be considered as a novel therapeutic approach to treat various neurodegenerative disorders by improving endogenous neurogenesis to mitigate neuronal loss in the central nervous system.

Regulator of G protein signaling 6 mediates exercise-induced recovery of hippocampal neurogenesis,learning,and memory in a mouse model of Alzheimer’s disease

Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s disease.However,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly understood.Recently,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in mice.Here,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse model.We found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control mice.This cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal neurogenesis.Adult hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor cells.RGS6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing neurons.Thus,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.

Relevance of Household Chemical Usage to Respiratory Diseases in Older Adults in China

Objective This study investigated the association between household chemical use and respiratory disease(RD)in older Chinese adults.Methods The data were from the 2018 China Longitudinal Health and Longevity Survey(CLHLS)database,which included 12,866 participants aged≥65 years.The prevalence of RD was based on self-reported medical history,and patients were divided into diseased and non-diseased groups.The frequency of household chemical usage was divided into four categories,and a total score for eight household chemical usage categories was constructed.Binary logistic regression was used to determine the relationship between the frequency of household chemical use and RD,and a restricted cubic spline was used to determine the dose-response association.Result After adjusting for all covariates,regular use of repellents[odds ratios(OR)=1.28,95%CI 1.06-1.55]and oil removers(OR=1.28,95%CI 1.03-1.58)were associated with RD.There was a dose-response association between the total score of household chemicals usage and RD risk(P non-linearity>0.05,P for trend<0.01).Using patients with the total score below 9 as a reference,the OR for patients with the total score ranging from 25 to 32 is 2.33(95%CI 1.25-4.09).Conclusion Regular use of repellents and oil removers increased the risk of RD,and the dose-dependent relationship was also observed.

Impact of Social Determinants of Health on Self-Perceived Resilience: An Exploratory Study of Two Cohorts of Adults with Congenital Heart Disease

Social determinants of health(SDOH)affect quality of life.We investigated SDOH impacts on self-perceived resilience among people with adult congenital heart disease(ACHD).Secondary analysis of data from two com-plementary studies:a survey study conducted May 2021–June 2022 and a qualitative study conducted June 2020–August 2021.Resilience was assessed through CD-RISC10 score(range 0–40,higher scores reflect greater self-perceived resilience)and interview responses.Sociodemographic and SDOH(education,employment,living situa-tion,monetary stability,financial dependency,area deprivation index)data were collected by healthcare record review and self-report.We used linear regression with robust standard errors to analyze survey data and performed a thematic analysis of interview data.Survey participants(N=127)mean age was 42±14 years;51%were female,87%white.ACHD was moderate(75%)or complex(25%);41%functional class C or D.Resilience(mean 30±7)varied by monetary stability:compared to people with difficulty paying bills,resilience was 15.0 points higher(95%CI:6.9–23.1,p<0.001)for people reporting having enough money and 14.2 points higher(95%CI:5.9–22.4,p=0.001)for those reporting just enough money.Interview participants’(N=25)mean age was 32 years(range 22–44);52%were female,72%white.ACHD was moderate(56%)or complex(44%);76%functional class C or D.Participants discussed factors affecting resilience aligned with each of the major SDOH,prominently,economic stability and healthcare access and quality.Financial stability may be important for supporting self-perceived resi-lience in ACHD.This knowledge can inform the development of resilience interventions for this population.

Loss to Specialized Cardiology Follow-Up in Adults Living with Congenital Heart Disease

Background:Much has been written about the loss to follow-up in the transition between pediatric and adult Congenital Heart Disease(CHD)care centers.Much less is understood about the loss to follow-up(LTF)after a successful transition.This is critical too,as patients lost to specialised care are more likely to experience mor-bidity and premature mortality.Aims:To understand the prevalence and reasons for loss to follow-up(LTF)at a large Australian Adult Congenital Heart Disease(ACHD)centre.Methods:Patients with moderate or highly complex CHD and gaps in care of>3 years(defined as LTF)were identified from a comprehensive ACHD data-base.Structured telephone interviews examined current care and barriers to clinic attendance.Results:Overall,407(22%)of ACHD patients(n=1842)were LTF.The mean age at LTF was 31(SD 11.5)years and 54%were male;311(76%)were uncontactable.Compared to adults seen regularly,lost patients were younger,with a greater socio-economic disadvantage,and had less complex CHD(p<0.05 for all).We interviewed 59 patients(14%).The top 3 responses for care absences were“feeling well”(61%),losing track of time(36%),and not needing fol-low-up care(25%).Conclusions:A large proportion of the ACHD population becomes lost to specialised cardiac care,even after a successful transition.This Australian study reports younger age,moderate complexity defects,and socio-economic disadvantage as predictive of loss to follow-up.This study highlights the need for novel approaches to patient-centered service delivery even beyond the age of transition and resources to maintain patient engagement within the ACHD service.

Adult minimal change disease:Clinicopathologic characteristics,treatment response and outcome at a single center in Pakistan

BACKGROUND Minimal change disease(MCD)is a significant cause of idiopathic nephrotic syndrome(INS)in adults,representing approximately 10%-15% of INS cases.The data is scanty on clinicopathological features,treatment responses,and long-term outcomes of MCD in adults.AIM To determine the clinicopathologic characteristics,treatment responses,and medium-term outcomes of adult patients with MCD in Pakistan.METHODS This retrospective cohort study included all adult patients with biopsy-proven MCD treated at the adult nephrology clinic,Sindh institute of urology and transplantation,between January 2010 and December 2020.The data was retrieved from the original renal biopsy request forms in the histopathology archives and the case files.Data on demographics,clinical presentation,laboratory findings,treatment regimens,and outcomes were collected and analyzed.Complete remission(CR),partial remission(PR),relapse,and steroid resistance were defined according to standard criteria.Statistical analyses were performed using statistical product and service solutions,Version 22.RESULTS The study cohort included 23 adults[15(65.2%males),mean age 26.34±10.28 years].Hypertension was found in 7(30.4%)and microscopic hematuria in 10(43.4%)of participants.Laboratory findings revealed a mean serum creatinine of 1.03±1.00 mg/dL,mean serum albumin of 1.94±0.90 g/dL and mean 24-hour urinary proteins of 4.53±2.43 g.The mean follow-up time was 38.09±22.3 months.Treatment with steroids was effective in 16/18(88.8%)of patients,with 10/16(62.5%)achieving CR and 6/16(37.5%)achieving PR.Two patients were resistant to steroids and required second-line immunosuppressive therapy.Relapse occurred in 4/20(19.04%)of patients,with a mean time to first relapse of 6.5±3.31 months.At the last follow-up,18/20(85.7%)of patients were in remission,and 16/20(76.1%)maintained normal renal function.No patients progressed to end-stage renal disease or died.CONCLUSION MCD in adults shows a favorable response to steroid therapy,with a majority achieving remission.However,relapses are common,necessitating second-line immunosuppressive treatments in some cases.The study highlights the need for standardized treatment guidelines for adult MCD to optimize outcomes.

Use of exclusive enteral nutrition in adults with Crohn's disease: A review

Exclusive enteral nutrition(EEN)is well-established as a first line therapy instead of corticosteroid(CS)therapy to treat active Crohn’s disease(CD)in children.It also has been shown to have benefits over and above induction of disease remission in paediatric populations.However,other than in Japanese populations,this intervention is not routinely utilised in adults.To investigate potential reasons for variation in response between adult studies of EEN and CS therapy.The Ovid database was searched over a 6-mo period.Articles directly comparing EEN and CS therapy in adults were included.Eleven articles were identified.EEN therapy remission rates varied considerably.Poor compliance with EEN therapy due to unpalatable formula was an issue in half of the studies.Remission rates of studies that only included patients with previously untreated/new CD were higher than studies including patients with both existing and new disease.There was limited evidence to determine if disease location,duration of disease or age of diagnosis affected EEN therapy outcomes.There is some evidence to support the use of EEN as a treatment option for a select group of adults,namely those motivated to adhere to an EEN regimen and possibly those newly diagnosed with CD.In addition,the use of more palatable formulas could improve treatment compliance.

Prediction of 10-year Atherosclerotic Cardiovascular Disease Risk among Adults Aged 40-79 Years in China:a Nationally Representative Survey

Objective To establish the distribution of 10-year atherosclerotic cardiovascular disease （ASCVD） risk among Chinese adults. Methods We estimated the 10-year ASCVD risk by applying the 2013 American College of Cardiology/ American Heart Association pooled cohort equations （PCEs） to the data obtained from the 2010 China Chronic Disease and Risk Factor Surveillance that involved 61,541 participants （representing 520,158,652 Chinese adults） aged 40-79 years. We also compared the ASCVD risk with the 10-year ischemic cardiovascular disease （ICVD） risk, which was calculated using the simplified scoring tables recommended by the Chinese Guidelines for Prevention of Cardiovascular Diseases （Chinese model）. Results Based on the PCEs, the average 10-year ASCVD risk among adults without self-reported stroke or myocardial infraction was 12.5%. Approximately 247 million （47.4%） and 107 million （20.6%） adults had 〉 7.5% and 〉 20% 10-year ASCVD risks, respectively. The 10-year ASCVD risk 〉 20% was higher among men, less educated individuals, smokers, drinkers, and physically inactive individuals than among their counterparts. Overall, 29.0% of adults categorized using the Chinese model were overclassified with the PCEs. Conclusion Our results define the distribution of 10-year ASCVD risk among Chinese adults. The 10-year ASCVD risk predicted by the PCEs was higher than the ICVD risk predicted by the Chinese model.

Primary prevention of cardiovascular disease in older adults in China

Over the past two decades, the percentage of Chinese who is 60 years or older has increased from 5.2% in 1995 to 10.5% in 2015. Approximately 16% of the population in China was 60 years old and above in 2015. Since 1990, cardiovascular disease(CVD) has been the leading cause of death in China. Cardiovascular medications of older adults are usually more complicated than younger age groups due to polypharmacy, the presence of comorbidities and more susceptible to treatmentrelated adverse outcomes. Therefore, effective primary prevention of CVD for older adults is important in sustaining the health of older adults and reducing the burden of the healthcare system. Proper management of CVD-related risk factors, such as hypertension, dyslipidemia, diabetes and obesity, can remarkably reduce risks of CVDs in older Chinese. These risk factors can be modified by managing blood pressure, glucose and lipids via lifestyle modifications or receiving medications. Smoking cessation, healthy diets, strict alcohol intake and moderate physical exercise are examples of recommended lifestyle changes for remarkably recovering health conditions of older adults who have hypertension, dyslipidemia, obesity, diabetes or complications. Treatment prescriptions of older adults, in general, are recommended to be individualized and to be initiated at a low dose. The future directions for better primary CVD prevention in older adults include establishing guidelines for primary prevention of CVD for different older adults and further research on better management strategies of CVD risks for elderly Chinese.

Effect of applying selenium fertilizer to improve soil and increase selenium level in food for prevention and treatment of Kaschin-Beck disease

For prevention and treatment of Kaschin-Beck disease by applying Se fertilizer to soil to increase Se up to normal level for the wheat grains is introduced in this paper. After use this measure the intake of Se by the residents in the exemplary area increased from 10.4μg to 33.6 μg per day in average. After supplementing Se to human body one year, there is no new patient found among 300 healthy children in the exemplary area but 4 patients found among 264 healthy children in the control area. It is shown that by applying Se fertilizer to KBD area is a effective way for preventing and cure this disease.

Out-of-hospital cardiac arrest in a young adult survivor with sequelae of childhood Kawasaki disease: A case report

BACKGROUND Kawasaki disease(KD)is an acute type of systemic vasculitis involving small to medium-sized muscular arteries and outbreaks during childhood.KD can cause myocardial ischemia,infarction,and sudden cardiac arrest.We present a case of a young adult survivor of out-of-hospital cardiac arrest as late KD sequelae.CASE SUMMARY A 29-year-old man with presumed acute KD history at the age of 5 suddenly lost consciousness while jogging and was diagnosed a sudden cardiac arrest by an emergency doctor.After about 10 min cardiopulmonary resuscitation,return of spontaneous circulation was achieved,and the patient was transferred to our hospital.A coronary computed tomography angiogram and coronary angiography revealed extensive calcifications of left anterior descending and right coronary artery aneurysms.The patient was an active individual who took exercise regularly and claimed no previous symptoms of chest pain or shortness of breath on exertion.The most possible cause of his sudden cardiac arrest could be presumed as a thrombus within the coronary artery aneurysms.After that,a thromboembolism induced extensive ischemia,and this ischemia-induced arrhythmia led to a cardiac arrest.CONCLUSION Few patients who suffer a late sequela of KD can survive from out-of-hospital cardiac arrest.Medications,surgical intervention,and active follow-up are extremely important for this patient to prevent occurrence of adverse events in the future.

Study on correlation between humic acid and selenium in Kaschin-Beck disease areas

The relationship between humic acid and selenium content was studied in this research. The results of calculation showed that there is more humic acid and less selenium in Kaschin-Beck disease areas in China. Fulvic acid in soil could increase selenium level in plants. The chemical bonding between humic acid and selenium was observed with an I.R. spectroscope. It was remarkable for the changes of absorption peak and frequency in 1100-1000 cm-1, 900-700 cm-1.

Clustering of Non-communicable Diseases Risk Factors in Healthy Adults Aged 35 Years and Older in Shenzhen,China

We assessed the prevalence of non‐ communicable diseases（NCDs） risk factors with a focus on their clustering among healthy adults in Shenzhen, China. Data from the 2011 China Health and Nutrition Survey, comprising a regionally representative sample of 806 healthy adults aged 35 years or older, were obtained to determine the prevalence of five risk factors for NCDs. The prevalence of current smoking, central obesity, impaired fasting glucose, borderline hypertension, and borderline high total cholesterol was 19.97%, 28.29%, 4.47%, 10.55%, and 36.10%, respectively. A total 63.77% of participants had at least one risk factor. Upon examination of risk factor clustering, we observed that 7.57% of participants had at least three risk factors. Using this threshold as a cutoff, clustering of risk factors was associated with sex [odds ratio（OR） = 3.336, 95% confidence interval（CI）： 1.782 to 6.246], physical activity（OR = 1.913, 95% CI： 1.009 to 3.628）, and BMI（OR = 7.376, 95% CI： 3.812 to 14.270）. The prevalence of risk factors for NCDs is fairly high among healthy adults in Shenzhen, with a clustering tendency.

Stable ischemic heart disease in the older adults

1 Introduction Ischemic heart disease is caused by atherosclerotic and/or thrombotic obstruction of coronary arteries. Clinical spec- trum of ischemic heart disease expands from asymptomatic atherosclerosis of coronary arteries to acute coronary syn- dromes （ACS） including unstable angina, acute myocardial infarction （non-ST elevation myocardial infarction and ST elevation myocardial infarction）. Stable ischemic heart dis- ease （SIHD） refers to patients with known or suspected SIHD who have no recent or acute changes in their symp- tomatic status, suggesting no active thrombotic process is underway.

Adult hippocampal neurogenesis and its impairment in Alzheimer's disease

Adult neurogenesis is the creation of new neurons which integrate into the existing neural circuit of the adult brain.Recent evidence suggests that adult hippocampal neurogenesis(AHN)persists throughout life in mammals,including humans.These newborn neurons have been implicated to have a crucial role in brain functions such as learning and memory.Importantly,studies have also found that hippocampal neurogenesis is impaired in neurodegenerative and neuropsychiatric diseases.Alzheimer’s disease(AD)is one of the most common forms of dementia affecting millions of people.Cognitive dysfunction is a common symptom of AD patients and progressive memory loss has been attributed to the degeneration of the hippocampus.Therefore,there has been growing interest in identifying how hippocampal neurogenesis is affected in AD.However,the link between cognitive decline and changes in hippocampal neurogenesis in AD is poorly understood.In this review,we summarized the recent literature on AHN and its impairments in AD.

Associations of Daytime Napping with Incident Cardiovascular Diseases and Hypertension in Chinese Adults:A Nationwide Cohort Study

Objective This study aimed to examine the associations of daytime napping with incident risks of cardiovascular diseases(CVDs)and hypertension(HTN).Methods Data for napping and CVD outcomes in 25 provinces were collected from baseline(2010)and three waves of follow-up(2012-2017)investigations of the China Family Panel Studies.Cox frailty models with random intercepts for the surveyed provinces were used to assess the longitudinal effects of daytime napping on CVD and HTN.Results Compared with non-nappers,30+min nappers had higher risks of CVD and HTN,while no significant associations were observed among<30 min nappers.Incident risks among 30-to<60-min nappers increased by 22%[hazard ratio(HR)1.22,95% confidence interval(CI)1.08-1.39]for CVD and 21%(1.21,1.04-1.41)for HTN,respectively,with corresponding HRs of CVD and HTN of 1.27(1.09-1.47)and 1.38(1.16-1.65)among≥60 min nappers.Nap-associated CVD risks varied by subgroups,with stronger associations in participants with lower body mass index(<24 kg/m^(2)),physically inactive persons,smokers,and participants with longer nighttime sleep(≥7 h/night).Significant effects of daytime napping were observed on rural and northern residents only,highlighting great regional variations in CVD risks associated with napping habits.Conclusions This cohort study revealed strong evidence that long daytime napping(≥30 min)is associated with an increased incidence of cardiovascular events.

Atrial tachyarrhythmia in adult congenital heart disease

The adult congenital heart disease (ACHD) population continues to grow and most cardiologists, emergency room physicians and family doctors will intermittently come into contact with these patients. Oftentimes this may be in the setting of a presentation with atrial tachyarrhythmia; one of the commonest late complications of ACHD and problem with potentially serious implications. Providing appropriate initial care and ongoing management of atrial tachyarrhythmia in ACHD patients requires a degree of specialist knowledge and an awareness of certain key issues. In ACHD, atrial tachyarrhythmia is usually related to the abnormal anatomy of the underlying heart defect and often occurs as a result of surgical scar or a consequence of residual hemodynamic or electrical disturbances. Arrhythmias significantly increase mortality and morbidity in ACHD and are the most frequent reason for ACHD hospitalization. Intra-atrial reentrant tachycardia and atrial fibrillation are the most prevalent type of arrhythmia in this patient group. In hemodynamically unstable patients, urgent cardioversion is required. Acute management of the stable patient includes anticoagulation, rate control, and electrical or pharmacological cardioversion. In ACHD, rhythm control is the preferred management strategy and can often be achieved. However, in the long-term, medication side-effects can prove problematic. Electrophysiology studies and catheter ablation are important treatments modalities and in certain cases, surgical or percutaneous treatment of the underlying cardiac defect has a role. ACHD patients, especially those with complex CHD, are at increased risk of thromboembolic events and anticoagulation is usually required. Female ACHD patients of child bearing age may wish to pursue pregnancies. The risk of atrial arrhythmias is increased during pregnancy and management of atrial tachyarrhythmia during pregnancy needs specific consideration.

Transition of pediatric to adult care in inflammatory bowel disease: Is it as easy as 1, 2, 3?

Inflammatory bowel disease(IBD)is a heterogeneous group of chronic diseases with a rising prevalence in the pediatric population,and up to 25%of IBD patients are diagnosed before 18 years of age.Adolescents with IBD tend to have more severe and extensive disease and eventually require graduation from pediatric care toadult services.The transition of patients from pediatric to adult gastroenterologists requires careful preparation and coordination,with involvement of all key players to ensure proper collaboration of care and avoid interruption in care.This can be challenging and associated with gaps in delivery of care.The pediatric and adult health paradigms have inherent differences between health care models,as well as health care priorities in IBD.The readiness of the young adult also influences this transition of care,with often times other overlaps in life events,such as school,financial independence and moving away from home.These patients are therefore at higher risk for poorer clinical disease outcomes.The aim of this paper is to review concepts pertinent to transition of care of young adults with IBD to adult care,and provides resources appropriate for an IBD pediatric to adult transition of care model.

Crohn's disease in adults: Observations in a multiracial Asian population

AIM： To determine the demography and clinical presentation of CD and secondly to determine any differences in the prevalence between the different ethnic groups in a multiracial Asian population. METHODS： Patients with CD who were seen in 2001- 2003 in the University of Malaya Medical Centre （UMMC） were enrolled in this study. Prevalence of disease was calculated for the group as a whole and by race with hospital admissions per ethnic group as the denominator. RESULTS： Thirty-four patients were diagnosed to have CD. Basic demographic data of patients; male：female 17：17; mean age 29.1 years （±13.5 years）; ethnic group： Malays 5 （14.7%）, Chinese 12 （35.3%） and Indians 17 （50%）. Twenty-six （76.5%） were diagnosed under the age of 40 and 8 （23.5%） were diagnosed over the age of 40. Location of the disease was as follows： ileocolonic 13 （38.2%）, terminal ileum only 9 （26.5%）, colon only 8 （23.5%）, and upper gastrointestinal 4 （11.8%）. Sixteen （47.1%） had penetrating disease, 9 （26.5%） had stricturing disease and 9 （26.5%） had nonpenetrating and non-stricturing disease. The hospital admission prevalence of CD was 26.0 overall, Indians 52.6, Chinese 6.9, and Malays 9.3 per 10^5 admissions per ethnic group. The difference between Indians and Malays： [OR 5.67 （1.97, 17.53）P〈 0.001] was statistically significant but not between the Indians and the Chinese [OR 1.95 （0.89, 4.35） P= 0.700]. The difference between the Chinese and the Malays was also not statistically significant. [OR 2.90 （0.95, 9.42）P= 0.063]. CONCLUSION： The clinical presentation of CD is similar to the Western experience. Although the overall prevalence is low, there appears to be a clear racial predominance among the Indians.

Perturbations in Amino Acid Metabolism in Children with Kaschin-Beck Disease: A Study of Urinary Target Metabolomics

Kaschin-Beck disease (KBD) is an endemic and chronic osteoarthropathy characterized by pathological aspects including chondrocyte degeneration, necrosis, progressive loss of articular cartilage, and secondary degenerative osteoarthrosis of epiphyseal cartilage, epiphyseal plate cartilage, and articular cartilage, during puberty[1]. The main clinical symptoms are limb joint pain, thickening, deformation, limited movement, muscle atrophy, and in case of more severely affected patients, short fingers (toes), short limbs, and even short stature[1].