RT @AlvaroKohn : Very interesting personalized cancer care symposium @Oslounivsykehus https://t.co/SXV1jE7uXg

RT @AlvaroKohn : Very interesting personalized cancer care symposium @Oslounivsykehus https://t.co/SXV1jE7uXg

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‘Silencer molecules’ switch off cancer’s ability to spread around body https://t.co/SeGbuV1e4S https://t.co/PWQwNLDlPB

‘Silencer molecules’ switch off cancer’s ability to spread around body https://t.co/SeGbuV1e4S https://t.co/PWQwNLDlPB

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RAS mutation is a prognostic biomarker in colorectal cancer patients with metastasectomy

Abstract

Studies have demonstrated a relationship between clinical outcomes after curative resection for colorectal cancer (CRC) and gene mutations of the EGFR pathway, however no studies have examined metastatic CRC (mCRC) patients with metastasectomy. The aim of this study was to evaluate the relationship between gene mutations of EGFR pathway and clinical outcomes after metastasectomy in mCRC patients. A total of 1053 patients histopathologically confirmed CRC received a genotyping test for the EGFR pathway from February 2012 to October 2013. Detailed information was obtained through review of medical records. Gene mutations of EGFR pathway were analyzed by Luminex assay. Overall survival (OS) and recurrence free survival (RFS) were estimated by the Kaplan-Meier method and the log-rank test was used to compare the survival outcomes by gene mutation status. A total of 132 patients received metastasectomy. The frequencies of KRAS exon 2, KRAS exon 3.4, NRAS, BRAF, and PIK3CA mutations were 38.6% (51/132), 3.6% (5/132), 5.1% (7/132), 5.1% (7/132), and 8.7% (12/132), respectively. With a median follow up of 84.1 months (57.2–NA) for a survivor, the 4-year OS rate was 65.6% for mCRC with RAS mutation, and 81.3% for mCRC with wild-type RAS (p < 0.05). We observed a statistically significant correlation for only the RAS mutation and OS. In multivariate analysis, RAS mutation and liver metastasis were independent factors for shorter OS. There were no significant differences between gene mutations of EGFR pathway and RFS.

RAS mutation in mCRC metastasectomy patients was associated with shorter overall survival. This article is protected by copyright. All rights reserved.

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Epidemiologic evidence of slow growing, non-progressive or regressive breast cancer: a systematic review

Abstract

The general aim of this systematic review is to mitigate breast cancer (BC) overdiagnosis and overtreatment. The specific aim is to summarize available data on the occurrence and features of indolent invasive or in situ (DCIS) BC, and precisely survival of untreated cases, prevalence of occult cancers found in autopsies, frequency of regressive BC.

PubMed, Embase and Cochrane Library were systematically searched up to 3/31/2014. Eligibility criteria were: cohort studies, case-control studies, uncontrolled case series assessing survival in women with a diagnosis of BC who did not receive treatment compared to treated women; case series of autopsies estimating the prevalence of undiagnosed BC; cohort studies, case-control studies, uncontrolled case series, case reports assessing the occurrence of spontaneous regression of BC in women with a confirmed histology diagnosis.

Untreated BC: 8 cohort studies and 12 case series (3593 BC) were included. In 3 controlled cohort studies (diagnoses 1978-2006), the 5-years overall survival was 19%-43%.

Occult BC: 8 case series (2279 autopsies) were included. The prevalence of invasive BC undiagnosed during lifetime range was 0-1.5%, while for DCIS the range was 0.2%-14.7%.

Spontaneous regression: 2 cohort studies, 3 case reports, 1 case series included. In the cohort studies the relative risk of regression for screen detected compared to non-screened BC was estimated as 1.2 and 1.1.

It seems plausible that around 10% of invasive BC are not symptomatic during life, and that one fith of BC patients if untreated would be alive after 5 years. Around 1 of 10 screen-detected BC may regress according two studies. This article is protected by copyright. All rights reserved.

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Human papillomavirus mRNA and DNA testing in women with atypical squamous cells of undetermined significance: A prospective cohort study

Abstract

In this prospective cohort study, we compared the performance of human papillomavirus (HPV) mRNA and DNA testing of women with atypical squamous cells of undetermined significance (ASC-US) during cervical cancer screening. Using a nationwide Danish pathology register, we identified women aged 30–65 years with ASC-US during 2005–2011 who were tested for HPV16/18/31/33/45 mRNA using PreTect HPV-Proofer (n=3,226) or for high-risk HPV (hrHPV) DNA using Hybrid Capture 2 (HC2) (n=9,405) or Linear Array HPV-Genotyping test (LA) (n=1,533). Women with ≥1 subsequent examination in the register (n=13,729) were followed for up to 9.5 years for high-grade cervical intraepithelial neoplasia (CIN) or cancer. After 3 years' follow-up, mRNA testing had higher specificity for CIN3 or worse (CIN3+) than HC2 testing (88.1% [95% confidence interval (CI): 86.8%–89.6%] versus 59.3% [95% CI: 58.1%–60.4%]) and higher positive predictive value (PPV) (38.2% [95% confidence interval [CI]: 33.8%–43.1%] versus 19.5% [95% CI: 17.8%–20.9%]). However, the sensitivity of mRNA testing was lower than that of HC2 testing (66.7% [95% CI: 59.3%–74.5%] versus 97.0% [95% CI: 95.5%–98.4%]), and women testing mRNA negative had higher 3-year risk for CIN3+ than those testing HC2 negative (3.2% [95% CI: 2.2%–4.2%] versus 0.5% [95% CI: 0.3%–0.7%]). Patterns were similar after 18 months and 5 years' follow-up; for CIN2+ and cancer as outcomes; across all age groups; and when comparing mRNA testing to hrHPV DNA testing using LA. In conclusion, the HPV16/18/31/33/45 mRNA test is not optimal for ASC-US triage due to its low sensitivity and the substantial risk for precancer following a negative test. This article is protected by copyright. All rights reserved.

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Use of thermo-coagulation as an alternative treatment modality in a ‘screen and treat' programme of cervical screening in rural Malawi

Abstract

The incidence of cervical cancer in Malawi is the highest in the world and projected to increase in the absence of interventions. Although Government policy supports screening using visual inspection with acetic acid (VIA), screening provision is limited due to lack of infrastructure, trained personnel, cost and availability of gas for cryotherapy. Recently, thermo-coagulation has been acknowledged as a safe and acceptable procedure suitable for low–resource settings. We introduced thermo-coagulation for treatment of VIA positive lesions as an alternative to cryotherapy within a cervical screening service based on VIA, coupled with appropriate, sustainable pathways of care for women with high grade lesions and cancers. Detailed planning was undertaken for VIA clinics, approvals were obtained from the Ministry of Health, and Regional and Village Chiefs. Educational resources were developed. Thermo-coagulators were introduced into hospital and health centre settings, with theoretical and practical training in safe use and maintenance of equipment. 7088 previously unscreened women attended VIA clinics between October 2013 and March 2015. Screening clinics were held daily in the hospital and weekly in the health centres. Overall VIA positivity was 6.1%. Almost 90% received same day treatment in the hospital setting, and 3-6 month cure rates of over 90% are observed. Thermo-coagulation proved feasible and acceptable in this setting. Effective implementation requires comprehensive training and provider support, ongoing competency assessment, quality assurance and improvement audit. Thermo-coagulation offers an effective alternative to cryotherapy and encouraged VIA screening of many more women. This article is protected by copyright. All rights reserved.

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Preferential Tumor Cellular Uptake and Retention of Indocyanine Green for In Vivo Tumor Imaging

Abstract

Indocyanine green (ICG) is a fluorescent agent approved for clinical applications by the Food and Drug Administration and European Medicines Agency. This study examined the mechanism of tumor imaging using intravenously administered ICG. The in vivo kinetics of intravenously administered ICG were determined in tumor xenografts using microscopic approaches that enabled both spatio-temporal and high-magnification analyses. The mechanism of ICG-based tumor imaging was examined at the cellular level in six phenotypically different human colon cancer cell lines exhibiting different grades of epithelioid organization. ICG fluorescence imaging detected xenograft tumors, even those < 1 mm in size, based on their preferential cellular uptake and retention of the dye following its rapid tissue-non-specific delivery, in contrast to its rapid clearance by normal tissue. Live-cell imaging revealed that cellular ICG uptake is temperature-dependent and occurs after ICG binding to the cellular membrane, a pattern suggesting endocytic uptake as the mechanism. Cellular ICG uptake correlated inversely with the formation of tight junctions. Intracellular ICG was entrapped in the membrane traffic system, resulting in its slow turnover and prolonged retention by tumor cells. Our results suggest that tumor-specific imaging by ICG involves non-specific delivery of the dye to tissues followed by preferential tumor cellular uptake and retention. The tumor cell-preference of ICG is driven by passive tumor-cell-targeting, the inherent ability of ICG to bind to cell membranes, and the high endocytic activity of tumor cells in association with the disruption of their tight junctions. This article is protected by copyright. All rights reserved.

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Prognostic factors and disease-specific survival among immigrants diagnosed with cutaneous malignant melanoma in Sweden

Abstract

Little is known about cutaneous malignant melanoma (CMM) among immigrants in Europe. We aimed to investigate clinical characteristics and disease-specific survival among first- and second-generation immigrants in Sweden This nationwide population-based study included 27,235 patients from the Swedish Melanoma Register diagnosed with primary invasive CMM 1990-2007. Data were linked to nationwide, population-based registers followed up through 2013. Logistic regression and Cox regression models were used to determine the association between immigrant status and stage and CMM prognosis, respectively. stage. After adjustments for confounders, first generation immigrant from Southern Europe were associated with significantly more advanced stages of disease compared to Swedish-born patients (Stage II vs I: Odds ratio (OR)=2.37, 95% CI=1.61 to 3.50. Stage III-IV vs I: OR=2.40, 95% CI = 1.08-5.37). stageThe ORsof stage II-IV vs stage I disease were increased among men (OR=1.9; 95% CI=1.1 - 3.3; P=0.020), and inwomen (OR=4.8; 95% CI=2.6 - 9.1; P < 0.001) in a subgroup of immigrants from former Yugoslavia compared to Swedish-born patients. In conclusion, the CMM-specific survival was significantly decreased among women from former Yugoslavia compared to Swedish-born women (hazard ratio (HR) = 2.2; 95% CI=1.1 - 4.2; P=0.043). After additional adjustment including stage, the survival difference was no longer significant. No survival difference between the second generation immigrant group and Swedish-born patients were observed. A worse CMM-specific survival in women from former Yugoslavia was associated with more advanced stages of CMM at diagnosis. Secondary prevention efforts focusing on specific groups may be needed to further improve CMM prognosis. This article is protected by copyright. All rights reserved.

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Development of ZMYM2-FGFR1 driven AML in human CD34+ cells in immunocompromised mice

Abstract

Acute myelogenous leukemia (AML) has an overall poor survival rate and shows considerable molecular heterogeneity in its etiology. In the WHO classification there are >50 cytogenetic subgroups of AML, many showing highly specific chromosome translocations that lead to constitutive activation of individual kinases. In a rare stem cell leukemia/lymphoma syndrome, translocations involving 8p11 lead to constitutive activation of the fibroblast growth factor receptor 1 (FGFR1) kinase. This disorder shows myeloproliferative disease with almost invariable progresses to AML and conventional therapeutic strategies are largely unsuccessful. Because of the rare nature of this syndrome, models that faithfully recapitulate the human disease are need to evaluate therapeutic strategies. The t(8;13)(p11;q12) chromosome translocation is most common rearrangement seen in this syndrome and creates a ZMYM2-FGFR1 chimeric kinase. To understand more about the molecular etiology of AML induced by this particular rearrangement, we have created a model human CD34+ cells transplanted into immunocompromized mice which develop myeloproliferative disease that progresses to AML with a long (> 12 months) latency period. As in humans, these mice show hepatospenomegaly, hypercellular bone marrow and a CD45+CD34+CD13+ immunophenotype. Molecular studies demonstrate upregulation of genes such as KLF4 and FLT3 that promote stemness, and overexpression of MYC, which is associated with suppression of myeloid cell differentiation. This murine model, therefore, provides a opportunity to develop therapeutic strategies against the most common subtype within these FGFR1 driven neoplasms and study the molecular etiology in more depth. This article is protected by copyright. All rights reserved.

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Hva er likheten mellom et oblat og en tablett?

Oppsiktsvekkende nok kan man sammenligne oblaten man får utdelt under nattverden med legemiddelbruk.

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Cross-modal symbolic processing can elicit either an N2 or a protracted N2/N400 response

Abstract

A cross-modal symbolic paradigm was used to elicit EEG activity related to semantic incongruence. Twenty-five undergraduate students viewed pairings of visual lexical cues (e.g., DOG) with congruent (50% of trials) or incongruent (50%) auditory nonlexical stimuli (animal vocalizations; e.g., sound of a dog woofing or a cat meowing). In one condition, many different pairs of congruent/incongruent stimuli were shown, whereas in a second condition only two pairs of stimuli were repeatedly shown. A typical N400-like pattern of incongruence-related activity (including activity in the N2 time window) was evident in the condition using many stimuli, whereas the incongruence-related activity in the two-stimuli condition was confined to differential N2-like activity. A supplementary analysis excluded stimulus characteristics as the source of this differential activity between conditions. We found that a single individual performing a fixed task can demonstrate either a protracted N400-like pattern of activity or a more temporally focused N2-like pattern of activity in response to the same stimulus, which suggests that the N2 may be a precursor to the protracted N400 response.

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Diminished heart rate reactivity to acute psychological stress is associated with enhanced carotid intima-media thickness through adverse health behaviors

Abstract

Recent evidence demonstrates that individuals with low heart rate (HR) reactions to acute psychological stress are more likely to be obese or smokers. Smoking and obesity are established risk factors for increased carotid intima-media thickness (IMT). The aim of this study was to examine the potential pathways linking intima-media thickness, smoking, body mass index (BMI), and HR stress reactivity. A total of 552 participants, 47.6% male, M (SD) age = 58.3 (0.94) years, were exposed to three psychological stress tasks (Stroop, mirror drawing, and speech) preceded by a resting baseline period; HR was recorded throughout. HR reactivity was calculated as the average response across the three tasks minus average baseline HR. Smoking status, BMI, and IMT were determined by trained personnel. Controlling for important covariates (e.g., socioeconomic status), structural equation modeling revealed that BMI and smoking mediated the negative relationship between HR reactivity and IMT. The hypothesized model demonstrated a good overall fit to the data, χ²(8) = 0.692, p = .403; CFI = 1.00; TLI = 1.00 SRMR = .01; RMSEA < .001 (90% CI < 0.01–0.11). HR reactivity was negatively related to BMI (β = −.16) and smoking (β = −.18), and these in turn were positively associated with IMT (BMI: β = .10; smoking: β = .17). Diminished HR stress reactivity appears to be a marker for enlarged IMT and appears to be exerting its impact through already established risks. Future research should examine this relationship longitudinally and aim to intervene early.

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Preventing (impulsive) errors: Electrophysiological evidence for online inhibitory control over incorrect responses

Abstract

In a rich environment, with multiple action affordances, selective action inhibition is critical in preventing the execution of inappropriate responses. Here, we studied the origin and the dynamics of incorrect response inhibition and how it can be modulated by task demands. We used EEG in a conflict task where the probability of compatible and incompatible trials was varied. This allowed us to modulate the strength of the prepotent response, and hence to increase the risk of errors, while keeping the probability of the two responses equal. The correct response activation and execution was not affected by compatibility or by probability. In contrast, incorrect response inhibition in the primary motor cortex ipsilateral to the correct response was more pronounced on incompatible trials, especially in the condition where most of the trials were compatible, indicating a modulation of inhibitory strength within the course of the action. Two prefrontal activities, one medial and one lateral, were also observed before the response, and their potential links with the observed inhibitory pattern observed are discussed.

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JCM, Vol. 5, Pages 40: Is there A Role for Alpha-Linolenic Acid in the Fetal Programming of Health?

The role of ω3 alpha linolenic acid (ALA) in the maternal diet during pregnancy and lactation, and its effect on the prevention of disease and programming of health in offspring, is largely unknown. Compared to ALA, ω3 docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids have been more widely researched due to their direct implication in fetal neural development. In this literature search we found that ALA, the essential ω3 fatty acid and metabolic precursor of DHA and EPA has been, paradoxically, almost unexplored. In light of new and evolving findings, this review proposes that ALA may have an intrinsic role, beyond the role as metabolic parent of DHA and EPA, during fetal development as a regulator of gene programming for the prevention of metabolic disease and promotion of health in offspring.

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Are Doctors Destroyed by their Frankensteins? - Daijiworld.com

Are Doctors Destroyed by their Frankensteins? Daijiworld.com He also looked at the outstretched tongue, probed the nose and the ears with a torch and pressed the stomach and other parts below the rib cage. And he asked questions about the lifestyle of the patient and the health and longevity of the ... For ...

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IJERPH, Vol. 13, Pages 355: Using a Hybrid Model to Forecast the Prevalence of Schistosomiasis in Humans

Background: We previously proposed a hybrid model combining both the autoregressive integrated moving average (ARIMA) and the nonlinear autoregressive neural network (NARNN) models in forecasting schistosomiasis. Our purpose in the current study was to forecast the annual prevalence of human schistosomiasis in Yangxin County, using our ARIMA-NARNN model, thereby further certifying the reliability of our hybrid model. Methods: We used the ARIMA, NARNN and ARIMA-NARNN models to fit and forecast the annual prevalence of schistosomiasis. The modeling time range included was the annual prevalence from 1956 to 2008 while the testing time range included was from 2009 to 2012. The mean square error (MSE), mean absolute error (MAE) and mean absolute percentage error (MAPE) were used to measure the model performance. We reconstructed the hybrid model to forecast the annual prevalence from 2013 to 2016. Results: The modeling and testing errors generated by the ARIMA-NARNN model were lower than those obtained from either the single ARIMA or NARNN models. The predicted annual prevalence from 2013 to 2016 demonstrated an initial decreasing trend, followed by an increase. Conclusions: The ARIMA-NARNN model can be well applied to analyze surveillance data for early warning systems for the control and elimination of schistosomiasis.

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IJERPH, Vol. 13, Pages 353: Salivary Alpha-Amylase Reactivity in Breast Cancer Survivors

The two main components of the stress system are the hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal-medullary (SAM) axes. While cortisol has been commonly used as a biomarker of HPA functioning, much less attention has been paid to the role of the SAM in this context. Studies have shown that long-term breast cancer survivors display abnormal reactive cortisol patterns, suggesting a dysregulation of their HPA axis. To fully understand the integrity of the stress response in this population, this paper explored the diurnal and acute alpha-amylase profiles of 22 breast cancer survivors and 26 women with no history of cancer. Results revealed that breast cancer survivors displayed identical but elevated patterns of alpha-amylase concentrations in both diurnal and acute profiles relative to that of healthy women, F (1, 39) = 17.95, p < 0.001 and F (1, 37) = 7.29, p = 0.010, respectively. The average area under the curve for the diurnal and reactive profiles was 631.54 ± 66.94 SEM and 1238.78 ± 111.84 SEM, respectively. This is in sharp contrast to their cortisol results, which showed normal diurnal and blunted acute patterns. The complexity of the stress system necessitates further investigation to understand the synergistic relationship of the HPA and SAM axes.

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IJERPH, Vol. 13, Pages 356: Heavy Physical Work: Cardiovascular Load in Male Construction Workers

This study aimed to elucidate cardiovascular loads (CVL) in construction workers during work and leisure by relative heart rate (RHR) over several days. Furthermore, we sought to evaluate the level of CVL in relation to individual factors, work ability, musculoskeletal pain and subjective general health. From a group of 255 construction workers responding to the baseline questionnaire, the CVL during work and leisure time was determined by recording RHR in 42 workers over 3–4 days. Almost 60% of the workday was spent below 20% RHR. The mean RHR during work for all participants was 16% RHR, with large differences between professions. On average, the 42 workers spent 14% of the workday at a RHR above 33%, and four subjects (10%) had a mean RHR above 33% during work. Eight (19%) of the participants had a mean length of their workday exceeding calculated maximal acceptable work time. Seven persons (17%) experienced on average one or more episode(s) of 5 min or more continuously above 33% RHR. The cardiovascular load at work was significantly associated with age and  V ˙O2max, but not with work ability, musculoskeletal pain or subjective general health.

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The Diagnostic Accuracy of Optical Coherence Tomography Angiography for Neovascular Age-Related Macular Degeneration: A Comparison with Fundus Fluorescein Angiography

Purpose. To describe the morphological characteristics and efficacy of OCTA in detecting CNV in nAMD. We retrospectively reviewed 53 patients (86 eyes) with suspected CNV secondary to wet AMD. All the patients underwent a multimodal assessment for CNV. Two independent readers calculated the sensitivity and specificity of OCTA in detecting CNV compared with FA. A qualitative analysis of OCTA was also performed to describe the morphological appearance of CNV. Among 86 eyes of 53 patients, 52 eyes were diagnosed as having CNV based on the FA imaging analysis. According to FA, CNV was classified as classic in 28 eyes, predominantly classic in 6 eyes, minimally classic in 9 eyes, and occult in 9 eyes. In 56 eyes, CNV was visualized on OCTA and corresponding OCT B-scans. In total, 46.4% (26/56) had well-circumscribed vessels, and 53.6% (30/56) showed poorly circumscribed vessels. There were 11 false positives and 7 false negatives using OCTA. The specificity of OCTA for the detection of CNV was 67.6%, with sensitivity of 86.5%. OCTA may help in the noninvasive diagnosis of CNV and may provide a method for monitoring the evolution of CNV.

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The Role of Initial Credit Distribution Scheme in Managing Network Mobility and Maximizing Reserve Capacity: Considering Traveler’s Cognitive Illusion

The role of initial credit distribution scheme (ICDS) in managing network mobility has long been overlooked in previous studies of tradable credit scheme (TCS), which may make their results disputable in the reality, as the travelers possessing leftover credits can get some subsidy from the credit market and offset part of travel cost. In this paper, the disequilibrium phenomenon of previous user equilibrium (UE) solution is shown when traveler’s cognitive illusion (CI) is considered. Then, a new UE condition with TCS is defined with the ICDS and CI explicitly considered. To comprehensively reveal the impacts of ICDS on UE solution, four different types of ICDS are introduced and analyzed in a unified variational inequality (VI) modeling framework. The uniqueness of the UE link flow and market equilibrium (ME) credit price is also investigated. Furthermore, the mathematical program with equilibrium constraint (MPEC) for the optimal ICDS design problem is established, with the optimization objective being maximizing network reserve capacity. A modified relaxation algorithm is adopted to solve the MPEC. The numerical example shows that a properly designed ICDS can not only improve the network reserve capacity, but also decrease the travel cost of all the travelers in the network simultaneously.

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HSP27 Alleviates Cardiac Aging in Mice via a Mechanism Involving Antioxidation and Mitophagy Activation

Aging-induced cardiac dysfunction is a prominent feature of cardiac aging. Heat shock protein 27 (HSP27) protects cardiac function against ischemia or chemical challenge. We hypothesized that HSP27 attenuates cardiac aging. Transgenic (Tg) mice with cardiac-specific expression of the HSP27 gene and wild-type (WT) littermates were employed in the experiments. Echocardiography revealed a significant decline in the cardiac function of old WT mice compared with young WT mice. In striking contrast, the aging-induced impairment of cardiac function was attenuated in old Tg mice compared with old WT mice. Levels of cardiac aging markers were lower in old Tg mouse hearts than in old WT mouse hearts. Less interstitial fibrosis and lower contents of reactive oxygen species and ubiquitin-conjugated proteins were detected in old Tg hearts than in old WT hearts. Furthermore, old Tg hearts demonstrated lower accumulation of LC3-II and p62 than old WT hearts. Levels of Atg13, Vps34, and Rab7 were also higher in old Tg hearts than in old WT hearts. Additionally, old Tg hearts had higher levels of PINK1 and Parkin than old WT hearts, suggesting that mitophagy was activated in old Tg hearts. Taken together, HSP27 alleviated cardiac aging and this action involved antioxidation and mitophagy activation.

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Integrated Power and Attitude Control Design of Satellites Based on a Fuzzy Adaptive Disturbance Observer Using Variable-Speed Control Moment Gyros

To satisfy the requirements for small satellites that seek agile slewing with peak power, this paper investigates integrated power and attitude control using variable-speed control moment gyros (VSCMGs) that consider the mass and inertia of gimbals and wheels. The paper also details the process for developing the controller by considering various environments in which the controller may be implemented. A fuzzy adaptive disturbance observer (FADO) is proposed to estimate and compensate for the effects of equivalent disturbances. The algorithms can simultaneously track attitude and power. The simulation results illustrate the effectiveness of the control approach, which exhibits an improvement of 80 percent compared with alternate approaches that do not employ a FADO.

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Development of a Robotic Assembly for Analyzing the Instantaneous Axis of Rotation of the Foot Ankle Complex

Ankle instantaneous axis of rotation (IAR) measurements represent a more complete parameter for characterizing joint motion. However, few studies have implemented this measurement to study normal, injured, or pathological foot ankle biomechanics. A novel testing protocol was developed to simulate aspects of in vivo foot ankle mechanics during mid-stance gait in a human cadaveric specimen. A lower leg was mounted in a robotic testing platform with the tibia upright and foot flat on the baseplate. Axial tibia loads (ATLs) were controlled as a function of a vertical ground reaction force (vGRF) set at half body weight (356 N) and a 50% vGRF (178 N) Achilles tendon load. Two specimens were repetitively loaded over 10 degrees of dorsiflexion and 20 degrees of plantar flexion. Platform axes were controlled within 2 microns and 0.008 degrees resulting in ATL measurements within ±2 N of target conditions. Mean ATLs and IAR values were not significantly different between cycles of motion, but IAR values were significantly different between dorsiflexion and plantar flexion. A linear regression analysis showed no significant differences between slopes of plantar flexion paths. The customized robotic platform and advanced testing protocol produced repeatable and accurate measurements of the IAR, useful for assessing foot ankle biomechanics under different loading scenarios and foot conditions.

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Dynamic Friction Parameter Identification Method with LuGre Model for Direct-Drive Rotary Torque Motor

Attainment of high-performance motion/velocity control objectives for the Direct-Drive Rotary (DDR) torque motor should fully consider practical nonlinearities in controller design, such as dynamic friction. The LuGre model has been widely utilized to describe nonlinear friction behavior; however, parameter identification for the LuGre model remains a challenge. A new dynamic friction parameter identification method for LuGre model is proposed in this study. Static parameters are identified through a series of constant velocity experiments, while dynamic parameters are obtained through a presliding process. Novel evolutionary algorithm (NEA) is utilized to increase identification accuracy. Experimental results gathered from the identification experiments conducted in the study for a practical DDR torque motor control system validate the effectiveness of the proposed method.

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In memoriam: Dr. Irene Claudia Floriani (1964–2016)

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Screening of endocrine organ-specific humoral autoimmunity in 47,XXY Klinefelter’s syndrome reveals a significant increase in diabetes-specific immunoreactivity in comparison with healthy control men

Abstract

The aim of this study was to evaluate the frequency of humoral endocrine organ-specific autoimmunity in 47,XXY Klinefelter’s syndrome (KS) by investigating the autoantibody profile specific to type 1 diabetes (T1DM), Addison’s disease (AD), Hashimoto thyroiditis (HT), and autoimmune chronic atrophic gastritis (AG). Sixty-one adult Caucasian 47,XXY KS patients were tested for autoantibodies specific to T1DM (Insulin Abs, GAD Abs, IA-2 Abs, Znt8 Abs), HT (TPO Abs), AD (21-OH Abs), and AG (APC Abs). Thirty-five of these patients were not undergoing testosterone replacement therapy TRT (Group 1) and the remaining 26 patients started TRT before the beginning of the study (Group 2). KS autoantibody frequencies were compared to those found in 122 control men. Six of 61 KS patients (9.8 %) were positive for at least one endocrine autoantibody, compared to 6.5 % of controls. Interestingly, KS endocrine immunoreactivity was directed primarily against diabetes-specific autoantigens (8.2 %), with a significantly higher frequency than in controls (p = 0.016). Two KS patients (3.3 %) were TPO Ab positive, whereas no patients were positive for AD- and AG-related autoantigens. The autoantibody endocrine profile of untreated and treated KS patients was not significantly different. Our findings demonstrate for the first time that endocrine humoral immunoreactivity is not rare in KS patients and that it is more frequently directed against type 1 diabetes-related autoantigens, thus suggesting the importance of screening for organ-specific autoimmunity in clinical practice. Follow-up studies are needed to establish if autoantibody-positive KS patients will develop clinical T1DM.

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Type of fish consumed and thyroid autoimmunity in pregnancy and postpartum

Abstract

Fish consumption or supplementation with omega-3 fatty acids was reported to cure and/or prevent autoimmune and nonautoimmune disorders. Serum positivity for thyroid autoantibodies is a predictive marker of postpartum thyroiditis and postpartum depression. We hypothesized that stable consumption of the omega-3-rich oily fish was associated with a more favorable profile of serum thyroid antibodies throughout pregnancy and early postpartum compared with stable consumption of swordfish, a predator that concentrates pollutants. We prospectively measured serum thyroglobulin antibodies and thyroperoxidase antibodies in pregnancy (first, second trimesters) and postpartum (day 4), in 236 thyroid disease-free, nonsmoker Caucasian women with stable dietary habits. We did not measure thyroid autoantibodies prior to pregnancy. Women were divided into groups A (n = 48; swordfish), B (n = 52; oily fish), C (n = 68; swordfish + other fish, not necessarily oily fish), and D (n = 68; fish other than swordfish and oily fish). Major endpoints were positivity rates and serum concentrations of the two autoantibodies. We resorted to previous studies for the estimated content of fatty acids and microelements in the consumed fish. Positivity rates and serum concentrations of both antibodies were the greatest in group A and the lowest in group B (P < 0.001 and P < 0.05 to < 0.001, respectively). Relationship between monthly fish consumption and serum concentrations of either antibody was direct in group A but inverse in group B. The estimated content of omega-3 fatty acids in fish consumed by group B was the greatest (P < 0.001 vs. any other group). These data reinforce recommendations that pregnant women should avoid consuming swordfish and indicate consumption of oily fish as a favorable alternative. Because thyroid autoantibodies are markers of autoimmune-related postpartum problems, our data suggest a dietary prophylaxis of such problems.

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New guideline addresses long-term needs of head and neck cancer survivors - EurekAlert (press release)

New guideline addresses long-term needs of head and neck cancer survivors EurekAlert (press release) ATLANTA - March 22, 2016-A new American Cancer Society guideline provides clinicians with recommendations on key areas of clinical follow-up care for survivors of head and neck cancer, a growing population numbering approximately 436,060 and ... and more »

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Statistical shape analysis of the human spleen geometry for probabilistic occupant models

Publication date: Available online 23 March 2016
Source:Journal of Biomechanics
Author(s): Keegan M. Yates, Yuan-Chiao Lu, Costin D. Untaroiu
Statistical shape models are an effective way to create computational models of human organs that can incorporate inter-subject geometrical variation. The main objective of this study was to create statistical mean and boundary models of the human spleen in an occupant posture. Principal component analysis was applied to fifteen human spleens in order to find the statistical modes of variation, mean shape, and boundary models. A landmark sliding approach was utilized to refine the landmarks to obtain a better shape correspondence and create a better representation of the underlying shape contour. The first mode of variation was found to be the overall volume, and it accounted for 69% of the total variation. The mean model and boundary models could be used to develop probabilistic finite element (FE) models which may identify the risk of spleen injury during vehicle collisions and consequently help to improve automobile safety systems.



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Ring apophysis fractures induced by low-load low-angle repetitive flexion in an ex-vivo cervine model

Publication date: Available online 22 March 2016
Source:Journal of Biomechanics
Author(s): Nicole C. Corbiere, Stacey L. Zeigler, Kathleen A. Issen, Arthur J. Michalek, Laurel Kuxhaus
Ring apophysis fratures of the spine occur in physically-active adolescents causing low back pain and the potential for chronic pain. Many of these fractures occur without memorable trauma, suggesting that the fractures occur during everyday movements and activities. The benign nature of this poorly understood potential mechanism of injury hampers appropriate diagnosis and early treatment. The purpose of this study was to establish an ex-vivo model of ring apophysis fracture and demonstrate that these fractures can be initiated by repetitive non-traumatic loading. Six 5-vertebra cervine lumbar (L1-L5) motion segments were cyclically loaded in low-angle low-load flexion (to 15° flexion, with peak load of 230 ± 50N), a representative movement component of daily activities for both human and deer lumbar spines. Pinned end conditions replicated physiologically realistic loading. Ring apophysis fractures were created under low-load low-angle conditions in healthy vertebrae of similar bone mineral density and a similar degree of skeletal maturity to adolescent humans. All specimens developed ring apophysis fractures; some as early as 1,400 cycles. The load-displacement data, and hysteresis loops during the cyclic loading, suggest that the fractures occurred gradually, i.e., without trauma. The ease at which these fractures were created suggests that ring apophysis fractures may be more prevalent than current diagnosis rates. Therefore, clinically, healthcare providers should include the potential for ring apophysis fracture in the differential diagnosis of all physically-active adolescents who present with back pain.



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EFFECTS OF THE FIBERS DISTRIBUTION IN THE HUMAN EARDRUM: A BIOMECHANICAL STUDY

Publication date: Available online 23 March 2016
Source:Journal of Biomechanics
Author(s): Fernanda Gentil, Marco Parente, Pedro Martins, Carolina Garbe, Carla Santos, Bruno Areias, Carla Branco, João Paço, Renato Natal Jorge
The eardrum separates the external ear from the middle ear and it is responsible to convert the acoustical energy into mechanical energy. It is divided by pars tensa and pars flaccida. The aim of this work is to analyze the susceptibility of the four quadrants of the pars tensa under negative pressure, to different lamina propria fibers distribution. The development of associated ear pathology, in particular the formation of retraction pockets, is also evaluated. To analyze these effects, a computational biomechanical model of the tympano-ossicular chain was constructed using computerized tomography images and based on the finite element method. Three fibers distributions in the eardrum middle layer were compared: case 1 (eardrum with a circular band of fibers surrounding all quadrants equally), case 2 (eardrum with a circular band of fibers that decreasing in thickness in posterior quadrants), case 3 (eardrum without circular fibers in the posterior/superior quadrant).A static analysis was performed by applying approximately 3000Pa in the eardrum. The pars tensa of the eardrum was divided in four quadrants and the displacement of a central point of each quadrant analyzed. The largest displacements of the eardrum were obtained for the eardrum without circular fibers in the posterior/superior quadrant.



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Milestones: Critical Elements in Clinical Informatics Fellowship Programs

Background: Milestones refer to points along a continuum of a competency from novice to expert. Resident and fellow assessment and program evaluation processes adopted by the ACGME include the mandate that programs report the educational progress of residents and fellows twice annually utilizing Milestones developed by a specialty specific ACGME working group of experts. Milestones in clinical training programs are largely unmapped to specific assessment tools. Residents and fellows are mainly assessed using locally derived assessment instruments. These assessments are then reviewed by the Clinical Competency Committee which assigns and reports trainee ratings using the specialty specific reporting Milestones. Methods and Results: The challenge and opportunity facing the nascent specialty of Clinical Informatics is how to optimally utilize this framework across a growing number of accredited fellowships. The authors review how a mapped milestone framework, in which each required sub-competency is mapped to a single milestone assessment grid, can enable the use of milestones for multiple uses including individualized learning plans, fellow assessments, and program evaluation. Furthermore, such a mapped strategy will foster the ability to compare fellow progress within and between Clinical Informatics Fellowships in a structured and reliable fashion. Clinical Informatics currently has far less variability across programs and thus could easily utilize a more tightly defined set of milestones with a clear mapping to sub-competencies. This approach would enable greater standardization of assessment instruments and processes across programs while allowing for variability in how those sub-competencies are taught. Conclusions: A mapped strategy for Milestones offers significant advantages for Clinical Informatics programs....

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John William Simmons Harris (1926–2013)

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Symposium on Primate Ecomorphology: introduction

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Why are there apes? Evidence for the co-evolution of ape and monkey ecomorphology

Abstract

Apes, members of the superfamily Hominoidea, possess a distinctive suite of anatomical and behavioral characters which appear to have evolved relatively late and relatively independently. The timing of paleontological events, extant cercopithecine and hominoid ecomorphology and other evidence suggests that many distinctive ape features evolved to facilitate harvesting ripe fruits among compliant terminal branches in tree edges. Precarious, unpredictably oriented, compliant supports in the canopy periphery require apes to maneuver using suspensory and non-sterotypical postures (i.e. postures with eccentric limb orientations or extreme joint excursions). Diet differences among extant species, extant species numbers and evidence of cercopithecoid diversification and expansion, in concert with a reciprocal decrease in hominoid species, suggest intense competition between monkeys and apes over the last 20 Ma. It may be that larger body masses allow great apes to succeed in contest competitions for highly desired food items, while the ability of monkeys to digest antifeedant-rich unripe fruits allows them to win scramble competitions. Evolutionary trends in morphology and inferred ecology suggest that as monkeys evolved to harvest fruit ever earlier in the fruiting cycle they broadened their niche to encompass first more fibrous, tannin- and toxin-rich unripe fruits and later, for some lineages, mature leaves. Early depletion of unripe fruit in the central core of the tree canopy by monkeys leaves a hollow sphere of ripening fruits, displacing antifeedant-intolerant, later-arriving apes to small-diameter, compliant terminal branches. Hylobatids, orangutans, Pan species, gorillas and the New World atelines may have each evolved suspensory behavior independently in response to local competition from an expanding population of monkeys. Genetic evidence of rapid evolution among chimpanzees suggests that adaptations to suspensory behavior, vertical climbing, knuckle-walking, consumption of terrestrial piths and intercommunity violence had not yet evolved or were still being refined when panins (chimpanzees and bonobos) and hominins diverged.

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Cancers, Vol. 8, Pages 39: NORE1A Regulates MDM2 Via β-TrCP

Mouse Double Minute 2 Homolog (MDM2) is a key negative regulator of the master tumor suppressor p53. MDM2 regulates p53 on multiple levels, including acting as an ubiquitin ligase for the protein, thereby promoting its degradation by the proteasome. MDM2 is oncogenic and is frequently found to be over-expressed in human tumors, suggesting its dysregulation plays an important role in human cancers. We have recently found that the Ras effector and RASSF (Ras Association Domain Family) family member RASSF5/NORE1A enhances the levels of nuclear p53. We have also found that NORE1A (Novel Ras Effector 1A) binds the substrate recognition component of the SCF-ubiquitin ligase complex β-TrCP. Here, we now show that NORE1A regulates MDM2 protein levels by targeting it for ubiquitination by SCF-β-TrCP. We also show the suppression of NORE1A protein levels enhances MDM2 protein expression. Finally, we show that MDM2 can suppress the potent senescence phenotype induced by NORE1A over-expression. Thus, we identify a mechanism by which Ras/NORE1A can modulate p53 protein levels. As MDM2 has several important targets in addition to p53, this finding has broad implications for cancer biology in tumor cells that have lost expression of NORE1A due to promoter methylation.

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Antibodies, Vol. 5, Pages 7: Development and Characterization of New Species Cross-Reactive Anti-Sialoadhesin Monoclonal Antibodies

Sialoadhesin (Sn) is a surface receptor expressed on a subset of macrophages in steady state conditions. During inflammation and diseases, Sn is highly upregulated on macrophages and blood monocytes. Therefore, therapies using monoclonal antibodies (mAbs) to target Sn-positive (Sn+) cells are a potential strategy for targeted treatment. It has been shown that Sn internalizes after binding with a mAb, though it is not clear whether this is species-specific. In this study, new Sn-specific mAbs were developed and analyzed for cross-reactivity between species. In addition, the newly developed mAbs were compared to mAbs used in previous research for their epitope recognition and other Sn-specific characteristics. Both species-specific and cross-reactive antibodies could be identified. Furthermore, sialic acid-binding of red blood cells (RBC) could be inhibited with mAbs recognizing different epitopes and all mAb showed internalization of Sn. The newly developed mAbs can be used as novel tools for Sn research and further analysis of Sn internalization in different species.

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A phase II prospective study of the trastuzumab combined with 5-weekly S-1 and CDDP therapy for HER2-positive advanced gastric cancer

Abstract

Background

We evaluated the efficacy and safety of 5-weekly S-1 and cisplatin combined with trastuzumab, a monoclonal antibody against human epidermal growth factor receptor type 2 (HER2) for HER2-positive advanced gastric cancer (AGC).

Methods

This phase II study treatment consisted of S-1 (80–120 mg per day) orally on day 1–21, cisplatin (60 mg/m²) intravenously on day 8, and trastuzumab (8 mg/kg on day 1 of the first cycle, followed by 6 mg/kg every 3 weeks) intravenously. The primary end point was 1-year survival rate. The secondary end points included overall survival, progression-free survival (PFS), response rate (RR), and safety.

Results

A total 22 patients from seven centers were enrolled. In the 20 patients evaluable for analysis, the 1-year survival rate was 70 % (95 % confidence interval (CI) 49.9–90.1 %), and median survival time, PFS, and RR were 15.3, 7.5 months and 41.2 %, respectively. Major grade 3/4 adverse events were neutropenia (30 %), anorexia (30 %), leukopenia (25 %), fatigue (20 %), and anemia (15 %).

Conclusions

Five-weekly S-1 and cisplatin combined with trastuzumab showed effective with favorable safety profile in patients with HER2-positive AGC.

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MRI unravels neuro complications of Zika virus

French experts have urged all clinical staff to keep aware that meningoencephalitis...

Read more on AuntMinnieEurope.com

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Light can image premature babies' lungs

Laser light can be used to image premature babies' lungs as an alternative...

Read more on AuntMinnieEurope.com

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MRI accurately pinpoints tubal pregnancy

Get savvy on neonatal chest x-rays

Belgian hospital reviews CT dose in pregnant patients

Postmortem MRI measures up for fetal autopsy

MRI provides answers on fetal facial clefts

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Invasive pericranial nerve interventions

Background

In many patients suffering from primary headaches, the available pharmacological and behavioural treatments are not satisfactory. This is a review of (minimally) invasive interventions targeting pericranial nerves that could be effective in refractory patients.

Methods

The interventions we will cover have in common pericranial nerves as targets, but are distinct according to their rationale, modality and invasiveness. They range from nerve blocks/infiltrations to the percutaneous implantation of neurostimulators and surgical decompression procedures. We have critically analysed the published data (PubMed) on their effectiveness and tolerability.

Results and conclusions

There is clear evidence for a preventative effect of suboccipital injections of local anaesthetics and/or steroids in cluster headache, while evidence for such an effect is weak in migraine. Percutaneous occipital nerve stimulation (ONS) provides significant long-term relief in more than half of drug-resistant chronic cluster headache patients, but no sham-controlled trial has tested this. The evidence that ONS has lasting beneficial effects in chronic migraine is at best equivocal. Suboccipital infiltrations are quasi-devoid of side effects, while ONS is endowed with numerous, though reversible, adverse events. Claims that surgical decompression of multiple pericranial nerves is effective in migraine are not substantiated by large, rigorous, randomized and sham-controlled trials.

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Abnormal tyrosine metabolism in chronic cluster headache

Objective

Episodic cluster headache is characterized by abnormalities in tyrosine metabolism (i.e. elevated levels of dopamine, tyramine, octopamine and synephrine and low levels of noradrenalin in plasma and platelets.) It is unknown, however, if such biochemical anomalies are present and/or constitute a predisposing factor in chronic cluster headache. To test this hypothesis, we measured the levels of dopamine and noradrenaline together with those of elusive amines, such as tyramine, octopamine and synephrine, in plasma of chronic cluster patients and control individuals.

Methods

Plasma levels of dopamine, noradrenaline and trace amines, including tyramine, octopamine and synephrine, were measured in a group of 23 chronic cluster headache patients (10 chronic cluster ab initio and 13 transformed from episodic cluster), and 16 control participants.

Results

The plasma levels of dopamine, noradrenaline and tyramine were several times higher in chronic cluster headache patients compared with controls. The levels of octopamine and synephrine were significantly lower in plasma of these patients with respect to control individuals.

Conclusions

These results suggest that anomalies in tyrosine metabolism play a role in the pathogenesis of chronic cluster headache and constitute a predisposing factor for the transformation of the episodic into a chronic form of this primary headache.

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The cavernous sinus in cluster headache - a quantitative structural magnetic resonance imaging study

Background

It has been hypothesized that a constitutionally narrow cavernous sinus might predispose individuals to cluster headache. Cavernous sinus dimensions, however, have never been assessed.

Methods

In this case–control study, we measured the dimensions of the cavernous sinus, skull base, internal carotid and pituitary gland with high-resolution T2-weighted magnetic resonance imaging in 25 episodic, 24 chronic and 13 probable cluster headache patients, 8 chronic paroxysmal hemicrania patients and 22 headache-free controls. Dimensions were compared between groups, correcting for age, sex and transcranial diameter.

Results

On qualitative inspection, no relevant pathology or anatomic variants that were previously associated with cluster headache or chronic paroxysmal hemicranias were observed in the cavernous sinus or paracavernous structures. The left-to-right transcranial diameter at the temporal fossa level (mean ± SD) was larger in the headache groups (episodic cluster headache: 147.5 ± 7.3 mm, p = 0.044; chronic cluster headache: 150.2 ± 7.3 mm, p < 0.001; probable cluster headache: 146.0 ± 5.3 mm, p = 0.012; and chronic paroxysmal hemicrania: 145.2 ± 9.4 mm, p = 0.044) compared with controls (140.2 ± 8.0 mm). After adjusting for transcranial diameter and correcting for multiple comparisons, there were no differences in the dimensions of the cavernous sinus and surrounding structures between headache patients and controls.

Conclusion

Patients with cluster headache or chronic paroxysmal hemicrania had wider skulls than headache-free controls, but the proportional dimensions of the cavernous sinus were similar.

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Cover Image

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Issue Information – TOC

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A 6-year Follow-up Survey of Health Status in Middle-Aged Women with Turner Syndrome

Abstract

Objective

Studies suggest younger women with Turner syndrome (TS) have good quality of life. Less is known about everyday functioning in adults with TS. In a 6-year follow-up study, multiple areas of functioning were compared between TS women and controls. Design: Women with TS and controls were mailed a self-report survey six years after a baseline study.

Patients

Fifty-seven women with TS (M age 40.6±11.1 years) and 101 controls (M age 38.8±10.6 years, ns) responded.

Measurements

Measures of background information, experienced life strain, and presence/impact of health conditions were developed for this study. The QPSNordic measured perceived workload challenges. The LiSat9 measured life satisfaction. The Rosenberg Self-Esteem Scale measured self-esteem.

Results

More TS women lived alone, fewer had biological children, and more had adoptive children. TS women reported fewer sex partners and less sexual confidence. Controls had higher education. There was no difference in employment status. More TS women received disability pensions. TS women reported their work as more physically challenging, less positively challenging, and requiring less knowledge skills. TS women experienced more life strain in school, adolescence, and late working life. Controls reported higher overall life-satisfaction, with no difference between samples on specific domains. TS women reported lower self-esteem. For TS women only, physical health at baseline predicted length of education, and mental health at baseline predicted self-esteem.

Conclusions

Women with TS face more challenges than controls on several domains of functioning. Early physical and mental health may influence later educational achievement and self-esteem for women with TS.

This article is protected by copyright. All rights reserved.

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Evidenz/Transparenz: HNO – Quo vadis?

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Ballondilatation der Tuba auditiva bei Mittelohroperationen

Zusammenfassung

Hintergrund

Die Entstehung von Mittelohrerkrankungen wird u. a. auf eine unzureichende Tubenfunktion zurückgeführt. In klinischen Fallserien wurde über die Ergebnisse der Ballondilatation zur Therapie von Tubendysfunktionen berichtet.

Ziel

Es soll untersucht werden, ob Patienten mit geplanter Operation aufgrund einer chronischen Mittelohrerkrankung von einer zusätzlichen Ballondilatation der Tuba auditiva profitieren.

Methoden

In eine randomisierte, kontrollierte, für Patienten und Untersucher verblindete Studie sollen 100 erwachsene Patienten mit geplanter Operation wegen chronischer Mittelohrerkrankung eingeschlossen werden. Im Rahmen der Operation soll randomisiert bei 50 % der Patienten zusätzlich eine Ballondilatation der Tuba auditiva der betroffenen Seite durchgeführt werden . Die Tubenfunktion wird beurteilt anhand des Valsalva-Manövers, der Tubenmanometrie nach Estève sowie durch Einschätzungen des Patienten. Verschiedene Scores wie der ETS-5 (Eustachian Tube Score 5), der erweiterte ETS-7 und der ETDQ-7 (Seven-Item Eustachian Tube Dysfunction Questionnaire) werden dokumentiert. Die Nachbeobachtung erfolgt nach 3, 6 und 12 Monaten.

Ergebnisse

Von Juni bis Dezember 2015 erfolgte bei 162 Patienten ein mikrochirurgischer Eingriff am Ohr. Hiervon erfüllten primär 90 Patienten nicht die Einschlusskriterien. Von den 72 Patienten mit chronischer Mittelohrerkrankung wurden bisher 17 % (n =12) in die Studie eingeschlossen. In 39 % der Fälle (n =28) lag keine nachweisbare Tubendysfunktion vor, und 44 % (n =32) konnten aus anderen Gründen nicht eingeschlossen werden.

Schlussfolgerung

Die Rekrutierungsrate ist damit geringer als bei der Studienplanung angenommen. In Abhängigkeit von Fallzahlberechnungen für im Rahmen der Studie identifizierte, besonders geeignete Zielgruppen können eventuell multizentrische Studien mit spezifischen Erkrankungsgruppen folgen.

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Maligner intraorbitaler Tumor: Primum oder Metastase?

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Ist Radio(chemo)therapie wirklich der zukünftige Standard für die Behandlung von Oropharynxkarzinomen?

Zusammenfassung

Die Behandlung von Patienten mit einem Plattenepithelkarzinom des Oropharynx (OPSCC) erfordert eine interdisziplinäre Zusammenarbeit. Therapieziel ist neben der Tumorkontrolle der Funktions- und Organerhalt. Hierzu wird die primäre gleichzeitige Radiochemotherapie (RCT) v. a. bei lokal fortgeschrittenen Kopf-Hals-Tumoren eingesetzt. Alternativ erfolgt die sequenzielle RCT, zunächst als Induktionschemotherapie durchgeführt und dann von einer alleinigen Radiatio oder einer RCT ergänzt. Zu beachten sind bei diesen Therapieansätzen die Funktionseinschränkungen im Bereich des Schluckapparats, die insbesondere durch radiogene Fibrosen bedingt sind, sowie die Toxizitäten, die durch eine cisplatinbasierte Chemotherapie entstehen. Der chirurgische Therapieansatz versucht, offen chirurgische Zugänge durch die Verwendung der transoralen Chirurgie zu vermeiden. Ein weiteres, weitaus wichtigeres Ziel ist es, die adjuvante R(C)T komplett zu vermeiden oder eine relevante Dosisreduktion zu ermöglichen. In Fällen, in denen eine adjuvante Therapie erforderlich wird, verringert sich der Vorteil einer primären Chirurgie gegenüber einer primären RCT, ist aber nicht notwendigerweise komplett eliminiert. Für die Gruppe der auf humanes Papillomvirus (HPV) positiven OPSCC sollte nicht übersehen werden, dass das primär chirurgische Vorgehen für HPV-bedingte Kopf-Hals-Karzinome gleichwertige, wenn nicht sogar größere Überlebensvorteile bietet und es keine eindeutigen Hinweise gibt, dass eine RCT gegenüber der primären Operation in dieser Patientengruppe einen klaren Vorteil bringt. Bei Einsatz der RCT werden deeskalierte Therapienansätze favorisiert, die durch die Verwendung einer Radioimmuntherapie sowie Dosisreduktion einer primären oder adjuvanten R(C)T langfristig Therapiemorbiditäten vermindern sollen.

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