Notes

Existing Helpful Evidence-Based Exercise, Nov 2021.
Antibiotic resistance of bacteria is a topical problem on a global scale. Sometimes vigorous human activity leads to an increase in the number of bacteria carrying resistance genes in the environment. Antimicrobial peptides (AMPs) and similar compounds are potential candidates for combating antibiotic-resistant bacteria. Previously, we proposed and successfully tested on Thermus thermophilus a new mechanism of AMP action. This mechanism of directed coaggregation is based on the interaction of a peptide capable of forming fibrils with a target protein. In this work, we discuss the criteria for choosing a target for the targeted action of AMP, describe the features of the "parental" S1 ribosomal proteins T. thermophilus and Escherichia coli and the studied peptides using bioinformatic analysis methods, assess the antimicrobial effect of the synthesized peptides on a model organism of E. coli and cytotoxicity on cells of human fibroblasts. The obtained results will be important for the creation of new AMPs for pathogenic organisms.Accumulation of genetic data in the field of Parkinson's disease research culminated in identifying risk factors and confident prediction of the disease occurrence. To find new gene-targets for diagnostics and therapy we have to reconstruct gene network of the disease, to cluster genes in the network, to reveal key (hub) genes with largest number of interactions in the network. Using the on-line bioinformatics tools OMIM, PANTHER, gProfiler, GeneMANIA, and STRING-DB, we have analyzed the current array of data related to Parkinson's disease, calculated the categories of gene ontologies for a large list of genes, visualized them, and built gene networks containing the identified key objects and their relationships. However, translating the results into biological understanding is still a promising major challenge. The analysis of the genes associated with the disease, the assessment of their place in the gene network (connectivity) allows us to evaluate them as target genes for medicinal effects.To search for new targets of therapy, it is necessary to reconstruct the gene network of the disease, and identify the interaction of genes, proteins, and drug compounds. Using the online bioinformatics tools we have analyzed the current data set related to the metabolism of xenobiotics, mediated by the N-acetyltransferase 2 (NAT2) gene. The study of allelic polymorphism of the NAT2 gene has a prognostic value, allowing to determine the risk of a number of oncological diseases, the degree of increased risk due to smoking and exposure to chemical carcinogens, including drugs. The aim of this study was to determine the frequencies of two important "slow" variants of the NAT2 gene (NAT2*5, rs1801280 and NAT2*7, rs1799931), which significantly affected the rate of xenobiotic acetylation among the indigenous Nenets population of Northern Siberia. The obtained frequencies of polymorphic variants among the Nenets occupy an intermediate value between those for Europeans and Asians, which might indicate specific features of adaptation. We present a model of the distribution of two polymorphic variants of the NAT2 gene involved in the biotransformation of xenobiotics to study the characteristics of their metabolism in the indigenous inhabitants of Yamal.Glioblastoma multiforme (GBM) is a highly malignant brain tumor with average survival time of 15 months. Less than 2% of the patients survive beyond 36 months. To understand the molecular mechanism responsible for poor prognosis, we analyzed GBM samples of TCGA microarray (n=560) data. We have identified 720 genes that have a significant impact upon survival based on univariate cox regression. We applied the Genome Enhancer pipeline to analyze potential mechanisms of regulation of activity of these genes and to build gene regulatory networks. We identified 12 transcription factors enriched in the promoters of these genes including the key molecule of GBM - STAT3. We found that STAT3 had significant differential expression across extreme survivor groups (short-term survivors- survival 36 months) and also had a significant impact on survival. In the next step, we identified master regulators in the signal transduction network that regulate the activity of these transcription factors. Master regulators are filtered based on their differential expression across extreme survivors groups and impact on survival. This work validates our earlier report on master regulators IGFBP2, PDGFA, OSMR, and AEBP1 driving short survival. Additionally, we propose CD14, CD44, DUSP6, GRB10, IL1RAP, FGFR3, and POSTN as master regulators driving poor survival. These master regulators are proposed as promising therapeutic targets to counter poor prognosis in GBM. Finally, the algorithm has prioritized several drugs for the further study as potential remedies to conquer the aggressive forms of GBM and to extend survival of the patients.Ionotropic glutamate receptors of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype play a key role in synaptic plasticity representing one of the mechanisms for learning and memory formation. They can also serve as targets for the development of novel classes of pharmaceuticals for the treatment or substantive correction of many serious neurodegenerative and psychoneurological disorders. The search and studies of various types of AMPA receptor ligands attract considerable attention from academic organizations and pharmaceutical companies all over the world. This review mainly focuses on recent advances in this field. KC7F2 cell line The architecture and operational mechanism of the receptor as well as its major binding sites and ligand types are considered. Special attention is paid to the studies of mechanisms of action and novel chemotypes of AMPA receptor agonists and competitive antagonists, positive and negative allosteric modulators, auxiliary protein-dependent allosteric modulators, and ion channel blockers.
We compared the outcomes of open surgical repair (OSR) versus EVAR with parallel graft technique (PG) in patients with juxtarenal abdominal aortic aneurysm (JAAA) excluded from fenestrated endovascular aortic repair (FEVAR) due to clinical, anatomical, technical or manufacturing time reasons.

A single-center analysis of consecutive patients who underwent elective and urgent (within 24-48 hours) repair of JAAA from January 2010 to January 2019 was performed. Two groups were compared patients excluded from FEVAR and respectively treated by OSR or by PG for JAAA. Perioperative clinical, anatomic and operative data were collected in a dedicated database. The endpoints were primary technical success, changes in renal function, early and long-term mortality, freedom from aortic related reinterventions (ARRs) and aortic related mortality (ARM).

118 consecutive patients were treated for JAAA, 32 of them (27.1%) with FEVAR. 86 patients were enrolled in the study (OSR group=61; PG group= 25). The mean age was 77. of proximal "hostile necks" with low rates of reoperation and a similar impact on the renal function compared to PG.
PG represents a feasible procedure for patients excluded from FEVAR due to clinical, anatomical, technical or device manufacturing time reasons, ensuring low rates of ARM. However, ARRs during the follow-up remain the Achilles heel of this technique. OSR is still the most durable procedure in the endovascular era, allowing the treatment of proximal "hostile necks" with low rates of reoperation and a similar impact on the renal function compared to PG.
Currently, only patients with ascending aorta diameter exceeding 55mm will undergo prophylactic surgery. However, diameter alone is insufficient for precise risk stratification. An International Registry of Acute Aortic Dissections study showed that nearly 60% of patients with type A aortic dissection had a diameter<55mm. This study aims to compare the tortuosity of the ascending aorta between ATAAD patients and healthy controls and evaluate correlations between aortic tortuosity/diameter and presence of ATAAD.

A total of 75 cases in the ATAAD group and 83 cases in the Control group were enrolled. Tortuosity was calculated as the ratio of the total curve length (Lc) of the centerline to the linear distance (d) between its two endpoints, as assessed by an electronic caliper. The measurements were made on all patients by just one cardiovascular radiologist using 3-dimensional computerized tomographic imaging. ROC analysis was used to reckon the best cut-off level that prognosis occurrence of ATAAD. Correg aortic Tortuosity. Adding tortuosity to the ATAAD prediction system will improve the ability to identify high-risk groups of ATAAD. When the tortuosity is more significant than 0.135, prophylactic surgical intervention should be considered.
Our study found that the occurrence of ATAAD showed a strong correlation with maximum diameter of the ascending aorta, and moderate correlation with ascending aortic Tortuosity. Adding tortuosity to the ATAAD prediction system will improve the ability to identify high-risk groups of ATAAD. When the tortuosity is more significant than 0.135, prophylactic surgical intervention should be considered.Zenker's diverticulum (ZD) is the most common hypopharyngeal diverticulum seen often in septuagenarian and octogenarian males. Oropharyngeal dysphagia is the most common presenting symptom. Treatment of ZD has been advancing with the introduction of a wide variety of accessory devices, primarily focusing on obliteration of the septum by complete transection of the cricopharyngeus muscle to recreate the common cavity and restore normal pharyngo-esophageal bolus outflow. This review aims to provide an overview of the various surgical and endoscopic treatment options for ZD, while focusing specifically on Z-POEM.
Common bile duct stones are a very frequent problem in the western world and endoscopic stone clearance is the method of choice for treatment. Despite its common use, endoscopic clearance of common bile duct stones is not always trivial especially in cases involving large or multiple stones.

A literature review regarding different endoscopic techniques was performed for this article and a recommended therapeutic algorithm developed based on the guidelines of the European Society of Gastrointestinal Endoscopy (ESGE) and the German Gastroenterological Society (DGVS).

This review gives an overview of currently applied endoscopic techniques, their success and complication rates as well as alternative methods used for cases involving anatomic anomalies. The purpose of this review is to recommend a therapeutic algorithm for the treatment of difficult common bile duct stones.

For the treatment of difficult common bile duct stones, combined sphincterotomy and endoscopic large balloon dilation should be first es, should be performed at specialised units.
The purpose of this study is to report how the palliative and end of life care community in one region of England worked together to create a new model for integrated palliative and end of life care to respond to the challenges of changing demography, the need to reduce unnecessary hospital admissions of people nearing the end of life and to improve the quality of provision in line with current policy.

A co-production approach to system transformation was adopted involving 73 members of the palliative and end of life care community in one region of England.

A new model for the delivery of integrated palliative and end of life care services was produced. The breadth of membership of the co-production working party and constructive/collaborative working helped ensure a viable model was produced.

Although systems' thinking perspectives can help address the challenges of large-scale transformation because they focus on promoting the value of relationships, recognise the nuances of context and the need to understand system behaviour over time, the potential for systems to benefit from this approach is limited by the complexity of the processes involved and the sheer number of issues to be addressed in practical terms by policy makers and change leaders.
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