Objective: To determine the effects of an integrated training device for strength and balance on extremity muscle strength, postural balance, and cognition in older adults using a combination with various rehabilitation training games, in which balance, strength, and cognitive training were configured in a single device. Methods: This prospective study included 20 healthy participants aged 65–85 years. Participants trained for 30 minutes daily, 3 days weekly, for 6 weeks with an integrated training device for strength and balance (SBT-120; Man&Tel Inc., Gumi, Korea). Main outcomes were measured using the Korean Mini-Mental State Examination (K-MMSE), Korean version of the Montreal Cognitive Assessment (K-MoCA), Timed Up and Go Test (TUG), Functional Reach Test (FRT), Berg Balance Scale (BBS), and Manual Muscle Test. Measurements were taken at three time points: T0 (pretreatment), T1 (immediately after treatment), and T2 (4 weeks after treatment). Results: All 20 patients completed the training, and TUG, FRT, and BBS scores significantly improved at T1 and T2 compared to T0. Mean TUG scores decreased by 0.99±2.00 at T1 and 1.05±1.55 at T2 compared to T0. Mean FRT scores increased by 6.13±4.26 at T1 and 6.75±4.79 at T2 compared to T0. BBS scores increased by 0.60±0.94 at T1 and 0.45±1.15 at T2 compared to T0. Moreover, muscle strength and cognition (K-MMSE and K-MoCA scores) increased after training. Conclusion Our findings suggest that an integrated training device for strength and balance can be a safe and useful tool for older adults.

Objective: To determine the effects of an integrated training device for strength and balance on extremity muscle strength, postural balance, and cognition in older adults using a combination with various rehabilitation training games, in which balance, strength, and cognitive training were configured in a single device. Methods: This prospective study included 20 healthy participants aged 65–85 years. Participants trained for 30 minutes daily, 3 days weekly, for 6 weeks with an integrated training device for strength and balance (SBT-120; Man&Tel Inc., Gumi, Korea). Main outcomes were measured using the Korean Mini-Mental State Examination (K-MMSE), Korean version of the Montreal Cognitive Assessment (K-MoCA), Timed Up and Go Test (TUG), Functional Reach Test (FRT), Berg Balance Scale (BBS), and Manual Muscle Test. Measurements were taken at three time points: T0 (pretreatment), T1 (immediately after treatment), and T2 (4 weeks after treatment). Results: All 20 patients completed the training, and TUG, FRT, and BBS scores significantly improved at T1 and T2 compared to T0. Mean TUG scores decreased by 0.99±2.00 at T1 and 1.05±1.55 at T2 compared to T0. Mean FRT scores increased by 6.13±4.26 at T1 and 6.75±4.79 at T2 compared to T0. BBS scores increased by 0.60±0.94 at T1 and 0.45±1.15 at T2 compared to T0. Moreover, muscle strength and cognition (K-MMSE and K-MoCA scores) increased after training. Conclusion Our findings suggest that an integrated training device for strength and balance can be a safe and useful tool for older adults.

Background: Silver-Russell syndrome (SRS) is a pre- or post-natal growth retardation disorder caused by (epi)genetic alterations. We evaluated the molecular basis and clinical value of sequential epigenetic analysis in pediatric patients with SRS. Methods: Twenty-eight patients who met ≥ 3 Netchine-Harbison clinical scoring system (NH-CSS) criteria for SRS were enrolled;26 (92.9%) were born small for gestational age, and 25 (89.3%) showed postnatal growth failure. Relative macrocephaly, body asymmetry, and feeding difficulty were noted in 18 (64.3%), 13 (46.4%), and 9 (32.1%) patients, respectively. Methylation-specific multiplex ligation-dependent probe amplification (MSMLPA) on chromosome 11p15 was performed as the first diagnostic step. Subsequently, bisulfite pyrosequencing (BP) for imprinting center 1 and 2 (IC1 and IC2) at chromosome 11p15, MEST on chromosome 7q32.2, and MEG3 on chromosome 14q32.2 was performed. Results: . Seventeen (60.7%) patients exhibited methylation defects, including loss of IC1 methylation (N = 14; 11 detected by MS-MLPA and three detected by BP) and maternal uniparental disomy 7 (N = 3). The diagnostic yield was comparable between patients who met three or four of the NH-CSS criteria (53.8% vs 50.0%). Patients with methylation defects responded better to growth hormone treatment. Conclusions NH-CSS is a powerful tool for SRS screening. However, in practice, genetic analysis should be considered even in patients with a low NH-CSS score. BP analysis detected additional methylation defects that were missed by MS-MLPA and might be considered as a first-line diagnostic tool for SRS.

Purpose: Factors associated with invasive recurrence (REC) of ductal carcinoma in situ (DCIS) are less known. This study was aimed at identifying better biomarkers to predict the prognosis of DCIS. Methods: RNA extracted from formalin-fixed paraffin-embedded blocks of twenty-four pure DCIS cases was subjected to differential gene expression analysis. The DCIS cases were selected by matching age and estrogen receptor status. Sixteen REC-free and 8 invasive-REC cases with disease-free interval of > 5 years were analyzed. Immunohistochemistry (IHC) staining was used to validate sixty-one independent pure DCIS cases, including invasive-REC (n = 16) and REC-free (n = 45) cases. Results: Eight differentially expressed genes (DEGs) were statistically significant (log 2-fold change [FC] < –1 or > 1 and p < 0.001). Less than ½ fold expression of CUL1, androgen receptor (AR), RPS27A, CTNNB1, MAP3K1, PRKACA, GNG12, MGMT genes was observed in the REC group compared to the no evidence of disease group. AR and histone deacetylase 1 (HDAC1) genes were selected for external validation (AR: log 2-FC − 1.35, p < 0.001, and HDAC1: log 2-FC − 0.774, p < 0.001). External validation showed that the absence of AR and high HDAC1 expression were independent risk factors for invasive REC (hazard ratio [HR], 5.04; 95% confidence interval [CI], 1.24–20.4; p = 0.023 and HR, 3.07; 95% CI, 1.04–9.04; p = 0.042). High nuclear grade 3 was also associated with long-term invasive REC. Conclusion Comparative gene expression analysis of pure DCIS revealed 8 DEGs among recurring cases. External validation with IHC suggested that the absence of AR and overexpression of HDAC1 are associated with a greater risk of long-term invasive REC of pure DCIS.

Androgen insensitivity syndrome (AIS) is a rare genetic disease caused by various abnormalities in the androgen receptor (AR). The AR is an essential steroid hormone receptor that plays a critical role in male sexual differentiation and development and preservation of the male phenotype. Mutations in the AR gene on the X chromosome cause malfunction of the AR so that a 46,XY karyotype male has some physical characteristics of a woman or a full female phenotype. Depending on the phenotype, AIS can be classified as complete, partial or mild. Here, we report 2 cases of complete AIS in young children who showed complete sex reversal from male to female as a result of AR mutations. They had palpable inguinal masses and normal female external genitalia, a blind-end vagina and absent Müllerian duct derivatives. They were both 46,XY karyotype and AR gene analysis demonstrated pathologic mutations in both. Because AIS is inherited in an X-linked recessive manner, we performed genetic analysis of the female family members of each patient and found the same mutation in the mothers of both patients and in the female sibling of case 2. Gonadectomy was performed in both patients to avoid the risk of malignancy in the undescended testicles, and estrogen replacement therapy is planned for their adolescence. Individuals with complete AIS are usually raised as females and need appropriate care.
Adolescent ; Androgen-Insensitivity Syndrome* ; Child ; Disorders of Sex Development ; Estrogen Replacement Therapy ; Female* ; Genitalia ; Humans ; Karyotype ; Male ; Mothers ; Phenotype ; Receptors, Androgen ; Sex Differentiation ; Siblings ; Testis ; Vagina ; X Chromosome

PURPOSE: Hypothalamic obesity in childhood-onset (CO-) craniopharyngioma patients may predispose to nonalcoholic fatty liver disease (NAFLD). This study reviewed the characteristics of NAFLD associated with CO-craniopharyngioma. METHODS: This study retrospectively reviewed 75 patients who underwent surgery for craniopharyngioma while younger than 15 years of age between 2000 and 2016. RESULTS: Elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) above 40 IU/L was observed in 51 of the 75 (68%) CO-craniopharyngioma patients. Imaging studies were performed in 32 patients with elevated liver enzymes. The estimated prevalence of NAFLD in CO-craniopharyngioma was 47%. NAFLD was detected in 22 patients (male 59%, 4.3±4.0 years after first surgery). The mean age at the time of the initial operation was 9.1±2.9 years. Six patients (27.3%) were diagnosed within 1 year. Among the 19 patients with initial height and weight data, the body mass index (BMI) z-score (BMI_Z) at the time of diagnosis with NAFLD was 1.37±1.01 (range, -0.75 to 3.18), with 4 patients (18.2%) being overweight and 9 (40.9%) being obese. BMI_Z increased above BMI_Z at the time of the operation in 13 patients (68.4%). The increment in BMI_Z was 1.13 (range, 0.10–2.84). Seventeen patients did not receive growth hormone. An insulin-like growth factor-I level < 3rd percentile was observed in 19 patients. CONCLUSION: NAFLD is common in survivors of CO-craniopharyngioma and may develop earlier. If the ALT or AST is above 40 IU/L, a diagnostic work-up should be started.
Alanine Transaminase ; Aspartate Aminotransferases ; Body Mass Index ; Craniopharyngioma* ; Diagnosis ; Growth Hormone ; Humans ; Hypothalamus ; Liver ; Non-alcoholic Fatty Liver Disease* ; Obesity ; Overweight ; Prevalence ; Retrospective Studies ; Survivors*

Antley-Bixler syndrome (ABS) is a rare form of syndromic craniosynostosis with additional systemic synostosis, including radiohumeral or radioulnar synostosis. Another characteristic feature of ABS is mid-facial hypoplasia that leads to airway narrowing after birth. ABS is associated with mutations in the FGFR2 and POR genes. Patients with POR mutations present with either skeletal manifestations or congenital adrenal hyperplasia with ambiguous genitalia. We report here two cases of ABS caused by mutations in FGFR2 and POR. Although the patients had craniosynostosis and radiohumeral synostosis in common and cranioplasty was performed in both cases, the male with POR mutations showed an elevated level of 17α-hydroxyprogesterone during newborn screening and was diagnosed with congenital adrenal hyperplasia by adrenocorticotropic hormone stimulation. This patient has been treated with hydrocortisone and fludrocortisone. He had no ambiguous genitalia but had bilateral cryptorchidism. On the other hand, the female with the FGFR2 mutation showed severe clinical manifestations: upper airway narrowing leading to tracheostomy, kyphosis of the cervical spine, and coccyx deformity. ABS shows locus heterogeneity, and mutations in two different genes can cause similar craniofacial and skeletal phenotypes. Because the long-term outcomes and inheritance patterns of the disease differ markedly, depending on the causative mutation, early molecular genetic testing is helpful.
Adrenal Hyperplasia, Congenital ; Adrenocorticotropic Hormone ; Antley-Bixler Syndrome Phenotype* ; Coccyx ; Congenital Abnormalities ; Craniosynostoses ; Cryptorchidism ; Disorders of Sex Development ; Female ; Fludrocortisone ; Hand ; Humans ; Hydrocortisone ; Infant, Newborn ; Inheritance Patterns ; Kyphosis ; Male ; Mass Screening ; Molecular Biology ; Parturition ; Phenotype ; Population Characteristics ; Spine ; Synostosis ; Tracheostomy

The 46,XX testicular disorder of sex development (DSD), also known as 46,XX male syndrome, is a rare form of DSD and clinical phenotype shows complete sex reversal from female to male. The sex-determining region Y (SRY) gene can be identified in most 46,XX testicular DSD patients; however, approximately 20% of patients with 46,XX testicular DSD are SRY-negative. The SRY-box 9 (SOX9) gene has several important functions during testis development and differentiation in males, and overexpression of SOX9 leads to the male development of 46,XX gonads in the absence of SRY. In addition, SOX9 duplication has been found to be a rare cause of 46,XX testicular DSD in humans. Here, we report a 4.2-year-old SRY-negative 46,XX boy with complete sex reversal caused by SOX9 duplication for the first time in Korea. He showed normal external and internal male genitalia except for small testes. Fluorescence in situ hybridization and polymerase chain reaction (PCR) analyses failed to detect the presence of SRY, and SOX9 intragenic mutation was not identified by direct sequencing analysis. Therefore, we performed real-time PCR analyses with specific primer pairs, and duplication of the SOX9 gene was revealed. Although SRY-negative 46,XX testicular DSD is a rare condition, an effort to make an accurate diagnosis is important for the provision of proper genetic counseling and for guiding patients in their long-term management.
46, XX Testicular Disorders of Sex Development ; Diagnosis ; Disorders of Sex Development ; Female ; Fluorescence ; Genes, sry ; Genetic Counseling ; Genitalia, Male ; Gonads ; Humans ; In Situ Hybridization ; Korea ; Male ; Phenotype ; Polymerase Chain Reaction ; Real-Time Polymerase Chain Reaction ; Sexual Development* ; Testis

Maple syrup urine disease (MSUD) is a disorder that involves the metabolism of branched chain amino acids, arising from a defect in branched-chain alpha-keto acid dehydrogenase complex. Mutations have been identified in the BCKDHA, BCKDHB, or DBT genes, which encode different subunits of the BCKDH complex. Although encephalopathy and progressive neurodegeneration are its major manifestations, the severity of the disease may range from the severe classic type to milder intermediate variants. We report two Korean siblings with the milder intermediate MSUD who were diagnosed with MSUD by a combination of newborn screening tests using tandem mass spectrometry and family genetic screening for MSUD. At diagnosis, the patients' plasma levels were elevated for leucine, isoleucine, valine, and alloisoleucine, and branched-chain alpha-keto acids and branched-chain alpha-hydroxy acids were detected in their urine. BCKDHA, BCKDHB, and DBT analysis was performed, and two novel mutations were identified in BCKDHB. Our patients were thought to have the milder intermediate variant of MSUD, rather than the classic form. Although MSUD is a typical metabolic disease with poor prognosis, better outcomes can be expected if early diagnosis and prompt management are provided, particularly for milder forms of the disease.
3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) ; Amino Acids ; Diagnosis ; Early Diagnosis ; Genetic Testing ; Humans ; Infant, Newborn ; Isoleucine ; Leucine ; Maple Syrup Urine Disease* ; Mass Screening ; Metabolic Diseases ; Metabolism ; Plasma ; Prognosis ; Siblings* ; Tandem Mass Spectrometry ; Valine

PURPOSE: The aim of the present study was to evaluate the effects of low-dose tamsulosin on sexual function in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 138 male LUTS patients aged more than 50 years with an International Prostate Symptom Score (IPSS) > or =8 were enrolled in this open-label, multicenter, prospective, noncomparative observational study. Clinical assessments included IPSS, quality of life (QoL) index, International Index of Erectile Function (IIEF), Danish Prostate Symptom Score (DAN-PSS), and an early morning erection questionnaire. The data were recorded at baseline and at 1 and 3 months after treatment with tamsulosin 0.2 mg/d. Adverse events were analyzed in all patients. RESULTS: During the study period of 3 months, the IPSS and QoL index significantly improved from baseline by -11.40+/-9.40 and -1.11+/-1.36, respectively (p<0.001). However, there were no clinically relevant changes in total IIEF score (mean difference, 1.63+/-15.50; p=0.406) or the 5 subdomains (p>0.05). Furthermore, DAN-PSS weighted scores (AxB) showed no clinically relevant changes (mean difference on Q1, Q2, and Q3: -0.45+/-2.94, 0.27+/-2.50, and -1.27+/-2.27, p>0.05). In addition, there were no clinically significant changes in responses on the early morning erection questionnaire. CONCLUSIONS: Tamsulosin at the dose of 0.2 mg significantly improved the IPSS and the QoL index compared with baseline. However, tamsulosin did not exhibit any significant impact on sexual function or any negative impact on ejaculatory function.
Aged ; Ejaculation ; Erectile Dysfunction ; Humans ; Lower Urinary Tract Symptoms ; Male ; Prospective Studies ; Prostate ; Prostatic Hyperplasia ; Quality of Life ; Sulfonamides