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Introduction: Improper glycemic control is associated with diabetic cognitive dysfunction. Several studies have confirmed the neuroprotective effects of metformin and insulin. This study aimed to investigate the effects of metformin and/or insulin therapy on neurocognitive functions in a type 2 diabetes mellitus (T2DM) rat model. Methods: Fifty adult male Wistar rats were used in this study and had free access to water and a normal chow diet. After an acclimatization period, 10 rats were kept on a normal chow diet and considered as the control group. T2DM was induced in the other 40 rats by a high-fat diet and low-dose streptozotocin method. Then, diabetic rats were randomly allocated into 4 equal groups: Non-treated diabetic group; Metformin-treated diabetic group (treated with metformin 250 mg/kg/day for 6 weeks); Insulin-treated diabetic group (treated with NPH insulin 40 U/kg for 6 weeks); and Metformin and insulin-treated diabetic group. Neurocognitive functions were assessed by footprint assay, Y-maze, open field test, and Morris water maze. Glycaemic profile, serum levels of amyloid A, interleukin-18, and nuclear factor-kappa B were analyzed. Brain malondialdehyde and total antioxidant capacity were measured. A histopathological examination of the frontal lobe was performed. Results: Treatment with metformin and/or insulin significantly improved the impaired neurocognitive dysfunction, brain oxidative stress, changes in biochemical parameters, and the associated histopathological changes in the frontal cortex of diabetic rats. The combined therapy showed a better effect than either monotherapy alone. Conclusion: Metformin and insulin therapy may be valuable for the prevention of neurocognitive dysfunction in T2DM. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a critical clinical event characterized by a reduction in the excretory function of the kidneys. N-acetylcysteine (NAC), N-acetylmethionine (NAM) and N-acetylglucosamine (NAG) are antioxidants with scanty known genetic mechanisms. We aimed to assess both kidney injury molecule-1 (KIM-1) and growth-arrested DNA damage-inducible gene-153 (GADD-153) genes expression in paracetamol (PA) induced AKI. Also, to recognize whether NAC, NAM and/or NAG have roles in altering the expression of these genes for ameliorating the AKI induced by PA.

Objectives: Lifetime DSM‐5 diagnoses generated by the lay‐administered Composite International Diagnostic Interview for DSM‐5 (CIDI) in the World Mental Health Qatar (WMHQ) study were compared to diagnoses based on blinded clinician‐administered reappraisal interviews. Methods: Telephone follow‐up interviews used the non‐patient edition of the Structured Clinician Interview for DSM‐5 (SCID) oversampling respondents who screened positive for five diagnoses in the CIDI: major depressive episode, mania/hypomania, panic disorder, generalized anxiety disorder, and obsessive‐compulsive disorder. Concordance was also examined for a diagnoses of post‐traumatic stress disorder based on a short‐form versus full version of the PTSD Checklist for DSM‐5 (PCL‐5). Results: Initial CIDI prevalence estimates differed significantly from the SCID for most diagnoses (χ12 ${\chi }_{1}^{2}$ = 6.6–31.4, p = 0.010 < 0.001), but recalibration reduced most of these differences and led to consistent increases in individual‐level concordance (AU‐ROC) from 0.53–0.76 to 0.67–0.81. Recalibration of the short‐form PCL‐5 removed an initially significant difference in PTSD prevalence with the full PCL‐5 (from χ12 ${\chi }_{1}^{2}$ = 610.5, p < 0.001 to χ12 ${\chi }_{1}^{2}$ = 2.5, p = 0.110) while also increasing AU‐ROC from 0.76 to 0.81. Conclusions: Recalibration resulted in valid diagnoses of common mental disorders in the Qatar National Mental Health Survey, but with inflated prevalence estimates for some disorders that need to be considered when interpreting results. [ABSTRACT FROM AUTHOR]

The present study aimed at evaluating the potential contribution of Phosphatase and Tensin Homolog (PTEN) and its gene polymorphism (PTEN rs701848 T/C) in relation to Wingless/integrase-1 (Wnt) signaling in childhood epilepsy and the impact of antiepileptic medications on their serum levels. This study included 100 children with epilepsy (50 pharmacoresistant and 50 pharmacoresponsive) and 50 matched controls. All subjects had their genotypes for the PTEN rs701848T/C polymorphism assessed using TaqManTM assays and real-time PCR. By using the sandwich ELISA technique, the blood concentrations of PTEN and Wnt3a were measured. Serum Wnt3a levels in epileptic patients were significantly higher than in the control group, p < 0.001. Children with epilepsy who received oxcarbazepine had considerably lower serum Wnt3a levels than those who didn't, p < 0.001.With an AUC of 0.71, the cutoff value for diagnosing epilepsy as serum Wnt3a > 6.2 ng/mL has a sensitivity of 55% and a specificity of 80%. When compared to controls, epileptic children had considerably more (TT) genotype and less (TC and CC) genotypes, p < 0.05 for all. Epileptic children had significantly higher (T) allele frequency than controls, p = 0.006 with OR (95%CI) = 1.962(1.206–3.192). Pharmacoresistant epileptic children had significantly higher (TT) genotype compared to pharmacoresponsive type (p = 0.020). We originally found a strong association between PTEN rs701848 T/C and childhood epilepsy, in particular pharmacoresistant type. Serum Wnt3a levels increased in epilepsy, but were not significantly different between different alleles of PTEN. In pharmaco-responsive children Wnt3a levels differed significantly between the different PTEN genotypes. Antiepileptics may affect Wnt3a levels. [ABSTRACT FROM AUTHOR]

Fifty diabetic nephropathy (DN) children with type 1 diabetes mellitus (T1DM) and 50 healthy matched controls were included. Chromatographic assays of 14 amino acids, free carnitine and 27 carnitine esters using high‐performance liquid chromatography/electrospray ionization–mass spectroscopy, and genetic testing for JAK2v617f mutation using real‐time PCR were performed. Patients had significantly lower levels of tyrosine, branched‐chain amino acids (BCAAs), and BCAA/AAA (aromatic chain amino acids) ratios, glycine, arginine, ornithine, free carnitine and some carnitine esters (C5, 6, 12 and 16) and higher phenylalanine, phenylalanine/tyrosine ratio and C18 compared with the controls and in the macro‐albuminuria vs. the microalbuminuria group (p < 0.05 for all) except for free carnitine. Plasma carnitine was negatively correlated with eGFR (r = −0.488, p = 0.000). There were significant positive correlations between tyrosine with UACR ratio (r = 0.296, p = 0.037). The plasma BCAA/AAA ratio showed significant negative correlations with UACR (r = −0.484, p = 0.000). There was a significantly higher frequency of the JAK2V617F gene mutation in diabetic nephropathy patients compared with the control group and in macro‐albuminuria than the microalbuminuria group (p = 0.000) for both. When monitoring children with T1DM, plasma free amino acids and acylcarnitine profiles should be considered, especially if they have tested positive for JAK2V617F for the early diagnosis of DN. [ABSTRACT FROM AUTHOR]

Background: Alterations in zinc and copper homeostasis may contribute to seizure susceptibility, development, termination, and response to antiepileptic medications. The current study examined the profile of zinc, copper, and their ratio in childhood epilepsy and its pharmacological variants (pharmacoresistant and pharmacoresponsive). Methods: The study included 100 epileptic children (50 pharmacoresistant and 50 pharmacoresponsive) and 50 healthy, age- and gender-matched controls. History, clinical examination, and assays of serum zinc and copper were performed. Zinc/copper ratio was calculated. Results: Serum zinc and the zinc/copper ratio were significantly lower in epileptic children than in controls (p < 0.001). Significantly lower zinc and zinc/copper ratio and higher copper levels were found in children treated with levetiracetam/sodium valproate/oxcarbazepine than those treated with levetiracetam alone or combined with sodium valproate (p < 0.05 for all). Epileptic children, particularly pharmacoresistant, exhibited significant negative correlations between the serum levels of zinc and copper (r = -0.279, p = 0.005, and r = -0.363 and p = 0.010, respectively). At cutoff value of zinc/copper ratio < 1.118 in diagnosing children with epilepsy, it gives a sensitivity of 64% and a specificity of 85% with the AUC = 0.8092. At cutoff value of zinc/copper ratio ≤ 0.7826 in distinguishing pharmacoresistant epilepsy, it produced 52% sensitivity, 64% specificity with AUC = 0.576 Conclusions: Low zinc and high copper levels were associated with childhood epilepsy especially those with pharmacoresistant type and treated with Oxcarbazepine. Zinc/copper ratio might be a potential biomarker in diagnosing childhood epilepsy and to some extent in predicting pharmacoresistant type. [ABSTRACT FROM AUTHOR]

Vitiligo pathogenesis is related to the macrophage migration inhibitory factor (MIF) protein. This study aimed to assess the lesional MIF levels and gene polymorphisms (rs755622G>C) in patients with vitiligo. To assess the consequences of combining narrow-band ultraviolet B with oral minipulse prednisolone as opposed to a combination with oral methotrexate on MIF levels in vitiligo patients, 50 unstable vitiligo patients and 50 controls were randomly chosen for comparison. MIF levels in skin homogenates and MIF (rs755622G>C) single nucleotide polymorphisms were assessed using the ELISA and the polymerase chain reaction restriction fragment length polymorphism (RFLP-PCR) techniques. We found significantly higher lesional MIF levels, a higher frequency of both (GC) and (CC) genotypes, and a significantly more frequent mutant allele (C) in patients than in controls. In addition, there was a significantly lower frequency of the allele (C) among patients who exhibited moderate to marked therapeutic improvement than among those who showed minimal to mild improvement. In conclusion, tissue MIF and gene polymorphisms were associated with vitiligo. In addition, oral corticosteroids, narrow-band ultraviolet B, methotrexate-targeted tissue MIF, and gene polymorphisms can improve unstable vitiligo. [ABSTRACT FROM AUTHOR]

Alfalfa roots are infected with several fungal pathogens under salinity conditions. The effect of two salts of NaCl and CaCO3 at three concentrations was studied in vitro. Mycelial growth and disease severity (DS%) were estimated to determine the relationship between (DS%) and water salinity. The highest effect on mycelial growth was detected at the electrical conductivity (ECW value) of 18.75 ds/m2 which ranged from 8.80 and 9.44% with NaCl and CaCO3, respectively. Furthermore, Exserohilum sp. was the most affected by water salinity. With the different levels of water salinity, the DS% of alfalfa root rot increased gradually with the increased water salinity level. The highest level of water salinity with NaCl and CaCO3 ECW value at 18.75 ds/m2 ranged (42.76 and 43.53% severity for NaCl) and (44.04 and 44.42% severity for CaCO3, respectively). Moreover, with water salinity NaCl and CaCO3, Fusarium sp. was the highest (DS%) with NaCl. Alfalfa root rot prediction model based on information gathered from the interaction of pathogen, water salinity, disease severity, and root and shoot length. It was found the relation between DS% with fungi, salt type, salt concentration, root and shoot length in the multiple regression model (r² =88.83%). [ABSTRACT FROM AUTHOR]

Background: Extreme body mass index (BMI) is an influential pathophysiological risk factor for serious illnesses following lower respiratory tract infection. The purpose of the current study was to examine how the BMI of Coronavirus disease-19 (COVID-19) patients affects their prognosis.Methods: Two hundred patients with COVID-19 admitted to Al-Azhar, Qena, Aswan, and Sohag University hospitals in Egypt were included and categorized into four groups according to their BMI. The diagnosis was made according to a real-time reverse transcription-polymerase chain reaction (rRT-PCR) positive result for the SARS-CoV-2 nucleic acid in swabs from upper respiratory tract. A detailed history, clinical examination, and outcomes (disease severity and complications, hospital stay, ICU admission, mortality) were recorded for all patients. SPSS version 24 software was used for data analysis.Results: Average age of participants (19– 90 years old), 92 (46%) males and 108 females (54%). ICU admission was significantly higher among underweight patients (75%) and obese patients (78.6%). The majority of underweight (62.5%) and obese (57.1%) patients had critical disease. Invasive mechanical ventilation (MV) is frequently used in underweight (50%) and obese patients (42.9%) patients. Adult respiratory distress syndrome (ARDS), cardiac, neurological, and hematological complications, and incidence of myalgia and bed sores were most frequent among obese and overweight patients. Acute kidney injury was significantly higher among underweight patients (37.5%) and obese patients (28.6%) than among other classes (p=0.004). Frequency of endocrine complications was significantly higher in underweight patients than that in other classes (p=0.01). The majority of underweight (75%) and obese patients (50%) deteriorated and died, whereas the majority of normal-weight patients (90.3%) and overweight patients (75.8%) improved and were discharged (p< 0.001).Conclusion: Body mass index is a major contributing factor to the outcome of patients with COVID-19, and patients with extreme of body mass index were associated with the worst prognosis. [ABSTRACT FROM AUTHOR]

Aim of the study: To evaluate the role of MIF gene polymorphism rs755622 G>C in occurrence and progression of hepatocellular carcinoma (HCC) among a cohort of Egyptian patients. Material and methods: This case-control study was conducted on 50 patients with HCC after chronic viral hepatitis and 50 healthy volunteers, recruited between July 2021 and January 2022. All patients with HCC were evaluated for severity of liver disease using a Child-Pugh score, and TNM and BCLC scoring systems. MIF 173 G>C (rs755622) single nucleotide polymorphism was performed for all participants by polymerase chain reaction using restriction fragment length polymorphism technique (RFLP-PCR). Results: Overall results showed significantly higher frequencies of GG (wild homozygous genotype) and mutant heterozygous genotype GC and G allele (OR = 6.303, 95% CI: 3.374-11.775) among patients with HCC compared to the control group (p = 0.001) for all. Also, significantly higher frequency of genotype GG was detected among patients with advanced Child scores (B and C) (p = 0.039) and TNM stages (III and IV) (p = 0.013). There was significantly higher frequency of the G allele among patients with multiple hepatic focal lesions compared to those with a single focal lesion (p = 0.01). Conclusions: An obvious role of MIF (rs755622) gene polymorphism could have an important role in susceptibility and progression of HCC among patients with chronic viral hepatitis induced liver cirrhosis. [ABSTRACT FROM AUTHOR]

Background. Obesity is a significant public health problem that is characterized by an increase in oxidative stress and enhanced inflammatory responses associated with immune cell invasion of adipose tissues. This study assessed several biochemical abnormalities, apoptosis, oxidative stress status, and associated histological changes in the liver, duodenum, and heart brought on by high-fat diet-induced obesity in rats. It also assessed the mechanistic benefits of curcumin in reversing these inflammatory, metabolic, and histological impairments. Methods. Rats were assigned into three groups each including ten rats: the control group (CD), the high-fat diet group (HFD), and the high-fat diet + curcumin (HFDC) group. Serum glucose, insulin, and triglycerides (TAGs) were observed. In addition, apoptosis (indicated by hepatic DNA fragmentation) and oxidative stress status (indicated by hepatic MPO, GSH, and SOD) were assessed. Histopathological examinations included the GIT (liver and duodenum) and heart in addition to quantitative real-time polymerase chain reaction (qRT-PCR) assays of the adipose tissue genetic expressions for inflammatory signaling pathways (TLR4, IL-6, and TNF-α). Results. The overall findings showed that the HFD group exhibited significantly higher levels of glucose, TAGs, and insulin than the control group (P < 0.01). The histological abnormalities of the studied organs in the HFD group were paralleled by these biochemical abnormalities, which were strongly associated with increased apoptosis, increased oxidative stress, and increased expression of the inflammatory signaling markers. There were significant improvements in the HFDC group in terms of biochemical, inflammatory, and histological investigations. Conclusions. This study's findings concluded that obesity is significantly associated with biochemical and microscopic alterations in many organs. Curcumin exerted potent antitoxic, antioxidant, tissue-protective, and antiobesity effects. Curcumin is recommended to be added to various dietary regimens to prevent or delay the organs' dysfunction among obese people. [ABSTRACT FROM AUTHOR]

Purpose: Anosmia or hyposmia, with or without taste changes, are common symptoms that occur in SARS-CoV-2 infection and frequently persist as post-COVID-19 manifestations. This is the first trial to assess the potential value of using local ivermectin in the form of a mucoadhesive nanosuspension nasal spray to treat post-COVID-19 anosmia. Methods: It is a controlled, randomized trial. Participants were recruited from South Valley University Hospitals in Qena, Upper Egypt, from the ENT and Chest Diseases Departments and outpatient clinics. Patients with persistent post COVID-19 anosmia were randomly divided into two groups, the first group "ivermectin group" included 49 patients treated by ivermectin nanosuspension mucoadhesive nasal spray (two puffs per day). The second group included 47 patients "placebo group" who received saline nasal spray. Follow- up of anosmia [using Visual analogue scale (VAS)] in all patients for three months or appearance of any drug related side effects was done. Results: The mean duration of pre-treatment post COVID-19 anosmia was 19.5± 5.8 days in the ivermectin group and 19.1±  5.9 days in the placebo group,p˃0.05. Regarding the median duration of anosmia recovery, the ivermectin group recovered from post COVID-19 anosmia in 13 days compared to 50 days in the placebo group, p˂  0.001. Following the first week of ivermectin nanosuspension mucoadhesive nasal spray therapy, the ivermectin group had a significantly higher percentage of anosmia recovery (59.2%) than the placebo group (27.7%), p˂ 0.01, with no significant differences in recovery rates between the two groups at 1, 2, and 3 months of follow up, p˃0.05. Conclusion: In the small number of patients treated, local Ivermectin exhibited no side effects. In persistent post-COVID-19 anosmia, it could be used for one week at the most as the treatment was extended to one, two and three months, with no difference in recovery compared to the placebo treatment. Trial Registration No: NCT04951362. [ABSTRACT FROM AUTHOR]

Introduction: Traumatic spinal cord injury (TSCI) is a life-threatening neurological disorder and there is a lack of biomarker research, particularly human studies that could help to categorize the severity and predict the outcome. We aimed to assess the role of serum Ubiquitin C-terminal hydrolase L1 (UCH-L1) and Neuroglobin (NGB) in predicting severity and outcome of TSCI. Methods: This prospective study included 63 participants categorized into 33 patients with various types of TSCI and 30 unrelated healthy volunteers. Neurosurgical [American spinal injury association (ASIA) impairment score (AIS)] and radiological [using spine computed tomography (CT) and magnetic resonance imaging (MRI)] assessments were performed on the included patients to determine the severity and the level of injury with neurological follow-up of patients within 6 months post-injury. Serum UCH-L1 and NGB were measured for all participants using commercially available ELISA assay kits. Results: Of the included patients, 20 (60.60%) had partial SCI and the remaining 13 patients (39.39%) had complete SCI. On follow-up, 19 patients (57.57%) showed improved AIS, while 14 cases (42.42%) did not show any improvement in their AIS scores. There was significantly higher median serum UCHL1 value among cases compared to controls (1723 pg/mL and 657 pg/mL, respectively), p ˂ 0.05. There was an insignificant rise of serum NGB levels among cases in comparison with the controls (15.2pg/mL and 7.52pg/mL, respectively, p ˃ 0.05). Significantly lower initial median serum UCHL1 levels (pg/mL) were observed in patients with improved AIS during the neurological follow-up compared with those who did not show any improvement in their AIS score (1723, and 4700 respectively, p ˂ 0.05), with lack of significant difference in the initial median serum NGB levels, p ˃ 0.05. Conclusion: Initial serum UCHL1 assay could be a helpful marker in reflecting the degree of TSCI and predicting its outcome, though NGB needs further assessment. [ABSTRACT FROM AUTHOR]