Publication date: Available online 11 August 2017
Source:Injury
Author(s): Shay Tenenbaum, Daniel Weltsch, Jason T. Bariteau, Adi Givon, Kobi Peleg, Ran Thein
IntroductionThe use of electric bicycles (E-bike) has dramatically increased. E-bikes offer convenient, environmental-friendly, and less expensive alternative to other forms of transport. However, E-bikes provide a new public health challenge in terms of safety and injury prevention.This study is the first to specifically investigate the E-bike related orthopaedic injuries, based on a national trauma registry.MethodsData from a National Trauma Registry were reviewed for patients hospitalized following E-bike related injuries. Between Jan 2014 to Dec 2015, a total of 549 patients were reviewed. Data were analyzed according to demography, type of orthopaedic injury, associated injuries and severity, injury mechanism and treatment in the operating room.ResultsA total of 360 (65%) patients sustained orthopaedic injuries, out of them 230 (63.8%) sustained limb/pelvis/spine fractures. Lower extremity fractures were more prevalent than upper extremity fractures (p<0.001). The tibia was the most fractured bone (19.2%). Patients over the age of 50 years were at the highest risk for spine (20. 5%, p=0.0001), pelvis (15.9%, p=0.0001) and femoral neck (15.9%, p=0.0172) fractures relative to other age groups. Approximately 42% of patients sustained associated injuries, with head/neck/face injuries being the most prevalent (30.3%). followed by chest (11.9%) and abdominal injury (13.3%). A collision between E-bike and a motorized vehicle was the mechanism of injury in 35% of cases. In this mechanism of injury, patients had 1.7 times the risk for associated injuries (p<0.0001) and the risk for major trauma (ISS score ≥16) was more than the double (p=0.03).One third of patients with orthopaedic injuries required treatment in the operating room.Treatment varied depending on the type of fracture.ConclusionsThis study provides unique information on epidemiological characteristics of orthpaedic injuries caused be E-bikes, pertinent both to medical care providers, as well as to health policy-makers allocating resources and formulating prevention strategies.
http://ift.tt/2vUiESg
Πέμπτη 10 Αυγούστου 2017
Orthopaedic Injuries among Electric Bicycle Users
Fluoropolymer Nanosheet as a Wrapping Mount for High-Quality Tissue Imaging
In the field of biological microscopy technology, it is still a practical challenge to obtain high-quality tissue images, due to the tissue desiccation that occurs during observations without an effective sample mounting. Inspired by the use of plastic food wrap, this study proposes the use of polymer thin films (also known as nanosheets) to fix the tissue samples. Water-repellent nanosheets composed of the amorphous fluoropolymer CYTOP are prepared with adjustable thicknesses and their hydrophobicity, transparency, and adhesion strength are evaluated. They show excellent water-retention effect and work well for sample fixation. By wrapping cleared mouse brain slices with a 133 nm thick CYTOP nanosheet, this study achieves high spatial resolution neuron images while scanning over a large area for a long period of time. No visible artifacts arising from sample shrinkage can be detected. This study also expects that nanosheet wrapping could be effective over a longer time span by combination with conventional agarose embedding.
Water-repellent nanosheets composed of amorphous fluoropolymer CYTOP are prepared, which shows excellent water retention and sample fixation properties. By wrapping cleared mouse brain slices with CYTOP nanosheet, high spatial resolution images are achieved over a large scan area. It is also expected that nanosheet wrapping could be effective over a longer time span by combination with agarose embedding.
http://ift.tt/2voIlsA
Bevacizumab in Colorectal Cancer: Current Role in Treatment and the Potential of Biosimilars
Abstract
Colorectal cancer (CRC) is a leading cause of tumor-related morbidity and mortality worldwide, with mortality most often attributable to metastatic disease. Bevacizumab, a humanized monoclonal antibody targeting vascular endothelial growth factor, has a significant role in the treatment of metastatic CRC (mCRC). However, patient access to bevacizumab may be limited in some regions or circumstances, owing to factors related to insurance coverage, reimbursement, patient out-of-pocket costs, or availability. As a result, outcomes for patients with mCRC may be worsened. Additionally, counterfeit bevacizumab has infiltrated legitimate supply chains, exposing patients to risk. Oncologists may also be affected detrimentally, since resolving access issues can be time-consuming and demoralizing. The imminent expiry of patents protecting bevacizumab provides other manufacturers with the opportunity to produce highly similar versions known as biosimilars. High-quality, safe, and effective biosimilars have the potential to expand access to bevacizumab. Most of the bevacizumab biosimilars currently in development are in clinical trials in patients with non-small-cell lung cancer, and future authorization for mCRC indications will, therefore, be based on extrapolation. This article reviews the current role of bevacizumab in the management of mCRC, the possible barriers associated with diminished access to bevacizumab, and the potential bevacizumab biosimilars in development. How biosimilars may impact the treatment of mCRC is also discussed.
http://ift.tt/2vKMbxm
Challenging the colonisation of birth: Koori women’s birthing knowledge and practice
Publication date: Available online 10 August 2017
Source:Women and Birth
Author(s): Karen Adams, Shannon Faulkhead, Rachel Stanfield, Petah Atkinson
BackgroundThe 2007 United Nations Declaration on the Rights of Indigenous Peoples states that Indigenous peoples have the right to self-determination for social and cultural development. This fundamental right has been impeded worldwide through colonisation where many Indigenous peoples have had to adapt to ensure continuation of cultural knowledge and practice. In South East Australia colonisation was particularly brutal interrupting a 65,000 year-old oral culture and archives have increasing importance for cultural revival.AimThe aim of this research was to collate archival material on South East Australian Aboriginal women's birthing knowledge and practice.MethodsArchivist research methods were employed involving a search for artefacts and compiling materials from these into a new collection. This process involved understanding the context of the artefact creation. Collaborative yarning methods were used to reflect on materials and their meaning.FindingsArtefacts found included materials written by non-Aboriginal men and women, materials written by Aboriginal women, oral histories, media reports and culturally significant sites. Material described practices that connected birth to country and the community of the women and their babies. Practices included active labour techniques, pain management, labour supports, songs for labour, ceremony and the role of Aboriginal midwives. Case studies of continuing cultural practice and revival were identified.ConclusionInclusion of Aboriginal women's birthing practices and knowledge is crucial for reconciliation and self-determination. Challenging the colonisation of birthing, through the inclusion of Aboriginal knowledge and practice is imperative, as health practices inclusive of cultural knowledge are known to be more effective.
http://ift.tt/2wzqVbz
Minimalizing bleeding and tearing at vaginal birth: One practitioner’s experience
Publication date: Available online 11 August 2017
Source:Women and Birth
Author(s): Judy Slome Cohain
http://ift.tt/2voPBFd
Pelvic fixation - biomechanics and complications
Publication date: Available online 10 August 2017
Source:Seminars in Spine Surgery
Author(s): Joseph Ferguson, David Love, Fred F. Mo
When extending a fusion construct to the sacrum in spinal deformity, there has long been difficulty in obtaining bony fusion at the L5-S1 level. This is due to a number of factors, including the altered morphology of the sacrum as compared to the lumbar vertebrae, adequate bone stock, and large cantilever forces at the lumbosacral junction, among others. This problem can be partially rectified by extending the construct to the pelvis, but even this does not result in a 100% fusion rate at the lumbosacral junction. The techniques currently used to fuse the spine to the pelvis primarily consist of iliac screws and S2-alar-iliac screws, but these techniques are not without complications. Here we review the biomechanics of pelvic fixation, techniques of these two screw types, and the complications associated with each.
http://ift.tt/2uM2hlF
Vertebral Column Resection for Complex Spinal Deformity
Publication date: Available online 10 August 2017
Source:Seminars in Spine Surgery
Author(s): Evan D. Sheha, Han Jo Kim, Matthew E. Cunningham
Vertebral Column Resection is a powerful tool in the management of complex spinal deformity. Indications for VCR include rigid or focal, angular kyphosis or coronal deformity, hemivertebrae, and post-tuberculous spinal deformity. We review the approach to the patient with complex spinal deformity, VCR surgical technique, intraoperative considerations and outcomes reported in the literature.
http://ift.tt/2uugl8d
Posterior osteotomies for kyphosis correction
Publication date: Available online 10 August 2017
Source:Seminars in Spine Surgery
Author(s): Andrew Z. Mo, Andrew A. Sama
Kyphotic deformity of the spine is a significant source of pain and disability. Sagittal and/or coronal malalignment of the spine can be secondary to numerous factors including trauma, infection, surgery (iatrogenic), congenital deformity, and degenerative changes. Surgical correction is often the definitive treatment for patients with severe or late stage deformity. There are several options for choice of osteotomy including the Smith-Peterson osteotomy, pedicle subtraction osteotomy, and vertebral resection osteotomy. This manuscript discusses the various types of osteotomies, indications, evaluation, and complications for the treatment of kyphosis.
http://ift.tt/2uM6YMr
Minimally Invasive Anterior Column Realignment for the Treatment of Adult Spinal Deformity: A Review of the Literature
Publication date: Available online 10 August 2017
Source:Seminars in Spine Surgery
Author(s): Jonathan G. Seavey, Theodore Steelman, Melvin Helgeson, David E. Gwinn
Surgical treatment of adult spine deformity requires correction in multiple planes. Currently employed open and minimally invasive techniques and instrumentation allow for robust rotational and coronal plane correction. However, large sagittal deformities frequently require vertebral osteotomies, which can increase morbidity and complications, particularly in an elderly population. Anterior column realignment has emerged as a technique that can provide significant sagittal plane correction through a minimally invasive approach. We will provide an overview of this procedure, technical challenges, risks, outcomes and review the recent literature on anterior column realignment for the treatment of adult spine deformity.
http://ift.tt/2utRxNQ
Review of surgical correction of cervical kyphosis
Publication date: Available online 10 August 2017
Source:Seminars in Spine Surgery
Author(s): Theodore J. Steelman, Daniel G. Kang, Jonathan G. Seavey, Tushar Ch. Patel
Kyphotic deformity of the subaxial cervical spine can be debilitating to the patient, as well as challenging to the spine surgeon. Cervical kyphotic deformity is frequently progressive and can result in neurologic decline that mirrors the increase in deformity thus requiring surgical correction to alter the natural progression of the deformity. We review common etiologies, clinical and diagnostic workup, as well as pearls and pitfalls of each of the approaches to the cervical spine. Indications and contraindications for anterior, posterior, and combined approach are addressed.
http://ift.tt/2uLBfuX
Pelvic Fixation Techniques and Impact on Sagittal Balance: A Literature Review
Publication date: Available online 10 August 2017
Source:Seminars in Spine Surgery
Author(s): Ian T. McNeill, Robert J. Rothrock, Samuel K. Cho, John M. Caridi
As adult spinal deformity (ASD) surgery advances, pelvic fixation techniques have evolved to confront several challenges such as pseudoarthrosis and instrumentation failure. Concurrently, ASD literature has identified sagittal balance as one of the preeminent factors in clinical outcomes in patients undergoing ASD surgery. However, despite advances in surgical technique and understanding of clinical outcome predictors, there is limited evaluation of the impact of pelvic instrumentation on global sagittal alignment. This review provides context on historical pelvic instrumentation options and assesses the advantages and disadvantages of modern pelvic fixation techniques in ASD surgery with respect to sagittal balance. Available data suggest that pre- and postoperative sagittal balance correction remains an important clinical outcome predictor, but such a correction can be undermined by postoperative complications such as pseudoarthrosis and instrumentation failure over the long term. Therefore, choice of instrumentation construct should not only consider intraoperative factors and immediate sagittal balance correction but also prevention of complications over patients′ full postoperative course. Future research should directly evaluate pelvic fixation techniques in the context of long-term postoperative clinical and radiologic outcomes, specifically sagittal balance.
http://ift.tt/2uutzls
Clinical and radiographic evaluation of adult spinal deformities
Publication date: Available online 10 August 2017
Source:Seminars in Spine Surgery
Author(s): Brian T. Sullivan, Amit Jain, Keith T. Aziz, A. Jay Khanna
Adult spinal deformity (ASD) is a heterogeneous group of disorders that affect spinal alignment. We review the clinical evaluation and radiographic assessment of ASD. Evaluation begins with a thorough patient history and a global and spine-specific physical examination. Thorough radiographic evaluation is essential for diagnosis, evaluation of deformity, planning of surgical procedures, and monitoring of outcomes. Spinopelvic parameters can be used to evaluate deformities; they are associated with quality of life, and they help characterize sagittal malalignment and pelvic compensation. Newly described radiographic parameters, including T1 pelvic angle and deformity angular ratio, assist surgeons in the evaluation of ASD.
http://ift.tt/2uLXKju
Novel 1L polyethylene glycol-based bowel preparation NER1006 for overall and right-sided colon cleansing: a randomized controlled phase 3 trial versus trisulfate
NER1006 is the first 32 fluid ounce (1L) polyethylene glycol-based bowel preparation. This randomized, multicenter, colonoscopist/central reader-blinded Phase 3 non-inferiority trial assessed the efficacy, safety, and tolerability of NER1006 versus trisulfate for bowel cleansing.
http://ift.tt/2uvIMi4
The Intersection of Gender, Sexuality, and Religion in Mormon Mixed-Sexuality Marriages
Abstract
Mixed-sexuality marriages (MSMs) are defined in the present study as those where one partner identifies as heterosexual and the other partner identifies as gay, lesbian, bisexual, queer or reports experiencing same-sex attraction. Members of conservative religions, such as Mormonism, may be more likely to enter MSMs given the religion's stance on homosexuality and doctrinal emphasis on heteronormative marriage. Using data from 56 interviews with individuals who either have been or currently are Mormon and in a MSM, we explore participants' ideas about gender roles and sexuality in the context of their ideas about Mormonism. We find that couples' ideas about gender, sexuality, and religion intersect to act as a resource or impediment to marital satisfaction. Among our sample, most couples maintain an outward appearance of heteronormativity; some view their private departure from the traditional gender order as a benefit to their relationship, whereas others view it as a source of strain and work hard to minimize gender deviance in their roles. The findings provide an important example of the way gender and religion are mutually constitutive and illustrate how notions of sexuality are sometimes used to reinforce a traditional gender order and religious beliefs, whereas at other times, the contradictions of MSMs challenge traditional gender norms and religious orthodoxy.
http://ift.tt/2votezw
Anticancer efficacy of the hypoxia-activated prodrug evofosfamide is enhanced in combination with proapoptotic receptor agonists against osteosarcoma
Abstract
Tumor hypoxia is a major cause of treatment failure for a variety of malignancies. However, hypoxia also leads to treatment opportunities as demonstrated by the development of compounds that target regions of hypoxia within tumors. Evofosfamide is a hypoxia-activated prodrug that is created by linking the hypoxia-seeking 2-nitroimidazole moiety to the cytotoxic bromo-isophosphoramide mustard (Br-IPM). When evofosfamide is delivered to hypoxic regions of tumors, the DNA cross-linking toxin, Br-IPM, is released leading to cell death. This study assessed the anticancer efficacy of evofosfamide in combination with the Proapoptotic Receptor Agonists (PARAs) dulanermin and drozitumab against human osteosarcoma in vitro and in an intratibial murine model of osteosarcoma. Under hypoxic conditions in vitro, evofosfamide cooperated with dulanermin and drozitumab, resulting in the potentiation of cytotoxicity to osteosarcoma cells. In contrast, under the same conditions, primary human osteoblasts were resistant to treatment. Animals transplanted with osteosarcoma cells directly into their tibiae developed mixed osteosclerotic/osteolytic bone lesions and consequently developed lung metastases 3 weeks post cancer cell transplantation. Tumor burden in the bone was reduced by evofosfamide treatment alone and in combination with drozitumab and prevented osteosarcoma-induced bone destruction while also reducing the growth of pulmonary metastases. These results suggest that evofosfamide may be an attractive therapeutic agent, with strong anticancer activity alone or in combination with either drozitumab or dulanermin against osteosarcoma.
In this study, we investigated the cytotoxic activity of the hypoxia-activated prodrug evofosfamide against human osteosarcoma cells in vitro as a single agent and in combination with proapoptotic receptor agonist's dulanermin and drozitumab. We then assessed the anticancer activity of evofosfamide alone and in combination with drozitumab using a clinically relevant orthotopic mouse model of osteosarcoma and on subsequent pulmonary metastases. Evofosfamide as a single agent reduced tumor burden in bone and cooperated with drozitumab to protect bone from osteosarcoma-induced bone destruction while also reducing the incidence of pulmonary metastases and importantly, evofosfamide alone and in combination with drozitumab was not toxic to normal bone metabolism in vivo.
http://ift.tt/2vK6afr
The Multiple Faces of Spinocerebellar Ataxia type 2
Abstract
Spinocerebellar ataxia type 2 (SCA2) is among the most common forms of autosomal dominant ataxias, accounting for 15% of the total families. Occurrence is higher in specific populations such as the Cuban and Southern Italian. The disease is caused by a CAG expansion in ATXN2 gene, leading to abnormal accumulation of the mutant protein, ataxin-2, in intracellular inclusions. The clinical picture is mainly dominated by cerebellar ataxia, although a number of other neurological signs have been described, ranging from parkinsonism to motor neuron involvement, making the diagnosis frequently challenging for neurologists, particularly when information about the family history is not available. Although the functions of ataxin-2 have not been completely elucidated, the protein is involved in mRNA processing and control of translation. Recently, it has also been shown that the size of the CAG repeat in normal alleles represents a risk factor for ALS, suggesting that ataxin-2 plays a fundamental role in maintenance of neuronal homeostasis.
http://ift.tt/2wzgkgN
Treatment of Patients With Hepatitis C Virus infection (Genotype 4) With Ledipasvir-Sofosbuvir in the Liver Transplant Setting.
http://ift.tt/2uvE2cl
Serum osmolarity in male patients with bipolar disorder manic episode
Abstract
Imbalance of water and electrolyte homeostasis has been suggested to be associated with the acute episodes of bipolar disorder. In this study we aimed to investigate, for the first time, the serum osmolarity in bipolar disorder manic episode. A total of 68 bipolar inpatients in manic episode and 60 age-gender matched healthy controls were included in the study. Serum osmolarity was calculated from Sodium (Na+), glucose and blood urea nitrogen (BUN) according to formula of (2 × Na+) + (BUN/2.8) + (Glucose/18). Significance level was accepted as P < 0.05. Serum osmolarity of manic patients was 295.34 ± 4.90 mOsm L−1 and control group was 298.46 ± 5.33 mOsm L−1. Serum osmolarity of manic group was significantly lower than controls (P < 0.001). When we compare the components of serum osmolarity; statistically significant difference was also observed between groups in terms of glucose (85.85 ± 12.25 mg dl−1 for manic, 92.95 ± 20.77 mg dl−1 for controls, P = 0.019) and Na+ (140.73 ± 2.06 mmol L−1 for manic, 142.06 ± 2.48 mmol L−1 for controls, P = 0.001). For BUN levels; there was no statistically significant difference between manic (25.50 ± 9.85 mg dl−1) and control (26.61 ± 6.64 mg dl−1) groups (P = 0.461). Our results demonstrate a diminished serum osmolarity in manic episode compared with healthy controls. This finding supports the hypothesis of a fluid and electrolyte imbalance during acute episodes. Decreased serum osmolarity may be a reflection of a relative hemodilution in mania. However, exploring the role of fluid and electrolyte homeostasis and mechanisms of related hormones may contribute to better understanding the etiology of bipolar disorder.
This article is protected by copyright. All rights reserved
http://ift.tt/2wzlfOG
Advances in Microbiology Vol.7,No.7 (July 2017)
Bacterial Pathogenicity, Biological Function, "Pathogenicity Islands", Infectious Diseases, Prokaryotic and Eukaryotic Organisms
Paper Information Full Paper: PDF (Size:245KB)
DOI: 10.4236/aim.2017.77042
Diet-Induced Alteration of the Murine Intestinal Microbiome Following Antibiotic Ablation
Mouse, Intestinal Microbiome, Antibiotics, Diet, Lactococcus
Paper Information Full Paper: PDF (Size:2319KB)
DOI: 10.4236/aim.2017.77043
Effects of Fermentation on the Proximate Composition of Irish (Solanum tuberosum) and Sweet Potato (Ipomoea batatas) Peels
Fermentation, Proximate Composition, Physicochemical Analysis, Microbial Load, Potato Peels
Paper Information Full Paper: PDF (Size:320KB)
DOI: 10.4236/aim.2017.77044
Effects of Hypobaric and Hyperbaric Pressures on Mycelial Growth of Isolated Strain of Wild Ophiocordyceps sinensis
Hypobaric Pressure, Hyperbaric Pressure, Ophiocordyceps sinensis
Paper Information Full Paper: PDF (Size:778KB)
DOI: 10.4236/aim.2017.77045
http://ift.tt/1lkzXmf
Organoid culture systems to study host–pathogen interactions
Devanjali Dutta | Hans Clevers
http://ift.tt/2utJjVV
Small molecule inhibitor prevents or impedes tooth cavities in a preclinical model
http://ift.tt/2wyUzxJ
Fecal immunological blood test is more appealing than the guaiac-based test for colorectal cancer screening
The reasons for participation in fecal immunological testing (FIT) of subjects who were previously non-respondents to guaiac fecal occult blood testing (g-FOBT) have not been assessed.
http://ift.tt/2vUgMIy
RIP3 AND pMLKL PROMOTE NECROPTOSIS-INDUCED INFLAMMATION AND ALTER MEMBRANE PERMEABILITY IN INTESTINAL EPITHELIAL CELLS
Necroptosis is an inflammatory form of programmed cell death requiring receptor-interacting protein kinase 3 (RIP3) and mixed lineage kinase domain-like protein (MLKL).
http://ift.tt/2uvAOWe
Transglutaminase 6 antibodies in gluten neuropathy
TG6 antibodies have been shown to be a marker of gluten ataxia but their presence in the context of other neurological manifestations of gluten sensitivity has not been explored.We investigated the presence of TG6 antibodies in gluten neuropathy(GN), defined as as an otherwise idiopathic peripheral neuropathy associated with serological markers of gluten sensitivity (one or more of antigliadin IgG and/or IgA, endomysial and transglutaminase-2 antibodies)
http://ift.tt/2vUEFzy
Pravastatin Sodium Tablets by International Laboratories: Recall - Mislabeling
Audience: Pharmacy, Patient [Posted 08/10/2017] ISSUE: International Laboratories, LLC is voluntarily recalling one (1) Lot of Pravastatin Sodium Tablets USP 40 mg packaged in bottles of 30 tablets, to the consumer level due to mislabeling. The...
http://ift.tt/2wyyvmF
Liquid Products Manufactured by PharmaTech and Distributed by Leader Brand, Major Pharmaceuticals, and Rugby Laboratories: Recall - Possible Product Contamination
Audience: Pharmacy, Patient [Posted 08/10/2017] ISSUE: The distribution firms Leader Brand, Major Pharmaceuticals, and Rugby Laboratories jointly issued a nationwide voluntary recall of all lots within expiry of all liquid products manufactured by...
http://ift.tt/2vnmphx
Prevalence and drug susceptibility pattern of group B Streptococci (GBS) among pregnant women attending antenatal care (ANC) in Nekemte Referral Hospital (NRH), Nekemte, Ethiopia
The main objective of this study was to determine the prevalence and drug susceptibility pattern of group B Streptococci (GBS) among pregnant women. The specific objectives include; (1) To determine the prevalenc...
http://ift.tt/2wzr3Yw
Seroprevalence of influenza A and B viruses among unvaccinated children in the United Arab Emirates: a cross-sectional study
Young children are at increased risk of severe influenza disease and, thus, are good candidates for receiving annual vaccination. Nevertheless, the influenza vaccine is infrequently given to children in our re...
http://ift.tt/2vo88RG
Large cholera outbreak in Brong Ahafo Region, Ghana
A nationwide outbreak of Vibrio cholerae occurred in Ghana in 2014 with Accra, the nation's capital as the epi-center. The outbreak spread to the Brong Ahafo Region (BAR) which is geographically located in the mi...
http://ift.tt/2wyU86g
Development and characterization of microsatellite markers for diploid populations of the wind-pollinated herb Mercurialis annua
Mercurialis annua is a wind-pollinated annual plant that has long been used as a model for the study of ploidy and sexual-systems evolution. However, no molecular markers are yet avail...
http://ift.tt/2vogcSu
Preventive medicine as a first- or second-choice course: a cross-sectional survey into students’ motivational differences and implications for information provision
Challenges in recruiting and retaining medical staff in preventive medical specialties have recently been the subject of numerous studies. To improve selection procedures, it is important to understand the car...
http://ift.tt/2wz7JKO
Pravastatin Sodium Tablets by International Laboratories: Recall - Mislabeling
Audience: Pharmacy, Patient [Posted 08/10/2017] ISSUE: International Laboratories, LLC is voluntarily recalling one (1) Lot of Pravastatin Sodium Tablets USP 40 mg packaged in bottles of 30 tablets, to the consumer level due to mislabeling. The...
http://ift.tt/2wyyvmF
Liquid Products Manufactured by PharmaTech and Distributed by Leader Brand, Major Pharmaceuticals, and Rugby Laboratories: Recall - Possible Product Contamination
Audience: Pharmacy, Patient [Posted 08/10/2017] ISSUE: The distribution firms Leader Brand, Major Pharmaceuticals, and Rugby Laboratories jointly issued a nationwide voluntary recall of all lots within expiry of all liquid products manufactured by...
http://ift.tt/2vnmphx
Effects of a Brief Educational Program on Optimization of Fluoroscopy to Minimize Radiation Exposure During Endoscopic Retrograde Cholangiopancreatography
Fluoroscopy during endoscopic retrograde cholangiopancreatography (ERCP) is increasingly performed by therapeutic endoscopists, many of whom have not received formal training in modulating fluoroscopy use to minimize radiation exposure. Exposure to ionizing radiation has significant health consequences for patients and endoscopists. We aimed to evaluate whether a 20-minute educational intervention for endoscopists would improve use of fluoroscopy and decrease ERCP-associated exposure to radiation for patients.
http://ift.tt/2wyPRzK
Development and Validation of Trigger Algorithms to Identify Delays in Diagnostic Evaluation of Gastroenterological Cancer
Colorectal cancer (CRC) and hepatocellular cancer (HCC) are common causes of death and morbidity, and patients benefit from early detection. However, delays in follow-up of suspicious findings are common, and methods to efficiently detect such delays are needed. We developed, refined, and tested trigger algorithms that identify patients with delayed follow-up evaluation of findings suspicious of CRC or HCC.
http://ift.tt/2vnr3w2
Risk of Pancreatitis Following Treatment of Irritable Bowel Syndrome with Eluxadoline
The Food and Drug Administration approved eluxadoline for the treatment of diarrhea-predominant irritable bowel syndrome despite cases of pancreatitis in early-stage trials. We investigated the frequency of pancreatitis attributed to eluxadoline in post-marketing surveillance.
http://ift.tt/2vnW4A1
Impact of depression treatment on health-related quality of life among adults with cancer and depression: a population-level analysis
Abstract
Purpose
Cancer diagnosis in adults is often accompanied by negative impacts, which increase the risk of depression thereby lowering health-related quality of life (HRQoL). We examined the association between depression treatment and HRQoL among US adults with cancer and depression.
Methods
Patients age 18 and above, with self-reported cancer and depression diagnoses were identified from Medical Expenditure Panel Survey database for 2006–2013. Baseline depression treatment was categorized as antidepressants only, psychotherapy with or without antidepressant use, and no reported use of antidepressants or psychotherapy. HRQoL was measured using SF-12 physical component summary (PCS) and mental component summary (MCS) scores. Adjusted ordinary least squares regressions estimated the association between type of depression treatment and HRQoL.
Results
Out of 450 (weighted per calendar year: 2.1 million) cancer adults included in the study, 51% received antidepressants only, while 16% received psychotherapy with or without antidepressants. In bivariate analyses, the mean MCS score was lowest among those who received psychotherapy with or without antidepressants compared to those receiving antidepressants only and those with no reported use of either modality, p < 0.05. In multivariate analyses, there was no significant difference in HRQoL by type of depression treatment.
Conclusion
Despite treatment for depression, HRQoL did not improve during the measurement timeframe. Quality of life is a priority health outcome in cancer treatment, yet our findings suggest that current clinical approaches to ameliorate depression in cancer patients appear to be suboptimal.
Implications for cancer survivors
Adults with cancer and comorbid depression should receive appropriate depression care in order to improve their HRQoL.
http://ift.tt/2wyCJL7
Language Growth in English Monolingual and Spanish-English Bilingual Children from 2.5 to 5 Years
To describe the trajectories of English and Spanish language growth in typically developing children from bilingual homes and compare those with the trajectories of English growth in children from monolingual homes, to assess effects of dual language exposure on language growth in typically developing children.
http://ift.tt/2wyxj2N
Long-term epilepsy-associated tumor in the amygdala of a 16-year-old boy: report of a rare case having intranuclear filaments
Abstract
The term "long-term epilepsy-associated tumor (LEAT)" encompasses brain lesions associated with drug-resistant epilepsy over a long duration (≥2 years). Notably, some LEATs do not fit into any of the classifications of the World Health Organization (WHO). Herein, we report a LEAT that occurred in the left amygdala of a 16-year-old patient with intractable epilepsy. Histological examination of the resected amygdala revealed diffusely infiltrating tumor cells in the cortex. Perineuronal satellitosis and perivascular aggregation of tumor cells were apparent, along with mild nuclear enlargement and cytologic atypia. Tumor cells were positive for oligodendrocyte transcription factor 2 and neuronal markers including NeuN, neurofilaments, and synaptophysin, but were negative for CD34 and nestin. The most intriguing finding was intranuclear filaments, which appeared as rod- or needle-like shapes under high-power view. Ancillary ultrastructural analysis revealed thin filamentous intranuclear structures in tumor cells. Based on the glioneuronal nature of these cells as well as the infiltrative growth pattern, a diagnosis of LEAT was rendered that was deemed WHO grade I to II; however, the clinicopathological implications of the intranuclear inclusions remain unknown. The patient is currently alive and well without seizures.
http://ift.tt/2hOYcvR
Moral Aggregation , by Iwao Hirose
http://ift.tt/2hOechU
Essays on the History of Moral Philosophy , by J. B. Schneewind
http://ift.tt/2fwK4qu
Puzzling Identities , by Vincent Descombes, translated by Stephen Adam Schwartz
http://ift.tt/2hPmqGx
Frankfurt’s Unwilling and Willing Addicts
http://ift.tt/2fwNARR
Varieties of Logic , by Stewart Shapiro
http://ift.tt/2hOdVLU
Talking with Vultures
http://ift.tt/2hPuNlv
Type-Ambiguous Names
http://ift.tt/2fwJKbg
Thinking About You
http://ift.tt/2hOdGjY
Why we Should Still Take it Easy
http://ift.tt/2fwNidJ
Backtracking Counterfactuals Revisited
http://ift.tt/2fwNf1x
De Ray: On the Boundaries of the Davidsonian Semantic Programme
http://ift.tt/2hOduRM
Objectivity and Bias
http://ift.tt/2hP8KeE
Ctenopharyngodon idella IKKβ interacts with PKR and IκBα
http://ift.tt/2wN6V4s
Effects of trigonelline inhibition of the Nrf2 transcription factor in vitro on Echinococcus granulosus
http://ift.tt/2wMROIj
Up-regulation of carcinoembryonic antigen-related cell adhesion molecule 1 in gastrointestinal cancer and its clinical relevance
http://ift.tt/2vTo2oR
The potential role of retinoic acid receptor α on glomerulosclerosis in rats and podocytes injury is associated with the induction of MMP2 and MMP9
http://ift.tt/2wN0u1o
Tetramethylpyrazine reverses intracerebroventricular streptozotocin-induced memory deficits by inhibiting GSK-3β
http://ift.tt/2vTnoYm
Expression of OTUB1 in hepatocellular carcinoma and its effects on HCC cell migration and invasion
http://ift.tt/2vTiWsF
Cell cycle-dependent control of homologous recombination
http://ift.tt/2wMEGD2
Fire department's new CPR equipment will give patients 'best possible chance'
The device goes under a person's back, while another part wraps over a person's chest and holds a device which applies the compressions
http://ift.tt/2vrjumu
Dermatofibrosarcoma Protuberans of the Breast—a Rare Entity
Abstract
Dermatofibrosarcoma protuberans (DFSP) represents about 1% of soft-tissue sarcomas with an estimated incidence of 0.8 to 5.0 cases per million per year. This lesion may occur anywhere in the body but more than 50% occur on the trunk, 20% on the head and neck and 30% on the extremities. DFSP of the breast is an extremely uncommon site of presentation. Data regarding DFSP of the breast is limited and mostly in the form of case reports. Clinical presentation is not uniform and may mimic benign skin lesions [1]. However, it typically presents as a nodular cutaneous mass in early or mid-adult life. We herein report a case of DFSP of the breast in a 33-year-old lady who was managed successfully in our institute and review the literature associated with it.
http://ift.tt/2wMpMwn
Assessing Tumor-infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method From the International Immunooncology Biomarkers Working Group: Part 1: Assessing the Host Immune Response, TILs in Invasive Breast Carcinoma and Ductal Carcinoma In Situ, Metastatic Tumor Deposits and Areas for Further Research
http://ift.tt/2vJjKjl
What is New in Gastrointestinal Stromal Tumor?
http://ift.tt/2vTjMG2
The Molecular Landscape of Noninvasive Follicular Thyroid Neoplasm With Papillary-like Nuclear Features (NIFTP): A Literature Review
http://ift.tt/2hOF7tJ
Social Media and Pathology: Where Are We Now and Why Does it Matter?
http://ift.tt/2vJ3aA6
Lichenoid Dermatitis of the Vulva: Diagnosis and Differential Diagnosis for the Gynecologic Pathologist
http://ift.tt/2vJvEd2
Hemosiderotic Fibrolipomatous Tumor, Pleomorphic Hyalinizing Angiectatic Tumor, and Myxoinflammatory Fibroblastic Sarcoma: Related or Not?
http://ift.tt/2vJQo4s
Cytologic-Histologic Discrepancies in Pathology of the Uterine Cervix: Analysis of the Clinical and Pathologic Factors
http://ift.tt/2vJpKZr
Measuring mRNA Levels Over Time During the Yeast S. cerevisiae Hypoxic Response
http://ift.tt/2fw4iRb
Curaplex® launches Stop the Bleed Kits as licensees of the Department of Homeland Security’s Stop the Bleed® Initiative
DUBLIN, Ohio – Curaplex®, the brand carried exclusively by Sarnova's family of companies, is adding Stop the Bleed kits to their product portfolio. Curaplex Stop the Bleed kits were designed to provide their end user with immediate access to products intended to stop traumatic hemorrhaging. These kits contain basic products for emergency responders or civilians to address a traumatic bleeding situation ...
http://ift.tt/2vTjGxM
Fire department's new CPR equipment will give patient 'best possible chance'
The device goes under a person's back, while another part wraps over a person's chest and holds a device which applies the compressions
http://ift.tt/2wMJgkO
Punch “scoring”: a technique that facilitates melanoma diagnosis of clinically suspicious pigmented lesions
Abstract
Aims
Early recognition and accurate diagnosis underpins melanoma survival. Identifying early melanomas arising in association with pre-existing lesions is often challenging. Clinically suspicious foci, however small, must be identified and examined histologically. This study assessed the accuracy of punch biopsy "scoring" of suspicious foci in excised atypical pigmented skin lesions to identify early melanomas.
Methods and results
Forty-one excised pigmented skin lesions with a clinically/dermoscopically focal area of concern for melanoma, with the suspicious focus marked prior to excision with a punch biopsy "score" (a partial incision into the skin surface), were analysed. Melanoma was diagnosed in 9/41 cases (22%). In 8/9 cases (89%), the melanoma was associated with a naevus, and in 7/9 (88%) cases the melanoma was preferentially identified by the scored focus. In 6/9 cases (67%), the melanoma was entirely encompassed by the scored focus. In one case of melanoma in situ, the diagnostic material was only identified on further levelling through the scored focus. In 28/32 of non-melanoma cases (88%), the scored focus identified either diagnostic features of a particular lesion or pathologic features that correlated with the clinical impression of change/atypia including altered architecture or distribution of pigmentation, features of irritation or regression.
Conclusions
The "punch scoring technique" allows direct clinicopathological correlation and facilitates early melanoma diagnosis by focussing attention to clinically suspicious areas. Furthermore, it does not require special expertise in ex vivo clinical techniques for implementation. Nevertheless, examination of the lesion beyond the scored focus is also necessary to make a diagnosis of melanoma in some cases.
This article is protected by copyright. All rights reserved.
http://ift.tt/2wyx1ZQ
Adeno-Associated Virus-Human Bocavirus 1 Chimeric Vectors: Ferreting Out Their Role in Airway Gene Therapy
Human Gene Therapy Aug 2017, Vol. 28, No. 8: 611-611.
http://ift.tt/2vr5PvX
In vivo Endocrine Secretion of Prostacyclin Following Expression of a Cyclooxygenase-1/Prostacyclin Fusion Protein in the Salivary Glands of Rats Via Nonviral Gene Therapy
Human Gene Therapy Aug 2017, Vol. 28, No. 8: 681-689.
http://ift.tt/2vqVlwx
British Society for Gene and Cell Therapy Annual Conference and Joint UK Regenerative Medicine Platform Meeting; Royal Welsh College of Music & Drama Cardiff, Wales, United Kingdom; ; Wednesday April 19–Friday April 21, 2017; Conference Abstracts
Human Gene Therapy Aug 2017, Vol. 28, No. 8: A1-A36.
http://ift.tt/2vISH7V
An Oncolytic Adenovirus Encoding Decorin and Granulocyte Macrophage Colony Stimulating Factor Inhibits Tumor Growth in a Colorectal Tumor Model by Targeting Pro-Tumorigenic Signals and via Immune Activation
Human Gene Therapy Aug 2017, Vol. 28, No. 8: 667-680.
http://ift.tt/2vqv1CF
Gene Therapy Using a miniCEP290 Fragment Delays Photoreceptor Degeneration in a Mouse Model of Leber Congenital Amaurosis
Human Gene Therapy , Vol. 0, No. 0.
http://ift.tt/2vJB9bA
Mutagenic Analysis of an Adeno-Associated Virus Variant Capable of Simultaneously Promoting Immune Resistance and Robust Gene Delivery
Human Gene Therapy , Vol. 0, No. 0.
http://ift.tt/2vIOfpA
Sterile Drug Products from Vital Rx, dba Atlantic Pharmacy and Compounding: FDA Alert - Lack of Sterility Assurance
Audience: Pharmacy, Health Professional, Patient [Posted 08/10/2017] ISSUE: FDA is alerting health care professionals and patients not to use drug products intended to be sterile that are produced and distributed nationwide by Vital Rx Inc., dba...
http://ift.tt/2uKkaS9
Liquid-filled Intragastric Balloon Systems: Letter to Healthcare Providers - Potential Risks
Audience: Surgery, Gastroenterology, Health Professional [Posted 08/10/2017] ISSUE: FDA is issuing an update to alert health care providers of five reports of unanticipated deaths that occurred from 2016 to present in patients with liquid-filled...
http://ift.tt/2hMJNQS
Long Non-coding RNAs and Prostate Cancer
Abstract
Long non-coding RNAs (lncRNAs) are RNA transcripts larger than 200 nucleotides that do not code for proteins whose aberrant expression has been documented in various types of cancer, including prostate cancer. The lack of appropriate sensitive and specific biomarkers for prostate cancer has led to over-diagnosis and overtreatment, making lncRNAs promising novel biomarkers as well as therapeutic targets for the disease. This review attempts to summarize the current knowledge of lncRNA expression patterns and mechanisms in prostate cancer, which contribute to carcinogenesis. Especially, we focused on lncRNAs regulated by androgen receptor and expressed in castration-resistant prostate cancer.
This article is protected by copyright. All rights reserved.
http://ift.tt/2uuw9DY
Modeling phenotypes of malignant gliomas
Abstract
Malignant gliomas are primary tumors of the central nervous system characterized by diffuse infiltration into the brain and a high recurrence rate. Advances in comprehensive genomic studies have provided unprecedented insight into the genetic and molecular heterogeneity of these tumors and refined our understanding of their evolution from low to high grade. However, similar levels of phenotypic characterization are indispensable to understanding the complexity of malignant gliomas. Experimental glioma models have also achieved great progress in recent years. Advances in transgenic technologies and cell culture have allowed the establishment of mouse models that mirror the human disease with increasing fidelity and which support single-cell resolution for phenotypic analyses. Here we review the major types of preclinical glioma models, with an emphasis on how recent developments in experimental modeling have shed new light on two fundamental aspects of glioma phenotype, their cell of origin and their invasive potential.
This article is protected by copyright. All rights reserved.
http://ift.tt/2vIa5ty
Facet-to-facet Linking of Shape-anisotropic Colloidal Cadmium Chalcogenide Nanostructures
http://ift.tt/2uKFAyr
Sterile Drug Products from Vital Rx, dba Atlantic Pharmacy and Compounding: FDA Alert - Lack of Sterility Assurance
Audience: Pharmacy, Health Professional, Patient [Posted 08/10/2017] ISSUE: FDA is alerting health care professionals and patients not to use drug products intended to be sterile that are produced and distributed nationwide by Vital Rx Inc., dba...
http://ift.tt/2uKkaS9
Liquid-filled Intragastric Balloon Systems: Letter to Healthcare Providers - Potential Risks
Audience: Surgery, Gastroenterology, Health Professional [Posted 08/10/2017] ISSUE: FDA is issuing an update to alert health care providers of five reports of unanticipated deaths that occurred from 2016 to present in patients with liquid-filled...
http://ift.tt/2hMJNQS
Colonoscopic full-thickness resection using an over-the-scope device: a prospective multicentre study in various indications
Objective
Endoscopic full-thickness resection (EFTR) is a novel treatment of colorectal lesions not amenable to conventional endoscopic resection. The aim of this prospective multicentre study was to assess the efficacy and safety of the full-thickness resection device.
Design181 patients were recruited in 9 centres with the indication of difficult adenomas (non-lifting and/or at difficult locations), early cancers and subepithelial tumours (SET). Primary endpoint was complete en bloc and R0 resection.
ResultsEFTR was technically successful in 89.5%, R0 resection rate was 76.9%. In 127 patients with difficult adenomas and benign histology, R0 resection rate was 77.7%. In 14 cases, lesions harboured unsuspected cancer, another 15 lesions were primarily known as cancers. Of these 29 cases, R0 resection was achieved in 72.4%; 8 further cases had deep submucosal infiltration >1000 µm. Therefore, curative resection could only be achieved in 13/29 (44.8%). In the subgroup with SET (n=23), R0 resection rate was 87.0%. In general, R0 resection rate was higher with lesions ≤2 cm vs >2 cm (81.2% vs 58.1%, p=0.0038). Adverse event rate was 9.9% with a 2.2% rate of emergency surgery. Three-month follow-up was available from 154 cases and recurrent/residual tumour was evident in 15.3%.
ConclusionEFTR has a reasonable technical efficacy especially in lesions ≤2 cm with acceptable complication rates. Curative resection rate for early cancers was too low to recommend its primary use in this indication. Further comparative studies have to show the clinical value and long-term outcome of EFTR in benign colorectal lesions.
Trial registration numberNCT02362126; Results.
http://ift.tt/2fvcwsU
Minimal access necrosectomy: the newest advance of many in the treatment of necrotising pancreatitis
This study by van Brunschott and international colleagues1 has shown that when possible in high-risk patients with severe acute necrotising pancreatitis, a minimal access approach for drainage combined with a necrosectomy, either via an operative (ie, laparoscopic like) or an endoscopic transgastric or transduodenal approach, decreases mortality of this horrible disease when compared with the classic open operation (laparotomy). These data are convincing and support the use of such minimal access approaches whenever feasible. This study reviews the data on another huge advance in our treatment and understanding of this horrific disease.
In this commentary, I want to use this study as an example of the marked changes in our thinking of pancreatitis over the last 40 years. Our current approach to the treatment of necrotising pancreatitis really had its origin in the 1970s with the introduction of the new concept of an operative 'necrosectomy' rather than just peripancreatic...
http://ift.tt/2hNTlv3
Combined antioxidant effects of Neem extract, bacteria, red blood cells and Lysozyme: possible relation to periodontal disease
The common usage of chewing sticks prepared from Neem tree (Azadirachta indica) in India suggests its potential efficacy in periodontal diseases. The objective of this study is to explore the antibacterial effect...
http://ift.tt/2ut0GWN
The ethanol extract of Aquilariae Lignum ameliorates hippocampal oxidative stress in a repeated restraint stress mouse model
Chronic stress contributes to the development of brain disorders, such as neurodegenerative and psychiatric diseases. Oxidative damage is well known as a causative factor for pathogenic process in brain tissue...
http://ift.tt/2uKf7B8
The cardioprotective and antiarrhythmic effects of Nardostachys chinensis in animal and cell experiments
Cardiovascular disease (CVD) is the leading cause of premature death throughout the world. An estimated 17.5 million people died from CVD in 2012, representing 31% of all global deaths. Nardostachys chinensis (NC...
http://ift.tt/2utIbNX
Flavonolignans inhibit the arachidonic acid pathway in blood platelets
Arachidonic acid metabolism by cyclooxygenase (COX) is a major pathway for blood platelets' activation, which is associated with pro-thrombotic platelet activity and the production of pro-inflammatory mediator...
http://ift.tt/2utqLVP
The functional property of royal jelly 10-hydroxy-2-decenoic acid as a melanogenesis inhibitor
It has been reported that royal jelly would reduce melanin synthesis and inhibit the expression of melanogensis related proteins and genes. In this study, we evaluate the anti-melanogenic and depigmenting acti...
http://ift.tt/2uKIVNR
Hospital treatment costs and length of stay associated with hypertension and multimorbidity after hemorrhagic stroke
Previous studies have identified various treatment and patient characteristics that may be associated with higher hospital cost after spontaneous intracerebral hemorrhage (ICH); a devastating type of stroke. P...
http://ift.tt/2vT6nNd
Quantitative Localization of a Golgi Protein by Imaging Its Center of Fluorescence Mass
http://ift.tt/2uKFl6h
Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS
http://ift.tt/2uK60QI
What's the future of EMS?
BOCA RATON, Fla. — The EMS community, through a two-year process facilitated by Mike Taigman, is creating a vision for what a patient-centered, evidence-based EMS system will look like in 30 years and how to get there. Paramedic chiefs and EMS leaders at the Pinnacle EMS conference were briefed on the top developments in the first 50 years of EMS by Jon Krohmer, MD, Director, NHTSA Office of EMS ...
http://ift.tt/2vSWEXl
Ill. fire department gets new CPR equipment to give patient 'best possible chance'
The device goes under a person's back, while another part wraps over a person's chest and holds a device which applies the compressions
http://ift.tt/2vqDdTv
Therapy-Related Clonal Hematopoiesis in Patients with Non-hematologic Cancers Is Common and Associated with Adverse Clinical Outcomes
Coombs et al. examined a large cohort of solid tumor patients who underwent deep-coverage, paired tumor/blood sequencing and demonstrated that clonal hematopoiesis is common and associated with increasing age, tobacco use, and prior radiation therapy and that it predicts an increased risk of hematologic cancers and shorter survival.
http://ift.tt/2vSoUZZ
Modeling of TREX1-Dependent Autoimmune Disease using Human Stem Cells Highlights L1 Accumulation as a Source of Neuroinflammation
Thomas et al. used human pluripotent stem cells to dissect the contribution of neurons and glia to the neuroinflammatory disorder Aicardi-Goutières syndrome (AGS). They found that mutant cells accumulate retroviral-like extrachromosomal nucleic acids that trigger a neurotoxic response, and they suggest that anti-retrovirals could potentially provide therapy for this disease.
http://ift.tt/2uu3LSc
Mucosa-associated invariant T cells infiltrate hepatic metastases in patients with colorectal carcinoma but are rendered dysfunctional within and adjacent to tumor microenvironment
Abstract
Mucosa-associated invariant T (MAIT) cells are innate-like T lymphocytes that are unusually abundant in the human liver, a common site of colorectal carcinoma (CRC) metastasis. However, whether they contribute to immune surveillance against colorectal liver metastasis (CRLM) is essentially unexplored. In addition, whether MAIT cell functions can be impacted by chemotherapy is unclear. These are important questions given MAIT cells' potent immunomodulatory and inflammatory properties. Herein, we examined the frequencies and functions of peripheral blood, healthy liver tissue, tumor-margin and tumor-infiltrating MAIT cells in 21 CRLM patients who received no chemotherapy, FOLFOX, or a combination of FOLFOX and Avastin before they underwent liver resection. We found that MAIT cells, defined as CD3ε+Vα7.2+CD161++ or CD3ε+MR1 tetramer+ cells, were present within both healthy and tumor-afflicted hepatic tissues. Paired and grouped analyses of samples revealed the physical proximity of MAIT cells to metastatic lesions to drastically influence their functional competence. Accordingly, unlike those residing in the healthy liver compartment, tumor-infiltrating MAIT cells failed to produce IFN-γ in response to a panel of TCR and cytokine receptor ligands, and tumor-margin MAIT cells were only partially active. Furthermore, chemotherapy did not account for intratumoral MAIT cell insufficiencies. Our findings demonstrate for the first time that CRLM-penetrating MAIT cells exhibit wide-ranging functional impairments, which are dictated by their physical location but not by preoperative chemotherapy. Therefore, we propose that MAIT cells may provide an attractive therapeutic target in CRC and that their ligands may be combined with chemotherapeutic agents to treat CRLM.
http://ift.tt/2fvyTyk
20 years of Critical Care
Professor Stephen Brett, Associate Editor for Critical Care, shares his thoughts on the journal which celebrates 20 years in publication this year
https://www.youtube.com/watch?v=qcLTx1AupS8
Gambogic acid sensitizes gemcitabine efficacy in pancreatic cancer by reducing the expression of ribonucleotide reductase subunit-M2 (RRM2)
Abstract
Background
Pancreatic cancer is susceptible to gemcitabine resistance, and patients receive less benefit from gemcitabine chemotherapy. Previous studies report that gambogic acid possesses antineoplastic properties; however, to our knowledge, there have been no specific studies on its effects in pancreatic cancer. Therefore, the purpose of this study was to explore whether increases the sensitivity of pancreatic cancer to gemcitabine, and determine the synergistic effects of gambogic acid and gemcitabine against pancreatic cancer.
Methods
The effects of gambogic acid on cell viability, the cell cycle, and apoptosis were assessed using 4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) and flow cytometry in pancreatic cancer cell lines. Protein expression was detected by western blot analysis and mRNA expression was detected using q-PCR. A xenograft tumor model of pancreatic cancer was used to investigate the synergistic effects of gambogic acid and gemcitabine.
Results
Gambogic acid effectively inhibited the growth of pancreatic cancer cell lines by inducing S-phase cell cycle arrest and apoptosis. Synergistic activity of gambogic acid combined with gemcitabine was observed in PANC-1 and BxPC-3 cells based on the results of MTT, colony formation, and apoptosis assays. Western blot results demonstrated that gambogic acid sensitized gemcitabine-induced apoptosis by enhancing the expression of cleaved caspase-3, cleaved caspase-9, cleaved-PARP, and Bax, and reducing the expression of Bcl-2. In particular, gambogic acid reduced the expression of the ribonucleotide reductase subunit-M2 (RRM2) protein and mRNA, a trend that correlated with resistance to gemcitabine through inhibition of the extracellular signal-regulated kinase (ERK)/E2F1 signaling pathway. Treatment with gambogic acid and gemcitabine significantly repressed tumor growth in the xenograft pancreatic cancer model. Immunohistochemistry results demonstrated a downregulation of p-ERK, E2F1, and RRM2 in mice receiving gambogic acid treatment and combination treatment.
Conclusions
These results demonstrate that gambogic acid sensitizes pancreatic cancer cells to gemcitabine in vitro and in vivo by inhibiting the activation of the ERK/E2F1/RRM2 signaling pathway. The results also indicate that gambogic acid treatment combined with gemcitabine might be a promising chemotherapy strategy for pancreatic cancer.
http://ift.tt/2wxH69m
Epulis-Like Presentation of Gingival Renal Cancer Metastasis
Mouth metastatic cancers are very rare and they usually represent the evidence of a widespread disease. Common primary tumors are lung carcinoma in men and breast carcinoma in women, followed by kidney cancer. In the oral soft tissues, the gingiva is the most common site, suggesting a possible role of inflammation in the attraction of circulating tumor cells. Oral metastasis has a serious prognosis. In this work, we describe the case of a 58-year-old man affected by renal cancer, who was brought to our attention for the appearance of a gingival swelling. Initially, the lesion was excised through a provisional clinical diagnosis of epulis. Subsequently, anatomopathological analysis showed a metastasis compatible with clear-cell carcinoma and specifically its renal origin was confirmed by immunohistochemical techniques.
Case Rep Oncol 2017;10:758–763
http://ift.tt/2wM3mvp
The Successful Treatment of Pulmonary Pleomorphic Carcinoma with Pembrolizumab: A Case Report
Pulmonary pleomorphic carcinomas are rare malignant tumors, and no standard treatments have been established. We herein report the successful treatment of a patient with pulmonary pleomorphic carcinoma with pembrolizumab. A 51-year-old man who was a current smoker presented to our hospital due to dyspnea and hemosputum. Chest X-ray showed right-sided pneumothorax with pleural effusion; chest tube drainage was therefore performed. Computed tomography after chest tube drainage showed a cavitary nodule in the right upper lobe and right hilar and bilateral mediastinal lymphadenopathy. Surgery was performed for the diagnosis and treatment. He was eventually diagnosed with pulmonary pleomorphic carcinoma corresponding to clinical stage IVB (cT2aN2M1c [PLE, ADR, HEP]). The giant cells strongly expressed programmed death ligand-1, and the tumor proportion score was more than 50%. Therefore, pembrolizumab was introduced as the first-line therapy. After 3 cycles of pembrolizumab, his right hilar and bilateral mediastinal lymphadenopathy and pleural dissemination notably decreased. Pembrolizumab might be an effective therapy for pulmonary pleomorphic carcinoma.
Case Rep Oncol 2017;10:752–757
http://ift.tt/2vSL3s6
The impact of personalized probabilistic wall thickness models on peak wall stress in abdominal aortic aneurysms
Summary
If computational models are ever to be used in high stakes decision making in clinical practice, the use of personalized models and predictive simulation techniques is a must. This entails rigorous quantification of uncertainties as well as harnessing available patient-specific data to the greatest extent possible. Although researcher are beginning to realize that taking uncertainty in model input parameters into account is a necessity, the predominantly used probabilistic description for these uncertain parameters are based on elementary random variable models. In this work, we set out for a comparison of different probabilistic models for uncertain input parameters using the example of an uncertain wall thickness in finite element models of abdominal aortic aneurysms. We provide the first comparison between a random variable and a random field model for the aortic wall and investigate the impact on the probability distribution of the computed peak wall stress. Moreover, we show that the uncertainty about the prevailing peak wall stress can be reduced if non-invasively available, patient-specific data is harnessed for the construction of the probabilistic wall thickness model. This article is protected by copyright. All rights reserved.
http://ift.tt/2utlARx
Mucosa-associated invariant T cells infiltrate hepatic metastases in patients with colorectal carcinoma but are rendered dysfunctional within and adjacent to tumor microenvironment
Abstract
Mucosa-associated invariant T (MAIT) cells are innate-like T lymphocytes that are unusually abundant in the human liver, a common site of colorectal carcinoma (CRC) metastasis. However, whether they contribute to immune surveillance against colorectal liver metastasis (CRLM) is essentially unexplored. In addition, whether MAIT cell functions can be impacted by chemotherapy is unclear. These are important questions given MAIT cells' potent immunomodulatory and inflammatory properties. Herein, we examined the frequencies and functions of peripheral blood, healthy liver tissue, tumor-margin and tumor-infiltrating MAIT cells in 21 CRLM patients who received no chemotherapy, FOLFOX, or a combination of FOLFOX and Avastin before they underwent liver resection. We found that MAIT cells, defined as CD3ε+Vα7.2+CD161++ or CD3ε+MR1 tetramer+ cells, were present within both healthy and tumor-afflicted hepatic tissues. Paired and grouped analyses of samples revealed the physical proximity of MAIT cells to metastatic lesions to drastically influence their functional competence. Accordingly, unlike those residing in the healthy liver compartment, tumor-infiltrating MAIT cells failed to produce IFN-γ in response to a panel of TCR and cytokine receptor ligands, and tumor-margin MAIT cells were only partially active. Furthermore, chemotherapy did not account for intratumoral MAIT cell insufficiencies. Our findings demonstrate for the first time that CRLM-penetrating MAIT cells exhibit wide-ranging functional impairments, which are dictated by their physical location but not by preoperative chemotherapy. Therefore, we propose that MAIT cells may provide an attractive therapeutic target in CRC and that their ligands may be combined with chemotherapeutic agents to treat CRLM.
http://ift.tt/2fvyTyk
Oncological outcomes in an Australian cohort according to the new prostate cancer grading groupings
Abstract
Background
A new 5-tiered grading grouping system has recently been endorsed for reporting of prostate cancer (PCa) grade to better reflect escalating risk of progression and cancer death. While several validations of the new grade groupings have been undertaken, most have involved centralised pathological review by specialist urological pathologists.
Methods
Participants included 4268 men with non-metastatic PCa diagnosed between 2006 and 2013 from the multi-institutional South Australia Prostate Cancer Clinical Outcomes Collaborative registry. PCa-specific survival and biochemical recurrence-free survival were compared across the five grade groups using multivariable competing risk regression.
Results
For the entire cohort, risk of PCa death increased with increasing grade groups (at biopsy) Adjusted subdistribution-hazard ratios [sHR] and 95% confidence intervals [95%CI] were: 2.2 (1.5–3.6); 2.5 (1.6–4.2); 4.1 (2.6–6.7) and 8.7 (4.5–14.0) for grade groups II (pattern 3 + 4), III (pattern 4 + 3), IV (total score 8) and V (total score 9–10) respectively, relative to grade group I (total score < =6). Clear gradients in risk of PCa death were observed for radical prostatectomy (RP), but were less clear for those who had radiotherapy (RT) with curative intent and those who were managed conservatively. Likewise, risk of biochemical recurrence increased across grade groups, with a strong and clear gradient for men undergoing RP [sHR (95%CI): 2.0 (1.4–2.8); 3.8 (2.9–5.9); 5.3 (3.5–8.0); 11.2 (6.5–19.2) for grade groups II, III, IV and V respectively, relative to grade group I], and a less clear gradient for men undergoing RT.
Conclusion
In general, the new five-tiered grade groupings distinguished PCa survival and recurrence outcomes for men with PCa. The absence of a clear gradient for RT may be due to heterogeneity in this patient group.
http://ift.tt/2wLMjcR
Prognostic significance of BRAF and NRAS mutations in melanoma: a German study from routine care
Abstract
Background
Hotspot mutations of the oncogenes BRAF and NRAS are the most common genetic alterations in cutaneous melanoma. Specific inhibitors of BRAF and MEK have shown significant survival benefits in large phase III trials. However, the prognostic significance of BRAF and NRAS mutations outside of clinical trials remains unclear.
Methods
The mutational status of BRAF (exon 15) and NRAS (exon 2 and 3) was determined in melanoma samples of 217 patients with pyrosequencing and Sanger sequencing. The genotypes were correlated with clinical outcomes and pathologic features of the primary tumors. Time to disease progression was calculated with the cumulative incidence function. Survival analyses were performed with Kaplan-Meier estimates and Cox proportional hazards regression analysis. Relative survival was calculated with the Ederer-II method. Treatment with BRAF and MEK inhibitors and immune checkpoint blockade (ICB) was allowed.
Results
Mutations in BRAF and NRAS were identified in 40.1 and 24.4% of cases, respectively. Concurrent mutations in both genes were detected in further 2.3%. The remaining 33.2% were wild type for the investigated exons (WT). BRAF mutations were significantly associated with younger age at first diagnosis (p < 0.001) and truncal localization of the culprit primary (p = 0.002). The nodular subtype was most common in the NRAS cohort. In addition, NRAS-mutant melanoma patients showed a higher frequency of nodal relapse (p = 0.013) and development of metastatic disease (p = 0.021). The time to loco-regional nodal relapse was shortest in NRAS-mutant melanoma (p = 0.002). Presence of NRAS mutation was an independent risk factor for disease progression in multivariate analysis (HR 2.01; 95% CI 1.02 – 3.98). BRAF-mutant melanoma patients showed a tendency for better overall and relative survival. Genotype was not a consistent risk factor in multivariate analysis. Instead, positive sentinel lymph node status (HR 2.65; 95% CI 1.15 – 6.10) and treatment with ICB in stage IV disease (HR 0.17; 95% CI 0.06–0.48) were significant multivariate risk factors.
Conclusions
NRAS-mutant tumors tended to behave more aggressively particularly in early stages of the disease in this high-risk melanoma population. Treatment with immune checkpoint blockade improved survival in stage IV disease in a real-world setting.
http://ift.tt/2wLnWfo
A lowered 26S proteasome activity correlates with mantle lymphoma cell lines resistance to genotoxic stress
Abstract
Background
Mantle cell lymphoma (MCL) is a B-cell hemopathy characterized by the t(11;14) translocation and the aberrant overexpression of cyclin D1. This results in an unrestrained cell proliferation. Other genetic alterations are common in MCL cells such as SOX11 expression, mutations of ATM and/or TP53 genes, activation of the NF-κB signaling pathway and NOTCH receptors. These alterations lead to the deregulation of the apoptotic machinery and resistance to drugs. We observed that among a panel of MCL cell lines, REC1 cells were resistant towards genotoxic stress. We studied the molecular basis of this resistance.
Methods
We analyzed the cell response regarding apoptosis, senescence, cell cycle arrest, DNA damage response and finally the 26S proteasome activity following a genotoxic treatment that causes double strand DNA breaks.
Results
MCL cell lines displayed various sensitivity/resistance towards genotoxic stress and, in particular, REC1 cells did not enter apoptosis or senescence after an etoposide treatment. Moreover, the G2/M cell cycle checkpoint was deficient in REC1 cells. We observed that three main actors of apoptosis, senescence and cell cycle regulation (cyclin D1, MCL1 and CDC25A) failed to be degraded by the proteasome machinery in REC1 cells. We ruled out a default of the βTrCP E3-ubiquitine ligase but detected a lowered 26S proteasome activity in REC1 cells compared to other cell lines.
Conclusion
The resistance of MCL cells to genotoxic stress correlates with a low 26S proteasome activity. This could represent a relevant biomarker for a subtype of MCL patients with a poor response to therapies and a high risk of relapse.
http://ift.tt/2vSZQTr
Polymorphisms of Plasmodium falciparum k13-propeller gene among migrant workers returning to Henan Province, China from Africa
Henan Province has been in the malaria elimination stage, with all reports of the disease being imported since 2012 and over 90% coming from Africa. Surveillance and population studies are essential for the ea...
http://ift.tt/2uszQho
Clinical and laboratory profiles of patients with early spontaneous healing in cutaneous localized leishmaniasis: a historical cohort study
Skin ulcers in American cutaneous leishmaniasis (ACL) may heal spontaneously after months/years. However, few cases may present quick heal even during diagnosis procedure (early spontaneous healing- ESH). The ...
http://ift.tt/2uKeuHv
Improving ART programme retention and viral suppression are key to maximising impact of treatment as prevention – a modelling study
UNAIDS calls for fewer than 500,000 new HIV infections/year by 2020, with treatment-as-prevention being a key part of their strategy for achieving the target. A better understanding of the contribution to tran...
http://ift.tt/2usfLbd
Sonim helps public safety get FirstNet-ready at APCO 2017
Field-tested, mission critical handsets and accessories available now SAN MATEO, Calif. — Sonim Technologies, the global leader in mission critical LTE-based handsets for public safety, is teaming up with more than a dozen technology leaders at the APCO Annual Conference and Expo in Denver, Aug. 13-16. Sonim has made public safety a priority and has collaborated with public safety professionals ...
http://ift.tt/2hNvRGj
The anti-vascular endothelial growth factor receptor-1 monoclonal antibody D16F7 inhibits invasiveness of human glioblastoma and glioblastoma stem cells
Abstract
Background
Glioblastoma (GBM) is a highly migratory, invasive, and angiogenic brain tumor. Like vascular endothelial growth factor-A (VEGF-A), placental growth factor (PlGF) promotes GBM angiogenesis. VEGF-A is a ligand for both VEGF receptor-1 (VEGFR-1) and VEGFR-2, while PlGF interacts exclusively with VEGFR-1. We recently generated the novel anti-VEGFR-1 monoclonal antibody (mAb) D16F7 that diminishes VEGFR-1 homodimerization/activation without affecting VEGF-A and PlGF binding.
Methods
In the present study, we evaluated the expression of VEGFR-1 in human GBM tissue samples (n = 42) by immunohistochemistry, in cell lines (n = 6) and GBM stem cells (GSCs) (n = 18) by qRT-PCR and/or western blot analysis. In VEGFR-1 positive GBM or GSCs we also analyzed the ability of D16F7 to inhibit GBM invasiveness in response to VEGF-A and PlGF.
Results
Most of GBM specimens stained positively for VEGFR-1 and all but one GBM cell lines expressed VEGFR-1. On the other hand, in GSCs the expression of the receptor was heterogeneous. D16F7 reduced migration and invasion of VEGFR-1 positive GBM cell lines and patient-derived GSCs in response to VEGF-A and PlGF. Interestingly, this effect was also observed in VEGFR-1 positive GSCs transfected to over-express wild-type EGFR (EGFRwt+) or mutant EGFR (ligand binding domain-deficient EGFRvIII+). Furthermore, D16F7 suppressed intracellular signal transduction in VEGFR-1 over-expressing GBM cells by reducing receptor auto-phosphorylation at tyrosine 1213 and downstream Erk1/2 activation induced by receptor ligands.
Conclusion
The results from this study suggest that VEGFR-1 is a relevant target for GBM therapy and that D16F7-derived humanized mAbs warrant further investigation.
http://ift.tt/2wLkTDN
Intraoperative imaging techniques for glioma surgery
Future Oncology, Ahead of Print.
http://ift.tt/2uJQjJp
Identification of key lncRNAs in colorectal cancer progression based on associated protein–protein interaction analysis
Abstract
Background
Colorectal cancer (CRC) was one of the most commonly diagnosed malignancies. The molecular mechanisms involved in the progression of CRC remain unclear. Accumulating evidences showed that long noncoding RNAs (lncRNAs) played key roles in tumorigenesis, cancer progression, and metastasis. Therefore, we aimed to explore the roles of lncRNAs in the progression of CRC.
Methods
In this study, we aimed to identify differentially expressed lncRNAs and messenger RNAs (mRNAs) in CRC by analyzing a cohort of previously published datasets: GSE64857. GO and KEGG pathway analyses were applied to give us insight in the functions of those lncRNAs and mRNAs in CRC.
Results
Totally, 46 lncRNAs were identified as differentially expressed between stage II and stage III CRC for the first time screening by microarray. GO and KEGG pathway analyses showed that differentially expressed lncRNAs were involved in regulating signal transduction, cell adhesion, cell differentiation, focal adhesion, and cell adhesion molecules.
Conclusions
We found three lncRNAs (LOC100129973, PGM5-AS1, and TTTY10) widely co-expressed with differentially expressed mRNAs. We also constructed lncRNA-associated PPI in CRC and found that these lncRNAs may be associated with CRC progression. Moreover, we found that high PGM5-AS1 expression levels were associated with worse overall survival in CRC cancer. We believe that this study would provide novel potential therapeutic and prognostic targets for CRC.
http://ift.tt/2vI1c36
-
Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
-
Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
-
heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
