OBJECTIVE: To summarize the clinical features and management of two brothers affected with X-linked inhibitor of apoptosis protein (XIAP) deficiency. METHODS: This study retrospectively analyzed the clinical presentations, treatment, and follow-up of two brothers with XIAP deficiency diagnosed at Shanghai Children's Hospital in 2020, and summarized similar cases recorded in databases such as PubMed, Wanfang, Chinese Medical Association Journals, and WIP from January 2006 to November 2024. This study was approved by the Medical Ethics Committee of our hospital (Ethics No.: 2025R128-E01). RESULTS: Patient 1 was the younger brother, who presented at 8 years of age with growth retardation, folliculitis, erythema nodosum, and perineal abscess. Sequencing revealed that he has carried a hemizygous c.566T>C (p.Leu189Pro) variant of the XIAP gene, which was inherited from his mother. He was allergic to infliximab treatment and underwent allogeneic stem cell transplantation (HSCT) in January 2021. During a follow-up of 3 years and 10 months post-transplantation, he showed no gastrointestinal symptoms and had a good outcome. Patient 2 was the elder brother, who presented at 10 years and 6 months of age with growth retardation, rash, and anal fistula. Genetic testing revealed the same variant. He was treated with oral azathioprine but did not have regular follow-ups. At 14-years-and-6-months of age, he had developed severe gastrointestinal infection and hemophagocytic lymphohistiocytosis, which was alleviated after treatment with antibiotics, glucocorticoids, immunoglobulin, and rituximab. He is currently being prepared for HSCT. A total of 13 publications were retrieved, which involved 64 patients from 23 families, with 23 different variants identified. The main clinical manifestations included splenomegaly (34 cases, 53.1%), hemophagocytic lymphohistiocytosis (27 cases, 42.2%), and inflammatory bowel disease or colitis (20 cases, 31.8%). There were significant phenotypic differences among patients from the same family. Thirteen patients (20.3%) underwent HSCT, with a survival rate of 61.5%. CONCLUSION For male children with early onset, poor treatment response, especially those with unexplained splenomegaly and IBD-like symptoms, early genetic testing is recommended. HSCT is a safe and effective treatment for XIAP deficiency. For patients with developmental delay, early onset, and severe IBD phenotype, early transplantation is recommended.
Humans ; Male ; X-Linked Inhibitor of Apoptosis Protein/deficiency* ; Child ; Genetic Diseases, X-Linked/therapy* ; Phenotype ; Siblings ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation

BACKGROUND AND OBJECTIVE

The Oswestry Disability Index (ODI)–English is a valid and reliable instrument for disability measurement in low back pain (LBP) patients. There is no existing ODI–Ilokano that evaluates LBP patients. This study aimed to cross-culturally adapt the ODI–English into Ilokano.

The ODI–English was cross-culturally adapted into Ilokano through a process that included forward translation, synthesis of the translations, back translation, expert committee review, and testing of the pre-final version.

Forward translation focused on capturing the essence of terms related to pain intensity, personal care, and daily activities, achieving consensus on phrases that accurately mirrored the original English meanings. Subsequent synthesis refined these translations, emphasizing idiomatic and conceptual equivalence over literal interpretations, particularly in nuanced areas like sleep disturbance and social life activities. Backward translation processes aligned Ilokano and English terms, especially for pain intensity and personal care, ensuring consistency across languages. The expert committee review addressed spelling, word choice, and sentence structure, making strategic adjustments for cultural relevance. Pilot testing with participants from Ilocos Norte and Ilocos Sur, Philippines highlighted comprehension challenges with specific terms, leading to adaptations like replacing 'milya' and 'yarda' with metric units and retaining culturally sensitive terms with supplementary English explanations.

This study refined the ODI–English into a culturally adapted Ilokano version, focusing on semantic, idiomatic, and cultural equivalence. Incorporating pilot testing feedback, such as modifying measurement units and addressing sensitive terms, highlighted the thorough adaptation process. The collaborative translation efforts and diverse patient input ensured a culturally resonant ODI version for Ilokano speakers. This adaptation enhances physical therapy practices by improving patient assessments and advocates for adapting patient-reported outcomes to diverse cultures, advancing patient-centered care.

BACKGROUND

Type 2 diabetes is the most common type of diabetes in the Philippines. Diabetic foot complications represent a prevalent and significant chronic concern for individuals with type 2 diabetes. This poses an immediate community health concern, as diabetic complications may threaten an individual's well-being.

This study intends to cross-culturally adapt the Diabetic Foot Knowledge Subscale (DFKS) and Foot Self-Care Behavior Scale (FSCBS) questionnaires into the Filipino language as an assessment tool among Filipinos with diabetes.

The study employed a psychometric research design, where it entailed Phase A and Phase B. Phase A involved the forward translation of the DFKS and FSCBS questionnaires, followed by the synthesis of the translations and backward translation. Subsequently, an expert committee reviewed the translations and concluded the final version. The final translated versions of the questionnaires ensured that it can be understood by an individual who has a Grade 6 level of reading proficiency. Phase B entailed the validity testing with the evaluation of the expert committee, and reliability testing of the said questionnaires with a sample size of 30 participants. A wash-out period of 24 hours was given for the test-retest reliability, followed by data analysis. The validity and reliability of the questionnaires were measured using the item and scale content validity indices and the internal consistency and test-retest reliability, respectively, to ensure their accuracy and appropriateness. The content validity of the questionnaires was evaluated individually by the experts using a Likert scale from 1-4, with 4 being the highest meaning the item was very relevant and succinct. Scores per item were between 3 and 4, which indicate that the translated version of the items were relevant and succinct or were relevant but needed minor revisions.

The validity scores for the translated DFKS and FSCBS questionnaires were obtained using the Scale Content Validity Index (S-CVI) with a score of 0.96 and 0.92, respectively. Moreover, all items in the questionnaires obtained an Item Content Validity Index (I-CVI) of 0.88-1.00. The DFKS also has an acceptable internal consistency with a Cronbach’s alpha of 0.72, while the FSCBS has a good internal consistency with a Cronbach’s alpha of 0.85. The test-retest reliability shows an acceptable Spearman’s correlation at 0.76 for the DFKS and a strong positive Pearson correlation coefficient at 0.73 for the FSCBS.

The validity of the two questionnaires was acceptable and the test-retest reliability showed a strong positive correlation among the items thereby making the cross-cultural adaptation of the questionnaires successful. The Filipino versions of the DFKS and FSCBS questionnaires accurately measure the knowledge and behavior of individuals with type 2 diabetes, respectively.

OBJECTIVE: Observational studies have shown inconsistent associations of loneliness or social isolation (SI) with ischemic heart disease (IHD), with unknown mediators. METHODS: Using data from genome-wide association studies of predominantly European ancestry, we performed a bidirectional two-sample Mendelian Randomization (MR) study to estimate causal effects of loneliness ( N = 487,647) and SI traits on IHD ( N = 184,305). SI traits included whether individuals lived alone, participated in various types of social activities, and how often they had contact with friends or family ( N = 459,830 to 461,369). A network MR study was conducted to evaluate the mediating roles of 20 candidate mediators, including metabolic, behavioral and psychological factors. RESULTS: Loneliness increased IHD risk ( OR= 2.129; 95% confidence interval [ CI]: 1.380 to 3.285), mediated by body fat percentage, waist-hip ratio, total cholesterol, and low-density lipoprotein cholesterol. For SI traits, only fewer social activities increased IHD risk ( OR= 1.815; 95% CI: 1.189 to 2.772), mediated by hypertension, high-density lipoprotein cholesterol, triglycerides, fasting insulin, and smoking cessation. No reverse causality of IHD with loneliness and SI was found. CONCLUSION These findings suggested more attention should be paid to individuals who feel lonely and have fewer social activities to prevent IHD, with several mediators as prioritized targets for intervention.
Loneliness/psychology* ; Humans ; Mendelian Randomization Analysis ; Social Isolation ; Myocardial Ischemia/etiology* ; Male ; Female ; Middle Aged ; Genome-Wide Association Study ; Risk Factors ; Aged

Case 1 was a 7-year-old girl; Case 2 was her 3-year-old younger brother. Both children developed pink urine shortly after birth and exhibited blistering on photo-exposed areas (face and hands), followed by ulceration, crusting, scarring, and joint contractures leading to impaired mobility. Genetic testing in both patients identified a homozygous variant in the UROS gene, c.776T>C (p.Leu259Pro), confirming autosomal recessive congenital erythropoietic porphyria due to UROS mutations. This case report highlights that congenital erythropoietic porphyria should be considered in infants and young children with unexplained hemolytic anemia, pink urine, and severe photosensitive dermatitis. Early genetic testing is recommended to facilitate timely intervention and improve outcomes.
Humans ; Porphyria, Erythropoietic/genetics* ; Female ; Child ; Child, Preschool ; Male ; Siblings ; Mutation ; Uroporphyrinogen III Synthetase/genetics*

BACKGROUND: Studies have shown that married couples often share similar lifestyles, as well as lifestyle-associated conditions such as diabetes, hypertension, and hyperlipidemia. This study aims to prospectively investigate the association between an individual's development of a non-communicable disease and the subsequent development of the same condition in their spouse. METHODS: This population-based cohort study utilized 12 waves of annual prospective surveys from 2005 onwards in Japan, with a discrete-time design. A total of 9,417 middle-aged couples (18,834 participants; discrete-time observations = 118,876) were included. Each participant whose spouse had developed one of six conditions was propensity score-matched with five controls whose spouses had not been diagnosed with the condition: diabetes [n = 1374 vs n = 6870], hypertension [n = 2657 vs n = 13285], hypercholesterolemia [n = 3321 vs n = 16605], stroke [n = 567 vs n = 2835], coronary heart disease (CHD) [n = 1093 vs n = 5465] or cancer [n = 923 vs n = 4615]. Using conditional logistic regression, we assessed participants' development of the same condition within three years following their spouse's diagnosis. RESULTS: Participants whose spouses had developed diabetes, hypertension, hypercholesterolemia, or CHD were more likely to develop the same condition within three years. The odds ratios (ORs) and 95% confidence intervals (CIs) were: 1.96 (1.53-2.50), 1.20 (1.06-1.36), 1.63 (1.47-1.81) and 1.43 (1.05-1.95), respectively. No significant associations were observed in stroke [1.69 (0.80-3.58)] or cancer [1.08 (0.75-1.54)]. CONCLUSION Spouses of individuals recently diagnosed with certain metabolic conditions are at a higher risk of developing those conditions themselves. These findings may provide valuable guidance for targeting and personalizing chronic disease screening and prevention efforts.
Humans ; Spouses/statistics & numerical data* ; Male ; Female ; Middle Aged ; Aged ; Japan/epidemiology* ; Longitudinal Studies ; Noncommunicable Diseases/epidemiology* ; Prospective Studies ; Neoplasms/epidemiology* ; Diabetes Mellitus/epidemiology* ; Risk Factors ; Aged, 80 and over ; Adult ; Hypertension/epidemiology*

Although salt-related behaviors may influence urinary salt excretion in early childhood, this relationship remains unclear. This study aimed to examine salt-related behaviors using data from a salt check sheet and urinary salt excretion parameters using spot urine samples from 4-year-old children. This cross-sectional study included all 4-year-old children who underwent health checkups in Ohnan Town, Shimane Prefecture. The study sample consisted of 109 children (49 boys). Measures from spot urine samples included estimated salt excretion (g/day) and the sodium-potassium (Na/K) ratio. Salt-related behaviors were assessed using a salt check sheet that was completed by the parents or guardians. The associations between salt-related behaviors and urinary salt excretion parameters were analyzed using a generalized linear model. The median (M) and interquartile range (IQR) for urinary measures in 4-year-old children were as follows: estimated salt excretion (M = 4.4, IQR: 3.3-6.2) and Na/K ratio (M = 2.3, IQR: 1.4-3.3). The low frequency of consumption of high-salt foods ("such as pickles, pickled plums, etc." and "noodles such as udon and ramen") was associated with low salt excretion and low Na/K ratio. However, in the case of "consumption of udon, ramen, or other soups", the Na/K ratio was higher for "About half a bowl" and "Some" than for "An entire bowl." Additionally, for "eating out or having convenience-store-bought bento (lunch plate) for lunch", the Na/K ratio was higher for "No" than for "Almost every day." In conclusion, the frequency of high-sodium food intake was associated with both urinary sodium excretion and the Na/K ratio in 4-year-old children. Longitudinal investigations using the 24-hour urine collection method are needed to confirm these salt-related behaviors.
Humans ; Child, Preschool ; Male ; Cross-Sectional Studies ; Female ; Sodium Chloride, Dietary/urine* ; Parents ; Sodium/urine* ; Japan ; Potassium/urine*

BACKGROUND: Growing up with a sibling with a chronic health problem or a disability requiring assistance can affect the lives of the family members in various ways. Previous studies documented health problems among siblings of children with a chronic health problem or a disability. However, these studies are limited in that they tend to rely on small convenience samples of children with specific illnesses/disabilities. This study aims to investigate mental health and self-rated health status of siblings of such children using data from a population study in Japan. METHODS: We used data from the 2016 wave of Japan's Comprehensive Survey of Living Conditions. The analytic sample included 16,510 adolescents aged 15-19 years who were living with a sibling with or without care needs. The outcomes were psychological distress as defined by K6 score of 13 or higher and poor self-rated health. We examined these health outcomes of adolescents who have a sibling with care needs to relative to adolescents with a sibling without such needs via logistic regression. RESULTS: Adolescents who live with a sibling with care needs were more likely to have psychological distress (Odds Ratio (OR) 2.47; 95% Confidence Interval (CI), 1.46-4.17) and poor self-rated health (OR 2.21; 95% CI, 1.30-3.75). These associations were more pronounced in post-high school age (18-19 years old) group than in high school age (15-18 years old) group. CONCLUSION The presence of a child with care needs in the household was associated with spillover psychological distress and poorer subjective health among siblings. Providing support for children/adolescents with care needs may have additional benefits in terms of well-being of their siblings.
Humans ; Adolescent ; Male ; Female ; Siblings/psychology* ; Young Adult ; Psychological Distress ; Japan/epidemiology* ; Health Status

Objective:To compare the outcomes of multiple scales, primarily the speech, spatial, and other qualities of hearing scale for parents（SSQ-P）, in children with ipsilateral vs. Contralateral cochleareimplantat ion（CRI）. Methods: A total of 69 children who received cochlear implantation surgery from April 1999 to June 2024 were included. Patients were divided into two groups based on whether the implantation was on the same side. General information such as gender, age, age at initial implantation and reimplantation was collected. The primary caregivers of the children were followed up by telephone using the categories of auditory performance（CAP）, speech intelligibility rating（SIR）, and SSQ-P questionnaires. Statistical methods including stepwise regression, linear regression, and permutation tests were employed to investigate if there were any statistically significant differences in the scores of CAP, SIR, SSQ-P total, SSQ-P speech perception, SSQ-P spatial hearing, and SSQ-P auditory quality dimensions between the ipsilateral and contralateral reimplantation groups. Results:Of the 69 children included, 62 were in the ipsilateral reimplantation group with a mean age of 11.1 years, and 7 were in the contralateral reimplantation group with a mean age of 11.7 years. Statistical analysis showed that patients in the contralateral reimplantation group had significantly lower SSQ-P total scores （P<0.05） and spatial hearing dimension scores （P<0.05） than those in the ipsilateral reimplantation group after controlling for the corresponding confounders. Conclusion:The effect of ipsilateral reimplantation of cochlear implants is superior to that of contralateral reimplantation in terms of overall auditory function and spatial hearing in daily life for children, but the mechanisms require further investigation.
Humans ; Cochlear Implantation ; Child ; Parents ; Speech Perception ; Male ; Cochlear Implants ; Female ; Hearing ; Surveys and Questionnaires ; Speech ; Child, Preschool

OBJECTIVES: To study the therapeutic mechanism of Tuihuang Mixture against cholestasis. METHODS: Forty-eight Wistar rats were randomized equally into blank group, model group, ursodeoxycholic acid group and Tuihuang Mixture group. Except for those in the blank group, all the rats were given α‑naphthylisothiocyanate (ANIT) to establish rat models of cholestasis, followed by treatments with indicated drugs or distilled water. Serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL of the rats were determined, and hepatic expressions IL-1β, IL-18, FXR, NLRP3, ASC, Caspase-1 and GSDMD were detected using q-PCR, ELISA or Western blotting. Histopathological changes of the liver tissues were observed using HE staining. RESULTS: The rat models of cholestasis had significantly increased serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL with increased mRNA and protein expressions of IL-1β and IL-18, decreased protein and mRNA expressions of FXR, and increased protein expressions of NLRP3 and Caspase-1 and mRNA expressions of NLRP3, ASC, Caspase-1 and GSDMD in the liver tissue, showing also irregular arrangement of liver cells, proliferation of bile duct epithelial cells and inflammatory cells infiltration. Treatment of the rat models with Tuihuang Mixture significantly decreased serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL, lowered IL-1β and IL-18 and increased FXR protein and mRNA expressions, and reduced NLRP3, ASC, Caspase-1 and GSDMD proteins and NLRP3, ASC and Caspase-1 mRNA expressions in the liver tissue. Tuihuang Mixture also significantly alleviated hepatocyte injury, bile duct epithelial cell proliferation and inflammatory cell infiltration in the liver of the rat models. CONCLUSIONS Tuihuang Mixture can effectively improve cholestasis in rats possibly by inhibiting NLRP3 inflammatosome-mediated pyroptosis via regulating FXR.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein ; Rats ; Receptors, Cytoplasmic and Nuclear/metabolism* ; Cholestasis/drug therapy* ; Rats, Wistar ; Inflammasomes/metabolism* ; 1-Naphthylisothiocyanate ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Interleukin-18/metabolism* ; Caspase 1/metabolism* ; Interleukin-1beta/metabolism* ; Liver/metabolism*