Medicine by Alexandros G.Sfakianakis: 03/23/18

Παρασκευή 23 Μαρτίου 2018

Primary male factor infertility due to asthenospermia in maturity-onset diabetes of the young type 5 (MODY 5): uncommon presentation of an uncommon disease

Mutations in hepatocyte nuclear factor-1β gene result in a multisystemic syndrome where a monogenic form of diabetes (maturity-onset diabetes of young type 5; MODY 5) and renal anomalies, usually bilateral multiple cysts are the most characteristic findings. Many of them have pancreatic structural abnormalities as well. A plethora of extrapancreatic manifestations like altered liver function tests, hypomagnesaemia, hyperuricaemia with/without gout and urogenital malformations, particularly in females are also components of the syndrome. Structural malformation of male urogenital tract is rare in MODY 5, even rarer is asthenospermia. We encountered a young non-obese individual having insulin-requiring diabetes following secondary oral agent failure with primary male factor infertility secondary to asthenospermia. A suggestive family history, lack of acanthosis, negative pancreatic autoimmunity, hypomagnesaemia, bilateral renal and epididymal cysts, and absence of body and tail of pancreas pointed towards underlying MODY 5.

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Superficial temporal artery pseudoaneurysm following facial trauma

A 68-year-old man presented with rapid swelling of the right forehead 11 days after sustaining a laceration secondary to a fall. Presumed to be an abscess due to retained foreign body, needle aspiration was performed and arterial blood obtained. Doppler ultrasound revealed a 3 cm mixed echogenicity lesion with 'see-sawing' internal Doppler flow arising from the superficial temporal artery (STA), in keeping with a pseudoaneurysm. Treatment options including interventional radiology and open surgery were considered. Open operative intervention with direct surgical ligation provided an excellent outcome. Delayed pseudoaneurysm of the STA is a rare complication of trauma but should be considered in the differential of a traumatic lateral forehead swelling to prevent complications and inappropriate investigations and management.

https://ift.tt/2IMqctG

Worm in anterior chamber of the eye

We report a case of a 42-year-old female patient who presented to the ophthalmology outpatient department with painful red eye for 1 month. Slit-lamp microscopy showed a live worm in the anterior chamber of left eye. The worm was surgically removed under topical anaesthesia. It was sent to the microbiology department for further identification and was found to be adult female Loaloa.

https://ift.tt/2INqBMl

Placenta accreta complicated with peripartum cardiomyopathy

A 33-year-old G2P1 was referred to our hospital due to placenta accreta. During perioperative preparations, the patient was diagnosed with having a peripartum cardiomyopathy. The patient underwent caesarean hysterectomy at 36 weeks with an associated 2 L blood loss. Haemodynamic maintenance and stabilisation during the operation were challenging, with the combinations of fluid therapy, blood transfusions as well as vasoactive, antifibrinolytic and haemostatic drug. Postoperatively, the patient was managed in the intensive care unit and was subsequently transferred to intermediate care after less than 24 hours' observation. She was stable enough to be moved to the obstetrics ward the next day.

https://ift.tt/2ubeoO8

Concurrent Sweets syndrome and myopericarditis following mesalamine therapy

Mesalamine, or 5-aminosalicylic acid, is a frequently used medication for the treatment of inflammatory bowel disease (IBD). We report the case of a 40-year-old woman recently diagnosed with IBD and started on mesalamine, who presented with new onset tender skin lesions 3 days following medication administration. One day following the onset of skin lesions, the patient developed acute chest pain, shortness of breath, ECG changes, troponemia, C-reactive protein elevation and pericardial enhancement on cardiac MRI consistent with myopericarditis. Subsequent skin biopsy confirmed the diagnosis of Sweet's syndrome. On cessation of the drug, both the skin lesions and the cardiac symptoms resolved in combination with anti-inflammatory therapy. While mesalamine has been previously associated with myocarditis and pericarditis, to our knowledge this is the first case of coexisting Sweet's syndrome with myopericarditis in the context of mesalamine therapy.

https://ift.tt/2IQzNje

Rapidly expanding venous intracerebral haemorrhage with spot sign

A 79-year-old woman was brought to the hospital with an acute-onset left haemiparesis. On initial examination, she had a pure sensorimotor syndrome with left-sided weakness and sensory disturbance. Her mental status was normal. She had normal visual fields to confrontation and no neglect. Her initial CT and CT angiogram revealed cerebral venous thrombosis with associated haemorrhage. A 'spot sign' was visible on CT angiogram. Immediately following the CT scan, the patient had a rapidly progressive decline in level of consciousness, requiring endotracheal intubation. A follow-up CT scan 70 min later showed the haemorrhage had expanded dramatically, with mass effect, midline shift and herniation. After a discussion with the family, the patient was extubated and died the following day. This is the first case of a cerebral venous thrombosis with associated spot sign-positive haemorrhage and published clinical details that the authors are aware of.

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Autoimmune pancreatitis with concomitant autoimmune haemolytic anaemia

Autoimmune pancreatitis (AIP) is an infrequent cause of acute pancreatitis, being more commonly associated with chronic pancreatitis. AIP can be associated with other autoimmune manifestations, including Sjögren's, inflammatory bowel disease, primary biliary cirrhosis, rheumatoid arthritis, hypothyroidism and sarcoidosis. Rarely, concurrent autoimmune haemolytic anaemia (AIHA) is observed, as seen in our case report of a 33-year-old postpartum woman.

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Pneumatosis intestinalis in small bowel obstruction

Description

We present a case of a 42-year-old woman with a history of acute myeloid leukaemia treated with bone marrow transplant. Her case was complicated by graft versus host disease involving the gastrointestinal tract, necessitating partial colectomy with ileostomy. She presented to the hospital with recurrent partial small bowel obstruction (SBO). Abdominal CT scan was consistent with partial SBO, and the patient was admitted for conservative treatment. She was deemed a poor surgical candidate given her multiple comorbidities and immunosuppressed state. Her clinical condition waxed and waned over the next week, and on hospital day 10 the patient developed decreased ileostomy output, increased nausea and vomiting. Abdominal radiographs revealed dilated bowel with increased intramural radiolucency (figure 1), and subsequent CT scan was confirmatory for extensive pneumatosis intestinalis (PI) (figure 2). The patient was treated conservatively with bowel rest and nasogastric suction with favourable outcome.

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Delayed neurological deficits after endovascular placement of a pipeline embolisation device: clinical manifestation and treatment

Endovascular treatment has been the mainstay of therapy for repair of both ruptured and unruptured cerebral aneurysms. Flow diverter devices offer a new option for the treatment of complex aneurysms that were previously not amenable to coiling. Procedural adverse effects include intracranial haemorrhage and ischaemic stroke, which usually occur on the same day. Delayed complications are rare. We report a case of a patient who underwent placement of a pipeline embolisation device and developed delayed neurological deficits, which were thought to be an inflammatory reaction to the hydrophilic coating used in guidewires and microcatheters. Our patient was treated with a course of steroids, with improvement of her neurological deficits and resolution of MRI findings. As the use of flow diverter devices has increased, variable and delayed complications of such therapy are increasingly being reported in the literature.

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Opioid use and harms associated with a sustained-release tapentadol formulation: a postmarketing study protocol

Introduction

It has been argued that tapentadol may pharmacologically have lower abuse potential than other pharmaceutical opioids currently available. However, there has been no comprehensive triangulation of data regarding use and harms associated with this formulation. A sustained-release formulation (SRF) of tapentadol (Palexia) was released in Australia in 2011 and listed for public subsidy in 2013. We summarise here the methods of a postmarketing study which will measure postintroduction: (1) population level availability, (2) extramedical use and diversion, (3) attractiveness for extramedical use and (4) associated harms, of tapentadol compared against other pharmaceutical opioids.

Methods and analysis

We evaluated key sources on pharmaceutical use and harms in Australia. This review indicateddata from four sources that disaggregate pharmaceutical opioid formulations and capture tapentadol SRF could be triangulated. These data sources comprised: (1) national pharmaceutical opioid community sales data from 2011 to 2017, (2) national pharmaceutical opioid poisonings reported to Poison Information Centres (PICs) from 2011 to 2017, (3) number of vendors on online marketplaces listing pharmaceutical opioids for sale and (4) data on pharmaceutical opioid extramedical use, attractiveness and harms from interviews with people who regularly inject drugs in Australia.

Ethics and dissemination

Ethics approval is not required for use of pharmaceutical sales data. Ethics approval has been obtained for use of national pharmaceutical opioid poisonings reported to PICs (LNR/16/SCHN/44) and for use of online marketplace data and interview data from people who inject drugs (HC12086). Key findings will be published mid-2018 in a peer-reviewed academic journal, and presented at various conferences and professional meetings.

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Development of the Combined Assessment of Risk Encountered in Surgery (CARES) surgical risk calculator for prediction of postsurgical mortality and need for intensive care unit admission risk: a single-center retrospective study

Introduction

Accurate surgical risk prediction is paramount in clinical shared decision making. Existing risk calculators have limited value in local practice due to lack of validation, complexities and inclusion of non-routine variables.

Objective

We aim to develop a simple, locally derived and validated surgical risk calculator predicting 30-day postsurgical mortality and need for intensive care unit (ICU) stay (>24 hours) based on routinely collected preoperative variables. We postulate that accuracy of a clinical history-based scoring tool could be improved by including readily available investigations, such as haemoglobin level and red cell distribution width.

Methodology

Electronic medical records of 90 785 patients, who underwent non-cardiac and non-neuro surgery between 1 January 2012 and 31 October 2016 in Singapore General Hospital, were retrospectively analysed. Patient demographics, comorbidities, laboratory results, surgical priority and surgical risk were collected. Outcome measures were death within 30 days after surgery and ICU admission. After excluding patients with missing data, the final data set consisted of 79 914 cases, which was divided randomly into derivation (70%) and validation cohort (30%). Multivariable logistic regression analysis was used to construct a single model predicting both outcomes using Odds Ratio (OR) of the risk variables. The ORs were then assigned ranks, which were subsequently used to construct the calculator.

Results

Observed mortality was 0.6%. The Combined Assessment of Risk Encountered in Surgery (CARES) surgical risk calculator, consisting of nine variables, was constructed. The area under the receiver operating curve (AUROC) in the derivation and validation cohorts for mortality were 0.934 (0.917–0.950) and 0.934 (0.912–0.956), respectively, while the AUROC for ICU admission was 0.863 (0.848–0.878) and 0.837 (0.808–0.868), respectively. CARES also performed better than the American Society of Anaesthesiologists-Physical Status classification in terms of AUROC comparison.

Conclusion

The development of the CARES surgical risk calculator allows for a simplified yet accurate prediction of both postoperative mortality and need for ICU admission after surgery.

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Randomised controlled trial of exercise to prevent shoulder problems in women undergoing breast cancer treatment: study protocol for the prevention of shoulder problems trial (UK PROSPER)

Musculoskeletal shoulder problems are common after breast cancer treatment. Early postoperative exercises targeting the upper limb may improve shoulder function. This protocol describes a National Institute for Health Research-funded randomised controlled trial (RCT) to evaluate the clinical and cost-effectiveness of an early supervised structured exercise programme compared with usual care, for women at high risk of developing shoulder problems after breast cancer surgery.

Methods

This pragmatic two-armed, multicentre RCT is underway within secondary care in the UK. PRevention Of Shoulder ProblEms tRial (PROSPER) aims to recruit 350 women from approximately 15 UK centres with follow-up at 6 weeks, 6 and 12 months after randomisation. Recruitment processes and intervention development were optimised through qualitative research during a 6-month internal pilot phase. Participants are randomised to the PROSPER intervention or best practice usual care only. The PROSPER intervention is delivered by physiotherapists and incorporates three main components: shoulder-specific exercises targeting range of movement and strength; general physical activity and behavioural strategies to encourage adherence and support exercise behaviour. The primary outcome is upper arm function assessed using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire at 12 months postrandomisation. Secondary outcomes include DASH subscales, acute and chronic pain, complications, health-related quality of life and healthcare resource use. We will interview a subsample of 20 participants to explore their experiences of the trial interventions.

Discussion

The PROSPER study is the first multicentre UK clinical trial to investigate the clinical and cost-effectiveness of supported exercise in the prevention of shoulder problems in high-risk women undergoing breast cancer surgery. The findings will inform future clinical practice and provide valuable insight into the role of physiotherapy-supported exercise in breast cancer rehabilitation.

Protocol version

Version 2.1; dated 11 January 2017

Trial registration number

ISRCTN35358984; Pre-results.

https://ift.tt/2pyMaaG

Comparison of incidence, rate and length of all-cause hospital admissions between adults with normoglycaemia, impaired fasting glucose and diabetes: a retrospective cohort study in Geelong, Australia

Objective

To determine whether adults with normoglycaemia, impaired fasting glucose (IFG) and diabetes differed according to the incidence, rate, length and primary reasons for hospital admission.

Design

Retrospective cohort study.

Setting

Barwon Statistical Division, Geelong, Australia.

Participants

Cohort included 971 men and 924 women, aged 20+ years, participating in the Geelong Osteoporosis Study. Glycaemic status was assessed at cohort entry using fasting plasma glucose, use of antihyperglycaemic medication and/or self-report.

Primary and secondary outcome measures

Primary outcome measure was any admission to the major tertiary public hospital in the study region over the follow-up period. Secondary outcome measures were admission rate and length (days).

Results

Over a median follow-up of 7.4 years (IQR 5.3–9.6), participants with diabetes, compared with those with normoglycaemia, were two times as likely to be hospitalised (OR 2.07, 95% CI 1.42 to 3.02), had a higher admission rate (incidence rate ratio 1.61, 95% CI 1.17 to 2.23) and longer hospital stay (third quartile difference 7.7, 95% CI 1.3 to 14.1 and ninth decile difference 16.2, 95% CI 4.2 to 28.3). IFG group was similar to normoglycaemia for the incidence, rate and length of admission. Cardiovascular disease-related diagnoses were the most common primary reasons for hospitalisation across all glycaemic categories.

Conclusions

Our results show increased incidence, rate and length of all-cause hospital admission in adults with diabetes as compared with normoglycaemia; however, we did not detect any associations for IFG. Interventions should focus on preventing IFG-to-diabetes progression and reducing cardiovascular risk in IFG and diabetes.

https://ift.tt/2IOHyG7

Projecting the effects of tobacco control policies in the USA through microsimulation: a study protocol

Introduction

Smoking remains the leading cause of preventable death in the USA but can be reduced through policy interventions. Computational models of smoking can provide estimates of the projected impact of tobacco control policies and can be used to inform public health decision making. We outline a protocol for simulating the effects of tobacco policies on population health outcomes.

Methods and analysis

We extend the Smoking History Generator (SHG), a microsimulation model based on data from the National Health Interview Surveys, to evaluate the effects of tobacco control policies on projections of smoking prevalence and mortality in the USA. The SHG simulates individual life trajectories including smoking initiation, cessation and mortality. We illustrate the application of the SHG policy module for four types of tobacco control policies at the national and state levels: smoke-free air laws, cigarette taxes, increasing tobacco control programme expenditures and raising the minimum age of legal access to tobacco. Smoking initiation and cessation rates are modified by age, birth cohort, gender and years since policy implementation. Initiation and cessation rate modifiers are adjusted for differences across age groups and the level of existing policy coverage. Smoking prevalence, the number of population deaths avoided, and life-years gained are calculated for each policy scenario at the national and state levels. The model only considers direct individual benefits through reduced smoking and does not consider benefits through reduced exposure to secondhand smoke.

Ethics and dissemination

A web-based interface is being developed to integrate the results of the simulations into a format that allows the user to explore the projected effects of tobacco control policies in the USA. Usability testing is being conducted in which experts provide feedback on the interface. Development of this tool is under way, and a publicly accessible website is available at http://www.tobaccopolicyeffects.org.

https://ift.tt/2I0zQHI

Early initiation of post-sternotomy cardiac rehabilitation exercise training (SCAR): study protocol for a randomised controlled trial and economic evaluation

Introduction

Current guidelines recommend abstinence from supervised cardiac rehabilitation (CR) exercise training for 6 weeks post-sternotomy. This practice is not based on empirical evidence, thus imposing potentially unnecessary activity restrictions. Delayed participation in CR exercise training promotes muscle atrophy, reduces cardiovascular fitness and prolongs recovery. Limited data suggest no detrimental effect of beginning CR exercise training as early as 2 weeks post-surgery, but randomised controlled trials are yet to confirm this. The purpose of this trial is to compare CR exercise training commenced early (2 weeks post-surgery) with current usual care (6 weeks post-surgery) with a view to informing future CR guidelines for patients recovering from sternotomy.

Methods and analysis

In this assessor-blind randomised controlled trial, 140 cardiac surgery patients, recovering from sternotomy, will be assigned to 8 weeks of twice-weekly supervised CR exercise training commencing at either 2 weeks (early CR) or 6 weeks (usual care CR) post-surgery. Usual care exercise training will adhere to current UK recommendations. Participants in the early CR group will undertake a highly individualised 2–3 week programme of functional mobility, strength and cardiovascular exercise before progressing to a usual care CR programme. Outcomes will be assessed at baseline (inpatient), pre-CR (2 or 6 weeks post-surgery), post-CR (10 or 14 weeks post-surgery) and 12 months. The primary outcome will be change in 6 min walk distance. Secondary outcomes will include measures of functional fitness, quality of life and cost-effectiveness.

Ethics and dissemination

Recruitment commenced on July 2017 and will complete by December 2019. Results will be disseminated via national governing bodies, scientific meetings and peer-reviewed journals.

Trial registration number

NCT03223558; Pre-results.

https://ift.tt/2IOehM3

Lifestyle and vascular risk effects on MRI-based biomarkers of Alzheimers disease: a cross-sectional study of middle-aged adults from the broader New York City area

Objective

To investigate the effects of lifestyle and vascular-related risk factors for Alzheimer's disease (AD) on in vivo MRI-based brain atrophy in asymptomatic young to middle-aged adults.

Design

Cross-sectional, observational.

Setting

Broader New York City area. Two research centres affiliated with the Alzheimer's disease Core Center at New York University School of Medicine.

Participants

We studied 116 cognitively normal healthy research participants aged 30–60 years, who completed a three-dimensional T1-weighted volumetric MRI and had lifestyle (diet, physical activity and intellectual enrichment), vascular risk (overweight, hypertension, insulin resistance, elevated cholesterol and homocysteine) and cognition (memory, executive function, language) data. Estimates of cortical thickness for entorhinal (EC), posterior cingulate, orbitofrontal, inferior and middle temporal cortex were obtained by use of automated segmentation tools. We applied confirmatory factor analysis and structural equation modelling to evaluate the associations between lifestyle, vascular risk, brain and cognition.

Results

Adherence to a Mediterranean-style diet (MeDi) and insulin sensitivity were both positively associated with MRI-based cortical thickness (diet: β_s≥0.26, insulin sensitivity β_s≥0.58, P≤0.008). After accounting for vascular risk, EC in turn explained variance in memory (P≤0.001). None of the other lifestyle and vascular risk variables were associated with brain thickness. In addition, the path associations between intellectual enrichment and better cognition were significant (β_s≥0.25 P≤0.001), as were those between overweight and lower cognition (β_s≥-0.22, P≤0.01).

Conclusions

In cognitively normal middle-aged adults, MeDi and insulin sensitivity explained cortical thickness in key brain regions for AD, and EC thickness predicted memory performance in turn. Intellectual activity and overweight were associated with cognitive performance through different pathways. Our findings support further investigation of lifestyle and vascular risk factor modification against brain ageing and AD. More studies with larger samples are needed to replicate these research findings in more diverse, community-based settings.

https://ift.tt/2HXq8Gk

Health outcomes of patients with chronic disease managed with a healthcare kiosk in primary care: protocol for a pilot randomised controlled trial

Introduction

The rising prevalence of chronic disease is leading to an increase in the demand for primary care services and a shortage of primary care physicians globally. Addressing these challenges calls for innovations in the healthcare delivery model with greater use of healthcare technology tools. We previously examined the feasibility of using an automated healthcare kiosk for the management of patients with stable chronic disease in the primary care setting. The aim of this follow-up study is to evaluate the health outcomes of patients with chronic disease who are on kiosk management compared with patients who are on routine management by nurse clinicians.

Methods and analysis

The pilot study will be a two-armed randomised controlled trial of 120 patients with well-controlled chronic disease on 4-monthly follow-up visits over a 12-month period. Patients with prior diagnoses of hypertension, hyperlipidaemia and/or diabetes will be included in the study and will be randomly assigned to intervention or control groups to receive kiosk or nurse management, respectively. The main primary outcome measure is the overall chronic disease control of the patients. Other primary outcome measures are the blood pressure and low-density lipoprotein cholesterol levels for patients without diabetes, and blood pressure, low-density lipoprotein cholesterol and haemoglobin A1c levels for patients with diabetes. Secondary outcome measures are visit duration, patient satisfaction with the management process, health-related quality of life and the occurrence of any adverse event. Data will be captured longitudinally at baseline, 4 months, 8 months and 12 months, and will be analysed using multiple regression models.

Ethics and dissemination

The study has been approved by the Singapore Health Services (SingHealth) Centralised Institutional Review Board (2017/2715). Findings of the study will be submitted for publication in peer-reviewed journals and presented at national and international conferences.

Trial registration number

NCT03274089; Pre-results.

https://ift.tt/2ILOtQq

Targeting human 8-oxoguanine DNA glycosylase to mitochondria protects cells from high glucose-induced apoptosis.

Targeting human 8-oxoguanine DNA glycosylase to mitochondria protects cells from high glucose-induced apoptosis.

Endocrine. 2018 Mar 21;:

Authors: Zou YL, Luo WB, Xie L, Mao XB, Wu C, You ZP

Abstract
PURPOSE: Diabetic retinopathy (DR) is a major vision threatening disease mainly induced by high glucose. Despite great efforts were made to explore the etiology of DR, the exact mechanism responsible for its pathogenesis remains elusive.
METHODS: In our study, we constructed diabetic rats via Streptozotocin (STZ) injection. TUNEL assay was employed to examine retinal cell apoptosis. The levels of mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were analyzed via flow cytometry. The mRNA and protein levels of mitochondrial respiratory chain were investigated by RT-qPCR and western blot.
RESULTS: Compared with normal rats, the retinal cell apoptosis rate in diabetic rats was significantly upregulated. What's more, the signals of 8-OHdG and the levels of Cytochrome C in diabetic rats were enhanced; however, the MnSOD signals and NADPH-1 levels were reduced. We investigated the effect of mitochondrialy targeted hOGG1 (MTS-hOGG1) on the primary rRECs under high glucose. Compared with vector-transfected cells, MTS-hOGG1-expressing cells blocked high glucose-induced cell apoptosis, the loss of MMP and the overproduction of ROS. In addition, under high glucose, MTS-hOGG1 transfection blocked the expression of Cytochrome C, but enhanced the expression of cytochrome c oxidase subunit 1 and NADPH-1.
CONCLUSIONS: These findings indicated that high glucose induced cell apoptosis by causing the loss of MMP, the overproduction of ROS and mtDNA damage. Targeting DNA repair enzymes hOGG1 in mitochondria partly mitigated the high glucose-induced consequences, which shed new light for DR therapy.

PMID: 29564753 [PubMed - as supplied by publisher]

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Overcoming erlotinib resistance in EGFR mutation-positive lung adenocarcinomas through repression of phosphoglycerate dehydrogenase.

http:--ivyspring.com-images-linkout-thno

https:--www.ncbi.nlm.nih.gov-corehtml-pm

Overcoming erlotinib resistance in EGFR mutation-positive lung adenocarcinomas through repression of phosphoglycerate dehydrogenase.

Theranostics. 2018;8(7):1808-1823

Authors: Dong JK, Lei HM, Liang Q, Tang YB, Zhou Y, Wang Y, Zhang S, Li WB, Tong Y, Zhuang G, Zhang L, Chen HZ, Zhu L, Shen Y

Abstract
How to improve the efficacy and reverse the resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as erlotinib, remains a major challenge in the targeted therapy of lung adenocarcinoma with EGFR-activating mutation. Phosphoglycerate dehydrogenase (PHGDH) is the key enzyme of de novo serine biosynthesis over-expressed in various types of cancer including lung cancer. Elevated PHGDH expression is correlated with a worse overall survival in clinical lung adenocarcinoma patients. Here we investigated the role of PHGDH in lung adenocarcinoma with the acquisition of resistance to erlotinib. Methods: The necessary genes required for the acquired erlotinib resistance in lung adenocarcinoma cells were screened out by RNA-Seq analysis. Then the protein and mRNA levels of PHGDH were confirmed by immunoblotting and qRT-PCR in the erlotinib resistant cells. The effects of PHGDH inhibition or overexpression on erlotinib resistance were examined using cell culture and tumor xenograft mouse models respectively. To explore mechanism, the ROS level and DNA damage marker, γH2AX, were tested by DCFH-DA staining and immunofluorescence after PHGDH inhibition. Results: We found that PHGDH level was significantly increased in the lung adenocarcinoma PC9ER4 and HCC827ER9 cells that acquired resistance to erlotinib. Perturbation of PHGDH by siPHGDH transfection or NCT-503, a small molecular PHGDH inhibitor, synergistically augmented the tumoricidal effect and restored sensitivity to erlotinib in cell lines and xenografts. Over-expression of PHGDH caused xenografts resistant to erlotinib. Furthermore, multiple DNA damage repair pathways related genes were changed by PHGDH depletion specifically in erlotinib resistant cells. ROS stress and DNA damage marker γH2AX were enhanced by siPHGDH and NCT-503, which was reversed by NAC. Conclusion: Our study indicated that PHGDH inhibition has potential therapeutic value in lung adenocarcinoma with the acquired resistance to EGFR-TKIs.

PMID: 29556358 [PubMed - in process]

https://ift.tt/2pvFSJy

Precision genome editing using CRISPR-Cas9 and linear repair templates in C. elegans.

https:--linkinghub.elsevier.com-ihub-ima

Precision genome editing using CRISPR-Cas9 and linear repair templates in C. elegans.

Methods. 2017 May 15;121-122:86-93

Authors: Paix A, Folkmann A, Seydoux G

Abstract
The ability to introduce targeted edits in the genome of model organisms is revolutionizing the field of genetics. State-of-the-art methods for precision genome editing use RNA-guided endonucleases to create double-strand breaks (DSBs) and DNA templates containing the edits to repair the DSBs. Following this strategy, we have developed a protocol to create precise edits in the C. elegans genome. The protocol takes advantage of two innovations to improve editing efficiency: direct injection of CRISPR-Cas9 ribonucleoprotein complexes and use of linear DNAs with short homology arms as repair templates. The protocol requires no cloning or selection, and can be used to generate base and gene-size edits in just 4days. Point mutations, insertions, deletions and gene replacements can all be created using the same experimental pipeline.

PMID: 28392263 [PubMed - indexed for MEDLINE]

https://ift.tt/2p2x24s

Gene editing in mouse zygotes using the CRISPR/Cas9 system.

Gene editing in mouse zygotes using the CRISPR/Cas9 system.

Methods. 2017 May 15;121-122:55-67

Authors: Wefers B, Bashir S, Rossius J, Wurst W, Kühn R

Abstract
The generation of targeted mouse mutants is a key technology for biomedical research. Using the CRISPR/Cas9 system for induction of targeted double-strand breaks, gene editing can be performed in a single step directly in mouse zygotes. This article covers the design of knockout and knockin alleles, preparation of reagents, microinjection or electroporation of zygotes and the genotyping of pups derived from gene editing projects. In addition we include a section for the control of experimental settings by targeting the Rosa26 locus and PCR based genotyping of blastocysts.

PMID: 28263886 [PubMed - indexed for MEDLINE]

http://ift.tt/2mhlN8G

Targeting Enox1 in tumor stroma increases the efficacy of fractionated radiotherapy.

http:--www.impactjournals.com-oncotarget

Targeting Enox1 in tumor stroma increases the efficacy of fractionated radiotherapy.

Oncotarget. 2016 Nov 22;7(47):77926-77936

Authors: Smith CA, Mont S, Traver G, Sekhar KR, Crooks PA, Freeman ML

Abstract
The goal of this investigation was to clarify the question of whether targeting Enox1 in tumor stroma would synergistically enhance the survival of tumor-bearing mice treated with fractionated radiotherapy. Enox1, a NADH oxidase, is expressed in tumor vasculature and stroma. However, it is not expressed in many tumor types, including HT-29 colorectal carcinoma cells. Pharmacological inhibition of Enox1 in endothelial cells inhibited repair of DNA double strand breaks, as measured by γH2AX and 53BP1 foci formation, as well as neutral comet assays. For 4 consecutive days athymic mice bearing HT-29 hindlimb xenografts were injected with a small molecule inhibitor of Enox1 or solvent control. Tumors were then administered 2 Gy of x-rays. On day 5 tumors were administered a single 'top-up' fraction of 30 Gy, the purpose of which was to amplify intrinsic differences in the radiation fractionation regimen produced by Enox1 targeting. Pharmacological targeting of Enox1 resulted in 80% of the tumor-bearing mice surviving at 90 days compared to only 40% of tumor-bearing mice treated with solvent control. The increase in survival was not a consequence of reoxygenation, as measured by pimonidazole immunostaining. These results are interpreted to indicate that targeting of Enox1 in tumor stroma significantly enhances the effectiveness of 2 Gy fractionated radiotherapy and identifies Enox1 as a potential therapeutic target.

PMID: 27788492 [PubMed - indexed for MEDLINE]

https://ift.tt/2eNZuEN

Regorafenib in the treatment of metastatic colorectal cancer

Future Oncology, Ahead of Print.

https://ift.tt/2uchKAy

Pathological assessment of gastrointestinal biopsies from patients with idelalisib-associated diarrhea and colitis

Future Oncology, Ahead of Print.

https://ift.tt/2FZgMNu

S100A11 promotes TGF-β1-induced epithelial-mesenchymal transition through SMAD2/3 signaling pathway in intrahepatic cholangiocarcinoma

Future Oncology, Ahead of Print.

https://ift.tt/2DOxFok

Clinical Trial of MGMT(P140K) Gene Therapy in the Treatment of Pediatric Patients with Brain Tumors

Human Gene Therapy, Ahead of Print.

https://ift.tt/2INWNPR

Pharmacogenetics and the treatment of chronic myeloid leukemia: how relevant clinically? An update

Pharmacogenomics, Ahead of Print.

https://ift.tt/2G559kg

PTEN deficiency and AMPK activation promote nutrient scavenging and anabolism in prostate cancer cells [Research Articles]

We report that PTEN-deficient prostate cancer cells use macropinocytosis to survive and proliferate under nutrient stress. PTEN loss increased macropinocytosis only in the context of AMPK activation revealing a general requirement for AMPK in macropinocytosis and a novel mechanism by which AMPK promotes survival under stress. In prostate cancer cells, albumin uptake did not require macropinocytosis, but necrotic cell debris proved a specific macropinocytic cargo. Isotopic labeling confirmed that macropinocytosed necrotic cell proteins fueled new protein synthesis in prostate cancer cells. Supplementation with necrotic debris, but not albumin, also maintained lipid stores suggesting that macropinocytosis can supply nutrients other than amino acids. Non-transformed prostatic epithelial cells were not macropinocytic, but patient-derived prostate cancer organoids and xenografts and autochthonous prostate tumors all exhibited constitutive macropinocytosis, and blocking macropinocytosis limited prostate tumor growth. Macropinocytosis of extracellular material by prostate cancer cells is a previously unappreciated tumor-microenvironment interaction that could be targeted therapeutically.

https://ift.tt/2pBEUeg

Protein Phosphatase 2A Is Essential for B-cell Tumor Redox Homeostasis [Research Watch]

PP2A mediates a metabolic switch from glycolysis to the PPP in B-cell malignancies.

https://ift.tt/2Ggx2cm

ctDNA Analysis for Cancer? Not So Fast [News in Brief]

Expert panel calls for more research before these tests are adopted in clinical practice.

https://ift.tt/2G5pplz

KDM6A Loss Induces Aggressive Pancreatic Cancer in Mice [Research Watch]

Loss of the X chromosome–encoded KDM6A aberrantly activates oncogenic superenhancers.

https://ift.tt/2pBER24

Checkpoint Inhibitors May Induce Myocarditis [News in Brief]

Database is helping researchers investigate rare but serious cardiac side effects associated with the drugs.

https://ift.tt/2Go0RHU

Durvalumab May Be Effective in Patients with EGFR+/ALK+ NSCLC [Research Watch]

PD-L1 blockade with durvalumab achieves responses in patients with EGFR⁺/ALK⁺ and EGFR^–/ALK^– NSCLC.

https://ift.tt/2G6FAzk

The MDA-9/Syntenin/IGF-1R/STAT3 axis directs prostate cancer invasion

Although prostate cancer (PCa) is clinically manageable during several stages of progression, survival is severely compromised once cells invade and metastasize to distant organs. Comprehending the pathobiology of invasion is required for developing efficacious targeted therapies against metastasis. Based on bioinformatics data, we predicted an association of melanoma differentiation associated gene-9 (syntenin, or syndecan binding protein (SDCBP)) in PCa progression. Using tissue samples from various Gleason stage PCa patients with adjacent normal tissue, a series of normal prostate and PCa cell lines (with differing tumorigenic/metastatic properties), mda-9/syntenin manipulated variants (including loss-of-function and gain-of-function cell lines), and CRISPR/Cas9 stable MDA-9/syntenin knockout cells, we now confirm the relevance of and dependence on MDA-9/syntenin in PCa invasion. MDA-9/syntenin physically interacted with insulin-like growth factor-1 receptor (IGF-1R) following treatment with insulin-like growth factor binding protein-2 (IGFBP-2), regulating downstream signaling processes that enabled STAT3 phosphorylation. This activation enhanced expression of MMP-2 and MMP-9, two established enzymes that positively regulate invasion. Additionally, MDA-9/syntenin-mediated upregulation of pro-angiogenic factors including IGFBP-2, IL-6, IL-8, and VEGF-A also facilitated migration of PCa cells. Collectively, our results draw attention to MDA-9/syntenin as a positive regulator of PCa metastasis, and the potential application of targeting this molecule to inhibit invasion and metastasis in PCa and potentially other cancers.

https://ift.tt/2Gh3sn1

Human Elongation Factor 4 Regulates Cancer Bioenergetics by Acting as a Mitochondrial Translation Switch

Mitochondria regulate cellular bioenergetics and redox states and influence multiple signaling pathways required for tumorigenesis. In this study, we determined that the mitochondrial translation elongation factor 4 (EF4) is a critical component of tumor progression. EF4 was ubiquitous in human tissues with localization to the mitochondria (mtEF4) and performed quality control on respiratory chain biogenesis. Knockout of mtEF4 induced respiratory chain complex defects and apoptosis, while its overexpression stimulated cancer development. In multiple cancers, expression of mtEF4 was increased in patient tumor tissues. These findings reveal that mtEF4 expression may promote tumorigenesis via an imbalance in the regulation of mitochondrial activities and subsequent variation of cellular redox. Thus, dysregulated mitochondrial translation may play a vital role in the etiology and development of diverse human cancers.

https://ift.tt/2pCc5hx

A large-scale, exome-wide association study of Han Chinese women identifies three novel loci predisposing to breast cancer

Genome-wide association studies have identified more than 90 susceptibility loci for breast cancer. However, the missing heritability is evident, and the contributions of coding variants to breast cancer susceptibility have not yet been systematically evaluated. Here we present a large-scale whole-exome association study for breast cancer consisting of 24,162 individuals (10,055 cases and 14,107 controls). In addition to replicating known susceptibility loci (e.g. ESR1, FGFR2 and TOX3), we identify two novel missense variants in C21orf58 (rs13047478, Pmeta = 4.52 × 10-8) and ZNF526 (rs3810151, Pmeta = 7.60 × 10-9) and one new non-coding variant at 7q21.11 (P < 5 × 10-8). C21orf58 and ZNF526 possessed functional roles in the control of breast cancer cell growth, and the two coding variants were found to be the eQTL for several nearby genes. rs13047478 was significantly (P < 5.00 x 10-8) associated with the expression of genes MCM3AP and YBEY in breast mammary tissues. rs3810151 was found to be significantly associated with the expression of genes PAFAH1B3 (P = 8.39 x 10-8) and CNFN (P = 3.77 x 10-4) in human blood samples. C21orf58 and ZNF526, together with these eQTL genes, were differentially expressed in breast tumors versus normal breast. Our study reveals additional loci and novel genes for genetic predisposition to breast cancer and highlights a polygenic basis of disease development.

https://ift.tt/2GioYrM

IL-22RA1/ STAT3 signaling promotes stemness and tumorigenicity in pancreatic cancer

Chronic inflammation is a feature of pancreatic cancer, but little is known about how immune cell or immune cell-related signal affects pancreatic cancer stemness and development. Our previous work showed that IL-22/IL-22RA1 plays a vital role in acute and chronic pancreatitis progression by mediating crosstalk between immune cells and acinar cells or stellate cells, respectively. Here we find IL-22RA1 is highly but heterogeneously expressed in pancreatic cancer cells, with high expression associated with poor prognosis of pancreatic cancer patients. The IL-22RA1hi population from pancreatic tumor harbored higher stemness potential and tumorigenicity. Notably, IL-22 promoted pancreatic cancer stemness via IL-22RA1/STAT3, which identified a functional signaling to regulate cancer stemness by microenvironmental factor. Moreover, STAT3 was indispensable for the maintenance of IL-22RA1hi cells. Overall, these findings provide a therapeutic strategy for PDAC patients with high expression of IL-22RA1.

https://ift.tt/2pD39sv

Therapeutic targeting of sunitinib-induced AR phosphorylation in renal cell carcinoma

Androgen receptor (AR) plays a crucial role in the development and progression of prostate cancer. AR expression has also been reported in other solid tumors, including renal cell carcinoma (RCC), but its biological role here remains unclear. Through integrative analysis of a reverse phase protein array (RPPA), we discovered increased expression of AR in an RCC patient-derived xenograft model of acquired resistance to the receptor tyrosine kinase inhibitor (RTKi) sunitinib. AR expression was increased in RCC cell lines with either acquired or intrinsic sunitinib resistance in vitro. An AR signaling gene array profiler indicated elevated levels of AR target genes in sunitinib-resistant cells. Sunitinib-induced AR transcriptional activity was associated with increased phosphorylation of serine 81 (pS81) on AR. Additionally, AR overexpression resulted in acquired sunitinib resistance, and the AR antagonist enzalutamide-induced AR degradation and attenuated AR downstream activity in sunitinib-resistant cells, also indicated by decreased secretion of human kallikrein 2 (KLK2). Enzalutamide-induced AR degradation was rescued by either proteasome inhibition or by knockdown of the AR ubiquitin ligase speckle-type POZ protein (SPOP). In vivo treatment with enzalutamide and sunitinib demonstrated that this combination efficiently induced tumor regression in an RCC model following acquired sunitinib resistance. Overall, our results suggest the potential role of AR as a target for therapeutic interventions, in combination with RTKi, to overcome drug resistance in RCC.

https://ift.tt/2GioMsy

Regulation of human dendritic cell immune functions by ion channels

Christophe Vandier | Florence Velge-Roussel

https://ift.tt/2DR7Fsf

Vascular liver diseases on the clinical side: definitions and diagnosis, new concepts

Abstract

The components of the hepatic vascular system (hepatic arteries, portal and hepatic veins, sinusoids, and lymphatics) can be damaged by various types of injury. Each of the resulting conditions is rare, which has limited knowledge and awareness. In the last two decades, international collaborations have allowed to reach critical masses of data, which has driven significant progresses in understanding and management of vascular disorders of the liver. The present paper discusses definitions, denominations, and diagnosis of such vascular disorders with the exception of those affecting hepatic arteries. Evolving pathogenic or pathophysiologic views relevant to the clinical aspects are also overviewed.

https://ift.tt/2INKV0j

Midlife tooth loss may compromise heart health

Midlife tooth loss is tied to higher risk of cardiovascular disease, independently of traditional risk factors such as high blood pressure, a study finds.

http://ift.tt/2IOvuET

Survivorship care plans: are randomized controlled trials assessing outcomes that are relevant to stakeholders?

Abstract

Purpose

The purpose of this study was to compare outcomes assessed in extant randomized controlled trials (RCTs) to outcomes that stakeholders expect from survivorship care plans (SCPs). To facilitate the transition from active treatment to follow-up care for the 15.5 million US cancer survivors, many organizations require SCP use. However, results of several RCTs of SCPs' effectiveness have been null, possibly because they have evaluated outcomes on which SCPs should be expected to have limited influence. Stakeholders (e.g., survivors, oncologists) may expect outcomes that differ from RCTs' outcomes.

Methods

We identified RCTs' outcomes using a PubMed literature review. We identified outcomes that stakeholders expect from SCPs using semistructured interviews with stakeholders in three healthcare systems in the USA and Canada. Finally, we mapped RCTs' outcomes onto stakeholder-identified outcomes.

Results

RCT outcomes did not fully address outcomes that stakeholders expected from SCPs, and RCTs assessed outcomes that stakeholders did not expect from SCPs. RCTs often assessed outcomes only from survivors' perspectives.

Conclusions

RCTs of SCPs' effectiveness have not assessed outcomes that stakeholders expect. To better understand SCPs' effectiveness, future RCTs should assess outcomes of SCP use that are relevant from the perspective of multiple stakeholders.

Implications for Cancer Survivors

SCPs' effectiveness may be optimized when used with an eye toward outcomes that stakeholders expect from SCPs. For survivors, this means using SCPs as a map to guide them with respect to what kind of follow-up care they should seek, when they should seek it, and from whom they should seek it.

https://ift.tt/2pFfFI6

Epidermal growth factor regulates apoptosis and oxidative stress in a rat model of spinal cord injury

Publication date: Available online 22 March 2018
Source:Injury
Author(s): Anil Murat Ozturk, Murat Celal Sozbilen, Elvin Sevgili, Taner Dagci, Halit Özyalcin, Guliz Armagan
Spinal cord injury (SCI) leads to vascular damage and disruption of blood-spinal cord barrier which participates in secondary nerve injury. Epidermal growth factor (EGF) is an endogenous protein which regulates cell proliferation, growth and differention. Previous studies reported that EGF exerts neuroprotective effect in spinal cord after SCI. However, the molecular mechanisms underlying EGF-mediated protection in different regions of nervous system have not shown yet. In this study, we aimed to examine possible anti-apoptotic and protective roles of EGF not only in spinal cord but also in brain following SCI.Twenty-eight adult rats were divided into four groups of seven animals each as follows: sham, trauma (SCI), SCI + EGF and SCI + methylprednisolone (MP) groups. The functional neurological deficits due to the SCI were assessed by behavioral analysis using the Basso, Beattie and Bresnahan (BBB) open-field locomotor test. The alterations in pro-/anti-apoptotic protein levels and antioxidant enzyme activities were measured in spinal cord and frontal cortex.In our study, EGF promoted locomotor recovery and motor neuron survival of SCI rats. EGF treatment significantly decreased Bax and increased Bcl-2 protein expressions both in spinal cord and brain when compared to SCI group. Moreover, antioxidant enzyme activities including catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) were increased following EGF treatment similar to MP treatment. Our experiment also suggests that alteration of the ratio of Bcl-2 to Bax may result from decreased apoptosis following EGF treatment. As a conclusion, these results show, for the first time, that administration of EGF exerts its protection via regulating apoptotic and oxidative pathways in response to spinal cord injury in different regions of central nervous system.

https://ift.tt/2G6Npoq

Center variation in episode-of-care costs for adult spinal deformity surgery: results from a prospective, multicenter database

Publication date: Available online 22 March 2018
Source:The Spine Journal
Author(s): Samrat Yeramaneni, Christopher P. Ames, Shay Bess, Doug Burton, Justin S. Smith, Steven Glassman, Jeffrey L. Gum, Leah Carreon, Amit Jain, Corinna Zygourakis, Ioannis Avramis, Richard Hostin
BACKGROUND CONTEXTAdult spinal deformity surgery (ASD) is associated with significant resource utilization, costing more than $958 million in charges for Medicare patients and over $1.7 billion in charges for managed care population in the last decade. Given the recent move towards bundled payment models, it is important to understand the various care components a patient receives over the course of a defined clinical episode, its associated cost, and the proportion of cost for each component towards the bundled payment.PURPOSETo examine the degree and determinants of variation in inpatient episode-of-care (EOC) cost, resource utilization, and patient reported outcomes for patients undergoing ASD surgery across four spine deformity centers in the United States.STUDY DESIGN/SETTINGRetrospective analysis of prospective, multicenter database.PATIENT SAMPLEConsecutive patients enrolled in an ASD database from four spinal deformity centers.OUTCOME MEASURESTotal in-patient EOC costs and short form (SF)-6D.METHODSThe study used a multicenter database of 210 consecutively enrolled operative patients from 2008 to 2013 at four participating centers in the United States. Demographic, surgical, and direct cost data, expressed in 2013 dollars, for the entire inpatient EOC were obtained from administrative databases from the respective hospitals. Mixed models and multivariable linear regression were used to evaluate the impact of center on total costs adjusting for patient characteristics, length of stay (LOS), and surgical factors.RESULTSA total of 126 patients with complete baseline and 2-year follow-up data were included. The percentages of patients from each center were: 36.5%, 7.1%, 24.6%, and 31.7%. Overall, the mean patient age was 58.4+12.6 years, 86% were women, and 94% were Caucasian. The proportion of total cost variation explained by the center at which the patient was treated was 17%. After adjusting for patient, LOS, and surgical factors the cost variation reduced to 4%. In multivariable analysis, each additional level fused increased total cost variation by $2500. While, recombinant human bone morphogenetic protein-2 (BMP) use and posterior-only surgical approach lowered total EOC costs by $10,500 and $9,400, respectively. No significant difference was observed in 2-year quality-adjusted life year across centers.CONCLUSIONSTotal EOC costs for ASD surgery varied significantly by center. Levels fused, BMP use, and surgical approach were the primary drivers of cost variation across centers. Differences in resource utilization had no impact on 2-year quality-adjusted life year improvement across centers.

https://ift.tt/2GlRlFl

How web-based ePCR provides a long-term solution for Miramar Fire-Rescue

Electronic health records and other reporting tools from ESO Solutions helped streamline documentation at a pioneering Florida agency

https://ift.tt/2GjsnXi

Electrochemiluminescence Assays for Human Islet Autoantibodies

Here, we presented the methods to detect human islet autoantibodies using electrochemiluminescence (ECL) assays. The protocol, used to predict type 1 diabetes, can be expanded upon to detect autoantibodies for other autoimmune diseases.

https://ift.tt/2FYE6el

BD Vacutainer Blood Collection Tubes by Becton, Dickinson and Company (BD): Class I Recall - Chemical Interference with Certain Tests

Audience: Risk Manager, Nursing, Laboratory BD Vacutainer EDTA Lavender, Tan, and Pink Top Tubes BD Vacutainer Lithium Heparin Green Top Tube [Posted 03/23/2018] ISSUE: BD is recalling their Vacutainer EDTA Blood Collection Tubes with lavender,...

https://ift.tt/2HZkq6G

Paraffin Embedding and Thin Sectioning of Microbial Colony Biofilms for Microscopic Analysis

We describe fixation, paraffin embedding, and thin sectioning techniques for microbial colony biofilms. In prepared samples, biofilm substructure and reporter expression patterns can be visualized by microscopy.

https://ift.tt/2IJAdrs

BD Vacutainer Blood Collection Tubes by Becton, Dickinson and Company (BD): Class I Recall - Chemical Interference with Certain Tests

Efficacy of bedside respiratory muscle training in patients with stroke: A randomized controlled trial

Objectives Inspiratory and the expiratory muscles are important for effective respiratory function. This study aimed to investigate the efficacy of bedside respiratory muscle training on pulmonary function and stroke-related disabilities in stroke rehabilitation. Design Patients with stroke (N=40) in a rehabilitation unit were randomly assigned to either the intervention group (N1=20) or control group (N2=20). Both groups participated in a conventional stroke rehabilitation program. During the study period, the intervention group received bedside respiratory muscle training twice a day for three weeks. The respiratory muscle training consisted of (1) a breath stacking exercise, (2) inspiratory muscle training, and (3) expiratory muscle training. The primary outcomes were measures of pulmonary function: forced vital capacity, forced expiratory volume in one second, and peak flow. Secondary outcomes were stroke-related disabilities assessed using the National Institutes of Health Stroke Scale, Modified Barthel Index, Berg Balance Scale, Fugl-Meyer Assessment, the Korean Mini-Mental State Examination, and pneumonia incidence. Results Pulmonary function was significantly improved in the intervention group after 3 weeks of respiratory muscle training (p

https://ift.tt/2IMbfaV

ULTRASONOGRAPHIC IMAGING OF THE MEDIAN NERVE WITH A STRUTHERS LIGAMENT

No abstract available

https://ift.tt/2G6jwF1

Increased enslaving in elderly is associated with changes in neural control of the extrinsic finger muscles

Abstract

Aging has consequences for hand motor control, among others affecting finger force enslaving during static pressing tasks. The aim of this study was to assess whether the extent of finger force enslaving changes with aging during a task that involves both static and dynamic phases. Ten right-handed young (22–30 years) and ten elderly subjects (67–79 years) were instructed to first exert a constant force (static phase) and then flex their index finger while counteracting constant resistance forces orthogonal to their fingertips (dynamic phase). The other fingers (non-instructed) were held in extension. EMG activities of the flexor digitorum superficialis (FDS) and extensor digitorum (ED) muscles in the regions corresponding to the index, middle and ring fingers together with their forces and position of index finger were measured. In both elderly and young, forces exerted by the non-instructed fingers increased (around 0.6 N for both young and elderly) during isotonic flexion of the index finger, but with a different delay of on average 100 ± 72 ms in elderly and 334 ± 101 ms in young subjects. Results also suggest different responses in activity of FDS and ED muscle regions of the non-instructed fingers to index finger flexion between elderly and young subjects. The enslaving effect was significantly higher in elderly than in young subjects both in the static (12% more) and dynamic (14% more) phases. These differences in enslaving can at least partly be explained by changes in neuromuscular control.

https://ift.tt/2pBwjIB

Correction to: From IB2 to IIIB locally advanced cervical cancers: report of a ten-year experience

Abstract

In the original publication [1] one author name was spelled incorrect.

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Cancer Medicine, Ahead of Print.

Cancer Medicine, Ahead of Print.

https://ift.tt/2pyAwxm

Cancer Medicine, Ahead of Print.

Cancer Medicine, Ahead of Print.

https://ift.tt/2I1uIDt

Cancer Medicine, Ahead of Print.

Cancer Medicine, Ahead of Print.

https://ift.tt/2uhgYm1

Cancer Medicine, Ahead of Print.

Cancer Medicine, Ahead of Print.

https://ift.tt/2HZYI2D

Cancer Medicine, Ahead of Print.

Cancer Medicine, Ahead of Print.

https://ift.tt/2HZF5Yk

Cancer Medicine, Ahead of Print.

Cancer Medicine, Ahead of Print.

https://ift.tt/2pyNECq

Cancer Medicine, Ahead of Print.

Cancer Medicine, Ahead of Print.

https://ift.tt/2pzCz4i

Cancer Medicine, Ahead of Print.

Cancer Medicine, Ahead of Print.

https://ift.tt/2HVlOXZ

Cancer Medicine, Ahead of Print.

Cancer Medicine, Ahead of Print.

https://ift.tt/2pA4ssV

Cancer Medicine, Ahead of Print.

Cancer Medicine, Ahead of Print.

https://ift.tt/2pz9XrY

Cancer Medicine, Ahead of Print.

Cancer Medicine, Ahead of Print.

https://ift.tt/2ugZUwg

Cancer Medicine, Ahead of Print.

Cancer Medicine, Ahead of Print.

https://ift.tt/2pzCyNM

Cancer Medicine, Ahead of Print.

Cancer Medicine, Ahead of Print.

https://ift.tt/2HVlEQn

Cancer Medicine, Ahead of Print.

Cancer Medicine, Ahead of Print.

https://ift.tt/2pwhPuf

Cancer Medicine, Ahead of Print.

Cancer Medicine, Ahead of Print.

https://ift.tt/2udn8DL

Cancer Medicine, Ahead of Print.

Cancer Medicine, Ahead of Print.

https://ift.tt/2pz5BRn

Cancer Medicine, Ahead of Print.

Cancer Medicine, Ahead of Print.

https://ift.tt/2HVlyZ1

A Recovery Cardiopulmonary Bypass Model Without Transfusion or Inotropic Agents in Rats

Here, we present a protocol to describe a simple recovery cardiopulmonary bypass model without transfusion or inotropic agents in a rat. This model allows the study of the long-term multiple organ sequelae of cardiopulmonary bypass.

https://ift.tt/2pzeMkL

A Method for Targeted 16S Sequencing of Human Milk Samples

A semi-automated workflow is presented for targeted sequencing of 16S rRNA from human milk and other low-biomass sample types.

https://ift.tt/2G6Gagg

Depleted polymorphonuclear leukocytes in human metastatic liver reflect an altered immune microenvironment associated with recurrent metastasis

Abstract

Background

Hepatic immunity, normally protective against neoplasia, is subverted in colorectal liver metastasis (CRLM). Here, we compare the inflammatory microenvironment of CRLM-bearing liver tissue to donor liver.

Methods

Twenty-five patients undergoing resection for CRLM were recruited, 13 of whom developed intrahepatic recurrence within 18 months. Biopsies were obtained from tumour and normal liver tissue adjacent to and distal from, the tumour. Donor liver biopsies were obtained during transplantation. Biopsies were cultured and conditioned media (CM) screened for 102 inflammatory mediators. Twelve of these were validated by Luminex assay. Transwell assays measured cancer cell chemotaxis. Polymorphonuclear leukocytes (PMN) and lymphocytes were quantified in H&E sections.

Results

Fewer periportal tissue-resident PMN were present in metastatic liver compared to donor liver. Patients with the fewest PMN in liver tissue distal to their tumour had a shorter time to intrahepatic recurrence (P < 0.001). IL-6, CXCL1, CXCL5, G-CSF, GM-CSF, VEGF, LIF, and CCL3 were higher in liver-bearing CRLM compared to donor tissue. Consequently, cancer cells migrated equally towards CM of all regions of metastatic liver but not towards donor liver CM.

Conclusions

The local inflammatory environment may affect both immune cell infiltration and cancer cell migration contributing to recurrence following resection for CRLM.

http://ift.tt/2G6cIY3

Technology Innovator to Deliver Keynote Address at Focused Ultrasound Symposium

Gary Shapiro, President and CEO of the Consumer Technology Association (CTA)™, which annually produces CES^®, the largest technology and innovation show in the world, will deliver a keynote address at the 6th International Symposium on Focused Ultrasound on Tuesday, October 23, 2018, in Reston, Virginia.

https://ift.tt/2IKbL9m

Diagnostic Cytopathology, Ahead of Print.

Diagnostic Cytopathology, Ahead of Print.

https://ift.tt/2G3Nk50

Diagnostic Cytopathology, Ahead of Print.

Diagnostic Cytopathology, Ahead of Print.

https://ift.tt/2pzG6iW

Diagnostic Cytopathology, Ahead of Print.

Diagnostic Cytopathology, Ahead of Print.

https://ift.tt/2G5LRvc

Dental oral craniofacial tissue regeneration consortia

The ability to robustly and predictably regenerate dental, oral and craniofacial (DOC) tissues through tissue engineering and/or regenerative medicine strategies is a major goal for clinicians. While many technologies have shown proof of principle in small animals, few have made it into the clinic.

http://ift.tt/2ILRm3L

A Systematic Review of Studies Comparing the Measurement Properties of the Three-Level and Five-Level Versions of the EQ-5D

Abstract

Background

Since the introduction of the five-level version of the EQ-5D (5L), many studies have comparatively investigated the measurement properties of the original three-level version (3L) with the 5L version.

Objective

The aim of this study was to consolidate the available evidence on the performance of both instruments.

Methods

A systematic literature search of studies in the English and German languages was conducted (2007–January 2018) using the PubMed, EMBASE, and PsycINFO (EBSCO) databases, as well as the EuroQol Research Foundation website. Data were extracted and assessed on missing values, distributional properties, informativity indices (Shannon's H′ and J′), inconsistencies, responsiveness, and test–retest reliability.

Results

Twenty-four studies were included in the review. Missing values and floor effects (percentage reporting the worst health state) were found to be negligible for both 3L and 5L (< 5%). From 18 studies, inconsistencies ranged from 0 to 10.6%, although they were generally well below 5%, with 9 studies reporting the most inconsistencies for Usual Activities (mean percentage 4.1%). Shannon's indices were always higher for 5L than for 3L, and all but three studies reported lower ceiling effects ('11111') for 5L than for 3L. There is mixed and insufficient evidence on responsiveness and test–retest reliability, although results on index values showed better performance for 5L on test–retest reliability.

Conclusion

Overall, studies showed similar or better measurement properties of the 5L compared with the 3L, and evidence indicated moderately better distributional parameters and substantial improvement in informativity for the 5L compared with the 3L. Insufficient evidence on responsiveness and test–retest reliability implies further research is needed.

https://ift.tt/2uf7iIt

Depleted polymorphonuclear leukocytes in human metastatic liver reflect an altered immune microenvironment associated with recurrent metastasis

Abstract

Background

Methods

Results

Conclusions

The local inflammatory environment may affect both immune cell infiltration and cancer cell migration contributing to recurrence following resection for CRLM.

http://ift.tt/2G6cIY3

Using ultrasound for firefighter health and wellness programs

Consider incorporating this diagnostic tool into firefighter physicals to support early diagnosis and intervention that can save lives

http://ift.tt/2IP3DVi

Postural responses to target jumps and background motion in a fast pointing task

Abstract

When reaching towards an object while standing, one's hand responds very quickly to visual perturbations such as the target being displaced or the background moving. Such responses require postural adjustments. When the background moves, its motion might be attributed to self-motion in a stable world, and thereby induce compensatory postural adjustments that affect the hand. The changes in posture associated with a given hand movement response may, therefore, be different for the two types of perturbations. To see whether they are, we asked standing participants to move their hand in the sagittal direction away from their body to targets displayed on a horizontal screen in front of them. The target displacements and background motion were in the lateral direction. We found hand movement responses that were in line with earlier reports, with a latency that was slightly shorter for target displacements than for background motion, and that was independent of target displacement size or background motion speed. The trunk responded to both perturbations with a modest lateral sway. The two main findings were that the upper trunk responded even before the hand did so and that the head responded to background motion but hardly responded to target displacements. These findings suggest that postural adjustments associated with adjusting the hand movement precede the actual adjustments to the movement of the hand, while at the same time, participants try to keep their head stable on the basis of visual information.

http://ift.tt/2GgFSXM

Comparison of nephrotoxicity of Colistin with Polymyxin B administered in currently recommended doses: a prospective study

The most important concern with polymyxins (Colistin and Polymyxin B) use is nephrotoxicity. There is no prospective data comparing nephrotoxicity of these two drugs, when administered in high doses and as per...

http://ift.tt/2INMScL

Genetic contexts related to the diffusion of plasmid-mediated CTX-M-55 extended-spectrum beta-lactamase isolated from Enterobacteriaceae in China

CTX-M-55 extended-spectrum beta-lactamases are being rapidly disseminated and transmitted in clinical practices around the world. The genetic contexts of the transferable plasmid-mediated blaCTX-M-55 gene in Ente...

http://ift.tt/2HZrHDJ

Factors associated to prevalence and treatment of carbapenem-resistant Enterobacteriaceae infections: a seven years retrospective study in three tertiary care hospitals

The increasing incidence of carbapenem-resistant Enterobacteriaceae (CRE), has resulted in a difficult problem in the current clinical anti-infective treatment. We performed a retrospective analysis of prevalence...

http://ift.tt/2IISvJo

Detection of Neisseria meningitidis in a paediatric patient with septic arthritis using multiplexed diagnostic PCR targeting meningitis/encephalitis (ME)

Neisseria meningitidis is associated with meningitis and septicemia. Septic meningococcal arthritis is relatively uncommon and its diagnosis associated with clinical and microbiological challenges. Early recognit...

http://ift.tt/2IMSxzR

Assessing the effects of different agro-residue as substrates on growth cycle and yield of Grifola frondosa and statistical optimization of substrate components using simplex-lattice design

Grifola frondosa is an economically important edible and medicinal mushroom usually produced on substrate consisting of sawdust supplemented with wheat bran. Cultivation of G. frondosa on crop straw (corn cob, co...

http://ift.tt/2HZfVsL

Mitochondrial contributions to neuronal development and function

Journal Name: Biological Chemistry
Issue: Ahead of print

http://ift.tt/2Gfuhbd

Kallikrein-related peptidase 14 is the second KLK protease targeted by the serpin vaspin

Journal Name: Biological Chemistry
Issue: Ahead of print

http://ift.tt/2DPHz8Z

Cerebral Perforating Artery Disease

Abstract

Purpose

Our aims were to evaluate the feasibility of high-resolution magnetic resonance imaging (HR-MRI) for displaying the cerebral perforating arteries in normal subjects and to discuss the value of HR-MRI for detecting the causes of infarctions in the territory of the lenticulostriate artery (LSA).

Methods

Included in this study were 31 healthy subjects and 28 patients who had infarctions in the territory supplied by the LSA. The T1-weighted imaging (T1WI), T2WI, diffusion-weighted imaging (DWI), and HR-MRI, including 3‑dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA) and 3D fast spin-echo T1WI (namely CUBE T1 in GE Healthcare), were applied on a 3-Tesla scanner. The numbers and route of the perforating arteries on both sides were independently confirmed on HR-MRI by two physicians. The Wilcoxon test was used to compare the differences.

Results

The numbers of perforating arteries in healthy subjects observed on 3D-TOF-MRA were as follows: numbers of the bilateral recurrent artery of Heubner (RAH) ranged from 0–3 (median 1), numbers of the left LSA ranged from 0–7 (median 3), numbers of the right LSA ranged from 0–5 (median 3), numbers of the bilateral anterior choroidal artery ranged from 1–2 (median 1) and the numbers of the bilateral thalamoperforating artery ranged from 1–2 (median 1). In the patients with lenticulostriate infarctions, the numbers of LSAs on the affected side were lower than on the opposite and ipsilateral sides in the healthy subjects. The results were statistically significant. An abnormality of the RAH may lead to a centrum semiovale infarct pattern, whereas an abnormality of the LSA is associated with a corona radiata infarct pattern.

Conclusion

The use of HR 3D-TOF-MRA and CUBE T1 had unique advantages in displaying the tiny perforating arteries in vivo. Moreover, effective recognition of the associated cerebral perforating artery and infarct patterns may enhance our understanding of the mechanism of stroke in patients with lenticulostriate infarctions.

http://ift.tt/2I1JASm

Pharmacy informatics in multihospital health systems: Opportunities and challenges [Special Feature]

Purpose

Challenges and opportunities in managing pharmacy-related technology in a multihospital health system are reviewed.

Summary

With electronic medical record (EMR) implementations, pharmacy technology deployments, and increased numbers of hospitals merging into single health systems, opportunities and challenges for pharmacy informatics (PI) teams have grown. Pharmacy leaders must consider the implications of using technology in a multihospital health-system environment, as well as the impact of the health system's organizational structures on technology implementations and dedicated support teams. Common challenges in achieving EMR and other technology implementation and standardization initiatives in multihospital health systems include harmonization of practices across hospitals of various sizes and types and issues of platform compatibility and interoperability. PI teams must collaborate with information technology teams at the system level to identify practical strategies for making the best use of available resources to implement pharmacy automation and software to help pharmacists continue to provide safe and effective patient care. The organizational structures that affect informatics teams, pharmacy integration and standardization initiatives, formulary management practices, data management and analytics, and clinical decision support systems all must be areas of focus.

Conclusion

An integrated pharmacy enterprise can be well positioned to leverage operational efficiencies gained from appropriate use of technology to enhance patient care. Careful attention must be paid to the manner in which these systems are designed, implemented, and managed in order to make the best use of the technological resources used by the health system.

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Pharmacists contribute to integrated health systems approaches to opioid safety [News]

http://ift.tt/2FXWDaG

Multihospital health systems: Seize the opportunity [Commentary]

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New drugs and dosage forms [News]

http://ift.tt/2FXPMOp

Reports offer window on medical aid in dying [News]

http://ift.tt/2G5t96S

Federal data indicate positive labor market for hospital pharmacists [News]

http://ift.tt/2FXPFSZ

Creating organizational value by leveraging the multihospital pharmacy enterprise [Special Feature]

Purpose

The results of a survey of multihospital pharmacy leaders are summarized, and a road map for creating organizational value with the pharmacy enterprise is presented.

Summary

A survey was designed to evaluate the level of integration of pharmacy services across each system's multiple hospitals, determine the most commonly integrated services, determine whether value was quantified when services were integrated, collect common barriers for finding value through integration, and identify strategies for successfully overcoming these barriers. The comprehensive, 59-question survey was distributed electronically in September 2016 to the top pharmacy executive at approximately 160 multihospital systems located throughout the United States. Survey respondents indicated that health systems are taking a wide range of approaches to integrating services systemwide. Several themes emerged from the survey responses: (1) having a system-level pharmacy leader with solid-line reporting across the enterprise increased the likelihood of integrating pharmacy services effectively, (2) integration of pharmacy services across a multihospital system was unlikely to decrease the number of pharmacy full-time equivalents within the enterprise, and (3) significant opportunities exist for creating value for the multihospital health system with the pharmacy enterprise, particularly within 4 core areas: system-level drug formulary and clinical standardization initiatives, supply chain initiatives, electronic health record integration, and specialty and retail pharmacy services.

Conclusion

Consistently demonstrating strong organizational leadership, entrepreneurialism, and the ability to create value for the organization will lead to the system-level pharmacy leader and the pharmacy enterprise being well-positioned to achieve positive outcomes for patients, payers, and the broader health system.

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Appointment [News]

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Creating a learning organization to help meet the needs of multihospital health systems [Special Feature]

Purpose

The considerations that leaders of multihospital health systems must take into account in developing and implementing initiatives to build and maintain an exceptional pharmacy workforce are described.

Summary

Significant changes that require constant individual and organizational learning are occurring throughout healthcare and within the profession of pharmacy. These considerations include understanding why it is important to have a succession plan and determining what types of education and training are important to support that plan. Other considerations include strategies for leveraging learners, dealing with a large geographic footprint, adjusting training opportunities to accommodate the ever-evolving demands on pharmacy staffs in terms of skill mix, and determining ways to either budget for or internally develop content for staff development. All of these methods are critically important to ensuring an optimized workforce. Especially for large health systems operating multiple sites across large distances, the use of technology-enabled solutions to provide effective delivery of programming to multiple sites is critical. Commonly used tools include live webinars, live "telepresence" programs, prerecorded programming that is available through an on-demand repository, and computer-based training modules. A learning management system is helpful to assign and document completion of educational requirements, especially those related to regulatory requirements (e.g., controlled substances management, sterile and nonsterile compounding, competency assessment).

Conclusion

Creating and sustaining an environment where all pharmacy caregivers feel invested in and connected to ongoing learning is a powerful motivator for performance, engagement, and retention.

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News brief [News]

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Association between hyperinsulinemia-euglycemia therapy and hyponatremia [Letter]

http://ift.tt/2pyyXOY

Multihospital health systems: Growing complexity of pharmacy enterprise brings opportunities and challenges [Editorials]

http://ift.tt/2G1tFH2

Utilizing big data to provide better health at lower cost [Special Feature]

Purpose

The efficient use of big data in order to provide better health at a lower cost is described.

Summary

As data become more usable and accessible in healthcare, organizations need to be prepared to use this information to positively impact patient care. In order to be successful, organizations need teams with expertise in informatics and data management that can build new infrastructure and restructure existing infrastructure to support quality and process improvements in real time, such as creating discrete data fields that can be easily retrieved and used to analyze and monitor care delivery. Organizations should use data to monitor performance (e.g., process metrics) as well as the health of their populations (e.g., clinical parameters and health outcomes). Data can be used to prevent hospitalizations, combat opioid abuse and misuse, improve antimicrobial stewardship, and reduce pharmaceutical spending. These examples also serve to highlight lessons learned to better use data to improve health. For example, data can inform and create efficiencies in care and engage and communicate with stakeholders early and often, and collaboration is necessary to have complete data. To truly transform care so that it is delivered in a way that is sustainable, responsible, and patient-centered, health systems need to act on these opportunities, invest in big data, and routinely use big data in the delivery of care.

Conclusion

Using data efficiently has the potential to improve the care of our patients and lower cost. Despite early successes, barriers to implementation remain including data acquisition, integration, and usability.

http://ift.tt/2pz6FE6

Safety concerns regarding selexipag in pulmonary arterial hypertension [Letter]

http://ift.tt/2FYCaCP

Strategies for success in creating an effective multihospital health-system pharmacy and therapeutics committee [Special Feature]

Purpose

Lessons learned from the creation of a multihospital health-system formulary management and pharmacy and therapeutics (P&T) committee are described.

Summary

A health system can create and implement a multihospital system formulary and P&T committee to provide evidence-based medications for ideal healthcare. The formulary and P&T process should be multidisciplinary and include adequate representation from system hospitals. The aim of a system formulary and P&T committee is standardization; however, the system should allow flexibility for differences. Key points for a successful multihospital system formulary and P&T committee are patience, collaboration, resilience, and communication. When establishing a multihospital health-system formulary and P&T committee, the needs of individual hospitals are crucial. A designated member of the pharmacy department needs to centrally coordinate and manage formulary requests, medication reviews and monographs, meeting agendas and minutes, and a summary of decisions for implementation. It is imperative to create a timeline for formulary reviews to set expectations, as well as a process for formulary appeals. Collaboration across the various hospitals is critical for successful formulary standardization. When implementing a health-system P&T committee or standardizing a formulary system, it is important to be patient and give local sites time to make practice changes. Evidence-based data and rationale must be provided to all sites to support formulary changes. Finally, there must be multidisciplinary collaboration.

Conclusion

There are several options for formulary structures and P&T committees in a health system. Potential strengths and barriers should be evaluated before selecting a formulary management process.

http://ift.tt/2G7O211

Safety concerns regarding selexipag in pulmonary arterial hypertension [Letter]

http://ift.tt/2G1tJGM

Development and innovation of system resources to optimize patient care [Special Feature]

Purpose

Various incremental and disruptive healthcare innovations that are occurring or may occur are discussed, with insights on how multihospital health systems can prepare for the future and optimize the continuity of patient care provided.

Summary

Innovation in patient care is occurring at an ever-increasing rate, and this is especially true relative to the transition of patients through the care continuum. Health systems must leverage their ability to standardize and develop electronic health record (EHR) systems and other infrastructure necessary to support patient care and optimize outcomes; examples include 3D printing of patient-specific medication dosage forms to enhance precision medicine, the use of drones for medication delivery, and the expansion of telehealth capabilities to improve patient access to the services of pharmacists and other healthcare team members. Disruptive innovations in pharmacy services and delivery will alter how medications are prescribed and delivered to patients now and in the future. Further, technology may also fundamentally alter how and where pharmacists and pharmacy technicians care for patients. This article explores the various innovations that are occurring and that will likely occur in the future, particularly as they apply to multihospital health systems and patient continuity of care.

Conclusion

Pharmacy departments that anticipate and are prepared to adapt to incremental and disruptive innovations can demonstrate value in the multihospital health system through strategies such as optimizing the EHR, identifying telehealth opportunities, supporting infrastructure, and integrating services.

http://ift.tt/2G6lRzJ

Association between hyperinsulinemia-euglycemia therapy and hyponatremia [Letter]

http://ift.tt/2FZ3alt

Designing organizational structures: Key thoughts for development [Special Feature]

Purpose

Current strategies and concepts to consider in developing a system-level organizational structure for the pharmacy enterprise are discussed.

Summary

There are many different ways to design an organizational structure for the pharmacy enterprise within a health system. The size of the organization, the number of states in which it operates, and the geographic spread and complexity of the pharmacy business lines should be among the key considerations in determining the optimal organizational and decision-making structures for the pharmacy enterprise. The structure needs to support incorporation of the pharmacy leadership (both system-level executives and local leaders) into all strategic planning and discussions at the hospital and health-system levels so that they can directly represent the pharmacy enterprise instead of relying on others to develop strategy on their behalf. It is important that leaders of all aspects of the pharmacy enterprise report through the system's top pharmacy executive, who should be a pharmacist and have a title consistent with those of other leaders reporting at the same organizational level (e.g., chief pharmacy officer).

Conclusion

Pharmacy leaders need to be well positioned within an organization to advocate for the pharmacy enterprise and use all resources to the best of their ability. As the scope and complexity of pharmacy services grow, it is critical to ensure that leadership of the pharmacy enterprise is unified under a single pharmacy executive team.

http://ift.tt/2pDgMro

The influence of a consumer-wearable activity tracker on sedentary time and prolonged sedentary bouts: secondary analysis of a randomized controlled trial

A recent meta-analysis surmised pedometers were a useful panacea to independently reduce sedentary time (ST). To further test and expand on this deduction, we analyzed the ability of a consumer-wearable activi...

http://ift.tt/2pvIkQv

Fecal microbiota transplantation against intestinal colonization by extended spectrum beta-lactamase producing Enterobacteriaceae: a proof of principle study

Infections with multidrug-resistant microorganisms are associated with increased hospitalization, medication costs and mortality. Based on our fecal microbiota transplantation (FMT) experience for Clostridium dif...

http://ift.tt/2G2iREt

Utilization of prevention of mother-to-child transmission (PMTCT) services among pregnant women in HIV care in Uganda: a 24-month cohort of women from pre-conception to post-delivery

We assessed the uptake of prevention of mother-to-child transmission (PMTCT) services in a cohort of HIV infected women in care at The AIDS Support Organization Jinja and Kampala in Uganda, who were trying to ...

http://ift.tt/2pye7A2

Electronic cigarettes use and perception amongst medical students: a cross sectional survey from Sindh, Pakistan

The manufacturers of electronic cigarettes (e-cigarettes) are actively marketing their product through electronic and social media. Undergraduate medical students are expected to have better knowledge and awar...

http://ift.tt/2G5X279

Developmental Psychobiology, Ahead of Print.

Developmental Psychobiology, Ahead of Print.

http://ift.tt/2HUUoBx

Disciplinary differences of the impact of altmetric

Abstract

The main objective of this work was to group altmetric indicators according to their relationships and detect disciplinary differences with regard to altmetric impact in a set of 3793 research articles published in 2013. Three of the most representative altmetric providers (Altmetric, PlumX and Crossref Event Data) and Scopus were used to extract information about these publications and their metrics. Principal component analysis was used to summarize the information on these metrics and detect groups of indicators. The results show that these metrics can be grouped into three components: social media, gathering metrics from social networks and online media; usage, including metrics on downloads and views; and citations and saves, grouping metrics related to research impact and saves in bookmarking sites. With regard to disciplinary differences, articles in the General category attract more attention from social media, Social Sciences articles have higher usage than Physical Sciences, and General articles are more cited and saved than Health Sciences and Social Sciences articles.

http://ift.tt/2pABj02

Variations in the relative abundance of Wolbachia in the gut of Nasutitermes arborum across life stages and castes

Abstract

There are multiple forms of interactions between termites and bacteria. In addition to their gut microbiota, which has been intensively studied, termites host intracellular symbionts such as Wolbachia. These distinct symbioses have been so far approached independently and mostly in adult termites. We addressed the dynamics of Wolbachia and the microbiota of the eggs and gut for various life stages and castes of the wood-feeding termite, Nasutitermes arborum, using deep-sequencing of the 16S rRNA gene. Wolbachia was dominant in eggs as expected. Unexpectedly, it persisted in the gut of nearly all stages and castes, indicating a wide somatic distribution in termites. Wolbachia-related sequences clustered into few operational taxonomic units, but these were within the same genotype, acquired maternally. Wolbachia was largely dominant in DNA extracts from the guts of larvae and pre-soldiers (59.1%–99.1% of reads) where gut-resident lineages were less represented and less diverse. The reverse was true for the adult castes. This is the first study reporting the age-dependency of the relative abundance of Wolbachia in the termite gut and its negative correlation with the diversity of the microbiota. The possible mechanisms underlying this negative interaction are discussed.

http://ift.tt/2pyBKIN

Cognitive Science, Ahead of Print.

Cognitive Science, Ahead of Print.

http://ift.tt/2pyO23Z

Cognitive Science, Ahead of Print.

Cognitive Science, Ahead of Print.

http://ift.tt/2Gd9oh5

Perturbed autophagy and DNA repair converge to promote neurodegeneration in amyotrophic lateral sclerosis and dementia

Abstract

Maintaining genomic stability constitutes a major challenge facing cells. DNA breaks can arise from direct oxidative damage to the DNA backbone, the inappropriate activities of endogenous enzymes such as DNA topoisomerases, or due to transcriptionally-derived RNA/DNA hybrids (R-loops). The progressive accumulation of DNA breaks has been linked to several neurological disorders. Recently, however, several independent studies have implicated nuclear and mitochondrial genomic instability, perturbed co-transcriptional processing, and impaired cellular clearance pathways as causal and intertwined mechanisms underpinning neurodegeneration. Here, we discuss this emerging paradigm in the context of amyotrophic lateral sclerosis and frontotemporal dementia, and outline how this knowledge paves the way to novel therapeutic interventions.

http://ift.tt/2uefPvl

The approach of visual stimuli influences expectations about stimulus types for subsequent somatosensory stimuli

Abstract

It is known that perceiving a visual stimulus influences the processing of subsequent somatosensory stimuli. In particular, an emotion-laden visual stimulus influences the processing of types of subsequent somatosensory stimuli. Additionally, visual stimuli approaching the body facilitate spatial and temporal expectations about subsequent somatosensory stimuli even if the visual stimuli do not contain emotional information; however, it remains unclear whether the approach of non-emotional visual stimuli also influences such expectations. To investigate whether the approach of non-emotional visual stimuli influences expectations about types of subsequent somatosensory stimuli, event-related brain potentials (ERPs) during a simple reaction time task using somatosensory stimuli were recorded. Specific colors of visual stimuli and types of somatosensory stimuli were combined to form congruent and incongruent trials. In the congruent trials, specific combinations (e.g., blue color and a single pulse) were presented (80% of the trials), whereas in the incongruent trials, different combinations (e.g., blue color and a train pulse) were presented (20% of the trials). Under the approach condition, the visual stimuli sequentially approached the wrist to which the somatosensory stimulus was presented. In the neutral condition, the visual stimuli did not approach. The results of the ERP analysis showed that incongruence evoked a P3 response with larger amplitude under the approach condition than under the neutral condition. This result suggests that visual stimuli that approach the body function as clues regarding the types of subsequent somatosensory stimuli even if the visual stimuli do not contain emotional information.

http://ift.tt/2pBgqSY

Some Vt. rural cell service, including 911, could end

It will be challenge to find a replacement, state officials said, but they are working on it

http://ift.tt/2Gl5y5w

Asian Journal of Endoscopic Surgery, Ahead of Print.

Asian Journal of Endoscopic Surgery, Ahead of Print.

http://ift.tt/2IOjx2a

Assessing linkage to and retention in care among HIV patients in Uganda and identifying opportunities for health systems strengthening: a descriptive study

While antiretroviral therapy (ART) availability for HIV patients has increased dramatically in Uganda, patient linkage to and retention in care remains a challenge. We assessed patterns of engagement in care i...

http://ift.tt/2IK3sdT

A new CFD based non-invasive method for functional diagnosis of coronary stenosis

Accurate functional diagnosis of coronary stenosis is vital for decision making in coronary revascularization. With recent advances in computational fluid dynamics (CFD), fractional flow reserve (FFR) can be d...

http://ift.tt/2pzfcb3

The in vitro estrogenic activity of the crude drugs found in Japanese herbal medicines prescribed for menopausal syndrome was enhanced by combining them

Japanese herbal medicines can be used as alternatives to estrogen therapy and are sometimes prescribed for menopausal syndrome because they have fewer side effects and are associated with better compliance tha...

http://ift.tt/2pzcRgk

4-Acetylantroquinonol B inhibits lipopolysaccharide-induced cytokine release and alleviates sepsis through of MAPK and NFκB suppression

Antrodia cinnamomea is an indigenous medicinal mushroom in Taiwan, commonly used for the treatment of cancers and inflammatory disorders. 4-acetylantroquinonol B (4AAQB) is one of the active component isolated fr...

http://ift.tt/2DPqiNb

Potentiating and synergistic effect of grapefruit juice on the antioxidant and anti-inflammatory activity of aripiprazole against hydrogen peroxide induced oxidative stress in mice

Dependence on antipsycotic drugs like aripriprazole (ARI) is increasing at alarming rate, hence, this study was undertaken to support the hypothesis that supplementation of Citrus paradisi (Grapefruit) juice havi...

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Food Science &Nutrition, Ahead of Print.

Food Science &Nutrition, Ahead of Print.

http://ift.tt/2pBbj4D

Food Science &Nutrition, Ahead of Print.

Food Science &Nutrition, Ahead of Print.

http://ift.tt/2pz5zsV

Annals of Clinical and Translational Neurology, Ahead of Print.

Annals of Clinical and Translational Neurology, Ahead of Print.

http://ift.tt/2IJJks6

Vancomycin-resistant Enterococcus faecium sequence type 796 - rapid international dissemination of a new epidemic clone

Vancomycin-resistant Enterococcus faecium (VRE) is a leading cause of hospital-acquired infections. New, presumably better-adapted strains of VRE appear unpredictably; it is uncertain how they spread despite impr...

http://ift.tt/2pzspzW

Poor agreement between repeated T-SPOT.TB in a short time period in a high TB burden country

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http://ift.tt/2pwJ3jw

The role of corneal hysteresis during the evaluation of patients with possible normal-tension glaucoma

http://ift.tt/2GkglwH

Switching from concomitant therapy to tafluprost/timolol fixed combination

http://ift.tt/2pAwaVI

ANZ Journal of Surgery, Ahead of Print.

ANZ Journal of Surgery, Ahead of Print.

http://ift.tt/2pyf9vp

ANZ Journal of Surgery, Ahead of Print.

ANZ Journal of Surgery, Ahead of Print.

http://ift.tt/2FZk7MR

ANZ Journal of Surgery, Ahead of Print.

ANZ Journal of Surgery, Ahead of Print.

http://ift.tt/2G1dLIv

Alimentary Pharmacology &Therapeutics, Ahead of Print.

Alimentary Pharmacology &Therapeutics, Ahead of Print.

http://ift.tt/2GhuQRL

Clinical Oral Implants Research, Ahead of Print.

Clinical Oral Implants Research, Ahead of Print.

http://ift.tt/2GjCiw4

Clinical Oral Implants Research, Ahead of Print.

Clinical Oral Implants Research, Ahead of Print.

http://ift.tt/2G6jtJr

Clinical Oral Implants Research, Ahead of Print.

Clinical Oral Implants Research, Ahead of Print.

http://ift.tt/2GjC4oI

How Do We Approach Benign Proliferative Lesions?

Abstract

Purpose of Review

The aim of this review is to summarize recently published literature addressing atypical ductal hyperplasia (ADH), lobular neoplasia (atypical lobular hyperplasia [ALH] and classic lobular carcinoma in situ [C-LCIS]), non-classic lobular carcinoma in situ (NC-LCIS), papillary lesions, and flat epithelial atypia (FEA).

Recent Findings

While ADH, ALN, and C-LCIS are well-established markers of an increased risk of future breast cancers, the risk implications are less clear for papillary lesions and FEA. NC-LCIS is the least well-characterized lesion, with scant published literature on its natural history and surgical management when encountered on needle biopsy.

Summary

Recent data suggest that lobular neoplasia on core biopsy of a BI-RADS ≤ 4 concordant lesion does not require an excision, while ADH, atypical papillomas, and NC-LCIS should be excised. Evidence on FEA and papillomas without atypia suggests a low risk of upgrade on excision, and prospective studies on the upgrade of these lesions are ongoing.

http://ift.tt/2pyicUg

Making a Difference Through Advocacy

By Nathan Douthit

At the annual meeting for the Consortium of Universities for Global Health this year, the theme was Health Disparities: A Time for Action. The keynote address was delivered by Stephen Lewis, former UN special envoy for HIV/AIDS, Canada's Ambassador to the UN, humanitarian and broadcaster. He spoke about, "The drama of disparities," as viewed through the three-part lens of climate change, tuberculosis and conflict and sexual violence.

Stephen Lewis delivering the keynote address for CUGH 2018

Lewis spoke passionately about how the consequences of climate change for human health "fall far more heavily on the poorest country". He described tuberculosis as "the exemplar of disparity and inequality," affecting more people than HIV and malaria combined; the sufferers are the marginalized, who are, "always beleaguered, mostly without voice." He also spoke about the epidemic of conflict and sexual violence, quoting statistics from the recent conflicts in Syria; he especially emphasized the "explosion of rape that strangles credulity." He also mentioned that as the Rohingya are suffering attempted genocide in Myanmar, no UN Security Council resolution has been issued on their behalf.

He explained that disparities in education, income, economic advancement have profound effects on human health. He made it clear that while attempts to raise awareness and to advocate for work to improve poverty, nutrition, sanitation, and education have had limited success in bringing about meaningful change, highlighting the consequences these issues have for human health may be what is necessary to generate the political will and innovation needed for change. "When you concentrate on health you touch the mind and the heart." He criticized the tendency of Medicine to do objectively analyze but not go on to see change implemented. He encouraged an indefatigable and constant pressure on the powers that be in order to see health equity achieved in our generation.

BMJ Case Reports was also at the conference.

We are an enormous repository for case reports. Our global health case reports analyze the literature on environmental health, tuberculosis, conflict and sexual violence, as well as a range of social determinants that profoundly impact the health of the patients the case reports are about. These case reports have an important role to play in advocacy for justice in our local societies and around the world. The patients are encouraged to add to the case reports in their own words. Writing and publishing these patient stories can make a difference in our world today.

BMJ Case Reports invites authors to publish cases that can be used to advocate for individual patients as we all work toward a more just society. Global health case reports can emphasize any social determinant of health, including:
-The effects of climate change on patient and population health
-How infectious disease afflicts the vulnerable and marginalized in society and what interventions increase resilience
-The disproportionate burden of conflict and sexual violence on individuals in economically and political unstable regions of the world – including the effects of migration and people trafficking

Manuscripts may be submitted by students, physicians, nurses and allied health professionals to BMJ Case Reports at http://casereports.bmj.com/. For more information, review our guidance on how to write a global health case report and look through our online collection.

Competing Interests

None Declared

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Αρχειοθήκη ιστολογίου

Αναζήτηση αυτού του ιστολογίου

Παρασκευή 23 Μαρτίου 2018

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