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Sugarcane bagasse-derived nanofibrillated cellulose (NFC), a type of cellulose with a fibrous structure, is potentially used in the pharmaceutical field. Regeneration of this cellulose using a green process offers a more accessible and less ordered cellulose II structure (amorphous cellulose; AmC). Furthermore, the preparation of cross-linked cellulose (NFC/AmC) provides a dual advantage by building a structural block that could exhibit distinct mechanical properties. 3D aerogel scaffolds loaded with risedronate were prepared in our study using NFC or cross-linked cellulose (NFC/AmC), then combined with different concentrations of chitosan. Results proved that the aerogel scaffolds composed of NFC and chitosan had significantly improved the mechanical properties and retarded drug release compared to all other fabricated aerogel scaffolds. The aerogel scaffolds containing the highest concentration of chitosan (SC-T3) attained the highest compressive strength and mean release time values (415 ± 41.80 kPa and 2.61 ± 0.23 h, respectively). Scanning electron microscope images proved the uniform highly porous microstructure of SC-T3 with interconnectedness. All the tested medicated as well as unmedicated aerogel scaffolds had the ability to regenerate bone as assessed using the MG-63 cell line, with the former attaining a higher effect than the latter. However, SC-T3 aerogel scaffolds possessed a lower regenerative effect than those composed of NFC only. This study highlights the promising approach of the use of biopolymers derived from agro-wastes for tissue engineering.

Background: The optimal timing of parenteral nutrition (PN) initiation in critically ill children remains controversial., Purpose: To identify the optimal timing of PN initiation in critically ill children., Methods: This randomized clinical trial was conducted in the pediatric intensive care unit (PICU) of Menoufia University Hospital. A total of 140 patients were randomized to receive early or late PN. The early PN group consisted of 71 well-nourished and malnourished patients who received PN on the first day of PICU admission. Malnourished (42%) and well-nourished children randomized to the late PN group (42%) started PN on the fourth versus seventh day after admission, respectively. Mechanical ventilation (MV) was the primary outcome, while PICU length of stay and mortality were secondary outcomes., Results: Patients who received early PN started enteral feeding significantly earlier (median, 6 days; interquartile range, 2-20 days) than those not provided early PN (median, 12 days; interquartile range, 3-30 days; P<0.001) and had a significantly lower risk of feeding intolerance (5.6% vs.18.8%, P=0.035). The median time required to obtain full calories enterally was shorter in the early versus late PN group (P=0.004). Furthermore, patients in the early versus late PN group had a significantly shorter median PICU stay (P<0.001) and were less likely to require MV (P=0.018)., Conclusion: Patients who received early PN had a lower MV need and duration than those who received later PN and had more favorable clinical outcomes in terms of morbidity.

Aims: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with a rising prevalence in boys rather than girls. G protein-coupled estrogen receptor (GPER) activation by its agonist G1 showed a neuroprotective effect, similar to estradiol. The present study aimed to examine the potential of the selective GPER agonist G1 therapy on the behavioral, histopathological, biochemical, and molecular alterations induced in a valproic acid (VPA)-rat model of autism., Main Methods: VPA (500 mg/kg) was intraperitoneally administered to female Wistar rats (on gestational day 12.5) to induce the VPA-rat model of autism. The male offspring were intraperitoneally administered with G1 (10 and 20 μg/kg) for 21 days. After the treatment process, rats performed behavioral assessments. Then, sera and hippocampi were collected for biochemical and histopathological examinations and gene expression analysis., Key Findings: GPER agonist G1 attenuated behavioral deficits, including hyperactivity, declined spatial memory and social preferences, anxiety, and repetitive behavior in VPA rats. G1 improved neurotransmission and reduced oxidative stress and histological alteration in the hippocampus. G1 reduced serum free T levels and interleukin-1β and up-regulated GPER, RORα, and aromatase gene expression levels in the hippocampus., Significance: The present study suggests that activation of GPER by its selective agonist G1 altered the derangements induced in a VPA-rat model of autism. G1 normalized free T levels via up-regulation of hippocampal RORα and aromatase gene expression. G1 provoked estradiol neuroprotective functions via up-regulation of hippocampal GPER expression. The G1 treatment and GPER activation provide a promising therapeutic approach to counteract the autistic-like symptoms., Competing Interests: Declaration of competing interest We declare that we have no conflict of interest. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To evaluate the effect of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism on plasma homocysteine (tHcy) and platelet-derived growth factor (PDGF-AA) levels in children with sickle cell disease (SCD), and ascertain their role in predicting high transcranial doppler velocity (TCD)., Methods: We estimated MTHFRC677T gene poly-morphism, plasma tHyc and PDGF-AA in 44 SCD patients and 44 healthy children., Results: The prevalence of mutant homozygous MTHFR (C677TT) in SCD was 13.6%. Significantly higher plasma tHcy was observed in mutant homozygous MTHFRC677TT patients. Significantly higher plasma tHcy and PDGF-AA levels were observed in SCD patients than in controls. Median (IQR) PDGF-AA levels were significantly higher in conditional and high-risk TCD patients as compared to low-riskTCD patients [325 (93.1-368) and 368 (111-480) vs 111 (56-201) pg/mL, respectively; P<0.001]. Mean (SD) tHcy levels were significantly higher in high-risk TCD children than low-risk TCD children (12.9 (2.7) vs 9.9 (2.5) µmol/L; P=0.006). The receiver operating characteristic revealed that the area under the curve (AUC) of PDGF-AA for high TCD velocity was 0.934 (95% CI 0.845-1.00; P<0.001) and tHcy had an AUC of 0.675 (95% CI 0.517-0.833; P=0.04)., Conclusion: PDGF-AA and tHcy levels could be used as predictive markers for stroke in SCD children. MTHFR Polymorphism contributes to elevated tHcy levels.

In the oil and gas industry, cementing is a very important process to maintain the stability of the well. The cement can provide an effective plug against fluid movement and at the same time supports the casing and formations. Based on the operation conditions, different types of additives are used to make the cement slurry, and incorporation of a new additive considerably affects all properties of the cement slurry and the solidified sheath. In this work, lab experiments were performed to investigate alteration of the Saudi Class G cement properties after incorporation of olive waste into the slurry, and the possibility of replacing the commercial retarder with olive waste was also studied in this work. Five samples with different olive waste content were prepared, and their rheological characteristics, thickening time, mechanical properties, and permeability were evaluated after 24 h of curing at 95 °C. The results indicated that olive waste could replace the use of a commercial retarder. The incorporation of olive waste did not affect the cement plastic viscosity, while the yield point, 10 s, and 10 min gel strengths of the cement were considerably increased with the increase in the olive waste content. The cement compressive strength was also increased with the incorporation of olive waste of a maximum of 0.375%, and the permeability decreased with the addition of a maximum of 0.25% olive waste., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: Haemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening syndrome characterized by an excessive inflammatory response. Limited data exist on adult HLH., Methods: In this national, retrospective cohort study, we analysed data from the US National Inpatient Sample database collected between October 1, 2006 and December 31, 2019. Using the International Classification of Diseases (ICD) codes, we identified all adult patients who were admitted non-electively with the diagnosis of HLH. We described demographic characteristics, triggers, and associated conditions. Trends of diagnosis, treatment, and in-hospital mortality were analysed using joinpoint models. In-hospital mortality rates were compared using multivariable logistic regression models that adjusted for demographic characteristics and associated conditions. Finally, we described resource utilization outcomes including cost of hospitalization and length of stay., Findings: We identified 16,136 non-elective adult HLH admissions. The population pyramid showed a bimodal distribution, with peaks in young adults (16-30 years) and older adults (56-70 years). Joinpoint regression analysis revealed a significant increase in HLH incidence per 100,000 admissions over the study period (Average Annual Percent Change [APC] = 25.3%, p < 0.0001), and no significant change in rates of in-hospital mortality (slope = -0.01; p = 0.95) or administration of in-hospital HLH treatment (slope = 0.46, p = 0.20). The most common associated conditions were malignancy (4953 admissions [30.7%]), infections (3913 admissions [24.3%]), autoimmune conditions (3362 admissions [20.8%]), organ transplant status (639 admissions [4%]), and congenital immunodeficiency syndromes (399 admissions [2.5%]). In-hospital mortality was higher in older adults and males. Furthermore, Congenital immunodeficiency syndromes had the worst in-hospital mortality rate (mortality rate 31.1%, adjusted OR 2.36 [1.56-3.59]), followed by malignancies (mortality rate 28.4%, adjusted OR 1.80 [1.46-2.22]), infections (mortality rate 21.4%, adjusted OR 1.33 [1.10-1.62]), other/no trigger (mortality rate 13.6%, adjusted OR 0.73 [0.58-0.92]), autoimmune (mortality rate 13%, adjusted OR 0.72 [0.57-0.92]), and post-organ transplant status (mortality rate 14.1%, adjusted OR 0.64 [0.43-0.97]). The overall mean length of stay was 14.3 ± 13.9 days, and the mean cost of hospitalization was $54,900 ± 59,800., Interpretation: We provide insight into the burden of adult HLH in the USA. The incidence has been increasing and the outcomes remain dismal. This signifies the growing need for the development of updated diagnosis and treatment protocols that are specific to adult HLH., Funding: None., Competing Interests: All authors declare no competing interests., (© 2023 The Author(s).)

Phthalates are common plasticizers present in medical-grade plastics and other everyday products. Di-ethylhexyl phthalate (DEHP) has been noted as a causative risk factor for the initiation and augmentation of cardiovascular functional disorders. G-CSF is a glycoprotein found in numerous tissues throughout the body and is currently applied in clinical practice and has been tested in congestive heart failure. We aimed to examine in depth the effect of DEHP on the histological and biochemical structure of the cardiac muscle in adult male albino rats and the mechanisms underlying the possible ameliorative effect of G-CSF. Forty-eight adult male albino rats were divided into control group, DEHP group, DEHP+ G-CSF group and DEHP-recovery group. We measured serum levels of aspartate aminotransferase (AST), creatine kinase MB isoenzyme (CK-MB) and lactate dehydrogenase (LDH). Left ventricular sections were processed for light and electron microscope examination, and immunohistochemical staining of Desmin, activated Caspase-3 and CD34. DEHP significantly increased enzyme levels, markedly distorted the normal architecture of cardiac muscle fibers, downregulated Desmin protein levels and enhanced fibrosis, and apoptosis. G-CSF treatment significantly decreased the enzyme levels compared to DEHP group. It enhanced CD34 positive stem cells recruitment to injured cardiac muscle, therefore improved the ultrastructural features of most cardiac muscle fibers via anti-fibrotic and anti-apoptotic effects in addition to increased Desmin protein expression levels. The recovery group showed partial improvement due to persistent DEHP effect. In conclusion, administration of G-CSF effectively corrected the histopathological, immunohistochemical and biochemical alterations in the cardiac muscle after DEHP administration by stem cells recruitment, Desmin protein regulation, antifibrotic and antiapoptotic mechanisms., (© 2023. The Author(s).)

Background: This study aims to compare the incidence of cardiac events and to identify its predictors in left breast cancer patients receiving adjuvant radiotherapy using breath-hold technique (DIBH) versus free breathing technique (FB)., Methods: We conducted a retrospective multi-center study of two arms; the free breathing arm included 208 patients who were treated with traditional radiotherapy treatment technique, while DIBH arm included 224 patients who were treated with breath-hold technique using The Varian Real-time Position Management (RPM). We retrospectively reviewed the medical records of the patients from January 2010 to December 2017., Results: The mean dose to the heart and left anterior descending artery were significantly lower in the DIBH arm (2.10 ± 0.39 and 6.16 ± 0.18 Gy) compared with (4.29 ± 0.60 Gy and 12.69 ± 0.93 Gy, respectively) in the FB arm. The incidence of cardiac events was higher in the FB arm than in the DIBH arm, but it was not statically significant. Our analysis revealed that age, diabetes, hypertension, smoking, mean LAD dose, and heart mean dose were significant prognostic factors for the occurrence of cardiac events in the breath-hold arm. Hypertension, smoking, as well as heart mean dose were independent risk factors for the occurrence of cardiac events., Conclusion: Use of the DIBH technique resulted in a significant reduction in doses to the heart, LAD and lesser cardiac events incidence compared to free breathing., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: We assessed serum concentrations of pancreatic stone protein (PSP), copeptin, and apolipoprotein A-V (APOA5) biomarkers for the diagnosis and prognosis of pediatric sepsis, a condition associated with high mortality., Methods: This prospective study included 180 children admitted to the Pediatric Intensive Care Unit and 100 healthy controls at Menoufia University Hospital. Pediatric Risk of Mortality (PRISM), Pediatric Index of Mortality-2 (PIM2), and Pediatric Sequential Organ Failure Assessment (pSOFA) scores were calculated. Serum PSP, copeptin and APOA5 were measured once within 24 h of admission., Results: PSP, copeptin, and APOA5 were significantly higher in the patients than in the controls (p < 0.001). PSP and copeptin were increased among children who required mechanical ventilation (MV), had multiple organ dysfunctions, and were non-survivors, but APOA5 was decreased in those children. Logistic regression analyses showed that high pSOFA, high PSP and copeptin, low APOA5, and use of MV were associated with mortality. The receiver operating characteristic revealed that the area under the curve (AUC) for APOA5, copeptin, and PSP (0.965, 0.960, and 0.868, respectively) demonstrated high sensitivity (96%, 94%, and 80%) for sepsis diagnosis. The AUC values for PSP, copeptin, and APOA5 were 0.709, 0.705, and 0.571, respectively, with sensitivities of 74%, 58%, and 58% for mortality prediction., Conclusions: PSP, copeptin, and APOA5 are promising diagnostic biomarkers for pediatric sepsis but inadequate predictors of mortality., Impact: Apolipoprotein A-V (APOA5), copeptin, and pancreatic stone protein (PSP) are acute-phase proteins with diagnostic value in evaluating critically ill pediatric patients with sepsis and detecting sepsis severity. PSP and copeptin had the power to discriminate non-survivors from survivors. APOA5 was less powerful than the other biomarkers in discriminating between survivors and non-survivors., (© 2023. The Author(s).)

Purpose: The study aimed to compare the dosimetric results and treatment delivery efficiency among four techniques to explore the preferred technique in prostate treatment., Materials and Methods: 7 IMRT, 9 IMRT, 1 ARC, and 2 ARC plans were created for 30 prostate cancer patients using the Eclipse™ treatment planning system (Varian Medical Systems). All the plans were designed to deliver 80.0 Gy in 40 fractions to the prostate planning target volume (PTV). Target coverage, organs at risk (OARs), number of monitor units, homogeneity, and conformity were compared across the four techniques to assess the quality of the plans., Results: The study revealed better Planning Target Volume (PTV) dose coverage in the VMAT-2A than in the other plans. At the same time, VMAT-2A plans were found to be significantly lower in terms of Bladder and rectum doses than other techniques. In addition, VMAT has the advantage of considerably reducing the number of monitor units and treatment time., Conclusion: For prostate cancer, VMAT may offer a favorable dose gradient profile, conformity, and MU and treatment time compared to IMRT., (© 2023. The Author(s).)

Skin wound healing is one of the most challenging processes for skin reconstruction, especially after severe injuries. In our study, nanofiber membranes were prepared for wound healing using an electrospinning process, where the prepared nanofibers were made of different weight ratios of polycaprolactone and bioactive glass that can induce the growth of new tissue. The membranes showed smooth and uniform nanofibers with an average diameter of 118 nm. FTIR and XRD results indicated no chemical interactions of polycaprolactone and bioactive glass and an increase in polycaprolactone crystallinity by the incorporation of bioactive glass nanoparticles. Nanofibers containing 5% w/w of bioactive glass were selected to be loaded with atorvastatin, considering their best mechanical properties compared to the other prepared nanofibers (3, 10, and 20% w/w bioactive glass). Atorvastatin can speed up the tissue healing process, and it was loaded into the selected nanofibers using a dip-coating technique with ethyl cellulose as a coating polymer. The study of the in vitro drug release found that atorvastatin-loaded nanofibers with a 10% coating polymer revealed gradual drug release compared to the non-coated nanofibers and nanofibers coated with 5% ethyl cellulose. Integration of atorvastatin and bioactive glass with polycaprolactone nanofibers showed superior wound closure results in the human skin fibroblast cell line. The results from this study highlight the ability of polycaprolactone-bioactive glass-based fibers loaded with atorvastatin to stimulate skin wound healing.

Engineered nanomaterials induce hazardous effects at the cellular and molecular levels. We investigated different mechanisms underlying the neurotoxic potential of zinc oxide nanoparticles (ZnONPs) on cerebellar tissue and clarified the ameliorative role of Quercetin supplementation. Forty adult male albino rats were divided into control group (I), ZnONPs-exposed group (II), and ZnONPs and Quercetin group (III). Oxidative stress biomarkers (MDA & TOS), antioxidant biomarkers (SOD, GSH, GR, and TAC), serum interleukins (IL-1β, IL-6, IL-8), and tumor necrosis factor alpha (TNF-α) were measured. Serum micro-RNA (miRNA): miRNA-21-5p, miRNA-122-5p, miRNA-125b-5p, and miRNA-155-3p expression levels were quantified by real-time quantitative polymerase-chain reaction (RT-QPCR). Cerebellar tissue sections were stained with Hematoxylin & Eosin and Silver stains and examined microscopically. Expression levels of Calbindin D28k, GFAP, and BAX proteins in cerebellar tissue were detected by immunohistochemistry. Quercetin supplementation lowered oxidative stress biomarkers levels and ameliorated the antioxidant parameters that were decreased by ZnONPs. No significant differences in GR activity were detected between the study groups. ZnONPs significantly increased serum IL-1β, IL-6, IL-8, and TNF-α which were improved with Quercetin. Serum miRNA-21-5p, miRNA-122-5p, miRNA-125b-5p, and miRNA-155-p expression levels showed significant increase in ZnONPs group, while no significant difference was observed between Quercetin-treated group and control group. ZnONPs markedly impaired cerebellar tissue structure with decreased levels of calbindin D28k, increased BAX and GFAP expression. Quercetin supplementation ameliorated cerebellar tissue apoptosis, gliosis and improved calbindin levels. In conclusion: Quercetin supplementation ameliorated cerebellar neurotoxicity induced by ZnONPs at cellular and molecular basis by different studied mechanisms. Abbreviations: NPs: Nanoparticles, ROS: reactive oxygen species, ZnONPs: Zinc oxide nanoparticles, AgNPs: silver nanoparticles, BBB: blood-brain barrier, ncRNAs: Non-coding RNAs, miRNA: Micro RNA, DMSO: Dimethyl sulfoxide, LPO: lipid peroxidation, MDA: malondialdehyde, TBA: thiobarbituric acid, TOS: total oxidative status, ELISA: enzyme-linked immunosorbent assay, H 2 O 2 : hydrogen peroxide, SOD: superoxide dismutase, GR: glutathione reductase, TAC: total antioxidant capacity, IL-1: interleukin-1, TNF: tumor necrosis factor alpha, cDNA: complementary DNA, RT-QPCR: Real-time quantitative polymerase-chain reaction, ABC: Avidin biotin complex technique, DAB: 3', 3-diaminobenzidine, SPSS: Statistical Package for Social Sciences, ANOVA: One way analysis of variance, Tukey's HSD: Tukey's Honestly Significant Difference, GFAP: glial fiberillar acitic protein, iNOS: Inducible nitric oxide synthase, NO: nitric oxide, HO-1: heme oxygenase-1, Nrf2: nuclear factor erythroid 2-related factor 2, NF-B: nuclear factor-B, SCI: spinal cord injury, CB: Calbindin.

Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening immune dysregulation disease. Patients with inflammatory bowel disease (IBD) can become profoundly immunocompromised due to immunosuppressive therapy, hence increasing the risk of viral infections that can trigger HLH. However, data on the association between IBD and HLH remains limited. We used data from the National Inpatient Sample (2012-2019) utilizing International Classification of Diseases (ICD)-9 or ICD-10 codes to identify individuals with IBD, either Crohn's disease (CD) or ulcerative colitis (UC), and HLH. The primary outcome was to compare the prevalence of HLH among patients with IBD with those without IBD. Secondary outcomes included in-hospital mortality, mean hospital length of stay, and description of HLH-associated triggers in IBD patients. A total of 513,322 hospitalizations included a diagnosis of IBD, 188,297 had UC and 325,025 had CD. Compared to the general population, patients with IBD were older (median age of 52 vs. 49 years, p < 0.05), more likely to be male, and of Asian/Pacific Islander descent, and had a higher median household income. There was also a higher prevalence of liver disease, autoimmune diseases, tobacco abuse, and hypothyroidism (all had p-value of < 0.001) in IBD patients. There were 94 hospitalizations identified with a diagnosis of HLH in IBD patients. Compared to patients without IBD, patients with IBD had increased odds of developing HLH (0.02% vs 0.01%, p-value < 0.001). After adjusting for various demographic characteristics, co-morbidities, and HLH-related conditions, IBD was an independent predictor for developing HLH (adjusted OR, 2.3; 95% CI, 1.847-2.866, p-value of < 0.001). There was no statistical difference between CD and UC in the odds of developing HLH. Compared to IBD patients without HLH, patients with IBD and HLH had a lower mean age at diagnosis (38 vs 52, p-value of < 0.001), higher in-hospital mortality (14.9% vs 1.5%, p-value of < 0.001), and longer mean hospital length of stay (days) (17 vs 5.4, p-value of < 0.001). Prevalence of different HLH-associated illnesses was identified in HLH patient's discharge data. Lymphoma was the most common associated malignancy (18.1%) and cytomegalovirus infection was the most common associated infection (16.0%). Our population-based study suggests that IBD is independently associated with developing HLH. Early recognition of IBD patients presenting with features suggestive of HLH is warranted to aide early diagnosis and aggressive treatment., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults, and its incidence is higher in elderly individuals. This study aims to examine the burden of CLL in the United States (US) by exploring the incidence-based rates (IBR) and incidence-based mortality (IBMR) across four decades., Research Design and Methods: CLL incidence data were obtained from the SEER-8 registry, covering 8.3% of the US population. Cases were identified using specific diagnostic codes and excluded if diagnosed on autopsy or death certificate. Age-standardized IBR and IBMR were calculated based on age, sex, and ethnicity/race. Joinpoint Regression Program was used to analyze changing trends in incidence and mortality., Results: Since 2011, males' and females' IBRs declined by -1.72%/year ( p  = 0.028) and -1.07%/year ( p  = 0.222), respectively. IBR of patients > 75 years increased by 4.01%/year ( p  < 0.001) form 1998-2010, then declined by 2.02%/year ( p  = 0.011). IBR of Blacks increased by 0.96%/year ( p  < 0.001) throughout the study period. CLL IBMR stabilized at -0.38%/year ( p  = 0.457) since 2012. Whites' IBMR plateaued at a rate of -0.10%/year ( p  = 0.857) form 2012-2019, while blacks' IBMR increased by 1.40%/year ( p  = 0.056) between 2000-2019., Conclusions: The analysis revealed a decline in CLL incidence since 2013, with stable mortality rates since 2012, indicating advancements in CLL management.

The severe acute respiratory syndrome coronavirus 2, first appeared in Wuhan, China, in December 2019. Since then, a variety of strains of the virus were spread throughout the world, prompting the World Health Organization to declare a pandemic in March 2020. Additionally, Coronavirus disease 2019 (COVID-19) can cause a variety of symptoms, ranging from fatigue and fever to severe respiratory and cardiovascular complications. This study evaluated the role of brain natriuretic peptide (BNP), troponin-I and D-dimer as biomarkers for death prediction in hospitalized patients with COVID-19. The study included 90 patients with COVID -19 diagnosed with PCR-RNA testing. They were divided into survivors and non-survivors. Also, 20 apparently healthy individuals age and sex matched were included as a control group. Plasma BNP and serum troponin-I were measured by enzyme linked immune-sorbent assay (ELISA) technique. D-dimer was measured by a turbidimetric technique. Patients with COVID-19 had significantly elevated levels of serum Troponin-I and plasma BNP in comparison to controls (p < 0.0001, for both). D-dimer, troponin-I and BNP levels were significantly higher in the non-survivors group when compared to the survivors group. Troponin-1 can predict COVID-19 severity with sensitivity, specificity, and accuracy of 55.1%, 66.7%, and 57.8%, respectively at a cutoff value of 0.075 (ng /ml); and area under the receiver operating characteristic (AUC) curve of 0.670 (95% CI: 0.551 - 0.790, p=0.018). BNP can predict COVID-19 severity with sensitivity, specificity, and accuracy of 98.6%, 71.4%, 92.2%, respectively at a cutoff value of 16.02 (Pg /ml) and AUC of 0.872 (95% CI: 0.778 - 0.965, p < 0.001). Univariate and multivariate logistic regression analysis showed that only BNP level can significantly predict death among COVID-19 infected patients. In conclusion, plasma BNP and serum troponin-I could be used as prognostic biomarkers for determination of the severity of COVID-19 and BNP could predict mortality., (Copyright© by the Egyptian Association of Immunologists.)

Background: Autoimmune hemolytic anemia (AIHA) is characterized by humoral and/or cellular immune-mediated hemolysis of red blood cells. The role of therapeutic plasma exchange (TPE) in AIHA is unclear., Study Design and Methods: We queried the National Inpatient Sample (NIS) for 2002-2019 to identify hospitalizations with the primary diagnosis of AIHA. We included hospitalizations with the highest severity subclass identified by All Patient Refined Disease Related Group (APR-DRG). We used multivariate regression analysis to compare in-hospital mortality and other relevant in-hospital outcomes between hospitalizations that received TPE and those that did not., Results: We identified 255 weighted hospitalizations in the TPE group and 4973 in the control group. Those in the control group were older (median age 67 vs. 48 years, p < .001) and had a higher prevalence of most comorbidities. The TPE group had higher odds of all-cause in-hospital mortality (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.19-2.11). They also had higher rates of many secondary outcomes, including requiring mechanical ventilation, developing circulatory shock, acute stroke, urinary tract infections, intracranial hemorrhage, acute kidney injury, and requiring new hemodialysis. No significant differences were noted in the rates of acute myocardial infarctions, bacterial pneumonia, sepsis/septicemia, thromboembolic events, and other bleeding events. Furthermore, the TPE group had a higher median length of hospital stay (19 vs. 9 days, p < .001)., Conclusion: Hospitalizations with severe AIHA that received TPE had higher rates of adverse in-hospital outcomes., (© 2023 AABB.)

Background: The risk of neurological complications is increased in children with sickle cell disease (SCD), such as silent cerebral infarction (SCI) and stroke. Brain-Derived Neurotrophic Factor (BDNF) is a nerve growth factor associated with elevated transcranial Doppler (TCD) velocities and increased risk of stroke in SCD patients. So, we assessed the BDNF level in children with SCD and its relation to neurological complication as silent stroke., Methods: A comparative cross-sectional study was conducted on 40 patients with SCD, recruited from the Hematology Unit, Pediatric Department, Menoufia University Hospital, and 40 healthy children as controls. Laboratory investigations including BDNF were done. TCD was done for all patients and Magnetic Resonance Imaging (MRI) was done on high-risk patients., Results: BDNF levels were significantly higher in children with SCD than in controls with a significant relation to TCD findings. There was a statistically significant diagnostic ability of BDNF in the prediction of SCD complications as its sensitivity was 89.5%, specificity (95% CI) was 80% with a cut-off point >0.69, AUC = 0.702, and p = 0.004)., Conclusion: Serum BDNF levels were higher in sickle disease patients who had abnormal transcranial Doppler. BDNF had a significant diagnostic ability in the detection of SCD complications., Impact: Silent stroke is a very serious complication in children with sickle cell disease, so regular follow up should be every six months. BDNF is considered a potential biomarker for stroke risk prediction in patients unable to receive TCD., (© 2023. The Author(s).)

In the present work, we describe the extraction of a natural product namely 1,4,9,9-tetramethyloctahydro-4,7-(epoxymethano)azulen-5(1 H )-one, and its structure was confirmed by single crystal X-ray diffraction analysis. The conformations of the 5-, 6-, and 7-membered rings in the title compound, C 15 H 24 O 2 , have been probed by a Cremer-Pople puckering analysis. C-H···O hydrogen bonds generate chains in the crystal that stretch along the c -axis direction. The Hirshfeld surface analysis method was used to stabilize the crystal packing of the natural compound. Accompanied by experimental studies, quantum chemical calculations were also performed to compare the structural elucidation and the results of these geometrical parameters exhibited excellent agreement. The compound was also docked with several drug targets of the SARS-CoV-2 virus and found to show the best binding with the main protease enzyme, having a binding energy of -12.31 kcal/mol and interacting with His41 and Cys145 residues. The dynamic stability deciphered the complex to be stable with an average RMSD of 3.8 Å. The compound dynamics with the enzyme showed the compound conformation to be highly stable. The intermolecular binding free energy determined the compound-main protease enzyme to show high interaction energy of < 40 kcal/mol. Together, these studies demonstrate the compound to be a lead structure against SARS-CoV-2., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Impaired renal functions have been reported with Hepatitis E virus (HEV) infections, especially with genotypes 3 and 4. These complications were reported during the acute and chronic phases of infection. HEV genotype 1 causes acute infection, and the effect of HEV-1 infections on renal functions is not known. We examined the kidney function parameters in the serum of HEV-1 patients (AHE, n = 31) during the acute phase of infection. All of the included patients developed an acute self-limiting course of infection, without progression to fulminant hepatic failure. We compared the demographic, laboratory, and clinical data between AHE patients with normal kidney function parameters and those with abnormal renal parameters. Out of 31 AHE patients, 5 (16%) had abnormal kidney function tests (KFTs) during the acute phase of infection. Three patients had abnormal serum urea and creatinine, and two patients had either abnormal urea or creatinine. Four out of five patients had an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m 2 . AHE patients with abnormal KFTs were older and had a lower level of albumin, but a slightly elevated alanine transaminase (ALT) compared to AHE patients with normal KFTs. There were no significant differences between the two groups in terms of age, sex, liver transaminase levels, and the viral load. Similarly, the clinical presentations were comparable in both groups. Interestingly, these KFTs in patients with abnormal renal parameters returned to normal levels at the recovery. The serum creatinine level was not correlated with patients' age or liver transaminase levels, but it was significantly negatively correlated with albumin level. In conclusion, this study is the first report that evaluated KFTs in patients during the acute phase of HEV-1 infections. Impaired KFTs in some AHE patients resolved at convalescence. KFTs and renal complications should be monitored during HEV-1 infections.

Background: The strategic position of the middle turbinate (MT) within the nasal cavity makes it the first kick start to resect pituitary pathology through Endoscopic Transnasal Transsphenoidal Surgery (ETTS). This research aimed to determine if the type of endonasal endoscopic approach, MT resection (MTres) versus MT preservation (MTpre), for pituitary surgery affects olfaction and sinonasal function within a subjective as well as objective manner., Patients & Methods: A prospective cohort comparative study was conducted to compare the sinonasal and olfaction outcomes pre and post operatively for both groups. Sinonasal symptoms were evaluated subjectively by Sino-Nasal Outcome Test (SNOT-22), while objectively by Peri-Operative Sinus Endoscope Score (POSE) along with Lund-Mackay radiological scoring system (LMS), and a Sniffin Sticks Identification test (SIT) (Burghart, Germany) was used to measure the olfaction intensity. In both groups were used on a pre-operative period and after one, three, and six months post operatively., Results: 96 patients were recruited within predetermined criteria. It is found that there are no significant differences in SIT between both groups with a ρ value 0.439 post operatively. The average change in score (delta) was an increase of 0.3, with changes ranging from -3 to +4. There was no significant difference in sinonasal symptoms score among both groups, with ρ 0.07 posts operatively. There was a minor upsurge in POSE score and LMS in the preservation group but without remarkable differences with ρ value 0.1 and 0.2 subsequently. It is found that there are no significant differences in SIT between both groups with a ρ value 0.439 post operatively., Conclusion: Despite these amendments to the nasal cavity, we approved that these changes do not affect the sinonasal functions., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Endocrine therapy (ET) is the standard of care for hormone receptor-positive early-stage breast cancer in the adjuvant setting. However, response to ET can vary across patient subgroups. Historically, hormone receptor expression and clinical stage are the main predictors of the benefit of ET. A "window of opportunity" trials has raised significant interest in recent years as a means of assessing the sensitivity of a patient's cancer to short-term neoadjuvant ET, which provides important prognostic information, and helps in decision-making regarding treatment options in a time-efficient and cost-efficient manner. In the era of genomics, molecular profiling has led to the discovery and evaluation of the prognostic and predictive abilities of new molecular profiles. To realize the goal of personalized medicine, we are in urgent need to explore reliable biomarkers or genomic signatures to accurately predict the clinical response and long-term outcomes associated with ET. Validation of these biomarkers as reliable surrogate endpoints can also lead to a revolution in the clinical trial designs, and potentially avoid the need for repeated tissue biopsies in the surveillance of disease response. The clinical potential of tumor genomic profiling marks the beginning of a new era of precision medicine in breast cancer treatment., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Monoclonal Gammopathy of Undetermined Significance (MGUS) is a premalignant plasma cell disorder which despite being clinically silent carries an increased risk of venous thromboembolism (VTE). We conducted a population-based study to investigate the risk of VTE in these patients., Methods: We utilized the National Inpatient Sample (NIS) for the year 2016 to compare the incidence of acute VTE between patients who carry the diagnosis of MGUS and those who don't. We excluded hospitalizations with age < 18 years and those that had a diagnosed lymphoma, leukemia, solid malignancy, or other plasma cell dyscrasia. We utilized the ICD-10-CM coding system to search the database for codes of VTE, MGUS, and other comorbid conditions. Multivariate logistic regression models were used for comparative analysis adjusting for demographic characteristics and comorbidities. Baseline comorbidities were described as frequencies and proportions for categorical variables and as medians with interquartile ranges for continuous variables., Results: A total of 33,115 weighted hospitalizations were included in the MGUS group. These were compared to 27,418,403 weighted hospitalizations without the diagnosis of MGUS. The MGUS group had higher odds of composite venous thromboembolism (adjusted OR 1.33, 95 % CI 1.22-1.44), deep vein thrombosis (adjusted OR 1.46, 95 % CI 1.29-1.65), and pulmonary embolism (adjusted OR 1.22, 95 % CI 1.09-1.37)., Conclusion: Patients with MGUS had increased odds of developing acute venous thromboembolism compared to patients with no history of MGUS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: The study assessed coronary artery bypass grafting (CABG) postoperative outcomes and associated factors in Saudi male and female patients. This was a retrospective cohort of patients who underwent CABG at the King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia, from January 2015 to December 2022.  Results: We included 392 patients, of whom 63 (16.1%) were female. Female undergoing CABG were significantly older (p=0.0001), had a significantly higher incidence of diabetes (p=0.0001), obesity (p=0.001), hypertension (p=0.001), and congestive heart failure (p=0.005), with a smaller body surface area (BSA) (p=0.0001) than male. Though renal dysfunction, previous cerebrovascular accident/transient ischemic attack (CVA/TIA), and myocardial infarction (MI), incidences were similar in both genders. Females were at significantly higher risk of mortality (p=0.0001), longer hospital stay (p=0.0001), and prolonged ventilation (p=0.0001). Preoperative renal dysfunction was the only statistically significant predictor of postoperative complications (p=0.0001). Female gender and preoperative renal dysfunction, were significant independent predictors of postoperative mortality and prolonged ventilation (p=0.005)., Conclusion: This study's findings indicated that females have worse CABG outcomes and a higher risk of morbidities and complications. Uniquely our study showed a higher incidence of prolonged ventilation in females postoperatively., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Alamri et al.)

Objectives: To examine the C-X-C Motif Chemokine Receptor 1 expression in breast cancer tissues prior to neo-adjuvant chemotherapy, and its relationship to neo-adjuvant chemotherapy effectiveness and other prognostic variables., Method: The prospective study was conducted at Kafrelsheikh University Hospital, Egypt, from November 2018 to March 2021, and comprised patients with recent histopathologically proven breast cancer cases eligible for chemotherapy. Paraffin blocks of tumourspecimens were stained by immunohistochemicalstain using concentrating rabbit anti-human C-X-C Motif Chemokine Receptor 1 polyclonal antibody kits. C-X-C Motif Chemokine Receptor 1 expression was classified into low and high categories. Patients were followed for 2 years for treatment response, disease recurrence and mortality. Data was analysed using SPSS 25., Results: Of the 100 females with mean age 50.2±12.1 years, 52(52%) had their left side affected, while 48(48%) had their rightside affected. There were 52(52%) cases with mean age 49.2±12.9 years having high C-X-C Motif Chemokine Receptor 1 expresssion, while 48(48%) with mean age 51.4±11.2 years had low expression. There was a significant association between high expression and advanced tumour grade, advanced tumourstage, higher frequency of triple negative breast cancer and higher frequency of Ki-67-positive cancers (p<0.05). Patients with high C-X-C Motif Chemokine Receptor 1 expression had significantly lower frequency of complete pathological response when compared with patients with low expression (p<0.001). Patients with high expression had higher frequency of recurrence, shorter disease-free survival, higher mortality and shorter overall survival, but the difference was not significant (p>0.05). Multivariate logistic regression analysis identified triple negative hormonal status (p=0.031) and high baseline C-X-C Motif Chemokine Receptor 1 expression (p<0.001) as significant predictors of complete pathological response., Conclusions: There was found to be a link between baseline C-X-C Motif Chemokine Receptor 1 expression in breast cancer tissues and pathological response to neoadjuvant therapy in breast cancer patients.

Objectives: Aneurysm of the pedal arteries is uncommon. I present a case of non-traumatic fusiform true aneurysm of the dorsalis pedis artery in an otherwise well 45-year-old man. Color flow duplex imaging revealed aneurysmal dilation, involving all layers of the artery wall, measuring 16.5 * 10 mm with irregular intraluminal thrombus across a 6.33-mm segment. Due to concerns over embolization, our patient underwent successful ligation of the dorsalis pedis artery. He had an uneventful post-operative recovery., Methods: Case report., Results: No postoperative complication or signs of ischemia., Conclusions: Treatment of asymptomatic dorsalis pedis artery aneurysm may be of value to prevent risk of thrombo-embolic complications, foot ischemia, or rupture without warning signs. Patency of the pedal arch is important to avoid foot ischemia in case of dorsalis pedis artery ligation.

Objectives: To examine the chemokine receptor type 1 expression in breast cancer tissues before and after neoadjuvant chemotherapy, and its relationship with pathological response to neoadjuvant chemotherapy and other clinical variables., Method: The prospective study was conducted at Kafrelsheikh University Hospital, Egypt, from November 2018 to March 2021, and comprised female patients with new histopathologically proven breast cancer eligible for chemotherapy. Paraffin blocks of tumourspecimens were stained immunohistochemically using concentrated rabbit anti-human chemokine receptor type 1 polyclonal antibody kits. The patients were followed up for treatment response, disease recurrence and mortality. Data was analysed using SPSS 25., Results: Of the 100 patients with mean age 50.2±12.1 years, 40(40%) in group A with mean age 55.1±9.3 showed marked response and 60(60%) in group B with mean age 47.0±12.7 yearsshowed mild/moderate response (p<0.001). Group A patients had significantly lower baseline and post-treatment chemokine receptor type 1 expression compared to group B patients (p<0.05). The change in chemokine receptor type 1 expression was not significantly different (p>0.05). Patients with tumour grade 3 had significantly higher baseline chemokine receptor type 1 expression compared to patients with tumour grade 2. Tumourstage and post-treatment chemokine receptor type 1 expression were also significantly interlinked (p<0.05). Multivariate regression analysisidentified patients'age, baseline chemokine receptor type 1 and post-treatment chemokine receptor type 1 expressions as predictors of treatment response., Conclusions: There was found to be an association between baseline and post-treatment chemokine receptor type 1 expression in breast cancer tissues and pathological response to neoadjuvant chemo therapy in such patients.

Background: The implementation and continuous improvement of patient safety learning systems (PSLS) is a principal strategy for mitigating preventable harm to patients. Although substantial efforts have sought to improve these systems, there is a need to more comprehensively understand critical success factors. This study aims to summarise the barriers and facilitators perceived by hospital staff and physicians to influence the reporting, analysis, learning and feedback within PSLS in hospitals., Methods: We performed a systematic review and meta-synthesis by searching MEDLINE (Ovid), EMBASE (Ovid), CINAHL, Scopus and Web of Science. We included English-language manuscripts of qualitative studies evaluating effectiveness of the PSLS and excluded studies evaluating specific individual adverse events, such as systems for tracking only medication side effects, for example. We followed the Joanna Briggs Institute methodology for qualitative systematic reviews., Results: We extracted data from 22 studies, after screening 2475 for inclusion/exclusion criteria. The included studies focused on reporting aspects of the PSLS, however, there were important barriers and facilitators across the analysis, learning and feedback phases. We identified the following barriers for effective use of PSLS: inadequate organisational support with shortage of resources, lack of training, weak safety culture, lack of accountability, defective policies, blame and a punitive environment, complex system, lack of experience and lack of feedback. We identified the following enabling factors: continuous training, a balance between accountability and responsibility, leaders as role models, anonymous reporting, user-friendly systems, well-structured analysis teams, tangible improvement., Conclusion: Multiple barriers and facilitators to uptake of PSLS exist. These factors should be considered by decision makers seeking to enhance the impact of PSLS., Ethics and Dissemination: No formal ethical approval or consent were required as no primary data were collected., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Multi-parametric magnetic resonance imaging may improve the detection of prostate cancer. The aim of this work is to compare between PI-RADS 3-5 and PI-RADS 4-5 as a threshold for targeted prostatic biopsy., Methods: This is a prospective clinical study that included 40 biopsy-naïve patients referred for prostate biopsy. Patients underwent prebiopsy multi-parametric (mp-MRI), followed by 12-core transrectal ultrasound-guided systematic biopsy and cognitive MRI/TRUS fusion targeted biopsy from each detected lesion. The primary endpoint was to assess the diagnostic accuracy of the PI-RAD 3-4 versus PI-RADS 4-5 lesion by mpMRI for prostate cancer detection in biopsy-naive men., Results: The overall prostate cancer detection rate and the clinically significant cancer detection rate were 42.5% and 35%, respectively. Targeted biopsies from PI-RADS 3-5 lesions showed a sensitivity of 100%, specificity of 44%, positive predictive value of 51.7%, and negative predictive value of 100%. Restricting targeted biopsies to PI-RADS 4-5 lesions resulted in a decrease in sensitivity and negative predictive value to 73.3% and 86.2%, respectively, while specificity and positive predictive value were increased to 100% for both parameters which was statistically significant (P value < 0.0001 and P value = 0.004, respectively)., Conclusions: Limiting the TBs to PI-RADS 4-5 lesions improves the performance of mp-MRI in the detection of prostate cancer especially aggressive tumors., (© 2023. The Author(s).)

Objectives: Our study aimed to assess the benefit of prolonging adjuvant temozolomide (TMZ) therapy beyond 6 cycles in glioblastoma multiform patients., Materials and Methods: The medical records of 329 patients in 2 cancer centers in Egypt were reviewed from January 2008 to December 2018 who were diagnosed with diffuse gliomas. Data were collected on patient demographics, presenting complaints, tumor size, treatment modalities (extent of surgery, radiotherapy dose and technique, concomitant TMZ, and the number of adjuvant TMZ cycles), and reported adverse events., Results: In the studied cohort, 105 patients were treated with adjuvant TMZ, 33 patients received <6 cycles (TMZL), 41 patients received the standard 6 cycles (TMZS), and 31 patients received >6 cycles (TMZE). Our results showed the median overall survival in the TMZL arm was 8.47 months compared with 15.83 months in the TMZS arm and 27.33 months in the TMZE arm ( P < 0.001). Furthermore, a median progression-free survival of 6.35 months was reported in the TMZL group versus, 12.7 and 22.90 months in (TMZS) and (TMZE) groups, respectively( P < 0.001). In the multivariate analysis, the extended adjuvant TMZ with a hazard ratio of 3.106 (95% CI: 2.43-14.46; P < 0.001) was statistically significantly associated with a better outcome., Conclusions: Extended adjuvant TMZ therapy beyond 6 cycles may significantly improve the progression-free survival and overall survival in patients with glioblastoma multiform., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Casing cementing is one of the most crucial operations in the oil well drilling process since it determines the durability and stability of the well throughout its life. Different additives have been mixed into the oil well cement slurry to improve the properties of both the cement slurry and the solidified cement sheath. Graphite is a waste material with a huge potential to be utilized in cementing to improve the properties of the oil well cement and reduce the graphite waste content in the environment. This study intends to analyze the effect of graphite on alteration in properties of the cement compressive and tensile strength, Poisson's ratio, Young's modulus, porosity, and permeability for three days of curing. Based on the trend of the properties during the three days of curing, equations were established to describe the future change in cement properties with time. Two formulas of cement, the base (with no graphite) and graphite-based (with 0.2% by weight of cement graphite) were prepared in this study. The results showed that the graphite successfully increased the compressive strength, tensile strength, and Poisson's ratio of the cement sheath, throughout the curing process. Young's modulus was decreased after the incorporation of graphite which indicates an enhancement in cement resistance to shear forces. The porosity and permeability were also decreased indicating formation of a more densified cement sheath., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Corrosion prevention has been a global phenomenon, particularly in metallic and construction engineering. Most inhibitors are expensive and toxic. Therefore, developing nontoxic and cheap corrosion inhibitors has been a way forward. In this work, L-arginine was successfully grafted on chitosan by the thermal technique using a reflux condenser. This copolymer was characterized by Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and X-ray diffraction (XRD). The corrosion inhibition performance of the composite polymer was tested on mild steel in 0.5M HCl by electrochemical methods. The potentiodynamic polarization (PDP) and electrochemical impedance spectroscopy (EIS) results were consistent. The inhibition efficiency at optimum concentration rose to 91.4%. The quantum chemical calculation parameters show good properties of the material as a corrosion inhibitor. The molecular structure of the inhibitor was subjected to density functional theory (DFT) to understand its theoretical properties, and the results confirmed the inhibition efficiency of the grafted polymer for corrosion prevention.

Thyroid cancer is the most common endocrine malignancy, and its incidence is increasing. Differentiated thyroid cancer is the most common type and papillary thyroid carcinoma is the most common type of differentiated thyroid cancer. This work aimed to study long noncoding (Lnc) RNA homeobox transcript antisense RNA (HOTAIR) expression in plasma and serum midkine, a heparin binding growth factor, as biomarkers of thyroid cancer. This study included 27 thyroid cancer patients, 29 patients with benign thyroid disease and 26 individuals as normal controls. HOTAIR expression was assessed by real time polymerase chain reaction and midkine by ELISA. These biomarkers were elevated in thyroid cancer patients than patients with benign thyroid diseases and controls. Patients with thyroid cancer stage III had higher midkine levels in comparison to those with stage-I and stage-II (p < 0.001). Patients with grade II had higher midkine in comparison to those with grade I (p < 0.001). Statistically significant elevation of HOTAIR expression was found in stage III and stage II (p=0.001), compared to stage I. However, no difference was observed between stage II and stage III (p=0.533). There was no difference in both biomarkers in different histopathological types of thyroid cancer. ROC analysis was used for detection of thyroid cancer, midkine had AUC of 0.95 at a cutoff 897.5 pg/ml with a sensitivity of 98.0%, and specificity of 81.5% (p < 0.001). HOTAIR had AUC of 1 at a cutoff 11.8-fold change with a sensitivity and specificity of 100 %, (p < 0.001). We concluded that HOTAIR has high sensitivity and specificity in detection of thyroid cancer. It was correlated with tumor stage but not with histopathological types., (Copyright© by the Egyptian Association of Immunologists.)

Purpose: Bariatric surgery is evolving as a successful tool for managing morbid obesity and T2DM. This study aimed to identify predictors of diabetes remission after two types of bariatric procedures., Methods: This prospective study enrolled 172 patients with morbid obesity associated with T2DM scheduled for bariatric surgery. Two laparoscopic bariatric procedures were done; single anastomosis gastric bypass (SAGB, n = 83) and sleeve gastrectomy (LSG, n = 68). Lipid accumulation product index (LAP) and quantitative insulin sensitivity check index (QUICKI) were used to evaluate lipid profile and insulin sensitivity. Two years after surgery condition of DM was evaluated as complete remission (CR), partial remission (PR), or improvement. The primary outcome measure was predictors of diabetes remission., Results: Two years after surgery, 151 patients were available for evaluation, where 75 patients (49.7%) achieved CR, while PR was found in 36 (23.8%). CR was significantly associated with younger age, shorter duration of DM (p < 0.001, for both), higher C-peptide and GLP-1 levels (p < 0.001 and p = 0.002, respectively), and bypass surgery (p = 0.027). On multivariate analysis, shorter duration of DM, lower BMI, and higher C-peptide levels were the independent factors predicting CR., Conclusion: Complete remission of T2DM can be achieved in nearly half of the patients two years after SG or SAGB. The duration of diabetes and preoperative BMI and C-peptide levels are the independent factors predicting complete remissions., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2022 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Background: Epilepsy is a neurological disease that requires long-term antiepileptic drugs (AEDs). The old generation of AEDs may affect serum homocysteine and asymmetric dimethylarginine (ADMA) and disturb lipid levels. The aim of the study was to evaluate serum ADMA, homocysteine, lipid profile, and carotid intima-media thickness (CIMT) in epileptic children., Methods: This study was implemented on 159 epileptic children who were subdivided into 3 subgroups, with 53 receiving sodium valproate, 53 receiving levetiracetam, and 53 receiving polytherapy, for over 6 months and 53 healthy children., Results: Low-density lipoprotein, triglycerides, and cholesterol levels were increased in epileptic children (p < 0.001), which were higher in those receiving multidrug followed by a valproate receiver. While high-density lipoprotein was lower in those receiving multidrug more than those receiving valproate. ADMA and homocysteine levels increased in epileptic patients than in controls (p < 0.001). Higher ADMA was also observed in the multidrug receiver (5.78 ± 0.62), followed by the levetiracetam group (5.56 ± 0.61). Homocysteine levels were significantly higher in multidrug and valproate-treated children than those treated with levetiracetam. CIMT was significantly higher in multidrug and valproate-treated patients (p < 0.001)., Conclusions: Long-term use of AEDs, especially old-generation polytherapy, can elevate lipid profiles, homocysteine, ADMA levels, and carotid intima-media thickness compared to the minimal effect of new AEDs., Impact: The long-term use of antiepileptic drugs, especially old-generation polytherapy, can increase lipid profiles, homocysteine levels, ADMA, and carotid intima thickness compared to the minimal effect of new antiepileptic generation. A routine follow-up of these markers and a lifestyle modification are recommended to avoid cerebrovascular events as much as possible., (© 2022. The Author(s).)

The eye is an invulnerable organ with intrinsic anatomical and physiological barriers, hindering the development of a pioneer ocular formulation. The aim of this work was to develop an efficient ocular delivery system that can augment the ocular bioavailability of the antifungal drug, terconazole. Mesoporous silica microparticles, Syloid ® 244 FP were utilized as the carrier system for terconazole. Preliminary studies were carried out using different drug:Syloid ® weight ratios. The optimum weight ratio was mixed with various concentrations (30 and 60%w/w) of poly (lactic-co-glycolic acid) (PLGA), ester or acid-capped and with different monomers-ratio (50:50 and 75:25) using the nano-spray dryer. Results revealed the superiority of drug:Syloid ® weight ratio of 1:2 in terms of yield percentage (Y%), SPAN and drug content percentage (DC%). Furthermore, incorporation of PLGA with lower glycolic acid monomer-ratio significantly increased Y%. In contrast, increasing the glycolic acid monomer-ratio resulted in higher DC% and release efficiency percentage (RE%). Additionally, doubling PLGA concentration significantly reduced Y%, DC%, drug loading percentage (DL%) and RE%. Applying desirability function in terms of increasing DC%, DL% besides RE% and decreasing SPAN, the selected formulation was chosen for DSC, XRD and SEM investigations. Results confirmed the successful loading of amorphized terconazole on PLGA-modified Syloid ® microparticles. Moreover, pharmacokinetic studies for the chosen formulation on male Albino rabbits' eyes revealed a 2, 6.7 and 25.3-fold increase in mean residence time, C max and AUC 0-24 -values, respectively, compared to the drug suspension. PLGA-modified Syloid ® microparticles represent a potential option to augment the bioavailability of ocular drugs.

Microfluidics is used to manipulate fluid flow in micro-channels to fabricate drug delivery vesicles in a uniform tunable size. Thanks to their designs, microfluidic technology provides an alternative and versatile platform over traditional formulation methods of nanoparticles. Understanding the factors that affect the formulation of nanoparticles can guide the proper selection of microfluidic design and the operating parameters aiming at producing nanoparticles with reproducible properties. This review introduces the microfluidic systems' continuous flow (single-phase) and segmented flow (multiphase) and their different mixing parameters and mechanisms. Furthermore, microfluidic approaches for efficient production of nanoparticles as surface modification, anti-fouling, and post-microfluidic treatment are summarized. The review sheds light on the used microfluidic systems and operation parameters applied to prepare and fine-tune nanoparticles like lipid, poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles as well as cross-linked nanoparticles. The approaches for scale-up production using microfluidics for clinical or industrial use are also highlighted. Furthermore, the use of microfluidics in preparing novel micro/nanofluidic drug delivery systems is presented. In conclusion, the characteristic vital features of microfluidics offer the ability to develop precise and efficient drug delivery nanoparticles.

Background/objective: Management of thyroid disorders depends on accurate clinical assessment, appropriate investigations and radionuclide imaging, which plays an established important role either qualitatively or quantitatively. The aim of this study was to assess the utility of the thyroid/salivary ratio (TSR) as an alternative to technetium-99m (Tc99m) pertechnetate thyroid uptake (TcU) percentage in the evaluation of thyroid function and in the same time to establish reference range for the thyroid uptake of Tc99m-pertechnetate and TSR among Egyptian populations., Patients and Methods: This retrospective study enrolled 270 patients, out of which 250 with different thyroid disorders and 20 without thyroid diseases, as a control group who all underwent full clinical examination, thyroid function tests and Tc99m pertechnetate thyroid scintigraphy. The TcU percentage and TSR were calculated and then correlated to the thyroid hormonal profile., Results: The normal reference ranges of TcU and TSR were 0.75-3.5% and 1.25-4.8%, respectively. The sensitivity and specificity of TSR to diagnose hyperthyroidism were slightly lower compared with TcU (84.5 and 92.3% vs. 86.2 and 98.3%, respectively) at TSR cutoff value of more than 4.8 and TcU cutoff value of more than 3.5. Meanwhile, they had comparable sensitivity and specificity to diagnose hypothyroidism (86.0 and 93.3% vs. 86.5 and 94.5%) at cutoff values <0.75 and <1.25, respectively., Conclusion: The current study established a reference range for TcU and TSR in our institution. TSR is comparable to TcU in the evaluation of thyroid function among hyper-and hypothyroid patients and TSR can be used in doubtful cases of mal-thyroid function for confirmation of the diagnosis., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: This prospective, double-blind, randomized, controlled trial compared the efficacy of two dexmedetomidine doses (50 and 100-μg) combined with levobupivacaine on sensory block duration in infraclavicular brachial plexus block. We hypothesized that perineural dexmedetomidine would extend sensory block duration dose-dependently., Methods: The study included 60 patients aged 20 to 60 years of both sex with an ASA I/II undergoing forearm and hand surgery. The patients were randomly assigned into three equal groups (n = 20) for ultrasound-guided infraclavicular brachial plexus block. The L group received 35-mL 0.5% levobupivacaine plus normal saline, the LD50 group received 35-mL 0.5% levobupivacaine plus 50-μg dexmedetomidine, and the LD100 group received 35-mL 0.5% levobupivacaine plus 100-μg dexmedetomidine. Patients were investigated for onset and duration of sensory blockade, time to first postoperative rescue analgesia, and the total 24-h postoperative morphine requirement., Results: The LD100 group had a longer sensory block duration (15.55 ± 1.1 h; 95% confidence interval (CI), 15.04-16.06) than the LD50 group (12.8 ± 1.2 h; 95% CI, 12.24-13.36 h) (p &lt; 0.001) or the L group (9.95 ± 1.05 h; 95% CI, 9.46-10.44 h) (p &lt; 0.001). The LD100 group took longer to request postoperative rescue analgesia and required fewer postoperative morphine doses than the LD50 and L groups (P &lt; 0.001)., Conclusions: Sensory block duration was longer with perineural 100-μg dexmedetomidine as an adjunct to levobupivacaine than with 50-μg dexmedetomidine., Trial Registration: This study was approved by the Ethics Committee of Aswan University Hospital (approval number: aswu/125/4/17) (date of registration: 04/04/2017). Furthermore, the trial was retrospectively registered at ClinicalTrial.gov (NCT04729868) with a verification date of January 2021., (© 2022. The Author(s).)

Background: Chronic kidney disease patients are at increased risk of mortality with cardiovascular diseases and infections as the two leading causes of death for end-stage kidney disease treated with hemodialysis (HD). Mortality from bacterial infections in HD patients is estimated to be 100-1000 times higher than in the healthy population., Methods: We comprehensively characterized highly pure circulating neutrophils from HD and healthy donors., Results: Protein levels and transcriptome of HD patients' neutrophils indicated massive neutrophil degranulation with a dramatic reduction in reactive oxygen species (ROS) production during an oxidative burst and defective oxidative cellular signaling. Moreover, HD neutrophils exhibit severely impaired ability to generate extracellular NET formation (NETosis) in NADPH oxidase-dependent or independent pathways, reflecting their loss of capacity to kill extracellular bacteria. Ectopic hydrogen peroxidase (H 2 O 2 ) or recombinant human SOD-1 (rSOD-1) partly restores and improves the extent of HD dysfunctional neutrophil NET formation., Conclusions: Our report is one of the first singular examples of severe and chronic impairment of NET formation leading to substantial clinical susceptibility to bacteremia that most likely results from the metabolic and environmental milieu typical to HD patients and not by common human genetic deficiencies. In this manner, aberrant gene expression and differential exocytosis of distinct granule populations could reflect the chronic defect in neutrophil functionality and their diminished ability to induce NETosis. Therefore, our findings suggest that targeting NETosis in HD patients may reduce infections, minimize their severity, and decrease the mortality rate from infections in this patient population., (© 2022. The Author(s).)

Background: Generating polygenic risk scores for diseases and complex traits requires high quality GWAS summary statistic files. Often, these files can be difficult to acquire either as a result of unshared or incomplete data. To date, bioinformatics tools which focus on restoring missing columns containing identification and association data are limited, which has the potential to increase the number of usable GWAS summary statistics files., Results: SumStatsRehab was able to restore rsID, effect/other alleles, chromosome, base pair position, effect allele frequencies, beta, standard error, and p-values to a better extent than any other currently available tool, with minimal loss., Conclusions: SumStatsRehab offers a unique tool utilizing both functional programming and pipeline-like architecture, allowing users to generate accurate data restorations for incomplete summary statistics files. This in turn, increases the number of usable GWAS summary statistics files, which may be invaluable for less researched health traits., (© 2022. The Author(s).)

Whole-genome data has become significantly more accessible over the last two decades. This can largely be attributed to both reduced sequencing costs and imputation models which make it possible to obtain nearly whole-genome data from less expensive genotyping methods, such as microarray chips. Although there are many different approaches to imputation, the Hidden Markov Model (HMM) remains the most widely used. In this study, we compared the latest versions of the most popular HMM-based tools for phasing and imputation: Beagle5.4, Eagle2.4.1, Shapeit4, Impute5 and Minimac4. We benchmarked them on four input datasets with three levels of chip density. We assessed each imputation software on the basis of accuracy, speed and memory usage, and showed how the choice of imputation accuracy metric can result in different interpretations. The highest average concordance rate was achieved by Beagle5.4, followed by Impute5 and Minimac4, using a reference-based approach during phasing and the highest density chip. IQS and R2 metrics revealed that Impute5 and Minimac4 obtained better results for low frequency markers, while Beagle5.4 remained more accurate for common markers (MAF>5%). Computational load as measured by run time was lower for Beagle5.4 than Minimac4 and Impute5, while Minimac4 utilized the least memory of the imputation tools we compared. ShapeIT4, used the least memory of the phasing tools examined with genotype chip data, while Eagle2.4.1 used the least memory phasing WGS data. Finally, we determined the combination of phasing software, imputation software, and reference panel, best suited for different situations and analysis needs and created an automated pipeline that provides a way for users to create customized chips designed to optimize their imputation results., Competing Interests: All authors are either employed by and/or hold stock or stock options in SelfDecode. In addition, PGY has equity in Systomic Health LLC and Ethobiotics LLC. There are no other relevant activities or financial relationships which have influenced this work. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Testicular dysfunction is caused by the continuous inflammation and oxidative stress that are present at the local site in ulcerative colitis (UC) spreading to the testes via systemic circulation. The influence of ozone and naringine on colitis-mediated testicular dysfunction was investigated in this study. Forty-eight adult male rats were divided into four groups: I control group, II dextran sodium sulfate (DSS) UC-induced group, III DSS+naringine, and IV DSS+ozone groups. UC was induced in groups II, III, and IV using 0.1 ml of 4% DSS in their drinking water per day for 6 days by gastric gavage. All animals were sacrificed 45 days from the start. Blood samples were obtained to estimate serum testosterone hormone. Testicular tissues were processed for measurement of tissue malondialdehyde (MDA) and examined by light and electron microscopes. Ultrastructurally, group II revealed a relatively thick basement membrane enveloping the seminiferous tubule. Sertoli cell cytoplasm appears rarified with wide intracellular spaces, vacuoles, and multiple lysosomes; distorted spermatogonia with electron dense nuclei and cytoplasm; and primary spermatocytes with small nuclei and electron dense cytoplasm. Abnormal sperm profiles were visible in middle pieces, mid, principle, and end pieces that were markedly affected with disorganization of axoneme and outer dense fibers. Leydig cells revealed dilated cisternae of smooth endoplasmic reticulum. Morphometric and statistical analyses were performed. Group III showed some improvement; however, group IV showed more improvement. The results indicated that ozone caused marked improvement than naringine against UC-induced testicular damage via their antioxidant and anti-inflammatory properties.