Κυριακή, 22 Μαΐου 2016

Randomized Summer Camp Crossover Trial in 5- to 9-Year-Old Children: Outpatient Wearable Artificial Pancreas Is Feasible and Safe.

Randomized Summer Camp Crossover Trial in 5- to 9-Year-Old Children: Outpatient Wearable Artificial Pancreas Is Feasible and Safe.

Diabetes Care. 2016 May 10;

Authors: Del Favero S, Boscari F, Messori M, Rabbone I, Bonfanti R, Sabbion A, Iafusco D, Schiaffini R, Visentin R, Calore R, Leal Moncada Y, Galasso S, Galderisi A, Vallone V, Di Palma F, Losiouk E, Lanzola G, Tinti D, Rigamonti A, Marigliano M, Zanfardino A, Rapini N, Avogaro A, Chernavvsky D, Magni L, Cobelli C, Bruttomesso D

Abstract
OBJECTIVE: The Pediatric Artificial Pancreas (PedArPan) project tested a children-specific version of the modular model predictive control (MMPC) algorithm in 5- to 9-year old children during a camp.
RESEARCH DESIGN AND METHODS: A total of 30 children, 5- to 9-years old, with type 1 diabetes completed an outpatient, open-label, randomized, crossover trial. Three days with an artificial pancreas (AP) were compared with three days of parent-managed sensor-augmented pump (SAP).
RESULTS: Overnight time-in-hypoglycemia was reduced with the AP versus SAP, median (25(th)-75(th) percentiles): 0.0% (0.0-2.2) vs. 2.2% (0.0-12.3) (P = 0.002), without a significant change of time-in-target, mean: 56.0% (SD 22.5%) vs. 59.7% (21.2%) (P = 0.430), but with increased mean glucose 173 mg/dL (SD 36) vs. 150 mg/dL (SD 39) (P = 0.002). Overall, the AP granted a threefold reduction of time-in-hypoglycemia (P < 0.001) at the cost of decreased time-in-target, 56.8% (SD 13.5) vs. 63.1% (SD 11.0) (P = 0.022) and increased mean glucose 169 mg/dL (SD 23) vs. 147 mg/dL (SD 23) (P < 0.001).
CONCLUSIONS: This trial, the first outpatient single-hormone AP trial in a population of this age, shows feasibility and safety of MMPC in young children. Algorithm retuning will be performed to improve efficacy.

PMID: 27208335 [PubMed - as supplied by publisher]



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Day and Night Closed-Loop Glucose Control in Patients With Type 1 Diabetes Under Free-Living Conditions: Results of a Single-Arm 1-Month Experience Compared With a Previously Reported Feasibility Study of Evening and Night at Home.

Day and Night Closed-Loop Glucose Control in Patients With Type 1 Diabetes Under Free-Living Conditions: Results of a Single-Arm 1-Month Experience Compared With a Previously Reported Feasibility Study of Evening and Night at Home.

Diabetes Care. 2016 May 5;

Authors: Renard E, Farret A, Kropff J, Bruttomesso D, Messori M, Place J, Visentin R, Calore R, Toffanin C, Di Palma F, Lanzola G, Magni P, Boscari F, Galasso S, Avogaro A, Keith-Hynes P, Kovatchev B, Del Favero S, Cobelli C, Magni L, DeVries JH, AP@home Consortium

Abstract
OBJECTIVE: After testing of a wearable artificial pancreas (AP) during evening and night (E/N-AP) under free-living conditions in patients with type 1 diabetes (T1D), we investigated AP during day and night (D/N-AP) for 1 month.
RESEARCH DESIGN AND METHODS: Twenty adult patients with T1D who completed a previous randomized crossover study comparing 2-month E/N-AP versus 2-month sensor augmented pump (SAP) volunteered for 1-month D/N-AP nonrandomized extension. AP was executed by a model predictive control algorithm run by a modified smartphone wirelessly connected to a continuous glucose monitor (CGM) and insulin pump. CGM data were analyzed by intention-to-treat with percentage time-in-target (3.9-10 mmol/L) over 24 h as the primary end point.
RESULTS: Time-in-target (mean ± SD, %) was similar over 24 h with D/N-AP versus E/N-AP: 64.7 ± 7.6 vs. 63.6 ± 9.9 (P = 0.79), and both were higher than with SAP: 59.7 ± 9.6 (P = 0.01 and P = 0.06, respectively). Time below 3.9 mmol/L was similarly and significantly reduced by D/N-AP and E/N-AP versus SAP (both P < 0.001). SD of blood glucose concentration (mmol/L) was lower with D/N-AP versus E/N-AP during whole daytime: 3.2 ± 0.6 vs. 3.4 ± 0.7 (P = 0.003), morning: 2.7 ± 0.5 vs. 3.1 ± 0.5 (P = 0.02), and afternoon: 3.3 ± 0.6 vs. 3.5 ± 0.8 (P = 0.07), and was lower with D/N-AP versus SAP over 24 h: 3.1 ± 0.5 vs. 3.3 ± 0.6 (P = 0.049). Insulin delivery (IU) over 24 h was higher with D/N-AP and SAP than with E/N-AP: 40.6 ± 15.5 and 42.3 ± 15.5 vs. 36.6 ± 11.6 (P = 0.03 and P = 0.0004, respectively).
CONCLUSIONS: D/N-AP and E/N-AP both achieved better glucose control than SAP under free-living conditions. Although time in the different glycemic ranges was similar between D/N-AP and E/N-AP, D/N-AP further reduces glucose variability.

PMID: 27208331 [PubMed - as supplied by publisher]



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Deficiency of HTRA2/Omi is associated with infantile neurodegeneration and 3-methylglutaconic aciduria.

Deficiency of HTRA2/Omi is associated with infantile neurodegeneration and 3-methylglutaconic aciduria.

J Med Genet. 2016 May 12;

Authors: Mandel H, Saita S, Edvardson S, Jalas C, Shaag A, Goldsher D, Vlodavsky E, Langer T, Elpeleg O

Abstract
BACKGROUND: Cell survival critically depends on the integrity of mitochondria, which play a pivotal role during apoptosis. Extensive mitochondrial damage promotes release of pro-apoptotic factors from the intermembrane space of mitochondria. Released mitochondrial proteins include Smac/DIABLO and HTRA2/Omi, which inhibit the cytosolic E3 ubiquitin ligase XIAP and other inhibitors of apoptosis proteins.
AIMS: Here we investigated the cause of extreme hypertonia at birth, alternating with hypotonia, with the subsequent appearance of extrapyramidal symptoms, lack of psychomotor development, microcephaly, intractable seizures and early death in four patients from two unrelated families. The patients showed lactic acidemia, 3-methylglutaconic aciduria, intermittent neutropenia, evolving brain atrophy and disturbed cristae structure in muscle mitochondria.
METHODS AND RESULTS: Using whole-exome sequencing, we identified missplicing mutation and a 5 bp deletion in HTRA2, encoding HTRA2/Omi. This protein was completely absent from the patients' fibroblasts, whose growth was impaired and which were hypersensitive to apoptosis. Expression of HtrA2/Omi or of the proteolytically inactive HTRA2/Omi protein restored the cells' apoptotic resistance. However, cell growth was only restored by the proteolytically active protein.
CONCLUSIONS: This is the first report of recessive deleterious mutations in HTRA2 in human. The clinical phenotype, the increased apoptotic susceptibility and the impaired cell growth recapitulate those observed in the Htra2 knockout mice and in mutant mice with proteolytically inactive HTRA2/Omi. Together, they underscore the importance of both chaperone and proteolytic activities of HTRA2/Omi for balanced apoptosis sensitivity and for brain development. Absence of HTRA2/Omi is associated with severe neurodegenerative disorder of infancy, abnormal mitochondria, 3-methylglutaconic aciduria and increased sensitivity to apoptosis.

PMID: 27208207 [PubMed - as supplied by publisher]



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Quantitative Assessment of Left Ventricular Diastolic Stiffness Using Cardiac Shear Wave Elastography: A Pilot Study.

Quantitative Assessment of Left Ventricular Diastolic Stiffness Using Cardiac Shear Wave Elastography: A Pilot Study.

J Ultrasound Med. 2016 May 20;

Authors: Song P, Bi X, Mellema DC, Manduca A, Urban MW, Greenleaf JF, Chen S

Abstract
OBJECTIVES: The purpose of this study was to systematically investigate the feasible echocardiographic views for human transthoracic cardiac shear wave elastography (SWE) and the impact of myocardial anisotropy on myocardial stiffness measurements.
METHODS: A novel cardiac SWE technique using pulse inversion harmonic imaging and time-aligned sequential tracking was developed for this study. The technique can measure the quantitative local myocardial stiffness noninvasively. Ten healthy volunteers were recruited and scanned by the proposed technique 3 times on 3 different days.
RESULTS: Seven combinations of echocardiographic views and left ventricular (LV) segments were found to be feasible for LV diastolic stiffness measurements: basal interventricular septum under parasternal short- and long-axis views; mid interventricular septum under parasternal short- and long-axis views; anterior LV free wall under parasternal short- and long-axis views; and posterior LV free wall under a parasternal short-axis view. Statistical analyses showed good repeatability of LV diastolic stiffness measurements among 3 different days from 70% of the participants for the basal interventricular septum and posterior LV free wall short-axis views. On the same LV segment, the mean diastolic shear wave speed measurements from the short-axis view were statistically different from the long-axis measurements: 1.82 versus 1.29 m/s for the basal interventricular septum; 1.81 versus 1.45 m/s for mid interventricular septum; and 1.96 versus 1.77 m/s for the anterior LV free wall, indicating that myocardial anisotropy plays a substantial role in LV diastolic stiffness measurements.
CONCLUSIONS: These results establish the preliminary normal range of LV diastolic stiffness under different scan views and provide important guidance for future clinical studies using cardiac SWE.

PMID: 27208201 [PubMed - as supplied by publisher]



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Early to Dialyze

Acute kidney injury (AKI) among hospitalized patients is common, consequential, and costly. Annually in the United States, approximately 10% of the estimated 5 million hospitalizations are complicated by AKI, with 0.4% of cases severe enough to require dialysis. Among patients with AKI requiring extracorporeal kidney support (dialysis), in-hospital mortality rates are consistently in excess of 20%, and may exceed 40% when accompanied by nonrenal organ system failure. Acute kidney injury results in prolonged hospital stay, and is associated with marked increase in hospital costs, with attributable costs estimated to be between $5 billion and $10 billion annually. Moreover, AKI has been linked with increased longer-term risks of chronic kidney disease (CKD), another condition associated with poor outcomes and high health care resource consumption, as well as of higher risks of hypertension.

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Early vs Delayed RRT in Critically Ill Patients With AKI

This randomized clinical trial compares the effects of early vs delayed initiation of renal replacement therapy on 90-day all-cause mortality among critically ill patients with AKI.

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quality of care; +39 new citations

39 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

quality of care

These pubmed results were generated on 2016/05/22

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.



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Segmentation of White Blood Cell from Acute Lymphoblastic Leukemia Images Using Dual-Threshold Method

We propose a dual-threshold method based on a strategic combination of RGB and HSV color space for white blood cell (WBC) segmentation. The proposed method consists of three main parts: preprocessing, threshold segmentation, and postprocessing. In the preprocessing part, we get two images for further processing: one contrast-stretched gray image and one H component image from transformed HSV color space. In the threshold segmentation part, a dual-threshold method is proposed for improving the conventional single-threshold approaches and a golden section search method is used for determining the optimal thresholds. For the postprocessing part, mathematical morphology and median filtering are utilized to denoise and remove incomplete WBCs. The proposed method was tested in segmenting the lymphoblasts on a public Acute Lymphoblastic Leukemia (ALL) image dataset. The results show that the performance of the proposed method is better than single-threshold approach independently performed in RGB and HSV color space and the overall single WBC segmentation accuracy reaches 97.85%, showing a good prospect in subsequent lymphoblast classification and ALL diagnosis.

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S-Propargyl-cysteine Exerts a Novel Protective Effect on Methionine and Choline Deficient Diet-Induced Fatty Liver via Akt/Nrf2/HO-1 Pathway

This study investigated the antioxidative effect of S-propargyl-cysteine (SPRC) on nonalcoholic fatty liver (NAFLD) by treating mice fed a methionine and choline deficient (MCD) diet with SPRC for four weeks. We found that SPRC significantly reduced hepatic reactive oxygen species (ROS) and methane dicarboxylic aldehyde (MDA) levels. Moreover, SPRC also increased the superoxide dismutase (SOD) activity. By Western blot, we found that this protective effect of SPRC was importantly attributed to the regulated hepatic antioxidant-related proteins, including protein kinase B (Akt), heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor 2 (Nrf2), and cystathionine γ-lyase (CSE, an enzyme that synthesizes hydrogen sulfide). Next, we examined the detailed molecular mechanism of the SPRC protective effect using oleic acid- (OA-) induced HepG2 cells. The results showed that SPRC significantly decreased intracellular ROS and MDA levels in OA-induced HepG2 cells by upregulating the phosphorylation of Akt, the expression of HO-1 and CSE, and the translocation of Nrf2. SPRC-induced HO-1 expression and Nrf2 translocation were abolished by the phosphoinositide 3-kinase (PI3K) inhibitor LY294002. Moreover, the antioxidative effect of SPRC was abolished by CSE inhibitor DL-propargylglycine (PAG) and HO-1 siRNA. Therefore, these results proved that SPRC produced an antioxidative effect on NAFLD through the PI3K/Akt/Nrf2/HO-1 signaling pathway.

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Thyroid Hormones, Autoantibodies, Ultrasonography, and Clinical Parameters for Predicting Thyroid Cancer

Our objective was to evaluate thyroid nodule malignancy prediction using thyroid function tests, autoantibodies, ultrasonographic imaging, and clinical data. We conducted a retrospective cohort study in 1400 patients with nodular thyroid disease (NTD). The thyroid stimulating hormone (TSH) concentration was significantly higher in patients with differentiated thyroid cancer (DTC) versus benign thyroid nodular disease (BTND) (). The receiver operating characteristic curve of TSH showed an AUC of 0.58 (95% CI 0.53–0.62, ), sensitivity of 74%, and specificity of 57% at a cut-off of 1.59 mIU/L. There was an incremental increase in TSH concentration along with the increasing tumor size (). Thyroglobulin antibody (TgAb) concentration was associated with an increased risk of malignancy (), but this association was lost when the effect of TSH was taken into account (). Thyroid ultrasonographic characteristics, including fewer than three nodules, hypoechoic appearance, solid component, poorly defined margin, intranodular or peripheral-intranodular flow, and punctate calcification, can be used to predict the risk of thyroid cancer. In conclusion, our study suggests that preoperative serum TSH concentration, age, and ultrasonographic features can be used to predict the risk of malignancy in patients with NTD.

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Improving Outcomes for Infants with Single Ventricle Physiology through Standardized Feeding during the Interstage

Congenital heart disease is identified as the most common birth defect with single ventricle physiology carrying the highest mortality. Staged surgical palliation is required for treatment, with mortality historically as high as 22% in the four- to six-month period from the first- to second-stage surgical palliation, known as the interstage. A standardized postoperative feeding approach was implemented through an evidence-based protocol, parent engagement, and interprofessional team rounds. Five infants with single ventricle physiology preprotocol were compared with five infants who received the standardized feeding approach. Mann-Whitney tests were conducted to evaluate the hypotheses that infants in the intervention condition would consume more calories and have a positive change in weight-to-age -score (WAZ) and shorter length of stay (LOS) following the first and second surgeries compared to infants in the control condition. After the protocol, the change in WAZ during the interstage increased by virtually one standard deviation from 0.05 to 0.91. Median LOS dropped 32% after the first surgery and 43% after the second surgery. Since first- and second-stage palliative surgeries occur within the same year of life, this represents savings of 500,000 to 800,000 per year in a 10-infant model. The standardized feeding approach improved growth in single ventricle infants while concurrently lowering hospital costs.

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Recipient Hyperbilirubinemia May Reduce Ischemia-Reperfusion Injury but Fails to Improve Outcome in Clinical Liver Transplantation

Background. Exogenous bilirubin may reduce experimental ischemia-reperfusion injury (IRI) due to its antioxidant properties. We studied if early graft exposure to high bilirubin levels in the recipient affects the early IRI and outcomes after liver transplantation (LTx). Methods. In 427 LTx patients, the AUROC curve based on bilirubin and AST at day 1 identified a cutoff of 2.04 mg/dL for the recipient pretransplant bilirubin. Recipients were grouped as having low (group L, ) or high (group H, ) bilirubin. Both groups had similar donor-related variables (age, preservation time, donor BMI > 28, and donor risk index (DRI)). Results. Alanine (ALT) and aspartate (AST) aminotransferase levels were higher in group L at day 1; ALT levels remained higher at day 2 in group L. LTx from high risk donors (DRI > 2) revealed a trend towards lower transaminases during the first two days after transplantation in group H. One month and 1-year patient survival were similar in groups L and H. High preoperative bilirubin did not affect the risk for early graft dysfunction (EGD), death, or graft loss during the first year after transplantation nor the incidence of acute rejection. LTx using donors with DRI > 2 resulted in similar rates of EGD in both groups. Conclusion. Increased bilirubin appears to reduce the early IRI after LTx yet this improvement was insufficient to improve the clinical outcome.

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MHM: A Multiple Handshaking MAC Protocol for Underwater Acoustic Sensor Networks

Underwater acoustic sensor networks (UWASNs) are effective tools for exploring and observing the ocean. Due to the nonnegligible physical restrictions of the underwater acoustic communication, most MAC protocols applied in the existing terrestrial wireless networks become inapplicable. In this paper, we propose a multiple handshaking MAC protocol for UWASNs called multihandshaking MAC (MHM). Using the method of multiple handshaking and competitive mechanism of control packets, our protocol is proposed to make the contending nodes share the underwater acoustic channel much more fairly and more efficiently. The main idea of MHM is to allow multiple nodes to transmit and receive data packets at the same time without packet collisions. We also propose a competitive mechanism of control packets, which can guarantee that there will not be data collisions in the process of multiple packet transmissions. Simulation results show that our protocol can achieve better performance, including throughput, delay, and fairness.

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Effector, Memory, and Dysfunctional CD8+ T Cell Fates in the Antitumor Immune Response

The adaptive immune system plays a pivotal role in the host’s ability to mount an effective, antigen-specific immune response against tumors. CD8+ tumor-infiltrating lymphocytes (TILs) mediate tumor rejection through recognition of tumor antigens and direct killing of transformed cells. In growing tumors, TILs are often functionally impaired as a result of interaction with, or signals from, transformed cells and the tumor microenvironment. These interactions and signals can lead to transcriptional, functional, and phenotypic changes in TILs that diminish the host’s ability to eradicate the tumor. In addition to effector and memory CD8+ T cells, populations described as exhausted, anergic, senescent, and regulatory CD8+ T cells have been observed in clinical and basic studies of antitumor immune responses. In the context of antitumor immunity, these CD8+ T cell subsets remain poorly characterized in terms of fate-specific biomarkers and transcription factor profiles. Here we discuss the current characterization of CD8+ T cell fates in antitumor immune responses and discuss recent insights into how signals in the tumor microenvironment influence TIL transcriptional networks to promote CD8+ T cell dysfunction.

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Respiratory Failure Associated with Ascariasis in a Patient with Immunodeficiency

In industrialized countries, risk groups for parasitic diseases include travelers, recent immigrants, and patients with immunodeficiency following chemotherapy and radiotherapy and AIDS. A 66-year-old Polish male was admitted in December 2012 to the Department of Haematology in a fairly good general condition. On the basis of cytological, cytochemical, immunophenotypic, and cytogenetic analysis of bone marrow, the patient was diagnosed with acute myeloblastic leukemia. On the 7th day of hospitalization in the Department of Haematology, patient was moved to the Intensive Care Unit (ICU) due to acute respiratory and circulatory failure. In March 2013, 3 months after the onset of respiratory failures, a mature form of Ascaris spp. appeared in the patient’s mouth. This report highlights the importance of considering an Ascaris infection in patients with low immunity presenting no eosinophilia but pulmonary failure in the central countries of Europe.

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Impacts of Fog Characteristics, Forward Illumination, and Warning Beacon Intensity Distribution on Roadway Hazard Visibility

Warning beacons are critical for the safety of transportation, construction, and utility workers. These devices need to produce sufficient luminous intensity to be visible without creating glare to drivers. Published standards for the photometric performance of warning beacons do not address their performance in conditions of reduced visibility such as fog. Under such conditions light emitted in directions other than toward approaching drivers can create scattered light that makes workers and other hazards less visible. Simulations of visibility of hazards under varying conditions of fog density, forward vehicle lighting, warning beacon luminous intensity, and intensity distribution were performed to assess their impacts on visual performance by drivers. Each of these factors can influence the ability of drivers to detect and identify workers and hazards along the roadway in work zones. Based on the results, it would be reasonable to specify maximum limits on the luminous intensity of warning beacons in directions that are unlikely to be seen by drivers along the roadway, limits which are not included in published performance specifications.

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A Study on Physical Performance for Poly(L-lactic acid) in Addition to Layered Strontium Phenylphosphonate

The organic-inorganic hybrid layered strontium phenylphosphonate (SrP) was synthesized by using strontium chloride and phenylphosphinic acid. And the influence of layered SrP on the crystallization behavior and thermal stability of poly(L-lactic acid) (PLLA) was investigated through DSC, XRD, and TGA. Both DSC and XRD results demonstrated that layered SrP had the powerful accelerated ability for PLLA crystallization, and in the range of studied concentration, 0.7 wt%–1 wt% is the optimum concentration range to achieve rapid crystallization of PLLA. Meantime, as a result, the increase of cooling rate in nonisothermal crystallization procedure seriously affected the crystallization accelerated efficiency of SrP. Thermal stability measurement showed that layered SrP could cause the onset decomposition temperature of PLLA to decrease, but the thermal decomposition behavior of PLLA hardly depended on the SrP concentration.

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Frequency of Specific Cardiovascular Disease Risk Factors among Cameroonian Patients on Dialysis: The Cases of Anaemia, Inflammation, Phosphate, and Calcium

Specific cardiovascular risk factors are known to contribute to increasing cardiovascular mortality in patients with chronic renal disease. However, little is known about their distribution in our population. This study aimed at determining the prevalence of anaemia, inflammation, and phosphocalcium disorders in Cameroonian patients on dialysis. Thirty-five participants with stage V chronic kidney disease (defined by glomerular filtration rate, GFR

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Differential contribution of three immune checkpoint (VISTA, CTLA-4, PD-1) pathways to antitumor responses against squamous cell carcinoma.

Differential contribution of three immune checkpoint (VISTA, CTLA-4, PD-1) pathways to antitumor responses against squamous cell carcinoma.

Oral Oncol. 2016 Jun;57:54-60

Authors: Kondo Y, Ohno T, Nishii N, Harada K, Yagita H, Azuma M

Abstract
V domain-containing Ig suppressor of T-cell activation (VISTA)/PD-1H is a novel immune checkpoint molecule for regulating T-cell activation. We examined the effects of anti-VISTA mAb monotherapy and combination therapy with CTLA-4 or PD-1 blockade in a squamous cell carcinoma (SCCVII) model. VISTA monotherapy did not show clear tumor growth regression, but efficiently induced CD8(+) T cell activation by converting resting and exhausted cells into functional effector cells. VISTA monotherapy did not inhibit recruitment of regulatory T cells (Tregs) in the tumor microenvironment (TME). As an additional treatment to VISTA, CTLA-4 blockade, but not PD-1 blockade, elicited further tumor regression. The CTLA-4 and VISTA combination efficiently inhibited Treg recruitment and increased the ratios of both CD8 T/Treg and CD4 conventional T (Tcon)/Treg in the TME, whereas the PD-1 and VISTA combination dramatically increased tumor-recruiting CD8(+) T cells, but markedly reduced the Tcon/Treg ratio. Our results demonstrate that VISTA blockade efficiently converts CD8(+) T cells into functional effector T cells, but is not sufficient to regress tumor growth due to weak Treg suppression in the TME. Our results suggest that combined CTLA-4 and VISTA blockade is more efficacious than combined PD-1 and VISTA blockade for tumors like head and neck squamous cell carcinoma in which Treg-mediated immune regulation is dominant.

PMID: 27208845 [PubMed - as supplied by publisher]



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The telomere proteins in tumorigenesis and clinical outcomes of oral squamous cell carcinoma.

The telomere proteins in tumorigenesis and clinical outcomes of oral squamous cell carcinoma.

Oral Oncol. 2016 Jun;57:46-53

Authors: Benhamou Y, Picco V, Pagès G

Abstract
The "Hallmarks of Cancer" describe the ways by which cancer cells bypass homeostasis. Escape from replicative senescence is one of the earliest features of cancer cells. Maintenance of the telomeres through reactivation of telomerase was initially associated with replicative immortality in various cancers. The shelterin complex, a telomeric hexaprotein association, plays a key role in telomere maintenance and in the hallmarks of cancer. Some shelterin proteins are overexpressed in diverse cancers and can promote tumorigenesis in animal models. Shelterin can also have an impact on tumor size, tumor growth and resistance to treatment. Studies into the expression level of shelterin in oral squamous cell carcinoma (OSCC) report contradictory results. Moreover, the exact role of these proteins in OSCC tumorigenesis remains uncertain. In this review, we examined the data linking telomeres and hallmarks of OSCC. Furthermore, we examined the literature concerning telomeres and the clinical outcome of OSCC. Finally, we propose a model encompassing the role of shelterin proteins in oral tumorigenesis and treatment outcome.

PMID: 27208844 [PubMed - as supplied by publisher]



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Do we need 5-FU in addition to cisplatin for chemoradiation of locally advanced head-and-neck cancer?

Do we need 5-FU in addition to cisplatin for chemoradiation of locally advanced head-and-neck cancer?

Oral Oncol. 2016 Jun;57:40-45

Authors: Rades D, Seidl D, Janssen S, Bajrovic A, Hakim SG, Wollenberg B, Schild SE

Abstract
OBJECTIVES: To compare chemoradiation with cisplatin alone or cisplatin plus 5-FU for locally advanced squamous cell carcinoma of the head-and-neck (SCCHN).
MATERIALS AND METHODS: The outcomes of 142 patients who received chemoradiation with cisplatin alone for locally advanced SCCHN were retrospectively compared to 170 patients who received cisplatin plus 5-fluorouracil (5-FU). The outcomes compared included loco-regional control (LRC), metastases-free survival (MFS), overall survival (OS) and adverse events.
RESULTS: Although patients who received cisplatin alone had a significantly worse performance status, 81% of these patients completed planned chemotherapy compared to 73% of patients in the cisplatin plus 5-FU group (p=0.18). Radiotherapy breaks >1week were necessary in 14% and 23% of patients, respectively (p=0.09). The 5-year LRC rates were 69% after cisplatin alone and 68% after cisplatin plus 5-FU (p=0.71). The 5-year MFS rates were 72% and 62%, respectively (p=0.37), and 5-year OS rates were 60% and 45%, respectively (p=0.066). On multivariate analysis, cisplatin alone was significantly associated with improved OS (RR 1.35; 95%-CI 1.09-1.69; p=0.006). Nausea/vomiting, pneumonia/sepsis and late adverse events occurred more common in the cisplatin plus 5-FU group.
CONCLUSION: Given the limitations of a retrospective study, chemoradiation with cisplatin alone appeared associated with fewer adverse events and better OS than with cisplatin plus 5-FU in patients with locally advanced SCCHN. Thus, 5-FU in addition to cisplatin may be omitted for these patients. A randomized trial is warranted to confirm these findings.

PMID: 27208843 [PubMed - as supplied by publisher]



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Image guided surgery in the management of head and neck cancer.

Image guided surgery in the management of head and neck cancer.

Oral Oncol. 2016 Jun;57:32-39

Authors: Iqbal H, Pan Q

Abstract
Complete resection of head and neck tumors relies on palpation and visual inspection. Achieving a negative margin in remote locations in the head and neck region, especially in close proximity to critical structures, is often difficult to achieve. Positive resection margins in head and neck cancer are at high risk to develop recurrent disease and associated with poor prognosis. Near-infrared fluorescence-guided optical imaging is an emerging technology with the potential to move the surgical field forward and facilitate surgeons to visualize tumors in real-time intra-operatively. In this review, our focus is to discuss the recent advances and the potential application of near infrared (NIR) fluorescent-guided surgery in the management of head and neck cancer.

PMID: 27208842 [PubMed - as supplied by publisher]



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Third party assessment of resection margin status in head and neck cancer.

Third party assessment of resection margin status in head and neck cancer.

Oral Oncol. 2016 Jun;57:27-31

Authors: Ransohoff A, Wood D, Solomon Henry A, Divi V, Colevas A

Abstract
BACKGROUND: Definitive assessment of primary site margin status following resection of head and neck cancer is necessary for prognostication, treatment determination and qualification for clinical trials. This retrospective analysis determined how often an independent reviewer can assess primary tumor margin status of head and neck cancer resections based on review of the pathology report, surgical operative report, and first follow-up note alone.
METHODS: We extracted from the electronic medical record pathology reports, operative reports, and follow-up notes from head and neck cancer resections performed at Stanford Hospital. We classified margin status as definitive or not. We labeled any pathology report clearly indicating a positive, negative, or close (<5mm) margin as definitive. For each non-definitive pathology report, we reviewed the operative report and then the first follow-up note in an attempt to clarify margin status. We also looked for associations between non-definitive status and surgeon, year, and primary site.
RESULTS: 743 unique cases of head and neck cancer resection were extracted. We discarded 255 as non-head and neck cancer cases, or cases that did not involve a definitive resection of a primary tumor site. We could not definitively establish margin status in 20% of resections by independent review of the medical record. There was no correlation between margin determination and surgeon, site, or year of surgery.
CONCLUSION: A substantial fraction (20%) of primary site surgical margins could not be definitively determined via independent EMR review. This could have implications for subsequent patient care decisions and clinical trial options.

PMID: 27208841 [PubMed - as supplied by publisher]



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Severe late dysphagia and cause of death after concurrent chemoradiation for larynx cancer in patients eligible for RTOG 91-11.

Severe late dysphagia and cause of death after concurrent chemoradiation for larynx cancer in patients eligible for RTOG 91-11.

Oral Oncol. 2016 Jun;57:21-26

Authors: Ward MC, Adelstein DJ, Bhateja P, Nwizu TI, Scharpf J, Houston N, Lamarre ED, Lorenz R, Burkey BB, Greskovich JF, Koyfman SA

Abstract
PURPOSE: The long-term results of RTOG 91-11 suggested increased deaths not attributed to larynx cancer after concomitant chemoradiotherapy (CRT) despite no apparent increase in late effects. Because the timing of events was not reported by RTOG 91-11, one possibility is that severe late dysphagia (SLD) develops beyond five years and leads to unreported treatment-related deaths. Here we explore the timing of SLD after CRT.
METHODS: Patients who would have met eligibility criteria for RTOG 91-11 and were treated with CRT between 1993 and 2013 were identified. Events occurring beyond 3months after treatment and suggestive of SLD were recorded including esophageal stricture dilations, hospital admissions for aspiration pneumonia or feeding-tube insertion. Feeding-tube dependence beyond one year was also considered SLD. The cumulative incidence of SLD and its components was quantified using Gray's competing risk analysis with recurrence or death considered competing risks.
RESULTS: Eighty-four patients were included with a median follow-up of 43months. The 5-year overall survival was 70% (95% CI 58-80%). No death was directly a result of treatment-induced late dysphagia. The 5-year incidence of SLD was 26.5%. While 15 of 18 (83%) first stricture dilations occurred within 5years after CRT, 3 of 5 (60%) aspiration admissions and 5 of 8 late feeding tube insertions occurred beyond five years from CRT.
CONCLUSIONS: SLD is common after CRT for larynx cancer and can occur beyond 5years from the end of treatment, emphasizing the importance of survivorship follow-up. Despite the incidence of SLD, death related to dysphagia is uncommon.

PMID: 27208840 [PubMed - as supplied by publisher]



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microRNA-21 and microRNA-375 from oral cytology as biomarkers for oral tongue cancer detection.

microRNA-21 and microRNA-375 from oral cytology as biomarkers for oral tongue cancer detection.

Oral Oncol. 2016 Jun;57:15-20

Authors: He Q, Chen Z, Cabay RJ, Zhang L, Luan X, Chen D, Yu T, Wang A, Zhou X

Abstract
OBJECTIVE: We previously performed a meta-analysis of microRNA profiling studies on head and neck/oral cancer (HNOC), and identified 11 consistently dysregulated microRNAs in HNOC. Here, we evaluate the diagnostic values of these microRNAs in oral tongue squamous cell carcinoma (OTSCC) using oral cytology samples.
MATERIALS AND METHODS: The levels of 11 microRNAs were assessed in 39 oral cytology samples (19 OTSCC and 20 normal subjects), and 10 paired OTSCC and adjacent normal tissues. The predictive power of these microRNAs was analyzed by receiver operating characteristic curve (ROC) and random forest (RF) model. A classification and regression trees (CART) model was generated using miR-21 and miR-375, and further validated using both independent oral cytology validation sample set (14 OTSCC and 11 normal subjects) and tissue validation sample set (12 paired OTSCC and adjacent normal tissues).
RESULTS: Differential expression of miR-21, miR-100, miR-125b and miR-375 was validated in oral cytology training sample set. Based on the RF model, the combination of miR-21 and miR-375 was selected which provide best prediction of OTSCC. A CART model was constructed using miR-21 and miR-375, and was tested in both oral cytology and tissue validation sample sets. A sensitivity of 100% and specificity of 64% was achieved in distinguishing OTSCC from normal in the oral cytology validation set, and a sensitivity of 83% and specificity of 83% was achieved in the tissue validation set.
CONCLUSION: The utility of microRNA from oral cytology samples as biomarkers for OTSCC detection is successfully demonstrated in this study.

PMID: 27208839 [PubMed - as supplied by publisher]



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Validation of metabolic tumor volume as a prognostic factor for oral cavity squamous cell carcinoma treated with primary surgery.

Validation of metabolic tumor volume as a prognostic factor for oral cavity squamous cell carcinoma treated with primary surgery.

Oral Oncol. 2016 Jun;57:6-14

Authors: Zhang H, Seikaly H, Nguyen NT, Abele JT, Dziegielewski PT, Harris JR, O'Connell DA

Abstract
BACKGROUND: Despite the promise of metabolic tumor volume (MTV) as a risk-stratifying marker, the retrospective design of the initial study limits its generalizability. Therefore, this study sought to validate MTV as a prognostic factor for oral cavity squamous cell carcinoma (OCSCC) treated with primary surgery within an independent data set.
METHODS: The validation data set consisted of 42 patients diagnosed with OCSCC between 2008 and 2012. The original cohort consisted of 80 patients. MTV and SUVmax were calculated for the primary tumor and nodal metastasis separately, as well as combined. Before statistical analysis, MTV and SUVmax values were divided into intertertile thirds to allow for intergroup survival analysis. Validation analysis was conducted on the validation data set alone. Data from both cohorts were then combined (n=122) to increase statistical power.
RESULTS: An increase in combined MTV of 17.5cm(3) was associated with statistically significant increase in risk of disease recurrence (HR=19.2, p<0.001) and death (HR=9.2, p<0.05). Combined SUVmax failed to predict overall (HR=1.0, p>0.05) and disease-free survival (HR=1.0, p>0.05). Increase in the MTV of the primary tumor was associated with an increase in the risk of disease recurrence (HR=21.7, p=0.0001) and risk of death (HR=7.0, p=0.0001), while increase in the MTV of the locoregional neck metastasis was not (p>0.05). An MTV cutoff value of greater than 10.2cm(3) was found to significantly affect survival.
CONCLUSION: Due to the reproducibility of MTV findings, this study validates MTV as an independent prognostic factor for OCSCC treated with primary surgery.

PMID: 27208838 [PubMed - as supplied by publisher]



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Osteoradionecrosis in patients with salivary gland malignancies.

Osteoradionecrosis in patients with salivary gland malignancies.

Oral Oncol. 2016 Jun;57:1-5

Authors: Tucker JR, Xu L, Sturgis EM, Mohamed AS, Hofstede TM, Chambers MS, Lai SY, Fuller CD, Beadle B, Gunn GB, Hutcheson KA

Abstract
PURPOSE: The present study was undertaken to evaluate osteoradionecrosis (ORN) in patients with salivary gland malignancies (SGM) after treatment with radiation therapy.
MATERIALS AND METHODS: The medical records of 172 patients treated with radiation therapy for SGM during a 12-year period (August 2001 to November 2013) were reviewed. Incidence, time to event, staging and management of ORN were analyzed.
RESULTS: Of the 172 patients, 7 patients (4%) developed ORN (median latency: 19months, range: 4-72months). Of those 7 patients, 4 required major surgery, 1 required hyperbaric oxygen therapy (HBO), one required minor debridement, and one required conservative management. Total prescribed radiation dose varied from 50Gy (1 case) to 70Gy (1 case) among those patients who developed ORN, and radiotherapy was delivered postoperatively after osseous resection in 4 of 7 cases. Three of the 7 cases of ORN occurred after traumatic injury to the bone. Of the 7 patients who developed ORN, 3 had SGM of the major glands, 3 had other sites of the oral cavity, and 1 had a sinonasal location.
CONCLUSION: While the rate of ORN after radiotherapy for SGM was somewhat lower (4%) than previously published data on patients with squamous cell carcinomas of the head and neck treated with radiation therapy (8-14%), ORN necessitating major surgery remains a clinically significant, possible late effect of radiotherapy in SGM survivors. Location of SGM is very important, with cases that developed ORN disproportionally having primary disease arising in the oral cavity.

PMID: 27208837 [PubMed - as supplied by publisher]



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Loss of glycine receptors containing the α3 subunit compromises auditory nerve activity, but not outer hair cell function.

Loss of glycine receptors containing the α3 subunit compromises auditory nerve activity, but not outer hair cell function.

Hear Res. 2016 May 18;

Authors: Dlugaiczyk J, Hecker D, Neubert C, Buerbank S, Campanelli D, Becker CM, Betz H, Knipper M, Rüttiger L, Schick B

Abstract
Inhibitory glycine receptors containing the α3 subunit (GlyRα3) regulate sensory information processing in the CNS and retina. In previous work, we demonstrated the presence of postsynaptic GlyR alpha3 immunoreactivity at efferent synapses of the medial and lateral olivocochlear bundle in the organ of Corti; however, the role of these alpha3-GlyRs in auditory signalling has remained elusive. The present study analyzes distortion-product otoacoustic emissions (DPOAEs) and auditory brainstem responses (ABRs) of knockout mice with a targeted inactivation of the Glra3 gene (Glra3(-/-)) and their wildtype littermates (Glra3(+/+)) before and seven days after acoustic trauma (AT; 4 to 16 kHz, 120 dB SPL, 1 h). Before AT, DPOAE thresholds were slightly, but significantly lower, and DPOAE amplitudes were slightly larger in Glra3(-/-) as compared to Glra3(+/+) mice. While click- and f-ABR thresholds were similar in both genotypes before AT, threshold-normalized click-ABR wave I amplitudes were smaller in Glra3(-/-) mice as compared to their wildtype littermates. Following AT, both the decrement of ABR wave I amplitudes and the delay of wave I latencies were more pronounced in Glra3(-/-) than Glra3(+/+) mice. Accordingly, correlation between early click-evoked ABR signals (0 to 2.5 ms from stimulus onset) before and after AT was significantly reduced for Glra3(-/-) as compared to Glra3(+/+) mice. In summary, these results show that loss of α3-GlyRs compromises suprathreshold auditory nerve activity, but not outer hair cell function.

PMID: 27208792 [PubMed - as supplied by publisher]



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End Binding 1 (EB1) overexpression in oral lesions and cancer: A biomarker of tumor progression and poor prognosis.

End Binding 1 (EB1) overexpression in oral lesions and cancer: A biomarker of tumor progression and poor prognosis.

Clin Chim Acta. 2016 May 18;

Authors: Kumar M, Mehra S, Thakar A, Shukla NK, Roychoudhary A, Sharma MC, Ralhan R, Chauhan SS

Abstract
INTRODUCTION: Oral squamous cell carcinoma (OSCC) patients are at high risk of loco-regional recurrence and despite the improvement in treatment strategy, 5-year survival rates are about 50%. Identification of patients at high risk of recurrence may enable rigorous personalized post-treatment management. In an earlier proteomics study we identified End Binding Protein (EB1) to be overexpressed in OSCC. We investigated the diagnostic and prognostic significance of alterations in expression of EB1 in oral cancer.
METHODS: In this retrospective study, the expression of EB1 protein was evaluated in 259 OSCCs, 41 dysplasia, 166 hyperplasia and 126 normal tissues using immunohistochemistry and correlated with clinical-pathological parameters and prognosis of OSCC patients over a follow-up period of up to 91months.
RESULTS: Significant overexpression of cytoplasmic EB1 was observed in hyperplasia [p<0.001, OR=7.2, 95% CI=4.1-12.8], dysplasia (p<0.001, OR=21.8, CI=8.8-50.2) and OSCCs (p<0.001, OR=10.1, CI=5.8-17.4) in comparison with normal mucosa. Univariate analysis revealed cytoplasmic EB1 association with tumor grade, tumor size and recurrence of the disease. Kaplan Meier survival analysis of EB1 expression showed significantly reduced disease free survival (DFS) (p=0.003). Notably, OSCC patients showing cytoplasmic EB1 overexpression demonstrated significantly reduced DFS (p=0.004, HR=2.1).
CONCLUSION: EB1 overexpression is an early event in oral tumorigenesis and cytoplasmic EB1 accumulation is associated with poor prognosis and tumor recurrence in OSCC patients.

PMID: 27208742 [PubMed - as supplied by publisher]



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TRAF3 Signaling: Competitive Binding and Evolvability of Adaptive Viral Molecular Mimicry.

TRAF3 Signaling: Competitive Binding and Evolvability of Adaptive Viral Molecular Mimicry.

Biochim Biophys Acta. 2016 May 18;

Authors: Guven-Maiorov E, Keskin O, Gursoy A, VanWaes C, Chen Z, Tsai CJ, Nussinov R

Abstract
BACKGROUND: The tumor necrosis factor receptor (TNFR) associated factor 3 (TRAF3) is a key node in innate and adaptive immune signaling pathways. TRAF3 negatively regulates the activation of the canonical and non-canonical NF-κB pathways and is one of the key proteins in antiviral immunity.
SCOPE OF REVIEW: Here we provide a structural overview of TRAF3 signaling in terms of its competitive binding and consequences to the cellular network. For completion, we also include molecular mimicry of TRAF3 physiological partners by some viral proteins.
MAJOR CONCLUSIONS: By out-competing host partners, viral proteins aim to subvert TRAF3 antiviral action. Mechanistically, dynamic, competitive binding by the organism's own proteins and same-site adaptive pathogen mimicry follow the same conformational selection principles.
GENERAL SIGNIFICANCE: Our premise is that irrespective of the eliciting event - physiological or acquired pathogenic trait - pathway activation (or suppression) may embrace similar conformational principles. However, even though here we largely focus on competitive binding at a shared site, similar to physiological signaling other pathogen subversion mechanisms can also be at play.

PMID: 27208423 [PubMed - as supplied by publisher]



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Development of a Low-Cost, Noninvasive, Portable Visual Speech Recognition Program.

Development of a Low-Cost, Noninvasive, Portable Visual Speech Recognition Program.

Ann Otol Rhinol Laryngol. 2016 May 19;

Authors: Kohlberg GD, Gal YK, Lalwani AK

Abstract
OBJECTIVES: Loss of speech following tracheostomy and laryngectomy severely limits communication to simple gestures and facial expressions that are largely ineffective. To facilitate communication in these patients, we seek to develop a low-cost, noninvasive, portable, and simple visual speech recognition program (VSRP) to convert articulatory facial movements into speech.
METHODS: A Microsoft Kinect-based VSRP was developed to capture spatial coordinates of lip movements and translate them into speech. The articulatory speech movements associated with 12 sentences were used to train an artificial neural network classifier. The accuracy of the classifier was then evaluated on a separate, previously unseen set of articulatory speech movements.
RESULTS: The VSRP was successfully implemented and tested in 5 subjects. It achieved an accuracy rate of 77.2% (65.0%-87.6% for the 5 speakers) on a 12-sentence data set. The mean time to classify an individual sentence was 2.03 milliseconds (1.91-2.16).
CONCLUSION: We have demonstrated the feasibility of a low-cost, noninvasive, portable VSRP based on Kinect to accurately predict speech from articulation movements in clinically trivial time. This VSRP could be used as a novel communication device for aphonic patients.

PMID: 27208007 [PubMed - as supplied by publisher]



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A clinical study of multimodal treatment for orbital organ preservation in locally advanced squamous cell carcinoma of the nasal cavity and paranasal sinus.

A clinical study of multimodal treatment for orbital organ preservation in locally advanced squamous cell carcinoma of the nasal cavity and paranasal sinus.

Jpn J Clin Oncol. 2016 May 20;

Authors: Chen NX, Chen L, Wang JL, Wang JY, Yan F, Ma L, Zhang XX

Abstract
OBJECTIVE: This study aimed to investigate the efficacy of induction chemotherapy followed by concurrent chemotherapy and helical tomotherapy in patients with T4b squamous cell carcinoma of the nasal cavity and paranasal sinus in regard to orbital organ preservation and quality of life.
METHODS: Clinical data of 28 cases of patients with orbital involvement of T4b squamous cell carcinoma of the nasal cavity and paranasal sinus who received multimodal treatment for orbital organ preservation between May 2008 and September 2015 were retrospectively analysed. The treatment efficacy and side effects were assessed. The study included 18 male and 10 female patients. All patients were treated with induction chemotherapy followed by concurrent chemoradiotherapy and/or epidermal growth factor receptor inhibitor. Helical tomotherapy was applied as radiotherapy. Adverse reactions to the chemotherapy were assessed according to Common Terminology Criteria for Adverse Events, Version 4. The overall survival rate, local control rate and rate of effective orbital preservation were calculated using the Kaplan-Meier method.
RESULTS: All patients completed the planned chemotherapy, and 27 (96.4%) of the patients completed the planned radiotherapy cycle. After the multimodal treatment, the 3-year overall survival, local control rate and rate of effective orbital preservation of the patients were 59.2%, 80.2% and 77.8%, respectively.
CONCLUSIONS: Multimodal treatment could preserve the orbital organs of patients with T4b squamous cell carcinoma of the nasal cavity and paranasal sinus, achieve relatively ideal organ protection and survival rates and improve the quality of life of patients with advanced squamous cell carcinoma of the nasal cavity and paranasal sinus, thus providing a new treatment option for these patients.

PMID: 27207888 [PubMed - as supplied by publisher]



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Afatinib against esophageal or head-and-neck cell squamous carcinoma: significance of activating oncogenic HER4 mutations in HNSCC.

Afatinib against esophageal or head-and-neck cell squamous carcinoma: significance of activating oncogenic HER4 mutations in HNSCC.

Mol Cancer Ther. 2016 May 20;

Authors: Nakamura Y, Togashi Y, Nakahara H, Tomida S, Banno E, Terashima M, Hayashi H, de Velasco MA, Sakai K, Fujita Y, Okegawa T, Nutahara K, Hamada S, Nishio K

Abstract
The prognosis for patients with advanced esophageal or head-and-neck squamous cell carcinoma (ESCC or HNSCC) remains poor, and the identification of additional oncogenes and their inhibitors is needed. In this study, we evaluated the sensitivities of several ESCC and HNSCC cell lines to HER inhibitors (cetuximab, erlotinib, and afatinib) in vitro and found two cell lines that were hypersensitive to afatinib. Sequence analyses for the afatinib-targeted HER family genes in the two cell lines revealed that one cell line had a previously reported activating EGFR L861Q mutation, while the other had a HER4 G1109C mutation of unknown function. No amplification of HER family genes was found in either of the two cell lines. The phosphorylation level of HER4 was elevated in the HER4 G1109C mutation-overexpressed HEK293 cell line, and the mutation had a transforming potential and exhibited tumorigenicity in an NIH3T3 cell line, indicating that this HER4 mutation was an activating oncogenic mutation. Afatinib dramatically reduced the phosphorylation level of EGFR or HER4 and induced apoptosis in the two cell lines. In vivo, tumor growth was also dramatically decreased by afatinib. In a database, the frequencies of HER family gene mutations in ESCC or HNSCC ranged from 0% to 5%. In particular, HER4 mutations have been found relatively frequently in HNSCC. Considering the addiction of cancer cells to activating oncogenic EGFR or HER4 mutations for proliferation, HNSCC or ESCC with such oncogenic mutations might be suitable for targeted therapy with afatinib.

PMID: 27207775 [PubMed - as supplied by publisher]



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Exploring the bacterial assemblages along the human nasal passage.

Exploring the bacterial assemblages along the human nasal passage.

Environ Microbiol. 2016 May 21;

Authors: Wos-Oxley ML, Chaves-Moreno D, Jáuregui R, Oxley AP, Kaspar U, Plumeier I, Kahl S, Rudack C, Becker K, Pieper DH

Abstract
The human nasal passage, from the anterior nares through the nasal vestibule to the nasal cavities, is an important habitat for opportunistic pathogens and commensals alike. This work sampled four different anatomical regions within the human nasal passage across a large cohort of individuals (n= 79) comprising individuals suffering from chronic nasal inflammation clinically known as chronic rhinosinusitis (CRS) and individuals not suffering from inflammation (CRS-free). While individuals had their own unique bacterial fingerprint that was consistent across the anatomical regions, these bacterial fingerprints formed into distinct delineated groups comprising core bacterial members, which were consistent across all four swabbed anatomical regions irrespective of health status. The most significant observed pattern was the difference between the global bacterial profiles of swabbed and tissue biopsy samples from the same individuals, being also consistent across different anatomical regions. Importantly, no statistically significant differences could be observed concerning the global bacterial communities, any of the bacterial species or the range of diversity indices used to compare between CRS and CRS-free individuals, and between two CRS phenotypes (without nasal polyps and with nasal polyps). Thus, the role of bacteria in the pathogenesis of sinusitis remains uncertain. This article is protected by copyright. All rights reserved.

PMID: 27207744 [PubMed - as supplied by publisher]



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Selected single-nucleotide polymorphisms in FOXE1, SERPINA5, FTO, EVPL, TICAM1 and SCARB1 are associated with papillary and follicular thyroid cancer risk: replication study in a German population.

Selected single-nucleotide polymorphisms in FOXE1, SERPINA5, FTO, EVPL, TICAM1 and SCARB1 are associated with papillary and follicular thyroid cancer risk: replication study in a German population.

Carcinogenesis. 2016 Apr 28;

Authors: Sigurdson AJ, Brenner AV, Roach JA, Goudeva L, Müller JA, Nerlich K, Reiners C, Schwab R, Pfeiffer L, Waldenberger M, Braganza M, Xu L, Sturgis EM, Yeager M, Chanock SJ, Pfeiffer RM, Abend M, Port M

Abstract
Several single-nucleotide polymorphisms (SNPs) have been associated with papillary and follicular thyroid cancer (PTC and FTC, respectively) risk, but few have replicated. After analyzing 17525 tag SNPs in 1129 candidate genes, we found associations with PTC risk in SERPINA5, FTO, HEMGN (near FOXE1) and other genes. Here, we report results from a replication effort in a large independent PTC/FTC case-control study conducted in Germany. We evaluated the best tagging SNPs from our previous PTC study and additionally included SNPs in or near FOXE1 and NKX2-1 genes, known susceptibility loci for thyroid cancer. We genotyped 422 PTC and 130 FTC cases and 752 controls recruited from three German clinical centers. We used polytomous logistic regression to simultaneously estimate PTC and FTC associations for 79 SNPs based on log-additive models. We assessed effect modification by body mass index (BMI), gender and age for all SNPs, and selected SNP by SNP interactions. We confirmed associations with PTC and SNPs in FOXE1/HEMGN, SERPINA5 (rs2069974), FTO (rs8047395), EVPL (rs2071194), TICAM1 (rs8120) and SCARB1 (rs11057820) genes. We found associations with SNPs in FOXE1, SERPINA5, FTO, TICAM1 and HSPA6 and FTC. We found two significant interactions between FTO (rs8047395) and BMI (P = 0.0321) and between TICAM1 (rs8120) and FOXE1 (rs10984377) (P = 0.0006). Besides the known associations with FOXE1 SNPs, we confirmed additional PTC SNP associations reported previously. We also found several new associations with FTC risk and noteworthy interactions. We conclude that multiple variants and host factors might interact in complex ways to increase risk of PTC and FTC.

PMID: 27207655 [PubMed - as supplied by publisher]



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Lipocalin 2 prevents oral cancer metastasis through carbonic anhydrase IX inhibition and is associated with favourable prognosis.

Lipocalin 2 prevents oral cancer metastasis through carbonic anhydrase IX inhibition and is associated with favourable prognosis.

Carcinogenesis. 2016 Apr 27;

Authors: Lin CW, Yang WE, Lee WJ, Hua KT, Hsieh FK, Hsiao M, Chen CC, Chow JM, Chen MK, Yang SF, Chien MH

Abstract
Lipocalin 2 (LCN2), a secreted glycoprotein, is up- or downregulated in different human cancers. At present, the functional role of LCN2 in the progression of oral squamous cell carcinoma (OSCC), which accounts for most head and neck cancers, remains poorly understood, particularly with respect to its involvement in invasion and metastasis. In this study, we observed that LCN2 expression decreased in patients with OSCC and lymph node metastasis compared with that in patients without metastasis. A higher LCN2 expression correlated with the survival of patients with OSCC. Furthermore, LCN2 overexpression in OSCC cells reduced in vitro migration and invasion and in vivo metastasis, whereas its silencing induced an increase in cell motility. Mechanistically, LCN2 inhibited the cell motility of OSCC cells through hypoxia-inducible factor (HIF)-1α-dependent transcriptional inhibition of the carbonic anhydrase IX (CAIX). CAIX overexpression relieved the migration inhibition imposed by LCN2 overexpression in OSCC cells. Moreover, a microRNA (miR) analysis revealed that LCN2 can suppress CAIX expression and cell migration through miR-4505 induction. Examination of tumour tissues from patients with OSCC and OSCC-transplanted mice revealed an inverse correlation between LCN2 and CAIX expression. Furthermore, patients with LCN2(strong)/CAIX(weak) revealed the lowest frequency of lymph node metastasis and the longest survival. Our findings suggest that LCN2 suppresses tumour metastasis by targeting the transcriptional and post-transcriptional regulation of CAIX in OSCC cells. LCN2 overexpression may be a novel OSCC treatment strategy and a useful biomarker for predicting OSCC progression.

PMID: 27207653 [PubMed - as supplied by publisher]



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Medial sural artery perforator flap in head and neck reconstruction.

Medial sural artery perforator flap in head and neck reconstruction.

Eur Arch Otorhinolaryngol. 2016 May 20;

Authors: Özkan HS, İrkören S, Aydın OE, Eryılmaz A, Karaca H

Abstract
Medial sural artery perforator (MSAP) flap is a relatively new flap which is a modification of medial gastrocnemius myocutaneous flap. Both radial forearm flap and MSAP has common benefits, such as thinness, long pedicle and pliability; however, MSAP has lower donor site morbidity when compared with radial forearm flap. Because of this reason, the MSAP flap has gained popularity during the last decade. The objective of this study was to determine clinical application results of this flap in reconstruction of post-oncologic defects in the head and neck region. 11 patients operated for head and neck post oncologic defects and reconstructed with MSAP between June 2014 and Dec 2015 were included in the study. Age, gender, histopathology, area of reconstruction, flap size, number of perforators were reviewed. Postoperatively recipient and donor site complications, hospital stay and additional surgical procedures were also analyzed. We had seven uncomplicated cases; one total flap failure due to arterial problem, in three cases due fistula formation and local wound healing problems additional surgeries were performed. All venous anastomosis were performed with 9/0 sutures, nine arterial anastomosis were performed with 9/0 and two arterial anastomosis were performed with 10/0 nylon sutures. Medial sural artery perforator flap is a good alternative in head and neck reconstruction, with the advantages of thin and pliable skin, a reliable vascular pedicle, straightforward intramuscular dissection. But there are certain drawbacks like tedious pedicle and perforator dissection, small arterial pedicle size which complicates anastomosis and obscurities of anatomy. Surgical team must always be ready for a difficult micro anastomosis and an alternative flap choice must be prepared and counseled with the patient in case of inadequate perforators.

PMID: 27207139 [PubMed - as supplied by publisher]



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Feasibility and Outcomes of the Third or More Episodes of Sequential Microvascular Reconstruction for Recurrent or Second Primary Oral Cancer.

Feasibility and Outcomes of the Third or More Episodes of Sequential Microvascular Reconstruction for Recurrent or Second Primary Oral Cancer.

Ann Surg Oncol. 2016 May 20;

Authors: Offodile AC, Chang KP, Chen HH, Loesch E, Hung SY, Kao HK

Abstract
BACKGROUND: This study was a robust examination of the clinical outcomes and technical feasibility of sequential microvascular reconstruction for recurrent or second primary oral cancer.
METHODS: A retrospective, cross-sectional analysis of adult patients undergoing microvascular reconstruction of head and neck oncologic defects was performed at Chang Gung Memorial Hospital, spanning 10 years. The patients were divided into three groups as follows: first episode, second episode, and third or more episodes of reconstruction. Demographics, operative details, and clinical outcomes were compared.
RESULTS: The study cohort included 3186, 319, and 62 patients who respectively received first, second, and third or more episodes of reconstruction. The most common tumor sites were the tongue (36.9 %) and the buccal region (36.8 %), with squamous cell carcinoma as the prevalent histology. The anterior lateral thigh was the most popular donor site used (76.1 %). The third or more episodes of microvascular reconstruction were associated with an increased incidence of flap failure (8.1 %) relative to the first (1.9 %; p = 0.003) and the second (1.6 %; p = 0.01) episodes. Re-exploration of venous occlusion (9.7 vs. 3.2 %), neck wound infections (53.2 vs. 35.5 %), fistula (17.7 vs. 8.1 %), and hospital stay (28.9 ± 14.6 vs. 25.3 ± 10.1) also showed significantly higher values for the third or more episodes group than for the first episode group.
CONCLUSIONS: Sequential microvascular reconstruction for recurrent or second primary oral cancer is associated with an increased incidence of postoperative complications. However, in appropriate candidates for repeat ablation, microvascular reconstruction remains the gold standard for attaining functional and cosmetic outcomes.

PMID: 27207095 [PubMed - as supplied by publisher]



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Tuberculous arthritis of the hip with Staphylococcus aureus superinfection

Publication date: Available online 21 May 2016
Source:Journal of Infection and Chemotherapy
Author(s): Yuki Moriyama, Yumi Sono, Hiroaki Nishioka
Skeletal tuberculosis (TB) accounts for a small percentage of all cases of TB. It is often difficult to diagnose, especially in the hip joint. TB arthritis can be masked by superinfection with other pathogens, leading to a delay in diagnosis and treatment. Trauma or surgery is a reported risk factor of TB arthritis. In contrast, descriptions of TB arthritis after a closed bone fracture are rare. We herein report a case involving an 81-year-old woman with septic arthritis superinfected with methicillin-resistant Staphylococcus aureus (MRSA) and Mycobacterium tuberculosis. Three months before presentation, she sustained a bone fracture of the left femur and was treated conservatively without surgery. She developed a fever at another hospital and was transferred to our institution. Computed tomography revealed the presence of abnormal fluid around the left hip joint. MRSA was detected from the fluid and blood cultures. The patient was diagnosed with MRSA arthritis and treated with antibiotics and surgical drainage. However, her fever persisted, and the abscess further developed and enlarged around the left hip. It was punctured and cultured again. Three weeks later, Mycobacterium tuberculosis was identified from the abscess culture. The septic arthritis was confirmed to have been caused by MRSA and M. tuberculosis. After the initiation of antituberculosis therapy, her fever subsided and the treatment was continued. This case demonstrates that the diagnosis of TB arthritis can be hindered by the existence of other pathogens and that TB arthritis can occur at a closed fracture site in the hip joint.



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Autoimmune conditions are associated with perioperative thrombotic complications in liver transplant recipients: A UNOS database analysis

End stage liver disease (ESLD) is associated with significant thrombotic complications. In this study, we attempted to determine if patients with ESLD, due to oncologic or autoimmune diseases, are susceptible ...

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Hematological, Biochemical, and Serological Findings in Healthy Canine Blood Donors after the Administration of CaniLeish® Vaccine

The aim of the study was to evaluate hematological, biochemical, and serological findings in healthy canine blood donors after the administration of CaniLeish® vaccine. Twenty-seven client-owned dogs were included in the study and arranged into 3 groups according to the vaccination stage. Complete blood count (CBC) with blood smear examination, serum biochemical profile (SBP), serum protein electrophoresis (SPE), and serological tests for L. infantum were performed at different times. Additionally, in a subgroup of dogs IgA, IgM, and IgG were quantified. No statistical significance for CBC and SBP was found. In 10.7% of cases slight hyperproteinemia occurred. In SPE absolute values β-1-globulins (Group 2 and Group 2-3) and β-2-globulins (Group 3) were found modified (). IgG values were statistically different () 6–8 months after the third immunisation (Group 2) and IgM and IgG values were statistically different after 2 months (Group 3). IFAT positive samples were 20.8% (Group 1), 15.0% (Group 2), and 52.8% (Group 3). Speed Leish ™ tests were always negative. The modifications found were probably attributed to the development of immune or inflammatory response due to the vaccine. Administration of CaniLeish vaccine in canine blood donors could be a safe practice and did not affect their health status.

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Probabilistic Analysis of Steady-State Temperature and Maximum Frequency of Multicore Processors considering Workload Variation

A probabilistic method is presented to analyze the temperature and the maximum frequency for multicore processors based on consideration of workload variation, in this paper. Firstly, at the microarchitecture level, dynamic powers are modeled as the linear function of IPCs (instructions per cycle), and leakage powers are approximated as the linear function of temperature. Secondly, the microarchitecture-level hotspot temperatures of both active cores and inactive cores are derived as the linear functions of IPCs. The normal probabilistic distribution of hotspot temperatures is derived based on the assumption that IPCs of all cores follow the same normal distribution. Thirdly and lastly, the probabilistic distribution of the set of discrete frequencies is determined. It can be seen from the experimental results that hotspot temperatures of multicore processors are not deterministic and have significant variations, and the number of active cores and running frequency simultaneously determine the probabilistic distribution of hotspot temperatures. The number of active cores not only results in different probabilistic distribution of frequencies, but also leads to different probabilities for triggering DFS (dynamic frequency scaling).

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Greater understanding of HPV in UAE may help reduce cervical cancer cases - The National


The National

Greater understanding of HPV in UAE may help reduce cervical cancer cases
The National
There are no visible symptoms of the virus that causes cervical cancer, which is why doctors are calling for screenings. HPV can also cause other cancers, such as cancer of the vulva, vagina, penis, or anus, the throat and base of the tongue and tonsils.

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Learning curve of MRI-based planning for high-dose-rate brachytherapy for prostate cancer

Publication date: Available online 21 May 2016
Source:Brachytherapy
Author(s): Simon Buus, Susanne Rylander, Steffen Hokland, Christian Skou Søndergaard, Erik Morre Pedersen, Kari Tanderup, Lise Bentzen
PurposeTo evaluate introduction of MRI-based high-dose-rate brachytherapy (HDRBT), including procedure times, dose-volume parameters, and perioperative morbidity.Methods and MaterialsStudy included 42 high-risk prostate cancer patients enrolled in a clinical protocol, offering external beam radiotherapy + two HDRBT 8.5 Gy boosts. Time was recorded for initiation of anesthesia (A), fixation of needle implant (B), end of MR imaging (C), plan approval (D), and end of HDRBT delivery (E). We defined time A–E as total procedure time, A–B as operating room time, B–C as MRI procedure time, C–D as treatment planning time, and D to E as treatment delivery time. Dose-volume parameters were retrieved from the dose planning system. Results from the first 21 patients were compared with the last 21 patients.ResultsTotal procedure time, operating room time, MRI procedure time, and treatment planning time decreased significantly from average 7.6 to 5.3 hours (p < 0.01), 3.6 to 2.4 hours (p < 0.01), 1.6 to 0.8 hours (p < 0.01), and 2.0 to 1.3 hours (p < 0.01), respectively. HDRBT delivery time remained unchanged at 0.5 hours. Clinical target volume prostate+3mmD90 fulfilled planning aim in 92% of procedures and increased significantly from average 8.3 to 9.0 Gy (p < 0.01). Urethral D0.1 cm3 and rectal D2 cm3 fulfilled planning aim in 78% and 95% of procedures, respectively, and did not change significantly. Hematuria occurred in (95%), hematoma (80%), moderate to strong pain (35%), and urinary retention (5%) of procedures.ConclusionsAfter introduction of MRI-based HDRBT, procedure times were significantly reduced. D90 Clinical target volumeprostate+3mm fulfilled constraints in most patients and improved over time, but not at expense of an increased urethral or rectal dose.



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Combined cutaneous z-plasty and z-tenotomy for correction of claw toe deformity



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Taxonomics—next-generation taxonomists

Abstract

“Taxonomics” is proposed as a short name for the discipline of discovering, recognising, describing and classifying biological entities.



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Seven nature-writing books that capture the spirit of animals

A selection of some of the best new writing, covering apes, coyotes, fish, birds and bees, shows that the lives of animals, caged or wild, can captivate us

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A Standalone Vision Sensing System for Pseudodynamic Testing of Tuned Liquid Column Dampers

Experimental investigation of the tuned liquid column damper (TLCD) is a primal factory task prior to its installation at a site and is mainly undertaken by a pseudodynamic test. In this study, a noncontact standalone vision sensing system is developed to replace a series of the conventional sensors installed at the TLCD tested. The fast vision sensing system is based on binary pixel counting of the portion of images steamed in a pseudodynamic test and achieves near real-time measurements of wave height, lateral motion, and control force of the TLCD. The versatile measurements of the system are theoretically and experimentally evaluated through a wide range of lab scale dynamic tests.

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General Quadratic-Additive Type Functional Equation and Its Stability

We investigate the general functional equation of the form − − , whose solutions are quadratic-additive mappings in connection with stability problems.

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IRON MAIDEN's NYC Show Proved They Are The Best Live Band In Heavy Metal History - Metal Injection.net


Metal Injection.net

IRON MAIDEN's NYC Show Proved They Are The Best Live Band In Heavy Metal History
Metal Injection.net
... around fans all around acted the same way..maybe alot of them wasn't familiar with there new material im not sure but as they played more old stuff fans started coming alive..bruce sounded great for his age and everything hes gone threw with cancer ...

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