Genetic Variants in the TBC1D2B Gene Are Associated with Ramon Syndrome and Hereditary Gingival Fibromatosis.

Ramon syndrome (MIM 266270) is an extremely rare genetic syndrome, characterized by gingival fibromatosis, cherubism-like lesions, epilepsy, intellectual disability, hypertrichosis, short stature, juvenile rheumatoid arthritis, and ocular abnormalities. Hereditary or non-syndromic gingival fibromatosis (HGF) is also rare and considered to represent a heterogeneous group of disorders characterized by benign, slowly progressive, non-inflammatory gingival overgrowth. To date, two genes, ELMO2 and TBC1D2B, have been linked to Ramon syndrome. The objective of this study was to further investigate the genetic variants associated with Ramon syndrome as well as HGF. Clinical, radiographic, histological, and immunohistochemical examinations were performed on affected individuals. Exome sequencing identified rare variants in TBC1D2B in both conditions: a novel homozygous variant (c.1879_1880del, p.Glu627LysfsTer61) in a Thai patient with Ramon syndrome and a rare heterozygous variant (c.2471A>G, p.Tyr824Cys) in a Cambodian family with HGF. A novel variant (c.892C>T, p.Arg298Cys) in KREMEN2 was also identified in the individuals with HGF. With support from mutant protein modeling, our data suggest that TBC1D2B variants contribute to both Ramon syndrome and HGF, although variants in additional genes might also contribute to the pathogenesis of HGF.

Comparison of educational environments in different sized rural hospitals during a longitudinal integrated clerkship in Thailand.

INTRODUCTION: The longitudinal integrated clerkship (LIC) curriculum model focuses on patient-centered care and continuity of clinical and cultural learning between medical students, patients, clinicians, and a system of care. In rural settings, participating medical students are expected to have an interest in rural medicine and an involvement in the community. Many schools in the USA, Canada, and Australia have implemented LICs in undergraduate programs in different ways. However, a few published reports in Asia are available. This is the first report of a modified rural LIC in Thailand. The objective was to assess the educational environment of a rural LIC using the Dundee Ready Education Environment Measure (DREEM) questionnaire and to compare students' response on the basis of year of study and different sizes of hospitals. METHODS: A cross-sectional study was conducted. The study population comprised 75 clinical-year students in 2020. The modified LIC was implemented as part of integrated multidisciplinary rural clerkships for fourth-year students, and for fifth-year students undertaking clinical placements. Clinical clerkships in rural settings took place over 12 weeks for fourth-year students and over 14 weeks for fifth-year students. Practical exposure included the clinical areas of internal medicine, psychiatry, surgery, pediatrics, obstetrics and gynecology, emergency medicine, and family medicine, in outpatient and inpatient settings. The DREEM questionnaire was used to evaluate students' perceptions of learning climate. Data analysis was performed to determine the different size of hospitals and other factors associated with a favorable educational environment. RESULTS: The response rate to the questionnaire was 96%. The overall DREEM score average was 137.7/200. Students' perceptions of learning and of teaching had mean scores of 30.1/48 and 35.7/44, respectively. Students' academic self-perceptions scored 18.7/32. Students' perceptions of atmosphere scored 30.4 of 48, and social self-perceptions scored 18.3/28. The academic subscale had the lowest percentage of scores regarded as confidence in knowledge gain. The factors associated with positive educational environment were staff as principal preceptors and large hospitals. CONCLUSIONS: LIC implementation in a community health system is a model for expanding clinical clerkships. Good infrastructure of the host hospital and enthusiastic preceptors are the key success factors. Staff supervision is essential to encourage student learning, especially in academic environments. Large hospitals have better infrastructure to support learning processes than small hospitals.

Safety in treatment of ventilator-associated pneumonia due to extensive drug-resistant Acinetobacter baumannii with aerosolized colistin in neonates: a preliminary report.

BACKGROUND: Infections caused by extensive drug-resistant Acinetobacter baumannii (XDR-AB) have been increasingly observed and are associated with a high mortality rate. We present our experience using aerosolized colistin for the treatment of ventilator-associated pneumonia (VAP) due to XDR-AB in neonates. METHODS: The clinical data of neonates who received aerosolized 4 mg per kg of colistin base twice daily as an adjunctive therapy for VAP caused by XDR-AB between July 2008 and September 2009 were retrospectively reviewed. The outcomes were compared with the neonates with VAP from XDR-AB in October 2006-September 2007 who did not receive aerosolized colistin. RESULTS: During the study period, eight neonates (three preterm and five term neonates) with VAP caused by XDR-AB received aerosolized colistin. All isolated pathogens from the tracheobronchial specimens of the eight patients were XDR-AB susceptible to colistin only. Six patients received aerosolized colistin without concomitant intravenous colistin. All children were cured with eradication of XDR-AB from respiratory secretions. Seven patients survived and were discharged from the hospital, and one died from bacterial sepsis unrelated to the VAP episode. There were no clinical or laboratory adverse events related to aerosolized colistin. Compared to the seven neonates in the earlier period, the neonates who received aerosolized colistin had higher birth weight and gestational age, and lower mortality rate (13% vs. 71%, P=0.04). CONCLUSIONS: Aerosolized colistin may be a useful adjunctive therapy in VAP due to XDR-AB. The use of aerosolized colistin in neonates should be investigated in a larger controlled study.