
https://ift.tt/2x6DYSQ
Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.
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Mahomet Allum was a flamboyant philanthropist and herbalist who worked in South Australia in the early part of last century, whose herbal therapies generated some controversy at the time. Two of his preparations have survived to the present day, a general tonic and a treatment for liver and kidney dysfunction. Given the frequent use of pharmaceutical drugs in "tonics" at the time, toxicological analysis was undertaken at Forensic Science SA, Adelaide with liquid chromatography/quadrupole-time-of-flight mass-spectrometer (LC-QTOF MS), liquid-chromatography/ diode array detector (LC/UV) and gas chromatography/ nitrogen phosphorous- detector/mass-spectrometer (GC-NPD/MS), to look for common drugs. In addition DNA analysis was also undertaken at Trace and Environmental DNA (TrEnD) Laboratory (Curtin University) to evaluate the types of plant products used to make these remedies. The general tonic contained genera from the Triticeae (wheat) family as well as the Medicago family (includes alfalfa), possibly as fillers. Other genera found included Utrica (nettle) and Passiflora (passion flower). The preparation for liver and kidney disease also contained genera from the Medicago family as well as genera Arctostaphylos (bear berry) which has traditionally been used for the treatment of dysuria and bladder stones. No common drugs were found. Thus it appears that the two treatments prepared by Mahomet Allum contained only herbal substances and not adulterant pharmaceutical agents. The herbals identified provide an insight into herbalist practices in the early twentieth century.
Asian Journal of Endoscopic Surgery, EarlyView.
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Due to limitations of conventional medicine for atopic eczema (AE), complementary and alternative medicine (CAM) is widely used as an alternative, maintaining, or simultaneous treatment for AE. We aimed to eva...
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Cancers, Vol. 10, Pages 358: Ovarian Tumor Microenvironment Signaling: Convergence on the Rac1 GTPase
Cancers doi: 10.3390/cancers10100358
Authors: Laurie G. Hudson Jennifer M. Gillette Huining Kang Melanie R. Rivera Angela Wandinger-Ness
The tumor microenvironment for epithelial ovarian cancer is complex and rich in bioactive molecules that modulate cell-cell interactions and stimulate numerous signal transduction cascades. These signals ultimately modulate all aspects of tumor behavior including progression, metastasis and therapeutic response. Many of the signaling pathways converge on the small GTPase Ras-related C3 botulinum toxin substrate (Rac)1. In addition to regulating actin cytoskeleton remodeling necessary for tumor cell adhesion, migration and invasion, Rac1 through its downstream effectors, regulates cancer cell survival, tumor angiogenesis, phenotypic plasticity, quiescence, and resistance to therapeutics. In this review we discuss evidence for Rac1 activation within the ovarian tumor microenvironment, mechanisms of Rac1 dysregulation as they apply to ovarian cancer, and the potential benefits of targeting aberrant Rac1 activity in this disease. The potential for Rac1 contribution to extraperitoneal dissemination of ovarian cancer is addressed.
A pharmacological probe identifies cystathionine β-synthase as a new negative regulator for ferroptosis
A pharmacological probe identifies cystathionine β-synthase as a new negative regulator for ferroptosis, Published online: 26 September 2018; doi:10.1038/s41419-018-1063-2
A pharmacological probe identifies cystathionine β-synthase as a new negative regulator for ferroptosisHMGB1 promotes ERK-mediated mitochondrial Drp1 phosphorylation for chemoresistance through RAGE in colorectal cancer
HMGB1 promotes ERK-mediated mitochondrial Drp1 phosphorylation for chemoresistance through RAGE in colorectal cancer, Published online: 26 September 2018; doi:10.1038/s41419-018-1019-6
HMGB1 promotes ERK-mediated mitochondrial Drp1 phosphorylation for chemoresistance through RAGE in colorectal cancerNeuroprotection of retinal ganglion cells by a novel gene therapy construct that achieves sustained enhancement of brain-derived neurotrophic factor/tropomyosin-related kinase receptor-B signaling
Neuroprotection of retinal ganglion cells by a novel gene therapy construct that achieves sustained enhancement of brain-derived neurotrophic factor/tropomyosin-related kinase receptor-B signaling, Published online: 26 September 2018; doi:10.1038/s41419-018-1041-8
Neuroprotection of retinal ganglion cells by a novel gene therapy construct that achieves sustained enhancement of brain-derived neurotrophic factor/tropomyosin-related kinase receptor-B signalingThe antipsychotic agent trifluoperazine hydrochloride suppresses triple-negative breast cancer tumor growth and brain metastasis by inducing G0/G1 arrest and apoptosis
The antipsychotic agent trifluoperazine hydrochloride suppresses triple-negative breast cancer tumor growth and brain metastasis by inducing G0/G1 arrest and apoptosis, Published online: 26 September 2018; doi:10.1038/s41419-018-1046-3
The antipsychotic agent trifluoperazine hydrochloride suppresses triple-negative breast cancer tumor growth and brain metastasis by inducing G0/G1 arrest and apoptosisThis review summarizes the latest scientific evidence, primarily from systematic reviews/meta-analyses and large cohort studies, on the impact of health issues among women of childbearing age and their effect on their offspring during pregnancy and from birth to adulthood.
Women of childbearing age with overweight/obesity, diabetes, and hypertension prior to pregnancy are at increased risk for adverse outcomes during pregnancy, such as excessive gestational weight gain, gestational diabetes mellitus, and hypertensive disorders of pregnancy. These adverse outcomes could complicate delivery and put their offspring at risk of developing overweight/obesity, diabetes, and hypertension (i.e., intergenerational transmission of health issues).
Interventions should target women of childbearing age, especially those who wish to conceive, in order to possibly stop the transmission of women's health issues to the offspring and favor a healthy pregnancy from the start. This could be one of the best strategies to promote both maternal and child health.
Optic cup is an important structure in ophthalmologic diagnosis such as glaucoma. Automatic optic cup segmentation is also a key issue in computer aided diagnosis based on digital fundus image. However, curren...
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Peripheral diagnostics for Alzheimer's disease (AD) continue to be developed. Diagnostics capable of detecting AD before the onset of symptoms are particularly desirable, and, given the fact that early detecti...
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The objective of this study was to compare the maxillary transverse dimensions between subjects with impacted maxillary canines and subjects without canine impactions, with similar vertical and sagittal features.
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The purpose of this study was to evaluate the short-term impact of rapid maxillary expansion (RME) on the eruption paths of ectopically and normally erupting maxillary canines in the mixed dentition.
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Current methods to evaluate root position either are inaccurate (panoramic radiograph) or expose patients to relatively large amounts of radiation (cone-beam computed tomography [CBCT]). A method to evaluate root position by generating an expected root position (ERP) setup was recently reported but has not been validated. The purpose of this study was to quantitatively assess the accuracy and reliability of the ERP setup with adequate statistical power.
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Bracket placement and removal are 2 of the most critical processes during orthodontic treatment, and indirect bonding is a clinical technique that has continued to rise in popularity as clinical efficiency has improved. Indirect bonding has advantages and disadvantages. The authors of this in-vitro study sought to compare shear bond strength, adhesive remnant index, and color change between self-etch and acid-etch primers, between direct and indirect bonding, and roughness of the enamel after debond between a 12-blade bur and an aluminum oxide polisher.
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Deepbites can be corrected by intrusion of mandibular anterior teeth. Direct anchorage with miniscrews simplifies complex tooth movements; however, few studies have reported their use for mandibular anterior intrusion. The purpose of this study was to evaluate, by means of the finite element method, initial tooth displacement and periodontal stress distribution using various mandibular anterior intrusion mechanics. Miniscrews were used as skeletal anchorage devices.
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Gary was your favorite classmate. He and his wife spent countless hours with you during your residency. Gary eventually established a practice a few miles from yours, facilitating your decades-long camaraderie. When he was diagnosed with ALS and he asked you to support his son's application to an orthodontic residency, you had no choice but to oblige him. You didn't know his son Chet well. But given your relationship with Gary, you planned to do anything you could to support Chet's application so that he could eventually assume his father's practice.
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The objectives of this research were to evaluate changes in occlusal components in 3 subperiods during a 10-year posttreatment time span and to examine the long-term effects of fixed retention on maxillary and mandibular anterior alignment.
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You had a patient with mandibular skeletal retrognathism and mandibular arch crowding. There were 2 viable treatment plans. In no particular order or implication of which is the better course of treatment, the first treatment plan called for mandibular premolar extractions and mandibular advancement surgery. The other treatment plan called for camouflage therapy without extractions to create the best possible alignment and intercuspation.
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We read with interest the article "Influence of orthodontic mini-implant penetration of the maxillary sinus in the infrazygomatic crest region" in the May 2018 issue of the AJO-DO,1 and we believe that this topic is relevant for current orthodontic practice. We want to point out some misunderstandings in the methodologic section and conclusions.
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A 33-year-old woman had a chief complaint of difficulty chewing, caused by a constricted mandibular arch and a unilateral full buccal crossbite (scissors-bite or Brodie bite). She requested minimally invasive treatment but agreed to anchorage with extra-alveolar temporary anchorage devices as needed. Her facial form was convex with protrusive but competent lips. Skeletally, the maxilla was protrusive (SNA, 86°) with an ANB angle of 5°. Amounts of crowding were 5 mm in the mandibular arch and 3 mm in the maxillary arch.
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We are pleased that our article attracted attention and would like to clarify some misunderstandings.1
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The aim of this investigation was to evaluate the effects of low-level laser therapy on interleukin-1β (IL-1β) levels in gingival crevicular fluid and its correlation with orthodontic tooth movement.
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I was the first one in my family to graduate from college. My father was a small-business owner with a high school diploma who employed many people during his career, including some with PhD degrees. I learned from him early on that having an advanced degree was no guarantee of success because all too often it stymied innovation. He also believed that those who have the good fortune of success have an unwritten social contract to give back to society, each in his or her own way.
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In this study, we aimed to determine the effect of regular probiotic consumption on microbial colonization in saliva in orthodontic patients and to comparatively evaluate the difference between the systemic consumption of probiotic products and the local application.
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Purpose: Despite a growing arsenal of approved drugs, therapeutic resistance remains a formidable and, often, insurmountable challenge in cancer treatment. The mechanisms underlying therapeutic resistance remain largely unresolved and, thus, examples of effective combinatorial or sequential strategies to combat resistance are rare. Here, we present Differential Sensitivity Analysis for Resistant Malignancies (DISARM), a novel, integrated drug screen analysis tool designed to address this dilemma. Experimental Design: DISARM, a software package and web-based application, analyzes drug response data to prioritize candidate therapies for models with resistance to a reference drug and to assess whether response to a reference drug can be utilized to predict future response to other agents. Using cisplatin as our reference drug, we applied DISARM to models from nine cancers commonly treated with frontline platinum chemotherapy including recalcitrant malignancies such as small cell lung cancer (SCLC) and pancreatic adenocarcinoma (PAAD). Results: In cisplatin-resistant models, DISARM identified novel candidates including multiple inhibitors of PI3K, MEK and BCL-2, among other classes, across unrelated malignancies. Additionally, DISARM facilitated the selection of predictive biomarkers of response and identification of unique molecular subtypes, such as contrasting ASCL1-low/cMYC-high SCLC targetable by AURKA inhibitors and ASCL1-high/cMYC-low SCLC targetable by BCL-2 inhibitors. Utilizing these predictions, we assessed several of DISARM's top candidates including inhibitors of AURKA, BCL-2, and HSP90 to confirm their activity in cisplatin-resistant SCLC models. Conclusions: DISARM represents the first validated tool to analyze large-scale in vitro drug response data to statistically optimize candidate drug and biomarker selection aimed at overcoming candidate drug resistance.
Purpose: Metastatic castration resistant prostate cancer (mCRPC) is a lethal but clinically heterogeneous disease, with patients having variable benefit from endocrine and cytotoxic treatments. Intra-patient genomic heterogeneity could be a contributing factor to this clinical heterogeneity. Here we used whole-genome sequencing (WGS) to investigate genomic heterogeneity in 21 previously treated CRPC metastases from 10 patients to investigate intra-patient molecular heterogeneity (IPMH). Experimental Design: WGS was performed on topographically separate metastases from patients with advanced metastatic prostate cancer (PCa). IPMH of the RB1 gene was identified and further evaluated by fluorescent in situ (FISH) and immunohistochemistry (IHC) assays. Results: WGS identified limited IPMH for putative driver events. However, heterogeneous genomic aberrations of RB1 were detected. We confirmed the presence of these RB1 somatic copy number aberrations (SCNA), initially identified by WG, with FISH, and identified novel structural variants (SV) involving RB1 in 6 samples from three of these ten patients (30%; 3/10). WGS uncovered a novel deleterious RB1 structural lesion constituted of an intra-genic tandem duplication involving multiple exons and associating with protein loss. Using RB1 IHC in a large series of mCRPC biopsies, we identified heterogeneous expression in ~28% of mCRPCs. Conclusion: mCRPCs have a high prevalence of RB1 genomic aberrations, with structural variants, including rearrangements, being common. Intra-patient genomic and expression heterogeneity favor RB1 aberrations as late, sub-clonal events that increase in prevalence due to treatment selective pressures.
The reduced acylation phenotype describes the inability of certain accessions of maize (Zea mays [L.]) to produce significant amounts of acylated anthocyanins, which are typically the most abundant pigments. Acylated anthocyanins are important for their association with stability and are therefore important for the various industries using anthocyanins as natural colorants to replace synthetic dyes. Many anthocyanin acyltransferases have been characterized in other species; however, no anthocyanin acyltransferases have been characterized in maize. Therefore, a mapping population was developed from a cross between mutant stock 707G and wild-type acylation line B73 to identify the locus associated with the reduced acylation trait. High-performance liquid chromatography was used to assay the pigment content and composition of 129 F2 lines generated in the mapping population. Recessive alleles of Colorless1, Colored1, and the reduced acylation mutant all decreased anthocyanin content while Intensifier1 increased anthocyanin content in aleurone tissue. The association of increased proportions of acylation with increased anthocyanin content indicates acylation may be important for increasing the stability of anthocyanins in vivo. Genotyping-by-sequencing was used to create SNP markers to map the reduced acylation locus. In the QTL analysis, a segment of Chromosome 1 containing transferase family protein GRMZM2G387394 was found to be significant. A UniformMu Mu transposon knockout of GRMZM2G387394 demonstrated this gene has anthocyanidin malonyltransferase activity and will therefore be named Anthocyanin Acyltransferase1 (AAT1). AAT1 is the first anthocyanin acyltransferase characterized in a monocot species and will increase our knowledge of all acyltransferase family members.
HIV is a major driver of the tuberculosis epidemic in sub-Saharan Africa. The population-level impact of antiretroviral therapy (ART) scale-up on tuberculosis rates in this region has not been well studied. We...
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Burkholderia pseudomallei is a gram negative bacteria that causes a spectrum of human diseases in the tropics. Although melioidosis is endemic in Southeast Asia, large clinical case series were rarely reported fr...
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Michael Grunstein, PhD, and C. David Allis, PhD, share prestigious prize.
We present a cohort of 41 patients with osimertinib resistance biopsies, including two with an acquired CCDC6-RET fusion. While RET fusions have been identified in resistant EGFR-mutant NSCLC, their role in acquired resistance to EGFR inhibitors is not well described. To assess the biological implications of RET fusions in an EGFR-mutant cancer, we expressed CCDC6-RET in PC9 (EGFR del19) and MGH134 (EGFR L858R/T790M) cells and found that CCDC6-RET was sufficient to confer resistance to EGFR-TKIs. The selective RET inhibitors BLU-667 or cabozantinib resensitized CCDC6-RET-expressing cells to EGFR inhibition. Finally, we treated two patients with EGFR-mutant NSCLC and RET-mediated resistance with osimertinib and BLU-667. The combination was well-tolerated and led to rapid radiographic response in both patients. This study provides proof-of-concept that RET fusions can mediate acquired resistance to EGFR TKIs and that combined EGFR and RET inhibition with osimertinib/BLU-667 may be a well-tolerated and effective treatment strategy for such patients.
The folate-coupled metabolic enzyme MTHFD2 is overexpressed in many tumor types and required for cancer cell proliferation, and is therefore of interest as a potential cancer therapeutic target. However, recent evidence suggests that MTHFD2 has a non-enzymatic function which may underlie the dependence of cancer cells on this protein. Understanding this non-enzymatic function is important for optimal targeting of MTHFD2 in cancer.
To identify potential non-enzymatic functions of MTHFD2, we defined its interacting proteins using co-immunoprecipitation and mass spectrometry and integrated this information with large-scale co-expression analysis, protein dynamics, and gene expression response to MTHFD2 knockdown.
We found that MTHFD2 physically interacts with a set of nuclear proteins involved in RNA metabolism and translation, including components of the small ribosomal subunit and multiple members of the RNA-processing hnRNP family. Interacting proteins were also in general co-expressed with MTHFD2 in experiments that stimulate or repress proliferation, suggesting a close functional relationship. Also, unlike other folate one-carbon enzymes, the MTHFD2 protein has a short half-life and responds rapidly to serum. Finally, shRNA against MTHFD2 depletes several of its interactors and yields an overall transcriptional response similar to targeted inhibition of certain ribosomal subunits.
Taken together, our findings suggest a novel function of MTHFD2 in RNA metabolism and translation.
Infections caused by multi-drug resistant gram-negative bacterial infections are the principle threats to the critically ill patients of intensive care units. Increasing reports of these infections from the Ne...
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Toxicopathological effects of herbs have always been a major concern. There is scant information available about the toxicopathological effects of Calotropis procera (C. procera) in the fetus. Since the chick embryo is a suitable preclinical model to evaluate the toxicopathological effects of chemicals, the objective of this study is to evaluate the lesions of various dosages of C. procera using a chick embryonic model. Fertile chicken eggs were divided into three equal treatment groups; phosphate buffered saline-injected group and C. procera-injected groups whose individuals were treated with C. procera extract at dosages of 50 or 100 mg/kg egg-weight. Embryos were re-incubated post-treatment and allowed to develop until day 18, after which they were examined for macroscopic and microscopic lesions. Although the embryos which were treated with 50 mg/kg egg-weight of C. procera extract macroscopically were normal as well as the controls, those treated with 100 mg/kg egg-weight were stunted and under developed. Microscopic evaluations showed that in embryos treated with 100 mg/kg egg-weight of C. procera, the brain was congested, and severe dilation of central veins and sinusoids as well as hepatocellular degeneration was occurred in liver. Moreover, the kidney and lung were under-developed, but the structure of the heart was normal. Based on our findings, C. procera at dosage of 100 mg/kg is toxic to the chick embryo or/maybe to human fetus during growing period. Further studies are needed to clarify the toxic effects of this plant on the development of fetus.
WEDNESDAY, Sept. 26, 2018 -- Among men who have sex with men (MSM), the change in the annual number of HIV diagnoses from 2008 to 2016 varies with age, according to research published in the Sept. 21 issue of the U.S. Centers for Disease Control and...
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WEDNESDAY, Sept. 26, 2018 -- For patients with left main coronary artery disease (LMCAD), those with and without chronic kidney disease (CKD) undergoing revascularization have similar long-term outcomes with percutaneous coronary intervention (PCI)...
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WEDNESDAY, Sept. 26, 2018 -- Symptoms of burnout and career choice regret are prevalent among U.S. resident physicians, according to a study published in the Sept. 18 issue of the Journal of the American Medical Association. Liselotte N. Dyrbye,...
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WEDNESDAY, Sept. 26, 2018 -- Variation in childhood socioeconomic position (SEP) partially accounts for cognitive performance in older age, with adverse childhood SEP associated with lower level of baseline cognitive performance, according to a...
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WEDNESDAY, Sept. 26, 2018 -- From 2006 through 2013, the weighted estimate of lawn-mower-related injuries was 51,151, with the most common injuries being lacerations, fractures, and amputations, according to a study published online Aug. 1 in Public...
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Colon cancer represents the third most common malignancy worldwide. New drugs with high efficaciousness and safety for the treatment of colon cancer are urgently needed in clinical context. Here, we were aimed to evaluate the antitumor activity of the natural compound α-hederin in human colon cancer cells. We treated SW620 cells with interleukin-6 (IL-6) in vitro to mimic the paracrine inflammatory microenvironment of tumor cells. α-Hederin concentration dependently reduced the viability of IL-6-stimulated SW620 cells. α-Hederin increased the number of IL-6-stimulated SW620 cells at the G2/M phase and reduced the mRNA and protein expression of cyclin B1 and CDK1. Moreover, α-hederin induced apoptosis and loss of mitochondrial membrane potential in IL-6-stimulated SW620 cells. α-Hederin downregulated Bcl-2 expression, upregulated Bax expression, and promoted cytochrome c release from mitochondria into cytoplasm. Additionally, α-hederin elevated the levels of cleaved-caspase-9, cleaved-caspase-3, and cleaved-PARP, but had little effects on the levels of cleaved-caspase-8. Moreover, α-hederin prevented the nuclear translocation of nuclear factor-κB (NF-κB) and reduced the phosphorylation of IκBα and IKKα, suggesting the blockade of NF-κB signaling. NF-κB inhibitor PDTC not only produced similar proapoptotic effects on IL-6-stimulated SW620 cells as α-hederin did, but also synergistically enhanced α-hederin's proapoptotic effects. Furthermore, α-hederin inhibited the phosphorylation of ERK in IL-6-stimulated SW620 cells, which was involved in α-hederin blockade of NF-κB nuclear translocation. Altogether, α-hederin suppressed viability, induced G2/M cell cycle arrest, and stimulated mitochondrial and caspase-dependent apoptosis in colon cancer cells, which were associated with disruption of NF-κB and ERK pathways, suggesting α-hederin as a promising candidate for intervention of colon cancer.
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The appropriate colonoscopy withdrawal times for individual colonic segments are not well known. The relationship between withdrawal time and adenoma/polyp detection rates in individual colonic segments was examined in this study.
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Point of care tests (POCTs) might be used to identify patients with undiagnosed celiac disease who require further evaluation. We performed a large multicenter study to determine the performance of a POCT for celiac disease and assessed celiac disease prevalence in endoscopy centers.
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As the importance of the gut microbiota in health and disease is increasingly recognized interest in interventions that can modulate the microbiota and its interactions with its host has soared. Apart from diet, prebiotics and probiotics represent the most commonly used substances taken in an effort to sustain a healthy microbiome or restore balance when it is believed bacterial homeostasis has been disturbed in disease. While a considerable volume of basic science attests to the ability of various prebiotic molecules and probiotic strains to beneficially influence host immune responses, metabolic processes and neuro-endocrine pathways, the evidence base from human studies leaves much to be desired.
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Endoscopic resection has become the first-line therapy for the management of superficial neoplasia throughout the gastrointestinal tract. Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are established yet distinct techniques for the treatment of superficial gastrointestinal neoplasia. EMR is simpler and faster but is limited by its ability to resect large lesions en-bloc. Limitations of piecemeal EMR of large lesions include a high rate of recurrence and a less than ideal tissue specimen for accurate histologic evaluation.
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Individuals with inflammatory bowel diseases (IBD) carry an increased risk of developing colorectal cancer (CRC). Though family history of CRC is a well-established risk factor in healthy individuals, its role in IBD patients is less clear. The aim of this study was to estimate the risk of CRC in a cohort of IBD patients from Utah and the significance of family history of CRC in a first-degree relative (FDR).
https://ift.tt/2xIJcoQ
Obesity is increasing in younger populations. Barrett's esophagus is associated with central obesity, so we investigated the occurrence of esophageal adenocarcinoma (EAC) in younger patients and compared them with older patients to determine differences in features at presentation and survival times.
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Among immunosuppressive- and biologic-naïve patients with moderate to severely active Crohn's disease (CD), a higher proportion of those treated with the combination of infliximab and azathioprine achieved corticosteroid-free remission at week 26 (CSFR26) than those given infliximab monotherapy; patients given the combination therapy also had higher serum concentrations of infliximab. Enhanced benefit of combination therapy may occur through synergistic modes of action or the influence of azathioprine on infliximab pharmacokinetics.
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Treatment of profound hyponatremia is challenging. Severe symptoms mandate correction by 4 to 6 mEq/L within hours, but with risk factors for osmotic demyelination, daily correction should be <8 mEq/L. With a therapeutic window this narrow, clinicians would like to know how serum sodium (SNa) concentration will respond to their therapy. Based on isotopic measurements, Edelman showed SNa level to be a function of exchangeable sodium and potassium divided by total-body water. Edelman defined this relationship with linear regression yielding an equation of the form y = mx + b, where y is SNa level, x is exchangeable sodium and potassium divided by total-body water, m is the slope, and b is the intercept.
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To assess longitudinal estimates of inpatient costs through early childhood in patients with critical congenital heart defects (CCHDs), for whom reliable estimates are scarce, using a population-based cohort of clinically validated CCHD cases.
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We sought to assess worldwide differences among pediatric patients undergoing hemodialysis. Because practices differ widely regarding nutritional resources, treatment practice, and access to renal replacement therapy, investigators from the Pediatric Investigation and Close Collaboration to examine Ongoing Life Outcomes, the pediatric subset of the MONitoring Dialysis Outcomes Cohort (PICCOLO MONDO) performed this cross-sectional study. We hypothesized that growth would be better in developed countries, possibly at the expense of bone mineral disease.
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Based on experiences and results from newborn screening for severe combined immunodeficiency (SCID), we evaluated the occurrence of chromosome 22q11.2 deletion syndrome (22q11.2DS) in newborns with different T cell receptor excision circles (TREC) results and established a second tier genetic test for 22q11.2DS.
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To describe the epidemiology, response to therapy, and outcomes of Kawasaki disease in a multiethnic community with a large Hispanic and Asian population.
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In 2009, approximately 200 child abuse pediatricians (CAPs) passed the first board certification examination. One major impetus for the new subspecialty was the high rate of missed child abuse cases and the dearth of high-quality research.1 In particular, a landmark 1999 study by Jenny et al demonstrated that in 32% of cases of abusive head trauma (AHT), there had been a previous missed opportunity to make a diagnosis.2
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To assess sound levels of 4 high-frequency neonatal ventilators to determine whether there is a safety benefit in using modern high-frequency ventilators compared with older models.
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To determine whether a monogenic basis explains sudden infant death syndrome (SIDS) using an exome-wide focus.
https://ift.tt/2IjMAdY
To evaluate whether the presence of patent ductus arteriosus (PDA) in preterm infants worsens long-term neurodevelopmental outcomes.
https://ift.tt/2IhzRIF
To assess whether body mass index (BMI) provides a better assessment of measured adiposity at age 1 month compared with weight-for-length (WFL).
https://ift.tt/2xH1Eyp
To determine whether privately owned ambulatory surgery centers (ASCs) increase pediatric tympanostomy tube use in their surrounding communities.
https://ift.tt/2IjMDqa
Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a subtype of Hodgkin lymphoma that frequently shows a nodal growth pattern with abundant reactive B cells in the microenvironment. Early NLPHL cases can be particularly difficult to differentiate from progressively transformed germinal centers (PTGC). Since PTGC have been described to be IgG4 associated in a relatively high proportion of cases, the aim of the present study was to determine if IgG4 immunostaining can be helpful in the differential diagnosis between NLPHL and PTGC. We furthermore aimed to learn if LP cells can express IgG4. For this purpose, 58 cases of PTGC and 56 cases of NLPHL were assessed using IgG4 immunostaining. We could confirm that a significant number of PTGC cases showed high numbers of IgG4-positive plasma cells (22/58, 38%), whereas hot spot areas of IgG4-positive plasma cells were not found in any of the NLPHL cases. In lymph node areas with the differential diagnosis of NLPHL and PTGC, IgG4 immunostaining can therefore provide a helpful diagnostic tool to rule out NLPHL when a high number of IgG4-positive plasma cells are encountered. We also assessed 13 cases with a combination of NLPHL and PTGC in the same lymph node. Five of these cases presented hot spot areas of IgG4-positive plasma cells in the PTGC regions, while no significant numbers of IgG4-positive plasma cells were observed in the NLPHL part of the lymph node. LP cells were never IgG4 positive. Furthermore, immunoglobulin heavy chain rearrangements of single IgG4-positive plasma cells were analyzed, revealing a polyclonal plasma cell population. In summary, our data suggest that IgG4 immunostaining can provide additional information in the diagnostic workup of cases with the differential diagnosis of NLPHL and PTGC. IgG4's inefficiency in clearing antigens may explain why lymph nodes with PTGC are usually strongly enlarged and develop a high number of hyperplastic germinal centers. Polyclonal immunoglobulin heavy chain rearrangements in IgG4-positive plasma cells further support the hypothesis that PTGC represent a misled immune reaction.
WEDNESDAY, Sept. 26, 2018 -- Older individuals with multiple sclerosis (MS) report less severe depressive symptoms and better physical quality of life (QOL), compared to younger patients, according to a brief report recently published in...
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WEDNESDAY, Sept. 26, 2018 -- Diet is an important component that impacts cardiovascular risk, and policies should be implemented to improve dietary composition, according to an article published in the Aug. 21 issue of the Journal of the American...
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WEDNESDAY, Sept. 26, 2018 -- Neonates with congenital heart disease (CHD) have enlarged kidneys on average, according to a study published online Sept. 11 in Pediatric Research. Noting that as part of the "brain-sparing phenomenon," blood flow is...
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WEDNESDAY, Sept. 26, 2018 -- Higher inpatient pain scores and postoperative opioid consumption are associated with persistent opioid use of up to six months among children and adolescents who have undergone cytoreductive surgery with hyperthermic...
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WEDNESDAY, Sept. 26, 2018 -- Use of a decision aid can improve parent knowledge for children with minor head injury at intermediate risk of clinically important traumatic brain injury (ciTBI), according to a study published online Sept. 21 in JAMA...
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WEDNESDAY, Sept. 26, 2018 -- Lorcaserin facilitates sustained weight loss without increasing the rate of major cardiovascular events among overweight or obese patients, according to a study published in the Sept. 20 issue of the New England Journal...
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WEDNESDAY, Sept. 26, 2018 -- More experienced surgeons are more confident in their assessments of perceived futility, according to a study recently published in the Journal of the American College of Surgeons. Rachel S. Morris, M.D., from the...
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WEDNESDAY, Sept. 26, 2018 -- Once low rheumatoid arthritis (RA) disease activity is achieved with tocilizumab (TCZ) plus methotrexate (MTX), patients can discontinue MTX without significant disease worsening, according to a study published in the...
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WEDNESDAY, Sept. 26, 2018 -- "Pod mods," which are small, rechargeable devices that aerosolize liquid solutions containing nicotine encapsulated in cartridges, pose a danger to adolescent users, according to a perspective article published in the...
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WEDNESDAY, Sept. 26, 2018 -- Many countries are falling short on targets to reduce mortality from non-communicable diseases (NCDs), according to a study published in the Sept. 22 issue of The Lancet. James E. Bennett, Ph.D., from Imperial College...
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In a small trial involving patients with slow-growing B-cell lymphoma, injecting the compound SD-101 directly into tumors (in situ vaccination) and giving low-dose radiation shrank the injected tumors and, frequently, tumors elsewhere in the body.
We describe a protocol to induce atherosclerosis in the aortic root of ApoE-/- mice fed with an atherogenic diet, through a continuous release of aldosterone. Methods to characterize plaque composition are also described.
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Publication date: Available online 25 September 2018
Source: The Spine Journal
Author(s): Tsai-Sheng Fu, Ying-Chih Wang, Chien-Hao Chen, Chia-Wei Chang, Tung-Yi Lin, Chak-Bor Wong, Dave Wei-Chih Chen, Chun-Yi Su
Bone marrow-derived mesenchymal stem cells (BMSCs) and periosteum-derived cells (PDCs) have shown great viability in terms of osteogenic potential and have been considered the major cellular source for skeletal tissue engineering. Using a PDCs-impregnated cell sheet to surround a BMSCs-impregnated tricalcium phosphate (TCP) scaffold might create a periosteum-bone biomimetic bone graft substitute to enhance spine fusion.
The purpose of this study was to determine the feasibility of using this newly tissue-engineered biomimetic bone graft for posterolateral spine fusion.
This study design was based on an animal model using adult male New Zealand White rabbits.
New Zealand White rabbits underwent operation and were divided into 3 groups based on the experimental material implanted in the bilateral L4-5 intertransverse space. Group 1 was BMSCs-free TCP wrapped in a PDCs-free cell sheet. Group 2 was BMSCs-loaded-TCP wrapped in a PDCs-free cell sheet. Group 3 was BMSCs-loaded-TCP wrapped in a PDCs-loaded cell sheet. After 12 weeks, 6 rabbits from each group were euthanized for computed tomography scanning, manual palpation, biomechanical testing, and histology. Each group had 12 radiographic fusion areas for analysis since the right and left intertransverse fusion areas were collected separately.
Radiographic union of 12 fusion areas for group 1, group 2, and group 3 was 0, 3, and 9, respectively. Group 3 had significantly higher fusion success than groups 1 and 2 (p< 0.001). Solid fusion of 6 fusion segments in each group by manual palpation was 0, 1, and 5, accordingly. Group 3 had a higher successful solid fusion rate than groups 1 and 2 (p= 0.005). The average maximal torques at failure was 727±136 N-mm, 627±91 N-mm, and 882±195 N-mm for groups 1, 2, and 3, accordingly. The maximal torque was significantly higher in group 3 than in group 2 (p= 0.028). Histological evaluation verified that new bone regeneration were greater in the group 3 samples.
The results indicated the potential of using a PDCs-impregnated cell sheet to surround the BMSCs-impregnated TCP scaffold for creating a periosteum-bone biomimetic bone graft substitute to enhance bone regeneration and posterolateral fusion success.
The systems-level mechanisms underlying loss of consciousness (LOC) under anesthesia remain unclear. General anesthetics suppress sensory responses within higher-order cortex and feedback connections, both critical elements of predictive coding hypotheses of conscious perception. Responses to auditory novelty may offer promise as biomarkers for consciousness. This study examined anesthesia-induced changes in auditory novelty responses over short (local deviant [LD]) and long (global deviant [GD]) time scales, envisioned to engage preattentive and conscious levels of processing, respectively. Electrocorticographic recordings were obtained in human neurosurgical patients (3 male, 3 female) from four hierarchical processing levels: core auditory cortex, non-core auditory cortex, auditory-related, and PFC. Stimuli were vowel patterns incorporating deviants within and across stimuli (LD and GD). Subjects were presented with stimuli while awake, and during sedation (responsive) and following LOC (unresponsive) under propofol anesthesia. LD and GD effects were assayed as the averaged evoked potential and high gamma (70–150 Hz) activity. In the awake state, LD and GD effects were present in all recorded regions, with averaged evoked potential effects more broadly distributed than high gamma activity. Under sedation, LD effects were preserved in all regions, except PFC. LOC was accompanied by loss of LD effects outside of auditory cortex. By contrast, GD effects were markedly suppressed under sedation in all regions and were absent following LOC. Thus, although the presence of GD effects is indicative of being awake, its absence is not indicative of LOC. Loss of LD effects in higher-order cortical areas may constitute an alternative biomarker of LOC.
SIGNIFICANCE STATEMENT Development of a biomarker that indexes changes in the brain upon loss of consciousness (LOC) under general anesthesia has broad implications for elucidating the neural basis of awareness and clinical relevance to mechanisms of sleep, coma, and disorders of consciousness. Using intracranial recordings from neurosurgery patients, we investigated changes in the activation of cortical networks involved in auditory novelty detection over short (local deviance) and long (global deviance) time scales associated with sedation and LOC under propofol anesthesia. Our results indicate that, whereas the presence of global deviance effects can index awareness, their loss cannot serve as a biomarker for LOC. The dramatic reduction of local deviance effects in areas beyond auditory cortex may constitute an alternative biomarker of LOC.
Changes in excitatory neuron and synapse structure have been recognized as a potential physical source of age-related cognitive decline. Despite the importance of inhibition to brain plasticity, little is known regarding aging-associated changes to inhibitory neurons. Here we test for age-related cellular and circuit changes to inhibitory neurons of mouse visual cortex. We find no substantial difference in inhibitory neuron number, inhibitory neuronal subtypes, or synapse numbers within the cerebral cortex of aged mice compared with younger adults. However, when comparing cortical interneuron morphological parameters, we find differences in complexity, suggesting that arbors are simplified in aged mice. In vivo two-photon microscopy has previously shown that in contrast to pyramidal neurons, inhibitory interneurons retain a capacity for dendritic remodeling in the adult. We find that this capacity diminishes with age and is accompanied by a shift in dynamics from balanced branch additions and retractions to progressive prevalence of retractions, culminating in a dendritic arbor that is both simpler and more stable. Recording of visually evoked potentials shows that aging-related interneuron dendritic arbor simplification and reduced dynamics go hand in hand with loss of induced stimulus-selective response potentiation (SRP), a paradigm for adult visual cortical plasticity. Chronic treatment with the antidepressant fluoxetine reversed deficits in interneuron structural dynamics and restored SRP in aged animals. Our results support a structural basis for age-related impairments in sensory perception, and suggest that declines in inhibitory neuron structural plasticity during aging contribute to reduced functional plasticity.
SIGNIFICANCE STATEMENT Structural alterations in neuronal morphology and synaptic connections have been proposed as a potential physical basis for age–related decline in cognitive function. Little is known regarding aging-associated changes to inhibitory neurons, despite the importance of inhibitory circuitry to adult cortical plasticity and the reorganization of cortical maps. Here we show that brain aging goes hand in hand with progressive structural simplification and reduced plasticity of inhibitory neurons, and a parallel decline in sensory map plasticity. Fluoxetine treatment can attenuate the concurrent age–related declines in interneuron structural and functional plasticity, suggesting it could provide an important therapeutic approach for mitigating sensory and cognitive deficits associated with aging.
Excitatory synapses are specialized cell–cell contacts located on actin-rich dendritic spines that mediate information flow and storage in the brain. The postsynaptic adhesion-G protein-coupled receptor (A-GPCR) BAI1 is a critical regulator of excitatory synaptogenesis, which functions in part by recruiting the Par3-Tiam1 polarity complex to spines, inducing local Rac1 GTPase activation and actin cytoskeletal remodeling. However, a detailed mechanistic understanding of how BAI1 controls synapse and spine development remains elusive. Here, we confirm that BAI1 is required in vivo for hippocampal spine development, and we identify three distinct signaling mechanisms mediating BAI1's prosynaptogenic functions. Using in utero electroporation to sparsely knock down BAI1 expression in hippocampal pyramidal neurons, we show that BAI1 cell-autonomously promotes spinogenesis in the developing mouse brain. BAI1 appears to function as a receptor at synapses, as its extracellular N-terminal segment is required for both its prospinogenic and prosynaptogenic functions. Moreover, BAI1 activation with a Stachel-derived peptide, which mimics a tethered agonist motif found in A-GPCRs, drives synaptic Rac1 activation and subsequent spine and synapse development. We also reveal, for the first time, a trans-synaptic function for BAI1, demonstrating in a mixed-culture assay that BAI1 induces the clustering of presynaptic vesicular glutamate transporter 1 (vGluT1) in contacting axons, indicative of presynaptic differentiation. Finally, we show that BAI1 forms a receptor complex with the synaptogenic cell-adhesion molecule Neuroligin-1 (NRLN1) and mediates NRLN1-dependent spine growth and synapse development. Together, these findings establish BAI1 as an essential postsynaptic A-GPCR that regulates excitatory synaptogenesis by coordinating bidirectional trans-synaptic signaling in cooperation with NRLN1.
SIGNIFICANCE STATEMENT Adhesion-G protein-coupled receptors are cell-adhesion receptors with important roles in nervous system development, function, and neuropsychiatric disorders. The postsynaptic adhesion-G protein-coupled receptor BAI1 is a critical regulator of dendritic spine and excitatory synapse development. However, the mechanism by which BAI1 controls these functions remains unclear. Our study identifies three distinct signaling paradigms for BAI1, demonstrating that it mediates forward, reverse, and lateral signaling in spines. Activation of BAI1 by a Stachel-dependent mechanism induces local Rac1 activation and subsequent spinogenesis/synaptogenesis. BAI1 also signals trans-synaptically to promote presynaptic differentiation. Furthermore, BAI1 interacts with the postsynaptic cell-adhesion molecule Neuroligin-1 (NRLN1) and facilitates NRLN1-dependent spine growth and excitatory synaptogenesis. Thus, our findings establish BAI1 as a functional synaptogenic receptor that promotes presynaptic and postsynaptic development in cooperation with synaptic organizer NRLN1.
Elevated iron deposition has been reported in Parkinson's disease (PD). However, the route of iron uptake leading to high deposition in the substantia nigra is unresolved. Here, we show a mechanism in enhanced Fe2+ uptake via S-nitrosylation of divalent metal transporter 1 (DMT1). While DMT1 could be S-nitrosylated by exogenous nitric oxide donors, in human PD brains, endogenously S-nitrosylated DMT1 was detected in postmortem substantia nigra. Patch-clamp electrophysiological recordings and iron uptake assays confirmed increased Mn2+ or Fe2+ uptake through S-nitrosylated DMT1. We identified two major S-nitrosylation sites, C23 and C540, by mass spectrometry, and DMT1 C23A or C540A substitutions abolished nitric oxide (NO)-mediated DMT1 current increase. To evaluate in vivo significance, lipopolysaccharide (LPS) was stereotaxically injected into the substantia nigra of female and male mice to induce inflammation and production of NO. The intranigral LPS injection resulted in corresponding increase in Fe2+ deposition, JNK activation, dopaminergic neuronal loss and deficit in motoric activity, and these were rescued by the NO synthase inhibitor l-NAME or by the DMT1-selective blocker ebselen. Lentiviral knockdown of DMT1 abolished LPS-induced dopaminergic neuron loss.
SIGNIFICANCE STATEMENT Neuroinflammation and high cytoplasmic Fe2+ levels have been implicated in the initiation and progression of neurodegenerative diseases. Here, we report the unexpected enhancement of the functional activity of transmembrane divalent metal transporter 1 (DMT1) by S-nitrosylation. We demonstrated that S-nitrosylation increased DMT1-mediated Fe2+ uptake, and two cysteines were identified by mass spectrometry to be the sites for S-nitrosylation and for enhanced iron uptake. One conceptual advance is that while DMT1 activity could be increased by external acidification because the gating of the DMT1 transporter is proton motive, we discovered that DMT1 activity could also be enhanced by S-nitrosylation. Significantly, lipopolysaccharide-induced nitric oxide (NO)-mediated neuronal death in the substantia nigra could be ameliorated by using l-NAME, a NO synthase inhibitor, or by ebselen, a DMT1-selective blocker.
Cancer Cytopathology, EarlyView.
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Cancer stem cells (CSC) are characterized by deregulated self-renewal, tumorigenicity, metastatic potential, aberrant stemness signaling pathways, resistance to conventional therapy, and the ability to give rise to a progeny of proliferating cells that constitute the bulk of tumors. Targeting CSC will provide novel treatments for cancer. Different investigations have focused on developing complementary approaches that involve natural compounds that decrease chemo-resistance and reduce the side effects of conventional therapies. Since, it has been reported that molecular iodine (I2) exhibits antineoplastic effects and decreases tumor progression in some cancer models, we evaluated the potential effect of I2 on cell cultures enriched in cervical cancer stem-like cells.
HeLa and SiHa cervical cancer cells were treated with 200uM I2 for 24 h. After time, cells were cultured in CSC-conditioned medium (cervospheres) and viability assays were performed. Following, tumorigenic capabilities in cervospheres treated with I2 were evaluated in NOD/SCID mice. HeLa monolayer cells untreated and their respective cervosphere cells treated or untreated with 200 μM of I2 for 24 h were xenotransplanted subcutaneously at different amounts and mice were monitored for at least 2 months.
In the present study, monolayer and CSC-enriched cultures (cervospheres) from cervical cancer-derived cell lines, HeLa and SiHa, showed that 200uM I2 supplementation inhibits proliferation of both and decreased their tumorigenic capacity, in vivo. This antineoplastic effect of I2 was accompanied by diminished expression of stemness markers including CD49f, CK17, OCT-4, NANOG, SOX2, and KLF4, as well as increased expression and activation of PPARγ receptors.
All this data led us to suggest a clinical potential use of I2 for targeting CSC and improve current treatments against cervical cancer.
Chimeric antigen receptor T (CAR T) cells immunotherapy is rapidly developed in treating cancers, especially relapsed or refractory B-cell malignancies.
To assess the efficacy and safety of CAR T therapy, we analyzed clinical trials from PUBMED and EMBASE.
Results showed that the pooled response rate, 6-months and 1-year progression-free survival (PFS) rate were 67%, 65.62% and 44.18%, respectively. We observed that received lymphodepletion (72% vs 44%, P = 0.0405) and high peak serum IL-2 level (85% vs 31%, P = 0.04) were positively associated with patients' response to CAR T cells. Similarly, costimulatory domains (CD28 vs CD137) in second generation CAR T was positively associated with PFS (52.69% vs 33.39%, P = 0.0489). The pooled risks of all grade adverse effects (AEs) and grade ≥ 3 AEs were 71% and 43%. Most common grade ≥ 3 AEs were fatigue (18%), night sweats (14%), hypotension (12%), injection site reaction (12%), leukopenia (10%), anemia (9%).
In conclusion, CAR T therapy has promising outcomes with tolerable AEs in relapsed or refractory B-cell malignancies. Further modifications of CAR structure and optimal therapy strategy in continued clinical trials are needed to obtain significant improvements.
Improved risk stratification, more effective therapy and better supportive care have resulted in survival rates after childhood cancer of around 80% in developed countries. Treatment however can be harsh, and three in every four childhood cancer survivors (CCS) develop at least one late effect, such as gonadal impairment. Gonadal impairment can cause involuntary childlessness, with serious consequences for the well-being of CCS. In addition, early menopause increases the risk of comorbidities such as cardiovascular disease and osteoporosis. Inter-individual variability in susceptibility to therapy related gonadal impairment suggests a role for genetic variation.
Currently, only one candidate gene study investigated genetic determinants in relation to gonadal impairment in female CCS; it yielded one single nucleotide polymorphism (SNP) that was previously linked with the predicted age at menopause in the general population of women, now associated with gonadal impairment in CCS. Additionally, one genome wide association study (GWAS) evaluated an association with premature menopause, but no GWAS has been performed using endocrine measurements for gonadal impairment as the primary outcome in CCS.
As part of the PanCareLIFE study, the genetic variability of chemotherapy induced gonadal impairment among CCS will be addressed. Gonadal impairment will be determined by anti-Müllerian hormone (AMH) levels or alternatively by fertility and reproductive medical history retrieved by questionnaire. Clinical and genetic data from 837 non-brain or non-bilateral gonadal irradiated long-term CCS will result in the largest clinical European cohort assembled for this late-effect study to date. A candidate gene study will examine SNPs that have already been associated with age at natural menopause and DNA maintenance in the general population. In addition, a GWAS will be performed to identify novel allelic variants. The results will be validated in an independent CCS cohort.
This international collaboration aims to enhance knowledge of genetic variation which may be included in risk prediction models for gonadal impairment in CCS.
There is a pressing need to reduce the burden of chronic disease and improve healthcare system sustainability through improved cancer and chronic disease prevention and screening (CCDPS) in primary care. We aim to create an integrated approach that addresses the needs of the general population and the special concerns of cancer survivors. Building on previous research, we will develop, implement, and test the effectiveness of an approach that proactively targets patients to attend an individualized CCDPS intervention delivered by a Prevention Practitioner (PP). The objective is to determine if patients randomized to receive an individualized PP visit (vs standard care) have improved cancer surveillance and CCDPS outcomes. Implementation frameworks will help identify and address facilitators and barriers to the approach and inform future dissemination and uptake.
The BETTER WISE project is a pragmatic two-arm cluster randomized controlled trial embedded in a mixed methods design, including a qualitative evaluation and an economic assessment. The intervention, informed by the expanded chronic care model and previous research, will be refined by engaging researchers, practitioners, policy makers, and patients. The BETTER WISE tool kit includes blended care pathways for cancer survivors (breast, colorectal, prostate) and CCDPS including lifestyle risk factors and screening for poverty. Patients aged 40–65, including both cancer survivors and general population patients, will be randomized at the physician level to an intervention group or to a wait-list control group. Once the intervention is completed, patients randomized to wait-list control will be invited to receive a prevention visit. The main outcome, calculated at 12-months follow-up, will be an individual patient-level summary composite index, defined as the proportion of CCDPS actions achieved relative to those for which the patient was eligible at baseline. A qualitative evaluation will capture information related to program outcome, implementation (facilitators and barriers), and sustainability. An economic assessment will examine the projected cost-benefit impact of investing in the BETTER WISE approach.
This project builds on existing work and engages end users throughout the process to develop, implement, and determine the effectiveness of a multi-faceted intervention that addresses CCDPS and cancer survivorship in primary care settings.
ISRCTN21333761. Registered on December 19, 2016
EMS professionals, educators rally to support and "take care of the next generation of providers"
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Here, we present a protocol to inject autologous muscle-derived stem cells in the proximity to the recurrent laryngeal nerve with the help of an electrical nerve stimulator. This novel technique may become useful for the treatment of equine recurrent laryngeal neuropathy.
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In vivo microdialysis has enabled collection of molecules present in brain interstitial fluid (ISF) from awake, freely-behaving animals. In order to analyze relatively large molecules in ISF, the current article specifically focuses on the microdialysis protocol using probes with high molecular weight cut off membranes.
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BOZEMAN, Mont. — Acela Truck Company recently announced that it has expanded its purpose-built High Water/Flood Rescue Truck line of response apparatus to include multiple new custom body configurations and larger 6x6 models of its Monterra high mobility chassis. Flooding is the leading cause of disaster or weather-related deaths in the United States and the number of coastal and inland...
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Description
A 27-year-old woman presented with complaints of pain in the epigastric region radiating to back for 20 days. She was treated initially at local hospital and was diagnosed as acute pancreatitis as her amylase and lipase levels were >1000 U/mL. She was managed with analgesics and intravenous fluids and was discharged in 4 days. She then presented to our emergency, with complaints of epigastric pain, awareness of lump in the epigastric region and non-passage of stool or flatus for past 3 days. She also gave history of fever and multiple episodes of bilious vomiting. Patient denied previous history of similar episodes in past and is non-alcoholic. On abdominal examination, a lump of size 20x15 cm was palpable in the epigastric region extending into the umbilical region. On ultrasonogram abdomen, a cystic swelling was seen along with multiple gall stones in the gall bladder. Contrast-enhanced CT (CECT) abdomen was suggestive of a large cystic...
Lymphatic filariasis is caused by nematode filariae Wuchereria bancrofti, Brugia malayi or Brugia timori. It is commonly seen in tropical and subtropical regions of the world and affects the lymphatic system of humans, who are the definitive host while mosquito is the intermediate host. The most common manifestation of the disease is hydrocele followed by lower limb lymphoedema and elephantiasis. Although filariasis is much more common entity in north India, its presentation as retroperitoneal cyst is very rare with reported incidence rate of 1/105 000. We present a case of primary retroperitoneal filariasis in a 52-year-old man, without any classic signsandsymptoms, diagnosed postoperatively after surgical resection following diagnostic uncertaintyandfailure of other medical therapies.
A gossypiboma is a mass within a patient's body comprising a cotton matrix surrounded by a foreign body granuloma. We describe an unusual presentation of a gossypiboma presenting in a 32-year-old man with acute epigastric pain and haematemesis. His surgical history revealed an emergency laparotomy following a road traffic accident 16 years ago. Initial gastroscopy showed extrinsic stomach compression. An abdominal ultrasound scan followed by a CT scan evidenced a large, well-defined, predominantly cystic mass with some solid areas occupying the left hypochondrium. Conservative management with insertion of a percutaneous drain proved to be inefficient. A laparotomy was performed; intraoperatively, the cyst was found to be ruptured and within it, a large surgical gauze was found. This was removed but required a distal pancreatectomy and gastrectomy for complete excision. He was discharged on day 74 of admission with outpatient follow-up.
A 4-year-old boy presented with fatigue and was found to have severe kidney injury requiring haemodialysis. A renal ultrasound demonstrated bilateral nephromegaly with mild loss of corticomedullary differentiation but preserved echogenicity. He had a persistent isolated monocytosis. Renal biopsy revealed extensive infiltration by primary renal diffuse large B-cell lymphoma. He required haemodialysis for 18 days and received chemotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab and intrathecal methotrexate. He achieved remission with an estimated glomerular filtration rate of 50 mL/min/1.73 m2, and his kidneys returned to normal size. Nephromegaly due to renal-limited haematolymphoid disease is extremely rare, especially in children.
Cervical cancer incidence and mortality is high in Uyghur ethnics. Their life style and dietary habit were different from other ethnics living together. Study on the role of trace elements in HPV infection and cervical lesion of Uyghur minority is needed for future intervention and prevention work.
In total, 833 Uyghur women were randomly selected from the screening site and hospital. The concentrations of the trace elements As, Fe, Cd, Ni, Cu, Zn, Mn, and Se were determined by atomic absorption spectrophotometry and inductively coupled plasma atomic emission spectroscopy. Univariate analysis was performed with chi-squared test between the HPV-positive and HPV-negative groups and between the case group and the control group. Multivariate analysis was performed with logistic regression.
An As concentration ≥ 0.02 mg/kg was a risk factor for HPV infection (OR > 1, P < 0.05), and Ni concentration ≥ 0.1232 mg/kg and Se concentration ≥ 0.02 mg/kg were protective factors (OR < 1, P < 0.05). Concentrations of Fe ≥ 6.9153 mmol/L and As ≥0.02 mg/kg were risk factors for CIN2+ (OR > 1, P < 0.05), and concentrations of Ni ≥0.0965 mg/kg and Se ≥0.02 mg/kg were protective factors (OR < 1, P < 0.05).
Low serum concentrations of Se and Ni and a high serum concentration of As might be related to HPV infection and CIN2+ in Uyghur women in rural China.
Breast cancer is the most common cancer in women. 12–15% of all tumors are triple-negative breast cancers (TNBC). So far, TNBC has been mainly associated with mutations in BRCA1. The presence of other predisposing genes seems likely since DNA damage repair is a complex process that involves several genes. Therefore we investigated if mutations in other genes are involved in cancer development and whether TNBC is an additional indicator of mutational status besides family history and age of onset.
We performed a germline panel-based screening of 10 high and low-moderate penetrance breast cancer susceptibility genes (BRCA1, BRCA2, ATM, CDH1, CHEK2, NBN, PALB2, RAD51C, RAD51D and TP53) in 229 consecutive individuals affected with TNBC unselected for age, family history or bilateral disease. Within this cohort we compared the number of mutation carriers fulfilling clinical selection criteria with the total number of carriers identified.
Age at diagnosis ranged from 23 to 80 years with an average age of 50.2 years. In 57 women (24.9%) we detected a pathogenic mutation, with a higher frequency (29.7%) in the group manifesting cancer before 60 years. Deleterious BRCA1 mutations occurred in 14.8% of TNBC patients. These were predominantly recurrent frameshift mutations (24/34, 70.6%). Deleterious BRCA2 mutations occurred in 5.7% of patients, all but one (c.1813dupA) being unique.
While no mutations were found in CDH1 and TP53, 10 mutations were detected in one of the six other predisposition genes. Remarkably, neither of the ATM, RAD51D, CHEK2 and PALB2 mutation carriers had a family history. Furthermore, patients with non-BRCA1/2 mutations were not significantly younger than mutation negative women (p = 0.3341). Most importantly, among the 57 mutation carriers, ten (17.5%) would be missed using current clinical testing criteria including five (8%) with BRCA1/2 mutations.
In summary, our data confirm and expand previous studies of a high frequency of germline mutations in genes associated with ineffective repair of DNA damage in women with TNBCs. Neither age of onset, contralateral disease nor family history were able to discern all mutation positive individuals. Therefore, TNBC should be considered as an additional criterion for panel based genetic testing.
Objectives
We sought the perspectives of lead public health officials working to improve health equity in the USA regarding the drivers of scientific evidence use, the supply of scientific evidence and the gap between their evidentiary needs and the available scientific evidence.
DesignWe conducted 25 semistructured qualitative interviews (April 2017 to June 2017) with lead public health officials and their designees. All interviews were transcribed and thematically analysed.
SettingPublic health departments from all geographical regions in the USA.
ParticipantsParticipants included lead public health officials (20) and their designees (5) from public health departments that were either accredited or part of the Big Cities Health Coalition.
ResultsMany respondents were using scientific evidence in the context of grant writing. Professional organisations and government agencies, rather than specific researchers or research journals, were the primary sources of scientific evidence. Respondents wanted to see more locally tailored cost-effectiveness research and often desired to participate in the planning phase of research projects. In addition to the scientific content recommendations, respondents felt the usefulness of scientific evidence could be improved by simplifying it and framing it for diverse audiences including elected officials and community stakeholders.
ConclusionsRespondents are eager to use scientific evidence but also need to have it designed and packaged in ways that meet their needs.
Introduction
Pre-eclampsia is a common disorder associated with serious maternal and fetal complications. It is associated with abnormal placentation, which significantly reduces flow, resulting in a relative hypoxic state. These pathophysiological changes lead to subtle macrovascular and cardiac structural and functional changes in the fetus. This can predispose the child with maternal history of pre-eclampsia to risk of premature cardiovascular disease.
Methods and analysisThe children will be identified from a cohort of women with pre-eclampsia. The study will be conducted at The Aga Khan University Hospital, Karachi. Inclusion criteria will be children who are between 2 and 5 years of age and have a maternal history of pre-eclampsia. The child's current weight, height and blood pressure will be recorded. A two-dimensional functional echocardiogram and vascular assessment will be performed to evaluate alterations in cardiac function as well as macrovascular remodelling in these children. Data will be presented as mean±SD, median (IQR) or percentages as appropriate. Independent t-test or Mann-Whitney U test will be used for testing of continuous variables (based on the assumption of normality). A p<0.05 will be used to determine statistical significance.
Ethics and disseminationEthical approval has been obtained from AKUH Ethics Review Committee. Findings will be disseminated through scientific publications and project summaries for the participants.
Researchers found that antibiotics actually kill the 'good' bacteria keeping infection and inflammation at bay.
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Publication date: Available online 26 September 2018
Source: Injury
Author(s): Montserrat Barceló, Esther Francia, Carlos Romero, Domingo Ruiz, Jordi Casademont, Olga Torres
Centenarians and nonagenarians constitute a rapidly growing age group in Western countries and they are expected to be admitted to hospital with hip fractures. The aim of this study was to compare outcomes of centenarian and nonagenarian patients following a hip fracture and to identify risk factors related to in-hospital and post-discharge mortality in both groups.
A prospective evaluation of centenarian patients and nonagenarian controls admitted to a tertiary university hospital in Barcelona with hip fractures over a period of 5 years and 9 months. Baseline characteristics and outcomes in both patient groups were compared. Variables associated with in-hospital, 30-day, 3-month and 1-year mortality were also analyzed.
Thirty-three centenarians and 82 nonagenarians were included. The most relevant statistically significant differences found were: Barthel index at admission (61.90 vs. 75.22), number of drugs before admission (4.21vs 5.55), in-hospital complication rates (97 vs. 78%), readmissions at 3 months and 1 year (0 vs 11.7% and 3.4 vs. 19.5% respectively) and mortality at 3 months and 1 year (41.4 vs. 20.8% and 62.1 vs. 29.9%, respectively). Mean number of complications, rapid atrial fibrillation, mean age, and urinary tract infection were risk factors associated with mortality.
Centenarian patients had similar in-hospital outcomes to nonagenarians, but experienced more complications and twice the 3-month and 1-year mortality rate. The mean number of complications was the risk factor most consistently related to in-hospital and post-discharge mortality. These findings emphasize the need to improve care in very old patients to prevent complications.
Background. There are still discrepancies among general/colorectal surgeons regarding closure of mesenteric defect in scientific literature. This study aimed to assess the long-term consequences of nonclosure of the mesenteric defect after open right colectomy. Methods. A 7-year retrospectively collected and continuous database revealed 212 consecutive patients who had undergone traditional right colectomy without closing the mesenteric defects at Kaohsiung Chung-Gung Memorial Hospital; all patients were operated by a single surgeon. Among these patients, 17 were excluded (those who died within 30 days after surgery or those who received an end ileostomy). The mean age of the 195 patients (58% men and 42% women) was 61.6 ± 12.6 years, and the follow-up period was 4.1 ± 2.8 years (interquartile range 0.09 ~ 10.4). Results. Forty-four patients (22.5%) encountered intestinal obstruction. Nine (20.4%) required surgical intervention. The cause of intestinal obstruction was adhesion (n=1), ventral hernia (n=1), and cancer recurrence (n=7). Conservative treatment was successful in 35 patients. The intestinal obstruction group (n = 44) were similar to the no-intestinal obstruction group (n = 151) in terms of the following parameters: age, sex, previous abdominal surgery, indication for colectomy, and procedure related complications. Carcinomatosis was found to increase the incidence of intestinal obstruction. No patient developed intestinal obstruction because of the nonclosure of mesenteric defects after right colectomy. Conclusion. This study suggested that routine procedure of closing the mesenteric defect after open right colectomy might not be beneficial. Additional studies with extended long-term follow-up periods are needed to confirm the benefits of the nonclosure.
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Low selenium status is associated with increased risk of Graves' disease (GD). While several trials have discussed the efficacy of selenium supplementation for thyroid function, in GD patients, the effectiveness of selenium intake as adjuvant therapy remains unclear. In this systematic review and meta-analysis, we aimed to determine the efficacy of selenium supplementation on thyroid function in GD patients. Two reviewers searched PubMed, Web of Science, the Cochrane Central Register of Controlled Trials, and four Chinese databases for studies published up to October 31, 2017. RCTs comparing the effect of selenium supplementation on thyroid hyperfunction in GD patients on antithyroid medication to placebo were included. Serum free thyroxine (FT4), free triiodothyronine (FT3), thyrotrophic hormone receptor antibody (TRAb), and thyroid-stimulating hormone (TSH) levels were assessed. Ten trials involving 796 patients were included. Random-effects meta-analyses in weighted mean difference (WMD) were performed for 3, 6, and 9 months of supplementation and compared to placebo administration. Selenium supplementation significantly decreased FT4 (WMD=-0.86 [confidence interval (CI)-1.20 to -0.53]; p=0.756; I2=0.0%) and FT3 (WMD=-0.34 [CI-0.66 to -0.02]; p=0.719; I2=0.0%) levels at 3 months, compared to placebo administration; these findings were consistent at 6 but not 9 months. TSH levels were more elevated in the group of patients taking selenium than in the control group at 3 and 6, but not 9 months. TRAb levels decreased at 6 but not 9 months. At 6 months, patients on selenium supplementation were more likely than controls to show improved thyroid function; however, the effect disappeared at 9 months. Whether these effects correlate with clinically relevant measures remains to be demonstrated.
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Objective. We aimed to investigate the effectiveness of acupoint polyglactin 910 (PGLA) embedding in patients with cervical spondylotic radiculopathy (CSR). Methods. A total of 102 CSR patients with neck and shoulder pain were recruited and assigned randomly into three groups: the sham acupoint embedding (SAE) group, the middle-layer acupoint PGLA embedding (MAPE) group, and the deep-layer acupoint PGLA embedding (DAPE) group. The primary outcomes were Visual Analog Scale (VAS) scores showing the analgesic effects of treatment. Secondary outcomes included clinical symptoms (evaluated by the Yasuhisa Tanaka 20 (YT-20) score and the neck disability index (NDI)) and patient health status (evaluated by the 36-item short-form survey (SF-36)) as reported in the trial. Results. Compared with the SAE group, VAS scores were significantly reduced at 1, 2, 3, 4, and 10 weeks after the first treatment in both the DAPE and MAPE groups (P
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The Newcastle-Ottawa scale (NOS) is one of many scales used to judge the quality of observational studies in systematic reviews. It was criticized for its arbitrary definitions of quality items in a commentary in 2010 in this journal. That commentary was cited 1,250 times through December 2016. We examined the citation history of this commentary in a random sample of 100 full papers citing it, according to the Web of Science. Of these, 96 were systematic reviews, none of which quoted the commentary directly. All but 2 of the 96 indirect quotations (98%) portrayed the commentary as supporting use of the NOS in systematic reviews when, in fact, the opposite was the case. It appears that the vast majority of systematic review authors who cited this commentary did not read it. Journal reviewers and editors did not recognize and correct these major quotation errors. Authors should read each source they cite to make sure their direct and indirect quotations are accurate. Reviewers and editors should do a better job of checking citations and quotations for accuracy. It might help somewhat for commentaries to include abstracts, so that the basic content can be conveyed by PubMed and other bibliographic resources.
Cancers, Vol. 10, Pages 357: Cell-Free DNA Methylation of Selected Genes Allows for Early Detection of the Major Cancers in Women
Cancers doi: 10.3390/cancers10100357
Authors: Sandra P. Nunes Catarina Moreira-Barbosa Sofia Salta Susana Palma de Sousa Inês Pousa Júlio Oliveira Marta Soares Licínio Rego Teresa Dias Jéssica Rodrigues Luís Antunes Rui Henrique Carmen Jerónimo
Background: Breast (BrC), colorectal (CRC) and lung (LC) cancers are the three most common and deadly cancers in women. Cancer screening entails an increase in early stage disease detection but is hampered by high false-positive rates and overdiagnosis/overtreatment. Aberrant DNA methylation occurs early in cancer and may be detected in circulating cell-free DNA (ccfDNA), constituting a valuable biomarker and enabling non-invasive testing for cancer detection. We aimed to develop a ccfDNA methylation-based test for simultaneous detection of BrC, CRC and LC. Methods: CcfDNA from BrC, CRC and LC patients and asymptomatic controls were extracted from plasma, sodium-bisulfite modified and whole-genome amplified. APC, FOXA1, MGMT, RARβ2, RASSF1A, SCGB3A1, SEPT9, SHOX2 and SOX17 promoter methylation levels were determined by multiplex quantitative methylation-specific PCR. Associations between methylation and standard clinicopathological parameters were assessed. Biomarkers’ diagnostic performance was also evaluated. Results: A “PanCancer” panel (APC, FOXA1, RASSF1A) detected the three major cancers with 72% sensitivity and 74% specificity, whereas a “CancerType” panel (SCGB3A1, SEPT9 and SOX17) indicated the most likely cancer topography, with over 80% specificity, although with limited sensitivity. Conclusions: CcfDNA’s methylation assessment allows for simultaneous screening of BrC, CRC and LC, complementing current modalities, perfecting cancer suspects’ triage, increasing compliance and cost-effectiveness.
Purpose
Results of a pilot project to improve the safety and efficiency of the discharge process by adding daily pharmacist review and preparation of discharge medication orders to an existing discharge medication reconciliation workflow are reported.
SummaryDue to patient capacity issues, the pharmacy department of a large tertiary medical center implemented changes to the existing medication discharge workflow. A steering committee was established, with subgroups responsible for workflow development, electronic medical record enhancement, and data collection designated. Patients admitted to 5 hospitalist services, 1 otolaryngology service, and 1 gynecology service were included in pilot testing of a new discharge workflow over a 7-week period. The new workflow included pharmacist daily prospective preparation of discharge medication orders by "pending" (i.e., managing all aspects of) orders for providers to sign. After implementation, a 22% relative reduction (p = 0.046) in pharmacist-identified medication-related problems was documented. Additionally, the proportion of discharges occurring before noon was increased on all services involved in the pilot project, including a significant increase (from 19% to 23%, p = 0.001) on the hospitalist services. Challenges identified during the pilot project included suboptimal initial provider acceptance and added pharmacist workload. On average, an additional 16.2 minutes of pharmacist time per patient was required for ordering of discharge medications throughout a patient stay.
ConclusionImplementation of a discharge process that incorporated pharmacist pending of discharge medication orders throughout the patient stay improved measures of safety and efficiency of the discharge process.