Obesity Enhances Non-Th2 Airway Inflammation in a Murine Model of Allergic Asthma.

Obese patients with asthma present with aggravated symptoms that are also harder to treat. Here, we used a mouse model of allergic asthma sensitised and challenged to house dust mite (HDM) extracts to determine whether high-fat-diet consumption would exacerbate the key features of allergic airway inflammation. C57BL/6 mice were intranasally sensitised and challenged with HDM extracts over a duration of 3 weeks. The impact of high-fat-diet (HFD) vs. normal diet (ND) chow was studied on HDM-induced lung inflammation and inflammatory cell infiltration as well as cytokine production. HFD-fed mice had greater inflammatory cell infiltration around airways and blood vessels, and an overall more severe degree of inflammation than in the ND-fed mice (semiquantitative blinded evaluation). Quantitative assessment of HDM-associated Th2 responses (numbers of lung CD4+ T cells, eosinophils, serum levels of allergen-specific IgE as well as the expression of Th2 cytokines (Il5 and Il13)) did not show significant changes between the HFD and ND groups. Interestingly, the HFD group exhibited a more pronounced neutrophilic infiltration within their lung tissues and an increase in non-Th2 cytokines (Il17, Tnfa, Tgf-b, Il-1b). These findings provide additional evidence that obesity triggered by a high-fat-diet regimen may exacerbate asthma by involving non-Th2 and neutrophilic pathways.

ONE3A: one-against-all authentication model for smartphone using GAN network and optimization techniques.

This study focuses on addressing computational limits in smartphones by proposing an efficient authentication model that enables implicit authentication without requiring additional hardware and incurring less computational cost. The research explores various wrapper feature selection strategies and classifiers to enhance authentication accuracy while considering smartphone limitations such as hardware constraints, battery life, and memory size. However, the available dataset is small; thus, it cannot support a general conclusion. In this article, a novel implicit authentication model for smartphone users is proposed to address the one-against-all classification problem in smartphone authentication. This model depends on the integration of the conditional tabular generative adversarial network (CTGAN) to generate synthetic data to address the imbalanced dataset and a new proposed feature selection technique based on the Whale Optimization Algorithm (WOA). The model was evaluated using a public dataset (RHU touch mobile keystroke dataset), and the results showed that the WOA with the random forest (RF) classifier achieved the best reduction rate compared to the Harris Hawks Optimization (HHO) algorithm. Additionally, its classification accuracy was found to be the best in mobile user authentication from their touch behavior data. WOA-RF achieved an average accuracy of 99.62 ± 0.40% with a reduction rate averaging 87.85% across ten users, demonstrating its effectiveness in smartphone authentication.

Sustainability consciousness among nursing students in Egypt: a cross-sectional study.

BACKGROUND: Recognizing nurses as pivotal change agents and urgent preparation for the next generation is crucial for addressing sustainability issues and cultivating a sustainable healthcare system. Reports highlight gaps in the integration of sustainable development goals (SDGs) into nursing curricula, prompting the International Council of Nurses to stress the importance of sustainable development in nursing education. The extent to which nursing students are aware of sustainability issues remains to be determined. This study addresses a global and Egyptian research gap by evaluating and comparing Sustainability Consciousness (SC) levels among nursing students at three universities, providing insights into awareness, attitudes, and behaviors related to sustainability. METHODS: This descriptive comparative study was conducted across three nursing faculties within three Egyptian public universities. The target population for this study was undergraduate nursing students enrolled in these universities during the academic year 2022-2023. This study used the extended version of the Sustainability Consciousness Questionnaire (SCQ-L) to measure individuals' knowingness, attitudes, and behaviors related to the three dimensions of sustainable development: environmental, social, and economic. RESULTS: More than half of the nursing students across the three universities expressed unfamiliarity with the SDGs. Social media was the most common source of information across the three universities. Sohag University recorded the highest median (IQR) scores in sustainability knowingness (72.0, IQR: 70.0-81.0), attitudes (56.0, IQR: 53.0-61.5), and behavior (65.0, IQR: 60.0-69.0) across their respective dimensions, as well as in overall SC (195, IQR: 184.5-208.5). This was followed by Damanhour University, with a median score of 179.0 (IQR: 124.5-194), and then Alexandria University, with a median score of 116.0 (IQR: 85.5-153), all of which were significantly different (all with p values=0.000). Older students from rural areas exhibited higher SC median scores, while students with insufficient family income and no familiarity with the SDGs had lower SC scores. CONCLUSIONS: This study highlighted the prevalent reliance on social media for information among nursing students across these universities, emphasizing the pivotal role of academic institutions in integrating sustainability development concepts in nursing education. Sohag University's notable commitment to sustainability practices has contributed to the higher SC of its students compared to Alexandria and Damanhour Universities. The study also identified age, place of residence, family income, and familiarity with the SDGs as consistent predictors of sustainability consciousness.

Phthalate Exposure and Coronary Heart Disease: Possible Implications of Oxidative Stress and Altered miRNA Expression.

The relationship between phthalate exposure and coronary heart disease (CHD) is still unclear. This study aimed to investigate the association between phthalate exposure and CHD and determine the possible atherogenic mechanisms of phthalates by assessing oxidative stress and altering miRNA expression. This case-control study included 110 participants (55 CHD patients and 55 healthy controls). The levels of oxidative stress markers, malondialdehyde (MDA), and superoxide dismutase (SOD), and the expression of miRNA-155 (miR-155) and miRNA-208a (miR-208a), were measured and correlated with the urinary mono-2-ethylhexyl phthalate (MEHP). Highly significant differences were detected between the CHD cases and the control group regarding MEHP, MDA, SOD, miR-155, and miR-208a (p-value < 0.001). Spearman correlations revealed a significant positive correlation between MDA and MEHP in urine (P = 0.001 and rs = 0.316) and a significant negative correlation between SOD and MEHP in urine (P < 0.001 and rs = -0.345). Furthermore, significant positive correlations were observed between miR-155 and urinary MEHP (P = 0.001 and rs = 0.318) and miR-208a and urinary MEHP (P < 0.001 and rs = -0.352). This study revealed an association between phthalate exposure, as indicated by urinary MEHP and CHD; altered expression of miR-155 and miR-208a and oxidative stress could be the fundamental mechanisms.

Insights into the growth and biochemical defense responses associated with fenitrothion toxicity and uptake by freshwater cyanobacteria.

The extensive use of fenitrothion (FNT) in agricultural practices induces its persistence in soil and waterways. Therefore, it is essential to implement effective management practices such as using cyanobacteria for FNT removal and accumulation, particularly under accidental contamination. To this end, we evaluated the responses of two freshwater cyanobacteria taxa, Nostoc muscorum and Anabaena laxa to mild (7.5 mg L-1) and high (15 mg L-1) levels of FNT over a period of 7 d. Compared to N. muscorum, A. laxa was more tolerant to FNT, exhibiting higher FNT uptake and removal efficiencies at mild (16.3%) and high (17.5%) levels. FNT induced a dose-dependent decrease in cell growth, Chl a, phosphoenolpyruvate carboxylase and ribulose-1,5-bisphosphate carboxylase/oxygenase activities, which were more pronounced in N. muscorum. Moreover, FNT significantly increased oxidative damage markers i.e., increased lipid peroxidation (MDA), protein oxidation, H2O2 levels and NADPH oxidase enzyme activity, to more extent in N. muscorum. Compared to N. muscorum, A. laxa had high antioxidant capacity (FRAP), glutathione and increased activities of glutathione-S-transferase, glutathione reductase, glutathione peroxidase and superoxide dismutase, suggesting a robust antioxidant defense mechanism to mitigate FNT toxicity. However, N. muscorum devoted the induction of ascorbate content and the activity of catalase, peroxidase, monodehydroascorbate reductase, ascorbate peroxidase, and dehydroascorbate reductase enzymes. Although A. laxa had greater intracellular FNT, it experienced less FNT-induced oxidative stress, likely due to over production of antioxidants. Consequently, A. laxa is considered as a promising candidate for FNT phycoremediation. Our findings provide fundamental information on species-specific toxicity of FNT among cyanobacteria and the environmental risk of FNT toxicity in aquatic environments.

Evaluation of Glycogen Synthase Kinase Pathway for Assessing the Antidepressant-like Effect of Glucosamine as a Radioprotector in Rats: Behavioral and Biochemical Studies.

Radiotherapy is a very important tool in the treatment of cancer; nevertheless, its side effects are a hindrance to its use. The present study is designed to evaluate glucosamine effects against radiation-induced brain oxidative stress and depression-like effect in rats. Four groups of female Wister rats were used as control, irradiated (4 × 2 Gy), glucosamine (1 g/kg P.O), and glucosamine + irradiated group. The behavioral responses are estimated. The brain hippocampi of the rats are separated to evaluate oxidative stress biochemical parameters and glycogen synthase kinase pathway in addition to the biogenic amines. Irradiation exposure led to disturbances in the behavioral assessments (forced swimming test, light-dark box, and open field test) and a significant decrease in brain GSH, neurotransmitters (serotonin, norepinephrine, and dopamine), phosphatidylinositol 3 kinase (PI3K), and phosphorylated protein kinase-B (p-AKT) levels. Additionally, MDA and ROS levels increased significantly post-irradiation along with the phosphorylated glycogen synthase kinase (p-GSK3). Glucosamine administration before irradiation caused improvement in the behavioral valuations and the biochemical parameters in the brain as well. Glucosamine might be used as a radioprotector to improve brain function and as an antidepressant drug. It could be promising as a future therapy in managing depression occurring during radiotherapy.

Synergistic effect of doxycycline and aqueous extract of irradiated khella on structure of nanobacteria isolated from kidney stones: In vitro and in vivo studies.

Kidney stones have been associated with an increased risk of chronic kidney diseases, end-stage renal failure. This study is devoted to isolate nanobacteria from patients with active urolithiasis and investigate the in vitro and in vivo antinanobacterial activity of some antibiotics alone or in combination with extracts of irradiated herbs from certain medicinal plants. Nanobacteria were detected using scanning (SEM) and transmission (TEM) electron microscopy, protein electrophoresis (SDS-PAGE) and DNA profile. The antimicrobial susceptibility of some biofilm-producing nanobacterial isolates was evaluated. The effect of medicinal plant extracts on growth was tested. A combination treatment between the most potent extracts and antibiotics was tested on biofilm production, protein profile, release of 260 nm absorbing material, protein content, and ultrastructure of the strongest biofilm producers. In vivo study of nanobacteria and its treatment by the most potent agents was evaluated on male rats. Renal function was measured in serum; histological examination and oxidative stress parameters were determined in kidney tissues. Results showed that streptomycin, trimethoprim/sulfamethoxazole, doxycycline, and water extracts of irradiated khella at 6 kGy had antinanobacterial activity. Meanwhile, the synergistic effect of the aqueous extract of irradiated Khella and doxycycline showed higher inhibition activity on microbial growth and biofilm production. They affected dramatically the strength of its cell membrane and subsequently its ultrastructure. Moreover, these results are confirmed by ameliorations in renal function and histological alterations. It could be concluded that the combination of DO and an aqueous extract of irradiated khella has an antinephrotoxic effect against nanobacteria-induced renal toxicity.

A feature selection framework for anxiety disorder analysis using a novel multiview harris hawk optimization algorithm.

Machine learning (ML) has demonstrated its ability to exploit important relationships within data collection, which can be used in the diagnosis, treatment, and prediction of outcomes in a variety of clinical contexts. Anxiety mental disorder analysis is one of the pending difficulties that ML can help with. A thorough study is demanded to gain a better understanding of this illness. Since the anxiety data is generally multidimensional, which complicates processing and as a result of technology improvements, medical data from several perspectives, known as multiview data (MVD), is being collected. Each view has its own data type and feature values, so there is a lot of diversity. This work introduces a novel preprocessing feature selection (FS) approach, multiview harris hawk optimization (MHHO), which has the potential to reduce the dimensionality of anxiety data, hence reducing analytical effort. The uniqueness of MHHO originates from combining a multiview linking methodology with the power of the harris hawk optimization (HHO) method. The HHO is used to identify the lowest optimal MVD feature subset, while multiview linking is utilized to find a promising fitness function to direct the HHO FS while accounting for all data views' heterogeneity. The complexity of MHHO is O(THL2), where T is the number of iterations, H is the number of involved harris hawks, and L is the number of objects. Using two publicly available anxiety MVDs, MHHO is validated against ten recent rivals in its category. The experimental findings show that MHHO has a considerable advantage in terms of convergence speed (converging in less than ten iterations), subset size (removing 75% of the views; reducing feature size by 66%), and classification accuracy (approaching 100%). Furthermore, statistical analyses reveal that MHHO is statistically different from its competitors, bolstering its applicability. Finally, feature importance is evaluated, shedding light on the most anxiety-inducing characteristics. The likelihood of developing additional disorders (such as depression or stress) is also investigated.

Ultrasound-guided fascia iliaca block versus quadratus lumborum block for perioperative analgesia in patients undergoing hip surgery. A randomised controlled trial.

INTRODUCTION: Femoral neck fractures are common orthopaedic fractures, especially in old age, and they represent a life-threatening condition requiring surgical intervention. In this study, we aimed to compare 2 regional techniques used to decrease perioperative pain. MATERIAL AND METHODS: In this parallel group randomized controlled clinical trial we enrolled 68 patients from both sexes scheduled for hip surgery after femoral neck fractures. The patients were randomly allocated to 2 equal groups with one receiving ultrasound- guided supra-inguinal fascia iliaca block (FIB) and the other receiving ultrasound- guided anterior quadratus lumborum block (QLB). Our primary outcome was the duration of postoperative analgesia. The secondary outcome was measuring the Visual Analog Scale (VAS) during patient positioning while applying the neuraxial block, the total analgesic requirement in the postoperative period, patient satisfaction in the postoperative period, and the frequency of adverse effects. RESULTS: The group receiving supra-inguinal FIB had a significantly longer time of postoperative analgesia 18 (4-24), compared to the group receiving anterior QLB 2 (1-24), P = 0.005. They consumed less morphine throughout 24 hours postoperatively, 5.3 ± 0.9 mg compared to 6.9 ± 1.87 mg (95% CI: 6.45-3.92, P = 0.008), and they showed less pain during positioning for spinal anaesthesia. CONCLUSIONS: Supra-inguinal FIB provides prolonged postoperative analgesia compared to anterior QLB in patients undergoing hip surgery. It was associated with less pain during positioning in spinal anaesthesia and decreased total morphine consumption.

Role of TLR4 signaling pathway in the mitigation of damaged lung by low-dose gamma irradiation.

Organisms frequently suffer negative effects from large doses of ionizing radiation. However, radiation is not as hazardous at lower doses as was once believed. The current study aims to evaluate the possible radio-adaptive effect induced by low-dose radiation (LDR) in modulating high-dose radiation (HDR) and N-nitrosodiethylamine (NDEA)-induced lung injury in male albino rats. Sixty-four male rats were randomly divided into four groups: Group 1 (control): normal rats; Group 2 (D): rats given NDEA in drinking water; Group 3 (DR): rats administered with NDEA then exposed to fractionated HDR; and Group 4 (DRL): rats administered with NDEA then exposed to LDR + HDR. In the next stage, malondialdehyde (MDA), glutathione reduced (GSH), catalase (CAT), and superoxide dismutase (SOD) levels in the lung tissues were measured. Furthermore, the enzyme-linked immunoassay analysis technique was performed to assess the Toll-like receptor 4 (TLR4), interleukin-1 receptor-associated kinase 4 (IRAK4), and mitogen-activated protein kinases (MAPK) expression levels. Histopathological and DNA fragmentation analyses in lung tissue, in addition to hematological and apoptosis analyses of the blood samples, were also conducted. Results demonstrated a significant increase in antioxidant defense and a reduction in MDA levels were observed in LDR-treated animals compared to the D and DR groups. Additionally, exposure to LDR decreased TLR4, IRAK4, and MAPK levels, decreased apoptosis, and restored all the alterations in the histopathological, hematological parameters, and DNA fragmentation, indicating its protective effects on the lung when compared with untreated rats. Taken together, LDR shows protective action against the negative effects of subsequent HDR and NDEA. This impact may be attributable to the adaptive response induced by LDR, which decreases DNA damage in lung tissue and activates the antioxidative, antiapoptotic, and anti-inflammatory systems in the affected animals, enabling them to withstand the following HDR exposure.

Potential impact of mesenchymal stem cells on nephrotoxicity induced by gamma irradiation and antiepileptic drugs cotherapy in rats.

The goal of this study was to assess the influence of bone marrow-derived mesenchymal stem cells (BM-MSCs) on the nephrotoxicity induced by fractionated doses of gamma irradiation (Rad) and the cotherapy of levetiracetam and oxcarbazepine in male rats. Adult rats were randomly divided into four groups. Group I: Control, Group II: antiepileptic drugs (AEDs), Group III: AEDs +Rad and Group IV: AEDs + Rad + MSCs. Rats treated with AEDs and exposed to fractionated doses of γ-irradiation displayed a discernible increase in serum urea, creatinine, kidney injury marker, kidney malondialdehyde, transforming growth factor beta (TGF-ß) and the relative expression of Smad3 along with a decrease in the relative expression of Smad7 and glutathione level. Alternatively, groups treated with BM-MSCs with AEDs and Rad showed a substantial modification in the majority of the evaluated parameters and looked to be successful in reducing the hazards of the combination therapy of AEDs and radiation. The reno-histopathological study supports the biochemical analysis. In conclusion, BM-MSCs exhibited therapeutic potential against nephrotoxicity induced by fractionated doses of γ-irradiation and AEDs. The outcome was brought about by the downregulation of the TGF-ß/Smad pathway. BM-MSCs might be suggested as a valuable therapeutic strategy to overcome kidney injury induced by gamma irradiation during AEDs cotherapy.

The protective effects of sesamol and/or the probiotic, Lactobacillus rhamnosus, against aluminum chloride-induced neurotoxicity and hepatotoxicity in rats: Modulation of Wnt/ß-catenin/GSK-3ß, JAK-2/STAT-3, PPAR-γ, inflammatory, and apoptotic pathways.

Introduction: Aluminium (Al) is accumulated in the brain causing neurotoxicity and neurodegenerative disease like Alzheimer's disease (AD), multiple sclerosis, autism and epilepsy. Hence, attenuation of Al-induced neurotoxicity has become a "hot topic" in looking for an intervention that slow down the progression of neurodegenerative diseases. Objective: Our study aims to introduce a new strategy for hampering aluminum chloride (AlCl3)-induced neurotoxicity using a combination of sesamol with the probiotic bacteria; Lactobacillus rhamnosus (L. rhamnosus) and also to test their possible ameliorative effects on AlCl3-induced hepatotoxicity. Methods: Sprague-Dawley male rats were randomly divided into five groups (n = 10/group) which are control, AlCl3, AlCl3 + Sesamol, AlCl3 + L. rhamnosus and AlCl3 + Sesamol + L. rhamnosus. We surveilled the behavioral, biochemical, and histopathological alterations centrally in the brain and peripherally in liver. Results: This work revealed that the combined therapy of sesamol and L. rhamnosus produced marked reduction in brain amyloid-ß, p-tau, GSK-3ß, inflammatory and apoptotic biomarkers, along with marked elevation in brain free ß-catenin and Wnt3a, compared to AlCl3-intoxicated rats. Also, the combined therapy exerted pronounced reduction in hepatic expressions of JAK-2/STAT-3, inflammatory (TNF-α, IL-6, NF-κB), fibrotic (MMP-2, TIMP-1, α-SMA) and apoptotic markers, (caspase-3), together with marked elevation in hepatic PPAR-γ expression, compared to AlCl3 -intoxicated rats. Behavioral and histopathological assessments substantiated the efficiency of this combined regimen in halting the effect of neurotoxicity. Discussion: Probiotics can be used as an add-on therapy with sesamol ameliorate AlCl3 -mediated neurotoxicity and hepatotoxicity.

Microneedling with glutathione versus microneedling alone in treatment of facial melasma: Split-face comparative study.

BACKGROUND: Melasma is a distressing disfiguring acquired pigmentary disorder especially affecting females and it is of high tendency of recurrence. Up till now, treatment of melasma is a challenging problem. OBJECTIVES: We evaluated the effectiveness of microneedling with glutathione versus microneedling alone in treatment of melasma. PATIENTS AND METHODS: In this study, 29 adult females with epidermal type of melasma (confirmed with Wood's light examination) were enrolled. The affected area was subjected to microneedling using dermapen followed by application of glutathione solution on the right side only. This session was performed every 2 weeks for 3 months (six sessions for every patient). The response to therapy was measured using modified melasma area and severity index (m MASI) that were calculated on each side of the face (Hemi- m MASI) before treatment sessions. RESULTS: There was statistically significant reduction in the mean of Hemi- m MASI score over the sessions on both sides of the face but the right side (microneedling with glutathione) showed more reduction and earlier response to therapy than the left side (microneedling alone). On the left side, mean of Hemi- m MASI score before and after sessions was (4.06 ± 1.91, 2.31 ± 1.450) and on the right side, it was (4.21 ± 2.08, 1.96 ± 1.30), respectively and this was statistically significant. Percentage of improvement on the left side was 46.92 ± 16.30 (%) while on the right side was 55.17 ± 15.50 (%) and this was statistically significant. CONCLUSIONS: Microneedling is an effective promising tool in treatment of melasma and its combination with glutathione as a whitening agent, increases and accelerates its efficacy. So, combined therapy is more preferred than monotherapy in treatment of facial melasma.

Hepatoprotective role of myricitrin isolated from Mimusops elengi Linn. leaves extract on γ-radiation-induced liver damage in rats: Phyto-biochemical investigations.

The hepatoprotective effects of methanol extract of Mimusops elengi Linn. (M. elengi L.) leaves and isolated pure myricitrin (3-, 4-, 5-, 5, 7-five hydroxyflavone-3-O-α-l-rhamnoside) (Myr) were evaluated in male rats exposed to γ-irradiation. The extraction of M. elengi L. leaves was performed using ethyl acetate (EtOAC). Seven groups of rats were used: control group, irradiated (IRR) group (6 Gy of γ-rays in a single dose), vehicle group (oral administration of 0.5% carboxymethyl cellulose for 10 days), EtOAC extract group (100 mg/kg body weight of extract, orally for 10 days), EtOAC + IRR group (administration of extract and exposure to γ-rays on Day 7), Myr group (50 mg/kg body weight Myr, orally for 10 days), and Myr + IRR group (administration of Myr and exposure to γ-rays on Day 7). High-performance liquid chromatography and 1H-nuclear magnetic resonance were used to isolate and characterize the compounds from M. elengi L. leaves. Enzyme-linked immunosorbent assay was used for biochemical analyses. Identified compounds were Myr, myricetin 3-O-galactoside, myricetin 3-O-rahmnopyranoside (1 → 6) glucopyranoside, quercetin, quercitol, gallic acid, α-,ß-amyrin, ursolic acid, and lupeol. Serum aspartate transaminase and alanine transaminase activities were significantly increased, while serum protein and albumin levels were significantly decreased after irradiation. Hepatic levels of tumor necrosis factor-α, prostaglandin 2, inducible nitric oxide synthase, interleukin-6 (IL-6), and IL-12 were increased following irradiation. Improvements were observed in most serological parameters after treatment with extract or pure Myr, with histological analyses confirming decreased liver injury in treated rats. Our study demonstrates that pure Myr has a greater hepatoprotective effect than M. elengi leaf extracts against irradiation-induced hepatic inflammation.

Beneficial Effect of Rosuvastatin Therapy on Spleen Injury Induced by Gamma Irradiation in Rats: Targeting Nrf2/EPRE Pathway.

Purpose: The present study investigates the new approach of rosuvastatin (RUV) administration as a drug for the management of spleen injury induced by gamma irradiation. Main Methods: Forty rats were used and divided equally into 4 groups: control group, irradiated group, IRR + rosuvastatin group (10 mg/Kg b. wt), and IRR + rosuvastatin group (20 mg/kg b. wt) for 7 days orally. Results: The possible curative effect can be illustrated via the improvement of hematopoietic cell count (Hb, RBCs, and WBCs) and oxidative stress markers (MDA and GST) in addition to biochemical parameters including [heme oxigenase-1 (HO-1), nuclear erythroid 2-related factor (Nrf2), NOD-, LRR- and pyrin domain- containing protein 3 (NLRP3) inflammasome] and immune assay of nuclear factor kappa beta (NF-kB P65) and inducible nitric oxide synthase (iNOS). Histological pictures emphasize the biochemical findings. Rosuvastatin treatments by using two different doses improve the tested parameters. High-dose administration of RUV (20 mg/kg p.o.) recorded better results than the low dose (10 mg/kg p.o.). Conclusion: Our results suggested that rosuvastatin reversed the radiation-induced spleen-damaging effects. So, RUV can be introduced to the market as a new therapy for the management of spleen damages.

A functional SNP in miR-146a and genetic susceptibility to drug-resistant epilepsy.

OBJECTIVES: The study aimed to assess the relationship between the functional single nucleotide polymorphism (SNP) (rs57095329) of miR-146a, the progression of drug-resistant epilepsy (DRE), and the severity of the disease (seizure frequency) in a group of Egyptian children epilepsy patients. SUBJECTS AND METHODS: 110 Egyptian children were recruited and divided into two groups, the epilepsy patients (n = 60) and the healthy control children (n = 50). The patient's group was equally subdivided into two subgroups: drug-resistant and drug-responsive epilepsy patients. Genomic DNA samples from all participants were screened for the incidence of the rs57095329 SNP of the miR-146a gene by the Real-Time PCR. RESULTS: There was no statistical significance between epilepsy patients compared to controls regarding the rs57095329 SNP genotypes and alleles. Contrarily, there was significant difference between the drug-resistant epilepsy and the drug-responsive cases (P < 0.05). The genotypes AG (P < 0.007, OR: 0.118, 95% CI (0.022-0.636)) and GG (P = 0.016, OR: 0.123, 95% CI (0.023-0.769)) were higher among the drug-resistant, while AA was higher among the drug-responsive patients. The alleles A and G were higher among all cases, with a statistically significant difference (P = 0.028, OR: 0.441, 95% CI (0.211-0.919)). A significant difference was reported in the dominant model (AA versus AG+GG) (P = 0.005, OR: 0.12395% CI (0.025-0.621)). CONCLUSION: Therefore, miR-146a might be a potential therapeutic target for epilepsy treatment. The study was limited by the low number of young epileptic patients, the refusal of some parents to participate, and the incomplete medical history of some cases in the study, which forced their exclusion. More studies might be necessary to investigate other effective drugs to overcome the resistance issues induced by miR-146a rs57095329 polymorphisms.

Occurrence and Molecular Study of Hypermucoviscous/Hypervirulence Trait in Gut Commensal K. pneumoniae from Healthy Subjects.

Hypervirulent Klebsiella pneumoniae (hvKp) is emerging worldwide. Hypermucoviscousity is the characteristic trait that distinguishes it from classic K. pneumoniae (cKp), which enables Kp to cause severe invasive infections. This research aimed to investigate the hypermucoviscous Kp (hmvKp) phenotype among gut commensal Kp isolated from healthy individuals and attempted to characterize the genes encoding virulence factors that may regulate the hypermucoviscosity trait. Using the string test, 50 identified Kp isolates from healthy individuals' stool samples were examined for hypermucoviscosity and investigated by transmission electron microscopy (TEM). Antimicrobial susceptibility profiles of Kp isolates were determined using the Kirby Bauer disc method. Kp isolates were tested for genes encoding different virulence factors by PCR. Biofilm formation was assayed by the microtiter plate method. All Kp isolates were multidrug-resistant (MDR). Phenotypically, 42% of isolates were hmvKp. PCR-based genotypic testing revealed the hmvKp isolates belonged to capsular serotype K2. All study Kp isolates harbored more than one virulence gene. The genes magA and rmpA were not detected, while the terW gene was present in all isolates. The siderophores encoding genes entB and irp2 were most prevalent in hmvKp isolates (90.5%) and non-hmvKp (96.6%), respectively. hmvKp isolates harbored the genes wabG and uge with rates of 90.5% and 85.7%, respectively. The outcomes of this research highlight the potential health risk of commensal Kp to cause severe invasive diseases, owing to being hmvKp and MDR, and harboring multiple virulence genes. The absence of essential genes related to hypermucoviscosity such as magA and rmpA in hmvKp phenotypes suggests the multifactorial complexity of the hypermucoviscosity or hypervirulence traits. Thus, further studies are warranted to verify the hypermucoviscosity-related virulence factors among pathogenic and commensal Kp in different colonization niches.

HSP70 Expression Signature in Renal Cell Carcinoma: A Clinical and Bioinformatic Analysis Approach.

Heat shock proteins (HSPs) are cytoprotective against stressful conditions, as in the case of cancer cell metabolism. Scientists proposed that HSP70 might be implicated in increased cancer cell survival. This study aimed to investigate the HSP70 (HSPA4) gene expression signature in patients with renal cell carcinoma (RCC) in correlation to cancer subtype, stage, grade, and recurrence, combining both clinicopathological and in silico analysis approaches. One hundred and thirty archived formalin-fixed paraffin-embedded samples, including 65 RCC tissue specimens and their paired non-cancerous tissues, were included in the study. Total RNA was extracted from each sample and analyzed using TaqMan quantitative Real-Time Polymerase Chain Reaction. Correlation and validation to the available clinicopathological data and results were executed. Upregulated HSP70 (HSPA4) gene expression was evident in RCC compared to non-cancer tissues in the studied cohort and was validated by in silico analysis. Furthermore, HSP70 expression levels showed significant positive correlations with cancer size, grade, and capsule infiltration, as well as recurrence in RCC patients. The expression levels negatively correlated with the overall survival (r = -0.87, p < 0.001). Kaplan-Meier curves showed lower survival rates in high HSP70 expressor group compared to the low expressors. In conclusion, the HSP70 expression levels are associated with poor RCC prognosis in terms of advanced grade, capsule infiltration, recurrence, and short survival.

Laser acupuncture improving functional chronic constipation in children: a randomized controlled trial.

Functional chronic constipation (FCC) is a disorder caused by low fiber consumption, lack of fluid intake, lack of mobility, or side effects of medications. The objective of this study was to compare the effects of laser acupuncture and the commonly used osmotic laxative, lactulose (as the control), both combined with behavioral therapy and dietary modification, on children with FCC in a randomized controlled trial (RCT). Forty children were randomly chosen, aged 5-15 years with FCC, and randomized into two equal groups (gender ratio (50% male; 50% female), mean ± SD weight (24.2 ± 6.27 kg and 25.7 ± 7.47 kg for groups A and B, respectively)). Study group (group A): used laser acupuncture (650 nm), 30 mW, 0.15 cm2 spot size, 90 s per acupuncture point (ST25, ST36, ST37, BL25, and LI11). Control group (group B): lactulose syrup (1 to 3 mL/kg/day) orally, in divided doses 3 times weekly for 4 weeks, and behavioral training for both groups. Evaluations were conducted before and after the study to assess the efficacy of the therapy. Median value frequency significantly increased in groups A and B post-treatment (4 (6.75-3) and 3 (3.75-2), respectively) compared to pre-treatment (2 (2-1) and 2 (2-0.25), respectively) (p = 0.0001), in favor of group A (p = 0.01). Significant improvement of stool consistency according to Bristol stool scale (BSS) in groups A and B (p = 0.0001), (p = 0.002) respectively in favor of group A (p = 0.03). T-test, Fisher, and Wilcoxon signed rank tests were conducted to compare groups. Non-invasive, painless laser acupuncture therapy can be considered as an alternative therapy for patients with FCC.

Biologically inspired stealth - Camouflaged strategies in nanotechnology for the improved therapies in various diseases.

Nanotechnology has received increasing attention in the past decade and it's being used as a model for developing better treatments for a variety of diseases. Despite the fact that nanotechnology-based therapy has greatly improved treatment regimens, it still faces challenges such as inadequate circulation, insufficient accumulation at the target region, and undesired toxicity. In this regard, scientists are working on producing cell-membrane camouflaged nanoparticles as a biomimetic technique for modifying the surface of existing nanoparticles to produce significant therapeutic benefits following imparting myriad of desired functionalities. Membranes originating from erythrocytes, white blood cells, cancer cells, stem cells, platelets, or bacterial cells have been used to coat nanoparticle surfaces and create biologically inspired camouflaged nanoparticles. These biomemitic delivery systems have been proven to have potential applications in diagnosing and treating vaiorus diseases, including drug administration, immunisation, immunological regulation, and detoxification. From its inception to the present, we provide a complete description of this advanced technique for functionalizing nanoparticle surfaces. The method of making these membrane coated nanoparticles as well as their characterisation have been thoroughly discussed. Following that, we focused on the diversity of cell membranes derived from distinct cells in the evolution of nanoparticles, emphasising how these biologically inspired stealth - camouflaged techniques have led to increased therapeutic efficacy in a variety of disease states.