Deep intronic variant c.5999-277G>A of F8 gene may be a hot spot mutation for mild hemophilia A patients without mutation in exonic DNA.

BACKGROUND: In 10%-18% of mild-type hemophilia A (HA) patients, mutations cannot be found by routine DNA analysis. OBJECTIVE: We aimed to identify the genetic defects by mRNA analysis of F8 gene in mild HA patients without mutation in exonic DNA. PATIENTS AND METHODS: From 2006 to 2016, we identified F8 exon mutations in 39 of 49 mild HA patients using routine genetic testing. We then evaluated the 10 remaining patients from six unrelated families without exonic DNA mutation by performing cDNA sequence analysis. RESULTS: Nine of the 10 (90%) patients were confirmed to have F8 gene mutation. Eight patients from four unrelated families were notably found to have presence of an aberrant 675-bp fragment. Sequencing of this fragment showed that there were two separate new alternative splicing exons of 35 bp and 55 bp within intron 18, which formed a 90-bp insertion between exon 18 and exon 19 (E18ins90bpE19) in the mRNA. Based on direct sequencing, this alternative splicing transcript appears to have resulted from deep intronic variant c.5999-277G>A of intron 18. CONCLUSIONS: Our study suggests that deep intronic variant of c.5999-277G>A may be a hot spot mutation for mild hemophilia patients without mutation in exonic DNA.

Luminescence Properties of Epitaxial Cu2O Thin Films Electrodeposited on Metallic Substrates and Cu2O Single Crystals.

The luminescent properties of epitaxial Cu2O thin films were studied in 10-300 K temperature range and compared with the luminescent properties of Cu2O single crystals. Cu2O thin films were deposited epitaxially via the electrodeposition method on either Cu or Ag substrates at different processing parameters, which determined the epitaxial orientation relationships. Cu2O (100) and (111) single crystal samples were cut from a crystal rod grown using the floating zone method. Luminescence spectra of thin films contain the same emission bands as single crystals around 720, 810 and 910 nm, characterizing VO2+, VO+ and VCu defects, correspondingly. Additional emission bands, whose origin is under discussion, are observed around 650-680 nm, while the exciton features are negligibly small. The relative mutual contribution of the emission bands varies depending on the thin film sample. The existence of the domains of crystallites with different orientations determines the polarization of luminescence. The PL of both Cu2O thin films and single crystals is characterized by negative thermal quenching in the low-temperature region; the reason of this phenomenon is discussed.

Angiotensin II type 1 receptor antagonist attenuates lung fibrosis in hyperoxia-exposed newborn rats.

Bronchopulmonary dysplasia (BPD) remains a major cause of morbidity and mortality during the first year of life, and many infants have significant respiratory problems throughout childhood. Currently no effective therapy is clinically available to prevent the long-term pulmonary sequelae of BPD. Previous research has demonstrated that the renin-angiotensin system is up-regulated in human lung fibroblasts. Angiotensin II type 1 receptor (AT1R) antagonists and AT1R short interfering RNA diminished hyperoxia-increased collagen expression, whereas AT2R antagonists did not have any effects on these hyperoxia-induced changes. The in vivo therapeutic effects of AT1R antagonists on hyperoxia-induced lung fibrosis remain unknown. The present study assessed the effects of an AT1R antagonist (losartan) on preventing hyperoxia-induced lung fibrosis in newborn rats. Rat pups were exposed to 7 days of > 95% O2 and an additional 2 weeks of 60% O2. AT1R antagonist-treated pups were injected intraperitoneally with losartan at a dose of 10 mg/kg/day from postnatal days 1 to 7 and a dose of 5 mg/kg/day from postnatal days 8 to 21. Control group pups were injected with an equal volume of normal saline. AT1R antagonist treatment attenuated the hyperoxia-induced lung fibrosis on postnatal days 7 and 21 and also decreased the hyperoxia-induced expression of extracellular signal-regulated protein kinase and α-smooth muscle actin. AT1R antagonist treatment did not affect body weight or lung weight of the rats. These data suggest that AT1R antagonist may offer a novel therapeutic strategy for preventing hyperoxia-induced lung fibrosis.

True vertical changes in patients with skeletal class III malocclusion after nonsurgical orthodontic treatment-a retrospective study comparing different vertical facial patterns.

Background/purpose: Rotating mandible backward downward is one of the treatment options in non-surgical skeletal class III malocclusion. The purpose of this study was to compare the true vertical changes after camouflage orthodontic treatment of adult patients with skeletal class III malocclusion categorized by vertical facial type. Materials and methods: This retrospective study included 27 adult patients (age >18 years) with skeletal class III malocclusion (ANB<1°) who underwent nonsurgical orthodontic treatment at Taipei Veterans General Hospital. The patients were divided into the low-angle (SN-MP<28°), high-angle (SN-MP>36°), and normal-angle (28°≤ SN-MP ≤ 36°) groups according to the original vertical facial pattern. Pretreatment (T1) and post-treatment (T2) lateral cephalograms were superimposed and treatment changes were evaluated. Results: In all cases, proper overjet and occlusion were achieved after treatment, and the lower anterior facial height increased with the backward rotation of the mandibular plane. Increase in vertical dimension was the most obvious in the high-angle group, while it was the least obvious in the low-angle group. Extrusion of both the maxillary and mandibular incisors was observed in the high-angle group; however, intrusion of the maxillary and mandibular incisors and decreased overbite were observed in the low-angle group. Conclusion: Camouflage orthodontic treatment of skeletal class III malocclusion improves the facial profile by increasing the vertical dimension and clockwise rotation of the mandible. According to our results, patients with a high mandibular plane angle showed better response to vertical dimension increment treatment mechanics than those with low and normal mandibular plane angles.

Navigational Transmaxillary Endoscopic Approach for Inferomedial Tumors.

Orbital tumors encompass a heterogeneous range of histopathology and usually variable in location. Traditionally, transconjunctival medial orbitotomy is used to access the medial orbital wall. However, it creates potential risk of soft tissue sequelae such as scarring, lid contracture, or entropion/ectropion. For the lesions close to the orbital apex, increased risk of optical nerve injury should be cautious during orbitotomy procedure. Transnasal endoscopic approach to the orbital walls has been applied since 1999. Although it provides good surgical visualization and prevents the soft tissue and neural complications, the narrow nasal corridor increases the surgical complexity. Extensive sphenoethmoidectomy is usually required to gaining access. Furthermore, the resultant medical orbital defect is difficult to repair. The maxillary sinus is the largest paranasal sinuses which is located beneath the orbital floor. It provides an ample working space for instrumentation. Meanwhile, repair of the orbital floor defect is feasible and with high degree of accuracy under navigation control. In this report, we propose a novel computer-assisted endoscopic protocol to excise the medial orbital tumors with immediate repair of the wall defect.

A digital photograph study evaluating facial taperness and square face perception of Taiwanese females.

BACKGROUND: This study assessed the perception of facial taperness in Taiwanese females among people with dental knowledge and laypersons. Additionally, this study also specified the criteria by which "square face" was defined regarding Taiwanese females' facial taperness. METHODS: A series of digitally modified photos with different levels of facial taperness (Gonion to Gonion/Zygoma point to Zygoma point-Go-Go/Zy-Zy ratio ranges from 65% to 90%) were randomly arranged and presented to the raters. Visual analog scale (VAS) lines were used for scoring the photos on a scale of 0-100. The true or false question about "defining square face" was incorporated in the same questionnaire. The reliability of the true/false square face question and the esthetic evaluation by VAS were assayed. The receiver operating characteristic curve was used to define the cutoff point on "square face." The effects on the raters' genders, orthodontic treatment experience, and their professional background on the perception of a square face were assayed. RESULTS: The overall reliability of the raters was within the acceptable range. The VAS score evaluation revealed that the average expectation for best facial taperness was 75%, whereas the facial taperness of over 83% was considered as the square face. The facial taperness reaching to 90% was regarded as the most unattractive. Gender, therapy, and professional experience have no impact on the standard of square facial form evaluation. CONCLUSION: A face with a taperness greater than 83% was evaluated as a square face, and a face with a taperness around 75% was considered as the most attractive.

Impact of diabetes mellitus on the prognosis of patients with oral squamous cell carcinoma: a retrospective cohort study.

BACKGROUND: Diabetes mellitus (DM) is a prevalent chronic metabolic disease reported to affect the treatment outcomes of malignancies. This study explores the impact of diabetes on the prognosis of oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Clinicopathological characteristics and survival in terms of overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival (CSS) of patients with OSCC who underwent surgical intervention at the Taipei Veterans General Hospital between 2002 and 2005 were stratified by diabetic status and compared. RESULTS: Patients with DM tend to have a lower OS, RFS, and CSS compared with nondiabetics (adjusted hazard ratio [HR] = 2.22, 2.42, and 2.16, respectively) even in less aggressive tumor stages (stage I and II). In advanced tumors, diabetic patients who were not prescribed adjuvant therapy had a significantly higher recurrence rate than nondiabetic patients (HR = 2.66). However, there was no significant difference in treatment outcome in patients with locally advanced tumors amenable to receive adjuvant therapy, even with the delayed initiation of adjuvant therapy in the DM group (49.1 +/- 22.3 days vs. 40.0 +/- 16.6 days, P = .04). DM was also associated with a higher frequency of perineural invasion (adjusted odds ratio [OR] = 2.53). CONCLUSION: DM status could be a prognostic factor for OSCC, particularly for its effect in the survival and perineural invasion. Although diabetes-associated comorbidities may impair decision making toward less aggressive therapeutic modality, adjuvant treatment may be essential for DM patients to improve their survival.

Evaluation of factors associated with the risk stratification of survivorship for stage IV squamous cell carcinoma of the oral cavity: A 10-year retrospective study.

BACKGROUND: Oral squamous cell carcinoma (OSCC) leads to thousands of deaths every year in Taiwan. Nearly 40% of OSCC patients are diagnosed with stage IV disease, which has a poor prognosis. Multimodality treatments including surgery and adjuvant therapy have been utilized, but their treatment outcomes are generally poor. In this study, we sought to identify possible clinical impact factors that may contribute to the survival of stage IV OSCC. METHODS: Data for patients with malignant neoplasms of the oral cavity registered in the Cancer Registry Database of Taipei Veterans General Hospital between 2002 and 2011 were retrieved. The study patients consisted of OSCC patients with clinical stage IV disease who had undergone a surgery and adjuvant therapy. The primary endpoints were the 5-year disease-free survival (DFS) and overall survival (OS) rates. The clinicopathological characteristics of the patients were also stratified and compared. RESULTS: A total of 191 OSCC patients were included for retrospective analysis. The different subgroups of stage IV disease presented different treatment outcomes. The 5-year OS versus DFS rates of each subgroup were as follows: T4N0: 70.9% versus 52.6%; T1-3N23: 66.1% versus 49.8%; T4N1: 49.6% versus 31.6%; and T4N23: 40.9% versus 31.0% (p < 0.01). Patients with diabetes, moderate or poor cell differentiation, perineural invasion, and extracapsular spread presented lower 5-year OS rates (hazard ratio [HR] = 1.87, 1.65, 2.42, and 2.14, respectively), and patients with perineural invasion, positive cut margin, and extracapsular spread presented lower 5-year DFS rates (HR = 1.57, 1.62, and 1.71, respectively). CONCLUSION: In this study, we elucidated the different survival rates of different subgroups of stage IV OSCC following the same treatment scheme. The results of the study provide clinical physicians with references by which to evaluate prognosis and determine post-operative disease monitoring timetables based upon different characteristics.

Factors associated with the stability of mini-implants for orthodontic anchorage: a study of 414 samples in Taiwan.

PURPOSE: To evaluate failure rates and factors associated with the stability of mini-implants used for orthodontic anchorage. PATIENTS AND METHODS: We enrolled 166 patients (35 male patients and 131 female patients) who had consecutively received mini-implants for orthodontic anchorage at the Section of Orthodontics and Pediatric Dentistry, Taipei Veterans General Hospital (Taipei, Taiwan) from January 2001 to December 2006. A total of 414 mini-implants with diameters ranging from 1.2 to 2.0 mm were evaluated. Clinical variables for analysis were divided into host-related and implant-related factors. Mini-implants that could be maintained for orthodontic anchorage for more than 6 months were considered to be successful. Statistical analysis was used to evaluate the failure rate in our study cohort and to identify possible associated factors. RESULTS: The overall failure rate was 10.1% (42 of 414 screws) with orthodontic force loading for more than 6 months. Most failures were due to loosening and occurred within the first 2 weeks. Differences in overall failure rates for the maxilla and mandible (9.3% and 16.3%, respectively) were not statistically significant. A lower failure rate was found for the maxilla with implant diameters equal to or less than 1.4 mm (P = .036). The left side had a lower failure rate than the right (6.7% vs 13.9%, P = .019). Length and type of mini-implants, age, and gender were not associated with mini-implant failure. CONCLUSIONS: Use of mini-implants for anchorage is reliable. In our study the overall success rate was 89.9%. Careful diameter selection for different locations is essential. In the maxilla an implant diameter equal to or less than 1.4 mm is recommended. In the mandible an implant diameter larger than 1.4 mm is suggested for better orthodontic anchorage. Hygienic care of implantation sites should also be emphasized for long-term success of mini-implant anchorage.

Comparison of upper airway measurement by lateral cephalogram in upright position and CBCT in supine position.

BACKGROUND/PURPOSE: Obstructive sleep apnea syndrome (OSAS) is a common form of sleep disorder. Lateral cephalograms and cone-beam computed tomography (CBCT) have been used for evaluation. However, it is lack of position comparison for these two assessments. Therefore, this study was aimed to evaluate the difference of upper airway measurements taken from lateral cephalograms in upright position and CBCT in supine position. MATERIAL AND METHODS: This retrospective study enrolled patients with lateral cephalograms and CBCT images due to diagnostic necessity. The anterior-posterior distance of most constricted area in pharynx (PASmin) and the distance from mandibular plane to hyoid bone (MP-H) were identified and measured from 21 normal subjects without obstructive sleep apnea (9 males and 12 females, mean age 21.2 years). A paired data were measured from lateral cephalograms taken in upright position and lateral cephalometric images derived from CBCT taken in supine position. Both images were taken within two months. All data were analyzed statistically. RESULTS: No significant difference was identified in intra-examiner reliability (P > 0.05). PASmin measured from lateral cephalograms in upright position was larger than that taken from CBCT derived cephalometric images, but without statistical significant difference (P = 0.073). Significant difference of MP-H length was identified between two different image taking methods (P = 0.000), and the measurement was significantly larger in cephalograms taken from upright position. No correlations were found among the variables (Body Mass Index (BMI), age, gender) in this study. The only two variables correlated were PASmin and MP-H, and they were negatively correlated (r = -0.535). CONCLUSION: The anterior-posterior distance of most constricted area in pharynx (PASmin) and distance of mandibular plane to hyoid bone (MP-H) can be influenced due to change of body position.

The significance of tumor budding in oral cancer survival and its relevance to the eighth edition of the American Joint Committee on Cancer staging system.

BACKGROUND: To explore the clinicopathological significance of tumor budding (TB) on oral squamous cell carcinoma (OSCC) prognosis. METHODS: Data of 200 patients with OSCC were retrieved from the cancer registration database in Taipei Veterans General Hospital. Clinicopathological characteristics and survival relevant to TB were analyzed. RESULTS: The data showed that TB was predominant in the tongue and floor of the mouth in younger patients with OSCC and correlated with several pathological factors, such as perineural invasion and lymphovascular invasion. Patients with TB have significantly lower recurrence-free survival (P ≤ .0001). TB was significantly associated with lymph node metastasis in patients with early cancer stage (P = .042). Multivariate analysis demonstrated extranodal extension and TB as independent predictors of lymph node recurrence (adjusted hazard ratio = 9.90 and 3.89, respectively). CONCLUSION: TB is a significant predictor of tumor aggression with locoregional failure even in the revised 8th American Joint Committee on Cancer staging system.

Comparing the reliability and accuracy of clinical measurements using plaster model and the digital model system based on crowding severity.

BACKGROUND: This study aims to clarify whether 3Shape™ digital model system could be applied in orthodontic diagnostic analysis with certainty, especially under different crowding condition. Reliability, accuracy and efficiency of 3Shape™ digital model system were assessed by comparing them with traditional plaster cast. METHODS: 29 plaster casts with permanent dentition were transformed into digital models by 3Shape™ D800 scanner. All 29 models were categorized into mild-crowding (arch length discrepancy <3 mm), moderate-crowding (arch length discrepancy >3 mm and <8 mm), and severe-crowding group (arch length discrepancy >8 mm). Fourteen linear measurements were made manually using a digital caliper on plaster casts and virtually using the 3Shape™ Ortho Analyzer software by two examiners. Intra-class Correlation Coefficient (ICC) was used to evaluate intra-examiner reliability, inter-examiner reliability and reliability between two model systems. Paired t test was used to evaluate accuracy between two model systems. Kruskal-Wallis test followed by Mann-Whitney U test was used to evaluate the measurement differences between 3 groups in two model systems. RESULTS: Both intra-examiner and inter-examiner reliability were generally excellent for all measurements made on 3Shape™ digital model and plaster cast (ICC: 0.752-0.993). Reliability between different model systems was also excellent (ICC: 0.897-0.998). Half of the accuracy test showed statistically significant differences (p < 0.05) when digital models were compared with plaster casts. Furthermore, while assessing measurement differences between 3 groups in two model systems, the mandibular required space showed significant difference (p = 0.012) between mild crowding group (0.27 + 0.01 mm) and severe crowding group (0.20 + 0.09 mm). However, the differences were less than 0.5 mm and would not affect clinical decision. CONCLUSION: Using 3Shape™ digital model system instead of plaster casts for orthodontic diagnostic measurements is clinically acceptable.

Comparison of job burnout and life satisfaction between native and foreign female direct care workers in disability institutions.

BACKGROUND: There is little information about the burnout and wellbeing of institutional caregivers working for people with intellectual and developmental disabilities; information is particularly limited in the understanding of experiences of direct care workers. OBJECTIVE: The aims of the study were to provide a profile of self-perceived burnout and wellbeing of direct-care caregivers working in disability institutions, and to compare the difference between native- and foreign caregivers. METHODS: A cross-sectional survey was conducted. We recruited 46 female living assistants of people with intellectual and developmental disabilities in two disability institutions in Taiwan. There were 23 subjects who were local residents and 23 subjects who were foreign providers of labor. A self-administered questionnaire which included scale of the Copenhagen Burnout Inventory (CBI), the Subjective Happiness Scale (SHS), and the Satisfaction with Life Scale (SWLS) were employed in the survey. RESULTS: Findings revealed the local caregivers were slightly higher than foreign caregivers in personal burnout score (PBS) and work-related burnout score (WBS), although there were no significant differences. Those caregivers from foreign countries seem to be slightly happier and have higher life satisfaction than native caregivers. CONCLUSIONS: In order to decrease the burnout and improve wellbeing of caregivers of people with intellectual and developmental disabilities, service providers should understand the experiences which caregivers encounter in their workplaces. Caregivers can benefit if they receive appropriate support to improve positive health while working for their service clients.

Use of "spare parts" in mutilated upper extremity injuries.

Management and treatment of complex mutilated upper extremity injuries often can be challenging and at times seemingly formidable. A reconstructive surgeon's ability to mobilize, transpose, and transfer tissues has allowed not only closure of complex wounds but also restoration of function and form. Use of "spare parts" from an otherwise unsalvageable limb represents the ultimate form of reconstruction that probes the creative mind and challenges the reconstructive knowledge of the surgeon. In this article, the authors review and discuss the use of various "spare parts" in the treatment of mutilating hand injuries.

Secondary procedures following mutilating hand injuries.

Mutilating hand injuries result in injury to multiple anatomic structures, which increases the possibility that secondary procedures or staged reconstruction will be necessary. Secondary procedures often are required to provide stable wound coverage, restore sensation, provide bony stability, increase range of motion, or allow prehension, all of which are performed to improve hand function. The patient, the surgeon, and the therapist must all work together to achieve the best functional result following a severe mutilating hand injury.

Hospital-based integrated diabetes care management: an overview.

To provide continuous, accessible, and quality care, a diabetes share-care program has been in place in Taiwan for several years. Lukang Christian Hospital, a member of the diabetes share-care network, endeavors to provide "patient-centered" care aimed at increasing care quality and reducing diabetic complications. Information technology has been employed by the hospital for monitoring care quality and analyzing cost-effectiveness. Structured health-care programs have also been developed to ensure the completeness of diabetes care and to encourage self-management of individuals at high risk for diabetes. The implementation of these strategies has led to progressive improvement in quality measures and spawned novel and creative ways to deliver care services.

Pharmacist-conducted medication reconciliation at hospital admission using information technology in Taiwan.

OBJECTIVES: Obtaining an accurate medication history upon admission to the hospital can be challenging and time-consuming. This study evaluated the efficacy of a medication reconciliation program, conducted by pharmacists, with the assistance of medication usage data from the Taiwan National Health Insurance (NHI). Characteristics of patients at high risk for drug discrepancies were also determined. METHODS: Patients admitted between May 2008 and September 2009 were recruited. The type and class of medication discrepancies reported by pharmacists, the medication discrepancy rate, physician acceptance rate, and time taken for the intervention were studied. The degree of harm that could have resulted from the discrepancies was independently evaluated by four pharmacists. The association between selected variables and the occurrence of drug discrepancies was analyzed. RESULTS: Among 3013 patients interviewed, the pharmacists identified 243 patients (8%) with at least one medication discrepancy between the patient's medication history and admission orders. There were 576 discrepancies identified. About 19% of the errors prevented could have potentially caused moderate to severe harm. The average time for one intervention was 18±9.8min. The number of preadmission medications, age, frequency of outpatient visits within 3 months prior to this hospital admission, and the number of specialist outpatient clinics the patient had visited within 3 months before the admission were determined to be risk factors for drug discrepancies. CONCLUSIONS: This medication reconciliation program, conducted by pharmacists, was made more efficient by medication usage data from the Taiwan NHI. Pharmacists can reconcile medications more effectively by selecting patients at high risk for unintentional drug discrepancies.

An exploratory study of health behaviors and the risks for triple H (hypertension, hyperlipidemia, and hyperglycemia) in young adults with disabilities between 20 and 39 years of age.

Metabolic syndrome is highly prevalent and has important implications for the health care sector. However, information on the implications of metabolic syndrome for people with disabilities is limited. The purpose of this study was to explore the relationship between health behaviors and the risk for triple H (hypertension, hyperlipidemia, and hyperglycemia) in young adults with disabilities. The present study analyzed the annual health examination charts of 705 young adults with disabilities between ages 20 and 39 in Taiwan. Results found that the prevalence of hyperglycemia, hyperlipidemia, and hypertension in adults with disabilities was 5%, 15% and 17.7%, respectively. These prevalence figures were higher than those for the general population of the same age group in Taiwan. Multivariate logistic regression analyses revealed that almost none of the health behaviors were significantly correlated with the occurrence of triple H disorders among young adults with disabilities. Only one factor, BMI, independently predicted the occurrence of triple H disorders. We suggest that future studies should scrutinize the effects of health behaviors on triple-H disorders in people with disabilities to initiate personalize health promotion programs for this group.

The renin-angiotensin system mediates hyperoxia-induced collagen production in human lung fibroblasts.

A high concentration of oxygen can cause lung injury and lead to pulmonary fibrosis. Angiotensin (Ang) II induces human lung fibroblast proliferation and stimulates collagen synthesis. However, the role of the renin-angiotensin system (RAS) in the pathogenesis of hyperoxia-induced collagen production is unclear. The aims of this study were to investigate the effects of hyperoxia on the components of the RAS and collagen expression in human lung fibroblasts (MRC-5). Hyperoxia increased total collagen, collagen type I, and alpha-smooth muscle actin (alpha-SMA) mRNA and protein expression. RAS components and Ang II production were also significantly increased after hyperoxic exposure. Hyperoxia induced Ang II type 1 receptor (AT1R) expression but did not alter AT2R expression, furthermore, silencing of AT1R signaling with small interfering RNA suppressed hyperoxia-induced phosphorylated-ERK (p-ERK) 1/2, alpha-SMA, and collagen type I expression. Ang II increased p-ERK 1/2 and collagen type I expression, and these increases were inhibited by the AT1R inhibitor, losartan, but not by the AT2R inhibitor, PD123319 under both normoxic and hyperoxic conditions. These data suggest Ang II-mediated signaling transduction via AT1R is involved in hyperoxia-induced collagen synthesis in human lung fibroblasts.