Donor-specific Cell-Free DNA as a Biomarker in Solid Organ Transplantation. A Systematic Review

Background There is increasing interest in the use of noninvasive biomarkers to reduce the risks posed by invasive biopsy for monitoring of solid organ transplants (SOT). One such promising marker is the presence of donor-derived cell-free DNA (dd-cfDNA) in the urine or blood of transplant recipients. Methods We systematically reviewed the published literature investigating the use of cfDNA in monitoring of graft health following SOT. Electronic databases were searched for studies relating cfDNA fraction or levels to clinical outcomes, and data including measures of diagnostic test accuracy (DTA) were extracted. Narrative analysis was performed. Results 95 manuscripts from 47 studies met the inclusion criteria (18 kidney, 7 liver, 11 heart, 1 kidney-pancreas, 5 lung, and 5 multiorgan). The majority were retrospective and prospective cohort studies, with 19 reporting DTA data. Multiple techniques for measuring dd-cfDNA were reported, including many not requiring a donor sample. dd-cfDNA falls rapidly within 2 weeks, with baseline levels varying by organ type. Levels are elevated in the presence of allograft injury, including acute rejection (AR) and infection, and return to baseline following successful treatment. Elevation of cfDNA levels are seen in advance of clinically apparent organ injury. Discriminatory power was greatest for higher grades of T cell mediated and antibody-mediated AR, with high negative predictive values. Conclusions cfDNA is a promising biomarker for monitoring the health of solid-organ transplants. Future studies will need to define how it can be used in routine clinical practice and determine clinical benefit with routine prospective monitoring. Corresponding Author: Simon R Knight, Oxford Transplant Centre, Nuffield Department of Surgical Sciences, Churchill Hospital, Old Road, Headington, OX3 7LE, United Kingdom. Tel: +44 (0) 1865 227131. E-mail: simon.knight@nds.ox.ac.uk Authorship SK conceived the study, authored the study protocol, developed and performed literature searches, screened references, analysed the data and wrote the manuscript. AT participated in study design, screened references, analysed the data and participated in the writing of the manuscript. MLF participated in study design and participated in the writing of the manuscript. Disclosures The authors declare no conflicts of interest relating to the content of this article. Funding This study received no external sources of funding. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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A worldwide survey of Live liver donor selection policies at 24 centers with a combined experience of 19 009 adult living donor liver transplants

Background While surgical technique in LDLT has evolved with a focus on donor safety and recipient challenges, the donor selection criteria remain considerably disparate. Methods A questionnaire on donor selection was sent to 41 centers worldwide. 24 centers with a combined experience of 19009 LDLTs responded. Results Centers were categorized into predominantly LDLT (18) or DDLT (6), and high (10) or low volume (14) centers. At the majority of centers, the minimum acceptable GRWR was 1 features of metabolic syndrome. On biopsy, all considered macrovesicular and 50% considered microvesicular steatosis important. Nearly all (92%) rejected donors for early fibrosis, and minority for nonspecific granuloma or mild inflammation. Most anatomical anomalies except portal vein type D/E were acceptable at high volume centers. There was no standard policy for pre or peroperative cholangiogram. Conclusions This first large live liver donor survey provides insight into donor selection practices that may aid standardization between centers, with potential expansion of the donor pool without compromising safety. Corresponding author: Dr. AS Soin, Chairman, Chief Liver Transplant and Hepatobiliary Surgeon, Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta-The Medicity, Gurgaon, Haryana 122001, India. e-mail IDs: absoin@gmail.com, arvinder.soin@medanta.org Authorship Page 1 Dr. Arvinder Singh Soin. FRCS. Chairman, Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta-The Medicity, Gurgaon, Haryana 122001, India. e-mail ID: absoin@gmail.com. 2. Dr. Rohan Jagat Chaudhary. MS. Associate Consultant, Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta-The Medicity, Gurgaon, Haryana 122001, India. e-mail ID: rohanjc1@gmail.com. 3. Dr. Hirak Pahari. MS. Fellow, Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta-The Medicity, Gurgaon, Haryana 122001, India. e-mail ID: hirak.pahari@gmail.com. 4. Dr. Elizabeth Pomfret. MD. Division of Transplant Surgery, University of Colorado School of Medicine, 1635 Aurora Court, Aurora, CO, 80045, USA. E-mail ID: elizabeth.pomfret@ucdenver.edu Contributions: AS Soin: Conception of the work; data analysis and interpretation. Drafting the work, critical revision for important intellectual content and final approval of the version to be published. R J Chaudhary: Data acquisition, analysis and interpretation, drafting and final approval. H Pahari: Data acquisition, analysis and interpretation, drafting and final approval. E A Pomfret: Conception, critical revision and final approval of the version to be published. Disclosures: None. No conflict of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Golgi stabilization, not its front-rear bias, is associated with EMT-enhanced fibrillar migration

Epithelial-to-mesenchymal transition (EMT) and maturation of collagen fibrils in the tumor microenvironment play a significant role in cancer cell invasion and metastasis. Confinement along fiber-like tracks enhances cell migration. To what extent and in what manner EMT further promotes migration in a microenvironment already conducive to migration is poorly understood. Here, we show that TGFβ-mediated EMT significantly enhances migration on fiber-like micropatterned tracks of collagen, doubling migration speed and tripling persistence relative to untreated mammary epithelial cells.

https://ift.tt/2OW4mts

Deciphering the Dynamics of Interlocked Feedback Loops in a Model of the Mammalian Circadian Clock

Mathematical models of fundamental biological processes play an important role in consolidating theory and experiments, especially if they are systematically developed, thoroughly characterized, and well tested by experimental data. In this work, we report a detailed bifurcation analysis of a mathematical model of the mammalian circadian clock network developed by Relogio et al. [16], noteworthy for its consistency with available data. Using one- and two-parameter bifurcation diagrams, we explore how oscillations in the model depend on the expression levels of its constituent genes and the activities of their encoded proteins.

https://ift.tt/2NDAFIS

Rigid Base Pair Monte Carlo Simulations of One-Start and Two-Start Chromatin Fiber Unfolding by Force

The organization of chromatin in 30 nm fibers remains a topic of debate. Here we quantify the mechanical properties of the linker DNA and evaluate the impact of these properties on chromatin fiber folding. We extended a rigid base-pair DNA model to include (un-)wrapping of nucleosomal DNA and (un-)stacking of nucleosomes in one-start and two-start chromatin fibers. Monte Carlo simulations that mimic single-molecule force spectroscopy experiments of folded nucleosomal arrays reveal different stages of unfolding as a function of force and are largely consistent with a two-start folding for 167 and one-start folding for 197 nucleosome repeat length fibers.

https://ift.tt/2NDAHjY

HTX-019: polysorbate 80- and synthetic surfactant-free neurokinin 1 receptor antagonist for chemotherapy-induced nausea and vomiting prophylaxis

Future Oncology, Ahead of Print.


https://ift.tt/2QMz5Xm

Impact of the use of local fidaxomicin treatment algorithms for managing Clostridium difficile infection in hospitalized patients in southeastern United States

Clostridium difficile-associated diarrhea (CDAD) is a major public health threat that results in increased length of stay, hospital readmissions, deaths, and economic burden. CDAD treatment is often guided by sev...

https://ift.tt/2NCb82J

Surface area wiped, product type, and target strain impact bactericidal efficacy of ready-to-use disinfectant Towelettes

Disinfectant products are often used on environmental surfaces (e.g. countertops, patient beds) and patient care equipment in healthcare facilities to help prevent the transmission of healthcare-associated inf...

https://ift.tt/2OhYL1f

Improving the competency of medical students in clinical breast examination through a standardized simulation and multimedia-based curriculum

Abstract

Purpose

Clinical breast examination (CBE) is an important step in the assessment of patients with breast-related complaints. We developed a standardized simulation and multimedia-based (SSMBI) curriculum using current evidenced-based recommendations. This study aimed to determine if SSMBI training resulted in better performance (examination scores and detection of abnormal findings) than the traditional teaching method.

Methods

Novice fourth-year medical students were exposed to the SSMBI curriculum (n = 68) or traditional (n = 52) training. The traditional group was taught by a lecture and attending weekly clinics where they had hands-on experience. The SSMBI group underwent a structured lecture followed by an instructional video and dedicated simulated teaching. Both groups were assessed through a written knowledge exam and an objective structured clinical examination (OSCE). Student's t test and χ² tests were used to assess differences in CBE technique and knoweldge.

Results

Students who underwent SSMBI training had significantly higher numbers of correct answers describing the different steps and justifications of CBE. OSCE performance was significantly higher in the SSMBI group. SSMBI-trained students were more likely to complete all the necessary CBE steps compared to traditionally-trained students (88.2% vs. 28.2%, p < 0.00001). The SSMBI group was also more systematic and more likely to perform adequate inspection, palpation, examination of the nipple-areolar complex, and identify and characterize a palpable lesion (p < 0.05).

Conclusions

Formal SSMBI training is an important asset when teaching medical students how to perform a CBE. Real clinical experience is still necessary to refine this skill and the physician–patient interaction.

https://ift.tt/2CbNKHB

Resilience priming: Translational models for understanding resiliency and adaptation to early life adversity

Developmental Psychobiology, EarlyView.


https://ift.tt/2Eeb2iD

Efficacy and safety of cefazolin versus antistaphylococcal penicillins for the treatment of methicillin-susceptible Staphylococcus aureus bacteremia: a systematic review and meta-analysis

Antistaphylococcal penicillins (ASPs) and cefazolin have become the most frequent choices for the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) infections. However, the best therapeutic agent ...

https://ift.tt/2C9Snlm

Multidrug resistant Pseudomonas aeruginosa in Estonian hospitals

We aimed to identify the main spreading clones, describe the resistance mechanisms associated with carbapenem- and/or multidrug-resistant P. aeruginosa and characterize patients at risk of acquiring these strains...

https://ift.tt/2CFMD3R

Mathematical modelling of vancomycin-resistant enterococci transmission during passive surveillance and active surveillance with contact isolation highlights the need to identify and address the source of acquisition

Clinical studies and mathematical simulation suggest that active surveillance with contact isolation is associated with reduced vancomycin-resistant enterococci (VRE) prevalence compared to passive surveillanc...

https://ift.tt/2C9Sk9a

Using simultaneous amplification and testing method for evaluating the treatment outcome of pulmonary tuberculosis

To evaluate the utility of Simultaneous Amplification and Testing (SAT-TB) Method for monitoring anti-TB treatment response.

https://ift.tt/2CGqAKz

Rapid detection of respiratory organisms with the FilmArray respiratory panel in a large children’s hospital in China

Respiratory tract infections (RTIs) are the most common illness in children, and rapid diagnosis is required for the optimal management of RTIs, especially severe infections.

https://ift.tt/2Ceta9c

Safe Motherhood Initiative: Early Impact of Severe Hypertension in Pregnancy Bundle Implementation

AJP Rep 2018; 08: e212-e218
DOI: 10.1055/s-0038-1673632

Objective To describe the implementation and early results of the American College of Obstetricians and Gynecologists District II Safe Motherhood Initiative's Severe Hypertension in Pregnancy bundle on the timely treatment of severe hypertension in New York State obstetric hospitals. Methods This is a retrospective comparative study of two time periods during voluntary implementation of the Severe Hypertension in Pregnancy bundle in New York State's obstetric hospitals. The main outcome measure was the administration of an appropriate antihypertensive agent within 1 hour of the second elevated value for all pregnant or postpartum patients with severe hypertension. Results Of the 117 obstetric hospitals participating in the Safe Motherhood Initiative, 111 (94.9%) submitted data included in this analysis. During the study period, 80 of the 111 (72.0%) hospitals reported implementing the hypertension bundle. Overall, 2.4% of pregnant women were diagnosed with severe hypertension, and 60 to 65% of patients were treated within an hour of the second elevated value. Although not statistically significant, a greater numbers of patients were treated within an hour of the second elevated value in the second time period compared with the first in most obstetric hospitals (overall 64.8 vs. 60.8%; p = 0.33). Conclusion There were increasing numbers of patients receiving timely treatment of severe hypertension during early implementation of a Severe Hypertension in Pregnancy bundle in New York State obstetric hospitals. However, bundle implementation requires significant financial and human resources and the long-term impact on maternal morbidity and mortality in our state remains uncertain. Precis There was a tendency toward more timely treatment of severe hypertension following implementation of a Severe Hypertension in Pregnancy bundle in New York obstetric hospitals.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  open access Full text

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Mouse Models for Cancer Immunotherapy Research [Mini Review]

Immunotherapy has revolutionized cancer therapy, largely attributed to the success of immune-checkpoint blockade. However, there are subsets of patients across multiple cancers who have not shown robust responses to these agents. A major impediment to progress in the field is the availability of faithful mouse models that recapitulate the complexity of human malignancy and immune contexture within the tumor microenvironment. These models are urgently needed across all malignancies to interrogate and predict antitumor immune responses and therapeutic efficacy in clinical trials. Herein, we seek to review pros and cons of different cancer mouse models, and how they can be used as platforms to predict efficacy and resistance to cancer immunotherapies.

Significance: Although immunotherapy has shown substantial benefit in the treatment of a variety of malignancies, a key hurdle toward the advancement of these therapies is the availability of immunocompetent preclinical mouse models that recapitulate human disease. Here, we review the evolution of preclinical mouse models and their utility as coclinical platforms for mechanistic interrogation of cancer immunotherapies. Cancer Discov; 8(11); 1–8. ©2018 AACR.

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Influence of low-level laser irradiation on osteocalcin protein and gene expression in bone tissue1

Abstract Purpose: To evaluate osteocalcin gene and protein expression in vitro and in an in vivo model of ostectomy. Methods: Twenty Wistar rats were assigned into two groups A (n=10, laser) and B (n=10, control). Ostectomy was performed in the femur diaphysis; the twenty fragments removed, composed in vitro groups named as in vivo (A and B) and cultivated in CO2 atmosphere for thirteen days. Low-level laser irradiation was performed in groups A (in vivo and in vitro) by an GaAlAs device (λ=808 nm, dose of 2J/cm2, power of 200mW, power density of 0.2W/cm2, total energy of 1.25J, spot diameter of 0.02mm) for 5 seconds, at one point, daily. It was performed immunocytochemistry assays in vivo and in vitro groups. In vitro groups were also submitted to RNA extraction, cDNA synthesis and gene expression by quantitative PCR. Statistical analysis was realized with p<0.05. Results: Immunocytochemistry scores showed no significant differences between control and laser groups either in vivo and in vitro. Gene expression also showed no statistical differences. Conclusion: Low-level laser irradiation did not alter osteocalcin protein and gene expression in vivo and in vitro in the studied period but it may have been expressed them in an earlier period.

https://ift.tt/2A6MUKH

Role of moxifloxacin-dexamethasone in cardiac histomorphometric findings among Wistar rats from infected mothers

Abstract Purpose: To investigate cardiac changes in young rats, whose mothers underwent autogenic fecal peritonitis, during organogenesis phase and to evaluate the role of intravenous administration of moxifloxacin and dexamethasone in preventing infection-related cardiac changes. Methods: A prospective histomorphometric study was performed on 29 hearts of Wistar four-month old rats. Animals were divided into three groups: Negative Control Group (NCG) included 9 subjects from healthy mothers; Positive Control Group (PCG) included 10 subjects from mothers with fecal peritonitis (intra-abdominal injection of 10% autogenic fecal suspension in the gestational period) and did not receive any treatment; and Intervention Group (IG), with 10 animals whose infected mothers received moxifloxacin and dexamethasone treatment 24 hours after induction of fecal peritonitis. Results: Nuclear count was higher in the IG group as compared to PCG (p = 0.0016) and in NCG as compared to PCG (p = 0.0380). There was no significant difference in nuclear counts between NCG and IG. Conclusion: Induced autogenic fecal peritonitis in pregnant Wistar rats determined myocardial changes in young rats that could be avoided by the early administration of intravenous moxifloxacin and dexamethasone.

https://ift.tt/2QLm3Jp

Oxidative stress on ischemia/reperfusion injury in mice with non-alcoholic hepatic steatosis or steatohepatitis

Abstract Purpose: To evaluate the oxidative stress, resulting from ischemia and hepatic reperfusion, in mice with non-alcoholic hepatic steatosis and steatohepatitis. Methods: C57BL/6 male mice were used. Part of them were ob/ob mice, and the other part was fed with standard or MCD diets - this last used to develop steatohepatitis. The animals - MCD-I/R, ob/ob-I/R and I/R groups - were submitted to 30 minutes of partial hepatic ischemia, followed by reperfusion for 24 hours. The blood was collected, for biochemical analysis of AST, and the liver removed for assessment of TBARS and nitrite, and of histology. Results: After the I/R, the animal fed with MCD diet presented higher AST levels (MCD-I/R: 967±349U/L / ob/ob-I/R: 606±18 U/L / I/R: 311±172 U/L), TBARS (MCD-I/R: 7±1 nM/mg protein / ob/ob-I/R: 3±1 nM/mg protein / I/R: 3±1 nM/mg protein) and nitrite (MCD-I/R: 614±87 µg/mL / ob/ob-I/R: 512±81 µg/mL / I/R: 459±29 µg/mL) than the ob/ob mice, when both groups were compared to animals fed with standard diet. Regarding histology, the steatosis level (azonal macrovesicular steatosis of level 3 - >66%) and hepatic fibrosis (periportal and perisinusoidal of level 2) was also more intense, but both animal models presented lobular inflammation of level 3 (>66%). Conclusions: The murine model fed with MCD diet is suitable for the assessment of oxidative stress in hepatic I/R injury associated with the nonalcoholic fatty liver disease. Although both murine models showed inflammatory infiltrate and macro and micro vesicular steatosis.

https://ift.tt/2A6dOm5

Tissue microarray technology and collagen evaluation to analyze surgical trauma performed with usual blade or ultrasonic harmonic scalpels in rats

Abstract Purpose: To compare wound healing performed with cold blade (CSB) and ultrasonic harmonic scalpel (UHS) in the abdominal aponeurosis of rats. Methods: Eighty Wistar rats divided into two groups and underwent midline incision in the linea alba with cold blade and harmonic ultrasonic scalpel. Analysis were performed in subgroups of 10 animals after 3, 7, 14 and 21 days. Macroscopically was observed the presence of hematoma, infection, wound dehiscence, fistula and adherences. Microscopically were used collagen and immunohistochemical staining methods. Results: Macroscopic, complications showed no statistical difference. Immunohistochemical analysis for MMP-9 was more intense in UHS group (p<0.05). TGF β presented its lower expression in UHS group at 14 and 21 days, with no statistical difference at 3 and 7 days (p<0.05). α-AML expression appeared higher in UHS group after 14 days and remained similar in others (p<0.05). Collagen deposition had no change in type I, and increased in type III in UHS; at 7th day the deposition was higher in CSB group; at 14th was similar in both groups (p<0.001). Conclusion: UHS compared to the CSB has higher lesion area at the time of the incision; as well as it led to the delay of regeneration and scar maturation process.

https://ift.tt/2QKR5RY

Rivastigmine prevents injury induced by ischemia and reperfusion in rat liver

Abstract Purpose: To evaluate whether pre-treatment with rivastigmine is able to attenuate the I/R induced lesions in rat liver. Methods: SHAM animals or those submitted to I/R, non-treated or pre-treated with rivastigminine (2mg/kg) either 50 or 15 minutes before ischemia, were used. After I/R protocol, these animals were killed and their livers were harvested to measurement of the mitochondrial swelling as well as the malondialdehyde (MDA), nitrite and nitrate tissue concentration. Blood was also harvested for serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) determinations. Results: I/R promoted a significant increase of mitochondrial swelling in the studied animals. This increase of mitochondrial swelling was partially prevented by rivastigmine, but only if administered 50 minutes before ischemia. No significant modification of MDA, nitrite or nitrate tissue concentrations was observed in consequence of I/R, followed or not by rivastigmine treatments. In addition, I/R elevated both AST and ALT. These elevations of serum enzymes were not reversed by the different rivastigmine treatments. Conclusions: Rivastigmine administered 50 minutes before ischemia attenuates I/R-induced mitochondrial swelling, that indicates liver injury. This protective effect may be related to a greater stimulation of α7nAChR present in the Kupffer cells by the non-methabolized ACh, leading to an attenuation of I/R-induced inflammation.

https://ift.tt/2A5o5P7

Intravascular and intraparenchymatous hepatic segmentary sclerosis

Abstract Purpose: To evaluate the morphological effects of injected sclerosing agents into the liver. Methods: This study was performed on twenty dogs, distributed into five groups: Group 1 (n = 5) - control, Group 2 (n = 5) - injection of 50% glucose solution inside hepatic parenchyma and animals followed during seven days, Group 3 (n = 10) - injection of ethanol inside hepatic parenchyma and animals distribution into two subgroups Subgroup 3A (n = 5) - followed during 24 hours and subgroup 3B (n = 5) - followed during seven days (group 3B), Group 4 (n = 5) - ethanol injection inside left portal vein branch and followed during 24 hours. Livers were macroscopically evaluated, submitted to hepatic arteriography and portography, then histology. Results: All animals in Group 4 died within 23 hours due to diffuse hepatic necrosis. The animals of groups 2 and 3 had a satisfactory evolution. Fibrosis formed in the segment reached by the sclerosant solution and interruption of the contrast flow injected into the portal system. Conclusion: Intrahepatic parenchymal ethanol injection is well tolerated and causes sclerosis restricted to a specific segment; however, intraportal ethanol injection causes massive hepatic necrosis and can lead to death.

https://ift.tt/2QKR2pg

Comparative study of fibrosis induced by Marlex®, Parietex Composite®, Vicryl® and Ultrapro® meshes1

Abstract Purpose: To evaluate the fibrosis induced by four different meshes: Marlex®, Parietex Composite®, Vicryl® and Ultrapro®. Methods: Histological cutouts of abdominal wall were analyzed with polarized light 28 days after the meshes implants and colorized by picrosirius to identify the intensity of collagen types I and III, and their maturation index. Results: When the four groups were compared, the total collagen area analyzed was bigger in groups A and D, with no difference between them. The collagen type I density was bigger in group A, with an average of 9.62 ± 1.0, and smaller in group C, with an average of 3.86 ± 0.59. The collagen type III density was similar in groups A, B and C, and bigger in group D. The collagen maturation index was different in each of the four groups, bigger in group A with 0.87, group B with 0.66, group D with 0.57 and group C with 0.33 (p = 0.0000). Conclusion: The most prominent fibrosis promotion in the given meshes was found on Marlex® (polypropylene mesh) and the Parietex Composite® (non-biodegradable polyester); the collagen maturation index was higher in the Marlex® mesh, followed by Ultrapro®, Parietex Composite® and Vicryl® meshes.

https://ift.tt/2A6xZQO

Oxidative stress effects in the uterus, placenta and fetus of pregnant rats submitted to acute and chronic stress

Abstract Purpose: To evaluate the effects of oxidative stress in pregnant rats submitted to acute and chronic stress, relating to alterations in the uterus, placenta and fetus. Methods: Twenty-four female Wistar albino (Rattus norvegicus), were divided into four groups, for induction of oxidative stress the animals were submitted to cold and physical immobilization. Plasma fasting glucose and MDA were determined in all groups and the fetuses and placentas were measured. Results: There were no statistical differences in the levels of malonic dialdehyde (MDA), however the averages of chronic stress group were higher compared to control groups, which could explain the observed adverse effects; there was no correlation between puppies' size, the weight of the placenta and MDA values. Conclusions: Chronic stress causes adverse effects, when compared to control groups; chronic stress group had fetuses, placentas and number of puppies, significantly lower compared to other groups. The rats exposed to chronic stress, also presented a higher frequency of fetal resorption.

https://ift.tt/2A5MBjq

Potencial of different hydroxyapatites as biomaterials in the bone remodeling

Abstract Purpose: To analyze the therapeutic potentials of different hydroxyapatites used for the correction of bone defects in rats. Methods: Forty rats, male, albino wistar, were distributed in 4 groups. They were submitted to a 3.5 mm defect in tibia. They received low purity hydroxyapatite, Strontium hydroxyapatite and hydroxyapatite doped with gallium, having a seven day evaluation time. Histopathology slides were stained with hematoxylin-eosin, for morphological evaluation. Were analyzed inflammatory processes, necrosis, presence of osteoclasts and osteoblasts, presence of the material, presence of white cells, neovascularization and bone neoformation. Results: It was observed that the groups HAPSr and HAPGa, presented better results of trabecular bone, hyaline cartilage and bone marrow more organized. Conclusion: There was improvement in the repair of the bone defect produced, showing that these hydroxyapatites are effective osteoinductive, osteoconductive, osteintegrant agents and have biocompatibility, and may be indicated for use in defect repairs.

https://ift.tt/2QNspbx

Hyperbaric oxygenation on adhesions prevention after laparotomy in rats

Abstract Purpose: To evaluate the effects of hyperbaric oxygenation on prevention of adhesions in the abdominal cavity after laparotomy. Methods: Fifty four rats underwent laparotomy; stitches were made in the four quadrant parietal peritoneum and abdominal cavity closure. Animals were divided into three groups: 1 - control; 2 - subjected to high pressures and oxygenation; 3 - subjected to 100% hyperbaric oxygenation. The animals in groups 2 and 3 were daily submitted to oxygenation hyperbaric chamber after surgery. On the seventh day another laparotomy, registration of procedure, assessment of adhesions and biopsies of the peritoneum were held. Professionals analyzed the videos and the biopsies. Results: Peritoneal cavity adhesions occurred in animals of three groups with no difference between them. In Group 3, the adhesions presented more fragile and vascular proliferation more pronounced, and there was no difference in comparison with the first and second groups. However, there was no significant difference in the evaluation of these parameters between the animals in groups 1 and 2. Conclusions: Postoperative hyperbaric oxygenation in rats submitted to laparotomy did not alter the frequency, but reduced the density of adhesions in the peritoneal cavity and promoted vascular proliferation. The change in atmospheric pressure alone had no influence on the results.

https://ift.tt/2A5MzIk

Preservation of the vagus nerves in subtotal esophagectomy without thoracotomy

Abstract Purpose: To evaluate the outcome of transhiatal esophagectomy without thoracotomy and with preservation of the vagal trunks for the treatment of advanced megaesophagus. Methods: Between March 2006 and September 2017, it was performed 136 transhiatal esophagectomies without thoracotomy by laparoscopy, with preservation of the vagus nerves. All patients were evaluated pre and postoperatively for respiratory and nutritional aspects Post operatively, some surgical aspects were evaluated like radiology and endoscopy of the digestive tract. Results: Follow-up for 7 months to 12 years by clinical, radiologic, endoscopic and pH monitoring revealed satisfactory and encouraging outcomes of the procedure. Conclusion: The laparoscopic transhiatal esophagectomy is a feasible and safe technique with good postoperative outcomes.

https://ift.tt/2QKQNdQ

Experiences with basic microsurgical training programs and skill assessment methods at the University of Debrecen, Hungary

Abstract During the past decades microsurgical training programs together with skill assessment methods had been developing intensively worldwide. Concerning the teaching of basic techniques at various levels, we aimed to summarize the education program types and experiences at our department, in order to define the way of continuity. All in the hope that this summary might contain useful information for other educators as well. About 50 years ago, in the late 1960s, microsurgical basic education had been established in Debrecen. Since the 1990s multilevel education programs have been developed, starting in undergraduate years up to the postgraduate training, residency and continuous medical education programs. In the last three decades about 2,300 participants completed courses, including over 470 residents. The ones who already succeeded microsurgical course as medical students, during residency program could reach better results and skill development. Concluding thoughts, the traditional methods and special experiences are highly important in microsurgical education. The necessary duration and individual training approach are emphasized. Standardization (self and international), comparability, accessibility, providing milestones of microsurgical skills are key factors. Proper feedback and skill assessment (experiences, internationally recognized scores, or combinations) are indispensable, but have to be fitted to the characteristic elements of the course.

https://ift.tt/2A5o79H

A technical note on low cost rat laparoscopy an initial experience

Abstract Purpose: To evaluate a novel and adapted low-cost set model for laparoscopic surgery in rats. Methods: Nine Wistar rats underwent two different laparoscopic procedures, splenectomy (n=3) and distal pancreatectomy with splenectomy (n = 6), after assembling a low-cost set replacing the conventional one (monitor, micro camera, image processor, light source, laparoscope and insufflator). The new set included an Android Tablet 10.5 ", a 5mm USB Endoscope and semiautomatic sphygmomanometer monitor. Results: The same surgeon performed the laparoscopic procedures. Total surgical time ranged from 36 to 60 minutes with a mean of 45.8 minutes. Three rats died during the distal pancreatic and splenectomy procedure (33.3%), due to respiratory failure (n = 1), uncontrolled abdominal hemorrhage (n=1) and iatrogenic gastric perforation (n = 1). We followed the other six rats (66.6%) for seven days with no further evidence of complications. Conclusions: The laparoscopic partial pancreatectomy and splenectomy can be performed with the novel low-cost set assembled in the present experimental study. Both specific training and skills development are required to validate more advanced laparoscopic procedures and achieve a desirable outcome.

https://ift.tt/2QIFZg5

FDA Approval Summary: Tisagenlecleucel for Treatment of Patients with Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia

Tisagenlecleucel (Kymriah, Novartis Pharmaceuticals, East Hanover, NJ) is a CD19-directed genetically-modified autologous T-cell immunotherapy. On August 30, 2017, the U.S. Food and Drug Administration approved tisagenlecleucel for treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse. Approval was based on the complete remission (CR) rate, durability of CR and minimal residual disease (MRD) < 0.01% in a cohort of 63 children and young adults with relapsed or refractory ALL treated on a single-arm trial (CCTL019B2202). Treatment consisted of fludarabine and cyclophosphamide followed 2 to 14 days later by a single dose of tisagenlecleucel. The CR rate was 63% (95% CI 50% - 75%) and all CRs had MRD < 0.01%. With a median follow-up of 4.8 months, the median duration of response was not reached. Cytokine release syndrome (79%) and neurological events (65%) were serious toxicities reported in the trial. With implementation of a Risk Evaluation and Mitigation Strategy, the benefit-risk profile was considered acceptable for this patient population with such resistant ALL. A study of safety with 15 years of follow-up is required as a condition of the approval.

https://ift.tt/2IRWAeC

Deep Learning to Distinguish Recalled but Benign Mammography Images in Breast Cancer Screening

Purpose: False positives in digital mammography screening lead to high recall rates, resulting in unnecessary medical procedures to patients and health care costs. This study aimed to investigate the revolutionary deep learning methods to distinguish recalled but benign mammography images from negative exams and those with malignancy.

Experimental Design: Deep learning convolutional neural network (CNN) models were constructed to classify mammography images into malignant (breast cancer), negative (breast cancer free), and recalled-benign categories. A total of 14,860 images of 3,715 patients from two independent mammography datasets: Full-Field Digital Mammography Dataset (FFDM) and a digitized film dataset, Digital Dataset of Screening Mammography (DDSM), were used in various settings for training and testing the CNN models. The ROC curve was generated and the AUC was calculated as a metric of the classification accuracy.

Results: Training and testing using only the FFDM dataset resulted in AUC ranging from 0.70 to 0.81. When the DDSM dataset was used, AUC ranged from 0.77 to 0.96. When datasets were combined for training and testing, AUC ranged from 0.76 to 0.91. When pretrained on a large nonmedical dataset and DDSM, the models showed consistent improvements in AUC ranging from 0.02 to 0.05 (all P > 0.05), compared with pretraining only on the nonmedical dataset.

Conclusions: This study demonstrates that automatic deep learning CNN methods can identify nuanced mammographic imaging features to distinguish recalled-benign images from malignant and negative cases, which may lead to a computerized clinical toolkit to help reduce false recalls. Clin Cancer Res; 1–8. ©2018 AACR.

https://ift.tt/2pO3LvG

CDC: Many Children With Heart Conditions Have Special Needs

THURSDAY, Oct. 11, 2018 -- Children with past and current heart conditions have more special health care needs compared with children without heart conditions, according to research published in the Sept. 29 issue of the U.S. Centers for Disease...

https://ift.tt/2CaEHXc

Spending Often Persists in High-Cost Medicare-Medicaid Eligible

THURSDAY, Oct. 11, 2018 -- More than half of patients who are dually eligible for Medicare and Medicaid and are designated as high-cost in one year remain persistently high-cost over three years, according to a study published online Oct. 2 in the...

https://ift.tt/2CC1QTq

Low-Dose Aspirin May Reduce Ovarian Cancer Risk

THURSDAY, Oct. 11, 2018 -- Low-dose aspirin use is associated with a reduced risk for ovarian cancer, according to a study published online Oct. 4 in JAMA Oncology. Mollie E. Barnard, Sc.D., from the Harvard T.H. Chan School of Public Health in...

https://ift.tt/2CaDejH

Infectious Diseases Society of America, Oct. 3-7

The Infectious Diseases Society of America Annual Meeting (ID Week 2018) The annual meeting of the Infectious Diseases Society of America was held from Oct. 3 to 7 in San Francisco and attracted more than 5,000 participants from around the world,...

https://ift.tt/2CCXCLj

Nine Cases of Polio-Like Illness Suspected in Children in Illinois

THURSDAY, Oct. 11, 2018 -- Nine recent cases of a rare, polio-like disorder in children are being investigated in Illinois, health officials said yesterday. All the patients with the condition, called acute flaccid myelitis (AFM), are younger than...

https://ift.tt/2Cbh8xx

PLZF play as an indirect facilitator of thymic retention for the innate-like T-cells to aquire innate-like functions

PLZF play as an indirect facilitator of thymic retention for the innate-like T-cells to aquire innate-like functions

PLZF play as an indirect facilitator of thymic retention for the innate-like T-cells to aquire innate-like functions, Published online: 11 October 2018; doi:10.1038/s41419-018-1075-y

PLZF play as an indirect facilitator of thymic retention for the innate-like T-cells to aquire innate-like functions

https://ift.tt/2pM6q9j

Integrative analysis of transcriptomics and clinical data uncovers the tumor-suppressive activity of MITF in prostate cancer

Integrative analysis of transcriptomics and clinical data uncovers the tumor-suppressive activity of MITF in prostate cancer

Integrative analysis of transcriptomics and clinical data uncovers the tumor-suppressive activity of MITF in prostate cancer, Published online: 11 October 2018; doi:10.1038/s41419-018-1096-6

Integrative analysis of transcriptomics and clinical data uncovers the tumor-suppressive activity of MITF in prostate cancer

https://ift.tt/2IPMgUJ

Long noncoding RNA neuroblastoma-associated transcript 1 gene inhibits malignant cellular phenotypes of bladder cancer through miR-21/SOCS6 axis

Long noncoding RNA neuroblastoma-associated transcript 1 gene inhibits malignant cellular phenotypes of bladder cancer through miR-21/SOCS6 axis

Long noncoding RNA neuroblastoma-associated transcript 1 gene inhibits malignant cellular phenotypes of bladder cancer through miR-21/SOCS6 axis, Published online: 11 October 2018; doi:10.1038/s41419-018-1090-z

Long noncoding RNA neuroblastoma-associated transcript 1 gene inhibits malignant cellular phenotypes of bladder cancer through miR-21/SOCS6 axis

https://ift.tt/2pO8zBj

Bone marrow infiltrated Lnc-INSR induced suppressive immune microenvironment in pediatric acute lymphoblastic leukemia

Bone marrow infiltrated Lnc-INSR induced suppressive immune microenvironment in pediatric acute lymphoblastic leukemia

Bone marrow infiltrated Lnc-INSR induced suppressive immune microenvironment in pediatric acute lymphoblastic leukemia, Published online: 11 October 2018; doi:10.1038/s41419-018-1078-8

Bone marrow infiltrated Lnc-INSR induced suppressive immune microenvironment in pediatric acute lymphoblastic leukemia

https://ift.tt/2IRxzQY

The impact of geriatric nutritional risk index on surgical outcomes after esophagectomy in patients with esophageal cancer

Abstract

Background

Geriatric Nutritional Index (GNRI) was shown to be closely associated with nutrition-related complications and mortality in elderly hospitalized patients. Impact of GNRI on postoperative outcomes in surgically treated esophageal squamous cell carcinoma (ESCC) patients has not been evaluated extensively.

Methods

A total of 240 patients with ESCC who underwent radical esophagectomy with two- or three-field lymphadenectomy between April 2000 and April 2012 were included in this retrospective study. GNRI formula was as follows: 1.489 × albumin (g/dl) + 41.7 × current weight/ideal weight. Patients were categorized as GNRI-low (GNRI < 92) or GNRI-high (GNRI ≥ 92) according to the receiver operating characteristics (ROC) curves generated for multiple logistic regression analysis using 5-year overall survival as the end point. The impact of GNRI status on short- and long-term outcomes of curative surgery for ESCC was examined.

Results

There were 44 (18.3%) and 196 (82.7%) patients in the GNRI-low and GNRI-high groups, respectively. Among the investigated demographic factors, the rate of nodal metastasis and pathological stage were significantly higher in the GNRI-low group than in the GNRI-high group (p < 0.01 and p < 0.01, respectively). Univariate analysis of postoperative complications revealed that the rate of lung complications was significantly higher in the GNRI-low group than in the GNRI-high group (p = 0.024), while GNRI was not an independent risk factor for the development of lung complications by multivariate analysis (Odds Ratio: 1.746; p = 0.126). 5-year overall survival (OS) was significantly lower in the GNRI-low group than in the GNRI-high group (p < 0.01). Moreover, GNRI was an independent prognostic factor for OS [Hazard ratio: 1.687; 95% confidence interval (CI): 1.038–2.742; p = 0.035], but not for cancer-specific survival. Analysis with stratification by tumor stage revealed that both OS and Cancer-Specific Survival (CSS) were worse in patients with low GNRI than those with high GNRI only among those with stage III ESCC (34.4% vs. 52.1%, p = 0.049 and 36.1% vs. 57.2%, p = 0.041, respectively). In the stage III ESCC, primary tumor size tends to be greater in the GNRI-low group than in the GNRI-high group (5.69 vs. 4.75 cm, p = 0.085) and the incidence of preoperative dysphagia was significantly higher in the GNRI-low group than in the GNRI-high group (74% vs. 45.9%, p = 0.032).

Conclusion

GNRI was closely associated with long-term survival after curative surgery in patients with stage III ESCC. Intensive follow-up after surgery should be performed for ESCC patients with low GNRI.

https://ift.tt/2ywDOEZ

CT, conventional, and functional MRI features of skull lymphoma: a series of eight cases in a single institution

Abstract

Objective

With the hypothesis that the combination of CT, conventional, and functional MRI can indicate a possible diagnosis of skull lymphoma, this study aimed to systematically explore CT, conventional, and functional MRI features of this rare entity.

Materials and methods

This retrospective study included eight patients with pathologically confirmed skull lymphomas. CT and conventional MRI findings, including the location, size, attenuation/signal intensity, cystic/necrosis, hemorrhage, calcification, enhancement, skull change, brain parenchyma edema and adjacent structure invasion, were reviewed. We also reviewed multi-parametric functional MR imaging features obtained from diffusion-weighted imaging (DWI, n = 4), susceptibility-weighted imaging (SWI, n = 3) and dynamic susceptibility-weighted contrast-enhanced perfusion-weighted imaging (DSC-PWI, n = 1).

Results

The eight patients in this series consisted of five males and three females, with a mean age of 51.1 years. All skull lymphomas showed the tumors extending to extra- and intra-cranial spaces with permeative destruction of the intervening skull. Intratumoral cystic/necrosis was seen in one case. Hemorrhage or calcification was absent. Dural mater infiltration was detected in all cases. Two clivus lymphomas encased internal carotid artery without narrowing the lumen. Three cases invaded brain parenchyma with moderate edema. The tumors demonstrated high signal on DWI with low ADC values comparing to muscles. SWI images showed little intratumoral hemorrhage and vessel. Low relative cerebral blood volume (rCBV) value was detected.

Conclusions

Skull lymphomas commonly presented as a homogenous solid tumor extending either intra- or extra-cranially with permeative bone destruction. Restricted diffusion, little intratumoral susceptibility signal, and lower perfusion may indicate a specific diagnosis. Multi-parametric functional MRI may be a promising tool for the diagnosis of skull lymphomas.

https://ift.tt/2IS3Nvl

Estimation of sodium and chloride storage in critically ill patients: a balance study

Nonosmotic sodium storage has been reported in animals, healthy individuals and patients with hypertension, hyperaldosteronism and end-stage kidney disease. Sodium storage has not been studied in ICU patients,...

https://ift.tt/2OiWJhs

The Use of N-of-1 Trials to Individualize Treatment in Patients With Renal Magnesium Wasting

Patients with chronic renal magnesium wasting often experience fatigue and neuromuscular symptoms. Most patients require lifelong treatment with high doses of magnesium salts. However, sufficient magnesium replenishment is difficult because high doses of magnesium salts induce diarrhea and other gastrointestinal symptoms. Another difficulty in treating hypomagnesemia is the lack of randomized controlled trials (RCTs) comparing different magnesium salts.1,2

https://ift.tt/2IRGPEu

Sex Disparities in Risk of Mortality Among Children With ESRD

In the general population, girls have lower mortality risk compared with boys. However, few studies have focused on sex differences in survival and in access to kidney transplantation among children with end-stage kidney disease.

https://ift.tt/2pNYIeX

Intractable Neck Pain in a Patient With Newly Diagnosed AML: An Underrecognized Cause of a Treatable Syndrome

Crowned dens syndrome (CDS) is a variant of pseudogout involving calcium pyrophosphate dihydrate (CPPD) deposition in the atlantoaxial junction. Imaging shows characteristic crownlike calcifications surrounding the dens1. Patients present with severe neck pain, rigidity, and high fever. Clinical presentations can be variable, including acute and chronic-relapsing types, and can mimic many other disease processes. Awareness of this rare, likely underrecognized, and treatable syndrome is crucial since palliative care providers care for patients at high risk for this disease.

https://ift.tt/2CEkw4S

Intra-Abdominal Cystic Lymphangioma

A term baby boy was delivered by elective caesarean delivery owing to increasing size of a cystic mass in the abdomen, which had been first detected antenatally using ultrasound examination. The differential diagnosis based on this antenatal scan was lymphangioma, mesenteric cyst, meconium peritonitis, meconium cyst, or bowel obstruction secondary to perforation. Fetal magnetic resonance imaging (T1-weighted) showed possible free fluid in the anterior abdominal cavity extending to the left side of the abdomen where umbilical vessels were seen traversing the fluid.

https://ift.tt/2ywQ9Js

Risk of Serious Infections Associated with Biologic Agents in Juvenile Idiopathic Arthritis: A Systematic Review and Meta-Analyses

To assess whether treatment with biologic response modifying agents during clinical trial study periods increases the risk of serious infections in children with juvenile idiopathic arthritis (JIA).

https://ift.tt/2ywya5K

Reply

We thank Dr Weinberger for his thoughts regarding our commentary. As he notes, there are limitations to the literature to date including a high rate of wheeze resolution in preschoolers with milder symptoms. We agree with Dr Weinberger's comment that preschool-age children have high hospitalization rates for asthma and that a "strong case" can be made for oral corticosteroid use in children at risk of either an emergency department visit or hospitalization. In our commentary we recommend use of oral corticosteroid therapy in those preschoolers at high risk of a more severe exacerbation (such as those with a history of atopy or recurrent wheeze episodes).

https://ift.tt/2OiTQgl

Screening and Serial Neutrophil Counts Do Not Contribute to the Recognition or Diagnosis of Late-Onset Neonatal Sepsis

To determine the validity of screening and serial neutrophil counts in predicting the absence/presence of late-onset sepsis (LOS) in infants with central venous catheters.

https://ift.tt/2Ohbjpz

Action in the face of uncertainty?

We read with interest the commentary by child neurologists Drs Gilbert, Mink, and Singer, who have been "personally involved in the evaluation and care of many children with suspected PANDAS or PANS" striving to facilitate "a clear and balanced approach when dealing with these controversial diagnoses."1 We appreciate their efforts toward aiding clinicians with clinical decision-making.

https://ift.tt/2OnLcxr

HIV Exposure and Formula Feeding Predict Under-2 Mortality in HIV-Uninfected Children, Botswana

To prospectively assess rates and detailed predictors of morbidity and mortality among HIV-exposed uninfected children and HIV-unexposed children in Botswana in a more recent era.

https://ift.tt/2ywTFDs

Oral corticosteroids for asthma exacerbations in preschool-age children: to treat or not to treat and when?

Abrams et al carefully considered the use of oral corticosteroids for asthma symptoms in toddlers.1 They recommend oral corticosteroids for these young children in the emergency department and hospital. However, they concluded that there is little evidence that administration of an oral corticosteroid is beneficial if administered earlier at home by a parent.

https://ift.tt/2ywQcoC

Pre-surgery age-adjusted Charlson Comorbidity Index is associated with worse outcomes in acute cholecystitis

Beneficial effects of cholecystectomy in acute cholecystitis (AC) might be weakened by complications. The age-adjusted Charlson Comorbidity Index (CCI) assesses disease relevance in the prediction of one-year mortality.

https://ift.tt/2CEUte0

A Quality Framework for Emergency Department Treatment of Opioid Use Disorder

Emergency clinicians are on the front lines of responding to the opioid epidemic and are leading innovations to reduce opioid overdose deaths through safer prescribing, harm reduction, and improved linkage to outpatient treatment. Currently, there are no nationally recognized quality measures or best practices to guide emergency department quality improvement efforts, implementation science researchers, or policymakers seeking to reduce opioid-associated morbidity and mortality. To address this gap, in May 2017, the National Institute on Drug Abuse's Center for the Clinical Trials Network convened experts in quality measurement from the American College of Emergency Physicians' (ACEP's) Clinical Emergency Data Registry, researchers in emergency and addiction medicine, and representatives from federal agencies, including the National Institute on Drug Abuse and the Centers for Medicare & Medicaid Services.

https://ift.tt/2OSPhZI

Among Low-Risk Patients, Does Functional Testing Decrease Referrals for Invasive Coronary Angiography Compared With Coronary Computed Tomographic Angiography?

Of 19,674 potentially relevant studies identified, authors included 18 trials (11,329 patients) evaluating patients at low risk for acute coronary syndrome. The meta-analysis included 6 different imaging modalities. In patients with low risk of acute coronary syndrome, several diagnostic tests were associated with fewer invasive referrals for angiography compared with coronary CT angiography, including stress echocardiography (OR 0.28; 95% CI 0.14 to 0.57), cardiovascular MRI (OR 0.32; 95% CI 0.15 to 0.71), and exercise ECG (OR 0.53; 95% CI 0.28 to 1.00).

https://ift.tt/2NDOCqq

A Certain Future for Regional Advanced Emergency Care

SEE RELATED ARTICLE, P. ■■■.

https://ift.tt/2NA5HS1

Treatment Delays for Patients With Acute Ischemic Stroke in an Iranian Emergency Department: A Retrospective Chart Review

We evaluate the extent and nature of treatment delays and the contributing factors influencing them for patients with acute ischemic stroke, as well as main barriers to stroke care in an Iranian emergency department (ED).

https://ift.tt/2OOmcib

240 Improved Cost and Quality Among Medicare Beneficiaries Dispositioned From the Emergency Department to Receive Home Health Care Compared to Inpatient Hospitalization

As the shift from volume to value in health care expands, efforts to develop alternatives to hospitalization are gaining momentum. This study explores home health care initiated directly from the emergency department (ED) using the Medicare-reimbursed home health benefit as a potential alternative to hospitalization. We address barriers to home-based care by comparing costs and quality of care for older adults dispositioned to home health care versus hospital admission.

https://ift.tt/2NCxgKD

Examining the most important and current EMS trends

Our co-hosts are joined by EMS1 columnist and co-founder Kris Kaull to discuss his "30 things in 30 minutes" conference presentation

https://ift.tt/2EfSkHr

Examining the most important and current EMS trends

Our co-hosts are joined by EMS1 columnist and co-founder Kris Kaull to discuss his "30 things in 30 minutes" conference presentation

https://ift.tt/2EfSkHr

A novel Serratia sp. ZS6 isolate derived from petroleum sludge secretes biosurfactant and lipase in medium with olive oil as sole carbon source

Biosurfactants emulsify lipids, facilitating their exposure to microorganisms in water. Secretion of biosurfactant together with lipase can enhance oil assimilation by microorganisms. In this study, we show th...

https://ift.tt/2Ccr5Ll

Effect of four trace elements on Paenibacillus polymyxa Pp-7250 proliferation, activity and colonization in ginseng

Trace elements are essential nutrients for the growth of microorganisms and play an important role in their proliferation. Hence, the purpose of this paper is to explore the optimal C and N sources for large-s...

https://ift.tt/2CF5xb5

Transcriptional profile of a bioethanol production contaminant Candida tropicalis

The fermentation process is widely used in the industry for bioethanol production. Even though it is widely used, microbial contamination is unpredictable and difficult to control. The problem of reduced produ...

https://ift.tt/2CdPvUm

Decomposing the Variance in Reading Comprehension to Reveal the Unique and Common Effects of Language and Decoding

Here we present a protocol for decomposing the variance in reading comprehension into the unique and common effects of language and decoding.

https://ift.tt/2CcK7RM

A null variant in PUS3 confirms its involvement in intellectual disability and further delineates the associated neurodevelopmental disease

Clinical Genetics, EarlyView.


https://ift.tt/2pLNN5n

Enteric duplication cysts in children: varied presentations, varied imaging findings

Abstract

Enteric duplication cysts (EDCs) are rare congenital malformations formed during the embryonic development of the digestive tract. They are usually detected prenatally or in the first years of life. The size, location, type, mucosal pattern and presence of complications produce a varied clinical presentation and different imaging findings. Ultrasonography (US) is the most used imaging method for diagnosis. Magnetic resonance (MR) and computed tomography (CT) are less frequently used, but can be helpful in cases of difficult surgical approach. Conservative surgery is the treatment of choice. Pathology confirms the intestinal origin of the cyst, showing a layer of smooth muscle in the wall and an epithelial lining inside, resembling some part of the gastrointestinal tract (GT). We review the different forms of presentation of the EDCs, showing both the typical and atypical imaging findings with the different imaging techniques. We correlate the imaging findings with the surgical results and the final pathological features.

Teaching Points

• EDCs are rare congenital anomalies from the digestive tract with uncertain pathogenesis.

• More frequently, diagnosis is antenatal, with most EDCs occurring in the distal ileum.

• Ultrasonography is the method of choice for diagnosis of EDCs.

• Complicated EDCs can show atypical imaging findings.

• Surgery is necessary to avoid complications.

https://ift.tt/2yc8OLi

Soluble CTLA-4 as a favorable predictive biomarker in metastatic melanoma patients treated with ipilimumab: an Italian melanoma intergroup study

Abstract

CTLA-4 blockade by means of ipilimumab (IPI) potentiates the immune response and improves overall survival (OS) in a minority of metastatic melanoma (MM) patients. We investigated the role of soluble CTLA-4 (sCTLA-4) as a possible biomarker for identifying this subset of patients. sCTLA-4 levels were analyzed at baseline in sera from 113 IPI-treated MM patients by ELISA, and the median value (200 pg/ml) was used to create two equally sized subgroups. Associations of sCTLA-4 with best overall response (BOR) to IPI and immune-related adverse events (irAEs) were evaluated through logistic regression. Kaplan–Meier and Cox regression methods were used to analyze OS. A remarkable association between sCTLA-4 levels and BOR was found. Specifically, the proportion of patients with sCTLA-4 > 200 pg/ml in irSD or irPD (immune-related stable or progressive disease) was, respectively, 80% (OR = 0.23; 95%CL = 0.03–1.88) and 89% (OR = 0.11; 95%CL = 0.02–0.71) and was lower than that observed among patients in irCR/irPR (immune-related complete/partial response). sCTLA-4 levels increased during IPI treatment, since the proportion of patients showing sCTLA > 200 pg/ml after 3 cycles was 4 times higher (OR = 4.41, 95%CL = 1.02–19.1) than that after 1 cycle. Moreover, a significantly lower death rate was estimated for patients with sCTLA-4 > 200 pg/ml (HR = 0.61, 95%CL = 0.39–0.98). Higher baseline sCTLA-4 levels were also associated with the onset of any irAE (p value = 0.029), in particular irAEs of the digestive tract (p value = 0.041). In conclusion, our results suggest that high sCTLA-4 serum levels might predict favorable clinical outcome and higher risk of irAEs in IPI-treated MM patients.

https://ift.tt/2pR1pfv

Micropuncture of Bowman's Space in Mice Facilitated by 2 Photon Microscopy

We present use of 2-photon microscopy to place a micropipette within Bowman's urinary space in mice, combining 2 foundational techniques of renal physiology. Use of 2-photon microscopy overcomes critical limitations of conventional microscopy for micropuncture renal physiology studies.

https://ift.tt/2QKIqP9

Soluble CTLA-4 as a favorable predictive biomarker in metastatic melanoma patients treated with ipilimumab: an Italian melanoma intergroup study

Abstract

CTLA-4 blockade by means of ipilimumab (IPI) potentiates the immune response and improves overall survival (OS) in a minority of metastatic melanoma (MM) patients. We investigated the role of soluble CTLA-4 (sCTLA-4) as a possible biomarker for identifying this subset of patients. sCTLA-4 levels were analyzed at baseline in sera from 113 IPI-treated MM patients by ELISA, and the median value (200 pg/ml) was used to create two equally sized subgroups. Associations of sCTLA-4 with best overall response (BOR) to IPI and immune-related adverse events (irAEs) were evaluated through logistic regression. Kaplan–Meier and Cox regression methods were used to analyze OS. A remarkable association between sCTLA-4 levels and BOR was found. Specifically, the proportion of patients with sCTLA-4 > 200 pg/ml in irSD or irPD (immune-related stable or progressive disease) was, respectively, 80% (OR = 0.23; 95%CL = 0.03–1.88) and 89% (OR = 0.11; 95%CL = 0.02–0.71) and was lower than that observed among patients in irCR/irPR (immune-related complete/partial response). sCTLA-4 levels increased during IPI treatment, since the proportion of patients showing sCTLA > 200 pg/ml after 3 cycles was 4 times higher (OR = 4.41, 95%CL = 1.02–19.1) than that after 1 cycle. Moreover, a significantly lower death rate was estimated for patients with sCTLA-4 > 200 pg/ml (HR = 0.61, 95%CL = 0.39–0.98). Higher baseline sCTLA-4 levels were also associated with the onset of any irAE (p value = 0.029), in particular irAEs of the digestive tract (p value = 0.041). In conclusion, our results suggest that high sCTLA-4 serum levels might predict favorable clinical outcome and higher risk of irAEs in IPI-treated MM patients.

https://ift.tt/2pR1pfv

Economic analysis of biomarker-based anti-EGFR therapies in metastatic colorectal cancer in the Austrian context

Summary

Background

In metastatic colorectal cancer (mCRC), multimodal therapeutic strategies and diagnostics have continuously improved patient survival. The aim of our investigation was to relate this enhanced clinical outcome to treatment costs based on predictive biomarker scenarios guiding epidermal growth factor receptor (EGFR) targeting in a developed country.

Methods

We performed a cost-effectiveness analysis for the combination of EGFR inhibitors with chemotherapy in the first-line treatment of mCRC. Resource use estimates were based on actual data from two oncological departments and on clinical outcomes adapted from published trials. Comparative analyses for the use of EGFR inhibitors were based on three biomarker scenarios (sensitivity: 35%, 55% and 75%) to estimate their incremental cost-effectiveness and were completed by sensitivity analyses.

Results

Using FOLFIRI+cetuximab, preselection for EGFR therapy with KRAS testing prolonged progression-free survival with average savings of 913 €/month/patient (scenario 1) and average savings of 1811 €/month/patient when testing the whole RAS-family (scenario 2). In a future but realistic scenario, up 39% of treatment costs could be saved with almost three life–years gained (LYG).

The incremental cost/LYG was 212,083 € (116,646–1,866,332 €) for unselected EGFR therapy, 32,251 € (30,294–43,488 €) for EGFR following KRAS testing, 19,172 € (15,369–28,611 €) for the all RAS scenario, and 12,369 € (3865–18,533 €) for a future biomarker scenario.

Conclusions

In the therapy of mCRC, predictive biomarker testing has shown to be effective and cost saving. For further improvement, a strong research focus on predictive biomarkers is considered highly efficient to promote precision oncology by alleviating the pressure on the healthcare system.

https://ift.tt/2A5BTt1

Aggressive variant and treatment-related neuroendocrine prostate cancer: two different terms for the same disease?

Summary

Previously assumed to be rare, the prevalence of aggressive variants of prostate cancer has increased rapidly. This histologically heterogeneous group of cancers, including different forms of the neuroendocrine carcinoma of the prostate, share a common clinical course associated with a poor response to androgen deprivation treatment and fatal prognosis. Currently, the most commonly used terms are aggressive variant of prostate cancer and treatment-related neuroendocrine prostate cancer. The best treatment of these tumors in clinical routine is still being debated. Here, we highlight the clinically most relevant aspects of this heterogeneous disease and summarize recommendations for clinical routine.

https://ift.tt/2QM5Tjj

Diet Less Important Than Genes for High Serum Urate Levels

THURSDAY, Oct. 11, 2018 -- Diet explains little of the variation in serum urate levels in the general population, while genetic factors make a greater contribution, according to a meta-analysis published online Oct. 10 in The BMJ. Tanya J. Major,...

https://ift.tt/2NBNNhK

Midlife PSA Predicts Aggressive Prostate Cancer in Black Men

THURSDAY, Oct. 11, 2018 -- Midlife levels of prostate-specific antigen (PSA) strongly predict future development of aggressive prostate cancer among black men, according to a study published online Sept. 17 in European Urology. Mark A. Preston,...

https://ift.tt/2OUOQOG

On a Given Day, 36.6 Percent of U.S. Adults Eat Fast Food

THURSDAY, Oct. 11, 2018 -- Overall, 36.6 percent of U.S. adults consumed fast food on a given day during 2013 to 2016, according to an October data brief published by the U.S. Centers for Disease Control and Prevention National Center for Health...

https://ift.tt/2NBYZeq

Wall Thickness Measured by MRI More Consistently Linked to CVD

THURSDAY, Oct. 11, 2018 -- Common carotid artery (CCA) wall thickness measured using magnetic resonance imaging (MRI) is more consistently associated with incident cardiovascular disease (CVD) outcomes than intima-media thickness measured by...

https://ift.tt/2OQWb1x

Poor Outcomes for Hispanic Infants With Congenital Heart Dz

THURSDAY, Oct. 11, 2018 -- For live-born infants with hypoplastic left heart syndrome (HLHS) and d-transposition of the great arteries (TGA), Hispanic ethnicity is associated with poor outcome, according to a study published online Oct. 10 in the...

https://ift.tt/2NyNzrT

Higher Perceived Stress Linked to Lower Fecundability in Women

THURSDAY, Oct. 11, 2018 -- Higher levels of perceived stress are associated with slight decreases in fecundability among women but not men, according to a study recently published in the American Journal of Epidemiology. Amelia K. Wesselink, Ph.D.,...

https://ift.tt/2OUOSpM

Sleeve Gastrectomy, Gastric Bypass May Be Better for Teens

THURSDAY, Oct. 11, 2018 -- Adolescents with severe obesity achieve substantial and sustainable weight loss with sleeve gastrectomy (SG) and gastric bypass procedures but not with gastric banding, according to a study published in the September issue...

https://ift.tt/2NyNvs9

Review: Vitamin D Does Not Appear to Prevent Fractures, Falls

THURSDAY, Oct. 11, 2018 -- Vitamin D supplementation does not prevent fractures or falls or have a clinically meaningful impact on bone mineral density in pooled analyses, according to a review and meta-analysis published online Oct. 4 in The Lancet...

https://ift.tt/2OQW8Tp

Low Recurrence With Shortened IV Abx Course in GBS Bacteremia

THURSDAY, Oct. 11, 2018 -- For infants with uncomplicated, late-onset group B Streptococcus (GBS) bacteremia, a shortened intravenous (IV) course of antibiotic therapy is sometimes prescribed and is associated with low rates of disease recurrence...

https://ift.tt/2NyNp3L

Payer Policies May Discourage Non-Pharma Tx for Low Back Pain

THURSDAY, Oct. 11, 2018 -- There is a need for public and private insurers to broaden their coverage policies for non-drug pain treatments for low back pain, according to a study published online Oct. 5 in JAMA Network Open. James Heyward, M.P.H.,...

https://ift.tt/2QKet1T

For HPV-Positive Women, Test Can Guide Cervical Cancer Screening Follow-Up

A new test can help to improve the clinical management of women who screen positive for HPV infection during routine cervical cancer screening, an NCI-led study has shown.

https://ift.tt/2yxwPM7

Selecting Multiple Biomarker Subsets with Similarly Effective Binary Classification Performances

Existing algorithms generate one solution for a biomarker detection dataset. This protocol demonstrates the existence of multiple similarly effective solutions and presents a user-friendly software to help biomedical researchers investigate their datasets for the proposed challenge. Computer scientists may also provide this feature in their biomarker detection algorithms.

https://ift.tt/2CEhyO3

A Ligated Intestinal Loop Model in Anesthetized Specific Pathogen Free Chickens to Study Clostridium Perfringens Virulence

Here we present a protocol to surgically create 'intestinal ligated loops' in chicken small intestines. This procedure allows for the comparison of multiple Clostridium perfringens strains' virulence in situ in a single host. This method markedly decreases the number of chickens usually necessary for similar in vivo experiments.

https://ift.tt/2C89pQW

Gold Cross EMS improves safety for patients and medics

AUGUSTA, Ga. — Gold Cross EMS is the first emergency medical service department in the state of Georgia to add the world's first Integrated Patient Transport and Loading System™, the iNʃX®, to their fleet. The iNʃX was developed by FERNO to eliminate lifting during patient transport, enhancing caregiver and patient safety. EMS is one of the most injurious occupations....

https://ift.tt/2Canopl

Keep these 2 tips in mind for a successful public access defibrillation program

Cardiac arrest is the third leading cause of death, but it can be stopped with more AED interventions

https://ift.tt/2CECV1F

Validity and prognostic significance of sperm protein 17 as a tumor biomarker for epithelial ovarian cancer: a retrospective study

Abstract

Background

Prior small studies have shown increased expression of sperm protein 17 (Sp17) in epithelial ovarian cancer (EOC) tissue and suggest Sp17 as a potential biomarker for EOC. However, how Sp17 expression varies with histology, grade, and stage of EOC and its expression in other ovarian neoplasms has not been defined. It is unknown whether patients with EOC have elevated serum Sp17 levels or if Sp17 expression is associated with survival outcomes.

Methods

The study included 982 patients with benign, borderline, and malignant ovarian neoplasms and normal ovary. There were 878 patients with tissue only, 39 with serum only, and 65 with matching serum and tissue. Immunohistochemical (IHC) staining with anti-Sp17 antibody was performed on tissue specimens and the intensity scored as weak, moderate, or strong. A sandwich enzyme-linked immunosorbent assay (ELISA) was performed to measure Sp17 sera concentrations.

Results

Sp17 expression was most commonly seen in serous cystadenomas (83%) and serous borderline tumors (100%). Of the 773 EOC specimens, 223 (30%) expressed Sp17. Grade and histology were significantly associated with Sp17 expression among EOC specimens (p < 0.001) on both univariate and multivariable analysis, with grade 1 serous adenocarcinomas showing the highest expression (51%). Sp17 expression was limited in other benign and non-epithelial malignant neoplasms. Neither Sp17 tissue expression nor serum concentration correlated with survival outcomes. Serum concentrations were higher in patients with Sp17 tissue expression, and the highest concentrations were noted among patients with serous and clear cell adenocarcinomas.

Conclusions

Sp17 is highly expressed in benign, borderline, and low grade malignant serous ovarian neoplasms and can be quantified in serum. Sp17 expression may have diagnostic significance in this subset of patients.

https://ift.tt/2QDZcj8

Optimal cutoff of pretreatment neutrophil-to-lymphocyte ratio in head and neck cancer patients: a meta-analysis and validation study

Abstract

Background

The prognostic role of neutrophil-to-lymphocyte ratio (NLR) has been proposed in head and neck squamous cell carcinoma (HNSCC). However, it is currently unclear which cutoff values of NLR could consistently and independently differentiate HNSCC patients to better and worse prognosis groups.

Methods

We performed a meta-analysis of prognostic significance of pretreatment NLR values, using data extracted from 24 relevant articles. Main outcomes were overall survival (OS) and disease-free survival (DFS) in HNSCC patients. Pooled hazard ratio (HR) and 95% confidence intervals (95%CI) were calculated using the random effect model for outcomes. Impacts of NLR cutoff values across the studies were assessed with a meta-regression analysis. Results were validated using an independent data set of patients (n = 540).

Results

Pretreatment high NLR values above the cutoff were significantly associated with shorter OS (HR = 1.96, 95%CI = 1.66–2.31) and DFS (HR = 1.90, 95%CI = 1.41–2.54). Of note, NLR cutoffs ranging from 1.9 to 6.0 did not affect HR of OS or DFS in meta-regression analyses. In an independent cohort, any NLR cutoff between 2 and 6 produced significant HR of OS, similarly. Instead of binary cutoffs, three subgroups of NLR (< 2, 2 to 6, and ≥ 6) showed significant differences of OS in survival analyses.

Conclusions

Meta-analyses confirmed that pretreatment NLR values above the cutoff were associated with shorter survival in HNSCC patients. However, the binary cutoffs of NLR values were variable across studies. Rather, pretreatment NLR values below 2 and above 6 using a three-tier classification (< 2, 2 to 6, and ≥ 6) could consistently imply better and worse prognosis in HNSCC patients, which could be readily translated to clinics.

https://ift.tt/2A4zYEU

Osteoporosis development and vertebral fractures after abdominal irradiation in patients with gastric cancer

Abstract

Background

Decrease in bone mineral density, osteoporosis development, bone toxicity and resulting insufficiency fractures as late effect of radiotherapy are not well known. Osteoporosis development related to radiotherapy has not been investigated properly and insufficiency fractures are rarely reported for vertebral bones.

Methods

Ninety-seven patients with gastric adenocarcinoma were evaluated for adjuvant treatment after surgery. While 73 out of 97 patients treated with adjuvant chemoradiotherapy comprised the study group, 24 out of 97 patients with early stage disease without need of adjuvant treatment comprised the control group. Bone mineral densities (BMD) of lumbar spine and femoral neck were measured by dual energy x-ray absorptiometry after surgery, and one year later in both groups.

Results

There was statistically significant decline in BMDs after one year in each group itself, however the decline in BMDs of the patients in the irradiated group was more pronounced when compared with the patients in the control group; p values were 0.02 for the decline in BMDs of lumbar spine, and 0.01 for femoral neck respectively. Insufficiency fractures were observed only in the irradiated patients (7 out of 73 patients) with a cumulative incidence of 9.6%.

Conclusions

Abdominal irradiation as in the adjuvant treatment of gastric cancer results in decrease in BMD and osteoporosis. Insufficiency fracture risk in the radiation exposed vertabral bones is increased. Calcium and vitamin D replacement and other measures for prevention of osteoporosis and insufficiency fractures should be considered after abdominal irradiation.

https://ift.tt/2QDZ5Ee

Post-transcriptional regulation of cancer/testis antigen MAGEC2 expression by TRIM28 in tumor cells

Abstract

Background

Cancer/testis antigen MAGEC2 (also known as HCA587) is highly expressed in a wide variety of tumors and plays an active role in promoting growth and metastasis of tumor cells. However, little is known for the regulation of MAGEC2 expression in cancer cells.

Methods

Western blotting and quantitative RT-PCR were performed to analyze MAGEC2 expression. Co-immunoprecipitation assay was applied for detecting the endogenous interaction of MAGEC2 and TRIM28 in tumor cells. Overexpression and knockdown assays were used to examine the effects of TRIM28 on the expression of MAGEC2 protein. Immunohistochemistry (IHC) staining was performed in hepatocellular carcinoma patients to evaluate the association between the expression of MAGEC2 and TRIM28. Proteasome inhibitors MG132 or PS-341 and lysosome inhibitor Chloroquine (CQ) were used to inhibit proteasomal or lysosomal-mediated protein degradation respectively.

Results

We demonstrate that MAGEC2 interacts with TRIM28 in melanoma cells and MAGEC2 expression in tumor cells depends on the expression of TRIM28. The expression level of MAGEC2 protein was significantly reduced when TRIM28 was depleted in tumor cells, and no changes were observed in MAGEC2 mRNA level. Furthermore, expression levels of MAGEC2 and TRIM28 are positively correlated in MAGEC2-positive human hepatocellular carcinoma tissues (p = 0.0011). Mechanistic studies indicate that the regulatory role of TRIM28 on MAGEC2 protein expression in tumor cells depends on proteasome-mediated pathway.

Conclusions

Our findings show that TRIM28 is necessary for MAGEC2 expression in cancer cells, and TRIM28 may serve as a new potential target for immunotherapy of cancer.

https://ift.tt/2A6HkrP

Polycystic Ovary Syndrome: Implication for Drug Metabolism on Assisted Reproductive Techniques—A Literature Review

Abstract

Polycystic ovary syndrome (PCOS) affects 6–10% of women and could be considered one of the most common endocrine alterations in women of reproductive age. The syndrome is characterized by several hormonal and metabolic alterations, including insulin resistance and hyperandrogenism, which play a severe detrimental role in the patient's fertility. We aimed to offer an overview about drug metabolism in the PCOS population. Nevertheless, we did not find any study that directly compared drug metabolism between PCOS and healthy women. We therefore decided to summarize briefly how hormonal and insulin sensitizer drugs act differently in healthy and PCOS women, who show altered steroidogenesis by theca cells and metabolic imbalance, focusing especially on assisted reproductive techniques. To date, data about drug metabolism in the PCOS population appears to be extremely limited. This important gap could have significant implications for therapeutic approaches and future perspectives: the dosage of drugs commonly used for the treatment of PCOS women should be tailored according to each patient's characteristics; we should implement new clinical trials in order to identify the best pharmacologic strategy for PCOS patients undergoing in vitro fertilization (IVF); it would be advisable to create an international expert panel to investigate the drug metabolism in the PCOS population.

https://ift.tt/2OlxtXy

Erratum: Identification of phenol- and p-cresol-producing intestinal bacteria by using media supplemented with tyrosine and its metabolites

https://ift.tt/2C9PP6D

Colostrum feeding shapes the hindgut microbiota of dairy calves during the first 12 h of life

Abstract

This study evaluated the effect of feeding non-heated and heated colostrum on the mucosa- and digesta-associated microbiota in the colon of dairy calves during the first 12 h of life. Thirty-two neonatal Holstein male calves were fed: no colostrum (NC, n=8), non-heated colostrum (FC, n=12), and heated colostrum (HC (60 °C, 60 min), n=12) immediately after birth. The abundances of mucosa- and digesta-associated total bacteria were higher in the colon of FC fed calves compared to those fed no colostrum (NC) at 12 h of life. Compare to NC calves, a higher proportion of mucosa and digesta-associated Clostridium cluster XIVa and Bifidobacterium, and a lower abundance of mucosa and digesta-associated E. coli were detected in the colon of FC and HC fed calves, as well as a tentatively lower relative abundance of Escherichia-Shigella genus in colon mucosa of HC fed calves. In addition, HC calves had lower abundances of E. coli and higher abundances of Bifidobacterium in mucosa-associated microbiota than FC fed calves. Our results suggest that feeding non-heated colostrum immediately after birth benefit neonatal calves with increased Bifidobacterium and decreased opportunistic pathogenic E. coli and Escherichia-Shigella genus in the colon, and feeding heated colostrum can fortify such effects.

https://ift.tt/2CDZh3u

Metaproteomic characterization of Vitis vinifera rhizosphere

Abstract

The rhizosphere is a hot spot of microbial activity where the release of root exudates stimulates bacterial density and diversity. The majority of the bacterial cells in soil results to be viable, unculturable, but active. Proteomic tools could be useful to gain information about microbial community activity and to better understand the real interactions pathways between roots and soil. The aim of this work was to characterize the bacterial community associated with Vitis vinifera cv. Pinot Noir roots using a metaproteome approach. Our results confirmed the large potentiality of proteomics in describing the environmental microbial communities and their activities: in particular, we showed that bacteria belonging to Streptomyces, Bacillus, Bradyrhizobium, Burkholderia and Pseudomonas genera are the most active in protein expression. Concerning the biological activity of these genera in the rhizosphere, we observed the exclusive presence of phosphorus metabolic process and the regulation of primary metabolic processes. To our knowledge this is the first study reporting the rhizosphere proteome of V. vinifera, describing the bacterial community structure and activity in such an important ecosystem for the Italian landscape, agriculture and economy.

https://ift.tt/2C9L0dB

https://ift.tt/2yAPzKu

https://ift.tt/2OijXnH

Interspecies interaction of Serratia plymuthica 4Rx13 and Bacillus subtilis B2g alters the emission of sodorifen

Abstract

Sodorifen is the major volatile of Serratia plymuthica 4Rx13. It is assumed to be a long-distance communication signal. However, so far the emission patterns of sodorifen had been studied using mono-cultures of S. plymuthica 4Rx13 neglecting that in natura bacteria live in communities. Here, we show that the structured co-cultivation of S. plymuthica 4Rx13 and Bacillus subtilis B2g in a low-diversity model community grown under nutrient rich conditions led to quantitative changes in sodorifen emission compared to self-paired mono-cultivations. Co-culturing revealed a decreased emission of sodorifen (50%) during exponential growth phase whereas in the late stationary stage of growth the amount of headspace sodorifen was increased compared to self-paired mono-cultivation (217% at 500 h of cultivation). Six other compounds which are most probably related to sodorifen or are isomers showed similar emission patterns. The data indicated that S. plymuthica 4Rx13 enhances its communication signal sodorifen as a consequence of interaction with B. subtilis B2g.

https://ift.tt/2pKfQ5g

Food-Grade Gene Transformation System Constructed in Lactobacillus plantarum using a GlmS-Encoding Selection Marker

Abstract

Food-grade gene expression systems in lactic acid bacteria enable production of functional proteins or product testing without antibiotic requirement. Here, we expanded the available selection markers by developing a novel food-grade genetic transformation system for Lactobacillus plantarum WCFS1 using the glucosamine-6-phosphate synthase gene (glmS1). A glmS-vector pSIPH497 was constructed by replacing the erythromycin resistance gene (erm) with L. plantarum glmS1 under control of the PldhL promoter from WCFS1. The selection efficiency and stability of the glmS-vector were shown to be comparable to those of the erm-based plasmid. Moreover, using mCherry expression as a reporter gene, we showed the feasibility of the system for producing foreign proteins. This food-grade host/vector system will provide an effective and safe technique for the application of lactic acid bacteria in the food and medical industries. Furthermore, this study provides a useful strategy for developing food-grade selection markers in other host/vector systems.

https://ift.tt/2IOrd4F

Prediction and identification of novel sRNAs involved in Agrobacterium strains by integrated genome wide and transcriptome based methods

Abstract

sRNAs are a class of gene regulators in bacteria, playing a central role in its response to environmental changes. Bioinformatic prediction facilitates the identification of sRNAs expressed at different conditions. We propose a novel method of prediction of sRNAs from the genome of Agrobacterium based on PWM matrix of conditional sigma factors. sRNAs predicted from the genome are integrated with the virulence specific transcriptome data to identify putative sRNAs that are over expressed during Agrobacterial virulence induction. A total of 384 sRNAs are predicted from transcriptome data analysis of Agrobacterium fabrum and 100–500 sRNAs from the genome of different Agrobacterial strains. In order to refine our study, a final set of 10 novel sRNAs with best features across different replicons targeting virulence genes are experimentally identified using semi-quantitative PCR. Since Ti plasmid plays major role in virulence, out of 10 sRNAs across the replicons, 4 novel sRNAs differentially expressed under virulence induced and non-induced conditions are predicted to be present in the Ti plasmid T-DNA region flanking virulence related genes like agrocinopine synthase, indole 3-lactate synthase, mannopine synthase and tryptophan monooxygenase. Further, validating the function of these sRNAs in conferring virulence would be relevant to explore its role in Agrobacterium-mediated plant transformation.

https://ift.tt/2pPR9V3

Effects of Climate and Latitude on Age at Maturity and Longevity of Lizards Studied by Skeletochronology

Abstract

Longevity and age at maturity are key life-history traits, directly linked to fitness attributes such as survival and reproductive output. It has been proposed that these traits are strongly influenced by environmental factors, such as temperature, seasonality, and precipitations, which determine the existence of a continuum of life-histories that goes from the "slow" life histories characterized by late maturity and high longevity of cold and highly seasonal climates to the "fast" life histories characterized by early maturity and low longevity, typical of the tropical climates. However, large-scale studies that address these topics in lizards are scarce and most of them are based on heterogeneous data, which may overlook the real patterns. Using skeletochronology, we studied age at maturity and longevity of two species of Phymaturus lizards, Phymaturus aguanegra from the Andes and P. zapalensis from the Patagonian steppe (Argentina). Then, we confronted longevity and age at maturity in these species with published skeletochronology-based data on 46 other lizard species to examine possible association of these life-history traits with latitude and mean annual temperature, thermal amplitude and precipitations. Both Phymaturus species showed late sexual maturity (7 years and 8-9 years, respectively) and high longevity (16 years and 14-15 years, respectively) in coincidence with the other species of the genus studied up to date. The phylogenetic comparative analysis revealed that the most important variable in the determination of longevity patterns in the species studied was latitude: at higher latitudes lizards tend to live longer. In contrast, age at sexual maturity was dependent on mean annual temperature most, especially in males, as lizards from hotter climates mature earlier than lizards from cold sites.

https://ift.tt/2A5gYXf

Pharmacologic Effect of Miao Medicine Illicium simonsii Maxim. on Collagen-Induced Arthritis in Rats

Objectives. To study the pharmacologic effect and mechanism of action of Miao medicine Illicium simonsii Maxim. (ISM) in treating rheumatoid arthritis. Methods. Sixty rats were randomly divided to six groups: normal control (normal), collagen-induced arthritis (CIA) model (model), CIA + tripterygium glycosides (TG), CIA + ISM high dose oral (ISM-H), CIA + ISM low-dose oral (ISM-L), and CIA + ISM topical application (ISM-T). The treatment doses were selected based on published reports and folk medicine practice. The outcome measurements included paw swelling, joint pathology, organ index, blood count, T helper 17 (Th17) cell count, and interleukin-6 (IL-6) level. Results. Compared to the CIA model group, all treatment groups showed a significant reduction in paw swelling, blood vessel pathology, Th17 cell count, and IL-6 levels (p

https://ift.tt/2QJqu7H

Generation of Bimaternal and Bipaternal Mice from Hypomethylated Haploid ESCs with Imprinting Region Deletions

Li et al. utilize haploid ESCs to overcome the uniparental reproductive barriers in mice. They found parent-specific erasure of DNA methylation between parthenogenetic and androgenetic haploid ESCs. After combining gametes and hypomethylated haploid ESCs with certain imprinted region deletions, the authors generated normally growing bimaternal mice and live bipaternal mice.

https://ift.tt/2NBBp1o

CRISPR Activation Screens Systematically Identify Factors that Drive Neuronal Fate and Reprogramming

Liu and colleagues developed a high-throughput CRISPR activation screening approach to systematically identify transcription factors that efficiently promote neuronal fate from ESCs. Some of these single and pairwise factors can further reprogram fibroblasts into neurons, showing that this approach may have broad utility for engineering cell lineages.

https://ift.tt/2OUQHmq

Potential influence of p16 immunohistochemical staining on the diagnosis of squamous cell lesions in cervical biopsy specimens: Observation from cytologic‐histologic correlation

Cancer Cytopathology, EarlyView.


https://ift.tt/2yfjiJJ

Surgical resection for recurrent retroperitoneal leiomyosarcoma and liposarcoma

Abstract

Background

Retroperitoneal soft tissue sarcomas (STS) include a number of histologies but are rare, with approximately 3000 cases in the USA per year. Retroperitoneal STS have a high incidence of local and distant recurrence. The purpose of this study was to review the University of Maryland Medical Center's (UMMC) treatment experience of retroperitoneal STS, where the patient population served represents a diverse socioeconomic and ethnic catchment.

Methods

IRB approval was obtained. We constructed a de-identified database of patients diagnosed with retroperitoneal liposarcomas (LPS) or leiomyosarcomas (LMS) treated at UMMC between 2000 and 2013. A total of 49 patients (Pts) with retroperitoneal STS met our eligibility criteria. Kaplan-Meier plots were used to graphically portray progression-free survival (PFS) and overall survival (OS). The log-rank test was used to compare time-to-event distributions.

Results

The median OS for all patients (Pts) was 6.3 years, and the 2-year OS rate was 81%. The median PFS for all Pts was 1.8 years, and the 2-year PFS rate was 45%. There was no difference in OS and PFS among LMS and LPS patients; the median OS for LMS was 3.8 years vs. LPS 6.4 years (p = 0.33), and the median PFS for LMS was 1.2 years vs. LPS 2.5 years (p = 0.28). There was a significant difference between histology and race (p = 0.001). LPS were primarily Caucasian 86% vs. 14% black, whereas LMS were primarily black 52% vs. 33% Caucasian. OS was influenced by functional status, gender, American Joint Committee on Cancer (AJCC) stage, grade, histology, tumor size, and extent of resection. PFS was influenced by AJCC stage, grade, and extent of resection. Neither adjuvant chemotherapy (1 Pt) nor neoadjuvant/adjuvant radiation therapy (18 Pts) influenced OS or PFS. There was a non-significant difference that Pts who could undergo resection of local recurrence had improved 2-year OS, with 100% LMS and LPS compared to 2-year OS of 71% (LMS) and 78% (LPS) not undergoing resection of local recurrence.

Conclusions

This study suggests a higher incidence of leiomyosarcoma in the African-American population. This study confirms the prognostic importance of grade, tumor size, AJCC stage, histology, and extent of resection in patient outcomes, at a large substantially diverse academic medical center. Future research into the biological features of liposarcoma and leiomyosarcoma Pts imparting these characteristics will be important to define.

https://ift.tt/2Ca6aID

Coexistence of gastric gastrointestinal stromal tumor, intro-abdominal and retroperitoneal liposarcomas –a case report

Abstract

Background

Gastric gastrointestinal stromal tumor (GIST), intro-abdominal and retroperitoneal neoplasms are distinct tumors arising from different cell layers; therefore, coexistence of such tumors is relatively rare.

Case presentation

A man complained of early satiety for 2 mouths, whose upper gastrointestinal (GI) endoscopy showed a tumor arising from the greater curvature of gastric body and extending into the lumen. Abdominal computed tomography (CT) revealed coexistence of gastric, intro-abdominal and retroperitoneal masses. Wedge resection for gastric tumor, resection for intro-abdominal and retroperitoneal tumors were done. The postoperative histological examination suggested simultaneous development of a gastric GIST, intro-abdominal and retroperitoneal myxoid liposarcomas.

Conclusion

Although both GISTs and liposarcomas originate from mesenchymal tissues, simultaneous development of a gastric GIST, intro-abdominal and retroperitoneal liposarcomas is the first such case to be reported in the literature.

https://ift.tt/2ywVhgz

Clinical outcomes of implants placed in ridge‐preserved versus nonpreserved sites: A 4‐year randomized clinical trial

Clinical Implant Dentistry and Related Research, EarlyView.


https://ift.tt/2PuJOp2

High patient satisfaction with a simplified BRCA1 / 2 testing procedure: long-term results of a prospective study

Abstract

Purpose

In the BRCAsearch study, unselected breast cancer patients were prospectively offered germline BRCA1/2 mutation testing through a simplified testing procedure. The purpose of the present study was to evaluate satisfaction with the BRCAsearch testing procedure and, furthermore, to report on uptake rates of prophylactic surgeries among mutation carriers.

Methods

Pre-test information was provided by a standardized invitation letter instead of in-person genetic counseling. The patients were offered contact with a genetic counselor for telephone genetic counseling if they felt a need for that. Mutation carriers were telephoned and given a time for a face-to-face post-test genetic counseling appointment. Non-carriers were informed about the test result through a letter. One year after the test results were delivered, a study-specific questionnaire was mailed to the study participants who had consented to testing. The response rate was 83.1% (448 of 539).

Results

A great majority (96.0%) of the responders were content with the method used for providing information within the study, and 98.7% were content with having pursued genetic testing. 11.1% answered that they would have liked to receive more oral information. In an adjusted logistic regression model, patients with somatic comorbidity (OR 2.56; P = 0.02) and patients born outside of Sweden (OR 3.54; P = 0.01) were more likely, and patients with occupations requiring at least 3 years of university or college education (OR 0.37; P = 0.06) were less likely to wanting to receive more oral information. All 11 mutation carriers attended post-test genetic counseling. At a median follow-up of 2 years, the uptake of prophylactic salpingo-oophorectomy was 100%, and the uptake of prophylactic mastectomy was 55%.

Conclusions

Satisfaction with a simplified BRCA1/2 testing procedure was very high. Written pre-test information has now replaced in-person pre-test counseling for breast cancer patients in our health care region.

https://ift.tt/2IQK1QW

More Than One Angle to Target Aplastic Anemia?

Cancer, EarlyView.


https://ift.tt/2CDFNvS

An evidence‐based approach to learning clinical anatomy: a guide for medical students, educators, and administrators

Clinical Anatomy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2OUWJU8

Plant-Derived Products for Treatment of Vascular Intima Hyperplasia Selectively Inhibit Vascular Smooth Muscle Cell Functions

Natural products are used widely for preventing intimal hyperplasia (IH), a common cardiovascular disease. Four different cells initiate and progress IH, namely, vascular smooth muscle, adventitial and endothelial cells, and circulation or bone marrow-derived cells. Vascular smooth muscle cells (VSMCs) play a critical role in initiation and development of intimal thickening and formation of neointimal hyperplasia. In this review, we describe the different originating cells involved in vascular IH and emphasize the effect of different natural products on inhibiting abnormal cellular functions, such as VSMC proliferation and migration. We further present a classification for the different natural products like phenols, flavonoids, terpenes, and alkaloids that suppress VSMC growth. Abnormal VSMC physiology involves disturbance in MAPKs, PI3K/AKT, JAK-STAT, FAK, and NF-κB signal pathways. Most of the natural isolate studies have revealed G1/S phase of cell cycle arrest, decreased ROS production, induced cell apoptosis, restrained migration, and downregulated collagen deposition. It is necessary to screen optimal drugs from natural sources that preferentially inhibit VSMC rather than vascular endothelial cell growth to prevent early IH, restenosis following graft implantation, and atherosclerotic diseases.

https://ift.tt/2OQXnSM

Anti-Inflammatory Activity of Rg3-Enriched Korean Red Ginseng Extract in Murine Model of Sepsis

Ginseng has therapeutic effects on various bodily disorders ranging from minor inflammation to major cardiovascular diseases. In our study, we explored the anti-inflammatory effects of Rg3-enriched red ginseng extract (Rg3-RGE), a ginsenoside belonging to the panaxadiol group. We employed nitric oxide assay (NO) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), western blot, and hematoxylin and eosin staining (H&E) to elucidate the anti-inflammatory activity of Rg3-RGE. Rg3-RGE potently suppressed NO production in the murine macrophage cell line, RAW 264.7 cells, without any cytotoxicity across dosages. Additionally, it inhibited the mRNA expression of proinflammatory mediators and cytokines like iNOS, COX-2, IL-1β, IL-6, and TNF-α. Moreover it also inhibited the levels of malondialdehyde levels in serum of septic shock mice. Immunoblot analysis showed that Rg3-RGE induced anti-inflammatory signal transduction via the NF-κB and MAPK pathways. A remarkable attenuation of inflammation by oral treatment with Rg3-RGE in mice was observed in the survival study. The in vivo study using a septic shock mouse model also showed similar results as the in vitro study. Our findings suggest that Rg3-RGE can potentially be a potent anti-inflammatory agent that likely mediates its anti-inflammatory effects via the NF-κB and MAPK pathways.

https://ift.tt/2NDxgtE

Development of a Donor Tissue Holding Technique for Descemet’s Membrane Endothelial Keratoplasty Using a 25-Gauge Graft Manipulator

Purpose: To report a modified surgical technique called the "donor tissue holding technique for Descemet's membrane endothelial keratoplasty (DMEK)" using a newly developed 25-gauge graft manipulator. Methods: Six consecutive patients exhibiting endothelial dysfunction were enrolled and treated by DMEK. In brief, after insertion of a DMEK donor into the anterior chamber, the edge of the roll was grasped using a graft manipulator and this grasp was maintained throughout the centering and opening of the roll (holding technique). The following parameters were evaluated in comparison to the previous 10 consecutive DMEK cases in which the no touch technique was used: time of graft unfolding, incidence of intra-/postoperative complications, and best spectacle-corrected visual acuity (BCVA) and endothelial cell density (ECD) 6 months after the procedure. Results: In both technique groups, neither intra- nor postoperative complications were noted in any case. No differences were observed between the two groups in postoperative BCVA (p = 0.88). Also, no differences were observed between the two groups in postoperative ECD (holding technique group: 2,108.3 cells/mm², no touch technique group: 1,491.7 cells/mm²) (p = 0.08) Most notably, the time of graft unfolding prior to filling with air was significantly reduced in the holding technique group (305.5 s) compared to that of the no touch technique group (1,310.0 s; p = 0.01). Conclusions: This donor tissue holding technique enabled rapid and safe DMEK in a reproducible manner, even in Asian eyes with shallow anterior chambers with high vitreous pressure.
Case Rep Ophthalmol 2018;9:431–438

https://ift.tt/2PABdkw

Brain-derived neurotrophic factor, a new soluble biomarker for malignant pleural mesothelioma involved in angiogenesis

Abstract

Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer related to asbestos exposure. The discovery of soluble biomarkers with diagnostic/prognostic and/or therapeutic properties would improve therapeutic care of MPM patients. Currently, soluble biomarkers described present weaknesses preventing their use in clinic. This study aimed at evaluating brain-derived neurotrophic factor (BDNF), we previously identified using transcriptomic approach, in MPM. We observed that high BDNF expression, at the mRNA level in tumors or at the protein level in pleural effusions (PE), was a specific hallmark of MPM samples. This protein presented significant but limited diagnostic properties (area under the curve (AUC) = 0.6972, p < 0.0001). Interestingly, high BDNF gene expression and PE concentration were predictive of shorter MPM patient survival (13.0 vs 8.3 months, p < 0.0001, in PE). Finally, BDNF did not affect MPM cell oncogenic properties but was implicated in PE-induced angiogenesis. In conclusion, BDNF appears to be a new interesting biomarker for MPM and could also be a new therapeutic target regarding its implication in angiogenesis.

https://ift.tt/2IOWRiw

Effect of exosomal miRNA on cancer biology and clinical applications

Abstract

Exosomes, extracellular vesicles with diameters ranging from 30 to 150 nm, are widely present in various body fluids. Recently, microRNAs (miRNAs) have been identified in exosomes, the biogenesis, release, and uptake of which may involve the endosomal sorting complex required for transport (ESCRT complex) and relevant proteins. After release, exosomes are taken up by neighboring or distant cells, and the miRNAs contained within modulate such processes as interfering with tumor immunity and the microenvironment, possibly facilitating tumor growth, invasion, metastasis, angiogenesis and drug resistance. Therefore, exosomal miRNAs have a significant function in regulating cancer progression. Here, we briefly review recent findings regarding tumor-derived exosomes, including RNA sorting and delivering mechanism. We then describe the intercommunication occurring between different cells via exosomal miRNAs in tumor microenvironmnt, with impacts on tumor proliferation, vascularization, metastasis and other biological characteristics. Finally, we highlight the potential role of these molecules as biomarkers in cancer diagnosis and prognosis and tumor resistance to therapeutics.

https://ift.tt/2pMSMmc