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Background: Aortic dissection is the most common acute aortic syndrome in the United States. Type B aortic dissection (TBAD) can be managed medically, through open surgical repair, or with thoracic endovascular repair (TEVAR). The present study sought to assess contemporary trends in the use and timing of TEVAR. Methods: Adult nonelective TBAD admissions were identified in the 2010 to 2020 Nationwide Readmissions Database. Patients were categorized as medical management (Medical Management), TEVAR at initial hospitalization (Early), or TEVAR during readmission (Delayed). Multivariable models were developed to assess associations with clinical outcomes and resource utilization. Results: Of 85,753 patients, 8.7% underwent TEVAR at index hospitalization (Early). From 2010 to 2020, the proportion undergoing TEVAR decreased significantly (from 11.3% to 9.6%; nptrend

Objective: Although national efforts have aimed to improve the safety of inpatient operations, income-based inequities in surgical outcomes persist, and the evolution of such disparities has not been examined in the contemporary setting. We sought to examine the association of community-level household income with acute outcomes of cardiac procedures over the past decade. Methods: All adult hospitalizations for elective coronary artery bypass grafting/valve operations were tabulated from the 2010-2020 Nationwide Readmissions Database. Patients were stratified into quartiles of income, with records in the 76th to 100th percentile designated as highest and those in the 0 to 25th percentile as lowest. To evaluate the change in adjusted risk of in-hospital mortality, complications, and readmission over the study period, estimates were generated for each income level and year. Results: Of approximately 1,848,755 hospitalizations, 406,216 patients (22.0%) were classified as highest income and 451,988 patients (24.4%) were classified as lowest income. After risk adjustment, lowest income remained associated with greater likelihood of in-hospital mortality (adjusted odds ratio, 1.61, 95% CI, 1.51-1.72), any postoperative complication (adjusted odds ratio, 1.19, CI, 1.15-1.22), and nonelective readmission within 30 days (adjusted odds ratio, 1.07, CI, 1.05-1.10). Overall adjusted risk of mortality, complications, and nonelective readmission decreased for both groups from 2010 to 2020 (P

Background: Multiagent neoadjuvant chemotherapy (NAT) has been linked with improved survival for locally advanced (LA) or borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC). However, the existence of disparities in its utilization remains to be elucidated. Methods: All adults with PDAC were tabulated from the 2011–2017 Nationwide Cancer Database. Tumor vascular involvement was determined using the clinical T stage and CS_EXTENSION variables. The significance of temporal trends was calculated using Cuzick's non-parametric test. A Cox proportional hazard model was used to assess the impact of NAT utilization on hazard of two-year mortality. A logistic regression model was developed to determine factors associated with receipt of NAT. Results: Of 3811 patients meeting inclusion criteria, 50.8 % received NAT. NAT utilization significantly increased over the study period, from 31.7 % in 2011 to 81.1 % in 2017 (p

Background: Failure to rescue (FTR) is increasingly recognized as a quality metric but remains understudied in emergency general surgery (EGS). We sought to identify patient and operative factors associated with FTR to better inform standardized metrics to mitigate this potentially preventable event. Methods: All adult (≥18 years) non-elective hospitalizations for large bowel resection, small bowel resection, repair of perforated ulcer, laparotomy and lysis of adhesions were identified in the 2016–2020 National Readmissions Database. Patients undergoing trauma-related operations or procedures ≤2 days of admission were excluded. FTR was defined as in-hospital death following acute kidney injury requiring dialysis (AKI), myocardial infarction, pneumonia, respiratory failure, sepsis, stroke, or thromboembolism. Multilevel mixed-effect models were developed to assess factors linked with FTR. Results: Among 826,548 EGS operations satisfying inclusion criteria, 298,062 (36.1 %) developed at least one MAE. Of those experiencing MAE, 43,477 (14.6 %) ultimately did not survive to discharge (FTR). Following adjustment for fixed hospital level effects, only 3.5 % of the variance in FTR was attributable to center-level differences. Relative to private insurance and the highest income quartile, Medicaid insurance (AOR 1.33; 95%CI, 1.23–1.43) and the lowest income quartile (AOR 1.22; 95%CI, 1.17–1.29) were linked with increased odds of FTR.A subset analysis stratified complication-specific rates of FTR by insurance status. Relative to private insurance, Medicaid coverage and uninsured status were linked with greater odds of FTR following perioperative sepsis, pneumonia, and AKI. Conclusion: Our findings underscore the need for increased screening and vigilance following perioperative complications to mitigate disparities in patient outcomes following high-risk EGS.

Background: Recent randomized trials have suggested non-operative management to be a safe alternative to appendectomy for acute uncomplicated appendicitis. Yet, there remains significant variability in treatment approach. This study sought to characterize center-level variation in non-operative management within a national cohort of adults presenting with appendicitis. Methods: The 2016–2020 Nationwide Readmissions Database was queried to identify all adult (≥18 years) hospitalizations for acute uncomplicated appendicitis. Hierarchical, mixed-effects models were developed to ascertain factors linked with non-operative management. Bayesian methodology was applied to predict random effects, which were then used to rank centers by increasing hospital-attributed rate of non-operative management. Institutions with high center-specific rates of non-operative management (>90th percentile) were considered low-operating hospitals (LOH). Results: Of an estimated 447,500 patients, 52,523 (11.7 %) were managed non-operatively. Compared to those undergoing appendectomy, the non-operative cohort was older, more commonly male, and of a higher comorbidity burden. Approximately 30 % in the variability of non-operative management was attributable to hospital effects, with absolute, risk-adjusted rates ranging from 0.5 to 22.5 %. Centers with non-operative management rates ≥90th percentile were considered LOH.Following risk adjustment, among patients undergoing appendectomy, care at LOH was linked with greater odds of postoperative infection, resource utilization, and non-elective readmission. Conclusions: We identified significant interhospital variation in the utilization of non-operative management for acute uncomplicated appendicitis. Further, we found LOH to be associated with inferior outcomes following surgical management. Future work is needed to assess the care pathways that contribute to increased utilization of non-operative strategies, and disseminate best practices across institutions.

Background: Black race has been associated with increased resource utilization after operation for small bowel obstruction (SBO). While prior literature has similarly demonstrated differences between urban and rural institutions, limited work has defined the impact of rurality on resource utilization by race. Methods: The 2016–2020 National Inpatient Sample was used to identify adults undergoing adhesiolysis after non-elective admission for SBO. The primary endpoint was hospitalization costs. Additional outcomes included surgical delay (≥ hospital day 3), length of stay (LOS), and nonhome discharge. Regression models were developed to identify the impact of Black race and rurality on the outcomes of interest with an interaction term to examine the incremental association of Black race on rurality. Results: Of an estimated 132,390 patients, 11.4 % were treated at an annual average of 377 rural hospitals (18.5 % of institutions). After adjustment, rural hospitals had higher costs (β + $4900, 95 % Confidence Interval [CI] [4200, 5700]), compared to others. However, rurality was associated with reduced odds of surgical delay (Adjusted Odds Ratio [AOR] 0. 76, CI[0.69, 0.85]), decreased LOS (β −1.66 days, CI[−1.99, −1.36]), and nonhome discharge (AOR 0.78, CI[0.70, 0.87]). While White patients experienced significant cost reductions at urban centers ($26,100 [25,800-26,300] vs $31,000 [30,300-31,700]), this was not noted for Black patients ($30,100 [29,400-30,700] vs $30,800 [29,300-32,400]). Conclusions: We found that Black patients do not benefit from the same cost protection afforded by urban settings as White patients after operative SBO admission. Future work should focus on setting-specific interventions to address drivers of disparities within each community.

Background: Obesity is a known risk factor for cholecystitis and is associated with technical complications during laparoscopic procedures. The present study seeks to assess the association between obesity class and conversion to open (CTO) during laparoscopic cholecystectomy (LC). Methods: Adult acute cholecystitis patients with obesity undergoing non-elective LC were identified in the 2017–2020 Nationwide Readmissions Database. Patients were stratified by obesity class; class 1 (Body Mass Index [BMI] = 30.0–34.9), class 2 (BMI = 35.0–39.9), and class 3 (BMI ≥ 40.0). Multivariable regression models were developed to assess factors associated with CTO and its association with perioperative complications and resource utilization. Results: Of 89,476 patients undergoing LC, 40.6 % had BMI ≥ 40.0. Before adjustment, class 3 obesity was associated with increased rates of CTO compared to class 1–2 (4.6 vs 3.8 %; p

In line with the United Nation's sustainable development goals (SDGs), the unsustainable use of scarce natural resources and worldwide environmental degradation call for the immediate implementation of green behaviors across all organizations. As environmental issues originate from human activities, they necessitate the realization and execution of employees' workplace pro-environmental behaviors (WPEB) and their stimulators. Drawing on social exchange and social identity theories, this study first investigates the mediating role of green organizational climate in the relationship between various forms of perceived corporate social responsibility (CSR) and employees' WPEB. It further examines the mediated moderation via green shared vision. An adapted survey questionnaire was distributed to senior-level and middle-level managers of large and medium-sized manufacturing firms in Pakistan, and 349 responses were gathered. The partial least-squares technique was used for data analysis. The findings indicate that all forms of perceived CSR positively correlate with a green organizational climate, which further significantly leads to employees' WPEB. The results also show that a strong shared green vision among employees can improve the relationship between the green organizational climate and employees' WPEB and vice versa. Moreover, multi-group analysis shows that the relationship between customer-centric perceived CSR and green organizational climate was stronger for medium-sized firms than large ones. Thus, to ensure the implementation of SDGs such as decent work and climate action, firms' top management must recognize the importance of investing in both internal and external CSR initiatives to foster a green organizational climate leading to employees' WPEB. Companies should communicate their participation in CSR activities to all stakeholders through public platforms to increase inspiration. Policymakers should further introduce CSR excellence awards and non-compliance penalties to encourage firms' extensive participation.

Background: With the growing opioid epidemic across the US, in-hospital utilization of opioids has garnered increasing attention. Using a national cohort, this study sought to characterize trends, outcomes, and factors associated with in-hospital opioid overdose (OD) following major elective operations. Methods: We identified all adult (≥18 years) hospitalizations entailing select elective procedures in the 2016–2020 National Inpatient Sample. Patients who experienced in-hospital opioid overdose were characterized as OD (others: Non-OD). The primary outcome of interest was in-hospital OD. Multivariable logistic and linear regression models were developed to evaluate the association between in-hospital OD and mortality, length of stay (LOS), hospitalization costs, and non-home discharge. Results: Of an estimated 11,096,064 hospitalizations meeting study criteria, 5375 (0.05 %) experienced a perioperative OD. Compared to others, OD were older (66 [57–73] vs 64 [54–72] years, p

Background: Racial disparities in access to preoperative evaluation for colorectal cancer remain unclear. Emergent admission may indicate lack of access to timely care. The present work aimed to evaluate the association of admission type with race among patients undergoing colorectal cancer surgery. Methods: All adults undergoing resection for colorectal cancer in 2011–2020 National Inpatient Sample were identified. Multivariable regression models were developed to examine the association of admission type with race. Primary outcome was major adverse events (MAE), including mortality and complications. Secondary outcomes included costs and length of stay (LOS). Interaction terms between year, admission type, and race were used to analyze trends. Results: Of 722,736 patients, 67.6 % had Elective and 32.4 % Emergent admission. Black (AOR 1.38 [95 % CI 1.33–1.44]), Hispanic (1.45 [1.38–1.53]), and Asian/Pacific Islander or Native American (1.25 [1.18–1.32]) race were associated with significantly increased odds of Emergent operation relative to White. Over the study period, non-White patients consistently comprised over 5 % greater proportion of the Emergent cohort compared to Elective. Furthermore, Emergent admission was associated with 3-fold increase in mortality and complications, 5-day increment in LOS, and $10,100 increase in costs. MAE rates among Emergent patients remained greater than Elective with a widening gap over time. Non-White patients experienced significantly increased MAE regardless of admission type. Conclusion: Non-White race was associated with increased odds of emergent colorectal cancer resection. Given the persistent disparity over the past decade, systematic approaches to alleviate racial inequities in colorectal cancer screening and improve access to timely surgical treatment are warranted.

This dataset integrates and helps examine the impact of green intellectual capital (GIC) which comprises of green human capital (GHC), green structural capital (GSC), and green relational capital (GRC) on green organizational culture (GOC). Secondly, it enables the investigation of GOC as a mediation phenomenon between GIC and sustainable business model innovation (SBMI). Moreover, it highlights the moderation of frugal innovation (FGL) on GOC and SBMI relationship. An online survey was designed using Google forms to collect data from 345 middle/ senior management employees working in medium and large manufacturing firms in Pakistan. Unit of analysis is the organization; thus, each response represents one firm. SPSS and Smart PLS 4 were used for data analysis. Dataset demonstrates that GHC, GSC, and GRC positively impact GOC, which subsequently enhances SBMI. Moreover, effective implementation of FGL can bolster the effect of GOC on SBMI. The dataset is valuable as it can be reproduced and reanalyzed. It offers insights for professionals to revolutionize their innovation for environmental initiatives particularly in the manufacturing sector and train their staff to use modern eco-friendly ingenuities leading to enhanced business performance as well as sustainable development goals. Furthermore, the dataset holds significance for policymakers involved in implementing green economic revitalization programs, enabling them to offer incentives or penalties to encourage compliance.

Objective: Frailty has been repeatedly associated with inferior outcomes after surgical hospitalizations. However, a thorough evaluation of the impact of frailty on the clinical and financial outcomes of patients undergoing solid-organ thoracic transplantation is sparse in the literature. We evaluated the association of frailty, as determined by an administrative tool, with postoperative outcomes and healthcare resource use after heart or lung transplantation. Methods: The Nationwide Readmissions Database was used to identify all adult hospitalizations for heart or lung transplant from 2014 to 2020. Patients were grouped as frail or nonfrail using International Classification of Diseases codes associated with conditions in the Johns Hopkins Adjusted Clinical Groups cluster. Multivariable regression models were developed to evaluate the association of frailty status on in-hospital mortality, complications, length of stay, costs, and unplanned readmissions. Results: Of an estimated 35,862 heart or lung transplant recipients, 7316 (20.4%) were considered frail. After multivariable adjustment, frailty in heart transplantation was associated with greater odds of in-hospital mortality (adjusted odds ratio, 1.54; 95% CI, 1.19-1.99) and infectious complications (adjusted odds ratio, 1.77; 95% CI, 1.45-2.15; P

Cystic echinococcosis (CE), or hydatid disease, is a parasitic infection caused by Echinococcus granulosus endemic to areas with considerable pastoral farming and animal husbandry. Typical presentations include hydatid cyst formation in the liver, lungs, brain, kidneys, or bones. An isolated splenic hydatid cyst is an extremely rare occurrence, accounting for only 0.5%-4% worldwide incidence rates, and recurrent cases are even more infrequent. Globalization, cross-border travel, and altered immigration patterns over time have shifted some of the burden of CE from the developing to the developed world, making the diagnosis challenging for these nonendemic areas. Judicious use of imaging modalities for prompt diagnosis and effective intervention is necessary to treat the initial disease and prevent a recurrence. Herein, we present the case of a 13-year-old male with recurrent isolated splenic hydatid cyst. The patient presented with chronic and nonradiating pain in his left hypochondrium. Physical examination revealed splenomegaly. Ultrasonography showed multiple cysts. Computerized tomography (CT) scan showed cystic lesions in splenic parenchyma with numerous internal enhancing septae. Surgical evacuation was performed for the management of disease.

Medical laboratory workers handle clinical specimens, which are a threat of exposure to infectious agents. Notably, medical laboratory science students report for internships with only theoretical knowledge of biosafety and biorisk management practices, predisposing them to a higher risk of laboratory hazards. In this study, we assessed the influence of entry-level students' adherence to practices and attitudes towards biosafety and biorisk management during the Internship. An online survey tool was used to explore the practices and attitudes towards laboratory biosafety and risk management. Of the 96 students, 60 (62.5%) anonymous responses were received, and of these, 60.3% were direct entrants, and 32.8% were diploma entrants. Most (91.7%) of the students attended hospital internships, with 60.2% in Biosafety Level (BSL)-2 laboratories and 70.2% rotating in all the core areas of laboratory medicine. The 8.3% who did not attend any internship were under the direct entry category. Exposure to biohazards was not significantly associated with laboratory safety level and student entry category (P> 0.05). Recommended laboratory biosafety practices were not significantly associated with the safety level of the laboratory and student entry category (P> 0.05). Poor attitudes towards certain laboratory biosafety practices were not significantly associated with the biosafety level of the training laboratory (P> 0.05), whereas training (P = 0.021) and clean-up procedures (P = 0.048) were associated with laboratory safety levels, respectively. The direct entrants had no access to BSL-3 laboratories, and this category of students had a negative attitude towards internship attendance. Therefore, there is a need to create a multi-channel full range laboratory biosafety and biorisk management teaching reforms based on practical application, real case studies, and laboratory simulation to be incorporated into the curriculum to benefit the direct entrant.

Around the world, the COVID-19 pandemic quickly led to the closure of educational institutions in the hope of reducing infections and fatalities due to this disease. Distant education is becoming a policy priority, although institutions and teachers are neither experienced nor accustomed to its use.The purpose of this study is to determine secondary school teachers' perceptions and requirements of distance education during confinement. To our knowledge, none of the similar studies conducted in this area has approached this issue in Morocco. To determine teachers' perceptions regarding distance education, we conducted an analytical and descriptive survey among secondary school teachers in May, June, and July 2020.The chi-square test has been used to test the association between all variables. The association was considered significant when the p-value < 0.05. The calculation of the chi² (X²) and the p-value is performed using R software.The grouping of responses show that most teachers have been teaching remotely during confinement using Whatsapp. They confirmed that this is a useful way to ensure pedagogical continuity during the break from classroom teaching, and they also indicated a preference for both face-to-face and hybrid tutoring.Statistical analysis showed a significant correlation between the subjects taught and distance education (X2= 67.4 with p = 0.01), and a low correlation between training follow-up and distance education during the confinement period r = 0.12.This national study, focused in the secondary school teachers, is pertinent and has showen the extent of the problems of continuous teacher training, as well as strategies that are not evaluated and which do not take into account the perceptions of the actors, including the teacher. This data will be valuable and can be used to establish appropriate measures for improving distance learning tools and the quality and competencies of the actors.

Lately, ensuring clear discrimination of the authenticity of natural honey is a concern not only to consumers but also to producers, traders and industries. The intrinsically simple nature of the honey composition, the distinguished health benefits as well as the high price make adulteration and falsification of the honey very common and the detection of authenticity very difficult. Samar honey (n = 59) and Talh honey (n = 64) produced from two species of Acacia trees (Acacia tortilis and Acacia gerrardii Benth, respectively) in different countries, including the United Arab Emirates, Saudi Arabia, Oman, and Yemen, has been studied by applying Multivariate Data Analysis. The discrimination is based on the official chemical quality parameters that inform about the nectary sources, including glucose, fructose, sucrose content, total reducing sugar, moisture content, acidity and diastase activity. Results show that the total reducing sugar, glucose and fructose were the most important positive loading descriptors that influence the quality of Samar and Talh honey. In addition, most of the Talh honey samples clustered at the top of the hierarchy, while Samar honey samples clustered at the bottom. The Multivariate Data Analysis indicates that the acidity and diastase activity are the most effective characteristics influencing the floral and geographical discrimination of both types of honey. This is the first study in the GCC area to discriminate between Samar and Talh honey using Multivariate Data Analysis by applying the principal component analysis and hierarchical cluster analysis. The Multivariate Data Analysis can be a helpful method to differentiate between Talh and Samar honey.

Centrifugal casting is one of the advanced casting techniques widely used in modern metallurgical industries. The current work is concerned and focuses on study the effects of a selected horizontal and vertical centrifugal casting parameters including, the type of the process, the mold rotation (spinning) speeds and the adding ratio of carbide silicone (SiC) micro powder on the quality of the hypoeutectic AlSi alloy hollow cylindrical fabricated workpieces by using the response surface methodology (RSM) and the full factorial design (FFD) for the design of experiments (DOE). After examined the qualities of the producing workpieces, it is found that the finest porosities were obtained when using the vertical centrifugal casting processes, especially at mold speed of 920 RPM without adding the SiC powder and the porosity sizes increased at higher mold speeds up to 1440 RPM. At these mold speeds the inner surfaces of the produced workpieces seen with lowest raining and shrinkage cavities defects, and with the best outer surfaces qualities especially when using the adding of 0.6% SiC powder. The maximum tensile strength obtained when using the higher mold speed and the corresponding G factor values, without using the added SiC mixed powder and when using the vertical centrifugal casting, reached 167 MPa. The maximum proof stresses were obtained when using the higher mold speed values, the added SiC mixed micro powder and using the vertical centrifugal casting, reached 13.6 MPa. Finally, the maximum percentage elongation was obtained when using the mold speed of 920 RPM, which equivalent to G factor value of 56 with using of the added SiC mixed powder and vertical centrifugal casting reached 1.6%. This means that the values of maximum tensile strength, proof stresses and percentage elongation obtained for the hypoeutectic Al-Si Alloy hollow cylindrical fabricated workpieces when using the centrifugal casting processes, increased by 355, 13.3 and 87,5%, respectively when comparing with the using of the conventional gravitational casting process. Keywords: Centrifugal casting, Response surface methodology (RSM), Hypoeutectic AlSi alloy, Design of experiments (DOE), Carbide silicone (SiC) micro powder, G factor

This paper deals with studying the effect of powder mixing electrical discharge machining (PMEDM) parameters using copper and graphite electrodes on the white layer thickness (WLT), the total heat flux generated and the fatigue life. Response surface methodology (RSM) was used to plan and design the experimental work matrices for two groups of experiments: for the first EDM group, kerosene dielectric was used alone, whereas the second was treated by adding the SiC micro powders mixing to dielectric fluid (PMEDM). The total heat flux generated and fatigue lives after EDM and PMEDM models were developed by FEM using ANSYS 15.0 software. The graphite electrodes gave a total heat flux higher than copper electrodes by 82.4%, while using the SiC powder and graphite electrodes gave a higher total heat flux than copper electrodes by 91.5%. The lowest WLT values of 5.0 µm and 5.57 µm are reached at a high current and low current with low pulse on time using the copper and graphite electrodes and the SiC powder, respectively. This means that there is an improvement in WLT by 134% and 110%, respectively, when compared with the use of same electrodes and kerosene dielectric alone. The graphite electrodes with PMEDM and SiC powder improved the experimental fatigue safety factor by 7.30% compared with the use of copper electrodes and by 14.61% and 18.61% compared with results using the kerosene dielectric alone with copper and graphite electrodes, respectively.

OBJECTIVE: Evaluate the incidence of mycobacterial disease and the colonization of the respiratory and gastrointestinal tracts by Mycobacterium avium complex (MAC) bacteria in AIDS patients. METHODS: Inclusion criteria: HIV-positive individuals with at least one CD4+ count < 100 cells/mm³. Exclusion criteria: Mycobacterial disease and MAC prophylaxis. Stool, sputum, and blood cultures were prospectively obtained every month from September, 1997, to December, 1999. The incidence was calculated using Poisson regression. Survival was estimated by the Kaplan Meier method and the Cox proportional hazard model. RESULTS: We followed-up 79 patients during a median period of 428 days. Blood cultures (n = 742) were negative for all mycobacteria. Positive cultures (25 samples) were obtained from non-sterile sites: Stools (19/703 specimens = 2.7%) and sputum (14/742 specimens = 1.9%). MAC was isolated in 7/703 stool samples (1%) and 1/32 sputum specimens (0.1%). The incidence of patient colonization with MAC was 0.09 /year (CI=0.05 - 0.18). CD4 counts in patients colonized with MAC were below 100 cells/mm³ in only 2 out of 8 cases. Restoration of CD4+ counts >100 cells/mm³ (HR = 0.18; CI = 0.05 - 0.70) predicted a lower risk of death (P

Aims: Roflumilast, a well-known phosphodiesterase-4 (PDE-4) inhibitor, possess an anti-inflammatory activity with approved indications in chronic obstructive pulmonary disease. This study aimed to evaluate the neuroprotective role of roflumilast in ovariectomy (OVX)-induced depressive-like behavior in female rats and to shed light on a potential autophagy enhancing effect., Main Methods: Rats were randomly divided into four groups: sham, OVX, OVX + roflumilast (1 mg/kg, p.o), and OVX + roflumilast + chloroquine (CQ) (50 mg/kg, i.p). Drugs were administered for 4 weeks starting 2 weeks after OVX., Key Findings: Roflumilast improved the depressive-like behaviors observed in OVX rats as evidenced by decreasing both forced swimming and open field immobility times while, increasing % sucrose preference and number of open field crossed squares. Histopathological analysis provides further evidence of roflumilast's beneficial effects, demonstrating that roflumilast ameliorated the neuronal damage caused by OVX. Roflumilast antidepressant potential was mediated via restoring hippocampal cAMP and BDNF levels as well as down-regulating PDE4 expression. Moreover, roflumilast revealed anti-inflammatory and anti-apoptotic effects via hindering TNF-α level and diminishing Bax/Bcl2 ratio. Roflumilast restored the autophagic function via up-regulation of p-AMPK, p-ULK1, Beclin-1 and LC3II/I expression, along with downregulation of P62 level and p-mTOR protein expression. The autophagy inhibitor CQ was used to demonstrate the suggested pathway., Significance: The present study revealed that roflumilast showed an anti-depressant activity in OVX female rats via turning on AMPK/mTOR/ULK1-dependent autophagy pathway; and neurotrophic, anti-inflammatory, and anti-apoptotic activities. Roflumilast could offer a more secure alternative to hormone replacement therapy for postmenopausal depression treatment., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aim: There is a well-founded relation between bullying and depression, which may eventually lead to suicidal behavior. Repurposing of antidiabetic drugs for the treatment of depression started to glow, which open new horizons to introduce the antidiabetic medications as new treatment picks in depression. Dulaglutide has been approved as remedy of type 2 diabetes mellitus (T2DM). Consequently, our scope of work is to investigate the ability of dulaglutide to indulgence depression via deeply reconnoitering the Glucagon-like peptide-1 receptor and cAMP/PKA Signaling Pathway., Materials and Methods: Eighty mice were divided into two groups; one with and the other without the induction of chronic social defeat stress (CSDS). Each group was subdivided into two subsets; the first one was treated with saline for 42 days, while the other was treated with saline for 20 days, then with dulaglutide (0.6 mg/kg/week) for four weeks., Key Findings: CSDS group showed a lessening in the social interaction ratio and sucrose consumption. They spent less exploration time in the open arms, and more time in the closed arms in elevated plus maze test as compared to controls. Furthermore, the CSDS group had a higher expression of NOD- like receptor protein-3 which explained the elevation in inflammatory biomarkers (IL-1β, IL-18, IL-6 and TNF-α) along with diminution in GLP-1R, cAMP/PKA levels. Treatment with dulaglutide markedly reversed the above-mentioned parameters via bolstering the GLP-1R/cAMP/PKA pathway., Significance: NLRP3 inflammasome activation expedites depression. Dulaglutide activates the GLP-1R/cAMP/PKA pathway, hence offering a novel therapeutic intervention to hinder depression., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disease characterized by involuntary bizarre movements, psychiatric symptoms, dementia, and early death. Several studies suggested neuroprotective activities of inosine; however its role in HD is yet to be elucidated. The current study aimed to demonstrate the neuroprotective effect of inosine in 3-nitropropionic acid (3-NP)-induced neurotoxicity in rats while investigating possible underlying mechanisms. Rats were randomly divided into five groups; group 1 received i.p. injections of 1% DMSO, whereas groups 2, 3, 4, and 5 received 3-NP (10 mg/kg, i.p.) for 14 days, concomitantly with inosine (200 mg/kg., i.p.) in groups 3, 4, and 5, SCH58261, a selective adenosine 2A receptor (A2AR) antagonist, (0.05 mg/kg, i.p.) in group 4, and PD98059, an extracellular signal-regulated kinase (ERK) inhibitor, (0.3 mg/kg, i.p.) in group 5. Treatment with inosine mitigated 3-NP-induced motor abnormalities and body weight loss. Moreover, inosine boosted the striatal brain-derived neurotrophic factor (BDNF) level, p-tropomyosin receptor kinase B (TrKB), p-ERK, and p-cAMP response element-binding protein (CREB) expression, which subsequently suppressed oxidative stress biomarkers (malondialdehyde and nitric oxide) and pro-inflammatory cytokines (tumor necrosis factor alpha and interleukin-1β) and replenished the glutathione content. Similarly, histopathological analyses revealed decreased striatal injury score, the expression of the glial fibrillary acidic protein, and neuronal loss after inosine treatment. These effects were attenuated by the pre-administration of SCH58261 or PD98059. In conclusion, inosine attenuated 3-NP-induced HD-like symptoms in rats, at least in part, via the activation of the A2AR/BDNF/TrKB/ERK/CREB signaling pathway., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aim: Alcohol abuse is a significant causative factor of death worldwide. The Notch1 signaling pathway is involved in alcohol tolerance, withdrawal and dependence. Agomelatine is a known antidepressant acting as a melatonin receptor (MT1/2) agonist and a 5-hydroxytryptamine receptor-2C antagonist. However, its effects on alcohol cravings and alcohol withdrawal symptoms have not been investigated. In this study, we assessed the possibility of using agomelatine for the treatment of these symptoms in a rat model of alcoholism and the possible role of Notch1 signaling., Main Methods: We induced alcoholism in rats using a free-choice drinking model for 60 days. From day 61, free-choice was continued until day 82 for the craving model, whereas only water was offered in the withdrawal model. Meanwhile, the treated groups for both models received agomelatine (50 mg/kg/day) orally from day 61 to 82, followed by behavioral, histopathological and biochemical assessment., Key Findings: Agomelatine treatment caused significant decrease in alcohol consumption with a positive effect on anxiety-like behavior in the open field, memory in the Morris water maze and immobility in the forced swim test. Moreover, agomelatine induced the expression of Notch1 pathway markers, including Notch1, NICD, CREB, CCNE-2, Hes-1, both total and phosphorylated ERK1/2, MMP9, Per2and RGS-2 in the hippocampal formation. By contrast, NMDAR expression was reduced. Furthermore, agomelatine normalized the serum levels of BDNF, cortisol, dopamine and glutamate which were disrupted by alcohol consumption., Significance: Based on these findings, agomelatine reversed alcohol cravings and withdrawal symptoms associated with alcohol dependence by modulating the Notch1 signaling pathway., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: Stroke has risen to the fifth and third most common causes of death in the United States and the rest of the world, respectively. Vortioxetine (VTX) is a multimodal antidepressant agent that balances 5-HT receptors and represses the serotonin transporter. Our study aimed to examine the neuroprotective impacts of VTX against cerebral ischemia caused by occluding the middle cerebral artery (MCA)., Main Methods: Until the middle cerebral artery occlusion (MCAO) induction, VTX (10 mg/kg/day) was taken orally for 14 days. Behavioral assessments were carried out 24 h after the MCAO technique. The hippocampal and cortical tissues of the brain were isolated to assess the histological changes and the levels of the biochemical parameters., Key Findings: MCAO damage led to severe neurological deficits and histopathological damage. However, VTX improved MCAO-induced neurological deficits and ameliorated histopathological changes in both hippocampal and cortical tissues of MCAO rats. Western blot analysis showed increments of p-PERK, CHOP, ASK-1, NICD, HES-1, HES-5, and p-eIF2α expression levels in MCAO rats. Moreover, ELISA revealed an increase in the levels of ATF4, IRE1, Apaf-1, and HIF-1α, while VTX administration ameliorated most of these perturbations induced after MCAO injury., Significance: This research suggests that VTX could be a potent neuroprotective agent against ischemic stroke by inhibiting a variety of oxidative, apoptotic, inflammatory, and endoplasmic reticulum stress pathways., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Dapagliflozin, a selective sodium-glucose co-transporter 2 (SGLT2) inhibitor, has featured marked anti-inflammatory effects in murine models of myocardial infarction, renal injury, and neuroinflammation. Yet, its potential impact on the pathogenesis of inflammatory bowel diseases (IBD) has not been previously investigated. The presented study aimed to explore the prospect of dapagliflozin to mitigate 2,4,6 trinitrobenzene sulfonic acid (TNBS)-induced rat colitis model which recapitulates several features of the human IBD. The molecular mechanisms pertaining to the dynamic balance between autophagy/apoptosis and colon injury were delineated, particularly, AMPK/mTOR, HMGB1/RAGE/NF-κB and Nrf2/HO-1 pathways. The colon tissues were examined using immunoblotting, ELISA, and histopathology. Dapagliflozin (0.1, 1 and 5 mg/kg; p.o.) dose-dependently mitigated colitis severity as manifested by suppression of the disease activity scores, macroscopic damage scores, colon weight/length ratio, histopathologic perturbations, and inflammatory markers. More important, dapagliflozin enhanced colonic autophagy via upregulating Beclin 1 and downregulating p62 SQSTM1 protein expression. In this context, dapagliflozin activated the AMPK/mTOR pathway by increasing the p-AMPK/AMPK and lowering the p-mTOR/mTOR ratios, thereby, favoring autophagy. Moreover, dapagliflozin dampened the colonic apoptosis via lowering the caspase-3 activity, cleaved caspase-3 expression, and Bax/Bcl-2 ratio. Furthermore, dapagliflozin attenuated the HMGB1/RAGE/NF-κB pathway via lowering HMGB1, RAGE, and p-NF-κBp65 protein expression. Regarding oxidative stress, dapagliflozin lowered the oxidative stress markers and augmented the Nrf2/HO-1 pathway. Together, the present study reveals, for the first time, the ameliorative effect of dapagliflozin against experimental colitis via augmenting colonic autophagy and curbing apoptosis through activation of AMPK/mTOR and Nrf2/HO-1 pathways and suppression of HMGB1/RAGE/NF-κB cascade., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Aims: Polycystic ovary syndrome (PCOS), the rifest endocrine disorder in women, is involved in disrupting many metabolic processes. However, the impact of PCOS on cognitive deficits is still uncertain. Recently, Notch signaling pathway was identified as a key modifier in regulating the pathological process in the ovary and various neurodegenerative disorders. Liraglutide has favourable neuroprotective effects that may protect against the possible cognitive dysfunction in PCOS., Main Methods: PCOS was induced in rats by administrating Letrozole orally for 21 successive days. Then, Liraglutide (LIR) was administered intraperitoneally for 30 days. Memory was examined using Y-maze, novel object recognition (NOR), and Morris water maze (MWM) tests. Western blotting, enzyme immunoassay, and quantitative real-time PCR were used to examine Notch signaling downstream targets, as well as assessing the expression of the components of various pathways cross talked with Notch signaling in memory impairment. Furthermore, histopathological examination was performed to examine neuronal changes., Key Findings: Notch signaling was overexpressed in PCOS rats, which increased Aβ aggregation, apoptosis, and neuroinflammation. Additionally, histopathological examination showed neuronal degeneration, which was marked by diminished acetylcholine levels in the PCOS rats' hippocampi. Finally, serum levels of insulin and testosterone were elevated while estradiol was reduced. Treatment with LIR repaired Notch signaling-attributed changes and improved the PCOS-induced memory impairment in rats., Significance: The obtained findings confirm that Notch signaling activation in the hippocampus of rats impairs cognitive functions in PCOS, which is mitigated by LIR. Therefore, LIR may offer a novel therapeutic intervention to impede PCOS-induced dementia., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Ketoprofen is a widely used NSAID which incurs gastric mucosal damage. The high mobility group Box 1 (HMGB1) protein is a DNA-binding protein which exerts robust inflammatory actions, however, its role in ketoprofen-induced gastric damage has not been explored. Additionally, no previous studies have linked HMGB1/RAGE/NF-κB, DJ-1/Nrf2/HO-1 and PI3K/mTOR pathways in ketoprofen-induced gastropathy. The current work aimed to explore the potential of morin, a flavonoid with marked antioxidant/anti-inflammatory actions, to protect against ketoprofen-evoked gastric damage. Moreover, the underlying mechanisms, including the impact of morin on HMGB1/RAGE/NF-κB, DJ-1/Nrf2/HO-1 and PI3K/mTOR pathways were addressed. Immunoblotting and ELISA were used to examine the expression of target signals. Morin (50 mg/kg, p. o.) attenuated the severity of gastric injury via lowering of ulceration/hemorrhage and macroscopic damage scores. Meanwhile, it attenuated the histopathologic aberrations/damage scores. In the context of inflammation, morin suppressed TNF-α and myeloperoxidase levels and enhanced IL-10. Furthermore, it inhibited HMGB1/RAGE/NF-κB pathway through downregulating HMGB1, RAGE and phospho-NF-κBp65 protein expression. Morin successfully inhibited gastric mucosal oxidative stress through lowering of lipid peroxides and boosting of reduced glutathione, glutathione peroxidase and total antioxidant capacity. It also boosted DJ-1/Nrf2/HO-1 pathway via upregulating DJ-1, Nrf2 and HO-1 protein expression. Additionally, morin counteracted the apoptotic events by downregulating the proapoptotic Bax and Bax/Bcl-2 ratio and augmenting the PI3K/mTOR pathway through upregulating PI3Kp110α and phospho-mTOR protein expression. In conclusion, the current study demonstrates, for the first time, that morin shows a promise for the management of ketoprofen-induced mucosal insult through targeting of HMGB1/RAGE/NF-κB, DJ-1/Nrf2/HO-1 and PI3K/mTOR pathways., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aims: Huntington's disease is a rare neurodegenerative disorder which is associated with defected glucose metabolism with consequent behavioral disturbance including memory and locomotion. 3-nitropropionic acid (3-NP) can cause, in high single dose, an acute striatal injury/Huntington's disease. Dapagliflozin, which is one of the longest duration of action of SGLTIs family, may be able to diminish that injury and its resultant behavioral disturbances., Material and Methods: Forty rats were divided into four groups (n = 10 in each group): normal control group (CTRL), dapagliflozin (CTRL + DAPA) group, 3-nitropropionic acid (3-NP) group, and dapagliflozin plus 3-nitropropionic acid (DAPA + 3-NP) group. Behavioral tests (beam walking test, hanging wire test, limb withdrawal test, Y-maze spontaneous alteration, elevated plus maze) were performed with evaluating neurological scoring. In striatum, neurotransmitters (glutamate, aspartate, GABA, ACh and AChE activity) were measured. In addition, apoptosis and glycolysis markers (NF-κB, Cyt-c, lactate, HK-II activity, P53, calpain, PEA15 and TIGAR) were determined. Inflammation (IL-1β, IL-6, IL-8 and TNF-α) and autophagy (beclin-1, LC3 and DRAM) indicators were measured. Additionally, histopathological screening was conducted., Key Findings: 3-Nitropropionic acid had the ability to perturb the neurotransmission which was reflected in impaired behavioral outcome. All of glycolysis, apoptosis and inflammation markers were elevated after 3-NP acute intoxication but autophagy parameters, except DRAM, were reduced. However, DAPA markedly reversed the abovementioned parameters., Significance: Dapagliflozin demonstrated anti-glycolytic, anti-apoptotic, anti-inflammatory and autophagic effects on 3-NP-damaged striatal cells and promoted the behavioral outcome., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Recently, oxidative stress was implicated in the environmental contaminant Di-(2-ethylhexyl) phthalate (DEHP)-induced testicular toxicity, however the mechanism is unclear. We investigated the role of oxidative stress-responsive microRNAs in DEHP-induced aberrations and the protective effect of the citrus flavonoid, hesperidin (HSP). Male Wistar rats were randomly allocated into four groups as vehicle-treated control, DEHP-alone group (500 mg/kg/day) for 30 days, and HSP (25 or 50 mg/kg) for 60 days; testicular damage was triggered by oral administration of DEHP (500 mg/kg/day) after thirty days of oral administration of HSP (25 or 50 mg/kg). DEHP administration reduced testis weight coefficient, serum testosterone, testicular 3β-hydroxysteroid dehydrogenase and antioxidant enzyme activities, and elevated serum fatty acid-binding protein-9, testicular malondialdehyde, and Bax/Bcl2 ratio. Aberrant testicular miR-126-3p and miR-181a expression was observed, along with decreased expression of sirtuin1 (SIRT1) and its targets; nuclear factor-erythroid 2-related factor2, haeme oxygenase-1, and superoxide dismutase2. HSP administration significantly ameliorated these changes and restored testicular function in a dose-dependent manner. We highlight a novel role of oxidative stress-miR-126/miR-181a-SIRT1 network in mediating DEHP-induced changes which were reversed by the antioxidant HSP., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Purpose: Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disease which poses a need to explore effective yet safe pharmacotherapeutic options. The current work aimed to study the therapeutic role of nicorandil in controlling RA., Experimental Approach: Complete Freund's adjuvant (CFA)-induced arthritis model was applied by injecting 400 μL of CFA in the right hind paw at day 0 and day 7. Four groups of rats were used as follows: normal-control (CTRL), CFA-induced arthritis (ART), CFA-induced arthritis treated with diclofenac (DIC) and CFA-induced arthritis treated with nicorandil (NIC). Both NIC and DIC were administered at day 14 for two weeks. Paw volume, knee joint diameter, pain behavior assessment as well as body weight were all periodically recorded throughout the experimental period. Following the sacrifice of animals at day 28, gene expressions of TLR-4, MyD88 and TRAF6 as well as extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), nuclear factor Kappa B (NF-κB) were quantified in hind paws tissue. Finally, the serum levels of the inflammatory biomarkers (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) together with the histopathological examination of sections in the rat hind paw were recorded., Results: Both NIC and DIC proved promising anti-arthritic potential mediated, at least in part through switching off TLR4-MyD88-TRAF6 axis as well as downstream TRAF6 dependent activated MAP kinases and NF-κB., Conclusion and Implications: Nicorandil, via interfering with TLR4 signaling, sheds light on a potential clinical role of the drug in pursuit for safe and effective regimens for RA., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aims: Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome. Paracetamol (APAP) causes, in high doses, a hepatic injury. Alogliptin (ALO), with its 100% oral bioavailability, may be able to reverse the acute hepatic injury and memory impairments., Materials and Methods: Forty rats were divided into four groups as follows; Normal Control Group, APAP intoxicated group, ALO and SIL groups. Behavioral tests (Morris water maze, Y-maze spontaneous alteration, and novel object recognition test) were performed together with evaluating HE score. Neurotransmitters (gamma-aminobutyric acid, glutamate, dopamine, serotonin, norepinephrine and acetylcholine), as well as acetylcholinesterase activity, were determined in the hippocampus. Also, hepatotoxicity markers (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and ammonia) were measured in blood. Additionally, transforming growth factor beta 1, tumor necrosis factor alpha, cytochrome c, granzyme B and caspase-3, coiled-coil Moesin-like BCL-interacting protein 1 "beclin-1", cellular FLICE-like inhibitory protein, protein 53, TNF-α related apoptosis-inducing ligand, Fas-ligand and alpha-smooth muscle actin were measured in liver homogenate. Moreover, the histopathological investigation was performed., Key Findings: APAP was able to disturb neurotransmitters which were mirrored in the performance of rats in the behavioral test. Most hepatotoxicity, apoptosis and inflammation indicators were elevated after APAP administration, while beclin-1 (autophagy marker) was declined. The tested drugs, both, reversed most of the last mentioned parameters but ALO was more efficient in reducing TGF-β1, α-SMA, TNF-α and ALP as well as increasing % alteration., Significance: ALO and SIL elicited anti-apoptotic, anti-inflammatory and autophagic effects on paracetamol-damaged liver cells and improved memory impairments of HE., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To detect co-infections in the culture-proven acanthamoebic keratitis (AK) cases, and to test the capability of biofilm formation in the isolated microbiota. The clinical findings, habit of wearing contact lens and in-vitro antibiotic resistance were analyzed further according to the biofilm formation capability., Methods: After clinical examination, corneal scraps and swabs were taken from 240 clinically suspected AK cases, for Acanthamoeba and microbiological cultures. In cases of keratoplasty, trimmed corneal tissue was collected and sent for histopathological examination. Scanning electron microscopy was done for some samples. Biofilm formation capability was investigated using a tissue culture plate method. Antibiotic resistance pattern was determined using a modified-Kirby-Bauer disc diffusion method., Results: In 102 AK culture proven cases, 11 had no co-infection, 74 had a single co-infection and 17 had double co-infections. Enterobactericae and Aspergillus were the commonest bacterial and fungal isolates, respectively. Regarding the biofilm formation, 64.7% of Enterobactericae, 50% of Pseudomonas aeuroginosa, 43.75% of Staph aureus, 76.92% of Streptococcus pneumoniae, 28.57% of Corynebacterium, 60% of α-haemolytic streptococci, 40% of Acinetobacter, 100% of Candida and 77.8% Aspergillus isolates were biofilm producers. Severe manifestations were more frequently reported in cases co-infected with biofilm producers than with non-biofilm producers. Generally, high percentages of the biofilm forming bacterial isolates were sensitive to antibiotics in-vitro., Conclusions: Routine investigations for co-infection and biofilm formation in addition to Acanthamoeba culture are strongly recommended in suspected AK cases. Co-infection with biofilm producers may precipitate extrinsic in-vivo drug resistance despite of the in-vitro sensitivity. Designing a biofilm-dissolving topical drug is highly recommended to enhance the response to the standard therapeutic regimen especially in the resistant AK cases., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: Statins are the most widely used to lower elevated low-density lipoprotein levels and preventing cardiovascular diseases in humans. However, about 20% of patients treated with this medication suffer from statin-related myalgia. To this end, this study investigated the potential effect of nano-particulate formulation in alleviating the muscles and liver damage either alone or when co-administered with nano coenzyme Q10 and nano vitamin E., Materials and Methods: Male Wistar rats were fed normal diet or high-fat diet for 12 weeks, following which rats were treated with either (i) atorvastatin (5 or 20 mg/kg/day, p.o.) or (ii) atorvastatin with CoQ10 (10 mg/kg/day, p.o.) (iii) and/or vitamin E (30 mg/kg/day, p.o.) in free particle or nanoparticle forms for another 4 weeks. In all rats, serum total cholesterol (CH), triglycerides (TGs), low (LDL) and high (HDL) density lipoproteins, alanine (ALT) and aspartate (AST) transaminases, alkaline phosphatase (ALP), creatine kinase (CK), albumin (ALB), as well as hepatic malondialdehyde (MDA) and antioxidants "reduced glutathione (GSH) and superoxide dismutase (SOD)" were measured. Additionally quadriceps muscles and liver tissues were used for histopathological examination., Key Findings: The antihyperlipidemic effect of statins was not altered when formulated as nanoparticles; albeit the former showed a prominent reduction in the liver and muscle enzymes and histopathological alterations together with a marked decline in the oxidative stress as compared to the free particulate form. These results were augmented when atorvastatin was combined with CoQ10 and/or Vit.E., Significance: Nanoparticulate formulation alleviated the statins induced liver and muscle damage especially when combined with CoQ10 and/or Vit.E., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: We evaluated the effect of time spent in the emergency department (ED) and process of care on mortality and length of hospital stay in patients with sepsis or septic shock., Methods: An observational cohort study was conducted on 117 patients who came through the University of Louisville Hospital ED and subsequently were directly admitted to the intensive care unit (ICU). Variables of interest were time in the ED from triage to physical transport to the ICU, from triage to antibiotic(s) ordered, and from triage to antibiotic(s) administered. Expected mortality was calculated according to the University Health System Consortium Database. Primary and secondary outcomes were in-hospital death and hospital length of stay in days, respectively., Results: We found no significant association between time in the ED and mortality between survivors and nonsurvivors (5.5 versus 5.7 hours, P = 0.804). After adjusting for expected mortality, a 22% increase in mortality risk was found for each hour delay from triage to antibiotic(s) ordered; a 15% increase in mortality risk was observed for each hour from triage to antibiotic(s) given. Both time from triage to antibiotic(s) ordered (hazard ratio [HR] = 0.8, P = 0.044) and time from triage to antibiotic(s) delivery (HR = 0.79, P = 0.0092) were independently associated with an increased hospital stay (HR = 0.79, P = 0.0092)., Conclusion: Though no significant association between mortality and ED time was demonstrated, we observed a significant increase in mortality in septic patients with both delays in antibiotic(s) order and administration. Delay in care also resulted in increased hospital stays both overall and in the ICU., (Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

This study aims to elucidate whether Trichinella spiralis infection or its crude antigen administration can stimulate recruitment of CD105 +ve /CD45 -ve cells that could represent MSCs in intestine and skeletal muscle of experimental BALB/c albino mice compared to healthy control mice. Studied mice were divided into: 20 healthy control, 20 with orally induced T. spiralis infection, 20 received adult worm crude antigen orally and 20 received larval crude antigen intramuscular. According to specific timing schedule, mice were sacrificed and tissue sections were examined for CD105 and CD45 immunohistochemical expression using image J image analyzing software, to compare different study groups. T. spiralis infection induced a significant increase in density of CD105 +ve /CD45 -ve cells that could represent MSCs in both intestinal and muscle sections, similarly the intramuscular injected larval crude antigen caused more infiltration of such cells in muscles compared to muscle sections from healthy control mice. However, no significant difference was noticed in intestinal sections after oral adult crude antigen administration compared to healthy control mice. So, injected T. spiralis crude antigen might be a successful stimulant to MSCs attraction and recruitment in tissues nearby injection site. This could be beneficial for cell regeneration and tissue repair in case of presence of a disease induced damage., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: It has been argued recently that ischemic preconditioning (IPre) and postconditioning (IPost) have beneficial effects in many ischemic disorders however; their effects on global ischemia/reperfusion (I/R) are poorly understood. Thus, the present work aimed to study the possible mechanisms underlying the neuroprotective effects of IPre and IPost., Methods: Animals were randomly allocated into 4 groups (n = 30): (1) Sham operated (SO); (2) I/R group, animals were subjected to 15 min global ischemia followed by 60 min reperfusion; (3) IPre, animals were subjected to 3 episodes of 5 min ischemia followed by 10 min reperfusion before I/R; (4) IPost, animals were subjected to three episodes of 10s of ischemia and 10s of reperfusion after the period of ischemia followed by a 60 min reperfusion period. Lactate dehydrogenase activity, oxidative stress, inflammatory and apoptotic biomarkers, as well as neurotransmitters, infarct size and histopathological examination were assessed., Results: I/R induced hippocampal damage through increasing oxidative stress, inflammatory, excitotoxic and apoptotic markers as well as lactate dehydrogenase activity and infarct size. Both, IPre and IPost attenuated most markers induced by I/R., Conclusions: IPre and IPost neuroprotective effects can be explained through their anti-oxidant, anti-inflammatory and anti-apoptotic mechanisms., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

To assess the effect of Schistosoma mansoni egg antigen immunization on the immunomodulation in dextran sodium sulfate (DSS) induced colitis as an experimental model of IBD in comparison to non immunization and healthy control. The study was performed on 180 mice; 25 healthy control, 15 to identify the inflammatory peak of DSS, 25 received DSS for 7 days; 90 infected with S. mansoni cercariae to collect eggs for antigen preparation, and 25 immunized with the prepared antigen then received DSS course. Disease activity index, macroscopic & microscopic inflammatory scores, FoxP3+ T regulatory cell count, myeloperoxidase activity, and Th1/Th2 cytokine profile were compared in studied groups. Immunization induced both FoxP3+ T(regs) and Th2 cytokines to establish a state of immune homeostasis and create a quiescent steadier immune response to DSS. S. mansoni egg antigen succeeded in acting like a prophylactic helminthic therapy as it has a profitable modulatory effect on DSS-induced colitis model., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The Western Harbor of Alexandria, the largest harbor of Egypt on the Mediterranean Sea, receives different internal and external untreated pollutants affecting dramatically its water, sediments and biota. Surface and bottom water samples were collected bimonthly from this harbor for studying vertical, regional and monthly distributions of total suspended matter (TSM), total dissolved lead (TDPb) and total particulate lead (TPPb). The high surface TSM values coincided with air-borne dust, organic aggregates, plankton productivity and discharged wastes. The high TSM averages in winter resulted mainly from turbulence of the water column by wind action. The highest averages of TDPb in the petroleum and coal basins in the Western Harbor reflect their effects on the water column, while the lowest averages of TDPb and TPPb were found at a location far away from pollution sources. For the water column, the maximum and minimum monthly averages of TPPb and TDPb respectively in June reflect the increase in the rate of lead uptake by phytoplankton abundant in summer, favored by temperature elevation. The annual mean concentration of TPPb was nearly double that of TDPb, indicating that lead was transported to the Western Harbor mainly in particulate form. This reflects the high TSM content in the harbor water onto which a considerable part of lead was adsorbed.

Data were compiled from selected heavy metal studies in both freshwater and marine ecosystems from the major African subregions, Northern, West and Central, Eastern, and Southern Africa. The concentrations of heavy metals were compared between different environmental compartments (water, sediments, fauna, and flora), between the different African subregions and with data from other areas in the world. Despite the scarcity of the existing information on Africa, some conclusions could be drawn: Metal concentrations in organisms were generally below WHO limits except for some localized sites, mostly with increased lead levels. There were no significant differences between inland water and coastal animals, but shellfish had higher concentrations of most metals than finfish. For aquatic plants the heavy metal levels were higher in inland waters. Compared to more industrialized regions and with the exception of some hot-spot sites, the concentrations of heavy metals in African aquatic systems were low and close to natural background levels. Nevertheless, in view of the expected increase in urbanization and socio-economic activities in Africa, sources and quantities of heavy metal discharges to aquatic environments have to be identified. Also, pollution control measures should be formulated in each country.

Histological study of the pedicles of long and short saphenous and cephalic venous flaps in fresh human cadavers and two clinical cases showed that one or two arterioles and multiple capillaries were present in the perivenous areolar tissue. This challenges the concept that these flaps are purely venous.