title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Usage patterns of biomarkers in non-small-cell lung cancer patients in India: Findings from a systematic review and survey. | Personalized medicine has facilitated improved management of non-small cell lung cancer (NSCLC) patients by identifying predictive and prognostic biomarkers for enhanced efficiency of detection and efficacy of treatment. This systematic review and survey assessed the patterns of biomarker usage, molecular testing techniques to diagnose patients with NSCLC in India and testing techniques recommended by cancer societies. Studies were retrieved from Embase, PubMed, and Cochrane databases for the last 12 years, using relevant search strategies as per the Cochrane methodology for systematic reviews. Outcomes of interest were biomarkers for NSCLC, patterns of biomarker testing, diagnostic methods, guidelines and cost of biomarker testing. In all, 499 studies were identified for screening and 17 primary publications were included in the review. Epidermal growth factor receptor (EGFR) expression and epithelial markers (particularly cytokeratins (CK)) were the most commonly reported biomarkers (7/17) and immunohistochemical (IHC) staining was the most common technique for detection of biomarkers. The frequency of EGFR mutations was higher among women than men. Significantly elevated levels of CK-18 were observed in patients with squamous cell carcinoma and of CK-19 in patients with adenocarcinoma, squamous cell carcinoma, and NSCLC (P < 0.001). Prognostic or predictive role of cytokines and angiogenic markers as well as DNA expression were evaluated. The survey also showed that IHC was the most common technique for detection of biomarkers. This systematic review and survey provides valuable information on biomarker usage in the Indian population, and highlights the need for initiatives required for future biomarker testing in India. | 25,125,812 | [
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Primary synovial sarcoma of lung. | A synovial sarcoma (SS) is a rare form of cancer which usually occurs near the joints of the arm, neck, or leg, but has been documented in most human tissues and organs, including the brain, prostate, and heart. Primary pulmonary SS is an extremely rare tumor. We report a case of primary SS of lung who presented with severe chest pain and a large right lung mass with right-sided pleural effusion in computed tomography (CT) scan of thorax. The diagnosis was made on the basis of CT-guided core biopsy and immunohistochemistry. On immunohistochemistry, tumor cell expressed epithelial membrane antigen, bcl 2, Vimentin and smooth muscle actin and were immunonegative for S100 and cytokeratin. So, the final diagnosis was primary SS. | 25,125,819 | [
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Evaluation of fracture resistance of roots obturated with resilon and thermoplasticized gutta-percha: An in vitro study. | To investigate and compare the fracture resistance of resilon and realseal filled root canals with those that were obturated with thermoplasticized gutta-percha and AH-plus endodontic sealer. Eighty extracted human mandibular single-rooted premolars stored in 10% formalin were used in this study. They were prepared by using a crown-down technique, debrided and irrigated with NaOCl, EDTA, and normal saline and divided into four groups. Group I = Negative control, canals prepared but no obturation was done; Group II = Positive control obturated with dual cure composite resin; Group III = Obturated with thermoplasticized GP and AH-plus; Group IV = Obturated with resilon and realseal. All root specimens were stored for two weeks in 100% humidity to allow for complete setting of the sealer. Each specimen was mounted in acrylic in a polyvinyl ring and tested for fracture resistance with a universal testing machine. The loading fixture of the machine was mounted with its spherical tip aligned with the center of the access opening of each root. A vertical loading force was applied until it fractured the root. The force values were subjected to statistical analysis: Kruskall-Wallis H-test and Mann-Whitney U-test. Group comparison revealed that Group II (positive control) had significantly higher values of resistance to fracture as compared to all the other groups. While Group IV (resilon with realseal) had significantly higher values of resistance to fracture as compared to Group I (negative control). On the basis of our findings, it can be concluded that filling the root canals with resilon and realseal increased the in vitro resistance to fracture of single-canal extracted teeth. resilon and realseal demonstrated high fracture-resistance values and could be an alternative to the conventional gutta-percha. | 25,125,849 | [
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Comparison of surface abrasion produced on the enamel surface by a standard dentifrice using three different toothbrush bristle designs: A profilometric in vitro study. | The aim was to assess, in vitro, the effect on surface abrasivity of enamel surface caused by three different types (flat trim, zig-zag, bi-level) of toothbrush bristle design. Twenty-four freshly extracted, sound, human incisor teeth were collected for this study. The enamel slab was prepared, which were mounted, on separate acrylic bases followed by subjected to profilometric analysis. The surface roughness was measured using the profilometer. The specimen were divided into three groups, each group containing eight mounted specimens, wherein, Group 1 specimens were brushed with flat trim toothbrush; Group 2 brushed with zig-zag and Group 3 with bi-level bristle design. A commercially available dentifrice was used throughout the study. A single specimen was brushed for 2 times daily for 2 min period for 1 week using a customized brushing apparatus. The pre- and post-roughness value change were analyzed and recorded. Kruskal-Wallis test and Mann-Whitney U-test. The results showed that surface abrasion was produced on each specimen, in all the three groups, which were subjected to brushing cycle. However, the bi-level bristle design (350% increase in roughness, P = 0.021) and zig-zag bristle design (160% increase in roughness, P = 0.050) showed significantly higher surface abrasion when compared with flat trim bristle design toothbrush. Flat trim toothbrush bristle produces least surface abrasion and is relatively safe for use. | 25,125,852 | [
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Comparison of the cleaning efficacy of EndoVac with conventional irrigation needles in debris removal from root canal. An in-vivo study. | The aims were to evaluate the root canal debris removal after irrigation with EndoVac system and to compare its efficacy with Max-i-Probe needles. Fifteen matched pairs of single canalled vital teeth with mature apices indicated for extraction were selected. After working length determination and biomechanical preparation, the teeth in the right quadrant were irrigated with EndoVac system and with Max-i-Probe needles in the left quadrant using 3% NaOCl and 17% ethylenediaminetetraacetic acid. Teeth were extracted and marked at 1 and 3 mm from working length and decalcified in Kristenson's solution. Stained histologic slides were observed under trinocular research microscope. Wilcoxon signed-rank test was used for statistical analysis. The statistical significance was set at P < 0.05 and the analysis was performed using SPSS version 11.0 software. No statistical significant difference was found at 3 mm level between the groups. Group I had significantly less debris at 1 mm level. EndoVac performed better in removing debris from the apical thirds of root canals. | 25,125,853 | [
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Type II canal configuration and Type I Dens invaginatus. | The prevalent notion about maxillary central incisor with normal external morphology is a tooth with single root and root canal. A case in which all four maxillary incisors were having Type II canal configurations (Vertucci's classification) is reported, in addition, the lateral incisors revealed dens invaginatus with a Type I pattern as suggested by Ohler's classification and a large periapical lesion was seen in relation to the right lateral incisor. The diagnosis was confirmed with the aid of spiral computed tomography (CT) and canals obturated. Nonsurgical healing of the lesion was assessed by reviewing the case at prefixed intervals of time. | 25,125,855 | [
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Cone beam computed tomography evaluation and endodontic management of permanent mandibular second molar with four roots: A rare case report and literature review. | The morphological variation in the number of roots and root canals, especially in multi-rooted teeth is a constant challenge for diagnosis and successful endodontic therapy. Knowledge of the most common anatomic characteristics and their possible variations is fundamental. Although, endodontic management of four-rooted mandibular first molars have been observed on a few occasions in the literature, to the best of our knowledge four-rooted mandibular second molars having two mesial and two distal roots have not been reported. This paper highlights endodontic management of mandibular second molar with four roots (two mesial and two distal) with one canal in each root and its cone beam computed tomography (CBCT) evaluation which was primarily done for post treatment assessment for diagnosing post-endodontic complications, at the same time confirmed our radiographic diagnosis of this variation. This also helped us portraying the anatomy of this rare variation. | 25,125,856 | [
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Use of quartz fiber post for reattachment of complex crown root fractures: A 4-year follow-up. | Dental hard tissue trauma is among the most common cases encountered in dental practice. Simple tooth fractures, which occur due to sharp blows, are widely seen in all age groups, especially in young adults. If in case of complex fractures the fractured tooth fragments are available to the dentist in a clean and hydrated state, reattachment of the tooth fragment is the most conservative and biological treatment option possible. Cases of enamel and dentin fractures not involving pulp are treated by reattaching the fragment with adhesives and composite resin. However, fractures involving the pulp require reinforcement by quartz fiber posts and resin luting cement. In cases of fractures extending subgingivally, an envelope flap helps to achieve the desired isolation and visibility. This article presents 2 case reports of reattachment of fractured tooth fragments. The first case showing a 4-year success was treated without raising a flap. The second case with a subgingival fracture was treated by raising a flap. Reattachment is the most economical, biologically acceptable and esthetic restorative option for dental trauma. | 25,125,857 | [
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Poor health related quality of life among patients of sickle cell disease. | Sickle cell disease (SCD) is characterized by chronic hemolytic anemia and vascular occlusion, causing recurrent painful episodes, neuro-cognitive deficits, organ failures and death in early adulthood. Besides the medical consequences, most of the families with a child of SCD have to cope with financial and social crisis. Quality of life (QOL) is a broad multidimensional concept that usually includes subjective evaluations of both positive and negative aspects of life. Other than health; emotional well being, social dysfunction, chronic pain and fatigability are also important aspects of overall quality of life that add to the complexity of its measurement. The present case control study was designed to determine the health related quality of life (HRQoL) in patients of sickle cell disease and to compare it with patients of other chronic non-communicable diseases. Case control study conducted at tertiary health care facility of Central India. The present study conducted to measure HRQoL among patients of SCD and patients of other chronic non-communicable diseases. A translated and pretested version of WHO SF-36 questionnaire was used to measure HRQoL. We observed that there was significantly lower HRQoL among SCD patients. Besides merely pharmacotherapy, restoration of overall quality of life should be the mainstay of management of patients with SCD. | 25,125,865 | [
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Quality of life in cancer patients undergoing chemotherapy in a tertiary care center in malwa region of punjab. | The objective of this prospective, non-interventional, 4-month observational study was to analyze and compare patient-reported quality of life (QOL) and their physical/psychosocial symptom burden during their respective chemotherapy sessions. A prospective and descriptive study was carried out jointly by Pharmacology and Oncology Departments of a tertiary care center in Malwa region of Punjab. The data collection was performed by administering validated questionnaire/response after taking informed consent. A total of 131 cancer patients were recruited with the mean age of 49.05 ± 14.35 (SD (standard deviation)) years. As per the QOL scoring of Global Health Status (GHS) and four items of symptom scale, that is, insomnia, pain, appetite loss, and constipation, and financial difficulties attained a significance difference. GHS significantly improved in group three as compared to group one, indicating that the patient's overall health/QOL improved as the chemotherapy session progressed. Although QOL scoring system did not show significant improvement in all areas (except insomnia, pain, appetite loss, constipation, and financial difficulties) with reference to their respective chemotherapy cycles, but a judicious diagnosis with an appropriate treatment including chemotherapy may lessen the negative perception of cancer as a deadly and fatal disease in our rural population. | 25,125,867 | [
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Rubus fruticosus (blackberry) use as an herbal medicine. | Wild grown European blackberry Rubus fruticosus) plants are widespread in different parts of northern countries and have been extensively used in herbal medicine. The result show that European blackberry plants are used for herbal medicinal purpose such as antimicrobial, anticancer, antidysentery, antidiabetic, antidiarrheal, and also good antioxidant. Blackberry plant (R. fruticosus) contains tannins, gallic acid, villosin, and iron; fruit contains vitamin C, niacin (nicotinic acid), pectin, sugars, and anthocyanins and also contains of berries albumin, citric acid, malic acid, and pectin. Some selected physicochemical characteristics such as berry weight, protein, pH, total acidity, soluble solid, reducing sugar, vitamin C, total antioxidant capacity, antimicrobial screening of fruit, leaves, root, and stem of R. fruticosus, and total anthocyanins of four preselected wild grown European blackberry (R. fruticosus) fruits are investigated. Significant differences on most of the chemical content detect among the medicinal use. The highest protein content (2%), the genotypes with the antioxidant activity of standard butylated hydroxyanisole (BHA) studies 85.07%. Different cultivars grown in same location consistently show differences in antioxidant capacity. | 25,125,882 | [
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Value addition in sesame: A perspective on bioactive components for enhancing utility and profitability. | Sesame seed is a reservoir of nutritional components with numerous beneficial effects along with health promotion in humans. The bioactive components present in the seed include vital minerals, vitamins, phytosterols, polyunsaturated fatty acids, tocopherols and unique class of lignans such as sesamin and sesamolin. The presence of phenylpropanoid compounds namely lignans along with tocopherols and phytosterols provide defense mechanism against reactive oxygen species and increases keeping quality of oil by preventing oxidative rancidity. In this article, we have reviewed the nutraceutical, pharmacological, traditional and industrial value of sesame seeds with respect to bioactive components that hold high antioxidant value. Valuable information on superior functional components of sesame will strongly promote the use of sesame seeds in the daily diet world-wide. In spite of huge repertoire of sesame germplasm collection, limited research efforts on the use of conventional and biotechnological methodologies have resulted in minimal success in developing nutritionally superior cultivars. In consequence, value addition efforts in sesame would enable development of genotypes with high antioxidant activity and subsequently prevention of free radical related diseases. Modification of bioactive components in sesame would enable production of stabilized sesame oil with enhanced shelf life and better market value. | 25,125,886 | [
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Safety of latex urinary catheters for the short time drainage. | In this study, we attempt to identify the most appropriate catheter (silicone vs. latex) for short-term urinary catheterization. We compared the post-operative clinico-pathological complications between latex and silicone for short term catheterization in rabbits with hypospadias. Forty rabbits were used in our study to compare complications of catheterization. They were divided in two groups. Hypospadias like defect was created by a 1 cm long excision of the ventral urethra. For urethroplasty, we used tubularized incised plate technique. Latex and silicon catheters were used in groups 1 and 2, respectively. Post-operatively, routine laboratory urine test and complications (allergy, infection, bleeding) were compared in groups. A total of 40 rabbits underwent hypospadias repair. Findings showed that there were no significant differences between groups based on urine test indices (P = NS). Urinary tract infection rate was 10% (2 rabbits) in latex and 0% in silicone groups (P = NS). There were no significant differences between groups regarding of cystitis grades between study groups (P = NS). It seems that urinary tract catheterization with latex catheters is a safe, feasible, and in-expensive procedure for short-term post-operative course in hypospadias surgery in patients without latex hypersensitivity. | 25,125,890 | [
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Functional hyposplenism. | Functional hyposplenism is a condition accompanying many diseases such as sickle cell disease, celiac disease, alcoholic liver disease, hepatic cirrhosis, lymphomas and autoimmune disorders. It is characterised mostly by defective immune responses against infectious agents, especially encapsulated organisms, since the spleen is thought to play an important role in the production and maturation of B-memory lymphocytes and other substances like opsonins, both of which are considered crucial elements of the immune system for fighting infections. It is also associated with thrombocytosis, which might lead to thromboembolic events. Functional hyposplenism is diagnosed by the presence of Howell-Jolly bodies and pitted erythrocytes in the peripheral blood smear, and by nuclear imaging modalities such as spleen scintigraphy with the use of Technetium-99m and/or spleen scintigraphy with the use of heat-damaged Technetium-99m labeled erythrocytes. Severe infections accompanying functional hyposplenism can lead to the overwhelming post infection syndrome, which can often be fatal. Identifying patients with functional hyposplenism is important because simple measures such as vaccination against common infective microorganisms (e.g. Streptococcus pneumonia, Neisseria meningitides and Haemophilous influenzae) and antibiotic therapy when needed are considered beneficial in diminishing the frequency and gravity of the infections accompanying the syndrome. | 25,125,944 | [
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Effect of exhaust emissions on carbon monoxide levels in employees working at indoor car wash facilities. | Exhaust emissions from motor vehicles threaten the environment and human health. Carbon monoxide (CO) poisoning, especially the use of exhaust gas CO in suicidal attempts is well known in the literature. Recently, indoor car wash facilities established in large shopping malls with closed parking, lots is a new risk area that exposes car wash employees to prolonged periods of high level CO emissions from cars. The aim of this study was to investigate how carboxyhemoglobin (COHb) blood levels of employees get affected in confined areas with relatively poor air circulation. Twenty male volunteers working in indoor parking car wash facilities were included in the study. Participants were informed about the aim of this study and their consent was obtained. Their pulse COHb levels were measured twice, at the beginning and at the end of the working day using Rad-57 pulse CO-oximeter device, allowing non-invasive measurement of COHb blood levels to compare the changes in their COHb levels before and after work. The mean age of the male volunteers was 29.8 ± 11.9 (range 18-55). While the mean COHb levels measured at the start of the working day was 2.1 ± 2.0 (range 0-9), it was increased to 5.2 ± 3.3 (range 1-15) at the end of work shift (Wilcoxon test, p <0.001). There was a statistically significant difference in COHb levels between the beginning and the end of the work shift in smoker subjects, while the difference was not significant in the non-smoking group (Wilcoxon test, p=0.001, p=0.102, respectively). The COHb blood levels of indoor car wash facility employees is directly impacted and gets elevated by motor vechile exhaust emissions. For the health of the employees at indoor parking car wash facilities, stricter precautions are needed and the government should not give permit to such operations. | 25,125,950 | [
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Memory Decline in Peri- and Post-menopausal Women: The Potential of Mind-Body Medicine to Improve Cognitive Performance. | Cognitive decline is a frequent complaint during the menopause transition and among post-menopausal women. Changes in memory correspond with diminished estrogen production. Further, many peri- and post-menopausal women report sleep concerns, depression, and hot flashes, and these factors may contribute to cognitive decline. Hormone therapy can increase estrogen but is contraindicated for many women. Mind-body medicine has been shown to have beneficial effects on sleep, mood, and hot flashes, among post-menopausal women. Further, mind-body medicine holds potential in addressing symptoms of cognitive decline post-menopause. This study proposes an initial framework for how mind-body interventions may improve cognitive performance and inform future research seeking to identify the common and specific factors associated with mind-body medicine for addressing memory decline in peri- and post-menopausal women. It is our hope that this article will eventually lead to a more holistic and integrative approach to the treatment of cognitive deficits in peri- and post-menopausal women. | 25,125,972 | [
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Subcutaneously administered methotrexate for rheumatoid arthritis, by prefilled syringes versus prefilled pens: patient preference and comparison of the self-injection experience. | This multicenter, randomized, crossover study compared preference, ease of use, acceptability, satisfaction, and safety of repeated subcutaneous (SC) self-administrations with prefilled pens and prefilled syringes delivering methotrexate (MTX), in patients with rheumatoid arthritis (RA). The study (ClinicalTrials.gov number NCT01793259) enrolled 120 patients requiring initiation or intensification of MTX therapy for RA. Patients were randomized to receive the test drug, a prefilled pen (Metex(®) PEN/Metoject(®) PEN), or the reference drug, a prefilled syringe (Metex(®)/Metoject(®)), at doses of 15, 17.5, or 20 mg MTX SC once a week for 3 weeks. This was followed by receipt of the reference drug (prefilled syringe) or the test drug (prefilled pen) in a crossover design, with each patient serving as his/her own control. Questionnaires regarding patient preference, the Self-Injection Assessment Questionnaire (SIAQ), and diaries regarding local tolerability were used to document outcomes. Overall patient preference for the MTX prefilled pen was 75% (P<0.0001). In a six-item questionnaire, 73% to 76% of the patients preferred the prefilled pen in relation to use, acceptability, and satisfaction, and 67% of the patients confirmed that it did not take much effort to overcome SC self-injection with the pen. The SIAQ showed no clinical differences, in any domain scores, between both devices. Overall patient attitude towards self-injection at baseline was positive, as was patient experience with both devices during the study. As well, 92% of physicians and study nurses indicated that they would recommend the MTX prefilled pen to patients for future MTX treatment. The formulations were generally well tolerated. SC self-injection of MTX with a prefilled pen was generally preferred, by patients with RA, over a prefilled syringe with regard to use, acceptability, and satisfaction. This is supported by the strong appreciation of their attending study nurses and physicians, for its convenience. | 25,125,973 | [
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Influence of diet and obesity on COPD development and outcomes. | The global increase in the prevalence and incidence of obesity has called serious attention to this issue as a major public health concern. Obesity is associated with many chronic diseases, including cardiovascular disease and diabetes, and recently the role of overweight and obesity in lung disease has received new interest. Independently of obesity, diet also plays a role as a risk factor for many chronic diseases, and evidence is accumulating to support a role for diet in the prevention and management of several lung diseases. Chronic obstructive lung disease is the third-leading cause of death globally, and both obesity and diet appear to play roles in its pathophysiology. Obesity has been associated with decreased lung-function measures in population-based studies, with increased prevalence of several lung diseases and with compromised pulmonary function. In contrast, obesity has a protective effect against mortality in severe chronic obstructive pulmonary disease (COPD). Nutrient intake and dietary patterns have also been associated with lung-function measures and the development and progression of COPD. Taken together, this suggests that a focus on obesity and diet should be part of public health campaigns to reduce the burden of lung disease, and could have important implications for clinicians in the management of their patients. Future research should also focus on elucidating these relationships in diverse populations and age-groups, and on understanding the complex interaction between behavior, environment, and genetics in the development and progression of COPD. The goal of this article is to review current evidence regarding the role that obesity and diet play in the development of COPD, and in COPD-related outcomes. | 25,125,974 | [
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Serum cytokine profiling and enrichment analysis reveal the involvement of immunological and inflammatory pathways in stable patients with chronic obstructive pulmonary disease. | Chronic obstructive pulmonary disease (COPD) is a major global health problem. It results from chronic inflammation and causes irreversible airway damage. Levels of different serum cytokines could be surrogate biomarkers for inflammation and lung function in COPD. We aimed to determine the serum levels of different biomarkers in COPD patients, the association between cytokine levels and various prognostic parameters, and the key pathways/networks involved in stable COPD. In this study, serum levels of 48 cytokines were examined by multiplex assays in 30 subjects (control, n=9; COPD, n=21). Relationships between serum biomarkers and forced expiratory volume in 1 second, peak oxygen uptake, body mass index, dyspnea score, and smoking were assessed. Enrichment pathways and network analyses were implemented, using a list of cytokines showing differential expression between healthy controls and patients with COPD by Cytoscape and GeneGo Metacore™ software (Thomson-Reuters Corporation, New York, NY, USA). Concentrations of cutaneous T-cell attracting chemokine, eotaxin, hepatocyte growth factor, interleukin 6 (IL-6), IL-16, and stem cell factor are significantly higher in COPD patients compared with in control patients. Notably, this study identifies stem cell factor as a biomarker for COPD. Multiple regression analysis predicts that cutaneous T-cell-attracting chemokine, eotaxin, IL-6, and stem cell factor are inversely associated with forced expiratory volume in 1 second and peak oxygen uptake change, whereas smoking is related to eotaxin and hepatocyte growth factor changes. Enrichment pathways and network analyses reveal the potential involvement of specific inflammatory and immune process pathways in COPD. Identified network interaction and regulation of different cytokines would pave the way for deeper insight into mechanisms of the disease process. | 25,125,975 | [
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Improvement of quality and safety in health care as a new interprofessional learning module - evaluation from students. | Interprofessional teamwork is in many ways a norm in modern health care, and needs to be taught during professional education. This study is an evaluation of a newly introduced and mandatory learning module where students from different health profession programs used Improvement of Quality and Safety as a way to develop interprofessional competence in a real-life setting. The intention of this learning module was to integrate interprofessional teamwork within the students' basic education, and to give students a basic knowledge about Improvement of Quality and Safety. This report focuses on evaluations from the participating students (n=222), mainly medical and nursing students. To evaluate this new learning module, a questionnaire was developed and analyzed using a mixed methods design, integrating both qualitative and quantitative methods. The evaluation addressed learning concepts, learning objectives, and interprofessional and professional development. A majority of students responded positively to the learning module as a whole, but many were negative towards specific parts of the learning module and its implementation. Medical students and male students were less positive towards this learning module. Improvements and alterations were suggested. | 25,125,983 | [
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Pediatricians' perceptions of clinical practice guidelines. | Clinical practice guidelines (CPGs) are propositions for health care providers about the care of patients and are usually described as "systematically developed statements to assist practitioners' and patients' decisions about appropriate health care for specific circumstances". The purpose of this study was to investigate pediatricians' perceptions of clinical practice guidelines at Hamad Medical Corporation (HMC) in Qatar. A cross-sectional study was conducted at HMC between May 1 and August 31, 2013 using a self-administered questionnaire that was distributed to 240 pediatricians. A total of 169/240 questionnaires were completed for a response rate of 70.4%. Our main finding was that pediatricians at all levels are familiar with CPGs and use them. In addition, our doctors believe that CPGs lead to good quality of care, are practical, provide standardized patient care, will keep them up-to-date, decrease the rate of litigation, are evidence-based, do not restrict continuity of self-education, do not alter physician esteem, lead to improvement of outcome, and are practical. However, barriers that might impede pediatricians' use of CPGs are that CPGs affect their clinical judgment, do not match with their practice style, and do not reduce health care costs. Pediatricians at HMC have positive perceptions of CPGs. The results of our study suggest that CPGs are likely to be implemented if more counseling and education are provided to pediatricians regarding the usefulness of evidence-based guidelines. In addition, a program should be initialized to remove barriers while simultaneously addressing physicians' concerns. | 25,125,984 | [
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Use of frameless intrauterine devices and systems in young nulliparous and adolescent women: results of a multicenter study. | The purpose of this study was to provide additional data on the experience with frameless copper and levonorgestrel (LNG) intrauterine devices (IUDs) in nulliparous and adolescent women. Nulliparous and adolescent women, 25 years of age or younger, using the frameless copper IUD or the frameless LNG-releasing intrauterine system (IUS), were selected from previous studies and a current multicenter post-marketing study with the frameless copper IUD. The small copper-releasing GyneFix(®) 200 IUD consists of four copper cylinders, each 5 mm long and only 2.2 mm wide. The frameless FibroPlant(®) LNG-IUS consists of a fibrous delivery system releasing the hormone levonorgestrel (LNG-IUS). The main features of these intrauterine contraceptives are that they are frameless, flexible, and anchored to the fundus of the uterus. One hundred and fifty-four nulliparous and adolescent women participated in the combined study. One pregnancy occurred with the GyneFix 200 IUD after unnoticed early expulsion of the device (cumulative pregnancy rate 1.1 at one year). Two further expulsions were reported, one with the GyneFix 200 IUD and the other with the FibroPlant LNG-IUS. The cumulative expulsion rate at one year was 1.1 with the copper IUD and 2.2 with the LNG-IUS. The total discontinuation rate at one year was low (3.3 and 4.3 with the copper IUD and LNG-IUS, respectively) and resulted in a high rate of continuation of use at one year (96.7 with the copper IUD and 95.7 with the LNG-IUS, respectively). Continuation rates for both frameless copper IUD and frameless LNG-IUS remained high at 3 years (>90%). There were no cases of perforations or pelvic inflammatory disease reported during or following insertion. This report confirms earlier studies with frameless devices and suggests that the high user continuation rate is attributable to the optimal relationship between the IUD and the uterine cavity. IUD studies have shown that an IUD that does not fit well will often lead to side effects (ie, pain, bleeding, embedment, expulsion) and subsequent removal of the IUD. Early discontinuation is not the aim of long-acting reversible contraception. | 25,125,987 | [
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Prevalence and factors associated with congenital malformations in tirana, Albania, during 2011-2013. | Congenital Malformations (CMs) represent a challenge especially for developing countries. Data about CMs in Albania are rather scarce. In this context, our aim was to assess the prevalence and factors associated with CMs in Tirana, the capital of Albania. Information on all CMs at birth during 2011-2013 was retrieved from the National CM Surveillance System. For each CM case, three controls (babies born without CM) were retrieved as well. Overall, 831 cases and 2522 controls were included in this study. The prevalence was calculated using the total number of live births in Tirana during the same period. Binary logistic regression was used to determine the factors associated with CMs adjusting for a number of covariates. The three-year prevalence of CMs was 23.41 per 1,000 live births. The most affected body systems were the musculoskeletal, cardiovascular and genital systems. CMs were more prevalent among male babies. Advanced mothers' age, lower education, unemployment status and lower gestational age were all positively associated with increased likelihood of CMs. Socio-demographic factors of mothers are linked to CMs in Albania. Future surveys are needed in Albania in order to establish determinants of CMs at a national level. | 25,126,007 | [
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Effect of cigarette smoking in pregnancy on infants anthropometric characteristics. | The main goal of this research is to correlate anthropometric characteristics of newborns in pregnant women who consume cigarettes during pregnancy. The study was conducted at the Obstetrics Clinic of the Clinical Center, University of Sarajevo. The retrospective study covered a period of two years. Main inclusion criteria for the study was that pregnant women consume cigarettes during pregnancy. The research included respondents who had a singleton pregnancy, without pathological conditions that can affect the outcome and duration of pregnancy. At the Obstetrics Clinic, Clinical Center University of Sarajevo in the period from January 1, 2012 to December 31, 2013. In that period 393 pregnant women completed labor who in the personal history had data on smoking during pregnancy. Of the total number of subjects enrolled in this study 38.17% smoked up to 10 cigarettes a day, 33.08 % smoked up to 20 cigarettes a day, while up to 30 cigarettes per day smoked 28.75 % of respondents. There was a significant difference in the average values of all anthropometric parameters, in relation to the number of cigarettes consumed by the subjects during the day. We also found negative correlation in the average values of anthropometric measures and the number of cigarettes consumed (p <0.05). | 25,126,013 | [
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Effects of lipoic Acid on acrylamide induced testicular damage. | Acrylamide is very toxic to various organs and associated with significant increase of oxidative stress and depletion of antioxidants. Alpha-lipoic acid enhances cellular antioxidant defense capacity, thereby protecting cells from oxidative stress. This study aimed to evaluate the protective role of alpha-lipoic acid on the oxidative damage induced by acrylamide in testicular and epididymal tissues. Forty adult male rats were divided into four groups (10 rats each). Control group; acrylamide treated group administered acrylamide 0.05% (w/v) in drinking water for 21 days; alpha-lipoic acid group received basal diet supplemented with 1% alpha-lipoic acid and forth group was exposed to acrylamide and treated with alpha-lipoic acid at the same doses and treatment regimen mentioned before. The administration of acrylamide resulted in significant elevation in testicular and epididymal malondialdehyde level (MDA) and significant reduction in the level of reduced glutathione (GSH) and the activities of glutathione-S-transferase (GST), glutathione peroxidase (GPX) and glutathione reductase (GR). Also, acrylamide significantly reduced serum total testosterone and progesterone but increased estradiol (E2) levels. Treatment with alpha-lipoic acid prior to acrylamide induced protective effects and attenuated these biochemical changes. Alpha-lipoic acid has been shown to possess antioxidant properties offering promising efficacy against oxidative stress induced by acrylamide administration. | 25,126,019 | [
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Pathomechanisms in coenzyme q10-deficient human fibroblasts. | Primary coenzyme Q10 (CoQ10) deficiency is a rare mitochondrial disorder associated with 5 major clinical phenotypes: (1) encephalomyopathy, (2) severe infantile multisystemic disease, (3) cerebellar ataxia, (4) isolated myopathy, and (5) steroid-resistant nephrotic syndrome. Growth retardation, deafness and hearing loss have also been described in CoQ10-deficient patients. This heterogeneity in the clinical presentations suggests that multiple pathomechanisms may exist. To investigate the biochemical and molecular consequences of CoQ10 deficiency, different laboratories have studied cultures of skin fibroblasts from patients with CoQ10 deficiency. In this review, we summarize the results obtained in these studies over the last decade. | 25,126,049 | [
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Learning to perceive in the sensorimotor approach: Piaget's theory of equilibration interpreted dynamically. | if understanding is required for perception, how can we learn to perceive something new, something we do not yet understand? According to the sensorimotor approach, perception involves mastery of regular sensorimotor co-variations that depend on the agent and the environment, also known as the "laws" of sensorimotor contingencies (SMCs). In this sense, perception involves enacting relevant sensorimotor skills in each situation. It is important for this proposal that such skills can be learned and refined with experience and yet up to this date, the sensorimotor approach has had no explicit theory of perceptual learning. The situation is made more complex if we acknowledge the open-ended nature of human learning. In this paper we propose Piaget's theory of equilibration as a potential candidate to fulfill this role. This theory highlights the importance of intrinsic sensorimotor norms, in terms of the closure of sensorimotor schemes. It also explains how the equilibration of a sensorimotor organization faced with novelty or breakdowns proceeds by re-shaping pre-existing structures in coupling with dynamical regularities of the world. This way learning to perceive is guided by the equilibration of emerging forms of skillful coping with the world. We demonstrate the compatibility between Piaget's theory and the sensorimotor approach by providing a dynamical formalization of equilibration to give an explicit micro-genetic account of sensorimotor learning and, by extension, of how we learn to perceive. This allows us to draw important lessons in the form of general principles for open-ended sensorimotor learning, including the need for an intrinsic normative evaluation by the agent itself. We also explore implications of our micro-genetic account at the personal level. | 25,126,065 | [
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Pydpiper: a flexible toolkit for constructing novel registration pipelines. | Using neuroimaging technologies to elucidate the relationship between genotype and phenotype and brain and behavior will be a key contribution to biomedical research in the twenty-first century. Among the many methods for analyzing neuroimaging data, image registration deserves particular attention due to its wide range of applications. Finding strategies to register together many images and analyze the differences between them can be a challenge, particularly given that different experimental designs require different registration strategies. Moreover, writing software that can handle different types of image registration pipelines in a flexible, reusable and extensible way can be challenging. In response to this challenge, we have created Pydpiper, a neuroimaging registration toolkit written in Python. Pydpiper is an open-source, freely available software package that provides multiple modules for various image registration applications. Pydpiper offers five key innovations. Specifically: (1) a robust file handling class that allows access to outputs from all stages of registration at any point in the pipeline; (2) the ability of the framework to eliminate duplicate stages; (3) reusable, easy to subclass modules; (4) a development toolkit written for non-developers; (5) four complete applications that run complex image registration pipelines "out-of-the-box." In this paper, we will discuss both the general Pydpiper framework and the various ways in which component modules can be pieced together to easily create new registration pipelines. This will include a discussion of the core principles motivating code development and a comparison of Pydpiper with other available toolkits. We also provide a comprehensive, line-by-line example to orient users with limited programming knowledge and highlight some of the most useful features of Pydpiper. In addition, we will present the four current applications of the code. | 25,126,069 | [
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An intraductal papillary neoplasm of the bile duct at the duodenal papilla. | In recent years, the disease concept of intraductal papillary neoplasm of the bile duct (IPNB) has been attracting attention as a biliary lesion that is morphologically similar to intraductal papillary mucinous neoplasm (IPMN), which is considered to be a counterpart of IPMN. However, there are few reports on IPNB, and a consensus regarding the features of this disease is thus lacking. We experienced an extremely rare case of IPNB occurring in the bile duct at the duodenal papilla, which is a tumor presentation that has not previously been reported. Herein, we report this interesting case and discuss the possible association between IPMN and IPNB. | 25,126,070 | [
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A Prospective Phase I/II Study: Combination Chemotherapy with Docetaxel and Pemetrexed as Second-Line Treatment in Patients with Stage IIIB/IV Non-Small Cell Lung Cancer. | Two standard single-agent chemotherapy treatments (docetaxel and pemetrexed) were combined in this trial and administered as second-line treatment in patients with non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the safety and feasibility of combining docetaxel with pemetrexed. Six patients were enrolled between August 2007 and March 2009 with stage IIIB/IV NSCLC. The dose-escalation model included a pemetrexed infusion on day 1 of 200-300 mg/m(2) followed by infusion of docetaxel on days 1, 8 and 15 at doses from 20 to 30 mg/m(2). Primary study endpoints included efficacy and safety variables, also progression-free, overall and 1-year survival and time to progression. The study was abandoned due to adverse effects defined in the protocol. The major toxicities were all of grade 3 and included fatigue, stomatitis/mucositis, diarrhea and in one case, an episode of febrile neutropenia. Two patients died during the study, but not as a direct result of the treatment. We recommend that docetaxel or pemetrexed monotherapies should continue to be considered the standard second-line chemotherapy treatment against NSCLC. The results of this study warrant no further investigation into this particular combination treatment due to the severe toxicity effects encountered. | 25,126,073 | [
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Lithium suppresses Aβ pathology by inhibiting translation in an adult Drosophila model of Alzheimer's disease. | The greatest risk factor for Alzheimer's disease (AD) is age, and changes in the ageing nervous system are likely contributors to AD pathology. Amyloid beta (Aβ) accumulation, which occurs as a result of the amyloidogenic processing of amyloid precursor protein (APP), is thought to initiate the pathogenesis of AD, eventually leading to neuronal cell death. Previously, we developed an adult-onset Drosophila model of AD. Mutant Aβ42 accumulation led to increased mortality and neuronal dysfunction in the adult flies. Furthermore, we showed that lithium reduced Aβ42 protein, but not mRNA, and was able to rescue Aβ42-induced toxicity. In the current study, we investigated the mechanism/s by which lithium modulates Aβ42 protein levels and Aβ42 induced toxicity in the fly model. We found that lithium caused a reduction in protein synthesis in Drosophila and hence the level of Aβ42. At both the low and high doses tested, lithium rescued the locomotory defects induced by Aβ42, but it rescued lifespan only at lower doses, suggesting that long-term, high-dose lithium treatment may have induced toxicity. Lithium also down-regulated translation in the fission yeast Schizosaccharomyces pombe associated with increased chronological lifespan. Our data highlight a role for lithium and reduced protein synthesis as potential therapeutic targets for AD pathogenesis. | 25,126,078 | [
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The cortical microstructural basis of lateralized cognition: a review. | The presence of asymmetry in the human cerebral hemispheres is detectable at both the macroscopic and microscopic scales. The horizontal expansion of cortical surface during development (within individual brains), and across evolutionary time (between species), is largely due to the proliferation and spacing of the microscopic vertical columns of cells that form the cortex. In the asymmetric planum temporale (PT), minicolumn width asymmetry is associated with surface area asymmetry. Although the human minicolumn asymmetry is not large, it is estimated to account for a surface area asymmetry of approximately 9% of the region's size. Critically, this asymmetry of minicolumns is absent in the equivalent areas of the brains of other apes. The left-hemisphere dominance for processing speech is thought to depend, partly, on a bias for higher resolution processing across widely spaced minicolumns with less overlapping dendritic fields, whereas dense minicolumn spacing in the right hemisphere is associated with more overlapping, lower resolution, holistic processing. This concept refines the simple notion that a larger brain area is associated with dominance for a function and offers an alternative explanation associated with "processing type." This account is mechanistic in the sense that it offers a mechanism whereby asymmetrical components of structure are related to specific functional biases yielding testable predictions, rather than the generalization that "bigger is better" for any given function. Face processing provides a test case - it is the opposite of language, being dominant in the right hemisphere. Consistent with the bias for holistic, configural processing of faces, the minicolumns in the right-hemisphere fusiform gyrus are thinner than in the left hemisphere, which is associated with featural processing. Again, this asymmetry is not found in chimpanzees. The difference between hemispheres may also be seen in terms of processing speed, facilitated by asymmetric myelination of white matter tracts (Anderson et al., 1999 found that axons of the left posterior superior temporal lobe were more thickly myelinated). By cross-referencing the differences between the active fields of the two hemispheres, via tracts such as the corpus callosum, the relationship of local features to global features may be encoded. The emergent hierarchy of features within features is a recursive structure that may functionally contribute to generativity - the ability to perceive and express layers of structure and their relations to each other. The inference is that recursive generativity, an essential component of language, reflects an interaction between processing biases that may be traceable in the microstructure of the cerebral cortex. Minicolumn organization in the PT and the prefrontal cortex has been found to correlate with cognitive scores in humans. Altered minicolumn organization is also observed in neuropsychiatric disorders including autism and schizophrenia. Indeed, altered interhemispheric connections correlated with minicolumn asymmetry in schizophrenia may relate to language-processing anomalies that occur in the disorder. Schizophrenia is associated with over-interpretation of word meaning at the semantic level and over-interpretation of relevance at the level of pragmatic competence, whereas autism is associated with overly literal interpretation of word meaning and under-interpretation of social relevance at the pragmatic level. Both appear to emerge from a disruption of the ability to interpret layers of meaning and their relations to each other. This may be a consequence of disequilibrium in the processing of local and global features related to disorganization of minicolumnar units of processing. | 25,126,082 | [
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Automatic blastomere recognition from a single embryo image. | The number of blastomeres of human day 3 embryos is one of the most important criteria for evaluating embryo viability. However, due to the transparency and overlap of blastomeres, it is a challenge to recognize blastomeres automatically using a single embryo image. This study proposes an approach based on least square curve fitting (LSCF) for automatic blastomere recognition from a single image. First, combining edge detection, deletion of multiple connected points, and dilation and erosion, an effective preprocessing method was designed to obtain part of blastomere edges that were singly connected. Next, an automatic recognition method for blastomeres was proposed using least square circle fitting. This algorithm was tested on 381 embryo microscopic images obtained from the eight-cell period, and the results were compared with those provided by experts. Embryos were recognized with a 0 error rate occupancy of 21.59%, and the ratio of embryos in which the false recognition number was less than or equal to 2 was 83.16%. This experiment demonstrated that our method could efficiently and rapidly recognize the number of blastomeres from a single embryo image without the need to reconstruct the three-dimensional model of the blastomeres first; this method is simple and efficient. | 25,126,108 | [
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ProBLM web server: protein and membrane placement and orientation package. | The 3D structures of membrane proteins are typically determined without the presence of a lipid bilayer. For the purpose of studying the role of membranes on the wild type characteristics of the corresponding protein, determining the position and orientation of transmembrane proteins within a membrane environment is highly desirable. Here we report a geometry-based approach to automatically insert a membrane protein with a known 3D structure into pregenerated lipid bilayer membranes with various dimensions and lipid compositions or into a pseudomembrane. The pseudomembrane is built using the Protein Nano-Object Integrator which generates a parallelepiped of user-specified dimensions made up of pseudoatoms. The pseudomembrane allows for modeling the desolvation effects while avoiding plausible errors associated with wrongly assigned protein-lipid contacts. The method is implemented into a web server, the ProBLM server, which is freely available to the biophysical community. The web server allows the user to upload a protein coordinate file and any missing residues or heavy atoms are regenerated. ProBLM then creates a combined protein-membrane complex from the given membrane protein and bilayer lipid membrane or pseudomembrane. The user is given an option to manually refine the model by manipulating the position and orientation of the protein with respect to the membrane. | 25,126,110 | [
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Cerebral aspergilloma in a SLE patient: A case report with short literature review. | Aspergillosis of brain is very rare, and commonly seen in immunocompromised or immunosuppressed patient. Here, we report a cerebral aspergillosis condition in a late teen girl who is a Systemic Lupus Erythromatosis patient with steroid therapy. She developed headaches, vomitings, and convulsions. On the basis of clinical and neuroimaging, a diagnosis of cerebral tuberculoma was made, and she was put on anti-TB therapy, but she did not respond. Later, surgical partial excision biopsy confirmed the diagnosis. Her cerebral lesions responded with antifungal itraconazole therapy. The case will be presented with short literature review. Such a report in the literature is rare. | 25,126,119 | [
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Multicystic oligodendroglioma with calvarial destruction. | Calvarial erosion is known to occur with some superficially located tumors. Very few case reports of calvarial erosion associated with oligodendroglioma are reported in the literature, but calvarial destruction with oligodendroglioma is very rare. To report an unusual case of multicystic frontoparietal oligodendroglioma with destruction of the calvaria and scalp involvement in the absence of prior surgery or radiation. A 30-year-old male presented with the history of left focal seizure with secondary generalization for last three to four years along with left sided weakness for the past one month. There was history of slowly progressive decreased vision in both eyes leading to complete blindness in both eyes for the past one month. On neurological examination, patient had left hemiparesis of grade-2/5 with perception of light absent in both eyes. Fundus examination revealed bilateral optic atrophy. Magnetic resonance imaging (MRI) of the brain showed a large supratentorial heterogenous multicystic ring enhancing mass lesion involving right frontal lobe, right frontotemporal opercular region, and posteriorly abutting the central sulcus and anteriorly destroying the calvaria. Patient underwent right frontoparietal craniotomy and near total excision of tumor. Histopathological examination revealed oligodendroglioma WHO grade-2. Patient received postoperative chemoradiotherapy. At nine month follow-up patient neurological status was same and his seizure was controlled on single AED. There was no recurrence of seizure at nine month of follow-up. Calvarial destruction in association with extra and intra axial neoplasm should include oligodendroglioma especially in patients with long history of symptoms, although calvarial destruction is very rare. However, the final diagnosis is established by means of histopathological examination. | 25,126,125 | [
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Impact of emergency contraception status on unintended pregnancy: observational data from a women's health practice. | This study aimed to determine if nonprescription emergency contraception (EC) availability impacted self-reported unintended pregnancy rates and to assess women's knowledge and awareness of EC prior to and after nonprescription availability. A survey regarding contraception use and knowledge was verbally administered to a cross-sectional, convenience sample of 272 pregnant women receiving prenatal care at a large urban community women's clinic between August 2003 and October 2008. Statistical analyses determined the differences between two groups (before [BA] and after, [AA] non-prescription EC availability in the U.S. drug market) in terms of self-reported unintended pregnancy rates, knowledge and awareness of EC. The AA group reported higher incidence of unintended pregnancy when compared to the BA group (90.7% vs. 72.7%, P = 0.0172). The majority of both groups reported that they were not using any contraception at the time of conception (BA-84.4%; AA-83.3%). There was no significant difference in the participants' awareness of EC between the two groups (BA-46.8% vs. AA-43.0%) nor was there a significant difference between the two groups in the self-reported willingness to use EC in the future (BA-53.1% vs. AA-63.4%). However, among participants who were unaware of EC, 61% reported they would consider using it in the future after receiving brief EC counseling from a pharmacist or student pharmacist. Neither age nor pregnancy intention was associated with self-reported EC awareness but there was an association with income (P = 0.0410) and education (P = 0.0021). The change from prescription-only to non-prescription status of EC in the U.S. drug market did not impact the unintended pregnancy rate in this patient population. Lack of knowledge and awareness is still a major barrier to widespread EC use. | 25,126,137 | [
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Adherence policy, education and practice - an international perspective. | Nonadherence to chronic therapy has become a large burden on the healthcare system of many countries. Community pharmacists are well positioned to address nonadherence as part of their overall patient care activities, and contribute to patients' quality use of medicines. Between 2008 and 2010, a series of narrative, peer-reviewed articles were published in Pharmacy Practice which focused on community pharmacists' activities in medication adherence, specifically in the areas of the education they receive, their practice, the research conducted and national or local policies. This editorial aims to summarise the key findings presented in the series, and highlight the pertinent issues and gaps in the literature. There is a need to implement global and long-term objectives focussing on enhancing the quality of education and competencies of community pharmacists and the research conducted in medication adherence, to develop guidelines for pharmacists and enhance the uptake of adherence promoting services in routine care. | 25,126,142 | [
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Granulocyte colony-stimulating factor use in a large British hospital: comparison with published experience. | Granulocyte colony-stimulating factors (G-CSF) are high-cost agents recommended as prophylaxis of febrile neutropenia or as adjunctive treatment of severe neutropenic sepsis. Their use in high-risk situations such as acute myeloid leukaemia, acute lymphocytic leukaemia, myelodysplastic syndrome and stem cell transplantation is also indicated. This audit assessed the use of G-CSF within the Oncology and Haematology Service Delivery Unit at Guy's and St. Thomas' hospital (London, United Kingdom). Patients who received G-CSF in April-May 2008 were identified retrospectively from the pharmacy labelling system, and chemotherapy front sheets, clinic letters and transplantation protocols were reviewed. Patients on lenograstim, in clinical trials or under non-approved chemotherapy protocols were excluded. A total of 104 G-CSF treatments were assessed. The most commonly treated malignancy was breast cancer (41.3%), with docetaxel 100 mg/m (2) (34.6%) being the most frequent chemotherapy regimen. The chemotherapy intent was curative in 66.3 % of cases. Pegfilgrastim was used in 73.1 % of cases and primary prophylaxis was the most common indication (54.8%). Stem cell transplantation was the first indication to meet the audit criterion (93.3%), followed by primary prophylaxis (89.5%). There was a considerable nonadherence for secondary prophylaxis (6.7%). The overall level of compliance with the audit criteria was 72.1%. The results for primary and secondary prophylaxis would have been different if FEC100 (fluorouracil, epirubicin, cyclophosphamide) and docetaxel 100 mg/m (2) had been considered a single chemotherapy regimen. Also, the lack of access to medical notes may have affected the reliability of the results for 'therapeutic' use. | 25,126,143 | [
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Evaluation of a pharmacist-managed diabetes medication therapy adherence clinic. | Patient adherence to prescribed medication regimens is important in diabetes care to prevent or delay microvascular and macrovascular complications such as retinopathy, nephropathy and myocardial infarction. In Penang Hospital, Malaysia, pharmacists collaborate with physicians in diabetes care through a pharmacist-managed Diabetes Medication Therapy Adherence Clinic (DMTAC) in the Endocrine Clinic, in operation since 2006. To evaluate the effectiveness of the pharmacist-managed DMTAC program in improving glycaemic control, lipid parameters and patients' medication adherence. A retrospective study among patients enrolled in the DMTAC program was conducted between September 2007 and December 2008. Data was included from patients with a glycosylated haemoglobin (HbA1c) >8% and who had completed eight visits with the pharmacists. Medical records and DMTAC forms that provided patients' demographics, medication regimens, adherence and laboratory parameters as well as pharmacists' interventions were reviewed. HbA1c, fasting blood glucose (FBG), low-density lipoprotein cholesterol (LDL), triglycerides (TG) and high-density lipoprotein cholesterol (HDL) were evaluated. Documented data of patients' adherence to medication regimen [Modified Morisky Medication Adherence Score (MMMAS); high adherence if score >8, medium adherence if score 6 to <8 and low adherence if score <6] was also evaluated. A total of 43 patients (53.5% females; 46.5% Malays, 44.2% Chinese and 9.3% Indians) were included in the analysis. A mean reduction in HbA1c of 1.73% (p<0.001), mean reduction in FBG of 2.65mmol/l (p=0.01) and mean reduction in LDL cholesterol of 0.38mmol/l (p=0.007) were achieved. The difference in TG and HDL cholesterol were not significant. Patients' adherence to medication regimens improved significantly with an increase in the mean MMMAS score from 7.00 to 10.84 (p<0.001) after completion of the DMTAC program. The pharmacist-managed DMTAC program resulted in significant improvements in HbA1c, glucose and LDL cholesterol levels as well as medication adherence in patients with diabetes. | 25,126,149 | [
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Steering Fluorescence Emission with Metal-Dielectric-Metal Structures of Au, Ag and Al. | Directional control over fluorescence emission is important for improving the sensitivity of fluorescence based techniques. In recent years, plasmonic and photonic structures have shown great promise in shaping the spectral and spatial distribution of fluorescence, which otherwise is typically isotropic in nature and independent of the observation direction. In this work we have explored the potential of metal-dielectric-metal (MDM) structures composed of Au, Ag or Al in steering the fluorescence emission from various probes emitting in the NIR, Visible or UV/blue region. We show that depending on the optical properties of the metal and the thickness of the dielectric layer, the emission from randomly oriented fluorophores embedded within the MDM substrate is transformed into beaming emission normal to the substrate. Agreement of the observed angular emission patterns with reflectivity calculations reveals that the directional emission is due to the coupling of the fluorescence with the electromagnetic modes supported by the MDM structure. | 25,126,154 | [
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Oropharyngeal airway changes after rapid maxillary expansion: the state of the art. | The aim of this article is to elucidate the state of the art about how rapid maxillary expansion (RME) produces changes in the oropharyngeal airways in terms of CBCT (Cone Beam Computed Tomography) data during the growth period, according to the available literature. Electronic search was done from January 2009 to April 2014 on PubMed and Scopus databases; in addition manual search was conducted as well. According to keywords, seven papers were eligible for our purpose, but definitely five papers were selected in agreement with the inclusion/exclusion criteria. The current literature suggests that the potential relationship between RME and oropharyngeal airway changes is still unclear. In fact, although the pharyngeal airway changes after the rapid palatal expansion are evident clinically, current orthodontic literature does not provide conclusive evidence about the nature of this relationship. | 25,126,159 | [
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Combined effects of astragalus soup and persistent Taiji boxing on improving the immunity of elderly women. | To observe the combined effects of astragalus soup and persistent Taiji boxing on improving the immunity of women of advanced years. 120 elderly women lacking daily exercise were chosen as the study subjects. By using the table of random numbers, they were then divided into the control group and the experiment group, consisting of 60 each. The control group practiced Taiji boxing for 45 minutes twice a day. The experiment group did the same, and, in addition, took astragalus soup after each boxing. Indexes related to physical immunity of the two groups were observed and compared when they were first chosen, when the alternative treatment was applied three, six and twelve months later, respectively. The two groups demonstrated no significant differences in general data and research indexes when chosen (P > 0.05). Three months after the two groups were chosen and treated differently, the control group demonstrated no significant improvement while most indexes of the experiment group improved considerably (P > 0.05). After six months, the related indexes of both groups improved substantially (P < 0.05) and the improvement with the experiment was even clearer (P < 0.05). Twelve months later, the improvement with the experiment group was more noticeable (P < 0.01 or P < 0.05). In a relatively short period of three months, Taiji boxing produces no noticeable effect on the improvement of immunity in elderly women. However, when they resume the exercise for another three months and longer, Taiji boxing has a noticeable advantage and the effect is the most favorable when it is combined with astragalus soup. | 25,126,193 | [
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Pulmonary epithelioid hemangioendothelioma coexisting with pulmonary nodular amyloidosis: case discussion and review of the literature. | A 38-year-old female was found to have multiple bilateral lung nodules in a routine chest X-ray examination. Thoracoscopy was performed with biopsy of three nodules from the right lower lobe and Congo red staining showed typical amyloid pattern. Initial diagnosis of pulmonary nodular amyloidosis was made. However, one nodule in the right upper lobe enlarged as detected by follow-up CT scan. The patient underwent F-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET)/CT and a significant high FDG uptake in the largest nodule in right upper lobe was observed while the uptake was normal or mildly increased in the other nodules. Meanwhile, right hilar and mediastinal lymph nodes adenopathy was noted. Right upper lobe was resected by thoracotomy. Surprisingly, histopathological findings showed pulmonary epithelioid hemangioendothelioma (PEH) with metastasis of hilar and mediastinal lymph nodes. To our knowledge, this is the first described case of PEH coexisting with pulmonary nodular amyloidosis. | 25,126,197 | [
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The beneficial effect of melatonin in brain endothelial cells against oxygen-glucose deprivation followed by reperfusion-induced injury. | Melatonin has a cellular protective effect in cerebrovascular and neurodegenerative diseases. Protection of brain endothelial cells against hypoxia and oxidative stress is important for treatment of central nervous system (CNS) diseases, since brain endothelial cells constitute the blood brain barrier (BBB). In the present study, we investigated the protective effect of melatonin against oxygen-glucose deprivation, followed by reperfusion- (OGD/R-) induced injury, in bEnd.3 cells. The effect of melatonin was examined by western blot analysis, cell viability assays, measurement of intracellular reactive oxygen species (ROS), and immunocytochemistry (ICC). Our results showed that treatment with melatonin prevents cell death and degradation of tight junction protein in the setting of OGD/R-induced injury. In response to OGD/R injury of bEnd.3 cells, melatonin activates Akt, which promotes cell survival, and attenuates phosphorylation of JNK, which triggers apoptosis. Thus, melatonin protects bEnd.3 cells against OGD/R-induced injury. | 25,126,203 | [
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When novelty is not enough. | Neither orderly nor fully rational, the current healthcare environment is a mosaic of providers, products, services, and intermediaries delivering healthcare, regulatory, and other government institutions, and consumers. The information required for informed healthcare decisions for novel pharmaceutical interventions varies appreciably with the audience, the therapeutic area, and the stage of product development. In this environment, the viability of new product introductions can be heavily influenced by perceived value as well as by mechanistic novelty. Correspondingly, research and development activities can be influenced profoundly by the use of incentive-based formularies, prior authorization requirements, or systems of reimbursement that mandate a stream of evidence confirming clinical utility in the presence of therapeutic uncertainty (eg, Centers for Medicare & Medicaid Services, Coverage with Evidence Development). The economic impact of innovative technology on the healthcare system, as well as the effects on the individual patient, can become a significant variable that influences the extent of research activities from the bench to the physician-patient-payor interface. | 25,126,215 | [
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Evaluation and management of diabetes mellitus. | Diabetes mellitus is a major public health problem with tremendous medical and economic burdens. It is the seventh leading cause of death and the number one cause of end-stage renal disease, adult blindness, impotence, and nontraumatic lower-limb amputation in the United States. People with diabetes are 2 to 4 times more likely to suffer from stroke or from cardiovascular disease, and are twice as likely to die compared with age-matched individuals without diabetes. Diabetes cost the United States around $174 billion in 2007, $58 billion of which was related to disability, work loss, and early mortality. Although there is currently no known cure for diabetes, much progress has been made over the past 2 decades to improve the diagnosis and management of diabetes. Evidence has shown that applying aggressive interventions early can prevent or delay progression to microvascular complications that increase the mortality rate in diabetes. The authors review the guidelines for optimal evaluation of diabetes mellitus and discuss the current and emerging therapeutic options available in the United States. | 25,126,259 | [
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Economic Evaluation of Quality-of-Life Improvement with Second-Generation Antihistamines and Montelukast in Patients with Allergic Rhinitis. | Allergic rhinitis causes significant economic losses and substantial reductions in quality of life. Improving a patient's symptoms can therefore enhance the patient's quality of life. To measure the relative cost-effectiveness of prescription second-generation antihistamines (levocetirizine, desloratadine, and fexofenadine) and montelukast based on their impact on quality of life in patients with uncomplicated allergic rhinitis. A retrospective, cost-effectiveness model was constructed using 1-year costs to managed care payers and using the Rhinoconjunctivitis Quality of Life Questionnaire to measure the quality of life in patients taking prescription second-generation antihistamines or montelukast for the treatment of allergic rhinitis. Clinical trial results for levocetirizine, desloratadine, fexofenadine (brand and generic), or montelukast were combined as standardized mean differences to create a pooled effectiveness measure. The costs of prescription drugs and physician office visits for allergic rhinitis were used as direct costs measures. Sensitivity was assessed by a Monte Carlo simulation run 1000 times. All the drugs in the study showed significant improvement in quality of life, with levocetirizine showing the greatest improvement. The incremental cost-effectiveness of levocetirizine dominated montelukast (incremental cost-effective ratio, -1317; 95% confidence interval, -7471, -212). The incremental cost-effectiveness favored levocetirizine compared with desloratadine and branded fexofenadine. There are significant differences in the cost-effectiveness of various oral prescription agents with regard to improving quality of life of patients with allergic rhinitis. | 25,126,304 | [
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Engaging providers in medication adherence: a health plan case study. | Nonadherence to treatment regimens is a common, costly, and complex problem that is often overlooked in a busy primary care setting. The goals of this study were to raise providers' awareness of nonadherence among their patients, to identify the reasons for lack of adherence, and engage physicians in addressing these barriers. Five primary care practices agreed to participate. The project began in the fall of 2008 with a therapy gap analysis, using prescription drug data from the previous 18 months to identify nonadherent patients. Initially, 237 members were identified as potential nonadherent patients. Each practice was presented with the data related to its patients; the group then narrowed its sample using a chart review and/or patient outreach. Each practice had to determine the barriers to adherence, and was then asked to create action steps to improve patient adherence based on the group's unique results and the specific patient population. Barriers to adherence identified included prescription drug cost, multiple medications and dosing schedules, and patient as well as family level of understanding and acceptance of disease state. Each group gained an awareness of nonadherence as it related to their patients. For example, in the internal medicine practice, 33% (n = 17) of the patients reported stopping their medication because of cost. A common reason for poor adherence in the pediatric groups was that parents decided to stop their child's medication on weekends and in the summer, without a physician's recommendation. Using such feedback, each practice then developed its own methods to improve medication adherence within its patient population. Although the final numbers in this case study were small, the providers gained valuable insights regarding nonadherence in their practice. This study shows the importance of engaging providers in medication adherence as a way to improve this common problem. Making this universal issue a personal problem for providers is key to overcoming many of the adherence barriers. | 25,126,330 | [
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Strategies to prevent opioid misuse, abuse, and diversion that may also reduce the associated costs. | The use of prescription opioid drugs has the potential to lead to patient abuse of these medications, addiction, and diversion. Such an abuse is associated with increased costs because of excessive healthcare utilization. Finding ways to minimize the risk for abuse and addiction can enhance patient outcomes and reduce costs to patients and to payers. To review current strategies that may reduce the risk for misuse and abuse of opioid medications, which in turn can enhance patient outcomes and lower costs to health insurers and patients. Implementing approaches that will encourage the use of safe practices (universal precautions) in pain management by providers can reduce the risk for abuse and misuse associated with chronic pain medications, especially opioids. These approaches include, but are not limited to, extensive physician and patient education regarding these medications and their associated risks for abuse; the development of prescription monitoring programs to detect physician or pharmacy shopping; the detection of inappropriate prescribing and medical errors; the use of physician-patient contracts concerning opioid treatment; the requirement of presenting a photo identification to pick up an opioid prescription at the pharmacy; urine drug toxicology screening; provisions for safe disposal of unused opioids; referrals to pain and addiction specialists; and potentially encouraging the use of opioid formulations aimed at reducing abuse. Supporting such approaches by health insurers and educating providers and patients on the risks associated with chronic pain medications can help minimize the risk of prescription opioid abuse, addiction, and diversion; reduce health services utilization associated with opioid abuse; improve patient outcomes; and reduce overall costs. | 25,126,342 | [
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Obesity in the workplace: impact on cardiovascular disease, cost, and utilization of care. | In forecasting the future of cardiovascular disease (CVD), the American Heart Association calls for preventive strategies with particular attention to obesity. The association between obesity and CVD, including coronary artery disease (CAD) and diabetes, is well established. The rising prevalence of obesity in the workforce may have additional implications for employers and employees besides the demonstrated effects on absenteeism and workers' compensation. This study was undertaken to determine the impact of population obesity on care utilization and cost of cardiovascular conditions such as hypertension, CAD, and cerebrovascular disease (or stroke) in a large US population of employees engaged in a major corporate wellness program. Using data from a single large industrial employer across 29 geographically distinct worksites in the United States, 179,708 episodes of care from 2004 to 2007 for 10,853 employees were included. The population-based economic impact of obesity was calculated on the basis of the frequency of episodes of care per 1000 employees and on the amount eligible for payment per episode of care in US dollars. Data were obtained from a wellness program databases, episode of illness inventories, and pharmacy and medical claims. High and low prevalence rates of obesity, by obesity quartile, were used to create linear mixed models to examine associations with disease outcomes, while controlling for correlation within each worksite. Worksites with a high rate of obesity (ie, in the fourth quartile) had 348.4 more episodes of care of any kind per 1000 employees (P <.001), 38.6 more hypertension episodes of care per 1000 employees (P <.001), and 2.5 more cerebrovascular disease episodes of care per 1000 employees (P = .017) compared with worksites in the lower 3 quartiles. A worksite in the fourth obesity rate quartile had $223 greater cost per any kind of episode (P <.001), $169 greater cost per hypertension episode (P = .003), and $1620 more per CAD episode (P = .005) compared with worksites in the lower 3 quartiles. The overall economic impact per 1000 employees was calculated by combining episode frequency and eligible amount for payment per episode. For sites in the lower 3 quartiles of obesity, the eligible amount per 1000 employees for any kind of care was $4.01 million. However, for sites in the highest obesity quartile, the eligible amount for payment per 1000 employees was $5.26 million. This translates into $1250 greater cost per employee. Similar calculations were used to evaluate the effect of obesity on the amount eligible for payment per employee for hypertension, CAD, and cerebrovascular disease episodes, with an estimated $69, $89, and $8 greater cost, respectively, per employee. Worksites with greater obesity prevalence rates were associated with numerically more frequent and more expensive episodes of care than worksites with low obesity prevalence. | 25,126,355 | [
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Impact of Treatment by NCQA-Certified Physicians on Diabetes-Related Outcomes. | The National Committee for Quality Assurance supports high-quality care for patients through the Diabetes Recognition Program (DRP). The DRP recognizes physicians and practices that are providing high-quality diabetes care as determined by 10 key measures. To examine the impact of treatment by DRP-certified physicians compared with non-DRP-certified physicians on patient outcomes. This retrospective claims analysis was conducted from January 1, 2007, through November 30, 2007, using a large US database of approximately 14 million commercially insured members. Physicians with DRP certification (N = 1188) were identified and matched 1:1 to physicians without DRP certification based on physician specialty, location (state) of practice, size of potential patient population, and number of patients with type 2 diabetes treated by the physician. Patients were included if they had type 2 diabetes and had been treated by a physician in the DRP group (N = 3836) or in the comparison group (N = 4175). Primary outcomes were medication use, medical resource utilization, and expenditures. Per-patient per-year (PPPY) medical and pharmacy utilization measures were analyzed using Poisson regression; PPPY expenditures were estimated using a generalized linear model with gamma distribution. Multivariate analysis showed that patients treated by DRP-certified physicians had more postindex diabetes-related office visits (mean PPPY, 4.69 vs 4.44, respectively; P <.001) and outpatient visits (mean PPPY, 0.93 vs 0.85, respectively; P <.001) than patients treated by non-DRP-certified physicians, but fewer emergency department visits (mean PPPY, 0.04 vs 0.07, respectively; P <.001) and inpatient visits (mean PPPY, 0.08 vs 0.10, respectively; P = .02). Prescribing rates for oral antihyperglycemic drugs and statins were higher among DRP-certified physicians than non-DRP-certified physicians. Total diabetes-related healthcare expenditures were lower for patients with type 2 diabetes managed by DRP-certified physicians compared with those managed by non-DRP-certified physicians (mean PPPY, $3424 vs $4097, respectively; P = .03). Significant differences in oral antihyperglycemic and statin drug use, and diabetes-related emergency department and inpatient visits and expenditures, were observed in this study between DRP-certified and non-DRP-certified physicians, showing overall improved outcomes for patients managed by DRP-certified physicians. | 25,126,367 | [
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Sensitivity of medication use to formulary controls in medicare beneficiaries: a review of the literature. | Several studies have examined the impact of formulary management strategies on medication use in the elderly, but little has been done to synthesize the findings to determine whether the results show consistent trends. To summarize the effects of formulary controls (ie, tiered copays, step edits, prior authorization, and generic substitution) on medication use in the Medicare population to inform future Medicare Part D and other coverage decisions. This systematic review included research articles (found via PubMed, Google Scholar, and specific scientific journals) that evaluated the impact of drug coverage or cost-sharing on medication use in elderly (aged ≥65 years) Medicare beneficiaries. The impact of drug coverage was assessed by comparing patients with some drug coverage to those with no drug coverage or by comparing varying levels of drug coverage (eg, full coverage vs $1000 coverage or capped benefits vs noncapped benefits). Articles that were published before 1995, were not original empirical research, were published in languages other than English, or focused on populations other than Medicare beneficiaries were excluded. All studies selected were classified as positive, negative, or neutral based on the significance of the relationship (P <.05 or as otherwise specified) between the formulary control mechanism and the medication use, and on the direction of that relationship. Included were a total of 47 research articles (published between 1995 and 2009) that evaluated the impact of drug coverage or cost-sharing on medication use in Medicare beneficiaries. Overall, 24 studies examined the impact of the level of drug coverage on medication use; of these, 96% (N = 23) supported the association between better drug coverage (ie, branded and generic vs generic-only coverage, capped benefit vs noncapped benefit, supplemental drug insurance vs no supplemental drug insurance) or having some drug coverage and enhanced medication use. Furthermore, 84% (N = 16) of the 19 studies that examined the effect of cost-sharing on medication use demonstrated that decreased cost-sharing was significantly associated with improved medication use. Current evidence from the literature suggests that restricting drug coverage or increasing out-of-pocket expenses for Medicare beneficiaries may lead to decreased medication use in the elderly, with all its potential implications. | 25,126,370 | [
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Endothelial progenitor cells in cardiovascular diseases. | Endothelial dysfunction has been associated with the development of atherosclerosis and cardiovascular diseases. Adult endothelial progenitor cells (EPCs) are derived from hematopoietic stem cells and are capable of forming new blood vessels through a process of vasculogenesis. There are studies which report correlations between circulating EPCs and cardiovascular risk factors. There are also studies on how pharmacotherapies may influence levels of circulating EPCs. In this review, we discuss the potential role of endothelial progenitor cells as both diagnostic and prognostic biomarkers. In addition, we look at the interaction between cardiovascular pharmacotherapies and endothelial progenitor cells. We also discuss how EPCs can be used directly and indirectly as a therapeutic agent. Finally, we evaluate the challenges facing EPC research and how these may be overcome. | 25,126,384 | [
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Biological Targeting of Plasmonic Nanoparticles Improves Cellular Imaging via the Enhanced Scattering in the Aggregates Formed. | Gold nanoparticles (AuNPs) demonstrate great promise in biomedical applications due to their plasmonically enhanced imaging properties. When in close proximity, AuNPs plasmonic fields couple together, increasing their scattering cross-section due to the formation of hot spots, improving their imaging utility. In the present study, we modified the AuNPs surface with different peptides to target the nucleus and/or the cell as a whole, resulting in similar cellular uptake but different scattering intensities. Nuclear-targeted AuNPs showed the greatest scattering due to the formation of denser nanoparticle clusters (i.e., increased localization). We also obtained a dynamic profile of AuNP localization in living cells, indicating that nuclear localization is directly related to the number of nuclear-targeting peptides on the AuNP surface. Increased localization led to increased plasmonic field coupling, resulting in significantly higher scattering intensity. Thus, biochemical targeting of plasmonic nanoparticles to subcellular components is expected to lead to more resolved imaging of cellular processes. | 25,126,388 | [
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Benefits of healthy adipose tissue in the treatment of diabetes. | The major malfunction in diabetes mellitus is severe perturbation of glucose homeostasis caused by deficiency of insulin. Insulin deficiency is either absolute due to destruction or failure of pancreatic β cells, or relative due to decreased sensitivity of peripheral tissues to insulin. The primary lesion being related to insulin, treatments for diabetes focus on insulin replacement and/or increasing sensitivity to insulin. These therapies have their own limitations and complications, some of which can be life-threatening. For example, exogenous insulin administration can lead to fatal hypoglycemic episodes; islet/pancreas transplantation requires life-long immunosuppressive therapy; and anti-diabetic drugs have dangerous side effects including edema, heart failure and lactic acidosis. Thus the need remains for better safer long term treatments for diabetes. The ultimate goal in treating diabetes is to re-establish glucose homeostasis, preferably through endogenously generated hormones. Recent studies increasingly show that extra-pancreatic hormones, particularly those arising from adipose tissue, can compensate for insulin, or entirely replace the function of insulin under appropriate circumstances. Adipose tissue is a versatile endocrine organ that secretes a variety of hormones with far-reaching effects on overall metabolism. While unhealthy adipose tissue can exacerbate diabetes through limiting circulation and secreting of pro-inflammatory cytokines, healthy uninflamed adipose tissue secretes beneficial adipokines with hypoglycemic and anti-inflammatory properties, which can complement and/or compensate for the function of insulin. Administration of specific adipokines is known to alleviate both type 1 and 2 diabetes, and leptin mono-therapy is reported to reverse type 1 diabetes independent of insulin. Although specific adipokines may correct diabetes, administration of individual adipokines still carries risks similar to those of insulin monotherapy. Thus a better approach is to achieve glucose homeostasis with endogenously-generated adipokines through transplantation or regeneration of healthy adipose tissue. Our recent studies on mouse models show that type 1 diabetes can be reversed without insulin through subcutaneous transplantation of embryonic brown adipose tissue, which leads to replenishment of recipients' white adipose tissue; increase of a number of beneficial adipokines; and fast and long-lasting euglycemia. Insulin-independent glucose homeostasis is established through a combination of endogenously generated hormones arising from the transplant and/or newly-replenished white adipose tissue. Transplantation of healthy white adipose tissue is reported to alleviate type 2 diabetes in rodent models on several occasions, and increasing the content of endogenous brown adipose tissue is known to combat obesity and type 2 diabetes in both humans and animal models. While the underlying mechanisms are not fully documented, the beneficial effects of healthy adipose tissue in improving metabolism are increasingly reported, and are worthy of attention as a powerful tool in combating metabolic disease. | 25,126,390 | [
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Type 2 diabetes and cardiovascular disease: Have all risk factors the same strength? | Diabetes mellitus is a chronic condition that occurs when the body cannot produce enough or effectively use of insulin. Compared with individuals without diabetes, patients with type 2 diabetes mellitus have a considerably higher risk of cardiovascular morbidity and mortality, and are disproportionately affected by cardiovascular disease. Most of this excess risk is it associated with an augmented prevalence of well-known risk factors such as hypertension, dyslipidaemia and obesity in these patients. However the improved cardiovascular disease in type 2 diabetes mellitus patients can not be attributed solely to the higher prevalence of traditional risk factors. Therefore other non-traditional risk factors may be important in people with type 2 diabetes mellitus. Cardiovascular disease is increased in type 2 diabetes mellitus subjects due to a complex combination of various traditional and non-traditional risk factors that have an important role to play in the beginning and the evolution of atherosclerosis over its long natural history from endothelial function to clinical events. Many of these risk factors could be common history for both diabetes mellitus and cardiovascular disease, reinforcing the postulate that both disorders come independently from "common soil". The objective of this review is to highlight the weight of traditional and non-traditional risk factors for cardiovascular disease in the setting of type 2 diabetes mellitus and discuss their position in the pathogenesis of the excess cardiovascular disease mortality and morbidity in these patients. | 25,126,392 | [
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Domino effect of hypomagnesemia on the innate immunity of Crohn's disease patients. | Digestive diseases play major role in development and complications of other disorders including diabetes. For example, Crohn's disease (CD) is an inflammatory bowel disease associated with Mycobacterium avium subspecies paratuberculosis. The inflammation is a complex process that involves the activity of both innate and adaptive immune responses. CD lesions are primarily due to T cell response, however; innate immune response has a significant role in initiating its pathogenesis. Toll-like receptors and NOD-like receptors promote the activity of nuclear factor (NF)-κB pathway for cytokines production. This results in the production of high levels of tumor necrosis factor-α, interleukin (IL)-1β and IL-6. Moreover, intestinal inflammation of CD is related to increased activity of NMDA receptors and the release of substance P. Imbalanced magnesium homeostasis in CD is a frequent finding in CD, Diabetes and others. The loss of such a major mineral affects many physiological processes in the body including its role as an immunomodulator. This review aims to (1) describe the significance of hypomagnesemia in the release of pro-inflammatory mediators in CD; (2) demonstrate effects of magnesium on pathways like NF-κB; (3) address the role of hypomagnesemia in the activity of CD; and (4) examine possible future research to establish a standard magnesium supplementation strategy; helping patients with CD or other disorders to maintain a sustained remission. | 25,126,398 | [
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Ocular trauma from the "knockout game". | The "knockout game" is a new form of urban violence receiving much attention in local and national media. Apart from the obvious head trauma, eye injuries may be subtle and overlooked. This report brings awareness of potential eye damage with this type of assault. This report is of a young woman, victim of the knockout game, who sustained a submacular hemorrhage. Beyond a neurologic evaluation for anyone knocked unconscious following the knockout game, patients should be counseled regarding potential ocular injury and encouraged to seek eye care promptly should symptoms develop. | 25,126,433 | [
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Cecal endometriosis presenting as acute appendicitis. | The aim of our paper is to show the diagnosis of Coecal endometriosis as an infrequent reason of right iliac fossa pain. cecal endometriosis manifesting with right lower quadrant pain is difficult to diagnose, and it may even sometimes require laparotomy for diagnosis and treatment. We report here a case of cecal endometriosis causing clinically resembled acute appendicitis. In our patient, a diagnosis of cecal endometriosis was made postoperatively by microscopic examination of excised right colon, and the patient symptoms and general condition were improved after the surgery (open right hemicolectomy and ileocolic anastomosis). | 25,126,441 | [
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Zosteriform cutaneous leishmaniasis diagnosed with the help of dermoscopy. | Cutaneous leishmaniasis is usually easy to recognize; however, several atypical features exist, which may pose a diagnostic challenge. Here we report a 55-year-old female patient, who presented with an itchy and painful eruption localized in a dermatomal distribution along the right upper chest. Although the clinical appearance of the lesions suggested the diagnosis of herpes zoster, dermoscopic evaluation revealed erythema, hyperkeratosis, burst star whitish appearance and hairpin vessels, compatible with the diagnosis of cutaneous leishmaniasis. Indeed, leishmania amastigotes were detected by smear from the lesions. Zosteriform presentation of cutaneous leishmaniasis, as exemplified by our patient, is especially rare. In our case dermoscopy has proven to be an accessible and easy tool to diagnose such atypical presentation of cutaneous leishmaniasis, and dermatologists in endemic areas should be familiar with its typical dermoscopic features. | 25,126,460 | [
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Arthroscopic hip labral repair: the iberian suture technique. | Arthroscopic hip labral repair has beneficial short-term outcomes; however, debate exists regarding ideal surgical labral repair technique. This technical note presents an arthroscopic repair technique that uses intrasubstance labral suture passage to restore the chondrolabral interface. This "Iberian suture technique" allows for an anatomic repair while posing minimal risk of damage to the labral and chondral tissues. | 25,126,502 | [
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Chocolate consumption and prevalence of metabolic syndrome in the NHLBI Family Heart Study. | Previous studies have suggested that cocoa products, which are rich sources of flavonoids, may lower blood pressure, serum cholesterol, fasting blood glucose and improve endothelial function. However, it is unclear whether consumption of cocoa products including chocolate influences the risk of metabolic syndrome (MetS). In a cross-sectional design, we sought to examine the association between chocolate consumption and the prevalence of MetS. We studied 4098 participants from the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study aged 25-93 years. Chocolate consumption was assessed using a semi-quantitative food-frequency questionnaire. MetS was defined using the NCEP III criteria. Generalized estimating equations were used to estimate prevalence odds ratios of MetS according to frequency of chocolate intake. Of the 4098 participants (mean age 51.7 y) included in the analyses, 2206 (53.8%) were female. The prevalence of metabolic syndrome in our population was 30.2%. Compared with those who did not consume any chocolate, multivariate adjusted odds ratios (95% CI) for MetS were 1.26 (0.94, 1.69), 1.15 (0.85, 1.55), and 0.99 (0.66, 1.51) among women who reported chocolate consumption of 1-3 times/ month, 1-4 times/week, and 5+ times/week, respectively. Corresponding values for men were: 1.13 (0.82, 1.57), 1.02 (0.74, 1.39), and 1.21 (0.79, 1.85). These data do not support an association between chocolate intake and the prevalence of MetS in US adult men and women. | 25,126,517 | [
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Formulation and optimization of polymeric nanoparticles for intranasal delivery of lorazepam using Box-Behnken design: in vitro and in vivo evaluation. | The aim of the present study was to optimize lorazepam loaded PLGA nanoparticles (Lzp-PLGA-NPs) by investigating the effect of process variables on the response using Box-Behnken design. Effect of four independent factors, that is, polymer, surfactant, drug, and aqueous/organic ratio, was studied on two dependent responses, that is, z-average and % drug entrapment. Lzp-PLGA-NPs were successfully developed by nanoprecipitation method using PLGA as polymer, poloxamer as surfactant and acetone as organic phase. NPs were characterized for particle size, zeta potential, % drug entrapment, drug release behavior, TEM, and cell viability. Lzp-PLGA-NPs were characterized for drug polymer interaction using FTIR. The developed NPs showed nearly spherical shape with z-average 167-318 d·nm, PDI below 0.441, and -18.4 mV zeta potential with maximum % drug entrapment of 90.1%. In vitro drug release behavior followed Korsmeyer-Peppas model and showed initial burst release of 21.7 ± 1.3% with prolonged drug release of 69.5 ± 0.8% from optimized NPs up to 24 h. In vitro drug release data was found in agreement with ex vivo permeation data through sheep nasal mucosa. In vitro cell viability study on Vero cell line confirmed the safety of optimized NPs. Optimized Lzp-PLGA-NPs were radiolabelled with Technitium-99m for scintigraphy imaging and biodistribution studies in Sprague-Dawley rats to establish nose-to-brain pathway. | 25,126,544 | [
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Gaining the Upper Hand on Pulmonary Drug Delivery. | Asthma, Chronic Obstructive Pulmonary Disease (COPD) and Cystic Fibrosis (CF) are all pulmonary diseases which are characterized by chronic inflammation and an increase in mucus production. Excess mucus in the airways correlates with pathophysiology such as a decline in lung function and prolonged bacterial infections. New drugs to treat these chronic respiratory diseases are currently being developed and include both inhaled and orally administered compounds. Whilst oral drugs may be easier to administer, they are more prone to side-effects due to higher bioavailability. Inhaled compounds may show reduced bioavailability, but face their own unique challenges. For example, thick mucus in the respiratory tracts of asthma, CF and COPD patients can act as a physical barrier that impedes drug delivery. Mucus also contains a high number of enzymes and proteases that may degrade compounds before they reach their site of action. Furthermore, some classes of drugs are rapidly absorbed across the respiratory epithelia into systemic circulation, which may limit their duration of action and/or cause off-target effects. This review discusses some of the different treatment options that are currently available and the considerations that need to be taken into account to produce new therapies for the treatment of chronic respiratory diseases. | 25,126,589 | [
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Cytotoxic constituents from the rhizomes of Curcuma zedoaria. | Curcuma zedoaria also known as Temu putih is traditionally used in food preparations and treatment of various ailments including cancer. The cytotoxic activity of hexane, dichloromethane, ethyl acetate, methanol, and the methanol-soxhlet extracts of Curcuma zedoaria rhizomes was tested on two human cancer cell lines (Ca Ski and MCF-7) and a noncancer cell line (HUVEC) using MTT assay. Investigation on the chemical components in the hexane and dichloromethane fractions gave 19 compounds, namely, labda-8(17),12 diene-15,16 dial (1), dehydrocurdione (2), curcumenone (3), comosone II (4), curcumenol (5), procurcumenol (6), germacrone (7), zerumbone epoxide (8), zederone (9), 9-isopropylidene-2,6-dimethyl-11-oxatricyclo[6.2.1.0(1,5)]undec-6-en-8-ol (10), furanodiene (11), germacrone-4,5-epoxide (12), calcaratarin A (13), isoprocurcumenol (14), germacrone-1,10-epoxide (15), zerumin A (16), curcumanolide A (17), curcuzedoalide (18), and gweicurculactone (19). Compounds (1-19) were evaluated for their antiproliferative effect using MTT assay against four cancer cell lines (Ca Ski, MCF-7, PC-3, and HT-29). Curcumenone (3) and curcumenol (5) displayed strong antiproliferative activity (IC50 = 8.3 ± 1.0 and 9.3 ± 0.3 μg/mL, resp.) and were found to induce apoptotic cell death on MCF-7 cells using phase contrast and Hoechst 33342/PI double-staining assay. Thus, the present study provides basis for the ethnomedical application of Curcuma zedoaria in the treatment of breast cancer. | 25,126,594 | [
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Graphs and matroids weighted in a bounded incline algebra. | Firstly, for a graph weighted in a bounded incline algebra (or called a dioid), a longest path problem (LPP, for short) is presented, which can be considered the uniform approach to the famous shortest path problem, the widest path problem, and the most reliable path problem. The solutions for LPP and related algorithms are given. Secondly, for a matroid weighted in a linear matroid, the maximum independent set problem is studied. | 25,126,607 | [
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Treatment planning and dental rehabilitation of a periodontally compromised partially edentulous patient: a case report - Part I. | When planning a prosthetic rehabilitation of a periodontally compromised case, the clinician is often confronted with difficulties and dilemmas related to selecting the appropriate treatment modality that would provide a long-term longevity in terms of function and esthetics. In such cases, a correct diagnosis and prognosis of the intraoral situation supported by evidence-based dentistry is the basis for the establishment of a proper treatment strategy. In this two-part treatment planning series, a systematic approach of patient examination and prognosis of each tooth is presented. Furthermore, different removable and fixed treatment possibilities are described and the rationale governing the decision-making process is revealed. The execution of the final treatment plan as specified by the concept of comprehensive dental care is outlined and the final outcome is discussed according to the literature. | 25,126,619 | [
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Comparison of marginal fit of Lava CAD/CAM crown-copings with two finish lines. | Marginal fit is valued as one of the most important criteria for the clinical quality and success of all-ceramic crowns. The aim of this in vitro study was to investigate the marginal fit of Lava Zirconia crown-copings on chamfer and shoulder preparations. Two acrylic model teeth were selected to simulate the clinical preparations: one molar was prepared with a chamfer finish line (C) and one premolar was prepared with a rounded shoulder finish line (RS). Each resin model was duplicated 10 times using silicon-based impression material and poured in type IV dental stone for the fabrication of working dies. A total of 20 copings were divided into two groups (n = 10 for each finish line). Fifty measuring locations were chosen randomly along the margin on the dies and the gap width - vertical marginal discrepancy - was measured under a light microscope with a magnification of x100. Measurements were made without cementation. The mean marginal gap widths and standard deviations were calculated and a one-way analysis of variance (ANOVA) was performed for different types of preparations in order to detect differences (α = 0.05). The mean marginal gap was 30 ± 3 μm for the C group and 28 ± 4 μm for the RS group. The one-way ANOVA showed no statistical significant difference between the two groups (P = 0.23). Within the limitations of this study, the marginal discrepancies were all within the clinical acceptable standard set at 120 μm. Chamfer and shoulder preparations did not show differences regarding the gap dimension. Bur design is an easily selected parameter before natural tooth preparation. Both tested finish lines are able to help clinicians in obtaining acceptable marginal fit values for the investigated zirconia copings. | 25,126,621 | [
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Effect of Er,Cr:YSGG laser treatment on microshear bond strength of zirconia to resin cement before and after sintering. | To evaluate the effect of Er,Cr:YSGG laser treatment on microshear bond strength of zirconia to resin cement before and after sintering. Ninety pre-sintered yttrium-stabilized tetragonal zirconia specimens (4 × 3 × 2 mm) were divided into 6 groups (n = 15). In group C, sintered zirconia was not treated (control group). In groups AS2 and AS3, sintered zirconia blocks were irradiated by Er,Cr:YSGG using a power of 2 and 3 W, respectively. Groups PS2 and PS3 consisted of pre-sintered blocks conditioned by Er,Cr:YSGG at 2 and 3 W, respectively. In group AA, sintered zirconia was air abraded with 50-μm alumina powder. One block was made using the same preparations as mentioned above and was morphologically assessed by SEM. Microcylinders of Panavia F 2.0 were placed on the treated surface of the groups. Samples were incubated at 37°C and 98% humidity for 48 h and then subjected to microshear bond strength testing. The mode of failure was evaluated. Data were analyzed by one-way ANOVA and Tukey's HSD test (p < 0.05). There was a statistically significant difference between group AA and the others (p < 0.0001). A significant difference was also noted between groups AS3 and C (p = 0.031). Complete surface roughness was seen in group AA and the bond failure was mostly cohesive, while in laser-treated groups, the surfaces roughness was much lower vs other groups, and the mode of failure was mostly adhesive. Laser treatment of pre-sintered Y-TZP cannot be recommended for improving the bond. Although sandblasting of sintered Y-TZP yielded better results than the rest of the groups, 3 W power after sintering can also be effective in enhancing the bonding strength of resin cement to zirconia. | 25,126,623 | [
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An idiosyncratic post-traumatic tetrad: compound odontome, dentigerous cyst, impaction, and double-dilaceration. | This report describes the case of a 13-year-old patient who experienced traumatic intrusion of the primary maxillary right central incisor and subsequently suffered an atypical tetrad, comprising of an unerupted compound odontoma associated with a dentigerous cyst, and an impacted, doubly dilacerated permanent maxillary right central incisor; however, the high interconnectivity of the occurrence of four pathologies together is unusual has not previously been reported. The pathologies were detected 7 years after trauma; surgical removal of odontome along with the dentigerous cyst was performed, followed by orthodontic extrusion of the impacted double-dilacerated permanent central incisor. The 18-month follow-up shows no pathology, no gingival recession, and normal probing depth. | 25,126,633 | [
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Rhodium(II)-catalysed tandem aziridination and ring-opening: stereoselective synthesis of functionalised tetrahydrofurans. | Aziridines formed upon treatment of allylic carbamates and homoallylic sulfamates with Rh(II) carboxylate catalysts under oxidative conditions are trapped by suitably-disposed hydroxyl groups to give functionalised tetrahydrofurans. | 25,126,655 | [
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Complementarity of EIS and SPR to reveal specific and nonspecific binding when interrogating a model bioaffinity sensor; perspective offered by plasmonic based EIS. | The present work compares the responses of a model bioaffinity sensor based on a dielectric functionalization layer, in terms of specific and nonspecific binding, when interrogated simultaneously by Surface Plasmon Resonance (SPR), non-Faradaic Electrochemical Impedance Spectroscopy (EIS), and Plasmonic based-EIS (P-EIS). While biorecognition events triggered a sensitive SPR signal, the related EIS response was rather negligible. Contrarily, even a limited nonspecific adsorption onto the surface of the metallic electrode, allowed by the intrinsic imperfect compactness of the functionalization layers, was signaled by EIS and not by SPR. The source of this finding has been addressed from both theoretical and experimental perspectives, demonstrating that EIS signals are mainly sensitive to adsorptions that alter the current pathway through defects of the functionalization layer exposing the electrode. These observations are of importance for those developing biosensors analyzed by SPR, EIS, or the novel combination of the two methods (P-EIS). A possible application of the observed complementarity of the two methods, namely assessment of sample purity in respect to a target analyte is highlighted. Moreover, the possibility of false-positive EIS responses (determined by nonspecific binding) when assessing samples containing complex matrices or consisting of small molecular weight analytes is emphasized. | 25,126,676 | [
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Camouflage effects following resin infiltration of postorthodontic white-spot lesions in vivo: One-year follow-up. | To assess camouflage effects by concealment of postorthodontic white-spot lesions (WSLs) to sound adjacent enamel (SAE) achieved over 12 months with resin infiltration (Icon, DMG, Hamburg, Germany). Twenty subjects (trial teeth nteeth = 111) who had received resin infiltration treatment of noncavitated postorthodontic WSLs were contacted for a 1-year follow-up assessment of CIE-L*a*b* colors (T12). Color and lightness (CIE-L*a*b*) data for WSLs and SAE were compared to baseline data assessed before infiltration (T0) and those assessed after 6 months (T6), using a spectrophotometer. The target parameter was the difference between the summarized color and lightness values (ΔEWSL/SAE). Intergroup (WSL, SAE) and intertime comparisons (T0 vs T6, T12) were performed using paired t-tests at a significance level of α = 5%. Nine subjects (trial teeth nteeth = 49; male/female ratio 5/4; age range 13-19 years) were available at T12. After the highly significant reduction of ΔEWSL/SAE discrepancies between T0 and T6, analysis of 12-month records revealed color and lightness discrepancy of WSL vs SAE that was significantly decreased compared with baseline, indicating an assimilation of WSL color to SAE appearance after infiltration, while an additional reduction of discrepancies between T6 and T12 was not significant. As color and lightness characteristics of the Icon infiltrant as well as the esthetic camouflage effects achieved by WSL infiltration were not altered significantly or clinically relevant after 12 months, the method of resin infiltration can be recommended for an enduring esthetic improvement of postorthodontic WSL. | 25,126,675 | [
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Normative sweep frequency impedance measures in healthy neonates. | Diagnosing middle ear disorders in neonates is a challenging task for both audiologists and otolaryngologists. Although high-frequency (1000 Hz) tympanometry and acoustic stapedial reflex tests are useful in diagnosing middle ear problems in this age group, they do not provide information about the dynamics of the middle ear in terms of its resonance frequency (RF) and mobility. The sweep frequency impedance (SFI) test can provide this information, which may assist in the diagnosis of middle ear dysfunction in neonates. This study aimed to investigate the feasibility of testing neonates using the SFI technique, establish normative SFI data for RF and mobility of the middle ear in terms of changes in sound pressure level (∆SPL in dB), and describe the dynamics of the middle ear in healthy Australian neonates. A prospective sample of 100 neonates (58 males, 42 females) with a mean gestational age of 39.3 wk (SD = 1.3 wk; range = 38-42 wk), who passed all three tests, namely, automated auditory brainstem response, transient evoked otoacoustic emissions, and 1000 Hz tympanometry, were included in this study. A SFI research prototype was used to collect the data. First, the SPL in the ear canal was measured as a probe-tone frequency was swept from 100-2000 Hz with the ear canal static pressure held constant at 200 daPa. Then, this measurement was repeated with the static pressure reduced in 50 daPa steps to -200 daPa. Additional measurement was also performed at the static pressure, where the peak of the 1000 Hz tympanogram occurred. A graph showing the variation of SPL against frequency at all static pressures was plotted. From this graph, the RF and ∆SPL at tympanometric peak pressure (TPP) were determined. Descriptive statistics and an analysis of variance (ANOVA) were applied to the RF and ∆SPL data with gender and ear as independent variables. The results showed two resonance regions of the outer/middle ear with the high RF (mean = 1236 Hz; 90% range: 830-1518 Hz) being approximately equal to four times that of the low RF (mean = 287 Hz; 90% range = 209-420 Hz). The low RF was more easily identifiable than the high RF. The ∆SPL at the low RF (mean = 8.2 dB; 90% range = 3.4-13 dB) was greater than that at the high RF (mean = 5.0 dB; 90% range = 1.5-8.1 dB). There were no significant differences or interactions between genders and ears. The study showed that the SFI is a feasible test of middle ear function in neonates. The SFI results revealed two regions of resonance with the lower resonance (287 Hz) possibly related to the movements of the outer ear canal wall and higher resonance (1236 Hz) related to the resonance of the middle ear. The normative data developed in this study will be useful in evaluating outer and middle ear function in neonates. | 25,126,682 | [
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Catalyst design in oxidation chemistry; from KMnO4 to artificial metalloenzymes. | Oxidation reactions are an important part of the synthetic organic chemist's toolkit and continued advancements have, in many cases, resulted in high yields and selectivities. This review aims to give an overview of the current state-of-the-art in oxygenation reactions using both chemical and enzymatic processes, the design principles applied to date and a possible future in the direction of hybrid catalysts combining the best of chemical and natural design. | 25,126,712 | [
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Inhibitory effects of p-alkylaminophenol on melanogenesis. | Melanin protects the skin against ultraviolet (UV) rays. It is produced in excess by UV radiation, which causes skin disorders and pigmentation. Retinoic acid (RA) decreases the levels of epidermal melanin by suppressing the expression of melanogenic enzymes including tyrosinase, which is the rate-limiting enzyme in melanin synthesis. However, RA shows inflammatory effects on the skin. In an effort to develop potent inhibitors of melanin synthesis, new aminophenol derivatives were synthesized based on structure-activity relationship studies of N-(4-hydroxyphenyl)retinamide (1), a derivative of RA. We investigated the inhibitory effects of a series of aminophenols on melanogenesis using B16 melanoma cells. p-Decylaminophenol (3) was the most potent agent examined, showing significant inhibition of B16 tyrosinase activities at concentrations less than what was required to achieve a similar level of inhibition by the well-known tyrosinase inhibitor, kojic acid. Compound 3 decreased melanin content and inhibited protein and mRNA expression for the tyrosinase-related protein-1 (TRP-1). It also inhibited the microphthalmia-associated transcription factor (MITF), a master transcription factor in melanogenesis. Compound 3 suppressed MEK/ERK signal pathways involved in the activation and expression of MITF. The data indicate that 3 inhibits TRP-1 expression by decreasing MITF expression through suppressing MEK/ERK signal pathways. This results in the reduction of melanin in B16 cells. Compound 3 might be an alternative to RA as a potent inhibitor of melanogenesis. | 25,126,713 | [
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[Endovascular versus surgical treatment in subarachnoid haemorrhage: Cost analysis]. | To analyse costs of endovascular versus surgical treatment in 80 patients with aneurysmal subarachnoid haemorrhage (aSAH). We analysed data on 80 consecutive patients with aSAH between January 2010 and June 2011. Endovascular treatment was used in 57 patients and surgical in 23 patients. Demographic (gender and age) and clinical data (Hunt-Hess and Fisher scales), length of stay (ICU and ward) and results at 6 months (Glasgow outcome scale,[GOS]) were collected. Costs including stay, follow-up, complications and retreatments were calculated. Age was higher in the endovascular group (statistically significant). There were no differences between the 2 groups in Hunt-Hess and Fisher scales. Results at 6 months were also similar, although slightly better in the surgical group. Length of stay was longer in surgical patients, both in ICU (mean 1.4 days) and ward (1.7 days). Hospitalisation length was also related to age and Hunt-Hess and Fisher scales. Costs from embolisation devices, follow-up and retreatment (12% in this series) made final endovascular treatment 4.1% more expensive than surgical treatment (€35,835 versus €34,404). Endovascular procedure (including retreatments) was 110% more expensive than surgical treatment (€8,015 versus €3,817). There are no differences between the 2 treatments in terms of morbidity and mortality. Stability of surgical treatment was higher than that of endovascular, with better occlusion and lower retreatment rates. Endovascular treatment is more expensive in ruptured aneurysms, principally due to embolisation device costs, long-term follow-up and retreatments, in retreatments, in spite of shorter hospital stay. In incidental aneurysms, which usually need shorter hospitalisation, differences between the 2 treatments could be even larger. | 25,126,710 | [
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Mechanical compression insults induce nanoscale changes of membrane-skeleton arrangement which could cause apoptosis and necrosis in dorsal root ganglion neurons. | In a primary spinal cord injury, the amount of mechanical compression insult that the neurons experience is one of the most critical factors in determining the extent of the injury. The ultrastructural changes that neurons undergo when subjected to mechanical compression are largely unknown. In the present study, using a compression-driven instrument that can simulate mechanical compression insult, we applied mechanical compression stimulation at 0.3, 0.5, and 0.7 MPa to dorsal root ganglion (DRG) neurons for 10 min. Combined with atomic force microscopy, we investigated nanoscale changes in the membrane-skeleton, cytoskeleton alterations, and apoptosis induced by mechanical compression injury. The results indicated that mechanical compression injury leads to rearrangement of the membrane-skeleton compared with the control group. In addition, mechanical compression stimulation induced apoptosis and necrosis and also changed the distribution of the cytoskeleton in DRG neurons. Thus, the membrane-skeleton may play an important role in the response to mechanical insults in DRG neurons. Moreover, sudden insults caused by high mechanical compression, which is most likely conducted by the membrane-skeleton, may induce necrosis, apoptosis, and cytoskeletal alterations. | 25,126,715 | [
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HMGB1-dependent and -independent autophagy. | HMGB1 (high mobility group box 1) is a multifunctional, ubiquitous protein located inside and outside cells that plays a critical role in various physiological and pathological processes including cell development, differentiation, inflammation, immunity, metastasis, metabolism, and death. Increasing evidence demonstrates that HMGB1-dependent autophagy promotes chemotherapy resistance, sustains tumor metabolism requirements and T cell survival, prevents polyglutamine aggregates and excitotoxicity, and protects against endotoxemia, bacterial infection, and ischemia-reperfusion injury in vitro or in vivo. In contrast, HMGB1 may not be required for autophagy in some organs such as the liver and heart. Understanding HMGB1-dependent and -independent autophagy in more detail will provide insight into the integrated stress response and guide HMGB1-based therapeutic intervention. | 25,126,737 | [
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Positive doping results caused by the single-dose local injection of triamcinolone acetonide. | Triamcinolone acetonide (TA) is classified as an S9 glucocorticoid in the 2014 Prohibited List published by the World Anti-Doping Agency, which caused it to be prohibited in-competition when administered orally, intravenously, intramuscularly or rectally. The Minimum Required Performance Level (MRPL) for the detection and identification of glucocorticoids is 30 ng/mL. Other common local injection routes, such as intraarticular, intratendinous, or intrabursal injection, are not prohibited. The purpose of this study was to analyze the TA and triamcinolone (T) concentrations in urine after a single injection of TA in patients to determine if it would produce a positive result. This study was performed on 40 patients with sports injuries or joint pains. TA was administered locally (doses varied from 12 to 80 mg). Samples were extracted using a solid-phase extraction column, followed by hydrolysis and liquid extraction using diethyl ether. The elution solvents were collected and dried. The dried residue was reconstituted and assayed by performing liquid chromatography-tandem mass spectrometry (LC-MS/MS) in positive ionization mode using electrospray ionization and multiple-reaction monitoring as the acquisition mode. The results demonstrated that the concentrations of both TA and T in urine exceeded the MRPL (30 ng/mL) after a single local injection. We obtained positive results for TA in 25 patients, and a positive result for T in one patient. Furthermore, the metabolic situation of TA, a long-acting glucocorticoid, was not an exact linear model. The highest concentrations of TA and T appeared 1-4h after injection. This information could be useful for limiting the misuse of TA by athletes. We suggest that athletes be aware when using TA injections during a competition period and obtain approval for therapeutic use exemption prior to using TA. | 25,126,738 | [
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Single Si nanowire (diameter ≤ 100 nm) based polarization sensitive near-infrared photodetector with ultra-high responsivity. | We report the fabrication and optical response of boron-doped single silicon nanowire-based metal-semiconductor-metal photodetector. Typical single nanowire devices with diameter of ∼80-100 nm and electrode spacing of ∼1 μm were made using electron-beam lithography from nanowires, grown by a metal-assisted chemical etching process. A high responsivity, of the order of 10(4) A W(-1), was observed even at zero bias in a single nanowire photodetector with peak responsivity in the near-infrared region. The responsivity was found to increase with increasing bias and decreasing nanowire diameter. Finite element based optical simulation was proposed to explain the diameter dependent performance of a single nanowire. The observed photoresponse is sensitive to the polarization of exciting light source, allowing the device to act as a polarization-dependent near-infrared photodetector. | 25,126,742 | [
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Prevalence and predictors of mental disorders in intentionally and unintentionally injured emergency center patients. | Little is known about the prevalence and predictors of mental disorders among injured emergency center (EC) patients in low- and middle-income countries (LMICs). Patients presenting with either an intentional or unintentional injury were recruited (N = 200). Mental health, injury, and psychological trauma histories were assessed. Descriptive statistics and logistic regressions were conducted, and predictors of current mental disorder were identified. Diagnostic criteria for a current mental disorder, including substance use disorders, were met by 59.5% of the participants. Compared with those with an unintentional injury, the intentionally injured participants were more likely to be diagnosed with a current mental disorder (66.9% vs. 48.8%, p = .01). High frequencies of previous intentional injuries predicted for current mental disorder (OR = 1.46, 95% CI 1.08-1.98), whereas male gender and witnessed community violence predicted substance use disorder diagnoses. The findings indicate that injured EC patients, particularly those with intentional injuries, are at risk for mental disorders. Psychosocial interventions in the EC context can potentially make an important contribution in reducing the burden of mental disorders and injuries in LMICs. | 25,126,754 | [
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Lights, X-rays, oxygen! | Photosystem II uses metal ions to oxidize water to form O2. Two recent papers employ the new technique of serial femtosecond crystallography utilizing X-ray free-electron lasers and nanocrystals to obtain initial structures of intermediate states of photosystem II catalysis at the site of oxygen production. | 25,126,779 | [
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Regulation of insulin sensitivity by adiponectin and its receptors in response to physical exercise. | Adiponectin is an adipocyte-derived abundant plasma protein, also called Acrp30 (adipocyte complement-related protein), adipoQ, ApM1 (AdiPose Most abundant Gene transcript 1), or GBP28 (gelatin-binding protein-28). Insulin resistance is a primary contributing factor in the pathogenesis of type 2 diabetes. Adiponectin binds to adiponectin receptors AdipoR1 and AdipoR2, and exerts antidiabetic effects via activation of AMPK and PPAR-α pathways, respectively. In the same sense chronic exercise has been showed to induce numerous metabolic factors that can improve insulin resistance. It has been reported that physical exercise training increases adiponectin receptors, which may mediate the improvement of insulin resistance in response to exercise, which is the focus of the present review. | 25,126,860 | [
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The effect of a sexuality education programme among out- of- school adolescents in Lagos, Nigeria. | This study was conducted to assess the effect of a community based sexuality education programme on the sexual health knowledge and practices of out of school female adolescents. This Intervention study was conducted in two markets within Lagos, Nigeria. Representative samples of adolescents were interviewed on their sexual health knowledge and practices. An Education- entertainment programme provided sexuality education to adolescents in Mushin market only (intervention group) followed by post intervention surveys in Mushin market and Sangrouse market (control group). The pre and post intervention surveys were compared 6 months post intervention to detect any changes. Sexual health knowledge and behaviour was similar among respondents in both markets pre intervention. Post intervention, the sexual health knowledge of the respondents in the intervention site improved significantly. (p<0.05) Fewer adolescents initiated sex in the intervention site than in the control site and contraceptive use increased. However among the sexually active, there was no significant change in their condom use and number of sexual partners. Community based health education programmes can be used to provide effective sexuality education for out of school adolescents. Provision should be made by government and non-governmental organisations during adolescent reproductive health programming for sexuality education targeted at out of school adolescents. | 25,126,865 | [
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Chiral gold nanowires with Boerdijk-Coxeter-Bernal structure. | A Boerdijk-Coxeter-Bernal (BCB) helix is made of linearly stacked regular tetrahedra (tetrahelix). As such, it is chiral without nontrivial translational or rotational symmetries. We demonstrate here an example of the chiral BCB structure made of totally symmetrical gold atoms, created in nanowires by direct chemical synthesis. Detailed study by high-resolution electron microscopy illustrates their elegant chiral structure and the unique one-dimensional "pseudo-periodicity". The BCB-type atomic packing mode is proposed to be a result of the competition and compromise between the lattice and surface energy. | 25,126,894 | [
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Size-resolved deposition rates for ultrafine and submicrometer particles in a residential housing unit. | We estimated the size-resolved particle deposition rates for the ultrafine and submicrometer particles using a nonlinear regression method with unknown particle background concentrations during nonsourced period following a controlled sourced period in a well-mixed residential environment. A dynamic adjustment method in conjunction with the constant injection of tracer gas was used to maintain the air exchange rate at three target levels across the range of 0.61-1.24 air change per hour (ACH). Particle deposition was found to be highly size dependent with rates ranging from 0.68 ± 0.10 to 5.03 ± 0.20 h(-1) (mean ± s.e.). Our findings also suggest that the effect of air exchange on the particle deposition under enhanced air mixing was relatively small when compared to both the strong influence of size-dependent deposition mechanisms and the effects of mechanical air mixing by fans. Nonetheless, the significant association between air exchange and particle deposition rates for a few size categories indicated potential influence of air exchange on particle deposition. In the future, the proposed approach can be used to explore the separate or composite effects between air exchange and air mixing on particle deposition rates, which will contribute to improved assessment of human exposure to ultrafine and submicrometer particles. | 25,126,897 | [
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Single-photon transistor using a Förster resonance. | An all-optical transistor is a device in which a gate light pulse switches the transmission of a target light pulse with a gain above unity. The gain quantifies the change of the transmitted target photon number per incoming gate photon. We study the quantum limit of one incoming gate photon and observe a gain of 20. The gate pulse is stored as a Rydberg excitation in an ultracold gas. The transmission of the subsequent target pulse is suppressed by Rydberg blockade, which is enhanced by a Förster resonance. The detected target photons reveal in a single shot with a fidelity above 0.86 whether a Rydberg excitation was created during the gate pulse. The gain offers the possibility to distribute the transistor output to the inputs of many transistors, thus making complex computational tasks possible. | 25,126,919 | [
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Beam-energy dependence of charge separation along the magnetic field in Au+Au collisions at RHIC. | Local parity-odd domains are theorized to form inside a quark-gluon plasma which has been produced in high-energy heavy-ion collisions. The local parity-odd domains manifest themselves as charge separation along the magnetic field axis via the chiral magnetic effect. The experimental observation of charge separation has previously been reported for heavy-ion collisions at the top RHIC energies. In this Letter, we present the results of the beam-energy dependence of the charge correlations in Au+Au collisions at midrapidity for center-of-mass energies of 7.7, 11.5, 19.6, 27, 39, and 62.4 GeV from the STAR experiment. After background subtraction, the signal gradually reduces with decreased beam energy and tends to vanish by 7.7 GeV. This implies the dominance of hadronic interactions over partonic ones at lower collision energies. | 25,126,911 | [
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Time-reversal-symmetry breaking in turbulence. | In three-dimensional turbulent flows, the flux of energy from large to small scales breaks time symmetry. We show here that this irreversibility can be quantified by following the relative motion of several Lagrangian tracers. We find by analytical calculation, numerical analysis, and experimental observation that the existence of the energy flux implies that, at short times, two particles separate temporally slower forwards than backwards, and the difference between forward and backward dispersion grows as t^{3}. We also find the geometric deformation of material volumes, defined by four points spanning an initially regular tetrahedron, to show sensitivity to the time reversal with an effect growing linearly in t. We associate this with the structure of the strain rate in the flow. | 25,126,923 | [
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Brain networks during free viewing of complex erotic movie: new insights on psychogenic erectile dysfunction. | Psychogenic erectile dysfunction (ED) is defined as a male sexual dysfunction characterized by a persistent or recurrent inability to attain adequate penile erection due predominantly or exclusively to psychological or interpersonal factors. Previous fMRI studies were based on the common occurrence in the male sexual behaviour represented by the sexual arousal and penile erection related to viewing of erotic movies. However, there is no experimental evidence of altered brain networks in psychogenic ED patients (EDp). Some studies showed that fMRI activity collected during non sexual movie viewing can be analyzed in a reliable manner with independent component analysis (ICA) and that the resulting brain networks are consistent with previous resting state neuroimaging studies. In the present study, we investigated the modification of the brain networks in EDp compared to healthy controls (HC), using whole-brain fMRI during free viewing of an erotic video clip. Sixteen EDp and nineteen HC were recruited after RigiScan evaluation, psychiatric, and general medical evaluations. The performed ICA showed that visual network (VN), default-mode network (DMN), fronto-parietal network (FPN) and salience network (SN) were spatially consistent across EDp and HC. However, between-group differences in functional connectivity were observed in the DMN and in the SN. In the DMN, EDp showed decreased connectivity values in the inferior parietal lobes, posterior cingulate cortex and medial prefrontal cortex, whereas in the SN decreased and increased connectivity was observed in the right insula and in the anterior cingulate cortex respectively. The decreased levels of intrinsic functional connectivity principally involved the subsystem of DMN relevant for the self relevant mental simulation that concerns remembering of past experiences, thinking to the future and conceiving the viewpoint of the other's actions. Moreover, the between group differences in the SN nodes suggested a decreased recognition of autonomical and sexual arousal changes in EDp. | 25,126,947 | [
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A double-blind, placebo-controlled trial related to the effects of melatonin on oxidative stress and inflammatory parameters of obese women. | Obesity, the global epidemic health problem, results in chronic disorders. Melatonin supplementation may prevent the adverse health consequences of obesity. The aim of this study was to assess the effects of melatonin supplementation on inflammatory and oxidative stress parameters in obese women. In randomized, double-blind, placebo-controlled trial, 44 obese women were randomly assigned to melatonin (n=22) and placebo (n=22) groups. Subjects were supplemented with a daily dose of 6 mg melatonin or placebo with low calorie diet for 40 days. Serum TNF-α, IL-6, hsCRP, TAC, and MDA levels were assessed before and after intervention. In the melatonin group, mean serum TNF-α, IL-6, hsCRP, and MDA levels decreased significantly (p<0.05) from 3.52±0.72 pg/ml, 27.12±6.32 pg/ml, 2.54±0.49 mg/l, and 3.81±0.29 nmol/l to 1.73±0.07, 16.34±6.32, 1.67±0.27, and 2.79±0.29, respectively. Whilst in the placebo group the decrease in values were not statistically significant. Mean TAC level increased slightly (from 1.11±0.30 to 1.14±0.45 mmol/l) in the melatonin group whereas it decreased slightly (from 1.13±0.15 to 1.08±0.21 nmol/l) in the placebo group. Significant differences were observed only for TNF-α (p=0.02) and IL-6 (p=0.03) between the 2 study groups. Considering the improvements in inflammatory and oxidative stress factors in obese women, it seems that melatonin supplementation may provide beneficial effects in obesity treatment by ameliorating some of its complications. However, further studies are needed to make concise conclusions. | 25,126,957 | [
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Comprehensive approach to systemic sclerosis patients during pregnancy. | Systemic sclerosis (SSc) is a connective tissue disease that usually affects women, with a male:female ratio of 1:4-10. It was thought that there was a prohibitive risk of fatal complications in the pregnancies of patients with SSc. It is now known that the majority of these women undergo a normal progression of pregnancy if the right time is chosen and a close obstetric care is delivered. The obstetric risk will depend on the subtype and clinical stage of the disease, and the presence and severity of the internal organ involvement during the pregnancy. The management of these pregnancies should be provided in a specialized center, with a multidisciplinary team capable of identifying and promptly treating complications. Treatment should be limited to drugs with no teratogenic potential, except when renal crises or severe cardiovascular complications develop. | 25,126,963 | [
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A pharmacogenetics-based warfarin maintenance dosing algorithm from Northern Chinese patients. | Inconsistent associations with warfarin dose were observed in genetic variants except VKORC1 haplotype and CYP2C9*3 in Chinese people, and few studies on warfarin dose algorithm was performed in a large Chinese Han population lived in Northern China. Of 787 consenting patients with heart-valve replacements who were receiving long-term warfarin maintenance therapy, 20 related Single nucleotide polymorphisms were genotyped. Only VKORC1 and CYP2C9 SNPs were observed to be significantly associated with warfarin dose. In the derivation cohort (n = 551), warfarin dose variability was influenced, in decreasing order, by VKORC1 rs7294 (27.3%), CYP2C9*3(7.0%), body surface area(4.2%), age(2.7%), target INR(1.4%), CYP4F2 rs2108622 (0.7%), amiodarone use(0.6%), diabetes mellitus(0.6%), and digoxin use(0.5%), which account for 45.1% of the warfarin dose variability. In the validation cohort (n = 236), the actual maintenance dose was significantly correlated with predicted dose (r = 0.609, P<0.001). Our algorithm could improve the personalized management of warfarin use in Northern Chinese patients. | 25,126,975 | [
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0... |
Environmental sampling for Clostridium difficile on alcohol-based hand rub dispensers in an academic medical center. | Clostridum difficile is a gram-positive, spore-forming anaerobic bacillus that has substantial associated morbidity, mortality, and associated healthcare burdens. Clostridium difficile spores are not destroyed by alcohol. Alcohol gel dispensers are used commonly as the hand sanitization method of choice in hospitals. It is possible that gel dispensers are fomites for C. difficile. Thirty alcohol-based gel dispenser handles outside of rooms of patients with active C. difficile infection were sampled. The samples were assessed for C. difficile by both culture and polymerase chain reaction (PCR). The samples were also assessed for other organisms by culture. No C. difficile was cultured or detected by PCR on any of the gel dispensers. Coagulase-negative Staphyloccus spp., diptheroids, and Bacillus spp. were the organisms detected most commonly. At our institution, C. difficile is not present on alcohol-based gel dispensers, but other potentially pathogenis are. | 25,126,976 | [
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Activating PI3-kinase to dampen inflammation. | Diterpene derivatives of the natural product acanthoic acid have potent anti-inflammatory effects in vivo. In this issue of Chemistry & Biolgy, Través and colleagues report that the primary molecular mechanism of action of diterpenes structurally related to acanthoic acid is the direct activation of PI3-kinase signaling in macrophages, which in turn inhibits NF-κB activation and suppresses proinflammatory gene expression. | 25,126,986 | [
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Rehabilitating mutant GCase. | Gaucher's disease is a hereditary deficiency of the enzyme β-glucocerebrosidase (GCase) that is most commonly treated by enzyme replacement therapy. In this issue of Chemistry & Biology, Tan and colleagues search for alternative ways to rehabilitate mutant GCase by understanding how it interacts with the proteostasis network. | 25,126,987 | [
-0.2708744,
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0.06179012,
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0.2325916,
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ERdj3 is an endoplasmic reticulum degradation factor for mutant glucocerebrosidase variants linked to Gaucher's disease. | Gaucher's disease (GD) is caused by mutations that compromise β-glucocerebrosidase (GCase) folding in the endoplasmic reticulum (ER), leading to excessive degradation instead of trafficking, which results in insufficient lysosomal function. We hypothesized that ER GCase interacting proteins play critical roles in making quality control decisions, i.e., facilitating ER-associated degradation (ERAD) instead of folding and trafficking. Utilizing GCase immunoprecipitation followed by mass-spectrometry-based proteomics, we identified endogenous HeLa cell GCase protein interactors, including ERdj3, an ER resident Hsp40 not previously established to interact with GCase. Depleting ERdj3 reduced the rate of mutant GCase degradation in patient-derived fibroblasts, while increasing folding, trafficking, and function by directing GCase to the profolding ER calnexin pathway. Inhibiting ERdj3-mediated mutant GCase degradation while simultaneously enhancing calnexin-associated folding, by way of a diltiazem-mediated increase in ER Ca(2+) levels, yields a synergistic rescue of L444P GCase lysosomal function. Our findings suggest a combination therapeutic strategy for ameliorating GD. | 25,126,989 | [
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0.04438488,
0.3702387,
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Synthesis of antifungal vaccines by conjugation of β-1,2 trimannosides with T-cell peptides and covalent anchoring of neoglycopeptide to tetanus toxoid. | Selective strategies for the construction of novel three component glycoconjugate vaccines presenting Candida albicans cell wall glycan (β-1,2 mannoside) and polypeptide fragments on a tetanus toxoid carrier are described. The first of two conjugation strategies employed peptides bearing an N-terminal thiopropionyl residue for conjugation to a trisaccharide equipped with an acrylate linker and a C-terminal S-acetyl thioglycolyl moiety for subsequent linking of neoglycopeptide to bromoacetylated tetanus toxoid. Michael addition of acrylate trisaccharides to peptide thiol under mildly basic conditions gave a mixture of N- and C- terminal glyco-peptide thioethers. An adaptation of this strategy coordinated S-acyl protection with anticipated thioester exchange equilibria. This furnished a single chemically defined fully synthetic neoglycopeptide conjugate that could be anchored to a tetanus toxoid carrier and avoids the introduction of exogenous antigenic groups. The second strategy retained the N-terminal thiopropionyl residue but replaced the C-terminal S-acetate functionality with an azido group that allowed efficient, selective formation of neoglycopeptide thioethers and subsequent conjugation of these with propargylated tetanus toxoid, but introduced potentially antigenic triazole linkages. | 25,126,994 | [
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0.1596635,
0.3876252,
0.1964867,
-0.05215688,
-... |
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