Quantitative comparison of the expression of antimicrobial peptides in the oral mucosa and extraoral skin

Antimicrobial peptides (AMP) defend epithelial surfaces against pathological micro-organisms. We know of no comparison of their expression between the oral mucosa and extraoral epithelium, but knowledge of differences in their quantities is of interest, possibly as a starting point for new treatments. Expression of AMP human beta-defensin (hBD)-1/-2/-3 and psoriasin in the oral mucosa and extraoral epithelium of the head and neck were measured by real-time polymerase chain reaction (RT-PCR) (n=14), immunohistochemistry (n=6), and western blot (n=8). RT-PCR showed that all the genes investigated were expressed significantly more in the oral mucosa than in the skin (hBD-1: p=0.002; hBD-2: p=0.006; hBD-3: p=0.035; psoriasin: p=0.02). Immunohistochemistry and western blot showed differential concentrations of proteins: hBD-2 (p=0.021) and hBD-3 (p=0.043) were pronounced in the oral mucosa, whereas psoriasin was raised in the extraoral skin (p=0.021). There was no difference in protein concentrations for hBD-1 (p=0.08). The observed differences in the expression of AMP may be important for new treatments such as topical application of AMP derivatives.     

Patient and Provider-Identified Factors Contributing to Surgical Readmission After Colorectal Surgery

Purpose: Nearly one in seven surgical patients is readmitted to the hospital within 30 days of discharge. Few studies have identified patient-centric factors that raise the risk of both preventable and nonpreventable postoperative readmissions. Materials and Methods: Over 6 months in 2012, 48 colorectal surgical patients were identified on re-admission within 30 days of discharge. We prospectively obtained information on the patient's and primary surgeon's views on factors that contributed to readmission, and compiled data to produce an external list of contributing factors. A standard cost analysis was performed. Results: 48 colorectal surgery patients participated, and 47 were included in this patient-centric evaluation of factors leading to readmission. The three primary readmission diagnoses included dehydration, fever, and ileus or small bowel obstruction. Of all readmissions, 23% were considered to be preventable. 38% of patients had scheduled follow-up appointments that were documented in the medical record at the time of discharge. Providers identified several factors contributing to readmission including difficulty understanding discharge plan, medication management and premature discharge. Per patient, the cost of preventable readmission was $15,366 (±20%; $12,293–$18,439). Total preventable cost was $169,025 (±20%; $135,220–$202,829). Conclusions: The ability to obtain an outpatient postoperative appointment and the understanding of their own postoperative care were the most commonly identified barriers. Interventions to help reduce unnecessary readmissions include a standard discharge process and coordinator, and routine (<7 days) postdischarge outpatient appointments. Successful reduction of preventable readmissions would result in approximately $3.6 million in cost savings per 1,000 colorectal readmissions.     

FLS – Drei Buchstaben verändern die sekundäre Frakturprävention

The increasing importance of preventive measures in the field of orthopedics and trauma surgery becomes apparent because of the demographic changes and the high risk for secondary fractures following osteoporotic fractures. Within the fracture treatment chain, orthopedics and trauma surgery are in the “pole position” to initiate these measures in geriatric patients. In the past orthopedists and trauma surgeons have constantly accused of neglecting secondary fracture prevention in fragility fracture patients. There are several reasons that speak in favor of us undertaking a role in secondary fracture prevention: osteoporosis medication is highly effective in fracture prevention when correctly indicated, the positive effects of osteoporosis therapy on fracture healing and legal issues. Arguments that have been used to justify neglect of secondary fracture prevention are undesired side effects related to osteoporosis medications, such as atypical femoral fractures and osteonecrosis of the jaws, interference of some specific drugs with fracture healing and the working conditions in emergency departments. These run contrary to the consideration of chronic diseases such as osteoporosis, secondary osteoporosis and the underlying disease could be overlooked and the increasing complexity of medicinal osteoporosis therapy.     

Dose Timing of Aminoglycosides in Hemodialysis Patients: A Pharmacology View

Aminoglycosides for patients undergoing intermittent hemodialysis (IHD) have traditionally been dosed at half the normal dose administered at the end of a hemodialysis session. Several investigations have suggested that administering higher doses preceding or with the initiation of dialysis would more readily optimize pharmacodynamic parameters. However, the selection of an optimal aminoglycoside dosing strategy in patients receiving IHD is complex and requires consideration of numerous factors, precluding a singular approach. By reviewing aminoglycoside pharmacokinetics, pharmacodynamics, risks for toxicity and resistance development, and practical considerations, we derive indication‐ and setting‐ specific recommendations. We identify some areas (definitive therapy of gram‐negative infections in patients receiving predictable hemodialysis sessions, for example) where dosing preceding or with the initiation of dialysis is optimal and feasible, and others (gram‐positive synergy, unstable patients with poor/unpredictable vascular access) where postdialysis dosing remains preferred. Finally, given the dearth of data exploring the pharmacodynamics and clinical outcomes of IHD patients receiving aminoglycoside therapy, we identify several key questions in need of investigation.     

Complexity of Host Micro‐RNA Response to Cytomegalovirus Reactivation After Organ Transplantation

Human (Homo sapiens) micro‐RNAs (hsa‐miRNAs) regulate virus and host‐gene translation, but the biological impact in patients with human cytomegalovirus (hCMV) infection is not well defined in a clinically relevant model. First, we compared hsa‐miRNA expression profiles in peripheral blood mononuclear cells from 35 transplant recipients with and without CMV viremia by using a microarray chip covering 847 hsa‐miRNAs. This approach demonstrated a set of 142 differentially expressed hsa‐miRNAs. Next, we examined the effect of each of these miRNAs on viral growth by using human fibroblasts (human foreskin fibroblast‐1) infected with the hCMV Towne strain, identifying a subset of proviral and antiviral hsa‐miRNAs. miRNA‐target prediction software indicated potential binding sites within the hCMV genome (e.g., hCMV‐UL52 and ‐UL100 [UL = unique long]) and host‐genes (e.g., interleukin‐1 receptor, IRF1). Luciferase‐expressing plasmid constructs and immunoblotting confirmed several predicted miRNA targets. Finally, we determined the expression of selected proviral and antiviral hsa‐miRNAs in 242 transplant recipients with hCMV‐viremia. We measured hsa‐miRNAs before and after antiviral therapy and correlated hsa‐miRNA expression levels to hCMV‐replication dynamics. One of six antiviral hsa‐miRNAs showed a significant increase during treatment, concurrent with viral decline. In contrast, six of eight proviral hsa‐miRNAs showed a decrease during viral decline. Our results indicate that a complex and multitargeted hsa‐miRNA response occurs during CMV replication in immunosuppressed patients. This study provides mechanistic insight and potential novel biomarkers for CMV replication.     

Clearance of levofloxacin by an in vitro model of continuous venovenous hemodialysis (CVVHD)

Information about the elimination and the adequate dosing of levofloxacin during renal replacement therapy is scarce. The aim of this study was to characterize in vitro the elimination of levofloxacin during continuous venovenous hemodialysis (CVVHD) and to investigate whether the CVVHD clearances of creatinine and urea are correlated with the levofloxacin clearance in order to facilitate dosage adjustments. An in vitro model of CVVHD was established using five dialyzer membranes at varying dialysate flow rates applied in the clinical setting (8, 16, 25, 33 and 41 ml/min). Plasma and dialysate samples were drawn for determination of levofloxacin, creatinine and urea concentrations to evaluate clearances by CVVHD. During CVVHD, the clearance of levofloxacin varied between 9.02 and 33.30 ml/min, depending on the chosen setup. Positive correlations (p<0.001) were received for: dialysate flow rate (QD) and creatinine/ urea clearances (R(2)>0.93); QD and levofloxacin clearance (R(2) 0.59-0.71); levofloxacin and creatinine clearance (R(2) 0.69-0.75); and levofloxacin and urea clearance (R(2) 0.56-0.75) as well. When dosing critically ill patients, therefore, extracorporeal as well as total clearance of levofloxacin should be considered.     

Early prenatal stress impact on coping strategies and learning performance is sex dependent

Diseases involving cognitive disorders and maladaptive stress-coping behaviors including autism and schizophrenia are present in children born to mothers exposed to stress during pregnancy. To determine the gestational time window when stress exposure produces the greatest impact on cognition, dams were exposed to chronic variable stress (CVS) early, mid-, or late in gestation and offspring learning performance and navigation strategies assessed. These studies utilized a modified version of the Barnes maze to allow investigation of coping responses to stress stimuli. In our study, males exposed to early gestational stress showed significantly impaired learning performance, requiring twice as long to locate the target following training. In stark contrast, early prenatal stress enhanced female performance, where these females located the target in a quarter of the time required by controls. Differences in search strategies whether cued, random, or serial accounted for divergent performances between sex and CVS groups. While control males' behavior expectedly evolved to a cued strategy, the early stressed offspring continued to rely on serial and random searching. Surprisingly, in a long-term memory recall test 6 weeks following previous maze exposure, these early stressed offspring now located the target significantly faster than controls suggesting gestational effects of stress on memory retention that were specific to prenatal time window of stress exposure. Overall, these results provide important insight into the temporal specificity of the effects of prenatal CVS revealing a remarkable vulnerability during early development and a sexually dichotomous influence on cognitive abilities and stress-coping strategies.     

The effectiveness of respiratory protection worn by communities to protect from volcanic ash inhalation. Part II: Total inward leakage tests

Inhalation of ash can be of great concern for affected communities, during and after volcanic eruptions. Governmental and humanitarian agencies recommend and distribute a variety of respiratory protection (RP), most commonly surgical masks. However, there is currently no evidence on how effective such masks are in protecting wearers from volcanic ash. In Part I of this study (Mueller et al., 2018), we assessed the filtration efficiency (FE) of 17 materials from different forms of RP against volcanic ash and a surrogate, low-toxicity dust, Aloxite. Based on those results, we now present the findings from a volunteer simulation study to test the effect of facial fit through assessment of Total Inward Leakage (TIL).Four different disposable RP types that demonstrated very high median FE (≥96% for Aloxite; ≥89% for volcanic ash) were tested without provision of training on fit. These were an industry-certified mask (N95-equiv.); a surgical mask from Japan designed to filter PM_2.5; a flat-fold basic mask from Indonesia; and a standard surgical mask from Mexico, which was also tested with an added medical bandage on top, as an additional intervention to improve fit.Ten volunteers (6 female, 4 male) were recruited. Each RP type was worn by volunteers under two different conditions simulating cleaning-up activities during/after volcanic ashfall. Each activity lasted 10?min and two repeats were completed for each RP type per activity. Dust (as PM_2.5) concentration inside and outside the mask was measured with two TSI SidePak aerosol monitors (Models AM510 and AM520, TSI, Minnesota, USA) to calculate TIL. A questionnaire was administered after each test to collect perceptions of fit, comfort, protection and breathability.The best-performing RP type, across both activities, was the industry-certified N95-equiv. mask with 9% mean TIL. The standard surgical mask and the basic flat-fold mask both performed worst (35% TIL). With the additional bandage intervention, the surgical mask mean TIL improved to 24%. The PM_2.5 surgical mask performed similarly, with 22% TIL. The N95-equiv. mask was perceived to provide the best protection, but was also perceived as being uncomfortable and more difficult to breathe through.This study provides a first objective evidence base for the effectiveness of a selection of RP types typically worn around the world during volcanic crises. The findings will help agencies to make informed decisions on the procurement and distribution of RP in future eruptions.