Analysing blood from intraosseous access: a systematic review

Intraosseous (IO) access is used widely as an optional vascular route for critically ill patients. It is still unclear whether the IO access can be used as a source for emergency blood samples. The aim of this study was to systematically review the existing literature on the usability of IO blood samples for analysing the parameters relevant to emergency care. We performed a data search from the Medline and Embase databases, the Cochrane Library and the Clinical trials registry. Animal studies and studies with healthy and ill adults and children were included in the search. The data were collected and reported following the PRISMA guidelines. The PROSPERO database registration number of this review is CRD42017064194. We found 27 studies comparing the blood samples from the IO space with arterial or venous samples, but only three of them followed the recommended guidelines for method comparison studies. The study populations were heterogeneous, and the sample sizes were relatively small (14, 17 and 20 individuals) in the three studies. The results of specific laboratory parameters were scarce and discordant. The evidence on the agreement between IO and arterial and venous samples is still weak. Existing studies with healthy volunteers and animal models provide important insight into the analyses of IO samples, but more evidence, especially from haemodynamically unstable patients, is needed for wider implementation of IO blood sampling in critically ill patients. Correspondence to Milla Jousi, MD, FinnHEMS Research and Development Unit, Lentäjäntie 3, 01530 Vantaa, Finland Tel: +358 50 586 9658; fax: +358 9 8565 7339; e-mail: milla.jousi@hus.fi Received March 29, 2018 Accepted July 31, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2wdI4Id

Molecular Subtypes of Bladder Cancer

Abstract

Purpose of Review

Recent whole genome characterizations of primary human bladder cancers revealed that they can be grouped into "intrinsic" basal and luminal molecular subtypes. Here, we provide an overview of the subtypes and discuss their biological and clinical properties.

Recent Findings

Basal cancers are characterized by advanced stage and metastatic disease at presentation. They tend to be enriched with squamous and small cell/neuroendocrine features and inactivating mutations and deletions of TP53 and RB1. Basal cancers can be divided into "epithelial" and "mesenchymal" (also known as "claudin low") subsets, and a portion of the latter form a "neuroendocrine/neuronal" subset that is associated with particularly poor survival. Luminal cancers are often enriched with papillary histopathological features and activating mutations in FGFR3, and they can also be divided into additional subsets based on differential stromal cell infiltration, relative genomic instability, and high- versus low-level expression of carcinoma in situ (CIS) gene expression signatures. Importantly, the bladder cancer molecular subtypes display differential sensitivities to neoadjuvant chemotherapy and immune checkpoint blockade, and preliminary data also suggest that they respond differently to radiation with or without hypoxia modulation. Ongoing studies are investigating the relevance of the molecular subtypes to the bladder cancer histopathological variants and to upper tract urothelial cancer.

Summary

The bladder cancer molecular subtypes were associated with different prognoses and responses to conventional and targeted therapies in retrospective studies. If validated in prospective studies, molecular subtyping will be integrated into bladder cancer clinical management.

https://ift.tt/2Phr1hn

Triple-Negative Breast Cancers: Systematic Review of the Literature on Molecular and Clinical Features with a Focus on Treatment with Innovative Drugs

Abstract

Purpose of Review

Triple-negative breast cancer (TNBC) accounts for 15–20% of diagnosed breast tumours, with higher incidence in young and African-American women, and it is frequently associated with BRCA germline mutations. Chemotherapy is the only well-established therapeutic option in both early- and advanced-stages of the disease. TNBC tumours relapse earlier after standard anthracycline- and/or taxane-based chemotherapy treatments, generally within 1–3 years after the diagnosis, and often develop visceral metastases, representing the subtype with a worse prognosis among all breast cancers. In the present review, we will provide an updated overview of the available results of recent clinical trials for this disease and we will describe the implications of the known molecular pathways representing novel targets for development of future therapies for TNBC patients.

Recent Findings

Over the past decade, the advent of gene expression micro-array technology has led to the identification of different actionable targets including various genomic alterations, androgen receptor, PARP, PI3K, VEGF and other proteins of the angiogenic pathway. Thus, novel targeted drugs have been tested in clinical trials reporting promising results in specific TNBC molecular subgroups.

Summary

Although cytotoxic chemotherapy remains the mainstay of treatment for TNBC patients, the identification of novel 'drugable' targets and pathways for developing personalized treatments represents a promising investigational approach in the management of the TNBC subtype.

https://ift.tt/2N3XdTI

Cancers, Vol. 10, Pages 275: The Impact of p53 Dysfunction in ATR Inhibitor Cytotoxicity and Chemo- and Radiosensitisation

Cancers, Vol. 10, Pages 275: The Impact of p53 Dysfunction in ATR Inhibitor Cytotoxicity and Chemo- and Radiosensitisation

Cancers doi: 10.3390/cancers10080275

Authors: Fiona K. Middleton John R. Pollard Nicola J. Curtin

Rad3-related kinase (ATR) signals replication stress and DNA damage to S and G2 arrest and promotes DNA repair. Mutations in p53, critical for G1 checkpoint control, are common in cancer and predicted to confer vulnerability to ATR inhibitors. Reported data on the impact of p53 status are variable possibly because of the use of unmatched cells and surrogate endpoints of survival. The cytotoxicity of VE-821 alone and its ability to potentiate radiation and gemcitabine cytotoxicity was determined in isogenic and unmatched p53 wild-type (wt) and null/mutant cells, as well as immortalised nonmalignant MCF10 (immortalised non-neoplastic) cells, by colony-forming assay. The effect on cell cycle checkpoints was determined by flow cytometry. The isogenic p53 defective cells were not more sensitive to VE-821 alone. Defective p53 consistently conferred greater chemo- and radiosensitisation, particularly at high dose levels in isogenic cells but not unmatched cells. VE-821 did not sensitise MCF10 cells. We conclude that p53 status is just one factor contributing to chemo- and radiosensitisation by ATR inhibition, the lack of chemo- or radiosensitisation in the noncancerous cells suggests an element of tumour-specificity that warrants further investigation. The greater sensitisation at high-dose irradiation suggests that ATR inhibitors may be most effective with hypofractionated radiotherapy.

https://ift.tt/2Brfrxa

Impact of Recent Studies for the Treatment of Intracerebral Hemorrhage

Abstract

Purpose of Review

The present review will cover most recent and important studies on acute treatment of intracerebral hemorrhage (ICH).

Recent Findings

Overly pessimistic prognostication in ICH may deny meaningful recovery achieved by specialized neurocritical care. Hematoma enlargement represents the most important target of acute ICH care, which is reduced by aggressive blood pressure management (targeting a systolic blood pressure of 140 mmHg) and appropriate hemostatic treatment especially in anticoagulation-associated ICH (INR reversal using prothrombin complex concentrates, eventually idarucizumab, andexanet, or tranexamic acid). Surgical treatment strategies involving fibrinolytics either used for direct hematoma lysis or used for intraventricular clot removal with/without additional lumbar drainage show great promise. Further novel treatment strategies are underway and need validation or evaluation strongly warranting well-designed future ICH research.

Summary

Several randomized and large-sized observational studies have considerably expanded the field and the evidence on how to treat acute ICH patients. Yet, the one breakthrough intervention to improve functional outcome is still missing, though various treatment concepts possibly interacting with one another have been evaluated and such treatment bundle may improve patients' outcome.

https://ift.tt/2L8CWe3

Book Review—Practical cytopathology: a diagnostic approach to fine needle aspiration biopsy, 1st edition

https://ift.tt/2vU6VRY

Book Review—Diagnostic pathology: bone, 2nd edition

https://ift.tt/2N14qnG

A young female case of primary renal carcinoid tumor mimicking fat-poor angiomyolipoma

Abstract

Renal mass biopsy is useful for the pathological diagnosis of a small renal mass difficult to distinguish fat-poor angiomyolipoma from renal cell carcinoma radiologically. Here, we report a young female case of a small renal mass suspected as fat-poor angiomyolipoma in imaging studies. The patient received a renal mass biopsy to obtain the correct pathological information. Unexpectedly, the pathological diagnosis was neuroendocrine tumor. She, finally, underwent a right radical nephrectomy as a curative treatment. This case indicates that the radiological findings of primary renal carcinoid tumor can be similar to those of fat-poor angiomyolipoma.

https://ift.tt/2BsXfU2

Medic Mindset Podcast: How to become an EMS ‘lifer’

Mitigate the effects a career in EMS can take to nurture your career longevity in EMS

https://ift.tt/2MpO8bJ

Estimation of the Composition of the Resting State fMRI Networks in Subjects with Mild Depression and Healthy Volunteers

Depressive disorders can be associated with changes in not only interaction between neural networks, but also in their composition. Resting state fMRI scanning was performed for 4 min twice for each subject and the results of patients with mild depression (N=15) and healthy subjects (N=19) were analyzed. The fMRI signal was reduced into the independent components and the contrasts between the groups and between the first and second records were constructed for each component. During the first scanning, the auditory network of individuals with depression involved greater volume in the left insular region and lower volume in the right hemisphere. In record 2, depression patients were characterized by expansion of the executive network in the left hemisphere in the region of the middle and inferior frontal cortex. In healthy people, from record 1 to record 2, representation of the dorsal default mode network (DMN) increased in the left medial prefrontal area, the precuneus network expanded in the left hemisphere, and presentation of the ventral DMN in the right precuneus decreased. In the depression group, the auditory network lost some part of the left temporo-insular cortex; the sensorimotor network expanded in the left hemisphere to the cerebellum or to the central parietal region depending on the evaluation method, and the visuospatial network included or excluded a cluster in the left parietal lobe (in different points). Our findings indicate that connection of the auditory network with the left insular cortex could be a possible depression marker and also demonstrate a possibility of evaluating the composition of cerebral networks in intergroup comparisons and in dynamics without interventions.

https://ift.tt/2nNmu9M

Experimental Analysis of the Chaotic Dynamics of Muscle Biopotentials under Various Static Loads

Arbitrary and involuntary movements were studied from the position of the new chaos—self-organization theory. Analysis of organization of tappingrams and tremorograms within the framework of N. A. Bernstein "repetition without repetitions" hypothesis leads to the Eskov—Zinchenko effect. In this case, there is no statistical stability for samples of parameters of electromyograms of any movements obtained in a row, i.e. f_j(x_i)≠f_j+1(x_i) with the probability p≥0.97. In this paper, the basic problem of motion physiology, stochastic instability establishment mechanisms, is solved in the analysis of muscle electromyogram parameters under conditions of permanent static force. Statistical instability of electromyograms within the framework of the Eskov—Zinchenko effect is proven.

https://ift.tt/2wcBimk

Expression of Mucins and Claudins in the Colon during Acute and Chronic Experimental Colitis

We studied changes in the expression of mRNA for mucins and claudins in the medial part of the colon in male C57Bl/6 mice on the model of acute and chronic colitis induced by substitution of drinking water with 1% solution of dextran sodium sulphate for 5 days. In acute colitis, the expression of the main structural component of glycocalyx, mucin Muc3, decreased and expression of pore-forming claudin Cldn2 increased, which reflected enhanced permeability of tight junctions. In the chronic colitis group, in comparison with the normal group, we observed an increase in expression of mRNA of main structural mucus component Muc2, enhanced of expression of Muc1 associated with carcinogenesis, and reduced expression of Muc13, which led to a more severe course of colitis; the expression of pore-forming claudin Cldn2 was elevated. These findings indicate that the imbalance in the expression of mucins and claudins plays an important role in the mechanisms of development of acute and chronic colitis.

https://ift.tt/2nR1VJL

Dynamics of Renin, Angiotensin II, and Angiotensin (1–7) during Pregnancy and Predisposition to Hypertension-Associated Complications

Changes in the levels of rennin, angiotensin II, and angiotensin (1–7) were studied during normal pregnancy. The blood was taken on gestation days 140-237 and 238-280. No significant changes in renin concentration were observed during normal pregnancy (p=0.423). The level of angiotensin II increased during normal pregnancy from 9.7±1.2 to 14.7±1.9 pg/ml (p=0.019). On the contrary, angiotensin (1–7) concentration decreased from 771.1±44.2 to 390.7±13.9 pg/ml (p<0.001). The shift in the proportion between vasoconstrictor angiotensin II and vasodilaltor angiotensin (1–7) attests to high predisposition of pregnant women to hypertension-related complications.

https://ift.tt/2OO4CXE

Dynamics of Metabolic Parameters in Rats during Repeated Exposure to Modulated Low-Intensity UHF Radiation

Metabolic parameters in rats were studied at various stages of repeated exposure to modulated low-intensity UHF radiation. The volume of O₂ consumption and level of heat release were reduced by day 4 of intermittent irradiation and remained low over the next 2 days in the absence of a source for electromagnetic radiation. The amount of expired CO₂ slightly increased over the first 3 sessions of irradiation, but significantly decreased in the recovery period on days 5 and 6. Changes in metabolic parameters were most significant on day 7 of the study. It was manifested in the decrease of O₂ consumption, CO₂ release, and intensity of heat exchange not only during irradiation, but also in the inter-exposure period. Electromagnetic radiation can induce a change of metabolic processes in mammals, which is most pronounced during repeated irradiation and persists even under physiological resting conditions.

https://ift.tt/2nRhhhp

Oral human papillomavirus infection in England and associated risk factors: a case-control study

Objectives

This study was conducted to determine the prevalence of and associated risk factors for infection with oral high-risk human papillomavirus (HR-HPV) in adult participants within England, and to explore any association with oral mucosal buccal epithelial cell and whole blood folate concentration.

Design

This was an observational study to determine oral HR-HPV prevalence in the study population. A case–control study was performed to explore the association between infection and folate status.

Setting

This study was conducted in Sheffield, UK, between April 2013 and August 2014.

Participants

Seven hundred participants, aged 18–60 years, were recruited from university students (n=179), university and hospital staff (n=163), dental hospital patients (n=13), Sexual Health Sheffield patients (n=122) and the general public (n=223).

Interventions

Participants completed a lifestyle and sexual behaviour questionnaire, provided an oral rinse and gargle sample for the detection of oral HR-HPV and an oral mucosal buccal epithelial cell sample for the measurement of oral mucosal buccal epithelial cell folate. A blood sample was collected for measurement of whole blood folate concentration.

Outcome measures

The prevalence of oral HR-HPV infection in the study population was the primary outcome measure. Secondary outcome measures included associations between risk factors, folate status and infection.

Results

The prevalence of oral HR-HPV infection in this cohort was 2.2% (15/680) with 0.7% (5/680) positive for HPV16 or HPV18. Twenty samples were excluded due to insufficient material for HPV detection. Participants with oral HR-HPV infection were more likely to be a former smoker, and have a greater number of sexual and oral sexual partners. Folate status was not linked to likelihood of HPV infection.

Conclusions

The prevalence of oral infection with HR-HPV in adult men and women in Sheffield in the North of England was low. Smoking and sexual behaviour were associated with HR-HPV positivity.

Trial registration number

ID14106.

https://ift.tt/2Bsa00U

A Cell-based Assay to Investigate Non-muscle Myosin II Contractility via the Folded-gastrulation Signaling Pathway in Drosophila S2R+ Cells

Here we describe a contractility assay using Drosophila S2R+ cells. The application of an exogenous ligand, folded gastrulation (Fog), leads to the activation of the Fog signaling pathway and cellular contractility. This assay can be used to investigate the regulation of cellular contractility proteins in the Fog signaling pathway.

https://ift.tt/2L6i8UA

Acellular and Cellular Lung Model to Study Tumor Metastasis

Here, we present a protocol for an ex vivo lung cancer model that mimics the steps of tumor progression and helps to isolate a primary tumor, circulating tumor cells, and metastatic lesions.

https://ift.tt/2MHRxCd

A High-performance Liquid Chromatography Measurement of Kynurenine and Kynurenic Acid: Relating Biochemistry to Cognition and Sleep in Rats

Alterations in the kynurenine pathway (KP) neuroactive metabolites are implicated in psychiatric illnesses. Investigating the functional outcomes of an altered kynurenine pathway metabolism in vivo in rodents may help elucidate novel therapeutic approaches. The current protocol combines biochemical and behavioral approaches to investigate the impact of an acute kynurenine challenge in rats.

https://ift.tt/2Pj6GIB

Wastewater Irrigation Impacts on Soil Hydraulic Conductivity: Coupled Field Sampling and Laboratory Determination of Saturated Hydraulic Conductivity

Here we present a methodology which matches a soil sample size and a hydraulic conductivity measurement device to prevent the so-called wall flow along the inside of the soil container from being erroneously included in water flow measurements. Its use is demonstrated with samples collected from a wastewater irrigation site.

https://ift.tt/2N0tw63

Corrigendum to “The Effect of Sanggua Drink Extract on Insulin Resistance through the PI3K/AKT Signaling Pathway”

https://ift.tt/2PnlmXa

Unsuspected Cause of Respiratory Distress: Unrecognized Esophageal Foreign Body

Summary. Foreign bodies in esophagus are avoidable accidents that occur most often in children younger than 3 years. The most common presenting symptoms are dysphagia, drooling, and vomiting. Revelation by respiratory distress is a rare and unusual condition. Objective. We describe and discuss the case of an esophageal foreign body, in which the patient presented with respiratory distress. Case report. A two-year-old child was admitted to the emergency department for acute respiratory distress. He had no history of choking episodes or dysphagia. Nevertheless, he was brought by his parents several times for a persistent cough and wheezing that was treated as asthma for a month. Pulmonary examination had revealed polypnea, suprasternal recession, scattered snoring, and diffuse wheeze. As part of his assessment, a chest X-ray was demanded. It had shown, as unexpected, a nonmetallic foreign body in the upper thoracic esophagus. A clothing button was removed by hypopharyngoscopy under sedation without any incident. Subsequent follow-up had not shown any complications related to this episode. Conclusion. Large esophageal foreign bodies can impinge on the trachea causing upper respiratory tract signs. We alert clinicians on variation in the presentation of foreign body ingestion, and we emphasize the importance of an early diagnosis and management.

https://ift.tt/2L6gwdj

Comment on “Effect of Riociguat and Sildenafil on Right Heart Remodeling and Function in Pressure Overload Induced Model of Pulmonary Arterial Banding”

https://ift.tt/2Brm42G

The Combination of Ephedrae herba and Coicis semen in Gambihwan Attenuates Obesity and Metabolic Syndrome in High-Fat Diet–Induced Obese Mice

Gambihwan is a herbal prescription used in Korean medicine to treat obesity. The authors evaluated the effects and mechanisms of two types of Gambihwan (GBH1 and 2) administered to high-fat diet– (HFD-) induced obese mice. Four-week-old C57BL/6 mice were fed a HFD for 8 weeks with or without GBH1 or 2 (100-200 mg/kg/day by oral gavage). All mice were subjected to glucose tolerance testing after the 8-week treatment period and then euthanized. Serum insulin, lipids, and inflammatory cytokine levels were analyzed using commercial kits. Hepatic enzyme levels and lipid profiles were also investigated. Liver section slides were stained with Oil Red O (ORO) or hematoxylin and eosin (H&E) to assess lipid accumulation. GBH1 and 2 both significantly decreased body, liver, or adipose tissue weights in HFD-fed mice and significantly improved glucose tolerance (p

https://ift.tt/2ONKTHD

DMD genomic deletions characterize a subset of progressive/higher-grade meningiomas with poor outcome

Abstract

Progressive meningiomas that have failed surgery and radiation have a poor prognosis and no standard therapy. While meningiomas are more common in females overall, progressive meningiomas are enriched in males. We performed a comprehensive molecular characterization of 169 meningiomas from 53 patients with progressive/high-grade tumors, including matched primary and recurrent samples. Exome sequencing in an initial cohort (n = 24) detected frequent alterations in genes residing on the X chromosome, with somatic intragenic deletions of the dystrophin-encoding and muscular dystrophy-associated DMD gene as the most common alteration (n = 5, 20.8%), along with alterations of other known X-linked cancer-related genes KDM6A (n =2, 8.3%), DDX3X, RBM10 and STAG2 (n = 1, 4.1% each). DMD inactivation (by genomic deletion or loss of protein expression) was ultimately detected in 17/53 progressive meningioma patients (32%). Importantly, patients with tumors harboring DMD inactivation had a shorter overall survival (OS) than their wild-type counterparts [5.1 years (95% CI 1.3–9.0) vs. median not reached (95% CI 2.9–not reached, p = 0.006)]. Given the known poor prognostic association of TERT alterations in these tumors, we also assessed for these events, and found seven patients with TERT promoter mutations and three with TERT rearrangements in this cohort (n = 10, 18.8%), including a recurrent novel RETREG1–TERT rearrangement that was present in two patients. In a multivariate model, DMD inactivation (p = 0.033, HR = 2.6, 95% CI 1.0–6.6) and TERT alterations (p = 0.005, HR = 3.8, 95% CI 1.5–9.9) were mutually independent in predicting unfavorable outcomes. Thus, DMD alterations identify a subset of progressive/high-grade meningiomas with worse outcomes.

https://ift.tt/2PmGwob

Preoperative Evaluation of Soleal Vein Diameter by Ultrasound Is Beneficial for Prophylaxis of Deep Vein Thrombosis after Total Knee or Hip Arthroplasty

Purpose. The purpose of this retrospective study was to determine the association between preoperative soleal vein (SV) diameter and deep vein thrombosis (DVT) following total joint arthroplasty (TJA). Methods. A total of 402 patients were enrolled, with 229 patients undergoing total knee arthroplasty (TKA) and 173 patients undergoing total hip arthroplasty (THA). Ultrasonography was performed 1-3 days preoperatively, on postoperative days 1, 3, and 7, or before discharge and during follow-up. The SV diameter was assessed preoperatively. Univariate analysis and multivariate logistic regression analysis were used to compare parameters between the DVT group and the non-DVT group. Results. 78 patients (19.4%) were found to have DVT during hospitalization and after discharge and 14 patients (3.5%) developed symptomatic DVT. Multiple regression analysis showed that SV diameter, advanced age, and surgery type were independent predictors of postoperative DVT. In the logistic regression analysis for symptomatic DVT, SV diameter was found to be the only predictor. In the receiver operating characteristics (ROC) analysis for the value of SV diameter in diagnosing DVT, the area under curve (AUC) was 0.701 ((95% CI 0.636-0.766), P

https://ift.tt/2vUUoOv

Liver Retraction Using n-Butyl-2-Cyanoacrylate (NBCA) Glue during Laparoscopic Splenectomy and Azygoportal Disconnection in Cirrhotic Patients

Background. Although liver retraction using n-butyl-2-cyanoacrylate (NBCA) glue has been applied to laparoscopic upper abdominal surgery in noncirrhotic patients, there is still no consensus on its safety and feasibility for cirrhotic patients. In this study, we aimed to investigate the safety and effectiveness of liver retraction using NBCA glue during laparoscopic splenectomy and azygoportal disconnection (LSD) for gastroesophageal varices and hypersplenism secondary to liver cirrhosis and portal hypertension. Methods. Thirty-nine gastroesophageal varices and hypersplenism secondary to liver cirrhosis and portal hypertension patients were included in our study. We performed LSD in the presence of NBCA glue (n = 22, NBCA group) and absence of NBCA glue (n = 17, n-NBCA group), respectively. The operation time, blood loss, postoperative hospitalization, and liver function were compared between the two groups. Results. There was no mortality during the operation. One patient in non-NBCA group received open surgery due to parenchyma hemorrhage. Postoperative pleural effusion occurred in 2 cases of the NBCA group and 1 of the non-NBCA group. One showed left subphrenic abscess in the non-NBCA group. No postoperative bleeding occurred after 9-30 months of follow-up. The time of operation in NBCA group was significantly shorter than those in n-NBCA group (198.86±17.86 versus 217.81±20.25min, P

https://ift.tt/2BppIKf

Alcohol consumption and probable rapid eye movement sleep behavior disorder

Annals of Clinical and Translational Neurology, EarlyView.


https://ift.tt/2vWYk0V

Epidemiology of Traffic Fatalities among Motorcycle Users in East Azerbaijan, Iran

Background. The aim of this study was to determine some epidemiological aspects of motorcycle user traffic fatalities including the crash mechanisms and injury patterns in East Azerbaijan, Iran (2006-2016). Methods. A total of 1840 motorcycle user mortal cases registered in East Azerbaijan forensic medicine database, in Iran, were analyzed over the time period between March 2006 and March 2016. The distribution and associations of both victim- and crash-related variables such as crash mechanism, types of involved vehicles, types of injuries, and demographic characteristics were investigated. Data were analyzed by Stata v.13 statistical software package. Results. Of the 9435 RTI deaths, 1840 (19.5%) were motorcycle users of whom 96.5% were male (mean age of 32.3 ± 18.5 years). The majority of accident mechanisms were motorcycle-vehicle crashes (77.8%), followed by rollover (11.8%). Cars were the leading counterpart crash vehicle comprising about 34.8% of the motorcycle user mortalities. Inner city traffic injuries were the reason for 744 (40.7%) of the motorcycle user mortalities. Head trauma was the main cause of death. About 82% of the victims were motorcycle riders and the remainder were pillion passengers. A decreasing trend of fatal traffic accidents was observed over the study period for both the motorcycle user fatalities and other traffic injuries. The percentage of motorcycle mortalities over all traffic mortalities had a decreasing trend over the past nine years from March 2007 to March 2016 reaching a figure as low as 15.2% through the last year of study. Conclusions. Motorcycle traffic fatalities, although having a decreasing trend during the last decade with a better slope than most other traffic injuries, remain to be a major public health in north-west of Iran. There is a need for effective interventional programs to reduce the burden of motorcycle fatalities.

https://ift.tt/2MCn7Rq

Therapeutic Efficacies of Artemisia capillaris Extract Cream Formulation in Imiquimod-Induced Psoriasis Models

A cream formulation containing Artemisia capillaris (AC) extract (ACE) was developed for psoriasis therapy. Although ACE can be dissolved in organic solvents, its topical application is restricted because of toxicities. Therefore, a cream formulation was developed for the convenient and safe local application of ACE on skin lesions. The antipsoriatic properties of the ACE cream were evaluated using an imiquimod- (IMQ-) induced psoriasis-like mouse model. In psoriasis-like mouse models, the cumulative score (redness, thickness, and scaling) of the IMQ + ACE cream group was significantly lower than those of the other groups on day 4 (p

https://ift.tt/2PmIpRO

Conservative Surgical Treatment of Bisphosphonate-Related Osteonecrosis of the Jaw with Er,Cr:YSGG Laser and Platelet-Rich Plasma: A Longitudinal Study

Introduction. The management of bisphosphonate-related osteonecrosis of the jaw (BRONJ), with no evidence-based guidelines, remains controversial. We aimed to evaluate the efficiency of a conservative surgical treatment combining Er,Cr:YSGG laser and platelet-rich plasma (PRP) for the treatment of BRONJ in cancer patients. Methods. We performed a longitudinal cohort study. Inclusion criteria were (1) age ≥ 18 years; (2) cancer diagnosis; (3) treatment with NBP because of the underlying cancer. Results. We consecutively recruited ten patients diagnosed with BRONJ in stage I or II. These patients underwent a surgical laser-assisted therapy together with autologous PRP. At the latest follow-up at 12 months, clinical improvement was observed in eight patients. Registration Number is IRCT20180329039159N1. Conclusion. We could successfully manage the BRONJ utilizing this combined protocol to heal the 30% of surgically treated sites and to improve the 50% of patients' lesions clinically. Our findings suggest that a surgical approach combined with Er,Cr:YSGG laser and PRP benefit cancer patients with general health issues.

https://ift.tt/2L12OZj

Survival effect of different lymph node staging methods on ovarian cancer: An analysis of 10 878 patients

Cancer Medicine, EarlyView.


https://ift.tt/2BpJyFn

Design, synthesis and biological evaluation of 2‐(4‐(methylsulfonyl)phenyl)pyridine derivatives as GPR119 agonists

Chemical Biology &Drug Design, Volume 0, Issue ja, -Not available-.


https://ift.tt/2BAGTc7

The activity and action mechanism of novel short selective LL‐37‐derived anticancer peptides against clinical isolates of Escherichia coli

Chemical Biology &Drug Design, Volume 0, Issue ja, -Not available-.


https://ift.tt/2Mza2sq

Local production of prolactin in lesions may play a pathogenic role in psoriatic patients and imiquimod‐induced psoriasis‐like mouse model

Experimental Dermatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2nNVVRL

Role of IL‐17A receptor blocking in melanocytes survival: A strategic intervention against vitiligo

Experimental Dermatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2wdRiEz

Attenuated nitric oxide bioavailability in systemic sclerosis: Evidence from the novel assessment of passive leg movement

Experimental Physiology, EarlyView.


https://ift.tt/2wdCnKA

Physiology on television

Experimental Physiology, EarlyView.


https://ift.tt/2nOHTiM

Introduction to Guest Editorials

Experimental Physiology, EarlyView.


https://ift.tt/2wg35Cl

Mitral cells and the glucagon‐like peptide 1 receptor: the sweet smell of success?

European Journal of Neuroscience, Volume 0, Issue ja, -Not available-.


https://ift.tt/2L70hwO

Targeted Sequencing and Intracranial Outcomes of Patients With Lung Adenocarcinoma Brain Metastases Treated With Radiotherapy

Cancer, EarlyView.


https://ift.tt/2MZY1cr

Absorption of Codonopsis pilosula Saponins by Coexisting Polysaccharides Alleviates Gut Microbial Dysbiosis with Dextran Sulfate Sodium-Induced Colitis in Model Mice

Objectives. Inflammatory Bowel Disease (IBD) is an autoimmune disease, and the gut microbiota has become a new therapeutic target. Herbal medicine (HM) has shown good efficacy in the clinical treatment of IBD; however, the synergistic actions of the dominant chemicals in HM decoctions are unclear. Methods. In this study, we explored whether the complicated interconnections between HM and the gut microbiota could allow crosstalk between HM ingredients. Saponins and polysaccharides, i.e., the dominant chemicals in the Codonopsis pilosula Nannf (CPN) decoction, were investigated in a dextran sulfate sodium- (DSS-) induced mouse model. Bacterial 16S rRNA sequencing analyzed the change of gut microbiota structure and diversity. Gas chromatography (GC) determined the content of short-chain fatty acids (SCFAs) in feces. ELISA detected the expression of proinflammatory and anti-inflammatory cytokines associated with TH17/Treg balance. UPLC-QTOF-MS technology combined with PKsolver software analyzed the absorption of the highest exposure for monomeric compounds of CPN saponins in serum. The results indicated that CPN polysaccharides showed prebiotic-like effects in mice with DSS-induced colitis by simultaneously stimulating the growth of three important probiotics, i.e., Bifidobacterium spp., Lactobacillus spp., and Akkermansia spp., and inhibiting the growth of pathogenic bacteria, including Desulfovibrio spp., Alistipes spp., and Helicobacter spp. Moreover, CPN polysaccharides improved intestinal metabolism, enhanced the production of short-chain fatty acids, upregulated the expression of anti-inflammatory cytokines and downregulated the secretion of proinflammatory cytokines correlated with Th17/Treg balance, promoted the absorption of certain CPN saponins in the serum, and stimulated recovery of the holistic gut microbiota. Conclusion. CPN polysaccharides have the good prebiotic properties and shown good application prospects in the prevention and treatment of acute colitis. These findings provide insights into the specific bacteria responsible for active, inactive biotransformation of HM ingredients and those that are altered by HM administration.

https://ift.tt/2ONkrxP

Hepatic zonation now on hormones!

Hepatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2MYQTNp

Liver complications following treatment of hematologic malignancy with anti‐cd22‐calicheamicin (Inotuzumab Ozogamicin)

Hepatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2vWPsIF

Estimating the impact of an organised screening programme on cervical cancer incidence: a 26‐year study from northern Italy

International Journal of Cancer, Volume 0, Issue ja, -Not available-.


https://ift.tt/2vUJCYg

Effects of Conventional Synthetic Disease-Modifying Antirheumatic Drugs on Response to Periodontal Treatment in Patients with Rheumatoid Arthritis

Rheumatoid arthritis (RA) and periodontitis are common chronic inflammatory diseases and periodontitis is known to be more common and more severe in patients with RA. Based on a paucity of studies about the relationship between common conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and periodontitis, this prospective study aimed to evaluate the adjunctive effect of csDMARDs on response to nonsurgical periodontal treatment in patients with RA. Thirty-two patients with RA (RA group) and 32 systemically healthy patients (control group) with periodontitis were included in this study. The RA group patients were treated with csDMARDs, such as methotrexate, hydroxychloroquine, and sulfasalazine. Conventional nonsurgical periodontal treatment with scaling and root planing was performed in both groups. The extent and severity of periodontitis were evaluated by plaque index (PI), gingival index (GI), probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP) at baseline and 4 weeks after periodontal treatment. There was no statistically significant difference of periodontal parameters between the RA and control groups at baseline. Four weeks after scaling and root planing, PD reduction, and CAL gain were higher in the RA group treated with csDMARDs compared to the control group, and the difference was statistically significant (P = 0.006 and 0.003, respectively). A post hoc analysis of the RA group showed no statistically significant difference on the response to nonsurgical periodontal treatment in multiple csDMARDs therapy and addition of NSAIDs and/or steroids to csDMARDs. In patients with RA, csDMARDs showed beneficial effect on periodontal clinical parameters following the nonsurgical periodontal treatment.

https://ift.tt/2Mlw5mQ

Divergent Evolutional Mode and Purifying Selection of the KIT Gene in European and Asian Domestic Pig Breeds

The recent geographic expansion of wild boars and the even more recent development of numerous domestic pigs have spurred exploration on pig domestic origins. The porcine KIT gene has been showed to affect pleiotropic effects, blood parameters, and coat colour phenotypes, especially the white colour phenotype formation in European commercial breeds. Here, we described the use of SNPs to identify different selection patterns on the porcine KIT gene and the phylogenetic relationships of the inferred haplotypes. The phylogenetic tree revealed four clades in European and Asian wild and domestic pigs: two major clades with European and Asian origins and one minor clade with Iberian origins as well as the other minor clade in Asia, consistent with the major introgression of domestic Asian pigs in Europe around 18th -19th century. The domestication history of pigs, which occurred in the domestication centers (Europe and Asia), has also been demonstrated by mtDNA analysis. Furthermore, both Asian and European domestic pigs evolved under purifying selection. This study indicated that domestic pigs in Europe and Asia have different lineage origins but the porcine KIT gene was undergoing a purifying selection during their evolutional histories.

https://ift.tt/2Bpklea

Folding and lipid composition determine membrane interaction of the disordered protein COR15A

Plants from temperate climates, such as the model plant Arabidopsis thaliana, are challenged with seasonal low temperatures that lead to increased freezing tolerance in fall in a process termed cold acclimation. Among other adaptations, this involves the accumulation of COld Regulated (COR) proteins, such as the intrinsically disordered chloroplast-localized protein COR15A. Together with its close homologue COR15B it stabilizes chloroplast membranes during freezing. COR15A folds into amphipathic α-helices in the presence of high concentrations of low-molecular-mass crowders or upon dehydration.

https://ift.tt/2nVo2ih

Synchronization of triggered waves in atrial tissue

When an atrial cell is paced rapidly calcium (Ca) waves can form on the cell boundary and propagate to the cell interior. These waves are referred to as "triggered waves" since they are initiated by Ca influx from the L-type Ca channel (LCC), and occur during the action potential (AP). However, the consequences of triggered waves in atrial tissue are not known. Here, we develop a phenomenological model of Ca cycling in atrial myocytes that accounts for the formation of triggered waves. Using this model we show that a fundamental requirement for triggered waves to induce abnormal electrical activity in tissue is that these waves must be synchronized over large populations of cells.

https://ift.tt/2OM3Ydc

Multiplex single-molecule DNA barcoding using an oligonucleotide ligation assay

Detection of specific nucleic acid sequences is invaluable in biological studies such as genetic disease diagnostics and genome profiling. Here we developed a highly sensitive and specific detection method that combines an advanced oligonucleotide ligation assay (OLA) with multi-color single-molecule fluorescence. We demonstrated that under our experimental conditions 7-nt long DNA barcodes have the optimal short length to ascertain specificity while being long enough for sufficient ligation. Using four spectrally separated fluorophores to label DNA barcodes, we simultaneously distinguished four DNA target sequences differing by only a single nucleotide.

https://ift.tt/2ONBnoa

Precise Binding of Tropomyosin on Actin Involves Sequence-Dependent Variance in Coiled-coil Twisting

Often considered an archetypal dimeric coiled-coil, tropomyosin nonetheless exhibits distinctive "non-canonical" core residues located at the hydrophobic interface between its component α-helices. Notably, a charged aspartate, D137, takes the place of non-polar residues otherwise present. Much speculation has been offered to rationalize potential local coiled-coil instability stemming from D137 and its effect on regulatory transitions of tropomyosin over actin filaments. While experimental approaches such as cryo-EM reconstruction are optimal for defining average tropomyosin positions on actin filaments, to date, these methods have not captured the dynamics of tropomyosin residues clustered around position 137 or elsewhere.

https://ift.tt/2nO4lIY