Derivatives of the Mouse Cathelicidin-Related Antimicrobial Peptide (CRAMP) Inhibit Fungal and Bacterial Biofilm Formation

We identified a 26-amino-acid truncated form of the 34-amino-acid cathelicidin-related antimicrobial peptide (CRAMP) in the islets of Langerhans of the murine pancreas. This peptide, P318, shares 67% identity with the LL-37 human antimicrobial peptide. As LL-37 displays antimicrobial and antibiofilm activity, we tested antifungal and antibiofilm activity of P318 against the fungal pathogen Candida albicans. P318 shows biofilm-specific activity as it inhibits C. albicans biofilm formation at 0.15 μM without affecting planktonic survival at that concentration. Next, we tested the C. albicans biofilm-inhibitory activity of a series of truncated and alanine-substituted derivatives of P318. Based on the biofilm-inhibitory activity of these derivatives and the length of the peptides, we decided to synthesize the shortened alanine-substituted peptide at position 10 (AS10; KLKKIAQKIKNFFQKLVP). AS10 inhibited C. albicans biofilm formation at 0.22 μM and acted synergistically with amphotericin B and caspofungin against mature biofilms. AS10 also inhibited biofilm formation of different bacteria as well as of fungi and bacteria in a mixed biofilm. In addition, AS10 does not affect the viability or functionality of different cell types involved in osseointegration of an implant, pointing to the potential of AS10 for further development as a lead peptide to coat implants.     

Determinants of survival after aortic valve replacement as treatment for symptomatic aortic valve disease in the elderly

BACKGROUND AND AIM OF THE STUDY: The effect of concurrent disease and cardiac comorbidity on survival after bioprosthetic valve replacement in elderly patients was assessed retrospectively. Risk factors were categorized as general, non-cardiac (age, diabetes, previously treated carcinoma) and cardiac (LVEF, three-vessel disease, previous CABG or valve replacement, and endocarditis). METHODS: A total of 400 elderly patients (median age 73 years; range: 71-76 years) was studied. Medical history included diabetes, previous CABG or aortic valve replacement (AVR), endocarditis and treatment of previous carcinoma. A left ventricular ejection fraction (LVEF) of <0.66 and presence of three-vessel disease were also investigated. Hospital deaths (and cause) were recorded; survival or date and cause of death after discharge were obtained by questionnaire. Kaplan-Meier univariate and Cox proportional hazards multivariate regression analyses were carried out. RESULTS: Mortality during follow up was 28.3%; hospital mortality was 3.8%. Univariate analysis showed five factors significantly to affect survival: LVEF, history of endocarditis, carcinoma, age and three-vessel disease. Fifteen of 38 patients with history of carcinoma died, 10 due to a malignancy. Of 76 patients with three-vessel disease, 26 died. A history of diabetes and previous CABG did not influence survival significantly. Four of eight patients with preoperative endocarditis died, all in hospital. Six of 11 patients died after redo-AVR, none before 36 months follow up. By Cox regression analysis, LVEF and histories of carcinoma and endocarditis remained significant. CONCLUSION: AVR should be performed before ventricular deterioration occurs. Previous CABG is not a contraindication for AVR. Endocarditis impaired survival. Long-term mortality after redo-AVR in this population was relatively high, but acceptable. AVR should also be performed in elderly patients with aortic valve disease. Since prognosis of symptomatic aortic valve disease is poor in the short term, AVR is indicated in patients treated for carcinoma.     

Mini-craniotomy as the primary surgical intervention for the treatment of chronic subdural hematoma—a retrospective analysis

Background

The incidence of chronic subdural hematoma (CSDH) is increasing, but optimal treatment remains controversial. Recent meta-analyses suggest burr hole (BH) drainage is the best treatment because it provides optimal balance between recurrence and morbidity. Mini-craniotomy may offer supplementary technical advantages while maintaining equal or better outcomes. This study investigates the outcome of mini-craniotomy as the sole treatment in patients with CSDH.

Method

We analyzed all patients operated on for CSDH with mini-craniotomy in our neurosurgical center between 2005–2010. Baseline patient characteristics (age, sex, comorbidities, imaging characteristics, known risk factors for development of CSDH and neurological examination at presentation) and outcomes (mortality, complications, recurrence and neurological examination at discharge) were recorded.

Results

One hundred twenty-six adult patients were included, mean age was 73.9 (range 18 to 95) years old, and the sex ratio (M:F) was 2:1. Eighty-four percent of the patients showed clinical improvement at discharge, as shown by a decrease in the Markwalder score postoperatively (with 57 % Markwalder 0 and 23 % Markwalder 1). Recurrence rate was 8.7 %. Overall complication rate was 34.1 % (27.8 % medical complications and 6.3 % surgical complications). In-hospital mortality was 13.5 % (8.7 % due to pulmonary infections and 1.6 % to surgical complications). Preoperative Markwalder grade correlated significantly with complication rate, as did the presence of a neurodegenerative disease (p?=?0.018). Factors significantly related to mortality in univariate analysis were arterial hypertension (p?=?0.038), heart failure (p?=?0.02), renal failure (p?=?0.017), neurodegenerative disease (p?=?0.001), cerebrovascular accident (p?=?0.008) and coagulopathy (p?=?0.019). Multivariate analysis was not able to confirm any significant relationship.

Conclusion

This is the first published series of CSDH in which all consecutive patients were operated on by mini-craniotomy. The invasiveness and complication rate of mini-craniotomy are equal to those of burr hole treatment, but visualization is superior, resulting in lower recurrences. A randomized controlled trial is indicated to identify the best surgical strategy for the treatment of CSDH.     

The stratified medicalisation of mental health symptoms: educational inequalities in the use of psychotropic medication in Belgium

Social Psychiatry and Psychiatric Epidemiology - Several studies have shown socioeconomic inequalities in psychotropic medication use, but most of these studies are inspired by Andersen’s...     

Comparison of three hemodialysis procedures with unipuncture.

Dialysis efficiency estimated by the decrease in urea, creatinine and phosphorus serum concentrations is higher with the double-lumen single-needle method, compared to the single-lumen needle unipuncture methods. This increased efficiency is related to a higher blood flow rate through the dialyser. Provided the superficial veins are not too small and/or tortuous, the double-lumen needle appears as a safe, simple and rewarding device and may be used in most patients on regular dialysis treatment.     

Mind the Gate: General Practitioner’s Attitudes Towards Depressed Patients with Diverse Migration Backgrounds

This study aims to examine (a) whether there are differences in general practitioners’ (GPs) attitudes towards native Belgian patients, patients of foreign descent and asylum seeking patients who all express symptoms of major depression, and (b) whether these differences depend on GPs’ experience with cultural competency training and interethnic contact. Using a video vignette study among 404 Flemish (Belgium) GPs, we find evidence of a provider bias. While GPs regard a patient of foreign descent as less trustworthy and less able to adhere to medical recommendations than a native Belgian patient, they also hold more pessimistic views on a potential recovery of an asylum seeking patient. In addition, we find that cultural competency training might alter GPs’ attitudes of asylum seeking patients in a positive way. Summarized, our research highlights the need to target stereotypes among GPs for interventions designed to reduce migration-based disparities in healthcare use and health status.

     

Self-regulation and obesity: the role of executive function and delay discounting in the prediction of weight loss

Obesity rates are rising worldwide. Executive function and delay discounting have been hypothesized to play important roles in the self-regulation of behavior, and may explain variance in weight loss treatment success. First, we compared individuals with obesity (n?=?82) to healthy weight controls (n?=?71) on behavioral and self-report measures of executive function (working memory, inhibition and shifting) and delay discounting. Secondly, the individuals with obesity took part in a multidisciplinary weight loss program and we examined whether executive function and delay discounting predicted weight change. Individuals with obesity displayed weaker general and food-specific inhibition, and weaker self-reported executive function. Better behavioral working memory and better self-reported inhibition skills in daily life were predictive of greater weight loss. As findings are correlational, future studies should investigate the causal relationship between executive function and weight loss, and test whether intervening on executive function will lead to better prevention and treatment of obesity.