Currently, around 3000 natural antimicrobial peptides from six kingdoms (bacteria, archaea, protists, fungi, plants, and animals) have been isolated and sequenced. However, only a few of them are under clinical trials and/or in the commercial development stage for the treatment of bacterial infections caused by antibiotic-resistant bacteria. Moreover, high structural complexity, poor pharmacokinetic properties, and low antibacterial activity of natural antimicrobial peptides hinder their progress in drug development. To overcome these hurdles, researchers have become increasingly interested in modification and nature-inspired synthetic antimicrobial peptides. This review discusses some of the recent studies reported on antimicrobial peptides.Biliary complications (BCs) following living donor liver transplantation (LDLT) can lead to significant morbidity and occasional mortality. The present study describes our experience of the all-knots-outside technique (AKOT) of biliary reconstruction (BR) and its impact on BCs. A retrospective analysis was performed using prospectively collected data of 330 consecutive adult patients undergoing LDLT from July 2011 to February 2018 with a minimal follow-up of 24 months. Only 2.8% required hepaticojejunostomy and were excluded. In an initial 122 patients, BR was performed with the standard technique (ST), and AKOT was performed in the subsequent 208 patients. In the AKOT group, a single anastomosis was attempted even for multiple ducts whenever feasible. A major BC was defined as requiring endoscopic, percutaneous, or surgical interventions. In the AKOT group, significantly more patients received a left lobe graft (5.7% versus 18.3%; P = 0.001), had shorter warm ischemia time (44.6 versus 27 minutes; P less then 0.001), and had a left hepatic artery (LHA) in the right lobe that was used for arterial reconstruction (48 [39.3%] versus 122 [58.6%]; P = 0.003). The incidence of BCs in the entire cohort was 47 (14.2%). For the ST versus AKOT groups, the overall BCs (27/122 [22.1%] versus 20/208 [9.6%]; P = 0.003) and major BCs (20.5% versus 6.7%; P less then 0.001) decreased significantly. In the multivariate analysis, the number of bile ducts (hazard ratio [HR], 4.18; 95% confidence interval [CI], 1.62-10.78; P = 0.003), number of anastomoses (HR, 2.03; 95% CI, 1.03-4.02; P = 0.04), and technique of anastomosis (HR, 0.36; 95% CI, 0.19-0.68; P = 0.002) predicted BCs. In conclusion, in adult LDLT, with standardization of the donor and recipient surgery, preferential use of LHA for right lobe arterial reconstruction, reduction in the number of anastomoses, and AKOT for BR significantly decreased the incidence of BCs.The therapeutic performance of DNAzyme-involved gene silencing is significantly constrained by inefficient conditional activation and insufficient cofactor supply. Herein, a self-sufficient therapeutic nanosystem was realized through the delicate design of DNAzyme prodrugs and MnO2 into a biocompatible nanocapsule with tumor-specific recognition/activation features. The indocyanine green (ICG)-modified DNA prodrugs are designed by splitting the DNAzyme and then reconstituted into the exquisite catalyzed hairpin assembly (CHA) amplification circuit. Based on the photothermal activation of ICG, the nanocapsule was disassembled to expose the MnO2 ingredient which was immediately decomposed into Mn2+ ions to supplement an indispensable DNAzyme cofactor on-demand with a concomitant O2 generation for enhancing the auxiliary phototherapy. The endogenous microRNA catalyzes the amplified assembly of DNA prodrugs via an exquisite CHA principle, leading to the DNAzyme-mediated simultaneous silencing of two key tumor-involved mRNAs. This self-activated theranostic nanocapsule could substantially expand the toolbox for accurate diagnosis and programmable therapeutics.Targeting the MAPK signaling pathway has transformed the treatment of metastatic melanoma. CRISPR-Cas9 genetic screens provide a genome-wide approach to uncover novel genetic dependencies that might serve as therapeutic targets. Here, we analyzed recently reported CRISPR-Cas9 screens comparing data from 28 melanoma cell lines and 313 cell lines of other tumor types in order to identify fitness genes related to melanoma. We found an average of 1,494 fitness genes in each melanoma cell line. We identified 33 genes, inactivation of which specifically reduced the fitness of melanoma. This set of tumor type-specific genes includes established melanoma fitness genes as well as many genes that have not previously been associated with melanoma growth. Several genes encode proteins that can be targeted using available inhibitors. We verified that genetic inactivation of DUSP4 and PPP2R2A reduces the proliferation of melanoma cells. DUSP4 encodes an inhibitor of ERK, suggesting that further activation of MAPK signaling activity through its loss is selectively deleterious to melanoma cells. Collectively, these data present a resource of genetic dependencies in melanoma that may be explored as potential therapeutic targets.The elimination of typhoid would have a substantial impact on the health of millions of people living in South and Southeast Asia and sub-Saharan Africa. Like many diseases before it, there are significant challenges to elimination, including access to safe drinking water and adequate sanitation practices, the availability of a vaccine, the identification and management of chronic carriers and the emergence of anti-microbial resistance. While provision of clean water and adequate sanitation must remain the ultimate goal, in the short term, required to cornerstone elimination in endemic areas, is an efficacious vaccine. Recent evidence of effectiveness with a tetanus-toxoid conjugate vaccine offers an opportunity for an immunogenic and safe vaccine able to be delivered to young children. Shown to be efficacious in Nepal, where infection is endemic, it may be a viable option in public health programmes moving towards elimination.

In children, the preoperative hydration status is an important part of the overall clinical assessment. The assumed preoperative fluid deficit is often routinely replaced during induction without knowing the child’s actual fluid status.

We investigated the predictive value of the Pleth Variability Index as a measure of fluid responsiveness in spontaneously breathing anesthetized children.

Pleth Variability Index, stroke volume and Cardiac Index, measured by electrovelocimetry, mean blood pressure, and heart rate were recorded during anesthesia induction in 50 pediatric patients <6years. Baseline values were compared to values recorded after administration of 10mL/kg of Ringer’s lactate and during two passive leg raising tests (before and after fluid administration). Fluid responsiveness was defined as an increase of ≥10% in stroke volume.

Only in fluid responsive patients, Pleth Variability Index values were higher before fluid administration than thereafter (21.4±5.9% vs 15.0±9.4%, 95% CI of differeathing anesthetized children. A significant overlap in baseline Pleth Variability Index values between fluid responsive and nonfluid responsive patients does not allow a reliable recommendation as to a cut off value.Ras has been found to be mutated in 30% of non-small cell lung cancers, and its mutation has been regarded as a causal factor underlying tumorigenesis. However, no successful medicine has been developed so far to inhibit Ras for lung cancer treatment. We have previously identified DHX33 as a Ras downstream effector, promoting cell cycle progression and cell growth. In this study, with the K-Ras (G12D);DHX33 (lox/lox) mouse model, we discovered that genetic ablation of DHX33 inhibited tumor development. We further found that ablation of DHX33 altered the expression of nearly 2000 genes which are critical in cancer development such as cell cycle, apoptosis, glycolysis, Wnt signaling, and cell migration. Our study for the first time demonstrates the pivotal role of the DHX33 in Ras-driven lung cancer development in vivo and highlights that pharmacological targeting DHX33 can be a feasible option in treating Ras-mutant lung cancers.

Ligation of the intersphincteric fistula tract (LIFT) is increasingly being used for surgical closure of high perianal fistulas in Crohn’s disease. Currently, data on postoperative MRI findings are scarce, although they are considered important for assessing healing and recurrence. Our aim, therefore, was to evaluate fistula characteristics on MRI and their relationship with clinical outcomes after LIFT.

Consecutive Crohn’s patients treated with LIFT between 2007 and 2018 who underwent baseline and follow-up MRI were retrospectively included. MRIs were scored by two radiologists according to characteristics based on the original and modified Van Assche indices. MRI findings, with emphasis on fibrosis, and the relationship with clinical healing, re-interventions and recurrences are described.

Twelve patients were included [four men, median age 34 (interquartile range 28-39) years]. Follow-up MRI was performed at a median of 5.5months (interquartile range 2.5-6.0) after LIFT. At baseline, all patients shoghly effective therapy. Unfavourable clinical outcomes were only present in patients with persisting granulation tissue, indicating the potential prognostic value of MRI.

To examine the relationship between physical and psychosocial work-related risk factors and perceived work ability (PWA) among nurses.

The work of nurses is challenging due to its high physical and mental workload. This might reduce PWA. A sustainable level of PWA is crucial to maintain well-being at work and to prevent early dropout. As a consequence, gaining a better understanding of which factors play a role in determining PWA is essential for health care organisations.

The associations between work-related risk factors and PWA were investigated among 114 nurses from Ghent University Hospital, Belgium. PWA and psychosocial factors were subjectively assessed. Occupational physical activity (OPA) was objectively measured over a period of 2-5days using two accelerometers.

No association between OPA and PWA was found. Multiple linear regression models revealed that job demands were negatively associated with PWA, whereas job control showed a positive association with PWA.

The results highlight the importance of psychosocial factors for more research on the PWA of nurses. Further investigation into the specific physical work demands of nurses is called for.

Giving attention to psychosocial factors is crucial to enhance the PWA and well-being of nurses.

Giving attention to psychosocial factors is crucial to enhance the PWA and well-being of nurses.

Patients undergoing hematopoietic stem cell transplant (HSCT) possess numerous risk factors for Clostridioides (formerly Clostridium) difficile infection (CDI) and experience a high rate of diarrhea. Colonization rates of Clostridiumdifficile vary greatly among subgroup analyses with recent studies demonstrating colonization rates in the blood and marrow transplant units up to nine times that of the general population.

The primary objectives of this study were to identify the rate of Cdifficile colonization and acquisition in HSCT patients admitted to the blood and marrow transplant unit. This was a prospective study that included all adult patients admitted for hematopoietic stem cell transplantation. Stool specimens were routinely collected on admission and weekly thereafter for a maximum of six samples per patient.

Forty-two patients met inclusion criteria and had baseline samples available for analysis. The rate of Cdifficile colonization on admission was 24%, and an additional 9% of patients acquired the organism during admission.