Study of microRNAs-21/221 as potential breast cancer biomarkers in Egyptian women

microRNAs (miRNAs) play an important role in cancer prognosis. They are small molecules, approximately 17–25 nucleotides in length, and their high stability in human serum supports their use as novel diagnostic biomarkers of cancer and other pathological conditions. In this study, we analyzed the expression patterns of miR-21 and miR-221 in the serum from a total of 100 Egyptian female subjects with breast cancer, fibroadenoma, and healthy control subjects. Using microarray-based expression profiling followed by real-time polymerase chain reaction validation, we compared the levels of the two circulating miRNAs in the serum of patients with breast cancer (n = 50), fibroadenoma (n = 25), and healthy controls (n = 25). The miRNA SNORD68 was chosen as the housekeeping endogenous control. We found that the serum levels of miR-21 and miR-221 were significantly overexpressed in breast cancer patients compared to normal controls and fibroadenoma patients. Receiver Operating Characteristic (ROC) curve analysis revealed that miR-21 has greater potential in discriminating between breast cancer patients and the control group, while miR-221 has greater potential in discriminating between breast cancer and fibroadenoma patients. Classification models using k-Nearest Neighbor (kNN), Naïve Bayes (NB), and Random Forests (RF) were developed using expression levels of both miR-21 and miR-221. Best classification performance was achieved by NB Classification models, reaching 91% of correct classification. Furthermore, relative miR-221 expression was associated with histological tumor grades. Therefore, it may be concluded that both miR-21 and miR-221 can be used to differentiate between breast cancer patients and healthy controls, but that the diagnostic accuracy of serum miR-21 is superior to miR-221 for breast cancer prediction. miR-221 has more diagnostic power in discriminating between breast cancer and fibroadenoma patients. The overexpression of miR-221 has been associated with the breast cancer grade. We also demonstrated that the combined expression of miR-21 and miR-221can be successfully applied as breast cancer biomarkers

Increased myeloperoxidase activity as an indicator of neutrophil-induced inflammation and sepsis in neonates

Background: MPO is an enzyme that contains heme secreted by phagocytic cells after the respiratory burst system activation. MPO is expressed mainly by neutrophils and monocytes in small quantities and it is very important to determine further process of hydrogen peroxide.Objective: to evaluate neutrophils activation and the MPO enzyme activity in plasma as an indicator of sepsis as well as sepsis severity in neonates with sepsis with correlation to their clinical and laboratory findings.Methods: were classified into 2 groups: sepsis group: included 45 neonates with gestational ages 28-40 weeks with sepsis, 15 of them had been subjected to follow up samples, control group: included 30 neonates proved to be free of sepsis. All neonates were subjected to history taking, clinical examination and measurement of plasma MPO enzyme.Results: this study revealed that MPO activity and neutrophil cell count are increased in sepsis group compared to the non-septic neonates. The ROC curve showed that the best cut off for MPO in prediction of septic patients and mortality was found >54 mu/ml and >83 mu/ml respectively. There was positive correlation between MPO enzyme activity and the total leukocyte count and neutrophil count. By following up some of sepsis group neonates there was significant decrease in MPO activity goes along with improvement in clinical state of neonates with sepsis. MPO enzyme activity was found to be low in septic shock patients who also have pancytopenia compared to septic patients without shock.Conclusion: plasma MPO enzyme proved to be a good marker of sepsis in neonates, with a good prognostic value in severe cases.Keywords: MPO, inflammatory response, neonates, sepsi

Cell-Type Specific Roles for PTEN in Establishing a Functional Retinal Architecture

BACKGROUND: The retina has a unique three-dimensional architecture, the precise organization of which allows for complete sampling of the visual field. Along the radial or apicobasal axis, retinal neurons and their dendritic and axonal arbors are segregated into layers, while perpendicular to this axis, in the tangential plane, four of the six neuronal types form patterned cellular arrays, or mosaics. Currently, the molecular cues that control retinal cell positioning are not well-understood, especially those that operate in the tangential plane. Here we investigated the role of the PTEN phosphatase in establishing a functional retinal architecture. METHODOLOGY/PRINCIPAL FINDINGS: In the developing retina, PTEN was localized preferentially to ganglion, amacrine and horizontal cells, whose somata are distributed in mosaic patterns in the tangential plane. Generation of a retina-specific Pten knock-out resulted in retinal ganglion, amacrine and horizontal cell hypertrophy, and expansion of the inner plexiform layer. The spacing of Pten mutant mosaic populations was also aberrant, as were the arborization and fasciculation patterns of their processes, displaying cell type-specific defects in the radial and tangential dimensions. Irregular oscillatory potentials were also observed in Pten mutant electroretinograms, indicative of asynchronous amacrine cell firing. Furthermore, while Pten mutant RGC axons targeted appropriate brain regions, optokinetic spatial acuity was reduced in Pten mutant animals. Finally, while some features of the Pten mutant retina appeared similar to those reported in Dscam-mutant mice, PTEN expression and activity were normal in the absence of Dscam. CONCLUSIONS/SIGNIFICANCE: We conclude that Pten regulates somal positioning and neurite arborization patterns of a subset of retinal cells that form mosaics, likely functioning independently of Dscam, at least during the embryonic period. Our findings thus reveal an unexpected level of cellular specificity for the multi-purpose phosphatase, and identify Pten as an integral component of a novel cell positioning pathway in the retina

BM-MSCs alleviate diabetic nephropathy in male rats by regulating ER stress, oxidative stress, inflammation, and apoptotic pathways

Introduction: Diabetic nephropathy (DN), a chronic kidney disease, is a major cause of end-stage kidney disease worldwide. Mesenchymal stem cells (MSCs) have become a promising option to mitigate several diabetic complications.Methods: In this study, we evaluated the therapeutic potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) in a rat model of STZ-induced DN. After the confirmation of diabetes, rats were treated with BM-MSCs and sacrificed at week 12 after treatment.Results: Our results showed that STZ-induced DN rats had extensive histopathological changes, significant upregulation in mRNA expression of renal apoptotic markers, ER stress markers, inflammatory markers, fibronectin, and intermediate filament proteins, and reduction of positive immunostaining of PCNA and elevated P53 in kidney tissue compared to the control group. BM-MSC therapy significantly improved renal histopathological changes, reduced renal apoptosis, ER stress, inflammation, and intermediate filament proteins, as well as increased positive immunostaining of PCNA and reduced P53 in renal tissue compared to the STZ-induced DN group.Conclusion: In conclusion, our study indicates that BM-MSCs may have therapeutic potential for the treatment of DN and provide important insights into their potential use as a novel therapeutic approach for DN

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

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&nbsp;years; 78.2% included were male with a median age of 37&nbsp;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

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

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised