Neuroglial Mechanisms Involved In The Anti-Inflammatory Effect Of Acetate Supplementation

Acetate supplementation increases brain acetyl-CoA and attenuates lipopolysaccharide (LPS)-induced neuroinflammation in vivo. To explain the anti-inflammatory effect of acetate treatment, we proposed that acetate treatment disrupts inflammatory signaling in microglia and astrocytes, and induces histone hyperacetylation known to be correlated with anti-inflammatory properties. To test this hypothesis, we measured the effects that LPS and acetate treatment had on histone acetylation, mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB), and eicosanoid signaling. A single oral dose of acetate treatment (6 g/kg) in normal animals induced a time- and site-specific pattern of histone hyperacetylation, associated with reduction of histone deacetylase (HDAC) activity and expression. Long-term acetate treatment over 28 days induced the same site-specific pattern of histone hyperacetylation, and reversed LPS-induced histone H3 at lysine 9 (H3K9) hypoacetylation and interleukin (IL)-1β expression. In LPS-stimulated BV-2 microglia, acetate treatment reversed LPS-induced H3K9 hypoacetylation, IL-1β, IL-6, tumor necrosis factor (TNF)-α, cyclooxygenase (Cox)-1 and 2 protein levels, and NF-κB p65 protein level and phosphorylation at serine 468. Further, acetate treatment increased IL-4 and transforming growth factor (TGF)-β1 expression, and NF-κB p65 acetylation at lysine 310. Conversely, acetate treatment did not alter LPS-induced cytosolic (c) phospholipase A2 (PLA2), transiently reduced MAPK p38 and JNK phosphorylation, and increased MAPK ERK1/2 phosphorylation. In LPS-stimulated astrocyte, acetate treatment induced H3K9 hyperacetylation, reversed LPS-induced increases in IL-1β, TNF-α, NF-κB p65, and Cox-1 protein levels, MAPK p38 and cPLA2 phosphorylation and PGE2 release, and reversed LPS-induced decreases in TGF-β1 and IL-4. Moreover, acetate treatment reduced basal levels of IL-6, phosphorylated ERK1/2 and NF-κB p65 at serine 536, sPLA2 IIA and PLCβ1. Acetate treatment also increased acetylated H3K9 bound to the promoters of the genes of Cox-1, Cox-2, IL-1β and NF-κB p65, but not IL-4 in BV-2 microglia, which suggests that acetate treatment-induced H3K9 hyperacetylation can potentially be involved in the alteration of the expression of these genes. These data suggest that acetate treatment has net anti-inflammatory effects in vivo and in vitro both in LPS-stimulated microglia and astrocyte cultures through neuroglial cell type-distinct mechanisms

Mucin1 expression and gustatory function in postmenopausal females : a case-control observational study

Investigating possible relationship between Mucin1 expression levels in saliva, gustatory function, and taste perception in postmenopausal females. Using whole mouth taste test, twenty-five post-menopausal females (51.35 ± 5.22 years) and twenty-five p

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

PON1 Inter-individual Enzymatic activity variation as a predictor of OPC toxicity in agricultural workers presented to PCCASU, Egypt

Organophosphate compounds result in numerous toxicities because of their widespread usage and easy accessibility especially in the developing world’s agricultural communities. PON1 activity towards OPCs shows inter individual variations. Isoforms of the enzyme differing in their PON1 activity result from amino acid substitutions at positions 192 which is glutamine (Q) to arginine (R) and at 55 which is leucine (L) to methionine (M) thus rendering the identifi cation of individuals’ PON1 all enzymes of value in treatment of patients suffering from OP intoxication The aim of this work is to study the infl uence of genetic variation of PON1 gene on paraoxonase enzyme activity in cases of acute organ phosphorus compound poisoning. These compounds exert their toxicity primarily through inhibiting acetyl cholinesterase (AChE) enzyme. This study was carried out at the Poison Control Center (PCC) of Ain Shams University Hospitals, Cairo, Egypt. Paraoxonase enzyme activity: It was determined according to the method of Furlong et al. (1988). Paraoxonase genotyping: Genomic DNA was isolated from peripheral white blood cells by an automated isolation method using the MagNA Pure LC Total Nucleic Acid Isolation Kit. From this study it is obvious that PON1 coding could be a predictor of individual sensitivity to OPC especially among risk groups as agricultural workers and workers in OP factories.</p

Frequency of Pathogenic Germline Mutations in Early and Late Onset Familial Breast Cancer Patients Using Multi-Gene Panel Sequencing: An Egyptian Study

Background: Precision oncology has been increasingly used in clinical practice and rapidly evolving in the oncology field. Thus, this study was performed to assess the frequency of germline mutations in early and late onset familial breast cancer (BC) Egyptian patients using multi-gene panel sequencing to better understand the contribution of the inherited germline mutations in BC predisposition. Moreover, to determine the actionable deleterious mutations associated with familial BC that might be used as biomarker for early cancer detection. Methods: Whole blood samples were collected from 101 Egyptian patients selected for BC family history, in addition to 50 age-matched healthy controls. A QIAseq targeted DNA panel (human BC panel) was used to assess the frequency of germline mutations. Results: A total of 58 patients (57.4%) out of 101 were found to have 27 deleterious germline mutations in 11 cancer susceptibility genes. Of them, 32 (31.6%) patients carried more than one pathogenic mutation and each one carried at least one pathogenic mutation. The major genes harboring the pathogenic mutations were: ATM, BRCA2, BRCA1, VHL, MSH6, APC, CHEK2, MSH2, MEN1, PALB2, and MUTYH. Thirty-one patients (30.6%) had BRCA2 mutations and twenty (19.8%) had BRCA1 mutations. Our results showed that exon 10 and exon 11 harbored 3 and 5 mutations, respectively, in BRCA1 and BRCA2 genes. Our analysis also revealed that the VHL gene significantly co-occurred with each of the BRCA2 gene (p = 0.003, event ratio 11/21), the MSH2 gene (p = 0.01, 4/10), the CHEK2 gene (p = 0.02, 4/11), and the MSH6 gene (p = 0.04, 4/12). In addition, the APC gene significantly co-occurred with the MSH2 gene (p = 0.01, 3/7). Furthermore, there was a significant mutually exclusive event between the APC gene and the ATM gene (p = 0.04, 1/36). Interestingly, we identified population specific germline mutations in genes showing potentials for targeted therapy to meet the need for incorporating precision oncology into clinical practice. For example, the mutations identified in the ATM, APC, and MSH2 genes. Conclusions: Multi-gene panel sequencing was used to detect the deleterious mutations associated with familial BC, which in turns mitigate the essential need for implementing next generation sequencing technologies in precision oncology to identify cancer predisposing genes. Moreover, identifying DNA repair gene mutations, with focus on non-BRCA genes, might serve as candidates for targeted therapy and will be increasingly used in precision oncology

The clinical musculoskeletal ultrasonography: Egyptian guidelines for structured musculoskeletal ultrasound scanning and reporting

Abstract Background The aim of this work is to set up the standards for performing musculoskeletal ultrasound scans and reporting as an additional procedure in the rheumatology setting. We used two rounds of the Delphi approach to get the consensus on a musculoskeletal ultrasound reporting. Results Fifteen expert panels had completed the two rounds of surveys. After the end of round two, eighteen recommendations distributed upon eight domains were released. The percentage of the agreement on the recommendations was 93.3 to 100 %. All eighteen key questions were answered at the end of the second round with agreement. Conclusion A musculoskeletal ultrasound report template has been developed by this study, based on outcomes of a Delphi process, by an international participants’ panel. All domains met the 80% voting threshold set in this work. The reporting template can be used for both clinical research as well as standard practice to provide guidance and standardize the musculoskeletal ultrasound reporting

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially