Gastrointestinal parasitic infections: Prevalence and risk factors in West Ismailia, Arab Republic of Egypt.

BACKGROUND: This study aimed to determine the prevalence of gastrointestinal parasites (GIP) in the rural community of West Ismailia and its associated risk factors. Human infection by GIP is natural and expected. There are few records concerning parasitic infection in the rural areas of the Ismailia Governorate. METHODS: From 520 individuals, sociodemographic and risk factors information were retrieved. Fecal samples were collected, concentrated, and tested for GIP infection using a microscopic examination. RESULTS: The West Ismailia study population had a 40.4% prevalence of GIP infection, including single and concomitant parasite infections. The most common cause of GIP infection was protists (38%). Entamoeba sp., Blastocystis sp., and G. duodenalis were the most common parasites. Poly-parasitism was prevalent within the West Ismailia region. Age, abdominal symptoms, perianal itching, ownership of numerous animal species, exposure to turbid water, previous parasitic infection (PPI), and non-treatment reception of PPI were all considered significant factors associated with GIP infection. Specific individuals from the same family have been observed to have identical GIP. CONCLUSION: GIP infection remains underestimated in rural areas. Periodic screening and treatment for GIP infection in children and public education on GIP hazards and prevention, focusing on personal hygiene, are recommended. Family members of affected individuals should be screened and treated for GIP.

Oleuropein attenuates the nephrotoxic effect of sunitinib in rats: Unraveling the potential role of SIRT6/Notch-1/NLRP-3/IL-1ß axis.

Sunitinib (SUN) is a chemotherapeutic agent clinically approved for treatment of metastatic renal carcinoma. Despite its remarkable benefits, various renal toxicities have been reported that limit its clinical uses. Oleuropein (OLE) is the main polyphenolic constituent of olive tree and mediates the majority of its valuable pharmacological activities. The current study examined the probable renoprotective effects of OLE against SUN-induced nephrotoxicity. Adult male albino rats were co-treated by SUN (25 mg/kg, 3 times/week, PO) with either a drug vehicle or OLE (60 mg/kg/day, daily, PO) for four weeks. A control group comprising of age-matched rats was used. Four weeks later, blood specimens were collected to assess kidney functions. Kidneys were harvested for biochemical and histopathological analyses. Administration of SUN induced kidney dysfunction, along with marked rises in endothelin-1 (ET-1) and monocyte chemotactic protein-1 (MCP-1) levels in renal tissues. Histological abnormalities were also detected in kidneys of SUN-treated rats including glomerular and tubular interstitial congestion along with interstitial fibrosis. On molecular levels, there was a decline in renal SIRT6 expression along with significant up-regulation of Notch-1, NLRP-3, interleukin -1ß (IL-1ß) and cleaved caspsase-3. All these changes were almost alleviated by OLE co-treatment. These findings suggest the implication of SIRT6/Notch-1/NLRP3/IL-1ß axis in the pathogenesis of SUN-induced nephrotoxicity and highlight OLE as a prospective renoprotective agent during SUN chemotherapy to halt its renal toxicity likely through promotion of SIRT6 and suppression of Notch-1/NLRP3/IL-1ß signaling pathway.

Comparative study between the effect of mesenchymal stem cells microvesicles versus ozone on induced liver injury in adult male albino rats (Histological & Immunohistochemical study).

Liver disease accounts for approximately 2 million deaths er year worldwide. Liver fibrisis results from chronic injury to the liver. If not effectively treated in time, liver fibrosis may transform into liver cirrhosis. MVs are recognized as potential biomarkers and important theraputic tools for a wide sectrum of diseases. Medical ozone has the ability to protect the body against pathological conditions caused by oxidative stress. The influence of ozone and MVs on CCL4 induced liver fibrosis was investigated in this study. Forty-eight adult male albino rats were divided into four equal groups. I control, II CCL4 group, III ozone and IV microvesicles groups. Liver fibrosis was induced in group II, III & IV using 12 SC injections (0.5 ml/kg body weight) of CCL4 dissolved in olive oil twice ber week for weeks. Blood samples were obtained to estimate serum ALT & AST. Liver tissues were processed for measurment of GSH & SOD, light and electron microscopic examination. H&E staine sections og group II showed dilated congested sinusoids and centralveins, mononuclear infiltrations, vacuolations and dark nuclei. Ultrastructurally, group II revealed irregular heterochromatic nuclei of hepatocytes, small scanty mitochondria & vacuolations. Morphometric & statistical analyses were performed. Group III showed some improvement, however, group IV showed more imrovement. The results indicates that MVs caused marked improvement than ozone against CCL4 induced liver damage via antioxidant & antiinflammatory properties.

Bifunctional role of some biogenic nanoparticles in controlling wilt disease and promoting growth of common bean.

In the present era, nanomaterials are emerging as a powerful tool for management of plant disease and improving crop production to meet the growing global need for food. Thus, this paper was conducted to explore the effectiveness of five different types of nanoparticles (NPs) viz., Co3O4NPs, CuONPs, Fe3O4NPs, NiONPs, and ZnONPs as treatments for Fusarium wilt as well as their role in promoting growth of the common bean plant. The five types of NPs were applied as a treatment for wilt in two ways, therapeutic and protective plans under greenhouse conditions. In vivo experiments showed that all types of NPs significantly increased disease control and diminished the symptoms of Fusarium wilt for both incidence and severity. The recorded values for disease control using the respective NPs during the protective plan were 82.77, 60.17, 49.67, 38.23, and 70.59%. Meanwhile these values were 92.84, 64.67, 51.33, 45.61, 73.84% during the therapeutic plan. Moreover, CuONPs during the protective plan were the best among the five types of NPs employed in terms of wilt disease management. Regarding the use of these NPs as growth promoters, the obtained results confirmed the effectiveness of the five types of NPs in enhancing vegetative growth of the plant under greenhouse conditions, in comparison with control. Among the five NPs, CuONPs improved the plant vegetative growth and particularly increased the content of the photosynthetic pigments; chlorophyll-a (2.96 mg/g), -b (1.93 mg/g), and total carotenoids (1.16 mg/g). These findings suggest the successful and potential exploitation of nanomaterials in agriculture deployed as nano-based products including nano-fungicides and nano-fertilizers. In terms of sustainability, this promising and exceptional multifunctional role of these nanomaterials will surely exert positive impacts on both the environment and sustainable agriculture.

Association between diabetes-related distress and glycemic control in primary care patients with Type 2 diabetes during the coronavirus disease 2019 (COVID-19) pandemic in Egypt.

BACKGROUND: Diabetes-related distress and glycemic control are of a particular concern to primary care physicians because of the impact of the coronavirus disease 2019 pandemic on diabetic patients' lifestyle, psychological well-being and healthcare access. Our aim was to evaluate the relationship between diabetes-related distress and glycemic control in diabetic patients with Type 2 diabetes mellitus (T2DM) in primary care settings during the pandemic. MATERIALS AND METHODS: This cross-sectional study was conducted at primary healthcare clinics in a rural area in Egypt among 430 patients with T2DM during the period from September 2020 to June 2021. All patients were interviewed for their sociodemographic, lifestyle, and clinical characteristics. Diabetes-related distress was measured by the problem areas in the diabetes scale (PAID), where a total score of ≥40 indicated a severe diabetes-related distress. The most recent glycosylated hemoglobin (HbA1c) measurements were used to indicate the glycemic control. Quantile regression model (0.50 quantile) was used to perform the multivariate analysis to identify significant factors associated with HbA1c level. RESULTS: Most of the participants had a suboptimal glycemic control (92.3%), while 13.3% had severe diabetes-related distress. HbA1c level was significantly and positively correlated with the total PAID score and all its sub-domains. Multivariate quantile regression revealed that obesity, multi-morbidity, and severe diabetes-related distress were the only significant determinants of the HbA1c median level. Obese patients had significantly higher median HbA1c compared to patients who were not obese (coefficient = 0.25, P < 0.001). Patients with two or more comorbidities (i.e., multimorbidity) had a significantly higher median HbA1c than patients with single or no chronic comorbidities (coefficient = 0.41, P < 0.001). Severe diabetes-related distress was significantly associated with higher median HbA1c compared to nonsevere diabetes-related distress (coefficient = 0.20, P = 0.018). CONCLUSION: Diabetes-related distress had a significant association with HbA1c level. Family physicians should implement multifaceted programs to optimize diabetes control and reduce any associated distress.

Rapid Detection of Recurrent Non-Muscle Invasive Bladder Cancer in Urine Using ATR-FTIR Technology.

Non-muscle Invasive Bladder Cancer (NMIBC) accounts for 80% of all bladder cancers. Although it is mostly low-grade tumors, its high recurrence rate necessitates three-times-monthly follow-ups and cystoscopy examinations to detect and prevent its progression. A rapid liquid biopsy-based assay is needed to improve detection and reduce complications from invasive cystoscopy. Here, we present a rapid spectroscopic method to detect the recurrence of NMIBC in urine. Urine samples from previously-diagnosed NMIBC patients (n = 62) were collected during their follow-up visits before cystoscopy examination. Cystoscopy results were recorded (41 cancer-free and 21 recurrence) and attenuated total refraction Fourier transform infrared (ATR-FTIR) spectra were acquired from urine samples using direct application. Spectral processing and normalization were optimized using parameter grid searching. We assessed their technical variability through multivariate analysis and principal component analysis (PCA). We assessed 35 machine learning models on a training set (70%), and the performance was evaluated on a held-out test set (30%). A Regularized Random Forests (RRF) model achieved a 0.92 area under the receiver operating characteristic (AUROC) with 86% sensitivity and 77% specificity. In conclusion, our spectroscopic liquid biopsy approach provides a promising technique for the early identification of NMIBC with a less invasive examination.

Subtypes and phylogenetic analysis of Blastocystis sp. isolates from West Ismailia, Egypt.

In Egypt, Blastocystis sp. is not yet on the diagnostic list of parasitology reports, and information about its subtypes (STs) is scarce. This study investigated its prevalence and its STs/alleles, performed phylogenetic analysis, and considered the distribution of risk factors associated with Blastocystis sp. infections in West Ismailia, Ismailia governorate. Sociodemographic data, exposure factors, and previous parasitic infection status were recorded for symptomatic and asymptomatic individuals. Microscopy, polymerase chain reaction, sequencing, and phylogenetic analysis for Blastocystis sp. isolated from fecal samples were performed. Eighty Blastocystis sp.-infected individuals (15.3%) were examined. The age of the individuals ranged between 0.60 and 85.0 (mean 17.10 ± 15.70), the male/female ratio was 33/47, and the asymptomatic/symptomatic ratio was 55/25. The findings demonstrate clear evidence of direct contact with animals, poor water quality, and previous parasitic infections. Eleven samples yielded three Blastocystis STs (ST1: allele 4, ST2: alleles 9 and 12, and ST3: allele 34), with ST3 (45.5%) representing the most common subtype. Phylogenetic analysis with a robust bootstrap revealed three distinct clades for isolates of each subtype. This study updates the epidemiological knowledge of the distribution of Blastocystis sp. STs in Egypt and expands the current understanding of the prevalence, risk factor frequencies, and genetic diversity of this protist in the studied area.

Comparative Effect of Allicin and Alcoholic Garlic Extract on the Morphology and Infectivity of Eimeria tenella Oocysts in Chickens.

Avian coccidiosis remains one of the major parasitic diseases that threaten the global poultry industry. Since prevention is superior to treatment, this study focuses on eliminating the infection outside the host. To determine their effect on the viability of Eimeria tenella oocysts in vitro, allicin and alcoholic garlic extract, which are natural, less toxic, and inexpensive products, were compared to KOH 5% (chemical disinfectant) using an in vitro culture system. Three concentrations of allicin (45, 90, and 180 mg/mL) and alcoholic garlic extract (90, 180, and 360 mg/mL, were used. Subsequently, destructive and sporulation-inhibiting effects on Eimeria oocysts were detected using light and electron microscopy. Young chickens were infected with treated sporulated oocysts to determine their effect on infectivity. After 7 days pi, the percentage of excreted oocysts (oocyst shedding) was determined, and the chickens were slaughtered for histopathological examination of the cecal tissues. Under an electron microscope, allicin at a concentration of 180 mg/mL and alcoholic garlic extract at a concentration of 360 mg/mL demonstrate a high oocysticidal activity with severe destruction of the oocyst wall and the appearance of pores. In addition, both concentrations directly affected the infectivity of sporulated oocysts by reducing the shedding of oocysts and the pathological lesions of infected young chickens. We concluded that the ability of Allicin and alcoholic garlic extract to eliminate Eimeria oocysts makes them superior to chemical disinfectants as a disinfectant.

Corrigendum: Psychometric properties of the arabic version of the problem areas in diabetes scale in primary care.

[This corrects the article DOI: 10.3389/fpubh.2022.843164.].

Thrombocytopenia in a cohort of primary and secondary antiphospholipid syndrome patients: Relation to clinical, laboratory manifestations and damage index.

Objectives: This study aims to evaluate the prevalence of thrombocytopenia in a cohort of patients with primary and secondary antiphospholipid syndrome (APS) and to examine the relation of thrombocytopenia to the clinical, laboratory findings, and damage index for antiphospholipid syndrome (DIAPS). Patients and methods: Between August 2018 and February 2019, a total of 168 patients (16 males, 152 females; mean age: 32.5±8.4 years; range, 18 to 59 years) who were followed in our clinic for APS were retrospectively analyzed. Medical records of the patients were screened and clinical data, laboratory investigations, and treatments applied were recorded. The DIAPS was calculated for all patients. The patients were divided into two groups according to the presence or absence of thrombocytopenia and both groups were compared regarding clinical, laboratory findings and DIAPS. Further subgroup analysis was done for patients with primary APS. Results: The most common clinical manifestations in our patients were obstetric manifestations (77.4% in pregnant women), musculoskeletal manifestations (69%) and peripheral vascular thrombosis (54.8%). The prevalence of thrombocytopenia in our study was 42.3%, and it was significantly associated with musculoskeletal manifestations (p=0.043), vascular thrombosis (p=0.043), neurological manifestations (p=0.030), cutaneous manifestations (p=0.006), and use of immunosuppressives (p=0.047). The DIAPS was significantly higher in the thrombocytopenia group (p=0.034). Further subgroup analysis of patients with primary APS revealed that neurological manifestations (p=0.010) were significantly higher in the thrombocytopenia group, while the DIAPS was higher in the thrombocytopenia group, but it did not reach statistical significance (p=0.082). Conclusion: Thrombocytopenia may be associated with a higher incidence of vascular thrombosis, neurological manifestations, musculoskeletal manifestations, use of immunosuppressive treatment, and DIAPS. In primary APS patients, thrombocytopenia may be a risk for neurological manifestations.

Gastrointestinal parasites diagnoses at the primary health care units: a comparative analysis of diagnostic abilities of parasitology staff technicians versus medical parasitologists in Ismailia, Egypt.

BACKGROUND: This study aims to compare parasitology technicians (ParaTechs) with medical staff parasitologists (MedParas) in terms of diagnostic ability and to assess the actual occurrence of gastrointestinal parasites in selected faecal samples from primary health care units (PHCUs). METHODS: The study included five PHCU ParaTechs in the El-Kassassin rural area, evaluated using a scoring system for their knowledge, skills, practices and parasitology laboratory facilities. Seventy-five faecal samples previously examined for ova and parasites by ParaTechs were chosen for re-evaluation by MedParas. RESULTS: The most deficient ParaTechs-related factor was the parasitological knowledge, which scored 23.9% of the maximum score, while ParaTechs had acceptable levels of skills and practices, scored 60% and 61%, respectively. Compared with MedParas, false positive ParaTech diagnoses made up 8.8% of all negative samples, while false negative diagnoses made up 85.4% of all positive samples. ParaTechs underestimated the count or misidentified the type of parasites in one-third of the true positive samples. The overall rate of misdiagnosis among ParaTechs was 53.3% of all samples. CONCLUSIONS: Regular ParaTech training, including culture and staining at parasitology labs, and collaboration between the Ministry of Health and Population and academic institutions are essential to increase ParaTechs diagnostic abilities.

Psychometric evaluation of the Arabic version of the 5-item Problem Areas in Diabetes (AR-PAID-5) scale.

BACKGROUND: Screening for diabetes distress is recommended when caring for patients with type 2 diabetes mellitus (T2DM) in primary healthcare (PHC). The 5-item Problem Areas in Diabetes (PAID-5) scale is widely used to measure diabetes distress, but its Arabic validation studies are scarce, so this study was carried to assess the psychometric properties of the Arabic version of the PAID-5 (AR-PAID-5) in Egyptian PHC patients with T2DM. METHODS: We conducted a cross-sectional study including 260 participants from six rural PHC settings in Ismailia governorate, Egypt. Internal consistency using Cronbach's α and one-month test-retest reliability using intraclass correlation coefficient (ICC) were investigated. Confirmatory factor analysis (CFA) was used to evaluate the one-factor structure of the AR-PAID-5. Correlations of the AR-PAID-5 with the Arabic versions of the 20-item Problem Areas in Diabetes (PAID), Patient Health Questionnaire 9 (PHQ-9), Generalized Anxiety Disorder 7 (GAD-7), 5-item World Health Organization Well-Being Index (WHO-5) scales and glycated hemoglobin (HbA1c) were investigated for supporting the convergent validity. Associations of the PAID-5 with sociodemographic, and clinical characteristics were assessed for demonstrating the discriminant validity. Criterion validity was also evaluated. RESULTS: There was a good internal consistency (α = 0.88) and a stable test-retest reliability (ICC = 0.74). The CFA confirmed the one-factor structure of the AR-PAID-5. Significant positive correlations existed between the AR-PAID-5 with diabetes distress evaluated by the Arabic version of the PAID (rho = 0.93, p < 0.001), depressive symptoms (PHQ-9) (rho = 0.56, p < 0.001), anxiety symptoms (GAD-7) (rho = 0.47, p < 0.001), emotional well-being (WHO-5) (rho = - 0.38, p < 0.001), and HbA1c (rho = 0.16, p = 0.003). A satisfactory discriminant validity, and an acceptable criterion validity were demonstrated. CONCLUSIONS: The AR-PAID-5 scale is a reliable and valid tool that can be used for diabetes distress screening and in research in Arabic speaking PHC patients with T2DM.

Prevalence and Associated Factors of Diabetes Distress, Depression and Anxiety Among Primary Care Patients With Type 2 Diabetes During the COVID-19 Pandemic in Egypt: A Cross-Sectional Study.

The prevalence of type 2 diabetes mellitus (T2DM) is growing worldwide. T2DM is often complicated by a range of psychological disorders that interfere with glycemic control and self-care. Previous studies have reported diabetes distress, depression, and anxiety among patients with T2DM; however; little is known about the burden of these comorbid mental disorders in primary care patients with T2DM treated in Egypt during the COVID-19 era. Participants were selected by convenient sampling from eight rural primary healthcare facilities from Ismailia in Egypt. Symptoms of diabetes distress, depression and anxiety were assessed by using the Arabic version of the 20-item Problem Areas in Diabetes (PAID), Patient Health Questionnaire 9, and Generalized Anxiety Disorder Scales, respectively. Multiple hierarchical logistic regression models were used to estimate the significant factors associated with diabetes distress, depression, and anxiety. A total of 403 individuals with T2DM were interviewed. The prevalence of severe diabetes distress was 13.4% (95% CI: 10.1-16.7), while prevalence of depressive and anxiety symptoms was 9.2% (95% CI: 6.4-12.0%), and 4.0% (95% CI: 2.1-5.9), respectively. In a series of hierarchical logistic regression models, significant predictors for diabetes distress were being married, illiterate, not-working, living with insufficient income, and having multi-comorbidities. Likewise, the significant predictors for depression and anxiety were elevated glycated hemoglobin level and the higher PAID total score, while having multi-comorbidities was a significant predictor for anxiety only. Diabetes distress was more prevalent than depressive and anxiety symptoms in this study population. Several sociodemographic and clinical characteristics were identified to be related with psychological problems among patients with T2DM, which necessitate a multidisciplinary team-based approach for optimal screening and management.

Exploiting the exceptional biosynthetic potency of the endophytic Aspergillus terreus in enhancing production of Co3O4, CuO, Fe3O4, NiO, and ZnO nanoparticles using bioprocess optimization and gamma irradiation.

Developing a suitable applicative process and scaling up the microbial synthesis of nanomaterials is an attractive and emerging prospect for a future sustainable industrial production. In this paper, optimization of fermentation conditions for enhanced production of Co3O4, CuO, Fe3O4, NiO, and ZnO nanoparticles by the endophytic A. terreus ORG-1 was studied. Different cultivation conditions were evaluated. Then, a response surface methodology program was used to optimize physical conditions controlling the biosynthesis of these NPs. Finally, the use of gamma irradiation for improvement of NPs' production was adopted. Under the optimum conditions and after gamma irradiation, the final yields of the respective NPs reached 545.71, 651.67, 463.19, 954.88, 1356.42 mg L-1. To the best of our knowledge, this is the first report on the production and enhancement of different types of nanomaterials from one microbial culture that can open up the way towards the industrialization of the microbial production of nanomaterials.

Psychrometric Properties of the Arabic Version of the Problem Areas in Diabetes Scale in Primary Care.

Background: The Problem Areas in Diabetes (PAID) scale is a reliable and valid tool that is widely used for diabetes-distress screening, but the Arabic version of the scale lacks validity and reliability analysis in primary healthcare (PHC) patients. Our study aimed to evaluate the psychometric properties of the Arabic version of the PAID (AR-PAID) scale among Egyptian patients with type 2 diabetes mellitus (T2DM) in PHC settings. Methods: We conducted a cross-sectional study on a convenience sample of 200 patients from six rural PHC settings in the Ismailia governorate. The confirmatory factor analysis (CFA) was performed to test the goodness-of-fit to the predefined models of the PAID. Convergent construct was evaluated through correlations with the Arabic versions of the Patient Health Questionnaire 9 (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7), and 5-item World Health Organization Well-Being Index (WHO-5), additionally glycated hemoglobin (HbA1c) levels. Discriminant validity was evaluated through associations with patients' sociodemographic and clinical characteristics. Reliability was evaluated through internal consistency (Cronbach's α) and test-retest reliability analysis (intraclass correlation coefficient, ICC). Results: The CFA demonstrated the best fit for a four-factor model. The AR-PAID was significantly correlated with the following measures: PHQ-9 (rho = 0.71, p < 0.001), GAD-7 (rho = 0.50, p < 0.001), WHO-5 (rho = -0.69, p < 0.001), and HbA1c (rho = 0.36, p < 0.001), supporting sound convergent validity. Discriminant validity was satisfactory demonstrated. Internal consistency was excellent (α = 0.96) and test-retest reliability was stable (ICC = 0.97). Conclusions: The AR-PAID scale is a valid and reliable instrument for diabetes-distress screening in primary care patients with T2DM that can be used in clinical settings and research. Further research is needed to validate short forms of the AR-PAID scale.

Mesenchymal stem cells microvesicles versus granulocytes colony stimulating factor efficacy in ameliorating septic induced acute renal cortical injury in adult male albino rats (Histological and Immunohistochemical Study).

Sepsis is the most common cause of acute kidney injury in ICU patients, with increasing mortalities. Treatment septic AKI is unsatisfactory; therefore, more effective therapies must be investigated. MSCs-MVs have the same effectiveness in tissue repair as their original cells. Granulocyte colony-stimulating factor (G-CSF) is considered a simple and convenient tool in regenerative medicine. This study aimed to compare the probable therapeutic effect of MSCs-MVs versus G-CSF on septic AKI in rats. Forty-eight adult male rats were divided into four groups; I control group (IA-ID), II induced-sepsis group, III G-CSF, and IV MSC-MVs groups. Sepsis was induced in groups II, III, IV through a single IV injection of 10 mg/ kg of E.Coli-LPS dissolved in 1 ml saline. Four hours later, group IV received a single IV injection of MSCs-MVs, while group III received a SC injection of Neupogen for 5 days. All animals were sacrificed 7 days from the start. Serum and tissue samples of each group were used for biochemical study. Sections from all groups were subjected to light and electron microscopic examination. A fluorescent microscope examination for subgroup ID and group IV was done. Morphometric and statistical analyses were performed. Group II showed features of acute tubular injury. Group III showed some improvement (biochemically, LM & EM level) however, group IV showed more improvement. MVs injection caused a marked improvement in septic AKI; G-CSF can also meliorate the degenerative effect of sepsis on renal cortex, but to a lesser extent than MSCs-MVs.

Acute and chronic metabolic effects of carvedilol in high-fructose, high-fat diet-fed mice: implication of ß-arrestin2 pathway.

We aimed to investigate the acute and chronic effects of carvedilol on insulin resistance in high-fructose, high-fat diet (HFrHFD) - fed mice and the implication of the ß-arrestin2 pathway. The acute effect of carvedilol (10 mg/kg, i.p.) on glucose tolerance and hepatic lipid signaling in normal and insulin resistant mice was investigated. Then, the chronic effect of carvedilol on insulin resistance and dyslipidemia in HFrHFD-fed mice was examined. Changes in ß-arrestin2 and its downstream signals in liver, skeletal muscle, and adipose tissue were measured. This involved measuring phosphatidylinositol 4,5-bisphosphate (PIP2) and diacylglycerol (DAG) levels and protein kinase B (AKT) activity. Carvedilol acutely reduced fasting blood glucose levels in both normal and insulin resistant mice without significantly affecting the glucose tolerance. These acute effects were associated with increased hepatic PIP2 but decreased hepatic DAG levels. Chronic administration of carvedilol significantly ameliorated insulin resistance and dyslipidemia in HFrHFD-fed mice. These chronic effects were associated with increased ß-arrestin2, PIP2, and AKT activity levels but decreased DAG levels in the classical insulin target tissues. In conclusion, carvedilol acutely maintains glucose homeostasis and chronically ameliorates insulin resistance and dyslipidemia in HFrHFD-fed mice. The insulin sensitizing effects of carvedilol are highly correlated with the upregulation of ß-arrestin2 pathway.

Design and Rationale of the National Tunisian Registry of Heart Failure (NATURE-HF): Protocol for a Multicenter Registry Study.

BACKGROUND: The frequency of heart failure (HF) in Tunisia is on the rise and has now become a public health concern. This is mainly due to an aging Tunisian population (Tunisia has one of the oldest populations in Africa as well as the highest life expectancy in the continent) and an increase in coronary artery disease and hypertension. However, no extensive data are available on demographic characteristics, prognosis, and quality of care of patients with HF in Tunisia (nor in North Africa). OBJECTIVE: The aim of this study was to analyze, follow, and evaluate patients with HF in a large nation-wide multicenter trial. METHODS: A total of 1700 patients with HF diagnosed by the investigator will be included in the National Tunisian Registry of Heart Failure study (NATURE-HF). Patients must visit the cardiology clinic 1, 3, and 12 months after study inclusion. This follow-up is provided by the investigator. All data are collected via the DACIMA Clinical Suite web interface. RESULTS: At the end of the study, we will note the occurrence of cardiovascular death (sudden death, coronary artery disease, refractory HF, stroke), death from any cause (cardiovascular and noncardiovascular), and the occurrence of a rehospitalization episode for an HF relapse during the follow-up period. Based on these data, we will evaluate the demographic characteristics of the study patients, the characteristics of pathological antecedents, and symptomatic and clinical features of HF. In addition, we will report the paraclinical examination findings such as the laboratory standard parameters and brain natriuretic peptides, electrocardiogram or 24-hour Holter monitoring, echocardiography, and coronarography. We will also provide a description of the therapeutic environment and therapeutic changes that occur during the 1-year follow-up of patients, adverse events following medical treatment and intervention during the 3- and 12-month follow-up, the evaluation of left ventricular ejection fraction during the 3- and 12-month follow-up, the overall rate of rehospitalization over the 1-year follow-up for an HF relapse, and the rate of rehospitalization during the first 3 months after inclusion into the study. CONCLUSIONS: The NATURE-HF study will fill a significant gap in the dynamic landscape of HF care and research. It will provide unique and necessary data on the management and outcomes of patients with HF. This study will yield the largest contemporary longitudinal cohort of patients with HF in Tunisia. TRIAL REGISTRATION: ClinicalTrials.gov NCT03262675; https://clinicaltrials.gov/ct2/show/NCT03262675. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/12262.

Novel mycosynthesis of Co3O4, CuO, Fe3O4, NiO, and ZnO nanoparticles by the endophytic Aspergillus terreus and evaluation of their antioxidant and antimicrobial activities.

Several fungal endophytes were isolated and screened for their ability to biosynthesize a variety of nanoparticles (NPs), as a potentially simple and eco-friendly method with low cost. Among these fungi, a promising isolate named ORG-1 was found able to synthesize five different NPs types: Co3O4NPs, CuONPs, Fe3O4NPs, NiONPs, and ZnONPs. The ORG-1 strain was identified as Aspergillus terreus according to the morphological and molecular studies. Synthesis of these NPs was initially monitored by UV-Vis spectroscopy and further characterized by Fourier transform infrared spectroscopy. X-ray diffraction patterns revealed their crystalline structure. Dynamic light scattering analysis was applied to study the particle size distribution and stability. Transmission electron microscope studies indicated the morphology of the synthesized NPs. Additionally, the biological activities of the in vitro antioxidant and antimicrobial potentials were evaluated. Co3O4NPs, CuONPs, Fe3O4NPs, NiONPs, and ZnONPs showed promising antioxidant activity with 50% inhibitory concentrations of 85.44, 96.74, 102.41, 87.41, and 108.67 µg mL-1, respectively. The synthesized NPs exhibited potent antimicrobial activities against several plant and human pathogens. To our knowledge, this is the first report on the use of one microbial strain for the synthesis of a variety of NPs. This study suggests endophytic fungi as new and alternate platforms with an exceptional potentiality for the synthesis of NPs with promising activities. KEY POINTS: • Discovery of a promising endophytic fungus for synthesis of five different types of NPs. • Mycosynthesis and characterization of all the synthesized NPs were investigated. • The synthesized NPs showed promising antioxidant and antimicrobial activities.

Antimicrobial activity of biosynthesised silver nanoparticles against multidrug-resistant microbes isolated from cancer patients with bacteraemia and candidaemia.

Background: In the past years, saprophytic bacteria and candida have been emerging as potential human pathogens causing life-threatening infections in patients with cancer. This study was designed to determine the bacteria and candida species, causing bloodstream infections in cancer patients and the assessment of their susceptibility to antibiotics and biosynthesised silver nanoparticles. Materials and Methods: Ninety-seven microbial pathogens recovered from blood samples of cancer patients were included in the present study. The microbial isolates were collected in a duration period extending from December 2016 to July 2018 at National Cancer Institute, Cairo, Egypt. The clinical samples were collected using microbiological methods and were cultivated on MacConkey agar, blood agar media and Sabouraud dextrose agar media. The microbial isolates were identified using both standard microbiological methods and VITEK 2 compact automated system. The antibiotic resistance pattern was determined by the VITEK 2 compact automatic system and disk diffusion method, according to the Clinical and Laboratory Standards Institute. The characterisation of nanoparticles was carried out using ultraviolet spectroscopy and electron microscope. The antimicrobial activity of bio (AgNPs) was evaluated. Results: A total of 97 microbial isolates recovered from collected blood samples from cancer patients were included in the study. Pathogenic bacteria and Candida were represented by 74 isolates (76.22%) and 23 isolates (23.69), respectively. Among the 74 bacterial isolates, Escherichia coli constituted (27.81%), Klebsiella pneumoniae (24.72%), Acinetobacter baummannii (11.33%), Pseudomonas aeruginosa (4.12%), Enterobacter spp. (3.09%) and) Staphylococcus aureus (2.06%). Cedecea davisae (1.03%), Burkholderia cepacia (1.03%) and Pantoea agglomerans (1.03%). Among the 23 Candida isolates, Candida tropicalis constituted (9.27%), Candida albicans (5.15%), Candida glabrata (5.15%) and Candida krusei (4.12%) from the total microbial isolates. The antibiotic susceptibility results revealed that amikacin and gentamycin were the most effective antibiotics against Gram-negative bacteria, while vancomycin and linezolid were most effective against S. aureus. Caspofungin was the most effective against candida species. The obtained stable biosynthesised silver nanoparticles ranged in size from 10 nm to 100 nm and were mostly spherical in shape. These biosilver nanoparticles showed the highest antimicrobial activity against most of the microbial isolates (bacteria and Candida). The in vitro cytotoxicity of biosynthesised AgNPs on HeLa cell lines revealed a dose-dependent potential. The IC50 value of AgNPs was found 6 and 5.6 µg/ml, respectively. Conclusion: The present study revealed a significant distribution of multidrug-resistant microbes, which may increase the burden of healthcare to prevent infections in cancer patients. Biosilver nanoparticles exhibit antimicrobial activity against multidrug-resistant microbes and could be considered as effective agents against these strains.