Abdominoperineal excision (APE) is the operation chosen when a patient has low rectal cancer unamenable to sphincter preserving surgery. Perineal flap reconstruction is associated with less wound morbidity but little is known about oncological outcomes. The objective was to compare outcomes in patients undergoing APE before and after the introduction of a program that utilized flap reconstruction of the perineum.

A retrospective review of a prospectively maintained database was performed. Patients who underwent APE followed by primary closure or flap reconstruction between 1998 and 2018 were selected. The cohorts were divided according to the implementation of the flap reconstruction program in July 2009. Clinicopathological data, recurrence and survival were compared between the cohorts.

One hundred and forty nine patients underwent APE for rectal adenocarcinoma between 1998 and 2018. There were 57 patients in the pre-flap era and 92 in the post-flap era. Forty-six patients underwent flap reconstruction in the latter cohort (50%). More patients in the post-flap era underwent neoadjuvant chemoradiotherapy (85.9% vs. 63.2%; p < .01). Margin positivity rates decreased from 21.1% in the pre-flap era to 10.9% in the post-flap era (p = .10) and there was an associated improvement in incidence and time to local recurrence (p = .03).

The use of perineal flap reconstruction is associated with a longer median time to local recurrence. Perineal flap reconstruction may contribute to reduced margin positivity.
The use of perineal flap reconstruction is associated with a longer median time to local recurrence. Perineal flap reconstruction may contribute to reduced margin positivity.Determining metabolomic differences among samples of different phenotypes is a critical component of metabolomics research. With the rapid advances in analytical tools such as ultrahigh-resolution chromatography and mass spectrometry, an increasing number of metabolites can now be profiled with high quantification accuracy. The increased detectability and accuracy raise the level of stringiness required to reduce or control any experimental artifacts that can interfere with the measurement of phenotype-related metabolome changes. One of the artifacts is the batch effect that can be caused by multiple sources. In this review, we discuss the origins of batch effects, approaches to detect interbatch variations, and methods to correct unwanted data variability due to batch effects. We recognize that minimizing batch effects is currently an active research area, yet a very challenging task from both experimental and data processing perspectives. Thus, we try to be critical in describing the performance of a reported method with the hope of stimulating further studies for improving existing methods or developing new methods.
To evaluate the accuracy of a deep learning-based auto-segmentation mode to that of manual contouring by one medical resident, where both entities tried to mimic the delineation "habits" of the same clinical senior physician.

This study included 125 cervical cancer patients whose clinical target volumes (CTVs) and organs at risk (OARs) were delineated by the same senior physician. Of these 125 cases, 100 were used for model training and the remaining 25 for model testing. In addition, the medical resident instructed by the senior physician for approximately 8months delineated the CTVs and OARs for the testing cases. The dice similarity coefficient (DSC) and the Hausdorff Distance (HD) were used to evaluate the delineation accuracy for CTV, bladder, rectum, small intestine, femoral-head-left, and femoral-head-right.

The DSC values of the auto-segmentation model and manual contouring by the resident were, respectively, 0.86 and 0.83 for the CTV (P<0.05), 0.91 and 0.91 for the bladder (P>0.05), 0.88 ent but with much better efficiency in this study. Furthermore, the auto-segmentation approach offers additional perceivable advantages of being consistent and ever improving when compared with manual approaches.The extremely important use of mobile phones in the world, at all ages of life, including children and adolescents, leads to significant exposure of these populations to electromagnetic waves of radiofrequency. The question, therefore, arises as to whether exposure to these radiofrequencies (RFs) could lead to deleterious effects on the body's biological systems and health. In the current article, we review the effects, in laboratory animals and humans, of exposure to RF on two hormones considered as endocrine markers melatonin, a neurohormone produced by the pineal gland and cortisol, a glucocorticosteroid synthesized by the adrenal glands. These two hormones are also considered as markers of the circadian system. The literature search was performed using PubMed, Medline, Web of Sciences (ISI Web of Knowledge), Google Scholar, and EMF Portal. From this review on RF effects on cortisol and melatonin, it appears that scientific papers in the literature are conflicting, showing effects, no effects, or inconclusive data. This implies the need for additional research on higher numbers of subjects and with protocols perfectly controlled with follow-up studies to better determine whether the chronic effect of RF on the biological functioning and health of users exists (or not). Bioelectromagnetics. 2021;425-17. © 2020 Bioelectromagnetics Society.Genetic, preclinical and clinical data link Parkinson's disease and Gaucher's disease and provide a rational entry point to disease modification therapy via enhancement of β-Glucocerebrosidase (GCase) activity. We discovered a new class of pyrrolo[2,3-b]pyrazine activators effecting both Vmax and Km. They bind to human GCase and increase substrate metabolism in the lysosome in a cellular assay. We obtained the first crystal structure for an activator and identified a novel non-inhibitory binding mode at the interface of a dimer, rationalizing the observed structure-activity relationship (SAR). The compound binds GCase inducing formation of a dimeric state at both endoplasmic reticulum (ER) and lysosomal pHs, as confirmed by analytical ultracentrifugation. Importantly, the pyrrolo[2,3-b]pyrazines have central nervous system (CNS) drug-like properties. Our findings are important for future drug discovery efforts in the field of GCase activation and provide a deeper mechanistic understanding of the requirements for enzymatic activation, pointing to the relevance of dimerization.Landscape anthropization has been identified as one of the main drivers of pathogen emergence worldwide, facilitating pathogen spillover between domestic species and wildlife. https://www.selleckchem.com/products/ag-1024-tyrphostin.html The present study investigated Carnivore protoparvovirus-1 infection using molecular methods in 98 free-ranging wild guignas (Leopardus guigna) and 262 co-occurring owned, free-roaming rural domestic cats. We also assessed landscape anthropization variables as potential drivers of infection. Protoparvovirus DNA was detected in guignas across their entire distribution range, with observed prevalence of 13.3% (real-time PCR) and 9% (conventional PCR) in guignas, and 6.1% (conventional PCR) in cats. Prevalence in guigna did not vary depending on age, sex, study area or landscape variables. Prevalence was higher in juvenile cats (16.7%) than in adults (4.4%). Molecular characterization of the virus by amplification and sequencing of almost the entire vp2 gene (1,746 bp) from one guigna and five domestic cats was achieved, showing genetic similarities to canine parvovirus 2c (CPV-2c) (one guigna and one cat), feline panleukopenia virus (FPV) (one cat), CPV-2 (no subtype identified) (two cats), CPV-2a (one cat). The CVP-2c-like sequence found in a guigna clustered together with domestic cat and dog CPV-2c sequences from South America, suggesting possible spillover from a domestic to a wild species as the origin of infection in guigna. No clinical signs of disease were found in PCR-positive animals except for a CPV-2c-infected guigna, which had haemorrhagic diarrhoea and died a few days after arrival at a wildlife rescue centre. Our findings reveal widespread presence of Carnivore protoparvovirus-1 across the guigna distribution in Chile and suggest that virus transmission potentially occurs from domestic to wild carnivores, causing severe disease and death in susceptible wild guignas.
The safety assessment of personal care products often entails determining dermal absorption of their ingredients. Such experiments are typically performed in human or animal skin in vitro; however, ethical and safety considerations are associated with obtaining these tissues. Several human skin equivalent models (HSEs) have been developed as alternatives to human tissue. The barrier function of such models however, is normally less developed than human skin. Here, we examine the permeability of the HSE LabSkin
to a model compound, 3-O-ethyl-l-ascorbic acid (EA) compared with human skin.

Skin uptake and permeation of EA was investigated in vitro using heat-separated human epidermis and LabSkin
. Finite dose (5 μL cm
) Franz-diffusion studies were conducted using 2 % (w/w) EA in a ternary solvent mixture comprising propylene glycol (PG), propylene glycol monolaurate (PGML), and isopropyl myristate (IPM). These excipients are commonly used in cosmetic products and they have been reported to promote perucibility and robustness of LabSkin
for delivery of other actives that span a range of physicochemical properties.
The permeation of EA in LabSkinTM compared well with results for human epidermis in terms of the permeation profiles and the cumulative amounts of EA that permeated. The data suggest that the skin barrier of the two models was similar with regard to their overall permeability to the hydrophilic active EA. The findings are promising for the use of LabSkinTM as a surrogate for human skin in permeability testing. Future studies will focus on exploring the reproducibility and robustness of LabSkinTM for delivery of other actives that span a range of physicochemical properties.
This study aimed to analyze the midterm outcomes of LUMiC® endoprosthetic reconstruction following periacetabular resection of primary bone sarcomas and carcinoma metastases.

We retrospectively reviewed the charts of 21 patients (11 male [52.3%], 10 female [47.6%]; mean age 47 ± 16 years) for whom a LUMiC® endoprosthesis (Implantcast) was used to reconstruct a periacetabular defect after internal hemipelvectomy. The tumor was pathologically diagnosed as Ewing's sarcoma in six (28.5%), chondrosarcoma in 10 (47.6%), and bone metastasis from carcinoma in five (23.8%) patients.

The median follow-up of patients was 57.8 months (95% confidence interval 51.9-63.7). The implant survival rate at 1, 2, and 5 years were 95.2%, 85.7%, and 80.9%, respectively. The overall complication rate was 33.3% (n = 7). Four (19%) complications resulted in reconstruction failure. Total reoperation rate was 28.5% (n = 6). The complications were soft tissue failure/dislocation in two patients, aseptic loosening in one, infection in two, and local recurrence in two. At the time of study, seven patients were alive with no evidence of disease, seven were alive with disease, and seven died of disease. The 5-year overall survival rate and local recurrence-free survival rates were 67% and 76%, respectively. The median Musculoskeletal Tumor Society score at final follow-up was 70% (range 50%-86.6%).

We conclude that LUMiC® endoprosthesis provides good functional outcomes and a durable reconstruct. Even though this reconstruction method presents some complications, it provides a stable pelvis in the management of periacetabular malignant tumors.
We conclude that LUMiC® endoprosthesis provides good functional outcomes and a durable reconstruct. Even though this reconstruction method presents some complications, it provides a stable pelvis in the management of periacetabular malignant tumors.