Eskildsenpiper1322

Graphical abstract.Oncolytic virus (OV) immunotherapy is characterized by viruses which specifically target cancer cells and cause their cytolysis. They provide a unique and promising new tool for the eradication of cancer as they interact with and affect the tumor microenvironment (TME), vasculature, and immune system. Advancements of genetic engineering have allowed for these viruses to be armed in such a way to have enhanced targeting, strong immunomodulation properties, and an ability to modify the TME. However, there are still major limitations in their use, mostly due to difficulties in delivering the viral particles to the tumors and in ensuring that the immunomodulatory properties are able to stimulate the host immune response to mount a complete response. Using novel delivery systems and using OVs as a complementary therapy in a combinatorial treatment have shown some significant successes. In this review, we discuss the major issues and difficulties in using OVs as anti-tumor agents and some of the strategies put in place so far to overcome these limitations. KEY POINTS • Oncolytic viruses (OVs) infect cancer cells and cause their cytolysis. • The major limitations in using OVs as anti-tumor therapy were discussed. • The potential strategies to overcome these limitations were summarized.Flagellar motility in bacteria is a highly regulated and complex cellular process that requires high energy investment for movement and host colonization. Motility plays an important role in the lifestyle of Vibrio spp. Adavosertib mouse in the aquatic environment and during host colonization. Flagellar motility in vibrios is associated with several cellular processes, such as movement, colonization, adhesion, biofilm formation, and virulence. The transcription of all flagella-related genes occurs hierarchically and is regulated positively or negatively by several transcription factors and regulatory proteins. The flagellar regulatory hierarchy is well studied in Vibrio cholerae and Vibrio parahaemolyticus. Here, we compared the regulatory cascade and molecules involved in the flagellar motility of V. cholerae and V. parahaemolyticus in detail. The evolutionary relatedness of the master regulator of the polar and lateral flagella in different Vibrio species is also discussed. Although they can form symbiotic associations of soociated infections.Here, we characterize two novel GH5 endoglucanases (GH5CelA and GH5CelB) from an uncultured bacterium identified in termite gut microbiomes. Both genes were codon-optimized, synthetized, cloned, and expressed as recombinant proteins in Escherichia coli for subsequent purification. Both enzymes showed activity on the pNPC and barley β-glucan substrates, whereas GH5CelB also showed low activity on carboxymethyl cellulose. The optimum conditions for both enzymes were an acid pH (5) and moderate temperature (35 to 50 °C). The enzymes differed in the kinetic profiles and patterns of the generated hydrolysis products. A structural-based modeling analysis indicated that both enzymes possess a typical (β/α)8-barrel fold characteristic of GH5 family, with some differential features in the active site cleft. Also, GH5CelB presents a putative secondary binding site. Furthermore, adjacent to the active site of GH5CelA and GH5CelB, a whole subdomain rarely found in GH5 family may participate in substrate binding and thermal stability.Therefore, GH5CelA may be a good candidate for the production of cello-oligosaccharides of different degrees of polymerization applicable for feed and food industries, including prebiotics. On the other hand, GH5CelB could be useful in an enzymatic cocktail for the production of lignocellulosic bioethanol, because of the production of glucose as a hydrolysis product. Key Points • Synthetic metagenomics is a powerful approach for discovering novel enzymes. • Two novel GH5 endoglucanases from nonculturable microorganisms were characterized. • Structural differences between them and other GH5 endoglucanases were observed. • The enzymes may be good candidates for feed, food, and/or bioethanol industries.

A serious complication after pancreatoduodenectomy (PD) is postoperative pancreatic fistula (POPF). The aim of this study was to analyse the incidence and predictive factors for POPF by using a large nationwide cohort.

Data from the Swedish National Registry for Pancreatic and Periampullary Cancer for all patients undergoing a PD from 2010 until 30th June 2018 were collected. The material was analysed in two groups, no POPF and clinically relevant (grade B and C) POPF.

A total of 2503 patients underwent PD, of which 245 (10%) developed POPF. Patients with POPF had significantly more overall complications (Clavien Dindo ≥3a, 75% vs. 21%, p < 0.001) and longer hospital stay (median 23 [16-35] vs. 11 [8-15], p < 0.001) than patients without POPF. The risk of POPF was higher with increased BMI (OR 1.08, p < 0.001). Preoperative presence of diabetes (OR 0.52, p = 0.012) and preoperative biliary drainage (OR 0.34, p < 0.001) reduced the risk of POPF. Reconstruction with pancreaticojejunostomy caused a more than two folded increase in POPF compared with pancreaticogastrostomy (OR 2.41, p < 0.001). Weight gain ≥2kg on postoperative day 1 was also a risk factor (OR 1.76, p < 0.001).

A high BMI, a pancreaticojejunostomy and postoperative weight gain were risk factors for developing POPF. Diabetes or preoperative biliary drainage was protective.

A high BMI, a pancreaticojejunostomy and postoperative weight gain were risk factors for developing POPF. Diabetes or preoperative biliary drainage was protective.

Sphingolipids are a diverse class of lipids with various roles in cell functions and subclasses such as ceramides have been associated with cardiovascular diseases (CVD) in previous studies.

We aimed to measure molecularly-distinct sphingolipids via a large-scale lipidomic analysis and expand the literature to an Asian population.

We performed a lipidomics evaluation of 79 molecularly distinct sphingolipids in the plasma of 2627 ethnically-Chinese Singaporeans.

During a mean follow-up of 12.9years, we documented 152 cases of major CVD (non-fatal myocardial infarction, stroke and cardiovascular death). Total ceramide concentrations were not associated with CVD risk [hazard ratio (HR), 0.99; 95% CI 0.81-1.21], but higher circulating total monohexosylceramides (HR, 1.22; 95% CI 1.03, 1.45), total long-chain sphingolipids (C16-C18) (HR, 1.22; 95% CI 1.02, 1.45) and total 181 sphingolipids (HR, 1.21; 95% CI 1.01, 1.46) were associated with higher CVD risk after adjusting for conventional CVD risk factors.

Our results do not support the hypothesis that higher ceramide concentrations are linked to higher CVD risk, but suggest that other classes of sphingolipids may affect CVD risk.

Our results do not support the hypothesis that higher ceramide concentrations are linked to higher CVD risk, but suggest that other classes of sphingolipids may affect CVD risk.

To analyze correlations between the realistic surgical difficulty of LaLIF and anatomic characteristics in radiographic images, in order to develop a simple classification to provide guiding information for case selection and evaluate the potential risks of the technique.

Ninety-six consecutive cases who underwent LaLIF surgeries at the L4-5 level with MR T2-weighted images were analyzed. A novel classification based on the anatomic relationships among the disk, great vessels, and psoas muscle was used for grouping. Clinical outcomes and realistic surgical difficulty parameters were recorded, and comparisons were made among different types of classifications.

Of the 96 analyzed cases, the time of surgical exposure was significantly longer for type C than for type B, and both of these were longer than that of type A. The VAS and ODI were significantly improved at a 1-year follow-up. There was no statistically significant difference among the three types. Type C had the highest incidence of complications, while Type A had the lowest. Analyses of another 304 MRI cases obtained in outpatient clinics showed that the distribution of the three types among these cases was consistent with that of the surgical cohort.

Our novel and simple classification provides useful information for case selection. Type A provided the best indication and is most appropriate for a beginner in this technique. Type C includes the most challenging situations, which may have a high incidence of complications and require sophisticated surgical skills to achieve satisfactory outcomes and avoid approach-related complications.

Our novel and simple classification provides useful information for case selection. Type A provided the best indication and is most appropriate for a beginner in this technique. Type C includes the most challenging situations, which may have a high incidence of complications and require sophisticated surgical skills to achieve satisfactory outcomes and avoid approach-related complications.This study aimed to define the maximum tolerated dose (MTD) of temozolomide (TMZ) concurrent with radiotherapy (RT) after high-dose methotrexate (HD-MTX) for newly diagnosed primary central nervous system lymphoma (PCNSL). Adult patients with PCNSL were treated according to a response-adapted strategy. HD-MTX (3.5 g/m2) was followed by concomitant RT and escalating TMZ (50-60-75 mg/m2/day, 5 days/week). The total radiation dose was modulated according to the patient's response to HD-MTX. All patients received 30 Gy to the whole brain plus leptomeninges to C2, including the third posterior of the orbital cavity (clinical target volume 2; CTV2), plus 6, 10, or 16 Gy to the primary site, including the residual mass (CTV1), if a complete response (CR), partial response (PR)/stable disease (SD), or progressive disease (PD) was observed, respectively. Acute toxicities were graded according to the RTOG-EORTC criteria. Dose-limiting toxicity (DLT) was defined as grade 4 hematological toxicity or grade 3-4 hepatic toxicity, although 75 mg/m2/day was the maximum dose regardless of DLT. Neurocognitive function was evaluated using the Mini-Mental State Examination. Three patients were enrolled at each TMZ dose level (total = 9 patients). Twelve lesions were treated. Six patients received 2 cycles of HD-MTX, while 3 received only 1 cycle because of hepatic or renal toxicity. All patients completed chemoradiotherapy without interruptions. No DLT events were recorded. TMZ appears to be tolerable at a dose of 75 mg/m2/day when administered concomitantly with radiotherapy and after HD-MTX.Both systemic inflammation and oxidative stress play crucial roles in the pathogenesis of vitiligo. In recent studies, monocyte to high-density lipoprotein cholesterol ratio (MHR), monocyte to lymphocyte ratio (MLR), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), mean platelet volume (MPV) and plateletcrit (PCT) have been shown to reflect inflammation and oxidative stress in chronic inflammatory and autoimmune diseases. In this study, we aimed to investigate the hematological and inflammatory parameters in patients with vitiligo and to evaluate their possible relationship with disease severity. The parameters including MHR, MLR, NLR, PLR, MPV, and PCT were retrospectively investigated in patients with vitiligo and healthy controls. Disease severity was evaluated using the vitiligo extent tensity index (VETI) score. A total of 180 patients with vitiligo, and age-gender-matched 180 healthy controls were enrolled in the study. MHR, MLR, PLR, PCT values were found to be significantly higher in patients with vitiligo (p  less then  0.