Transcatheter Mitral-Valve Repair in Patients with Heart Failure

New England Journal of Medicine, Ahead of Print.


https://ift.tt/2QU14VG

Patient Uncertainty as a Predictor of 30‐day Return Emergency Department Visits: An Observational Study

Academic Emergency Medicine, Volume 0, Issue ja, -Not available-.


https://ift.tt/2xMfONJ

Combining National Early Warning Score With Soluble Urokinase Plasminogen Activator Receptor (suPAR) Improves Risk Prediction in Acute Medical Patients: A Registry-Based Cohort Study

Objectives: Soluble urokinase plasminogen activator receptor is a prognostic biomarker associated with critical illness, disease progression, and risk of mortality. We aimed to evaluate whether soluble urokinase plasminogen activator receptor adds prognostic value to a vital sign-based score for clinical monitoring of patient risk (National Early Warning Score) in acute medical patients. Design: Registry-based observational cohort study of consecutively admitted acute medical patients. Setting: The Acute Medical Unit, Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark. Patients: Acute medical patients admitted between November 18, 2013, and September 30, 2015. Interventions: None. Measurements and Main Results: Of 17,312 included patients, admission National Early Warning Score was available for 16,244 (93.8%). During follow-up, 587 patients (3.4%) died in-hospital, 859 (5.0%) within 30 days, and 1,367 (7.9%) within 90 days. High soluble urokinase plasminogen activator receptor was significantly associated with in-hospital-, 30-day-, and 90-day mortality within all National Early Warning Score groups, in particular in patients with a low National Early Warning Score; for 30-day mortality, mortality rate ratios ranged from 3.45 (95% CI, 2.91–4.10) for patients with National Early Warning Score 0–1, to 1.86 (95% CI, 1.47–2.34) for patients with National Early Warning Score greater than or equal to 9 for every doubling in soluble urokinase plasminogen activator receptor (log2-transformed). Combining National Early Warning Score, age, and sex with soluble urokinase plasminogen activator receptor improved prediction of in-hospital-, 30-day-, and 90-day mortality, increasing the area under the curve (95% CI) for 30-day mortality from 0.86 (0.85–0.87) to 0.90 (0.89–0.91), p value of less than 0.0001, with a negative predictive value of 99.0%. Conclusions: The addition of soluble urokinase plasminogen activator receptor to National Early Warning Score significantly improved risk prediction of both low- and high-risk acute medical patients. Patients with low National Early Warning Score but elevated soluble urokinase plasminogen activator receptor had mortality risks comparable to that of patients with higher National Early Warning Score. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. The study was performed at the Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark. The funder had no role in the design of the study and collection, analysis, and interpretation of data and in writing the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Drs. Rasmussen and Haupt have received funding for travel from ViroGates A/S, Denmark, the company that produces the suPARnostic assays; she is supported by a grant from the Lundbeck Foundation (grant number R180-2014–3360). Mr. Ladelund received funding from Novo Nordisk. Dr. Eugen-Olsen is a co-founder, shareholder, and Chief Scientific Officer (currently) of ViroGates A/S. Drs. Eugen-Olsen and Andersen are named inventors on patents on soluble urokinase plasminogen activator receptor as a prognostic biomarker; the patents are owned by Copenhagen University Hospital Amager and Hvidovre, Denmark, and licensed to ViroGates A/S. Dr. Ellekilde disclosed that she does not have any potential conflicts of interest. For information regarding this article, E-mail: line.jee.hartmann.rasmussen@regionh.dk Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

https://ift.tt/2I9Zb3h

Long-Term Functional Outcome Data Should Not in General Be Used to Guide End-of-Life Decision-Making in the ICU

No abstract available

https://ift.tt/2I9FEQp

Peripherally Inserted Central Catheters in the ICU: A Retrospective Study of Adult Medical Patients in 52 Hospitals

Objectives: To quantify variation in use and complications from peripherally inserted central catheters placed in the ICU versus peripherally inserted central catheters placed on the general ward. Design: Retrospective cohort study. Setting: Fifty-two hospital Michigan quality collaborative. Patients: Twenty-seven–thousand two-hundred eighty-nine patients with peripherally inserted central catheters placed during hospitalization. Measurements and Main Results: Descriptive statistics were used to summarize patient, provider, and device characteristics. Bivariate tests were used to assess differences between peripherally inserted central catheters placed in the ICU versus peripherally inserted central catheters placed on the ward. Multilevel mixed-effects generalized linear models adjusting for patient and device factors with a logit link clustered by hospital were used to examine the association between peripherally inserted central catheter complications and location of peripherally inserted central catheter placement. Variation in ICU peripherally inserted central catheter use, rates of complications, and appropriateness of use across hospitals was also examined. Eight-thousand two-hundred eighty patients (30.3%) received peripherally inserted central catheters in the ICU versus 19,009 (69.7%) on the general ward. The commonest indication for peripherally inserted central catheter use in the ICU was difficult IV access (35.1%) versus antibiotic therapy (53.3%) on wards. Compared with peripherally inserted central catheters placed in wards, peripherally inserted central catheters placed in the ICU were more often multilumen (59.5% vs 39.3; p

https://ift.tt/2px5yFz

Evaluation of a Measurement System to Assess ICU Team Performance

Objective: Measuring teamwork is essential in critical care, but limited observational measurement systems exist for this environment. The objective of this study was to evaluate the reliability and validity of a behavioral marker system for measuring teamwork in ICUs. Design: Instances of teamwork were observed by two raters for three tasks: multidisciplinary rounds, nurse-to-nurse handoffs, and retrospective videos of medical students and instructors performing simulated codes. Intraclass correlation coefficients were calculated to assess interrater reliability. Generalizability theory was applied to estimate systematic sources of variance for the three observed team tasks that were associated with instances of teamwork, rater effects, competency effects, and task effects. Setting: A 15-bed surgical ICU at a large academic hospital. Subjects: One hundred thirty-eight instances of teamwork were observed. Specifically, we observed 88 multidisciplinary rounds, 25 nurse-to-nurse handoffs, and 25 simulated code exercises. Interventions: No intervention was conducted for this study. Measurements and Main Results: Rater reliability for each overall task ranged from good to excellent correlation (intraclass correlation coefficient, 0.64–0.81), although there were seven cases where reliability was fair and one case where it was poor for specific competencies. Findings from generalizability studies provided evidence that the marker system dependably distinguished among teamwork competencies, providing evidence of construct validity. Conclusions: Teamwork in critical care is complex, thereby complicating the judgment of behaviors. The marker system exhibited great potential for differentiating competencies, but findings also revealed that more context specific guidance may be needed to improve rater reliability. This work was performed at the Johns Hopkins University. Portions of the data collection and analyses that are reported were a part of Dr. Dietz's dissertation work. The views presented in this article are those of the authors and do not necessarily reflective of the Johns Hopkins University, Johns Hopkins Hospital, Rice University, the University of Central Florida, or the Gordon and Betty Moore Foundation. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Supported, in part, by grants from the Gordon and Betty Moore Foundation (grant number: 3186.01). Dr. Dietz and Ms. Dwyer's institutions received funding from the Gordon and Betty Moore Foundation. Dr. Mendez-Tellez received support for article research from the National Institutes of Health. Ms. Dwyer received support for article research from the Gordon and Betty Moore Foundation. Dr. Rosen's institution received funding from the Gordon and Betty Moore Foundation (grant number: 3186.01), Agency for Healthcare Research and Quality, Centers for Disease Control and Prevention, and Jhpiego - Global Health Services, Treatment & Prevention; and he disclosed that he is a co-investigator on a project funded through the National Aeronautics and Space Administration. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: mrosen44@jhmi.edu Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

https://ift.tt/2IepNAt

Estimating the False Positive Rate of Absent Somatosensory Evoked Potentials in Cardiac Arrest Prognostication

Objectives: Absence of somatosensory evoked potentials ("absent somatosensory evoked potentials") is considered a nearly perfect predictor of poor outcome after cardiac arrest. However, reports of good outcomes despite absent somatosensory evoked potentials and high rates of withdrawal of life-sustaining therapies have raised concerns that estimates of the prognostic value of absent somatosensory evoked potentials may be biased by self-fulfilling prophecies. We aimed to develop an unbiased estimate of the false positive rate of absent somatosensory evoked potentials as a predictor of poor outcome after cardiac arrest. Data Sources: PubMed. Study Selection: We selected 35 studies in cardiac arrest prognostication that reported somatosensory evoked potentials. Data Extraction: In each study, we identified rates of withdrawal of life-sustaining therapies and good outcomes despite absent somatosensory evoked potentials. We appraised studies for potential biases using the Quality in Prognosis Studies tool. Using these data, we developed a statistical model to estimate the false positive rate of absent somatosensory evoked potentials adjusted for withdrawal of life-sustaining therapies rate. Data Synthesis: Two-thousand one-hundred thirty-three subjects underwent somatosensory evoked potential testing. Five-hundred ninety-four had absent somatosensory evoked potentials; of these, 14 had good functional outcomes. The rate of withdrawal of life-sustaining therapies for subjects with absent somatosensory evoked potential could be estimated in 14 of the 35 studies (mean 80%, median 100%). The false positive rate for absent somatosensory evoked potential in predicting poor neurologic outcome, adjusted for a withdrawal of life-sustaining therapies rate of 80%, is 7.7% (95% CI, 4–13%). Conclusions: Absent cortical somatosensory evoked potentials do not infallibly predict poor outcome in patients with coma following cardiac arrest. The chances of survival in subjects with absent somatosensory evoked potentials, though low, may be substantially higher than generally believed. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, or the National Institutes of Health. Drs. Bianchi and Westover are co-senior authors. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Supported, in part, by National Institutes of Health 1K23NS090900, T32HL007901, T90DA22759, T32EB001680; Neurocritical Care Society research training fellowship; American Heart Association postdoctoral fellowship; Andrew David Heitman Neuroendovascular Research Fund; Rappaport Foundation; and Salerno foundation. Dr. Amorim is supported by the Neurocritical Care Society and the American Heart Association. Dr. Amorim's institution received funding from the National Institutes of Health (NIH), Neurocritical Care Society, and the American Heart Association; he disclosed he is supported by the Andrew David Heitman Neuroendovascular Research Fund, Rappaport Foundation, and Salerno foundation. Dr. Ghassemi is supported by the Salerno foundation. Dr. Lee's institution received funding from the NIH-NINDS (R03NS091864), and he received funding from SleepMed/DigiTrace and Advance Medical. Dr. Greer received funding from Bard Medical (research grant), and he received funding from medical-legal consultation. Dr. Kaplan received funding from Wiley Blackwell (royalties), Cadwell, and Lundbeck; and as an expert witness on quantitative electroencephalogram. Dr. Cash received support from NIH-National Institute of Neurological Diseases and Stroke (NINDS) NINDS RO1-NS062092, and NINDS-K24-NS088568). Dr. Westover received support from the NIH (1K23NS090900, 1R01NS102190, 1R01NS102574, 1R01NS107291), Andrew David Heitman Neuroendovascular Research Fund, and Rappaport Foundation. Drs. Amorim, Ghassemi, Cole, and Westover received support for article research from the NIH. Dr. Bianchi received support from the Massachusetts General Hospital, the Center for Integration of Medicine and Innovative Technology, the Milton Family Foundation, and the American Sleep Medicine Foundation; he has a patent pending on a home sleep monitoring device; he has received travel funding from Servier; has consulting and research contracts with Foramis, MC10, Insomnisolv, International Flavors and Fragrances, and GrandRounds; and has provided expert testimony in sleep medicine. For information regarding this article, E-mail: edilbertoamorim@gmail.com Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

https://ift.tt/2pw5fKZ

Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: EOLIA and Beyond

No abstract available

https://ift.tt/2puaYRz

Minimal Impact of Implemented Early Warning Score and Best Practice Alert for Patient Deterioration

Objectives: Previous studies have looked at National Early Warning Score performance in predicting in-hospital deterioration and death, but data are lacking with respect to patient outcomes following implementation of National Early Warning Score. We sought to determine the effectiveness of National Early Warning Score implementation on predicting and preventing patient deterioration in a clinical setting. Design: Retrospective cohort study. Setting: Tertiary care academic facility and a community hospital. Patients: Patients 18 years old or older hospitalized from March 1, 2014, to February 28, 2015, during preimplementation of National Early Warning Score to August 1, 2015, to July 31, 2016, after National Early Warning Score was implemented. Interventions: Implementation of National Early Warning Score within the electronic health record and associated best practice alert. Measurements and Main Results: In this study of 85,322 patients (42,402 patients pre-National Early Warning Score and 42,920 patients post-National Early Warning Score implementation), the primary outcome of rate of ICU transfer or death did not change after National Early Warning Score implementation, with adjusted hazard ratio of 0.94 (0.84–1.05) and 0.90 (0.77–1.05) at our academic and community hospital, respectively. In total, 175,357 best practice advisories fired during the study period, with the best practice advisory performing better at the community hospital than the academic at predicting an event within 12 hours 7.4% versus 2.2% of the time, respectively. Retraining National Early Warning Score with newly generated hospital-specific coefficients improved model performance. Conclusions: At both our academic and community hospital, National Early Warning Score had poor performance characteristics and was generally ignored by frontline nursing staff. As a result, National Early Warning Score implementation had no appreciable impact on defined clinical outcomes. Refitting of the model using site-specific data improved performance and supports validating predictive models on local data. Drs. O'Brien and Goldstein are co-senior authors. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Supported, in part, by grants from National Institute of Diabetes and Digestive and Kidney Diseases & Allergy and Infectious Diseases; Health and Human Services (HHS)|National Institutes of Health (NIH)|National Institute of Allergy and Infectious Diseases: T32-AI007392 (to Dr. Clement); HHS|NIH|National Institute of Diabetes and Digestive and Kidney Diseases: K25-DK097279 and Duke Center for Integrative Health (to Dr. Goldstein); and Duke Center for Integrative Health (to Drs. Steorts and O'Brien). The funding bodies had no role in the study's design, conduct, review, or reporting or the decision to submit the article for publication. Drs. Bedoya, Clement, and Goldstein received support for article research from the National Institutes of Health. Dr. Clement received funding from UpToDate (royalties). Dr. Steorts received funding from employment with U.S. Census Bureau; she holds an National Science Foundation (NSF) Career grant and NSF privacy grant (both not related to this study); and she received support for article research from a seed grant from Duke University. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: armando.bedoya@duke.edu Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

https://ift.tt/2I8SWNk

Cancers, Vol. 10, Pages 350: Prognostic Factors in Merkel Cell Carcinoma: A Retrospective Single-Center Study in 90 Patients

Cancers, Vol. 10, Pages 350: Prognostic Factors in Merkel Cell Carcinoma: A Retrospective Single-Center Study in 90 Patients

Cancers doi: 10.3390/cancers10100350

Authors: Marco Rastrelli Beatrice Ferrazzi Francesco Cavallin Vanna Chiarion Sileni Jacopo Pigozzo Alessio Fabozzi Saveria Tropea Antonella Vecchiato Alessandra Costa Alessandro Parisi Carlo Riccardo Rossi Paolo Del Fiore Mauro Alaibac

Merkel Cell Carcinoma (MCC) is a rare but highly aggressive neuroendocrine neoplasm of the skin. This study aimed at describing characteristics, treatment, and prognosis of a series of consecutive cases of MCC patients, in order to contribute to the investigation of this rare malignancy and provide better patient care. This is a retrospective cohort study including all 90 patients diagnosed and/or treated for MCC between 1991 and 2018 at the Veneto Institute of Oncology in Padua (Italy). Patient and tumor characteristics, treatment, and immunohistochemical data were extracted from a prospectively collected local database. There were 68 primary (76%) and 22 non-primary (15 occult primary, three metastatic, four recurrence) tumors (24%). CK20 expression was associated with reduced overall (HR 2.92, 95% CI 1.04–8.16) and disease-specific (HR 4.62, 95% CI 1.31–16.28) survival. Immunomodulatory regimens for treatment of other comorbidities were associated with reduced disease-specific ((HR 2.15, 95% CI 1.06–4.36) and recurrence-free (HR 3.08, 95% CI 1.44–6.57) survival. Iatrogenic immunomodulation resulted as the main factor associated with impaired prognosis. Lack of CK20 expression was associated with better survival.

https://ift.tt/2MXTN3X

Mucosal defect closure using a dental floss O‐ring clip after endoscopic duodenal submucosal dissection

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


https://ift.tt/2zpSzeg

Not another consultation process: a critique of the implementation of Bill C-277 Framework on Palliative Care in Canada [Letters]

https://ift.tt/2MYpqdJ

Care setting and 30-day hospital readmissions among older adults: a population-based cohort study [Research]

BACKGROUND:

Despite the fact that many older adults receive home or long-term care services, the effect of these care settings on hospital readmission is often overlooked. Efforts to reduce hospital readmissions, including capacity planning and targeting of interventions, require clear data on the frequency of and risk factors for readmission among different populations of older adults.

METHODS:

We identified all adults older than 65 years discharged from an unplanned medical hospital stay in Ontario between April 2008 and December 2015. We defined 2 preadmission care settings (community, long-term care) and 3 discharge care settings (community, home care, long-term care) and used multinomial regression to estimate associations with 30-day readmission (and death as a competing risk).

RESULTS:

We identified 701 527 individuals (mean age 78.4 yr), of whom 414 302 (59.1%) started in and returned to the community. Overall, 88 305 in dividuals (12.6%) were re admitted within 30 days, but this proportion varied by care setting combination. Relative to individuals returning to the community, those discharged to the community with home care (adjusted odds ratio [OR] 1.43, 95% confidence interval [CI] 1.39–1.46) and those returning to long-term care (adjusted OR 1.35, 95% CI 1.27–1.43) had a greater risk of readmission, whereas those newly admitted to long-term care had a lower risk of readmission (adjusted OR 0.68, 95% CI 0.63–0.72).

INTERPRETATION:

In Ontario, about 40% of older people were discharged from hospital to either home care or long-term care. These discharge settings, as well as whether an individual was admitted to hospital from long-term care, have important implications for understanding 30-day readmission rates. System planning and efforts to reduce readmission among older adults should take into account care settings at both admission and discharge.

https://ift.tt/2xudCez

Managing frailty in primary care: evidence gaps cannot be ignored [Commentary]

https://ift.tt/2MZYTwG

Identification and management of frailty in the primary care setting [Review]

https://ift.tt/2xzsxE9

Ontario health providers protest pause on overdose prevention [News]

https://ift.tt/2MXLftT

Myasthenia gravis [Practice]

https://ift.tt/2xxZWiy

Adopt US recommendation on vision screening in older adults [Letters]

https://ift.tt/2MZYLgG

Extramammary Paget disease of the glans penis [Practice]

https://ift.tt/2xyxDkd

Students tidy online presence before applying to medical school and residency [News]

https://ift.tt/2MZYI4u

The mathematics of Crohn disease [Humanities]

https://ift.tt/2xudziT

Telemedicine on the rise but lagging in Canada [News]

https://ift.tt/2MXvUtp

Varicella causing remission of Cushings disease

An 18-year-old male with Cushing's disease presented with generalised skin eruptions and backache. He was diagnosed with varicella infection. During the course of the illness, he developed persistent vomiting. Hormonal evaluation suggested adrenal insufficiency. MRI of brain showed features of pituitary apoplexy. Initially, he required hydrocortisone replacement. Later on his hypothalamic–pituitary–adrenal axis recovered and he is currently asymptomatic without any treatment.

https://ift.tt/2OIWIzn

Extreme scoliosis from CKD-MBD resulting in respiratory failure and death

Description 

A 64-year-old man presented to our hospital because of dyspnoea. Twenty years ago, he had started peritoneal dialysis (PD) for chronic kidney disease. He had been diagnosed with secondary hyperparathyroidism 7 years before his presentation to our hospital, with an intact parathyroid hormone (PTH) 1227 pg/mL (normal range 10–60 pg/mL), calcium level of 10.1 mg/dL (normal range 8.8–10.5 mg/dL), phosphorus level of 5.5 mg/dL (normal range 2.4–4.1 mg/dL) and alkaline phosphatase level of 377 IU/L (normal range 140–338 IU/L). His medications included cinacalcet. Ultrasonography showed a 5-milimetre nodule at the lower pole of the parathyroid, but  99mTc-hexakis2- methoxyisobutylisonitrile (MIBI)scintigraphy revealed no abnormal accumulation.

The patient's intact PTH increased to 2606 pg/mL 6 years prior to presentation. At that time, the patient deferred parathyroidectomy. A year later, he switched from PD to haemodialysis. Intact PTH remained elevated to more than 4000 pg/mL. His thorax became scoliotic curving to the left. He had experienced dyspnoea on...

https://ift.tt/2zqqzrf

Barriers to healthcare for female patients in Papua New Guinea

A 25-year-old woman presented to hospital in the remote highlands of Papua New Guinea (PNG) with a 3-year history of increasing abdominal distension, amenorrhoea and syncope. Ultrasound showed a large unilocular ovarian cyst. During her work-up, she was found to be HIV positive. She was treated with antiretroviral therapy, and once her CD4 count improved, she underwent a laparotomy and removal of the ovarian cyst with immediate improvement in symptoms. PNG has high levels of HIV particularly in young women and children.¹ This is partly due to a lack of screening and treatment facilities and partly due to significant gender discrimination. PNG is considered one of the most dangerous places in the world for females; women are treated as second-class citizens with few human rights or access to services such as healthcare.² Rape, sexual assault and domestic violence are common, and their lives are dictated to them by their husbands or male relatives.^{2 3} The lack of healthcare resources and significant levels of gender discrimination meant that this patient had a delayed presentation resulting in potentially grave complications.

https://ift.tt/2OJ0VmM

On a knife-edge: clinical uncertainty with an extensive knife blade in situ in the craniofacial region

A 25-year-old man presented to the trauma department following a penetrating stab wound to his left infraorbital margin with retained knife blade causing superoposterior displacement of the globe. Plain skull X-ray revealed an extensive retained blade with subsequent CT imaging revealing the tip of the blade had reached the right styloid process with no neurovascular compromise. Initial concern was primarily for the left eye leading to ophthalmology being the first specialty requested to review the patient. However, once the extent of the injury was established, ophthalmology requested further review from maxillofacial, ENT and neurosurgery. This resulted in an 84 hours wait between the initial injury and the removal of the knife blade. Incredibly, the patient had no initial sequelae from such an extensive injury and had an unremarkable recovery with no further complications aside from a laceration to the left inferior rectus muscle that was conservatively managed.

https://ift.tt/2zqqyUd

Mast cell deposition and activation may be a new explanation for epiploic appendagitis

Epiploic appendagitis is as an acute painful condition of the fat on the outside of the intestine. Thus far, there have been no publications to our knowledge that appendagitis can be caused by mast cells or can be associated with chronic pain. A patient with multisystemic disorders suffered with both chronic and acute attacks of abdominal pain for a year. The worst attack led to surgical resection of an enlarged sigmoid colon epiploic appendage. Careful review of her complex medical history and mast cell stains of gastrointestinal biopsies led to the diagnosis of mast cell activation syndrome. Re-examination of the resected appendage using an immunohistochemical stain demonstrated a high mast cell density which is a new histopathological finding. Treatment of mast cell activation syndrome and other related syndromes led to marked improvement in her health, including all types of chronic abdominal pain.

https://ift.tt/2OH9caG

Spontaneous resolution of a 'ping-pong fracture at birth

'Ping-pong' fractures are depressed skull fractures in newborn infants that occur as inward buckling of the calvarial bones, forming a cup shape. These fractures are often associated with maintenance of bone continuity. These fractures may occur spontaneously during the intrauterine period or secondary to birth trauma. Currently, there is no standard protocol for the management of depressed skull fractures. Neurosurgical or non-surgical approaches may be administered depends on the severity of the fracture. Most untreated ping-pong fractures resolve spontaneously within 6 months. Therefore, it is recommended to reserve surgical elevation or non-surgical techniques for infants not demonstrating spontaneous resolution during this period. In addition, neurosurgical interventions are usually considered for cases with intracranial pathology or neurological deficits or for infants who do not respond to conservative treatment. Herein, we report a case of a newborn infant with a spontaneous intrauterine ping-pong fracture, which spontaneously resolved, without surgical or non-surgical intervention.

https://ift.tt/2zpCHbH

External auditory canal lesion: colorectal metastatic adenocarcinoma

The patient presented to the ear, nose and throat clinic with failed conservative treatment of persistent right otitis externa. On examination, the roof of the right ear canal was polypoid and the tympanic membrane could not be visualised. There was a fragile mass noted in the external auditory canal (EAC) which on microsuction started to bleed. CT internal auditory meatus and MRI internal auditory meatus identified soft tissue mass in the EAC. The patient underwent urgent examination under anaesthetic of the ear and biopsies were taken. He had a background of ascending colon cancer; Duke's C1, pT4, N1 M0, R0 resection and had undergone laparoscopic right hemicolectomy with adjuvant chemotherapy, in the previous year. The biopsy results proved that the mass in the EAC was due to metastatic deposit of colorectal primary tumour. The patient also had a full body CT which revealed other new metastases. The patient is being treated with palliative chemotherapy.

https://ift.tt/2OIWGrf

Delusional infestation in the treatment of ADHD with atomoxetine

The case describes an adult diagnosed with attention deficit hyperactivity disorder and treated with atomoxetine who quickly developed a florid case of delusional infestation. The patient described very distressing experiences that were significantly impacting her daily life. The symptoms improved with the withdrawal of atomoxetine and resolved completely with antipsychotic medications. Atomoxetine is proposed as the putative causative agent in this case.

https://ift.tt/2zqqcgl

Uncommon cause of pelvic inflammatory disease leading to toxic shock syndrome

A 44-year-old Caucasian female with a history of endometriosis is admitted to the intensive care unit due to severe left lower quadrant abdominal pain, nausea and vomiting. With patients' positive chandelier sign on pelvic examination, leucocytosis, elevated erythrocyte sedimentation rate and elevated C-reactive protein indicated that she had pelvic inflammatory disease (PID). PCR tests were negative for Neisseria gonorrhoeae and Chlamydia trachomatis; however, her blood and urine cultures grew Group A streptococci (GAS) with a negative rapid Streptococcus throat swab and no known exposure to Streptococcus. On further review, patient met criteria for GAS toxic shock syndrome based on diagnostic guidelines. The patient was promptly treated with intravenous antibiotics and supportive care, and she acutely recovered. This case demonstrates a rare cause of PID and an atypical aetiology of severe sepsis. It illuminates the importance of considering PID as a source of infection for undifferentiated bacteraemia.

https://ift.tt/2OL5FYV

Novel mutation in the CHST14 gene causing musculocontractural type of Ehlers-Danlos syndrome

Musculocontractural type of Ehlers-Danlos syndrome (MC-EDS) is a recently recognised connective tissue disorder. MC-EDS is caused by homozygous or compound heterozygous mutation in the carbohydrate sulfotransferase 14 (CHST14) gene on chromosome 15q15. Herein, we report a case of a 3-year-old boy with MC-EDS in whom a novel mutation in the CHST14 gene was discovered. Besides being the second report of this rare disorder from India, the child till 3 years has not had any bleeding tendency as described in the earlier reports of this disorder.

https://ift.tt/2zqqbch

Expand the differential...think beyond rheumatoid arthritis

A 31-year-old male patient with severe, migratory arthralgias presented to our academic medical centre after being erroneously diagnosed and treated for rheumatoid arthritis for over 1 year. Multiple immunomodulatory therapies for rheumatoid arthritis were attempted with no relief of symptoms. Eventually, the pain was so bothersome that the patient became bedridden for 1 month prior to presenting to our facility. Our assessment revealed that the patient met the diagnostic criteria, known as the Yamaguchi criteria, needed to diagnose adult-onset Still's disease. Yamaguchi criteria include migratory inflammatory arthritis, quotidian fevers, leucocytosis and a salmon-coloured maculopapular rash. These signs and symptoms may go unnoticed or overlooked if adult-onset Still's disease is not considered. The patient was treated with anakinra (a recombinant human IL-1 receptor antagonist) and had rapid improvement in his symptoms, with the restoration of mobility.

https://ift.tt/2OLkk6v

Posterior urethral valve associated with a foreign body in posterior urethra: a first of its kind report

Posterior urethral valve and foreign body are among the important causes of male urethral obstruction. Although one is congenital and the other is acquired, both entities are rare in children with only a few reported cases. Because of myriad of symptoms associated with both conditions, a conclusive diagnosis requires both physical examination and radiological imaging. We report a first of its kind association of posterior urethral valve with foreign body in the posterior urethra in a 6-year-old male child which was eventually managed by endoscopic intervention.

https://ift.tt/2zqq9Bb

Management of C-shaped root canal configuration in mandibular second molar

Description 

The C-shaped root canal configuration is an anatomical variation of root fusion and a type of taurodontism commonly seen in the mandibular second molar with prevalence ranging from 2.7% to 45.5% in different populations.1 In this configuration, the root canals are connected by slit or web with varying anatomy along the root length which makes thorough debridement obstacle for the clinician.2 Cone-beam CT (CBCT) is a three-dimensional imaging technique that facilitates and improves understanding the complex morphology. This article presents a case of C-shaped root canal configuration of mandibular second molar managed by using CBCT and modification in obturation techniques.

A 40-year-old female patient reported with pain in the lower left back teeth region. Medical history of the patient was unremarkable. Intraoral examination revealed deep class I carious lesion on tooth 37 with tenderness on percussion. Thermal test was performed to check the vitality...

https://ift.tt/2ONBCQi

Over-the-counter drug-induced lung injuries with both diffuse alveolar haemorrhage and diffuse alveolar damage

Description 

A 41-year-old Japanese man with no underlying disease was admitted to our hospital with haemoptysis and dyspnoea. Two weeks prior to admission, he had caught a cold and took an over-the-counter drug (topikku GX), subsequently general fatigue and cough were worsening progressively. Hence, he presented to another hospital, owing to acute onset of dyspnoea on effort and haemoptysis, where chest X-ray was taken and revealed bilateral abnormal shadow in the middle lung fields, after that he was referred to our hospital.

On examination, his general appearance was moderately ill; blood pressure was 126/72 mm Hg, heart rate was 90 beats/min, oxygen saturation was 90% under ambient air, respiratory rate was 20 breath/min and body temperature was 38.2°. Chest auscultation revealed bilateral inspiratory mid to late crackles. Laboratory blood test showed mild elevation of liver function tests (Aspartate aminotransferase 42 IU/L, Alanine aminotransferase 34 IU/L), Lactate dehydrogenase 379 IU/L, C-reactive protein 28.2 mg/L, the rest of...

https://ift.tt/2zpbMgc

Skin metastasis: a rare presentation in testicular germ cell tumour

A 35-year-old man presented with a history of cough, haemoptysis, weight loss for 2 months along with ulceroproliferative lesions on the chin and the scalp. On evaluation he was found to have non-seminomatous germ cell tumour, stage 3 c, poor risk with Eastern Cooperative Oncology Group Performance Status of 4. The skin lesions were proven to be metastasis by fine-needle aspiration cytology. He showed significant improvement with a 3-day protocol of abbreviated etoposide and cisplatin chemotherapy and is planned for 4 cycles of VIP. This case describes an uncommon presentation of germ cell tumour in the form of skin metastasis with excellent response to chemotherapy.

https://ift.tt/2OM0kR2

Chronic cutaneous lupus erythematosus and topical clindamycin

Description 

A 64-year-old Caucasian woman was seen in our office for several years for management of her chronic cutaneous lupus erythematosus (CCLE). Her condition consisted of violaceous papules and plaques with some focal atrophy distributed over the upper arms, face and scalp. Histopathology from two 4 mm punch biopsies performed on separate occasions demonstrated features on H&E stain consistent with CCLE: epidermal atrophy and interface dermatitis with superficial perivascular, deep dermal and periadnexal lymphohistiocytic infiltrates containing some plasma cells. Her rash had frustrated her for over 5 years, worsening with increased sun exposure. Her collagen vascular serologies were negative. She had been managed with potent topical corticosteroids with improvement, however, the patient preferred to reserve this for flares of her condition. Interestingly, the patient had correlated dramatic clearing of her CCLE inadvertently after 3 months of applying topical clindamycin gel 1% twice daily (figures 1 and 2),...

https://ift.tt/2zpMSNq

Primary tonsillar tuberculosis

Upper aerodigestive tract involvement with tuberculosis is relatively rare and may be seen in up to 2% of patients with pulmonary tuberculosis. Isolated tonsil involvement with tuberculosis is not commonly seen in clinical practice. We report a case of a 22-year-old postpartum mother who presented with odynophagia, fever, loss of weight and submandibular swelling of 3 months' duration. Clinical examination revealed a submandibular node, and oropharyngeal examination revealed necrotic slough overlying an enlarged left tonsil. Fine-needle aspiration cytology of the node and histopathological examination of the left tonsillectomy specimen revealed necrotising epithelioid cell granulomas, and stain for acid-fast bacilli was positive in the latter. She was diagnosed with tonsillar tuberculosis and was started on antituberculous treatment following which she improved clinically. This case serves to demonstrate an uncommon presentation of primary tuberculosis and reminds us to consider tuberculosis also as a microbiological aetiology for tonsillitis.

https://ift.tt/2OSKT9G

Microbiota — an amplifier of autoimmunity

Alexis Vogelzang | Matteo M Guerrini | Nagahiro Minato | Sidonia Fagarasan

https://ift.tt/2I7K36A

Extracellular matrix and the maintenance and loss of peripheral immune tolerance in autoimmune insulitis

Carlos O Medina | Nadine Nagy | Paul L Bollyky

https://ift.tt/2I7K22w

UGT1A1 polymorphisms in rectal cancer associated with the efficacy and toxicity of preoperative chemoradiotherapy using irinotecan

Cancer Science, Volume 0, Issue ja, -Not available-.


https://ift.tt/2PZvSTI

Decision making and mental health in EMS

Recognizing three common patient care decisions that contribute to cumulative stress on EMS providers

https://ift.tt/2QU6m3x

Firefighter training can be fun and serious at the same time

By taking an innovative and creative approach, training drills can maintain their educational value while also adding an element of fun

https://ift.tt/2I8sVxE

Ibrutinib for Treating Relapsed or Refractory Mantle Cell Lymphoma: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

Abstract

As part of its Single Technology Appraisal process, the UK National Institute for Health and Care Excellence (NICE) invited the manufacturer of ibrutinib (Janssen) to submit evidence on the clinical effectiveness and cost effectiveness of ibrutinib for the treatment of relapsed or refractory (R/R) mantle cell lymphoma (MCL). The School of Health and Related Research Technology Assessment Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence contained within the company's submission to NICE. The clinical effectiveness evidence for ibrutinib included one randomised controlled trial comparing ibrutinib and temsirolimus and two single-arm studies. The company's indirect comparison of ibrutinib versus rituximab plus chemotherapy (R-chemo) produced a hazard ratio (HR) for progression-free survival (PFS) of 0.28. The ERG's random effects network meta-analysis (NMA) indicated that the treatment effect on PFS was highly uncertain (HR 0.27; 95% credible interval (CrI) 0.06–1.26). The company's Markov model assessed the cost effectiveness of ibrutinib versus R-chemo for the treatment of R/R MCL from the perspective of the National Health Service (NHS) and Personal Social Services over a lifetime horizon. Based on a re-run of the company's model by the ERG, the incremental cost-effectiveness ratio (ICER) for ibrutinib versus R-chemo [including the company's original patient access scheme (PAS)] was expected to be £76,014 per quality-adjusted life-year (QALY) gained. The ERG had several concerns regarding the company's model structure and the evidence used to inform its parameters. The ERG's preferred analysis, which used the ERG's NMA and the observed Kaplan–Meier curve for time to ibrutinib discontinuation and excluded long-term disutilities for R-chemo, produced ICERs of £63,340 per QALY gained for the overall R/R MCL population and of £44,711 per QALY gained for patients with one prior treatment. Following an updated PAS and consideration of evidence from a later data-cut of the RAY trial, the appraisal committee concluded that the most plausible ICER for the one prior treatment subgroup was likely to be lower than the company's estimate of £49,848 per QALY gained. The company's ICER for the overall R/R MCL population was higher, at £62,650 per QALY gained. The committee recommended ibrutinib as an option for treating R/R MCL in adults only if they have received only one previous line of therapy and the company provides ibrutinib with the discount agreed in the commercial access agreement with NHS England.

https://ift.tt/2Ie1Vgl

A novel methodological approach using superimposed Micro‐CT and STL images to analyze hard and soft tissue volume in immediate and delayed implants with different cervical designs

Clinical Oral Implants Research, EarlyView.


https://ift.tt/2NZEooD

Histological and micro‐CT analysis of peri‐implant soft and hard tissue healing on implants with different healing abutments configurations

Clinical Oral Implants Research, EarlyView.


https://ift.tt/2Q1wlFb

Origin of the Autophagosome Membrane in Mammals

Autophagy begins with the nucleation of phagophores, which then expand to give rise to the double-membrane autophagosomes. Autophagosomes ultimately fuse with lysosomes, where the cytosolic cargoes are degraded. Accumulation of autophagosomes is a hallmark of autophagy and neurodegenerative disorders including Alzheimer's and Huntington's disease. In recent years, the sources of autophagosome membrane have attracted a great deal of interests, even so, the membrane donors for autophagosomes are still under debate. In this review, we describe the probable sources of autophagosome membrane.

https://ift.tt/2QUsuuT

Silencing ELMO3 Inhibits the Growth, Invasion, and Metastasis of Gastric Cancer

ELMO3 is a member of the engulfment and cell motility (ELMO) protein family, which plays a vital role in the process of chemotaxis and metastasis of tumor cells. However, remarkably little is known about the role of ELMO3 in cancer. The present study was conducted to investigate the function and role of ELMO3 in gastric cancer (GC) progression. The expression level of ELMO3 in gastric cancer tissues and cell lines was measured by means of real-time quantitative PCR (qPCR) and Western blot analysis. RNA interference was used to inhibit ELMO3 expression in gastric cancer cells. Then, wound-healing assays, Transwell assays, MTS assays, flow cytometry, and fluorescence microscopy were applied to detect cancer cell migration, cell invasion, cell proliferation, the cell cycle, and F-actin polymerization, respectively. The results revealed that ELMO3 expression in GC tumor tissues was significantly higher than in the paired adjacent tissues. Moreover, knockdown of ELMO3 by a specific siRNA significantly inhibited the processes of cell proliferation, invasion, metastasis, regulation of the cell cycle, and F-actin polymerization. Collectively, the results indicate that ELMO3 participates in the processes of cell growth, invasion, and migration, and ELMO3 is expected to be a potential diagnostic and prognostic marker for GC.

https://ift.tt/2xJcyCH

Thoracic Organ Doses and Cancer Risk from Low Pitch Helical 4-Dimensional Computed Tomography Scans

Purpose. To investigate the dose depositions to organs at risk (OARs) and associated cancer risk in cancer patients scanned with 4-dimensional computed tomography (4DCT) as compared with conventional 3DCT. Methods and Materials. The radiotherapy treatment planning CT image and structure sets of 102 patients were converted to CT phantoms. The effective diameters of those patients were computed. Thoracic scan protocols in 4DCT and 3DCT were simulated and verified with a validated Monte Carlo code. The doses to OARs (heart, lungs, esophagus, trachea, spinal cord, and skin) were calculated and their correlations with patient effective diameter were investigated. The associated cancer risk was calculated using the published models in BEIR VII reports. Results. The average of mean dose to thoracic organs was in the range of 7.82-11.84 cGy per 4DCT scan and 0.64-0.85 cGy per 3DCT scan. The average dose delivered per 4DCT scan was 12.8-fold higher than that of 3DCT scan. The organ dose was linearly decreased as the function of patients' effective diameter. The ranges of intercept and slope of the linear function were 17.17-30.95 and -0.0278--0.0576 among patients' 4DCT scans, and 1.63-2.43 and -0.003--0.0045 among patients' 3DCT scans. Relative risk of cancer increased (with a ratio of 15.68:1) resulting from 4DCT scans as compared to 3DCT scans. Conclusions. As compared to 3DCT, 4DCT scans deliver more organ doses, especially for pediatric patients. Substantial increase in lung cancer risk is associated with higher radiation dose from 4DCT and smaller patients' size as well as younger age.

https://ift.tt/2QS3qo9

Transcranial Direct Current Stimulation (tDCS) in Mice

Transcranial direct current stimulation (tDCS) is a therapeutic technique proposed to treat psychiatric diseases. An animal model is essential for understanding the specific biological alterations evoked by tDCS. This protocol describes a tDCS mouse model that uses a chronically implanted electrode.

https://ift.tt/2I6gLVP

Fabrication of Three-Dimensional Graphene-Based Polyhedrons via Origami-Like Self-Folding

Here, we present a protocol for fabrication of 3D graphene-based polyhedrons via origami-like self-folding.

https://ift.tt/2pxtOaC

The Combined Use of Transcranial Direct Current Stimulation and Robotic Therapy for the Upper Limb

The combined use of transcranial direct current stimulation and robotic therapy as an add-on for conventional rehabilitation therapy may result in improved therapeutic outcomes due to modulation of brain plasticity. In this article, we describe the combined methods used in our institute for improving motor performance after stroke.

https://ift.tt/2MUxLze

Expression of Cementitious Pore Solution and the Analysis of Its Chemical Composition and Resistivity Using X-ray Fluorescence

This protocol describes the procedure to express fresh pore solution from cementitious systems and the measurement of its ionic composition using X-ray fluorescence. The ionic composition can be used to calculate pore solution electrical resistivity, which can be used, together with concrete electrical resistivity, to determine the formation factor.

https://ift.tt/2pvcxyw

An Available Technique for Preparation of New Cast MnCuNiFeZnAl Alloy with Superior Damping Capacity and High Service Temperature

Here we present a protocol to obtain a novel Mn-Cu-based alloy with excellent comprehensive performances by a high-quality smelting technology and reasonable heat treatment methods.

https://ift.tt/2I8d4Pw

Is PNPT1‐related hearing loss ever non‐syndromic? Whole exome sequencing of adult siblings expands the natural history of PNPT1‐related disorders

American Journal of Medical Genetics Part A, EarlyView.


https://ift.tt/2DmAZfm

Extending the ALDH18A1 clinical spectrum to severe autosomal recessive fetal cutis laxa with corpus callosum agenesis

American Journal of Medical Genetics Part A, EarlyView.


https://ift.tt/2Nz0Vcw

A mosaic intragenic microduplication of LAMA1 and a constitutional 18p11.32 microduplication in a patient with keratosis pilaris and intellectual disability

American Journal of Medical Genetics Part A, EarlyView.


https://ift.tt/2DoQBPC

Further delineation of the clinical spectrum of de novo TRIM8 truncating mutations

American Journal of Medical Genetics Part A, EarlyView.


https://ift.tt/2NA1Adq

Small 4p16.3 deletions: Three additional patients and review of the literature

American Journal of Medical Genetics Part A, EarlyView.


https://ift.tt/2DwSyJA

Phenotypic and molecular insights into PQBP1‐related intellectual disability

American Journal of Medical Genetics Part A, EarlyView.


https://ift.tt/2NAF4kU

Identification of novel PIEZO1 variants using prenatal exome sequencing and correlation to ultrasound and autopsy findings of recurrent hydrops fetalis

American Journal of Medical Genetics Part A, EarlyView.


https://ift.tt/2DqimY5

22q and two: 22q11.2 deletion syndrome and coexisting conditions

American Journal of Medical Genetics Part A, EarlyView.


https://ift.tt/2NvXq6u

UHPLC-Q-TOF MS-Based Metabolic Analysis for the Therapeutic Efficacy of “Xuebijing Injection” against Sepsis-Induced Acute Lung Injury

"Xuebijing Injection" (XBJ) is a traditional Chinese medicine and has been wildly used in the treatment of sepsis in China. However, few studies have reported the use of XBJ in sepsis with acute lung injury (ALI). This study aimed to investigate the therapeutic efficacy of XBJ against sepsis-induced ALI. Generally a total of 27 mice were equally randomized into three groups: a sham group was given saline before sham operation. A sepsis group received the cecal ligation and puncture (CLP) operation only. A sepsis+XBJ group, XBJ, was injected at 72, 48, and 24 h before CLP operation. The lung tissue was collected for UHPLC-Q-TOF/MS profiling analysis, biomarker identification, and pathway analysis. With the analysis of principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), forty-five purine, amino acid, and sphingolipid metabolites in lung tissues were identified as potential biomarkers of sepsis-induced ALI, among which 22 were reversed in the sepsis+XBJ group significantly. Conclusively, our results suggest that purine metabolic pathway, glutathione metabolic pathway, sphingomyelin metabolic pathway, arachidonic acid metabolic pathway, and phospholipid metabolic pathway may be the potential therapeutic pathways to overcome sepsis-induced acute lung injury and we provided the potential mechanisms of protective effects of XBJ against ALI.

https://ift.tt/2xMwjcu

The polyploid state restricts hepatocyte proliferation and liver regeneration

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


https://ift.tt/2NyJsRl

Identification of Candidate Biomarkers in Malignant Ascites from Patients with Hepatocellular Carcinoma by iTRAQ-Based Quantitative Proteomic Analysis

Almost all the patients with hepatocellular carcinoma (HCC) at advanced stage experience pathological changes of chronic liver cirrhosis, which generally leads to moderate ascites. Recognition of novel biomarkers in malignant ascites could be favorable for establishing a diagnosis for the HCC patients with ascites, and even predicting prognosis, such as risk of distant metastasis. To distinguish the proteomic profiles of malignant ascites in HCC patients from those with nonmalignant liver cirrhosis, an iTRAQ pipeline was built up to analyze the differentially distributed proteins in the malignant ascites from HCC patients (n=10) and benign ascites from hepatic decompensation (HD) controls (n=9). In total, 112 differentially distributed proteins were identified, of which 69 proteins were upregulated and 43 proteins were downregulated (ratio 1.3, respectively) in the malignant ascites. Moreover, 19 upregulated proteins (including keratin 1 protein and rheumatoid factor RF-IP20, ratio>1.5) and 8 downregulated proteins (including carbonic anhydrase 1, ratio

https://ift.tt/2MV21tR

Direct and transdentinal biostimulatory effects of grape seed extract rich in proanthocyanidin on pulp cells

International Endodontic Journal, Volume 0, Issue ja, -Not available-.


https://ift.tt/2NwQK8n

Association of Antibiotic Resistance, Cell Adherence, and Biofilm Production with the Endemicity of Nosocomial Klebsiella pneumoniae

Klebsiella pneumoniae is a leading cause of multiple nosocomial infections, some of which are associated with high mortality. The increasing prevalence of antibiotic-resistant strains highlights their clinical importance and how complicated managing treatment can be. In this study, we investigated antimicrobial resistance, cell adherence, and biofilm production of nosocomial K. pneumoniae strains isolated from surveillance studies in a Mexican tertiary hospital and evaluated the potential association of these phenotypes with endemicity. The great majority of the clones exhibited adhesion to cultured epithelial cells and were strong biofilm producers. A direct relationship between adhesion phenotypes, biofilm production, and endemicity was not always apparent. Biofilm formation and production of ESBL did not appear to be directly associated. Notably, all the endemic strains were multidrug-resistant. This study emphasizes that while endemic strains possess various virulence-associated properties, antimicrobial resistance appears to be a determining factor of their endemicity.

https://ift.tt/2MWhgT7

Mendelian Disease Genes More Prone to Copy Number Changes Than Previously Thought: Clinically relevant copy number variants are distinct from those that contribute to normal variation in human disease genes

American Journal of Medical Genetics Part A, Volume 176, Issue 9, Page 1793-1794, September 2018.


https://ift.tt/2PZ6dut

USP48 May Be Potential Therapeutic Target in Fanconi Anemia: Inactivation of USP48 reduced chromosomal instability of Fanconi anemia defective cells and highlights a role for this enzyme in controlling DNA repair

American Journal of Medical Genetics Part A, Volume 176, Issue 9, Page 1794-1795, September 2018.


https://ift.tt/2PZ6opD

Table of Contents, Volume 176A, Number 9, September 2018

American Journal of Medical Genetics Part A, Volume 176, Issue 9, Page 1787-1791, September 2018.


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Cover Image, Volume 176A, Number 9, September 2018

American Journal of Medical Genetics Part A, Volume 176, Issue 9, September 2018.


https://ift.tt/2PZ6QnP

Publication schedule for 2018

American Journal of Medical Genetics Part A, Volume 176, Issue 9, Page 1792-1792, September 2018.


https://ift.tt/2O2hehb

In This Issue

American Journal of Medical Genetics Part A, Volume 176, Issue 9, Page 1796-1796, September 2018.


https://ift.tt/2O2hbSx

Better together: A qualitative exploration of women’s perceptions and experiences of group antenatal care

Publication date: Available online 22 September 2018

Source: Women and Birth

Author(s): Louise J. Hunter, Giordana Da Motta, Christine McCourt, Octavia Wiseman, Juliet L. Rayment, Penny Haora, Meg Wiggins, Angela Harden

Abstract

Problem

Childbearing women from socio-economically disadvantaged communities and minority ethnic groups are less likely to access antenatal care and experience more adverse pregnancy outcomes.

Background

Group antenatal care aims to facilitate information sharing and social support. It is associated with higher rates of attendance and improved health outcomes.

Aims

To assess the acceptability of a bespoke model of group antenatal care (Pregnancy Circles) in an inner city community in England, understand how the model affects women's experiences of pregnancy and antenatal care, and inform further development and testing of the model.

Methods

A two-stage qualitative study comprising focus groups with twenty six local women, followed by the implementation of four Pregnancy Circles attended by twenty four women, which were evaluated using observations, focus groups and semi-structured interviews with participants. Data were analysed thematically.

Findings

Pregnancy Circles offered an appealing alternative to standard antenatal care and functioned as an instrument of empowerment, mediated through increased learning and knowledge sharing, active participation in care and peer and professional relationship building. Multiparous women and women from diverse cultures sharing their experiences during Circle sessions was particularly valued. Participants had mixed views about including partners in the sessions.

Conclusions

Group antenatal care, in the form of Pregnancy Circles, is acceptable to women and appears to enhance their experiences of pregnancy. Further work needs to be done both to test the findings in larger, quantitative studies and to find a model of care that is acceptable to women and their partners.

https://ift.tt/2PZ6ayN

Hsa_circ_0008309 May Be a Potential Biomarker for Oral Squamous Cell Carcinoma

Objective. Oral squamous cell carcinoma (OSCC) is the most common cancer of the head and neck region. The circular RNA (circRNA) is known to serve an important role in the carcinogenesis of different types of cancer. However, the circRNA role of OSCC remains unclear. Methods. 8 pairs of OSCC tissues and adjacent normal tissues were obtained to detect circRNAs expression by high-throughput sequencing, and 45 pairs of OSCC tissues were selected to verify the differentially significant circRNAs by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). To further investigate the role of hsa_circ_0008309, the circRNA-microRNA (miR)-mRNA network was predicted using bioinformatics databases. The expression levels of hsa_circ_0008309, miR-1290, miR-136-5P, and miR-382-5P in SCC-15 and CAL27 cell lines were detected by RT-qPCR. Western blotting was performed to detect the protein level of Ataxin 1 (ATXN1). Results. The high-throughput sequencing results demonstrated that circRNAs were abundantly expressed in OSCC, and 16 circRNAs were significantly differentially expressed. Hsa_circ_0008309 was significantly downregulated in 45 pairs of OSCC tissue samples and was statistically correlated with pathological differentiation. The bioinformatics databases suggested that hsa_circ_0008309 could combine with miR-1290, miR-136-5P, and miR-382-5P, respectively, to regulate the expression of ATXN1. It was subsequently identified that hsa_circ_0008309 may inhibit miR-136-5P and miR-382-5P expression and increase ATXN1 expression in the OSCC cell lines. Conclusion. In summary, the results of the present study revealed that OSCC tissues have abundant circRNAs and, to the best of our knowledge, we firstly explore the regulatory role of the hsa_circ_0008309-miR-136-5P/hsa-miR-382-5P-ATXN1 network in OSCC. The results indicated that hsa_circ_0008309 may be a potential biomarker for OSCC.

https://ift.tt/2NuVtqS

Neuropsychiatric Disorder Associated with Group G Streptococcus Infection

Immune-mediated central nervous system manifestations of group A β-hemolytic Streptococcus (GABHS) infection include Sydenham's chorea, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS)—which includes tic and obsessive compulsive disorders—and a variety of neurobehavioral disorders. We report a case of Streptococcus dysgalactiae subspecies equisimilis (group G Streptococcus) (GGS) infection associated with involuntary movements, complex tics, and emotional lability in an 11-year-old Japanese girl. Serum IgM and IgG antibodies to lysoganglioside were positive, and she responded rapidly to intravenous immunoglobulin treatment. Neuropsychiatric disorder associated with GGS infection was ultimately diagnosed. The present findings suggest that neuropsychiatric disorders can result from GGS infection and that the pathogenic mechanism is similar to that of GABHS infection. Future large-scale studies should examine the relation between GGS infection and onset of neuropsychiatric disorder.

https://ift.tt/2OKLiuQ

Five decades of research on mitochondrial NADH-quinone oxidoreductase (complex I)

Journal Name: Biological Chemistry
Issue: Ahead of print


https://ift.tt/2OKCwgv

Influence of the Physical Training on Muscle Function and Walking Distance in Symptomatic Peripheral Arterial Disease in Elderly

Introduction. A typical symptom of chronic lower-limb ischaemia is lower-limb pain, which occurs during walking forcing the patient to stop, intermittent claudication (IC). Exercise rehabilitation is the basic form of treatment for these patients. Aim. The aim of this study was to compare the effectiveness of three types of physical training programmes conducted over a 12-week period in patients with chronic lower-limb arterial insufficiency. Materials and Methods. Ninety-five people qualified for the 3-month supervised motor rehabilitation programme, conducted three times a week. The respondents were assigned to three types of rehabilitation programmes using a pseudo-randomization method: Group I (TW), subjects undertaking treadmill walking training; Group II (NW), subjects undertaking Nordic walking training; Group III (RES+NW), subjects undertaking resistance and Nordic walking training. Treadmill test, 6 Minute Walk Test (6MWT), and isokinetic test were repeated after 3 months of rehabilitation, which 80 people completed. Results. Combined training (RES+NW) is more effective than Nordic walking alone and supervised treadmill training alone for improving ankle force-velocity parameters (p

https://ift.tt/2zoJAdo

Investigating Pathogenic and Hepatocarcinogenic Mechanisms from Normal Liver to HCC by Constructing Genetic and Epigenetic Networks via Big Genetic and Epigenetic Data Mining and Genome-Wide NGS Data Identification

The prevalence of hepatocellular carcinoma (HCC) is still high worldwide because liver diseases could develop into HCC. Recent reports indicate nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NAFLD&NASH) and primary biliary cirrhosis and primary sclerosing cholangitis (PBC&PSC) are significant of HCC. Therefore, understanding the cellular mechanisms of the pathogenesis and hepatocarcinogenesis from normal liver cells to HCC through NAFLD&NASH or PBC&PSC is a priority to prevent the progression of liver damage and reduce the risk of further complications. By the genetic and epigenetic data mining and the system identification through next-generation sequencing data and its corresponding DNA methylation profiles of liver cells in normal, NAFLD&NASH, PBC&PSC, and HCC patients, we identified the genome-wide real genetic and epigenetic networks (GENs) of normal, NAFLD&NASH, PBC&PSC, and HCC patients. In order to get valuable insight into these identified genome-wide GENs, we then applied a principal network projection method to extract the corresponding core GENs for normal liver cells, NAFLD&NASH, PBC&PSC, and HCC. By comparing the signal transduction pathways involved in the identified core GENs, we found that the hepatocarcinogenesis through NAFLD&NASH was induced through DNA methylation of HIST2H2BE, HSPB1, RPL30, and ALDOB and the regulation of miR-21 and miR-122, and the hepatocarcinogenesis through PBC&PSC was induced through DNA methylation of RPL23A, HIST2H2BE, TIMP1, IGF2, RPL30, and ALDOB and the regulation of miR-29a, miR-21, and miR-122. The genetic and epigenetic changes in the pathogenesis and hepatocarcinogenesis potentially serve as potential diagnostic biomarkers and/or therapeutic targets.

https://ift.tt/2PWWk0o

Preserved miR-361-3p Expression Is an Independent Prognostic Indicator of Favorable Survival in Cervical Cancer

In this study, we aimed to assess the independent prognostic value of miR-361-3p in terms of overall survival (OS) and recurrence-free survival (RFS) in cervical cancer, as well as its possible regulative network. A retrospective analysis was performed by using data from the Cancer Genome Atlas-Cervical Cancer (TCGA-CESC). Results showed that decreased miR-361-3p expression was associated with lymphovascular invasion and poor responses to primary therapy. The patients with recurrence and the deceased cases had substantially lower miR-361-3p expression compared to their respective controls. By generating Kaplan-Meier curves of OS and RFS, we found that high miR-361-3p expression was associated with better survival outcome. More importantly, univariate and multivariate analysis confirmed that high miR-361-3p expression was an independent indicator of favorable OS (HR: 0.377, 95% CI: 0.233–0.608, ) and RFS (HR: 0.398, 95% CI: 0.192–0.825, ). By performing bioinformatic analysis, we identified 24 genes that were negatively correlated with miR-361-3p expression. Among the potential targeting genes, SOST, MTA1, TFRC, and YAP1 are involved in some important signaling pathways modulating cervical cancer cell invasion, migration, and drug sensitivity. Therefore, it is meaningful to verify the potential regulative effect of miR-361-3p on the expression of these genes in the future.

https://ift.tt/2O2xjmZ

Chimeric Antigen Receptor T‐Cells: Successful Translation of the First Cell and Gene Therapy From Bench to Bedside

Clinical and Translational Science, EarlyView.


https://ift.tt/2xwyJwy

NYX‐2925, a Novel N‐methyl‐D‐aspartate Receptor Modulator: A First‐in‐Human, Randomized, Double‐blind Study of Safety and Pharmacokinetics in Adults

Clinical and Translational Science, Volume 0, Issue ja, -Not available-.


https://ift.tt/2MXN0Ye

Regulatory B cells in myasthenia gravis are differentially affected by therapies

Annals of Clinical and Translational Neurology, EarlyView.


https://ift.tt/2px7EVS

Psoriasis and Respiratory Comorbidities: The Added Value of Fraction of Exhaled Nitric Oxide as a New Method to Detect, Evaluate, and Monitor Psoriatic Systemic Involvement and Therapeutic Efficacy

Psoriasis is a chronic inflammatory systemic disease characterized by a wide range of comorbidities. Respiratory comorbidities are currently poorly characterized and with discordant results. The systemic state of inflammation caused by psoriasis acts de novo on respiratory tissues and amplifies preexisting inflammation from asthma or chronic obstructive pulmonary disease. Because the lungs act as a gas exchanger between the internal and external environment, the impact of chronic psoriasis inflammation may be easily assessed through the analysis of exhaled breath. The fraction of exhaled nitric oxide test (FeNO) is a potential noninvasive solution that can provide quantitative and qualitative indices of respiratory airway inflammation. FeNO is routinely used to screen and manage asthmatic patients. Recent pilot studies contain encouraging data that underscore its possible use with systemic inflammatory nonpulmonary diseases, such as psoriasis. FeNO may therefore be a useful tool to evaluate underestimated airway inflammation and at the same time globally evaluate the impact of systemically antipsoriatic therapies.

https://ift.tt/2O5WEN1

Violence Experience among Immigrants and Refugees: A Cross-Sectional Study in Italy

The objectives of this cross-sectional investigation among a random sample of immigrants and refugees in Italy were to gain an insight into the extent and type of the episodes of violence and to assess their association with different characteristics. Data was collected from September 2016 to July 2017 using a face-to-face structured interview. A total of 503 subjects participated. Overall, 46.5% and 40% of the sample reported having experienced some form of violence in Italy at least once since they arrived and during the last 12 months. Psychological violence was the most common form experienced by 53.2% of the participants, 40.3% experiencing physical violence, 18.9% economic violence, and only 6.5% intimate partner violence. The risk of experiencing at least one form of violence in the last 12 months in Italy was more likely to occur among immigrants who have been in Italy much longer and less likely in those who lived in a camp. The number of episodes of violence experienced since they arrived in Italy was significantly higher in female, in those who have been in Italy much longer and in those who had experienced at least one racially discriminatory episode of violence, whereas those with middle and high school or above educational level and those who did not experience psychological consequences of the violence had experienced a lower number of episodes. These results must be used to strengthen interventions and policies aimed at preventing violence among this population.

https://ift.tt/2PWK289

A Novel Curcumin-Galactomannoside Complex Delivery System Improves Hepatic Function Markers in Chronic Alcoholics: A Double-Blinded, randomized, Placebo-Controlled Study

Considering the recent interest in free (unconjugated) curcuminoids delivery, the present study investigated the efficacy of a novel food-grade free-curcuminoids delivery system (curcumin-galactomannoside complex; CGM) in improving the hepatic function markers (inflammation and oxidative stress) in chronic alcoholics. The double-blinded, placebo-controlled study randomized 48 subjects with elevated serum transaminases and gamma-glutamyl transferase (GGT) levels, who were allocated to two groups (n=24) and to receive either placebo or CGM at (250 mg × 2)/day for 8 weeks. While liver function markers (transaminases and GGT) in the placebo group showed an increase (~ 9.5%), CGM group indicated a significant decrease in transaminases (31%) and GGT (29%) from the baseline levels. The beneficial effect of CGM was also clear from the significant increase (p

https://ift.tt/2O0yF1O

Reconstruction of Vocal Tract Geometries from Biomechanical Simulations

International Journal for Numerical Methods in Biomedical Engineering, Volume 0, Issue ja, -Not available-.


https://ift.tt/2O25DyF

Genioglossus muscle activity during sniff and reverse sniff in healthy men

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


https://ift.tt/2Dogmj2

Differential expression of HSPs and activation of MAPKs in A549 alveolar epithelial cells exposed to cigarette smoke extract

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


https://ift.tt/2NytTt0

ATP in the lateral hypothalamus/perifornical area enhances the CO2 chemoreflex control of breathing

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


https://ift.tt/2DogiQk

Mechanisms shaping the mutational landscape of the FRA3B/FHIT‐deficient cancer genome

Genes, Chromosomes and Cancer, Volume 0, Issue ja, -Not available-.


https://ift.tt/2I7Aq7U

Effects of low temperature solvent fractionation on the thermal oxidative stability and antioxidant activity of refined hoki oil and its derived fractions

European Journal of Lipid Science and Technology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2DpXYq5

Fatty ester‐based hydroxy carbamates – Synthesis and investigation as lubricant additives

European Journal of Lipid Science and Technology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2NuUiYC

The Biomedical Use of Silk: Past, Present, Future

Advanced Healthcare Materials, EarlyView.


https://ift.tt/2xCWrqf

Hepatitis B Virus Serum DNA and RNA Levels in Nucleos(t)ide Analog‐Treated or Untreated Patients During Chronic and Acute Infection

Hepatology, EarlyView.


https://ift.tt/2PTnDIS

Rituximab Is Ineffective for Treatment of Fatigue in Primary Biliary Cholangitis: A Phase 2 Randomized Controlled Trial

Hepatology, EarlyView.


https://ift.tt/2O5Iv2c

Acute‐on‐Chronic Liver Failure: Getting Ready for Prime Time?

Hepatology, EarlyView.


https://ift.tt/2PTaTSG

CD97 Promotes Tumor Aggressiveness Through the Traditional G Protein–Coupled Receptor–Mediated Signaling in Hepatocellular Carcinoma

Hepatology, EarlyView.


https://ift.tt/2O2PKIt

Assessment of Advanced Liver Fibrosis and the Risk for Hepatic Decompensation in Patients With Congestive Hepatopathy

Hepatology, EarlyView.


https://ift.tt/2PYdnit

Serum Metabolomics Analysis of Asthma in Different Inflammatory Phenotypes: A Cross-Sectional Study in Northeast China

Background and Objective. Asthma as a chronic heterogeneous disease seriously affects the quality of life. Incorrect identification for its clinical phenotypes lead to a huge waste of medical resources. Metabolomic technique as a novel approach to explore the pathogenesis of diseases have not been used to study asthma based on their clear defined inflammatory phenotypes. This study is aimed to distinguish the divergent metabolic profile in different asthma phenotypes and clarify the pathogenesis of them. Methods. Participants including eosinophilic asthmatics (EA, n=13), noneosinophilic asthmatics (NEA, n=16), and healthy controls (HC, n=15) were enrolled. A global profile of untargeted serum metabolomics was identified with Ultra Performance Liquid Chromatography–Mass Spectrometry technique. Results. Multivariate analysis was performed and showed a clear distinction between EA, NEA, and HC. A total of 18 different metabolites were recognized between the three groups based on OPLS-DA model and involved in 10 perturbed metabolic pathways. Glycerophospholipid metabolism, retinol metabolism, and sphingolipid metabolism were identified as the most significant changed three pathways (impact > 0.1 and -log(P) > 4) between the phenotypes. Conclusions. We showed that the different inflammatory phenotypes of asthma involve the immune regulation, energy, and nutrients metabolism. The clarified metabolic profile contributes to understanding the pathophysiology of asthma phenotypes and optimizing the therapeutic strategy against asthma heterogeneity.

https://ift.tt/2I7aCc5

More Frequent Surveillance Following Lung Cancer Resection Is Not Associated With Improved Survival: A Nationally Representative Cohort Study

Objective: To evaluate whether an association exists between the intensity of surveillance following surgical resection for non–small cell lung cancer (NSCLC) and survival. Background: Surveillance guidelines following surgical resection of NSCLC vary widely and are based on expert opinion and limited evidence. Methods: A Special Study of the National Cancer Database randomly selected stage I to III NSCLC patients for data reabstraction. For patients diagnosed between 2006 and 2007 and followed for 5 years through 2012, registrars documented all postsurgical imaging with indication (routine surveillance, new symptoms), recurrence, new primary cancers, and survival, with 5-year follow-up. Patients were placed into surveillance groups according to existing guidelines (3-month, 6-month, annual). Overall survival and survival after recurrence were analyzed using Cox Proportional Hazards Models. Results: A total of 4463 patients were surveilled with computed tomography scans; these patients were grouped based on time from surgery to first surveillance. Groups were similar with respect to age, sex, comorbidities, surgical procedure, and histology. Higher-stage patients received more surveillance. More frequent surveillance was not associated with longer risk-adjusted overall survival [hazard ratio for 6-month: 1.16 (0.99, 1.36) and annual: 1.06 (0.86–1.31) vs 3-month; P value 0.14]. More frequent imaging was also not associated with postrecurrence survival [hazard ratio: 1.02/month since imaging (0.99–1.04); P value 0.43]. Conclusions: These nationally representative data provide evidence that more frequent postsurgical surveillance is not associated with improved survival. As the number of lung cancer survivors increases over the next decade, surveillance is an increasingly important major health care concern and expenditure.

https://ift.tt/2Qqdk08

Metformin inhibits IgE‐ and aryl hydrocarbon receptor‐mediated mast cell activation in vitro and in vivo

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


https://ift.tt/2DxiVzs

The tyrosine kinase inhibitor dasatinib reduces the growth of intracellular Mycobacterium tuberculosis despite impairing T‐cell function

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


https://ift.tt/2Nzgtg4

Inhibition of Ca2+‐activated chloride channel ANO1 suppresses ovarian cancer through inactivating PI3K/Akt signaling

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


https://ift.tt/2NzZFWi

Association between Trichomonas vaginalis and prostate cancer mortality

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


https://ift.tt/2Dole7M

Thyroid Cancer “Epidemic” also Occurs in Low‐ and Middle‐income countries

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


https://ift.tt/2NzZFFM

Effect of an Intrinsically Disordered Plant Stress Protein on the Properties of Water

Dehydrins are plant proteins that are able to protect plants from various forms of dehydrative stress, such as drought, cold, and high salinity. Dehydrins can prevent enzymes from losing activity after freeze/thaw treatments. Previous studies had suggested that the dehydrins function by a molecular shield effect, essentially preventing a denatured enzyme from aggregating with another enzyme. Therefore, the larger the dehydrin, the larger the shield and theoretically the more effective the protection.

https://ift.tt/2xwiHmm

Acoustic Compressibility of Caenorhabditis elegans

The acoustic compressibility of Caenorhabditis elegans is a necessary parameter for further understanding the underlying physics of acoustic manipulation techniques of this widely used model organism in biological sciences. In this work, numerical simulations were combined with experimental trajectory velocimetry of L1 C. elegans larvae to estimate the acoustic compressibility of C. elegans. A method based on bulk acoustic wave (BAW) acoustophoresis was used for trajectory velocimetry experiments in a microfluidic channel.

https://ift.tt/2xAveW5

Stabilizing Effect of Inherent Knots on Proteins Revealed by Molecular Dynamics Simulations

A growing number of proteins are identified to be knotted in their native structures, with such entangled topological feature being expected to play stabilizing roles maintaining both the global fold and the nature of proteins. However, the molecular mechanism underlying the stabilizing effect is ambiguous. Here, we combine unbiased and mechanical atomistic molecular dynamics (MD) simulations to investigate how a protein is stabilized by an inherent knot by directly comparing chemical, thermal and mechanical denaturing properties of two proteins having the same sequence and secondary structures but differing in the presence or absence of an inherent knot.

https://ift.tt/2MVLsxH