title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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[Gaucher disease--guidelines for diagnosis and management of adult patients]. | Gaucher disease is an autosomal recessive disorder, characterized by decreased levels of the lysosomal enzyme glucocerebrosidase. This deficiency results in a decreased breakdown of this glycosphingolipid glucocerebroside, which accumulates in the lysosomes of the monocyte-macrophage system. It is the most common form of sphingolipidosis. Clinically, the principle signs of Gaucher's disease are hepatosplenomegaly, bone involvement, hematological changes and CNS involvement. The diagnosis of Gaucher disease has to be confirmed by the measurement of the activity of the enzyme glucocerebrosidase in leukocytes or fibroblasts and genetic testing. An effective therapy for Gaucher disease has now been available for more than 10 years. It consists of life-long intravenous replacement of the deficient enzyme--glucocerebrosidase. If enzyme replacement therapy is started early enough, it leads to significant improvement in patient's general condition and quality of life. The aim of this document is to provide to the Croatian medical audience the guidelines for diagnosis and management of adult patients with Gaucher disease. These guidelines are produced by specialists who have long lasting experience with patients with rare metabolic diseases working in the Division of Metabolic Diseases, Department of Internal Medicine, University Hospital Center Zagreb which is the Referral Center for Rare and Metabolic diseases of the Ministry of Health, Republic of Croatia. They were endorsed by the Croatian Society for Rare Diseases, Croatian Medical Association. These are the first guidelines published in Croatia on diagnosis, treatment and follow-up of Gaucher disease. | 25,154,180 | [
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[The Polish Task Force position statement on safety of biologic treatment with monoclonal antibodies and soluble receptors]. | The introduction of biologic therapies for treatment in many fields of medicine such as rheumatology oncology, dermatology, hematology and allergology, became one of the most important achievements of the modem medicine. The first biological therapeutics have already reached patent expiration date and corresponding biosimilars were approved by EMA (European Medicine Agency) and FDA (Food and Drug Administration). Many more biosimilar products are currently under review for marketing authorization around the world. The approval of products similar, but not identical to already known innovative biologics, due to complexity of structure and manufacturing technology, stirs a lot of discussions regarding safety concerns related to differences in posttranslational processing and in immunogenicity between reference and biosimilar products, and relevance of these differences to the clinical practice. Critical issues involve extrapolation to different clinical indication, automatic substitution and switching. Despite EMA recommendation and advocacy for biosimilars, it is beyond this regulatory authority to establish definitive regulation for each EU member, which it is expected to be country related. The aim of the study was an attempt to define the stance regarding particular aspects of biological treatment conducted in Poland is undertaken. The Task Force of 13 experts involved in various aspects of biologic therapies in Poland was established. A modified Delphi voting was performed to achieve consensus regarding the most important aspects of biologic treatment in Poland, with particular concern of biosimilars. Ten final statements were discussed and voted upon. The statements cover general aspects of biosimilars including expected cost-benefit ratios, extrapolation of clinical indications, interchange switching, patient information and requirement of patient consent. The state of post marketing pharmacovigilance of biologics (innovative ones as well as biosimilars) was also discussed. The Task Force agreed that introduction of biosimilars is an important achievement in the biological therapies, with potential for reduction of treatment cost and increased treatment availability. Experts also agree that the safety of biological treatment should be monitored more carefully in Poland. Other discussed issues sparked more questions. There is no consensus among experts as to the automatic interchangeability of biosimilar and their innovative biopharmaceuticals. However, the switching might be acceptable in clinical practice on the case by case basis. There is an unmet need in Poland to create registry collecting data sufficient for assessment of safety and efficacy of both biosimilars and reference products in accordance with the experience and principles introduced in the European countries. | 25,154,192 | [
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[Fecal lactoferrin in identifying and management of inflammatory bowel disease]. | Inflammatory bowel disease is a group of chronic inflammatory conditions of gastrointestinal tract, including ulcerative colitis and Crohn's disease. Diagnosis of inflammatory bowel disease is based on clinical symptoms, lower and/or upper gastrointestinal tract endoscopy with biopsies and histological results. These procedures are invasive for patients and highly expensive. Thus, efforts are underway to establish new noninvasive tests appropriate to diagnosis and management of inflammatory bowel disease. Commonly used, blood markers of inflammation or scales of inflammatory bowel disease activity has been demonstrated to be insufficient. Recently, there has been increasing interest in identifying biomarkers, i.e. calprotectin, lactoferrin, mieloperoxidasis or S100A12 protein in faeces. These proteins are produced by neutrophil granulocytes and clearly reflect inflammation directly in bowel. It should be highlighted that these tests are noninvasive and may be perform repetitiously. | 25,154,203 | [
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[Socio-demographic differences in the prevalence of cardiovascular diseases among women and men in Poland--results from the Courage in Europe Project]. | The aim of the study was to assess differences in cardiovascular diseases (CVD) (hypertension, coronary artery disease - CAD, stroke) in women and men in relation to demographic and social characteristics in adult population in Poland. Study was performed in the representative group of 4071 individuals (18+) in Poland. Face to face interviews were done using structured questionnaire. Chi-squared test and decision tree analysis have been used to assess the presence of difference between groups and to determine characteristics typical for the ill. Age was a factor significantly associated with the diversity of CVD prevalence in women and men. Similar role played the level of education and marital status. Low income was additional significant determinant of the CVD for both women and men. Analysis based on decision trees additionally confirmed the differences in characteristics of ill persons in younger age groups. Our results indicate that especially in younger age groups it may be more than expected number of women suffering from early stage ischemic heart disease. Due to atypical or less severe symptoms some cases remain probably undiagnosed on the level of health care system. Our finding is supported by the consistency between the frequency of physician diagnosed CAD and WHO algorithm in 60-79 age category. | 25,154,206 | [
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[Difficulties in diagnostics in rhythm disturbances in women]. | Available data suggest that there is a disconnect in the way physicians diagnose and treat heart disease in women versus men. Such situation leads to higher cardiovascular risk in women. On the one hand there are no rhythm disturbances exclusively characteristic for females, but on other hand there are important gender-specific pathophysiologic differences in cardiac arrhythmias. Like in many other cardiac diseases in women establishing a proper diagnosis becomes a challenge. A longer time to diagnosis, later referral for invasive procedures has been noted for women probably because they are older and have more comorbidities than men. They wait longer time for ablation despite severe symptoms. To the time of the procedure they use more antyarrhythmic drugs than men. Clinicians should take gender into account as an important factor in diagnostics of arrhythmias. More studies focused on underlying mechanisms of gender differences in arrhythmias are needed to help facilitate diagnosis and to refer women for proper diagnostics and treatment on time. | 25,154,211 | [
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[Maternal arrhythmias during pregnancy. Practical review]. | Pregnancy is accompanied by a variety of cardiovascular changes in normal women, and these changes can increased incidence of maternal cardiac arrhythmias. Supraventricular and ventricular arrhythmias reguiring treatment are rarely seen during pregnancy in healthy women. Structural cardiac defects or residual defects after repair may contribute to the occurrence of clinically relevant arrhythmias. Arrhythmias during pregnancy include a wide spectrum. The most common are simple ventricular and atrial ectopy, sinusal tachycardia and supraventricular tachycardia. The foetus may suffer both haemodynamic alternations and adverse effects of the treatment (teratogenic risk, foetal growth and development). The management of arrhythmias in pregnant women is similar to that taken in patients who are not pregnant. | 25,154,218 | [
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[Current surgical management of cancer of the ampulla of Vater]. | Pancreatoduodenectomy (PD) is the standard radical treatment for cancer of the ampulla of Vater. Among patients we have treated in whom lymph node metastasis of cancer of the ampulla of Vater occurred, more positive lymph nodes surrounding the superior mesenteric artery were seen in one (patient No. 14), whereas more positive lymph nodes surrounding the anterior and posterior pancreas head were seen in another (No. 13). Six patients with lymph node metastasis achieved long-term survival after PD with lymph node dissection. This appears to be an adequate surgical treatment for cancer of the ampulla of Vater. From the viewpoint of radical treatment, local resection (LR) of the ampulla of Vater cannot be selected as a less-invasive procedure. However, LR of the ampulla of Vater can be performed in very elderly patients and patients in poor general condition for whom PD is considered excessively invasive due to small tumor size. | 25,154,238 | [
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[Concept of perihilar cholangiocarcinoma in the General Rules for Clinical and Pathological Studies on Cancer of the Biliary Tract, 6th edition]. | Hilar cholangiocarcinoma is clinically characterized by biliary obstruction in the porta hepatis. Because the boundary between the intrahepatic and extrahepatic bile duct is unclear, hilar cholangiocarcinoma can potentially arise from both ducts. Therefore, the definition of hilar cholangiocarcinoma remains under debate. In November 2013, the 6th edition of the General Rules for Clinical and Pathological Studies on Cancer of the Biliary Tract was released, following the American Joint Committee on Cancer (AJCC) or International Union Against Cancer (UICC) TNM system. In that edition, as an alternative to "hilar cholangiocarcinoma," the new term "perihilar cholangiocarcinoma" is defined as cholangiocarcinoma involving the perihilar bile duct, despite the presence or absence of a significant liver mass component. This definition clearly indicates that some intrahepatic as well as extrahepatic perihilar tumors are involved in the perihilar tumor category. From the clinical point of view, there is no need for a differential diagnosis between intrahepatic or extrahepatic tumors therefore, the new definition is readily applicable in multidisciplinary team management. Japanese clinicians were previously required to distinguish between the proper use of the AJCC/UICC and the Japanese staging systems, but now the current revision will allow the more convenient use of a single, globally standardized staging system in daily practice. | 25,154,239 | [
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Protective effect of pomegranate seed oil against mercuric chloride-induced nephrotoxicity in rat. | Heavy metals such as mercury can induce the generation of free radicals and oxidative stress which are associated with tissue injury. The present study was designed to evaluate the protective effect of pomegranate seed oil against HgCl2-induced nephrotoxicity. Twenty-four W/A adult rats were randomly divided into four groups. Group I received corn oil (1 mL/kg). Group II received HgCl2 (5 mg/kg) for 3 days. Group III and IV received PSO 0.4 mL/kg and 0.8 mL/kg, respectively one hour before HgCl2 administration for 3 days. Blood samples were taken by cardiac puncture and used for the measurement of urea and creatinine concentration. Twenty-hour-hour urine samples were collected to measure protein and glucose. The right kidney was fixed in formalin for histological examination and the left kidney was homogenized for measuring malondialdehyde (MDA) and total sulfhydryl groups. Significant elevation of serum creatinine and urea levels as well as urine glucose and protein concentrations, a significant decrease in total thiol content and a significant increase in MDA levels in kidney homogenate samples were observed after administration of HgCl2 as compared with control group. PSO pretreatment resulted in a significant decrease in serum creatinine and urea levels as well as urine glucose and protein concentrations when compared with HgCl2 treated (group II). PSO also significantly reversed the HgCl2-induced depletion in thiol content and elevation in MDA content. Histological studies revealed milder kidney lesions in PSO treated groups (groups III and IV) compared to HgCl2 treated group. Our results suggest that PSO has a protective effect against HgCl2-induced nephrotoxicity in rats. | 25,154,291 | [
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Effects of two field continuous incremental tests on cardiorespiratory responses in Standardbred trotters. | In humans, cardiorespiratory responses are widely evaluated from field incremental exercise tests. On the contrary, equine exercise physiology faces a huge lack of oxygen consumption measurements (VO2) in field conditions due to technical concerns. The aim of this study was to test the effects of two incremental continuous field tests on cardiorespiratory responses in Standardbred trotters. The two protocols were realized at trot and ended when horses galloped. The tests started at 4.2 m/s (T1) and 6.4 m/s (T2), with speed increments of 1.4 m/s every 3 min for T1 and 0.8 m/s every 2 min for T2. Velocity (v), heart rate (HR) and gas exchanges were recorded continuously, and blood lactate concentration [La(-)] was measured before and after tests. Values recorded at the end of the tests were considered as peak values. The vpeak values were 10.6 ± 0.3 and 10.7 ± 0.7 m/s for T1 and T2 respectively. Horses reached higher VO2peak (T1: 116.6 ± 11.5 ml/min/kg; T2: 88.9 ± 10.2 ml/min/kg; p < 0.05) and HRpeak (T1: 217 ± 5 bpm; T2: 209 ± 3 bpm; p < 0.05) during T1 compared with T2. T1 was significantly longer than T2 (17.5 ± 1.9 vs. 12.9 ± 1.6 min respectively, p < 0.01), and the number of steps entirely ran tended to be different (T1: 5.6 ± 0.6; T2: 6.2 ± 0.8, p = 0.07). Compared to T2, the design of T1 appeared easier to implement and allowed higher cardiorespiratory responses. The relationship between HR-VO2 obtained through T1 gave a better correlation between the two variables than T2. These findings suggest that T1 might be better than T2 for evaluating cardiorespiratory adaptations to exercise and for estimating aerobic energy expenditure in exercising trotters. | 25,154,293 | [
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Estimating survival of patients receiving radiosurgery alone for cerebral metastasis from melanoma. | This study aimed to identify clinical factors associated with survival and to develop a prognostic tool in patients receiving radiosurgery alone for very few cerebral metastases from melanoma. Ten characteristics of 69 patients treated with radiosurgery alone for 1-3 cerebral metastases from melanoma were retrospectively analyzed for survival. Serum lactate dehydrogenase levels before radiosurgery, Karnofsky performance score, maximum diameter of all irradiated cerebral lesions, and extracranial lesions were significantly associated with survival and included in the tool. Twelve-month survival rate (in %) divided by 10 was calculated for each of these four factors. The four scores were summed resulting in total scores ranging 9-22 points. Based on the 12-month survival rates, three groups were formed: less than 15 points (group I, n = 25); 15-20 points (group II, n = 34); and more than 20 points (group III, n = 10). Corresponding 12-month survival rates were 10 ± 6%, 51 ± 9% and 90 ± 9%, respectively (P < 0.001). In group I, death within 12 months following radiosurgery occurred mostly due to extracranial progression, whereas cerebral progression was the major cause of death in group II. In group III, only one of 10 patients died within 1 year. This new prognostic tool helps predict the survival time following radiosurgery of very few cerebral metastases from melanoma. An individual treatment approach should consider a patient's survival time and the most likely cause of death (cerebral or extracranial progression). | 25,154,301 | [
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Feasibility of 8-OHdG formation and hOGG1 induction in PBMCs for assessing oxidative DNA damage in the lung of COPD patients. | Oxidative stress has long been recognized to play a role in chronic obstructive pulmonary disease (COPD); however, approaches for assessing oxidative stress are lacking. The objective of this study was to address the feasibility of measuring 8-oxo-7, 8-dihydro-2'-deoxyguanosine (8-OHdG) formation and human 8-oxoguanine DNA glycosylase (hOGG1) induction in peripheral blood mononuclear cell (PBMC) to assess oxidative deoxyribonucleic acid (DNA) damage in the lung of smoking COPD patients. PBMC were obtained from 412 participants including 129 smokers with COPD, 143 healthy smokers and 140 healthy non-smokers. Lung tissue specimens and PBMC were obtained from smoker COPD (n = 12), healthy smokers (n = 12) and healthy non-smokers (n = 10). 8-OHdG and hOGG1 were detected, and correlation analysis was conducted for assessing the feasibility. Oxidative DNA damage (8-OHdG formation) along with impaired induction of hOGG1 expression in the lung was a prominent feature for smokers COPD patients. PBMC originated from smokers COPD patients also displayed similar features to that of lung tissues. Correlation analysis suggests that PBMC could be used as a surrogate for oxidative DNA damage in lung of smokers COPD patients. Indeed, 8-OHdG levels in PBMC DNA were negatively correlated with lung function, while hOGG1 induction in PBMC was associated with improved lung function in smokers COPD patients. COPD patients manifest oxidative DNA damage of 8-OHdG along with impaired hOGG1 expression in the lung, whereas 8-OHdG formation and hOGG1 induction in PBMC could be a biomarker of oxidative DNA damage in the lung. | 25,154,311 | [
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Etiology and outcomes for patients infected with HIV in intensive care units in a tertiary care hospital in China. | Although the National Free Antiretroviral Treatment Program (NFATP) has resulted in a significant reduction in the incidence of AIDS-defining illnesses in China, severe complications in patients infected with HIV may require aggressive treatment and critical care support. The objective for this study was to investigate the etiology and outcomes of patients infected with HIV admitted to intensive care units in Ditan Hospital, China. The evaluation of the etiology and outcomes of patients infected with HIV admitted to intensive care units was conducted using the clinical data from 122 patients infected with HIV (129 occasions) admitted to the Beijing Ditan hospital from January 1, 2009, to October 1, 2013. Over the five-year study period, 129 occasions occurred for 122 patients infected with HIV admitted to intensive care units. Respiratory failure was the most common condition (53.4%) among the 129 occasions analyzed. This was followed by pneumothorax (12.4%), infectious shock (8.5%), neurological problems (8.5%), renal failure (7.8%), post-operative complications and trauma (5.4%), coronary heart disease (3.1%), adverse effects of HAART (3.1%), lymphoma (2.4%), and liver failure (0.8%). Mortality in intensive care units was 64.5% while in-hospital mortality was 65.9%. The strongest protective predictor for in-hospital mortality was earlier admission to an intensive care unit (OR = 0.050, CI = 0.020-0.126, P < 0.001). Respiratory failure was the most common condition in patients infected with HIV admitted to intensive care units, and the outcome for the patients was poor. Mortality was negatively associated with earlier admission to an intensive care unit, but was not associated with HAART. | 25,154,318 | [
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Charge-induced phase separation in lipid membranes. | Phase separation in lipid bilayers that include negatively charged lipids is examined experimentally. We observed phase-separated structures and determined the membrane miscibility temperatures in several binary and ternary lipid mixtures of unsaturated neutral lipid, dioleoylphosphatidylcholine (DOPC), saturated neutral lipid, dipalmitoylphosphatidylcholine (DPPC), unsaturated charged lipid, dioleoylphosphatidylglycerol (DOPG((-))), saturated charged lipid, dipalmitoylphosphatidylglycerol (DPPG((-))), and cholesterol. In binary mixtures of saturated and unsaturated charged lipids, the combination of the charged head with the saturation of the hydrocarbon tail is a dominant factor in the stability of membrane phase separation. DPPG((-)) enhances phase separation, while DOPG((-)) suppresses it. Furthermore, the addition of DPPG((-)) to a binary mixture of DPPC/cholesterol induces phase separation between DPPG((-))-rich and cholesterol-rich phases. This indicates that cholesterol localization depends strongly on the electric charge on the hydrophilic head group rather than on the ordering of the hydrocarbon tails. Finally, when DPPG((-)) was added to a neutral ternary system of DOPC/DPPC/cholesterol (a conventional model of membrane rafts), a three-phase coexistence was produced. We conclude by discussing some qualitative features of the phase behaviour in charged membranes using a free energy approach. | 25,154,325 | [
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Relationships of intraosseous and systemic pressure waveforms in a Swine model. | Despite some focus on the use of intraosseous (IO) catheters to obtain laboratory samples, very little is known about the potential for obtaining other forms of clinical data. Largely unstudied is the relationship between IO pressures (IOPs) and systemic hemodynamic pressures such as mean arterial pressure (MAP) and central venous pressures (CVP). The objective was to explore the relationship between hemodynamic parameters (blood pressures) measured through an IO catheter and intravascular catheters placed in the arterial and central venous circulation. Eight pigs (Sus scrofa) weighing 30 to 45 kg were sedated with a short-acting agent, intubated with a cuffed endotracheal tube, and anesthetized with 2% to 3% isoflurane. Intravascular catheters were placed into the femoral or carotid artery and the femoral or jugular vein for MAP and CVP measurements. IO catheters, 15 mm for the sternum and 25 mm for the long bones, were placed percutaneously into the proximal tibia, proximal femur, proximal humerus, right proximal ulna, and/or sternum. Pressures were recorded during normotension, hypotension, and hypertension. Averaged across all eight animals, the means (ranges) for baseline systemic pressures were as follows: MAP = 66.5 (55.6 to 76.7) mm Hg, tibia IOP = 17.4 (9.3 to 34.5) mm Hg, femur IOP =18.4 (3.3 to 33.1) mm Hg, humerus IOP = 15.7 (2.8 to 28.9) mm Hg, ulna IOP = 16.0 (7.9 to 25.6) mm Hg, sternum IOP = 5.7 (-0.5 to 47.9) mm Hg, and CVP = 2.7 mm Hg (-3.3 to 7.9) mm Hg. The best median correlation occurred between femur IOP and mean MAP (r = 0.65). The four highest correlations between IOP and MAP were associated with mean femur IOP. Only one IO site had a correlation coefficient over 0.50 for CVP. The long bones tended to correlate better with the MAP and the sternum tended to correlate better with the CVP. Nonlinearity was observed in the actively rising pressure phases, which can be explained by a hysteresis model. The relationship between IOP and MAP or CVP is variable by site, with the MAP and CVP tending to be estimated by the femur and sternum, respectively. The relationship to actively rising pressures is nonlinear and a hysteresis model is proposed to explain the phase change. Further experimentation is needed to refine the IOP relationship to the MAP and CVP and assess the potential of these measurements to provide clinically relevant information. | 25,154,326 | [
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Clinical experience of anti-Xa monitoring in critically ill dogs receiving dalteparin. | To describe a population of critically ill dogs receiving dalteparin monitored with an anti-Xa assay, to assess the potential utility of serial monitoring, and to investigate the association between pre-treatment thromboelastography (TEG) and the ability to achieve targeted anti-Xa activity. Descriptive retrospective study. Veterinary teaching hospital. Thirty-eight client-owned dogs receiving dalteparin and monitored with an anti-Xa assay. None. Medical records were retrospectively reviewed for signalment, underlying disease, clinicopathological data, occurrence of thromboembolic events, complications, and outcome. Thirty-eight dogs receiving dalteparin were monitored with an anti-Xa assay. Diseases included hematological disease, protein-losing disease, neoplastic disease, and septic processes. Pretreatment hypercoagulability was present in 34/35 dogs by assessment of TEG. Five cases of thromboembolism were confirmed prior to starting treatment and 4 cases occurred during hospitalization. Bleeding complications were rare (3/38) and 29/38 dogs survived to discharge. Interpretation of the anti-Xa assay allowed for dose adjustment although reliable achievement of target anti-Xa activity was not demonstrated. Dogs with higher G values on pretreatment TEG were significantly less likely to achieve the target anti-Xa activity (ie, be above or below the target range). Dalteparin was well tolerated in a heterogeneous population of dogs. However, dose adjustment in response to anti-Xa activity interpretation inconsistently resulted in subsequent attainment of the target anti-Xa range. Development of guidelines may be warranted to more consistently achieve the target range. Dogs that appear more hypercoagulable on pre-treatment TEG may require closer monitoring and greater dose adjustment to achieve the target anti-Xa range. | 25,154,357 | [
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Role of allogeneic stem cell transplantation in mantle cell lymphoma. | Despite a wide spectrum of treatment options, mantle cell lymphoma (MCL) remains a challenging hematologic malignancy to manage. Advances in front-line therapy, including the monoclonal antibody rituximab and increasing use of cytarabine, have improved remission rates. Autologous hematopoietic cell transplantation (HCT) can effectively consolidate remission of MCL, leading to encouraging survival beyond 5 yr. However, nearly all patients with MCL will relapse and require salvage therapy. Novel agents such as ibrutinib, bortezomib, and lenalidomide have dramatically expanded the options for treating relapsed MCL. In this review, we summarize the clinical evidence supporting the use of allogeneic donor HCT in MCL and make recommendations on indications for its use. Data suggest that allogeneic donor HCT is the only curative therapy for patients with poor prognosis or aggressive MCL. Patient selection, timing, and optimal use remain a matter of scientific debate and given the rapidly changing therapeutic landscape of MCL, the outcomes of allogeneic HCT should be interpreted in the context of novel therapeutics. | 25,154,430 | [
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A comparison of assessments and relationships of stress of conscience, perceptions of conscience, burnout and social support between healthcare personnel working at two different organizations for care of older people. | The aim of this cross-sectional, descriptive study was to compare assessments and relationships of stress of conscience, perceptions of conscience, burnout and social support between healthcare personnel (HCP) working in two different organisations for care of older people. This cross-sectional, descriptive comparative study was performed among Registered Nurses and nurse assistants working in two different organisations (n(1) = 98, n(2) = 488) for residential care of older people. The organisations were chosen to be as different as possible, and data were collected using four different questionnaires. Hierarchical cluster analysis with multiscale bootstrap resampling was used to compare the associations between all items in the questionnaires. Descriptive statistics, 95% confidence intervals, chi-squared tests, Cohen's d, Cramer's V and the φ coefficient were all used to judge differences between the organisations. The associations between stress of conscience, perceiving one's conscience as a burden, and burnout were similar in both organisations. Perceiving one's conscience as far too strict and having a troubled conscience from being unable to live up to one's standards were associated with stress of conscience and burnout in one organisation. Women had higher levels of stress of conscience and reported lower social support from co-workers compared with men. This study shows that associations between perceptions of conscience, stress of conscience and burnout are common experiences that are similar among HCP despite great differences in the characteristics of organisations. It can be burdensome for HCP to be unable to realise their ambitions to provide good care, and sex/gender can be an important factor to consider in the development of measures against the negative effects of stress of conscience. More studies are needed about how HCP's ambition to provide good care and sex/gender are related to perceptions of conscience, stress of conscience and burnout. | 25,154,457 | [
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Effective charge separation in the rutile TiO2 nanorod-coupled α-Fe2O3 with exceptionally high visible activities. | Herein, we have fabricated rutile TiO2 nanorod-coupled α-Fe2O3 by a wet-chemical process. It is demonstrated that the visible activities for photoelectrochemical water oxidation and for degrading pollutant of α-Fe2O3 are greatly enhanced after coupling a proper amount of rutile nanorods. The enhanced activity is attributed to the prolonged lifetime and improved separation of photogenerated charges mainly by the transient surface photovoltage responses. Interestingly, the observed EPR signals (with g⊥ = 1.963 and g|| = 1.948) of Ti(3+) in the fabricated TiO2-Fe2O3 nanocomposite at ultra low temperature (1.8 k) after visible laser excitation, along with the electrochemical impedance spectra and the normalized photocurrent action spectra, testify evidently that the spacial transfers of visible-excited high-energy electrons of α-Fe2O3 to TiO2 could happen. Moreover, it is confirmed that it is more favorable for the uncommon electron transfers of α-Fe2O3 to rutile than to anatase. This is responsible for the much obvious enhancement of visible activity of Fe2O3 after coupling with rutile TiO2, compared with anatase and phase-mixed P25 ones. This work would help us to deeply understand the uncommon photophysical processes, and also provide a feasible route to improve the photocatalytic performance of visible-response semiconductor photocatalyst for water splitting and pollutant degradation. | 25,154,460 | [
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Lysosomal pH rise during heat shock monitored by a lysosome-targeting near-infrared ratiometric fluorescent probe. | Heat stroke is a life-threatening condition, featuring a high body temperature and malfunction of many organ systems. The relationship between heat shock and lysosomes is poorly understood, mainly because of the lack of a suitable research approach. Herein, by incorporating morpholine into a stable hemicyanine skeleton, we develop a new lysosome-targeting near-infrared ratiometric pH probe. In combination with fluorescence imaging, we show for the first time that the lysosomal pH value increases but never decreases during heat shock, which might result from lysosomal membrane permeabilization. We also demonstrate that this lysosomal pH rise is irreversible in living cells. Moreover, the probe is easy to synthesize, and shows superior overall analytical performance as compared to the existing commercial ones. This enhanced performance may enable it to be widely used in more lysosomal models of living cells and in further revealing the mechanisms underlying heat-related pathology. | 25,154,475 | [
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Complex-shaped microbial biominerals for nanotechnology. | Single-celled microorganisms such as diatoms and coccolithophores produce inorganic microparticles with genetically controlled hierarchical nanopatterns. Besides serving as paradigms to inspire new routes for materials synthesis, biominerals themselves, particularly diatom biosilica, are increasingly utilized as templates for the synthesis of novel functional materials. Over the past decade, a large variety of methods have been established that allow not only for the attachment or coating of desired materials onto diatom biosilica but also for complete chemical conversion without altering the characteristic micro- and nanoscale morphology. Examples include the synthesis of materials for photonics (surface-enhanced Raman spectroscopy, SERS, extraordinary optical transmission, EOT), ultraresponsive and sensitive gas sensors, gas storage materials, and highly active catalysts. More recently, emerging insight into the cellular mechanisms of biosilica formation has enabled the in vivo functionalization of diatom biosilica through advanced cultivation techniques and genetic engineering. As a naturally renewable material, biominerals hold the promise of serving as an inexpensive and easily available resource for a future nanotechnology-based industry. | 25,154,474 | [
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Use of the 2-μm continuous wave thulium laser for the resection of oral squamous cell carcinomas does not impair pathological assessment. | Current resection modalities for oral squamous cell carcinomas (OSCC) vary from cold steel over CO2 laser to monopolar electro-surgery (MO). We compared thulium laser (TL) as a new modality with MO with regards to pathological assessment. Forty-two patients who were treated for OSCC by either TL or MO were included. All resected specimens were assessed with special attention to margin interpretation and thermal damage. Depth of thermal damage ranged from 1.0 to 3.5 mm in the TL group compared to 1.0-4.0 mm in the MO group without interfering with the pathological assessment. The percentage of positive margin resections was three times higher in the MO group compared with the TL group. This study shows resections done by TL do not impair pathological assessment when compared to MO resections. | 25,154,492 | [
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Experimental evidence needed to demonstrate inter- and trans-generational effects of ancestral experiences in mammals. | Environmental factors routinely influence an organism's biology. The inheritance or transmission of such influences to descendant generations would be an efficient mode of information transfer across generations. The developmental stage at which a specific environment is encountered by the ancestral generation, and the number of generations over which information about that environment is registered, determines an inter- vs. trans-generational effect of ancestral influence. This commentary will outline the distinction between these influences. While seductive in principle, inter- and trans-generational inheritance in mammals is a hotly debated area of research inquiry. We present constructive criticism of such inheritance, and suggest potential experimental avenues for reconciliation. Finally, epigenetic mechanisms present an avenue for gene regulation that is dynamic. We briefly discuss how such malleability affords the potential for a reversal of any detrimental environmental influences that might have adversely impacted ancestral or descendant generations. | 25,154,497 | [
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New targets for antibody therapy of pediatric B cell lymphomas. | Antibody therapy has become standard of care for adult B cell lymphoma patients. It is a potentially less toxic and more targeted approach for lymphoma therapy and should therefore be applied to treat pediatric B cell lymphoma patients as well. In pediatric lymphoma patients, however, clinical experience with monoclonal antibodies is very limited. This is in part due to smaller patient numbers and very good outcome with conventional chemotherapy. In addition, pediatric patient and lymphoma biology differ significantly from that found in adults often precluding extrapolation of the adult experience to children. This review focuses on targeting pediatric B cell lymphoma with monoclonal antibody therapy. The special characteristics of B cell lymphomas found in children are reviewed and six potential new lymphoma target antigens are discussed. | 25,154,500 | [
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Multilevel analyses of school and children's characteristics associated with physical activity. | Children spend most of their awake time at school, and it is important to identify individual and school-level correlates of their physical activity (PA) levels. This study aimed to identify the between-school variability in Portuguese children PA and to investigate student and school PA correlates using multilevel modeling. The sample included 1075 Portuguese children of both sexes, aged 6-10 years, from 24 schools. Height and weight were measured and body mass index (BMI) was estimated. Physical activity was estimated using the Godin and Shephard questionnaire (total PA score was used); cardiorespiratory fitness was estimated with the 1-mile run/walk test. A structured inventory was used to access information about the school environment. A multilevel analysis (level-1: student-level; level-2: school-level) was used. Student-level variables (age, sex, 1-mile run/walk test) explained 7% of the 64% variance fraction of the individual-level PA; however, school context explained approximately 36% of the total PA variance. Variables included in the model (school size, school setting, playground area, frequency and duration of physical education class, and qualification of physical education teacher) are responsible for 80% of the context variance. School environment is an important correlate of PA among children, enhancing children's opportunities for being active and healthy. | 25,154,531 | [
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Risk and protective factors for depression that adolescents can modify: a systematic review and meta-analysis of longitudinal studies. | Adolescence is a peak time for the onset of depression, but little is known about what adolescents can do to reduce their own level of risk. To fill this gap, a review was carried out to identify risk and protective factors for depression during adolescence that are modifiable by the young person. Employing the PRISMA method, we conducted a systematic review and meta-analysis of longitudinal studies to identify risk and protective factors during the adolescent period (aged 12-18 years) that are potentially modifiable by the young person without professional intervention or assistance. Stouffer׳s method of combining p values was used to determine whether associations between variables were reliable, and meta-analyses were conducted to estimate the mean effect sizes of associations. We identified 113 publications which met the inclusion criteria. Putative risk factors implicated in the development of depression for which there is a sound evidence base, and which are potentially modifiable during adolescence without professional intervention, are: substance use (alcohol, tobacco, cannabis, other illicit drugs, and polydrug use); dieting; negative coping strategies; and weight. Modifiable protective factors with a sound evidence base are healthy diet and sleep. Limitations include not systematically reviewing moderators and mediators, the lack of generalisability across cultures or to younger children or young adults, and the inability to conduct a meta-analysis on all included studies. Findings from this review suggest that future health education campaigns or self-help prevention interventions targeting adolescent depression should aim to reduce substance use (alcohol, tobacco, cannabis, other illicit drugs, and polydrug use); dieting; and negative coping strategies; and promote healthy weight; diet; and sleep patterns. | 25,154,536 | [
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Comparison of methods used for assessing the viability and vitality of yeast cells. | Determination of cell viability is the most commonly used method for assessing the impact of various types of stressors in toxicity research and in industrial microbiology studies. Viability is defined as a percentage of live cells in a whole population. Although cell death is one of the consequences of toxicity, chemical or physical factors may exert their toxic effects through a number of cellular alterations that may compromise cell ability to divide without necessarily leading to cell death. This aspect represents the term 'cell vitality' defined as physiological capabilities of cells. It is important to note that cell viability and cell vitality represent two different aspects of cell functions, and both are required for the estimation of the physiological state of a cell after exposure to various types of stressors and chemical or physical factors. In this paper, we introduced a classification of available methods for estimating both viability and vitality in Saccharomyces cerevisiae yeast cells (wild-type and Δsod1 mutant) in which the effects of selected oxidants causing oxidative stress is evaluated. We present the advantages as well as disadvantages of the selected methods and assess their usefulness in different types of research. | 25,154,541 | [
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Supportive relationships within ongoing families: cross-lagged effects between components of support and adjustment in parents and young adult children. | Italy is the first country in which the phenomenon of cohabitation of parents and young adult children was examined. From the earliest studies, it seemed clear that the transition to adulthood occurs within the family of origin: indeed, the successful outcome of this transition depends on the quality of family relationships. Using the Social Relations Model, this study examines the importance of the components of support within family relationships during the transition of young adults from university to job contexts (Kenny & La Voie, 1984). The cross-lagged influence among the components of perceived support and the adjustment of family members has also been investigated. Findings show that family components of support are significant for perception in both parents and young adults. Furthermore, cross-lagged models reveal different results for parents than for young adults. Discussion of results regarding the transition to adulthood and family theory is provided. | 25,154,544 | [
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Occupation and its relationship with health and wellbeing: the threshold concept for occupational therapy. | We introduce the educational framework of 'threshold concepts' and discuss its utility in understanding the fundamental difficulties learners have in understanding ways of thinking and practising as occupational therapists. We propose that the relationship between occupation and health is a threshold concept for occupational therapy because of students' trouble in achieving lasting conceptual change in relation to their understanding of it. The authors present and discuss key ideas drawn from educational writings on threshold concepts, review the emerging literature on threshold concepts in occupational therapy, and pose a series of questions in order to prompt consideration of the pedagogical issues requiring action by academic and fieldwork educators. Threshold concepts in occupational therapy have been considered in a primarily cross-disciplinary sense, that is, the understandings that occupational therapy learners grapple with are relevant to learners in other disciplines. In contrast, we present a more narrowly defined conception that emphasises the 'bounded-ness' of the concept to the discipline. A threshold concept that captures the essential nature of occupational therapy is likely to be (highly) troublesome in terms of a learner's acquisition of it. Rather than simplifying these learning 'jewels' educators are encouraged to sit with the discomfort that they and the learner may experience as the learner struggles to grasp them. Moreover, they should reshape their curricula to provoke such struggles if transformative learning is to be the outcome. | 25,154,548 | [
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Endovascular balloon occlusion is associated with reduced intraoperative mortality of unstable patients with ruptured abdominal aortic aneurysm but fails to improve other outcomes. | Proximal aortic control by endovascular balloon occlusion (EBO) is an alternative to conventional aortic cross-clamping (CAC) in hemodynamically unstable patients presenting with a ruptured abdominal aortic aneurysm (rAAA). The aim of this study was to evaluate the potential clinical benefit of EBO over CAC. Data from 72 patients with rAAA treated at our institution from 2001 to 2013 were retrospectively analyzed. All patients were hemodynamically unstable (mean arterial blood pressure at admission <65 mm Hg or associated unconsciousness, cardiac arrest, or emergency endotracheal intubation). Clinical end points of hemodynamic restoration, mortality rate, and major postoperative complications were assessed for CAC (group 1) and EBO (group 2). At admission, 72 patients were unstable. CAC was performed in 40 and EBO in 32. Intraoperative mortality was 43% in group 1 vs 19% in group 2 (P = .031). In group 1, the approach for CAC (thoracotomy [n = 23] vs laparotomy [n = 17]) did not influence intraoperative mortality (43% vs 41%). There was no significant difference in 30-day (75% vs 62%) and in-hospital (77% vs 69%) mortality rates between groups. After EBO, the treatment-open vs endovascular repair-did not influence the intraoperative mortality rate (31% vs 43%; P = .5). Eight surgical complications were secondary to CAC (1 vena cava injury, 3 left renal vein injuries, 1 left renal artery injury, 1 pancreaticoduodenal vein injury, and 2 splenectomies), but no EBO-related complication was noted (P = .04). Differences in colon ischemia (15% vs 28%) and renal failure (12% vs 9%) were not statistically significant. Abdominal compartment syndrome occurred in four patients in group 2 and in no patients in group 1. Compared with CAC, EBO is a feasible and valuable strategy and is associated with reduced intraoperative mortality of unstable rAAA patients, but not in-hospital mortality, in this retrospective study. | 25,154,564 | [
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Functional connectivity of hippocampal and prefrontal networks during episodic and spatial memory based on real-world environments. | Several recent studies have compared episodic and spatial memory in neuroimaging paradigms in order to understand better the contribution of the hippocampus to each of these tasks. In the present study, we build on previous findings showing common neural activation in default network areas during episodic and spatial memory tasks based on familiar, real-world environments (Hirshhorn et al. (2012) Neuropsychologia 50:3094-3106). Following previous demonstrations of the presence of functionally connected sub-networks within the default network, we performed seed-based functional connectivity analyses to determine how, depending on the task, the hippocampus and prefrontal cortex differentially couple with one another and with distinct whole-brain networks. We found evidence for a medial prefrontal-parietal network and a medial temporal lobe network, which were functionally connected to the prefrontal and hippocampal seeds, respectively, regardless of the nature of the memory task. However, these two networks were functionally connected with one another during the episodic memory task, but not during spatial memory tasks. Replicating previous reports of fractionation of the default network into stable sub-networks, this study also shows how these sub-networks may flexibly couple and uncouple with one another based on task demands. These findings support the hypothesis that episodic memory and spatial memory share a common medial temporal lobe-based neural substrate, with episodic memory recruiting additional prefrontal sub-networks. | 25,154,600 | [
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Antiretroviral therapy response among HIV-2 infected patients: a systematic review. | Few data are available on antiretroviral therapy (ART) response among HIV-2 infected patients. We conducted a systematic review on treatment outcomes among HIV-2 infected patients on ART, focusing on the immunological and virological responses in adults. Data were extracted from articles that were selected after screening of PubMed/MEDLINE up to November 2012 and abstracts of the 1996-2012 international conferences. Observational cohorts, clinical trials and program reports were eligible as long as they reported data on ART response (clinical, immunological or virological) among HIV-2 infected patients. The determinants investigated included patients' demographic characteristics, CD4 cell count at baseline and ART received. Seventeen reports (involving 976 HIV-2 only and 454 HIV1&2 dually reactive patients) were included in the final review, and the analysis presented in this report are related to HIV-2 infected patients only. There was no randomized controlled trial and only two cohorts had enrolled more than 100 HIV-2 only infected patients. The median CD4 count at ART initiation was 165 cells/mm3, [IQR; 137-201] and the median age at ART initiation was 44 years (IQR: 42-48 years). Ten studies included 103 patients treated with three nucleoside reverse transcriptase inhibitors (NRTI). Protease inhibitor (PI) based regimens were reported by 16 studies. Before 2009, the most frequent PIs used were Nelfinavir and Indinavir, whereas it was Lopinavir/ritonavir thereafter. The immunological response at month-12 was reported in six studies and the mean CD4 cell count increase was +118 cells/μL (min-max: 45-200 cells/μL). Overall, clinical and immuno-virologic outcomes in HIV-2 infected individuals treated with ART are suboptimal. There is a need of randomized controlled trials to improve the management and outcomes of people living with HIV-2 infection. | 25,154,616 | [
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Soluble urokinase-type plasminogen activator receptor levels in patients with schizophrenia. | The etiology of schizophrenia remains largely unknown but alterations in the immune system may be involved. In addition to the psychiatric symptoms, schizophrenia is also associated with up to 20 years reduction in life span. Soluble urokinase-type plasminogen activator receptor (suPAR) is a protein that can be measured in blood samples and reflects the levels of inflammatory activity. It has been associated with mortality and the development of type 2 diabetes and cardiovascular disease. suPAR levels in patients with schizophrenia were compared to healthy controls from the Danish Blood Donor Study. SuPAR levels were dichotomized at >4.0 ng/ml, which is considered the threshold for low grade inflammation. A multiple logistic regression model was used and adjusted for age, sex, and current smoking. In total we included 1009 subjects, 105 cases with schizophrenia (10.4%) and 904 controls (89.6%). The mean suPAR values were 4.01 ng/ml (SD = 1.43) for the cases vs 1.91 ng/ml (SD = 1.35) for the controls (P < .001). Multiple logistic regression with odds ratio (OR) for suPAR levels >4.0 ng/ml yielded: schizophrenia, OR: 46.15 95% CI 22.69-93.87, P < .001; age, OR: 1.02 95% CI 0.99-1.02, P = .15; male sex, OR: 0.70 95% CI 0.35-1.36, P = .29; and current smoking, OR: 3.51 95% CI 1.78-6.94, P < .001. Patients with schizophrenia had significantly higher suPAR levels than healthy controls. Further studies are warranted to clarify if elevated suPAR levels are involved in the pathophysiology of schizophrenia and/or the increased mortality found in patients with schizophrenia. | 25,154,621 | [
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Comparison of two comorbidity scoring systems for older adults with traumatic injuries. | The purpose of this study was to determine the mortality predictive value of two different comorbidity scores, Comorbidity-Polypharmacy Score (CPS) and Charlson scoring system, in a large sample of older trauma patients. At an urban tertiary care Level I trauma center, trauma patients aged 55 years and older who were initially admitted to critical care were included. This retrospective chart review was conducted at Harborview Medical Center in Seattle, WA. Older trauma patients admitted from January 1, 2010 through December 31, 2010 were screened for inclusion. One-year mortality data were obtained from the Washington State Department of Health. Covariates included age, presence of hypotension, traumatic brain injury, and Injury Severity Score. Records for 667 older trauma patients were reviewed. In multivariate analyses, CPS was an independent predictor of fatal outcomes. Higher CPS was associated with greater mortality, however, it was not superior to Charlson methodology in predicting 1-year mortality in this patient cohort. The addition of a comorbidity score improves multivariate models predicting long-term mortality in older trauma patients. There was no advantage to using CPS instead of Charlson score, and each was an independent predictor of fatal outcomes. | 25,154,672 | [
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Trends in organ donor management: 2002 to 2012. | Refinements in donor management have resulted in increased numbers and quality of grafts after neurologic death. We hypothesize that the increased use of hormone replacement therapy (HRT) has been accompanied by improved outcomes over time. Using the Organ Procurement and Transplant Network donor database, all brain-dead donors procured from July 1, 2001 to June 30, 2012 were studied. Hormone replacement therapy was identified by an infusion of thyroid hormone. An expanded criteria donor was defined as age 60 years or older. Incidence of HRT administration and number of donors and organs recovered were calculated. Using the Organ Procurement and Transplant Network thoracic recipient database transplant list, wait times were examined. There were 74,180 brain-dead donors studied. Hormone replacement therapy use increased substantially from 25.6% to 72.3% of donors. However, mean number of organs procured per donor remained static (3.51 to 3.50; p = 0.083), and the rate of high-yield donors decreased (46.4% to 43.1%; p < 0.001). Incidence of traumatic brain injury donors decreased (42.1% to 33.9%; p < 0.001) relative to an increased number of expanded criteria donors (22.1% to 26%). Despite this, there has been an increase in the raw number of donors (20,558 to 24,308; p < 0.001) and organs (5,857 to 6,945; p < 0.001). There has been an increase in organs per traumatic brain injury donor (4.02 to 4.12; p = 0.002) and a decrease in days on the waiting list (462.2 to 170.4 days; p < 0.001) for a thoracic transplant recipient. The marked increase in the use of HRT in the management of brain-dead donors has been accompanied by increased organ availability overall. Potential mechanisms might include successful conversion of previously unacceptable donors and improved recovery in certain subsets of donors. | 25,154,673 | [
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Prospective study of depression and anxiety in female fertility preservation and infertility patients. | To prospectively assess anxiety, depression, coping, and appraisal in female fertility preservation (FP) patients compared with infertile patients. Prospective pre- and post-treatment survey. Academic medical center. Forty-seven women with cancer (FP patients) and 91 age-matched infertile patients. None. Depression, anxiety, coping, infertility-related stress, appraisal of treatment, and medical outcomes. FP patients reported more symptoms of anxiety and depression than infertile patients, but infertile patients' symptoms worsened over time; 44% of FP and 14% of infertile patients' scores exceeded the clinical cutoff for depression before treatment. The interval between surveys and medical treatment data did not predict changes in mood symptoms. Coping strategies and infertility-related stress did not differ between groups, and avoidant coping predicted higher depression and anxiety scores. FP patients reported more anxiety and depression than infertile patients at enrollment in treatment, with more than one-third of FP patients reporting clinically significant depressive symptoms. However, infertile patients' anxiety and depressive symptoms increased across treatment. This increase was not related to time between registration for IVF and oocyte retrieval or the medical aspects of treatment. FP and infertile patients should be provided psychologic consultation before treatment to identify mood and anxiety symptoms and to refer patients for counseling as needed to prevent worsening of symptoms. | 25,154,674 | [
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Blastocyst euploidy and implantation rates in a young (<35 years) and old (≥35 years) presumed fertile and infertile patient population. | To examine the relationship between blastocyst euploidy and implantation rates in a presumed fertile patient population. Retrospective analysis. Private IVF clinic. IVF patients undergoing comprehensive chromosome screening (CCS). Embryo biopsy at the blastocyst stage with preimplantation genetic screening using CCS. Euploidy, chemical pregnancy, and implantation rates. There was no significant difference in the number of euploid blastocysts between presumed fertile (68/118, 57.6%) and infertile (75/132, 56.8%) patients<35 years old. Likewise, there was no significant difference in the number of euploid blastocysts between presumed fertile (42/86, 48.8%) and infertile (97/206, 47.1%) patients≥35 years old. When those same patients underwent a corresponding frozen embryo transfer cycle, presumed fertile patients demonstrated a significantly higher chemical pregnancy rate when compared with infertile patients, 28/33 (84.8%) and 50/81 (61.7%), respectively. Moreover, presumed fertile patients exhibited significantly higher implantation rates compared with infertile patients, 36/42 (85.7%) and 54/109 (66.7%), respectively. When subdivided by maternal age, no significant difference was seen in blastocyst euploidy rates between presumed fertile and infertile patients; however, chemical pregnancy and implantation rates were significantly higher in a presumed fertile patient population even when transferring only euploid blastocysts. This would indicate that infertility, as a disease, may encompass other aspects such as uterine or other unknown embryological factors that can influence outcomes. | 25,154,676 | [
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[Functional diarrhea - pathophysiology, investigation and treatment]. | The most important reason for functional diarrhea in clinical practice is diarrhea-predominant irritable bowel syndrome (IBS) which is characterized by chronic intermittent diarrhea and abdominal pain. The pathophysiology underlying IBS is complex and includes visceral hypersensitivity, abnormal gut motility and autonomous nervous system dysfunction as well as genetic and psychosocial factors. Treatment should be tailored to the individual's symptoms and involves general measures, pharmacological treatments, dietary interventions, psychotherapy and complementary and alternative approaches. The following manuscript will give an overview over pathophysiology, reasonable investigations and treatment of IBS. | 25,154,691 | [
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PLASTID MOVEMENT IMPAIRED1 mediates ABA sensitivity during germination and implicates ABA in light-mediated Chloroplast movements. | The plant hormone abscisic acid (ABA) controls many aspects of plant growth and development, including seed development, germination and responses to water-deficit stress. A complex ABA signaling network integrates environmental signals including water availability and light intensity and quality to fine-tune the response to a changing environment. To further define the regulatory pathways that control water-deficit and ABA responses, we carried out a gene-trap tagging screen for water-deficit-regulated genes in Arabidopsis thaliana. This screen identified PLASTID MOVEMENT IMPAIRED1 (PMI1), a gene involved in blue-light-induced chloroplast movement, as functioning in ABA-response pathways. We provide evidence that PMI1 is involved in the regulation of seed germination by ABA, acting upstream of the intersection between ABA and low-glucose signaling pathways. Furthermore, PMI1 participates in the regulation of ABA accumulation during periods of water deficit at the seedling stage. The combined phenotypes of pmi1 mutants in chloroplast movement and ABA responses indicate that ABA signaling may modulate chloroplast motility. This result was further supported by the detection of altered chloroplast movements in the ABA mutants aba1-6, aba2-1 and abi1-1. | 25,154,696 | [
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Impaired 6-min walk test, heart rate recovery and cardiac function post pulmonary embolism in long-term survivors. | The functional capacity of long-term survivors of submassive pulmonary embolism (PE) is unreported. A six-minute walk distance (6MWD) <350 m and reduced heart rate recovery (HRR) indicate adverse prognosis in various chronic diseases. Long-term survivors of acute PE (January 2000-June 2005) were invited to undergo prospectively planned six-minute walk test (6MWT), transthoracic echocardiogram (TTE), clinical and biochemical evaluation with cardiac biomarkers. HRR was calculated as the difference between heart rate at 6-min during and at 1-min post 6MWT. 120 patients (52 males; mean age [±standard deviation] - 65 ± 14 years) were identified 7.7 ± 1.4 years after PE. 6MWD was significantly lower than that predicted after adjustment for age, sex, and height (448 ± 114 m vs 475 ± 89 m, p = 0.005), and 16% (17/104) had 6MWD <350 m. Among patients with no baseline comorbidities at follow-up (Charlson comorbidity index = 0), 8% (4/52) had 6MWD <350 m. Resting TTE identified 29% of patients had raised right ventricular (RV) pulmonary pressure (pulmonary arterial systolic pressure [PASP] >36 mmHg) and 13% had impaired RV function. Patients with 6MWD <85% predicted had significantly greater impairment of RV longitudinal function (p < 0.001), higher PASP (p < 0.001) and pulmonary vascular resistance (p < 0.001), elevated NT-proBNP (p = 0.03) and high-sensitivity troponin-T (HsTropT, p = 0.03), but similar left ventricular systolic and diastolic function, to those with normal 6MWT. Apparently well, long-term survivors of PE demonstrate impaired exercise capacity, heart rate recovery, mild pulmonary hypertension, raised PVR and right ventricular dysfunction associated with elevated NT-proBNP and HsTropT. | 25,154,698 | [
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The effect of baicalin in a mouse model of retinopathy of prematurity. | Baicalin is a flavonoid derived from the dried root of Scutellaria baicalensis. In this study, oxygen-induced retinopathy was used to characterize the anti-angiogenic properties of baicalin in mice. Pups were exposed to a hyperbaric oxygen environment to induce retinal angiogenesis and were subjected to intraperitoneal injection of baicalin. Avascular area, neovascular tufts, and neovascular lumens were quantified from digital images. Compared to the vehicle, baicalin clearly reduced the central avascular zone and the number of neovascular tufts and lumens. High-dose baicalin (10 mg/kg) significantly reduced the expression of matrix metalloproteinase-2 (MMP-2), MMP-9, angiotensin II, and vascular endothelial growth factor (VEGF). These results show that baicalin is a powerful antiangiogenic compound that attenuates new vessel formation in the retina after systemic administration, and is a candidate substance for therapeutic inhibition of retinal angiogenesis. | 25,154,719 | [
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Non-ablative fractional laser provides long-term improvement of mature burn scars--a randomized controlled trial with histological assessment. | Non-ablative fractional laser-treatment is evolving for burn scars. The objective of this study was to evaluate clinical and histological long-term outcome of 1,540 nm fractional Erbium: Glass laser, targeting superficial, and deep components of mature burn scars. Side-by-side scar-areas were randomized to untreated control or three monthly non-ablative fractional laser-treatments using superficial and extra-deep handpieces. Patient follow-up were at 1, 3, and 6 months. Primary outcome was improvement in overall scar-appearance on a modified-Patient-and-Observer-Scar-Assessment-Scale (mPOSAS, 1 = "normal skin", 10 = "worst imaginable scar"). Secondary outcomes included histology, patient satisfaction (0-10), patient-assessed improvement, and safety. Study was completed by 17 of 20 randomized patients with normotrophic (n = 11), hypertrophic (n = 5) or atrophic (n = 1) scars. Scar-appearance improved from laser-treatments (P < 0.001 vs. untreated) and histology at 6 months supported collagen-remodeling. Improvement appeared continuously during the post-operative period (mPOSAS baseline: 7 [5-8], 6 months: 4 [3-5] P = < 0.001). At 6 months, patients were satisfied with treatment (6 [3-9]) and 82% reported improved scar-texture. Treatments caused mild to moderate pain (4 [2-7]). Adverse effects decreased during follow-up and at final assessment, discrete erythema, hyperpigmentation or imprints from laser-grid were present in 11 patients. No patients experienced worsening of scar-appearance. Combined superficial and deep non-ablative fractional laser-treatments induce long-term clinical and histological improvement of mature burn scars. | 25,154,734 | [
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Investigation of DNA repair gene variants on myelodysplastic syndromes in a Turkish population. | The aim of this study was to assess the possible influence of genetic polymorphisms in hOGG1, XRCC1, XRCC3, XPD, XPG and APE1 on the observed DNA damage in a group of Turkish myelodysplastic syndrome (MDS) patients. A total of 39 patients with myelodysplastic syndrome and 78 age-matched healthy control subjects were included in our study. Polymerase chain reaction/restriction fragment length polymorphism analysis was performed for the detection of DNA repair gene variants. No significant differences in DNA repair enzymes APE1, XRCC1 and XPG were found between MDS patients and controls. On the other hand, XRCC3, XPD and hOGG1 were associated with an increased risk of MDS (p=0.004, p=0.000, p=0.017, respectively). Specifically, Thr/Met genotype was more relevant in patients (p=0.026) in XRCC3; in hOGG1, Cys+ genotype was found higher in patients (p=0.017); and in XPD, Gln/Gln genotypes were found higher in the patient (p=0.001). In conclusion, XRCC3, XPD and hOGG1 genotypes are associated with an increased MDS risk, suggesting their possible involvement in the pathogenesis and biology of this disease. | 25,154,760 | [
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Live birth after PGD with confirmation by a comprehensive approach (karyomapping) for simultaneous detection of monogenic and chromosomal disorders. | Preimplantation genetic diagnosis (PGD) for monogenic disorders has the drawback of time and cost associated with tailoring a specific test for each couple, disorder, or both. The inability of any single assay to detect the monogenic disorder in question and simultaneously the chromosomal complement of the embryo also limits its application as separate tests may need to be carried out on the amplified material. The first clinical use of a novel approach ('karyomapping') was designed to circumvent this problem. In this example, karyomapping was used to confirm the results of an existing PGD case detecting both chromosomal abnormalities and a monogenic disorder (Smith-Lemli-Opitz [SLO] syndrome) simultaneously. The family underwent IVF, ICSI and PGD, and both polar body and cleavage stage biopsy were carried out. Following whole genome amplification, array comparative genomic hybridisation of the polar bodies and minisequencing and STR analysis of single blastomeres were used to diagnose maternal aneuploidies and SLO status, respectively. This was confirmed, by karyomapping. Unlike standard PGD, karyomapping required no a-priori test development. A singleton pregnancy and live birth, unaffected with SLO syndrome and with no chromosome abnormality, ensued. Karyomapping is potentially capable of detecting a wide spectrum of monogenic and chromosome disorders and, in this context, can be considered a comprehensive approach to PGD. | 25,154,779 | [
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Identification of a breast cancer family double heterozygote for RAD51C and BRCA2 gene mutations. | Next-generation sequencing has entered routine genetic testing of hereditary breast cancer. It has provided the opportunity to screen multiple genes simultaneously, and consequently has identified new complex genotypes. Here we report the first identification of a woman double heterozygote for mutations in the RAD51C and BRCA2 genes. The RAD51C missense mutation p.Arg258His has previously been identified in a homozygous state in a patient with Fanconi anemia. This mutation is known to affect the DNA repair function of the RAD51C protein. The BRCA2 p.Leu3216Leu synonymous mutation has not been described before and mini-gene splicing experiments revealed that the mutation results in skipping of exon 26 containing a part of the DNA-binding domain. We conclude that the woman has two potential disease-causing mutations and that predictive testing of family members should include both the RAD51C and BRCA2 mutation. This study illustrates the advantage of sequencing gene panels using next-generation sequencing in terms of genetic testing. | 25,154,786 | [
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Systematic review of various laser intervention strategies for proliferative diabetic retinopathy. | Diabetic retinopathy (DR) is a common complication of diabetes. DR obstructs blood supply to the retina and has serious and long-lasting detrimental effects on quality of life. Panretinal photocoagulation, a laser surgical intervention, is advocated for early treatment of DR to prevent visual loss; however, results from studies reporting its efficacy vary markedly. In this review, we systematically conducted a database search of randomized controlled trials that investigated the safety and efficacy of different types of laser interventions, alone or in combination with adjunct intravitreal steroid utilization, in patients with DR. Data from 14 studies demonstrated that panretinal photocoagulation can be a safe and effective option for reducing visual loss and blindness in patients with DR. | 25,154,790 | [
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Magnetic analysis of a tetranuclear octahedral high-spin cobalt(II) complex based on a newly derived magnetic susceptibility equation. | Here we report a versatile magnetic susceptibility equation for tetranuclear octahedral high-spin cobalt(ii) complexes and a magnetic analysis for a tetranuclear defect cubane cobalt(ii) complex based on this equation. We concluded that the interaction is essentially ferromagnetic despite the decrease in the χT product on cooling from 300 K, and the decrease is due to the spin-orbit coupling. | 25,154,808 | [
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Involvement of an antioxidant defense system in the adaptive response to cadmium in maize seedlings (Zea mays L.). | Chemical and biological analyses were used to investigate the growth response and antioxidant defense mechanism of maize seedlings (Zea mays L.) grown in soils with 0-100 mg kg(-1) Cd. Results showed that maize seedlings have strong abilities to accumulate and tolerate high concentrations of Cd. For soil with 50 mg kg(-1) Cd, the Cd contents in roots and shoots of maize seedlings are as large as 295.6 and 153.0 mg kg(-1) DW, respectively, without visible symptoms of toxicity. Lower soil Cd concentrations lead to a decrease in reduced glutathione (GSH) content in leaves of maize seedlings, whereas higher soil Cd concentrations resulted in an increase in the activities of superoxide dismutase, guaiacol peroxidase, catalase, and ascorbate peroxidase. Maize seedlings have strong capacities to adapt to low concentrations of Cd by consuming GSH and to develop an antioxidative enzyme system to defend against high-Cd stress. | 25,154,813 | [
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Randomized phase III trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III to IV head and neck carcinoma: RTOG 0522. | Combining cisplatin or cetuximab with radiation improves overall survival (OS) of patients with stage III or IV head and neck carcinoma (HNC). Cetuximab plus platinum regimens also increase OS in metastatic HNC. The Radiation Therapy Oncology Group launched a phase III trial to test the hypothesis that adding cetuximab to the radiation-cisplatin platform improves progression-free survival (PFS). Eligible patients with stage III or IV HNC were randomly assigned to receive radiation and cisplatin without (arm A) or with (arm B) cetuximab. Acute and late reactions were scored using Common Terminology Criteria for Adverse Events (version 3). Outcomes were correlated with patient and tumor features and markers. Of 891 analyzed patients, 630 were alive at analysis (median follow-up, 3.8 years). Cetuximab plus cisplatin-radiation, versus cisplatin-radiation alone, resulted in more frequent interruptions in radiation therapy (26.9% v. 15.1%, respectively); similar cisplatin delivery (mean, 185.7 mg/m2 v. 191.1 mg/m2, respectively); and more grade 3 to 4 radiation mucositis (43.2% v. 33.3%, respectively), rash, fatigue, anorexia, and hypokalemia, but not more late toxicity. No differences were found between arms A and B in 30-day mortality (1.8% v. 2.0%, respectively; P = .81), 3-year PFS (61.2% v. 58.9%, respectively; P = .76), 3-year OS (72.9% v. 75.8%, respectively; P = .32), locoregional failure (19.9% v. 25.9%, respectively; P = .97), or distant metastasis (13.0% v. 9.7%, respectively; P = .08). Patients with p16-positive oropharyngeal carcinoma (OPC), compared with patients with p16-negative OPC, had better 3-year probability of PFS (72.8% v. 49.2%, respectively; P < .001) and OS (85.6% v. 60.1%, respectively; P < .001), but tumor epidermal growth factor receptor (EGFR) expression did not distinguish outcome. Adding cetuximab to radiation-cisplatin did not improve outcome and hence should not be prescribed routinely. PFS and OS were higher in patients with p16-positive OPC, but outcomes did not differ by EGFR expression. | 25,154,822 | [
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Effects of enamel fluorosis and dental caries on quality of life. | The objectives of this study were to determine the impact of enamel fluorosis and dental caries on oral health-related quality of life (OHRQoL) in North Carolina schoolchildren and their families. Students (n = 7,686) enrolled in 398 classrooms in grades K-12 were recruited for a onetime survey. Parents of students in grades K-3 and 4-12 completed the Early Childhood Oral Health Impact Scale (ECOHIS) and Family Impact Scale (FIS), respectively. Students in grades 4-12 completed the Child Perceptions Questionnaire (CPQ8-10 in grades 4-5; CPQ11-14 in grades 6-12). All students were examined for fluorosis (Dean's index) and caries experience (d2-3fs or D2-3MFS indices). OHRQoL scores (sum response codes) were analyzed for their association with fluorosis categories and sum of d2-3fs and D2-3MFS according to ordinary least squares regression with SAS procedures for multiple imputation and analysis of complex survey data. Differences in OHRQoL scores were evaluated against statistical and minimal important difference (MID) thresholds. Of 5,484 examined students, 71.8% had no fluorosis; 24.4%, questionable to very mild fluorosis; and 3.7%, mild, moderate, or severe fluorosis. Caries categories were as follows: none (43.1%), low (28.6%), and moderate to high (28.2%). No associations between fluorosis and any OHRQoL scales met statistical or MID thresholds. The difference (5.8 points) in unadjusted mean ECOHIS scores for the no-caries and moderate-to-high caries groups exceeded the MID estimate (2.7 points) for that scale. The difference in mean FIS scores (1.5 points) for the no-caries and moderate-to-high groups exceeded the MID value (1.2 points). The sum of d2-3fs and D2-3MFS scores was positively associated with CPQ11-14 (B = 0.240, p < .001), ECOHIS (B = 0.252, p ≤ .001), and FIS (B = 0.096, p ≤ .01) scores in ordinary least squares regression models. A child's caries experience negatively affects OHRQoL, while fluorosis has little impact. | 25,154,834 | [
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[Application of percutaneous pedicle screw fixation for lumbar degenerative disease]. | To evaluate the accuracy and safety of mini-invasive and percutaneous pedicle screw fixation with fluoroscopy for lumbar degenerative disease. For this retrospective study, 64 cases of lumbar degenerative disease underwent mini-invasive transforaminal lumbar interbody fusion (TLIF) under microscope plus percutaneous pedicle screw fixation with fluoroscopy of lumbar spine from March 2012 to October 2013. The parameters of operative duration, intraoperative blood loss volume, hospital stay and complications were recorded and analyzed. The clinical outcomes were assessed with visual analog scale (VAS), Oswestry disability index (ODI) and Short Form Health Survey-36 (SF-36). The relevant examinations included plain radiography, dynamic radiology and lumbar magnetic resonance imaging (MRI) and computed tomography (CT). The mean estimated blood loss volume was (193 ± 100) ml, mean length of hospital stay (7 ± 2) days, mean operative duration (3.4 ± 0.9) hours and an overall complication rate 7.8%. Significant differences existedin mean VAS score and ODI between pre- and post-operation (P < 0.01). During a mean follow-up of 3 months, the improvement rate of ODI was 50.8% and mean SF-36 86.2%. A total of 316 screws were implanted into 64 patients. Among them, 306 were well-positioned and 10 fairly. The success rate of screw implantation was 100%. And solid fusion was achieved in 64 patients (96%). Mini-invasive and percutaneous pedicle screw fixation with fluoroscopy for lumbar degenerative disease is both efficacious and safe. And it may be combined with TLIF technique under microscope. | 25,154,836 | [
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FEN1 -69G>A and 4150G>T polymorphisms and cancer risk in Chinese population. | Previous studies have investigated the associations between FEN1 -69G>A (rs174538) and 4150G>T (rs4246215) polymorphisms and cancer risk in Chinese population. However, the results were controversial. We therefore carried out a meta-analysis to derive a more precise estimation of the associations. PubMed Database was systematically searched to identify potentially eligible literatures. Crude odds ratios (ORs) and their 95% confidence intervals (CIs) were used to assess the strength of associations between FEN1 -69G>A and 4150G>T polymorphisms and cancer risk in Chinese population. A total of 4 articles, including 5,108 cases and 6,382 controls, were used to evaluate the effect of the two polymorphisms on cancer risk. The pooled ORs indicated that FEN1 -69G>A and 4150G>T polymorphisms were significantly associated with cancer risk in Chinese population. In stratified analyses by cancer type, significant associations were also observed in digestive system cancer. In addition, haplotypes consisting of -69G>A and 4150G>T polymorphisms were closely associated with cancer risk. Interestingly, significantly correlation between FEN1 -69G>A polymorphism and mRNA expression was observed. In conclusion, this meta-analysis suggests that FEN1 -69G>A and 4150G>T polymorphisms may be associated with cancer susceptibility in Chinese population. However, further investigation on large population and different ethnicities are warranted. | 25,154,853 | [
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Computed tomographic arthrography of the normal canine elbow. | Comprehensive evaluation of canine elbow joint dysfunction includes assessment of articular cartilage, which can noninvasively be performed with contrast arthrography. Aims of this prospective study were to compare positive contrast computed tomographic (CT) arthrography and histomorphometry measures of cartilage thickness in normal canine elbows, and to determine the optimal contrast medium concentration. Thirty-two canine cadaver elbows were examined using multidetector CT, before and after intra-articular administration of iohexol at one of three different concentrations. Articular cartilage thickness was measured on both the CT arthrography images and corresponding histologic specimens. Mean difference (bias) between the CT arthrography and histomorphologic measurements was 0.18 and 0.19 mm in the sagittal and dorsal planes, respectively. Mean bias and precision of CT arthrography measurements made in the sagittal or dorsal reformations were not significantly different from one another. Computed tomographic arthrography measurements from elbows with 75 mg I/ml were significantly larger and had greater bias compared to other contrast medium groups (150 and 37.5 mg I/ml). There was no significant difference in CT arthrography measurement precision between different contrast medium concentrations. Histomorphologic thickness of the articular cartilage overlying the cranial aspect of the ulna (mean 0.32 mm) was significantly thinner than cartilage of the radius (0.36 mm) or humerus (0.36 mm). Findings from this cadaver study indicated that CT arthrography delineates articular cartilage of the normal canine elbow; yields cartilage thickness measures slightly greater than histomorphometry measures; and provides high measurement precision regardless of image plane, contrast medium concentration, or anatomic zone. | 25,154,869 | [
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Deciphering the unusual HLA-A2/Melan-A/MART-1-specific TCR repertoire in humans. | The Melan-A/MART-1(26-35) antigenic peptide is one of the best studied human tumor-associated antigens. It is expressed in healthy melanocytes and malignant melanoma and is recognized by CD8(+) T cells in the context of the MHC class I molecule HLA-A*0201. While an unusually large repertoire of CD8(+) T cells specific for this antigen has been documented, the reasons for its generation have remained elusive. In this issue of the European Journal of Immunology, Pinto et al. [Eur. J. Immunol. 2014. 44: 2811-2821] uncover one important mechanism by comparing the thymic expression of the Melan-A gene to that in the melanocyte lineage. This study shows that medullary thymic epithelial cells (mTECs) dominantly express a truncated Melan-A transcript, the product of misinitiation of transcription. Consequently, the protein product in mTECs lacks the immunodominant epitope spanning residues 26-35, thus precluding central tolerance to this antigen. In contrast, melanocytes and melanoma tumor cells express almost exclusively the full-length Melan-A transcript, thus providing the target antigen for efficient recognition by HLA-A2-restricted CD8(+) T cells. The frequency of these alternative gene transcription modes may be more common than previously appreciated and may represent an important factor modulating the efficiency of central tolerance induction in the thymus. | 25,154,881 | [
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Self-assembly of hybridized ligands on gold nanodots: tunable photoluminescence and sensing of nitrite. | Highly photoluminescent gold nanodots (Au NDs) via etching and co-deposition of hybridized ligands [11-mercaptoundecanol (11-MU) and its complexes with amphiphilic ligands] on gold nanoparticles (∼3 nm) have been prepared and employed for the detection of nitrite based on the analyte-induced photoluminescence quenching. | 25,154,909 | [
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[Surgical treatment of chronic thromboembolic pulmonary hypertension]. | Chronic thromboembolic pulmonary hypertension is a rare but underdiagnosed disease. The development of imaging played a crucial role for the screening and the decision of operability over the past few years. Indeed, chronic thromboembolic pulmonary hypertension is the only type of pulmonary hypertension with a potential curative treatment: pulmonary endarterectomy. It is a complexe surgical procedure performed under cardiopulmonary bypass with deep hypothermia and circulatory arrest. The aim of the procedure is to completely remove the scar tissue inside the pulmonary arteries down to the segmental and sub-segmental levels. Compared to lung transplantation, which carries a postoperative mortality of 15-20% and a 5-year survival of 50%, pulmonary endarterectomy is a curative treatment with a postoperative mortality of less than 3%. However, lung transplantation remains an option for young patients with inoperable distal disease or after pulmonary endarterectomy failure. Considering that medical history of deep venous thrombosis or pulmonary embolism is lacking in 25 to 50%, the diagnosis of chronic thromboembolic pulmonary hypertension remains challenging. The lung V/Q scan is useful for the diagnosis showing ventilation and perfusion mismatches. Lesions located at the level of the pulmonary artery, the lobar or segmental arteries may be accessible to surgical removal. The pulmonary angiogram with the lateral view and the pulmonary CT scan help to determine the level of the intravascular lesions. If there is a correlation between the vascular obstruction assessed by imaging and the pulmonary resistance, pulmonary endarterectomy carries a postoperative mortality of less than 3% and has a high rate of success. If the surgery is performed at a later stage of the disease, pulmonary arteriolitis developed mainly in unobstructed territories and participated in the elevated vascular resistance. At this stage, postoperative risk is higher. | 25,154,908 | [
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Genetic strategies to understand physiological pathways regulating body weight. | Body weight is a highly heritable trait across species. In humans, genetic variation plays a major role in determining the inter-individual differences in susceptibility or resistance to environmental factors which influence energy intake and expenditure. In this review, I discuss how genetic studies have contributed to our understanding of the central pathways that govern energy homeostasis. The study of individuals harboring highly penetrant genetic variants that disrupt the leptin-melanocortin pathway has informed our understanding of the physiological pathways involved in mammalian energy homeostasis. | 25,154,910 | [
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Impact of alkaline-hydrolyzed biosolids (Lystek) addition on the anaerobic digestibility of TWAS in lab--and full-scale anaerobic digesters. | The effect of different Lystek biosolids doses on the anaerobic digestability of thickened waste activated sludge (TWAS) was evaluated in a lab- and full-scale anaerobic digester. The overall findings of this study emphasize the beneficial impact of Lystek addition to the lab- and full-scale anaerobic digesters in terms of enhanced biogas production and increased volatile suspended solids reduction (VSSR) efficiency. Lystek added at 4% by volume to TWAS increased the methane yield from 0.22 to 0.26 L CH4/g VSSadded at an solids retention time (SRT) of 10 days, and from 0.27 to 0.29 L CH4/g VSS(added) at an SRT of 15 days. Furthermore, the VSSRs of 37% and 47% were observed for the TWAS, and the TWAS with 4% Lystek, while at an SRT of 15 days, the observed VSSR were 49% and 58%, respectively. The lab-scale study showed that the influence of Lystek addition on methane yield and solids destruction efficiencies was more pronounced at the shorter SRT, 20% enhancement (SRT of 10d) vs. 9% enhancement (SRT of 15 d) for methane yield, and 27% (SRT of 10d) vs. 22% (SRT of 15 d) for VSS destruction efficiency improvement. Furthermore, addition of 4% of Lystek to the feed of the full-scale anaerobic digester at St. Marys wastewater treatment plant (WWTP) resulted in a 50% increase in the average specific methanogenic activity and 23% increase in methane yield of the biochemical methane potential tests after eight months. The results showed that Lystek degradation kinetics were 40% faster than the TWAS, as reflected by first order kinetic coefficients of 0.053 d(-1) and 0.073 d(-1) for TWAS and Lystek at an SRT of 10 days. | 25,154,917 | [
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Cationic amphipathic D-enantiomeric antimicrobial peptides with in vitro and ex vivo activity against drug-resistant Mycobacterium tuberculosis. | Tuberculosis (TB) is the leading cause of bacterial death worldwide. Due to the emergence of multi-drug resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB), and the persistence of latent infections, a safe and effective TB therapy is highly sought after. Antimicrobial peptides (AMPs) have therapeutic potential against infectious diseases and have the ability to target microbial pathogens within eukaryotic cells. In the present study, we investigated the activity of a family of six AMPs containing all-D amino acids (D-LAK peptides) against MDR and XDR clinical strains of Mycobacterium tuberculosis (Mtb) both in vitro and, using THP-1 cells as a macrophage model, cultured ex vivo. All the D-LAK peptides successfully inhibited the growth of Mtb in vitro and were similarly effective against MDR and XDR strains. D-LAK peptides effectively broke down the heavy clumping of mycobacteria in broth culture, consistent with a 'detergent-like effect' that could reduce the hydrophobic interactions between the highly lipidic cell walls of the mycobacteria, preventing bacteria cell aggregation. Furthermore, though not able to eradicate the intracellular mycobacteria, D-LAK peptides substantially inhibited the intracellular growth of drug-resistant Mtb clinical isolates at concentrations that were well tolerated by THP-1 cells. Finally, combining D-LAK peptide with isoniazid could enhance the anti-TB efficacy. D-LAK peptide, particularly D-LAK120-A, was effective as an adjunct agent at non-toxic concentration to potentiate the efficacy of isoniazid against drug-resistant Mtb in vitro, possibly by facilitating the access of isoniazid into the mycobacteria by increasing the surface permeability of the pathogen. | 25,154,927 | [
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The evaluation of family functioning by the family assessment device: a systematic review of studies in adult clinical populations. | A large body of research, documenting the impact of a family's functioning on health outcomes, highlights the importance of introducing the evaluation of patients' family dynamics into clinical judgment. The Family Assessment Device (FAD) is a self-report questionnaire designed to assess specific dimensions of family functioning. This qualitative systematic review, which follows PRISMA guidelines, aimed to identify the FAD's clinimetric properties and to report the incremental utility of its inclusion in clinical settings. A thorough literature search was performed, using both computerized and manual searches, yielding a total of 148 studies that were included in this review. The FAD has been extensively used in a variety of research contexts. In the majority of studies it was able to discriminate between clinical populations and controls and among groups of patients with different illnesses. The FAD also showed good test-retest and concurrent reliability, and modest sensitivity to change after treatment. FAD-dysfunctional family functioning was related to several patient clinical outcomes, including lower recovery rates and adherence to treatment, longer recovery time, poorer quality of life, and increased risk of relapse and drop-out. The present review demonstrates that the FAD is a suitable instrument for the evaluation of family functioning both in clinical and research settings. | 25,154,959 | [
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A 2DRF pulse sequence for bolus tracking in hyperpolarized 13C imaging. | A novel application of two-dimensional (2D) spatially selective radiofrequency (2DRF) excitation pulses in hyperpolarized 13C imaging is proposed for monitoring the bolus injection with highly efficient sampling of the initially polarized substrate, thus leaving more polarization available for detection of the subsequently generated metabolic products. A 2DRF pulse was designed with a spiral trajectory and conventional clinical gradient performance. To demonstrate the ability of our 2DRF bolus tracking pulse sequence, hyperpolarized [1-(13)ruvate in vivo imaging experiments were performed in normal rats, with a comparison to 1DRF excitation pulses. Our designed 2DRF pulse was able to rapidly and efficiently monitor the injected bolus dynamics in vivo, with an 8-fold enhanced time resolution in comparison with 1DRF in our experimental settings. When applied at the pyruvate frequency for bolus tracking, our 2DRF pulse demonstrated reduced saturation of the hyperpolarization for the substrate and metabolic products compared to a 1DRF pulse, while being immune to ±0.5 ppm magnetic field inhomogeneity at 3T. 2DRF pulses in hyperpolarized 13C imaging can be used to efficiently monitor the bolus injection with reduced hyperpolarization saturation compared to 1DRF pulses. The parameters of our design are based on clinical scanner limits, which allows for rapid translation to human studies. | 25,154,961 | [
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[Clinical characteristics and efficiency of interventional therapy for coronary artery involvement in Takayasu's arteritis]. | To explore the clinical characteristics and efficacies of interventional therapy for coronary artery involvement in Takayasu's arteritis (TA). A total of 98 consecutive hospitalized TA patients with more than 50% diameter reduction of coronary artery by angiography were retrospectively analyzed from 2000 to 2013 at Peking Union Medical College Hospital. Six cases (6/98, 6.1%) had coronary artery involvement of TA. All were females with an age range of 15-51 (32 ± 16) years. The manifestations included typical angina pectoris with a depression of ST segment on electrocardiogram. Among them, myocardial enzyme elevated in 5 cases and fulfilled the diagnosis of non-ST elevated myocardial infarction.Four cases had peripheral arterial involvement while another 2 cases had only coronary involvement. Coronary angiography was useful for definitive diagnosis. Coronary ostia was the most frequently involved.Five patients received successful coronary revascularization with drug-eluting stent and the symptom of angina pectoris improved.However, 1 patient developed restenosis in stent 3 months after percutaneous coronary intervention (PCI). Coronary artery involvement in TA is not rare, especially ostia. The patients usually present with non-ST elevated myocardial infarction. PCI with drug-eluting stent may improve the symptoms, but the long-term effect should be investigated further. | 25,154,992 | [
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A rare cause of gastro-intestinal hemorrhage in a patient with a Roux-en-Y gastric bypass. | This case illustrates a rare cause of gastro-intestinal bleeding following bariatric surgery. Though it is essential to rule out common causes of variceal formation accompanied by intermittent, profuse bleeding, there should be a high degree of suspicion of this rare etiology in patients who have previously undergone alteration of their anatomy, especially Roux-en-Y gastric bypass (RYGB). The case emphasizes the need for a multidisciplinary medical-surgical team in evaluating and treating patients who present with complex intra-abdominal pathology. | 25,155,016 | [
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Expression of p8 in Human Oral Squamous Cell Carcinoma. | The present study investigated the expression of p8, a transcription factor upregulated in some human cancers, in oral squamous cell carcinomas (OSCCs). Immunohistochemical analysis of p8 expression was carried out on 20 archived surgical specimens of human OSCCs, and expression correlated with clinical outcome parameters in a retrospective study. Expression of p8 in a number of OSCC cell lines also was investigated by western blot and RT-PCR analyses. p8 was expressed in 80 % (16/20) of the samples with levels of expression exhibiting a significant difference (χ(2) = 8.352, df = 3, p = 0.039) by patient age. Furthermore, greater levels of p8 immunoreactivity was significantly associated with advanced tumor grade (p = 0.008). p8 also was upregulated in OSCC cell lines. p8 is expressed in a significant proportion of OSCCs, and in human OSCC cell lines, suggesting a potential value of p8 as a diagnostic and/prognostic tool for oral cancers. | 25,155,047 | [
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Retention behavior of alkylated polycyclic aromatic sulfur heterocycles on immobilized ionic liquid stationary phases. | Polycyclic aromatic sulfur heterocycles (PASH) are prevalent components of fossil fuel-based pollutants, and their accurate analysis is of critical importance in risk assessment and hazardous waste site remediation. PASH, however, have a wide range of volatilities and polarities and, as such, often coelute with one another and other sample components on the non-polar gas chromatography (GC) columns commonly used in their analysis. Immobilized ionic liquid (IL)-based stationary phases have been shown to provide better separation of polar compounds than non-polar columns, while withstanding higher temperatures than typical polar columns. In this way, they offer the opportunity of improved performance in the analysis of PASH in complex environmental samples and as the "more polar" column in GC×GC/MS analyses. In this study, the retention behavior of 119 PASH on four commercially-available IL stationary phases is reported and compared to behavior on three polydimethylsiloxane-based columns of varying polarities (DB-5, DB-17, and DB-200). Additionally, the utility of IL columns in GC×GC analyses of PASH-containing coal tar samples is examined. | 25,155,062 | [
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Depletion of foxp3(+) T cells abrogates tolerance of skin and heart allografts in murine mixed chimeras without the loss of mixed chimerism. | The relative contribution of central and peripheral mechanisms to the generation and maintenance of allograft tolerance is of considerable interest. Here, we present new evidence that regulatory T cells (Foxp3(+) ) maintain skin and heart allograft tolerance in mixed hematopoietic chimeric mice. Transient depletion of both donor- and recipient-derived Foxp3(+) cells was necessary and sufficient to induce decisive rejection of long-accepted skin and heart allografts. In contrast, stable hematopoietic chimerism remained, and there was no detectable induction of donor-specific reactivity to hematopoietic cells. Foxp3(+) cell depletion did not result in the rejection of skin grafts of only MHC-disparate donors (B6.C-H2(d) /bByJ), indicating that MHC antigens were not the target in the graft. We conclude that two different mechanisms of tolerance are present in mixed chimeras. Hematopoietic chimerism, resistant to Foxp3(+) depletion, is probably due to deletional tolerance to MHC antigens, as supported by previous studies. In contrast, regulatory tolerance mechanisms involving Foxp3(+) cells are required to control reactivity against non-MHC antigens not present on hematopoietic lineages. | 25,155,089 | [
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Opioid use and depression in chronic pelvic pain. | Opioid pain medications and antidepressants are commonly prescribed to patients for chronic non-cancer pain. However, little evidence exists for their effectiveness in most pain states, including chronic pelvic pain. Whenever possible, initiation of opioid pain medications in chronic non-cancer pain should be avoided. If patients present for evaluation of disease states such as endometriosis or interstitial cystitis already using regular narcotics, physicians should be aware of ways to mediate misuse and diversion. Women with chronic pain should be screened for depression as well as a history of prior sexual abuse, and treatment or referral initiated when indicated. | 25,155,127 | [
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Attitudes of physicians and pharmacists towards International Non-proprietary Name prescribing in Belgium. | International Non-proprietary Name (INN) prescribing is the use of the name of the active ingredient(s) instead of the brand name for prescribing. In Belgium, INN prescribing began in 2005 and a major policy change occurred in 2012. The aim was to explore the opinions of Dutch-speaking general practitioners (GPs) and pharmacists. An electronic questionnaire with 39 five-point Likert scale statements and one open question was administered in 2013. Multivariate analysis was performed with multiple linear regression on a sum score for benefit statements and for drawback statements. Answers to the open question were qualitatively analysed. We received 745 valid responses with a representable sample for both subgroups. Participants perceived the motives to introduce INN prescribing as purely economic (to reduce pharmaceutical expenditures for the government and the patient). Participants accepted the concept of INN prescribing, but 88% stressed the importance of guaranteed treatment continuity, especially in older, chronic patients, to prevent patient confusion, medication non-adherence and erroneous drug use. In conclusion, the current way in which INN prescribing is applied in Belgium leads to many concerns among primary health professionals about patient confusion and medication adherence. Slightly adapting the current concept of INN prescribing to these concerns can turn INN prescribing into one of the major policies in Belgium to reduce pharmaceutical expenditures and to stimulate rational drug prescribing. | 25,155,133 | [
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Prostaglandin E2 receptors in asthma and in chronic rhinosinusitis/nasal polyps with and without aspirin hypersensitivity. | Chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma frequently coexist and are always present in patients with aspirin exacerbated respiratory disease (AERD). Although the pathogenic mechanisms of this condition are still unknown, AERD may be due, at least in part, to an imbalance in eicosanoid metabolism (increased production of cysteinyl leukotrienes (CysLTs) and reduced biosynthesis of prostaglandin (PG) E2), possibly increasing and perpetuating the process of inflammation. PGE2 results from the metabolism of arachidonic acid (AA) by cyclooxygenase (COX) enzymes, and seems to play a central role in homeostasis maintenance and inflammatory response modulation in airways. Therefore, the abnormal regulation of PGE2 could contribute to the exacerbated processes observed in AERD. PGE2 exerts its actions through four G-protein-coupled receptors designated E-prostanoid (EP) receptors EP1, EP2, EP3, and EP4. Altered PGE2 production as well as differential EP receptor expression has been reported in both upper and lower airways of patients with AERD. Since the heterogeneity of these receptors is the key for the multiple biological effects of PGE2 this review focuses on the studies available to elucidate the importance of these receptors in inflammatory airway diseases. | 25,155,136 | [
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Whole blood metal ion measurement reproducibility between different laboratories. | Monitoring patients' metal ion blood concentrations can be useful in cases of problematic metal on metal hip implants. Our objective was to evaluate the reproducibility of metal ion level values measured by two different laboratories. Whole blood samples were collected in 46 patients with metal on metal hip arthroplasty. For each patients, two whole blood samples were collected and analyzed by two laboratories. Laboratory 1 had higher results than laboratory 2. There was a clinically significant absolute difference between the two laboratories, above the predetermined threshold, 35% of Cr samples and 38% of Co samples. All laboratories do not use the same technologies for their measurements. Therefore, decision to revise a metal on metal hip arthroplasty should rely on metal ion trends and have to be done in the same laboratory. | 25,155,139 | [
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PKCδ is required for porcine reproductive and respiratory syndrome virus replication. | Protein kinase C (PKC) that transduces signals to modulate a wide range of cellular functions has been shown to regulate a number of viral infections. Herein, we showed that inhibition of PKC with the PKC inhibitor GF109203X significantly impaired porcine reproductive and respiratory syndrome virus (PRRSV) replication. Inhibition of PKC led to virus yield reduction, which was associated with decreased viral RNA synthesis and lowered virus protein expression. And this inhibitory effect by PKC inhibitor was shown to occur at the early stage of PRRSV infection. Subsequently, we found that PRRSV infection activated PKCδ in PAMs and knockdown of PKCδ by small interfering RNA (siRNA) suppressed PRRSV replication, suggesting that novel PKCδ may play an important factor in PRRSV replication. Taken together, these data imply that PKC is involved in PRRSV infection and beneficial to PRRSV replication, extending our understanding of PRRSV replication. | 25,155,198 | [
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Is rotator cuff repair appropriate in patients older than 60 years of age? prospective, randomised trial in 103 patients with a mean four-year follow-up. | The objective of this randomised trial was to compare surgical rotator cuff repair to simple decompression by acromioplasty and biceps tenotomy in patients older than 60 years of age with a mean follow-up of 4 years. Tendon repair produces better functional outcomes than simple decompression and prevents progression towards cuff tear arthropathy in the longer term. Of 130 initially included patients older than 60 years of age and having rotator cuff tears deemed amenable to surgical repair, 103 (79%) were evaluated after a mean of 4 years. These patients had been randomly allocated to acromioplasty and tenotomy (AT group, n=49) or to acromioplasty, tenotomy, and tendon suture (CR group, n=54). The tear was distal in 41 patients, intermediate in 40, and retracted in 22. At last follow-up, the evaluation included the clinical Constant's Score, radiographs and, in the CR group, ultrasonography. The complication rate was 4%. The mean Constant Score was 44 preoperatively; values after 4 years were 76 overall (P=0.01), 78 in the CR group, and 73 in the AT group (P=0.01). The tendon-healing rate as assessed using ultrasonography was 63%. The Constant Score was significantly better when tendon healing was achieved (82/73, P<0.001). In the AT group, the acromio-humeral distance was significantly shorter (6.9 mm/7.8mm, P=0.03) and eccentric humeral head position was more common (44%/26%, P=0.01). Arthroscopic rotator cuff repair provides better functional outcomes than does simple decompression in patients older than 60 years and prevents cuff tear arthropathy with eccentric humeral head position in the medium term. Tendon healing is the main determinant of outcomes after rotator cuff repair. II, randomised trial. | 25,155,203 | [
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The surgical management of gallbladder cancer. | Among biliary tract cancers, gallbladder cancer (GBC) is a potentially lethal malignancy with abysmal long-term survival. Surgery is central to the management of GBC, and presently, provides the only ray of hope for long-term survival. Radical cholecystectomy, which includes cholecystectomy with a limited hepatic resection, regional lymphadenectomy and adjacent organ resection if required is used to encompass the tumor with negative margins - R'0' resection is the standard surgical treatment for the management of GBC. Absence of randomized controlled trials to address various surgical controversies due to rarity of disease in western world, advanced disease at presentation, high frequency of unresectability/inoperability at surgery, deficient neoadjuvant/adjuvant strategies and nihilistic views of oncologists due to aggressive disease biology has resulted in marked heterogeneity in surgical strategies employed to manage GBC across the surgical centers globally. | 25,155,211 | [
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The effect of magnetic resonance imaging noise on cochlear function in dogs. | Noise produced by magnetic resonance imaging (MRI) scanners (which can peak at a sound pressure level of 131 dB) has been shown to cause noise-induced cochlear dysfunction in people. The aim of this study was to investigate whether noise produced during MRI had a deleterious effect on cochlear function in dogs, using distortion product otoacoustic emission (DPOAE) testing, which allows frequency specific, non-invasive assessment of cochlear function. DPOAE testing was performed before and after MRI in one or both ears under general anaesthesia at 14 frequency pairs (f2 frequency ranging from 0.84 kHz to 8.0 kHz). A control group comprised dogs undergoing anaesthesia of a similar duration for quiet procedures. Thirty-six dogs (66 ears) and 17 dogs (28 ears) were included in the MRI and control groups respectively. There was a reduction in DPOAE at all frequencies tested in the MRI group; a similar effect was not evident in the control group. This reduction in the MRI group was statistically significant in five of the 14 frequencies assessed (P < 0.05). These results demonstrate that exposure to MRI noise results in a significant reduction in frequency-specific cochlear function in dogs, although it is not known whether this is reversible or permanent. This suggests that all dogs undergoing MRI studies should be provided with ear protection as a routine precautionary measure. | 25,155,216 | [
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Prevalence of canine influenza virus A (H3N8) in dogs in Germany. | The aim of this study was to investigate the prevalence of CIV H3N8 in dogs in Germany. Blood samples from 272 clinically healthy dogs and 35 dogs with acute respiratory signs were screened for antibodies against influenza virus by ELISA and haemagglutination inhibition (HI) assay; positive samples were further tested by fluorescent antibody test (FAT) and subtype-specific HI assay. Nasal and pharyngeal swabs from all sick dogs were submitted for real-time (RT)-PCR for influenza virus RNA; PCR results were negative in all cases. One healthy and one sick dog tested positive for antibodies against influenza virus nucleoprotein by ELISA, but both were negative by subtype-specific HI assay and FAT, and were therefore considered false positive results. Thus, antibody prevalence against CIV H3N8 was 0% (0-1.24%, 95% CI). Currently, the risk for CIV H3N8 infection in the German dog population seems very low. | 25,155,218 | [
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Bone-prosthesis composite with rotating hinged-knee prosthesis in limb salvage surgery for high-grade sarcoma around the knee. | Bone prosthesis composite (BPC) had been widely-used in reconstruction after wide excision of malignant tumors around the knee. However, implant selection for BPC remains a dilemma. Forty-one patients with high-grade malignant bone tumors around the knee who underwent excision and reconstruction with BPC and rotating hinged knee (RHK) prosthesis were included. The mean follow-up time was 54 months (range, 31-78 months). The average Musculoskeletal Tumor Society Rating score was 93.4% (range, 73-100%). The mean range of motion was 125°. Complications included 2 local recurrences, 2 nonunions, and 1 peri-prosthetic fracture. The reconstruction with BPC using the RHK prosthesis provided consistently good functional results with a low complication rate. The RHK prosthesis is a promising choice for BPC reconstruction. | 25,155,237 | [
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Alteration of hindfoot alignment after total knee arthroplasty using a novel hindfoot alignment view. | This study examined the coronal alignment of the hindfoot in varus osteoarthritis of the knee before and after total knee arthroplasty (TKA) in 100 legs using a novel imaging method. We categorized the preoperative hindfoot alignment into varus (30 legs) and valgus (70 legs) groups; imaging of the hindfoot was conducted preoperatively and postoperatively, and the varus-valgus angle (VVA) was measured as the hindfoot alignment. The femorotibial angle improved significantly after TKA. We found that the VVA improved significantly after TKA in the hindfoot valgus group (P<0.001), but not in the varus group (P=0.554), and we speculate that the hindfoot alignment in the valgus group improved as a result of a residual compensatory capacity in the hindfoot. | 25,155,238 | [
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The disproportionation of [Ni(tacn)]2+ in Ni2+ and [Ni(tacn)2]2+ crystallographically demonstrated (tacn = 1,4,7-triazacyclononane). | From an EtOH/H2O solution, 0.3 M each of Ni(2+) and cyclic triamine tacn (2; tacn = 1,4,7-triazacyclononane), after 10 min refluxing and cooling at room temperature, copious and comparable amounts of blue crystals (containing the complex [Ni(tacn)(H2O)3](2+)) and pink crystals (containing in the same cell both [Ni(H2O)6](2+) and [Ni(tacn)2](2+)) precipitated. This unusual behaviour is ascribed to the fact that at the refluxing temperature the three species are present at the equilibrium in similar concentrations, which are frozen on cooling, due to the inertness of the macrocyclic complexes [Ni(tacn)(H2O)3](2+) and [Ni(tacn)2](2+). | 25,155,239 | [
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Linking neocortical, cognitive, and genetic variability in autism with alterations of brain plasticity: the Trigger-Threshold-Target model. | The phenotype of autism involves heterogeneous adaptive traits (strengths vs. disabilities), different domains of alterations (social vs. non-social), and various associated genetic conditions (syndromic vs. nonsyndromic autism). Three observations suggest that alterations in experience-dependent plasticity are an etiological factor in autism: (1) the main cognitive domains enhanced in autism are controlled by the most plastic cortical brain regions, the multimodal association cortices; (2) autism and sensory deprivation share several features of cortical and functional reorganization; and (3) genetic mutations and/or environmental insults involved in autism all appear to affect developmental synaptic plasticity, and mostly lead to its upregulation. We present the Trigger-Threshold-Target (TTT) model of autism to organize these findings. In this model, genetic mutations trigger brain reorganization in individuals with a low plasticity threshold, mostly within regions sensitive to cortical reallocations. These changes account for the cognitive enhancements and reduced social expertise associated with autism. Enhanced but normal plasticity may underlie non-syndromic autism, whereas syndromic autism may occur when a triggering mutation or event produces an altered plastic reaction, also resulting in intellectual disability and dysmorphism in addition to autism. Differences in the target of brain reorganization (perceptual vs. language regions) account for the main autistic subgroups. In light of this model, future research should investigate how individual and sex-related differences in synaptic/regional brain plasticity influence the occurrence of autism. | 25,155,242 | [
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Nonalcoholic fatty liver disease (NAFLD) in the Veterans Administration population: development and validation of an algorithm for NAFLD using automated data. | In practice, nonalcoholic fatty liver disease (NAFLD) is diagnosed based on elevated liver enzymes and confirmatory liver biopsy or abdominal imaging. Neither method is feasible in identifying individuals with NAFLD in a large-scale healthcare system. To develop and validate an algorithm to identify patients with NAFLD using automated data. Using the Veterans Administration Corporate Data Warehouse, we identified patients who had persistent ALT elevation (≥2 values ≥40 IU/mL ≥6 months apart) and did not have evidence of hepatitis B, hepatitis C or excessive alcohol use. We conducted a structured chart review of 450 patients classified as NAFLD and 150 patients who were classified as non-NAFLD by the database algorithm, and subsequently refined the database algorithm. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) for the initial database definition of NAFLD were 78.4% (95% CI: 70.0-86.8%), 74.5% (95% CI: 68.1-80.9%), 64.1% (95% CI: 56.4-71.7%) and 85.6% (95% CI: 79.4-91.8%), respectively. Reclassifying patients as having NAFLD if they had two elevated ALTs that were at least 6 months apart but within 2 years of each other, increased the specificity and PPV of the algorithm to 92.4% (95% CI: 88.8-96.0%) and 80.8% (95% CI: 72.5-89.0%), respectively. However, the sensitivity and NPV decreased to 55.0% (95% CI: 46.1-63.9%) and 78.0% (95% CI: 72.1-83.8%), respectively. Predictive algorithms using automated data can be used to identify patients with NAFLD, determine prevalence of NAFLD at the system-wide level, and may help select a target population for future clinical studies in veterans with NAFLD. | 25,155,259 | [
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Association of JARID2 polymorphisms with non-syndromic orofacial clefts in northern Chinese Han population. | Non-syndromic orofacial clefts (NSOC) are the most common human craniofacial malformation in all worldwide populations. Recently, the jumoji AT-rich interaction domain 2 (JARID2) had been reported to be a novel candidate gene for non-syndromic cleft lip with or without cleft palate (CL/P). The SNPs rs2076056, rs2237138 and rs2299043 in JARID2 were highly significant in Italian families. In the current research, a case-control study was conducted to examine the association between these three SNPs and NSOC in a northern Chinese Han population. Genotyping of the three SNPs were performed using SNaPshot minisequencing technique. Distribution of rs2237138 genotypes in CL/P group was different from those in the control group (P = 0.04), but significant results did not persist after Benjamini and Hochberg false discovery rate (FDR) correction for multiple tests. Further logistic regression analysis showed that rs2237138 GG genotypes were associated with decreased CL/P susceptibility (OR = 0.34, 95% CI = 0.13-0.84), compared with the AA wild-type homozygote. For the haplotype CGT, a statistically difference was identified between the CL/P group and controls (P = 0.04). And carriers of GAT haplotype were considered to be less frequent among cleft palate only group as compared to controls (P = 0.02). However, both of the haplotypes association did not remain statistically significant after Benjamini and Hochberg FDR correction. We got a weak association between these polymorphisms and NSOC in both single-marker and haplotype analyses. Our data further strengthen the conclusion that JARID2 polymorphisms are associated with NSOC susceptibility. | 25,155,265 | [
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A new paper-based platform technology for point-of-care diagnostics. | Currently, the Lateral flow Immunoassays (LFIAs) are not able to perform complex multi-step immunodetection tests because of their inability to introduce multiple reagents in a controlled manner to the detection area autonomously. In this research, a point-of-care (POC) paper-based lateral flow immunosensor was developed incorporating a novel microfluidic valve technology. Layers of paper and tape were used to create a three-dimensional structure to form the fluidic network. Unlike the existing LFIAs, multiple directional valves are embedded in the test strip layers to control the order and the timing of mixing for the sample and multiple reagents. In this paper, we report a four-valve device which autonomously directs three different fluids to flow sequentially over the detection area. As proof of concept, a three-step alkaline phosphatase based Enzyme-Linked ImmunoSorbent Assay (ELISA) protocol with Rabbit IgG as the model analyte was conducted to prove the suitability of the device for immunoassays. The detection limit of about 4.8 fm was obtained. | 25,155,271 | [
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Genomic characterization of the LEED..PEEDs, a gene family unique to the medicago lineage. | The LEED..PEED (LP) gene family in Medicago truncatula (A17) is composed of 13 genes coding small putatively secreted peptides with one to two conserved domains of negatively charged residues. This family is not present in the genomes of Glycine max, Lotus japonicus, or the IRLC species Cicer arietinum. LP genes were also not detected in a Trifolium pratense draft genome or Pisum sativum nodule transcriptome, which were sequenced de novo in this study, suggesting that the LP gene family arose within the past 25 million years. M. truncatula accession HM056 has 13 LP genes with high similarity to those in A17, whereas M. truncatula ssp. tricycla (R108) and M. sativa have 11 and 10 LP gene copies, respectively. In M. truncatula A17, 12 LP genes are located on chromosome 7 within a 93-kb window, whereas one LP gene copy is located on chromosome 4. A phylogenetic analysis of the gene family is consistent with most gene duplications occurring prior to Medicago speciation events, mainly through local tandem duplications and one distant duplication across chromosomes. Synteny comparisons between R108 and A17 confirm that gene order is conserved between the two subspecies, although a further duplication occurred solely in A17. In M. truncatula A17, all 13 LPs are exclusively transcribed in nodules and absent from other plant tissues, including roots, leaves, flowers, seeds, seed shells, and pods. The recent expansion of LP genes in Medicago spp. and their timing and location of expression suggest a novel function in nodulation, possibly as an aftermath of the evolution of bacteroid terminal differentiation or potentially associated with rhizobial-host specificity. | 25,155,275 | [
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Venous thromboembolism risk factors in Chinese non-small cell lung cancer patients. | Certain clinicopathological factors contribute to the development of venous thromboembolism (VTE) in lung cancer. The aim of the current study was to assess the incidence of and the potential risk factors associated with the development of VTE in Chinese lung cancer patients. Patients with lung cancer in our center were screened for VTE from January 2004 to July 2013. One VTE case was matched with two controls according to gender, pathology, clinical stage, and anticancer therapy. Among the 4,726 patient records screened, 61 (1.3 %) VTE cases with non-small cell lung cancer (NSCLC) were identified, including 58 (95.1 %) with adenocarcinoma and 59 (96.7 %) with advanced stage tumors (IIIb and IV). Serous effusion (OR 2.089, 95 % CI 1.022-4.270, P = 0.043), fever (OR 8.999, 95 % CI 1.688-47.968, P = 0.010), increased leukocytes (OR 4.136, 95 % CI 1.957-8.738, P < 0.001), hyponatremia (< 130 mmol/L, OR 5.335, 95 % CI 1.366-20.833, P = 0.016), and increased alanine aminotransferase (ALT) (OR 3.879, 95 % CI 1.514-9.936, P = 0.005) were associated with an increased risk of VTE. Patients with poor performance status (PS) (≥ 2 vs. < 1) (HR 1.574, 95 % CI 1.112-2.228, P = 0.010) and serous effusion (HR 1.571, 95% CI 1.114-2.215, P = 0.010) tended to have a poor prognosis. There was no difference in overall survival between VTE (median 15.2 months, 95 % CI 11.6-18.9) and control patients (median 16.3 months, 95 % CI 14.1-18.4, P = 0.184; HR 1.273, 95 % CI 0.890-1.820, P = 0.185). Clinical characteristics such as serous effusion, fever, increased leukocytes, hyponatremia, and increased ALT are potential risk factors for VTE in NSCLC. Poor PS and serous effusion imply poor prognosis for NSCLC patients, most of which have adenocarcinomas and advanced stage. | 25,155,313 | [
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In vitro investigation on extensively destroyed vital teeth: is fracture force a limiting factor for direct restoration? | To evaluate the in vitro fracture load of extensively damaged vital teeth after either direct or indirect restauration, severe tooth substance loss was simulated for 96 molars. Subsequently, two cavities were prepared with little (design 1) or more substantial (design 2) residual tooth support. All molars were provided with a 2-mm ferrule design and then divided into 12 test groups based on their occlusal surface size. They were restored with composite or with either of two types of single crown (cast metal or milled zirconia). After thermal ageing (10,000 cycles at 6.5 and 60 °C), 1.2 million cycles of chewing simulation were applied (64 N). Maximum fracture load was determined with a loading angle of 45°. Statistical analysis was performed by use of Kaplan-Meier modelling, Student's t-tests, one-way anova, post hoc Tukey's HSD tests and linear regression analysis. Regarding mean fracture load without ageing, the indirect restorations outperformed composite (design 1: direct: 508 ± 123 N, indirect: 741 ± 248 N; design 2: direct: 554 ± 167 N, indirect: 903 ± 221 N). After artificial ageing, however, these differences were no longer significant (design 1: direct: 328 ± 189 N, indirect: 506 ± 352 N; design 2: direct 399 ± 208 N, indirect 577 ± 292 N). Instead, the fracture load of the aged composite restorations was comparable with that for zirconia (design 1) and cast metal (design 2) crowns. Fracture loads of direct composite restorations after artificial ageing might fulfil clinical requirements. | 25,155,353 | [
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Pim1 kinase is upregulated in glioblastoma multiforme and mediates tumor cell survival. | The current therapy for glioblastoma multiforme (GBM), the most aggressive and common primary brain tumor of adults, involves surgery and a combined radiochemotherapy that controls tumor progression only for a limited time window. Therefore, the identification of new molecular targets is highly necessary. Inhibition of kinases has become a standard of clinical oncology, and thus the oncogenic kinase Pim1 might represent a promising target for improvement of GBM therapy. Expression of Pim1 and associated signaling molecules was analyzed in human GBM samples, and the potential role of this kinase in patients' prognosis was evaluated. Furthermore, we analyzed the in vivo role of Pim1 in GBM cell growth in an orthotopic mouse model and examined the consequences of Pim1 inhibition in vitro to clarify underlying pathways. In comparison with normal brain, a strong upregulation of Pim1 was demonstrated in human GBM samples. Notably, patients with short overall survival showed a significantly higher Pim1 expression compared with GBM patients who lived longer than the median. In vitro experiments with GBM cells and analysis of patients' GBM samples suggest that Pim1 regulation is dependent on epidermal growth factor receptor. Furthermore, inhibition of Pim1 resulted in reduced cell viability accompanied by decreased cell numbers and increased apoptotic cells, as seen by elevated subG1 cell contents and caspase-3 and -9 activation, as well as modulation of several cell cycle or apoptosis regulatory proteins. Altogether, Pim1 could be a novel therapeutic target, which should be further analyzed to improve the outcome of patients with aggressive GBM. | 25,155,357 | [
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Serous neoplasms of the pancreas share many, but not all aspects of their microvascular and angiogenic profile with low-grade clear cell renal cell carcinomas. | Similarly to clear cell renal cell carcinomas (CCRCC), serous neoplasms (SN) of the pancreas frequently show inactivation of VHL gene, clear cell histology and abundant microvasculature. Data on the microvascular and angiogenic profile of SN are scarce. Aiming to examine further the striking resemblance of clear cell epithelial neoplasia in pancreas and kidney, we compared the microvascular profile and expression of pro-angiogenic factors in SN and in CCRCC using immunohistochemical stains. SN and CCRCC shared a predominance of differentiated blood vessels, scarcity of lymphatic vessels, presence of CD105 and claudin-5 in tumoral vessels, expression of vascular endothelial growth factor (VEGF)-A, cyclooxygenase-2 (COX-2), carbonic anhydrase IX in tumoral cells, and lack of VEGF-C in tumoral cells. In contrast to CCRCC, SN showed lower pericyte coverage of vessels, lower blood vessel endothelial cell proliferaction fraction, more pronounced VEGF receptor (VEGFR)-2 and glucose transporter-1 expression, higher inducible (iNOS) but lower endothelial nitric oxide synthase (eNOS) expression, as well as presence of VEGFR-3 and D2-40 expression in epithelial cells. In conclusion, we found a significant similarity but not equality of microvascular biology of SN and CCRCC. We recognized VEGFR-2, VEGFR-3, COX-2, iNOS, eNOS and D2-40 as new markers of epithelial cells of SN of the pancreas. | 25,155,377 | [
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Comparison of three ECG criteria for athlete pre-participation screening. | Controversy regarding adding the ECG to the evaluation of young athletes centers on the implications of false positives. Several guidelines have been published with recommendations for criteria to distinguish between ECG manifestations of training and markers of risk for cardiovascular (CV) sudden death. With an athlete dataset negative of any CV related abnormalities on follow-up, we applied three athlete screening criteria to identify the one with the lowest rate of abnormal variants. High school, college, and professional athletes underwent 12L ECGs as part of routine physicals. All ECGs were recorded and processed using CardeaScreen (Seattle, WA). The European (2010), Stanford (2011), and Seattle criteria (2013) were applied. From March 2011 to February 2013 1417 ECGs were collected. Mean age was 20±4years (14-35years), 36% female, 38.5% non-white (307 high school, 836 college and 284 professional). Rate of abnormal variants differed by criteria, predominately due to variation in interval thresholds for QT interval and QRS duration. There was a four-fold difference in abnormal variants between European and Seattle criteria (26% v 6%). The Seattle criterion was the most conservative resulting in 78% fewer abnormal variants than the European criteria. Variation was most evident with thresholds for QT prolongation, short QT interval, and intraventricular conduction delay. Continued research is needed to further understand normal training related adaptations and to improve modern ECG screening criteria for athletes. | 25,155,389 | [
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Improved survival in osteosarcoma patients with atypical low vascularization. | Osteosarcoma is considered a highly vascularized bone tumor with early metastatic dissemination through intratumoral blood vessels mostly into the lung. Novel targets for therapy such as tumor vascularization are highly warranted since little progress has been achieved in the last 30 years. However, proof of relevance for vascularization as a major prognostic parameter has been hampered by tumor heterogeneity, difficulty in detecting microvessels by immunohistochemistry, and small study cohorts. Most recently, we demonstrated that highly standardized whole-slide imaging could overcome these limitations (Kunz et al., PloS One 9(3):e90727, 2014). In this study, we applied this method to a multicenter cohort of 131 osteosarcoma patients to test osteosarcoma vascularization as a prognostic determinant. Computer-assisted whole-slide analysis, together with enzymatic epitope retrieval, was used for CD31-based microvessel quantification in 131 pretreatment formalin-fixed and paraffin-embedded biopsies from three bone tumor centers. Kaplan-Meier-estimated survival and chemoresponse were determined and multivariate analysis was performed. Conventional hot-spot-based microvessel density (MVD) determination was compared with whole-slide imaging. We detected high estimated overall (p ≤ 0.008) and relapse-free (p ≤ 0.004) survival in 25 % of osteosarcoma patients with low osteosarcoma vascularization in contrast to other patient groups. Furthermore, all patients with low osteosarcoma vascularization showed a good response to neoadjuvant chemotherapy. Comparison of conventional MVD determination with whole-slide imaging suggests false high quantification or even exclusion of samples with low osteosarcoma vascularization due to difficult CD31 detection in previous studies. Low intratumoral vascularization at the time of diagnosis is a strong predictor for prolonged survival and good response to neoadjuvant chemotherapy in osteosarcoma. | 25,155,396 | [
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The spectrum of β-thalassemia mutations in Hatay, Turkey: reporting three new mutations. | β-Thalassemia (β-thal) is an important health problem in Hatay, Southern Turkey, because of its high carrier frequency and the frequency of consanguinity. The aim of this study was to reveal the spectrum of β-thal mutations and to provide a foundation for prenatal genetic testing that will be a part of an effective prevention program for β-thal disease in Hatay. We determined the spectrum of β-thal mutations in 93 unrelated affected patients. Using a direct sequencing method, we identified a large number of β-thal mutations. We found different results from other parts of Turkey. A total of 16 different β-thal mutations were characterized in the parents. The most common mutations were: IVS-I-110 (G>A), IVS-I-6 (T>C), IVS-I-1 (G>A), frameshift codon (FSC) 8 (-AA), codon 39 (C>T) and IVS-II-745 (C>G). Since our region has seen many Syrian and Iraqi immigrants, we report that the prevalence of the thalassemia traits are different from other regions of Turkey. Our study demonstrates the spectrum of β-thal mutations in the Hatay region, and that there was great molecular heterogeneity. | 25,155,404 | [
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Do the intestinal microbiotas differ between paddlefish (Polyodon spathala) and bighead carp (Aristichthys nobilis) reared in the same pond? | A study was conducted to compare the intestinal microbial compositions of two fish species with similar feeding strategy; paddlefish (Polyodon spathala) and bighead carp (Aristichthys nobilis) reared in the same pond. Age-0 paddlefish and bighead carp with mean average body lengths of 43·39 ± 2·78 and 19·33 ± 3·68 cm, respectively, were reared with natural prey items in the same pond (20 m(2)). After 30 days of rearing, the intestinal microbiota of the two fish species was assessed by pyrosequencing of 16S rRNA genes. Interestingly, deviations were observed in the microbial communities of the two fish species according to the alpha- and beta-diversity measurements and detrended correspondence analysis (DCA). Shannon diversity (P = 0·015) and Pielou.evenness (P = 0·035) revealed significant lower diversity of the intestinal microbiota of paddlefish. Moreover, different core intestinal microbiota was noticed in the two fish species. Proteobacteria (57·3%), Firmicutes (11·9%), Fusobacteria (8·9%), Planctomycetes (7·3%), Actinobacteria (6·0%) and Verrucomicrobia (3·2%) were detected in bighead carp, while the dominant phyla in paddlefish intestines were Bacteroidetes (37·0%), Fusobacteria (35·1%), Firmicutes (14·8%) and Proteobacteria (12·6%). Our results revealed that the intestinal microbiota differed between paddlefish and bighead carp reared in the same pond when fed similar nature food. The potential host factors, such as the genetic background, gut histology and physiology are assumed to be involved in the intestinal bacterial compositions. Considering the similar feeding strategy of paddlefish and bighead carp, this study presents basic knowledge for evaluation of the importance of host factors (genetic background and gut anatomy) on intestinal microbial composition. | 25,155,438 | [
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Characterization of a chemically modified plant cell culture expressed human α-Galactosidase-A enzyme for treatment of Fabry disease. | Fabry disease is an X-linked recessive disorder caused by the loss of function of the lysosomal enzyme α-Galactosidase-A. Although two enzyme replacement therapies (ERTs) are commercially available, they may not effectively reverse some of the Fabry pathology. PRX-102 is a novel enzyme for the therapy of Fabry disease expressed in a BY2 Tobacco cell culture. PRX-102 is chemically modified, resulting in a cross-linked homo-dimer. We have characterized the in-vitro and in-vivo properties of PRX-102 and compared the results with the two commercially produced α-Galactosidase-A enzymes. Results show that PRX-102 has prolonged in-vitro stability in plasma, after 1h incubation it retains 30% activity compared with complete inactivation of the commercial enzymes. Under lysosomal-like conditions PRX-102 maintains over 80% activity following 10 days of incubation, while commercial enzymes become inactive after 2days. Pharmacokinetic profile of PRX-102 measured in male Fabry mice shows a 10 fold increase in t1/2 in mice (581min) compared to approved drugs. The enzyme has significantly different kinetic parameters to the alternative ERTs available (p-value<0.05, one way ANOVA), although these differences do not indicate any significant biochemical variations. PRX-102 is uptaken to primary human Fabry fibroblasts. The repeat administration of the enzyme to Fabry mice caused significant reduction (p-value<0.05) of Gb3 in various tissues (the measured residual content was 64% in kidney, liver was cleaned, 23% in heart, 5.7% in skin and 16.2% in spleen). PRX-102 has a relatively simple glycosylation pattern, characteristic to plants, having mainly tri-mannose structures with the addition of either α(1-3)-linked fucose or β(1-2)-linked xylose, or both, in addition to various high mannose structures, while agalsidase beta has a mixture of sialylated glycans in addition to high mannose structures. This study concludes that PRX-102 is equivalent in functionality to the current ERTs available, with superior stability and prolonged circulatory half-life. Therefore we propose that PRX-102 is a promising alternative for treatment of Fabry disease. | 25,155,442 | [
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Safety and efficacy of thrombopoietin-receptor agonists in myelodysplastic syndromes: a systematic review and meta-analysis of randomized controlled trials. | Thrombocytopenia is common (40-65%) and potentially serious in myelodysplastic syndromes (MDS). A systematic review was conducted to determine the safety and efficacy of adding a thrombopoietin-receptor (THPO-R) agonist to standard MDS treatment. MEDLINE, EMBASE and CENTRAL databases were searched. We included randomized controlled trials comparing a THPO-R agonist to placebo. A meta-analysis of the effects was performed. Endpoints included bleeding and platelet transfusion rates, risk of progression to acute myeloid leukaemia (AML) and mortality. Three hundred and eighty four patients from five trials were included, four using romiplostim and one using eltrombopag. Overall, the relative risk (RR) of bleeding with romiplostim versus placebo was 0·84 [95% confidence interval (CI): 0·57-1·24]. However, compared to placebo, romiplostim significantly decreased the exposure-adjusted bleeding rate (RR 0·92; 95% CI: 0·86-0·99), as well as the exposure-adjusted platelet transfusion rate (RR 0·69; 95% CI: 0·53-0·88). The RR of AML progression with romiplostim was 1·36 (95% CI: 0·54-3·40), however the outcome data were judged as higher risk of bias. Romiplostim is promising in its ability to decrease patient-important outcomes: bleeding and platelet transfusion need. Although the risk of AML progression was not increased, due to unclear risk of bias in the data, this safety concern is difficult to assess. Therefore, romiplostim cannot yet be routinely recommended. Early eltrombopag data is promising. | 25,155,450 | [
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Evaluating tumor metastatic potential by imaging intratumoral acidosis via pH-activatable near-infrared fluorescent probe. | Metastasis accounts for the vast majority of cancer deaths. To minimize metastasis-associated mortality, it is crucially important to evaluate the metastatic potential (M.P.), that is, defined as a tendency of a primary tumor to colonize a distant organ. Dysregulated pH in solid tumors, especially the acidification of extracellular pH (pHe ) promotes dormant metastasis by driving protease-mediated digestion, disrupting cell-matrix interaction and increasing migration of cancer cells. Therefore, imaging intratumoral acidosis creates a unique opportunity to evaluate the M.P. In this work, a novel pH activatable probe was developed, in which two near-infrared (NIR) fluorophores were conjugated via a flexible and acid liable linkage. While the fluorescence of this probe is quenched due to intramolecular dimeric aggregate under neutral environment, the cleavage of pH liable linkage with the concomitant disruption of aggregates in acidic tumor microenvironment results in a remarkable fluorescence enhancement. This probe not only visualized the primary tumors with high target to background (T/B) signal ratio in vivo, but also revealed the correlation between the M.P. and acidosis distribution pattern in tumor. While the acidosis locate dispersedly at tumor periphery in highly metastatic tumor, it distribute more widely in lowly metastatic tumor and the acidification degree increases substantially from the margin to core areas. This pH activatable NIR fluorescent probe holds the potential to evaluate the M.P., monitor the therapeutic response and predict the prognosis by delineating acidosis in tumors. | 25,155,456 | [
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0.09561937,
0.4413798,
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-0.2282426,
-0.1942092,
0.1954906,
-0.07417129,
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0.2328247,
0.3060394,
0.2941964,
0.2809042,
0.3133398,
-0.130822,
... |
The phylogenetic position of Kofoidia loriculata (Parabasalia) and its implications for the evolution of the Cristamonadea. | Kofoidia loriculata is a parabasalid symbiont inhabiting the hindgut of the lower termite Paraneotermes simplicicornis. It was initially described as a lophomonad due to its apical tuft of multiple flagella that disintegrate during cell division, but its phylogenetic relationships have not been investigated using molecular evidence. From single cell isolations, we sequenced the small subunit rRNA gene and determined that K. loriculata falls within the Cristamonadea, but is unrelated to other lophomonads. This analysis further demonstrates the polyphyly of the lophomonads and the necessity to re-assess the morphological and cellular evolution of the Cristamonadea. | 25,155,455 | [
0.2850047,
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0.1907696,
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0.04586703,
0.2485403,
-0.035... |
A surface with a biomimetic micropattern reduces colonization of Mycobacterium abscessus. | Nontuberculous mycobacteria (NTM) are ubiquitous organisms found in soil, water, and biofilms. Engineered surface topography has been proposed as a method to reduce microbial biofilm formation. The Sharklet(®) micropattern silicone surface has been shown to reduce biofilm formation of pyogenic bacteria. We hypothesized that this micropattern surface will also reduce colonization by Mycobacterium abscessus, a human pathogen. Smooth and micropattern silicone samples were incubated with 1 × 10(6) M. abscessus mL(-1) for 2 and 4 days. After processing to optimize recovery of adhered mycobacteria, there was a 75% and 50% reduction in the number of viable M. abscessus recovered from the micropattern surfaces compared to the smooth surfaces at 2 and 4 days after inoculation, respectively. Ziehl-Neelsen staining after measures to remove the adherent microorganisms revealed fewer residual M. abscessus on the micropattern samples as compared to smooth samples, validating the quantitative culture results. Microscopic observation of 2, 4, and 8 day M. abscessus cultures on micropattern samples showed that the organisms preferentially colonized within the channels between the rectangular features. In summary, a micropattern surface reduces the colonization of a pathogenic NTM. It remains to be seen whether this micropattern can reduce infections in humans. | 25,155,501 | [
0.1718239,
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0.1281296,
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0.1668553,
-0.228... |
Actin is required for IFT regulation in Chlamydomonas reinhardtii. | Assembly of cilia and flagella requires intraflagellar transport (IFT), a highly regulated kinesin-based transport system that moves cargo from the basal body to the tip of flagella [1]. The recruitment of IFT components to basal bodies is a function of flagellar length, with increased recruitment in rapidly growing short flagella [2]. The molecular pathways regulating IFT are largely a mystery. Because actin network disruption leads to changes in ciliary length and number, actin has been proposed to have a role in ciliary assembly. However, the mechanisms involved are unknown. In Chlamydomonas reinhardtii, conventional actin is found in both the cell body and the inner dynein arm complexes within flagella [3, 4]. Previous work showed that treating Chlamydomonas cells with the actin-depolymerizing compound cytochalasin D resulted in reversible flagellar shortening [5], but how actin is related to flagellar length or assembly remains unknown. Here we utilize small-molecule inhibitors and genetic mutants to analyze the role of actin dynamics in flagellar assembly in Chlamydomonas reinhardtii. We demonstrate that actin plays a role in IFT recruitment to basal bodies during flagellar elongation and that when actin is perturbed, the normal dependence of IFT recruitment on flagellar length is lost. We also find that actin is required for sufficient entry of IFT material into flagella during assembly. These same effects are recapitulated with a myosin inhibitor, suggesting that actin may act via myosin in a pathway by which flagellar assembly is regulated by flagellar length. | 25,155,506 | [
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0.2413913,
0.1352049,
-0.01643468,
... |
Decoupling physical from biological processes to assess the impact of viruses on a mesoscale algal bloom. | Phytoplankton blooms are ephemeral events of exceptionally high primary productivity that regulate the flux of carbon across marine food webs [1-3]. Quantification of bloom turnover [4] is limited by a fundamental difficulty to decouple between physical and biological processes as observed by ocean color satellite data. This limitation hinders the quantification of bloom demise and its regulation by biological processes [5, 6], which has important consequences on the efficiency of the biological pump of carbon to the deep ocean [7-9]. Here, we address this challenge and quantify algal blooms' turnover using a combination of satellite and in situ data, which allows identification of a relatively stable oceanic patch that is subject to little mixing with its surroundings. Using a newly developed multisatellite Lagrangian diagnostic, we decouple the contributions of physical and biological processes, allowing quantification of a complete life cycle of a mesoscale (∼10-100 km) bloom of coccolithophores in the North Atlantic, from exponential growth to its rapid demise. We estimate the amount of organic carbon produced during the bloom to be in the order of 24,000 tons, of which two-thirds were turned over within 1 week. Complimentary in situ measurements of the same patch area revealed high levels of specific viruses infecting coccolithophore cells, therefore pointing at the importance of viral infection as a possible mortality agent. Application of the newly developed satellite-based approaches opens the way for large-scale quantification of the impact of diverse environmental stresses on the fate of phytoplankton blooms and derived carbon in the ocean. | 25,155,511 | [
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0.372025,
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-0... |
Arabidopsis inositol pentakisphosphate 2-kinase, AtIPK1, is required for growth and modulates phosphate homeostasis at the transcriptional level. | Inositol hexakisphosphate (IP6 ) provides a phosphorous reservoir in plant seeds; in addition, along with its biosynthesis intermediates and derivatives, IP6 also plays important roles in diverse developmental and physiological processes. Disruption of the Arabidopsis inositol pentakisphosphate 2-kinase coding gene AtIPK1 was previously shown to reduce IP6 content in vegetative tissues and affect phosphate (Pi) sensing. Here we show that AtIPK1 is required for sustaining plant growth, as null mutants are non-viable. An incomplete loss-of-function mutant, atipk1-1, exhibited disturbed Pi homeostasis and overaccumulated Pi as a consequence of increased Pi uptake activity and root-to-shoot Pi translocation. The atipk1-1 mutants also showed a Pi deficiency-like root system architecture with reduced primary root and enhanced lateral root growth. Transcriptome analysis indicated that a subset of Pi starvation-responsive genes was transcriptionally perturbed in the atipk1-1 mutants and the expression of multiple genes involved in Pi uptake, allocation, and remobilization was increased. Genetic and transcriptional analyses suggest that disturbance of Pi homeostasis caused by atipk1 mutation involved components in addition to PHR1(-like) transcription factors. Notably, the transcriptional increase of a number of Pi starvation-responsive genes in the atipk1-1 mutants is correlated with the reduction of histone variant H2A.Z occupation in chromatin. The myo-inositol-1-phosphate synthase mutants, atmips1 and atmips2 with comparable reduction in vegetative IP6 to that in the atipk1-1 mutants did not overaccumulate Pi, suggesting that Pi homeostasis modulated by AtIPK1 is not solely attributable to IP6 level. This study reveals that AtIPK1 has important roles in growth and Pi homeostasis. | 25,155,524 | [
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0.1305475,
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0.3186394,
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0.2126641,
0.4416499,
-0.06964159,... |
Cancer survivors' uptake and adherence in diet and exercise intervention trials: an integrative data analysis. | The health benefits of diet and exercise interventions for cancer survivors are well documented. However, little is known regarding demographic and medical predictors of survivors' willingness to participate in diet and exercise intervention trials, study enrollment, intervention adherence, and study completion. To assist in interpreting the generalizability of trial findings and to improve the design of future trials, this study examined predictors of these process measures. An integrative data analysis was performed on data from 3 of the largest home-based diet and exercise intervention trials for cancer survivors (n = 23,841). Demographic and medical factors (ie, sex, race, age, time since diagnosis, and cancer type) were examined as predictors of willingness to participate, study enrollment, intervention adherence, and study completion in the pooled sample. A 99% confidence interval was used to determine statistical significance. Across trials, 11.1% of contacted survivors were willing to participate, and 5.7% were eligible and enrolled. Among enrollees, 53.4% demonstrated ≥75% adherence to the intervention, and 91.1% completed the study. Race (Caucasian vs others), age, time since diagnosis, and cancer type predicted survivors' willingness to participate (P < .01). All examined predictors were associated with the likelihood of study enrollment (P < .01). No significant predictors of intervention adherence or study completion were found among study enrollees (P ≥ .01). Cancer survivors' demographic and medical characteristics predicted their interest and participation in diet and exercise intervention trials. These findings have implications for the generalizability of results and can help to guide procedures used in future trials to enhance patient representation. | 25,155,573 | [
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0.1415528,
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0.1039702,
-0.1949543,
... |
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