Τετάρτη, 1 Μαρτίου 2017

Liver

Liver: The largest solid organ in the body, situated in the upper part of the abdomen on the right side. The liver has a multitude of important and complex functions, including to manufacture proteins, including albumin (to help maintain the volume of blood) and blood clotting factors; to synthesize, store, and process fats, including fatty acids (used for energy) and cholesterol; to metabolize and store carbohydrates (used as the source for the sugar in blood); to form and secrete bile that contains bile acids to aid in the intestinal absorption of fats and the fat-soluble vitamins A, D, E, and K; to eliminate, by metabolizing or secreting, the potentially harmful biochemical products produced by the body, such as bilirubin, from the breakdown of old red blood cells and ammonia from the breakdown of proteins; and to detoxify, by metabolizing and/or secreting, drugs, alcohol, and environmental toxins.



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Arthritis drug can block metabolic PTEN pathway

Mount Sinai researchers have discovered that a rheumatoid arthritis drug can block a metabolic pathway that occurs in tumours with a common cancer-causing gene mutation, offering a new possible therapy for aggressive cancers with few therapeutic options,...

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Newly discovered vulnerability in an aggressive breast cancer provides therapeutic target

Physicians currently have no targeted treatment options available for women diagnosed with an aggressive form of breast cancer known as triple-negative breast cancer (TNBC), leaving standard-of-care chemotherapies as a first line of defense against the...

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Absent tumour-suppressors allow melanoma to thwart immunotherapy

It’s what’s missing in the tumour genome, not what’s mutated, that thwarts  treatment  of metastatic melanoma with immune checkpoint blockade drugs, researchers at The University of Texas MD Anderson Cancer Center report in Science Translational...

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Effect of Macroanatomic Bone Type and Estrogen Loss on Osteocyte Lacunar Properties in Healthy Adult Women

Abstract

This is the first study to examine clinical human bone specimens by three-dimensional imaging to characterize osteocyte lacunar properties as a function of macroanatomic bone type and estrogen loss. We applied laboratory-based instrumentation [3D X-ray microscope (3DXRM), MicroXCT-200; Carl Zeiss/Xradia, Inc.] that reaches the same resolution as synchrotron microscopy. We used serial transiliac bone biopsy specimens to examine the effect of macroanatomic bone type and estrogen status on osteocyte lacunar properties. These properties include lacunar size (volume, axes lengths of the ellipsoidal lacunar voids), distribution (density, average near-neighbor lacunar distance), and shape factors (sphericity ratio, average eigenvalues, degree of equancy, elongation, and flatness) in both cortical and trabecular bone tissue. The lacunar properties (volume, surface area, density, near-neighbor distance, etc.) and the shape factors (E1, L1, L2, degree of equancy, degree of elongation) were different between cortical and trabecular bone regardless of estrogen status. In cortical bone and trabecular nodes, the lacunar void volume and surface area were either smaller or tended to be smaller in postmenopausal as compared to premenopausal women. The void volume-to-bone volume ratio of cortical bone showed declining trends with estrogen loss. While there were differences between trabecular and cortical bone tissue, the lacunar void sphericity ratio for trabecular struts shows decreasing trends in postmenopausal women. These data suggest that using 3DXRM can provide new insight into osteocyte lacunar properties in transiliac bone biopsies from patients with various skeletal disease/conditions and pharmaceutical treatments.



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Retrospective Study on the Impact of Adherence in Achieving Glycemic Goals in Type 2 Diabetes Mellitus Patients Receiving Canagliflozin

Abstract

Introduction

Adherence is poor among patients taking antihyperglycemic agents (AHAs) for type 2 diabetes mellitus (T2DM). Inadequate adherence has been linked to decreased glycemic control and increased healthcare costs and hospitalizations. We examined the impact of real-world adherence on glycemic control in T2DM patients treated with canagliflozin.

Methods

This retrospective study used US administrative claims data from commercial and Medicare Advantage healthcare enrollees. Study subjects were adult T2DM patients with baseline HbA1c ≥7.0% and a pharmacy claim for canagliflozin between April 01, 2013 and August 31, 2014. Outcomes included treatment patterns, HbA1c reductions and goal attainment, pharmacy costs, and patient characteristics. Adherence, measured by the proportion of days covered (PDC), was calculated as the number of days of canagliflozin availability divided by the length of the follow-up period. Results were analyzed overall and compared between patients who were highly adherent (HA) (PDC ≥0.8) versus less than highly adherent (LHA) (PDC <0.8).

Results

The study population included 2261 patients. At the end of follow-up, patients had an overall mean reduction in HbA1c of 0.97%. Those HA had larger reductions in HbA1c than those LHA (1.17% versus 0.73%, respectively, p < 0.001); 24.6% and 59.4% of patients achieved HbA1c goals of <7.0% and <8.0%, respectively. Highly adherent patients were more likely to achieve goals than those LHA. Less than highly adherent patients increased insulin use by 5.4% in the follow-up period, while HA patients decreased the use of most oral AHAs and had no change in insulin use.

Conclusions

Patients had an HbA1c reduction of 0.97% in the 12 months following the first canagliflozin fill. Highly adherent patients achieved a greater reduction in HbA1c at the end of the follow-up period and were more likely to reach HbA1c goals. Highly adherent patients also had reductions in the use of most oral AHAs, while LHA patients saw a small increase in insulin use.



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Deep Neuromuscular Blockade Improves Laparoscopic Surgical Conditions: A Randomized, Controlled Study

Abstract

Introduction

Sustained deep neuromuscular blockade (NMB) during laparoscopic surgery may facilitate optimal surgical conditions. This exploratory study assessed whether deep NMB improves surgical conditions and, in doing so, allows use of lower insufflation pressures during laparoscopic cholecystectomy. We further assessed whether use of low insufflation pressure improves patient pain scores after surgery.

Methods

This randomized, controlled, blinded study (NCT01728584) compared use of deep (1–2 post-tetanic-counts) or moderate (train-of-four ratio 10%) NMB, and lower (8 mmHg) or higher (12 mmHg; ‘standard’) insufflation pressure in a 2 × 2 factorial design. Primary endpoint was surgeon’s overall satisfaction with surgical conditions, rated at end of surgery using an 11-point numerical scale. Post-operative pain scores were also evaluated. Data were analyzed using analysis of covariance.

Results

Of 127 randomized patients, 120 had evaluable data for the primary endpoint. Surgeon’s score of overall satisfaction with surgical conditions was significantly higher with deep versus moderate NMB indicated by a least-square mean difference of 1.1 points (95% confidence interval 0.1–2.0; P = 0.026). Furthermore, strong evidence of an effect was observed for standard versus low pressure: least-square mean difference of 3.0 points (95% confidence interval 2.1–4.0; P < 0.001). No significant difference was observed in average pain scores within 24 h post-surgery for low versus standard pressure [0.17 (95% confidence interval −0.67 to +0.33); P = 0.494].

Conclusions

Although associated with significantly improved surgical conditions, deep NMB alone was insufficient to promote use of low insufflation pressure during laparoscopic cholecystectomy. Furthermore, low insufflation pressure did not result in reduced pain, compared with standard pressure.

Clinical Trial Registration: ClinicalTrials.gov identifier, NCT01728584.

Funding: Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.



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A Review of Minimally Invasive Strabismus Surgery (MISS): Is This the Way Forward?

Abstract

Minimally invasive surgery is rapidly becoming the norm in medicine, as it often leads to better outcomes and earlier rehabilitation. This article reviews the principles and different techniques employed to perform minimally invasive strabismus surgery (MISS). In these techniques, strabismus surgery is performed through keyhole openings, thus reducing the risk of postoperative corneal complications, minimizing postoperative discomfort, and better preserving muscle function. MISS can be used to perform all types of strabismus surgery, namely rectus muscle recessions, resections, plications, reoperations, retroequatorial myopexy, transpositions, oblique muscle recessions, or plications even in the presence of limited motility. Of note, ocular alignment outcomes with MISS versus more traditional techniques have not been compared in randomized trials. Consequently, more controlled evidence is still needed to better delineate the future role and value of MISS in clinical management.



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A modified intraoral and extraoral approach osteotomy for the prominent mandibular angle

A prominent mandibular angle (PMA) is a relatively common condition in Asians, and surgeons typically use the intraoral approach to treat it. However, the approach can have many drawbacks due to the limited operative field and view. The procedures of the osteotomy are not easily performed, and an exact resection is difficult. In addition, major complications can occur readily. This article presents a modified osteotomy method for the PMA that avoids these disadvantages and makes the procedure easier to execute.

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Correction of tuberous breast deformity: a retrospective study comparing lipofilling versus breast implant augmentation

Breast implants and more recently autologous fat grafting are the two most common treatments used to correct tuberous breast deformity (TBD). Post-surgical quality of life between the two techniques is not well demonstrated. The purpose of this study is to compare satisfaction and health-related quality of life in patients affected of TBD between these two techniques.All TBD patients operated between January 2008 and May 2015 were retrospectively identified and only those treated with implants or lipofilling were included.

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IJERPH, Vol. 14, Pages 246: “Looking over the Backyard Fence”: Householders and Mosquito Control

(1) Background: Vector-borne diseases are a significant public health problem in Western Australia. Mosquitoes are responsible for the transmission of a number of pathogens and may pose a serious nuisance problem. Prevention efforts in the State are multi-faceted and include physical, chemical, and cultural control methods for restricting mosquito breeding. This is less complex where breeding areas are located within public open spaces. In Australia’s developed urban areas, breeding sites are, however, frequently located within private residential landholdings, where the scope of public health officials to act is constrained by law and practicality. Consequently, mosquito prevention in these locations is predominantly the responsibility of the residents. This research addressed a gap, both in understanding the degree to which “backyard” mosquito breeding has the potential to contribute to local mosquito problems, and in assessing what residents “think and do” about mosquito control within their home environment. (2) Methods: The study was conducted in the Town of Bassendean, a metropolitan Local Government Area of Perth, Western Australia, in close proximity to two natural, productive mosquito breeding sites, namely Ashfield Flats and Bindaring Park. A total of 150 householders were randomly surveyed during the summer of 2015–2016, to gauge residents’ knowledge, attitudes, and practices (KAP (knowledge, attitudes, and practices) Survey) in regards to mosquitoes, their breeding and ecology, and avoidance or minimization strategies. The survey comprised nine questions covering residents’ knowledge (3 questions), attitudes (3 questions), and practices (3 questions), as well as additional questions regarding the basic demographics of the resident. Larvae were collected from backyard containers and reared to adults for species identification. A series of Encephalitis Vector Surveillance carbon dioxide (EVS CO2) traps were also deployed, to assess adult mosquito density and species composition. (3) Results: Aedes notoscriptus (Skuse), a known container-inhabiting species, accounted for just over 50% of all mosquitoes identified. Most residents were aware of mosquito-borne disease and its risk in their local area. While the majority (79%) of the sample correctly identified Ross River virus as the most common infection in WA, a significant gap in the general knowledge of residents in regards to mosquito biology and breeding habits, was noted. Furthermore, only 50% of residents reported using personal protective measures to reduce mosquito bites and only one in six residents undertook physical or chemical mosquito control around their home. Additionally, 60% of respondents believed that mosquito control was “a job for the council and the state government”, rather than for individual householders. (4) Conclusions: A significant gap in the knowledge of residents in the study area existed in regards to the general knowledge of mosquitoes and their breeding habits; types of treatments that could be employed within the home; and the residents’ responsibility for the management of mosquito breeding on their private property. A public education campaign has been deployed to educate the residents.

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Long-term outcomes of induction carboplatin and gemcitabine followed by concurrent radiotherapy with low-dose paclitaxel and gemcitabine for stage III non-small cell lung cancer

We report the long-term outcomes of 142 protocol and non-protocol patients with stage III non-small cell lung cancer who were treated with induction carboplatin and gemcitabine followed by chemo-radiation. In addition to having a favorable toxicity profile, this regimen appears to have similar clinical outcomes as those associated with immediate concurrent chemo-radiation.

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APPLE trial: Feasibility and activity of AZD9291 (osimertinib) treatment on Positive PLasma T790M in EGFR mutant NSCLC patients. EORTC 1613

APPLE is a randomized, open-label, multicenter, three-arm, phase II study in advanced, EGFR-mutant and EGFR TKI naïve NSCLC patients, to evaluate the best strategy for sequencing gefitinib and osimertinib.Advanced EGFR-mutant NSCLC patients, WHO Performance Status 0-2 who are EGFR tyrosine kinase inhibitors treatment-naïve and eligible to receive first-line treatment with EGFR TKI will be randomized to:• arm A: osimertinib until RECIST 1.1 progression• arm B: gefitinib until emergence of circulating tumour DNA (ctDNA) T790M positive status and then switch to osimertinib until RECIST 1.1 progression• arm C: gefitinib until RECIST 1.1 progression and then switch to osimertinib until second radiologic progressionIn all arms, plasmatic ctDNA T790M test will be performed by central laboratory at the Medical University of Gdansk (Poland) but will be applied as a predictive marker for making treatment decision only in arm B.

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Comparative analysis for diagnostic yield of small cell lung cancer by cytology and histology during the same bronchoscopic procedure

Forceps biopsy, bronchial brushing, and TBNA are the most common methods for diagnosis of SCLC during the same diagnostic bronchoscopic procedure. We have used a retrospective method to analyze the pathological results obtained by bronchoscopy in 140 patients and showed that diagnostic yield of SCLC by cytology of brushing and TBNA is superior to histology of HE and immunohistochemistry.

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A comprehensive analysis of programmed cell death ligand-1 expression with the clone SP142 antibody in non-small cell lung cancer patients

We examined PD-L1 expression in 499 surgically resected NSCLC patients using the clone SP142 and four different cut-off values. PD-L1 expression in NSCLC was shown to vary greatly according to different cut-off values, and to be associated with poor survival in NSCLC patients. This study might be a useful reference to understand the results of POPLAR and OAK studies.

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An Open-Label, Randomized, Controlled Phase II Study of Paclitaxel-Carboplatin Chemotherapy Plus Necitumumab versus Paclitaxel-Carboplatin Alone in First-Line Treatment of Patients With Stage IV Squamous Non-Small Cell Lung Cancer

This open-label, randomized, phase II study was intended to compare paclitaxel-carboplatin plus necitumumab versus paclitaxel-carboplatin alone for the first-line treatment of advanced squamous non-small cell lung cancer. Addition of necitumumab to chemotherapy resulted in an objective response rate of 48.9% versus 40.0% for chemotherapy alone. There were no unexpected safety concerns for an epidermal growth factor receptor monoclonal antibody.

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Huntingtin-associated protein-1 (HAP1) regulates endocytosis and interacts with multiple trafficking-related proteins

Publication date: Available online 1 March 2017
Source:Cellular Signalling
Author(s): Kimberly D Mackenzie, Yoon Lim, Michael D Duffield, Timothy Chataway, Xin-Fu Zhou, Damien J Keating
Huntingtin-associated protein 1 (HAP1) was initially identified as a binding partner of huntingtin, mutations in which underlie Huntington's disease. Subcellular localization and protein interaction data indicate that HAP1 may be important in vesicle trafficking, cell signalling and receptor internalization. In this study, a proteomics approach was used for the identification of novel HAP1-interacting partners to attempt to shed light on the physiological function of HAP1. Using affinity chromatography with HAP1-GST protein fragments bound to Sepharose columns, this study identified a number of trafficking-related proteins that bind to HAP1. Interestingly, many of the proteins that were identified by mass spectrometry have trafficking-related functions and include the clathrin light chain B and Sec23A, an ER to Golgi trafficking vesicle coat component. Using co-immunoprecipitation and GST-binding assays the association between HAP1 and clathrin light chain B has been validated invitro. This study also finds that HAP1 co-localizes with clathrin light chain B. In line with a physiological function of the HAP1-clathrin interaction this study detected a dramatic reduction in vesicle retrieval and endocytosis in adrenal chromaffin cells. Furthermore, through examination of transferrin endocytosis in HAP1−/− cortical neurons, this study has determined that HAP1 regulates neuronal endocytosis. In this study, the interaction between HAP1 and Sec23A was also validated through endogenous co-immunoprecipitation in rat brain homogenate. Through the identification of novel HAP1 binding partners, many of which have putative trafficking roles, this study provides us with new insights into the mechanisms underlying the important physiological function of HAP1 as an intracellular trafficking protein through its protein-protein interactions.



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Consensus statement for the treatment of infantile haemangiomas with propranolol

Abstract

Although most infantile haemangiomas do not require treatment due to a natural history of spontaneous involution, some require early intervention. The Australasian Vascular Anomalies Network and the Australasian Paediatric Dermatology Network have developed a consensus statement for the treatment of infantile haemangiomas with oral propranolol. Infants with haemangiomas that are life threatening, at risk of ulceration, or at risk of causing a significant functional impairment, psychological impact or physical deformity should be treated early with oral propranolol. Oral propranolol is safe and effective and in most healthy infants oral propranolol can be started in an outpatient setting.



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Burden of human scabies in sub-Saharan African prisons: Evidence from the west region of Cameroon

Abstract

Background/Objectives

There is little data on the profile and magnitude of scabies in sub-Saharan African prisons. The present study aimed to assess the prevalence and determinants of scabies in prisons of the west region of Cameroon.

Methods

We conducted a cross-sectional study from March to August 2014, and consecutively recruited volunteer detainees of three randomly selected prisons in the West Region of Cameroon. The diagnosis was based on clinical findings after assessment by two experienced and well-trained dermatologists.

Results

We enrolled 755 prisoners, 17 (2%) of whom were women. Their mean age was 32 ± 12 years. There were 242 cases (32%) of scabies, with significantly more cases in the most crowded prison (P < 0.0001). Men were significantly more affected than women (P = 0.004) and the prevalence of scabies significantly decreased when the level of education increased (P < 0.0001). In addition to a low level of education (adjusted odds ratio (aOR) 1.90; P < 0.0001), sharing clothes/bedding (aOR 2.72; P < 0.0001) and the number of detainees per cell > 10 (aOR 1.89; P = 0.002), but not age, duration of incarceration, number of baths/week and washing/week, were independent drivers of scabies occurrence.

Conclusion

Almost one-third of prisoners suffered from scabies in our prisons. A low educational level, the sharing of clothes/bedding and number of detainees/cell > 10 were independent determinants of the disease. Urgent measures must be undertaken to reduce the burden of scabies in our prisons.



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Immobilization of laccase from Aspergillus oryzae on graphene nanosheets

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Publication date: June 2017
Source:International Journal of Biological Macromolecules, Volume 99
Author(s): Everton Skoronski, Diego Hoefling Souza, Cyntia Ely, Felipe Broilo, Mylena Fernandes, Agenor Fúrigo, Marcos Gomes Ghislandi
Laccase enzymes of Aspergillus oryzae were immobilized on graphene nanosheets by physical adsorption and covalent bonding. Morphological features of the graphene sheets were characterized via microscopy techniques. The immobilization by adsorption was carried out through contact between graphene and solution of laccase enzyme dissolved in deionized water. The adsorption process followed a Freundlich model, showing no tendency to saturation within the range of values used. The process of immobilization by covalent bonding was carried out by nitration of graphene, followed by reduction of sodium borohydride and crosslinking with glutaraldehyde. The process of immobilization by both techniques increased the pH range of activity of the laccase enzyme compared to the free enzyme and increased its operating temperature. On operational stability, the enzyme quickly loses its activity after the second reaction cycle when immobilized via physical adsorption, while the technique by covalent bonding retained around 80% activity after six cycles.



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Structural changes induced by L50P and I61T single mutations of ubiquitin affect cell cycle progression while impairing its regulatory and degradative functions in Saccharomyces cerevisiae

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Publication date: June 2017
Source:International Journal of Biological Macromolecules, Volume 99
Author(s): Ankita Doshi, Mrinal Sharma, C. Ratna Prabha
Posttranslational conjugation of ubiquitin to proteins either regulates their function directly or concentration through ubiquitination dependent degradation. High degree of conservation of ubiquitin’s sequence implies structural and functional importance of the conserved residues. Ubiquitin gene of Saccharomyces cerevisiae was evolved in vitro by us to study the significance of conserved residues. Present study investigates the structural changes in the protein resulting from the single mutations UbS20F, UbA46S, UbL50P, UbI61T and their functional consequences in the SUB60 strain of S. cerevisiae. Expression of UbL50P and UbI61T decreased Cdc28 protein kinase, enhanced Fus3 levels, caused dosage dependent lethality and at sublethal level produced drastic effects on stress tolerance, protein sorting, protein degradation by ubiquitin fusion degradation pathway and by lysosomes. UbS20F and UbA46S produced insignificant effects over the cells. All four mutations of ubiquitin were incorporated into polyubiquitin. However, polyubiquitination with K63 linkage decreased significantly in cells expressing UbL50P and UbI61T. Structural studies on UbL50P and UbI61T revealed distorted structure with greatly reduced α-helical and elevated β-sheet contents, while UbS20F and UbA46S show mild structural alterations. Our results on functional efficacy of ubiquitin in relation to structural integrity may be useful for designing inhibitors to investigate and modulate eukaryotic cellular dynamics.



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Bufadienolides from Kalanchoe daigremontiana as thrombin inhibitors—In vitro and in silico study

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Publication date: June 2017
Source:International Journal of Biological Macromolecules, Volume 99
Author(s): Joanna Kolodziejczyk-Czepas, Malgorzata Sieradzka, Barbara Moniuszko-Szajwaj, Łukasz Pecio, Michal B. Ponczek, Pawel Nowak, Anna Stochmal
Thrombin is an active plasma coagulation factor II, critical for the formation of fibrin clot during blood coagulation. For that reason, this protein is also a crucial target for different anti-thrombotic therapies. The work is based on in vitro evaluation of the inhibitory effect of bufadienolide-rich fraction, isolated from roots of Kalanchoe daigremontiana (1–50μg/ml) on enzymatic properties of a serine proteinase – thrombin. The efficacy of the inhibition of amidolytic activity of thrombin (measured as a hydrolysis of the chromogenic substrate S-2238, Chromogenix) attained about 10 and 66%, respectively. The IC50, established for the examined bufadienolide fraction was 2.79μg/ml, while the IC50 calculated for argatroban (reference compound) was 0.78μg/ml. Linearization conducted using Lineweaver-Burk plot indicated that the K. daigremontiana fraction contains compounds that are uncompetitive inhibitors of thrombin. K. daigremontiana fraction was also able to reduce the proteolytic activity of thrombin towards its physiological substrate, i.e. fibrinogen. Additionally, this study is supported by in silico analysis of interactions of the most common compounds, identified in the examined in Kalanchoe extract to crystal structure of this enzyme.



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Protein hydration: Investigation of globular protein crystal structures

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Publication date: June 2017
Source:International Journal of Biological Macromolecules, Volume 99
Author(s): Oliviero Carugo
The positions of water molecules have been analyzed in high quality protein X-ray crystal structures. About 70% of these water molecules are in contact with protein atoms at the protein surface and constitute the first hydration layer. About 20% of them are close to the first hydration layer but are not in contact with protein atoms and constitute the second hydration layer. The rest of the water molecules are either buried in the protein core or close to hetero-atoms (inorganic ions and small organic molecules). Upper layers (third, fourth, etc.) are not observed in the dataset of protein crystal structures examined here. Water molecules of both layers are not, in general, surrounded by a tetrahedral arrangement of atoms, as it should be expected on the basis of the electronic structure of water. Usually there are less than four atoms around water molecules and even when there are four atoms, the stereochemistry is often distorted. Water molecules are more mobile than protein atoms, more in the second hydration layer than in the first.



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Preparation and characterization of novel super-artificial hair fiber based on biomass materials

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Publication date: June 2017
Source:International Journal of Biological Macromolecules, Volume 99
Author(s): Lijun Yang, Jing Guo, Sen Zhang, Yumei Gong
A novel super-artificial hair fiber basing on sodium alginate (SA) and Antarctic Krill protein (AKP) was prepared by wet spinning successfully. Such SA/AKP fiber did not only have similar crystalline structure with human hair, but also had super flame resistance and mechanical performance. It should be noted that the whole preparation process was green without any incorporation of non-toxic solution. Moreover, comparing with human hair, the SA/AKP fiber had a lot of unique groove upon the fiber surface, which contributed a lot to excellent hygroscopicity. Meanwhile, the dyeing performance could be improved notably due to incorporation of protein into the matrix. Herein, the SA/AKP fiber with superior mechanical and functional performance had practical value for application in the field of synthetic wig.



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Expression analysis and ATR-FTIR characterization of the secondary structure of recombinant human TNF-α from Escherichia coli SHuffle® T7 Express and BL21 (DE3) cells

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Publication date: June 2017
Source:International Journal of Biological Macromolecules, Volume 99
Author(s): Hossein Safarpour, Sahar Barzegari Banadkoki, Zahra Keshavarzi, Mohammad Hossein Morowvat, Mahdieh Soleimanpour, Shokoufeh Pourmolaei, Farshad H. Shirazi
TNF-α, a prototype member of the TNF family of ligands, has both pro-inflammatory and immune-regulatory functions, which make it as an appropriate therapeutic target for selective blockade in antibody therapy of many diseases like in rheumatoid arthritis. Using two models of SHuffle® T7 Express and BL21 (DE3) cells, we have expressed this protein and recognized it by SDS-PAGE analysis. FTIR biospectroscopy of the resulted purified proteins has been performed and mathematical calculations has been done for further identification of the structural and conformational differences between the two products. Our results showed some differences in disulfide bond formation and β-sheet turns between these two recombinant proteins. To the best of our knowledge, this is the first study that compare secondary structure of recombinant proteins in both conventional and next generation Escherichia coli based expression systems using reliable, simple, rapid and economic ATR-FTIR analysis. Whether these differences might have significant effects on TNF-α inflammatory and immune-regulatory function in biological systems might be very much important and need further investigations.



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Prevalence of drugs in oral fluid from truck drivers in Brazilian highways

Traffic accidents have reached alarming heights around the world and are causing about 1.25 million deaths per year worldwide. Traffic accidents are the most common cause of death among those aged 15-29 years. The World Health Organization estimates that by 2050 it will be responsible for 2.4 million deaths if no measures are taken [1]. In 2010, the United Nations declared the decade from 2011 to 2020 as the Decade of Action for Road Safety as an attempt to reduce in half the number of traffic accidents and saving millions of lives [1].

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The everlasting issue of GHB cut-offs in biological samples: how important it is to be careful when interpreting values

We have read with attention and interest the manuscript of Thomsen et al. [1] entitled: “Postmortem concentrations of gamma-hydroxybutyrate (GHB) in peripheral blood and brain tissue − differentiating between postmortem formation and antemortem intake”.

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DDX17 nucleocytoplasmic shuttling promotes acquired gefitinib resistance in non-small cell lung cancer cells via activation of β-catenin

Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are effective for non-small cell lung cancer (NSCLC) patients with EGFR mutations, almost all these patients will eventually develop acquired resistance to EGFR-TKI. However, the molecular mechanisms responsible for gefitinib resistance remain still not fully understood. Here, we report that elevated DDX17 levels are observed in gefitinib-resistant NSCLC cells than gefitinib-sensitive cells. Upregulation of DDX17 enhances the gefitinib resistance, whereas DDX17-silenced cells partially restore gefitinib sensitivity.

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Inhibition of MAPKinase pathway sensitizes thyroid cancer cells to ABT-737 induced apoptosis

Bcl2 family proteins play an important role in the resistance of thyroid cancer cells to apoptosis induced by chemotherapeutic drugs and targeted therapies. BH3-profiling of seven fresh primary papillary thyroid cancer (PTC) tumors showed dependence for survival on Bcl-xL (2/7), Bcl2 (2/7), and Mcl-1 (2/7), while the majority of thyroid cell lines were mainly dependent on Bcl-xL. Targeting Bcl2 family proteins with the BH3 mimetic, ABT-737, while simultaneously inhibiting ERK pathway proteins with PLX4720 and PD32590 was shown to induce significantly high apoptosis in the majority of cell lines (8505c, SW1736, HTh7, BCPAP) and moderate apoptosis in the TPC-1 cell line.

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Resistance to Metronomic Chemotherapy and Ways to Overcome it

Therapeutic resistance is amongst the major determinants of cancer mortality. Contrary to initial expectations, antivascular therapies are equally prone to inherent or acquired resistance as other cancer treatment modalities. However, studies into resistance to vascular endothelial growth factor pathway inhibitors revealed distinct mechanisms of resistance compared to conventional cytotoxic therapy. While some of these novel mechanisms of resistance also appear to be functional regarding metronomic chemotherapy, herein we summarize available evidence for mechanisms of resistance specifically described in the context of metronomic chemotherapy.

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Locally advanced colon cancer with cutaneous invasion: case report

Locally advanced colon cancer with direct abdominal wall and skin invasion is an extremely rare finding with most data being derived from case reports, historical autopsy-based or single-center retrospective s...

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Diagnostic and therapeutic challenges of an ambiguous cystic kidney disease in a resource limited setting: a case report

Unilateral renal cystic disease is a rare condition that shares morphological similarities with multicystic dysplastic kidney, the former often distinguished from the latter on some clinical and histopathologi...

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Multidimensional Assessment of the Effectiveness of Group Voice Therapy

Group voice therapy has been successfully used in patients with dysphonia, but there is little objectively documented evidence of its effects on voice quality and the self-perception of voice fatigue. The aim of this study was to investigate the effectiveness of group therapy in patients with functional dysphonia and minor anatomic vocal fold pathologies linked by appearance and history to voice use in an objective and multidimensional manner.

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Anatomic distribution of cervicofacial lymphatic malformations based on lymph node groups

Lymphatic malformations (LM) are rare benign congenital malformations of lymphatic vessels [1]. The incidence of head and neck LM is approximately 1 of every 2000 to 4000 live births [2]. These lesions typically present as soft, colorless masses that generally grow proportionally with the child. Approximately 90% of lesions are diagnosed by five years of age and can be subject to rapid growth with infection or trauma [3]. Symptoms are commonly related to the size of the malformation and encasement of adjacent structures.

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Self-reported postoperative recovery in children after tonsillectomy compared to tonsillotomy

Tonsil surgery is associated with significant morbidity during recovery. Patient-reported outcome measures (PROM) are the golden standard for the planning and follow-up of delivered care, which should also be an axiom for children. The current aims were to describe self-reported postoperative recovery in children after tonsil surgery, and to compare tonsillotomy and tonsillectomy in this respect.

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Regulation of DENND3, the exchange factor for the small GTPase Rab12 through an intramolecular interaction [Membrane Biology]

The Rab family of small GTPases function in multiple aspects of cellular membrane trafficking. Proteins bearing a DENN (differentially expressed in normal and neoplastic cells) domain have emerged as the largest family of Rab-activating guanine nucleotide exchange factors (GEFs). Rab12 functions in the initiation of starvation-induced autophagy and our previous work revealed that its activator, DENND3 is phosphorylated and activated upon starvation. However, how the GEF activity of DENND3 towards Rab12 is regulated at the molecular level is still not understood. Here we combine size-exclusion chromatography, Forster resonance energy transfer, pull-down and in vitro GEF assays to demonstrate that regulation of GEF activity is achieved through an intramolecular interaction that is controlled by a key residue in DENND3, tyrosine 940. Our study sheds light on the regulation of Rab12 activation, and lays the groundwork for characterizing the regulation of other DENN domain-containing proteins.

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A Structural Organization for Disrupted in Schizophrenia 1, Identified by High-Throughput Screening, Reveals Distinctly Folded Regions Which Are Bisected by Mental Illness-Related Mutations [Molecular Bases of Disease]

Disrupted in Schizophrenia 1 (DISC1) is a scaffolding protein of significant importance for neurodevelopment and a prominent candidate protein in the pathology of major mental illness. DISC1 modulates a number of critical neuronal signaling pathways through protein-protein interactions; however, the mechanism by which this occurs and how DISC1 causes mental illness is unclear, partly because knowledge of the structure of DISC1 is lacking. A lack of homology with known proteins has hindered attempts to define its domain composition. Here, we employed the high-throughput Expression of Soluble Proteins by Random Incremental Truncation (ESPRIT) technique to identify discretely folded regions of human DISC1 via solubility assessment of tens of thousands of fragments of recombinant DISC1. We identified four novel structured regions, named D, I, S, and C, at amino acids 257-383, 539-655, 635-738, and 691-836, respectively. One region (D) is located in a DISC1 section previously predicted to be unstructured. All regions encompass coiled-coil or α- helical structures and three are involved in DISC1 oligomerization. Crucially, three of these domains would be lost or disrupted in a chromosomal translocation event after amino acid 597, which has been strongly linked to major mental illness. Furthermore, we observed that a known illness-related frameshift mutation after amino acid 807 causes the C region to form aberrantly multimeric and aggregated complexes with an unstable secondary structure. This newly revealed domain architecture of DISC1, therefore, provides a powerful framework for understanding the critical role of this protein in a variety of devastating mental illnesses.

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Long-term follow-up of two patients with retained intraosseous sternal needles

Sternal intraosseous devices are widely used in both civilian and military trauma when vascular access is difficult to establish. We discuss a rare complication of intraosseous needle insertion in two patients where the needle tip remained in the sternum after the device had been removed. Neither patient had evidence of any complication of the retained intraosseous needle tip after >6 years of follow-up.



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Syk expression and IgE-mediated histamine release in basophils as biomarkers for predicting the clinical efficacy of omalizumab

Omalizumab is a treatment for asthma that has a success rate of approximately 40% to 50%.1 Recent mechanistic studies have suggested that basophil behavior may explain some of the variability in response to therapy. First, the biological changes that occur during treatment with omalizumab have suggested that changes in basophil IgE-mediated reactivity occur faster than changes in the mast cell response.2,3 Other studies have shown that the IgE-mediated response of basophils results largely from limitations in the expression of the early required tyrosine kinase syk.

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Susceptibility to influenza virus infection of bronchial biopsies in asthma

Influenza causes significant morbidity and mortality, especially in patients with chronic lung diseases.1 Infection results in inflammatory cell influx and leads to either resolution or increased lung immunopathology and resulting morbidity,2 especially in patients with chronic airways diseases where viruses exacerbate inflammation and, subsequently, symptoms. Those with asthma are more susceptible to influenza and are, therefore, the most common population hospitalized, although, interestingly, they are less likely to develop severe disease or die than those without asthma.

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Human passive cutaneous anaphylaxis in the 21st century: Worth the risk?

“In 1921, Otto Carl W. Prausnitz (Giles) (1876-1963) identified what was later called ‘reagin,’ now known to be immunoglobulin E (IgE) antibody, found in higher quantities in the serum of allergic individuals than in nonallergic individuals. Prausnitz and his colleague, Heinz Küstner (1897-1963), discovered that a serum factor from an allergic patient (Küstner) could transfer skin-sensitizing properties to another individual (Prausnitz). Twenty-four hours after injecting serum from Küstner, who was allergic to fish, into Prausnitz's skin, they injected fish extract into the same area.

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Monoclonal antibody drug superior to chemotherapy for advanced acute lymphoblastic leukaemia

A Phase III clinical trial involving 101 centers in 21 countries revealed the monoclonal antibody blinatumomab to be more effective than standard chemotherapy for treatment of advanced acute lymphoblastic leukaemia (ALL). Study findings were published in...

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Two migration proteins boost predictive value of pancreatic cancer biomarker

Adding two blood-borne proteins associated with cancer cell migration increases the predictive ability of the current biomarker for pancreatic cancer to detect early stage disease, a research team from The University of Texas MD Anderson Cancer Center...

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Amine oxidase activity regulates the development of pulmonary fibrosis [Research]

In pulmonary fibrosis, an inflammatory reaction and differentiation of myofibroblasts culminate in pathologic deposition of collagen. Amine oxidase copper containing-3 (AOC3) is a cell-surface expressed oxidase that regulates leukocyte extravasation. Here we analyzed the potential role of AOC3 using gene-modified and inhibitor-treated mice in a bleomycin-induced pulmonary fibrosis model. Inflammation and fibrosis of lungs were assessed by histologic, flow cytometric, and quantitative PCR analysis. AOC3-deficient mice showed a 30–50% reduction in fibrosis, collagen synthesis, numbers of myofibroblasts, and accumulation of CD4+ lymphocytes, NK T cells, macrophages, and type 2 innate lymphoid cells compared with wild-type control mice. AOC3 knock-in mice, which express a catalytically inactive form of AOC3, were also protected from lung fibrosis. In wild-type mice, a small-molecule AOC3 inhibitor treatment reduced leukocyte infiltration, myofibroblast differentiation, and fibrotic injury both in prophylactic and early therapeutic settings by about 50% but was unable to reverse the established fibrosis. AOC3 was also induced in myofibroblasts in human idiopathic pulmonary fibrosis. Thus, the oxidase activity of AOC3 contributes to the development of lung fibrosis mainly by regulating the accumulation of pathogenic leukocyte subtypes, which drive the fibrotic response.—Marttila-Ichihara, F., Elima, K., Auvinen, K., Veres, T. Z., Rantakari, P., Weston, C., Miyasaka, M., Adams, D., Jalkanen, S., Salmi, M. Amine oxidase activity regulates the development of pulmonary fibrosis.



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Healthier central England or North-South divide? Analysis of national survey data on smoking and high-risk drinking

Objectives

This paper compares patterns of smoking and high-risk alcohol use across regions in England, and assesses the impact on these of adjusting for sociodemographic characteristics.

Design

Population survey of 53 922 adults in England aged 16+ taking part in the Alcohol and Smoking Toolkit Studies.

Measures

Participants answered questions regarding their socioeconomic status (SES), gender, age, ethnicity, Government Office Region, smoking status and completed the Alcohol Use Disorders Identification Test (AUDIT). High-risk drinkers were defined as those with a score of 8 or more (7 or more for women) on the AUDIT.

Results

In unadjusted analyses, relative to the South West, those in the North of England and East Midlands were more likely to smoke, while those from the East of England, South East and London were less likely. After adjustment for sociodemographics, smoking prevalence was no higher in North East (RR 0.97, p>0.05), North West (RR 0.98, p>0.05) or Yorkshire and the Humber (RR 1.03, p>0.05) but was less common in the East and West Midlands (RR 0.86, p<0.001; RR 0.91, p<0.05), East of England (RR 0.86, p<0.001), South East (RR 0.92, p<0.05) and London (RR 0.87, p<0.001). High-risk drinking was more common in the North but was less common in the Midlands, London and East of England. Adjustment for sociodemographics had little effect. There was a higher prevalence in the North East (RR 1.67, p<0.001), North West (RR 1.42, p<0.001) and Yorkshire and the Humber (RR 1.35, p<0.001); lower prevalence in the East Midlands (RR 0.69, p<0.001), West Midlands (RR 0.77, p<0.001), East of England (RR 0.72, p<0.001) and London (RR 0.71, p<0.001); and a similar prevalence in the South East (RR 1.10, p>0.05)

Conclusions

In adjusted analyses, smoking and high-risk drinking appear less common in ‘central England’ than in the rest of the country. Regional differences in smoking, but not those in high-risk drinking, appear to be explained to some extent by sociodemographic disparities.



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Early rehabilitation for the prevention of postintensive care syndrome in critically ill patients: a study protocol for a systematic review and meta-analysis

Introduction

Postintensive care syndrome (PICS) is defined as a new or worsening impairment in cognition, mental health and physical function after critical illness. There is little evidence regarding treatment of patients with PICS; new directions for effective treatment strategies are urgently needed. Early physiotherapy may prevent or reverse some physical impairments in patients with PICS, but no systematic reviews have investigated the effectiveness of early rehabilitation on PICS-related outcomes. The purpose of this systematic review is to evaluate whether early rehabilitative interventions in critically ill patients can prevent PICS and decrease mortality.

Methods

We will conduct a systematic review and meta-analysis of early rehabilitation for the prevention of PICS in critically ill adults. We will search PubMed, EMBASE and the Cochrane Central Register of Controlled Trials for published randomised controlled trials. We will screen search results and assess study selection, data extraction and risk of bias in duplicate, resolving disagreements by consensus. We will pool data from clinically homogeneous studies using a random-effects meta-analysis; assess heterogeneity of effects using the 2 test of homogeneity; and quantify any observed heterogeneity using the I2 statistic. We will use the Grading of Recommendations Assessment, Development and Evaluation approach to rate the quality of evidence.

Discussion

This systematic review will present evidence on the prevention of PICS in critically ill patients with early rehabilitation.

Ethics

Ethics approval is not required.

Dissemination

The results will be disseminated via peer-reviewed journal publication, conference presentation(s) and publications for patient information.

Trial registration number

CRD42016039759.



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Parallel multicentre randomised trial of a clinical trial question prompt list in patients considering participation in phase 3 cancer treatment trials

Objective

To evaluate the effect of a clinical trial question prompt list in patients considering enrolment in cancer treatment trials.

Setting

Tertiary cancer referral hospitals in three state capital cities in Australia.

Participants

88 patients with cancer attending three cancer centres in Australia, who were considering enrolment in phase 3 treatment trials, were invited to enrol in an unblinded randomised trial of provision of a clinical trial question prompt list (QPL) before consenting to enrol in the treatment trial.

Interventions

We developed and pilot tested a targeted QPL for patients with cancer considering clinical trial participation (the clinical trial QPL). Consenting patients were randomised to receive the clinical trial QPL or not before further discussion with their oncologist and/or trial nurse about the treatment trial.

Primary and secondary outcomes

Questionnaires were completed at baseline and within 3 weeks of deciding on treatment trial participation. Main outcome measure: scores on the Quality of Informed Consent questionnaire (QuIC).

Results

88 patients of 130 sought for the study were enrolled (43 males), and 45 received the clinical trial QPL. 49% of trials were chemotherapy interventions for patients with advanced disease, 35% and 16% were surgical adjuvant and radiation adjuvant trials respectively. 70 patients completed all relevant questionnaires. 28 of 43 patients in the control arm compared with 39 of 45 patients receiving the clinical trial QPL completed the QuIC (p=0.0124). There were no significant differences in the QuIC scores between the randomised groups (QuIC part A p=0.08 and QuIC part B p=0.92). There were no differences in patient satisfaction with decisions or in anxiety levels between the randomised groups.

Conclusions

Use of a question prompt list did not significantly change the QuIC scores in this randomised trial. ANZCTR 12606000214538 prospectively registered 31/5/2006.

Trial registration number

Results, ACTRN12606000214538.



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Awareness, knowledge and practice of dyslipidaemia management among postgraduate primary care trainees in Malaysia: a cross-sectional study

Objectives

Dyslipidaemia is one of the main risk factors for cardiovascular disease, the leading cause of death in Malaysia. This study assessed the awareness, knowledge and practice of lipid management among primary care physicians undergoing postgraduate training in Malaysia.

Design

Cross sectional study.

Setting

Postgraduate primary care trainees in Malaysia.

Participants

759 postgraduate primary care trainees were approached through email or hard copy, of whom 466 responded.

Method

A self-administered questionnaire was used to assess their awareness, knowledge and practice of dyslipidaemia management. The total cumulative score derived from the knowledge section was categorised into good or poor knowledge based on the median score, where a score of less than the median score was categorised as poor and a score equal to or more than the median score was categorised as good. We further examined the association between knowledge score and sociodemographic data. Associations were considered significant when p<0.05.

Results

The response rate achieved was 61.4%. The majority (98.1%) were aware of the national lipid guideline, and 95.6% reported that they used the lipid guideline in their practice. The median knowledge score was 7 out of 10; 70.2% of respondents scored 7 or more which was considered as good knowledge. Despite the majority (95.6%) reporting use of guidelines, there was wide variation in their clinical practice whereby some did not practise based on the guidelines. There was a positive significant association between awareness and the use of the guideline with knowledge score (p<0.001). However there was no significant association between knowledge score and sociodemographic data (p>0.05).

Conclusions

The level of awareness and use of the lipid guideline among postgraduate primary care trainees was good. However, there were still gaps in their knowledge and practice which are not in accordance with standard guidelines.



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Systematic review of the methodological quality of controlled trials evaluating Chinese herbal medicine in patients with rheumatoid arthritis

Objectives

We appraised the methodological and reporting quality of randomised controlled clinical trials (RCTs) evaluating the efficacy and safety of Chinese herbal medicine (CHM) in patients with rheumatoid arthritis (RA).

Design

For this systematic review, electronic databases were searched from inception until June 2015. The search was limited to humans and non-case report studies, but was not limited by language, year of publication or type of publication. Two independent reviewers selected RCTs, evaluating CHM in RA (herbals and decoctions). Descriptive statistics were used to report on risk of bias and their adherence to reporting standards. Multivariable logistic regression analysis was performed to determine study characteristics associated with high or unclear risk of bias.

Results

Out of 2342 unique citations, we selected 119 RCTs including 18 919 patients: 10 108 patients received CHM alone and 6550 received one of 11 treatment combinations. A high risk of bias was observed across all domains: 21% had a high risk for selection bias (11% from sequence generation and 30% from allocation concealment), 85% for performance bias, 89% for detection bias, 4% for attrition bias and 40% for reporting bias. In multivariable analysis, fewer authors were associated with selection bias (allocation concealment), performance bias and attrition bias, and earlier year of publication and funding source not reported or disclosed were associated with selection bias (sequence generation). Studies published in non-English language were associated with reporting bias. Poor adherence to recommended reporting standards (<60% of the studies not providing sufficient information) was observed in 11 of the 23 sections evaluated.

Limitations

Study quality and data extraction were performed by one reviewer and cross-checked by a second reviewer. Translation to English was performed by one reviewer in 85% of the included studies.

Conclusions

Studies evaluating CHM often fail to meet expected methodological criteria, and high-quality evidence is lacking.



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Changes in drug disposition of lithium during pregnancy: a retrospective observational study of patient data from two routine therapeutic drug monitoring services in Norway

Objectives

Pregnancy may cause changes in drug disposition, dose requirements and clinical response. For lithium, changes in disposition during pregnancy have so far been explored in a single-dose study on 4 participants only. The aim of this study was to determine the effect of pregnancy on serum levels of lithium in a larger patient material in a naturalistic setting.

Design

A retrospective observational study of patient data from 2 routine therapeutic drug monitoring services in Norway, linked to the Medical Birth Registry of Norway.

Setting

Norway, October 1999 to December 2011.

Measurements

Dose-adjusted drug concentrations of lithium during pregnancy were compared with the women's own baseline (non-pregnant) values, using a linear mixed model.

Results

Overall, coupling 196 726 serum concentration measurements from 54 393 women to the national birth registry identified 25 serum lithium concentration analyses obtained from a total of 14 pregnancies in 13 women, and 63 baseline analyses from the same women. Dose-adjusted serum concentrations in the third trimester were significantly lower than baseline (–34%; CI –44% to –23%, p<0.001).

Conclusions

Pregnancy causes a clinically relevant decline in maternal lithium serum concentrations. In order to maintain stable lithium concentrations during the third trimester of pregnancy, doses generally need to be increased by 50%. Individual variability in decline implies that lithium levels should be even more closely monitored throughout pregnancy and in the puerperium than in non-pregnant women to ensure adequate dosing.



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Epitaxial Halide Perovskite Lateral Double Heterostructure

TOC Graphic

ACS Nano
DOI: 10.1021/acsnano.7b00724
ancac3?d=yIl2AUoC8zA


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Effects of Traumatic Stress Induced in the Juvenile Period on the Expression of Gamma-Aminobutyric Acid Receptor Type A Subunits in Adult Rat Brain

Studies have found that early traumatic experience significantly increases the risk of posttraumatic stress disorder (PTSD). Gamma-aminobutyric acid (GABA) deficits were proposed to be implicated in development of PTSD, but the alterations of GABA receptor A (GABAAR) subunits induced by early traumatic stress have not been fully elucidated. Furthermore, previous studies suggested that exercise could be more effective than medications in reducing severity of anxiety and depression but the mechanism is unclear. This study used inescapable foot-shock to induce PTSD in juvenile rats and examined their emotional changes using open-field test and elevated plus maze, memory changes using Morris water maze, and the expression of GABAAR subunits (γ2, α2, and α5) in subregions of the brain in the adulthood using western blotting and immunohistochemistry. We aimed to observe the role of GABAAR subunits changes induced by juvenile trauma in the pathogenesis of subsequent PTSD in adulthood. In addition, we investigated the protective effects of exercise for 6 weeks and benzodiazepine (clonazepam) for 2 weeks. This study found that juvenile traumatic stress induced chronic anxiety and spatial memory loss and reduced expression of GABAAR subunits in the adult rat brains. Furthermore, exercise led to significant improvement as compared to short-term BZ treatment.

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Antioxidative and Anti-Inflammatory Activities of Galloyl Derivatives and Antidiabetic Activities of Acer ginnala

Chromatographic isolation of the 80% MeOH extract of Acer ginnala (AG) yielded seven galloyl derivatives: gallic acid (1), ginnalin B (2), acertannin (3), maplexin D (4), maplexin E (5), quercetin-3-O-(2′′-galloyl)-α-L-rhamnopyranoside (6), and kaempferol-3-O-(2′′-galloyl)-α-L-rhamnopyranoside (7). This is the first study to report the isolation of compounds 4 and 5 from AG. Galloyl derivatives 3–7 exhibited potent radical scavenging activities, with 5 and 7 showing particularly strong inhibitory activities against nitric oxide production in lipopolysaccharides- (LPS-) stimulated RAW264.7 cells. In addition, oral administration of AG extract (500 mg/kg b.w.) improved symptoms of hyperglycemia and blunted the increases in serum GOT/GPT levels in a rat model of streptozotocin-induced diabetes. These results suggest that galloyl derivatives (1–7) are antioxidant and anti-inflammatory agents and that AG extract has potential as a functional material or novel herbal medicine for treating diabetes mellitus.

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An Accelerating Iterative Learning Control Based on an Adjustable Learning Interval

An iterative learning control algorithm with an adjustable interval is proposed for nonlinear systems to accelerate the convergence rate of iterative learning control. For -norm, the monotonic convergence of ILC was analyzed, and the corresponding convergence conditions were obtained. The results showed that the convergence rate was mainly determined by the controlled object, the control law gain, the correction factor, and the iteration interval size and that the control law gain was corrected in real time in the modified interval and the modified interval shortened as the number of iterations increased, further accelerating the convergence. The numerical simulation shows the effectiveness of the proposed method.

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A Wandering Abdominal Mass in a Neonate: An Enteric Duplication Cyst Mimicking an Ovarian Cyst

Enteric duplication cysts are rare congenital anomalies that are prenatally diagnosed through antenatal ultrasonography (US). In female patients, however, attention must be paid since these formations might be confused with ovarian cysts. Herein, we present a case of a low birth weight female infant with an enteric duplication cyst. A cystic lesion was detected in the right abdomen of the fetus on antenatal US and magnetic resonance imaging (MRI). Serial US and MRI examinations performed after birth showed a single cyst that wandered from side to side in the abdomen; the initial diagnosis was thought to be an ovarian cyst. During laparotomy, however, it was found to be an enteric duplication cyst with volvulus. To our knowledge, there has been no report of an enteric duplication cyst presenting as a wandering abdominal mass. Our experience indicates that early intervention is necessary for patients who have a wandering abdominal mass to avoid complications and urgent surgery, whether it is an ovarian cyst or an enteric duplication cyst.

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Involvement of Normalized Glial Fibrillary Acidic Protein Expression in the Hippocampi in Antidepressant-Like Effects of Xiaoyaosan on Chronically Stressed Mice

The research has only yielded a partial comprehension of MDD and the mechanisms underlying the antidepressant-like effects of XYS. Therefore, in this study, we aimed to explore the effects of XYS on chronic unpredictable mild stress- (CUMS-) induced changes in the neuronal and the astrocytic markers in the mouse hippocampus. The physical states and depressive-like behaviors in mice with CUMS were recorded. The serum contents of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) were measured. The protein and mRNA expressions and the immunoreactivities of glial fibrillary acidic protein (GFAP) and neuronal nuclei (NeuN) in mouse hippocampus were detected using a Western blot, qRT-PCR, and immunohistochemical staining, respectively. XYS treatment markedly improved the physical state and depressive-like behaviors in mice subjected to CUMS compared with the model group, and the serum contents of BDNF and GDNF were significantly upregulated. XYS treatment also elevated the protein and mRNA levels, as well as the immunoreactivity of GFAP in the hippocampus. However, CUMS did not influence NeuN expression. In conclusion, these results reveal that chronic administration of XYS elicits antidepressant-like effects in a mouse model of depression and may normalize glial fibrillary acidic protein expression in the hippocampi of mice with CUMS.

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Rare Case of a Well-Differentiated Paratesticular Sarcoma of the Spermatic Cord in a 60-Year-Old Patient

Introduction. Liposarcomas are tumors that occur mostly in the retroperitoneum. Of all liposarcomas only 3 to 7% are found in the paratesticular region. The spermatic cord is the main site of origin in these cases. The patients ages range from 50 to 60 years. This malignant disease can result in a loss of fertility aside from life-threatening sequelae. Case. We present a case of a liposarcoma of the paratesticular region. A 60-year-old man was referred with a painless mass in the scrotum and the right inguinal region. The patient underwent surgery and the mass was removed along with the right testis, the spermatic cord, and the soft tissues to the internal inguinal ring. Histopathological examination found a well-differentiated liposarcoma of  mm. The surgical margins were negative. The adjuvant treatment consisted in radiation therapy of the right inguinoscrotal area to the dose of 54 Gray, 2 Gy per session, 5 times a week. Conclusion. Paratesticular liposarcomas are rare tumors. Surgery with large margin resections was the main treatment in all reported cases. The adjuvant treatment is still unclear especially when the surgical margins are negative. The main factor that indicated this adjuvant treatment was the size of the tumor and the histologic subtype.

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Maxillary Sinus Augmentation with Decellularized Bovine Compact Particles: A Radiological, Clinical, and Histologic Report of 4 Cases

Background. One of the most problematic regions for endosseous implants is the posterior maxilla, not only having poor bone density, but also lacking adequate vertical height as a result of sinus pneumatization. The purpose of the present study was a radiologic, histological, and histomorphometrical evaluation, in humans, of specimens retrieved from sinuses augmented with decellularized bovine compact particles, after a healing period of 6 months. Methods. Four patients, with atrophic resorbed maxillas, underwent a sinus lift augmentation with decellularized bovine compact bone from bovine femur. The size of the particles used was 0.25–1 mm. A total of four grafts and 5 biopsies were retrieved and processed to obtain thin ground sections with the Precise 1 Automated System. Results. The mean volume after graft elevation calculated for each of the 4 patients was 2106 mm3 in the immediate postoperative period (5–7 days), ranging from 1408.8 to 2946.4 mm3. In the late postoperative period (6 months) it was 2053 mm3, ranging from 1339.9 to 2808.9 mm3. Histomorphometry showed that newly formed bone was % and marrow spaces were %, while the residual graft material was %. Conclusion. In conclusion, based on the outcome of the present study, Re-Bone® can be used with success in sinus augmentation procedures and 6 months are considered an adequate time for maturation before implant placement.

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Modelling the Evaporation Rate in an Impingement Jet Dryer with Multiple Nozzles

Impinging jets are often used in industry to dry, cool, or heat items. In this work, a two-dimensional Computational Fluid Dynamics model is created to model an impingement jet dryer with a total of 9 pairs of nozzles that dries sheets of metal. Different methods to model the evaporation rate are studied, as well as the influence of recirculating the outlet air. For the studied conditions, the simulations show that the difference in evaporation rate between single- and two-component treatment of moist air is only around 5%, hence indicating that drying can be predicted with a simplified model where vapor is included as a nonreacting scalar. Furthermore, the humidity of the inlet air, as determined from the degree of recirculating outlet air, has a strong effect on the water evaporation rate. Results show that the metal sheet is dry at the exit if 85% of the air is recirculated, while approximately only 60% of the water has evaporated at a recirculation of 92,5%.

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Ethnic Differences in Risk Factors for Obesity among Adults in California, the United States

Little attention has been given to differences in obesity risk factors by racial/ethnic groups. Using data from the 2011-2012 California Health Interview Survey, we examined differences in risk factors for obesity among Whites, Latinos, Asians, and African Americans among 42,935 adults (24.8% obese). Estimates were weighted to ensure an unbiased representation of the Californian population. Multiple logistic and linear regression analyses were used to examine the differences in risk factors for obesity. Large ethnic disparities were found in obesity prevalence: Whites (22.0%), Latinos (33.6%), African Americans (36.1%), and Asians (9.8%). Differences in risk factors for obesity were also observed: Whites (gender, age, physical activity, smoking, arthritis, and diabetes medicine intake), Latinos (age, arthritis, and diabetes medicine intake), Asians (age, binge drinking, arthritis, and diabetes medicine intake), and African Americans (gender, physical activity, smoking, binge drinking, and diabetes medicine intake). Females were more likely to be obese among African Americans (odds ratio (OR) = 1.43, 95% confidence interval (CI) = 1.05–1.94), but less likely among Whites (OR = 0.80, 95% CI = 0.74–0.87). Race/ethnicity should be considered in developing obesity prevention strategies.

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Long-Term Body Weight Maintenance among StrongWomen–Healthy Hearts Program Participants

Background. The repeated loss and regain of body weight, referred to as weight cycling, may be associated with negative health complications. Given today’s obesity epidemic and related interventions to address obesity, it is increasingly important to understand contexts and factors associated with weight loss maintenance. This study examined BMI among individuals who had previously participated in a 12-week, evidence-based, nationally disseminated nutrition and physical activity program designed for overweight and obese middle-aged and older women. Methods. Data were collected using follow-up surveys. Complete height and weight data were available for baseline, 12-week program completion (post-program) and follow-up (approximately 3 years later) for 154 women (response rate = 27.5%; BMI characteristics did not differ between responders and nonresponders). Results. Mean BMI decreased significantly from baseline to post-program (−0.5, ) and post-program to follow-up (−0.7, ). Seventy-five percent of survey respondents maintained or decreased BMI post-program to follow-up. Self-efficacy and social support for healthy eating behaviors (but not physical activity) were associated with BMI maintenance or additional weight loss. Conclusions. These findings support the durability of weight loss following participation in a relatively short-term intervention.

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CPAP Treatment Adherence in Women with Obstructive Sleep Apnea

Untreated obstructive sleep apnea (OSA) has numerous negative health-related consequences. Continuous positive airway pressure (CPAP) is generally considered the treatment of choice for OSA, but rates of nonadherence are high. It is believed that OSA is more prevalent among men; therefore understanding how OSA presents among women is limited and treatment adherence has received little research attention. For this study, 29 women were recruited from primary care offices. They completed a questionnaire battery and underwent a night of nocturnal polysomnography (PSG) followed by a visit with a sleep specialist. Women diagnosed with OSA were prescribed CPAP; 2 years later CPAP adherence was evaluated. Results show that approximately half the sample was adherent. There were no significant differences between adherent and nonadherent women on OSA severity; however CPAP adherent women had worse nocturnal and daytime functioning scores at the time of diagnosis. Moreover, when the seven nocturnal and daytime variables were used as predictors in a discriminant analysis, they could predict 87% of adherent and 93% of the nonadherent women. The single most important predictor was nonrefreshing sleep. We discuss the implications of the findings for identifying women in primary care with potential OSA and offer suggestions for enhancing treatment adherence.

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Modeling for the Calcination Process of Industry Rotary Kiln Using ANFIS Coupled with a Novel Hybrid Clustering Algorithm

Rotary kiln is important equipment in heavy industries and its calcination process is the key impact to the product quality. Due to the difficulty in obtaining the accurate algebraic model of the calcination process, an intelligent modeling method based on ANFIS and clustering algorithms is studied. In the model, ANFIS is employed as the core structure, and aiming to improve both its performance in reduced computation and accuracy, a novel hybrid clustering algorithm is proposed by combining FCM and Subtractive methods. A quasi-random data set is then hired to test the new hybrid clustering algorithm and results indicate its superiority to FCM and Subtractive methods. Further, a set of data from the successful control activity of sophisticated workers in manufacturing field is used to train the model, and the model demonstrates its advantages in both fast convergence and more accuracy approaching.

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Radiographic Findings in Patients with Medication-Related Osteonecrosis of the Jaw

A retrospective study was conducted of the records and panoramic radiographs of 35 patients treated with bisphosphonates (BP) and diagnosed with MRONJ. Panoramic radiography was used for evaluation, by two examiners, the following findings were subject of search: osteolysis (OT), cortical bone erosion (EC), bone sclerosis focal (FS) and diffuse (DS), bone sequestration (BS), thickening of lamina dura (TD), prominence of the inferior alveolar nerve canal (IAN), persisting alveolar sockets (SK), and the presence of a pathological fracture (PF). Medical information and staging were also recorded in order to correlate with radiographic findings. Bone sclerosis was the most frequent alteration, followed by OT and TD. The mandible was more affected than the maxilla. There was no significant difference between genders or significant correlation between the number of injuries with age and duration of BP usage. Considering the association between the radiographic findings and MRONJ staging, EC was predominant in stage 3 and DS in stage 2. IAN and PF demonstrated greater association with stage 3. In conclusion, the higher the clinical staging, the greater the severity of the bone alteration. Panoramic radiographic examination is a useful screening tool in patients submitted to antiresorptive therapy.

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Effect of Herbal and Fluoride Mouth Rinses on Streptococcus mutans and Dental Caries among 12–15-Year-Old School Children: A Randomized Controlled Trial

To assess and compare the effect of herbal and fluoride mouth rinses on Streptococcus mutans count and glucan synthesis by Streptococcus mutans and dental caries, a parallel group placebo controlled randomized trial was conducted among 240 schoolchildren (12–15 years old). Participants were randomly divided and allocated into Group I (0.2% fluoride group), Group II (herbal group), and Group III (placebo group). All received 10 ml of respective mouth rinses every fortnight for a period of one year. Intergroup and intragroup comparison were done for Streptococcus mutans count and glucan synthesis by Streptococcus mutans and dental caries. Streptococcus mutans count showed a statistically significant difference between Group I and Group III () and also between Group II and Group III (). Glucan concentration levels showed a statistically significant difference () between Group II and Group III at 12th month. Mean DMF scores showed no statistical difference between the three groups (). No difference in the level of significance was seen in the intention-to-treat and per-protocol analysis. The present study showed that both herbal and fluoride mouth rinses, when used fortnightly, were equally effective and could be recommended for use in school-based health education program to control dental caries. Trial registration number is CTRI/2015/08/006070.

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Vitamin D Deficiency and Its Determinants in Adults: A Sample from Community-Based Settings in the United Arab Emirates

Background. Vitamin D deficiency (VDD) is a public health concern in adults worldwide. This study aims to explore the extent of VDD and its associated factors among adults in the United Arab Emirates (UAE). Subjects and Methods. Quantitative, cross-sectional research was used to assess VDD and its associated factors in 216 adults recruited from randomly selected community-based healthcare settings over a six-month period. Recent values of vitamin D and glycated hemoglobin (HbA1c) were abstracted from medical records, followed by interviews with participants to obtain information on factors related to VDD and other covariates and to measure their heights and weights. Results. A total of 74% of participants demonstrated VDD (vitamin D serum  nmol/L). Emirati participants had higher odds of having VDD compared to non-Emiratis (OR: 2.95; 95% CI: 1.58–5.52), with also significantly increased odds of the condition appearing in older, less educated, and employed adults. Diabetes type 2 (), depression, and obesity were significantly associated with an increased likelihood of VDD after accounting for other covariates. Conclusion. VDD is a significant problem for UAE adults and requires attention by public health policy makers. Diabetes, obesity, and depression need to be considered when screening for vitamin D.

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Outcome and Genetic Factors in IgG4-Associated Autoimmune Pancreatitis and Cholangitis: A Single Center Experience

Introduction. Most investigations on autoimmune pancreatitis (AIP) were published on Asian cohorts while those on Caucasians are limited. However, there might be differences related to the origin. Patients and Methods. We analyzed 36 patients and compared type 1 (AIP1) with type 2 (AIP2). Results. The majority of patients suffered from AIP1 (55.6%). AIP1 patients were significantly older than AIP2 patients (54.4 versus 40.8 years). Moreover, 85.0% of AIP1 patients had concurrent autoimmune cholangitis (AIC) while 18.8% of AIP2 patients suffered from overlap to ulcerative colitis (UC). However, AIP1 patients revealed a cholestatic course and had significantly higher immunoglobulin G4 levels (IgG4). When compared to allele frequencies in healthy controls, in patients with AIP1 HLA-B8 reached statistical significance. Response to steroids was excellent in both groups, but we noticed high rates of relapse especially in AIP1 patients. Finally, 3 patients with AIP1 were diagnosed with cholangiocellular carcinoma (CCC). Conclusion. In contrast to Asian studies, we found an almost equal distribution of AIP1 and AIP2 patients in our German cohort. AIP2 patients were younger and mostly of female gender whereas AIP1 patients revealed higher IgG4 levels and involvement of the biliary tract in sense of IgG4-associated cholangitis.

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A Density-Based Ramp Metering Model Considering Multilane Context in Urban Expressways

As one of the most effective intelligent transportation strategies, ramp metering is regularly discussed and applied all over the world. The classic ramp metering algorithm ALINEA dominates in practical applications due to its advantages in stabilizing traffic flow at a high throughput level. Although ALINEA chooses the traffic occupancy as the optimization parameter, the classic traffic flow variables (density, traffic volume, and travel speed) may be easier obtained and understood by operators in practice. This paper presents a density-based ramp metering model for multilane context (MDB-RM) on urban expressways. The field data of traffic flow parameters is collected in Chengdu, China. A dynamic density model for multilane condition is developed. An error function represented by multilane dynamic density is introduced to adjust the different usage between lanes. By minimizing the error function, the density of mainstream traffic can stabilize at the set value, while realizing the maximum decrease of on-ramp queues. Also, VISSIM Component Object Model of Application Programming Interface is used for comparison of the MDB-RM model with a noncontrol, ALINEA, and density-based model, respectively. The simulation results indicate that the MDB-RM model is capable of achieving a comprehensive optimal result from both sides of the mainstream and on-ramp.

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Reliability of Baropodometry on the Evaluation of Plantar Load Distribution: A Transversal Study

Introduction. Baropodometry is used to measure the load distribution on feet during rest and walking. The aim of this study was to evaluate changes in plantar foot pressures distribution due to period of working and due to stretching exercises of the posterior muscular chain. Methods. In this transversal study, all participants were submitted to baropodometric evaluation at two different times: before and after the working period and before and after stretching the muscles of the posterior chain. Results. We analyzed a total of 54 feet of 27 participants. After the working period, there was an average increase in the forefoot pressure of 0.16 Kgf/cm2 and an average decrease in the hindfoot pressure of 0.17 Kgf/cm2. After stretching the posterior muscular chain, the average increase in the forefoot pressure was 0.56 Kgf/cm2 and the hindfoot average pressure decrease was 0.56 Kgf/cm2. These changes were not statistically significant. Discussion. It was reported that the strength of the Achilles tendon generates greater forefoot load transferred from the hindfoot. In our study, no significant variation in the distribution of plantar pressure was observed. It can be inferred that baropodometry was a reliable instrument to determine the plantar pressure, regardless of the tension of the posterior chain muscles.

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Cost of Living with Parkinson’s Disease over 12 Months in Australia: A Prospective Cohort Study

Background. Parkinson disease (PD) is a costly chronic condition in terms of managing both motor and nonmotor symptoms. The burden of disease is high for individuals, caregivers, and the health system. The aim of this study is to estimate the annual cost of PD from the household, health system, and societal perspectives. Methods. A prospective cohort study of newly referred people with PD to a specialist PD clinic in Melbourne, Australia. Participants completed baseline and monthly health resource use questionnaires and Medicare data were collected over 12 months. Results. 87 patients completed the 12-month follow-up assessments. The mean annual cost per person to the health care system was $32,556 AUD. The burden to society was an additional $45,000 per annum per person with PD. The largest component of health system costs were for hospitalisation (69% of total costs). The costs for people with moderate to severe disease were almost 4 times those with mild PD ($63,569 versus $17,537 ). Conclusion. PD is associated with significant costs to individuals and to society. Costs escalated with disease severity suggesting that the burden to society is likely to grow with the increasing disease prevalence that is associated with population ageing.

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Autotransplantation of Ectopic Permanent Maxillary Incisors

The report presents examples of successful cases of autotransplantation of ectopic teeth as donor in the treatment of clinically missing maxillary anterior teeth in young patients. The transplanted teeth were either severely ectopic, inverted, rotated or in an unfavourable position that they are commonly sacrificed as a result. Details of surgical technique as well as clinical and radiographic assessments were discussed.

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Which Bay Leaf is in Your Spice Rack? – A Quality Control Study

10-1055-s-0043-103963_pma1035-1.jpg

Planta Med
DOI: 10.1055/s-0043-103963

The accurate identification of bay leaf in natural products commerce may often be confusing as the name is applied to several different species of aromatic plants. The true “bay leaf”, also known as “bay laurel” or “sweet bay”, is sourced from the tree Laurus nobilis, a native of the Mediterranean region. Nevertheless, the leaves of several other species including Cinnamomum tamala, Litsea glaucescens, Pimenta racemosa, Syzygium polyanthum, and Umbellularia californica are commonly substituted or mistaken for true bay leaves due to their similarity in the leaf morphology, aroma, and flavor. Substitute species are, however, often sold as “bay leaves”. As such, the name “bay leaf” in literature and herbal commerce may refer to any of these botanicals. The odor and flavor of these leaves are, however, not the same as the true bay leaf, and for that reason they should not be used in cooking as a substitute for L. nobilis. Some of the bay leaf substitutes can also cause potential health problems. Therefore, the correct identification of the true bay leaf is important. The present work provides a detailed comparative study of the leaf morphological and anatomical features of L. nobilis and its common surrogates to allow for correct identification.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



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Clinical Parameters following Multiple Oral Dose Administration of a Standardized Andrographis paniculata Capsule in Healthy Thai Subjects

10-1055-s-0043-104382_pma0925-1.jpg

Planta Med
DOI: 10.1055/s-0043-104382

Andrographis paniculata has been widely used in Scandinavian and Asian counties for the treatment of the common cold, fever, and noninfectious diarrhea. The present study was carried out to investigate the physiological effects of short-term multiple dose administration of a standardized A. paniculata capsule used for treatment of the common cold and uncomplicated upper respiratory tract infections, including blood pressure, electrocardiogram, blood chemistry, hematological profiles, urinalysis, and blood coagulation in healthy Thai subjects. Twenty healthy subjects (10 males and 10 females) received 12 capsules per day orally of 4.2 g of a standardized A. paniculata crude powder (4 capsules of 1.4 g of A. paniculata, 3 times per day, 8 h intervals) for 3 consecutive days. The results showed that all of the measured clinical parameters were found to be within normal ranges for a healthy person. However, modulation of some parameters was observed after the third day of treatment, for example, inductions of white blood cells and absolute neutrophil count in the blood, a reduction of plasma alkaline phosphatase, and an induction of urine pH. A rapid and transient reduction in blood pressure was observed at 30 min after capsule administration, resulting in a significant reduction of mean systolic blood pressure. There were no serious adverse events observed in the subjects during the treatment period. In conclusion, this study suggests that multiple oral dosing of A. paniculata at the normal therapeutic dose for the common cold and uncomplicated upper respiratory tract infections modulates various clinical parameters within normal ranges for a healthy person.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



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Recombinant Human Acidic Fibroblast Growth Factor (aFGF) Expressed in Nicotiana benthamiana Potentially Inhibits Skin Photoaging

10-1055-s-0043-103964_pma0755-1.jpg

Planta Med
DOI: 10.1055/s-0043-103964

Responding to the need for recombinant acidic fibroblast growth factor in the pharmaceutical and cosmetic industries, we established a scalable expression system for recombinant human aFGF using transient and a DNA replicon vector expression in Nicotiana benthamiana. Recombinant human-acidic fibroblast growth factor was recovered following Agrobacterium infiltration of N. benthamiana. The optimal time point at which to harvest recombinant human acidic fibroblast growth factor expressing leaves was found to be 4 days post-infiltration, before necrosis was evident. Commassie-stained SDS-PAGE gels of His-tag column eluates, concentrated using a 10 000 molecular weight cut-off column, showed an intense band at the expected molecular weight for recombinant human acidic fibroblast growth factor. An immunoblot confirmed that this band was recombinant human acidic fibroblast growth factor. Up to 10 µg recombinant human-acidic fibroblast growth factor/g of fresh leaves were achieved by a simple affinity purification protocol using protein extract from the leaves of agroinfiltrated N. benthamiana. The purified recombinant human acidic fibroblast growth factor improved the survival rate of UVB-irradiated HaCaT and CCD-986sk cells approximately 89 and 81 %, respectively. N. benthamiana-derived recombinant human acidic fibroblast growth factor showed similar effects on skin cell proliferation and UVB protection compared to those of Escherichia coli-derived recombinant human acidic fibroblast growth factor. Additionally, N. benthamiana-derived recombinant human acidic fibroblast growth factor increased type 1 procollagen synthesis up to 30 % as well as reduced UVB-induced intracellular reactive oxygen species generation in fibroblast (CCD-986sk) cells.UVB is a well-known factor that causes various types of skin damage and premature aging. Therefore, the present study demonstrated that N. benthamiana-derived recombinant human acidic fibroblast growth factor effectively protects skin cell from UVB, suggesting its potential use as a cosmetic or therapeutic agent against skin photoaging.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



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Diagnosis of cardiac surgery-associated acute kidney injury: differential roles of creatinine, chitinase 3-like protein 1 and neutrophil gelatinase-associated lipocalin: a prospective cohort study

A common and serious complication of cardiac surgery prompting early detection and intervention is cardiac surgery-associated acute kidney injury (CSA-AKI). Urinary chitinase 3-like protein 1 (UCHI3L1) was fou...

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Liver radiofrequency ablation as emergency treatment for a ruptured hepatocellular carcinoma: a case report

Hemoperitoneum is a possible complication of hepatocellular carcinoma that may require emergency surgery as an alternative to radiological locoregional therapies.

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Video from ECR 2017: Dr. Afshin Gangi on turf battles

2017_03_01_12_51_58_97_ECR_2017_video_GaVIENNA - Turf battles are an everyday reality in medicine today, but how can...


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Behavioural disorders in 6-year-old children and pyrethroid insecticide exposure: the PELAGIE mother-child cohort

Objective

The potential impact of environmental exposure to pyrethroid insecticides on child neurodevelopment has only just started to receive attention despite their widespread use. We investigated the associations between prenatal and childhood exposure to pyrethroid insecticides and behavioural skills in 6-year-olds.

Methods

The PELAGIE cohort enrolled 3421 pregnant women from Brittany, France between 2002 and 2006. 428 mothers were randomly selected for the study when their children turned 6, and 287 (67%) agreed to participate. Children's behaviour was assessed using the Strengths and Difficulties Questionnaire (SDQ). Three subscales (prosocial behaviour, internalising disorders and externalising disorders) were considered. Five pyrethroid metabolites were measured in maternal and child urine samples collected between 6 and 19 gestational weeks and at 6 years of age, respectively. Logistic regression and reverse-scale Cox regression models were used to estimate the associations between SDQ scores and urinary pyrethroid metabolite concentrations, adjusting for organophosphate metabolite concentrations and potential confounders.

Results

Increased prenatal cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (DCCA) concentrations were associated with internalising difficulties (Cox p value=0.05). For childhood 3-phenoxybenzoic acid (PBA) concentrations, a positive association was observed with externalising difficulties (Cox p value=0.04) and high ORs were found for abnormal or borderline social behaviour (OR 2.93, 95% CI 1.27 to 6.78, and OR 1.91, 95% CI 0.80 to 4.57, for the intermediate and highest metabolite categories, respectively). High childhood trans-DCCA concentrations were associated with reduced externalising disorders (Cox p value=0.03).

Conclusions

The present study suggests that exposure to certain pyrethroids, at environmental levels, may negatively affect neurobehavioral development by 6 years of age.



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Autoimmune disorders linked to an increased risk of dementia

People with conditions like multiple sclerosis and psoriasis are more likely to develop dementia, and cardiovascular problems could be to blame

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Identifying high risk individuals for targeted lung cancer screening: Independent validation of the PLCOM2012 risk prediction tool

Abstract

Lung cancer screening with computerised tomography holds promise, but optimising the balance of benefits and harms via selection of a high risk population is critical. PLCOm2012 is a logistic regression model based on U.S. data, incorporating sociodemographic and health factors, which predicts 6-year lung cancer risk among ever-smokers, and thus may better predict those who might benefit from screening than criteria based solely on age and smoking history. We aimed to validate the performance of PLCOm2012 in predicting lung cancer outcomes in a cohort of Australian smokers. Predicted risk of lung cancer was calculated using PLCOm2012 applied to baseline data from 95,882 ever-smokers aged ≥45 years in the 45 and Up Study (2006-2009). Predictions were compared to lung cancer outcomes captured to June 2014 via linkage to population-wide health databases; a total of 1035 subsequent lung cancer diagnoses were identified. PLCOm2012 had good discrimination (area under the receiver-operating-characteristic-curve; AUC 0.80, 95%CI 0.78-0.81) and excellent calibration (mean and 90th percentiles of absolute risk difference between observed and predicted outcomes: 0.006 and 0.016, respectively). Sensitivity (69.4%, 95%CI, 65.6-73.0%) of the PLCOm2012 criteria in the 55-74 year age group for predicting lung cancers was greater than that using criteria based on ≥30 pack-years smoking and ≤15 years quit (57.5%, 53.3-61.3%; p<.0001), but specificity was lower (72.0%, 71.7-72.4% versus 75.2%, 74.8-75.6%, respectively; p<.0001). Targeting high risk people for lung cancer screening using PLCOm2012 might improve the balance of benefits versus harms, and cost-effectiveness of lung cancer screening. This article is protected by copyright. All rights reserved.



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