Σάββατο, 20 Μαΐου 2017

Syphilis

Syphilis: A sexually transmitted disease caused by Treponema pallidum, a microscopic organism called a spirochete. This worm-like, spiral-shaped organism infects people by burrowing into the moist mucous membranes of the mouth or genitals. From there, the spirochete produces a non-painful ulcer known as a chancre. There are three stages of syphilis:

  • The first (primary) stage: This involves the formation of the chancre. At this stage, syphilis is highly contagious. The primary stage can last one to five weeks. The disease can be transmitted from any contact with one of the ulcers, which are teeming with spirochetes. If the ulcer is outside of the vagina or on the scrotum, the use of condoms may not help in preventing transmission. Likewise, if the ulcer is in the mouth, merely kissing the infected individual can spread syphilis. Even without treatment, the early infection resolves on its own in most women.
  • The second (secondary) stage: However, 25 percent of cases will proceed to the secondary stage of syphilis, which lasts four to six weeks. This phase can include hair loss; a sore throat; white patches in the nose, mouth, and vagina; fever; headaches; and a skin rash. There can be lesions on the genitals that look like genital warts, but are caused by spirochetes rather than the wart virus. These wart-like lesions, as well as the skin rash, are highly contagious. The rash can occur on the palms of the hands, and the infection can be transmitted by casual contact.
  • The third (tertiary) stage: This final stage of the disease involves the brain and heart, and is usually no longer contagious. At this point, however, the infection can cause extensive damage to the internal organs and the brain, and can lead to death.

Diagnosis is by blood test, either the rapid plasma reagin (RPR) or Venereal Disease Research Laboratory (VDRL) test. Treatment is with antibiotics.

Syphilis remains a major health problem. About 12 million new cases of syphilis occur every year. More than 90% of them are in developing nations where congenital syphilis remains a leading cause of stillbirths and newborn deaths. In North America and Western Europe, syphilis is disproportionately common and rising among men who have sex with men and among persons who use cocaine or other illicit drugs.

The name "syphilis" was coined by Hieronymus Fracastorius (Girolamo Fracastoro). Fracastorius was a true Renaissance man; he wrote on the temperature of wines, the rise of the Nile, poetry, the mind, and the soul; he was an astronomer, geographer, botanist, mathematician, philosopher and, last but not least in the present context, a physician. In 1530 he published the poem "Syphilis sive morbus gallicus" (Syphilis or the French Disease) in which the name of the disease first appeared. Perhaps more importantly, Fracastorius went on in 1546 to write "On Contagion" ("De contagione et contagiosis morbis et curatione"), the first known discussion of the phenomenon of contagious infection: a landmark in the history of infectious disease.



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Building a bio-based industry in the Middle East through harnessing the potential of the Red Sea biodiversity

Abstract

The incentive for developing microbial cell factories for production of fuels and chemicals comes from the ability of microbes to deliver these valuable compounds at a reduced cost and with a smaller environmental impact compared to the analogous chemical synthesis. Another crucial advantage of microbes is their great biological diversity, which offers a much larger "catalog" of molecules than the one obtainable by chemical synthesis. Adaptation to different environments is one of the important drives behind microbial diversity. We argue that the Red Sea, which is a rather unique marine niche, represents a remarkable source of biodiversity that can be geared towards economical and sustainable bioproduction processes in the local area and can be competitive in the international bio-based economy. Recent bioprospecting studies, conducted by the King Abdullah University of Science and Technology, have established important leads on the Red Sea biological potential, with newly isolated strains of Bacilli and Cyanobacteria. We argue that these two groups of local organisms are currently most promising in terms of developing cell factories, due to their ability to operate in saline conditions, thus reducing the cost of desalination and sterilization. The ability of Cyanobacteria to perform photosynthesis can be fully exploited in this particular environment with one of the highest levels of irradiation on the planet. We highlight the importance of new experimental and in silico methodologies needed to overcome the hurdles of developing efficient cell factories from the Red Sea isolates.



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Self-protection against triptolide-induced toxicity in human hepatic cells via Nrf2-ARE-NQO1 pathway

Abstract

Objective

To find the signaling pathway of triptolide (TP)-induced liver injury and to reveal whether NF-E2-related factor 2 (Nrf2) plays an important role in cellular self-protection.

Methods

The L-02 and HepG2 cells were cultured and treated with various concentrations of TP. The cell viability was observed, and the cell medium was collected for detecting the aspartate aminotransferase (ALT), alanine aminotransferase (AST), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and L-glutathione production (GSH) levels. Nrf2 and its downstream target NAD(P)H: quinine oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1) expression, the nuclear translocation of Nrf2, and the binding ability of Nrf2 and antioxidant response element (ARE) were also identifified. Meanwhile, shRNA was used to silence Nrf2 in L-02 cells to fifind out whether Nrf2 plays a protective role.

Results

The viability of the L-02 and HepG2 cells treated with TP decreased in a doseand time-dependent manner, and TP (20–80 μg/mL) markedly induced the release of ALT, AST and LDH (P<0.05, P<0.01), reduced the levels of SOD and GSH (P<0.01), and increased the intracellular reactive oxygen species. Meanwhile, TP augmented the Nrf2 expression in L-02 and HepG2 cells (P<0.05, P<0.01), induced Nrf2 nuclear translocation, increased the Nrf2 ARE binding activity, and increased HO-1 and NQO1 expressions. Nrf2 knockdown revealed a more severe toxic effect of TP (P<0.05, P<0.01).

Conclusions

Human hepatic cells treated with TP induced oxidative stress, and led to cytotoxicity. Self-protection against TP-induced toxicity in human hepatic cells might be via Nrf2-ARE-NQO1 transcriptional pathway.



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Microenvironment of liver regeneration in liver cancer

Abstract

The occurrence and development of liver cancer are essentially the most serious outcomes of uncontrolled liver regeneration. The progression of liver cancer is inevitably related to the abnormal microenvironment of liver regeneration. The deterioration observed in the microenvironment of liver regeneration is a necessary condition for the occurrence, development and metastasis of cancer. Therefore, the use of a technique to prevent and treat liver cancer via changes in the microenvironment of liver regeneration is a novel strategy. This strategy would be an effective way to delay, prevent or even reverse cancer occurrence, development and metastasis through an improvement in the liver regeneration microenvironment along with the integrated regulation of multiple components, targets, levels, channels and time sequences. In addition, the treatment of “tonifying Shen (Kidney) to regulate liver regeneration and repair by affecting stem cells and their microenvironment” can regulate “the dynamic imbalance between the normal liver regeneration and the abnormal liver regeneration”; this would improve the microenvironment of liver regeneration, which is also a mechanism by which liver cancer may be prevented or treated.



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Idiosyncratic Drug-Induced Liver Injury Linked to Polygonum multiflorum : A Case Study by Pharmacognosy



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Lipid Oxidation, Color Changes, and Microbiological Quality of Frozen Beef Burgers Incorporated with Shirazi Thyme, Cinnamon, and Rosemary Extracts

In this study, the oxidative stability of beef burgers incorporated with Shirazi thyme, cinnamon, and rosemary extracts was compared with that of BHT-incorporated and antioxidant-free samples. The chemical composition, TBARS, metmyoglobin, pH, color, and microbial and sensory characteristics were evaluated during storage at −18°C for 2 months. The results indicated that Shirazi thyme and cinnamon extracts did not change the colorimetric properties significantly (). Incorporating natural antioxidants led to a significant () reduction in TBARS (36.58–46.34%) and metmyoglobin (16.25–18.47%) as compared to control. Except for the control sample, total microbial counts of burgers were lower than the maximum allowed limit. Burgers formulated with Shirazi thyme revealed the lowest amount of total count. Regarding the sensory characteristics, the overall acceptability of different samples decreased in the order of cinnamon > BHT > Shirazi thyme > rosemary > control. Finally, the results showed that these plant extracts can be utilized as an alternative to synthetic antioxidants in formulation of burgers.

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Event-Triggered Discrete-Time Distributed Consensus Optimization over Time-Varying Graphs

This paper focuses on a class of event-triggered discrete-time distributed consensus optimization algorithms, with a set of agents whose communication topology is depicted by a sequence of time-varying networks. The communication process is steered by independent trigger conditions observed by agents and is decentralized and just rests with each agent’s own state. At each time, each agent only has access to its privately local Lipschitz convex objective function. At the next time step, every agent updates its state by applying its own objective function and the information sent from its neighboring agents. Under the assumption that the network topology is uniformly strongly connected and weight-balanced, the novel event-triggered distributed subgradient algorithm is capable of steering the whole network of agents asymptotically converging to an optimal solution of the convex optimization problem. Finally, a simulation example is given to validate effectiveness of the introduced algorithm and demonstrate feasibility of the theoretical analysis.

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Lipid Droplets: Formation to Breakdown

Abstract

One of the most exciting areas of cell biology during the last decade has been the study of lipid droplets. Lipid droplets allow cells to store non-polar molecules such as neutral lipids in specific compartments where they are sequestered from the aqueous environment of the cell yet can be accessed through regulated mechanisms. These structures are highly conserved, appearing in organisms throughout the phylogenetic tree. Until somewhat recently, lipid droplets were widely regarded as inert, however progress in the field has continued to demonstrate their vast roles in a number of cellular processes in both mitotic and post-mitotic cells. No doubt the increase in the attention given to lipid droplet research is due to their central role in current pressing human diseases such as obesity, type-2 diabetes, and atherosclerosis. This review provides a mechanistic timeline from neutral lipid synthesis through lipid droplet formation and size augmentation to droplet breakdown.



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Hydrolysis of Phosphatidylcholine-Isoprostanes (PtdCho-IP) by Peripheral Human Group IIA, V and X Secretory Phospholipases A 2 (sPLA 2 )

Abstract

Biologically active F- and E/D-type-prostane ring isomers (F2-IP and E2/D2-IP, respectively) are produced in situ by non-enzymatic peroxidation of arachidonic acid esterified to GroPCho (PtdCho-IP) and are universally distributed in tissue lipoproteins and cell membranes. Previous work has shown that platelet-activating factor acetylhydrolases (PAF-AH) are the main endogenous PLA2 involved in degradation of PtdCho-IP. The present study shows that the PtdCho-IP are also subject to hydrolysis by group IIA, V and X secretory PLA2, which also have a wide peripheral tissue distribution. For this demonstration, we compared the LC/MS profiles of PtdCho-IP of auto-oxidized plasma lipoproteins after incubation for 1–4 h (37 °C) in the absence or presence of recombinant human sPLA2 (1–2.5 µg/ml). In the absence of exogenously added sPLA2 the total PtdCho-IP level after 4 h incubation reached 15.9, 21.6 and 8.7 nmol/mg protein of LDL, HDL and HDL3, respectively. In the presence of group V or group X sPLA2 (2.5 µg/ml), the PtdCho-IP was completely hydrolyzed in 1 h, while in the presence of group IIA sPLA2 (2.5 µg/ml) the hydrolysis was less than 25% in 4 h, although it was complete after 8–24 h incubation. This report provides the first demonstration that PtdCho-IP are readily hydrolyzed by group IIA, V and X sPLA2. A co-location of sPLA2 and the substrates in various tissues has been recorded. Thus, the initiation of interaction and production of isoprostanes in situ are highly probable.



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Automatic inspection of aeronautic components

Abstract

Industrial processes are costly in terms of time, money and customer satisfaction. The global economic pressures have gradually led businesses to improve these processes to become more competitive. As a result, the demand of intelligent visual inspection systems aimed at ensuring the high quality in production lines is increasing. In this paper, we present a computer vision system that, using only images, is able to address two main problems: (i) model checking: automatically check whether a component meets given specifications or rules, (ii) visual inspection: defect inspection on irregular surfaces, in particular, decolourization and scratches detection. In the experimental results, we show the effectiveness of our system and the readiness of such technologies for their integration in industrial processes.



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A double blind randomized prospective study comparing prilocaine versus ropivacaine in upper eyelid blepharoplasty

Dr. Ensat et al. [1] have to be eulogized for their aim to conduct their prospective randomized controlled trial. De facto, upper eyelid blepharoplasty is a very common surgical procedure which can be performed under local anaesthesia. Hence, we read this manuscript with extreme interest. In fact, we agree with the authors that one of the main elements to be considered during this procedure are bleeding and postoperative oedema. For this reason, any technical improvements in this particular field can potentially be a relevant step towards the achievement of better outcomes and post-operative quality of life.

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Reconstruction of combined thumb amputation at metacarpal base level and index amputation at metacarpal level with pollicization and bilateral double toe composite transfer

The aim of this study is to describe the technique and report our experience with reconstruction of combined proximal thumb amputations at the metacarpal base and index finger amputation at metacarpal level with pollicization and bilateral double toe composite transfer.

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Flowmetry evolution in microvascular surgery: A systematic review

This review aims to provide a summary of the flowmeter devices used in microvascular surgery, and assesses their contribution to improving the clinical outcomes of free-tissue transfer. Flowmeters are widely accepted as the standard method of intra-operative assessment of the patency of coronary vascular anastomoses, providing thresholds that predict outcome. There is limited evidence regarding the use of flow measurements in Plastic Surgery microvascular anastomoses; however, flowmetry appears to have some role in post-operative free flap monitoring and prevention of complications.

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Commentary on “Does intramuscular gluteal augmentation using implants affect sensitivity in the buttocks?”

none.

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Post-reconstruction dermatitis of the breast

Approximately one-third of women diagnosed with breast cancer undergo mastectomy with subsequent implant-based or autogenous tissue-based reconstruction. Potential complications include infection, capsular contracture, and leak or rupture of implants with necessity for explantation. Skin rashes are infrequently described complications of patients who undergo mastectomy with or without reconstruction.

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Body contouring after obesity surgery is associated with a weight loss benefit among patients

Patients who undergo obesity surgery often require body contouring procedures to eliminate excess skin. Recent studies suggest that body contouring surgery may provide psychological benefits to patients after obesity surgery. However, it is unclear how body contouring may impact weight loss maintenance after obesity surgery.

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Endoscopic DIEP flap dissection (eDIEP): an experimental cadaveric study

Over the last decades, DIEP (deep inferior epigastric perforator) flap has gradually replaced the TRAM (transverse rectus muscle abdominis) as the gold standard in autologous breast reconstruction [1]. The DIEP flap has reduced the risk of postoperative abdominal wall complications (hernia and bulging) by half compared to the TRAM [2].

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Measuring Satisfaction with Appearance: Validation of the FACE-Q Scales for double-eyelid blepharoplasty with minor incision in young Asians- Retrospective study of 200 cases

Double eye-lid surgery is one of the most popular performed aesthetic procedures in young Asians. Reliable measurement of patient reported outcomes is crucial for facial aesthetics. The FACE-Q is a new patient-reported outcome tool (PRO) composed of numerous independently functioning scales and checklists designed to measure outcomes. Here we described FACE-Q scales for double eye-lid surgery with minor incision in young Asians.

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Two-artery replantation for digital tip amputation

In digital tip replantation, as the amputation level becomes more distal, venous repair becomes more challenging. Indeed, venous insufficiency has a significant impact on the failure rate of fingertip replantation1. To solve this problem, we attempted to anastomose two arteries whenever possible based on the brief that internal circulation is provided through arteriovenous communication and that a greater blood flow is necessary to restore the severely damaged tissue. From May 1998 to December 2015, 38 fingertip replantations with 2 arteries repair were performed in 38 patients.

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Preventing the Complications of Tissue Expansion Using Fat Grafting Under Expanded Skin

Soft tissue expansion is a widely used technique for repairing soft tissue defects because of its multiple advantages. However, the limiting regenerative capacity of skin always leads to many complications with an occurrence rate of 3.65% for tissue necrosis and 1.68% for expander exposure(1, 2). Fortunately, we can observe several early signs before these complications, like skin thinning, telangiectasia, embolism and striae. Without timely and effective treatment, these early signs will turn into complications and the treatment will finally fail (Figure 1).

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Complications after prominent ear correction – A systematic review of the literature

There is great diversity in reported post-operative outcomes for otoplasty, with the incidence of haematoma or infection ranging from 0 percent to 15.6 percent and 0 percent to 10 percent respectively. With such variability it is difficult to determine an overall “average” incidence of common post-operative complications.

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Cost Analysis of Percutaneous Fixation of Hand Fractures in the Main Operating Room Versus the Ambulatory Setting

To date, there have been no studies identifying the cost differential for performing closed reduction internal fixation (CRIF) of hand fractures in the operating room (OR) versus an ambulatory setting. Our goal was to analyze the cost and efficiency of performing CRIF in these two settings and to investigate current practice trends in Canada.

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Income is an independent risk factor for worse asthma outcomes

Asthma outcomes are worse in low income groups, regardless of race, BMI, perceived stress, inhaled corticosteroid dose or adherence, baseline asthma control, and second-hand smoke exposure. This suggests that clinicians and researchers should consider income when managing patients and designing interventions.

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Prognostic value of lymph node density in buccal squamous cell carcinoma

Lymph node density(LND) has been shown to be a better prognosticator than conventional nodal classification to predict prognosis for squamous cell carcinoma(SCC) of the oral cavity. However, studies focusing on subsites of oral cancer are meager. The role of LND for buccal SCC was evaluated in this study.

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Compound Mechanism of Fatal Neck Injury: A Case Report of a Tiger Attack in a Zoo

Cases of attacks by large wild cats (tigers, leopards, pumas, lions) on humans are reported relatively rarely in the medical literature, including forensic reports, a fact highlighted by most authors of published case reports [1–22]. Some of the reported cases concern: attacks on zoo employees [1–4]; an attack on a zoo visitor during an attempt to feed an animal [5]; an accident in a private zoo [6]; an attack on a tiger trainer during a show [7]; an attack in an animal sanctuary in Oklahoma [8]; uncommon case of suicide in a lions’ den of a zoo [9]; and an attack on 2year-old girl by her father’s pet leopard [10].

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Further evidence for GHB naturally occurring in common non-alcoholic beverages

The identification and quantitation of gamma-hydroxybutyric acid (GHB) in beverages is considered challenging in forensic evidence. GHB has been implicated in many cases of suspected surreptitious administration with the purpose of increasing victim vulnerability to sexual assault. For this reason, some studies have focused on the determination of GHB in spiked alcoholic and non-alcoholic beverages [1]. However, previously the presence of endogenous (or naturally occurring) GHB in beverages has been reported in various publications [2–4].

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Roles of Purinergic P2X7 Receptor in Glioma and Microglia in Brain Tumors

This review considers evidence suggesting that activation of the ionotropic purinergic receptor P2X7 (P2X7R) is a contributing factor in the growth of brain tumors. Importantly, expression of P2X7R may be upregulated in both glioma cells and in immune responding microglial cells with possible differential effects on tumor progression. The recruitment of immune cells into tumor regions may not only be involved in supporting an immunosuppressive environment aiding tumor growth but activated microglia could secrete inflammatory factors promoting neoangiogenesis in expanding tumors.

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Comment on “Circular RNA profile identifies circPVT1 as a proliferative factor and prognostic marker in gastric cancer,” Cancer Lett. 2017 Mar 1; 388(2017): 208-219

With great interest, we read a recent article in Cancer Letters by Chen et al [1], which reported that a novel circular RNA, circPVT1, was screened from ribo-minus RNA sequencing data of gastric cancer (GC) tissues. Afterwards, circPVT1 was analysed up-regulated in both GC tissues and cells. In addition, this circular RNA was proved to inhibit the proliferation of gastric cancer (GC) cells by silencing, which was very significant. Surprisingly, circPVT1 was proved to be negatively associated with T4 stage and nervous invasion.

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Tg737 regulates epithelial-mesenchymal transition and cancer stem cell properties via a negative feedback circuit between Snail and HNF4α during liver stem cell malignant transformation

Determining the origin of liver cancer stem cells is important for treating hepatocellular carcinoma. Tg737 deficiency plays an important role in the malignant transformation of liver stem cells, but the underlying mechanism remains unclear. Here we established a chemical-induced mouse hepatoma model and found that Tg737 and hepatocyte nuclear factor 4-alpha (HNF4α) expression decreased and epithelial-mesenchymal transition (EMT)-related marker expression increased during liver cancer development.

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Chemosensitization and Inhibition of Pancreatic Cancer Stem Cell Proliferation by Overexpression of microRNA-205

Treatment of pancreatic cancer with gemcitabine (GEM) is limited due to its rapid plasma metabolism and development of chemoresistance. MicroRNA (miRNA) regulates cancer stem cell (CSC) maintenance and induces chemoresistance in cancer cells. In this study, we observed differential downregulation of miR-205 (miR-205-5p) in human pancreatic cancer tissues and cells. Compared to GEM-sensitive MIA PaCa-2 cells, miR-205 was highly downregulated in GEM-resistant MIA PaCa-2R cells. Lentivirus-mediated overexpression of miR-205 inhibits MIA PaCa-2R cell proliferation after GEM-treatment.

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Melittin, a major peptide component of bee venom, and its conjugates in cancer therapy

Melittin (MEL), a major peptide component of bee venom, is an attractive candidate for cancer therapy. This agent has shown a variety of anti-cancer effects in preclinical cell culture and animal model systems. Despite a convincing efficacy data against variety of cancers, its applicability to humans has met with challenges due to several issues including its non-specific cytotoxicity, degradation and hemolytic activity. Several optimization approaches including utilization of nanoparticle based delivery of MEL have been utilized to circumvent the issues.

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The Individual and Population Genetics of Antibody Immunity

Publication date: Available online 20 May 2017
Source:Trends in Immunology
Author(s): Corey T. Watson, Jacob Glanville, Wayne A. Marasco
Antibodies (Abs) produced by immunoglobulin (IG) genes are the most diverse proteins expressed in humans. While part of this diversity is generated by recombination during B-cell development and mutations during affinity maturation, the germ-line IG loci are also diverse across human populations and ethnicities. Recently, proof-of-concept studies have demonstrated genotype–phenotype correlations between specific IG germ-line variants and the quality of Ab responses during vaccination and disease. However, the functional consequences of IG genetic variation in Ab function and immunological outcomes remain underexplored. In this opinion article, we outline interconnections between IG genomic diversity and Ab-expressed repertoires and structure. We further propose a strategy for integrating IG genotyping with functional Ab profiling data as a means to better predict and optimize humoral responses in genetically diverse human populations, with immediate implications for personalized medicine.



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Usefulness of 11C-methionine-PET for predicting the efficacy of carbon ion radiation therapy for head and neck mucosal malignant melanoma

Publication date: Available online 20 May 2017
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): M. Hasebe, K. Yoshikawa, R. Nishii, K. Kawaguchi, T. Kamada, Y. Hamada
The aim of this study was to determine whether l-methyl-[11C]-methionine (MET) positron emission tomography (PET) allows the prediction of outcomes in patients with head and neck mucosal malignant melanoma treated with carbon ion radiation therapy (CIRT). This was a retrospective cohort study involving 85 patients who underwent a MET-PET or MET-PET/computed tomography (CT) examination before and after CIRT. MET uptake in the tumour was evaluated semi-quantitatively using the tumour-to-normal tissue ratio (TNR). Local recurrence, metastasis, and outcome predictions were studied in terms of TNR before CIRT (TNRpre), TNR after CIRT (TNRpost), and the TNR change ratio. Kaplan–Meier curves revealed significant differences between patients with higher TNRpre values and those with lower TNRpre values in regard to local recurrence, metastasis, and outcome (log-rank test P<0.0001 for all three). There were also significant differences in metastasis rates and outcomes between patients with higher and lower TNRpost values (log-rank test P=0.0105 and P=0.027, respectively). The Cox proportional hazards model revealed TNRpre to be a factor significantly influencing the risk of local recurrence (hazard ratio (HR) 29.0, P<0.001), risk of metastasis (HR 2.67, P=0.024), and the outcome (HR 6.3, P<0.001). MET-PET or MET-PET/CT is useful for predicting the outcomes of patients with head and neck mucosal malignant melanoma treated with CIRT.



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Allergen immunotherapy for the treatment of respiratory allergies in the elderly.

Purpose of review: Respiratory allergies, including asthma and allergic rhinitis can also occur in the elderly. Allergen immunotherapy for allergic diseases is the only disease-modifying treatment for patients with allergies available thus far. Here, we review current evidence supporting the use of allergen immunotherapy in the elderly and discuss its efficacy and utility for the treatment of respiratory allergic diseases in this setting. Recent findings: Subcutaneous and/or sublingual immunotherapy are effective therapeutic options in not only young but also older patients. Allergen immunotherapy reduces medication and symptom scores in the elderly and can thus be safely prescribed in this population. Summary: Elderly individuals with proven, clinically relevant immunoglobulin E sensitization to inhalant allergens may benefit from allergen immunotherapy for respiratory allergic diseases. Older patients without contraindications should therefore be considered for treatment, with the additional benefit of reduced medication and symptom scores. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Combined effects of Chinese medicine feed and ginger extract bath on co-infection of Ichthyophthirius multifiliis and Dactylogyrus ctenopharyngodonid in grass carp

Abstract

Dactylogyrus ctenopharyngodonid and Ichthyophthirius multifiliis are two important ectoparasites of freshwater fish. Co-infection by the two parasites leads to high fish mortality and results in heavy economic losses. This study aimed to evaluate the efficacy of medicated feed and a ginger extract bath against D. ctenopharyngodonid and I. multifiliis on grass carp and investigate the hematological response of grass carp co-infected by the two parasites. These results demonstrated that red blood cell (RBC) and thrombocyte percentage among leucocytes significantly decreased after grass carp were co-infected by D. ctenopharyngodonid and I. multifiliis. The monocyte and neutrophil percentages significantly increased with the increment of parasite mean intensities, while the lymphocyte percentage decreased. The activities of serum acid phosphatase (ACP), alkaline phosphatase (AKP), lysozyme (LZM), and superoxide dismutase (SOD) significantly increased after co-infection. When grass carp treated with medicated feed containing 4% of Astragalus membranaceus, Allium sativum, Morus alba, and Glycyrrhiza uralensis, the activities of ACP, AKP, LZM, and SOD were significantly enhanced, and the mean intensities of D. ctenopharyngodonid and I. multifiliis were significantly decreased. When grass carp was treated with medicated feed and a 4-mg/L ginger extract bath, all parasites were eliminated during 28 days. The bath of ginger extract at a concentration of 4 mg/L kept a low mean intensity of I. multifiliis and D. ctenopharyngodonid, then the two parasites were eliminated by oral administration of the medicated feed with an immunostimulant (Chinese medicine compound).



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Evaluating the role of autologous mesenchymal stem cell seeded on decellularized pericardium in the treatment of myocardial infarction: an animal study

Abstract

Inappropriate left ventricular remodeling following myocardial infarction (MI) can result in subsequent severe dysfunction. In this study, we tested the hypothesis that decellularized pericardium (DP) or seeded pericardial patch with autologous adipose-derived mesenchymal stem cells (ADMSCs) could be safely used in a MI scar and could improve heart function. Twelve rabbits were randomly divided into three equal groups. Four weeks after MI induction by ligation of the left anterior descending artery in 12 rabbits, animals of G1 (n = 4) received DP patch with labeled ADMSCs. DP patch was implanted in animals of G2 (n = 4). Rabbits of G3 (n = 4) remained without any intervention after MI induction (control group). Serial examinations including echocardiography, electrocardiography (ECG), scanning electron microscopy, histology and immunohistochemistry (IHC) were performed to evaluate the efficacy of the implanted scaffolds on recovery of the infracted myocardium. The results demonstrated that left ventricular contractile function and myocardial pathological changes were significantly improved in rabbits implanted with either DP or ADMSC-seeded pericardium. However, the seeded pericardium was more effective in scar repairing 2 months after the operation, IHC staining with Desmin and CD34 and positive immunofluorescence staining verified the differentiation of ADMSCs to functional cardiomyocytes. This approach may involve the application of autologous ADMSCs seeded on pericardial patch in an attempt to regenerate a contractible myocardium in an animal model of MI.



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Preparation of allogeneic bone for alveolar ridge augmentation

Abstract

Implant treatment is safe and predictable with sufficient amount and quality of bone tissue. In case of severely reduced bone tissue after a tooth was lost, augmentation of such tissue is necessary before implant embedment. Retrospective evaluation covered 380 alveolar ridge reconstructions. The study material consisted of human grafts prepared by the Department of Transplantology and Central Tissue Bank, Medical University of Warsaw. Presentation of laboratory procedures in the context of physical parameters of frozen, radiation sterilised, allogeneic corticocancellous material was presented. The preparation process makes it possible to obtain two types of bone material: granules and blocks. Women underwent 164 procedures with the use of bone granules and 61 augmentations with bone blocks. In case of men 122 packages of granules were used as well as 33 bone blocks. Based on the results an evaluation of usability of available allogeneic grafts was performed with reference to planned alveolar ridge augmentation procedures, which they were used for.

  1. The opportunity to prepare allogeneic material of different textures allowed selection to meet augmentation requirements while providing biological safety.

  2. Allogeneic granules should be used in multi-wall defects, such as a double, closed sinus lift and post-extraction socket augmentation.

  3. Owing to their superior mechanical parameters, bone blocks were successfully used in extending the width and height of the alveolar ridge and in open sinus lifts with one-wall or two-wall defects and adequate location of the lamellar bone in a graft prevented substantial graft resorption.



http://ift.tt/2rDpfem

Cosmological parameters in a generalized multi-function gravitation model $$f(T,\theta )$$ f ( T , θ )

Abstract

The aim of the present article was to study the cosmological model \(f(T,\theta )\) . By introducing and examining this model as well as a number of other proposed \(f(T,\theta )\) models, certain cosmological parameters were analyzed in this framework, and their behaviors were investigated. Ultimately, the results were qualitatively compared with the observational data. It was found that by employing proper coefficients, phantom crossing division occured for the equation of state, thus pointing to the existence of a bouncing universe scenario. Furthermore, it was revealed that by creating a potential in the model, inflation could be produced, and the early cosmos could be studied.



http://ift.tt/2pXeR41

Preparation and anticancer activity evaluation of an amorphous drug nanocomposite by simple heat treatment

imageThe solubility of drug molecules is closely related to its bioactivity as it affects the dissolution rate and bioavailability, especially in the case of BCS IV drugs like camptothecin (CPT), a potential broad-spectrum anticancer agent. In this study, we construct a novel boric acid (BA)-coated CPT nanocomposite by means of a simple heat-treatment approach, which combines nanoscale size range and amorphous solid state together to improve the overall dissolution rate of CPT. This new CPT formulation showed a rod-like structure with nanoscale size and amorphous solid nature. These BA-coated CPT nanocomposites exhibited a dramatically improved dissolution rate, water dispersion property, and long-term chemical and physical stability. More importantly, the specific reactivity of BA groups to diols in the cell glycocalyx facilitated a rapid cross-membrane translocation of the drug nanocomposite, leading to efficient intracellular drug delivery. When tested on A549 cells and SKBR3 cells, this formulation demonstrated a much higher anticancer activity in comparison with free CPT, naked amorphous CPT nanoparticles, and control CPT nanocrystals. This formulation has great potential for clinical application; it is easy to scale up and be applied on other hydrophobic drugs.

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Bortezomib pharmacokinetics in tumor response and peripheral neuropathy in multiple myeloma patients receiving bortezomib-containing therapy

imageThe usefulness of pharmacokinetics of bortezomib for multiple myeloma (MM) with respect to the maximum response to bortezomib and bortezomib-induced peripheral neuropathy (BIPN) development was studied. Maximum response to subcutaneous bortezomib therapy and BIPN occurrence for the first 12 weeks of treatment in 35 MM patients treated by bortezomib–dexamethasone (VD) and bortezomib–melphalan–prednisone (VMP) were evaluated. On day 1 of cycle 1, seven whole-blood samples were collected for 3 h after dosing completion to obtain the maximum plasma concentration and area under the time–concentration curve during 3 h postdose (AUC0–3) in each patient. A total of 35 patients with complete data were analyzed and the overall response rate was 91.4%. Complete response (CR) was observed in 42.9% patients. The maximum plasma concentration (Cmax) was significant for the CR rate in two different models [full model: odds ratio (OR)=1.092; P=0.038, final model: OR=1.081; P=0.038]. In addition, Cmax was associated with a progression-free survival advantage. Overall, 48.6% of patients developed BIPN including peripheral sensory neuropathy and neuralgia. The VMP-treated patients had a higher risk compared with the VD-treated patients (OR=21.662; P=0.029). Cmax had a tendency to affect the occurrence of BIPN (≥grade 2) (OR=1.064; P=0.092). In real-world clinical practice using bortezomib for MM patients, Cmax among pharmacokinetic factors significantly affected the achievement of CR. The VMP-treated patients showed vulnerability to BIPN, suggesting the necessity for more careful monitoring.

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Baicalin inhibits human osteosarcoma cells invasion, metastasis, and anoikis resistance by suppressing the transforming growth factor-β1-induced epithelial-to-mesenchymal transition

imageThe epithelial–mesenchymal transition (EMT) plays an important role in inducing cancer metastasis. Baicalin, a flavone derivative isolated from Scutellaria spp., shows a series of pharmacological and physiological activities. However, the possible role of baicalin in the EMT is unclear. In this study, we attempted to investigate the potential use of baicalin as an inhibitor of transforming growth factor-β1 (TGF-β1)-induced EMT in U2OS cells. We found that TGF-β1 induced the EMT to promote U2OS cells migration, invasion, and anoikis resistance. Western blotting showed that baicalin inhibited U2OS cells’ invasion and migration, increased the expression of the epithelial phenotype marker E-cadherin, repressed the expression of the mesenchymal phenotype marker vimentin, as well as decreased the level of EMT-inducing transcription factors Snail1 and Slug during the initiation of TGF-β1-induced EMT. Baicalin also inhibited the TGF-β1-induced increase in cell migration, invasion, and anoikis resistance in TGF-β1-induced U2OS cells. In addition, the TGF-β1-mediated phosphorylated levels of Smad2/3 were inhibited by baicalin pretreatment. Above all, we conclude that baicalin suppresses human osteosarcoma cells’ migration, invasion, and anoikis resistance in vitro through suppression of TGF-β1-induced EMT.

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Isatin inhibits SH-SY5Y neuroblastoma cell invasion and metastasis through MAO/HIF-1α/CXCR4 signaling

imageIsatin was reported to possess anticancer activities through its effect on tumor proliferation, apoptosis, and metastasis in vitro and in vivo. This study aimed to elucidate the underlying mechanism behind isatin’s ability to inhibit neuroblastoma cell metastasis. Our results demonstrated that isatin could inhibit neuroblastoma cell proliferation, invasion, and migration in a dose-dependent manner. Moreover, isatin inhibited the expression level of monoamine oxidase A as well as that of its downstream protein hypoxia-inducible factor 1α. Further study indicated that isatin inhibited reactive oxygen species production, extracellular signal-regulated kinase activation, vascular endothelial growth factor receptor-1 phosphorylation, and chemokine receptor type 4 expression. All results support the potential antimetastatic effect of isatin in neuroblatoma cells.

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MicroRNA-148a promotes apoptosis and suppresses growth of breast cancer cells by targeting B-cell lymphoma 2

imageMicroRNAs (miRNAs) contribute toward tumorigenesis through the modulation of tumor-related genes. MiR-148a has been characterized as a tumor-suppressing miRNA and its downregulation has been reported in tumors of a variety of cancers. However, the functional role of miR-148a in breast cancer is not yet fully understood. Using both in-vitro and in-vivo models, we confirmed that miR-148a acts to inhibit the proliferation of breast cancer cells. Through the use of bioinformatic approaches in miRNA target prediction, we determined that B-cell lymphoma 2 (BCL-2) is a likely target of miR-148a. The overexpression and tumorigenic effects of BCL-2 have already been confirmed in cancerous tumors of the breast. A dual-luciferase assay was performed to confirm that miR-148a targets the 3′-untranslated region of BCL-2. In this study, we first characterized the downregulation of miR-148a in breast cancer tissues. We then found that restoring expression of miR-148a suppressed the expression of BCL-2 at the level of both mRNA and protein. Upregulation of miR-148a caused a subsequent reduction of proliferation and an increase in apoptosis. In conclusion, we have confirmed the role of miR-148a as a pivotal regulator in breast cancer through its targeting of BCL-2. This evidence strongly suggests that miR-148a could prove to be a novel therapeutic target in breast cancer.

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Protein kinase B: emerging mechanisms of isoform-specific regulation of cellular signaling in cancer

imageThe serine/threonine protein kinase B (PKB), also known as Akt, is one of the multifaceted kinases in the human kinome, existing in three isoforms. PKB plays a vital role in phosphoinositide 3-kinase (PI3K)-mediated oncogenesis in various malignancies and is one of the attractive targets for cancer drug discovery. Recent studies have shown that the functional significance of an individual isoform of PKB is not redundant in cancer. It has been found that PKB isoforms play distinct roles in the regulation of cellular invasion and migration during tumorigenesis. PKB activation plays a central role during epithelial–mesenchymal transition, a cellular program required for the cancer cell invasion and migration. However, the differential behavior of each PKB isoform has been shown in the regulation of epithelial–mesenchymal transition. Recent studies have suggested that PKBα (Akt1) plays a conflicting role in tumorigenesis by acting either as a pro-oncogenic factor by suppressing the apoptotic machinery or by restricting tumor invasion. PKBβ (Akt2) promotes cell migration and invasion and similarly PKBγ (Akt3) has been reported to promote tumor migration. As PKB is known for its pro-oncogenic properties, it needs to be unraveled how three isoforms of PKB compensate during tumor progression. In this review, we attempted to sum up how different isoforms of PKB play a role in cancer progression, metastasis, and drug resistance.

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Activation of a c-Jun N-terminal kinase-mediated autophagy pathway attenuates the anticancer activity of gemcitabine in human bladder cancer cells

imageThe role of autophagy in the anticancer activity of gemcitabine (GEM) in bladder cancer is unclear. The aim of this study is to determine whether GEM activates autophagy, the role of autophagy in the anticancer activity of GEM, and the underlying mechanism by which GEM induces autophagy. Human bladder cancer cell lines T24 and BIU87 were treated with GEM in vitro. Cell viability was measured using the Cell Counting Kit-8 assay. Apoptosis was detected by annexin V assay and western blot. Autophagy was measured by western blot and transmission electron microscopy. c-Jun N-terminal kinase (JNK) activation was detected by western blot. Chemical inhibitors were used for intervention of JNK and autophagy. GEM killed bladder cancer cells, which was associated with apoptosis induction. Autophagy was effectively activated by GEM. Suppressing autophagy in GEM-treated cells significantly decreased cell viability, which was associated with increased apoptosis. GEM-induced JNK activation and suppressed B-cell lymphoma 2 expression. The JNK inhibitor SP600125 inhibited GEM-induced autophagy activation and increased GEM’s cytotoxicity. GEM kills bladder cancer cells through apoptosis. Meanwhile, JNK-mediated autophagy was activated, which protects the cells against apoptosis. Therefore, inhibition of autophagy could be exploited to enhance the anticancer efficacy of GEM for treating bladder cancer.

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The aurora kinase inhibitor AMG 900 increases apoptosis and induces chemosensitivity to anticancer drugs in the NCI-H295 adrenocortical carcinoma cell line

imageAdrenocortical tumor (ACT) is a malignancy with a low incidence rate and the current therapy for advanced disease has a limited impact on overall patient survival. A previous study from our group suggested that elevated expression of aurora-A and aurora-B is associated with poor outcome in childhood ACT. Similar results were also reported for adult ACTs. The present in-vitro study shows that AMG 900 inhibits aurora kinases in adrenocortical carcinoma cells. AMG 900 inhibited cell proliferation in NCI-H295 cells as well as in the ACT primary cultures and caused apoptosis in the cell line NCI-H295. Furthermore, it potentialized the mitotane, doxorubicin, and etoposide effects on apoptosis induction and acted synergistically with mitotane and doxorubicin in the inhibition of proliferation. In addition, we found that AMG 900 activated Notch signaling and rendered the cells sensitive to the combination of AMG 900 and Notch signaling inhibition. Altogether, these data show that aurora kinases inhibition using AMG 900 may be an adjuvant therapy to treat patients with invasive or recurrent adrenocortical carcinomas.

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Pseudolaric acid B induces endometrial cancer Ishikawa cell apoptosis and inhibits metastasis through AKT-GSK-3β and ERK1/2 signaling pathways

imagePseudolaric acid B (PAB) is the most active constituent extracted from the bark of Pseudolarix kaempferi, which has been used as an antifungal remedy in traditional Chinese medicine. It is reported to have cytotoxicity to many tumor cell lines. In this study, we investigated the effects of PAB against human endometrial cancer Ishikawa cells. We found that PAB inhibited Ishikawa cell proliferation, and induced cell apoptosis and G2/M phase arrest through a mechanism involving AKT-GSK-3β and ERK1/2 signaling pathways. PAB also suppressed the Ishikawa cell adhesion, invasion, migration, and colony formation ability by increasing the expression of E-cadherin, Ezrin, and Kiss-1, and decreasing the expression of matrix metalloproteinase-9 and vascular endothelial growth factor. Taken together, these data indicated that PAB can be expected to be a novel treatment agent for endometrial cancer therapy.

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Weekly paclitaxel after first-line failure in patients with advanced non-small-cell lung cancer: everyday clinical practice in a single centre

imageTo assess the activity of weekly paclitaxel (wPCT) in pretreated patients with advanced non-small-cell lung cancer (aNSCLC). In 2005, we included wPCT 80 mg/m2 for 6 consecutive weeks, followed by a 2-week interval in our department’s everyday clinical practice guidelines for the second-line (or subsequent) treatment of patients with nonsquamous histologies who have previously received pemetrexed-based treatments and patients with squamous histology. In the absence of clinical evidence of disease progression, patients repeat the pretreatment staging procedures after 16 weeks (two cycles) and, in the absence of disease progression or severe toxicity, continue treatment for a maximum of four courses. Between May 2005 and December 2013, we treated 60 patients (47 in second-line and 13 in third/fourth line), who received a median of two courses (range: 1–4). The most frequent toxicity was grade 1–2 neutropaenia (five patients); only four patients experienced grade 3–4 toxicity. When used as a second-line treatment, wPCT led to a disease control rate of 36.2%, with a median progression-free survival of 3.7 months and a median overall survival of 9.0 months; when used in the third/fourth line, the disease control rate was 41.7%, the median progression-free survival was 5.0 months and the median overall survival was 10.3 months. Our data confirm that wPCT is active and well tolerated in an unselected patient population with aNSCLC and can be considered a valuable alternative to docetaxel in a second-line treatment.

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Oxytocin inhibits head and neck squamous cell carcinoma cell migration by early growth response-1 upregulation

imageThe effect of oxytocin (OXT) on cancer invasion is controversial. Few studies have examined the effect of early growth response-1 (EGR1) on the invasion of head and neck squamous cell carcinoma (HNSCC). Here, we evaluated how EGR1 affects HNSCC cell migration through the molecular mechanism of OXT in exerting anti-invasion activity. Matrigel invasion and wound-healing assays were used to measure the in-vitro cell migration. The molecular mechanism of OXT was assessed by knockdown or overexpression of EGR1 in HNSCC cells. Three-dimensional (3-D) spheroids formation, followed by the image analysis for quantification was performed. OXT at 500 nmol/l increased mRNA and protein expression of E-cadherin without cytotoxicity. OXT upregulated mRNA and protein expression of EGR1 in 6 h. p53, phosphatase and tensin, and p21 expression was increased in an EGR1-dependent manner with OXT treatment. In addition, OXT significantly downregulated 3-D spheroids’ formation according to spheroids’ number and size. Our data showed that OXT downregulated HNSCC cell migration by EGR1 upregulation. OXT inhibited spheroids’ formation of HNSCC cells under 3-D culture conditions.

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The incidence of radiation necrosis following stereotactic radiotherapy for melanoma brain metastases: the potential impact of immunotherapy

imageStereotactic radiotherapy (SRT) is the standard treatment for patients with limited number of brain metastases. In the past few years, newer immunotherapies (immune checkpoint inhibitors) have been proven to prolong survival in patients with metastatic melanoma. The safety of the combination of SRT and immunotherapy for brain metastases is unknown. We retrospectively identified patients with melanoma brain metastases treated with SRT between 2007 and 2015. Patients who did not have at least 3 months of follow-up with imaging after SRT were excluded from the analysis. Outcomes were compared between patients who were treated with or without immunotherapy. A total of 58 patients were included; of these, 29 were treated with SRT and immunotherapy. MAPK inhibitors (BRAF, MEK inhibitors) were used more often in the immunotherapy group (nine vs. two patients). There was a higher incidence of intracranial complications in patients treated with immunotherapy and SRT. Eight patients had radiation necrosis; all occurred in patients who were treated with immunotherapy. Nine patients had hemorrhage, of which seven occurred in patients who were treated with immunotherapy (P=0.08). However, patients treated with immunotherapy and SRT had a significant overall survival advantage compared with SRT without immunotherapy (15 vs. 6 months, P=0.0013). Patients treated with SRT and immunotherapy have a higher incidence/risk of intracranial complications, but a longer overall survival.

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A multi-gene panel study in hereditary breast and ovarian cancer in Colombia

Abstract

Germline mutations in BRCA1 and BRCA2 account for approximately 50% of inherited breast and ovarian cancers. Three founder mutations in BRCA1/2 have been reported in Colombia, but the pattern of mutations in other cancer susceptibility genes is unknown. This study describes the frequency and type of germline mutations in hereditary breast and/or ovarian cancer genes in a referral cancer center in Colombia. Eighty-five women referred to the oncogenetics unit of the Instituto de Cancerologia Las Americas in Medellin (Colombia), meeting testing criteria for hereditary breast and ovarian cancer syndrome (NCCN 2015), who had germline testing with a commercial 25-gene hereditary cancer panel, were included in the analysis. Nineteen patients (22.4%) carried a deleterious germline mutation in a cancer susceptibility gene: BRCA1 (7), BRCA2 (8), PALB2 (1), ATM (1), MSH2 (1) and PMS2 (1). The frequency of mutations in BRCA1/2 was 17.6%. One BRCA2 mutation (c.9246dupG) was recurrent in five non-related individuals and is not previously reported in the country. Seventeen mutation-carriers had a diagnosis of breast cancer (median age of diagnosis of 36 years) and two of ovarian cancer. All BRCA1 mutation-carriers with breast cancer had triple negative tumors (median age of diagnosis of 31 years). Variants of unknown significance were reported in 35% of test results. This is the first report of a multi-gene study for hereditary breast and/or ovarian cancer in a Latin American country. We found a high frequency and a wide spectrum of germline mutations in cancer susceptibility genes in Colombian patients, some of which were not previously reported in the country. We observed a very low frequency of known Colombian founder BRCA1/2 mutations (1.2%) and we found mutations in other genes such as PALB2, ATM, MSH2 and PMS2. Our results highlight the importance of performing multi-gene panel testing, including comprehensive BRCA1/2 analysis (full gene sequencing and large rearrangement analysis), in high-risk breast and/or ovarian cancer patients in Colombia.



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Loss of MSH2 and MSH6 due to heterozygous germline defects in MSH3 and MSH6

Abstract

Lynch Syndrome (LS) is the most common dominantly inherited colorectal cancer (CRC) predisposition and is caused by a heterozygous germline defect in one of the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, or PMS2. High microsatellite instability (MSI-H) and loss of MMR protein expression in tumours reflecting a defective MMR are indicators for LS, as well as a positive family history of early onset CRC. MSH2 and MSH6 form a major functional heterodimer, and MSH3 is an alternative binding partner for MSH2. So far, the role of germline MSH3 variants remains unclear, as to our knowledge heterozygous truncating variants are not regarded causative for LS, but were detected in patients with CRC, and recently biallelic MSH3 defects have been identified in two patients with adenomatous polyposis. By gene screening we investigated the role of MSH3 in 11 LS patients with truncating MSH6 germline variants and an unexplained MSH2 protein loss in their corresponding MSI-H tumours. We report the first two LS patients harbouring heterozygous germline variants c.1035del and c.2732T>G in MSH3 coincidentally with truncating variants in MSH6. In the patient with truncating germline variants in MSH3 and MSH6, two additional somatic second hits in both genes abrogate all binding partners for the MSH2 protein which might subsequently be degraded. The clinical relevance of MSH3 germline variants is currently under re-evaluation, and heterozygous MSH3 defects alone do not seem to induce a LS phenotype, but might aggravate the MSH6 phenotype in affected family members.



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Ustekinumab: A Review in Moderate to Severe Crohn’s Disease

Abstract

Ustekinumab (Stelara®) has been recently approved in the EU and the USA as intravenous induction and subcutaneous maintenance therapy for adult patients with moderately to severely active Crohn's disease who have failed or were intolerant to treatment with immunomodulators, corticosteroids or at least one tumour necrosis factor (TNF) antagonist. Ustekinumab, a monoclonal antibody to the shared p40 subunit of the proinflammatory interleukin (IL)-12 and IL-23 cytokines, has a unique mechanism of action distinct from that of TNF antagonists. In pivotal phase III trials, compared with placebo, ustekinumab induction therapy improved clinical response and remission rates in patients who had previously failed or were intolerant to conventional therapies or at least one TNF antagonist. When administered as subcutaneous maintenance therapy, ustekinumab continued to offer benefits over placebo for clinical response and remission in patients who had clinically responded to the induction therapy. Ustekinumab was generally well tolerated as both induction and maintenance therapy; serious infections and malignancies were rare. Thus, ustekinumab presents a promising alternative treatment option in patients with moderately to severely active Crohn's disease who have failed or are intolerant to treatment with conventional therapies or TNF antagonists.



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Clinical investigation of chronic subdural hematoma with impending brain herniation on arrival

Abstract

Chronic subdural hematoma (CSDH) with brain herniation signs is rarely seen in the emergent department. As such, there are few cumulative data to analyze such cases. In this study, we evaluated the clinical features, risk factors, and rates of completion with impending brain herniation on arrival in a cohort study. We analyzed 492 consecutive patients with CSDH between January 2010 and October 2015. First, we analyzed the clinical factors and compared them between patients with or without brain herniation signs on admission. Second, we compared clinical factors between patients with or without completion of brain herniation after operation among patients who had brain herniation signs on arrival. Eleven (2.2%) patients showed brain herniation signs on arrival, and six patients (1.2%) progressed to complete brain herniation. Patients with brain herniation signs on arrival were significantly older (P = 0.03) and more frequently hospitalized with a concomitant illness (P < 0.0001). Niveau formation (P = 0.0005) and acute-on CSDH (P = 0.0001) on computed tomography were also more frequently seen in patients with brain herniation signs. Multivariate logistic regression analysis showed that age older than 75 years (OR 2.16, P < 0.0001), niveau formation (OR 3.09, P < 0.0001), acute-on CSDH (OR 14, P < 0.0001), and admitted to another hospital (OR 52.6, P < 0.0001) were independent risk factors for having had brain herniation signs on arrival. On the other hand, having a history of head injury (P = 0.02) and disappearance of the ambient cistern (P = 0.0009) were significantly associated with completion of brain herniation. The prognosis was generally poor if the patient had presented with brain herniation signs on admission. Our results demonstrate that the diagnosis is often made late, despite hospitalization for a concomitant illness. When the elderly show mild disturbance of consciousness, physicians except neurosurgeons need to consider the possibility of CSDH regardless of a recent history of head injury.



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Cul3 neddylation is crucial for gradual lipid droplet formation during adipogenesis

Publication date: August 2017
Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1864, Issue 8
Author(s): Dawadschargal Dubiel, Willem Bintig, Thilo Kähne, Wolfgang Dubiel, Michael Naumann
Cullin 3 (Cul3) belongs to the family of cullins (Cul1–7) providing the scaffold for cullin-RING ubiquitin (Ub) ligases (CRLs), which are activated by neddylation and represent essential E3 ligases of the Ub proteasome system. During adipogenic differentiation neddylated Cul3 accumulates in LiSa-2 preadipocytes. Downregulation of Cul3 and inhibition of neddylation by MLN4924 blocks the formation of lipid droplets (LDs), the lipid storage organelles and markers of adipogenesis. Neddylation of Cul3 coincides with an increase of Rab18, a GTPase associated with LDs. Immunoprecipitation and confocal fluorescence microscopy revealed physical association of Cul3 and Rab18 at the membrane of LDs. RhoA, a suppressor of adipogenesis decreased during differentiation. Our results in LiSa-2 cells, but also mouse embryonic fibroblasts revealed a connection between Cul3, Rab18 and RhoA. Downregulation of Cul3 led to a marked increase in RhoA protein expression after 6days of LiSa-2 cell differentiation, suggesting that Cul3 is involved in the regulation of RhoA stability.



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Penetration of Vancomycin into the Cerebrospinal Fluid: A Systematic Review

Abstract

Introduction

Infectious disease and pharmacokinetic textbooks indicate that vancomycin has poor penetration into the central nervous system due to its hydrophilic nature and high molecular weight. Recent literature suggests that penetration of vancomycin into cerebrospinal fluid (CSF) is higher than previously reported; therefore, we conducted a systematic review to assess the penetration of vancomycin into CSF.

Methods

We searched the MEDLINE, EMBASE, and CENTRAL electronic databases for English-language human studies evaluating serum and CSF concentrations of intravenous vancomycin.

Results

In 13 identified studies, the CSF-to-serum ratio of vancomycin varied from 0.00 to 0.81. CSF penetration ranged 0.06–0.81 in patients with meningitis, 0.05–0.17 in ventriculitis, 0.00–0.36 in other infections, and 0–0.13 in patients without infection. Despite variable CSF penetration, 83% of patients with meningitis and 100% of patients with ventriculitis achieved clinical cure. No factor predicted vancomycin CSF penetration.

Conclusion

Contrary to prior belief, studies included in our review did not show universally low penetration of vancomycin into CSF. CSF vancomycin levels were variable and did not predict clinical cure.



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Early prediction of hypocalcemia following thyroid surgery. A prospective randomized clinical trial

Abstract

Purpose

The aim of this randomized-controlled trial was to validate the results of a previous prospective single-cohort observational study conducted in the same surgical unit regarding the use of concomitant intact parathyroid hormone (iPTH) and serum calcium measurement in predicting hypocalcemia after total thyroidectomy.

Methods

From January 2014 to January 2015, 150 patients underwent total thyroidectomy in our department and were randomized into two groups. The experimental group was submitted to iPTH assay 6 h after surgery while the control group was submitted to a daily assay of serum calcium and phosphorus. Sensitivity and specificity of different serum measurements have been calculated using the receiver-operator characteristics (ROC) curve.

Results

The prevalence of hypocalcemia was 14.25% in both groups. The assay of iPTH 6 h after surgery combined with the serum calcium assay 24 h after surgery yielded the highest diagnostic accuracy in predicting hypocalcemia using ROC curves, with 100% sensitivity and 100% specificity.

Conclusions

According to our previous study, the combined measurement of iPTH 6 h after surgery and of serum calcium 24 h after surgery are highly predictive of early postoperative hypocalcemia. These results are important in selecting the patients eligible for early discharge and those who need calcium and vitamin D supplementation.



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High-Resolution Manometry Evaluation of Pressures at the Pharyngo-upper Esophageal Area in Patients with Oropharyngeal Dysphagia Due to Vagal Paralysis

Abstract

The motility of the pharynx, upper esophageal sphincter (UES), and proximal esophagus in patients with oropharyngeal dysphagia is still not entirely understood. High-resolution manometry (HRM) was recently added to the armamentarium for the study of this area. This study aims to describe HRM findings in patients with vagal paralysis. Sixteen patients (mean age 54 years, 69% females) with oropharyngeal dysphagia due to unilateral vagal paralysis were prospectively studied. All patients underwent HRM. Motility of the UES and at the topography of the velopharynx and epiglottis were recorded. (1) UES relaxation is compromised in a minority of patients, (2) epiglottis pressure does not follow a specific pattern, (3) vellum is hypotonic in half of the patients, (4) dysphagia is related to a low pharyngeal pressure, not to a flow obstruction at the level of the UES, and (5) aspiration is related to low pressures at the level of the UES and epiglottis and higher pressures at the level of the vellum. Pharyngeal motility is significantly impaired in patients with oropharyngeal dysphagia and unilateral vagal paralysis. In half of the cases, UES resting pressure is preserved due to unilateral innervation and relaxation is normal in most patients. Dysphagia therapy in these patients must be directed toward improvement in the oropharyngeal motility not at the UES.



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Sagittal Plane Kinematics of the Jaw and Hyolingual Apparatus During Swallowing in Macaca mulatta

Abstract

Studies of mechanisms of feeding behavior are important in a society where aging- and disease-related feeding disorders are increasingly prevalent. It is important to evaluate the clinical relevance of animal models of the disease and the control. Our present study quantifies macaque hyolingual and jaw kinematics around swallowing cycles to determine the extent to which macaque swallowing resembles that of humans. One female and one male adult Macaca mulatta were trained to feed in a primate chair. Videofluoroscopy was used to record kinematics in a sagittal view during natural feeding on solid food, and the kinematics of the hyoid bone, thyroid cartilage, mandibular jaw, and anterior-, middle-, and posterior-tongue. Jaw gape cycles were defined by consecutive maximum gapes, and the kinematics of the swallow cycles were compared with those of the two consecutive non-swallow cycles preceding and succeeding the swallow cycles. Although there are size differences between macaques and humans, and macaques have shorter durations of jaw gape cycles and hyoid and thyroid upward movements, there are several important similarities between our macaque data and human data reported in the literature: (1) The durations of jaw gape cycles during swallow cycles are longer than those of non-swallow cycles as a result of an increased duration of the jaw-opening phase; (2) Hyoid and thyroid upward movement is linked with a posterior tongue movement and is faster during swallow than non-swallow cycles; (3) Tongue elevation propagates from anterior to posterior during swallow and non-swallow cycles. These findings suggest that macaques can be a useful experimental model for human swallowing studies.



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The unresolved riddle of glucocorticoid withdrawal

Abstract

Glucocorticoid (GC) therapy is the most common cause of adrenal insufficiency (AI). The real prevalence of AI after GC is unknown but it could involve more than 30% of patients. Some gene variation has been associated with the variability of hypothalamic-pituitary-adrenal (HPA) axis and this issue could contribute to the individual variation of adrenal function after GC treatment. Symptoms and signs of AI are nonspecific and frequently the diagnosis is delayed. Dosage, duration of treatment, administration route and serum cortisol value are not completely useful to predict AI. Clinical estimation of HPA suppression is difficult and biochemical testing is needed to confirm the diagnosis of AI. The different tapering regimens are based on a very low quality of evidence and considering the sizable individual variation, it is improbable that future research will find a secure GC tapering schedule for all patients. The aim of this review is to address the most important aspects in management of GC withdrawal in light of current knowledge.



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Tall cell and diffuse sclerosing variants of papillary thyroid cancer: outcome and predicting value of risk stratification methods

Abstract

Purpose

Tall cell (TCV) and diffuse sclerosing (DSV) variants are aggressive variants of papillary thyroid cancer (PTC). We compared the risk of recurrent/persistent disease in patients with TCV, DSV and classical PTC (cPTC) and evaluated the prognostic accuracy of initial vs. ongoing risk stratification.

Methods

A consecutive series of DSV (n = 54), TCV (n = 72) and cPTC (n = 184) patients was retrospectively analyzed. TCV and DSV patients were first risk stratified for recurrent/persistent disease without considering the histotype as a risk factor and subsequently, 6–24 months after initial treatment, re-classified on the basis of the response to therapy (ongoing risk stratification).

Results

Extrathyroidal extension was more frequent in DSV than in TCV and cPTC patients (p < 0.05); moreover, only DSV tumors had a higher rate of recurrent/persistent disease when compared to cPTC treated with the same protocol (total thyroidectomy followed by 131I treatment) (p < 0.01). After initial treatment, 54.2% of TCV and 20.4% of DSV patients were classified at low risk, while at ongoing risk stratification, the excellent response (low risk) was higher for both TCV (77.8%) and DSV (50.0%) patients relative to initial stratification (both p < 0.01). Using ongoing risk classification, positive predictive value (PPV) for persistent/recurrent disease was higher relative to initial risk stratification for both TCV (PPV = 93.8 vs. 39.4%) and DSV (PPV = 63.0 vs. 34.9%), p < 0.05 for both.

Conclusions

In our series DSV, but not TCV patients, had poorer outcome than cPTC treated with the same protocol. Moreover, the ongoing risk stratification predicted outcome better than the initial classification in both TCV and DSV patients.



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Benefits of a regular vs irregular rhythm-based training programme on physical fitness and motor skills in obese girls

Abstract

Purpose

The aim of the current study was to examine the impact of a physical exercise programme including rhythmic elements (regular and irregular tempos) on physiological variables, motor skills (MS), and jump performances in obese girls.

Methods

Thirty-six obese girls (age: 10.4 ± 0.9 years, body mass: 58.7 ± 4.0 kg, height: 1.37 ± 0.04 m, body mass index: 31.2 ± 2.1) participated in three weekly physical exercise sessions for 6 weeks, with each session consisting of basic fundamental locomotor movements. The participants were divided into two groups: a control group (CG) and an experimental group (EG). CG performed the exercise in a quiet setting (i.e., without rhythmic accompaniment), whereas regular and irregular rhythmic accompaniments were prescribed in EG. The physical exercise programme included three sessions per week for 6 weeks. Each session was composed of three parts: 15 min of warm-up, followed by 40 min of exercises based on basic locomotor movements (i.e., running, hopping, skipping, jumping, leaping, sliding, galloping, throwing, catching, kicking, dribbling, and striking) and then 5 min of stretching. Each exercise was demonstrated by the teacher. Before and after the intervention period, cardiovascular measures (i.e., resting blood pressures, recovery for heart rate and systolic blood pressure, and recovery rate-pressure product) were made and five MS (i.e., running, hopping, leaping, jumping and dribbling) were evaluated in two conditions (i.e., during exercise with regular and irregular tempos). Moreover, performances on vertical jump tests (squat and countermovement jump tests) were measured.

Results

EG exhibited greater improvement in MS with a regular tempo (and sometimes an irregular tempo), cardiovascular components, and jump performances.

Conclusion

These findings demonstrate that physical exercise at various tempos is useful for improving physical fitness, developing MS, and thus probably preventing obesity complications.



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Consent: an event or a memory in lumbar spinal surgery? A multi-centre, multi-specialty prospective study of documentation and patient recall of consent content

Abstract

Study design

Prospective, multi-centre, multi-specialty medical notes review and patient interview.

Purpose

The consenting process is an important communication tool which also carries medico-legal implications. While written consent is a pre-requisite before spinal surgery in the UK, the standard and effectiveness of the process have not been assessed previously. This study assesses standard of written consent for elective lumbar decompressive surgery for degenerative disc disease across different regions and specialties in the UK; level of patient recall of the consent content; and identifies factors which affect patient recall.

Methods

Consent forms of 153 in-patients from 4 centres a, b, c, d were reviewed. Written documentation of intended benefits, alternative treatments and operative risks was assessed. Of them, 108 patients were interviewed within 24 h before or after surgeries to assess recall.

Results

The written documentation rates of the operative risks showed significant inter-centre variations in haemorrhage and sphincter disturbance (P = 0.000), but not for others. Analysis of pooled data showed variations in written documentation of risks (P < 0.0005), highest in infection (96.1%) and lowest in recurrence (52.3%). For patient recall of these risks, there was no inter-centre variation. Patients' recall of paralysis as a risk was highest (50.9%) and that of recurrence was lowest (6.5%). Patients <65 years old recalled risks better than those ≥65, significantly so for infection (29.9 vs 9.7%, P = 0.027). Patients consented >14 days compared to <2 days before their surgeries had higher recall for paralysis (65.2 vs 43.7%) and recurrence (17.4 vs 2.8%). Patient recall was independent of consenter grade.

Conclusion

Overall, the standard of written consent for elective lumbar spinal decompressive surgery was sub-optimal, which was partly reflected in the poor patient recall. While consenter seniority did not affect patient recall, younger age and longer consent-to-surgery time improved it.



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Full endoscopic treatment of dural tears in lumbar spine surgery

Abstract

Purpose

An incidental durotomy is a common complication of spinal surgery. Its treatment remains challenging, especially in endoscopic procedures. The objective of this study is to describe a technique for endoscopic dural closure which is safe and effective.

Methods

From a prospective database all endoscopic spinal procedures with incidental durotomy were identified. Retrospectively, video recordings were analysed with a special reference to the applied technique of dural closure. Additionally 1, 6 and 12 week follow-up examinations were evaluated for clinical outcome and associated complications.

Results

Out of 212 consecutive patients, an intraoperative dural tear was observed in nine patients (4.2%). A dural tear occurred in 1.1% of cases of lumbar disc herniation, in 7.9% of cases with lumbar spinal stenosis, in 37.5% of cases with a synovial cyst. An autologous muscle sample was harvested within the operative field and grafted at the dural defect in several layers. Fixation of the transplantation and watertight closure were achieved by the application of fibrin sealant with gelfoam. The mean time for dural closure was 209 s (range 47–420 s). Postoperatively no CSF fistula, no new deficits nor worsening of a pre-existing neurological deficit occurred. None of the patients had problems with wound healing, or discomfort which could be related to the CSF leak.

Conclusions

Dural closure with an autologous muscle graft in combination with fibrin sealant patch is a fast, safe and alternative technique for the management of dural tear in microendoscopic surgery.



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Accuracy of a new intraoperative cone beam CT imaging technique (Artis zeego II) compared to postoperative CT scan for assessment of pedicle screws placement and breaches detection

Abstract

Purpose

The goal of this study was to compare the accuracy of a novel intraoperative cone beam computed tomography (CBCT) imaging technique with that of conventional computed tomography (CT) scans for assessment of pedicle screw placement and breach detection.

Methods

Three hundred and forty-eight pedicle screws were inserted in 58 patients between October 2013 and March 2016. All patients had an intraoperative CBCT scan and a conventional CT scan to verify the placement of the screws. The CBCT and CT images were reviewed by two surgeons to assess the accuracy of screw placement and detect pedicle breaches using two established classification systems. Agreement on screw placement between intraoperative CBCT and postoperative CT was assessed using Kappa and Gwet's coefficients. Using CT scanning as the gold standard, the sensitivity, specificity, positive predictive value, and negative predictive value were calculated to determine the ability of CBCT imaging to accurately evaluate screw placement.

Results

The Kappa coefficient was 0.78 using the Gertzbein classification and 0.80 using the Heary classification, indicating a substantial agreement between the intraoperative CBCT and postoperative CT images. Gwet's coefficient was 0.94 for both classifications, indicating almost perfect agreement. The sensitivity, specificity, positive predictive value and negative predictive value of the CBCT images were 77, 98, 86, and 96%, respectively, for the Gertzbein classification and 79, 98, 88, and 96%, respectively, for the Heary classification.

Conclusions

Intraoperative CBCT provides accurate assessment of pedicle screw placement and enables intraoperative repositioning of misplaced screws. This technique may make postoperative CT imaging unnecessary.



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Intra-abdominal Infections After Abdominal Organ Injuries

Abstract

Purpose of Review

This review is focusing on intra-abdominal infections after abdominal injuries which are a major source of morbidity following abdominal trauma.

Recent Findings

Intra-abdominal infections after abdominal injuries pose a diagnostic and therapeutic challenge to the trauma surgeon. Its diagnosis is based on clinical and radiological findings. Once an intra-abdominal infection is diagnosed, the next step is to achieve prompt and efficient source control coupled with early initiation of broad-spectrum antibiotics. Over the past several years, research has found some predictors for intra-abdominal infections after abdominal trauma. However, the role of prophylactic and therapeutic antibiotics remains unclear. The operative strategy for these patients is largely based on the trauma surgeon experience. However, temporary abdominal closure with negative pressure wound therapy seems to be the best approach to managing post-traumatic intra-abdominal infections.

Summary

Early administration of broad-spectrum antimicrobials coupled with rapid and efficient source control is of paramount importance for improving outcomes in patients with post-traumatic intra-abdominal infections.



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Blood Transfusion from the Military’s Standpoint: Making Last Century’s Standard Possible Today

Abstract

Purpose of Review

The purpose of this review was to evaluate past, present and emerging concepts in transfusion medicine as it pertains to combat casualty care. Transfusion practices have paramount historical significance in military medicine and battlefield care. An understanding of transfusion history during recent wars have helped inform some current practices and must not be forgotten, especially as we define the future of battlefield transfusion as it pertains to the importance and implementation of whole blood.

Recent Findings

The implementation of damage control resuscitation during the recent wars in Iraq and Afghanistan has changed the face of modern transfusion practices in both military and civilian trauma. The value of whole blood has been recognized clinically and is considered the best fluid for hemorrhagic shock; however, despite being readily available during walking blood banks, widespread adoption and standardized availability remain a challenge.

Summary

Transfusion is an essential capability and saves lives on the battlefield. Whole blood, followed by component therapy using the proper ratios, is the best fluid for hemorrhagic shock. There is a growing body of evidence regarding the detrimental effects of crystalloid use in hemorrhagic shock. The timing of blood product transfusion is critically important—minutes matter. Lessons learned in previous wars regarding the value of whole blood transfusion have been rediscovered and should be codified into military and civilian surgical practices.



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Erratum to: S -(3-Aminobenzanthron-2-yl)cysteine in the globin of rats as a novel type of adduct and possible biomarker of exposure to 3-nitrobenzanthrone, a potent environmental carcinogen



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Human cost burden of exposure to endocrine disrupting chemicals. A critical review

Abstract

Recently published papers have alleged that exposures to endocrine disrupting chemicals (EDCs) are causing substantial disease burdens in the EU and US and are consequently costing society hundreds of billions of dollars annually. To date, these cost estimates have not undergone adequate scientific scrutiny, but nevertheless are being used aggressively in advocacy campaigns in an attempt to fundamentally change how chemicals are tested, evaluated and regulated. Consequently, we critically evaluated the underlying methodology and assumptions employed by the chief architects of the disease burden cost estimates. Since the vast majority of their assigned disease burden costs are driven by the assumption that “loss of IQ” and “increased prevalence of intellectual disability” are caused by exposures to organophosphate pesticides (OPPs) and brominated flame retardants (PBDEs), we have taken special care in describing and evaluating the underlying toxicology and epidemiology evidence that was relied upon. Unfortunately, our review uncovered substantial flaws in the approach taken and the conclusions that were drawn. Indeed, the authors of these papers assumed causal relationships between putative exposures to EDCs and selected diseases, i.e., “loss of IQ” and “increased prevalence of intellectual disability”, despite not having established them via a thorough evaluation of the strengths and weaknesses of the underlying animal toxicology and human epidemiology evidence. Consequently, the assigned disease burden costs are highly speculative and should not be considered in the weight of evidence approach underlying any serious policy discussions serving to protect the public and regulate chemicals considered as EDCs.



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Effectiveness of Acellular Dermal Matrix on Autologous Split-Thickness Skin Graft in Treatment of Deep Tissue Defect: Esthetic Subjective and Objective Evaluation

Abstract

Background

A split-thickness skin graft (STSG) is performed to cover a large full-thickness skin defect. Esthetic and functional deficits can result, and many studies have sought to overcome them. This study compared the effectiveness of the acellular dermal matrix (ADM) graft and STSG concerning esthetic and functional effectiveness of ADM on scar quality.

Methods

Of the patients who underwent anterolateral thigh free flap from 2011 to 2015, patients who received skin graft only (n = 10) or skin graft with ADM (n = 20) for coverage of the donor site were enrolled. In all cases, autologous STSG was performed with 1:1.5 meshed 0.008–0.010-inch-thick skin. In the skin graft with ADM group, 0.008–0.013-inch-thick meshed ADM (CGderm®; CGBio, Inc., Seungnam, Korea) was co-grafted. Negative-pressure wound therapy (CuraVAC®; CGBio, Inc., Seungnam, Korea) was applied to both groups in continuous mode at −120 mmHg. We investigate early outcomes (skin loss rate, duration of negative-pressure wound therapy, days to removal of stitches, days to achieve complete healing, and complications) and late outcomes in terms of scar quality (vascularity, pigmentation, pliability and height) and graft-related symptoms (itching sensation and pain). Assessments used the Vancouver Scar Scale and the Patient and Observer Scar Assessment Scale. Skin fold was measured to evaluate the elasticity of scar tissue.

Results

In the Vancouver Scar Scale, vascularity subscore (p = 0.003) and total score (p = 0.016) were significantly lower in the skin graft with ADM group. In Patient and Observer Scar Assessment Scale, the pain (p = 0.037) and stiffness subscores (p = 0.002), and total score (p = 0.017) were significantly lower in the skin graft with ADM group.

Conclusions

Skin graft with ADM results in better scar quality in objective and subjective aspects.

Level of Evidence IV

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://ift.tt/18t7xNj.



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Mycobacterium Chelonae Infection of the Buttocks Secondary to Lipofilling: A Case Report and Review of the Literature

Abstract

Mycobacterium chelonae is a nontuberculous mycobacterium, classified as a Runyon type IV mycobacterium. In relation to humans, it is most commonly associated with tissue trauma or pulmonary infections. The majority of medical reports describe finding M. chelonae in the surgical setting, attributing infection to inadequate sterilization of surgical equipment. Symptoms are often nonspecific and include pain, erythema, and draining subcutaneous nodules and skin lesions. Therefore, the diagnosis of M. chelonae is often difficult to establish without prior suspicion of the disease, but can be confirmed with culture. We will describe the case of a 40-year-old female who contracted M. chelonae infection of the buttocks after abdominal liposuction and gluteal fat injection. We will describe her symptomatology, diagnosis, and successful treatment with surgical excision and antibiotics.

Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://ift.tt/18t7xNj.



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Pancreatic Cysts and Guidelines

Abstract

Pancreatic cysts, especially incidental asymptomatic ones seen on noninvasive imaging such as CT or MR imaging, remain a clinical challenge. The etiology of such cysts may range from benign cysts without any malignant potential such as pancreatic pseudocysts and serous cystadenomas to premalignant or frankly malignant cysts such as mucinous cystic neoplasms, intraductal papillary mucinous neoplasms, cystic degeneration associated with solid tumors such as pancreatic ductal adenocarcinoma or pancreatic endocrine neoplasms, and solid pseudopapillary neoplasms. The clinical challenge in 2017 is to accurately preoperatively diagnose them and their malignant potential before deciding about surgery, surveillance or doing nothing. This review will focus on the currently available clinical guidelines for doing so.



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The Association Between Primary Source of Healthcare Coverage and Colorectal Cancer Screening Among US Veterans

Abstract

Background

Colorectal cancer (CRC) is a deadly but largely preventable disease. Screening improves outcomes, but screening rates vary across healthcare coverage models. In the Veterans Health Administration (VA), screening rates are high; however, it is unknown how CRC screening rates compare for Veterans with other types of healthcare coverage.

Aims

To determine whether Veterans with Veteran-status-related coverage (VA, military, TRICARE) have higher rates of CRC screening than Veterans with alternate sources of healthcare coverage.

Methods

We conducted a cross-sectional analysis of Veterans 50–75 years from the 2014 Behavioral Risk Factor Surveillance System survey. We examined CRC screening rates and screening modalities. We performed multivariable logistic regression to identify the role of coverage type, demographics, and clinical factors on screening status.

Results

The cohort included 22,138 Veterans. Of these, 76.7% reported up-to-date screening. Colonoscopy was the most common screening modality (83.7%). Screening rates were highest among Veterans with Veteran-status-related coverage (82.3%), as was stool-based screening (10.8%). The adjusted odds of up-to-date screening among Veterans with Veteran-status-related coverage were 83% higher than among Veterans with private coverage (adjusted OR = 1.83, 95% CI = 1.52–2.22). Additional predictors of screening included older age, black race, high income, access to medical care, frequent medical visits, and employed or married status.

Conclusions

CRC screening rates were highest among Veterans with Veteran-status-related coverage. High CRC screening rates among US Veterans may be related to system-level characteristics of VA and military care. Insight to these system-level characteristics may inform mechanisms to improve CRC screening in non-VA settings.



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Utility of MR imaging in the evaluation of colon cancer: emphasis on distinguishing tumor tissue from fibrosis and role of contrast media



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Contrast-induced nephropathy (CIN) of patients with renal dysfunction in CT examination

Abstract

Purpose

To investigate the incidence and risk factors of contrast induced nephropathy (CIN) after contrast enhanced (CE) computed tomography (CT) in patients with renal dysfunction.

Materials and methods

Two hundred sixteen inpatients with estimated glomerular filtration rates (eGFR) <60 ml/min/1.73 m2 underwent CE CT using iodine doses of 420 or 480 mg I/kg. Data of all enrolled patients was collected for baseline serum creatinine level (SCr), post-CE CT SCr within 3 days after CE CT, and conditions considered risk factors for CIN [renal dysfunction, contrast media dose, advanced age, diabetes mellitus, no intravenous hydration, cardiac dysfunction (left ventricular ejection fraction <60%) and intensive-care unit (ICU) admission]. CIN was defined as an increase in SCr level of more than 0.5 mg/dl or more than 25% from baseline within 3 days post-CE CT without any other identifiable cause of acute kidney injury.

Results

The incidence of CIN was 11/216 (5.1%) and was associated with cardiac dysfunction [odds ratio (OR) 6.540; 95% confidence interval (CI) 1.090–39.300; p = 0.040] and ICU admission (OR 11.500; 95% CI 2.050–64.100; p = 0.005).

Conclusion

Our results suggested that cardiac dysfunction and ICU admission may be risk factors for CIN in patients with preexisting renal dysfunction.



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Changes in deviation of absorbed dose to water among users by chamber calibration shift

Abstract

Purpose

The JSMP01 dosimetry protocol had adopted the provisional 60Co calibration coefficient \(N__{ 0} }}^\) , namely, the product of exposure calibration coefficient N C and conversion coefficient k D,X. After that, the absorbed dose to water D w standard was established, and the JSMP12 protocol adopted the \(N__{ 0} }}^\) calibration. In this study, the influence of the calibration shift on the measurement of D w among users was analyzed.

Materials and methods

The intercomparison of the D w using an ionization chamber was annually performed by visiting related hospitals. Intercomparison results before and after the calibration shift were analyzed, the deviation of D w among users was re-evaluated, and the cause of deviation was estimated.

Results

As a result, the stability of LINAC, calibration of the thermometer and barometer, and collection method of ion recombination were confirmed. The statistical significance of standard deviation of D w was not observed, but that of difference of D w among users was observed between N C and \(N__{ 0} }}^\) calibration.

Conclusion

Uncertainty due to chamber-to-chamber variation was reduced by the calibration shift, consequently reducing the uncertainty among users regarding D w. The result also pointed out uncertainty might be reduced by accurate and detailed instructions on the setup of an ionization chamber.



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The new issue is now available.Journal of Lipid Nutrition

Vol.26 No.1

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The new issue is now available.Hyomen Kagaku

Vol.38 No.5

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The new issue is now available.Annals of the Association of Economic Geographers

Vol.47 No.4

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The new issue is now available.Annals of the Association of Economic Geographers

Vol.54 No.2

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The new issue is now available.Annals of the Association of Economic Geographers

Vol.54 No.3

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The new issue is now available.Annals of the Association of Economic Geographers

Vol.49 No.1

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The new issue is now available.Annals of the Association of Economic Geographers

Vol.42 No.2

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The new issue is now available.Annals of the Association of Economic Geographers

Vol.44 No.2

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The new issue is now available.Annals of the Association of Economic Geographers

Vol.43 No.2

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Working Memory in the Processing of Long-Distance Dependencies: Interference and Filler Maintenance

Abstract

During the temporal delay between the filler and gap sites in long-distance dependencies, the "active filler" strategy can be implemented in two ways: the filler phrase can be actively maintained in working memory ("maintenance account"), or it can be retrieved only when the parser posits a gap ("retrieval account"). The current study tested whether filler content is maintained during the processing of dependencies. Using a self-paced reading paradigm, we compared reading times on a noun phrase (NP) between the filler and gap sites in object relative clauses, to reading times on an NP between the antecedent and ellipsis sites in ellipsis sentences. While in the former type of dependency a filler by hypothesis can be maintained, in the latter there is no indication for the existence of a dependency prior to the ellipsis site, and hence no maintenance. By varying the amount of similarity-based interference between the antecedent and integration sites, we tested the influence of holding an unresolved dependency on reading times. Significantly increased reading times due to interference were found only in the object relative condition, and not in the ellipsis condition, demonstrating filler maintenance costs. The fact that these costs were measured as an effect on similarity-based interference indicates that the maintained representation of the filler must include at least some of the features shared by the interfering NP.



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