Detection and typing of molluscum contagiosum virus in skin lesions by using a simple lysis method and polymerase chain reaction

A polymerase chain reaction (PCR) assay for the rapid detection and typing of molluscum contagiosum virus (MCV) was developed. The target DNA was a 393 base pair (bp) segment, which is present in the coding region of the MCV p43K gene product. Release of MCV DNA from skin lesions was performed by using a simple procedure that provided suitable template DNA for amplification, and allowed detection of MCV directly in clinical material. The PCR yielded a unique 393 bp product when MCV DNA was used as template. This product was not shown with DNA from other viruses and bacterial pathogens causing skin diseases. The specific PCR product was obtained with individual lesions from all patients clinically diagnosed with MCV infection, whereas no products were detected with skin samples from healthy individuals. Sequencing of this PCR product allowed determination of the virus subtype on the basis of previously described nucleotide differences between subtypes MCVI and MCVII. To avoid the sequencing process, a second PCR assay was developed, in which the target DNA sequence included a MCVI-specific recognition site for the restriction endonuclease BamHI. This PCR assay yielded a unique 575 bp product with lesions from either MCVI- or MCVII-infected patients. However, only the MCVI-derived product was susceptible to BamHI digestion, which generated two fragments of 291 and 284 bp, respectively. Amplification of specific MCV DNA sequences from single, individual lesions provides a sensitive and reliable method for laboratory diagnosis and molecular epidemiology studies of molluscum contagiosum. © 1996 Wiley-Liss, Inc.     

A randomized,multicenter trial assessing the effects of rapastinel compared to ketamine,alprazolam, and placebo on simulated driving performance

N‐methyl‐D‐aspartate ionotropic glutamatergic receptor (NMDAR) modulators, including rapastinel and ketamine, elicit rapid and sustained antidepressant responses in patients with treatment‐resistant major depressive disorder. This phase I, randomized, multicenter, placebo‐controlled, five‐period, crossover, single‐dose study evaluated simulated driving performance of healthy participants (N = 107) after single doses of rapastinel slow intravenous (i.v.) bolus 900 and 1800 mg, alprazolam oral 0.75 mg (positive control), ketamine i.v. infusion 0.5 mg/kg (clinical comparator), and placebo ~ 45 min before driving. The primary end point was SD of lateral position (SDLP) during the 60‐min 100‐km simulated driving scenario. Additional measures of driving performance, sleepiness, and cognition were also evaluated. To assess effects over time, mean SDLP was calculated for each 10‐min interval of driving. Sensitivity of the assays was confirmed with alprazolam (all placebo comparisons p < 0.02). Rapastinel 900 and 1800 mg did not significantly affect simulated driving performance compared to placebo (both p > 0.5). Both rapastinel doses resulted in significantly less impaired driving compared to alprazolam or ketamine (all p < 0.002); ketamine significantly impaired driving compared to placebo (p = 0.0001). Results for the additional measures were similar to the primary end point. No new safety signals were observed for any study interventions. This first study of rapastinel effects on simulated driving found that rapastinel 900 and 1800 mg did not impair driving performance, but ketamine 0.5 mg/kg resulted in significantly impaired driving performance. Ketamine’s effects on driving were maintained for at least 105 min, indicating that clinicians should be vigilant to prevent or postpone driving in patients after ketamine treatment.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Prior to this current study, the effects of rapastinel, an N‐methyl‐D‐aspartate ionotropic glutamatergic receptor (NMDAR) modulator, on driving performance were unknown. Ketamine, a current treatment for major depressive disorder, also an NMDAR modulator, has previously been shown to impair driving. Its effects have not been investigated in a large placebo‐controlled randomized control trial or over multiple time points following dosing.

• WHAT QUESTION DID THIS STUDY ADDRESS?

What are the effects of rapastinel compared to placebo and ketamine on driving performance and driving‐related measures?

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

This is the first study investigating the effects of rapastinel on driving performance that showed single doses of rapastinel (900 or 1800 mg) did not impair driving performance or affect driving‐related measures compared to placebo. An i.v. infusion of ketamine 0.5 mg/kg impaired driving and related measures for up to 105 min following dosing when compared to placebo, rapastinel 900 mg, and rapastinel 1800 mg.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

Clinicians will become aware of the risk of impaired driving in patients treated with ketamine.     

Surgical management of Ebstein anomaly: impact of the adult congenital heart disease anatomical and physiological classifications

OBJECTIVESOur goal was to evaluate the impact of the adult congenital heart disease anatomical and physiological (ACHD AP) classification system on the surgical management of Ebstein anomaly (EA) in adult patients.METHODSFrom February 2000 through August 2017, data of patients aged at least 16 years, who underwent primary EA surgery, were retrospectively evaluated. The cohort was divided in 2 groups according to their ACHD AP classification: the moderate EA group (IIB, IIC) and the severe EA group (IID). Survival, freedom from reoperation and freedom from occurrence of major adverse advents were estimated.Open in a separate windowRESULTSThere were 33 patients (21 women, 12 men). Eighteen belonged to the moderate group, 15 to the severe group. There were 12 female patients (80%) in the severe group. Patients in the moderate group were younger than those in the severe group (P = 0.02): 32 ± 12 vs 44 ± 15 years old. Thirty tricuspid valve repairs and 3 replacements were performed. Repair was mainly performed in the moderate group (P = 0.02). Overall survival was 90.1 ± 5.4% at 9 months after the operation and did not change in the later follow-up period. It was 100% for patients in the moderate group and 80.0 ± 10.3% in the severe group (P = 0.07), and 75.0 ± 12.5% for female patients of in the severe group compared to 100% for the remaining patients (P = 0.025). Survival free from major adverse events, including reoperation, at 10 years was 60.0 ± 12.6% in the moderate and 38.1% ± 12.9% in the severe group (P = 0.03). No patient in the moderate group evolved to be in the severe group at late follow-up.CONCLUSIONAdult EA patients should undergo surgery earlier when they are still in the moderate ACHD AP classification.     

Therapeutic effect of recombinant vaccinia virus expressing the 60-kd heat-shock protein on adjuvant arthritis

Objective. To analyze the effects of recombinant viruses for 2 heat-shock proteins in the treatment of adjuvant arthritis. Methods. Virus vaccinia recombinant for mycobacterial heat-shock protein 65 (hsp65-VV) and human hsp60 (hsp60-VV) were administered to rats during different stages of adjuvant arthritis. Arthritis score and immunity to the recombinant virus were analyzed. Results. When delivered at the pre-arthritis stage, both constructs ameliorated arthritis; greater protection was observed with hsp60-VV. A specific T cell response to the recombinant proteins was detected. Furthermore, hsp60-VV displayed a clear therapeutic effect on established arthritis. Conclusion. Our results suggest novel avenues of therapeutic intervention in autoimmune arthritis associated with immunity to hsp60.     

Colonic Microbiota Profile Characterization of the Responsiveness to Dietary Fibre Treatment in Hypercholesterolemia

This study aimed to determine how the microbiota profile might be predisposed to a better response in blood lipid profiles due to dietary fibre supplementation. A three-arm intervention study that included three different fibre types (mainly insoluble, soluble, and antioxidant fibre) supplemented (19.2 g/day) during 2 months in individuals with hypercholesterolemia was developed. Changes in faecal microbiota and blood lipid profile after fibre supplementation were determined. In all volunteers, regardless of fibre type, an increase in the abundance of Bifidobacterium was observed, and similarly, an inverse relationship between faecal propionic acid and blood LDL-cholesterol, LDL particle size, and LDL/HDL particle ratio (p-values 0.0067, 0.0002, and 0.0067, respectively) was observed. However, not all volunteers presented an improvement in lipid profile. The non-responders to fibre treatment showed a decrease in microbiota diversity (Shannon and Simpson diversity index p-values of 0.0110 and 0.0255, respectively) after the intervention; where the reduction in short-chain fatty acids (SCFAs) producing bacterial genera such as Clostridium XIVa and Ruminococcus after dietary fibre treatment was the main difference. It was concluded that the non-responsiveness to dietary fibre treatment might be mediated by the lack of ability to maintain a stable SCFA producing bacteria diversity and composition after extra fibre intake.     

Exogenous hormone use and cutaneous melanoma risk in women: The European Prospective Investigation into Cancer and Nutrition

Evidence suggests an influence of sex hormones on cutaneous melanoma risk, but epidemiologic findings are conflicting. We examined the associations between use of oral contraceptives (OCs) and menopausal hormone therapy (MHT) and melanoma risk in women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Information on exogenous hormone use at baseline was derived from country-specific self-administered questionnaires. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over 1992–2015, 1,696 melanoma cases were identified among 334,483 women, whereof 770 cases among 134,758 postmenopausal women. There was a positive, borderline-significant association between OC use and melanoma risk (HR = 1.12, 95% CI = 1.00–1.26), with no detected heterogeneity across countries (p_homogeneity = 0.42). This risk increased linearly with duration of use (p_trend = 0.01). Among postmenopausal women, ever use of MHT was associated with a nonsignificant increase in melanoma risk overall (HR = 1.14, 95% CI = 0.97–1.43), which was heterogeneous across countries (p_homogeneity = 0.05). Our findings do not support a strong and direct association between exogenous hormone use and melanoma risk. In order to better understand these relations, further research should be performed using prospectively collected data including detailed information on types of hormone, and on sun exposure, which may act as an important confounder or effect modifier on these relations.     

Theoretical potential for endometrial cancer prevention through primary risk factor modification: Estimates from the EPIC cohort

Endometrial cancer (EC) incidence rates vary ~10-fold worldwide, in part due to variation in EC risk factor profiles. Using an EC risk model previously developed in the European EPIC cohort, we evaluated the prevention potential of modified EC risk factor patterns and whether differences in EC incidence between a European population and low-risk countries can be explained by differences in these patterns. Predicted EC incidence rates were estimated over 10 years of follow-up for the cohort before and after modifying risk factor profiles. Risk factors considered were: body mass index (BMI, kg/m²), use of postmenopausal hormone therapy (HT) and oral contraceptives (OC) (potentially modifiable); and, parity, ages at first birth, menarche and menopause (environmentally conditioned, but not readily modifiable). Modeled alterations in BMI (to all ≤23 kg/m²) and HT use (to all non-HT users) profiles resulted in a 30% reduction in predicted EC incidence rates; individually, longer duration of OC use (to all ≥10 years) resulted in a 42.5% reduction. Modeled changes in not readily modifiable exposures (i.e., those not contributing to prevention potential) resulted in ≤24.6% reduction in predicted EC incidence. Women in the lowest decile of a risk score based on the evaluated exposures had risk similar to a low risk countries; however, this was driven by relatively long use of OCs (median = 23 years). Our findings support avoidance of overweight BMI and of HT use as prevention strategies for EC in a European population; OC use must be considered in the context of benefits and risks.     

Subclinical affective and cognitive fluctuations in Parkinson's disease: a randomized double-blind double-dummy study of Oral vs. Intrajejunal Levodopa

Journal of Neurology - Chronic levodopa treatment in Parkinson’s disease (PD) may promote undesirable motor and non-motor fluctuations. Compared to chronic oral levodopa treatment, continuous...     

The effect of chronic neuroglycopenia on resting state networks in GLUT1 syndrome across the lifespan

Glucose transporter type I deficiency syndrome (GLUT1DS) is an encephalopathic disorder due to a chronic insufficient transport of glucose into the brain. PET studies in GLUT1DS documented a widespread cortico‐thalamic hypometabolism and a signal increase in the basal ganglia, regardless of age and clinical phenotype. Herein, we captured the pattern of functional connectivity of distinct striatal, cortical, and cerebellar regions in GLUT1DS (10 children, eight adults) and in healthy controls (HC, 19 children, 17 adults) during rest. Additionally, we explored for regional connectivity differences in GLUT1 children versus adults and according to the clinical presentation. Compared to HC, GLUT1DS exhibited increase connectivity within the basal ganglia circuitries and between the striatal regions with the frontal cortex and cerebellum. The excessive connectivity was predominant in patients with movement disorders and in children compared to adults, suggesting a correlation with the clinical phenotype and age at fMRI study. Our findings highlight the primary role of the striatum in the GLUT1DS pathophysiology and confirm the dependency of symptoms to the patients' chronological age. Despite the reduced chronic glucose uptake, GLUT1DS exhibit increased connectivity changes in regions highly sensible to glycopenia. Our results may portrait the effect of neuroprotective brain strategy to overcome the chronic poor energy supply during vulnerable ages.