Background/Aims: Chronic constipation is prevalent yet under-diagnosed across Asia, compromising quality of life and burdening healthcare systems. Cultural stigma, varied diets, and limited access to standardized diagnostic tools delay timely care. Methods: The Bali Chronic Constipation Roundtable in November 2024, brought together experts from 11 Asian countries. The group reviewed epidemiological data, analyzed multinational questionnaire on clinical practice pattern, and conducted structured discussions to identify key barriers and propose region-specific recommendations. Results: Chronic constipation prevalence varies across Asia, ranging from 1.8% in India to 16.6% in Japan, with women and the elderly disproportionately affected. Under-reporting persists owing to cultural taboos and widespread self treatment with laxatives and traditional medications. Although the Rome IV criteria remains the global standard, they may not fully reflect Asian symptom profiles, and diagnosis is limited by scarce motility laboratories. First line therapies such as dietary-fiber optimization and osmotic laxatives are widely available, but newer pharmacotherapies (prucalopride, linaclotide, lubiprostone, and elobixibat) remain costly and unevenly accessible. Biofeedback for dyssynergic defecation is underutilized due to limited availability. Experts recommend expanded regional research on to refine diagnostic criteria, coupled with enhanced physician education and public awareness. They advocate accessibility to second-line and novel therapies that incorporate culturally attuned regional guidelines, and improved access to gastrointestinal motility testing. Conclusions The Bali Chronic Constipation Roundtable highlighted Asia’s need for region specific diagnostics and management. Addressing diagnostic and treatment gaps will improve outcomes, while ongoing researcher clinician policy collaboration must standardize guidelines, advance research, and ensure equitable care across Asia.

Dermatomyositis (DM) is a rare autoimmune connective tissue disease with characteristic skin manifestations and possible muscle involvement. Recent advances in classification system to include skin-predominant subtypes, understanding underlying pathogenic mechanisms and the relationship between clinical phenotypes and myositis-specific autoantibodies have led to development of novel therapeutic options. This corresponds with efforts to develop better outcome measures to accurately catch the patients’ current disease status and treatment-induced improvements. This report will review the updates in newer treatments and outcome measures of DM, specifically from a dermatologic point of view.

Ameloblasts are specialized cells derived from the dental epithelium that produce enamel, a hierarchically structured tissue comprised of highly elongated hydroxylapatite (OHAp) crystallites. The unique function of the epithelial cells synthesizing crystallites and assembling them in a mechanically robust structure is not fully elucidated yet, partly due to limitations with in vitro experimental models. Herein, we demonstrate the ability to generate mineralizing dental epithelial organoids (DEOs) from adult dental epithelial stem cells (aDESCs) isolated from mouse incisor tissues. DEOs expressed ameloblast markers, could be maintained for more than five months (11 passages) in vitro in media containing modulators of Wnt, Egf, Bmp, Fgf and Notch signaling pathways, and were amenable to cryostorage. When transplanted underneath murine kidney capsules, organoids produced OHAp crystallites similar in composition, size, and shape to mineralized dental tissues, including some enamel-like elongated crystals. DEOs are thus a powerful in vitro model to study mineralization process by dental epithelium, which can pave the way to understanding amelogenesis and developing regenerative therapy of enamel.
Mice ; Animals ; Durapatite/metabolism* ; Dental Enamel/metabolism* ; Ameloblasts/metabolism* ; Amelogenesis ; Stem Cells ; Organoids

Objective: Female sex workers (FSWs) are at high risk of human papillomavirus (HPV) infections and cervical cancer due to their high number of sexual partners. The objectives of this study were to determine the prevalence of HPV and identify risk factors for high-risk HPV infection among FSWs in Hanoi and Ho Chi Minh City (HCMC), Viet Nam. Methods: A cross-sectional study was conducted in Hanoi and HCMC between December 2017 and May 2018. We surveyed and screened 699 FSWs aged ≥18 years for HPV infection and abnormal cytology. A multivariable modified Cox regression model was used to determine risk factors for high-risk HPV infection. Results The overall prevalence of any HPV, high-risk HPV and HPV-16/18 infection in the 699 FSWs was 26.3%, 17.6% and 4.0%, respectively, and were similar in both cities. Multiple infections were identified in 127 participants (69.0%).HPV-52 was the most prevalent (7%), followed by HPV-58 (6%). Abnormal cytology was detected in 91 participants (13.0%). FSWs who are divorced (adjusted prevalence ratio [aPR]: 1.96, 95% confidence interval [CI]: 1.01–3.81), widowed (aPR: 3.26, 95% CI: 1.49–7.12) or living alone (aPR: 1.85, 95% CI: 1.01–3.39) were associated with a higher prevalence of high-risk HPV infection.

Objective: Ischemic cardiomyopathy (ICM) is the leading cause of heart failure. Proteomic and genomic studies have demonstrated ischemic preconditioning (IPC) can assert cardioprotection against ICM through mitochondrial function regulation. Considering IPC is conducted in a relatively brief period, regulation of protein expression also occurs very rapidly, highlighting the importance of protein function modulation by post-translational modifications. This study aimed to identify and analyze novel phosphorylated mitochondrial proteins that can be harnessed for therapeutic strategies for preventing ischemia/reperfusion (I/R) injury. Methods: Sprague-Dawley rat hearts were used in an ex vivo Langendorff system to simulate normal perfusion, I/R, and IPC condition, after which the samples were prepared for phosphoproteomic analysis. Employing human cardiomyocyte AC16 cells, we investigated the cardioprotective role of CKMT2 through overexpression and how site-directed mutagenesis of putative CKMT2 phosphorylation sites (Y159A, Y255A, and Y368A) can affect cardioprotection by measuring CKMT2 protein activity, mitochondrial function and protein expression changes. Results: The phosphoproteomic analysis revealed dephosphorylation of mitochondrial creatine kinase (CKMT2) during ischemia and I/R, while preserving its phosphorylated state during IPC. CKMT2 overexpression conferred cardioprotection against hypoxia/reoxygenation (H/R) by increasing cell viability and mitochondrial adenosine triphosphate level, preserving mitochondrial membrane potential, and reduced reactive oxygen species (ROS) generation, while phosphomutations, especially in Y368, nullified cardioprotection by significantly reducing cell viability and increasing ROS production during H/R. CKMT2 overexpression increased mitochondrial function by mediating the proliferator-activated receptor γ coactivator-1α/ estrogen-related receptor-α pathway, and these effects were mostly inhibited by Y368A mutation. Conclusion These results suggest that regulation of quantitative expression and phosphorylation site Y368 of CKMT2 offers a unique mechanism in future ICM therapeutics.

Objective: Ischemic cardiomyopathy (ICM) is the leading cause of heart failure. Proteomic and genomic studies have demonstrated ischemic preconditioning (IPC) can assert cardioprotection against ICM through mitochondrial function regulation. Considering IPC is conducted in a relatively brief period, regulation of protein expression also occurs very rapidly, highlighting the importance of protein function modulation by post-translational modifications. This study aimed to identify and analyze novel phosphorylated mitochondrial proteins that can be harnessed for therapeutic strategies for preventing ischemia/reperfusion (I/R) injury. Methods: Sprague-Dawley rat hearts were used in an ex vivo Langendorff system to simulate normal perfusion, I/R, and IPC condition, after which the samples were prepared for phosphoproteomic analysis. Employing human cardiomyocyte AC16 cells, we investigated the cardioprotective role of CKMT2 through overexpression and how site-directed mutagenesis of putative CKMT2 phosphorylation sites (Y159A, Y255A, and Y368A) can affect cardioprotection by measuring CKMT2 protein activity, mitochondrial function and protein expression changes. Results: The phosphoproteomic analysis revealed dephosphorylation of mitochondrial creatine kinase (CKMT2) during ischemia and I/R, while preserving its phosphorylated state during IPC. CKMT2 overexpression conferred cardioprotection against hypoxia/reoxygenation (H/R) by increasing cell viability and mitochondrial adenosine triphosphate level, preserving mitochondrial membrane potential, and reduced reactive oxygen species (ROS) generation, while phosphomutations, especially in Y368, nullified cardioprotection by significantly reducing cell viability and increasing ROS production during H/R. CKMT2 overexpression increased mitochondrial function by mediating the proliferator-activated receptor γ coactivator-1α/ estrogen-related receptor-α pathway, and these effects were mostly inhibited by Y368A mutation. Conclusion These results suggest that regulation of quantitative expression and phosphorylation site Y368 of CKMT2 offers a unique mechanism in future ICM therapeutics.

Background: Universal Health Care law calls for strong primary care where essential services are responsive to the health needs of individuals, families, and communities. Similar to other countries, family physicians are the biggest workforce in primary care, but little is known about the kind of care that they provide. This study aimed to determine the process of care rendered by family physicians in the country to assess their readiness in implementing the standards of primary care services according to the Universal Health Care law. Methods: Cross-sectional survey using a questionnaire that includes 6 key elements of UHC was conducted to family physicians participating in the pilot project of the Philippine Academy of Family Physicians practice networks. Process of care is part of the big data collected in the survey. The process of care variables was analyzed using descriptive statistics. Results: There were 195 family physicians who completed the survey. There were about 14.87% from Luzon, 18.46% from NCR, 27.18% from the Visayas, and 39.49% from Mindanao. Overall, the participants provide comprehensive, coordinated, and continuing care. Few utilized electronic medical records (9%). Preventive services provided are immunization (82.05%), alcohol and smoking cessation (77.44%), nutrition advice (76.92%), and exercise prescription (73.33%). Conclusion Family physicians in the pilot sites provide comprehensive, coordinated, and continuing care. The majority also offer common preventive services such as immunization, smoking cessation, nutrition advice, and exercise prescription. Some process needed for UHC needs improvement such as the use of EMR and quality assurance activities.
Primary Health Care ; Universal Health Care ; Family Practice

PURPOSE: A soft tissue sarcoma (STS) is a rare type of cancer, accounting for 1% of adult solid cancers. The aim of the present study is to determine the incidence of localized and advanced STS in Korean patients, their treatment patterns, and the survival of patients by disease status. MATERIALS AND METHODS: The STS patient cohort was defined using National Health Insurance Service medical data from 2002 to 2015. Incidence, distribution, anatomical location of tumors, survival rates (Kaplan-Meyer survival function) and treatment patterns were analyzed by applying different algorithms to the STS cohort containing localized and advanced STS cases. RESULTS: A total of 7,813 patients were diagnosed with STS from 2007 to 2014, 4,307 were localized STS and 3,506 advanced STS cases. The total incidence of STS was 2.49 per 100,000 person- years: 1.37 per 100,000 person-years for localized STS and 1.12 per 100,000 person-years for advanced STS. The 5-year survival rate after diagnosis was 56.4% for all STS, 82.4% for localized, and 27.2% for advanced STS. Half of the advanced STS patients (49.98%) received anthracycline-containing chemotherapy as initial treatment after diagnosis. CONCLUSION: This study provides insights into localized and advanced STS epidemiology, treatment patterns and outcomes in Korea, which could be used as fundamental data in improving clinical outcomes of STS patients in the future.
Adult ; Cohort Studies ; Diagnosis ; Drug Therapy ; Epidemiology ; Humans ; Incidence ; Korea ; National Health Programs ; Sarcoma ; Survival Rate

OBJECTIVE: To evaluate the clinical efficacy and safety following percutaneous disc decompression, using navigable disc decompression device for cervical herniated nucleus pulposus (HNP). METHODS: Twenty subjects diagnosed with cervical HNP and refractory to conservative management were enrolled for the study. The herniated discs were decompressed under fluoroscopic guidance, using radiofrequency ablation device with navigable wand. The sagittal and axial plain magnetic resonance images of the clinically significant herniated disc, decided the space between the herniated base and outline as the target area for ablation. Clinical outcome was determined by Numeric Rating Scale (NRS), Neck Disability Index (NDI), and Bodily Pain scale of Short Form-36 (SF-36 BP), assessed after 48 weeks. After the procedure, we structurally matched the magnetic resonance imaging (MRI) and C-arm images through bony markers. The wand position was defined as being ‘correct’ if the tip was placed within the target area of both AP and lateral views; if not, the position was stated as ‘incorrect’. RESULTS: The average NRS fell from 7 to 1 at 48 weeks post procedure (p<0.05). In addition, statistically significant improvement was noted in the NDI and SF-36BP (p<0.05). The location of the wand tip resulted in 16 correct and 4 incorrect placements. Post-48 weeks, 3 of the incorrect tip cases and 1 correct tip case showed unsuccessful outcomes. CONCLUSION: The study demonstrated the promising results and safety of the procedure. Thus, focal plasma ablation of cervical HNP with navigable wand can be another effective treatment option.
Catheter Ablation ; Decompression* ; Humans ; Intervertebral Disc Displacement ; Magnetic Resonance Imaging ; Neck ; Neck Pain ; Plasma ; Treatment Outcome*

PURPOSE: Studies suggested the existence of a 'trial effect', in which for a given treatment, participation in a clinical trial is associated with a better outcome. Sunitinib is a standard treatment for metastatic renal cell carcinoma (mRCC). We aimed to study the effect of clinical trial participation on the outcome of mRCC patients treated with sunitinib, which at present, is poorly defined. MATERIALS AND METHODS: The records of mRCC patients treated with sunitinib between 2004-2013 in 7 centers across 2 countries were reviewed. We compared the response rate (RR), progression free survival (PFS), and overall survival (OS), between clinical trial participants (n=49) and a matched cohort of non-participants (n=49) who received standard therapy. Each clinical trial participant was individually matched with a non-participant by clinicopathologic factors. PFS and OS were determined by Cox regression. RESULTS: The groups were matched by age (median 64), gender (male 67%), Heng risk (favorable 25%, intermediate 59%, poor 16%), prior nephrectomy (92%), RCC histology (clear cell 86%), pre-treatment NLR (>3 in 55%, n=27), sunitinib induced hypertension (45%), and sunitinib dose reduction/treatment interruption (41%). In clinical trial participants versus non-participants, RR was partial response/stable disease 80% (n=39) versus 74% (n=36), and progressive disease 20% (n=10) versus 26% (n=13) (p=0.63, OR 1.2). The median PFS was 10 versus 11 months (HR=0.96, p=0.84), and the median OS 23 versus 24 months (HR=0.97, p=0.89). CONCLUSION: In mRCC patients treated with sunitinib, the outcome of clinical trial participants was similar to that of non-participants who received standard therapy.
Carcinoma, Renal Cell* ; Cohort Studies ; Disease-Free Survival ; Humans ; Hypertension ; Nephrectomy