An observational study of hydrodynamic impact on water mass transport due to tidal power generation.

The world's largest Sihwa Tidal Power Plant (TPP), located on the west coast of Korea, was built in 2011 for the purpose of improving water quality and producing renewable energy. After several years of actual operation, most of the original purpose was achieved, but unexpected coastal environmental changes such as tidal flat damage and sediment accumulation also occurred. In this study, in order to understand the causes of these environmental changes, field observations were conducted near TPP, and spatial and temporal variability of flow structure and water exchange process were investigated. Three-dimensional velocity data were collected along the closed line surrounding the outside of the TPP for 11 h during spring tide and analyzed according to two discharge phases: power generation phase (PGP) and drainage phase (DP). The results show that the depth-averaged maximum current velocity was more than three times greater at DP than at PGP. Jet-like flow during DP caused very high horizontal shear, whereas vertical shear was relatively weak, indicating that the horizontal and vertical flow structures were very different. The most notable result is that the mass transport patterns between PGP and DP are significantly different, i.e., during PGP, mass transport is dominated on the left side of the TPP, whereas during DP, it occurs at the front of the TPP. This means that there is a strong spatiotemporal asymmetry between the inflow from the downstream (outside of the TPP) during PGP and the outflow from the upstream (inside of the TPP) during DP. These asymmetric processes can have a significant impact on the material exchange and sediment transport near the TPP. Since observational studies on TPP are extremely rare, this study is expected to contribute to future TPP related research, such as numerical modeling.

Familial patellar dislocation associated with t(15;20) (q24;q13.1).

Patellar instability is a common debilitating injury affecting young active individuals. It accounts for approximately 3% of all knee injuries. We report a family, of which five members across three generations, who suffered from autosomal dominant familial recurrent patellar dislocation as well as short stature. All of them have recurrent patellar dislocations before the age of 15. The affected patients in all three generations have been genetically screened. Genotypical evaluation revealed a balanced translocation of chromosomes 15 and 20.

Proliferative leukoplakia: Proposed new clinical diagnostic criteria.

OBJECTIVE: We aimed to characterize proliferative verrucous leukoplakia (PVL) from a clinical and histopathological standpoint and suggest an updated classification. SUBJECTS AND METHODS: Records of patients seen at three oral medicine centers with a clinical diagnosis of PVL were reviewed for clinical and histopathological features and malignant transformation (MT). RESULTS: There were 42 patients (median age: 69 years [range: 36-88]; 35 females). 12.2% were current smokers. Family history of cancer was present in 43.7% of patients. Partial demarcation of lesion margins was present in 31.3% of lesions, followed by verrucous (27.5%), smooth (22.7%) erythematous (22.3%), and fissured (18.3%) appearance. Large and contiguous and multisite and non-contiguous lesions comprised 57.1% (24/42) and 35.7% (15/42) of PVL cases, respectively. 19.1% had prominent erythema (erythroleukoplakia). The most common histopathological diagnosis at first visit was hyperkeratosis without dysplasia (22/42; 56.4%). MT occurred in 71.4% patients after a median of 37 months [range: 1-210] from initial visit; erythroleukoplakia exhibited MT in 100% of cases. CONCLUSION: The generic term "proliferative leukoplakia (PL)" may be more appropriate than PVL because 18.3% were fissured and 22.7% erythematous. We also propose the term proliferative erythroleukoplakia to more accurately describe the subset of PL with prominent erythema, which had the highest MT rate.

Immunohistopathological characterization and the impact of topical immunomodulatory therapy in oral chronic graft-versus-host disease: A pilot study.

OBJECTIVE: To characterize the immunohistopathological features of oral chronic graft-versus-host disease (cGVHD), and the impact of topical immunomodulatory therapy on the infiltrating cells. MATERIAL AND METHODS: Paired oral cGVHD biopsies obtained before (n = 12) and 1 month after treatment (n = 12) with topical dexamethasone (n = 8) or tacrolimus (n = 4) were characterized by immunohistochemistry using a panel of CD1a, CD3, CD4, CD8, CD20, CD31, CD62E, CD103, CD163, c-kit, and FoxP3. Controls included acute GVHD (aGVHD; n = 3), oral lichen planus (OLP; n = 5), and normal tissues (n = 5). RESULTS: Oral cGVHD specimens prior to treatment were mainly characterized by basal cell squamatization, lichenoid inflammation, sclerosis, apoptosis, and lymphocytic exocytosis. The infiltrating cells in oral cGVHD primarily consisted of CD3+ , CD4+ , CD8+ , CD103+ , CD163+ , and FoxP3+ cells, which were higher than in normal tissues. Topical dexamethasone or tacrolimus reduced neutrophilic exocytosis, basal cell squamatization, and lichenoid inflammation in oral cGVHD, and dexamethasone reduced the number of CD4+ and CD103+ cells. CONCLUSION: The high expression of CD3, CD4, CD8, CD103, CD163, and FoxP3 confirms that oral cGVHD is largely T-cell-driven with macrophage participation. The impact of topical immunomodulatory therapy was variable, reducing histological inflammatory features, but with a weak clinicopathological correlation. Topical dexamethasone reduced the expression of CD4 and CD103, which may offer novel therapeutic targets.

Tumor PD-L1 expression is associated with improved survival and lower recurrence risk in young women with oral cavity squamous cell carcinoma.

Young patients with oral cavity squamous cell carcinoma (OCSCC) are often recognized as a distinct epidemiological cohort. In this study, genomic and immune-based metrics were correlated with long-term outcomes for a young patient population treated at a single institution. A fully clinically annotated, retrospective cohort of 81 patients aged ≤45 years with OCSCC is described, and the impact of clinicopathological features on long-term survival outcomes is reported. Genomic and immune parameters were integrated utilizing a whole-exome sequencing and immunohistochemical approach among females in the cohort. It was found that young OCSCC patients had favorable outcomes (10-year disease-free survival 79.1%, overall survival 80.0%) regardless of sex, particularly if they presented with oral tongue primaries and early stage disease. While mutational analysis appeared similar to that of older patients with OCSCC who lack a smoking history, a comparatively high degree of PD-L1 expression and PD-1/L1 concordance (P=0.001) was found among young female OCSCC patients. Subjects with greater membranous PD-L1 positivity and the presence of tumor-infiltrating lymphocytes had a decreased risk of recurrence (P=0.01 and P=0.01, respectively) and improved survival (P=0.04 and P=0.03, respectively). These findings warrant further validation and support the investigation of immunotherapeutic approaches targeting PD-1/L1 interactions in young OCSCC patients.

Scoring systems for Oral Lichen Planus used by differently experienced raters.

BACKGROUND: Scoring systems have been widely used to evaluate the severity and activity of oral lichen planus (OLP). The aim of the present study was to compare two existing (one modified) scoring systems in the evaluation of OLP severity and correlation with pain. Three differently experienced raters were involved. MATERIALS AND METHODS: Consecutive patients with OLP were assessed for pain using the Visual Analogue Scale and examined at 10 intraoral sites before starting (T0) and three weeks after (T1) steroid therapy (Clobetasol). Three differently experienced raters evaluated photographs using two scoring systems designated White-Erosive-Atrophic (WEA) modified from an older WEA system (WEA-MOD) and Reticular-erythematous-Ulcerative (REU) systems. WEA-MOD Kendall's W and interclass correlation coefficient were calculated and correlation between REU/WEA-MOD and pain was calculated using Spearman coefficient. RESULTS: Most patients showed lesions on buccal mucosa (85-93,5%) and maxillary/mandibular gingivae (31,8-31,2%), predominantly reticular. At T0, Kendall-W coefficients of 0.89 and 0.74 were obtained for the REU and WEA respectively. At T1, Kendall-W coefficients of 0.83 and 0.58 were obtained for the REU and WEA respectively. Interclass correlation coefficient ranged from 0.87 to 0.90 for REU and from 0.58 to 0.87 for WEA. REU and WEA scores significantly decreased after therapy (p<0.000) as well as VAS (p<0.05). REU score showed correlation with VAS. CONCLUSION: All the raters achieved comparable measures using REU whereas WEA and WEA-MOD seem less reproducible. REU seems to correlate to disease activity and pain.

Oral mucous membrane pemphigoid and pemphigus vulgaris-a retrospective two-center cohort study.

OBJECTIVES: Few studies have compared oral mucous membrane pemphigoid (MMP) and pemphigus vulgaris (PV). Descriptive analysis of oral features, extent of extra-oral involvement, and management outcomes were performed. SUBJECTS AND METHODS: Patients with PV and MMP, the latter with exclusive oral involvement at first presentation, were included. RESULTS: There were 26 MMP (46%) and 31 PV (54%) patients. Desquamative gingivitis was evident in 84% of MMP cases compared to 28% of PV cases (P < 0.05). Non-gingival lesions were noted in 6% of MMP cases compared to 55% of PV cases (P < 0.01). Management of MMP consisted of only topical corticosteroids in 88% of cases while 12% of cases required concomitant systemic therapy. All PV cases (100%) required systemic therapy. No patients with MMP developed scarring or ocular lesions, and one patient (4%) developed cutaneous lesions. Five PV cases (16%) had oral cavity involvement only with three (60%) developing pharyngeal involvement and two (40%) developing cutaneous lesions on follow-up. CONCLUSION: Oral MMP presents primarily as desquamative gingivitis, infrequently involving extragingival sites, and is highly amenable to topical therapy, while PV is a systemic mucocutaneous disease with extensive non-gingival oral lesions that almost always requires systemic therapy.

Atypical periprosthetic femoral fracture: a case report.

We report an 82-year-old woman who underwent fixation with a long-spanning cable-plate for a bisphosphonate-induced Vancouver B1 periprosthetic femoral fracture. Non-union and breakage of the plate occurred at 16 months and necessitated revision surgery using a long-stem femoral prosthesis augmented with a cable-plate construct. Bone union was achieved eventually after 10 months.

Resource utilization in cancer patients with bisphosphonate-associated osteonecrosis of the jaw.

BACKGROUND AND OBJECTIVE: Bisphosphonate-associated osteonecrosis of the jaw (BONJ) is an emerging oral complication that occurs most commonly in the setting of high-dose bisphosphonate therapy for cancer. The purpose of this study was to estimate the health care-related costs associated with a diagnosis of BONJ in patients with cancer evaluated and managed at one tertiary oral medicine practice. METHODS: This was a retrospective electronic medical record review of cancer patients with BONJ. All health care-related resources were abstracted using a structured chart abstraction tool; data captured included medications, imaging studies, laboratory investigations, procedures, and visits. Standardized references were used to assign costs in 2010 US dollars. RESULTS: Ninety-two cancer patients with BONJ were identified who were followed for a median of 12 months. The median cost of a case of BONJ was $1667 (interquartile range from $976 to $3350). Medication costs comprised the majority (42%) of the total costs, followed by procedural interventions (22%), clinic visits (19.5%), and imaging studies (13.8%). Patient factors associated with higher median costs included a greater number of involved oral quadrants and more advanced BONJ stage. CONCLUSION: There are considerable costs associated with the diagnosis and management of BONJ in patients with cancer, with medications accounting for nearly half of resource expenditures.

Defining the epidemiology of bisphosphonate-associated osteonecrosis of the jaw: prior work and current challenges.

UNLABELLED: Bisphosphonate-related osteonecrosis of the jaw (BONJ) is an adverse effect of bisphosphonate use with a poorly described epidemiology in osteoporosis patients. We examined the literature and two new cohorts for BONJ. The literature suggests an incidence rate of 0.028 % to 4.3 %. Our cohort studies found an incidence of 0.02 % (95 % CI 0.004 %-0.11 %). INTRODUCTION: We examined the epidemiology of BONJ associated with osteoporosis dosing of bisphosphonates. METHODS: First, we systematically searched the literature about osteoporosis BONJ. Identified studies were abstracted by two authors. Second, we attempted to estimate the relative risk of BONJ among bisphosphonate users with osteoporosis. Two different large insurance databases, one from 2005-2007 and another from 2007-2010, combined with medical record review, were searched. The older dataset did not include the International Classification of Diagnoses (ICD) diagnosis code for osteonecrosis of the jaw (ONJ; ICD 733.45). Incidence rates and relative risks were estimated using Cox regression. RESULTS: The literature review produced nine studies of varying quality. The incidence rates for BONJ among osteoporosis patients varied from 0.028 % to 4.3 %. Two prior studies estimated the relative risk of ONJ related to bisphosphonates and found odds ratios of 7.2 and 9.2. Our attempts to estimate the incidence rate of BONJ encompassed 41,957 in the dataset from 2005-2007 and 466,645 in a separate dataset from 2007-2010. From the older dataset, we found 51 potential cases of BONJ using a broad definition of possible ONJ. One case was confirmed by a dentist for a prevalence of 0.02 % (95 % CI 0.004 %-0.11 %) among bisphosphonate users. From the newer dataset, we found 13 possible cases, but none could be confirmed. Most subjects with the ONJ diagnosis code appeared to have had an osteoporosis-related fracture and not ONJ. CONCLUSIONS: The literature suggests a broad range of possible values for the prevalence of BONJ; our estimate fell within the range from prior literature.

Hyaluronic acid instillation following arthroscopic anterior cruciate ligament reconstruction: a double-blinded, randomised controlled study.

PURPOSE: To assess the effect of hyaluronic acid instillation after arthroscopic anterior cruciate ligament (ACL) reconstruction for improving pain, range of movement, and function of the knee. METHODS: 28 men and 4 women underwent arthroscopic ACL reconstruction for isolated ACL rupture (partial or complete) and instability after recreational sports injury 2 to 120 months earlier. They were randomised to undergo arthroscopic ACL reconstruction followed by intra-articular viscoseal instillation (13 men and 3 women) or arthroscopic ACL reconstruction alone (15 men and 1 woman). The knee injury osteoarthritis outcome score (for pain, symptoms, activities of daily living, sport and recreation function, and quality of life), range of movement, knee circumference, and analgesic use were assessed on days -1, 1, and 2, and weeks 2, 6 and 12. RESULTS: Patient demographics were similar at baseline. At postoperative days 1 and 2, all subscales of the knee injury osteoarthritis outcome score (except for quality of life) were significantly higher in the viscoseal group. At weeks 2, 6, and 12, improvement in both groups equalised. Knee swelling (change in knee circumference) was significantly less in the viscoseal group at days 1 and 2 (p=0.009 and p=0.038, respectively, Mann-Whitney U test). Only one patient in the viscoseal group had a limited range of movement. No patient developed any adverse reaction. CONCLUSION: Intra-articular viscoseal instillation improved pain control and swelling 2 days after arthroscopic ACL reconstruction.

A role of oral bacteria in bisphosphonate-induced osteonecrosis of the jaw.

No consensus has yet been reached to associate oral bacteria conclusively with the etio-pathogenesis of bisphosphonate-induced osteonecrosis of the jaw (BONJ). Therefore, the present study examined the effects of oral bacteria on the development of BONJ-like lesions in a mouse model. In the pamidronate (Pam)-treated mice, but not control non-drug-treated mice, tooth extraction followed by oral infection with Fusobacterium nucleatum caused BONJ-like lesions and delayed epithelial healing, both of which were completely suppressed by a broad-spectrum antibiotic cocktail. Furthermore, in both in vitro and in vivo experiments, the combination of Pam and Fusobacterium nucleatum caused the death of gingival fibroblasts (GFs) and down-regulated their production of keratinocyte growth factor (KGF), which induces epithelial cell growth and migration. Therefore, in periodontal tissues pre-exposed to bisphosphonate, bacterial infection at tooth extraction sites caused diminished KGF expression in GFs, leading to a delay in the epithelial wound-healing process that was mitigated by antibiotics.

Oral epithelial dysplasia and squamous cell carcinoma following allogeneic hematopoietic stem cell transplantation: clinical presentation and treatment outcomes.

Late complications of allogeneic hematopoietic stem cell transplantation (HSCT) include a risk of secondary malignancies. Optimization for early diagnosis and treatment of oral premalignant or malignant lesions requires an assessment of potential predisposing risk factors. The medical records of patients who developed oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC) following allogeneic-HSCT were reviewed. Data on HSCT course, chronic graft-versus-host disease (cGVHD), and clinical outcome were recorded; landmark survival was calculated. Twenty-six patients with OED (n=8) and OSCC (n=18) were identified with a median follow-up of 26.5 and 21.5 months, respectively. Premalignant and malignant oral lesions were diagnosed at a median time of 2.5 and 8 years after HSCT, respectively. Chronic GVHD was present in 96% of patients and of these, 96% had oral involvement. Multifocal oral cancer was found in 28% of cases, and localized recurrence was observed in 44% of cases. These results suggest that oral cGVHD may be considered a potential risk factor for the development of OSCC following allogeneic-HSCT. The observation that oral cancers were frequently multifocal and recurred locally suggests that these cancers may be more aggressive. Vigilant follow-up and coordination of care are critical.

Genetics/epigenetics of oral premalignancy: current status and future research.

Squamous cell carcinoma (SCC) of the oral and oropharyngeal region is the sixth most common malignancy in the world today. Despite numerous advances in treatment, long-term survival from this disease remains poor. Early detection can decrease both morbidity and mortality associated with this neoplasm. However, screening for potentially malignant disease is typically confounded by difficulty in discriminating between reactive/inflammatory lesions vs those lesions that are premalignant in nature. Furthermore, the histologic diagnosis of dysplasia can be subjective and is thus prone to a considerable range of interpretation. Similarly, no definitive, validated criteria exist for predicting which dysplastic lesions are most likely to progress to cancer over time. Given this state of science, the presence of dysplasia can only be used to indicate that an oral lesion may have an increased risk of malignant transformation. Molecular biomarkers capable of identifying the subset of lesions likely to progress to cancer are required to eliminate this clinical diagnostic dilemma. The purpose of this review is to assess the current state of knowledge regarding genetic/epigenetic alterations observed in oral mucosal premalignancy. In addition, recommendations for future research studies directed at defining the predictive capacity of specific biomarkers in this modeling are presented.

Sirolimus oral ulcer with Cedecea davisae superinfection.

Cedecea davisae is a member of the Enterobacteriaceae family and is an uncommon pathogen. This organism has been isolated from the blood, sputum, and cutaneous ulcers of only a handful of patients, most of these being elderly or otherwise medically compromised. This is a report of a patient, status post renal transplantation, who developed an oral ulcer associated with sirolimus use and superinfected with C. davisae. According to the literature, this is the first case of C. davisae detected in the oral cavity. Antibiotic therapy led to prompt resolution of this very large ulcer.

Comparison of total knee arthroplasty using computer-assisted navigation versus conventional guiding systems: a prospective study.

PURPOSE: To compare knee alignments in total knee arthroplasty (TKA) using computer-assisted navigation versus conventional guiding systems. METHODS: Five men and 49 women aged 49 to 79 years underwent TKA for primary osteoarthritis of the knee with varus deformity. All valgus knees were associated with inflammatory arthritis and thus excluded. Computer-assisted navigation was used for the first 35 TKAs, whereas conventional extramedullary tibial and intramedullary femoral guiding systems were used for the next 35 TKAs. The mechanical axis, coronal tibial and femoral angles, sagittal tibial and femoral angles in the 2 groups were compared. RESULTS: Sagittal tibial and femoral angles aligned more optimally in TKAs using computer-assisted navigation. In the respective computer-assisted navigation and conventional guiding systems, 33 (94%) and 26 (74%) of the TKAs attained a postoperative mechanical axis of <3 degrees varus/valgus. CONCLUSION: Computer-assisted navigation gives a more consistent alignment correction and reduces outliers during implant positioning.

The binding of zinc and copper ions to nerve growth factor is differentially affected by pH: implications for cerebral acidosis.

It has recently been shown that transition metal cations Zn2+ and Cu2+ bind to histidine residues of nerve growth factor (NGF) and other neurotrophins (a family of proteins important for neuronal survival) leading to their inactivation. Experimental data and theoretical considerations indicate that transition metal cations may destabilize the ionic form of histidine residues within proteins, thereby decreasing their pK(a) values. Because the release of transition metal cations and acidification of the local environment represent important events associated with brain injury, the ability of Zn2+ and Cu2+ to bind to neurotrophins in acidic conditions may alter neuronal death following stroke or as a result of traumatic injury. To test the hypothesis that metal ion binding to neurotrophins is influenced by pH, the effects of Zn2+ and Cu2+ on NGF conformation, receptor binding and NGF tyrosine kinase (trkA) receptor signal transduction were examined under conditions mimicking cerebral acidosis (pH range 5.5-7.4). The inhibitory effect of Zn2+ on biological activities of NGF is lost under acidic conditions. Conversely, the binding of Cu2+ to NGF is relatively independent of pH changes within the studied range. These data demonstrate that Cu2+ has greater binding affinity to NGF than Zn2+ at reduced pH, consistent with the higher affinity of Cu2+ for histidine residues. These findings suggest that cerebral acidosis associated with stroke or traumatic brain injury could neutralize the Zn2+-mediated inactivation of NGF, whereas corresponding pH changes would have little or no influence on the inhibitory effects of Cu2+. The importance of His84 of NGF for transition metal cation binding is demonstrated, confirming the involvement of this residue in metal ion coordination.