Κυριακή 6 Μαρτίου 2016
A Meta-Analysis of Studies Evaluating Visual and Anatomical Outcomes in Patients with Treatment Resistant Neovascular Age-Related Macular Degeneration following Switching to Treatment with Aflibercept
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Radiology and the law in Colombia: From practice to reality
Colombia is forging ahead when it comes to implementing laws and regulations...
Read more on AuntMinnieEurope.com
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From flat into concave shape in soft tissue free flaps in oral cavity reconstruction: The origami technique.
From flat into concave shape in soft tissue free flaps in oral cavity reconstruction: The origami technique.
Oral Oncol. 2016 Mar 1;
Authors: Tsao CK, Megias Barrera J, Loh CY
PMID: 26944346 [PubMed - as supplied by publisher]
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quality of care; +26 new citations
26 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2016/03/06
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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Food allergy is associated with colonization in children with atopic dermatitis
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Initial findings using the V8 hourglass-shaped valvuloplasty balloon for postdilatation in treating paravalvular leaks associated with transcatheter self-expanding aortic valve prosthesis
Objectives
The aim of this study was to assess the effect of a novel hourglass-shaped balloon on reduction of paravalvular leak (PVL) in patients undergoing transcatheter aortic valve replacement (TAVR) with self-expanding prostheses.
Background
An important limitation of TAVR compared with surgical aortic valve replacement remains the higher incidence of PVL. A commonly used strategy to treat PVL is balloon postdilatation (BPD); however, the optimal technique for treating PVL after TAVR is unknown.
Methods
We examined consecutive patients with severe, symptomatic aortic stenosis who underwent TAVR with the Medtronic CoreValve followed by BPD with an InterValve V8 balloon for PVL grade ≥2+. Data from echocardiographic, multidetector computed tomographic, and angiographic images were reviewed. The primary endpoint was successful reduction in PVL to grade 1+ or less as assessed by intraprocedural echocardiography.
Results
Eleven patients were studied (median age, 82 years; 64% female). Ten patients (91%) demonstrated successful reduction in PVL after V8 BPD. In three patients, PVL was reduced to zero or trace. PVL remained unchanged in one patient (2+). Two patients had complete heart block associated with valve deployment and received permanent pacemakers. There were no occurrences of annular injury or major adverse clinical events.
Conclusions
BPD with the V8 hourglass-shaped balloon was feasible in reducing PVL from self-expanding TAVR prostheses. © 2016 Wiley Periodicals, Inc.
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Neonatal Adiposity Increases with Rising Cord Blood IGF-1 Levels
Abstract
Objective
Infants with higher adiposity at birth may be at greater risk of developing obesity later in life. IGF-1 is important for intrauterine growth and may be a useful early life marker of adiposity, and thus later obesity risk. The aim of this study was to determine the relationship between cord blood IGF-1, neonatal anthropometrics, and markers of neonatal adiposity.
Design, Patients, and Measurements
A cross-sectional study design was utilized to study a multiethnic cohort of full term neonates born to healthy mothers without gestational diabetes at a large university hospital. Neonatal cord blood was collected after birth and assayed for IGF-1, leptin, and c-peptide. Neonatal body composition was measured between 24-72 hours of life using the method of air displacement plethysmography.
Results
Cord blood IGF-1 was positively and significantly associated with markers of neonatal adiposity in models adjusted for maternal age at delivery, race, maternal pre-pregnancy BMI, gestational age at delivery, and neonatal sex: birth weight (r=0.62, p<0.001), leptin (r=0.33, p=0.018), fat mass (r=0.52, p<0.001), and percent body fat (r=0.51, p<0.001). Cord blood IGF-1 was not associated with cord blood c-peptide.
Conclusions
Cord blood IGF-1 is strongly associated with all measures of neonatal adiposity suggesting that IGF-1 may be an important contributor to in-utero neonatal fat accumulation.
This article is protected by copyright. All rights reserved.
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Case of isolated epidermolytic acanthoma: Genetic and immunohistochemical analysis
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Effects of systemic propranolol treatment on physical growth of patients with infantile hemangiomas
Abstract
Propranolol has been widely used in the treatment of infantile hemangiomas since 2008. This study aimed to investigate complications of systemic propranolol therapy for infantile hemangiomas, especially its effect on infants' physical growth. In this study, propranolol was given at a dose of 2 mg/kg per day. Abnormal symptoms and growth parameters were recorded in detail during the therapy. Follow-up visits were arranged to continue at least through the age of 2 years. A total of 76 patients with complete growth parameters were enrolled into the study. Complications of propranolol were minor, and mainly included sleeping disorders, diarrhea, decrease in fasting glucose, bronchial hyperactivity and hyperkalemia. Four (5.26%) patients' growth curve dropped off more than 20 percentiles during therapy and half of them returned to normal after withdrawal of the medications. None of them suffered from underweight, wasting or stunning when medication was stopped. Systemic propranolol was proved to be a safe treatment for problematic infantile hemangiomas and did not affect the physical growth.
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Superficial CD34-positive fibroblastic tumor: A new case from Japan
Abstract
A 48-year-old Japanese woman presented with a painless, slow-growing, brown nodule of 15 mm in diameter on the left thigh. She noticed the nodule a few years before the first presentation to our hospital. She underwent total resection of the nodule. On histopathological examination, a relatively well-defined tumor with infiltrative growth was located in the dermis and extended into the subcutis. The tumor was composed of spindle to polygonal cells with pleomorphic nuclei arranged in a sheet-like or fascicular pattern. Tumor cells with granular cytoplasm were also scattered. Immunohistochemical examination revealed that the tumor cells were strongly positive for CD34. The fusion transcripts of the collagen type 1 alpha 1 platelet-derived growth factor beta chain were not detected. After excluding other fibroblastic tumors through histopathological and immunohistochemical examinations, a diagnosis of superficial CD34-positive fibroblastic tumor (SCPFT) was made. SCPFT is a recently proposed fibroblastic tumor that is characterized by striking pleomorphism, granular cytoplasm, low mitotic rate and diffuse CD34 expression. Only two reports with 20 cases have been reported so far. The present case is the first that corresponds to SCPFT in Japan.
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Serum levels of soluble programmed death-1 and programmed death ligand-1 in systemic sclerosis: Association with extent of skin sclerosis
Abstract
The interaction of programmed death-1 (PD-1) with its ligand, programmed death ligand-1 (PD-L1), has been considered to play a key role in the negative regulation of immune responses. Patients with diffuse cutaneous systemic sclerosis (SSc) had higher levels of soluble PD-1 (sPD-1) than those with limited cutaneous SSc and healthy individuals. Serum sPD-1 levels positively correlated with the severity of skin sclerosis. In contrast, serum sPD-L1 levels were significantly increased in patients with SSc compared with healthy individuals. Moreover, serum sPD-L1 levels were not associated with the extent of skin sclerosis and were elevated not only in patients with diffuse cutaneous SSc, but also in those with limited cutaneous SSc. These results suggested that serum sPD-1 levels may increase in patients with SSc and correlate with the severity of skin sclerosis. PD-1/PD-L1 interaction may contribute to the development of skin sclerosis in SSc.
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Is bevacizumab a culprit of intractable skin ulcers?
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Pemphigus with features of both vulgaris and foliaceus variants localized to the nose
Abstract
We report the case of a 74-year-old man affected by an unusual variant of pemphigus. He presented with a crusty and scaly lesion of the nose. We performed reflectance confocal microscopy and optical coherence tomography on the lesion, which suggested an unexpected diagnosis of pemphigus. Therefore, to confirm our diagnostic suspicions, we executed indirect immunofluorescence and two biopsies, one for histopathological examination and one for direct immunofluorescence. Histopathological evaluation showed acantholysis with formation of clefts in the granular and spinous layers of the epidermis. Direct immunofluorescence revealed immunoglobulin G and C3 deposit to the full thickness of the epidermis. Indirect immunofluorescence showed intercellular antibodies at a titer of 1:40 in the suprabasal epidermis. The immunoblot analysis using epidermal extract revealed the presence of circulating antibodies directed to 130- and 160-kDa antigens in the patient's serum. These two antigens were evidenced from nitrocellulose membrane with colorimetric AP systems, which highlighted the presence of autoantibodies against desmoglein (Dsg)1 and Dsg3 (sodium dodecylsulfate polyacrylamide gel electrophoresis). We also performed an enzyme-linked immunoassay. All these findings suggested that this patient's pemphigus had features of both vulgaris and foliaceus variants.
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Erosive oral lichen planus as a sign of paraneoplastic pemphigus
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Management of erythematous skin lesions in bullous pemphigoid associated with atopic dermatitis
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Spindle cell hemangioma in an elderly patient: Uncommon benign vascular neoplasm
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Acupuncture and Related Therapies for Symptom Management in Palliative Cancer Care: Systematic Review and Meta-Analysis.
Acupuncture and Related Therapies for Symptom Management in Palliative Cancer Care: Systematic Review and Meta-Analysis.
Medicine (Baltimore). 2016 Mar;95(9):e2901
Authors: Lau CH, Wu X, Chung VC, Liu X, Hui EP, Cramer H, Lauche R, Wong SY, Lau AY, Sit RS, Ziea ET, Ng BF, Wu JC
Abstract
Available systematic reviews showed uncertainty on the effectiveness of using acupuncture and related therapies for palliative cancer care.The aim of this systematic review and meta-analysis was to summarize current best evidence on acupuncture and related therapies for palliative cancer care.Five international and 3 Chinese databases were searched. Randomized controlled trials (RCTs) comparing acupuncture and related therapies with conventional or sham treatments were considered. Primary outcomes included fatigue, paresthesia and dysesthesias, chronic pain, anorexia, insomnia, limb edema, constipation, and health-related quality of life, of which effective conventional interventions are limited.Thirteen RCTs were included. Compared with conventional interventions, meta-analysis demonstrated that acupuncture and related therapies significantly reduced pain (2 studies, n = 175, pooled weighted mean difference: -0.76, 95% confidence interval: -0.14 to -0.39) among patients with liver or gastric cancer. Combined use of acupuncture and related therapies and Chinese herbal medicine improved quality of life in patients with gastrointestinal cancer (2 studies, n = 111, pooled standard mean difference: 0.75, 95% confidence interval: 0.36-1.13). Acupressure showed significant efficacy in reducing fatigue in lung cancer patients when compared with sham acupressure. Adverse events for acupuncture and related therapies were infrequent and mild.Acupuncture and related therapies are effective in reducing pain, fatigue, and in improving quality of life when compared with conventional intervention alone among cancer patients. Limitations on current evidence body imply that they should be used as a complement, rather than an alternative, to conventional care. Effectiveness of acupuncture and related therapies for managing anorexia, reducing constipation, paresthesia and dysesthesia, insomnia, and limb edema in cancer patients is uncertain, warranting future RCTs in these areas.
PMID: 26945382 [PubMed - as supplied by publisher]
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Annual Average Changes in Adult Obesity as a Risk Factor for Papillary Thyroid Cancer: A Large-Scale Case-Control Study.
Annual Average Changes in Adult Obesity as a Risk Factor for Papillary Thyroid Cancer: A Large-Scale Case-Control Study.
Medicine (Baltimore). 2016 Mar;95(9):e2893
Authors: Hwang Y, Lee KE, Park YJ, Kim SJ, Kwon H, Park DJ, Cho B, Choi HC, Kang D, Park SK
Abstract
We evaluated the association between weight change in middle-aged adults and papillary thyroid cancer (PTC) based on a large-scale case-control study.Our study included data from 1551 PTC patients (19.3% men and 80.7% women) who underwent thyroidectomy at the 3 general hospitals in Korea and 15,510 individually matched control subjects. The subjects' weight history, epidemiologic information, and tumor characteristics confirmed after thyroidectomy were analyzed. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were determined for the annual average changes in weight and obesity indicators (body mass index (BMI), body surface area, and body fat percentage (BF%) in subjects since the age of 35 years.Subjects with a total weight gain ≥10 kg after age 35 years were more likely to have PTC (men, OR, 5.39, 95% CI, 3.88-7.49; women, OR, 3.36, 95% CI, 2.87-3.93) compared with subjects with a stable weight (loss or gain <5 kg). A marked increase in BMI since age 35 years (annual average change of BMI ≥0.3 kg/m/yr) was related to an elevated PTC risk, and the association was more pronounced for large-sized PTC risks (<1 cm, OR, 2.34, 95% CI, 1.92-2.85; ≥1 cm, OR, 4.00, 95% CI, 2.91-5.49, P heterogeneity = 0.005) compared with low PTC risks.Weight gain and annual increases in obesity indicators in middle-aged adults may increase the risk of developing PTC.
PMID: 26945379 [PubMed - as supplied by publisher]
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Stressful Life Events as a Predictor for Nonsuicidal Self-Injury in Southern Chinese Adolescence: A Cross-Sectional Study.
Stressful Life Events as a Predictor for Nonsuicidal Self-Injury in Southern Chinese Adolescence: A Cross-Sectional Study.
Medicine (Baltimore). 2016 Mar;95(9):e2637
Authors: Tang J, Yang W, Ahmed NI, Ma Y, Liu HY, Wang JJ, Wang PX, Du YK, Yu YZ
Abstract
Stressful life events have been implicated in the etiology of kinds of psychopathology related to nonsuicidal self-injury (NSSI); however, few studies have examined the association between NSSI and stressful life events directly in Chinese school adolescents. In this study, we aim to estimate the prevalence rate of NSSI and examine its association with stressful life events in Southern Chinese adolescents. A total sample of 4405 students with age ranged from 10 to 22 years was randomly selected from 12 schools in 3 cities of Guangdong Province, China. NSSI, stressful life events, self-esteem, emotional management, and coping methods were measured by structured questionnaires. Multinomial logistic regression was used to examine the association of NSSI with stressful life events. Results showed the 1 year self-reported NSSI was 29.2%, with 22.6% engaged in "minor" NSSI (including hitting self, pulling hair, biting self, inserting objects under nails or skin, picking at a wound) and 6.6% in "moderate/sever" NSSI (including cutting/carving, burning, self-tattooing, scraping, and erasing skin). Self-hitting (15.9%), pulling hair out (10.9%), and self-inserting objects under nails or skin picking areas to dram blood (18.3%) were the most frequent types of NSSI among adolescents. Results also showed that "Minor NSSI" was associated with stressful life events on interpersonal, loss and health adaption, and "moderate/severe NSSI" was associated with life events on interpersonal, health adaption in Southern Chinese adolescents, even after adjusted for sex, age, residence, self-esteem, coping style, and emotional management. Results further suggested stressful life events were significantly associated with less risk of NSSI in those who had good emotional management ability.
PMID: 26945351 [PubMed - as supplied by publisher]
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Ratiometric electrochemical immunoassay based on internal reference value for reproducible and sensitive detection of tumor marker.
Ratiometric electrochemical immunoassay based on internal reference value for reproducible and sensitive detection of tumor marker.
Biosens Bioelectron. 2016 Feb 27;81:173-180
Authors: Cai X, Weng S, Guo R, Lin L, Chen W, Zheng Z, Huang Z, Lin X
Abstract
A ratiometric assay in an electrochemical immunosensor for tumor marker, herein carcinoembryonic antigen (CEA) was chosen as a model analyte, was developed to improve simplicity and accuracy. The immunosensor was fabricated via the simple expedient way of using Polythionine-gold (PTh-Au) as electrode modified material to be an internal reference signal and K3[Fe(CN)6] in electrolyte as an indicator signal. When the CEA was fixed on the modified electrode via immunoreaction, only the indicator signal sensitively altered; by contrast, the internal reference signal of PTh-Au remained constant at a suitable pH of the electrolyte. The ratio between the alterations of the indicator signal of K3[Fe(CN)6] and the constant internal reference signal can be used to monitor the concentration of CEA reliably, reproducibly, and sensitively. The prepared ratiometric electrochemical immunosensor could detect CEA with good specificity within a wide linear range from 0.005ng/ml to 40ng/ml with a detection limit of 2.2pg/ml. Additionally, experimental results confirm that our proposed method is practical. Thus, this method can expand to recognize and test other protein markers.
PMID: 26945184 [PubMed - as supplied by publisher]
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Effect of Gaze Position and Blur on Stepping Accuracy in Older Adults.
Effect of Gaze Position and Blur on Stepping Accuracy in Older Adults.
Optom Vis Sci. 2016 Mar 4;
Authors: Black AA, Drager D, Parker L, Richardson M, Urquhart T, Wood JM
Abstract
PURPOSE: To examine the effects of gaze position and optical blur, similar to that used in multifocal corrections, on stepping accuracy for a precision stepping task among older adults.
METHODS: Nineteen healthy older adults (mean age, 71.6 ± 8.8 years) with normal vision performed a series of precision stepping tasks onto a fixed target. The stepping tasks were performed using a repeated-measures design for three gaze positions (fixating on the stepping target as well as 30 and 60 cm farther forward of the stepping target) and two visual conditions (best-corrected vision and with +2.50DS blur). Participants' gaze position was tracked using a head-mounted eye tracker. Absolute, anteroposterior, and mediolateral foot placement errors and within-subject foot placement variability were calculated from the locations of foot and floor-mounted retroreflective markers captured by flash photography of the final foot position.
RESULTS: Participants made significantly larger absolute and anteroposterior foot placement errors and exhibited greater foot placement variability when their gaze was directed farther forward of the stepping target. Blur led to significantly increased absolute and anteroposterior foot placement errors and increased foot placement variability. Furthermore, blur differentially increased the absolute and anteroposterior foot placement errors and variability when gaze was directed 60 cm farther forward of the stepping target.
CONCLUSIONS: Increasing gaze position farther ahead from stepping locations and the presence of blur negatively impact the stepping accuracy of older adults. These findings indicate that blur, similar to that used in multifocal corrections, has the potential to increase the risk of trips and falls among older populations when negotiating challenging environments where precision stepping is required, particularly as gaze is directed farther ahead from stepping locations when walking.
PMID: 26945174 [PubMed - as supplied by publisher]
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Use of technology in follow-up of HIV positive pregnant women and their babies till 18 months of age- an innovation by Maharashtra State AIDS Control Society (MSACS), India.
Use of technology in follow-up of HIV positive pregnant women and their babies till 18 months of age- an innovation by Maharashtra State AIDS Control Society (MSACS), India.
Curr Opin HIV AIDS. 2016 Mar 3;
Authors: Gupta RS, Yewale K, Hegde AS, Mulik T, Bamrotiya M, Yadav S, Rane T, Pardeshi K, Balakrishnan S, Reddy DC
Abstract
OBJECTIVE: The purpose of this study is to assess the utility of web-based mobile technology monitoring tool, for ensuring linkages, and tracking of HIV-exposed child until 18 months of age.
METHODS: The 'early infant diagnosis (EID) Follow-up System' was designed as a tool for reminding the field level staff for follow-up of HIV-exposed babies. Using Java Swing Framework, software was developed which generates automatic advance SMS alerts regarding patient information to the Counsellor of the respective Integrated Counselling and Testing Center and district supervisor, 7 days prior to due dates. Simultaneously, system generated e-mail is sent to district program officer for monitoring and updating the line-list.
RESULTS: Before the introduction of 'EID Follow-up System' in June 2013, only 55.9% (637/1139) of the HIV-exposed babies born were tested at 6 weeks for DNA-Polymerase Chain Reaction during April 2011-March 2012. However, after its introduction, 68.4% (1117/1631) of them were tested during April 2012-March 2013. Correspondingly, the 18 months confirmatory HIV testing in eligible babies increased from 45.6% (934/2044) to 54.7%(1118/2044) during the same period.
CONCLUSION: The replicable technology driven initiative would help in strengthening the follow-up mechanisms and reach every HIV-exposed child for EID.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://ift.tt/OBJ4xP.
PMID: 26945142 [PubMed - as supplied by publisher]
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Local and systemic factors and implantation: what is the evidence?
Local and systemic factors and implantation: what is the evidence?
Fertil Steril. 2016 Mar 2;
Authors: Fox C, Morin S, Jeong JW, Scott RT, Lessey BA
Abstract
Significant progress has been made in the understanding of embryonic competence and endometrial receptivity since the inception of assisted reproductive technology. The endometrium is a highly dynamic tissue that plays a crucial role in the establishment and maintenance of normal pregnancy. In response to steroid sex hormones, the endometrium undergoes marked changes during the menstrual cycle that are critical for acceptance of the nascent embryo. There is also a wide body of literature on systemic factors that impact assisted reproductive technology outcomes. Patient prognosis is impacted by an array of factors that tip the scales in her favor or against success. Recognizing the local and systemic factors will allow clinicians to better understand and optimize the maternal environment at the time of implantation. This review will address the current literature on endometrial and systemic factors related to impaired implantation and highlight recent advances in this area of reproductive medicine.
PMID: 26945096 [PubMed - as supplied by publisher]
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The Effects of an Educational Intervention on Preventing Cervical Cancer Among Vietnamese Women in Southern Taiwan.
The Effects of an Educational Intervention on Preventing Cervical Cancer Among Vietnamese Women in Southern Taiwan.
J Cancer Educ. 2016 Mar 5;
Authors: Lee FH, Wang HH, Yang YM, Tsai HM, Huang JJ
Abstract
This paper aims to conduct and evaluate an educational intervention on preventing cervical cancer among married immigrant women of Vietnamese origin. The study design was a quasi-experimental method with two groups. In total, 260 married immigrant women of Vietnamese origin with national health insurance at least 30 years of age were recruited from November 2013 to January 2015 in southern Taiwan. The effects of the educational intervention, including cervical cancer and Papanicolaou test knowledge, attitudes towards cervical cancer, fatalism, barriers to receiving Papanicolaou tests, intention for receiving Papanicolaou tests within the next year, and intention for receiving Papanicolaou tests within the next 3 years, were evaluated. Repeated measures analyses of variance showed significant interactions between the intervention group and time for cervical cancer knowledge, knowledge of Papanicolaou test, attitudes towards cervical cancer, and intention for receiving a Papanicolaou test within the next 3 years; in addition, 71.4 % reported being satisfied or very satisfied with the intervention. The results of this study can provide information for governments to make appropriate health policies for screening behavior of cervical cancer, increase healthcare professionals' competencies towards Vietnamese women, and increase Papanicolaou test screening rates to decrease cervical cancer mortality. Effective interventions may require particular consideration of married immigrant women.
PMID: 26944985 [PubMed - as supplied by publisher]
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Using a tailored health information technology- driven intervention to improve health literacy and medication adherence in a Pakistani population with vascular disease (Talking Rx) - study protocol for a randomized controlled trial.
Using a tailored health information technology- driven intervention to improve health literacy and medication adherence in a Pakistani population with vascular disease (Talking Rx) - study protocol for a randomized controlled trial.
Trials. 2016;17(1):121
Authors: Kamal AK, Muqeet A, Farhat K, Khalid W, Jamil A, Gowani A, Muhammad AA, Zaidi F, Khan D, Elahi T, Sharif S, Raz S, Zafar T, Bokhari SS, Rahman N, Sultan FA, Sayani S, Virani SS
Abstract
BACKGROUND: Vascular disease, manifesting as myocardial infarction and stroke, is a major cause of morbidity and mortality, especially in low- and middle-income countries. Current estimates are that only one in six patients have good adherence to medications and very few have sufficient health literacy. Our aim is to explore the effectiveness and acceptability of Prescription Interactive Voice Response (IVR) Talking Prescriptions (Talking Rx) and SMS reminders in increasing medication adherence and health literacy in Pakistani patients with vascular disease.
METHODS: This is a randomized, controlled, single center trial. Adult participants, with access to a cell phone and a history of vascular disease, taking multiple risk-modifying medications (inclusive of anti-platelets and statins) will be selected from cerebrovascular and cardiovascular clinics. They will be randomized in a 1:1 ratio via a block design to the intervention or the control arm with both groups having access to a helpline number to address their queries in addition to standard of care as per institutional guidelines. Participants in the intervention group will also have access to Interactive Voice Response (IVR) technology tailored to their respective prescriptions in the native language (Urdu) and will have the ability to hear information about their medication dosage, correct use, side effects, mechanism of action and how and why they should use their medication, as many times as they like. Participants in the intervention arm will also receive scheduled SMS messages reminding them to take their medications. The primary outcome measure will be the comparison of the difference in adherence to anti-platelet and statin medication between baseline and at 3-month follow-up in each group measured by the Morisky Medication Adherence Scale. To ascertain the impact of our intervention on health literacy, we will also compare a local content-validated and modified version of Test of Health Literacy in Adults (TOFHLA) between the intervention and the control arm. We estimate that a sample size of 86 participants in each arm will be able to detect a difference of 1 point on the MMAS with a power of 90 % and significance level of 5 %. Accounting for an attrition rate of 15 %, we plan to enroll 100 participants in each arm (total study population = 200). We hypothesize that a linguistically tailored health IT intervention based on IVR and SMS will be associated with an improvement in adherence (to anti-platelet and lipid-lowering medications) and an improvement in health literacy in Pakistani patients with vascular disease.
DISCUSSION: This innovative study will provide early data for the feasibility of the use of IT based prescriptions in an lower middle incorme country setting with limited numeracy and literacy skills.
TRIAL REGISTRATION: Clinical Trials.gov: NCT02354040 - 2 February 2015.
PMID: 26944938 [PubMed - as supplied by publisher]
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Influenza Vaccination Reduces Dementia Risk in Chronic Kidney Disease Patients: A Population-Based Cohort Study.
Influenza Vaccination Reduces Dementia Risk in Chronic Kidney Disease Patients: A Population-Based Cohort Study.
Medicine (Baltimore). 2016 Mar;95(9):e2868
Authors: Liu JC, Hsu YP, Kao PF, Hao WR, Liu SH, Lin CF, Sung LC, Wu SY
Abstract
Taiwan has the highest prevalence of chronic kidney disease (CKD) worldwide. CKD, a manifestation of vascular diseases, is associated with a high risk of dementia. Here, we estimated the association between influenza vaccination and dementia risk in patients with CKD.Data from the National Health Insurance Research Database of Taiwan were used in this study. The study cohort included all patients diagnosed with CKD (according to International Classification of Disease, Ninth Revision, Clinical Modification codes) at healthcare facilities in Taiwan (n = 32,844) from January 1, 2000, to December 31, 2007. Each patient was followed up to assess dementia risk or protective factors: demographic characteristics of age and sex; comorbidities of diabetes, hypertension, dyslipidemia, cerebrovascular diseases, parkinsonism, epilepsy, substance and alcohol use disorders, mood disorder, anxiety disorder, psychotic disorder, and sleep disorder; urbanization level; monthly income; and statin, metformin, aspirin, and angiotensin-converting enzyme inhibitor (ACEI) use. A propensity score was derived using a logistic regression model for estimating the effect of vaccination by accounting for covariates that predict receiving the intervention (vaccine). A time-dependent Cox proportional hazard model was used to calculate the hazard ratios (HRs) of dementia among vaccinated and unvaccinated CKD patients.The study population comprised 11,943 eligible patients with CKD; 5745 (48%) received influenza vaccination and the remaining 6198 (52%) did not. The adjusted HRs (aHRs) of dementia decreased in vaccinated patients compared with those in unvaccinated patients (influenza season, noninfluenza season, and all seasons: aHRs = 0.68, 0.58, and 0.64; P < 0.0001, P < 0.0001, and P < 0.0001, respectively). In the sensitivity analysis, adjustments were made to estimate the association of age and sex; diabetes, dyslipidemia, hypertension, cerebrovascular diseases, anxiety disorder; and statin, metformin, ACEI, and aspirin use with the incidence of dementia in various models. A stronger protective effect against dementia risk was demonstrated during the noninfluenza season. Regardless of comorbidities or drug use, influenza vaccination was an independent protective factor and dose-dependently reduced the risk of dementia in CKD patients.Influenza vaccination exerts dose-response and synergistic protective effects against dementia in CKD patients with dementia risk factors by reducing the incidence of dementia.
PMID: 26945371 [PubMed - as supplied by publisher]
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Patient-reported Outcomes in Asian Patients With Chronic Hepatitis C Treated With Ledipasvir and Sofosbuvir.
Patient-reported Outcomes in Asian Patients With Chronic Hepatitis C Treated With Ledipasvir and Sofosbuvir.
Medicine (Baltimore). 2016 Mar;95(9):e2702
Authors: Younossi ZM, Stepanova M, Chan HL, Lee MH, Yu ML, Dan YY, Choi MS, Henry L
Abstract
Prevalence of chronic hepatitis C (CH-C) infection in patients of Asian ancestry ranges between 1% and 20%. Interferon (IFN)- and ribavirin (RBV)-containing regimens for CH-C have a negative impact on patient-reported outcomes (PROs) during treatment.The aim of this study was to assess the impact of IFN-free RBV-free sofosbuvir (SOF)-based regimens on PROs in CH-C patients of Asian ancestry.In this observational retrospective study, the PRO data from 12 multicenter multinational phase 3 clinical trials (2012-2015, conducted in Europe, North America, Australia, and New Zealand) of SOF-based regimens with and without IFN, ledipasvir (LDV), and/or RBV were used. At baseline, during treatment, and post-treatment, patients completed 4 validated PRO questionnaires (SF-36, CLDQ-HCV, FACIT-F, and WPAI:SHP). The resulting PROs in Asian patients were compared across the treatment regimens.Of 4485 of the trials' participants, 106 patients were of Asian ancestry (55.7% male, 69.8% treatment-naïve, 17.0% cirrhotic). In comparison with other patients, the Asian CH-C cohort was younger, had lower BMI, and lower rates of pre-treatment psychiatric comorbidities (anxiety, depression, sleep disorders) (all P < .05). At baseline, Asian patients also had lower SF-36 physical functioning scores (on average, by -5.6% on a normalized 0-100% PRO scale, P = .001). During treatment, Asian CH-C patients experienced a decline in their PRO scores while receiving IFN and/or RBV-containing regimens (up to -19.6%, P < .001). In contrast, patients receiving LDV/SOF experienced no PRO decrement and improvement of some PRO scores during treatment (+9.0% in general health of SF-36, P = .03). After achieving SVR-12, some of the PRO scores in Asian patients improved regardless of the regimen (up to +9.3%, P < .001). In multivariate analysis of Asian patients, the use of LDV/SOF was independently associated with higher PRO scores during and soon after the end of treatment (betas +15.0% to +29.3%, all P < .05). Other predictors of PRO impairment included depression, type 2 diabetes mellitus, and cirrhosis.The use of IFN- and RBV-free LDV/SOF regimens leads to PRO improvement in Asian patients with CH-C during treatment. Achieving SVR-12 results in improvement of PRO scores.
PMID: 26945356 [PubMed - as supplied by publisher]
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The impact of sleep amount and sleep quality on glycemic control in type 2 diabetes: A systematic review and meta-analysis.
The impact of sleep amount and sleep quality on glycemic control in type 2 diabetes: A systematic review and meta-analysis.
Sleep Med Rev. 2016 Feb 9;
Authors: Lee SW, Ng KY, Chin WK
Abstract
Recent epidemiological studies have suggested that there is an association between glycemic control and sleep disturbances in patients with type 2 diabetes, but the extent is unclear. A systematic literature search was performed in nine electronic databases from inception until August 2015 without any language restriction. The search identified 20 studies (eight studies reporting duration of sleep and 15 studies evaluating sleep quality), and 15 were included in the meta-analysis. Short and long sleep durations were associated with an increased hemoglobin A1c (HbA1c) (weighted mean difference (WMD): 0.23% [0.10-0.36], short sleep; WMD: 0.13% [0.02-0.25], long sleep) compared to normal sleep, suggesting a U-shaped dose-response relationship. Similarly, poor sleep quality was associated with an increased HbA1c (WMD: 0.35% [0.12-0.58]). Results of this study suggest that amount of sleep as well as quality of sleep is important in the metabolic function of type 2 diabetes patients. Further studies are needed to identify for the potential causal role between sleep and altered glucose metabolism.
PMID: 26944909 [PubMed - as supplied by publisher]
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The Clustering of Lifestyle Behaviours in New Zealand and their Relationship with Optimal Wellbeing.
The Clustering of Lifestyle Behaviours in New Zealand and their Relationship with Optimal Wellbeing.
Int J Behav Med. 2016 Mar 4;
Authors: Prendergast KB, Mackay LM, Schofield GM
Abstract
PURPOSE: The purpose of this research was to determine (1) associations between multiple lifestyle behaviours and optimal wellbeing and (2) the extent to which five lifestyle behaviours-sleep, physical activity, sedentary behaviour, sugary drink consumption, and fruit and vegetable intake-cluster in a national sample.
METHOD: A national sample of New Zealand adults participated in a web-based wellbeing survey. Five lifestyle behaviours-sleep, physical activity, sedentary behaviour, sugary drink consumption, and fruit and vegetable intake-were dichotomised into healthy (meets recommendations) and unhealthy (does not meet recommendations) categories. Optimal wellbeing was calculated using a multi-dimensional flourishing scale, and binary logistic regression analysis was used to calculate the relationship between multiple healthy behaviours and optimal wellbeing. Clustering was examined by comparing the observed and expected prevalence rates (O/E) of healthy and unhealthy two-, three-, four-, and five-behaviour combinations.
RESULTS: Data from 9425 participants show those engaging in four to five healthy behaviours (23 %) were 4.7 (95 % confidence interval (CI) 3.8-5.7) times more likely to achieve optimal wellbeing compared to those engaging in zero to one healthy behaviour (21 %). Clustering was observed for healthy (5 %, O/E 2.0, 95 % CI 1.8-2.2) and unhealthy (5 %, O/E 2.1, 95 % CI 1.9-2.3) five-behaviour combinations and for four- and three-behaviour combinations. At the two-behaviour level, healthy fruit and vegetable intake clustered with all behaviours, except sleep which did not cluster with any behaviour.
CONCLUSION: Multiple lifestyle behaviours were positively associated with optimal wellbeing. The results show lifestyle behaviours cluster, providing support for multiple behaviour lifestyle-based interventions for optimising wellbeing.
PMID: 26944753 [PubMed - as supplied by publisher]
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Diagnostic yield of electromagnetic navigational bronchoscopy.
Diagnostic yield of electromagnetic navigational bronchoscopy.
Ther Adv Respir Dis. 2016 Mar 4;
Authors: Al-Jaghbeer M, Marcus M, Durkin M, McGuire FR, Iftikhar IH
Abstract
OBJECTIVES: Peripheral lung nodules (PLNs) are a common and diagnostically challenging finding. Electronavigational bronchoscopy (ENB) is used to increase the diagnostic yield and is considered safe. Multiple factors have been correlated with a better diagnostic yield. We sought to assess the effect of nodule characteristics and prior workup on the diagnostic yield in ENB.
METHODS: This was a retrospective chart review of 98 ENB procedures in a community referral center. Two investigators reviewed patients' charts and images independently. Multiple logistic regression analyses was used to determine if factors such as bronchus sign, ground glass opacification (GGO), distance from pleura, prior use of endobronchial ultrasound (EBUS) and positron emission tomography (PET) had an impact on the diagnostic yield.
RESULTS: We evaluated 98 ENBs performed in 92 patients. Most of the lesions were in the upper lobes. The diagnostic yield was 60%. A PET scan was performed prior to ENB in 47% of cases. EBUS was performed in 24% of cases. Bronchus sign was present in 60% of cases and GGO in only 6% of nodules. The odds ratio for diagnostic yield with a bronchus sign was 1.89 [95% confidence interval (CI): 0.83-4.33] and with nodules showing GGO characteristics it was 4.51 (95% CI: 0.51-39.68). Pneumothorax occurred in 6% of cases.
CONCLUSION: In our cohort, diagnostic yield was 60% with a 6% pneumothorax rate. A suggestive trend for the presence of bronchus sign on computed tomography scan, albeit statistically nonsignificant, as a predictor for improved diagnostic yield needs to be validated in a larger cohort.
PMID: 26944363 [PubMed - as supplied by publisher]
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The syndrome of polymicrogyria, thalamic hypoplasia, and epilepsy with CSWS.
The syndrome of polymicrogyria, thalamic hypoplasia, and epilepsy with CSWS.
Neurology. 2016 Mar 4;
Authors: Bartolini E, Falchi M, Zellini F, Parrini E, Grisotto L, Cosottini M, Posar A, Parmeggiani A, Ambrosetto G, Ferrari AR, Santucci M, Salas-Puig J, Barba C, Guerrini R
Abstract
OBJECTIVE: We explored the long-term follow-up of continuous spike-and-wave complexes during sleep (CSWS) in polymicrogyria and the anatomic volumetric variables that influence the risk of developing this age-related epileptic encephalopathy.
METHODS: We performed prospective follow-up of 27 patients with polymicrogyria/CSWS (mean follow-up 14.3 years; range 2-31 years) and comparative volumetric analysis of the polymicrogyric hemispheres and ipsilateral thalami vs 3 subgroups featuring polymicrogyria without CSWS, benign rolandic epilepsy (BRE), and headache. Receiver operator characteristic analysis of the power of volumetric values was determined to predict CSWS.
RESULTS: CSWS peaked between 5 and 7 years (mean age at onset 4.7 years). Remission occurred within 2 years from onset in 21%, within 4 years in 50%, and by age 13 years in 100%. We found smaller thalamic and hemispheric volumes in polymicrogyria/CSWS with respect to polymicrogyria without CSWS (p = 0.0021 for hemispheres; p = 0.0003 for thalami), BRE, and controls with headache (p < 0.0001). Volumes of the malformed hemispheres and ipsilateral thalami reliably identified the risk of incurring CSWS, with a 68-fold increased risk for values lower than optimal diagnostic cutoffs (436,150 mm(3) for malformed hemispheres or 4,616 mm(3) for ipsilateral thalami; sensitivity 92.54%; specificity 84.62%). The risk increased by 2% for every 1,000 mm(3) reduction of the polymicrogyric hemispheres and by 15% for every 100 mm(3) reduction of ipsilateral thalami.
CONCLUSIONS: The polymicrogyria/CSWS syndrome is likely caused by a cortico-thalamic malformation complex and is characterized by remission of epilepsy within early adolescence. Early assessment of hemispheric and thalamic volumes in children with polymicrogyria and epilepsy can reliably predict CSWS.
PMID: 26944271 [PubMed - as supplied by publisher]
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Eat, play, view, sleep: Exploring Mexican American mothers' perceptions of decision making for four behaviors associated with childhood obesity risk.
Eat, play, view, sleep: Exploring Mexican American mothers' perceptions of decision making for four behaviors associated with childhood obesity risk.
Appetite. 2016 Mar 1;
Authors: Davis RE, Cole SM, Blake CE, McKenney-Shubert SJ, Peterson KE
Abstract
OBJECTIVE: This mixed methods study sought to understand who makes decisions about whether preschool-aged Mexican American children engage in eating, outdoor play, sleep, and screen time behaviors.
METHODS: Forty Mexican American mothers of children ages 3-4 participated in two interviews, during which both closed and open-ended questions elicited perceptions of who made decisions for the four behaviors, as well as who was present, mealtime rules, and food choice values. Interviews were transcribed, coded for emergent themes, and compared across participants.
RESULTS: Participants generally perceived themselves to be primary decision makers for all four behaviors; however, food decisions often seemed to be made collaboratively with the child. Fathers were most likely to participate in evening television decisions. Other family members were rarely mentioned. Selecting foods that children liked was a strong food choice value, while cost was rarely mentioned. Participants appeared to have low perceived control over their child's behaviors relative to their perceived roles in decision making.
CONCLUSIONS: Mothers may be the primary audience for obesity prevention messages for preschool-aged, Mexican American children; however, health promotion programs may need to increase mothers' awareness of their control over children's behaviors. Understanding how children's behaviors are regulated is an important aspect of obesity prevention for lowincome, Mexican American children.
PMID: 26944228 [PubMed - as supplied by publisher]
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Orthostatic hypotension and cardiac sympathetic denervation in Parkinson disease patients with REM sleep behavioral disorder.
Orthostatic hypotension and cardiac sympathetic denervation in Parkinson disease patients with REM sleep behavioral disorder.
J Neurol Sci. 2016 Mar 15;362:59-63
Authors: Kim JS, Park HE, Oh YS, Lee SH, Park JW, Son BC, Lee KS
Abstract
BACKGROUND: Rapid eye movement (REM) sleep behavioral disorder (RBD), orthostatic hypotension (OH), and cardiac sympathetic denervation were commonly observed in PD and are related in both the premotor and motor periods. This study is intended to evaluate if the OH and cardiac sympathetic denervation found in PD are associated with RBD.
METHODS: Among 94 non-medicated and mild PD patients, 53 had RBD. Orthostatic vital signs and ambulatory 24-hour blood pressure values were recorded. (123)I-metaiodobenzylguanidine (MIBG) cardiac scintigraphy as obtained in all patients. The association between orthostatic hypotension, supine hypertension, nocturnal hypertension, non-dipping, myocardial MIBG uptake, and RBD was analyzed.
RESULTS: RBD was associated with orthostatic hypotension. Patients with RBD had higher systolic blood pressure changes during orthostasis and lower myocardial MIBG uptake than patients without RBD and controls. Patients with OH also had lower mean H/M ratios those in the non-OH group.
CONCLUSION: This study showed that RBD was closely associated with OH and cardiac sympathetic denervation in patients with early and mild PD. The result also suggests that impaired cardiac sympathetic innervation could be the mechanism behind OH in PD. This association may be closely correlated with Braak alpha-synuclein pathogenetic sequences, which would account for the clinical spectrum of PD.
PMID: 26944118 [PubMed - in process]
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Longitudinal course of mild parkinsonian signs in elderly people: A population-based study in Japan.
Longitudinal course of mild parkinsonian signs in elderly people: A population-based study in Japan.
J Neurol Sci. 2016 Mar 15;362:7-13
Authors: Wada-Isoe K, Tanaka K, Uemura Y, Nakashita S, Tajiri Y, Tagashira S, Yamamoto M, Yamawaki M, Kishi M, Nakashima K
Abstract
We aimed to clarify the longitudinal course of mild parkinsonian signs (MPS) and their association with dementia and functional disability by conducting a comprehensive epidemiological study, including brain MRI, and assessments of cognition, depression, and sleep, in people aged ≥65years living in Ama-cho. We diagnosed MPS and parkinsonism (PS) using a modified Unified Parkinson's Disease Rating Scale. The phase I study was conducted between 2008 and 2010 (n=729) and the phase II between 2011 and 2013 (n=436). By phase II, 8.5% of the phase I participants without PS had developed PS. In addition to older age, a lower Mini-Mental State Examination (MMSE) score, and lower body mass index, the MPS rigidity subtype was a significant independent predictor of PS onset. By phase II, 10.1% of the participants without dementia or PS at phase I had developed dementia. Older age, lower MMSE score, and the axial dysfunction and tremor MPS subtypes were significant independent predictors of dementia development. By phase II, 38.8% of participants with MPS at phase I showed no motor symptoms. Younger age and adequate sleep were significant predictors for this reversion. Periventricular and deep white matter hyperintensity Fazekas scores increased with the evolution of parkinsonian signs. MPS is therefore critically, although sometimes reversibly, associated with PS and dementia development in elderly people.
PMID: 26944110 [PubMed - in process]
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A Context-Driven Worker Selection Framework for Crowd-Sensing
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Is It Time to Phase Out the Austin Moore Hemiarthroplasty? A Propensity Score Matched Case Control Comparison versus Cemented Hemiarthroplasty
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Existence of Infinitely Many Periodic Solutions for Perturbed Semilinear Fourth-Order Impulsive Differential Inclusions
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Surface Potential Analysis of Nanoscale Biomaterials and Devices Using Kelvin Probe Force Microscopy
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An Improved Rigid Multibody Model for the Dynamic Analysis of the Planetary Gearbox in a Wind Turbine
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Peculiar Presentation of Ulcerative Colitis
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The Diagnostic Role of Adiponectin in Pulmonary Embolism
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Modeling and Extended State Observer Based Dynamic Surface Control for Cold Rolling Mill System
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Danger of 'gadolinium phobia' looms in Europe
VIENNA - There's a serious risk of a phobia developing over the use of gadolinium-based...
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Algorithm quantifies airway disease at CT
VIENNA - A fully automated algorithm to evaluate airway disease produced good...
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Immunotherapy and targeted therapy provide new options for head and neck cancer - Biotechin.Asia
Biotechin.Asia |
Immunotherapy and targeted therapy provide new options for head and neck cancer
Biotechin.Asia Novel strategies are on the way for difficult-to-treat and advanced head and neck cancer, the most heterogeneous group of malignancies which are generally associated with poor survival, and encouraging results have been presented at the first ESMO Asia ... |
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Former Brazilian leader Lula is implicated in huge corruption probe - The Japan Times
The Japan Times |
Former Brazilian leader Lula is implicated in huge corruption probe
The Japan Times SAO PAULO – Luiz Inacio Lula da Silva, a former metalworker who rose to become one of the most popular presidents in Brazilian history, now sees his legacy under threat after being implicated in a huge corruption probe. Lula, as he is known to all in ... Ex-Brazilian President Lula da Silva questioned as part of corruption probeCNN all 1,155 news articles » |
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Transgenic Drosophila for Investigating DUX4 and FRG1, Two Genes Associated with Facioscapulohumeral Muscular Dystrophy (FSHD)
by Takako I. Jones, Megan Parilla, Peter L. Jones
Facioscapulohumeral muscular dystrophy (FSHD) is typically an adult onset dominant myopathy. Epigenetic changes in the chromosome 4q35 region linked to both forms of FSHD lead to a relaxation of repression and increased somatic expression of DUX4-fl (DUX4-full length), the pathogenic alternative splicing isoform of the DUX4 gene. DUX4-fl encodes a transcription factor expressed in healthy testis and pluripotent stem cells; however, in FSHD, increased levels of DUX4-fl in myogenic cells lead to aberrant regulation of target genes. DUX4-fl has proven difficult to study in vivo; thus, little is known about its normal and pathogenic roles. The endogenous expression of DUX4-fl in FSHD-derived human muscle and myogenic cells is extremely low, exogenous expression of DUX4-fl in somatic cells rapidly induces cytotoxicity, and, due in part to the lack of conservation beyond primate lineages, viable animal models based on DUX4-fl have been difficult to generate. By contrast, the FRG1 (FSHD region gene 1), which is linked to FSHD, is evolutionarily conserved from invertebrates to humans, and has been studied in several model organisms. FRG1 expression is critical for the development of musculature and vasculature, and overexpression of FRG1 produces a myopathic phenotype, yet the normal and pathological functions of FRG1 are not well understood. Interestingly, DUX4 and FRG1 were recently linked when the latter was identified as a direct transcriptional target of DUX4-FL. To better understand the pathways affected in FSHD by DUX4-fl and FRG1, we generated transgenic lines of Drosophila expressing either gene under control of the UAS/GAL4 binary system. Utilizing these lines, we generated screenable phenotypes recapitulating certain known consequences of DUX4-fl or FRG1 overexpression. These transgenic Drosophila lines provide resources to dissect the pathways affected by DUX4-fl or FRG1 in a genetically tractable organism and may provide insight into both muscle development and pathogenic mechanisms in FSHD.from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/21eEDb9
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Integration of HIV Care into Community Management of Acute Childhood Malnutrition Permits Good Outcomes: Retrospective Analysis of Three Years of a Programme in Lusaka
by Beatrice Amadi, Mercy Imikendu, Milika Sakala, Rosemary Banda, Paul Kelly
BackgroundWhile HIV has had a major impact on health care in southern Africa, there are few data on its impact on acute malnutrition in children in the community. We report an analysis of outcomes in a large programme of community management of acute malnutrition in the south of Lusaka.
Programme Activities and AnalysisOver 3 years, 68,707 assessments for undernutrition were conducted house-to-house, and children with severe acute malnutrition (SAM) or moderate acute malnutrition (MAM) were enrolled into either Outpatient Therapeutic Programme (OTP) or Supplementary Feeding Programme (SFP) respectively. Case records were analysed using tabulation and unconditional logistic regression.
Findings1,859 children (889 boys, 970 girls; median age 16 months) with MAM (n = 664) or SAM (n = 1,195) were identified. Of 1,796 children whose parents consented to testing, 185 (10.3%) were HIV positive. Altogether 1,163 (62.6%) were discharged as recovered from acute malnutrition. Case fatality while in the programme was 4.2% in children with SAM and 0.5% in those with MAM (RR of SAM 10.9; 95%CI 3.4,34.8; PPPP = 0.04) all increased mortality. Children with HIV infection who were able to initiate antiretroviral therapy had lower mortality (RR 0.23; 95%CI 0.10, 0.57; P = 0.0008).
InterpretationOur programme suggests that a comprehensive community malnutrition programme, incorporating HIV care, can achieve low mortality even in a population heavily affected by HIV.
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PI-3K Inhibitors Preferentially Target CD15+ Cancer Stem Cell Population in SHH Driven Medulloblastoma
by Alok R. Singh, Shweta Joshi, Muamera Zulcic, Michael Alcaraz, Joseph R. Garlich, Guillermo A. Morales, Yoon J. Cho, Lei Bao, Michael L. Levy, Robert Newbury, Denise Malicki, Karen Messer, John Crawford, Donald L. Durden
Sonic hedgehog (SHH) medulloblastoma (MB) subtype is driven by a proliferative CD15+ tumor propagating cell (TPC), also considered in the literature as a putative cancer stem cell (CSC). Despite considerable research, much of the biology of this TPC remains unknown. We report evidence that phosphatase and tensin homolog (PTEN) and phosphoinositide 3-kinase (PI-3K) play a crucial role in the propagation, survival and potential response to therapy in this CD15+ CSC/TPC-driven malignant disease. Using the ND2-SmoA1 transgenic mouse model for MB, mouse genetics and patient-derived xenografts (PDXs), we demonstrate that the CD15+TPCs are 1) obligately required for SmoA1Tg-driven tumorigenicity 2) regulated by PTEN and PI-3K signaling 3) selectively sensitive to the cytotoxic effects of pan PI-3K inhibitors in vitro and in vivo but resistant to chemotherapy 4) in the SmoA1Tg mouse model are genomically similar to the SHH human MB subgroup. The results provide the first evidence that PTEN plays a role in MB TPC signaling and biology and that PI-3K inhibitors target and suppress the survival and proliferation of cells within the mouse and human CD15+ cancer stem cell compartment. In contrast, CD15+ TPCs are resistant to cisplatinum, temozolomide and the SHH inhibitor, NVP-LDE-225, agents currently used in treatment of medulloblastoma. These studies validate the therapeutic efficacy of pan PI-3K inhibitors in the treatment of CD15+ TPC dependent medulloblastoma and suggest a sequential combination of PI-3K inhibitors and chemotherapy will have augmented efficacy in the treatment of this disease.from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1M0Xhw1
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Sneaker Alert! - The Swazi Observer
The Swazi Observer |
Sneaker Alert!
The Swazi Observer Rudolf passed on in 1974 of lung cancer, and his son ran the company. In 1989, Armin and ... It was the first shoe to have an internal inflation mechanism that regulated a unique fitting cushion in the lower and upper tongue to provide locking around ... and more » |
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