Role of IL-6/IL-10 ratio in the diagnosis and in the assessment of the severity of obsessive-compulsive disorder

Abstract

Obsessive-compulsive disorder (OCD) has a genetic and environmental pathogenesis. The immunologic changes in OCD have been proven in many studies, but those tackling cytokine in OCD are still limited. The present study aims to evaluate the diagnostic performance of IL-6, IL-10, and the IL-6/IL-10 ratio in the OCD patient group, and to show their correlation with the clinical parameters of OCD. Eighty subjects (60 OCD patients and 20 matched controls) were participating in this study. The enzyme-linked immunosorbent assay was run to quantify the IL-6 and IL-10. Serum IL-6 exhibited a higher result in OCD patients than controls (p = 0.002) but serum IL-10 levels had no significant difference (p > 0.05). IL-6/IL-10 ratio showed significantly higher values in OCD patients than controls (p < 0.0001). Serum IL-6 and IL-6/IL-10 ratio were negatively correlated with age of onset but were directly correlated with disease duration and disease severity. IL-6/IL-10 ratio showed 86.7% sensitivity and 90% specificity in OCD diagnosis. An immune activation is implicated in the OCD pathogenesis. This was confirmed by the high serum levels of IL-6 in OCD patients. IL-6/IL-10 ratio showed a considerable sensitivity and specificity in the OCD diagnosis. IL-6 and IL-6/IL-10 ratio are correlated positively with the OCD intensity.

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Clinical Correlation of Cytomegalovirus Infection with CMV-Specific CD8+ T Cell Immune Competence Score and Lymphocyte Subsets in Solid Organ Transplant Recipients

Introduction Control of cytomegalovirus (CMV) infection after solid organ transplantation (SOT) requires a functional immune system. We assessed the association between quantitation and function of CMV-specific CD8+ T cells and CMV infection in SOT recipients. Methods During a 10-year period, selected kidney, heart, lung, pancreas, liver and composite tissue recipients were tested for CMV-specific CD8+ T cells immune competence (CMV-CD8+), as measured by enumeration, interferon-gamma production and CD107a/b degranulation. Quantitative and functional data were used to assemble T cell immune competence (TIC) score. CMV infection was diagnosed by PCR in blood and other samples, or histopathology. Results Of 130 patients tested, 59 had CMV infection or disease. The median onset to CMV infection was 10.5 months (IQR 5.5-18.7). Gastrointestinal disease (28.8%), pneumonia (20.3%), and CMV syndrome (17%) were most common presentation. An impaired nonspecific or CMV-CD8+ TIC score was associated with tissue-invasive disease (HR 2.84, 95% CI 1.03-11.81; p=.04). Patients with impaired CMV-CD8+ TIC score had longer viremia duration (42.4 vs. 18.8 days, p<.001 patients with impaired nonspecific or cmv-cd8 tic score had higher risk of relapse vs. hr ci p="0.03)." cmv infection disease lower median absolute lymphocyte count cells and cd4 t cell conclusion cmv-specific cd8 function correlated the course after sot measuring these has potential to assist in its clinical management. correspondence: roshini s. abraham ph.d. department laboratory medicine pathology mayo clinic rochester mn abraham.rochini raymund r. razonable m.d. division infectious diseases razonable.raymund authorship page atibordee meesing: participation performance research data collection analysis writing manuscript abraham: reviewing razonable: design approving disclosures: none funding: copyright wolters kluwer health inc. all rights reserved.>

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Role of 18F-FDG PET/CT in Restrictive Allograft Syndrome after lung transplantation

Background Differential diagnosis of phenotypes of chronic lung allograft dysfunction (CLAD) remains troublesome. We hypothesized that 18F-FDG PET/CT may help in differential diagnosis of CLAD phenotypes, as it showed promising results regarding diagnosis and prognosis in interstitial lung diseases. Methods A monocentric, retrospective study was performed including all lung transplant recipients suffering from bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS) who underwent 18F-FDG PET/CT scan, in comparison with stable lung transplant recipients. Maximum standardized uptake value (SUVmax) was associated with pulmonary function and survival. Proof-of-concept microCT and glucose transporter-1 (GLUT1) staining served as morphologic validation for regions with different SUVmax. Results SUVmax was higher in RAS (median 2.6, n=29) compared to BOS (median 1.0, n=15) and stable patients (median 0.59, n=8) (p

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Patient Functional Status at Transplant and Its Impact on Posttransplant Survival of Adult Deceased-Donor Kidney Recipients

Background Recorded at the time of transplant and reported to the Organ Procurement and Transplantation Network (OPTN), patient's functional status is measured using the Karnofsky Performance Score (KPS), ranging 0-100. Functional status analysis may provide insights on candidate listing and posttransplant survival outcomes for deceased-donor kidney transplants (DDKT). Methods The cohort consisted of adult DDKT recipients transplanted beginning January 2007. One-year and 3-year Cox models for posttransplant survival were fitted with current Scientific Registry of Transplant Recipients (SRTR) variables and KPS. Comparative analyses were performed between the SRTR model without KPS and the augmented model with it. Using the augmented model, we examined the impact of Kidney Donor Profile Index (KDPI) on posttransplant survivals for 5 different KPS strata: 10-30, 40-50, 60-70, 80-90, and 100. Results Comparative analyses showed that KPS was a statistically significant predictor for posttransplant survival: it improved model calibration, discrimination, and predictive accuracy. From the augmented model, the survival curves illustrated that recipients with KPS 40-50 and kidneys with KDPI as high as 99 have expected survival probabilities of above 90% in 1 year and above 80% in 3 years. The expected survival probabilities improve as KPS increases. Recipients with KPS 10-30 have the worst survival probability, even if they received high-quality kidneys. Conclusions Insights from the survival analyses recommend possible inclusion of functional status into SRTR's risk-adjusted models. Moreover, they invite further examination of its use in order to improve current listing and transplantation strategies at transplant centers and potentially reduce deceased-donor kidney discard rate. Corresponding Author: Sanjay Mehrotra, PhD, Professor of Industrial Engineering and Management Sciences, 2145 Sheridan Road, Tech C246, Evanston, IL 60208, Phone: 847-491-3155, Fax: 847-491-8005, E-mail: mehrotra@northwestern.edu Authorship Information Kevin Bui1 MS, Vikram Kilambi2 PhD, James R. Rodrigue3 PhD, Sanjay Mehrotra4 PhD, 1Developed research design, conducted data analysis, and drafted the article; 2Reviewed research design and edited article; 3Reviewed and edited article; 4Developed research design, supervised data analysis, and edited the article; Authors have no conflicts of interest to disclose. This work is funded by National Institutes for Health award 1R21DK108104-01. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Living Donors: Caring for the Trailblazers of Progress in Transplantation

No abstract available

https://ift.tt/2vyJq11

Submandibular Gland-preserving Technique for Heterotopic Cervical Heart Transplantation in Mice

No abstract available

https://ift.tt/2ARW0xf

DONOR HYPOTHERMIA AND ORGAN TRANSPLANTATION

No abstract available

https://ift.tt/2OPKdlX

Changes in Simultaneous Liver Kidney Transplant Allocation Policy May Impact Post Liver Transplant Outcomes

Background Previous simultaneous liver-kidney transplant (SLK) allocation was based on serum creatinine, a metric that disadvantaged women relative to men. A recent SLK policy change utilizes eGFR, which accounts for sex-based differences in creatinine. Methods To understand the impact of this new policy, we analyzed nonstatus 1 adults listed for liver transplantation (LT) from 5/2007-7/2014, excluding those with exceptions. We defined patients who met the new SLK policy as having an eGFR

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Reducing proinflammatory signalling and enhancing insulin secretion with the application of oxygen persufflation in human pancreata

No abstract available

https://ift.tt/2vtWGUr

EFFECT OF DONOR AGE ON OUTCOME OF LUNG TRANSPLANTATION STRATIFIED BY RECIPIENT DIAGNOSIS: A NORDIC MULTICENTER STUDY

Background Organs from older donors are increasingly used in lung transplantation, and studies have demonstrated that this could be safe in selected recipients. However, which recipient groups that have the largest benefit of older organs are unclear. This multicenter study reviews all bilateral lung transplantations (BLTx) from donors ≥55 years stratified by recipient diagnosis, and compares outcomes with transplantations from younger donors. Methods All BLTx recipients (excluding ReTx) at 5 Scandiatransplant centers between 2000 and 2013 were included (n=913). Recipients were stratified to diagnosis groups including cystic fibrosis (CF), Chronic Obstructive Pulmonary Disease (COPD), interstitial lung disease (ILD) and "Other". Intensive care unit (ICU) length of stay (LOS) and survival were assessed. Results Overall, there was no difference in survival among patients transplanted from donors ≥ 55 years compared to younger donors. However, in CF-recipients, donor age ≥55 years was associated with inferior survival (p=0.014), and this remained significant in a multivariate model (HR 5.0, CI 1.8 – 14.1, p=0.002). There was no significant effect of donor age on survival in recipients with COPD, ILD or in the "Other"-group in multivariate models. Utilization of older donors was associated with increased ICU LOS for recipients with CF and ILD, but not in the COPD or "Other"-group. Conclusions BLTx recipients with CF had inferior survival and longer ICU LOS when receiving organs from donors ≥55 years. Recipients with COPD, ILD or in the "Other"-group did not have inferior survival in multivariate models. Authorship information Author-Areas of participation Auråen H-Research design, writing, performance of research, data analysis Durheim MT-Research design, writing, performance of research, data analysis Dellgren G-Writing, performance of research Hämmäinen P-Writing, performance of research Larsson H-Writing, performance of research Geiran O-Writing, performance of research Lawaetz Schultz HH-Writing, performance of research Leuckfeld I-Writing, performance of research Iversen M-Writing, performance of research Fiane AE-Writing, performance of research Holm AM-Research design, writing, performance of research, data analysis Conflict of interest statement: The authors declare no conflicts of interest. Funding: First author Auråen H received funding from The Norwegian Respiratory Society to conduct this research. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2APhTND

Effect of institutional case volume on in-hospital mortality after living donor liver transplantation: Analysis of 7073 cases between 2007 and 2016 in Korea

Background The relationship between institutional case volume and clinical outcomes after living donor liver transplantation is not clarified. Methods We conducted a nationwide retrospective cohort study using the database of Korean National Healthcare Insurance Service. Between January 2007 and December 2016, 7073 adult living donor liver transplantations were performed at 50 centers in Korea. Centers were categorized according to the average annual number of liver transplantations: >50, 10 to 50, and 50 liver transplantations/year) had better outcomes after living donor liver transplantation, including in-hospital mortality and long-term mortality, compared to centers with lower case volume (≤50 liver transplantations/year). Seokha Yoo and Eun Jin Jang contributed equally to this work and are co-first authors. Corresponding author: Ho Geol Ryu, MD, PhD, Seoul National University Hospital, Seoul National University College of Medicine, Daehak-ro 101, Jongno-gu, Seoul, 03080, Republic of Korea, E-mail: hogeol@gmail.com Authorship S.Y.: Study design, Data analysis, First draft of manuscript E.J.J.: Data acquisition, Data analysis, First draft of manuscript N.J.Y.: Revision of manuscript G.H.K.: Data acquisition, Data analysis D.H.K.: Data acquisition, Data analysis H.L.: Study conception, Revision of manuscript C.W.J.: Study design, Revision of manuscript H.G.R.: Study conception, Study design, Revision of manuscript Disclosure The authors declare no conflicts of interest. Funding None. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Expression of programmed death ligand-1 and programmed death-1 in samples of invasive ductal carcinoma of the breast and its correlation with prognosis

The aim of the current study is to investigate programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) expressions and to analyze the relationship between the expression of PD-L1 and PD-1 proteins and the molecular type, clinicopathological factors, and prognosis of invasive ductal carcinoma. We enrolled 136 patients with invasive ductal carcinoma of the breast. The expression of PD-L1 in tumor cells and that of PD-1 on paratumor-infiltrating immune cells was detected by immunohistochemistry, and the data were analyzed using SPSS software. The positive expression rates of PD-L1 and PD-1 in triple-negative breast cancer (TNBC) were 47.8 and 43.5%, which were higher than those of other subtypes (P

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The autopsy evaluation of “straightforward” fire deaths

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Cannibalism amongst penitentiary escapees from Sarah Island in nineteenth century Van Diemen’s Land

Abstract

Alexander Pearce was an Irish convict incarcerated on Sarah Island on the west coast of Van Diemen's Land (modern day Tasmania, Australia) in 1822, following his transportation to the colony from the United Kingdom for seven years in 1819. On two occasions he escaped from the island, in September 1822 and again in November 1823, and was only able to survive the harsh conditions by killing and consuming his fellow escapees. Given that Pearce utilized the only sustenance that was at hand (i.e. his five companions), and that there was a temporal separation between the two episodes, this may represent a separate category of anthropophagy, that of serial opportunistic cannibalism.

https://ift.tt/2vtreFL

The correlation between the Aquatic Decomposition Score (ADS) and the post-mortem submersion interval measured in Accumulated Degree Days (ADD) in bodies recovered from fresh water

Abstract

The Aquatic Decomposition Score (ADS) made by van Daalen et al., was developed to approximate the Post-Mortem Submersion Interval (PMSI) in bodies recovered in salt water. Since the decomposition process in salt water differs from the process in fresh water due to salinity, the temperature, and the depth of the water, we wanted to investigate whether there is a correlation between the ADS and the PMSI and if the ADS can be used to make an estimation of the PMSI in bodies recovered from fresh water. For the latter, the PMSI was measured using Accumulated Degree Days (ADD). In our study we included seventy-six human remains found outdoors in fresh water. Their decomposition was measured using the ADS. A strong correlation was found between the ADS and the PMSI. Also, it was found that the ADS can significantly estimate the ADD. Despite the more varied circumstances under which bodies in fresh water are found when compared to those found in salt water, the ADS can be used to measure the decomposition and accurately estimate the ADD, and thus the PMSI. More research is needed to validate our method and make a prediction model with smaller confidence intervals.

https://ift.tt/2B2e4oH

Extracellular Matrix and Adhesion Molecule Gene Expression in the Normal and Injured Murine Intervertebral Disc

Objectives To determine the transcription profile of the mouse nucleus pulposus (NP) and annulus fibrosus (AF) with an unbiased method. Furthermore, pathophysiological relevance of selected genes was demonstrated in the mouse tail intervertebral disc (IVD) injury model. Design Paired normal mouse NP and AF tissue from C57BL/6j mice was examined by a polymerase chain reaction (PCR) array. Key gene expression in the normal and injured IVDs were confirmed by Real-Time PCR. Results Among the 84 genes studied, 63 were expressed higher in AF than in NP; only 4 genes were expressed higher in NP than in AF (n=4, p≤0.05). Real-time PCR confirmed that cadherin (cdh)-2 gene expression was higher in NP than in AF, and type I collagen (col1) gene expression was higher in the AF than in NP (n=8, p

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Tertiary education regarding stillbirth for student midwives: The tears 4 SMS project

Publication date: Available online 7 August 2018

Source: Women and Birth

Author(s): Jane Warland, Pauline Glover

Abstract

Problem

Undergraduate education for midwives in the area of stillbirth may be lacking.

Background

When a baby dies the families are usually cared for, at some stage in their pregnancy or birth journey, by midwives, however, midwives may not be adequately prepared to care for them.

Aim

The aim of this study was to investigate the current content of stillbirth education in undergraduate midwifery curricula in Australia.

Methods

Nineteen midwifery program leaders from each of the Australian Universities that deliver undergraduate midwifery education were invited to respond to an online survey regarding content related to stillbirth risk, prevention and/or bereavement care.

There were 10 complete surveys. Quantitative survey data were analysed and described using percentages, and data from the free text comments collected verbatim.

Findings

Responses indicated that there is a diverse inclusion of material relating to the topic of stillbirth, with different approaches to teaching the content and the amount of time devoted to the topic is relatively small.

Discussion

This small study in scoping curricula from participating Australian Universities indicated that more could be done to strengthen stillbirth related content. Stillbirth is a complex issue and therefore it is important for midwives to understand not only bereavement care but also the physiological underpinnings of issues that could be an antecedent cause or precursor for stillbirth.

Conclusion

There is room to improve and standardise appropriate stillbirth curriculum nationally. It is imperative that midwives are able to provide sensitive and knowledgeable care to all women and their families.

https://ift.tt/2vUjNHl

GENOME REPORT: Highly Contiguous Genome Assemblies of 15 Drosophila Species Generated Using Nanopore Sequencing

The Drosophila genus is a unique group containing a wide range of species that occupy diverse ecosystems. In addition to the most widely studied species, Drosophila melanogaster, many other members in this genus also possess a well-developed set of genetic tools. Indeed, high-quality genomes exist for several species within the genus, facilitating studies of the function and evolution of cis-regulatory regions and proteins by allowing comparisons across at least 50 million years of evolution. Yet, the available genomes still fail to capture much of the substantial genetic diversity within the Drosophila genus. We have therefore tested protocols to rapidly and inexpensively sequence and assemble the genome from any Drosophila species using single-molecule sequencing technology from Oxford Nanopore. Here, we use this technology to present highly contiguous genome assemblies of 15 Drosophila species: 10 of the 12 originally sequenced Drosophila species (ananassae, erecta, mojavensis, persimilis, pseudoobscura, sechellia, simulans, virilis, willistoni, and yakuba), four additional species that had previously reported assemblies (biarmipes, bipectinata, eugracilis, and mauritiana), and one novel assembly (triauraria). Genomes were generated from an average of 29x depth-of-coverage data that after assembly resulted in an average contig N50 of 4.4 Mb. Subsequent alignment of contigs from the published reference genomes demonstrates that our assemblies could be used to close over 60% of the gaps present in the currently published reference genomes. Importantly, the materials and reagents cost for each genome was approximately $1,000 (USD). This study demonstrates the power and cost-effectiveness of long-read sequencing for genome assembly in Drosophila and provides a framework for the affordable sequencing and assembly of additional Drosophila genomes.

https://ift.tt/2McgSUg

Breast Milk Iodine Concentration Rather than Maternal Urinary Iodine Is a Reliable Indicator for Monitoring Iodine Status of Breastfed Neonates

Abstract

There is no scientific consensus on whether breast milk iodine concentration (BMIC) accurately reflects iodine status in lactating mothers and breastfed infants. This study aimed to compare BMIC and maternal urinary iodine concentration (UIC) as indicators of iodine status in breastfed neonates. In this cross-sectional study, 147 lactating mothers and their neonates (3–5 days postpartum) were randomly selected from health care centers. Breast milk and urine samples were collected from each mother and neonate, and a heel-prick blood sample was taken from all neonates as part of a congenital hypothyroidism screening program. According to the World Health Organization criteria, median urinary iodine concentration (UIC) ≥ 100 μg/L in lactating mothers and neonates indicates iodine sufficiency. In areas of iodine sufficiency, median BMIC ≥ 100 μg/L is considered an adequate level. Overall, 129 (89.0%) and 16 (11.0%) mothers had BMICs ≥ 100 and ˂ 100 μg/L, respectively. Median (interquartile range [IQR]) maternal UIC was 70 μg/L (42–144 μg/L) and 37 μg/L (25–100 μg/L) in mothers with breast milk iodine levels ≥ 100 and ˂ 100 μg/L, respectively (P = 0.047); values for UIC of neonates born to mothers with BMICs ≥ 100 and ˂ 100 μg/L were 230 μg/L (114–310 μg/L) and 76 μg/L (41–140 μg/L), respectively (P < 0.001). In the linear regression model, neonate UIC was positively associated with BMIC in both unadjusted (β = 0.558, P < 0.001) and adjusted analysis (β = 0.541, P < 0.001). A similar result was found in logistic regression analysis, indicating that neonates born to mothers with BMIC ≥ 100 μg/L were more likely to have UIC ≥ 100 μg/L compared to those whose mothers had BMIC < 100 μg/L in both unadjusted (OR = 7.93, P < 0.001) and adjusted analysis (OR = 7.29, P = 0.001). The present findings indicate that BMIC is a more sensitive indicator than maternal UIC for assessment of iodine status in breastfed neonates. To address low levels of maternal UIC, further studies on the prescription of supplements containing 150 μg/day iodine during lactation period are warranted.

https://ift.tt/2AR3Yqv

MHC Expression Predicts Checkpoint Blockade Response [News in Brief]

Class I and II proteins associated with differential responses to PD-1 and CTLA4 inhibitors.

https://ift.tt/2vHxwku

Antioxidant and Cytoprotective Activity of Oxydiacetate Complexes of Cobalt(II) and Nickel(II) with 1,10-Phenantroline and 2,2′-Bipyridine

Abstract

The antioxidant properties of oxydiacetate complexes of cobalt(II) and nickel(II) with 1,10-phenantroline and 2,2′-bipyridine have been investigated towards the superoxide radical using the nitro blue tetrazolium chloride (NBT) test and the cyclic voltammetry (CV). Moreover, the biological activity of the complexes under study has been investigated in the Human Dermal Fibroblasts adult (HDFa) cell line. In the first step, the cytotoxic and the antiproliferative activities of the complexes were examined. Subsequently, the cytoprotective properties of the complexes have been investigated in an oxidative stress conditions induced by H₂O₂.

https://ift.tt/2voRi58

Environment-Friendly Synthesis of Trace Element Zn, Sr, and F Codoping Hydroxyapatite with Non-cytotoxicity and Improved Osteoblast Proliferation and Differentiation

Abstract

Hydroxyapatite (HAp, Ca₁₀[PO₄]₆[OH]₂) doped with numerous trace elements possesses sensational biochemical effects in natural bones. To study the biochemical function of Zn, Sr, and F elements, a series of neoteric HAp biomaterials with Zn, Sr, and F concentrations close to natural bones are firstly synthesized by one-pot hydrothermal method. These materials are characterized through powder X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscope (SEM). All the synthesized materials are HAp phase. The morphology of these materials is nanorods. The phenomenon that L929 cells can live even at 400 μg/mL powder concentration indicates that these materials are non-cytotoxic. The active effects of samples on proliferation and differentiation of osteoblast cells (MC3T3-E1) are certified by MTT and alkaline phosphatase (ALP) activity assays. The adhesion and proliferation of osteoblast measurement manifest that amounts of MC3T3-E1 advances about 1.86 times for ZnSrF/HAp compared with undoped HAp. This achievement may inspire us on the artificial design of new-style bionic bone grafts using trace bioactive elements and also suggest its latent applications in orthopedic surgery and bone osseointegration.

https://ift.tt/2ASd06E

Correction to: Biomonitoring of Trace Metals in the Keban Dam Reservoir (Turkey) Using Mussels ( Unio elongatulus eucirrus ) and Crayfish ( Astacus leptodactylus )

Abstract

The original version of this article contained mistakes: the units mg/kg^-1 and μg/kg^-1 found on tables 1, 2, 4, 5 and 6 should be mg kg⁻¹ and μg kg⁻¹, respectively.

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Protective Effects of Selenium on Cyclophosphamide-Induced Oxidative Stress and Kidney Injury

Abstract

Cyclophosphamide (CP) is a common anticancer drug, but its use in cancer treatment is limited due to its severe toxicities induced mainly by oxidative stress in normal cells. Reactive oxygen species (ROS) lead to multiple organ injuries, including the kidneys. Selenium (Se) is a nutritionally essential trace element with antioxidant properties. In the present study, the possible protective effect of Se on CP-induced acute nephrotoxicity was investigated. Forty-two Sprague-Dawley rats were equally divided into six groups of seven rats in each. The control group received saline, and other groups were injected with CP (150 mg/kg), Se (0.5 or 1 mg/kg), or CP + Se intraperitoneally. Total antioxidant capacity (TAC), total oxidant state (TOS), oxidative stress index (OSI), creatinine, and cystatin C (Cys C) levels were measured in the sera. In addition, kidney tissues were examined histologically. In the CP alone treated rats, creatinine, Cys C, TOS, and OSI levels increased, while TAC level decreased. CP-induced histological damages were decreased by co-treatment of Se and biochemical results supported the microscopic observations. In conclusion, our study points to the therapeutic potential of Se and indicates a significant role of ROS in CP-induced kidney toxicity.

https://ift.tt/2AOUCLL

Cadmium Profiles in Dental Calculus: a Cross-Sectional Population-Based Study in Hunan Province of China

Abstract

We aimed to investigate whether the cadmium concentrations differ in human dental calculus obtained from the residents with no smoking living in the contaminated area and those with no smoking living in noncontaminated area. In total, there were 260 samples of dental calculus from the adults (n = 50) with no smoking living in contaminated area, the adults (n = 60) with no smoking living in mountainous area, and the adults (n = 150) with no smoking living in low altitude area in Hunan province of China. All samples were analyzed by inductively coupled plasma mass spectrometry (ICP-MS) for cadmium levels. The cadmium levels in dental calculus were significantly higher in the adults with no smoking living in contaminated area than those living in mountainous area and in low altitude area (p < 0.01). The cadmium levels in dental calculus were also higher in the adults with no smoking living in low altitude area than those living in mountainous region (p < 0.01). The results suggested that measuring cadmium levels in dental calculus may be a useful noninvasive method for analysis of environmental exposure to cadmium in the human oral cavity. The low altitude region may have an area contaminated with cadmium in Hunan province of China.

https://ift.tt/2ORUJZT

The Content of Mercury in Herbal Dietary Supplements

Abstract

The dietary supplement market in Poland has been growing rapidly, and the number of registered products and their consumption increases steadily. Among the most popular and the easiest to get are herbal supplements, available in any supermarket. The aim of this paper was to investigate the mercury content in the herbal supplements. The dietary supplements that have been examined (24) are available on the Polish market and contain one or more herbal ingredients. Supplements were pulverized in porcelain mortar and identified by AMA 254 atomic absorption spectrometer. The range of variations for all tested supplements was within 0.02–4293.07 μg/kg. The arithmetic mean of the total result was 193.77 μg/kg. A higher mercury content then this mean was found in preparations—bamboo shoots and alga Chlorella pyrenoidosa. The studies have shown that mercury is present in every examined herbal supplement, and its content exceeds in two preparations (with bamboo and alga) the permissible limit of 0.10 mg/kg. There were statistically significant differences in the occurrence of mercury depending on the herbal ingredient in the supplement. The lowest content was found in the preparation with Tanacetum parthenium and the highest with bamboo shoots. The mercury content in the tested herbal supplements was statistically significant in the form of a supplement—a tablet and a capsule. Daily, weekly, monthly, and yearly consumption of mercury with examined supplements was calculated—the results did not exceed the PTWI—provisional tolerable weekly intake of mercury. To increase consumer safety, it is imperative to conduct further research on dietary supplements and implement a stricter quality control of the dietary supplements.

https://ift.tt/2ARhdHF

Low, but Not High, Doses of Copper Sulfate Impair Synaptic Plasticity in the Hippocampal CA1 Region In Vivo

Abstract

Previous studies have shown the inhibitory effect of the in vitro application of copper sulfate on hippocampal long-term potentiation. While in vivo administration of copper did not affect spatial learning and memory. To find possible answers to this controversial issue, we evaluate the effect of different doses of copper sulfate on in vivo long-term potentiation, synaptic transmission, and paired-pulse behavior of CA1 pyramidal cells. Thirty-two male Wistar rats were divided into four groups: control, 5, 10, and 15 mg of copper sulfate. Field excitatory postsynaptic potential from the stratum radiatum of CA1 neurons was recorded following Schaffer collateral stimulation in rats. Spike amplitude, long-term potentiation and paired-pulse index were measured in all groups. The results of this study showed that 5 mg/kg copper sulfate increased synaptic transmission and inhibited long-term potentiation and decreased the hippocampal paired-pulse ratio, while 10 and 15 mg/kg copper sulfate did not affect CA1 synaptic transmission properties. Low, but not high, doses of copper sulfate affect synaptic plasticity. This finding may explain the difference between the effect of copper on synaptic plasticity and spatial learning and memory.

https://ift.tt/2vsypya

Methylmercury Intoxication Promotes Metallothionein Response and Cell Damage in Salivary Glands of Rats

Abstract

Environmental and occupational mercury exposure is considered a major public health issue. Despite being well known that MeHg exposure causes adverse effects in several physiologic functions, MeHg effects on salivary glands still not completely elucidated. Here, we investigated the cellular MeHg-induced damage in the three major salivary glands (parotid, submandibular, and sublingual) of adult rats after chronic, systemic and low doses of MeHg exposure. Rats were exposed by 0.04 mg/kg/day over 60 days. After that, animals were euthanized and all three glands were collected. We evaluated total Hg accumulation, metallothionein I/II (MT I/II), α-smooth muscle actin (α-SMA), and cytokeratin 18 (CK18) immune expression. Our results have showed that MeHg is able to disrupt gland tissue and to induce a protective mechanism by MT I/II expression. We also showed that cell MT production is not enough to protect gland tissue against cellular structural damage seen by reducing marking of cytoskeletal proteins as CK18 and α-SMA. Our data suggest that chronic MeHg exposure in low-daily doses is able to induce cellular damage in rat salivary glands.

https://ift.tt/2ARMf2d

Comparative Proteomics of Chromium-Transformed Beas-2B Cells by 2D-DIGE and MALDI-TOF/TOF MS

Abstract

Chromium (Cr) is a highly toxic, common heavy metal used in industrial production. There are two types of Cr in nature: hexavalent chromium (Cr(VI)) and chromium trichloride (Cr(III)). Cr(III) is involved in the metabolism of sugars and lipids, whereas Cr(VI) is absorbed through the respiratory tract and skin and generates free radicals that result in secondary toxicity. Cr(VI) leads to cancer in the occupational population and is therefore recognized as a human carcinogen by the International Agency for Research on Cancer. The specific mechanism underlying Cr-induced carcinogenesis is complex. In this study, two-dimensional fluorescence difference gel electrophoresis and matrix-assisted laser desorption ionization-time-of-flight/time-of-flight mass spectrometry-based techniques were performed to analyze differentially expressed proteins between Beas-2B human bronchial epithelial cells and Cr(VI)-transformed Beas-2B cells. Many differentially expressed proteins were identified in the cells after malignant transformation, including serine/threonine kinase 11, endothelial nitric oxide synthase 3, apolipoprotein A1, vinculin, and lamin A/C. These proteins are involved in many signaling and metabolic pathways, including apoptosis, autophagy, the PI3K/Akt signaling pathway, focal adhesion, cell motility, and actin cytoskeleton rearrangement.

https://ift.tt/2vtluf7

Challenging Case: Mediastinal Mammary Malignancy

A 47-year-old woman presented with a left-sided, 10-cm breast mass with inflammatory skin changes. She had palpable left axillary and supraclavicular lymph nodes. Biopsy of the breast mass and both nodes demonstrated invasive ductal carcinoma, grade 3, estrogen receptor positive, progesterone receptor positive, and HER-2/neu negative.

https://ift.tt/2LZ6b8z

Meetings

September 5-8, 2018

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Two Sides of the Same Coin: Head and Neck Cancer Treatment De-Intensification and Intensification with Induction Chemotherapy

The terms "intensification" and "de-intensification" are ubiquitous in the lexicon of head and neck oncology as the field moves toward individualizing treatment strategies on the basis of clinical factors such as TNM staging and biomarkers such as human papillomavirus (HPV). In this edition of Oncology Scan, we feature 3 articles linked by the theme of induction chemotherapy (IC), a treatment paradigm used for both intensification and de-intensification. The first 2 articles, by Marur et al (1) and Chen et al (2), study HPV-associated oropharyngeal cancer and examine the role of IC to select patients for radiation dose de-escalation.

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Erratum to: Ho AY, Olm-Shipman M, Zhang Z, et al. A Randomized Trial of Mometasone Furoate 0.1% to Reduce High Grade Acute Radiation Dermatitis in Breast Cancer Patients Receiving Postmastectomy Radiation. Int J Radiat Oncol Biol Phys 2018;101;325-333.

The primary institutional affiliation for Alice Y. Ho, M.D., Molly Olm-Shipman, R.N., and Brittany B. Arnold, B.A. is the Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center. This study was designed, performed, conducted and analyzed at the Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center.

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Lymphedema: Time for an Update

Improvements in cancer survivorship have led to increased recognition of treatment-related toxicities, some of which may not occur until years after the conclusion of treatment (1, 2). For breast cancer survivors, lymphedema is one of the most dreaded complications of surgery, radiation therapy, and taxane-based chemotherapy. Lymphedema involves a build-up of extracellular fluid within the upper extremity and results in swelling and, at times, chronic skin changes, fibrosis, loss of sensation, deformity, and pain (3).

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Systemic Therapy with Radiation to the Chest Wall Alone

This case highlights the therapeutic dilemma encountered in patients with limited metastatic disease, who have both a substantial risk of local–regional recurrence (LRR) and a large competing risk of distant metastases (1). If the patient had presented without metastatic disease, her initial tumor burden would have warranted radiation. However, in the setting of metastatic disease, treatment recommendations are less clear. The available retrospective literature in women with inflammatory disease suggests that aggressive local treatment improves local control (2) and may even benefit overall survival (3), but these data are limited in their generalizability owing to biases in patient selection.

https://ift.tt/2vOxA1I

Radiation Oncology in Mexico: Toward a Unified Model

The United Mexican States, best known as Mexico, has a population of approximately 120 million and a territory of approximately 750,000 square miles, encompassing a wide variety of natural and human-made wonders. The size, geographical location, and geology of the territory allows for a great variety of landscapes, from desert to rainforest to dramatic coastlines, that are habitats for diverse animal and plant species (10% of all those that exist on the planet). Although Mexico is located in North America, from cultural and economic points of view, it is considered a part of Latin America and is the principal tourist destination of that region.

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Putting the “BR” in SBRT

This patient presents with stage IV, cT4dN3cM1 oligometastatic inflammatory breast cancer (IBC) (1). The initial treatment would be neoadjuvant chemotherapy (NAC). In the absence of progression with NAC, we would recommend mastectomy with axillary lymph node dissection and postmastectomy radiation therapy (PMRT). Given IBC's penchant for locoregional recurrence and progression to carcinoma en cuirasse, an aggressive approach to PMRT is warranted, despite the presence of initial limited metastatic disease.

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Issue Highlights

Margalit and Lin

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In Regard to Beadle and Anderson

We were pleased to read the thoughtful editorial by Drs Beadle and Anderson entitled "CTV Guidance for Head and Neck Cancers" (1) and wanted to call attention to the availability of these guidelines for download by the worldwide oncology community at the Head and Neck Cancer Intergroup (HNCIG) website.

https://ift.tt/2vU87V1

Erratum to: Schreibmann E, Schuster D, Rossi P, et al. Image Guided Planning for Prostate Carcinomas With Incorporation of Anti-3-[18F]FACBC (Fluciclovine) Positron Emission Tomography: Workflow and Initial Findings From a Randomized Trial. Int J Radiat Oncol Biol Phys 2016;96:206-213.

En error was identified by the authors in the abstract. Instead of "11 (20%) in the prostate bed, 10 (18%) in the prostate," the text should read "21 (38%) in the prostate bed." All patients in this study underwent radical retropubic prostatectomy. The authors regret the error. The data is written correctly in the body of the paper.

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Aggressive Systemic Therapy with Response-Based Radiation

Kirk: I take it the odds are against us and the situation is grim.Picard: You could say that.Kirk: You know if Spock were here, he'd say I was an irrational, illogical human being for going on a mission like that. [pause] Sounds like fun!- Star Trek: Generations

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Loss of Function of Canonical Notch Signaling Drives Head and Neck Carcinogenesis

Purpose:Head and neck squamous cell carcinoma (HNSCC), a common cancer worldwide, is etiologically associated with tobacco use, high alcohol consumption and high risk human papillomaviruses (HPV). The Notch signaling pathway, which is involved in cell differentiation decisions with differential downstream targets and effects depending on tissue type and developmental stage, has been implicated in human HNSCC. Notch1 is among the most frequently mutated genes in both HPV-positive and HPV-negative HNSCC. These mutations are predicted to inactivate the function of Notch. Other studies have argued the opposite - that Notch signaling is increased in HNSCC. Experimental Design:To assess the role of Notch signaling in HPV-positive and HPV-negative HNSCC, we utilized genetically engineered mouse (GEM) models for conventional keratinizing HNSCC, in which either HPV16 E6 and E7 oncoproteins or a gain of function mutant p53 are expressed, and in which we inactivated canonical Notch signaling via expression of a dominant negative form of MAML1 (DNMAML1), a required transcriptional co-activator of Notch signaling. Results:Loss of canonical Notch signaling increased tumorigenesis in both contexts and also caused an increase in nuclear b-catenin, a marker for increased tumorigenic potential. When combined with loss of canonical Notch signaling, HPV oncogenes led to the highest frequency of cancers overall and the largest number of poorly differentiated (high grade) cancers. Conclusions:These findings inform on the contribution of loss of canonical Notch signaling in head and neck carcinogenesis.

https://ift.tt/2OQO4iI

Intraoperative Tap Test for Coronal Syndesmotic Instability: A cadaveric study

Publication date: Available online 7 August 2018

Source: Injury

Author(s): Cesar de Cesar Netto, Martim Pinto, Lauren Roberts, Sung Ro Lee, Andrew R. Roney, Sameer Naranje, Alexandre Leme Godoy-Santos, Ashish Shah

ABSTRACT

Introduction

Precise diagnosis of distal tibiofibular syndesmotic injury is challenging, and a gold standard diagnostic test has still not been established. Tibiofibular clear space identified on radiographic imaging is considered the most reliable indicator of the injury. The Cotton test is the most widely used intraoperative technique to evaluate the syndesmotic integrity although it has its limitations. We advocate for a novel intra operative test using a 3.5 mm blunt cortical tap.

Methods

Tibiofibular clear space was assessed in nine cadaveric specimens using three sequential fluoroscopic images. The first image was taken prior to the application of the tap test (intact, non-stressed). Then, a 2.5 mm hole was drilled distally on the lateral fibula, and a 3.5 mm cortical tap was then threaded in the hole. The tap test involved gradually advancing the blunt tip against the lateral tibia, providing a tibiofibular separation force (intact, stressed). This same stress was then applied after all syndesmotic ligaments were released (injured, stressed). Measurements were compared by one-way ANOVA and paired Student's t-test. Intra and inter-observer agreements were evaluated by intraclass correlation coefficient (ICC). P-values <.05 were considered significant.

Results

We found excellent intra-observer (0.97) and inter-observer (0.98) agreement following the imaging assessment. Significant differences were found in the paired comparison between the groups (p < .05). When using an absolute value for TFCS >6 mm as diagnostic for coronal syndesmotic instability, the tap test demonstrated a 96.3% sensitivity and specificity, a 96.3% PPV and NPV and a 96.3% accuracy in diagnosing coronal syndesmotic instability.

Conclusions

Our cadaveric study demonstrated that this novel coronal syndesmotic instability test using a 3.5 mm blunt cortical tap is a simple, accurate and reliable technique able to demonstrate significant differences in the tibiofibular clear space when injury was present. It could represent a more controlled and stable alternative to the most used Cotton test.

https://ift.tt/2nnC0c5

Laparotomy for organ evisceration from abdominal stab wounds: A South African experience

Publication date: Available online 7 August 2018

Source: Injury

Author(s): V.Y. Kong, R. Weale, J.M. Blodgett, J. Buitendag, J.L. Bruce, G.L. Laing, D.L. Clarke

Abstract

Introduction

Organ evisceration following abdominal SW is currently considered as an absolute indication for mandatory laparotomy due to the high incidence of associated intra-abdominal injuries, but literature describing the spectrum of organ injury encountered is limited.

Materials and Methods

We reviewed our experience of 301 consecutive patients who were subjected to mandatory laparotomy over an eight year period at a major trauma centre in South Africa.

Results

Of the 301 patients with organ evisceration, 92% were male (mean age 28 years). Ninety percent (270/301) of the laparotomies were positive (85% (229/270) therapeutic, 15% (41/270) non-therapeutic. The frequencies of eviscerated organs were small bowel (70%), large bowel (26%), and stomach 3%. Three (1%) patients had combined evisceration of more than one of the above organ. The most commonly injuries organs were small bowel, and large bowel. The mean length of stay was 9 days. Seven present required intensive care admission. The morbidity was rate was 21% and mortality was 2%.

Conclusions

The spectrum of injury associated with abdominal SW with organ evisceration is similar to smaller published series. Multiple organ injuries are common. The most common eviscerated organs were small bowel, large bowel and stomach while the commonly injured organs were small bowel and colon.

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Increased synthesis of MCL-1 protein underlies initial survival of EGFR mutant lung cancer to EGFR inhibitors and provides a novel drug target

Purpose: EGFR inhibitors (EGFRi) are effective against EGFR mutant lung cancers. The efficacy of these drugs however is mitigated by the outgrowth of resistant cells, most often driven by a secondary acquired mutation in EGFR, T790M. We recently demonstrated that T790M can arise de novo during treatment (Hata et al., Nature Medicine 2016); it follows that one potential therapeutic strategy to thwart resistance would be identifying and eliminating these cells (referred to as drug tolerant cells (DTCs)) prior to acquiring secondary mutations like T790M. Experimental Design: We have developed DTCs to EGFRi in EGFR mutant lung cancer cell lines. Subsequent analyses of DTCs included RNA-seq, high-content microscopy, and protein translational assays. Based on these results, we tested the ability of MCL-1 BH3 mimetics to combine with EGFR inhibitors to eliminate DTCs and shrink EGFR mutant lung cancer tumors in vivo. Results: We demonstrate surviving EGFR mutant lung cancers upregulate the anti-apoptotic protein MCL-1 in response to short-term EGFRi treatment. Mechanistically, DTCs undergo a protein biosynthesis enrichment resulting in increased mTORC1-mediated mRNA translation of MCL-1, revealing a novel mechanism in which lung cancer cells adapt to short-term pressures of apoptosis-inducing kinase inhibitors. Moreover, MCL-1 is a key molecule governing the emergence of early EGFR mutant DTCs to EGFRi and we demonstrate it can be effectively co-targeted with clinically-emerging MCL-1 inhibitors both in vitro and in vivo. Conclusions: Altogether, these data reveal that this novel therapeutic combination may delay the acquisition of secondary mutations, therefore prolonging therapy efficacy.

https://ift.tt/2OPlI8y

Subjugation of TGF{beta} Signaling by Human Papilloma Virus in Head and Neck Squamous Cell Carcinoma Shifts DNA Repair from Homologous Recombination to Alternative End-Joining

Purpose: Following cytotoxic therapy, 70% of patients with human papillomavirus (HPV) positive oropharyngeal head and neck squamous cell carcinoma (HNSCC) are alive at 5 years compared to 30% of those with similar HPV-negative cancer, which is thought to be due to dysregulation of DNA repair. Loss of transforming growth factor β (TGFβ) signaling is a poorly studied consequence of HPV that could contribute to this phenotype. Experimental Design: Human HNSCC cell lines (n=9), patient-derived xenografts (n=9), tissue microarray (n=194), TCGA expression data and primary tumor specimens (n=10) were used to define the relationship between TGFβ competency, response to DNA damage, and type of DNA repair. Results: Analysis of HNSCC specimens in situ and in vitro showed that HPV associates with loss of TGFβ signaling that increases the response to radiation or cisplatin. TGFβ suppressed miR-182 that inhibited both BRCA1, necessary for homologous recombination repair, and FOXO3, which is required for ATM kinase activity. TGFβ signaling blockade by either HPV or inhibitors released this control, compromised HRR and increased response to PARP inhibition. Antagonizing miR-182 rescued the homologous recombination deficit in HPV+ cells. Loss of TGFβ signaling unexpectedly increased error-prone, alternative end-joining repair. Conclusions: HPV-positive HNSCC cells are unresponsive to TGFβ. Abrogated TGFβ signaling compromises homologous recombination and shifts reliance on alt-EJ repair that provides a mechanistic basis for sensitivity to PARP inhibitors. The effect of HPV in HNSCC provides critical validation of TGFβ's role in DNA repair proficiency and further raises the translational potential of TGFβ inhibitors in cancer therapy.

https://ift.tt/2AScANC

BMI1 drives metastasis of prostate cancer in Caucasian and African-American men and is a potential therapeutic target: hypothesis tested in race-specific models

Purpose: Metastasis is the major cause of mortality in prostate cancer (CaP) patients. Factors such as genetic makeup and race play critical role in the outcome of therapies. This study was conducted to investigate the relevance of BMI1 in metastatic CaP disease in Caucasian and African-Americans. Experimental Design: We employed race-specific CaP models, clinical specimens, clinical data mining, gene-microarray, transcription-reporter assay, chromatin-immunoprecipitation (ChIP), immunohistochemistry, transgenic-(tgfl/fl) zebrafish and mouse metastasis models. Results: BMI1 expression was observed to be elevated in metastatic tumors (lymph nodes, lungs, bones, liver) of Caucasian and African-American CaP patients. The comparative analysis of stage III/IV tumors showed an increased BMI1 expression in African-Americans than Caucasians. TCGA and NIH/GEO clinical data corroborated to our findings. We show that BMI1 expression (i) positively correlates to metastatic (MYC, VEGF, cyclin D1) and (ii) negative correlates to tumor suppressor (INKF4A/p16, PTEN) levels in tumors. The correlation was prominent in African-American tumors. We show that BMI1 regulates the transcriptional activation of MYC, VEGF, INKF4A/p16, and PTEN. We show the effect of pharmacological inhibition of BMI1 on the metastatic genome and invasiveness of tumor cells. Next, we show the anti-metastatic efficacy of BMI1-inhibitor in transgenic zebrafish and mouse metastasis models. Docetaxel as monotherapy has poor outcome on the growth of metastatic tumors. BMI1 inhibitor as an adjuvant improved the taxane therapy in race-based in vitro and in vivo models. Conclusion: BMI1, a major driver of metastasis, represents a promising therapeutic target for treating advanced CaP in patients (including those belonging to high-risk group).

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In-vitro osteoblast proliferation and in-vivo anti-osteoporotic activity of Bombax ceiba with quantification of Lupeol, gallic acid and β-sitosterol by HPTLC and HPLC

Bombax ceiba is used traditionally to treat bone disorders, rheumatism, and joint pain. The aim of the study is to carry out osteogenic activity in-vitro and anti-osteoporotic activity in-vivo of stem bark of B. ...

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New Tick Species Spreading in the United States

TUESDAY, Aug. 7, 2018 -- The first new tick species to appear in the United States in 50 years is spreading rapidly in the east and has been confirmed in seven states and the suburbs of New York City. In its home range, the Asian longhorned tick...

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Overtreatment of Thyroid Cancers Seems Common

TUESDAY, Aug. 7, 2018 -- Overtreatment of thyroid cancers is common, according to a perspective article published in the July 25 issue of the New England Journal of Medicine. Noting that mortality due to thyroid cancer has remained stable despite...

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HIV, Syphilis Screening Low With ED-Diagnosed PID in Adolescents

TUESDAY, Aug. 7, 2018 -- HIV and syphilis screening rates are low among adolescents who are diagnosed with pelvic inflammatory disease (PID) in the emergency department, according to a study published in the August issue of Pediatrics. Amanda...

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AMA Proposes Policy Opposing Medicaid 'Lockout' Provisions

TUESDAY, Aug. 7, 2018 -- A new policy opposing lockout provisions that block Medicaid patients from the program for lengthy periods and instead supporting allowing patients to reapply immediately for redetermination was adopted by the American...

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PCP Statin Prescribing Up With Automated Patient Dashboard

TUESDAY, Aug. 7, 2018 -- Guideline-concordant statin prescribing rates are increased modestly with use of an automated dashboard using active choice framing and peer comparison, according to a study published online July 27 in JAMA Network...

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Unwise opioids for wisdom teeth: Study shows link to long-term use in teens and young adults

Getting wisdom teeth removed may be a rite of passage for many teens and young adults, but the opioid painkiller prescriptions that many receive could set them on a path to long-term opioid use, a new study finds. Young people ages 13 to 30 who filled an opioid prescription immediately before or after they had their wisdom teeth out were nearly 2.7 times as likely as peers to still be filling opioid prescriptions months later.

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Delayed Birth-Related Femur Fracture after Cesarean Section: A Case Report

AJP Rep 2018; 08: e158-e160
DOI: 10.1055/s-0038-1667190

Background Birth-related femur fractures are rare. They have been reported following difficult delivery and are commonly diagnosed immediately after birth or on the following day. However, some birth-related femur fractures are diagnosed several days after birth. Mechanisms underlying the development of delayed femur fracture are incompletely understood. Case We report the case of a girl diagnosed with a left spiral femur fracture with associated edema and hypoesthesia on postpartum day 9. A nondisplacement femur fracture was identified on plain radiography at birth after cesarean section; however, it was undiagnosed due to the lack of symptoms. She was treated with plaster cast fixation; the physical examination at age 1 was normal. Herein, the diagnosis of birth-related femur fracture according to plain radiography findings suggests that the symptoms related to birth trauma develop several days after birth. Conclusion Birth-related fracture should be considered in all neonatal femur fracture cases and in patients with no symptoms at birth. Neonates delivered in the breech presentation by cesarean section should be carefully monitored after birth. The findings of the present case further our understanding of the pathogenic mechanisms underlying delayed diagnosis of birth-related femur fracture.
[...]

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

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Effect of Different Morphology of Titanium Surface on the Bone Healing in Defects Filled Only with Blood Clot: A New Animal Study Design

Background. The objective of the present histologic animal study was to analyze whether roughness of the titanium surface can influence and/or stimulate the bone growth in defects filled with the blood using a rabbit tibia model. Materials and Methods. Forty sets (implant and abutment), dental implant (3.5 mm in diameter and 7 mm in length) plus healing abutment (2.5 mm in diameter), were inserted in the tibiae of 10 rabbits. Moreover, twenty titanium discs were prepared. The abutment and discs were treated by 4 different methods and divided into 4 groups: (group A) machined abutments (smooth); (group B) double acid etching treatment; (group C) treatment with blasting with particles of aluminum oxide blasted plus acid conditioning; (group D) treatment with thorough blasting with particles of titanium oxide plus acid conditioning. The discs were used to characterize the surfaces by a profilometer and scanning electronic microscopy. Results. After 8 weeks, the new bone formation around the sets of the samples was analyzed qualitatively and quantitatively in relation to bone height from the base of the implant and presence of osteocytes. Group C (1.50±0.20 mm) and group D (1.62±0.18 mm) showed bone growth on the abutment with higher values compared to group A (0.94±0.30 mm) and group B (1.19±0.23 mm), with significant difference between the groups (P

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Rapid and precise diagnosis of disseminated T.marneffei infection assisted by high-throughput sequencing of multifarious specimens in a HIV-negative patient: a case report

Talaromyces marneffei, is an opportunistic pathogenic fungus that is most commonly reported in Southeast Asia and disseminated T.marneffei infection predominantly occurs in patients with immunodeficiency. With a ...

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Bilateral osteomyelitis and liver abscess caused by hypervirulent Klebsiella pneumoniae- a rare clinical manifestation (case report)

Hypervirulent strains of Klebsiella pneumoniae are a recognized cause of a distinct invasive syndrome that results in pyogenic liver abscesses and metastatic complications, particularly in the Asia Pacific region...

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Severe epidemic myalgia with an elevated level of serum interleukin-6 caused by human parechovirus type 3: a case report and brief review of the literature

Human parechovirus type 3 (HPeV-3) is known to cause cold-like symptoms, diarrhea, or severe infections such as sepsis in infants and children. In adults, HPeV-3 infection is rarely diagnosed because the sympt...

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Evidence of human leptospirosis cases in a cohort of febrile patients in Bangui, Central African Republic: a retrospective study, 2012–2015

In spite of a local favorable environment, leptospirosis has never been described in Central African Republic so far mainly because of the weakness of diagnostic tests and differential diagnostic strategy for ...

https://ift.tt/2M483gl

SERO-prevalence of herpes simplex virus type 1 and type 2 among women attending routine Cervicare clinics in Ghana

Herpes simplex virus infection is a global health concern with disproportionately high burden in low and middle-income countries. There is a paucity of data on the prevalence of HSV infection in Ghana, which n...

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Evaluation of patients with relapsing-remitting multiple sclerosis using tract-based spatial statistics analysis: diffusion kurtosis imaging

Diffusion kurtosis imaging (DKI) has the potential to provide microstructural insights into myelin and axonal pathology with additional kurtosis parameters. To our knowledge, few studies are available in the c...

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Advancing synoptic cancer reports beyond English: the University of Bern/PathoLink approach

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EGFR gene copy number decreases during anti-EGFR antibody therapy in colorectal cancer

Epidermal growth factor receptor (EGFR) gene copy number (GCN) increase is associated with a favourable anti-EGFR antibody treatment response in RAS wild-type metastatic colorectal cancer. However, there are limited comparative data regarding the EGFR GCN in primary colorectal cancer tumours and corresponding metastases or the effect of anti-EGFR antibody treatment on EGFR GCN in recurrent disease. Additionally, little is known about the potential EGFR GCN changes during anti-EGFR therapy in comparison to other treatment regimens.

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An Automated Intervention Did Not Improve Adherence to Oral Oncolytic Agents While Managing Symptoms: Results from a Two-arm Randomized Controlled Trial

An increasing number of oral cancer treatments require patient adherence and symptom self-management.

https://ift.tt/2vP9T9A

Rectal administration of baclofen at the end of life

Spasticity can be a complicating symptom of a variety of neurological conditions such as multiple sclerosis, motor neuron disease, Creutzfeldt-Jakob disease, or post-stroke. Several pharmacological treatment options are available, including baclofen, tizanidine, gabapentin, botulinum toxin A and tetrahydrocannabinol/canabidiol (1, 2). However, treatment feasibility decreases as the end of life approaches, e.g. when patients are no longer able to tolerate oral medications, the onset of action would be too long, or the initiation of parenteral drug therapy (intravenous, intrathecal) is no longer indicated or appropriate.

https://ift.tt/2nkYdI7

Do the phenotypes of symptom fluctuation differ among motor subtypes in patients with delirium?

This study compared phenotypes of diurnal fluctuation among different delirium subtypes using a prospective design.

https://ift.tt/2vMfvRX

Quality of life trends in people with and without cancer referred to volunteer provided palliative care services (ELSA): A longitudinal study

Trends in symptoms and functional ability are known towards the end of life, but less is understood about quality of life, particularly prospectively following service referral.

https://ift.tt/2LYBnEE

Using routinely collected data to ascertain concordance with advance care planning preferences

One of the key outcomes of Advance Care Planning (ACP) is whether patients had received care that was consistent with their expressed goals and preferences.

https://ift.tt/2vP9DaC

Secondary Breast Cancers in Childhood Cancer Male Survivors – Characteristics and Risks

Male breast cancer (MBC) is uncommon, accounting for less than 1% of all breast cancers. Secondary breast cancers among childhood cancer survivors have been well described in the literature but less is known about MBC.

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Person-Centered Approach to Deciding on Long-Term Dialysis

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Commentary on Complications of Immunosuppressive Treatments for Glomerulonephritis

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Genetic Contribution to Risk for Diabetic Kidney Disease

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Communication Strategies to Address Conflict about Dialysis Decision Making for Critically Ill Patients

https://ift.tt/2nh9uJo

Meeting the Palliative Care Needs of Maintenance Hemodialysis Patients: Beyond the Math

https://ift.tt/2vQndLc

Rebuilding the Pipeline of Investigators in Nephrology Research in the United States

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Metabolic Changes with Base-Loading in CKD

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Risks and Benefits of Direct Oral Anticoagulants across the Spectrum of GFR among Incident and Prevalent Patients with Atrial Fibrillation

Background and objectives

All randomized trials of direct oral anticoagulants in atrial fibrillation excluded patients with severe kidney disease. The safety and effectiveness of direct oral anticoagulants across the range of eGFR in real-world settings is unknown. Our objective is to quantify the risk of bleeding and benefit of ischemic stroke prevention for direct oral anticoagulants compared with warfarin in patients with atrial fibrillation with and without CKD.

Design, setting, participants, & measurements

We created a propensity score–matched cohort of 3206 patients with atrial fibrillation and direct oral anticoagulant use and 3206 patients with atrial fibrillation using warfarin from October of 2010 to February of 2017 in an electronic health record (Geisinger Health System). The risks of bleeding and ischemic stroke were compared between direct oral anticoagulant and warfarin users using Cox proportional hazards regression, stratified by eGFR (≥60 and <60 ml/min per 1.73 m²).

Results

The mean (SD) age of the 6412 participants was 72 (12) years, 47% were women, and average eGFR was 69 (21) ml/min per 1.73 m². There were 1181 bleeding events and 466 ischemic strokes over 7391 person-years of follow-up. Compared with warfarin use, the hazard ratios (HRs) (95% confidence interval [95% CI]) of bleeding associated with direct oral anticoagulant use were 1.01 (0.88 to 1.17) and 1.23 (1.02 to 1.48) for those with eGFR≥60 and eGFR<60 ml/min per 1.73 m², respectively (P-interaction=0.10). There was no difference between direct oral anticoagulant and warfarin users in the risk of ischemic stroke: HRs (95% CI) of 0.94 (0.74 to 1.18) and 1.02 (0.76 to 1.37) for those with eGFR≥60 and eGFR<60 ml/min per 1.73 m², respectively (P-interaction=0.70). Similar findings were observed with individual drugs.

Conclusions

In a large health care system, patients with eGFR<60 ml/min per 1.73 m² who took direct oral anticoagulants for atrial fibrillation had slightly higher risk of bleeding compared with those on warfarin, but similar benefits from prevention of ischemic stroke.

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Opportunities for Increasing the Rate of Preemptive Kidney Transplantation

https://ift.tt/2LWPZod

Long-Term Administration of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease

Background and objectives

In the 3-year Tolvaptan Efficacy and Safety in Management of ADPKD and Its Outcomes (TEMPO) 3:4 and 1-year Replicating Evidence of Preserved Renal Function: an Investigation of Tolvaptan Safety and Efficacy in ADPKD (REPRISE) trials, tolvaptan slowed the decline of eGFR in patients with autosomal dominant polycystic kidney disease at early and later stages of CKD, respectively. Our objective was to ascertain whether the reduction associated with the administration of tolvaptan is sustained, cumulative, and likely to delay the need for kidney replacement therapy.

Design, setting, participants, & measurements

One hundred and twenty-eight patients with autosomal dominant polycystic kidney disease participated in clinical trials of tolvaptan at the Mayo Clinic. All had the opportunity to enroll into open-label extension studies. Twenty participated in short-term studies or received placebo only. The remaining 108 were analyzed for safety. Ninety seven patients treated with tolvaptan for ≥1 year (mean±SD, 4.6±2.8; range, 1.1–11.2) were analyzed for efficacy using three approaches: (1) comparison of eGFR slopes and outcome (33% reduction from baseline eGFR) to controls matched by sex, age, and baseline eGFR; (2) Stability of eGFR slopes with duration of follow-up; and (3) comparison of observed and predicted eGFRs at last follow-up.

Results

Patients treated with tolvaptan had lower eGFR slopes from baseline (mean±SD, –2.20±2.18 ml/min per 1.73 m² per year) and from month 1 (mean±SD, –1.97±2.44 ml/min per 1.73 m² per year) compared with controls (mean±SD, –3.50±2.09 ml/min per 1.73 m² per year; P<0.001), and lower risk of a 33% reduction in eGFR (risk ratio, 0.63; 95% confidence interval, 0.38 to 0.98 from baseline; risk ratio, 0.53; 95% confidence interval, 0.31 to 0.85 from month 1). Annualized eGFR slopes of patients treated with tolvaptan did not change during follow-up and differences between observed and predicted eGFRs at last follow-up increased with duration of treatment.

Conclusions

Follow-up for up to 11.2 years (average 4.6 years) showed a sustained reduction in the annual rate of eGFR decline in patients treated with tolvaptan compared with controls and an increasing separation of eGFR values over time between the two groups.

https://ift.tt/2vKYacc

Proximal Tubular Secretory Clearance: A Neglected Partner of Kidney Function

The secretion of small molecules by the proximal tubules of the kidneys represents a vital homeostatic function for rapidly clearing endogenous solutes and medications from the circulation. After filtration at the glomerulus, renal blood flow is directed through a network of peritubular capillaries, where transporters of the proximal tubules actively secrete putative uremic toxins and hundreds of commonly prescribed drugs into the urine, including protein-bound substances that cannot readily cross the glomerular basement membrane. Despite its central physiologic importance, tubular secretory clearance is rarely measured or even estimated in clinical or research settings. Major barriers to estimating tubular solute clearance include uncertainty regarding optimal endogenous secretory markers and a lack of standardized laboratory assays. The creation of new methods to measure tubular secretion could catalyze advances in kidney disease research and clinical care. Differences in secretory clearance relative to the GFR could help distinguish among the causes of CKD, particularly for disorders that primarily affect the tubulointerstitium. As the primary mechanism by which the kidneys excrete medications, tubular secretory clearance offers promise for improving kidney medication dosing, which is currently exclusively on the basis of filtration. The differing metabolic profiles of retained solutes eliminated by secretion versus glomerular filtration suggest that secretory clearance could uniquely inform uremic toxicity, refine existing measures of residual kidney function, and improve prediction of cardiovascular and kidney disease outcomes. Interdisciplinary research across clinical, translational, and laboratory medicine is needed to bring this often neglected kidney function into the limelight.

https://ift.tt/2nkM8CF

COL4A3 Gene Variants and Diabetic Kidney Disease in MODY

Background and objectives

Despite advances in identifying genetic factors of diabetic kidney disease (DKD), much of the heritability remains unexplained. Nine maturity-onset diabetes in young (MODY) probands with kidney biopsy-proven DKD were selected and included in this study. The probands had more severe DKD compared with their parents with MODY, with overt proteinuria or rapid progression to ESKD. We aimed to explore the contribution of the variants in susceptibility genes of DKD to the severity of kidney phenotype between the probands and their parents.

Design, setting, participants, & measurements

Whole-exome sequencing was performed to identify suspected MODY probands and their families. Known DKD susceptibility genes were reviewed. Variants reported to be associated with DKD, or those with minor allele frequency <0.05 and predicted to be pathogenic, were selected and analyzed. Immunofluorescence staining of COL4α3 was performed in kidney specimens of patients with DKD with or without R408H and M1209I of COL4A3 variants.

Results

HNF1B-MODY, CEL-MODY, PAX4-MODY, and WFS1-MODY were diagnosed among nine families. We identified 196 selected variants of 25 DKD susceptibility genes among the participants. Analysis of phenotype between probands and parents, gene function, and protein–protein interaction networks revealed that COL4A3 variants were involved in the progression of DKD. Weak granular staining of COL4α3 was observed in the glomerular basement membrane of patients with the R408H and M1209I variants, whereas strong consecutive staining was observed in patients without these variants. Moreover, more number of DKD variants were identified in probands than in their parents with MODY.

Conclusions

The genetic effect of more pathogenic variants in various DKD susceptibility genes, especially variants in the COL4A3 gene, partially explained the more severe kidney phenotype in probands with kidney biopsy-proven DKD.

https://ift.tt/2vMSvCF

ABO-Incompatible Kidney Transplant Outcomes: A Meta-Analysis

Background and objectives

ABO blood group–incompatible kidney transplantation is considered a safe procedure, with noninferior outcomes in large cohort studies. Its contribution to living kidney transplantation programs is substantial and growing. Outcomes compared with center-matched ABO blood group–compatible control patients have not been ascertained.

Design, setting, participants, & measurements

Comprehensive searches were conducted in Embase, Medline, Cochrane, Web-of-Science, and Google Scholar. Meta-analyses Of Observational Studies in Epidemiology study guidelines for observational studies and Newcastle Ottawa bias scale were implemented to assess studies. Meta-analysis was performed using Review Manager 5.3. A subgroup analysis on antibody removal technique was performed.

Results

After identifying 2728 studies addressing ABO-incompatible kidney transplantation, 26 studies were included, describing 1346 unique patients who were ABO-incompatible and 4943 ABO-compatible controls. Risk of bias was low (all studies ≥7 of 9 stars). Baseline patient characteristics revealed no significant differences in immunologic risk parameters. Statistical heterogeneity of studies was low (I² 0% for graft and patient survival). One-year uncensored graft survival of patients who were ABO-incompatible was 96% versus 98% in ABO-compatible controls (relative risk, 0.97; 95% confidence interval, 0.96 to 0.98; P<0.001). Forty-nine percent of reported causes of death in patients who were ABO-incompatible were of infectious origin, versus only 13% in patients who were ABO-compatible (P=0.02). Antibody-mediated rejection (3.86; 95% confidence interval, 2.05 to 7.29; P<0.001), severe nonviral infection (1.44; 95% confidence interval, 1.13 to 1.82; P=0.003), and bleeding (1.92; 95% confidence interval, 1.36 to 2.72; P<0.001) were also more common after ABO-incompatible transplantation.

Conclusions

ABO-incompatible kidney transplant recipients have good outcomes, albeit inferior to center-matched ABO-compatible control patients.

https://ift.tt/2LYtEXa

End of Life, Withdrawal, and Palliative Care Utilization among Patients Receiving Maintenance Hemodialysis Therapy

Background and objectives

Withdrawal from maintenance hemodialysis before death has become more common because of high disease and treatment burden. The study objective was to identify patient factors and examine the terminal course associated with hemodialysis withdrawal, and assess patterns of palliative care involvement before death among patients on maintenance hemodialysis.

Design, setting, participants, & measurements

We designed an observational cohort study of adult patients on incident hemodialysis in a midwestern United States tertiary center, from January 2001 to November 2013, with death events through to November 2015. Logistic regression models evaluated associations between patient characteristics and withdrawal status and palliative care service utilization.

Results

Among 1226 patients, 536 died and 262 (49% of 536) withdrew. A random sample (10%; 52 out of 536) review of Death Notification Forms revealed 73% sensitivity for withdrawal. Risk factors for withdrawal before death included older age, white race, palliative care consultation within 6 months, hospitalization within 30 days, cerebrovascular disease, and no coronary artery disease. Most withdrawal decisions were made by patients (60%) or a family member (33%; surrogates). The majority withdrew either because of acute medical complications (51%) or failure to thrive/frailty (22%). After withdrawal, median time to death was 7 days (interquartile range, 4–11). In-hospital deaths were less common in the withdrawal group (34% versus 46% nonwithdrawal, P=0.003). A third (34%; 90 out of 262) of those that withdrew received palliative care services. Palliative care consultation in the withdrawal group was associated with longer hemodialysis duration (odds ratio, 1.19 per year; 95% confidence interval, 1.10 to 1.3; P<0.001), hospitalization within 30 days of death (odds ratio, 5.78; 95% confidence interval, 2.62 to 12.73; P<0.001), and death in hospital (odds ratio, 1.92; 95% confidence interval, 1.13 to 3.27; P=0.02).

Conclusions

In this single-center study, the rate of hemodialysis withdrawals were twice the frequency previously described. Acute medical complications and frailty appeared to be driving factors. However, palliative care services were used in only a minority of patients.

https://ift.tt/2vMSoad

Correction

https://ift.tt/2M3QPjb

Association of Inpatient Palliative Care with Health Care Utilization and Postdischarge Outcomes among Medicare Beneficiaries with End Stage Kidney Disease

Background and objectives

Palliative care may improve quality of life and reduce the cost of care for patients with chronic illness, but utilization and cost implications of palliative care in ESKD have not been evaluated. We sought to determine the association of inpatient palliative care with health care utilization and postdischarge outcomes in ESKD.

Design, setting, participants, & measurements

In analyses stratified by whether patients died during the index hospitalization, we identified Medicare beneficiaries with ESKD who received inpatient palliative care, ascertained by provider specialty codes, between 2012 and 2013. These patients were matched to hospitalized patients who received usual care using propensity scores. Primary outcomes were length of stay and hospitalization costs. Secondary outcomes were 30-day readmission and hospice enrollment.

Results

Inpatient palliative care occurred in <1% of hospitalizations lasting >2 days. Among the decedent cohort (n=1308), inpatient palliative care was associated with a 21% shorter length of stay (–4.2 days; 95% confidence interval, –5.6 to –2.9 days) and 14% lower hospitalization costs (–$10,698; 95% confidence interval, –$17,553 to –$3843) compared with usual care. Among the nondecedent cohort (n=5024), inpatient palliative care was associated with no difference in length of stay (0.4 days; 95% confidence interval, –0.3 to 1.0 days) and 11% higher hospitalization costs ($4275; 95% confidence interval, $1984 to $6567) compared with usual care. In the 30-day postdischarge period, patients who received inpatient palliative care had higher likelihood of hospice enrollment (hazard ratio, 8.3; 95% confidence interval, 6.6 to 10.5) and lower likelihood of rehospitalization (hazard ratio, 0.8; 95% confidence interval, 0.7 to 0.9).

Conclusions

Among patients with ESKD who died in the hospital, inpatient palliative care was associated with shorter hospitalizations and lower costs. Among those who survived to discharge, inpatient palliative care was associated with no difference in length of stay and higher hospitalization costs but markedly higher hospice use and fewer readmissions after discharge.

https://ift.tt/2vokMzS

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis

We report methods for characterization of MLKL-mediated plasma membrane rupture in necroptosis including conventional and confocal live-cell microscopy imaging, scanning electron microscopy, and NMR-based lipid binding.

https://ift.tt/2MbPBBA

Preparation of Polyoxometalate-based Photo-responsive Membranes for the Photo-activation of Manganese Oxide Catalysts

Here, we present a protocol to prepare charge transfer chromophores based on a polyoxometalate/polymer composite membrane.

https://ift.tt/2Oh4QXa

Devitalization of adjacent teeth following maxillary sinus floor augmentation: A retrospective radiographic study

Clinical Implant Dentistry and Related Research, EarlyView.


https://ift.tt/2KzNLWi

Primary Appendicular Malignancy Presenting as Abdominal Wall Abscess with Secondary Tuberculosis Infection: an Interesting Case Report

Abstract

Cancers of the appendix are rare. Most of them are found accidentally on appendectomies performed for appendicitis. When reviewed, majority of the tumors were carcinoid, adenoma, and lymphoma. Adenocarcinomas of the appendix are only 0.08% of all cancers, and the treatment remains controversial. It can present as appendicitis or lump or abscess. Gastrointestinal tuberculosis most commonly involves the ileocecal region. Disruption of the integrity of mucosal barriers and impairment in cell-mediated immunity associated with cancerous growth are known to predispose to bacterial infection. The role of antituberculosis therapy and chemotherapy is unclear due to lacking randomized trials but seems to be accepted if there is lymph node involvement or peritoneal seeding. Here, we are reporting a 69-year-old lady presented with symptoms of abdominal wall abscess with tuberculosis infection which was then diagnosed with mucinous adenocarcinoma of the appendix. The patient was treated with incision and drainage followed by the right hemicolectomy. Up to date, she remains asymptomatic and continuing with chemotherapy.

https://ift.tt/2vNE1lX

Metabolic Analysis of Drosophila melanogaster Larval and Adult Brains

We present a protocol for measuring oxygen consumption and extracellular acidification in Drosophila melanogaster larval and adult brains. A metabolic analyzer is utilized with an adapted and optimized protocol. Micro-tissue restraints are a critical component of this protocol and were designed and created specifically for their use in this analysis.

https://ift.tt/2njC2SB

A Mobile Outside-in Technique of Transforaminal Lumbar Endoscopy for Lumbar Disc Herniations

Here we present a protocol of a novel outside-in technique of transforaminal endoscopic discectomy for lumbar disc herniations. The technical aspects of the technique, the wide indications of use, and the results of the treatment in 184 patients are described in detail.

https://ift.tt/2KBD6ds

Microenvironment proteinases, proteinase-activated receptor regulation, cancer and inflammation

Journal Name: Biological Chemistry
Issue: Ahead of print


https://ift.tt/2ANY4pU

Forced Salivation As a Method to Analyze Vector Competence of Mosquitoes

For efficient control of mosquito borne virus transmission, the knowledge of the vector potential of respective mosquitoes is of particular interest. We describe forced salivation as a method to analyze vector competence of Aedes albopictus and three different Culex taxa for the transmission of Zika virus.

https://ift.tt/2M9Z4Jv

Conducting Elevated Temperature Normal and Combined Pressure-Shear Plate Impact Experiments Via a Breech-end Sabot Heater System

Here, we present a detailed protocol of a new approach for conducting elevated temperature reverse normal plate impact, and combined pressure-and-shear plate impact. The approach involves the use of a breech-end resistive coil heater to heat a sample held at the front-end of a heat-resistant sabot to the desired temperature.

https://ift.tt/2MtiTs6

No more hiding: I am a caregiver with depression

Acknowledging my depression to family, friends and colleagues and getting help is not a sign of weakness, but rather a sign of resilience and strength

https://ift.tt/2vrKt2t

https://ift.tt/2Mo5AJG

FBXW7: a critical tumor suppressor of human cancers

Abstract

The ubiquitin-proteasome system (UPS) is involved in multiple aspects of cellular processes, such as cell cycle progression, cellular differentiation, and survival (Davis RJ et al., Cancer Cell 26:455-64, 2014; Skaar JR et al., Nat Rev Drug Discov 13:889-903, 2014; Nakayama KI and Nakayama K, Nat Rev Cancer 6:369-81, 2006). F-box and WD repeat domain containing 7 (FBXW7), also known as Sel10, hCDC4 or hAgo, is a member of the F-box protein family, which functions as the substrate recognition component of the SCF E3 ubiquitin ligase. FBXW7 is a critical tumor suppressor and one of the most commonly deregulated ubiquitin-proteasome system proteins in human cancer. FBXW7 controls proteasome-mediated degradation of oncoproteins such as cyclin E, c-Myc, Mcl-1, mTOR, Jun, Notch and AURKA. Consistent with the tumor suppressor role of FBXW7, it is located at chromosome 4q32, a genomic region deleted in more than 30% of all human cancers (Spruck CH et al., Cancer Res 62:4535-9, 2002). Genetic profiles of human cancers based on high-throughput sequencing have revealed that FBXW7 is frequently mutated in human cancers. In addition to genetic mutations, other mechanisms involving microRNA, long non-coding RNA, and specific oncogenic signaling pathways can inactivate FBXW7 functions in cancer cells. In the following sections, we will discuss the regulation of FBXW7, its role in oncogenesis, and the clinical implications and prognostic value of loss of function of FBXW7 in human cancers.

https://ift.tt/2M4cFSL

NFATc1 is a tumor suppressor in hepatocellular carcinoma and induces tumor cell apoptosis by activating the FasL‐mediated extrinsic signaling pathway

Cancer Medicine, EarlyView.


https://ift.tt/2Ok7MCn

Excess Zinc in Muscles May Drive Cancer-Related Wasting

TUESDAY, Aug. 7, 2018 -- ZRT- and IRT-like protein 14 (ZIP14) upregulation in skeletal muscles may play a role in cancer-related muscle loss, according to a study published online June 6 in Nature Medicine. Gang Wang, Ph.D., from Columbia University...

https://ift.tt/2vJesT5

Death Records Estimate 1,139 Deaths Due to Hurricane Maria

TUESDAY, Aug. 7, 2018 -- Based on death records following Hurricane Maria, the hurricane-related mortality burden of excess deaths through December 2017 is estimated to be 1,139, higher than the official death toll of 64, according to a research...

https://ift.tt/2nkMOIk

Thyroid Dysfunction Linked to Gestational Diabetes

TUESDAY, Aug. 7, 2018 -- Higher free triiodothyronine (fT3) levels, but not free thyroxine (fT4) or thyroid-stimulating hormone (TSH) levels, are associated with gestational diabetes mellitus (GDM), according to a study published in the July 1 issue...

https://ift.tt/2vK78q3

Factors Examined for End-of-Life Spending Levels in Cancer Care

TUESDAY, Aug. 7, 2018 -- Geographic variation in end-of-life spending can be explained by availability of services and physicians' beliefs, but not patients' beliefs, according to a study published in the July issue of Health Affairs. Nancy L....

https://ift.tt/2ngwQ1M

Postmortem Cardiac Implantable Device Interrogation Useful

TUESDAY, Aug. 7, 2018 -- Postmortem cardiac implantable electronic device (CIED) interrogation can improve the accuracy of identification of the time and cause of death at forensic autopsy, according to a study published in the June 19 issue of...

https://ift.tt/2vJdupV

AMA Calls for Greater Electronic Cigarette Regulation

TUESDAY, Aug. 7, 2018 -- The American Medical Association (AMA) has adopted several policies to improve the regulation of tobacco products, including electronic cigarettes (e-cigarettes), according to an article published in the association's AMA...

https://ift.tt/2nk8vIv

Disparities Remain in Prevalence of Cancer Screening Tests

TUESDAY, Aug. 7, 2018 -- There are persistent disparities in recommended cancer screening tests among U.S. adults, particularly among the uninsured, according to a study published online July 26 in the U.S. Centers for Disease Control and...

https://ift.tt/2vLuGe9

Most Online Reviews for Spine Surgeons Are Surgeon-Dependent

TUESDAY, Aug. 7, 2018 -- Spine surgeons are more likely to receive favorable online reviews for factors pertaining to outcomes and likeability/character and negative reviews based on ancillary staff interactions and office environment, according to...

https://ift.tt/2nifaCX

Routine X-Ray Not Needed After US-Guided Central Line Insertion

TUESDAY, Aug. 7, 2018 -- Pneumothorax and catheter misplacement after ultrasound-guided central venous catheter (CVC) insertion are rare and thus do not justify post-procedural chest X-ray (CXR), according to a study published in the July issue of...

https://ift.tt/2vJdczl

'Good' Cholesterol May Not Be So in Postmenopausal Women

TUESDAY, Aug. 7, 2018 -- Elevated high-density lipoprotein cholesterol (HDL-C) may not always be cardioprotective in postmenopausal women, according to a study published online July 19 in Arteriosclerosis, Thrombosis, and Vascular Biology. Samar R....

https://ift.tt/2nj6T1r

EMCrit – Propranolol Versus Metoprolol for Treatment of Electrical Storm by Kristina Kipp PharmD

Are non-selective b-blockers better for electrical storm?

EMCrit Project by Kristina Kipp.

https://ift.tt/2KAERYv

Plasma Heme Oxygenase-1 Levels in Patients with Coronary and Peripheral Artery Diseases

Aims. Heme oxygenase-1 (HO-1) is an intracellular enzyme that catalyzes the oxidation of heme to generate CO, biliverdin, and iron. Since these products have antiatherogenic properties, HO-1 may play a protective role against the progression of atherosclerosis. However, plasma HO-1 levels in patients with atherosclerotic diseases, such as coronary artery disease (CAD) and peripheral artery disease (PAD), have not been clarified yet. Methods. We investigated plasma HO-1 levels by ELISA in 410 consecutive patients undergoing elective coronary angiography who also had an ankle-brachial index (ABI) test for PAD screening. Results. Of the 410 study patients, CAD was present in 225 patients (55%) (1-vessel (1-VD), ; 2-vessel (2-VD), ; 3-vessel disease (3-VD), ). PAD (ABI 

https://ift.tt/2AP13hV

Tracing back multidrug-resistant bacteria in fresh herb production: from chive to source through the irrigation water chain

Abstract

Environmental antibiotic-resistant bacteria (ARB) can be transferred to humans through foods. Fresh produce in particular is an ideal vector due to frequent raw consumption. A major contamination source of fresh produce is irrigation water. We hypothesized that water quality significantly affects loads of ARB and their diversity on fresh produce despite various other contamination sources present under agricultural practice conditions. Chive irrigated from an open-top reservoir or sterile-filtered water (control) was examined. Heterotrophic plate counts (HPC) and ARB were determined for water and chive with emphasis on Escherichia coli and Enterococcus spp. High HPC of freshly planted chive decreased over time and were significantly lower on control- versus reservoir-irrigated chive at harvest (1.3 log (CFU/g) lower). Ciprofloxacin- and ceftazidime-resistant bacteria were significantly lower on control-irrigated chive at harvest and end of shelf life (up to 1.8 log (CFU/g) lower). E. coli and Enterococcus spp. repeatedly isolated from water and chive proved resistant to up to 6 or 4 antibiotic classes (80% or 49% multidrug-resistant, respectively). Microbial source tracking identified E. coli-ST1056 along the irrigation chain and on chive. Whole-genome sequencing revealed that E. coli-ST1056 from both environments were clonal and carried the same transmissible multidrug-resistance plasmid, proving water as source of chive contamination. These findings emphasize the urgent need for guidelines concerning ARB in irrigation water and development of affordable water disinfection technologies to diminish ARB on irrigated produce.

https://ift.tt/2vsarD3

A metagenomic window into the 2 km-deep terrestrial subsurface aquifer revealed multiple pathways of organic matter decomposition

Abstract

We have sequenced metagenome of the microbial community of a deep subsurface thermal aquifer in the Tomsk Region of the Western Siberia, Russia. Our goal was the recovery of near-complete genomes of the community members to enable accurate reconstruction of metabolism and ecological roles of the microbial majority, including previously unstudied lineages. The water, obtained via a 2.6 km deep borehole 1-R, was anoxic, with a slightly alkaline pH, and a temperature around 45°C. Microbial community, as revealed by 16S rRNA gene profiling over 2 years, mostly consisted of sulfate-reducing Firmicutes and Deltaproteobacteria, and uncultured lineages if the phyla Chlorofexi, Ignavibacteriae and Aminicenantes (OP8). 25 composite genomes with more than 90% completeness were recovered from metagenome and used for metabolic reconstruction. Members of uncultured lineages of Chlorofexi and Ignavibacteriae are likely involved in degradation of carbohydrates by fermentation, and are also capable of aerobic and anaerobic respiration. The Chlorofexi bacterium has the Wood-Ljungdahl pathway of CO₂ fixation. The recently identified candidate phylum Riflebacteria accounted for 5–10% of microbial community. Metabolic reconstruction of a member of Riflebacteria predicted that it is an anaerobe capable to grow on carbohydrates by fermentation or dissimilatory Fe(III) reduction.

https://ift.tt/2AOFoqe

Microbial community composition of a hydrocarbon reservoir 40 years after a CO2 enhanced oil recovery flood

Abstract

Injecting CO₂ into depleted oil reservoirs to extract additional crude oil is a common enhanced oil recovery (CO₂-EOR) technique. However, little is known about how in situ microbial communities may be impacted by CO₂ flooding, or if any permanent microbiological changes occur after flooding has ceased. Formation water was collected from an oil field that was flooded for CO₂-EOR in the 1980s, including samples from areas affected by or outside of the flood region, to determine the impacts of CO₂-EOR on reservoir microbial communities. Archaea, specifically methanogens, were more abundant than Bacteria in all samples, while identified Bacteria exhibited much greater diversity than the Archaea. Microbial communities in CO₂-impacted and non-impacted samples did not significantly differ (ANOSIM: Statistic R = -0.2597, significance = 0.769). However, several low abundance Bacteria were found to be significantly associated with the CO₂-affected group; very few of these species are known to metabolize CO₂ or are associated with CO₂-rich habitats. Although this study had limitations, on a broad scale, either the CO₂ flood did not impact the microbial community composition of the target formation, or microbial communities in affected wells may have reverted back to pre-injection conditions over the ca. 40 years since the CO₂-EOR.

https://ift.tt/2vwQzPp

Endoscopic Diagnosis of Cystic Lesions of the Pancreas

Digestive Endoscopy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2M44R3r

PCBP1 depletion promotes tumorigenesis through attenuation of p27 Kip1 mRNA stability and translation

Abstract

Background

Poly C Binding Protein 1 (PCBP1) is an RNA-binding protein that binds and regulates translational activity of subsets of cellular mRNAs. Depletion of PCBP1 is implicated in various carcinomas, but the underlying mechanism in tumorigenesis remains elusive.

Methods

We performed a transcriptome-wide screen to identify novel bounding mRNA of PCBP1. The bind regions between PCBP1 with target mRNA were investigated by using point mutation and luciferase assay. Cell proliferation, cell cycle, tumorigenesis and cell apoptosis were also evaluated in ovary and colon cancer cell lines. The mechanism that PCBP1 affects p27 was analyzed by mRNA stability and ribosome profiling assays. We analyzed PCBP1 and p27 expression in ovary, colon and renal tumor samples and adjacent non-tumor tissues using RT-PCR, Western Blotting and immunohistochemistry. The prognostic significance of PCBP1 and p27 also analyzed using online databases.

Results

We identified cell cycle inhibitor p27^Kip1 (p27) as a novel PCBP1-bound transcript. We then demonstrated that binding of PCBP1 to p27 3'UTR via its KH1 domain mainly stabilizes p27 mRNA, while enhances its translation to fuel p27 expression, prior to p27 protein degradation. The upregulated p27 consequently inhibits cell proliferation, cell cycle progression and tumorigenesis, whereas promotes cell apoptosis under paclitaxel treatment. Conversely, knockdown of PCBP1 in turn compromises p27 mRNA stability, leading to lower p27 level and tumorigenesis in vivo. Moreover, forced depletion of p27 counteracts the tumor suppressive ability of PCBP1 in the same PCBP1 over-expressing cells. Physiologically, we showed that decreases of both p27 mRNA and its protein expressions are well correlated to PCBP1 depletion in ovary, colon and renal tumor samples, independent of the p27 ubiquitin ligase Skp2 level. Correlation of PCBP1 with p27 is also found in the tamoxifen, doxorubincin and lapatinib resistant breast cancer cells of GEO database.

Conclusion

Our results thereby indicate that loss of PCBP1 expression firstly attenuates p27 expression at post-transcriptional level, and subsequently promotes carcinogenesis. PCBP1 could be used as a diagnostic marker to cancer patients.

https://ift.tt/2vpXKbK

Long noncoding RNA HEGBC promotes tumorigenesis and metastasis of gallbladder cancer via forming a positive feedback loop with IL-11/STAT3 signaling pathway

Abstract

Background

Gallbladder cancer (GBC) is a highly malignant cancer with poor prognosis. Several long noncoding RNAs (lncRNAs) have been reported to be involved in the tumorigenesis and progression of GBC. However, the expressions, clinical significances, and roles of most other lncRNAs in GBC are still unknown.

Methods

The differentially expressed lncRNAs in GBC were screened through re-analyzing the public available microarray datasets. The expression of lncRNA high expressed in gallbladder cancer (lncRNA-HEGBC) in GBC was measured by qRT-PCR. The correlations between HEGBC with clinicopathological characteristics and prognosis were analyzed by Pearson chi-square test and log-rank test. A series of in vitro and in vivo, gain-of and loss-of function assays were performed to investigate the roles of HEGBC in GBC cell proliferation, apoptosis, migration, tumor growth and metastasis. The interactions between HEGBC and IL-11/STAT3 signaling were explored using chromatin isolation by RNA purification (ChIRP), chromatin immunoprecipitation (ChIP), enzyme linked immunosorbent assay (ELISA), qRT-PCR, western blot, and luciferase reporter assays.

Results

We identified a novel lncRNA HEGBC, which is upregulated in GBC and positively associated with advanced TNM stages and poor prognosis of GBC patients. Overexpression of HEGBC increased GBC cell viability, inhibited GBC cell apoptosis, promoted GBC cell migration, and promoted GBC tumor growth and metastasis in vivo. Conversely, depletion of HEGBC decreased GBC cell viability, promoted GBC cell apoptosis, inhibited GBC cell migration, and inhibited GBC tumor growth and metastasis in vivo. Mechanistic investigations showed that HEGBC bound to the promoter of IL-11, increased IL-11 transcription, induced IL-11 autocrine, and activated IL-11/STAT3 signaling pathway. Furthermore, STAT3 also bound to the promoter of HEGBC and activated HEGBC expression. Thus, HEGBC/IL-11/STAT3 formed a positive regulatory loop in GBC. Depletion of IL-11 attenuated the oncogenic roles of HEGBC in GBC.

Conclusions

Our findings identified a novel lncRNA HEGBC, which is upregulated and indicts poor prognosis of GBC. HEGBC exerts oncogenic roles in GBC via forming a positive regulatory loop with IL-11/STAT3 signaling. Our data suggested that HEGBC could be a potential prognostic biomarker and therapeutic target for GBC.

https://ift.tt/2AWVIFA

CRMP4a suppresses cell motility by sequestering RhoA activity in prostate cancer cells

.


https://ift.tt/2MnKfQA

Comparing treatment outcomes of concurrent chemoradiotherapy with or without nimotuzumab in patients with locoregionally advanced nasopharyngeal carcinoma

.


https://ift.tt/2M70eWc

Successful treatment using apatinib in intractable brain edema: A case report and literatures review

.


https://ift.tt/2OjR06n

Electron-Microscopy-Based Epitope Mapping Defines Specificities of Polyclonal Antibodies Elicited during HIV-1 BG505 Envelope Trimer Immunization

Comprehensive epitope mapping is fundamental to understanding immune responses. Bianchi et al. applied electron microscopy to study polyclonal antibody responses in HIV-Env-immunized rabbits. Different antibody specificities were identified and followed over time, revealing the source of neutralization, a distinct class of antibodies, and a highly convergent structural evolution of the neutralizing antibodies.

https://ift.tt/2ONcTMF

LAG3+ Regulatory T Cells Restrain Interleukin-23-Producing CX3CR1+ Gut-Resident Macrophages during Group 3 Innate Lymphoid Cell-Driven Colitis

Treg cells control of tissue resident macrophages and ILC3 function has not been elucidated. Bauche et al. demonstrate that LAG-3+ Treg cells suppress the production of pro-inflammatory cytokines by CX3CR1+ macrophages and thereby inhibit ILC3-driven colitis.

https://ift.tt/2AP98Db

Deficiency in hormone-sensitive lipase accelerates the development of pancreatic cancer in conditional KrasG12D mice

Abstract

Background

Hormone sensitive lipase (HSL) is a neutral lipase that preferentially catalyzes the hydrolysis of diacylglycerol contributing to triacylglycerol breakdown in the adipose tissue. HSL has been implicated to play a role in tumor cachexia, a debilitating syndrome characterized by progressive loss of adipose tissue. Consequently, pharmacological inhibitors of HSL have been proposed for the treatment of cancer-associated cachexia. In the present study we used the conditional KrasG12D (KC) mouse model of pancreatic ductal adenocarcinoma (PDAC) with a deficiency in HSL to determine the impact of HSL suppression on the development of PDAC.

Methods

KC;Hsl^+/+ and KC;Hsl^−/− mice were fed standard rodent chow for 20 weeks. At sacrifice, the incidence of PDAC was determined and inflammation in the mesenteric adipose tissue and pancreas was assessed histologically and by immunofluorescence. To determine statistical significance, ANOVA and two-tailed Student's t-tests were performed. To compare PDAC incidence, a two-sided Fisher's exact test was used.

Results

Compared to KC;Hsl^+/+ mice, KC;Hsl^−/− mice gained similar weight and displayed adipose tissue and pancreatic inflammation. In addition, KC;Hsl^−/− mice had reduced levels of plasma insulin and leptin. Importantly, the increased adipose tissue and pancreatic inflammation was associated with a significant increase in PDAC incidence in KC;Hsl^−/− mice.

Conclusions

HSL deficiency is associated with adipose tissue and pancreatic inflammation and accelerates PDAC development in the KC mouse model.

https://ift.tt/2vrUL2H

Liver cancer mortality trends in South Africa: 1999–2015

Abstract

Background

In South Africa (SA), liver cancer (LC) is a public health problem and information is limited.

Methods

Joinpoint regression analysis was computed for the most recent LC mortality data from Statistics South Africa (StatsSA), by age group, sex and population group. The mortality-to-incidence ratios (MIRs) were calculated as the age-adjusted mortality rate divided by the age-adjusted incidence rate.

Results

From 1999 to 2015, the overall LC mortality significantly decreased in men (− 4.9%) and women (− 2.7%). Overall a significant decrease was noted in black African men aged 20–29 and 40–49 years, and white women older than 60 years but mortality rates increased among 50–59 and 60–69 year old black African men (from 2010/2009–2015) and women (from 2004/2009–2015). The mortality rates increased with age, and were higher among blacks Africans compared to whites in all age groups - with a peak black African-to-white mortality rate ratio of six in men and three in women at ages 30–39 years. The average MIR for black African men and women was 4 and 3.3 respectively, and 2.2 and 1.8 in their white counterparts. Moreover, decreasing LC mortality rates among younger and the increase in rates in older black Africans suggest that the nadir of the disease may be near or may have passed.

Conclusions

Findings of population-age subgroup variations in LC mortality and the number of underdiagnosed cases can inform surveillance efforts, while more extensive investigations of the aetiological risk factors are needed. Impact: There was a large race, sex and age differences in trends of LC mortality in SA. These findings should inform more extensive evaluation of the aetiology and risk factors of LC in the country in order to guide control efforts.

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