Rejected

Bile acids are a large family of atypical steroids which exert their functions by binding to a family of ubiquitous cell membrane and nuclear receptors. There two receptors, FXR and GPBAR1, that are exclusively activated by bile acids while other receptors RORγT, S1PR2, CAR, LXRs, PXR and VDR are activated by bile acids in addition to other more selective endogenous ligands. In the intestine, activation of FXR and GPBAR1 promotes the release of FGF15/19 and GLP1 which integrate their signaling with direct effects exerted by the two receptors in target tissues. This network is tuned in a time ordered manner by circadian rhythm and is critical for the regulation of metabolic process including autophagy, fast-to-feed transition, lipid and glucose metabolism, energy balance and immune responses. In the last decade FXR ligands have entered clinical trials but development of systemic FXR agonists has been proven challenging because their side effects including increased levels of cholesterol and Low Density Lipoproteins cholesterol (LDL-c) and reduced High-Density Lipoprotein cholesterol (HDL-c). In addition, pruritus has emerged as a common, dose related, side effect of FXR ligands. Intestinal-restricted FXR and GPBAR1 agonists and dual FXR/GPBAR1 agonists have been developed. Here we review the last decade in bile acids physiology and pharmacology.

The CDC Guideline for Prescribing Opioids for Chronic Pain cautioned against high dose prescribing but did not provide guidance on type of opioid for new pain episodes. We determined if new prescriptions for Schedule II opioids vs. tramadol decreased in the 18 months after vs. before the CDC guideline and if this decrease was associated with physician specialty. New opioid prescriptions, provider type and covariates were measured using a nationally distributed, Optum® de-identified Electronic Health Record (EHR) data base. Eligible patients were free of cancer and HIV and started a new prescription for Schedule II opioids (i.e. codeine, hydrocodone, oxycodone) or Schedule IV (tramadol) in the 18 months before (n = 141,219) or 18 months after (n = 138,216) guideline publication. Fully adjusted multilevel multinomial models estimated the association between provider type (anesthesiology/pain medicine, surgical specialty, emergency, hospital, primary care, other specialty and unknown) before and after adjusting for covariates. New oxycodone prescriptions were most common among surgical and anesthesia/pain management, and new tramadol prescriptions were most common in primary care. The greatest decreases in odds of a Schedule II opioid vs. tramadol were observed in emergency care (oxycodone vs. tramadol OR = 0.82; 95%CI:0.76-0.88) and primary care (hydrocodone vs. tramadol OR = 0.85; 95%CI:0.81-0.89). Surgical specialists were least likely to start opioid therapy with tramadol. In the 18 months after vs. before the CDC guideline, emergency care and primary care providers increased tramadol prescribing. Guidelines tailored to specialists that frequently begin opioid therapy with oxycodone may enhance safe opioid prescribing.

Numerous evidence indicates that hyperglycemia is a pivotal driver of the vascular complications of diabetes. However, the mechanisms of hyperglycemia-induced endothelial dysfunction in diabetes remain incompletely understood. This study aims to expound on the underlying mechanism of the endothelial dysfunction induced by hyperglycemia from the perspective of long non-coding RNAs (lncRNA).

The use of electroconvulsive therapy (ECT) in children and adolescents is based on a limited evidence base in the medical literature. We report outcomes of a cohort of youth treated with ECT at a single US academic medical center.

Cerebral venous sinus thrombosis(CVST) is considered to be a rare, high-risk, easily misdiagnosed disease with a mortality rate of 9.4%. Early diagnosis and timely anticoagulant thrombolytic therapy can reduce the mortality and disability rate and improve the prognosis of patients. This report describes the situation of a young male patient with bilateral tonsillectomy who, after going under low temperature plasma and general anesthesia surgery, presented with headache on the 4th day after the operation, and was diagnosed to be CVST by computed tomography(CT) and Magnetic Resonance Imaging(MRI). Due to severe pharynx swallowing pain after the surgery, his total daily intake was less than 2000 ml. After treatment, his prognosis was optimistic. The rarity and high risk of CVST after tonsillectomy suggest that we should pay attention to the related problems in the perioperative management of tonsillectomy include Bacterial infections, high condensation state of dehydration, using hemostatic drugs sparingly, etc.

Effective and sustained perioperative analgesia in thoracic surgery and pulmonary resection is beneficial to patients by reducing both postoperative pulmonary complications and the incidence of chronic pain. In this review, the indication of thoracic epidural anaesthesia in video- (VATS) and robotic-assisted (RATS) thoracoscopy shall be critically objectified and presented in a differentiated way.

(1) Background: internal jugular vein thrombosis (IJVthr) is a potentially life-threating disease but no comprehensive reviews on etiology, symptomatology, diagnosis and current treatment guidelines are yet available; (2) Methods: we prospectively developed a protocol that defined objectives, search strategy for study identification, criteria for study selection, data extraction, study outcomes, and statistical methodology, according to the PRISMA standard. We performed a computerized search of English-language publications listed in the various electronic databases. We also retrieved relevant reports from other sources, especially by the means of hand search in the Glauco Bassi Library of the University of Ferrara; (3) Results: using the predefined search strategy, we retrieved and screened 1490 titles. Data from randomized control trials were few and limited to the central vein catheterization and to the IJVthr anticoagulation treatment. Systematic reviews were found just for Lemierre syndrome, the risk of pulmonary embolism, and the IJVthr following catheterization. The majority of the information required in our pre-defined objectives comes from perspectives observational studies and case reports. The methodological quality of the included studies was from moderate to good. After title and abstract evaluation, 1251 papers were excluded, leaving 239 manuscripts available. Finally, just 123 studies were eligible for inclusion. We found out the description of 30 different signs, symptoms, and blood biomarkers related to this condition, as well as 24 different reported causes of IJVthr. (4) Conclusions: IJVthr is often an underestimated clinical problem despite being one of the major sources of pulmonary embolism as well as a potential cause of stroke in the case of the upward propagation of the thrombus. More common symptoms are neck pain and headache, whereas swelling, erythema and the palpable cord sign beneath the sternocleidomastoid muscle, frequently associated with fever, are the most reported clinical signs. An ultrasound of the neck, even limited to the simple and rapid assessment of the compression maneuver, is a quick, economic, cost-effective, noninvasive tool. High quality studies are currently lacking.

Important policy developments in dementia and palliative care in nursing homes between 2010 and 2015 in Flanders, Belgium might have influenced which people die in nursing homes and how they die. We aimed to examine differences between 2010 and 2015 in the prevalence and characteristics of residents with dementia in nursing homes in Flanders, and their palliative care service use and comfort in the last week of life. We used two retrospective epidemiological studies, including 198 residents in 2010 and 183 in 2015, who died with dementia in representative samples of nursing homes in Flanders. We found a 15%-point increase in dementia prevalence (-value < 0.01), with a total of 11%-point decrease in severe to very severe cognitive impairment ( = 0.04). Controlling for residents' characteristics, in the last week of life, there was an increase in the use of pain assessment (+20%-point; < 0.03) but no change in total comfort. The higher prevalence of dementia in nursing homes with no change in residents' total comfort while dying emphasizes an urgent need to better support nursing homes in improving their capacities to provide timely and high-quality palliative care services to more residents dying with dementia.

This study was undertaken at the Department of Obstetrics and Gynaecology of the Charlotte Maxeke Johannesburg Academic Hospital to determine if the use of formal guidelines and a standardised surgical technique would increase the rate of vaginal hysterectomy (VH) and result in an overall decline in open abdominal hysterectomy (AH).