The emergence and spread of drug-resistant strains of Mycobacterium tuberculosis is worsening the global threat of tuberculosis (TB). There is a need and urgency for the development of new treatments for TB, for the management of drug resistant TB (MDR-TB) and for improved regimens against drug-susceptible TB, with the goal of reducing toxicity and length of therapy that will boost patience compliance. The paucity of new drugs is a major obstacle to design new regimens while host-directed therapies (HDTs) are emerging as a promising area of research and are opening new avenues to fight TB. In this review, we discuss examples of potentially promising strategies aimed at improving the host response to M. tuberculosis, and argue how a better understanding of TB pathogenesis, with the fine characterization of the immunological mediators involved, may pave the way for the design of new therapies, the identification of new drugs or the repurposing of some already in use for other diseases. We emphasize that any HDTs shall be included as adjunct therapy to the drug-combination regimens already in use for TB, with the goal to reduce tissue damage and immunopathology and enhance bacterial clearance. We anticipate that the benefits of HDTs against TB will be highest against MDR-TB, where the activity of current regimens is poor and the cost high.
Chemotherapy 2018;63:172–180
https://ift.tt/2LyfJ5X
Πέμπτη 19 Ιουλίου 2018
Host Directed Therapies for Tuberculosis: Futures Strategies for an Ancient Disease
Survival Analysis and Interpretation of Time-to-Event Data: The Tortoise and the Hare
https://ift.tt/2LxwRsq
Occult Gallbladder Carcinoma Presenting as a Primary Ovarian Tumour: a Case Report and Review of Literature
Abstract
The ovary is a common site of metastasis from various organs. However, little is known about gallbladder carcinoma metastasising to the ovaries and presenting as a primary ovarian tumour. We report a case of a metastatic gallbladder carcinoma which mimicked a primary ovarian tumour in a 31-year-old woman who presented with menstrual symptoms and an ovarian mass without obvious signs and symptoms related to gallbladder carcinoma. Postoperatively histopathological examination diagnosed primary ovarian germ cell tumour for further chemotherapy. However, postoperative re-evaluation with radiology suggested the possibility of a primary gallbladder carcinoma. Exact diagnosis could only be made after repeat histopathological evaluation of the ovarian mass.
https://ift.tt/2zVRixW
Nephron Sparing Surgery for Synchronous Bilateral Wilms—Operative Steps
Abstract
Approximately 5% of children with Wilms tumor present with bilateral disease. The treatment challenge is to achieve a high cure rate while maintaining adequate long-term renal function. We report the feasibility and outcome of nephron sparing surgery in a child with bilateral Wilms tumor who was treated at our institution.
https://ift.tt/2uNS7TS
Margin Status and Duration of Surgery in Resection of Tongue Carcinoma with Ultrasound Coagulation Device: a Comparative Study
Abstract
Tongue is one of the most common subsites involved by oral cancer. Improved surgical care and adjuvant therapy, along with better rehabilitation has significantly improved long-term survival and quality of life in patients with oral cancer. Primary surgical treatment is the preferred modality of treatment in cancers of the oral tongue. Although the surgical techniques have remained unchanged, various devices have been used to aid primary tumour resection, with a view to reduce bleeding and scarring. The purpose of this study is to compare resection of oral tongue tumours using ultrasonic coagulation device with conventional electrodiathermy. This study was conducted to compare histological margins and duration of surgery between ultrasonic coagulation device and electrodiathermy in the resection of oral tongue tumours. A retrospective analysis was performed comprising patients undergoing wide excision for squamous cell carcinoma of the lateral tongue, with either ultrasonic coagulation device or conventional electrodiathermy at Our Institute in Mumbai, India, from October 2015 to December 2016. Single factor ANOVA with the level of significance set at 95% and alpha value of 0.05. Patients who underwent excision with ultrasonic coagulation device better histologically tumour-free margins (except posterior margin) (p values—anterior margin, posterior margin, lateral margin and deep margin 0.0045, 0.59, 0.011 and 0.00013 respectively) and lesser operative time when compared with conventional electrodiathermy. Ultrasonic coagulation device was effective in providing adequate oncologically safe margins in carcinoma tongue.
https://ift.tt/2mu3Bbh
The Role of Canonical Wnt Signaling in Regulating Radioresistance.
 | Related Articles |
The Role of Canonical Wnt Signaling in Regulating Radioresistance.
Cell Physiol Biochem. 2018 Jul 18;48(2):419-432
Authors: Zhao Y, Tao L, Yi J, Song H, Chen L
Abstract
Radioresistance is a major obstacle in radiotherapy for cancer, and strategies are needed to overcome this problem. Currently, radiotherapy combined with targeted therapy such as inhibitors of phosphoinosotide 3-kinase/Akt and epidermal growth factor receptor signaling have become the focus of studies on radiosensitization. Apart from these two signaling pathways, which promote radioresistance, deregulation of Wnt signaling is also associated with the radioresistance of multiple cancers. Wnts, as important messengers in the tumor microenvironment, are involved in cancer progression mainly via canonical Wnt signaling. Their role in promoting DNA damage repair and inhibiting apoptosis facilitates cancer resistance to radiation. Thus, it seems reasonable to target Wnt signaling as a method for overcoming radioresistance. Many small-molecule inhibitors that target the Wnt signaling pathway have been identified and shown to promote radiosensitization. Therefore, a Wnt signaling inhibitor may help to overcome radioresistance in cancer therapy.
PMID: 30021193 [PubMed - as supplied by publisher]
https://ift.tt/2zRDq7R
Naturally produced type I IFNs enhance human myeloid dendritic cell maturation and IL-12p70 production and mediate elevated effector functions in innate and adaptive immune cells.
 | Related Articles |
Naturally produced type I IFNs enhance human myeloid dendritic cell maturation and IL-12p70 production and mediate elevated effector functions in innate and adaptive immune cells.
Cancer Immunol Immunother. 2018 Jul 13;:
Authors: Sköld AE, Mathan TSM, van Beek JJP, Flórez-Grau G, van den Beukel MD, Sittig SP, Wimmers F, Bakdash G, Schreibelt G, de Vries IJM
Abstract
There has recently been a paradigm shift in the field of dendritic cell (DC)-based immunotherapy, where several clinical studies have confirmed the feasibility and advantageousness of using directly isolated human blood-derived DCs over in vitro differentiated subsets. There are two major DC subsets found in blood; plasmacytoid DCs (pDCs) and myeloid DCs (mDCs), and both have been tested clinically. CD1c+ mDCs are highly efficient antigen-presenting cells that have the ability to secrete IL-12p70, while pDCs are professional IFN-α-secreting cells that are shown to induce innate immune responses in melanoma patients. Hence, combining mDCs and pDCs poses as an attractive, multi-functional vaccine approach. However, type I IFNs have been reported to inhibit IL-12p70 production and mDC-induced T-cell activation. In this study, we investigate the effect of IFN-α on mDC maturation and function. We demonstrate that both recombinant IFN-α and activated pDCs strongly enhance mDC maturation and increase IL-12p70 production. Co-cultured mDCs and pDCs additionally have beneficial effect on NK and NKT-cell activation and also enhances IFN-γ production by allogeneic T cells. In contrast, the presence of type I IFNs reduces the proliferative T-cell response. The mere presence of a small fraction of activated pDCs is sufficient for these effects and the required ratio between the subsets is non-stringent. Taken together, these results support the usage of mDCs and pDCs combined into one immunotherapeutic vaccine with broad immunostimulatory features.
PMID: 30019146 [PubMed - as supplied by publisher]
https://ift.tt/2JANnWU
Therapeutic Prospects of Extracellular Vesicles in Cancer Treatment.
 | Related Articles |
Therapeutic Prospects of Extracellular Vesicles in Cancer Treatment.
Front Immunol. 2018;9:1534
Authors: Chulpanova DS, Kitaeva KV, James V, Rizvanov AA, Solovyeva VV
Abstract
Extracellular vesicles (EVs) are released by all cells within the tumor microenvironment, such as endothelial cells, tumor-associated fibroblasts, pericytes, and immune system cells. The EVs carry the cargo of parental cells formed of proteins and nucleic acids, which can convey cell-to-cell communication influencing the maintenance and spread of the malignant neoplasm, for example, promoting angiogenesis, tumor cell invasion, and immune escape. However, EVs can also suppress tumor progression, either by the direct influence of the protein and nucleic acid cargo of the EVs or via antigen presentation to immune cells as tumor-derived EVs carry on their surface some of the same antigens as the donor cells. Moreover, dendritic cell-derived EVs carry major histocompatibility complex class I and class II/peptide complexes and are able to prime other immune system cell types and activate an antitumor immune response. Given the relative longevity of vesicles within the circulation and their ability to cross blood-brain barriers, modification of these unique organelles offers the potential to create new biological-tools for cancer therapy. This review examines how modification of the EV cargo has the potential to target specific tumor mechanisms responsible for tumor formation and progression to develop new therapeutic strategies and to increase the efficacy of antitumor therapies.
PMID: 30018618 [PubMed]
https://ift.tt/2mtPxi3
Diagnostic performance of 18 F-PSMA-1007 PET/CT in patients with biochemical recurrent prostate cancer
Abstract
Purpose
The introduction of ligands targeting prostate-specific membrane antigen (PSMA), especially 68Ga-PSMA-11, has changed the management of patients with prostate cancer (PCa). 18F-Labelled ligands can be produced in larger amounts and therefore can improve availability for a larger group of patients. The aim of this study was to evaluate the diagnostic performance of the recently introduced 18F-PSMA-1007 in patients with recurrent PCa.
Methods
This retrospective analysis included 100 consecutive patients with biochemical relapse (mean age 68.75 ± 7.6 years) referred for PSMA PET/CT. Whole-body PET/CT imaging (from the lower limbs to the skull) was performed in all patients 120 min after injection of 338 ± 44.31 MBq 18F-PSMA-1007. Prostatectomy, radiation beam therapy of the prostate bed and androgen-deprivation therapy had been performed in 92%, 45% and 27% of the patients, respectively. Radiation beam therapy of the prostate bed had been performed in addition to surgery in 38 patients (38%) and 10 patients (10%) had received all three therapy modalities. The probability of a 18F-PSMA-1007 PET/CT scan suggestive of pathology was compared with the Gleason score (GS) and PSA level.
Results
Of the 100 patients, 95 (95%) showed at least one pathological finding on 18F-PSMA-1007 PET/CT. The overall median PSA level was 1.34 ng/ml (range 0,04–41.3 ng/ml). The rates of pathological scans were 86%, 89%, 100% and 100% among patients with PSA levels ≤0.5, 0.51–1.0, 1.1–2.0 and > 2.0 ng/ml, respectively. The median GS was 7 (range 5–10). The majority of patients (70) with a GS available had a score in the range 7–9. The rate of pathological scans in these patients was 93% (65/70). The median SUVmax values of the pathological findings were 10.25, 14.32, 13.16 and 28.87 in patients with PSA levels ≤0.5, 0.51–1.0, 1.1–2.0 and >2.0 ng/ml, respectively. The median SUVmax in patients with a PSA level of >2.0 ng/ml was significantly higher than in all other PSA groups.
Conclusion
18F-PSMA-1007 PET/CT can detect recurrent PCa in a high percentage of patients with biochemical relapse. The probability of a pathological 18F-PSMA-1007 PET/CT scan seems to be high even in patients with a low PSA level ≤0.5 ng/ml, and this may have a significant impact on the management of this relevant group of patients.
https://ift.tt/2mur6AY
Effect of CYP2C19 and CYP2D6 genotype on tamoxifen treatment outcome indicates endogenous and exogenous interplay
Pharmacogenomics, Ahead of Print.
https://ift.tt/2L8guqr
Association of ABCC2 polymorphism and gender with high-density lipoprotein cholesterol response to simvastatin
Pharmacogenomics, Ahead of Print.
https://ift.tt/2Luy1oJ
Issue Information
Cancer Cytopathology, Volume 126, Issue 7, Page 437-442, July 2018.
https://ift.tt/2LxaV0y
A Patient Rallies, and a Field Awakens
Cancer Cytopathology, Volume 126, Issue 7, Page 443-444, July 2018.
https://ift.tt/2uzYr1U
Family dynamics in transthyretin‐related familial amyloid polyneuropathy Val30Met: does genetic risk affect family functioning?
Clinical Genetics, Volume 0, Issue ja, -Not available-.
https://ift.tt/2LbEPLZ
Novel SUZ12 mutations in Weaver‐like syndrome
Clinical Genetics, Volume 0, Issue ja, -Not available-.
https://ift.tt/2LvAZcp
A novel homozygous frame‐shift variant in the LHCGR gene is associated with primary ovarian insufficiency in a Pakistani family
Clinical Genetics, EarlyView.
https://ift.tt/2L7jyCZ
The power of the Mediator complex ‐ expanding the genetic architecture and phenotypic spectrum of MED12‐related disorders
Clinical Genetics, Volume 0, Issue ja, -Not available-.
https://ift.tt/2LvATS5
Dual Antibacterial and Anticancer Activity of 4-Benzoyl-1-dichlorobenzoylthiosemicarbazide Derivatives
Objective/Method: A group of 4-benzoyl-1-dichlorobenzoylthiosemicarbazides endowed with antibacterial activity was evaluated for its cytotoxic properties against breast cancer cells (MCF-7, MDA-MB-231) and head and neck squamous cell carcinomas (FaDu, SCC-25). Cytotoxicity of the investigated compounds was measured using MTT and [3H]-thymidine incorporation bioassays.
Result: 1-(2,3-Dichlorobenzoyl)-4-(2-methylbenzoyl)thiosemicarbazide (TA-4), 1-(2,4-dichlorobenzoyl)- 4-(2-methylbenzoyl)thiosemicarbazide (TA-18), and 1-(2,4-dichlorobenzoyl)-4-(4-nitrolbenzoyl)- thiosemicarbazide (TA-20) were found to possess anticancer activity equipotent or even stronger than that of reference drug – etoposide. In order to clarify the molecular mode of action of the mentioned compounds, the relaxation assay kit for human DNA topoisomerase II was used. It turned out that reduction of viability of cancer cells was a result of inhibition of human DNA topoII. Molecular docking studies proved that 4-benzoyl-1-dichlorobenzoylthiosemicarbazides strongly interact with DNAdependent subunit of that enzyme.
https://ift.tt/2L9dGJu
Pelvic Exenteration Put into Therapeutical and Palliative Perspective: It Is Worth to Try
Abstract
Pelvic exenteration (PE) is one of the most drastic operations in surgical oncology, associated with severe morbidity and mortality. The objective of our study was to review our experience of PE in terms of surgical characteristics, complications, and overall survival. All patients who had PE surgery between January 1999 and December 2015 were identified. Patients with verified distant metastatic disease were excluded. Patients with advanced pelvic tumors experiencing incapacitating postradiation severe damages were included. The following parameters were recorded: age, sex, indication for surgery, tumor histology, type of exenteration, urinary tract and colon reconstruction methods, operative time, blood transfusion, intensive care unit admissions, length of hospital stay and readmissions, and characteristics of perioperative morbidity and mortality. A total of 25 patients were submitted to PE by our surgical team. Most of the patients suffered from cervical cancer followed by bowel cancer. There was no perioperative mortality. Early postoperative complications ensued in 56% of the patients. Most complications involved the urinary system. Five years survival was estimated at 38%. Most patients (n = 9, 36%) died due to their primary disease, 5 (20%) died because of complications following operation, and 2 (8%) died because they denied oral feeding, which was associated with depression. Patients with a variety of malignancies can benefit from PE. Meticulous surgical technique, perioperative care, counseling, and nutritional support play an important role.
https://ift.tt/2JCJ6m3
An accelerated nonlocal Poisson‐Boltzmann equation solver for electrostatics of biomolecule
International Journal for Numerical Methods in Biomedical Engineering, Volume 0, Issue ja, -Not available-.
https://ift.tt/2mtkHWH
Correlation of flow complexity parameter with aneurysm rupture status
International Journal for Numerical Methods in Biomedical Engineering, Volume 0, Issue ja, -Not available-.
https://ift.tt/2A0PAM2
Cover
Clinical Oral Implants Research, Volume 29, Issue 7, Page i-i, July 2018.
https://ift.tt/2uPz0IP
Intra‐ and inter‐examiner agreement when assessing radiographic implant bone levels: Differences related to brightness, accuracy, participant demographics and implant characteristics
Clinical Oral Implants Research, Volume 29, Issue 7, Page 756-771, July 2018.
https://ift.tt/2mtDstd
Peri‐implant tissue healing at implants with different designs and placement protocols: An experimental study in dogs
Clinical Oral Implants Research, EarlyView.
https://ift.tt/2uPms4n
Do we have to consider acidosis induced by exercise as deleterious in sickle cell disease?
Experimental Physiology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Lur5YJ
Nicotinamide riboside supplementation dysregulates redox and energy metabolism in rats: Implications for exercise performance
Experimental Physiology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2uwDyon
Essential preanalytics in PD‐L1 immunocytochemistry
Histopathology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Lym3ui
Pathological features of total gastrectomy specimens from asymptomatic hereditary diffuse gastric cancer patients and implications for clinical management
Histopathology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2LccvJm
Characteristic morphological changes in anti‐VEGF therapy induced glomerular microangiopathy
Histopathology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2LuYRgq
A morphological and molecular study of proposed early forms of the traditional serrated adenoma
Histopathology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2L89fyL
Morphology and tumor‐infiltrating lymphocytes in high‐stage, high‐grade serous ovarian carcinoma correlated with long‐term survival
Histopathology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2JEtWN0
Prognostic value of H3S10 phosphorylation and H4K12 acetylation in oral squamous cell carcinoma
Histopathology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2L6xfCd
A rare case of a solitary fibrous tumour of bone showing NAB2–STAT6 exon 3–exon 19 fusion
Histopathology, EarlyView.
https://ift.tt/2LBMvDu
Impact of Breast Cancer Grade Discordance on Prediction of Outcome
Histopathology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2JDaAaU
MYB Rearrangement and Immunohistochemical Expression in Adenomyoepithelioma of the Breast: A Comparison with Adenoid Cystic Carcinoma
Histopathology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2LadNEM
Concordance of PD‐L1 expression in matched urothelial bladder cancer specimens
Histopathology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2JDdbSi
Isocitrate Dehydrogenase 1 (IDH1) Mutations in Melanoma Frequently Co‐Occur with NRAS Mutations
Histopathology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Lcur6w
Predicting complications in hepatic resection for colorectal liver metastasis: the lymphocyte‐to‐monocyte ratio
ANZ Journal of Surgery, EarlyView.
https://ift.tt/2L6gQxH
Influence of dentine debris and organic tissue on the properties of sodium hypochlorite solutions
International Endodontic Journal, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Lx1uhK
Incidence and outcome of Guillain‐Barré syndrome in Iceland: A population‐based study
Acta Neurologica Scandinavica, EarlyView.
https://ift.tt/2zQni6C
Effects of ball milling treatment on physicochemical properties and digestibility of Pacific oyster (Crassostrea gigas) protein powder
Food Science &Nutrition, EarlyView.
https://ift.tt/2LuWWse
Incidence and farmers’ knowledge of aflatoxin contamination and control in Eastern Democratic Republic of Congo
Food Science &Nutrition, EarlyView.
https://ift.tt/2LceuNX
Salmonella spp. and Campylobacter spp. in poultry feces and carcasses in Ouagadougou, Burkina Faso
Food Science &Nutrition, EarlyView.
https://ift.tt/2JCdLQp
Pasting alters glycemic index, antioxidant activities, and starch‐hydrolyzing enzyme inhibitory properties of whole wheat flour
Food Science &Nutrition, EarlyView.
https://ift.tt/2L6tSv3
Polyunsaturated fatty acids, inflammation, and metabolic syndrome in South Asian Americans in Maryland
Food Science &Nutrition, EarlyView.
https://ift.tt/2JA6eBz
Natural extracts from fresh and oven‐dried winemaking by‐products as valuable source of antioxidant compounds
Food Science &Nutrition, EarlyView.
https://ift.tt/2Lb6Hzy
Utilization of potato peel as eco‐friendly products: A review
Food Science &Nutrition, EarlyView.
https://ift.tt/2LvBzHb
Issue Information
Cognitive Science, Volume 42, Issue 5, Page 1407-1409, July 2018.
https://ift.tt/2L6tNHL
“Girls Are as Good as Boys at Math” Implies That Boys Are Probably Better: A Study of Expressions of Gender Equality
Cognitive Science, July 2018.
https://ift.tt/2JD8UhC
Translating the ICAP Theory of Cognitive Engagement Into Practice
Cognitive Science, July 2018.
https://ift.tt/2Lb6ufK
Surgical resection of ripple onset predicts outcome in pediatric epilepsy
Annals of Neurology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2L9dslr
Age‐related changes in the gut microbiota influence systemic inflammation and stroke outcome
Annals of Neurology, EarlyView.
https://ift.tt/2JCbXa5
The Charcot Marie Tooth Health Index: Evaluation of a Patient Reported Outcome
Annals of Neurology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2LaOfqX
Women in Neurology: A WIN‐Win
Annals of Neurology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2JAcQzS
Multi‐crossover randomized controlled trial designs in Alzheimer's disease
Annals of Neurology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2L6subP
Long‐range genomic regulators of THBS1 and LTBP4 modify disease severity in Duchenne muscular dystrophy
Annals of Neurology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2JAcIjS
CHCHD10 variants in Amyotrophic Lateral Sclerosis: Where is the evidence?
Annals of Neurology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2LcqKha
Neurofilament light: A candidate biomarker of pre‐symptomatic ALS and phenoconversion
Annals of Neurology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2LxMnoh
The natural history of Vanishing White Matter
Annals of Neurology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Lc8YuA
Clinical validation of blood/brain glutamate grabbing in acute ischemic stroke
Annals of Neurology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2JII5cc
Spreading depolarizations trigger caveolin‐1‐dependent endothelial transcytosis
Annals of Neurology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2L8CdP0
Cerebellar atrophy and its contribution to cognition in frontotemporal dementias
Annals of Neurology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2LuhjWx
Sustainable method for Alzheimer's prediction in Mild Cognitive Impairment: EEG connectivity and graph theory combined with ApoE
Annals of Neurology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Laaz48
A novel autoantibody against plexin D1 in patients with neuropathic pain
Annals of Neurology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2JElcpY
BRAF mutation leading to central nervous system Rosai‐Dorfman disease
Annals of Neurology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2L94IMk
Effect of BDNFVal66Met on disease markers in dominantly inherited AD
Annals of Neurology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Luh9hT
Pathogenicity of human antibodies against myelin oligodendrocyte glycoprotein
Annals of Neurology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2LblcDw
Structural signature of SCA3: from presymptomatic to late disease stages
Annals of Neurology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2JDXpqk
Sub‐cellular origin of mtDNA deletions in human skeletal muscle
Annals of Neurology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Laayx6
Haploinsufficiency of CUX1 causes non‐syndromic global developmental delay with possible catch‐up development
Annals of Neurology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2JCtkaK
Same-Day Appointment System Implemented in Health Network
THURSDAY, July 19, 2018 -- A same-day appointment system can feasibly be introduced, according to the experiences of one health network presented in an article published in Managed Healthcare Executive. Kenyokee Crowell, the senior vice president of...
https://ift.tt/2LudqnW
FDA Recalls Drugs Containing Active Ingredient Valsartan
THURSDAY, July 19, 2018 -- Several drug products containing the active ingredient valsartan, used to treat high blood pressure and heart failure, are being recalled due to an impurity, N-nitrosodimethylamine, that has been found in the recalled...
https://ift.tt/2JCtbEb
Atopic Dermatitis Places Heavy Burden on Patients
THURSDAY, July 19, 2018 -- Atopic dermatitis (AD) dramatically impacts the quality of life of patients, according to a study published online July 16 in the Annals of Allergy, Asthma & Immunology. Jonathan I. Silverberg, M.D., Ph.D., from...
https://ift.tt/2LmImpX
Liver Disease-Related Deaths Up Sharply From 1999 to 2016
THURSDAY, July 19, 2018 -- Liver disease-related deaths, particularly due to cirrhosis, have been increasing in the United States since 2009, according to a study published online July 18 in The BMJ. Elliot B Tapper, M.D., and Neehar D Parikh, M.D.,...
https://ift.tt/2uSbaMW
Salmonella Outbreak in 26 States Linked to Raw Turkey Products
THURSDAY, July 19, 2018 -- A Salmonella outbreak that has sickened 90 people in 26 states has been linked to a variety of raw turkey products, the U.S. Centers for Disease Control and Prevention says. Illnesses in this outbreak began between Nov....
https://ift.tt/2Loztfu
Development of psoriasis by continual neutrophil infiltration into the epidermis
Experimental Dermatology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2uLq7Ac
Rapamycin ameliorates psoriasis by regulating the expression and methylation levels of Tropomyosin via ERK1/2 and mTOR pathways in vitro and in vivo
Experimental Dermatology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2mtw9Sd
Noninvasive analysis and minimally invasive in vivo experimental challenges of the skin barrier
Experimental Dermatology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2zR8Dby
Murine type VII collagen distorts outcome in human skin graft mouse model for dystrophic epidermolysis bullosa
Experimental Dermatology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2mtXQdy
Assessing the skin barrier via corneocyte morphometry
Experimental Dermatology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2uLq1sk
Maintenance of tight junction barrier integrity in cell turnover and skin diseases
Experimental Dermatology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2mu3WuH
Likelihood Ratios for the Emergency Physician
Academic Emergency Medicine, EarlyView.
https://ift.tt/2zRu2RV
Pushing Hard: The Mandate to Improve Care of Pediatric Cardiopulmonary Arrest
Academic Emergency Medicine, Volume 0, Issue ja, -Not available-.
https://ift.tt/2mteZnJ
LOw dose MAGnesium sulfate versus HIgh dose in the early management of rapid atrial fibrillation: randomised controlled double blind study
Academic Emergency Medicine, Volume 0, Issue ja, -Not available-.
https://ift.tt/2uPlNA5
Referring Hospital Characteristics Associated with Potentially Avoidable Emergency Department Transfers
Academic Emergency Medicine, Volume 0, Issue ja, -Not available-.
https://ift.tt/2mwv1xo
Priorities to overcome barriers impacting data science application in emergency care research
Academic Emergency Medicine, Volume 0, Issue ja, -Not available-.
https://ift.tt/2uQXHEQ
Injury‐Based Geographic Access to Trauma Centers
Academic Emergency Medicine, Volume 0, Issue ja, -Not available-.
https://ift.tt/2mu7yg8
A Systematic Review and Meta‐analysis of Ketamine as an Alternative to Opioids for Acute Pain in the Emergency Department
Academic Emergency Medicine, EarlyView.
https://ift.tt/2uPsj9H
Response to:Reliability of HEARTSMAP as a tool for evaluating psychosocial assessment documentation practices in emergency departments for pediatric mental health complaints: a methodological issue
Academic Emergency Medicine, Volume 0, Issue ja, -Not available-.
https://ift.tt/2msW2Bz
Reliability of HEARTSMAP as a tool for evaluating psychosocial assessment documentation practices in emergency departments for pediatric mental health complaints: A methodological issue
Academic Emergency Medicine, Volume 0, Issue ja, -Not available-.
https://ift.tt/2A1pGaC
Malt1 self‐cleavage is critical for regulatory T cell homeostasis and anti‐tumor immunity in mice
European Journal of Immunology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2LqteYD
Natural T‐cell ligands that are created by genetic variants can be transferred between cells by extracellular vesicles
European Journal of Immunology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2uScm2S
Dimethyl fumarate‐induced IL‐17lowIFN‐γlowIL‐4+ Th cells protect mice from severe encephalomyelitis
European Journal of Immunology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2LtqOZ8
IFN‐γ stimulates CpG‐induced IL‐10 production in B cells via p38 and JNK signalling pathways
European Journal of Immunology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2JCCwMn
Carbon Nanolayer‐Coated Na3V2(PO4)3 Nanocrystals Embedded in Conductive Carbon Matrix as High‐Performance Cathode for Sodium‐Ion Batteries
Advanced Materials, July 2018.
https://ift.tt/2NqFrtN
Scanning Nanowelding Lithography for Rewritable One‐Step Patterning of Sub‐50 nm High‐Aspect‐Ratio Metal Nanostructures
Advanced Materials, EarlyView.
https://ift.tt/2O3vnI5
Performance Improvements in Conjugated Polymer Devices by Removal of Water‐Induced Traps
Advanced Materials, EarlyView.
https://ift.tt/2NpKJ8E
Palladium‐Catalyzed Carbonylative Cyclization of Terminal Alkynes and Anilines to 3‐Substituted Maleimides
Advanced Materials, July 2018.
https://ift.tt/2L85Xvp
Nacre‐Inspired Graphene/Metal Hybrid by In Situ Cementation Reaction and Joule Heating
Advanced Materials, July 2018.
https://ift.tt/2L98oOe
MoS2–Carbon Nanotube Porous 3 D Network for Enhanced Oxygen Reduction Reaction
Advanced Materials, July 2018.
https://ift.tt/2JCscUv
Highly Nitrogen‐Doped Porous Carbon Derived from Zeolitic Imidazolate Framework‐8 for CO2 Capture
Advanced Materials, July 2018.
https://ift.tt/2L7PLKq
Strong Graphene 3D Assemblies with High Elastic Recovery and Hardness
Advanced Materials, EarlyView.
https://ift.tt/2O5o6rl
Strong, Conductive, Foldable Graphene Sheets by Sequential Ionic and π Bridging
Advanced Materials, EarlyView.
https://ift.tt/2JCs6w7
Active Materials for Organic Electrochemical Transistors
Advanced Materials, EarlyView.
https://ift.tt/2O0ZFLI
Recent Progress in High‐Mobility Organic Transistors: A Reality Check
Advanced Materials, EarlyView.
https://ift.tt/2NvoPRA
Hierarchically Porous Fe2CoSe4 Binary‐Metal Selenide for Extraordinary Rate Performance and Durable Anode of Sodium‐Ion Batteries
Advanced Materials, EarlyView.
https://ift.tt/2LcckOl
Mechanically Robust Atomic Oxygen‐Resistant Coatings Capable of Autonomously Healing Damage in Low Earth Orbit Space Environment
Advanced Materials, EarlyView.
https://ift.tt/2LBFuCE
High‐Mobility Helical Tellurium Field‐Effect Transistors Enabled by Transfer‐Free, Low‐Temperature Direct Growth
Advanced Materials, EarlyView.
https://ift.tt/2L7bGkV
A Novel Top‐Down Synthesis of Ultrathin 2D Boron Nanosheets for Multimodal Imaging‐Guided Cancer Therapy
Advanced Materials, EarlyView.
https://ift.tt/2JCrQ07
Iron Vacancies Induced Bifunctionality in Ultrathin Feroxyhyte Nanosheets for Overall Water Splitting
Advanced Materials, EarlyView.
https://ift.tt/2L9Gfq3
Resonance‐Enhanced Absorption in Hollow Nanoshell Spheres with Omnidirectional Detection and High Responsivity and Speed
Advanced Materials, EarlyView.
https://ift.tt/2JD7eEW
Low‐Temperature Heteroepitaxy of 2D PbI2/Graphene for Large‐Area Flexible Photodetectors
Advanced Materials, July 2018.
https://ift.tt/2L6aM8p
Polyphenolic‐Chemistry‐Enabled, Mechanically Robust, Flame Resistant and Superhydrophobic Membrane for Separation of Mixed Surfactant‐Stabilized Emulsions
Advanced Materials, July 2018.
https://ift.tt/2JCAEDl
The long non‐coding RNA n339260 promotes vasculogenic mimicry and cancer stem cell development in hepatocellular carcinoma
Cancer Science, Volume 0, Issue ja, -Not available-.
https://ift.tt/2LaK9iz
Pancreas‐sparing, ampulla‐preserving duodenectomy for major duodenal (D1–D2) perforations
BJS, EarlyView.
https://ift.tt/2msqpYO
Effect of aspirin in vascular surgery in patients from a randomized clinical trial (POISE‐2)
BJS, EarlyView.
https://ift.tt/2zV84NN
Profile of exhaled‐breath volatile organic compounds to diagnose pancreatic cancer
BJS, EarlyView.
https://ift.tt/2mwdSUt
Outcomes of pancreas retransplantation in patients with pancreas graft failure
BJS, EarlyView.
https://ift.tt/2A1o8NQ
Multicentre international trial of laparoscopic lavage for Hinchey III acute diverticulitis (LLO Study)
BJS, EarlyView.
https://ift.tt/2zUHjZH
Network meta‐analysis of surgical management of gastro‐oesophageal reflux disease in adults
BJS, EarlyView.
https://ift.tt/2mtvtML
Meta‐analysis of the prognostic role of perioperative platelet count in posthepatectomy liver failure and mortality
BJS, EarlyView.
https://ift.tt/2mwdOUJ
Outcomes of patients receiving a massive transfusion for major trauma
BJS, EarlyView.
https://ift.tt/2uPt56z
Survival and risk of breast cancer recurrence after breast reconstruction with deep inferior epigastric perforator flap
BJS, EarlyView.
https://ift.tt/2mu8jpq
Meta‐analysis of prognostic factors for overall survival in patients with resected hilar cholangiocarcinoma
BJS, EarlyView.
https://ift.tt/2muNha7
A curcumin analog, GO‐Y078, overcomes resistance to tumor angiogenesis inhibitors
Cancer Science, Volume 0, Issue ja, -Not available-.
https://ift.tt/2L91EQk
Altered editing level of microRNAs is a potential biomarker in lung adenocarcinoma
Cancer Science, Volume 0, Issue ja, -Not available-.
https://ift.tt/2JCZJxL
A 5‐day regimen of azacitidine for lower‐risk myelodysplastic syndromes (RA or RARS): a prospective single‐arm phase 2 trial
Cancer Science, Volume 0, Issue ja, -Not available-.
https://ift.tt/2LtZF59
Heterogeneity of tumor lymphangiogenesis: progress and prospects
Cancer Science, Volume 0, Issue ja, -Not available-.
https://ift.tt/2LbzGTZ
Exosomal zinc transporter ZIP4 promotes cancer growth and is a novel diagnostic biomarker for pancreatic cancer
Cancer Science, Volume 0, Issue ja, -Not available-.
https://ift.tt/2LyyLt3
Cost‐effectiveness of aprepitant in Japanese patients treated with cisplatin‐containing highly emetogenic chemotherapy
Cancer Science, Volume 0, Issue ja, -Not available-.
https://ift.tt/2LbfgKK
Application of Multifunctional Nanomaterials in Radioprotection of Healthy Tissues
Advanced Healthcare Materials, EarlyView.
https://ift.tt/2uP7Im3
Recent Advances in Tracking the Transplanted Stem Cells Using Near‐Infrared Fluorescent Nanoprobes: Turning from the First to the Second Near‐Infrared Window
Advanced Healthcare Materials, EarlyView.
https://ift.tt/2Lm8rFE
Nanocatalyst Complex Can Dephosphorylate Key Proteins in MAPK Pathway for Cancer Therapy
Advanced Healthcare Materials, EarlyView.
https://ift.tt/2uP7ECP
Recent Progress in Isolation and Detection of Extracellular Vesicles for Cancer Diagnostics
Advanced Healthcare Materials, EarlyView.
https://ift.tt/2LqwCmq
Addressing Unmet Clinical Needs with 3D Printing Technologies
Advanced Healthcare Materials, EarlyView.
https://ift.tt/2JCfc1d
Acceleration of Diabetic Wound Regeneration using an In Situ–Formed Stem‐Cell‐Based Skin Substitute
Advanced Healthcare Materials, EarlyView.
https://ift.tt/2LiARR1
“Smart” Nanoprobes for Visualization of Tumor Microenvironments
Advanced Healthcare Materials, EarlyView.
https://ift.tt/2uPnzRw
Tunable Enzymatically Cross‐Linked Silk Fibroin Tubular Conduits for Guided Tissue Regeneration
Advanced Healthcare Materials, EarlyView.
https://ift.tt/2Llhir1
Paroxysmal motor disorders: expanding phenotypes lead to coalescing genotypes
Annals of Clinical and Translational Neurology, EarlyView.
https://ift.tt/2JD4V4A
Primary resistance of human patients to botulinum neurotoxins A and B
Annals of Clinical and Translational Neurology, EarlyView.
https://ift.tt/2LjQN5v
Reply to: Comment on: Zika virus and Guillain–Barré syndrome in Bangladesh
Annals of Clinical and Translational Neurology, EarlyView.
https://ift.tt/2JD4CqC
Comment on: Zika virus and Guillain–Barré syndrome in Bangladesh
Annals of Clinical and Translational Neurology, EarlyView.
https://ift.tt/2LqrpuL
Issue Information
Annals of Clinical and Translational Neurology, Volume 5, Issue 7, Page 785-787, July 2018.
https://ift.tt/2uKnTAU
Corrigendum
Annals of Clinical and Translational Neurology, Volume 5, Issue 7, Page 895-895, July 2018.
https://ift.tt/2Lua1pa
Emergency department neuroimaging for epileptic seizures
Epilepsia, EarlyView.
https://ift.tt/2uPD23U
Genome‐wide association study: Exploring the genetic basis for responsiveness to ketogenic dietary therapies for drug‐resistant epilepsy
Epilepsia, EarlyView.
https://ift.tt/2LpNsBC
A PRRT2 variant in a Chinese family with paroxysmal kinesigenic dyskinesia and benign familial infantile seizures results in loss of interaction with STX1B
Epilepsia, EarlyView.
https://ift.tt/2uWyTLZ
Seizure duration and latency of hypermotor manifestations distinguish frontal from extrafrontal onset in sleep‐related hypermotor epilepsy
Epilepsia, EarlyView.
https://ift.tt/2LtpEge
Altered circadian rhythms and oscillation of clock genes and sirtuin 1 in a model of sudden unexpected death in epilepsy
Epilepsia, EarlyView.
https://ift.tt/2uKnyhC
Unilateral temporal interictal epileptiform discharges correctly predict the epileptogenic zone in lesional temporal lobe epilepsy
Epilepsia, EarlyView.
https://ift.tt/2Lnmefg
FENS‐Kavli winter symposium: review and perspectives on neurological diseases
European Journal of Neuroscience, Volume 0, Issue ja, -Not available-.
https://ift.tt/2mt8txh
Similar effect of intermittent theta burst and sham stimulation on corticospinal excitability: a 5‐day repeated sessions study
European Journal of Neuroscience, Volume 0, Issue ja, -Not available-.
https://ift.tt/2zV04fF
Macaque parvocellular mediodorsal thalamus: dissociable contributions to learning and adaptive decision‐making
European Journal of Neuroscience, Volume 0, Issue ja, -Not available-.
https://ift.tt/2mt8qS7
Repurposing an established drug: an emerging role for methylene blue in L‐DOPA‐induced dyskinesia
European Journal of Neuroscience, Volume 0, Issue ja, -Not available-.
https://ift.tt/2uLfvBn
A review of plasticity induced by auditory and visual tetanic stimulation in humans
European Journal of Neuroscience, Volume 0, Issue ja, -Not available-.
https://ift.tt/2mtsqUJ
Temporal information in tones, broadband noise and natural vocalizations is conveyed by differential spiking responses in the Superior Paraolivary Nucleus
European Journal of Neuroscience, Volume 0, Issue ja, -Not available-.
https://ift.tt/2uLfpcZ
Changes of motor corticobulbar projections following different lesion types affecting the central nervous system in adult macaque monkeys
European Journal of Neuroscience, Volume 0, Issue ja, -Not available-.
https://ift.tt/2mvNw55
Auditory motion does not modulate spiking activity in the middle temporal and medial superior temporal visual areas
European Journal of Neuroscience, Volume 0, Issue ja, -Not available-.
https://ift.tt/2uPYNRp
zolpidem ameliorates motor impairments in the unilaterally 6‐hydroxydopamine‐lesioned rat
European Journal of Neuroscience, Volume 0, Issue ja, -Not available-.
https://ift.tt/2mwQV3y
In Vitro Characterisation of Intrinsic Properties and Local Synaptic Inputs to Pyramidal Neurons in Macaque Primary Motor Cortex
European Journal of Neuroscience, Volume 0, Issue ja, -Not available-.
https://ift.tt/2zWrwd6
Mapping of Fine Scale Rat Prefrontal Cortex Connections: Evidence for Detailed Ordering of Inputs and Outputs Connecting the Temporal Cortex and Sensory‐Motor Regions
European Journal of Neuroscience, Volume 0, Issue ja, -Not available-.
https://ift.tt/2mx2oA4
Neural mechanisms of sensorimotor transformation and action selection
European Journal of Neuroscience, Volume 0, Issue ja, -Not available-.
https://ift.tt/2uLf2z7
The β‐adrenoceptor blocker propranolol ameliorates compulsive‐like gambling behaviour in a rodent slot machine task: implications for iatrogenic gambling disorder
European Journal of Neuroscience, Volume 0, Issue ja, -Not available-.
https://ift.tt/2mszalP
Issue Information
European Journal of Neuroscience, Volume 48, Issue 1, Page i-iii, July 2018.
https://ift.tt/2uLeU2B
Resection of the Inferior Vena Cava for Retroperitoneal Sarcoma: Six Cases and a Review of Literature
Abstract
Resection of the inferior vena cava (IVC) for malignancy is a technically demanding procedure. We present a series of six cases of resection of the IVC for retroperitoneal sarcomas, four of which were primary caval tumors. We outline the technical difficulties faced in these complex procedures and discuss the oncological outcomes of these rare tumors. We performed a retrospective review of six patients operated for retroperitoneal masses involving the inferior vena cava between April 2015 and July 2016 at our tertiary care institute. Six patients underwent resection of the IVC, three of which required a multivisceral resection. An artificial prosthesis was used to reconstruct the IVC in three patients, whereas two patients underwent primary repair of the vein wall. One patient did not require any reconstruction. Margins were microscopically positive in two out of six patients. All patients received radiotherapy, either in the neo-adjuvant or adjuvant setting. Two patients developed local recurrences with a median follow-up of 24.5 months. Resection of the IVC for extirpation of retroperitoneal sarcomas is a technically complex and difficult procedure. The availability of a multidisciplinary team of surgeons and state-of-the-art intensive care support is essential for good outcomes.
https://ift.tt/2mxPvWd
Computerized feedback during colonoscopy training leads to improved performance: a randomized trial
Simulation-based training in colonoscopy is increasingly replacing the traditional apprenticeship method to avoid patient-related risk. Mentoring during simulation is necessary to provide feedback and to motivate, but expert supervisors are a scarce resource. We aimed to determine whether computerized feedback in simulated colonoscopy would improve performance, optimize time spent practicing, and optimize the pattern of training.
https://ift.tt/2uwjsdV
Tethered capsule endomicroscopy for unsedated microscopic imaging of the esophagus, stomach, and duodenum in humans (with video)
Patients with many different digestive diseases undergo repeated esophagogastroduodenoscopy throughout their life. Tethered capsule endomicroscopy (TCE) is a less invasive method for obtaining high-resolution images of the gastrointestinal mucosa for diagnosis and treatment planning of diseases. In this paper, we present our results from a single center, aimed at testing the safety and the feasibility of TCE for imaging the esophagus, stomach, and duodenum.
https://ift.tt/2uASzFM
Impact of fellow training level on adverse events and operative time for common pediatric GI endoscopic procedures
Previous studies on pediatric endoscopic training have not examined if adverse events (AEs) are affected by the fellow's training level in detail. We aimed to determine whether trainee presence and educational level increases AEs or operative time (OT) for pediatric intestinal endoscopy.
https://ift.tt/2LxXwFI
Single Nucleotide Polymorphisms in TAOK3 Are Associated with High Opioid Requirement for Pain Management in Patients with Advanced Cancer Admitted to a Tertiary Palliative Care Unit
Different amounts of opioid are required for the relief of cancer pain in different individuals, raising the possibility that genetic factors play a role. We tested the hypothesis that genetic variations in the TAOK3 (TAO kinase 3, encoding serine/threonine-protein kinase) explain some of the inter-individual variations related to the morphine equivalent daily dose (MEDD) in cancer patients.
https://ift.tt/2muupbh
MRI Phenotype of RELA -fused Pediatric Supratentorial Ependymoma
Abstract
Purpose
Epigenetic profiling has recently identified clinically and molecularly distinct subgroups of ependymoma. The 2016 World Health Organization (WHO) classification recognized supratentorial ependymomas (ST-EPN) with REL-associated protein/p65 (RELA) fusion as a clinicopathological entity. These tumors represent 70% of pediatric ST-EPN characterized by recurrent C11orf95-RELA fusion transcripts, which lead to pathological activation of the nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NF-κB) signaling pathway. Cyclin-dependent kinase inhibitor 2A (CDKN2A) inactivation has also been reported to correlate with poor prognosis. Here, we systematically describe magnetic resonance imaging (MRI) characteristics of RELA-fused ST-EPN, with respect to CDKN2A deletion status.
Methods
Our cohort of patients with ST-EPN (n = 57) was obtained from the database of the German Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy (DGNN), and tumors were diagnosed according to the 2016 WHO classification. Molecular characterization identified 47 RELA-fused tumors. We analyzed the preoperative MRI according to standardized criteria, and comparison was performed between CDKN2A altered (n = 21) and CDKN2A wild type (n = 26) tumors.
Results
The RELA-fused ST-EPN showed a spectrum of predominantly hemispheric tumors with cysts and necrosis. Statistical analysis on CDKN2A status revealed significant differences in terms of younger manifestation age (p =0.002) and more intratumoral hemorrhage in T2-weighted imaging (T2WI) (p =0.010) in wild type tumors; however, the location was not a parameter for differentiation.
Conclusion
This study first provides comprehensive MRI data for RELA-fused ST-EPN as a distinct entity, with further interest on CDKN2A genomic status. Patient stratification by morphological MRI alone seems difficult at present. The results may support ongoing research in ST-EPN within the framework of the radiogenomics concept.
https://ift.tt/2JzDxVn
First-Generation and Second-Generation Bruton Tyrosine Kinase Inhibitors in Waldenström Macroglobulinemia
Waldenström macroglobulinemia (WM) is an indolent B-cell lymphoma that is heavily dependent on Bruton tyrosine kinase (BTK) hyperactivation. Ibrutinib is a first-generation BTK inhibitor that has shown high activity and durable responses in patients with relapsed/refractory WM. Newer and more selective BTK inhibitors are currently being tested in several clinical trials and are expected to address the toxicity and the acquired resistance observed in patients receiving ibrutinib. Updates on ibrutinib and second-generation BTK inhibitors are summarized in this review.
https://ift.tt/2uID6CG
Novel Approaches in Waldenström Macroglobulinemia
Recent advances in the understanding of Waldenström macroglobulinemia (WM) biology have paved the way for development of a plethora of novel therapeutic strategies. The success of ibrutinib in WM has shifted treatment paradigms away from conventional chemoimmunotherapy approaches. Recognition of high-risk genomic subgroups as well as mechanisms of acquired resistance to ibrutinib have led to targeting of additional pathways. In this article, the authors review ongoing and emerging trials of novel therapies in WM that target the B-cell receptor pathway beyond ibrutinib, toll-like receptor pathway, chemokine signaling, apoptotic pathway, chromatin remodeling, protein transport, the immune microenvironment, and CD19-directed immunotherapy.
https://ift.tt/2mwmA5a
P66. Long term follow-up in bilateral deep brain stimulation of VIM in MS-related tremor
Tremor in Multiple Sclerosis is an important cause for disability. As medical treatment often does not provide a sufficient reduction of tremor amplitude, deep brain stimulation is an important option in these patients. Because in previous studies often unilateral stimulation of the VIM was performed, the aim of our retrospective analysis was to evaluate the effect of bilateral stimulation on tremor amplitude, activities of daily living, and due to an additional effect on axial tremor, improvement of global disability (EDSS) and mobility.
https://ift.tt/2LidxTt
Characteristics of Severe Hypoglycemia Identified in T2DM
THURSDAY, July 19, 2018 -- For patients with type 2 diabetes, characteristics of those with severe hypoglycemia include having a prior diagnosis of non-severe hypoglycemia and hemoglobin A1c (HbA1c) <6 percent, according to a study published in...
https://ift.tt/2LzYqlf
Link for Asbestos-Free Talcum Powder, Cancer Not Clear
THURSDAY, July 19, 2018 -- Talcum powder, made from talc, which contains asbestos is considered carcinogenic to humans, while the carcinogenicity of talc without asbestos is unclear, according to the American Cancer Society. Talcum powder is widely...
https://ift.tt/2JzsMCh
Both High and Low Uric Acid Levels Tied to Higher Mortality
THURSDAY, July 12, 2018 -- Both high and low uric acid levels are associated with an increased risk of dying, according to a study published in the July issue of Arthritis & Rheumatology. Sung Kweon Cho, M.D., Ph.D., from Sungkyunkwan University...
https://ift.tt/2L7PdV4
Patients Care About the Clothes Doctors Wear
THURSDAY, July 19, 2018 -- Patients do in fact care what doctors wear, according to a study recently published in BMJ Open. Christopher M. Petrilli, M.D., from the VA Ann Arbor Healthcare System in Michigan, and colleagues conducted a survey among a...
https://ift.tt/2L8iS0i
Variations in Practice Patterns Seen in Patients Treated for COPD
THURSDAY, July 19, 2018 -- There are significant variations in practice patterns and resource utilization in patients treated by teaching staff for acute exacerbations of chronic obstructive pulmonary disease (AECOPD), compared to non-teaching...
https://ift.tt/2JEkkBN
Ten Questions Screen Helps ID Disability in HIV+ Children
THURSDAY, July 19, 2018 -- The Ten Questions (TQ) screen is an effective way to screen HIV-positive children for neurodevelopmental problems in resource-poor areas, according to a study published online July 3 in PLOS ONE. Justin Knox, M.P.H., from...
https://ift.tt/2LwKlVr
L-Glutamine Reduces Number of Pain Crises in Sickle Cell Disease
THURSDAY, July 19, 2018 -- For patients with sickle cell-related pain, those receiving oral therapy with L-glutamine have a lower median number of pain crises, according to a study published in the July 19 issue of the New England Journal of...
https://ift.tt/2L8iNd0
Hand-Holding, Stress Ball Don't Cut Anxiety in Skin CA Removal
THURSDAY, July 19, 2018 -- Hand-holding and squeezing a stress ball do not provide anxiety reduction among patients during excisional removal of non-melanoma skin cancer, according to a study published online July 18 in JAMA Dermatology. Arianna F....
https://ift.tt/2L8iLBU
Do site and type of metastasis in breast cancer show a changing pattern with increased age? A cross comparison of clinicopathological characteristics between age groups
Abstract
Background
In here, we evaluated pattern of metastasis and cross-compared clinicopathological features between different age groups with breast cancer (BC).
Methods
This study was conducted in the Shiraz Breast Cancer Registry (largest BC registry in Iran). Patients were classified as < 30 years old (group 1), 30–60 years old (group 2), and > 60 years old (group 3). The three age groups were compared regarding clinical and baseline characteristics.
Results
Overall, 564 individuals entered group 1, 4519 group 2, and 670 group 3.
Group 1 had lower rates of tumor necrosis (p < 0.001), higher lymphatic or vascular invasion (p = 0.002), estrogen receptor-negative individuals, and HER2-positive individuals (p ≤ 0.001).
Younger groups had more stage 3 BC (31.1, 25.6, and 19.7% for groups 1, 2, and 3, respectively) (p = 0.016), grade 3 BC (27.4, 20.6, and 16.5% for groups 1, 2, and 3, respectively) (p = 0.001), and grade 3 nucleus (43.1, 34.5, and 27.6% for groups 1, 2, and 3, respectively) (p < 0.001).
Group 1 had higher rates of regional metastasis (4.7 vs. 1.5 and 2.1% for groups 2 and 3, respectively). Younger individuals had higher rates of brain metastasis (13.3, 5.4, and 1.1% for groups 1, 2, and 3, respectively). Moreover, those > 60 years old had more lung metastasis (33 vs. 12.6 and 6.7% for groups 2 and 1, respectively) (p < 0.001).
Younger groups had more < 5-year recurrence (16.3, 11.7, and 8.9%, for groups 1, 2, and 3, respectively) (p = 0.023).
Conclusion
Pattern and site of recurrence changes according to age in BC. This brings up the question whether age is an independent predictor of organ of metastasis or is site of metastasis the result of other clinicopathological determinants which differ between age groups.
https://ift.tt/2LpZ8o7
The efficiency of electronic list-based multidisciplinary team meetings in management of gastrointestinal malignancy: a single-center experience in Southern China
Abstract
Background
The multidisciplinary team (MDT) discussion has earned increasing popularity for the delivery of cancer care. However, MDT meeting (MDTM) is time and resource intensive, and some efforts to optimize discussion processes are required. This study aims to investigate the efficiency of electronic list-based MDTM in treatment of gastrointestinal (GI) malignancy.
Methods
Between January 2015 and December 2016, patients with GI cancers were retrospectively reviewed. Patients permitting an MDTM with our novel technique (eMDT group) were compared with those undergoing a traditional discussion (cMDT group). The efficiency of MDT working, including time cost per meeting or case and overall number of reviewed cases, was checked, with accuracy of clinical staging and other outcomes explored meanwhile.
Results
Three thousand six hundred seventy-four patients were included, with 2156 (58.7%) and 1518 (41.3%) cases for eMDT and cMDT groups, respectively. Comparisons in age (P = 0.529), gender (P = 0.844), cancer type (P = 0.218), treatment plan (P = 0.737), and pathological stage (P = 0.098) were not significant between groups. However, the average time cost in both each meeting (149.4 vs. 205.1 min; P < 0.001) and each case (3.1 vs. 6.2 min; P < 0.001) was markedly reduced. Besides, this novel technique was associated with improved accuracy of clinical staging (P = 0.070) and reduced hospital stay (P < 0.001) compared with the traditional approach, with similar incidence of complications observed (P = 0.243).
Conclusions
The MDT working based on an intelligent checklist could save considerable time while not affecting treatment of GI malignancies. The improved efficiency also earns an increased capacity of hospital admission and in-patient care.
https://ift.tt/2JDrAxT
GD2 ganglioside-binding antibody 14G2a and specific aurora A kinase inhibitor MK-5108 induce autophagy in IMR-32 neuroblastoma cells
Abstract
The process of autophagy and its role in survival of human neuroblastoma cell cultures was studied upon addition of an anti-GD2 ganglioside (GD2) 14G2a mouse monoclonal antibody (14G2a mAb) and an aurora A kinase specific inhibitor, MK-5108. It was recently shown that combination of these agents significantly potentiates cytotoxicity against IMR-32 and CHP-134 neuroblastoma cells in vitro, as compared to the inhibitor used alone. In this study we gained mechanistic insights on autophagy in the observed cytotoxic effects exerted by both agents using cytotoxicity assays, RT-qPCR, immunoblotting, and autophagy detection methods. Enhancement of the autophagy process in the 14G2a mAb- and MK-5108-treated IMR-32 cells was documented by assessing autophagic flux. Application of a lysosomotropic agent—chloroquine (CQ) affected the 14G2a mAb- and MK-5108-stimulated autophagic flux. It is our conclusion that the 14G2a mAb (40 μg/ml) and MK-5108 inhibitor (0.1 μM) induce autophagy in IMR-32 cells. Moreover, the combinatorial treatment of IMR-32 cells with the 14G2a mAb and CQ significantly potentiates cytotoxic effect, as compared to CQ used alone. Most importantly, we showed that interfering with autophagy at its early and late step augments the 14G2a mAb-induced apoptosis, therefore we can conclude that inhibition of autophagy is the primary mechanism of the CQ-mediated sensitization to the 14G2a mAb-induced apoptosis. Although, there was no virtual stimulation of autophagy in the 14G2a mAb-treated CHP-134 neuroblastoma cells, we were able to show that PHLDA1 protein positively regulates autophagy and this process exists in a mutually exclusive manner with apoptosis in PHLDA1-silenced CHP-134 cells.
https://ift.tt/2LmKhuM
Association of Genetic Variants in NF-kB with Susceptibility to Breast Cancer: a Case Control Study
Abstract
Insofar as altered NF-κB signaling stemming from the presence of specific genetic variants in NF-κB gene contribute to cancer pathogenesis, this study evaluated the association between NF-κB rs147574894/I552V, rs148626207/M860T rs3774937 and rs1598859 variants and breast cancer and associated features and complications. This was a retrospective case-control study, which involved 207 women with breast cancer, and 214 cancer-free women who served as controls. NF-κB genotyping was done by real-time PCR. Significantly higher rs3774937 minor allele frequencies (MAF), and lower rs147574894 MAF were seen among breast cancer patients, thereby imparting disease susceptibility and protective nature to these variants, respectively. Significant association of rs3774937 and rs147574894 genotypes with breast cancer was seen under the dominant model. Histological type and grade, molecular type, Her2 positivity and ER+/Her2- correlated positively, while distant metastasis negatively correlated with rs3774937. On the other hand, rs147574894 negatively correlated with histological type and grade, tumor size, Her2 positivity, molecular type, and ER+/Her2-, while rs148626207 correlated positively with histological grade, but negatively with distant metastasis and triple-negative status. Breast cancer-susceptible and –protective 4-locus haplotypes were also identified. This is the first report that addresses the contribution of NF-κB variants to the pathogenesis of breast cancer in Middle Eastern-North African population, and the first to document positive association of rs3774937 with breast cancer.
https://ift.tt/2Nq1VLt
Lab-Scale Model to Evaluate Odor and Gas Concentrations Emitted by Deep Bedded Pack Manure
A protocol has been developed to measure gases, odors, and nutrient composition in lab-scaled bedded manure packs, which can be used to study ways to improve air quality in commercial cattle facilities using deep-bedded manure packs.
https://ift.tt/2zTv0Ns
Microglia control the spread of neurotropic virus infection via P2Y12 signalling and recruit monocytes through P2Y12-independent mechanisms
Abstract
Neurotropic herpesviruses can establish lifelong infection in humans and contribute to severe diseases including encephalitis and neurodegeneration. However, the mechanisms through which the brain's immune system recognizes and controls viral infections propagating across synaptically linked neuronal circuits have remained unclear. Using a well-established model of alphaherpesvirus infection that reaches the brain exclusively via retrograde transsynaptic spread from the periphery, and in vivo two-photon imaging combined with high resolution microscopy, we show that microglia are recruited to and isolate infected neurons within hours. Selective elimination of microglia results in a marked increase in the spread of infection and egress of viral particles into the brain parenchyma, which are associated with diverse neurological symptoms. Microglia recruitment and clearance of infected cells require cell-autonomous P2Y12 signalling in microglia, triggered by nucleotides released from affected neurons. In turn, we identify microglia as key contributors to monocyte recruitment into the inflamed brain, which process is largely independent of P2Y12. P2Y12-positive microglia are also recruited to infected neurons in the human brain during viral encephalitis and both microglial responses and leukocyte numbers correlate with the severity of infection. Thus, our data identify a key role for microglial P2Y12 in defence against neurotropic viruses, whilst P2Y12-independent actions of microglia may contribute to neuroinflammation by facilitating monocyte recruitment to the sites of infection.
https://ift.tt/2A0DVfQ
Surgical Techniques for Catheter Placement and 5/6 Nephrectomy in Murine Models of Peritoneal Dialysis
This article shows the method for the surgical placement in mice of an intraperitoneal catheter attached to an access port that is positioned at the back of the animal. Moreover, it explains the procedure for a 5/6 nephrectomy to resemble the uremic state of PD patients.
https://ift.tt/2uJvPSY
Targeting USP7 identifies a metastasis-competent state within bone marrow-resident melanoma CTCs
Systemic metastasis is the major cause of death from melanoma, the most lethal form of skin cancer. Although most melanoma patients exhibit a substantial gap between onset of primary and metastatic tumors, signaling mechanisms implicated in the period of metastatic latency remain unclear. We hypothesized that melanoma circulating tumor cells (CTCs) home to and reside in the bone marrow (BM) during the asymptomatic phase of disease progression. Using a strategy to deplete normal cell lineages (Lin-neg), we isolated CTC-enriched cell populations from blood of metastatic melanoma patients, verified by the presence of putative CTCs characterized by melanoma-specific biomarkers and upregulated gene transcripts involved in cell survival and pro-development functions. Implantation of Lin-neg population in NSG mice (CTC-derived xenografts, i.e. CDXs), and subsequent transcriptomic analysis of ex vivo bone marrow-resident tumor cells (BMRTC) vs. CTC identified protein ubiquitination as a significant regulatory pathway of BMRTC signaling. Selective inhibition of USP7, a key deubiquinating enzyme, arrested BMRTC in BM locales and decreased systemic micro-metastasis. This study provides first time evidence that the asymptomatic progression of metastatic melanoma can be recapitulated in vivo using patient-isolated CTC. Furthermore, these results suggest that USP7 inhibitors warrant further investigation as a strategy to prevent progression to overt clinical metastasis.
https://ift.tt/2zR0X8Z
Oncogenic BRAFV600E governs regulatory T cell recruitment during melanoma tumorigenesis
Regulatory T cells (Tregs) are critical mediators of immune suppression in established tumors, although little is known about their role in restraining immune surveillance during tumorigenesis. Here we employ an inducible autochthonous model of melanoma to investigate the earliest Treg and CD8 effector T cell responses during oncogene-driven tumorigenesis. Induction of oncogenic BRAFV600E and loss of Pten in melanocytes led to localized accumulation of FoxP3+ Tregs, but not CD8 T cells, within 1 week of detectable increases in melanocyte differentiation antigen expression. Melanoma tumorigenesis elicited early expansion of shared tumor/self antigen-specific, thymically derived Tregs in draining lymph nodes and induced their subsequent recruitment to sites of tumorigenesis in the skin. Lymph node egress of tumor-activated Tregs was required for their C-C chemokine receptor 4 (Ccr4)-dependent homing to nascent tumor sites. Notably, BRAFV600E signaling controlled expression of Ccr4-cognate chemokines and governed recruitment of Tregs to tumor-induced skin sites. BRAFV600E expression alone in melanocytes resulted in nevus formation and associated Treg recruitment, indicating that BRAFV600E signaling is sufficient to recruit Tregs. Treg depletion liberated immunosurveillance, evidenced by CD8 T cell responses against the tumor/self-antigen gp100, which was concurrent with the formation of microscopic neoplasia. These studies establish a novel role for BRAFV600E as a tumor cell-intrinsic mediator of immune evasion and underscore the critical early role of Treg-mediated suppression during autochthonous tumorigenesis.
https://ift.tt/2msEPID
Identification of Metastatic Lymph Nodes in MR Imaging with Faster Region-based Convolutional Neural Network
Magnetic resonance imaging (MRI) is the gold standard for confirming a pelvic lymph node metastasis diagnosis. Traditionally, medical radiologists have analyzed MRI image features of regional lymph nodes to make diagnostic decisions based on their subjective experience; this diagnosis lacks objectivity and accuracy. This study trained a faster region-based convolutional neural network (Faster R-CNN) with 28,080 MRI images of lymph node metastasis, allowing the Faster R-CNN to read those images and to make diagnoses. For clinical verification, 414 cases of rectal cancer at various medical centers were collected, and Faster R-CNN-based diagnoses were compared with imaging expert diagnoses using receiver operating characteristic curves (ROCs). The area under the Faster R-CNN ROC was 0.912, indicating a more effective and objective diagnosis. The Faster R-CNN diagnosis time was 20 s/case, which was much shorter than the average time (600 s/case) of the imaging expert diagnoses.
https://ift.tt/2uI8tNI
Matrix stiffening and EGFR cooperate to promote the collective invasion of cancer cells.
In squamous cell carcinoma (SCC), tissue invasion by collectively invading cells requires physical forces applied by tumor cells on their surrounding extracellular matrix (ECM). Cancer-related ECM is composed of thick collagen bundles organized by carcinoma-associated fibroblasts (CAF) within the tumor stroma. Here we show that SCC cell collective invasion is driven by the matrix-dependent mechano-sensitization of EGF signaling in cancer cells. Calcium (Ca2+) was a potent intracellular second messenger that drove acto-myosin contractility. Tumor-derived matrix stiffness and EGFR signaling triggered increased intracellular Ca2+ through CaV1.1 expression in SCC cells. Blocking L-type calcium channel expression or activity using Ca2+ channel blockers verapamil and diltiazem reduced SCC cell collective invasion both in vitro and in vivo. These results identify verapamil and diltiazem, two drugs long used in medical care, as novel therapeutic strategies to block the tumor-promoting activity of the tumor niche.
https://ift.tt/2mt2BUI
The MDM2/MDMX-p53 antagonist PM2 radiosensitizes wild-type p53 tumors
Radiotherapy amplifies p53 expression in cancer cells with wild-type (wt) p53. Blocking the negative regulators MDM2 and MDMX stabilizes p53 and may therefore potentiate radiotherapy outcomes. In this study, we investigate the efficacy of the novel anti-MDM2/X stapled peptide PM2 alone and in combination with external gamma radiation in vitro and in vivo. PM2 therapy combined with radiotherapy elicited synergistic therapeutic effects compared to monotherapy in cells with wt p53 in both in vitro and in vivo assays, whereas these effects did not manifest in p53 -/- cells. Biodistribution and autoradiography of 125I-PM2 revealed high and retained uptake homogenously distributed throughout the tumor. In mice carrying wt p53 tumors, PM2 combined with radiotherapy significantly prolonged the median survival by 50%, whereas effects of PM2 therapy on mutant and p53 -/- tumors were negligible. PM2-dependent stabilization of p53 was confirmed with ex vivo immunohistochemistry. These data demonstrate the potential of the stapled peptide PM2 as a radiotherapy potentiator in vivo and suggest that clinical application of PM2 with radiotherapy in wt p53 cancers might improve tumor control.
https://ift.tt/2zUumPN
A rare missense variant in TCF7L2 associates with colorectal cancer risk by interacting with a GWAS-identified regulatory variant in the MYC enhancer
Genome-wide association studies (GWAS) of colorectal cancer (CRC) have identified several common susceptible variants in gene regulatory regions. However, low-frequency or rare coding risk variants have not been systematically investigated in CRC patients from Chinese populations. In this study, we performed an exome-wide association analysis with 1,062 CRC patients and 2,184 controls from a Chinese population. Promising associations were further replicated in two replication sets: replication stage I with 2,478 cases and 3,880 controls, and replication stage II with 3,761 cases and 4,058 controls. We identified two variants significantly associated with CRC risk: a novel rare missense variant in TCF7L2 (rs138649767, OR = 2.08, 95% CI: 1.69-2.57, P = 5.66×10-12) and a previous European GWAS-identified 3'-UTR variant in ATF1 (rs11169571, OR = 1.18, 95% CI: 1.13-1.24, P = 1.65×10-12). We found a significant interaction between the TCF7L2 missense variant rs138649767 and a previous GWAS-identified regulatory variant rs6983267 in the MYC enhancer (Pinteraction = 0.0002). Functional analysis of this variant revealed that TCF7L2 with rs138649767-A allele harbored the ability to activate the MYC enhancer with rs6983267-G allele and enhance CRC cell proliferation. Additionally, the ATF1 rs11169571 variant significantly correlated with ATF1 expression by affecting hsa-miR-1283 and hsa-miR-520d-5p binding. Further ChIP-seq and gene co-expression analyses showed that oncogenes NRAS and BRAF were activated by ATF1 in CRC. These results widen our understanding of the molecular basis of CRC risk and provide insight into pathways that might be targeted to prevent CRC.
https://ift.tt/2mt99D1
Oligosaccharyltransferase Inhibition Overcomes Therapeutic Resistance to EGFR Tyrosine Kinase Inhibitors
Asparagine (N)-linked glycosylation is a post-translational modification essential for the function of complex transmembrane proteins. However, targeting glycosylation for cancer therapy has not been feasible due to generalized effects on all glycoproteins. Here we perform sensitivity screening of 94 lung cancer cell lines using NGI-1, a small molecule inhibitor of the oligosaccharyltransferase (OST) that partially disrupts N-linked glycosylation, and demonstrate a selective loss of tumor cell viability. This screen revealed NGI-1 sensitivity in just 11/94 (12%) cell lines, with a significant correlation between OST and EGFR inhibitors. In EGFR mutant NSCLC with EGFR TKI resistance (PC9-GR, HCC827-GR, and H1975-OR), OST inhibition maintained its ability to induce cell cycle arrest and a proliferative block. Addition of NGI-1 to EGFR TKI treatment was synthetic lethal in cells resistant to gefitinib, erlotinib, or osimertinib. OST inhibition invariably disrupted EGFR N- linked glycosylation and reduced activation of receptors either with or without the T790M TKI resistance mutation. OST inhibition also dissociated EGFR signaling from other co-expressed receptors like MET via altered receptor compartmentalization. Translation of this approach to preclinical models was accomplished through synthesis and delivery of NGI-1 nanoparticles, confirmation of in vivo activity through molecular imaging, and demonstration of significant tumor growth delay in TKI resistant HCC827 and H1975 xenografts. This therapeutic strategy breaks from kinase-targeted approaches and validates N-linked glycosylation as an effective target in tumors driven by glycoprotein signaling.
https://ift.tt/2zR0yDv
Targeting CCR8 induces protective antitumor immunity and enhances vaccine-induced responses in colon cancer
CCR8 is a chemokine receptor expressed principally on regulatory T cells (Tregs) and is known to be critical for CCR8+ Treg-mediated immunosuppression. Recent studies have demonstrated that CCR8 is uniquely upregulated in human tumor-resident Tregs of breast, colon, and lung cancer patients when compared to normal tissue-resident Tregs. Therefore, CCR8+ tumor-resident Tregs are rational targets for cancer immunotherapy. Here we demonstrate that monoclonal antibody (mAb) therapy targeting CCR8 significantly suppresses tumor growth and improves long-term survival in colorectal tumor mouse models. This antitumor activity correlated with increased tumor-specific T cells, enhanced infiltration of CD4+ and CD8+ T cells, and a significant decrease in the frequency of tumor-resident CD4+CCR8+ Tregs. Tumor-specific CD8+ T cells displayed lower expression of exhaustion markers as well as increased functionality upon restimulation. Treatment with anti-CCR8 mAb prevented de novo induction and suppressive function of Tregs without affecting CD8+ T cells. Initial studies explored a combinatorial regimen using anti-CCR8 mAb therapy and a Listeria monocytogenes (Lm)-based immunotherapy. Anti-CCR8 mAb therapy synergized with Lm-based immunotherapy to significantly delay growth of established tumors and prolong survival. Collectively, these findings identify CCR8 as a promising new target for tumor immunotherapy and provide a strong rationale for further development of this approach, either as a monotherapy or in combination with other immunotherapies.
https://ift.tt/2mrLQcF
Loss of XIST in Breast Cancer Activates MSN-c-Met and Reprograms Microglia via Exosomal miRNA to Promote Brain Metastasis
Up to 30% of patients with metastatic breast cancer eventually develop brain metastasis, yet the pathologic mechanism behind this development remains poorly understood. Here, we profiled long noncoding RNAs in brain metastatic tumors from patients with breast cancer and found that the X-inactive–specific transcript (XIST) was significantly downregulated in these tissues. XIST expression levels inversely correlated with brain metastasis, but not with bone metastasis in patients. Silencing of XIST preferentially promoted brain metastatic growth of XISThigh cells in our xenograft models. Moreover, knockout of XIST in mice mammary glands accelerated primary tumor growth as well as metastases in the brain. Decreased expression of XIST stimulated epithelial–mesenchymal transition and activated c-Met via MSN-mediated protein stabilization, which resulted in the promotion of stemness in the tumor cells. Loss of XIST also augmented secretion of exosomal miRNA-503, which triggered M1–M2 polarization of microglia. This M1–M2 conversion upregulated immune suppressive cytokines in microglia that suppressed T-cell proliferation. Furthermore, we screened an FDA-approved drug library and identified fludarabine as a synthetic lethal drug for XISTlow breast tumor cells and found that fludarabine blocked brain metastasis in our animal model. Our results indicate that XIST plays a critical role in brain metastasis in breast cancer by affecting both tumor cells and the tumor microenvironment and that the XIST-mediated pathway may serve as an effective target for treating brain metastasis.Significance: These findings describe mechanisms of how loss of the lncRNA XIST promotes brain metastasis in breast cancer and identify fludarabine as a potential therapeutic agent that specifically eliminates XISTlow tumor cells in the brain. Cancer Res; 78(15); 1–15. ©2018 AACR.
https://ift.tt/2uJs3ZO
Protocatechuic acid mitigates adriamycin-induced reproductive toxicities and hepatocellular damage in rats
Abstract
Adriamycin (ADR) is an anticancer drug that has a wide report of toxicity in various organs including testes and liver. This has brought limitation to its use in chemotherapy. Protocatechuic acid (PCA) is a phenolic acid present in several foods of plant origins. The aim of this study is to assess the possible action of PCA in ADR-induced reproductive and hepatic toxicities in rats. Thirty adult male rats of about 160–180 g in weight were separated into five groups: group 1 was given normal saline and served as control group, group 2 was administered 20 mg/kg of ADR intraperitoneally, groups 3 and 4 were administered ADR and separate doses of PCA (10 and 20 mg/kg body weight) respectively, while the group 5 rats received only 20 mg/kg of PCA. Pre-treatment with PCA significantly improved sperm motility, sperm count, and viability in ADR-induced rats. Furthermore, elevated levels of testes and liver malondialdehyde were significantly reduced in rats treated with PCA. Also, the increased serum alkaline phosphatase, aspartate transaminase, total cholesterol, triglyceride total protein, and albumin levels in ADR-induced rats were brought near the control value by PCA treatment. Conversely, reduction in the levels of testes and liver glutathione as well as the serum high-density lipoprotein (HDL) cholesterol level in ADR group was significantly raised in PCA-treated rats. Therefore, PCA may represent a natural and promising compound for mitigating against oxidative stress-mediated toxicities.
https://ift.tt/2mqD12K
The SAVE Technique
Abstract
Background
The stent retriever assisted vacuum-locked extraction (SAVE) technique was introduced as an effective thrombectomy method in stroke patients suffering from intracranial large vessel occlusion (LVO). This article presents our multicenter, large-scale experience with SAVE.
Methods
The study involved a retrospective core team analysis of 200 patients undergoing mechanical thrombectomy using the SAVE technique due to intracranial LVO at 4 German centers. Primary endpoints were first-pass and overall complete/near complete reperfusion, defined as a modified thrombolysis in cerebral infarction (mTICI) score of 2c and 3. Secondary endpoints were the number of passes, time from groin puncture to reperfusion, embolization to new territories (ENT), postinterventional symptomatic intracranial hemorrhage (sICH), and favorable outcome at discharge, defined as a modified Rankin Scale (mRS) score ≤ 2.
Results
The median age was 78 years (interquartile range IQR 68–85). Median National Institutes of Health stroke scale (NIHSS) at admission was 16 (IQR 12–20). Occlusions sites were: internal carotid artery (ICA-T) in 39/200 (19.5%), M1 in 126/200 (63%), M2 in 30/200 (15%), and others in 5/200 (2.5%) cases. The primary endpoints were documented in 114/200 (57% first pass mTICI 2c or 3) and 154/200 (77% overall mTICI 2c or 3) patients, respectively. The overall median time from groin puncture to reperfusion was 34 min (IQR 25–52) with a median of 1 (IQR 1–2) attempts. An ENT was observed in 3 patients (1.5%) and the rate of sICH was 2.6%. The rate of successful reperfusion (mTICI ≥ 2b) on final angiograms was 95%. At discharge, 73/200 (36.5%) patients revealed a favorable outcome.
Conclusion
Mechanical thrombectomy using the SAVE technique seems to be effective, fast and safe. First-line use of SAVE leads to high rates of complete and near complete reperfusion.
https://ift.tt/2O3AuID
Role of tyrosine residue (Y213) in nuclear retention of PCNA1 in human malaria parasite Plasmodium falciparum
https://ift.tt/2uOmtFx
A yeast for all seasons – is Pichia pastoris a suitable chassis organism for future bioproduction?
https://ift.tt/2mryGMN
Characterisation and pure culture of putative health-associated oral bacterium BU063 (Tannerella sp. HOT-286) reveals presence of a potentially novel glycosylated S-layer
https://ift.tt/2uOtpCy
Dysbiosis and early mortality in zebrafish larvae exposed to subclinical concentrations of streptomycin
https://ift.tt/2msKEpp
Simulation and modeling of dietary changes in the infant gut microbiome
https://ift.tt/2mrgmTQ
A comparison of prokaryotic symbiont communities in nonnative and native ascidians from reef and harbor habitats
https://ift.tt/2uyMFoB
Thiosulfate- and hydrogen-driven autotrophic denitrification by a microbial consortium enriched from groundwater of an oligotrophic limestone aquifer
https://ift.tt/2uJULtL
Bacterial community assemblages in the rhizosphere soil, root endosphere and cyst of soybean cyst nematode-suppressive soil challenged with nematodes
https://ift.tt/2uOaE29
The effectiveness of chlorhexidine is limited in preventing infections in oral procedures
A large number of bacteria are present in human mouths and may pass into the blood when procedures such as the removal of a tooth are carried out. Chlorhexidine mouthwashes have a powerful antimicrobial effect, but there are opposing positions on its use in these cases.
https://ift.tt/2Lpqf2D
Somatic Cell Nuclear Transfer Reprogramming: Mechanisms and Applications
Matoba and Zhang discuss recent advances in somatic cell nuclear transfer technology, particularly new methods to overcome epigenetic barriers, and highlight the potential applications of this cloning technology for both reproductive efforts and therapy.
https://ift.tt/2NvCibV
Functional Dissection of the Enhancer Repertoire in Human Embryonic Stem Cells
Barakat et al. use a combination of chromatin immunoprecipitation and a massively parallel reporter assay to identify functional enhancers in primed and naive human embryonic stem cells. This genome-wide catalog of validated enhancers provides a valuable resource for the further dissection of the regulatory genome.
https://ift.tt/2O0MlHb
Loss of H3K27me3 Imprinting in Somatic Cell Nuclear Transfer Embryos Disrupts Post-Implantation Development
Matoba et al. show that mouse cloning efficiency can be significantly improved by simultaneously overcoming two reprogramming barriers, Xist and H3K9me3, although efficiency is still low in comparison with IVF. Comprehensive analyses showed that SCNT embryos can have complete loss of H3K27me3 imprinting, likely explaining this low efficiency.
https://ift.tt/2NsYy6s
Correction to: Iron-free and iron-saturated bovine lactoferrin inhibit survivin expression and differentially modulate apoptosis in breast cancer
After publication of the original article [1], the authors found that Fig. 3 contained an incorrect version of Fig. 3c. This does not affect the Figure legend, results and conclusions of the article.
https://ift.tt/2Nrd3rm
Knowledge Level, Attitude, and Behaviors of Farmers in Çukurova Region regarding the Use of Pesticides
Introduction and Purpose. Farmers are particularly at high risk of pesticide exposure due to added risk from occupational exposure. The aim of this study is to evaluate knowledge level of farmers in the Çukurova region of the effects of pesticides, toxic symptoms, and protective equipment as well as assessing their attitudes and practices regarding pesticides. Material and Method. A total of 420 seasonal agricultural workers in Karataş District of Adana Province, Turkey, were included in the study. The questionnaire form consisting of 3 sections was administered using face-to-face interview method. Results. The mean age of the participants was years. They were engaged in farming for a mean duration of years. All of them used pesticides, but none of them had been trained on the use of pesticides. Only 26.2% of them stored pesticides in a private depot. The farmers who took empty pesticide containers to special collection bins or centers constituted only 4.3% of them. While 84.0% of them thought that pesticides could have a negative impact on human health, 5.0% of them had experienced a medical problem and 1.0% of them were poisoned after applying pesticides. Conclusion. The results show that knowledge level of farmers of safe use of pesticides is very inadequate. This lack of knowledge adversely affects workers' quality of life as well as occupational health and safety. Appropriate training programs should be organized to increase their level of knowledge.
https://ift.tt/2O0VEa4
Traditional Mongolian, Traditional Chinese, and Western Medicine Hospitals: System Review and Patient Survey on Expectations and Perceptions of Quality of Healthcare in Inner Mongolia, China
Background. In Inner Mongolia of China, traditional Mongolian medicine (TMM), traditional Chinese medicine (TCM), and western medicine (WM) are all supported by the government. This study compares the background and performance of these three types of medicines. Methods. The World Health Organization's Six Building Blocks framework was used for the system review. Data were collected from literature review and key informant interviews. A cross-sectional survey was conducted in three types of hospitals at the provincial, municipal (city), and prefectural (county) levels from April to August, 2016. Eight hospitals were included and, within each one, patients from four outpatient departments were selected. A total of 1,322 patients were interviewed about their expectations and perceptions of the health service. Results. Government support for TMM includes higher budget allocation and a higher reimbursement rate. TMM is preferred by Mongolian people, those living in pasturing areas, and those seeking treatment for musculoskeletal problems/injuries. Patients attending TMM hospitals had the highest expectations and perceptions of the health service in general. However, human resources and research capacity of TMM are relatively limited. Conclusion. To further enhance the role of the popular TMM for local minority's health, human resources and research capacity strengthening are essential.
https://ift.tt/2zVm1LG
Primary Diffuse B-Cell Thyroid Lymphoma: Case Report and Literature Review
Case Rep Oncol 2018;11:505–510
https://ift.tt/2zVlRny
Efficacy of capecitabine in patients with locally advanced or metastatic breast cancer with or without prior treatment with fluoropyrimidine: a retrospective study
Abstract
Purpose
We conducted a retrospective study to assess the outcomes of capecitabine for advanced breast cancer (ABC) after perioperative fluoropyrimidines (FPs).
Methods
The charts of patients with ABC who received capecitabine between 2008 and 2016 at the National Cancer Center Hospital (Tokyo, Japan) were reviewed. Progression-free survival (PFS), overall survival (OS), tumor response, and adverse events (AEs) were compared between two groups: an FP group (prior perioperative FP use) and a non-FP group (no prior FP use).
Results
Overall, 288 patients (FP n = 105; non-FP n = 183) were analyzed. The two groups had similar patient characteristics. The FP group had significantly poorer PFS than the non-FP group (multivariate hazard ratio [HR] 1.33; 95% confidence interval [CI] 1.02–1.73; p = 0.036), although the OS did not differ significantly between the groups (multivariate HR 1.00; 95% CI 0.67–1.50; p = 0.994). With different cut-off values (relapse-free interval [RFI] = 3, 4, and 5 years), multivariate HRs for PFS were 1.32–1.67 (short RFI), and 1.00–1.25 (long RFI). A trend for a larger HR in the FP group compared to the non-FP group with short RFI than in that with long RFI was also seen for OS. Response rate (RR) and disease control rate (DCR) did not differ significantly between the groups (RR in FP vs non-FP 13.8 vs 21.0%; p = 0.173; DCR 54.0 vs 59.9%; p = 0.418). No significant difference in AEs existed between the groups.
Conclusions
Extra caution is needed when capecitabine is considered for patients with ABC who used perioperative FP, especially those who had early recurrence.
https://ift.tt/2zVjnFK
Phase II study of pazopanib in combination with paclitaxel in patients with metastatic melanoma
Abstract
Purpose
This phase II study evaluated the safety and clinical activity of pazopanib, a potent and mutlitargeted tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptors (VEGFRs)-1, -2 and -3, platelet-derived growth factor receptor (PDGFR)-α and β, and cKit, in combination with metronomic paclitaxel in patients with metastatic melanoma.
Experimental design
Sixty chemotherapy-naive patients received pazopanib at a starting dose of 800 mg daily in combination with metronomic dosing of paclitaxel 80 mg/m2 weekly thrice every 4 weeks. The primary endpoint was 6-month progression-free survival (PFS) rate, while secondary endpoints included 1-year overall survival rate, RECIST response rates, progression-free survival rates and median overall survival. Prior BRAF-targeted therapy or checkpoint inhibitors were permitted.
Results
The 6-month PFS rate was 68%, with a 1-year OS rate of 48%. Objective response rate was 37% comprising one complete and 20 partial responses. Stable disease at 8 weeks was noted in 32 patients (55%) with an overall clinical benefit rate of 93%. Six-month median progression-free survival was 8 months and median OS was 12.7 months. The most frequently (> 15%) reported non-hematologic, treatment-related adverse events were fatigue, diarrhea, hypertension, transaminitis and peripheral neuropathy. Treatment-related non-fatal bowel perforation, a known class effect, occurred in one patient. No significant association was noted between plasma levels of pazopanib and response.
Conclusions
The combination of pazopanib and metronomic paclitaxel was well-tolerated, demonstrating significant activity in metastatic melanoma. Further evaluation of this combination is warranted.
https://ift.tt/2uwJNbw
Clinical pharmacokinetics and safety profile of single agent arsenic trioxide by continuous slow-rate infusion in patients with newly diagnosed acute promyelocytic leukemia
Abstract
Purpose
This study evaluated pharmacokinetics (PK) and safety profiles of single agent arsenic trioxide (ATO, As2O3) administrated as continuous slow-rate infusion in patients with newly diagnosed acute promyelocytic leukemia.
Patients and methods
Patients received 0.16 mg/kg ATO per day. ATO was given for 40 min infusion on the first day followed by 18–20 h daily at a very slow rate with infusion speed of 8 drips/min. During the first week, plasma samples were collected immediately before next administration on each day, and 0.5, 1, 2, 4, 8, 12 h after administration, at the end of infusion (18 h) on day 7. Total arsenic was determined by ICPMS. Arsenic species, arsenious acid (AsIII) and its metabolites, monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV), were quantified by UHPLC-ICPMS. Safety assessment and PK analysis was conducted.
Results
Hyperleukocytosis occurred in two patients and no severe toxicity was observed. Total arsenic gradually accumulated from 15.84 to 34.12 ng/mL during the first week of therapy. MMAV/iAs increased and remained stable at value about 0.6 after day 4, while DMAV/MMAV declined under 2 after day 4. Compared with 2 h infusion, clearance (CL) of AsIII was significantly lower (0.8 ± 0.2 vs. 2.7 ± 1.7 L/kg/h, P = 0.002) while AUC0–t of AsIII was significantly increased (213.9 ± 38.6 vs. 82.6 ± 55.7 L/kg/h, P = 0.028).
Conclusion
Continuous slow-rate ATO infusion provided an alternative administration for ATO therapy with few toxic effects. Degree of methylation from MMA to DMA is inconsistent with that from iAs to MMA. PK of arsenic species is considered important for clinical use of ATO.
https://ift.tt/2LA1i1u
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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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Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
