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Machine learning is a rapidly growing subset of artificial intelligence (AI) which involves computer algorithms that automatically build mathematical models based on sample data. Systems can be taught to learn from patterns in existing data in order to make similar conclusions from new data. The use of AI in facial emotion recognition (FER) has become an area of increasing interest for providers who wish to quantify facial emotion before and after interventions such as facial reanimation surgery. While FER deep learning algorithms are less subjective when compared to layperson assessments, the databases used to train them can greatly alter their outputs. There are currently many well-established modalities for assessing facial paralysis, but there is also increasing interest in a more objective and universal measurement system to allow for consistent assessments between practitioners. The purpose of this article is to review the development of AI, examine its existing uses in facial paralysis assessment, and discuss the future directions of its implications.

Lymph node status is regarded as an important factor in the prognosis of oesophageal cancer. T1 oesophageal adenocarcinoma management has to include endoscopic management as part of the algorithm. We reviewed the literature to assess the true risk of lymph node metastasis in patients with T1 oesophageal adenocarcinoma. Medline, Embase, PubMed and Cochrane where searched for manuscripts in English reviewing lymph node metastasis in superficial (T1) oesophageal adenocarcinoma. The main outcome was probability of lymph node metastasis in T1a and T1b oesophageal adenocarcinoma. Secondary outcome was the rate of lymph node metastasis of submucosal involvement of T1b (SM1, SM2 and SM3). There were 38 studies identified. 22 studies were excluded due to low lymph node yield (

Purpose Over the past two decades, the proliferation of endovascular surgery has changed the approach to abdominal aortic aneurysm (AAA) repair. In Australia, close to two-thirds of surgical procedures are performed in the private healthcare system. We aimed to describe the trends in AAA repair in the Australian private sector throughout the early 21st century. Materials and Methods Medicare Benefits Schedule (MBS) statistics were accessed to determine the number of infrarenal open AAA repair (OAR) and endovascular AAA repair (EVAR) procedures performed between January 2000 and December 2019. Population data were extracted from the Australian Bureau of Statistics and used to calculate incidence per 100,000 population. Further analysis was performed according to age, gender, and state. Results During the study period, 13,193 (67.0%) EVARs and 6504 (33.0%) OARs were performed in the Australian private sector. OARs fell from 70.5% (n=567) of AAA repairs in 2000 to 15.7% (n=237) in 2019, while EVARs rose from 29.5% (n=151) to 84.3% (n=808). The frequency of EVAR surpassed OAR in 2004. The overall incidence of AAA repair varied minimally over the time period (range: 4.9–6.5 per 100,000 adults per year). AAA repair was more common in males than females (9.7 vs 1.7 per 100,000 population) and more common in older age groups. There was a 4-fold increase in EVAR among males older than 85 years (12.8–57.4 per 100,000 population), the largest rise of any group. The overall EVAR:OAR ratio increased from 0.4 to 5.4. There were considerable state-based discrepancies. Conclusion The landscape of AAA repair in Australian private sector has drastically changed with a clear preference toward EVAR. EVAR saw increased use across all genders, age groups and states, despite stable rates of AAA surgery. Further research is necessary to compare our findings to national trends in the Australian public sector.

PURPOSE Diabetic foot ulcers afflict a quarter of type-2 diabetes mellitus patients and are associated with higher mortality rates among people with diabetes. Routine primary and preventive care is essential to both prevent and treat foot ulcers before they can contribute to further adverse outcomes. One approach for expanding this care to people with diabetes in rural communities is increasing the practice authority of nurse practitioners. This study examines whether the presence of nurse practitioner practice authority is associated with fewer foot ulcer complications in rural populations as measured through the incidence of foot debridement-a common procedure for addressing severe diabetic foot ulcers. METHODS This study uses medical claims to estimate the incidence of foot debridement for US counties. A multivariable linear regression was performed to examine the association between nurse practitioner practice authority and the county incidence of foot debridement after adjusting for measures of local health care workforce and sociodemographics. FINDINGS Nurse practitioner practice authority was associated with 219.4 fewer foot debridements per 10,000 enrollees (P < .001) in rural counties. Rural health clinics (P < .03) and skilled nursing facilities (P < .03) were also associated with fewer rural debridements. The number of nurse practitioners (P < .69) and primary care physicians (P < .69) per enrollee were not significant. No measure of health care workforce was associated with the incidence of foot debridement in urban counties. CONCLUSIONS Expanding nurse practitioner practice authority may be an effective solution for preventing complications from diabetic foot ulcers in rural communities.

Obesity is common comorbidity in patients with schizophrenia. Previous studies have reported that homocysteine (Hcy) is increased in schizophrenia. However, no study has reported the association between BMI and Hcy levels in schizophrenia. This cross-sectional naturalistic study aimed to evaluate the relationship between BMI, Hcy and clinical symptoms in Chinese Han patients with chronic schizophrenia. Clinical and anthropometric data as well as plasma Hcy level and glycolipid parameters were collected. Psychopathology was measured with the Positive and Negative Syndrome Scale (PANSS). Our results showed that compared with the low BMI group, the high BMI group had a higher PANSS general psychopathology subscore, higher levels of blood glucose, total cholesterol and high-density lipoprotein (HDL) cholesterol (all p p p

Background: The availability and diversity of lower limb revascularization procedures have increased in England in the past decade. We investigated whether these developments in care have translated to improvements in patient pathways and outcomes. Methods: Individual-patient records from Hospital Episode Statistics were used to identify 103 934 patients who underwent endovascular (angioplasty) or surgical (endarterectomy, profundaplasty, or bypass) lower limb revascularization for infrainguinal peripheral artery disease in England between January 2006 and December 2015. Major lower limb amputations and deaths within 1 year after revascularization were ascertained from Hospital Episode Statistics and Office for National Statistics mortality records. Competing risks regression was used to estimate the cumulative incidence of major amputation and death, adjusted for patient age, sex, comorbidity score, indication for the intervention (intermittent claudication, severe limb ischemia without record of tissue loss, severe limb ischemia with a record of ulceration, severe limb ischemia with a record of gangrene/osteomyelitis), and comorbid diabetes mellitus. Results: The estimated 1-year risk of major amputation decreased from 5.7% (in 2006–2007) to 3.9% (in 2014–2015) following endovascular revascularization, and from 11.2% (2006–2007) to 6.6% (2014–2015) following surgical procedures. The risk of death after both types of revascularization also decreased. These trends were observed for all indication categories, with the largest reductions found in patients with severe limb ischemia with ulceration or gangrene. Overall, morbidity increased over the study period, and a larger proportion of patients was treated for the severe end of the peripheral artery disease spectrum using less invasive procedures. Conclusions: Our findings show that from 2006 to 2015, the overall survival increased and the risk of major lower limb amputation decreased following revascularization. These observations suggest that patient outcomes after lower limb revascularization have improved during a period of centralization and specialization of vascular services in the United Kingdom.

A vailable tyrosine kinase inhibitors for chronic myeloid leukemia bind in an adenosine 5′-triphosphate-binding pocket and are affected by evolving mutations that confer resistance. Rebastinib was identified as a switch control inhibitor of BCR-ABL1 and FLT3 and may be active against resistant mutations. A Phase 1, first-in-human, single-agent study investigated rebastinib in relapsed or refractory chronic or acute myeloid leukemia. The primary objectives were to investigate the safety of rebastinib and establish the maximum tolerated dose and recommended Phase 2 dose. Fifty-seven patients received treatment with rebastinib. Sixteen patients were treated using powder-in-capsule preparations at doses from 57 mg to 1200 mg daily, and 41 received tablet preparations at doses of 100 mg to 400 mg daily. Dose-limiting toxicities were dysarthria, muscle weakness, and peripheral neuropathy. The maximum tolerated dose was 150 mg tablets administered twice daily. Rebastinib was rapidly absorbed. Bioavailability was 3- to 4-fold greater with formulated tablets compared to unformulated capsules. Eight complete hematologic responses were achieved in 40 evaluable chronic myeloid leukemia patients, 4 of which had a T315I mutation. None of the 5 patients with acute myeloid leukemia responded. Pharmacodynamic analysis showed inhibition of phosphorylation of substrates of BCR-ABL1 or FLT3 by rebastinib. Although clinical activity was observed, clinical benefit was insufficient to justify continued development in chronic or acute myeloid leukemia. Pharmacodynamic analyses suggest that other kinases inhibited by rebastinib, such as TIE2, may be more relevant targets for the clinical development of rebastinib (clinicaltrials.gov Identifier:00827138).

To explore the preventive effect of a prophylactic oral and maxillofacial treatment to reduce bisphosphonate associated necrosis of the jaws (BRONJ) in metastatic prostate cancer (PC) patients treated with zoledronic acid (4.0 mg i.v./months).253 PC patients with bone metastases were prospectively randomized. All patients received baseline assessments including a dental panoramic tomogram. Group A was monitored and treated where deemed necessary by the patient's dentist and were re-evaluated once a year. In group B patients were monitored and treated where necessary by the authors at 12 week intervals. We compared the incidence rate per year (IR) and incidence proportion (IP) in both cohorts and assessed independent risk factors for BRONJ.Patients in group A were evaluated 3.2 (range 2-4) vs. 6.8 times (range 4-24) in group B. A significantly higher proportion of dental extractions was performed in group B vs. A (26.7% vs. 22.7%, p = 0.006). A BRONJ was detected with an IP of 23.3% vs. 2.2% in group A vs. B, revealing a 2.59 fold higher relative risk for group A (p = 0.01, 95% CI 0.01-0.56). The IR in group A was 0.073 cases/year while the IR in group B was significantly decreased by 82% to 0.0131 (p 0.001). Extraction therapy was the only independent risk factor for BRONJ (p 0.0001; 95% CI 21.22-189.06).Preventive oral and maxillofacial treatment before bisphosphonate application combined with 3-monthly dental follow-ups significantly reduces the occurrence and risk of BRONJ in PC patients. Therefore this approach should be implemented in the specific treatment algorithms.

Endothelial dysfunction is a hallmark of systemic inflammatory response underlying multiple organ failure. Here we report a novel function of DHHC-containing palmitoyl acyltransferases (PATs) in mediating endothelial inflammation. Pharmacological inhibition of PATs attenuates barrier leakage and leucocyte adhesion induced by endothelial junction hyperpermeability and ICAM-1 expression during inflammation. Among 11 DHHCs detected in vascular endothelium, DHHC21 is required for barrier response. Mice with DHHC21 function deficiency (Zdhhc21dep/dep) exhibit marked resistance to injury, characterized by reduced plasma leakage, decreased leucocyte adhesion and ameliorated lung pathology, culminating in improved survival. Endothelial cells from Zdhhc21dep/dep display blunted barrier dysfunction and leucocyte adhesion, whereas leucocytes from these mice did not show altered adhesiveness. Furthermore, inflammation enhances PLCβ1 palmitoylation and signalling activity, effects significantly reduced in Zdhhc21dep/dep and rescued by DHHC21 overexpression. Likewise, overexpression of wild-type, not mutant, PLCβ1 augments barrier dysfunction. Altogether, these data suggest the involvement of DHHC21-mediated PLCβ1 palmitoylation in endothelial inflammation., Breaking down the endothelial barrier is a hallmark of systemic inflammatory response syndrome. Here the authors show that palmitoylation, a post-translational modification of proteins, plays a critical role in altering endothelial function during inflammation, and suggest the targeting of palmitoyl acyltransferase DHHC21 as potential disease therapy.

In the surgical management of oral squamous cell carcinoma (SCC) we aim to resect the tumour with clear margins in all planes. The aim of this study was to identify and compare overall survival in a group of 591 patients who had resections, and to relate this to the clearance of margins at the tumour bed. We used life tables to calculate survival at one, two, three, five, and 10 years after diagnosis by margin (clear=5mm or more; close=2-5mm; and involved=less than 2mm). Kaplan-Meier curves were produced for the margins alone, which were defined as clear in 480 patients (81%), close in 63 (11%), and involved in 48 (8%). Five-year survival was 81%, 75%, and 54% for clear, close, and involved margins, respectively, which highlights the importance of clear margins for survival. There is a significant prognostic implication associated with close, and particularly with involved, margins.

Background Although treatment of mild peri-prosthetic infection in implant-based breast reconstruction results in high rates of resolution, successful management of severe peri-prosthetic infection remains a significant challenge. Methods In this case series, a protocol utilizing a novel dressing – negative pressure wound therapy with instillation (NPWTi) – for the management of severe peri-prosthetic infection in breast reconstruction patients is described. This is an operative technique involving: (i) explantation of the breast prosthesis and application of the NPWTi dressing to the implant pocket; (ii) change of the NPWTi dressing; (iii) intraoperative fluid/tissue cultures; and (iv) reimplantation of the breast prosthesis when cultures yield no growth. Results This protocol was utilized in six cases of severe peri-prosthetic infection in five patients with immediate breast reconstruction for breast cancer or risk-reducing surgery. Cultures of fluid/tissue grew typical and/or unusual organisms. Only one case did not yield an organism. The hospital length of stay upon completion of the protocol ranged from 7–16 days (mean, 12 days). Successful implant salvage was achieved in five of six cases. The protocol was aborted in one case to allow for completion of adjuvant chemotherapy. Conclusions Early findings from this case series suggest that in cases of severe peri-prosthetic infection this novel operative protocol may result in successful implant salvage for breast reconstruction patients. Further studies are needed to more fully elaborate the role of NPWTi to achieve implant salvage in challenging cases of peri-prosthetic infection.

Patient reported outcomes following head and neck cancer are of great importance, given the functional, psychological, and social impacts of the disease and its treatment. In addition, not only is the number of publications on health-related quality of life (HRQOL) increasing in a variety of specialties, but there is also a growing awareness of the potential role of HRQOL in practice. Therefore, we aimed to investigate the HRQOL of head and neck cancer patients following different oncologic interventions, using an internationally established test. In this cross-sectional study, we included three different groups of 32 patients each. Participants had histologically confirmed invasive oral squamous cell carcinoma (OSCC) in the anterior floor of the mouth. Group allocation was based on treatment modality, as follows: only surgery (group 1), operation and adjuvant radiotherapy (XRT) (group 2), and the additional presence of osteoradionecrosis (ORN) (group 3). All patients were questioned about their HRQOL, using the standardized University of Washington Quality of Life Questionnaire (UW-QOL). Surveys for groups 1 and 2 were conducted at least 24 months after the end of tumor-related treatment, in cases of ORN (group 3) 12 months after completion of disease-related treatment. A total of 96 patients were included into this study. The mean age was 62.79 ± 8.93 years. The patients in groups 1 and 2 revealed a reduced quality of life, of a greater magnitude after radiation therapy. Patients felt that radiotherapy was much worse than surgery; however, half of the patients stated that they would repeat radiation therapy if necessary. The subjective evaluation of the HRQOL after surgery and radiotherapy was a valuable instrument for assessing the rehabilitation of patients in the context of their function and quality of life. Radiation therapy can be considered a trigger of functional limitations and emotional distress that contributes to decreased HRQOL in patients with head and neck cancer.

It is now widely accepted that cancer is a chronic disease, and in this context we have previously highlighted shortcomings in the assessment of problems with intimacy and sexuality in patients treated for cancer of the head and neck. In this paper we introduce established strategies for the diagnosis and treatment of psychosexual problems to support these patients, and describe our early experiences of their use. We include brief narratives and case reports to show how they have made a difference to patients and their partners.

Problems with intimacy in patients with cancer of the head and neck may not be recognised. Our aim was to review published papers on patient-reported outcomes that record concerns about intimacy, sex, and function, to help develop a tool for use in head and neck cancer. We specifically looked for instruments with evidence of validation in patients with cancer, which could be used to identify problems with intimacy and sexuality. After evaluating 2563 papers, we identified 20 that satisfied our inclusion criteria, and these have been presented in a tabulated form. This review has shown the need to develop a questionnaire on intimacy that is specific to patients with cancer of the head and neck. It is an important issue that must be addressed by clinical and research teams, and will be done most effectively if it is linked to specific interventions.

In September 2014 the Joint Committee on Vaccination and Immunisation (JCVI) recommended a small extension to the provision of human papillomavirus (HPV) vaccination beyond girls aged 12–13 years. This applied to men who have sex with men and shows a limited receptiveness to existing evidence in relation to the concept of ‘herd protection’ as well as the increasing incidence of HPV-driven oropharyngeal cancer (in both sexes, but men more than women) and anal cancer (in both sexes but particularly in women).

Primary ciliary dyskinesia (PCD) is a genetically and phenotypically heterogeneous disorder characterized by destructive respiratory disease and laterality abnormalities due to randomised left-right body asymmetry. PCD is mostly caused by mutations affecting components of the core axoneme structure of motile cilia that are essential for cilia movement. In addition, there is a growing group of PCD genes that encode proteins essential for the assembly of the ciliary dynein motors and the active transport process that delivers them from their cytoplasmic assembly site into the axoneme. We screened a cohort of affected individuals for disease-causing mutations using a targeted next generation sequencing panel and identified 2 unrelated families (3 affected children) with mutations in the uncharacterized C11orf70 gene. The affected children share a consistent PCD phenotype from early life with laterality defects and immotile respiratory cilia displaying combined loss of inner and outer dynein arms (IDA+ODA). Phylogenetic analysis shows C11orf70 is highly conserved, distributed across species similarly to proteins involved in the intraflagellar transport (IFT)-dependant assembly of axonemal dyneins. Paramecium C11orf70 RNAi knockdown led to combined loss of ciliary IDA+ODA with reduced cilia beating and swim velocity. Fluorescently tagged C11orf70 in Paramecium and Chlamydomonas localises mainly in the cytoplasm with a small amount in the ciliary component, its abundance in the axoneme being IFT-dependant. During ciliogenesis, C11orf70 accumulates at the ciliary tips in a similar distribution to the IFT-B protein IFT46. In summary, C11orf70 is essential for IFT-dependant assembly of dynein arms and C11orf70 mutations cause defective cilia motility and PCD.

BACKGROUND The objective of this study was to identify molecular alterations associated with disease outcomes for white and black patients with endometrioid endometrial cancer (EEC). METHODS EEC samples from black (n = 17) and white patients (n = 13) were analyzed by proteomics (liquid chromatography–tandem mass spectrometry) and transcriptomics (RNA-seq). Coordinate alterations were validated with RNA-seq data from black (n = 49) and white patients (n = 216). Concordantly altered candidates were further tested for associations with race-specific progression-free survival (PFS) in black (n = 64) or white patients (n = 267) via univariate and multivariate Cox regression modeling and log-rank testing. RESULTS Discovery analyses revealed significantly altered candidate proteins and transcripts between black and white patients, suggesting modulation of tumor cell viability in black patients and cell death signaling in black and white patients. Eighty-nine candidates were validated as altered between these patient cohorts, and a subset significantly correlated with differential PFS. White-specific PFS candidates included serpin family A member 4 (SERPINA4; hazard ratio [HR], 0.89; Wald P value = .02), integrin subunit α3 (ITGA3; HR, 0.76; P = .03), and Bet1 Golgi vesicular membrane trafficking protein like (BET1L; HR, 0.48; P = .04). Black-specific PFS candidates included family with sequence similarity 228 member B (FAM228B; HR, 0.13; P = .001) and HEAT repeat containing 6 (HEATR6; HR, 4.94; P = .047). Several candidates were also associated with overall survival (SERPINA4 and ITGA3) as well as PFS independent of disease stage, grade and myometrial invasion (SERPINA4, BET1L and FAM228B). CONCLUSIONS This study has identified and validated molecular alterations in tumors from black and white EEC patients, including candidates significantly associated with altered disease outcomes within these patient cohorts. Cancer 2017;123:4004-12. © 2017 American Cancer Society.

The TNM classification is used to assess cancers of the oral cavity, and advancements in imaging techniques have revealed clear variations in tumor volume at presentation. This study therefore aimed to clarify whether preoperative imaging, with exact measurements of the tumor, could affect post-surgery survival after controlling for demographic, clinical, and tumor characteristics. We included 437 patients with histologically confirmed, stage T1–4, N1–3, M0, invasive squamous cell carcinoma of the tongue. Participants were assessed for recurrence every 3 months for the first 2 years, every 6 months for another 2 years, and annually thereafter; routine computed tomography was performed annually. Associations were determined using the Kaplan–Meier estimator, univariate log-rank test, and Cox proportional hazards regression models. The mean survival of all patients was 68.1 ± 48.2 months. The 2- and 5-year overall survival rates were 82.2 and 66.7 %, respectively. The mean primary tumor volume was 7.14 cm3 with a range of 1.3–24.21 cm3. The ROC curve and Youden Index analysis revealed that the optimal cutoff volume was between ≤5.9 and ≤18.3 cm3 for three different volume groups (p

Understanding the role of environmental support that home offers and the measures older adults take to deal with memory issues can provide useful insights in the design of memory support systems. One of the main objectives of this research was to understand the nature and context of memory failures and successes older adults experience in the home. In particular we compared the specifics of memory issues within health and social domains and the strategies and support aids used to address those issues. Self-reports about memory functioning were gathered from 26 independently living older adults (65-80 years in age) through structured interviews and a memory questionnaire. Overall, more problems, more frequent forgetting, and less effective strategies were reported for remembering names and conversations compared to other social/interpersonal activities and health-related tasks. We infer that strategies and memory supports that work for prospective memory do not work as well for retrospective social tasks.

Osteosarcomas of the craniomaxillofacial region in adults are rare malignant tumors with many sites of origin. The purpose of this study was to analyze the outcome of adult patients suffering from osteosarcomas and investigate whether neoadjuvant chemotherapy would be beneficial to overall outcome.The medical records of 36 patients treated during 2002-2012 were reviewed. All patients suffered from primary osteosarcomas of the craniomaxillofacial region.The mean survival of patients was 64.49 ± 23.52 months. The 2- and 5-year overall survival rates in the neoadjuvant treatment group were 100 and 66.7 %; in the surgery only group, the overall survival rates were 66.7 and 41.7 %, respectively. The neoadjuvant treatment (p = 0.017), tumor size (p = 0.004), tumor location (p = 0.02), and age (p 0.0001) were significant parameters influencing survival, whereas other tumor-related or demographic factors had no significant influence on survival.Early identification of osteosarcoma of the craniomaxillofacial region and combined treatment by neoadjuvant chemotherapy with radical surgery are the most important strategies in dealing with these sarcomas. If possible, this treatment option should be followed unless contraindicated by other factors.

The treatment of end stage renal failure is renal replacement therapy. This may be by dialysis (blood or peritoneal) or by kidney transplantation. The outlook for those who have a successful renal transplant has improved massively over the past 20 years with graft survival of a mean of 14 years from non-heart beating donation and 18 years for live donated transplant. Unfortunately the number of renal transplants fails to meet the demand from patients on the transplant waiting list. The shortfall has to be managed by dialysis. The life expectancy of a patient on haemodialysis is a fifth to a quarter of that of age-matched healthy population, but doubles following successful transplantation. To provide blood or peritoneal dialysis, patients require a portal of access to the circulation or the peritoneum. This patient group requires timely and well-planned renal access surgery. Their access is their lifeline and failure of access coupled with the need for emergency admission is a major cause of morbidity and mortality.

The aim of this study was to evaluate the impact of expression of epidermal growth factor receptor (EGFR), mesenchymal-epithelial transition factor (c-Met), and insulin-like growth factor receptor 1 (IGF-1R) protein on response to treatment and survival in patients with oral and oropharyngeal squamous cell carcinoma (SCC). EGFR, c-Met, and IGF-1R immunohistochemical (IHC) scores were generated based on the incidence and intensity of expression of the biomarkers evaluated in paraffin-embedded sections of biopsy specimens taken before treatment from 113 patients given neoadjuvant chemoradiotherapy followed by resection for primary locally advanced oral and oropharyngeal SCC. Correlations were assessed between the IHC of the biomarkers and the patients' clinicopathological variables using Spearman's rank test. Cox's regression models were used to evaluate the impact of EGFR, c-Met, and IGF-1R, expression on survival. Almost all the patients showed expression of EGFR, c-Met, and IGF-1R (99%, 100%, and 100%, respectively). None of the biomarkers examined predicted response to neoadjuvant chemoradiotherapy or were associated with survival. In multivariate analysis, age (p=0.05), alcohol consumption (p=0.03), and pathological size/extent of the primary tumour after neoadjuvant treatment (ypT) status (p=0.009) were significantly associated with recurrence-free survival. Age (p=0.02) and alcohol consumption (p=0.02) were independently associated with overall survival. Although none of the biomarkers evaluated could be used as prognostic indicators, their common expression suggested a strong rationale for targeting EGFR, c-Met, and IGF-1R in the treatment of oral and oropharyngeal SCC.

Objectives Treatment outcome of patients with oral and oropharyngeal squamous cell carcinoma (OOSCC) achieving complete pathologic response at the primary site (ypT0) but incomplete response in loco-regional lymph nodes after preoperative chemoradiation (ypN+) is poorly described in the literature. This study's objective was to assess the survival of patients with OOSCC with ypT0N+ disease. Study Design 176 patients with primary locally advanced OOSCC undergoing preoperative chemoradiotherapy were stratified according to the pathologic TNM classification into 6 groups: ypT0N0M0 (46%), ypT0N+M0 (10%), ypTNM I (24%), ypTNM II (4%), ypTNM III (6%), and ypTNM IV (10%). Results Three-year overall survival (OS) and recurrence-free survival (RFS) rates for the ypT0N+M0 group were both 61.8% and were similar to those of the ypTNM I group (OS 62.4%; RFS rate of 59.2%). Conclusions Survival analyses showed that patients with OOSCC with ypT0N+ disease have a similar prognosis to those with pathologic TNM stage I.

Central obesity promotes gastroesophageal reflux, which may be related to increased intra-abdominal pressure. We investigated the effect of increasing abdominal pressure by waist belt on reflux in patients with reflux disease.We performed a prospective study of patients with esophagitis (n = 8) or Barrett's esophagus (n = 6); median age was 56 years and median body mass index was 26.8. Proton pump inhibitors were stopped at least 7 days before the study and H2 receptor antagonists were stopped for at least 24 hours before. The severity of upper GI symptoms was assessed and measurements of height, weight, and waist and hip circumference taken. Combined high-resolution pH measurement and manometry were performed in fasted state for 20 minutes and for 90 minutes following a standardized meal. The squamocolumnar junction was marked by endoscopically placed radiopaque clips. The procedures were performed with and without a waist belt (a weight-lifter belt applied tightly and inflated to a constant cuff pressure of 50 mmHg). We compared variables between groups using the Wilcoxon Signed Rank test and tested for correlations using Spearman Rho bivariate analysis.Without the belt, intragastric pressure correlated with waist circumference (r = 0.682; P = .008), with the range in pressure between smallest and largest waist circumference being 15 mmHg. The belt increased intragastric pressure by a median of 6.9 mmHg during fasting (P = .002) and by 9.0 mmHg after the meal (P = .001). Gastroesophageal acid reflux at each of the pH sensors extending 5.5 cm proximal to the peak lower esophageal sphincter pressure point was increased by approximately 8-fold by the belt (all P.05). Following the meal, the mean number of reflux events with the belt was 4, vs 2 without (P = .008). Transient lower esophageal sphincter relaxations were not increased by the belt, but those associated with reflux were increased (2 vs 3.5; P = .04). The most marked effect of the belt was impaired esophageal clearance of refluxed acid (median values of 23.0 seconds without belt vs 81.1 seconds with belt) (P = .008). The pattern of impaired clearance was that of rapid re-reflux after peristaltic clearance.In a prospective study of patients with esophagitis or Barrett's esophagus, we found belt compression increased acid reflux following a meal. The intragastric pressure rise inducing this effect is well within the range associated with differing waist circumference and likely to be relevant to the association between obesity and reflux disease.

Background Atherosclerosis is a known risk factor for flap loss in microsurgery. Several microsurgical techniques, like plaque removal, have been proposed for atherosclerotic vessels, but these techniques often induce intimal injuries. The aim of this study was to investigate the impact of various endothelial defects on the risk of thrombosis in a rat acute intimal injury model. Methods Endothelial defects of various forms and sizes were created in the abdominal aorta of 30 male Wistar rats following a strict protocol. Defect sizes were measured and classified as round, horizontal, or vertical based on their configuration. An hour after reestablishing the blood flow, the abdominal aorta was harvested and the operation site was assessed for signs of thrombosis clinically and using light microscopy. Univariate and multiple linear regression analysis were performed to identify possible influencing factors on thrombosis. Results The mean defect size was 2.65 ± 1.19 mm2. Intimal lesions were classified as round in 36.7%, horizontal in 33.3%, and vertical in 30% of specimens. Thrombus formation was detected in 46.7% clinically and in 50% histologically. Univariate regression analysis revealed that defect size (p = 0.048) and vertical form (p = 0.017) were significantly associated with thrombus formation. Multiple regression analysis corroborated vertical defects as a risk factor for thrombosis (p = 0.03). Conclusion Endothelial injuries are associated with a high risk of thrombosis with highest risks associated with vertical defects. Arteries should be carefully examined for intimal defects before microvascular anastomosis, especially in the atherosclerotic patient.

Objectives: The incidence of esophageal adenocarcinoma (EAC) is increasing while adenocarcinoma of the stomach is decreasing. We have investigated whether the incidences of these two cancers and their time trends might be inversely related pointing to a common environmental factor exerting opposite effects on these cancers.\ud Methods: For cross-sectional analyses data were abstracted from “Cancer Incidence in Five Continents” (CI5) Volume X and GLOBOCAN 2012. Relevant ICD-10 codes were used to locate esophageal and gastric cancers anatomically, and ICD-O codes for the histological diagnosis of EAC. For longitudinal analyses, age standardized rates (ASRs) of EAC and total gastric cancer (TGC) were extracted from CI5C-Plus.\ud Results: Estimated (2012) ASRs were available for 51 countries and these showed significant negative correlations between EAC and both TGC (males: correlation coefficient (CC)=−0.38, P=0.006, females: CC=−0.41, P=0.003) and non-cardia gastric cancer rates (males: CC=−0.41, P=0.003 and females: CC=−0.43, P=0.005). Annual incidence trends were analyzed for 38 populations through 1989–2007 and showed significant decreases for TGC in 89% and increases for EAC in 66% of these, with no population showing a fall in the latter. Significant negative correlation between the incidence trends of the two cancers was observed in 27 of the 38 populations over the 19–50 years of available paired data. Super-imposition of the longitudinal and cross-sectional data indicated that populations with a current high incidence of EAC and low incidence of gastric cancer had previously resembled countries with a high incidence of gastric cancer and low incidence of EAC.\ud Conclusions: The negative association between gastric cancer and EAC in both current incidences and time trends is consistent with a common environmental factor predisposing to one and protecting from the other.

Hiatus hernia (HH) is a key mediator of gastro-oesophageal reflux disease but little is known about its significance in the general population. We studied the structure and function of the gastro-oesophageal junction in healthy volunteers with and without HH.We compared 15 volunteers with HH, detected by endoscopy or MRI scan, but without gastro-oesophageal reflux disease with 15 controls matched for age, gender and body weight. Jumbo biopsies were taken across the squamocolumnar junction (SCJ). High-resolution pH metry (12 sensors) and manometry (36 sensors) were performed upright and supine, before and after a meal. The SCJ was marked with an endoscopically placed clip and visualised fluoroscopically.Cardiac mucosa was longer in volunteers with HH (3.5 vs 2.5 mm, p=0.01). There was no excessive acid reflux 5 cm above the upper border of the lower oesophageal sphincter (LOS) in either group but those with HH had short segment reflux 11 mm above the pH transition point after the meal when supine (pH4 for 5.5% vs 0.3% of time, p=0.01). The SCJ and pH transition point were proximally displaced within the gastro-oesophageal junction in those with HH versus controls (p0.05). The pH transition point was proximal to the peak LOS pressure point in HH subjects but distal to it in controls after the meal (p0.05). When supine, the postprandial pH transition point crossed the SCJ in those with HH (p=0.03).Healthy volunteers with HH have increased intrasphincteric reflux and lengthening of cardiac mucosa in the absence of traditional transsphincteric reflux.

Aim (1) Investigate incidence, magnitude and bacterial diversity of bacteraemia due to flossing compared with scaling and root planing (SRP) and (2) Identify any associations with clinical parameters. Materials and Methods Full-mouth flossing and single quadrant SRP were performed at separate visits for 30 patients with chronic periodontitis. Baseline blood samples and at 30 s and 10 min. after completion of flossing, 5 min. after initiation of SRP and 30 s and 10 min. after completion of SRP were obtained. Total bacteraemia and viridans streptococcal bacteraemia (VSB) were investigated. Results Total bacteraemia incidence was 30% for flossing and 43.3% for SRP (no significant difference; p = 0.21). Flossing and SRP caused the same incidence of VSB (26.7%). Flossing caused a higher mean magnitude of total bacteraemia than SRP (7.4 ± 16.2 CFU/ml versus 2 ± 3.4 CFU/ml), but the difference was not significant (p = 0.2). Flossing caused a higher mean magnitude of VSB than SRP (1.2 ± 1.6 CFU/ml versus 0.4 ± 0.2 CFU/ml), but the difference was not significant (p = 0.09). Viridans streptococci comprised 11.4% of flossing bacteraemia isolates and 7.6% in SRP. No correlations were found between clinical parameters and incidence or magnitude of bacteraemia following flossing. Gingival inflammation was significantly associated with incidence of total bacteraemia (p = 0.01) and VSB (p = 0.001) following SRP. No correlations were found for any parameter and magnitude of total bacteraemia or VSB following SRP. Conclusions No differences were found between flossing and SRP in the incidence or magnitude of total bacteraemia or VSB. This finding is important in the ongoing re-evaluation of antibiotic prophylaxis to prevent infective endocarditis.

Ultraviolet radiation (UVR) exposure to internal tissues for diagnostic, therapeutic and cosmetic procedures has increased dramatically over the past decade. The greatest increase in UVR exposure of internal tissues occurs in the cosmetic industry where it is combined with oxidizing agents for teeth whitening, often in conjunction with indoor tanning. To address potential carcinogenic risks of these procedures, we analyzed the formation and repair of the DNA photoproducts associated with the signature mutations of UVR. Radioimmunoassay was used to quantify the induction and repair of cyclobutane pyrimidine dimers and pyrimidine(6-4)pyrimidone photoproducts in DNA purified from three reconstructed tissues, EpiDerm(TM) , EpiGingival(TM) and EpiOral(TM) . We observed comparable levels of DNA damage in all tissues immediately after UVR exposure. In contrast, repair was significantly reduced in both oral tissues compared with EpiDerm(TM) . Our data suggest that UVR exposure of oral tissues can result in accumulation of DNA damage and increase the risk for carcinoma and melanoma of the mouth. Because NER is a broad-spectrum defense against DNA damage caused by a variety of agents in addition to UVR, our data suggest that the relatively low NER efficiency observed in oral tissues may have wide-ranging consequences in this highly exposed environment.

Nucleotide excision repair (NER) is the primary defense against the DNA damage implicit in skin cancer formation and is negatively affected by chronic exposure to UVB radiation. However, in-situ and in-vitro studies consistently yield equivocal results when addressing individual DNA repair capacity and melanoma susceptibility. The primary objective of this study was to determine if individual global NER capacity is a risk factor for melanoma formation in a prominent UVB inducible melanoma model, hybrid Xiphophorus fishes. After neonatal UVB irradiation, adult tumor-bearing and tumor-free fish were given a challenge UVB dose and (6-4) photoproduct repair was quantified in individual fish at 24 h using radioimmunoassay. Despite considerable inter-individual variation in repair capacity, ranging from 13% to 91%, we found no difference in mean NER capacity between fish with and without melanomas, thus detaching global NER from melanomagenesis. Furthermore, despite epidemiological data indicating that sex and age are important risk factors underlying melanoma susceptibility, we found no difference in mean NER rates among the sexes or as a function of age. We conclude with a discussion of the apparent paradox of how inter-individual variation in NER is not a risk factor given the clear evidence that DNA damage underlies melanoma susceptibility.

Histological analysis of tumour resection for squamous cell carcinoma (SCC) of the tongue yields prognostic information. We analysed histological slides of biopsy and tumour resection specimens using an adapted malignancy grading score and analysed variables of neck dissections. There was moderate correlation between biopsy and tumour resection using malignancy grading scores (correlation coefficient 0.45); good agreement of tumour grade (79%), tumour depth (76%), and type of invasive front (80%), but correlation was only fair to moderate (κ = 0.38, κ = 0.51, and κ = 0.41, respectively). Correlation of the biopsy grading score and invaded nodes in the neck, extra capsular spread, and soft tissue disease was not significant.

The relationship between DNA damage, mutations and the initiation and progression of sunlight-induced melanoma has not yet been resolved. Recently, it has become apparent that the etiology of sunlight-induced melanoma is fundamentally different from sunlight-induced carcinoma, although both appear to be dependent on specific photoproducts produced in DNA by ultraviolet radiation (UVR). How DNA photoproducts are involved in the unique etiology of cutaneous malignant melanoma (CMM) compared to other types of skin cancer is central to understanding the nature of this disease and its prevention. Based on our results and published data, we propose a model for melanoma distinct from carcinoma, in which different types of DNA damage contribute to different stages of tumorigenesis.

Background Lymph node status is regarded as the most important factor for prognosis for oesophageal cancer. T1 oesophageal adenocarcinoma management has shifted from oesophagectomy only to include endoscopic management as part of the algorithm, with some bodies (National Comprehensive Cancer Network (NCCN) 2016) recommending it for management of T1a disease and selected T1b disease. We reviewed the literature to assess the true risk of lymph node metastasis in patients with T1 oesophageal adenocarcinoma. Methods Medline, Embase, Pubmed and Cochrane where searched for manuscripts in english reviewing the lymph node metastasis in superficial (T1) oesophageal adenocarcinoma. The main outcome was reviewing the risk of lymph node metastasis in T1a and T1b oesophageal adenocarcinoma. Secondary outcomes looked at the rate of lymph node metastasis for T1b cancers based on degree of submucosal involvement (SM1, SM2 and SM3). Studies were excluded if neo-adjuvant chemotherapy or radiotherapy were received and if the surgical lymph node yield was Results 38 Studies were identified. 22 studies were excluded due to low lymph node yield ( Conclusion Early oesophageal adenocarcinoma (T1) is increasing in prevalence due to surveillance of pre-malignant conditions (Barrett's Oesophagus). Recently some bodies recommend the use of endoscopic mucosal resection as first line therapy for T1a disease. It is important to inform our patients the risk of lymph node metastasis is low but significant (2%). Given in specialised units, oesophagectomy can be performed with low mortality ( Disclosure All authors have declared no conflicts of interest.

Background and Objective Sarcomas of the head and neck in adults are malignant tumors with many histological subtypes and sites of origin. The purpose of this study was to analyze the outcome of adult patients suffering from head and neck sarcomas and to identify any clinical and histological predictors of outcome. Materials and Methods The medical records of 74 patients treated during 1999–2008 were reviewed. All patients suffered from primary head and neck sarcomas. Results The mean survival of patients was 44.49 ± 32.25 months. The 2- and 5-year overall survival rates were 83.78% and 60.81%. The nodal status (P = 0.032), tumor size (P

The treatment of end stage renal failure is renal replacement therapy. This may be by dialysis (blood or peritoneal) or by kidney transplantation. The outlook for those who have a successful renal transplant has improved significantly over the past 20 years: graft survival from non-heart-beating donation is now a mean of 14 years, and 18 years for live donor transplants. Unfortunately the number of renal transplants fails to meet the demand from patients on the transplant waiting list. The shortfall has to be managed by dialysis. Life expectancy of a patient on haemodialysis is one-fifth to one-quarter of that of the age-matched healthy population, but doubles following successful transplantation. The predominant type of dialysis is blood dialysis. To provide this, patients require a portal of access to the circulation. This patient group requires timely and well-planned renal access surgery. Circulatory access is their lifeline. Failure of access, coupled with the need for emergency admission, is a major cause of morbidity and mortality.

We examined the wavelength dependence of ultraviolet (UV) ra-diation (UVR)-induced melanoma in a Xiphophorus backcross hybrid model previously reported to be susceptible to melanoma induction by ultraviolet A (UVA) and visible light. Whereas ultraviolet B (UVB) irradiation of neonates yielded high frequencies of melanomas in pigmented fish, UVA irradiation resulted in melanoma frequencies that were not significantly different from unirradiated fish. Spontaneous and UV-induced melanoma frequencies correlated with the degree of pigmentation as expected from previous studies, and the histopathology phenotypes of the melanomas were not found in significantly different proportions in UV-treated and -untreated tumor-bearing fish. Our results support the conclusion that a brief early-life exposure to UVB radiation causes melanoma formation in this animal model. These data are consistent with an essential role for direct DNA damage, including cyclobutane dimers and (6-4) photoproducts, in the etiology of melanoma.

P>Experimental animal models are extremely valuable for the study of human diseases, especially those with underlying genetic components. The exploitation of various animal models, from fruitflies to mice, has led to major advances in our understanding of the etiologies of many diseases, including cancer. Cutaneous malignant melanoma is a form of cancer for which both environmental insult (i.e., UV) and hereditary predisposition are major causative factors. Fish melanoma models have been used in studies of both spontaneous and induced melanoma formation. Genetic hybrids between platyfish and swordtails, different species of the genus Xiphophorus, have been studied since the 1920s to identify genetic determinants of pigmentation and melanoma formation. Recently, transgenesis has been used to develop zebrafish and medaka models for melanoma research. This review will provide a historical perspective on the use of fish models in melanoma research, and an updated summary of current and prospective studies using these unique experimental systems.

Ultraviolet (UV) light is a primary environmental risk factor for melanoma, a deadly form of skin cancer derived from the pigmented cells called melanocytes. UVB irradiation causes DNA damage, mainly in the form of pyrimidine dimers (cis-syn cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidone photoproducts), and organisms have developed complex multiprotein repair processes to cope with the DNA damage. Zebrafish is becoming an important model system to study the effects of UV light in animals, in part because the embryos are easily treated with UV irradiation, and the DNA damage repair pathways appear to be conserved in zebrafish and mammals. We are interested in exploring the effects of UV irradiation in young adult zebrafish, so that we can apply them to the study of gene-environment interactions in models of skin cancer. Using the Xiphophorus UV melanoma model as a starting point, we have developed a UV irradiation treatment chamber, and established UV treatment conditions at different ages of development. By translating the Xiphophorus UV treatment methodology to the zebrafish system, we show that the adult zebrafish skin is competent for nucleotide excision DNA damage repair, and that like in mammalian cells, UV treatment promotes phosphorylation of H2AX and a p53-dependent response. These studies provide the groundwork for exploring the role of UV light in melanoma development in zebrafish.

A novel neurochemical method was applied for studying the activity of sympathetic nerves in the human cerebral vascular system. The aim was to investigate whether noradrenaline plasma kinetic measurements made with internal jugular venous sampling reflect cerebrovascular sympathetic activity. A database was assembled of fifty-six healthy subjects in whom total body noradrenaline spillover (indicative of whole body sympathetic nervous activity), brain noradrenaline spillover and brain lipophlic noradrenaline metabolite (3,4-dihydroxyphenolglycol (DHPG) and 3-methoxy-4-hydroxyphenylglycol (MHPG)) overflow rates were measured. These measurements were also made following ganglion blockade (trimethaphan, n = 6), central sympathetic inhibition (clonidine, n = 4) and neuronal noradrenaline uptake blockade (desipramine, n = 13) and in a group of patients (n = 9) with pure autonomic failure (PAF). The mean brain noradrenline spillover and brain noradrenaline metabolite overflow in healthy subjects were 12.5 +/- 1.8, and 186.4 +/- 25 ng min(-1), respectively, with unilateral jugular venous sampling for both. Total body noradrenaline spillover was 605.8 ng min(-1) +/- 34.4 ng min(-1). As expected, trimethaphan infusion lowered brain noradrenaline spillover (P = 0.03), but perhaps surprisingly increased jugular overflow of brain metabolites (P = 0.01). Suppression of sympathetic nervous outflow with clonidine lowered brain noradrenaline spillover (P = 0.004), without changing brain metabolite overflow (P = 0.3). Neuronal noradrenaline uptake block with desipramine lowered the transcranial plasma extraction of tritiated noradrenaline (P = 0.001). The PAF patients had 77% lower brain noradrenaline spillover than healthy recruits (P = 0.06), indicating that in them sympathetic nerve degeneration extended to the cerebral circulation, but metabolites overflow was similar to healthy subjects (P = 0.3). The invariable discordance between noradrenline spillover and noradrenaline metabolite overflow from the brain under these different circumstances indicates that the two measures arise from different sources, i.e. noradrenaline spillover originates from the cerebral vasculature outside the blood-brain barrier, and the noradrenaline metabolites originate primarily from brain noradrenergic neurons. We suggest that measurements of transcranial plasma noradrenaline spillover have utility as a method for assessing the sympathetic nerve activity of the cerebral vasculature.

The persistence of self in individuals with probable Alzheimer's disease was investigated via language and visual self-recognition. Seventy-eight adults (ages 66—103) participated: 26 with mild cognitive impairments, 26 with moderate cognitive impairments, and 26 without impairment. Although frequency of language usage (during an interview) declined across impairment levels, there were no significant differences in either rates or proportions of pronoun and attribute usage. When asked to identify themselves in photographs taken with an instant camera, cognitively impaired individuals — in spite of forgetting the photographic session only minutes earlier — exhibited unimpaired self-recognition, a dissociation consistent with a preserved self. Taken together, these findings indicate a persistence of self in individuals with dementia, and have implications for how Alzheimer's is characterized and experienced, and how individuals are cared for.

— The relative biological importance of(5–5,6–6) cyclobutane and(6–4) pyrimidine-pyrimidone dimers in mammalian cells has been determined in a xeroderma pigmentosum (XP) revertant that repairs only the(6–4) photoproduct. Surprisingly, the majority of biological effects of UV light, including cell killing, sister chromatid exchange, mutagenesis, and inhibition and recovery of DNA and RNA synthesis, appear to be due to the(6–4) photoproduct and not to the cyclobutane dimer. Although the XP revertant repairs its own genomic DNA, it fails to repair damage in shuttle vectors, including the pZ189 mutational and chloramphenicol acetyl transferase transcriptional assay systems. The revertant is therefore a cell line for which shuttle vectors are inappropriate as models for genomic DNA repair, and may highlight a general weakness of shuttle vectors for the study of infrequent DNA lesions.

Objective Patients requiring access for hemodialysis in whom radiocephalic or brachiocephalic arteriovenous fistulas cannot be formed or have failed present a significant clinical challenge. We compare outcomes in patients undergoing transposed brachiobasilic arteriovenous fistulas (BBAVF) with expanded polytetrafluoroethylene brachioaxillary access grafts in a single European center. Methods We identified all patients undergoing a first upper limb tertiary-access procedure—that is, either BBAVF or brachioaxillary access graft for hemodialysis—between January 1, 2000, and December 31, 2005. The median follow-up was 18.1 months (interquartile range, 8.7-34.9 months). Successful use for dialysis, primary patency, secondary patency, and patient survival was assessed. Results A total of 185 patients were identified; 71 had a BBAVF, and 114 had an access graft. The median age was 64.3 years (interquartile range, 50.7-74.4 years). The groups were well matched for age, sex, ethnicity, diabetes, and number of prior access procedures. Significantly fewer BBAVFs were successfully used for dialysis: 69.0% BBAVFs compared with 89.4% access grafts ( P = .001; χ 2 ). One- and two-year primary patency rates were 45.3% and 40.0%, respectively, for BBAVF and were 56.4% and 43.2% for access grafts ( P = .579; log rank). Furthermore, there was no significant difference in secondary patency between the two procedures ( P = .868; log rank). We found that surgeons in training had no influence on the primary patency of either BBAVF or access grafts. However, infective complications necessitating an operation were significantly higher in the access graft group (6.2% vs 0%; P = .031; Fisher exact test). Conclusions Although more difficult to establish, BBAVFs provide patency at least equivalent to that of brachioaxillary access grafts. However, infective complications are fewer in the BBAVF group. As such, we believe that BBAVF should be the first choice of the vascular access surgeon when fistulas using the cephalic vein are not possible or have failed.

Mammalian skin is vulnerable to the photocarcinogenic and photoaging effects of solar UV radiation and defends itself using a variety of photoprotective responses including epidermal thickening, tanning and the induction of repair and antiradical systems. We treated Skh-1 albino hairless mice for 60 days with ultraviolet-A (UVA) or ultraviolet-B (UVB) radiation and measured the frequency of cyclobutane pyrimidine dimers and pyrimidine(6–4)pyrimidone photoproducts induced by a single acute sunburn dose of UVB at different stages of the chronic treatment. We found that both UVA and UVB exposure produced a photoprotective response in the dermis and epidermis and that the degree of photoproduct attenuation was dependent on dose, wavelength and the type of damage induced. Although epidermal thickening was important, our data suggest that UV protective compounds other than melanin may be involved in mitigating the damaging effects of sunlight in the skin.

Selected hybridization in the fish genus Xiphophorus has been used for many years to study the genetics of malignant melanoma. Because DNA damage caused by ultraviolet radiation is implicated in the etiology of sunlight-induced melanoma, the heritability of mechanisms that mitigate DNA damage is a matter of some interest. We examined nucleotide excision repair of the two major types of DNA-damage induced by sunlight; the cyclobutane pyrimidine dimer (CPD) and the pyrimidine(6-4)pyrimidone dimer [(6-4)PD]. In most cases, removal of the (6-4)PD was more rapid than the CPD, and in many cases, the F1 hybrid showed reduced repair efficiency compared with the parental species. These data demonstrate reduced function in multienzyme hybrid systems and provide molecular support for potential reduced fitness in hybrid fish under conditions of environmental stress.