High parasite-specific antibody levels are generally associated with low susceptibility to Plasmodium falciparum malaria. This has been supported by several studies in which clinical malaria cases of P. falciparu...
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Παρασκευή 8 Σεπτεμβρίου 2017
Antibody responses to P. falciparum blood stage antigens and incidence of clinical malaria in children living in endemic area in Burkina Faso
Hemato-immunological and plasma biochemical responses of silvery-black porgy ( Sparidentex hasta ) fed protein and essential amino acid deficient diets
Abstract
A 6-week feeding trial was conducted to evaluate the effects of protein free (PF) and essential amino acid deficient (EAAD) diets on the physiological responses of silvery-black porgy (Sparidentex hasta) juveniles. Three experimental diets were formulated: a control diet in which 60% of dietary nitrogen was provided by intact protein (fish meal) and 40% by crystalline AA [(blends of essential amino acids (EAAs) and non-essential amino acids (NEAAs)]; an essential amino acid deficient diet in which 60% of dietary N was provided by intact protein, whereas the rest was provided by NEAAs; and a protein free (PF) diet, which based on carbohydrate sources. Fish fed the PF and EAAD showed signs of anemia including lower red blood cells counts, hemoglobin, and hematocrit levels than control group. Plasma lysozyme activity and complements C3 and C4, as well as total immunoglobulin levels were drastically reduced in fish fed PF and EAAD diets. Plasma and liver alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and alkaline phosphatase were significantly increased, but superoxide dismutase was decreased in fish fed PF and EAAD diets. Plasma total protein, albumin, high density lipoprotein, calcium, and inorganic phosphorous significantly decreased in fish fed PF and EAAD diets. The information obtained from this study testing to extreme diets (EAAD and PF diets) may serve for better understanding the impact of protein nutritional imbalances in fish.
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Endobronchial lipoma, the initial evaluation and appropriate management
Abstract
The endobronchial lipomas are extremely rare and consist of 0.1 to 0.5% of all lung tumors and 1.4–13% of benign lung neoplasms. We present a 42-year-old woman with endobronchial lipoma and the initial evaluation and appropriate management. A 42-year-old woman presented with history of dry cough and wheeze for eight months was candidate for bronchoscopy study. Histopathology examination of excised lesion confirmed endobronchial lipoma of the left lower lobe bronchus. The post-bronchoscopy period was uneventful. The patient was disease free in the following three years. The physicians, especially at major referral lung centers, are much more likely to be familiar with endobronchial lipoma and its clinical awareness, because misdiagnosis can delay the start of an appropriate treatment.
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The Translational Science Benefits Model: A New Framework for Assessing the Health and Societal Benefits of Clinical and Translational Sciences
We report the development of the Translational Science Benefits Model (TSBM), a framework designed to support institutional assessment of clinical and translational research outcomes to measure clinical and community health impacts beyond bibliometric measures. The TSBM includes 30 specific and potentially measurable indicators that reflect benefits that accrue from clinical and translational science research such as products, system characteristics, or activities. Development of the TSBM was based on literature review, a modified Delphi method, and in-house expert panel feedback. Three case studies illustrate the feasibility and face validity of the TSBM for identification of clinical and community health impacts that result from translational science activities. Future plans for the TSBM include further pilot testing and a resource library that will be freely available for evaluators, translational scientists, and academic institutions who wish to implement the TSBM framework in their own evaluation efforts.
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Wear profile of canal wall surfaces and bond strength of endodontic sealers after in situ acid challenge
Abstract
Aim
To evaluate the wear of root wall surfaces, the bond strength of sealers to dentine and the demineralization around filling material after the canals were exposed to acid challenge.
Methodology
Eighty-seven roots of mandibular incisors were selected. Thirty-two were used in the bond strength in vitro study (n=8) and 55 in the in situ study (n=11). Root canals were prepared biomechanically and then filled with gutta-percha and AH Plus, MTA Fillapex, Sealapex or Endofill. For 14 days, 11 participants used intraoral devices with 5 sterilized roots (4 experimental and 1 control – only canal prepared). Drops of sucrose were dripped onto roots allowing the accumulation of biofilm on canal surfaces. Roots were removed, sectioned and analysed for: bond strength of filling material using a push-out test and also wear profile and dentine demineralization using confocal microscopy. Bond strength (MPa) was evaluated by two-way ANOVA and Tukey test (α=0.05) and wear profile was assessed by Kruskal-Wallis and t-tests (α=0.05).
Results
AH Plus had the highest bond strength values. Intermediate results were found in roots with MTA Fillapex and Endofill, whilst Sealapex had inferior results (P <0.05). No significant differences were found among root thirds (P >0.05). For wear profile, samples had degradation of the filling materials after exposure to the oral environment (P <0.05). Roots had signs of demineralization around the filling material when Sealapex and Endofill were used.
Conclusions
Sealers were not able to prevent degradation of the adhesive interface and dentine. AH Plus and MTA Fillapex had superior bond strength to dentine and less intense demineralization around the root filling.
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Long-term patient reported outcomes following radiation therapy for oropharyngeal cancer: cross-sectional assessment of a prospective symptom survey in patients ≥65 years old
Abstract
Background
Given the potential for older patients to experience exaggerated toxicity and symptoms, this study was performed to characterize patient reported outcomes in older patients following definitive radiation therapy (RT) for oropharyngeal cancer (OPC).
Methods
Cancer-free head and neck cancer survivors (>6 months since treatment completion) were eligible for participation in a questionnaire-based study. Participants completed the MD Anderson Symptom Inventory-Head and Neck module (MDASI-HN). Those patients ≥65 years old at treatment for OPC with definitive RT were included. Individual and overall symptom severity and clinical variables were analyzed.
Results
Of the 79 participants analyzed, 82% were male, 95% white, 41% T3/4 disease, 39% RT alone, 27% induction chemotherapy, 52% concurrent, and 18% both, and 96% IMRT. Median age at RT was 71 yrs. (range: 65–85); median time from RT to MDASI-HN was 46 mos. (2/3 > 24 mos.). The top 5 MDASI-HN items rated most severe in terms of mean (±SD) ratings (0–10 scale) were dry mouth (3.48 ± 2.95), taste (2.81 ± 3.29), swallowing (2.59 ± 2.96), mucus in mouth/throat (2.04 ± 2.68), and choking (1.30 ± 2.38) reported at moderate-severe levels (≥5) by 35, 29, 29, 18, and 13%, respectively. Thirty-nine % reported none (0) or no more than mild (1–4) symptoms across all 22 MDASI-HN symptoms items, and 38% had at least one item rated as severe (≥7). Hierarchical cluster analysis resulted in 3 patient groups: 1) ~65% with ranging from none to moderate symptom burden, 2) ~35% with moderate-severe ratings for a subset of classically RT-related symptoms (e.g. dry mouth, mucus, swallowing) and 3) 2 pts. with severe ratings of most items.
Conclusions
The overall long-term symptom burden seen in this older OPC cohort treated with modern standard therapy was largely favorable, yet a higher symptom group (~35%) with a distinct pattern of mostly local and classically RT-related symptoms was identified.
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Rapamycin treatment attenuates age-associated periodontitis in mice
Abstract
Interventions that target biological mechanisms of aging have great potential to enhance quality of life by delaying morbidity and mortality. The FDA-approved drug rapamycin is a compelling candidate for such an intervention. In a previous study, it was reported that 3 months of rapamycin treatment is sufficient to increase life expectancy and remodel the gut microbiome in aged mice. Transient treatment with rapamycin or a rapamycin derivative has also been shown to delay immune stem cell senescence and rejuvenate immune function in aged mice and elderly people. Periodontal disease is an important age-related disease involving altered immune function, pathological changes to the oral microbiome, and systemic inflammation. Periodontal disease is defined clinically by loss of alveolar bone and by connective tissue degeneration. Here, we describe significant alveolar bone loss during aging in two different mouse strain backgrounds and report that rapamycin treatment is sufficient to reverse age-associated periodontal disease in mice. Partial restoration of youthful levels of alveolar bone is observed in 22-month-old rapamycin-treated mice as rapidly as 8 weeks after initiation of treatment. To the best of our knowledge, this represents the first intervention shown to substantially prevent or reverse age-associated alveolar bone loss. These findings suggest the possibility that inhibition of mTOR with rapamycin or other pharmacological agents may be useful to treat a clinically relevant condition for which there is currently no effective treatment.
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Variation of the epidermal expression of glucocorticoid receptor-beta as potential predictive marker of bullous pemphigoid outcome
Abstract
Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease in Western countries. Although topical and/or systemic glucocorticoids treatment efficacy is widely recognized, up to 30% of patients with BP may undergo a relapse during the first year of treatment. We investigated the protein expression of the total glucocorticoid receptor and GRβ isoform in the skin biopsy specimens from patients with BP, and wondered whether such investigation at baseline provided a tool to predict disease outcome. Total GR and GRβ protein expressions were detected by immunohistochemistry at baseline on 12 patients who later relapse and 11 patients who remained on remission in comparison with 14 control patients. The expression of GRβ in the epidermis of patients with BP who later relapse was significantly higher than that in the epidermis of patients with BP controlled upon corticosteroid treatment, which was also higher than control patients. Thus, our results suggest that increased protein expression of GRβ in skin epithelial cells is predictive of reduced steroid treatment efficacy, and therefore of increased risk of disease relapse in patients with BP.
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Monitoring UV-induced signaling pathways in an ex vivo skin organ culture model using phospho-antibody array
Abstract
We investigated UV-induced signaling in an ex vivo skin organ culture model using phospho-antibody array. Phosphorylation modulations were analyzed in time-course experiments following exposure to solar-simulated UV and validated by western blot analyses. We found that UV induced P-p38 and its substrates, P-ERK1/2 and P-AKT which were previously shown to be upregulated by UV in cultured keratinocytes and in vivo human skin. This indicates that phospho-antibody array applied to ex vivo skin organ culture is a relevant experimental system to investigate signaling events following perturbations. Since the identified proteins are components of pathways implicated in skin tumorigenesis, UV-exposed skin organ culture model could be used to investigate the effect on these pathways of NMSC cancer drug candidates. In addition, we found that phospho-HCK is induced upon UV exposure, producing a new candidate for future studies investigating its role in the skin response to UV and UV-induced carcinogenesis.
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Activation of NLRP3 signaling accelerates skin wound healing
Abstract
The process of skin wound healing involves the following three steps: inflammation, tissue formation, and tissue remodeling. These optimal steps are required for the development of normal wound healing. Recent reports demonstrated that inflammasomes are involved in the innate immune response. In the present study, we examined whether the activation of inflammasomes affects the process of skin wound repair. The skin wound repair model was established using wild-type (WT), NACHT, LRR and PYD domains-containing protein 3 (NALP3) knockout (KO) and ASC-KO mice. The wounds were observed every other day and changes in wound size over time were calculated using photography. Wound repair in NALP3-KO and ASC-KO mice was significantly impaired compared with WT mice. Isoliquiritigenin, an inhibitor of NALP3, decreased the rate of wound repair in WT mice. mRNA expression of pro-inflammatory cytokines in the wound sites of NALP3-KO mice was markedly decreased compared with WT mice. Treatment with adenosine triphosphate (ATP), a ligand of NALP3, up-regulated the mRNA expression of pro-inflammatory cytokines at the wound site and accelerated wound healing in the WT mice. Scratch assay revealed that ATP accelerated wound closure in mouse embryonic fibroblasts from WT mice but not from NALP3-KO mice. In conclusion, the present study demonstrated that NALP3 pathway activation is involved in wound repair, and the topical use of ATP may be useful as an effective treatment for accelerating wound healing.
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Human Tissue Inhibitor of Metalloproteinases-1 Improved Wound Healing in Diabetes through Its Anti-apoptotic Effect
Abstract
Impaired wound healing accompanies severe cell apoptosis in diabetic patients. Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) was known to have effects on promoting growth and anti-apoptosis for cells. we aimed to determine the actual levels of TIMP-1 and cell apoptosis in: 1) the biopsies of diabetic and non-diabetic foot tissue; 2) the human fibroblasts with or without treatments of Advanced Glycation End Products (AGEs). Next, in both human fibroblasts and the animal model of diabetic rats, to determine the improved levels of cell apoptosis and wound healing after the treatments of either active protein of TIMP-1 or in vivo expression of gene therapy vector-mediated TIMP-1. The levels of TIMP-1 were significantly reduced in diabetic skin tissues and in AGEs-treated fibroblasts. Both AGEs-treated cells were effectively protected from apoptosis by active protein of TIMP-1 at appropriate dose level. So did the induced in vivo TIMP-1 expression after gene delivery. Similar effects were also found on the significant improvement of impaired wound healing in diabetic rats. We concluded that TIMP-1 improved wound healing through its anti-apoptotic effect. Treatments with either active protein TIMP-1 or TIMP-1 gene therapy delivered in local wound sites may be used as a strategy for accelerating diabetic wound healing.
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Evidence for a contributory role of a xenogeneic immune response in experimental epidermolysis bullosa acquisita
Abstract
Autoimmune diseases affect a large fraction of the population in Western countries. To elucidate the underlying causes, autoantibody transfer-induced mouse models have been established that greatly contributed to the understanding of the pathophysiology of these diseases. However, the role of a potentially co-occurring murine xenogeneic immune response to commonly utilized rabbit anti-mouse IgG remains poorly understood. Using the established rabbit anti-mouse type VII collagen (COL7) IgG-induced mouse model of the mucocutaneous blistering disorder epidermolysis bullosa acquisita (EBA), we found in this study a profound T and B cell response along with an altered cytokine expression profile in draining lymph nodes of mice injected with the xenogeneic IgG. This was associated with the formation of circulating and skin-bound mouse anti-rabbit IgG in wild-type but not CD154-deficient or B-cell deficient JHT mice challenged with pathogenic rabbit IgG. Development of EBA skin lesions was attenuated in the two mouse strains lacking a B cell response at later observation time points, but was not affected in mice treated with the T cell trafficking blocker FTY720. Collectively, our results implicate a host's xenoreactive immune response to rabbit anti-mouse COL7 IgG, a confounding effect that may contribute to immune complex-driven inflammation and tissue damage in this antibody transfer-induced EBA mouse model, especially at later time points. In this regard, it may be recommended to finish the evaluation of results obtained by experiments employing antibody-transferred mouse models within the first 2 weeks after the pathogenic antibody injection.
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“The Heart Desires but the Body Refuses”: Sexual Scripts, Older Men’s Perceptions of Sexuality, and Implications for Their Mental and Sexual Health
Abstract
We use sexual scripting theory in the present paper to gain a better understanding of older men's perceptions of their sexuality in relation to dominant Tanzanian cultural norms of masculinity. Qualitative in-depth interviews were conducted with 15 older men, and ten focus group discussions were conducted with 60 men aged 60–82. Participants' recruitment was guided by theoretical sampling strategies. Consistent with the principles of grounded theory, data collection and analysis occurred simultaneously. Our findings indicate that Jando (male initiation rites) serves as a script for male sexuality that outlines the expectations and rewards of male sexuality. Adhering to masculine sexual script affects older men's perceptions of their sexuality in later life and has detrimental effects on their well-being. Older men were concerned with changes in their sexual life, such as the decline in their sexual performance. The majority of the participants said they felt emotionally distressed about the age-related decline in their body and in their sexuality, and they reported that their inability to conform to male sexual scripts undermined their sense of masculinity. Several of the participants reported that in an effort to regain their previous sexual performance, they had turned to remedies and strategies of questionable appropriateness and effectiveness. Our study suggests that older men may benefit from age-related interventions tailored to their cultural background. These interventions may require trained health care providers on mental health issues to bridge the gap between the internalized scripts of ideal male sexuality and the reality of aging.
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Osimertinib May Be an Effective First-Line Therapy in EGFR-Mutant NSCLC [Research Watch]
Osimertinib achieved objective responses in 77% of patients with treatment-naïve NSCLC.
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LMO1 Cooperates with MYCN to Promote Neuroblastomagenesis and Metastasis [Research Watch]
Transgenic expression of LMO1 promotes neuroblastoma metastasis in a MYCN-driven zebrafish model.
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Altered Vasculature in Bone Marrow Drives Leukemogenesis [Research Watch]
Nitric oxide promotes vascular permeability and hypoxia in the bone marrow to drive AML.
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First-Ever CAR T-cell Therapy Approved in U.S. [News in Brief]
Tisagenlecleucel earns green light for treatment of some patients with ALL.
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Z-endoxifen Is Active in Endocrine-Refractory Metastatic Breast Cancer [Research Watch]
The tamoxifen metabolite Z-endoxifen has acceptable tolerability and antitumor activity.
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Biomarker-Stratified Phase III Clinical Trials: Enhancement with a Subgroup-Focused Sequential Design
Among various design approaches to phase III clinical trials with a predictive biomarker, the marker-stratified all-comers design is advantageous because it allows for establishing the utility of both treatment and biomarker, but it is often criticized for requiring large sample sizes, since the design includes both marker-positive and marker-negative patients. In this paper, we propose a simple but flexible subgroup-focused design for marker-stratified trials that allows both sequential assessment across marker-defined subgroups and adaptive subgroup selection, while retaining an assessment using the entire patient cohort at the final analysis stage, possibly using established marker-based multiple testing procedures. Numerical evaluations indicate that the proposed marker-stratified design has a robustness property in preserving statistical power for detecting various profiles of treatment effects across the subgroups, while effectively reducing the number of randomized patients in the marker-negative subgroup with presumably limited treatment efficacy. In contrast, the traditional all-comers and sequential enrichment designs could suffer from low statistical power for some possible profiles of treatment effects. The latter also need long study durations and a large number of marker screened patients. We also provide an application to SWOG S0819, a trial to assess the role of cetuximab in treating non-small cell lung cancers. These evaluations indicate that the proposed subgroup-focused approach can enhance the efficiency of the marker-stratified design for definitive evaluation of treatment and biomarker in phase III clinical trials.
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Short- and long-term exposure to imidacloprid disturbs the elemental composition and free amino acid profile in muscles of Labeo rohita
Abstract
Imidacloprid [1-(6-chloro-3-pyridylmethyl)-N-nitro-imidazolidin-2-ylideneamine] is among the most extensively used pesticide in Pakistan. The aim of this investigation was to report the changes in concentration of different elements and amino acid in the muscle of Labeo rohita upon imidacloprid exposure. Juvenile Labeo rohita (N = 480) were treated with 120mgL−1 imidacloprid under short and long-term experimental conditions. At the end of each experiment, fish muscle was used for elemental concentration (determination by an atomic absorption spectrophotometer) and amino acid estimation (by high-performance liquid chromatography (HPLC)). Our results indicated that sodium, potassium, calcium, magnesium, iron, aluminum, and lead concentrations were significantly different (P < 0.05) when compared between imidacloprid-treated and untreated L. rohita and changes were more pronounced in short-term experimental groups. HPLC-generated data analysis showed that proline, isoleucine, and glycine concentrations increased while the levels of phenylalanine, alanine, and leucine decreased significantly (P < 0.05) in muscles of fish exposed to imidacloprid under short-term conditions. On the other hand, serine, arginine, and glycine increased significantly and alanine decreased significantly in L. rohita exposed to pesticide under long-term experimental conditions. It is concluded that imidacloprid (120 mg L−1) exposure to L. rohita for a variable duration has significantly changed the elemental composition and studied amino acid concentrations in fish muscles making it unsuitable for human consumption.
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Anti-inflammatory effect of Astaxanthin in phthalic anhydride-induced atopic dermatitis animal model
Abstract
In this study, we investigated anti-dermatitic effects of Astaxanthin (AST) in phthalic anhydride (PA)-induced atopic dermatitis (AD) animal model as well as in vitro model. AD-like lesion was induced by the topical application of 5% PA to the dorsal skin or ear of Hos:HR-1 mouse. After AD induction, 100 μl of 1 mg/ml and 2 mg/ml of AST (10 μg or 20 μg/cm2) was spread on the dorsum of ear or back skin three times a week for four weeks. We evaluated dermatitis severity, histopathological changes and changes in protein expression by Western blotting for inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear factor-κB (NF-κB) activity. We also measured tumor necrosis factor- α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and immunoglobulinE (IgE) concentration in the blood of AD mice by enzyme-linked immunosorbent assay (ELISA). AST treatment attenuated the development of PA-induced AD. Histological analysis showed that AST inhibited hyperkeratosis, mast cells and infiltration of inflammatory cells. AST treatment inhibited expression of iNOS and COX-2, and NF-κB activity as well as release of TNF-α, IL-1β, IL-6, and IgE. In addition, AST (5, 10, and 20μM) potently inhibited lipopolysaccharide (LPS) (1 μg/ml)-induced nitric oxide (NO) production, expression of iNOS and COX-2, and NF-κB DNA binding activities in RAW 264.7 macrophage cells. Our data demonstrated that AST could be a promising agent for AD by inhibition of NF-κB signaling.
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CD8+ lineage dendritic cells determine adaptive immune responses to inflammasome activation upon sterile skin injury
Abstract
The molecular links between sterile inflammation and induction of adaptive immunity have not been fully identified. Here, we examine how damage associated molecular patterns (DAMPs), as opposed to pathogen associated molecules (PAMPs), regulates the immune response to non-self-antigens presented at the site of the physical injury. Heat applied briefly to the skin invokes sterile inflammation, characterised by local cell death and caspase-1 activation without demonstrably disrupting skin integrity. Co-delivery of ovalbumin (OVA) with heat injury induces OVA-specific CD8+ T cell responses and this is dependent on caspase-1 activation and MyD88 signalling. Using Id2flox/flox-CD11cCre+ mice, we demonstrate that CD8+ lineage DCs are required to induce OVA-specific CD8+ T cell responses following heat injury. Consistent with this observation, intradermal administration of CD8+ lineage DCs but not CD11b+ lineage DCs restores priming of CD8+ T cell responses in Casp-1-/- mice. Thus, we conclude that a sterile injury induces CD8+ T cell immune responses to local antigen through caspase-1 activation and requires CD8+ lineage DCs, a finding of significance for immunotherapy and for the pathogenesis of autoimmunity.
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Structural proteins of the dermal-epidermal junction targeted by autoantibodies in pemphigoid diseases
Abstract
The dermal-epidermal junction consists of a network of several interacting structural proteins which strengthen adhesion and mediate signaling events. This structural network consists of hemidesmosomal-anchoring filament complexes connecting the basal keratinocytes to the basement membrane. The anchoring filaments in turn interact with the anchoring fibrils to attach the basement membrane to the underlying dermis. Several of these structural proteins are recognized by autoantibodies in pemphigoid diseases, a heterogeneous group of clinically and immunopathologically diverse entities. Targeted proteins include the two intracellular plakins plectin isoform 1a and BP230 (also called bullous pemphigoid antigen (BPAG) 1 isoform e (BPAG1e)), which are connected to the intermediate filaments and to the cell surface receptor α6β4 integrin, which in turn is connected to laminin 332, a component of the anchoring filaments. Further essential adhesion proteins are BP180, a transmembrane protein, laminin γ1, and type VII collagen. Latter protein is the major constituent of the anchoring fibrils. Additionally, a 105 kDa protein of the lower lamina lucida has been described as autoantigen. Mutations in the corresponding genes of these adhesion molecules lead to inherited epidermolysis bullosa emphasizing the importance of these proteins for the integrity of the dermal-epidermal junction. This review will provide an overview on the structure and function of the proteins situated in the dermal-epidermal junction targeted by autoantibodies.
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Durvalumab after Chemoradiotherapy in Stage III Non–Small-Cell Lung Cancer
Approximately one third of patients with non–small-cell lung cancer (NSCLC) have stage III, locally advanced disease at diagnosis. The standard of care for patients with a good performance status and unresectable stage III NSCLC is platinum-based doublet chemotherapy concurrent with radiotherapy…
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Prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in retail food in Singapore
We characterised 227 Staphylococcus aureus isolates from retail food and food handlers' gloves samples obtained through food surveillance and risk assessment studies between 2011 and 2014. Of 227 isolates, five (...
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Endoscopic Mucosal Resection is Superior to Rectal Suction Biopsy for Analysis of Enteric Ganglia in Constipation and Dysmotility
Patients with chronic constipation or motility disorders may be referred for rectal suction biopsy (RSB) to rule out Hirschsprung's disease (HD). RSB may not be successful beyond infancy due to the increased thickness of rectal mucosa. Endoscopic mucosal resection (EMR) could improve the diagnostic yield for HD when compared with traditional RSB because of the larger and deeper samples acquired for analysis.
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Passport to pathology: transforming the medical student pathology elective from a passive educational experience to an exciting, immersive clinical rotation
In the United States, third- and fourth-year medical students are exposed to a variety of rigorous clinical rotations ranging from four to twelve weeks in duration. Regardless of the specialty that a student ultimately plans to pursue, all medical students are required to take clinical rotations including surgery, medicine, pediatrics, obstetrics and gynecology, psychiatry, neurology, and outpatient/family practice. A student planning to specialize in psychiatry, for example, is not exempt from closing an incision in an operative case or from assisting in a laparoscopic procedure during a general surgery rotation.
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A randomized, phase 2 study of cetuximab plus cisplatin with or without paclitaxel for the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck
Abstract
Background
B490 (EudraCT# 2011-002564-24) is a randomized, phase 2b, noninferiority study investigating the efficacy and safety of first-line cetuximab plus cisplatin with/without paclitaxel (CetCis versus CetCisPac) in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). Patients and methods
Eligible patients had confirmed R/M SCCHN (oral cavity/oropharynx/larynx/hypopharynx/paranasal sinus) and no prior therapy for R/M disease. Cetuximab was administered on day 1 (2-h infusion, 400 mg/m2), then weekly (1-h infusions, 250 mg/m2). Cisplatin was given as a 1-h infusion (CetCis arm: 100 mg/m2; CetCisPac arm: 75 mg/m2) on day 1 of each cycle for a maximum of six cycles. Paclitaxel was administered as a 3-h infusion (175 mg/m2) on day 1 of each cycle. After six cycles, maintenance cetuximab was administered until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). We assumed a noninferiority margin of 1.40 as compatible with efficacy. Results
A total of 201 patients were randomized 1 : 1 to each regimen; 191 were assessable. PFS with CetCis (median, 6 months) was noninferior to PFS with CetCisPac (median, 7 months) [HR for CetCis versus CetCisPac 0.99; 95% CI: 0.72–1.36, P = 0.906; margin of noninferiority (90% CI of 1.4) not reached]. Median overall survival was 13 versus 11 months (HR = 0.77; 95% CI: 0.53–1.11, P = 0.117). The overall response rates were 41.8% versus 51.7%, respectively (OR = 0.69; 95% CI: 0.38–1.20, P = 0.181). Grade ≥3 adverse event rates were 76% and 73% for CetCis versus CetCisPac, respectively, while grade 4 toxicities were lower in the two-drug versus three-drug arm (14% versus 33%, P = 0.015). No toxic death or sepsis were reported and cardiac events were negligible (1%). Conclusion
The two-drug CetCis regimen proved to be noninferior in PFS to a three-drug combination with CetCisPac. The median OS of both regimens is comparable with that observed in EXTREME, while the life-threatening toxicity rate appeared reduced. Clinical trial number
EudraCT# 2011-002564-24.http://ift.tt/2vU5t4g
P 12 Integrating nTMS motor mapping of the M1 tongue area into diffusion tractography to reconstruct motor-speech pathways
The preservation of important white matter tracts is extremely important to optimize the functional long-term outcome after brain tumour surgery. The integration of functional localizer data such as navigated transcranial magnetic stimulation (nTMS) as starting region of interest (ROI) within the primary motor cortex (M1) into diffusion-tensor-imaging- (DTI-) tractography algorithms represents a recent advancement of the methodology with regard to the reconstruction of the corticospinal tract (CST).
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P 170 A potential signature for ongoing pain in mice
Chronic pain is a major health care problem nowadays with no convincing treatment yet (Apkarian et al., 2009). One challenge of research and treatment of pain is that it cannot be objectively quantified. Only indirect measurements like the Visual Analogue Scale for humans and responses to mechanical or thermal stimuli for animals are used. Electrophysiological changes in brain activity are a possible candidate for a direct measurement of pain and could be easily obtained by EEG recordings. However most of the studies with this scope are focused on evoked potentials of short lasting pain stimuli (ms to s) (Zhang et al., 2012) and only few studies have been conducted on longer lasting pain (Leblanc et al., 2014).
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P 165 Incidence, clinical characteristics and longterm course of headache in patients with stroke (DMKG multicenter study)
Post stroke headache is a symptom which is generally not further differentiated. According to previous European and American studies, it is a common phenomenon. Nevertheless, other symptoms of stroke, such as palsy or aphasia, are dominating clinical assessments. However, the symptom "headache" can be an essential part of the clinical picture as in subarachnoid bleeding or cerebral venous thrombosis and it is unclear which risk factors modulate the symptoms and the occurrence of headache in stroke.
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P 161 Coupling of brain arousal and autonomic regulation in the transition from wakefulness to sleep onset during an auditory oddball task in the resting state
Simultaneous downregulation of the autonomic and central nervous system activity enables the gradual physiological state change from wakefulness to sleep onset. Dysregulation of central or autonomic arousal has been found in neurological (Silvani et al., 2016) and psychiatric disorders (Hegerl and Hensch, 2014; Hegerl et al., 2012; Schulz et al., 2016; Schwabedal et al., 2016), often associated with dysregulated sleep-wake patterns.
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P 14 Motor component of speech errors in rTMS language mapping
Using neuronavigated repetitive transcranial magnetic stimulation (rTMS) to disrupt language function during an online-task (e.g., picture naming) is a novel mapping technique which has recently been introduced for presurgical diagnostics in brain tumor patients. However, the method has some limitations due to its rather low specificity. Beyond its dependency on the task, the distinct error categories may have a major effect on the mapping results. We, here, studied the reliability and the spatial localization of rTMS-induced naming errors related to motor-speech function in contrast to semantic language errors.
http://ift.tt/2eTLXh0
P 13 Congruency between speech-related areas investigated by fMRI and three rTMS protocols with different frequencies
Recently, language mapping by repetitive transcranial magnetic stimulation (rTMS) has gained a lot of interest in preoperative planning to preserve language function. However, the improvement of rTMS protocols is still a matter of debate since rTMS-evoked speech-errors appear relatively widespread over the brain and are rather poorly reliable, depending on the type of the speech-errors. We, therefore, investigated how rTMS-evoked speech-errors of distinct categories are located relatively to speech-related functional MRI (fMRI) clusters (serving as a widely used method for language mapping).
http://ift.tt/2jcX6dY
P 172 Endogenous pain modulation in patients with syringomyelia
Syringomyelia is a rare disease affecting the spinal cord. Some patients have no symptoms, but often dissociated sensory disturbances and neuropathic pain can be found.Aim of this study was to analyse endogenous pain modulation and stress-induced analgesia in patients with syringomyelia.
http://ift.tt/2jcWQM2
P 168 Prevalence and characteristics of headache induced by inhalation or ingestion of a cold stimulus (HICS) in a group of adult subjects
Headache attributed to ingestion or inhalation of a cold stimulus (HICS) is a well-known phenomenon. Previously published data documented the prevalence in healthy subjects in childhood. Also an association between HICS and migraine is assumed. HICS is classified as a primary headache (IHS 4.5.2). Data on prevalence in adults does not exist as of now.
http://ift.tt/2eUdleF
P 166 Case presentation – apoplex due to partial occlusion of the medial cerebral artery with sinistral hemiparesis, word-finding disorder, memory impairment and writing disorder
S. had helped her sister to move. She experienced dizziness and everything went black. She choked on something to drink. Then she went out on the balcony, fell due to weakness of her right leg, and she could not move the right half of the body (right arm, right leg). The right angle of his mouth hung slightly with saliva, and she slurred her speech. She was put down. Then she was unconscious for about 5min and was hospitalised by the emergency physician with suspicion of epilepsy.Additional anamnestic data collected later: Was frequently beaten by a violent friend.
http://ift.tt/2jcBnTK
P 164 Parietal stroke mimicking the Heidenhain variant of Creutzfeldt-Jakob Disease
The Heidenhain variant of Creutzfeldt-Jakob disease (CJD) is a rapidly progressive neurodegenerative disease with an occipito-parietal focus.It initially presents with visual disturbances such as visual agnosia or cortical blindness (Kropp et al., 1999).After presentation of early visual symptoms, rapid progression of dementia and death follows.While the Heidenhain variant matches neuropathological criteria of CJD, differential diagnosis from other neurological disorders using biomarkers from electroencephalography (EEG), magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) reveal low sensitivity and specificity.As a consequence, these tools may lead to an erroneous diagnosis of the Heidenhain variant.
http://ift.tt/2eU0JEt
P 162 Rhythmic Auditory Stimulation (RAS) as an additional treatment for chronic stroke patients in the outpatient setting: a randomized controlled trial
Rhythmic Auditory Stimulation (RAS) is a rhythmic sensory cueing to enhance gait patterns. Aim of the study was to research the effectiveness of RAS as an additional treatment for chronic stroke patients.
http://ift.tt/2jcRpwD
Acute histological inflammatory activity is associated with clinical relapse in patients with ulcerative colitis in clinical and endoscopic remission.
It has been suggested that acute histological activity has a prognostic value in the outcome of ulcerative colitis (UC) patients in clinical and endoscopic remission. Our aim was to assess the role of histology as a risk factor for clinical relapse (CR) in patients in both clinical and endoscopic remission.
http://ift.tt/2jccTtz
IGRT strategies for pelvic lymph node irradiation in high-risk prostate cancer: motion and margins
Definition of margins to determine the optimal image-guided radiotherapy (IGRT) strategy for pelvic lymph node irradiation is essential in high-risk prostate cancer. In this work, these margins were derived from systematic and random motions measured using repeated CT scans in 19 patients, based on matching to either bony anatomy or prostate for a 3 or 6 degrees-of-freedom (DOF) couch. When matching to bony anatomy, margins were smaller for lymph nodes than when matching to prostate, but larger for prostate and seminal vesicles. The prostate and seminal vesicle margins were unchanged when using a 3 vs 6 DOF couch, but lymph node margins were smaller in the anterior-posterior direction.
http://ift.tt/2jcOxjD
A systematic review of synthetic CT generation methodologies for use in MRI-only radiotherapy
MRI offers superior soft tissue contrast as compared to CT, which is conventionally used for radiotherapy treatment planning (RTP) and patient positioning verification, resulting in improved target definition. The two modalities are co-registered for RTP, however this introduces a systematic error. Implementing an MRI-only radiotherapy workflow would be advantageous as this error would be eliminated, the patient pathway simplified and patient dose reduced. Unlike CT, in MRI there is no direct relationship between signal intensity and electron density, however various methodologies for MRI-only RTP have been reported.
http://ift.tt/2eTCYfQ
Paediatric nuclear medicine imaging
Abstract
Background
Nuclear medicine imaging explores tissue viability and function by using radiotracers that are taken up at cellular level with different mechanism. This imaging technique can also be used to assess blood flow and transit through tubular organs. Nuclear medicine imaging has been used in paediatrics for decades and this field is continuously evolving. Sources of data
The data presented comes from clinical experience and some milestone papers on the subject. Areas of agreement
Nuclear medicine imaging is well-established in paediatric nephro-urology in the context of urinary tract infection, ante-natally diagnosed hydronephrosis and other congenital renal anomalies. Also, in paediatric oncology, I-123-meta-iodobenzyl-guanidine has a key role in the management of children with neuroblastic tumours. Bone scintigraphy is still highly valuable to localize the source of symptoms in children and adolescents with bone pain when other imaging techniques have failed. Thyroid scintigraphy in neonates with congenital hypothyroidism is the most accurate imaging technique to confirm the presence of ectopic functioning thyroid tissue. Areas of controversy
Radionuclide transit studies of the gastro-intestinal tract are potentially useful in suspected gastroparesis or small bowel or colonic dysmotility. However, until now a standardized protocol and a validated normal range have not been agreed, and more work is necessary. Research is ongoing on whether magnetic resonance imaging (MRI), with its great advantage of great anatomical detail and no ionizing radiations, can replace nuclear medicine imaging in some clinical context. On the other hand, access to MRI is often difficult in many district general hospitals and general anaesthesia is frequently required, thus adding to the complexity of the examination. Growing points
Patients with bone pain and no cause for it demonstrated on MRI can benefit from bone scintigraphy with single photon emission tomography and low-dose computed tomography. This technique can identify areas of mechanical stress at cortical bone level, difficult to demonstrate on MRI, which can act as pain generators. Positron emission tomography (PET) is being tested in the staging, response assessment and at the end of treatment of several paediatric malignancies. PET is becoming more widely utilized in neurology in the pre-surgical assessment of some children with drug resistant epilepsy. Areas timely for developing research
The use of PET/MRI scanners is very attractive as it combines benefits of MR imaging with the assessment of cellular viability and metabolism with PET in one examination. This imaging technique will allow important research on tumour in-vivo metabolism (possible applications include lymphomas, neuroblastomas, malignant germ cell tumours andbrain tumours), with the aim of offering a personalized biological profile of the tumour in a particular patient. Ground-breaking research is also envisaged in neurosciences, especially in epilepsy, using PET tracers that would enable a better identification of the epileptogenic focus, and in psychiatry, with the use of radiolabeled neurotransmitters. In paediatric nephro-urology, the identification of the asymptomatic child with ante-natally diagnosed hydronephrosis at risk of losing renal parenchymal function if left untreated is another area of active research involving radionuclide renography.http://ift.tt/2wPktiS
Think adult—think child! Why should staff caring for dying adults ask what the death means for children in the family?
Abstract
Introduction
Bereaved children and young people in the UK are 'hidden mourners'. Sources of data
Review of primary and secondary evidence on childhood bereavement. Area of agreement
Children experience grief that varies according to the circumstance of death and their cognitive ability. Voluntary organizations can be supportive, but provision is patchy and vulnerable to austerity. Areas of concern
Adult-centric denial of the importance and long-term consequences of childhood grief; uncertainty in how best to relate to bereaved children in faiths and in schools. Growing points
Increased awareness of the immediate and long-term consequences of childhood bereavement; even young children can experience loss through death. Areas timely for research
Better knowledge of the numbers of affected children; longitudinal data to track experiences and outcomes; measuring effectiveness of different approaches; identifying risk factors for early intervention in complicated or prolonged grief; the importance of faith and rituals around death; mapping the provision of services to monitor the impact of austerity. Recommendations
'Think adult—think child' means that all staff caring for dying adults should take responsibility for asking what the death means for the children in the family, with schools, primary care and faith organizations having protocols and expertise available to support grieving children; recent catastrophes expose need for agencies to have management plans that focus on vulnerable children and young people.http://ift.tt/2wfq4LS
Genomic medicine and data sharing
Abstract
Introduction
Effective data sharing does not occur in the UK despite being essential for the delivery of high-quality genomic services to patients across clinical specialities and to optimize advances in genomic medicine. Sources of data
Original papers, reviews, guidelines, policy papers and web-resources. Areas of agreement
Data sharing for genomic medicine requires appropriate infrastructure and policies, together with acceptance by health professionals and the public of the necessity of data sharing for clinical care. Areas of controversy
There is ongoing debate around the different technical approaches and safeguards that could be used to facilitate data sharing while minimizing the risks to individuals of identification. Lack of consensus undermines trust and confidence. Growing points
Ongoing policy developments around genomics and health data create opportunities to ensure systems and policies are in place to support proportionate, effective and safeguarded data sharing. Areas timely for developing research
Mechanisms to improve public trust.http://ift.tt/2wPku6q
Transtendon repair in partial articular supraspinatus tendon tear
Abstract
Introduction
Partial thickness rotator cuff tears (PTRCTs) are common, with an incidence between 17% and 37%, and a high prevalence in throwing athletes. Different surgical procedures are suggested when partial tears involve the articular portion of the rotator cuff, including arthroscopic debridement of the tear, debridement with acromioplasty, tear completion and repair, and lately transtendon repair. This systematic review describes the transtendon repair and examines indications, contraindications, complications and clinical outcome. Source of data
We identified clinical studies listed in the Pubmed Google Scholar, CINAHL, Cochrane Central and Embase Biomedical databases in English and Italian concerning the clinical outcomes following treatment of partial articular supraspinatus tendon tear using transtendon surgical repair. Areas of agreement
Eighteen studies fulfilled our inclusion criteria. All were published between 2005 and 2016, three were retrospective, and 15 prospective. The total number of patients was 507 with a mean age of 50.8 years. Areas of controversy
Tear completion and repair and transtendon repair alone produce similar results. Growing points
Transtendon surgical repair allows to obtain good-excellent results in the treatment of partial articular supraspinatus tendon tears. Areas timely for developing research
Further studies are needed to produce clear guidelines in the treatment of partial articular supraspinatus tendon tears. Level of evidence
IV.http://ift.tt/2wOtVTo
Pricing as a means of controlling alcohol consumption
Abstract
Background
Reducing the affordability of alcohol, by increasing its price, is the most effective strategy for controlling alcohol consumption and reducing harm. Sources of data
We review meta-analyses and systematic reviews of alcohol tax/price effects from the past decade, and recent evaluations of tax/price policies in the UK, Canada and Australia. Areas of agreement
While the magnitudes of price effects vary by sub-group and alcoholic beverage type, it has been consistently shown that price increases lead to reductions in alcohol consumption. Areas of controversy
There remains, however, a lack of consensus on the most appropriate taxation and pricing policy in many countries because of concerns about effects by different consumption level and income level and disagreement on policy design between parts of the alcoholic beverage industries. Growing points
Recent developments in the research highlight the importance of obtaining accurate alcohol price data, reducing bias in estimating price responsiveness, and examining the impact on the heaviest drinkers. Areas timely for developing research
There is a need for further research focusing on the substitution effects of taxation and pricing policies, estimation of the true tax pass-through rates, and empirical analysis of the supply-side response (from alcohol producers and retailers) to various alcohol pricing strategies.http://ift.tt/2wfDMhC
The contribution of genetics and environment to obesity
Abstract
Background
Obesity is a global health problem mainly attributed to lifestyle changes such as diet, low physical activity or socioeconomics factors. However, several evidences consistently showed that genetics contributes significantly to the weight-gain susceptibility. Sources of data
A systematic literature search of most relevant original, review and meta-analysis, restricted to English was conducted in PubMed, Web of Science and Google scholar up to May 2017 concerning the contribution of genetics and environmental factors to obesity. Areas of agreement
Several evidences suggest that obesogenic environments contribute to the development of an obese phenotype. However, not every individual from the same population, despite sharing the same obesogenic environment, develop obesity. Areas of controversy
After more than 10 years of investigation on the genetics of obesity, the variants found associated with obesity represent only 3% of the estimated BMI-heritability, which is around 47–80%. Moreover, genetic factors per se were unable to explain the rapid spread of obesity prevalence. Growing points
The integration of multi-omics data enables scientists having a better picture and to elucidate unknown pathways contributing to obesity. Areas timely for developing research
New studies based on case–control or gene candidate approach will be important to identify new variants associated with obesity susceptibility and consequently unveiling its genetic architecture. This will lead to an improvement of our understanding about underlying mechanisms involved in development and origin of the actual obesity epidemic. The integration of several omics will also provide insights about the interplay between genes and environments contributing to the obese phenotype.http://ift.tt/2wOREmD
Dystonia
Abstract
Introduction
Dystonia is a clinically heterogeneous group of hyperkinetic movement disorders. Recent advances have provided a better understanding of these conditions with significant clinical impact. Sources of data
Peer reviewed journals and reviews. PubMed.gov. Areas of agreement
A recent consensus classification, including the assessment of phenomenology and identification of the dystonia syndromes, has provided a helpful tool for the clinical assessment. New forms of monogenic dystonia have been recently identified. Areas of controversy
Despite recent advances in the understanding of dystonia, treatment remains symptomatic in most patients. Growing points
Recent advances in genetics have provided a better understanding of the potential pathogenic mechanisms involved in dystonia. Deep brain stimulation has shown to improve focal and combined forms of dystonia and its indications are constantly expanding. Areas timely for developing research
Growing understanding of the disease mechanisms involved will allow the development of targeted and disease-modifying therapies in the future.http://ift.tt/2wfDDL1
Anticoagulation after coronary stenting: a systemic review
Abstract
Introduction or background
Anticoagulant therapy is mainly used to prevent patients from suffering coronary and systemic thromboembolism after stenting. Many studies have been done to formulate an optimized regimen of a post-PCI or long-time anticoagulant therapy. Recent advances in the selection and duration of anticoagulant agents will be conducive to the management of patients who are considered to need anticoagulant therapy after stenting. Sources of data
Key recent published literature, including international guidelines and relevant reviews. Areas of agreement
Anticoagulant therapy has been acknowledged to improve the prognosis of patients after stenting by reducing the risk of coronary and systemic thromboembolism. Areas of controversy
Firstly, the benefit–risk ratio of post-PCI parenteral anticoagulation to prevent stent thrombosis locally in the coronary artery is still unclear. Secondly, the efficacy and safety of bivalirudin deserve to be discussed. Furthermore, the recommendation to use long-time oral anticoagulant therapy to prevent systemic thromboembolism after stenting should also be emphasized. Growing points
Studies of anticoagulant therapy in patients after stenting add to the understanding of an optimized anticoagulant regimen and contribute to improving clinical outcomes. Areas for developing research
- The safety and efficacy of bivalirudin, a direct thrombin inhibitor, need to be further investigated by more large-scale randomized clinical trials.
- Based on the widespread use of ticagrelor and prasugrel for patients who need long-time oral anticoagulant therapy, further study is needed to find an optimal strategy that balances the risk of bleeding and ischemic events after coronary stenting.
http://ift.tt/2wOUh7H
Is elimination of hepatitis C from the UK by 2030 a realistic goal?
Abstract
Introduction
Highly effective, combination therapy for chronic hepatitis C virus (HCV) infection is now available. Current cure rates are close to 100% and applicable to all patients irrespective of race, age, severity of liver disease or viral genotype. Remarkably for persistent infection, current treatment is recommended for as little as 12 weeks; recent studies suggest even shorter courses. In contrast to interferon-based therapy, present regimens have few side effects and serious adverse events are rare. The success and safety of these regimens has stimulated interest in the possible eventual elimination of HCV. Barriers to elimination include cost of drugs and finding patients in the community less likely to interact with medical services who are a potential reservoir of infection. Sources of data
Pubmed. Areas of agreement
Antiviral agents already available are highly effective. Areas of controversy
The cost of the newer antiviral agents is very high, restricting treatment numbers in the UK in 2015/16 and focusing therapy on those patients with significant fibrosis. Recently, patients with less severe disease have been offered therapy, but delivery may be slowed by high costs. Many believe that insufficient pressure has been brought to bear to reduce costs. Eventual elimination will depend first on reducing treatment costs for those known to have chronic HCV infection and then finding patients in the community with infection unaware of their illness or reluctant/unable to engage with medical services. Areas for developing research
Determining the most effective strategies to identify 'invisible' patients in the community with chronic HCV infection.http://ift.tt/2wfb5S7
Management of combined injuries of the posterior cruciate ligament and posterolateral corner of the knee: a systematic review
Abstract
Background
Approximately 60% of posterior cruciate ligament (PCL) injury are associated with a posterolateral corner (PLC) tear. Sources of data
We performed a systematic review of the literature according to the PRISMA guidelines. The following key words were searched on Medline, Cochrane, EMBASE, Google Scholar, and Ovid: 'posterior cruciate ligament' or 'PCL' with 'posterolateral corner' or 'PLC' and 'chronic'; 'injury'; 'management'; 'reconstruction'; 'outcomes'; 'complications'. Areas of agreement
There was a statistically significant improvement of all clinical scores after surgery regardless of the procedure performed to reconstruct both PCL and PLC. Areas of controversy
No randomized control trials were identified on the topic. Standardized methods of functional outcomes assessment are necessary to improve communication on the functional results of the management of PC–PLC. Growing points
Single stage surgical reconstruction of PCL and PLC is recommended in patients with posterolateral rotatory instability of the knee. Areas timely for developing research
Adequately powered randomized trials with appropriate subjective and objective outcome measures are necessary to reach definitive conclusions.http://ift.tt/2wP8eCZ
Exercise-Induced Catecholamines Activate the Hippo Tumor Suppressor Pathway to Reduce Risks of Breast Cancer Development
Strong epidemiologic evidence documents the protective effect of physical activity on breast cancer risk, recurrence, and mortality, but the underlying mechanisms remain to be identified. Using human exercise–conditioned serum for breast cancer cell incubation studies and murine exercise interventions, we aimed to identify exercise factors and signaling pathways involved in the exercise-dependent suppression of breast cancer. Exercise-conditioned serum from both women with breast cancer (n = 20) and healthy women (n = 7) decreased MCF-7 (hormone-sensitive) and MDA-MB-231 (hormone-insensitive) breast cancer cell viability in vitro by 11% to 19% and reduced tumorigenesis by 50% when preincubated MCF-7 breast cancer cells were inoculated into NMRI-Foxn1nu mice. This exercise-mediated suppression of cell viability and tumor formation was completely blunted by blockade of β-adrenergic signaling in MCF-7 cells, indicating that catecholamines were the responsible exercise factors. Both epinephrine (EPI) and norepinephrine (NE) could directly inhibit breast cancer cell viability, as well as tumor growth in vivo. EPI and NE activate the tumor suppressor Hippo signaling pathway, and the suppressive effect of exercise-conditioned serum was found to be mediated through phosphorylation and cytoplasmic retention of YAP and reduced expression of downstream target genes, for example, ANKRD1 and CTGF. In parallel, tumor-bearing mice with access to running wheels showed reduced growth of MCF-7 (–36%, P < 0.05) and MDA-MB-231 (–66%, P < 0.01) tumors and, for the MCF-7 tumor, increased regulation of the Hippo signaling pathway. Taken together, our findings offer a mechanistic explanation for exercise-dependent suppression of breast cancer cell growth. Cancer Res; 77(18); 1–11. ©2017 AACR.
http://ift.tt/2gRM2Cz
ATG5 mediates a positive feedback loop between Wnt signaling and autophagy in melanoma
Autophagy mediates resistance to various anticancer agents. In melanoma, resistance to targeted therapy has been linked to expression of Wnt5A, an intrinsic inhibitor of β-catenin, which also promotes invasion. In this study, we assessed the interplay between Wnt5A and autophagy by combining expression studies in human clinical biopsies with functional analyses in cell lines and mouse models. Melanoma cells with high Wnt5A and low β-catenin displayed increased basal autophagy. Genetic blockade of autophagy revealed an unexpected feedback loop whereby knocking down the autophagy factor ATG5 in Wnt5Ahigh cells decreased Wnt5A and increased β-catenin. To define the physiological relevance of this loop, melanoma cells with different Wnt status were treated in vitro and in vivo with the potent lysosomotropic compound Lys05. Wnt5Ahigh cells were less sensitive to Lys05 and could be reverted by inducing β -catenin activity. Our results suggest the efficacy of autophagy inhibitors might be improved by taking the Wnt signature of melanoma cells into account.
http://ift.tt/2eTO7gB
Optimization of Human NK Cell Manufacturing: Fully Automated Separation, Improved Ex Vivo Expansion Using IL-21 with Autologous Feeder Cells, and Generation of Anti-CD123-CAR-Expressing Effector Cells
Human Gene Therapy , Vol. 0, No. 0.
http://ift.tt/2eTXWv5
Hemophilia Gene Therapy: Ready for Prime Time?
Human Gene Therapy , Vol. 0, No. 0.
http://ift.tt/2jbKNPr
The use of methylphenidate to relieve fatigue.
Purpose of review: To review recent evidence on the efficacy and safety of methylphenidate as a symptomatic treatment of patients with cancer-related fatigue (CRF). Recent findings: Five clinical trials published since 2011 were identified. Two of these concluded that methylphenidate is more efficacious than placebo in providing relief from CRF, but the remaining three showed no difference in favour of methylphenidate. The studies were heterogeneous as per the dosage, scales used for evaluating fatigue and the target group studied. None of the studies detected serious reactions, and only mild and infrequent side-effects of methylphenidate were reported. Three new metanalyses show the slightly superior effect of methylphenidate compared to placebo in CRF. Summary: Overall, literature supports the existence of moderate benefit of methylphenidate in CRF, backed up by weak evidence. Future studies should aim at better identifying the profile of patients who would benefit most from this pharmacological intervention. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2xjy6rU
http://ift.tt/2xjy6rU
Research on advanced intervention using novel bone marrOW stem cell (RAINBOW): a study protocol for a phase I, open-label, uncontrolled, dose-response trial of autologous bone marrow stromal cell transplantation in patients with acute ischemic stroke
Stroke is a leading cause of death and disability, and despite intensive research, few treatment options exist. However, a recent breakthrough in cell therapy is expected to reverse the neurological sequelae o...
http://ift.tt/2wfXfPi
Supernumerary phantom limb in a patient with basal ganglia hemorrhage - a case report and review of the literature
Supernumerary phantom limb (SPL) is a rare neurologic phenomenon, in which a patient misperceives an extra limb in addition to the original set of limbs. We report a case of SPL in a patient with a right basal...
http://ift.tt/2wP14ye
New dental imaging method uses squid ink to fish for gum disease
http://ift.tt/2vStysp
Baby Organic Liquid Formula by Garden of Life: Recall - Directions For Use May Be Misinterpreted
Audience: Consumer [Posted 09/08/2017] ISSUE: Garden of Life, LLC is issuing a voluntary precautionary recall of its new supplement for infants, Baby Organic Liquid, because the product, as labeled, includes directions for use that may be...
http://ift.tt/2vLgBML
Evaluation of Xpert MTB/RIF testing for rapid diagnosis of childhood pulmonary tuberculosis in children by Xpert MTB/RIF testing of stool samples in a low resource setting
Children with tuberculosis (TB) remain underdiagnosed due to difficulty in testing for Mycobacterium tuberculosis (MTB) infection. We evaluated the Xpert MTB/RIF assay for respiratory and stool testing in childre...
http://ift.tt/2xUyhH2
Correlation of cord blood telomere length with birth weight
Intrauterine growth restriction affects 3% of newborns; and the lightest 10% of whom are classified as small for gestational age (SGA). These low-birth weight newborns are at increased risk of neonatal morbidi...
http://ift.tt/2vU10yE
Is it a supplementary benefit to use anti-inflammatory agents in the treatment of type 2 diabetes?
The aim of this study was to investigate an independent correlation between high sensitivity C-reactive protein (hs-CRP) and glycated haemoglobin (HbA1c) on one side and between hs-CRP and arterial pressure in...
http://ift.tt/2vU7YUf
Effects of bacitracin methylene disalicylate and diet change on gastrointestinal integrity and endotoxin permeability in the duodenum of broiler chicken
To determine the effect of bacitracin methylene disalicylate (BMD) and feed changes on gastrointestinal integrity, endotoxin permeability, and morphometric parameters in the duodenum of broilers.
http://ift.tt/2xVdZNO
Prevalence of antibodies to Brucella species in commercial raw bovine milk in Southwestern Uganda
The purpose and objective of this research was to explore the prevalence of antibodies against Brucella species in raw milk samples collected in Southwestern Uganda, one of the biggest milk producing regions in t...
http://ift.tt/2vU0ZL6
Baby Organic Liquid Formula by Garden of Life: Recall - Directions For Use May Be Misinterpreted
Audience: Consumer [Posted 09/08/2017] ISSUE: Garden of Life, LLC is issuing a voluntary precautionary recall of its new supplement for infants, Baby Organic Liquid, because the product, as labeled, includes directions for use that may be...
http://ift.tt/2vLgBML
Synthesis, Quality Control and Bio-evaluation of 99mTc-cyclophosphamide
Abstract
Cancer is found to be the leading cause of death worldwide characterized by uncontrolled cell division. Nuclear medicines imaging by using radiopharmaceuticals have pronounced potential for the diagnosis and treatment of cancers. Cyclophosphamide (CPH) is an antineoplastic drug which targets selectively cancer cells. In the present work, labelling of CPH with Tc-99m is performed for diagnostic purpose, which gave labelling yield as high as 99% by using 20μg SnCl2.2H2O, 200μg of ligand at pH 7 for 10 min reaction time at room temperature. The characterization of the prepared complex was performed by using ITLC, electrophoresis and HPLC. In vitro stability was analyzed in the presence of human serum at 37◦C which have maximum value of 94±0.5. The biodistribution studies of 99mTc-CPH were performed in normal and tumor bearing Swiss Webster mice. The high accumulation of 99mTc-CPH was observed in liver and tumours respectively at 4h after injection. Biodistribution results revealed that 99mTc-CPH may be a potential tumour diagnostic agent simultaneously with chemotherapy.
This article is protected by copyright. All rights reserved.
The 99mTc-labled-CPH was prepared very efficiently through a simple method. Biodistribution results revealed that 99mTc-CPH may be a potential tumour diagnostic agent simultaneously with chemotherapy.
http://ift.tt/2vLxYwQ
In the search for a lead structure among series of potent and selective hydantoin 5-HT7R agents: the drug-likeness in vitro study
Abstract
Since the year 1993, when 5-HT7 receptor (5-HT7R) was discovered, there is no selective 5-HT7R ligand introduced to the pharmaceutical market. One out of the main reasons disqualifying the 5-HT7R ligands are weak drugability properties, including metabolic instability or low permeability. This study is focused on the search of a lead compound by "drug-likeness" estimation of the first series of selective and potent 5-HT7R ligands among 5-(4-fluorophenyl)-3-(2-hydroxy-3-(4-aryl-piperazin-1-yl)propyl)-5-methyl-imidazolidine-2,4-dione derivatives (11-16). The most important drugability parameters, i.e. permeability, metabolic stability and safety, have been evaluated. The main metabolic pathways were determined. The forced swim test (FST) in mice was performed as a primary in vivo assay for compound 13 and the reference 2. The experiments showed promising drug-like properties for all ligands, with special attention to the benzhydryl (diphenylmethyl) derivative 13. The studies have also indicated in vivo activity of the compound 13 that was observed as a significant and specific antidepressant-like activity in the FST. Taking into account the beneficial properties of 13, i.e. good drug-like parameters, the significant antagonistic action, high selectivity to 5-HT7R and its in vivo antidepressant-like activity, the compound should be considered as a new lead in the search for drugs acting on CNS via 5-HT7 receptor.
This article is protected by copyright. All rights reserved.
his study is focused on the search of a lead compound by "drug-likeness" estimation of the first series of selective and potent 5-HT7R ligands among 5-(4-fluorophenyl)-3-(2-hydroxy-3-(4-aryl-piperazin-1-yl)propyl)-5methyl-imidazolidine-2,4-dione derivatives (11-16). The drugability parameters: permeability,metabolic stability and safety,have been successfully evaluated.The experiments showed promising drung-like properties of all ligands, with special attention to compound 13 with the benzhydryl (diphenylmethyl)substituent.The forced sim test in mice has confirmed a good in vivo action of 13,showing its distinct antidepressant-like action
http://ift.tt/2gQH0WG
Diagnostic Utility of Increased STIR Signal in the Posterior Atlanto-Occipital and Atlantoaxial Membrane Complex on MRI in Acute C1-C2 Fracture [SPINE]
BACKGROUND AND PURPOSE:
Acute C1–C2 fractures are difficult to detect on MR imaging due to a paucity of associated bone marrow edema. The purpose of this study was to determine the diagnostic utility of increased STIR signal in the posterior atlanto-occipital and atlantoaxial membrane complex (PAOAAM) in the detection of acute C1–C2 fractures on MR imaging.
MATERIALS AND METHODS:Eighty-seven patients with C1–C2 fractures, 87 with no fractures, and 87 with other cervical fractures with acute injury who had both CT and MR imaging within 24 hours were included. All MR images were reviewed by 2 neuroradiologists for the presence of increased STIR signal in the PAOAAM and interspinous ligaments at other cervical levels. Sensitivity and specificity of increased signal within the PAOAAM for the presence of a C1–C2 fracture were assessed.
RESULTS:Increased PAOAAM STIR signal was seen in 81/87 patients with C1–C2 fractures, 6/87 patients with no fractures, and 51/87 patients with other cervical fractures with 93.1% sensitivity versus those with no fractures, other cervical fractures, and all controls. Specificity was 93.1% versus those with no fractures, 41.4% versus those with other cervical fractures, and 67.2% versus all controls for the detection of acute C1–C2 fractures. Isolated increased PAOAAM STIR signal without increased signal in other cervical interspinous ligaments showed 89.7% sensitivity versus all controls. Specificity was 95.3% versus those with no fractures, 83.7% versus those with other cervical fractures, and 91.4% versus all controls.
CONCLUSIONS:Increased PAOAAM signal on STIR is a highly sensitive indicator of an acute C1–C2 fracture on MR imaging. Furthermore, increased PAOAAM STIR signal as an isolated finding is highly specific for the presence of a C1–C2 fracture, making it a useful sign on MR imaging when CT is either unavailable or the findings are equivocal.
http://ift.tt/2wNoOnf
Influence of Carotid Siphon Anatomy on Brain Aneurysm Presentation [INTERVENTIONAL]
BACKGROUND AND PURPOSE:
Intracranial aneurysm is a devastating disease of complex etiology that is not fully understood. The purpose of this study was to assess the implications of carotid siphon anatomy for the formation and development of intracranial aneurysms.
MATERIALS AND METHODS:Between January 2007 and May 2015, lateral view digital subtraction angiographic images of 692 consecutive patients with intracranial aneurysms treated in our department of interventional neuroradiology were reviewed and had their angles measured. Data on the location, presentation, and size of the lesions were collected and evaluated by multivariate analysis in relation to the measured angles.
RESULTS:Of 692 aneurysms, 225 (32.51%) ruptured and 467 (67.49%) unruptured, 218 (31.50%) were in the carotid siphon and 474 (68.50%) were distal to the siphon, and the mean aneurysm size was 7.99 ± 6.95 mm. Multivariate analysis showed an association between angles of >15.40° and rupture (P = .005), postsiphon location (P = .034), and aneurysm size of >1.001 mm (P = .015). Multivariate analysis also showed that every 1-year increase in patient age produced an increase of 1.002 mm in aneurysm size (P = .015).
CONCLUSIONS:There was a significant independent direct relation of greater anterior knee angle with intracranial aneurysms located distal to the carotid siphon, larger aneurysms, and greater risk of rupture. These findings may be associated with the hemodynamic interactions of blood flow and the curvature of the carotid siphon.
http://ift.tt/2wNYI3w
How Common Is Signal-Intensity Increase in Optic Nerve Segments on 3D Double Inversion Recovery Sequences in Visually Asymptomatic Patients with Multiple Sclerosis? [HEAD & NECK]
BACKGROUND AND PURPOSE:
In postmortem studies, subclinical optic nerve demyelination is very common in patients with MS but radiologic demonstration is difficult and mainly based on STIR T2WI. Our aim was to evaluate 3D double inversion recovery MR imaging for the detection of subclinical demyelinating lesions within optic nerve segments.
MATERIALS AND METHODS:The signal intensities in 4 different optic nerve segments (ie, retrobulbar, canalicular, prechiasmatic, and chiasm) were evaluated on 3D double inversion recovery MR imaging in 95 patients with MS without visual symptoms within the past 3 years and in 50 patients without optic nerve pathology. We compared the signal intensities with those of the adjacent lateral rectus muscle. The evaluation was performed by a student group and an expert neuroradiologist. Statistical evaluation (the Cohen test) was performed.
RESULTS:On the 3D double inversion recovery sequence, optic nerve segments in the comparison group were all hypointense, and an isointense nerve sheath surrounded the retrobulbar nerve segment. At least 1 optic nerve segment was isointense or hyperintense in 68 patients (72%) in the group with MS on the basis of the results of the expert neuroradiologist. Student raters were able to correctly identify optic nerve hypersignal in 97%.
CONCLUSIONS:A hypersignal in at least 1 optic nerve segment on the 3D double inversion recovery sequence compared with hyposignal in optic nerve segments in the comparison group was very common in visually asymptomatic patients with MS. The signal-intensity rating of optic nerve segments could also be performed by inexperienced student readers.
http://ift.tt/2f9K6BI
Syringomyelia Fluid Dynamics and Cord Motion Revealed by Serendipitous Null Point Artifacts during Cine MRI [SPINE]
SUMMARY:
Dynamic MR imaging was used to evaluate a cervical syrinx in an adolescent boy with an associated hindbrain herniation. Null artifacts were present on one of the sequences that allowed simultaneous high-resolution visualization of syrinx fluid motion and the anatomy of the syrinx walls. A brief review of the theories of syrinx formation and propagation is provided with a comment on why the Williams "slosh" theory of syrinx progression is supported by our unique imaging.
http://ift.tt/2wNWHnV
Value of Thrombus CT Characteristics in Patients with Acute Ischemic Stroke [ADULT BRAIN]
BACKGROUND AND PURPOSE:
Thrombus CT characteristics might be useful for patient selection for intra-arterial treatment. Our objective was to study the association of thrombus CT characteristics with outcome and treatment effect in patients with acute ischemic stroke.
MATERIALS AND METHODS:We included 199 patients for whom thin-section NCCT and CTA within 30 minutes from each other were available in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute ischemic stroke in the Netherlands (MR CLEAN) study. We assessed the following thrombus characteristics: location, distance from ICA terminus to thrombus, length, volume, absolute and relative density on NCCT, and perviousness. Associations of thrombus characteristics with outcome were estimated with univariable and multivariable ordinal logistic regression as an OR for a shift toward better outcome on the mRS. Interaction terms were used to investigate treatment-effect modification by thrombus characteristics.
RESULTS:In univariate analysis, only the distance from the ICA terminus to the thrombus, length of >8 mm, and perviousness were associated with functional outcome. Relative thrombus density on CTA was independently associated with functional outcome with an adjusted common OR of 1.21 per 10% (95% CI, 1.02–1.43; P = .029). There was no treatment-effect modification by any of the thrombus CT characteristics.
CONCLUSIONS:In our study on patients with large-vessel occlusion of the anterior circulation, CT thrombus characteristics appear useful for predicting functional outcome. However, in our study cohort, the effect of intra-arterial treatment was independent of the thrombus CT characteristics. Therefore, no arguments were provided to select patients for intra-arterial treatment using thrombus CT characteristics.
http://ift.tt/2wO3huS
Sigmoid Sinus Diverticulum, Dehiscence, and Venous Sinus Stenosis: Potential Causes of Pulsatile Tinnitus in Patients with Idiopathic Intracranial Hypertension? [HEAD & NECK]
BACKGROUND AND PURPOSE:
Pulsatile tinnitus is experienced by most patients with idiopathic intracranial hypertension. The pathophysiology remains uncertain; however, transverse sinus stenosis and sigmoid sinus diverticulum/dehiscence have been proposed as potential etiologies. We aimed to determine whether the prevalence of transverse sinus stenosis and sigmoid sinus diverticulum/dehiscence was increased in patients with idiopathic intracranial hypertension and pulsatile tinnitus relative to those without pulsatile tinnitus and a control group.
MATERIALS AND METHODS:CT vascular studies of patients with idiopathic intracranial hypertension with pulsatile tinnitus (n = 42), without pulsatile tinnitus (n = 37), and controls (n = 75) were independently reviewed for the presence of severe transverse sinus stenosis and sigmoid sinus diverticulum/dehiscence according to published criteria. The prevalence of transverse sinus stenosis and sigmoid sinus diverticulum/dehiscence in patients with idiopathic intracranial hypertension with pulsatile tinnitus was compared with that in the nonpulsatile tinnitus idiopathic intracranial hypertension group and the control group. Further comparisons included differing degrees of transverse sinus stenosis (50% and 75%), laterality of transverse sinus stenosis/sigmoid sinus diverticulum/dehiscence, and ipsilateral transverse sinus stenosis combined with sigmoid sinus diverticulum/dehiscence.
RESULTS:Severe bilateral transverse sinus stenoses were more frequent in patients with idiopathic intracranial hypertension than in controls (P < .001), but there was no significant association between transverse sinus stenosis and pulsatile tinnitus within the idiopathic intracranial hypertension group. Sigmoid sinus dehiscence (right- or left-sided) was also more common in patients with idiopathic intracranial hypertension compared with controls (P = .01), but there was no significant association with pulsatile tinnitus within the idiopathic intracranial hypertension group.
CONCLUSIONS:While our data corroborate previous studies demonstrating increased prevalence of sigmoid sinus diverticulum/dehiscence and transverse sinus stenosis in idiopathic intracranial hypertension, we did not establish an increased prevalence in patients with idiopathic intracranial hypertension with pulsatile tinnitus compared with those without. It is therefore unlikely that these entities represent a direct structural correlate of pulsatile tinnitus in patients with idiopathic intracranial hypertension.
http://ift.tt/2wNOjVP
Current and Emerging Therapies in Multiple Sclerosis: Implications for the Radiologist, Part 1--Mechanisms, Efficacy, and Safety [ADULT BRAIN]
SUMMARY:
Imaging for the diagnosis and follow-up of patients with suspected or confirmed multiple sclerosis is a common scenario for many general radiologists and subspecialty neuroradiologists. The field of MS therapeutics has rapidly evolved with multiple new agents now being used in routine clinical practice. To provide an informed opinion in discussions concerning newer MS agents, radiologists must have a working understanding of the strengths and limitations of the various novel therapies. The role of imaging in MS has advanced beyond monitoring and surveillance of disease activity to include treatment complications. An understanding of the new generation of MS drugs in conjunction with the key role that MR imaging plays in the detection of disease progression, opportunistic infections, and drug-related adverse events is of vital importance to the radiologist and clinical physician alike. Radiologists are in a unique position to detect many of the described complications well in advance of clinical symptoms. Part 1 of this review outlines recent developments in the treatment of MS and discusses the published clinical data on the efficacy and safety of the currently approved and emerging therapies in this condition as they apply to the radiologist. Part 2 will cover pharmacovigilance and the role the neuroradiologist plays in monitoring patients for signs of opportunistic infection and/or disease progression.
http://ift.tt/2f9LNyQ
New Ultrasound Measurements to Bridge the Gap between Prenatal and Neonatal Brain Growth Assessment [PEDIATRICS]
BACKGROUND AND PURPOSE:
Most ultrasound markers for monitoring brain growth can only be used in either the prenatal or the postnatal period. We investigated whether corpus callosum length and corpus callosum–fastigium length could be used as markers for both prenatal and postnatal brain growth.
MATERIALS AND METHODS:A 3D ultrasound study embedded in the prospective Rotterdam Periconception Cohort was performed at 22, 26 and 32 weeks' gestational age in fetuses with fetal growth restriction, congenital heart defects, and controls. Postnatally, cranial ultrasound was performed at 42 weeks' postmenstrual age. First, reliability was evaluated. Second, associations between prenatal and postnatal corpus callosum and corpus callosum–fastigium length were investigated. Third, we created reference curves and compared corpus callosum and corpus callosum–fastigium length growth trajectories of controls with growth trajectories of fetuses with fetal growth retardation and congenital heart defects.
RESULTS:We included 199 fetuses; 22 with fetal growth retardation, 20 with congenital heart defects, and 157 controls. Reliability of both measurements was excellent (intraclass correlation coefficient ≥ 0.97). Corpus callosum growth trajectories were significantly decreased in fetuses with fetal growth restriction and congenital heart defects (β = –2.295; 95% CI, –3.320–1.270; P < .01; β = –1.267; 95% CI, –0.972–0.562; P < .01, respectively) compared with growth trajectories of controls. Corpus callosum–fastigium growth trajectories were decreased in fetuses with fetal growth restriction (β = –1.295; 95% CI, –2.595–0.003; P = .05).
CONCLUSIONS:Corpus callosum and corpus callosum–fastigium length may serve as reliable markers for monitoring brain growth from the prenatal into the postnatal period. The clinical applicability of these markers was established by the significantly different corpus callosum and corpus callosum–fastigium growth trajectories in fetuses at risk for abnormal brain growth compared with those of controls.
http://ift.tt/2wNrLo3
Current and Emerging Therapies in Multiple Sclerosis: Implications for the Radiologist, Part 2--Surveillance for Treatment Complications and Disease Progression [ADULT BRAIN]
SUMMARY:
An understanding of the new generation of MS drugs in conjunction with the key role MR imaging plays in the detection of disease progression, opportunistic infections, and drug-related adverse effects is of vital importance to the neuroradiologist. Part 1 of this review outlined the current treatment options available for MS and examined the mechanisms of action of the various medications. It also covered specific complications associated with each form of therapy. Part 2, in turn deals with the subject of pharmacovigilance and the optimal frequency of MRI monitoring for each individual patient, depending on his or her unique risk profile. Special attention is given to the diagnosing of progressive multifocal leukoencephalopathy in patients treated with natalizumab as this is a key area in which neuroradiologists can contribute to improved patient outcomes. This article also outlines the aims of treatment and reviews the possibility of "no evidence of disease activity" becoming a treatment goal with the availability of more effective therapies. Potential future areas and technologies including image subtraction, brain volume measurement and advanced imaging techniques such as double inversion recovery are also reviewed. It is anticipated that such advancements in this rapidly developing field will improve the accuracy of monitoring an individual patient's response to treatment.
http://ift.tt/2wNHa7S
Syringohydromyelia in Patients with Chiari I Malformation: A Retrospective Analysis [SPINE]
BACKGROUND AND PURPOSE:
The association of syringohydromyelia with Chiari I malformation has a wide range, between 23% and 80% of cases in the current literature. In our experience, this range might be overestimated compared with our observations in clinical practice. Because there is an impact of Chiari I malformation–associated syringohydromyelia on morbidity and surgical intervention, its diagnosis is critical in this patient population. Identifying related variables on the basis of imaging would also help identify those patients at risk of syrinx formation during their course of disease.
MATERIALS AND METHODS:We performed a retrospective analysis of the MR imaging studies of 108 consecutive cases of Chiari I malformation. A multitude of factors associated with syrinx formation were investigated, including demographic, morphometric, osseous, and dynamic CSF flow evaluation.
RESULTS:Thirty-nine of 108 (36.1%) patients with Chiari I malformation had syringohydromyelia. On the basis of receiver operating characteristic curve analysis, a skull base angle (nasion-sella-basion) of 135° was found to be a statistically significant classifier of patients with Chiari I malformation with or without syringohydromyelia. Craniocervical junction osseous anomalies (OR = 4.3, P = .001) and a skull base angle of >135° (OR = 4.8, P = .0006) were most predictive of syrinx formation. Pediatric patients (younger than 18 years of age) who developed syringohydromyelia were more likely to have associated skull base osseous anomalies than older individuals (P = .01).
CONCLUSIONS:Our findings support evidence of the role of foramen magnum blockage from osseous factors in the development of syringohydromyelia in patients with Chiari I malformation.
http://ift.tt/2wNHXWr
Comparison of Gadoterate Meglumine and Gadobutrol in the MRI Diagnosis of Primary Brain Tumors: A Double-Blind Randomized Controlled Intraindividual Crossover Study (the REMIND Study) [ADULT BRAIN]
BACKGROUND AND PURPOSE:
Effective management of patients with brain tumors depends on accurate detection and characterization of lesions. This study aimed to demonstrate the noninferiority of gadoterate meglumine versus gadobutrol for overall visualization and characterization of primary brain tumors.
MATERIALS AND METHODS:This multicenter, double-blind, randomized, controlled intraindividual, crossover, noninferiority study included 279 patients. Both contrast agents (dose = 0.1 mmol/kg of body weight) were assessed with 2 identical MRIs at a time interval of 2–14 days. The primary end point was overall lesion visualization and characterization, scored independently by 3 off-site readers on a 4-point scale, ranging from "poor" to "excellent." Secondary end points were qualitative assessments (lesion border delineation, internal morphology, degree of contrast enhancement, diagnostic confidence), quantitative measurements (signal intensity), and safety (adverse events). All qualitative assessments were also performed on-site.
RESULTS:For all 3 readers, images of most patients (>90%) were scored good or excellent for overall lesion visualization and characterization with either contrast agent; and the noninferiority of gadoterate meglumine versus gadobutrol was statistically demonstrated. No significant differences were observed between the 2 contrast agents regarding qualitative end points despite quantitative mean lesion percentage enhancement being higher with gadobutrol (P < .001). Diagnostic confidence was high/excellent for all readers in >81% of the patients with both contrast agents. Similar percentages of patients with adverse events related to the contrast agents were observed with gadoterate meglumine (7.8%) and gadobutrol (7.3%), mainly injection site pain.
CONCLUSIONS:The noninferiority of gadoterate meglumine versus gadobutrol for overall visualization and characterization of primary brain tumors was demonstrated.
http://ift.tt/2f9jzEk
Diagnostic Performance of a 10-Minute Gadolinium-Enhanced Brain MRI Protocol Compared with the Standard Clinical Protocol for Detection of Intracranial Enhancing Lesions [ADULT BRAIN]
BACKGROUND AND PURPOSE:
The development of new MR imaging scanners with stronger gradients and improvement in coil technology, allied with emerging fast imaging techniques, has allowed a substantial reduction in MR imaging scan times. Our goal was to develop a 10-minute gadolinium-enhanced brain MR imaging protocol with accelerated sequences and to evaluate its diagnostic performance compared with the standard clinical protocol.
MATERIALS AND METHODS:Fifty-three patients referred for brain MR imaging with contrast were scanned with a 3T scanner. Each MR image consisted of 5 basic fast precontrast sequences plus standard and accelerated versions of the same postcontrast T1WI sequences. Two neuroradiologists assessed the image quality and the final diagnosis for each set of postcontrast sequences and compared their performances.
RESULTS:The acquisition time of the combined accelerated pre- and postcontrast sequences was 10 minutes and 15 seconds; and of the fast postcontrast sequences, 3 minutes and 36 seconds, 46% of the standard sequences. The 10-minute postcontrast axial T1WI had fewer image artifacts (P < .001) and better overall diagnostic quality (P < .001). Although the 10-minute MPRAGE sequence showed a tendency to have more artifacts than the standard sequence (P = .08), the overall diagnostic quality was similar (P = .66). Moreover, there was no statistically significant difference in the diagnostic performance between the protocols. The sensitivity, specificity, and accuracy values for the 10-minute protocol were 100.0%, 88.9%, and 98.1%.
CONCLUSIONS:The 10-minute brain MR imaging protocol with contrast is comparable in diagnostic performance with the standard protocol in an inpatient motion-prone population, with the additional benefits of reducing acquisition times and image artifacts.
http://ift.tt/2wNCsa5
Intracranial Perishunt Catheter Fluid Collections with Edema, a Sign of Shunt Malfunction: Correlation of CT/MRI and Nuclear Medicine Findings [ADULT BRAIN]
SUMMARY:
Fluid collections with edema along the intracranial tract of ventriculoperitoneal shunt catheters in adults are rare and are more frequently seen in children. The imaging appearance of these fluid collections is frequently confusing and presents a diagnostic dilemma. We present 6 cases of adult patients noted to have collections with edema along the tract of ventriculoperitoneal shunt catheters. To our knowledge, there are no previous studies correlating the CT/MR imaging findings with nuclear medicine scans in this entity. We hypothesized that when seen in adults, the imaging findings of a CSF-like fluid collection around the intracranial ventriculoperitoneal shunt catheter on CT/MR imaging may suggest areas of CSF accumulation with interstitial edema. It is important to recognize this rare ventriculoperitoneal shunt complication in adults to prevent misdiagnosis of an abscess or cystic tumor.
http://ift.tt/2wNrRfp
A Cell Culture Model of Resistance Arteries
A cell culture model of resistance arteries is described, allowing for the dissection of signaling pathways in endothelium, smooth muscle, or between endothelium and smooth muscle (the myoendothelial junction). The selective application of agonists or protein isolation, electron microscopy, or immunofluorescence can be utilized using this cell culture model.
http://ift.tt/2wOth8F
Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
Resistance to cancer therapies contributes to disease progression and death. Determining the mechanistic underpinnings of resistance is crucial for improving therapeutic response. This manuscript details the protocol to generate taxane-resistant cell models of prostate cancer (PC) to help dissecting the pathways involved in progression to Docetaxel resistance in PC patients.
http://ift.tt/2weuOBc
Identifying subsets of patients with single-level degenerative disc disease for lumbar fusion: the value of prognostic tests in surgical decision making
Publication date: Available online 7 September 2017
Source:The Spine Journal
Author(s): Victor E. Staartjes, Pieter-Paul A. Vergroesen, Dick J. Zeilstra, Marc L. Schröder
Background ContextFusion surgery for degenerative disc disease (DDD) has become a standard of care, albeit not without controversy. Outcomes are inconsistent and a superiority over conservative treatment is debatable. Proper patient selection is key to clinical success, and a comprehensive understanding of prognostic tests does not currently exist.PurposeTo investigate the value of prognostic tests and sociodemographic factors in predicting outcomes following lumbar fusion surgery for DDD.Study DesignThis is a retrospective analysis of prospectively collected data.Patient SampleWe included patients who underwent fusion surgery for DDD between 2010 and 2016.Outcome MeasuresThe outcome measures included pre- and postoperative Visual Analogue Scale and Oswestry Disability Index scores.Materials and MethodsProspectively collected patient data was reviewed for preoperative tests, perioperative data and clinical outcomes. Prognostic tests used were discography, pantaloon cast test, Modic changes and a summary of physical symptoms, coined "loading factor". By means of multivariate stepwise regression, prognostic factors that were useful in predicting outcomes were identified. VS, PV and DZ declare no potential conflicts of interest. MS is a consultant to Mazor Robotics, Ltd.ResultsA total of 91 patients fit the inclusion criteria, with a mean follow-up of 33±16 months. Discography, Modic changes and loading factor were of no value for predicting outcome scores (p > 0.05). A positive pantaloon cast test predicted improved outcomes in back pain severity, but only in patients without prior surgery (p = 0.02). Demographic factors which showed a consistent reduction in back pain were female sex (p = 0.021) and no prior surgery at index level (p = 0.009). No other sociodemographic factors were of predictive value (p > 0.05).ConclusionsIn patients without prior surgery, the pantaloon cast test appears to be the most promising prognostic tool. Other prognostic selection tools such as discography and Modic changes yield disappointing results. In this study female patients and those without prior spine surgery appear to be most likely to benefit from fusion surgery for DDD.
http://ift.tt/2vTDkKD
A new iPhone® application for measuring active craniocervical range of motion in patients with non-specific neck pain: a reliability and validity study
Publication date: Available online 7 September 2017
Source:The Spine Journal
Author(s): Mohammad Reza Pourahmadi, Rasool Bagheri, Morteza Taghipour, Ismail Ebrahimi Takamjani, Javad Sarrafzadeh, Mohammad Ali Mohseni-Bandpei
Background ContextMeasurement of cervical spine range of motion (ROM) is often considered to be an essential component of cervical spine physiotherapy assessment.PurposeTo investigate the reliability and validity of an iPhone® app (Goniometer Pro©) for measuring active craniocervical ROM (ACCROM) in patients with non-specific neck pain.Study Design/SettingA cross-sectional study was conducted at the musculoskeletal biomechanics laboratory located at Iran University of Medical Sciences.Patient SampleForty non-specific neck pain patients participated in this study.Outcome MeasuresACCROM including flexion, extension, lateral flexion, and rotation.MethodFollowing the recruitment process, ACCROM was measured using a universal goniometer and iPhone® 7 app. Two blinded examiners each utilized the universal goniometer and iPhone® to measure ACCROM in the following sequences: flexion, extension, lateral flexion, and rotation. The second (2 h later) and third (48 h later) sessions were carried out in the same manner as the first session. Intraclass correlation coefficient (ICC) models were used to determine the intra-rater and inter-rater reliability. The Pearson's correlation coefficients were used to establish concurrent validity of the iPhone® app. Minimum detectable change at the 95% confidence level (MDC95) was also computed.ResultsGood intra-rater and inter-rater reliability was demonstrated for the goniometer with ICC values of ≥ 0.66 and ≥ 0.70 and the iPhone® app with ICC values of ≥ 0.62 and ≥ 0.65, respectively. The MDC95 ranged from 2.21° to 12.50° for the intra-rater analysis and from 3.40° to 12.61° for the inter-rater analysis. The concurrent validity between the two instruments was high, with r values of ≥ 0.63. The magnitude of the differences between the UG and iPhone® app values (effect sizes) was small with Cohen's d values of ≤ 0.17.ConclusionsThe iPhone® app possesses good reliability and high validity. It seems that this app can be used for measuring ACCROM.
http://ift.tt/2jaJdwY
Biased numerical cognition impairs economic decision-making in Parkinson's disease
Abstract
Objective
Previous findings suggest a context-dependent bihemispheric allocation of numerical magnitude. Accordingly, we predicted that lateralized motor symptoms in Parkinson's disease (PD), which reflect hemispheric asymmetries, would induce systematic lateralized biases in numerical cognition and have a subsequent influence on decision-making.
Methods
In 20 PD patients and matched healthy controls we assessed numerical cognition using a number-pair bisection and random number generation task. Decision-making was assessed using both the dictator game and a validated questionnaire.
Results
PD patients with predominant right-sided motor symptoms exhibited pathological biases toward smaller numerical magnitudes and formulated less favorable prosocial choices during a neuroeconomics task (i.e., dictator game). Conversely, patients with left-sided motor symptoms exhibited pathological biases toward larger numerical magnitudes and formulated more generous prosocial choices. Our account of context-dependent hemispheric allocation of numerical magnitude in PD was corroborated by applying our data to a pre-existing computational model and observing significant concordance. Notably, both numerical biasing and impaired decision-making were correlated with motor asymmetry.
Interpretation
Accordingly, motor asymmetry and functional impairment of cognitive processes in PD can be functionally intertwined. To conclude, our findings demonstrate context-dependent hemispheric allocation and encoding of numerical magnitude in PD and how biases in numerical magnitude allocation in Parkinsonian patients can correspondingly impair economic decision-making.
http://ift.tt/2vTsnJc
Improved diagnosis of Parkinson's disease from a detailed olfactory phenotype
Abstract
Objective
To assess the predictive potential of the complete response pattern from the University of Pennsylvania Smell Identification Test for the diagnosis of Parkinson's disease.
Methods
We analyzed a large dataset from the Arizona Study of Aging and Neurodegenerative Disorders, a longitudinal clinicopathological study of health and disease in elderly volunteers. Using the complete pattern of responses to all 40 items in each subject's test, we built predictive models of neurodegenerative disease, and we validated these models out of sample by comparing model predictions against postmortem pathological diagnosis.
Results
Consistent with anatomical considerations, we found that the specific test response pattern had additional predictive power compared with a conventional measure – total test score – in Parkinson's disease, but not Alzheimer's disease. We also identified specific test questions that carry the greatest predictive power for disease diagnosis.
Interpretation
Olfactory ability has typically been assessed with either self-report or total score on a multiple choice test. We showed that a more accurate clinical diagnosis can be made using the pattern of responses to all the test questions, and validated this against the "gold standard" of pathological diagnosis. Information in the response pattern also suggests specific modifications to the standard test that may optimize predictive power under the typical clinical constraint of limited time. We recommend that future studies retain the individual item responses for each subject, and not just the total score, both to enable more accurate diagnosis and to enable additional future insights.
http://ift.tt/2jaJ9xe
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
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Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
