Safety and immunogenicity of fully liquid and lyophilized formulations of an investigational trivalent group B streptococcus vaccine in healthy non-pregnant women: Results from a randomized comparative phase II trial.

Background: We evaluated the safety and immunogenicity of liquid and lyophilized formulations of an investigational trivalent group B streptococcus (GBS) vaccine in non-pregnant women and assessed the formulations' equivalence in terms of serotype-specific immune response.

Methods: This phase II, randomized, comparative, observer-blind trial enrolled healthy non-pregnant women 18-40 years of age. Women received a single dose of fully liquid (n = 529) or lyophilized (n = 521) trivalent GBS vaccine on day 1.

The Mechanism of Action of Ethoxidol on Oxidative Stress Indices in Heart Failure and Hypotension.

Unlabelled: was to study the effect of 2-ethyl-6-methyl-3-hydroxypyridine malate (Ethoxidol) on the concentration of oxidative stress metabolites in patients with chronic heart failure (CHF) and hypertension.

Materials And Methods: 126 patients with FC I-III CHF have been examined. In addition to their individual therapy these patients received intravenous infusions of Ethoxidol.

The role of acetylsalicylic acid and circulating microRNAs in primary prevention of cardiovascular events in patients with Diabetes Mellitus Type 2 - A Review.

Introduction: Type 2 diabetes mellitus (T2DM) is a common metabolic disorder, which carries a risk for atherosclerosis and cardiovascular impairment. The purpose of this review is to demonstrate the role of acetylsalicylic acid (ASA) in primary cardiovascular prevention in T2DM patients, as well as present an outline of microRNAs (miRNA) relevant to ASA therapy and should be evaluated as targets to improve treatment.

Brief Description Of State Of Knowledge: Although the etiology of hypercoagulable state in T2DM is considered multifactorial, attention mainly focuses on platelet disturbances.

Management of neuropathic pain induced by surgery: Review of the literature by a group of experts specialized in pain management, anesthesia and surgery.

Chronic postsurgical neuropathic pain (CPSNP) is frequent. While prevalence varies considerably according to type of operation and means of evaluation, it can reach 37% following breast surgery. Identification of risk factors related to the procedure and to the patient and taking into account the development of new, minimally invasive surgical techniques is increasingly nerve-sparing and reduces the likelihood of injury.

Criterion-related validity in a sample of migraine outpatients: the diagnostic criteria for psychosomatic research.

Objective: The Diagnostic Criteria for Psychosomatic Research (DCPR) are those of psychosomatic syndromes that did not find room in the classical taxonomy. More recently, the DCPR were updated, called DCPR-revised (DCPR-R). The present study was conducted to test the criterion-related validity of the DCPR-R.

Endothelial Response to Pathophysiological Stress.

Located in the innermost layer of the vasculature and directly interacting with blood flow, endothelium integrates various biochemical and biomechanical signals to maintain barrier function with selective permeability, vascular tone, blood fluidity, and vascular formation. Endothelial cells respond to laminar and disturbed flow by structural and functional adaption, which involves reprogramming gene expression, cell proliferation and migration, senescence, autophagy and cell death, as well as synthesizing signal molecules (nitric oxide and prostanoids, etc) that act in manners of autocrine, paracrine, or juxtacrine. Inflammation occurs after infection or tissue injury.

[Aortic valve degenerative disease with patent ductus arteriosus infective endocarditis: A case report].

Infective endocarditis (IE) refers to the pathogenic microbial infect the endocardium, valves or intima adjacent to the cardiac arteries through the bloodstream with the formation of vegetations. Valves are the most frequently affected sites. Here, we described a 49-year-old female, who admitted to respiratory outpatient department in the Third Xiangya Hospital, Central South University for long time of fever.

Phase 1 Clinical Trial of a Conditionally Replication-Defective Human Cytomegalovirus (CMV) Vaccine in CMV-Seronegative Subjects.

Background: A conditionally replication-defective human cytomegalovirus (CMV) vaccine (V160) derived from AD169 and genetically engineered to express CMV pentameric complex (gH/gL/pUL128/pUL130/pUL131) was developed and evaluated for phase 1 vaccine safety and immunogenicity in CMV-seronegative and CMV-seropositive adults.

Methods: Subjects received 3 doses of V160 or placebo on day 1, month 1, and month 6. Four vaccine dose levels, formulated with or without aluminum phosphate adjuvant, were evaluated.

Development of a simultaneous quantitation for short-, medium-, long-, and very long-chain fatty acids in human plasma by 2-nitrophenylhydrazine-derivatization and liquid chromatography-tandem mass spectrometry.

Fatty acids (FA) have been important in clinical diagnosis for long, which makes the increasing need for a fast, reliable, and economic approach to determine FA of short-, medium-, long-, and very long-chain by widely available equipment and with high-throughput capacity. In the present work, 2‑nitrophenylhydrazine derivatization coupling with LC-MS/MS detection was utilized to simultaneously quantitate 18 FAs ranging from C4 to C26 in human plasma. The sample preparation protocol was optimized and extracting with diethyl ether‑potassium phosphate buffer twice was found as the highest efficiency along with economic feasibility.

Catheter-Based Renal Denervation Attenuates Kidney Interstitial Fibrosis in a Canine Model of High-Fat Diet-Induced Hypertension.

Background/aims: Catheter-based renal denervation (RDN) has emerged as an innovative interventional approach for reducing blood pressure (BP), suppressing ventricular substrate remodeling, and attenuating heart failure, which suggests that it might reduce kidney fibrosis in a canine model of high-fat diet-induced hypertension. This study thus sought to assess whether RDN could reduce kidney fibrosis and halt the progression of renal impairment in a canine model of high-fat diet-induced hypertension.

Methods: Thirty-two beagles were randomized into either the normal control group (normal diet, n = 10) or the hypertension group (high-fat diet, n = 22).

Pharmacokinetics of Sublingual Buprenorphine Tablets Following Single and Multiple Doses in Chinese Participants With and Without Opioid Use Disorder.

Background: Two phase I studies assessed the pharmacokinetics of buprenorphine, its metabolite norbuprenorphine, and naloxone following administration of buprenorphine/naloxone sublingual tablets in Chinese participants.

Methods: In the first phase I, open-label, single ascending-dose (SAD) study, 82 opioid-naïve volunteers received a single buprenorphine/naloxone dose ranging from 2 mg/0.5 mg to 24 mg/6 mg while under naltrexone block.

Investigation into attitudes toward epilepsy among non-/neurological doctors and nurses in southern China.

Purpose: To assess attitudes concerning epilepsy among non-/neurological medical personnel from basic-level hospitals in southern China and identify significant predictive factors for future stigma reduction interventions.

Method: The Chinese Public Attitudes Toward Epilepsy (CPATE) scale was administered to 184 neurological and 264 non-neurological medical staff members from basic-level hospitals in southern China. Positively stated items in the PATE scale were reversely scored; in this case, a higher score would indicate a more negative attitude.

No Effect of Digoxin on Rosuvastatin Pharmacokinetics in Healthy Subjects: Utility of Oita Combination for Clinical Drug-Drug Interaction Study.

This study evaluated the utility of combination of digoxin (0.25 mg) and rosuvastatin (5 mg) as a new transporter (P-glycoprotein/breast cancer resistance protein/organic anion-transporting polypeptide (OATP)1B1/OATP1B3) probe cocktail (Oita combination) for drug-drug interaction (DDI) studies by demonstrating lack of DDI of digoxin on the pharmacokinetics (PKs) of rosuvastatin, as it was already known that rosuvastatin did not affect digoxin PK. This was an open-label, two-period study in which the primary end points were the geometric mean ratio (GMR) of the area under the plasma rosuvastatin concentration-time curve from time zero to last (AUC ) after rosuvastatin administration combined with digoxin to that after rosuvastatin administration alone and its 90% confidence interval (CI).

Histological evaluation of nintedanib in non-alcoholic steatohepatitis mice.

Aims: In addition to potentially progressing to either cirrhosis or hepatocellular carcinoma, non-alcoholic steatohepatitis (NASH) is currently the leading indication for liver transplantation. Nintedanib has been clinically used to treat idiopathic pulmonary fibrosis for many years, but its effects in an animal model of NASH have not been tested. The purpose of this study was to evaluate the effects of nintendanib on NASH in choline-deficient, l-amino acid-defined, high-fat diet (CDAHFD)-fed mice.

The cyclooxygenase-1/mPGES-1/endothelial prostaglandin EP4 receptor pathway constrains myocardial ischemia-reperfusion injury.

The use of nonsteroidal anti-inflammatory drugs that inhibit cyclooxygenase (COX)-1 and COX-2, increases heart failure risk. It is unknown whether microsomal (m) prostaglandin (PG) E synthase (S)-1, a target downstream of COX, regulates myocardial (M) ischemia/reperfusion (I/R) injury, a key determinant of heart failure. Here we report that COX-1 and mPGES-1 mediate production of substantial amounts of PGE and confer cardiac protection in MI/R.

Marsdenia tenacissima extract dilated small mesenteric arteries via stimulating endothelial nitric oxide synthase and inhibiting calcium influx.

Ethnopharmacological Relevance: Marsdenia tenacissima is a traditional Chinese medicine that is known to be effective in combating cancer as well as reducing blood pressure. The efficacy and mechanisms of Marsdenia tenacissima in treating cancer have been well described. However, the potential vasoactivities of Marsdenia tenacissima remain poorly known.

Sirolimus and mTOR Inhibitors: A Review of Side Effects and Specific Management in Solid Organ Transplantation.

Inhibitors of mechanistic target of rapamycin (mTOR inhibitors) are used as antiproliferative immunosuppressive drugs and have many clinical applications in various drug combinations. Experience in transplantation studies has been gained regarding the side effect profile of these drugs and the potential benefits and limitations compared with other immunosuppressive agents. This article reviews the adverse effects of mTOR inhibitors in solid organ transplantation, with special attention given to mechanisms hypothesized to cause adverse events and their management strategies.

Mental Pain Questionnaire: An item response theory analysis.

Background: The Mental Pain Questionnaire (MPQ) is a self-report questionnaire developed to assess mental pain. The aim of the present study was to test the clinimetric properties of the MPQ.

Methods: A sample of 200 migraine outpatients were enrolled; homogeneity of MPQ was assessed by Mokken Analysis; item-level severity and item-level sensitivity were calculated via Two-Parameter Logistic model; Total Information Function was evaluated to assess reliability of MPQ; internal consistency was calculated via Cronbach's alpha and Sijtsma and Molenaar rho; sensitivity and specificity were assessed via Receiver Operating Characteristic curves.

Modeling and Simulation of GAT1: A Mechanistic Investigation of the GABA Transport Process.

Human γ-Aminobutyric acid transporter 1 (GAT1) is a Na/Cl dependent co-transporter that plays a key role in the inhibitory neurotransmission of GABA in the brain. Due to the lack of structural data, the exact co-transport mechanism of GABA reuptake by GAT1 remains unclear. To examine the roles of the co-transport ions and the nature of their interactions with GABA, homology modeling and molecular dynamics simulations of the GAT1 in the open-to-out conformation were carried out.

Protocol and methods for testing the efficacy of well-being therapy in chronic migraine patients: a randomized controlled trial.

Background: Chronic migraine is a chronic medical condition associated with resistance to pharmacological treatment and poor benefits from the psychological interventions studied to date, including acceptance and commitment therapy or mindfulness. This manuscript describes the rationale and methods for a pilot feasibility study designed to (1) establish and (2) evaluate the feasibility and acceptability of research procedures and interventions to investigate whether well-being therapy improves outcomes relative to a control condition.

Methods: The current intervention will use a randomized controlled trial design, wherein 30 outpatients with chronic migraine will be randomized (1:1) to well-being therapy (n = 15) or to a control condition (n = 15).

Clinical Drug-Drug Interaction Potential of BFE1224, Prodrug of Antifungal Ravuconazole, Using Two Types of Cocktails in Healthy Subjects.

BFE1224, prodrug of ravuconazole, is a novel, once-daily, oral, triazole antifungal drug, and currently in development for the treatment of onychomycosis. The clinical drug-drug interaction (DDI) potential of BFE1224 with cytochrome P450 (CYP) and transporter was assessed by using two types of cocktails in healthy subjects in separate clinical studies. The CYP and transporter cocktails consisted of caffeine/tolbutamide/omeprazole/dextromethorphan/midazolam used in study 1 and digoxin/rosuvastatin used in study 2.

The Effect of Molecular Structure on Cytotoxicity and Antitumor Activity of PEGylated Nanomedicines.

Fundamental studies on the cellular uptake and drug release of PEGylated nanomedicines are beneficial to understand their fate in vivo and construct ideal nanoparticle formulations. In this work, the detailed metabolic process of PEGylated doxorubicin (Dox) nanomedicines were investigated via confocal laser scanning microscopy (CLSM), flow cytometry (FCM), cytotoxicity test, fluorescence imaging in vivo (FLIV) and liquid chromatography tandem mass spectrometry (LC-MS/MS). Among them, only LC-MS/MS could accurately determine the content of PEGylated Dox and Dox in vitro and in vivo.

Protective Role of mPGES-1 (Microsomal Prostaglandin E Synthase-1)-Derived PGE (Prostaglandin E) and the Endothelial EP4 (Prostaglandin E Receptor) in Vascular Responses to Injury.

Objective: Deletion of mPGES-1 (microsomal prostaglandin E synthase-1)-an anti-inflammatory target alternative to COX (cyclooxygenase)-2-attenuates injury-induced neointima formation in mice. This is attributable to the augmented levels of PGI (prostacyclin)-a known restraint of the vascular response to injury, acting via IP (I prostanoid receptor). To examine the role of mPGES-1-derived PGE (prostaglandin E) in vascular remodeling without the IP.