Molecular characterization and immunopathological investigation of Avian reticuloendotheliosis virus in breeder flocks in Egypt.

BACKGROUND: Reticuloendotheliosis virus (REV) is an oncogenic immunosuppressive retrovirus that infects different kinds of avian species; posing significant economic losses to the poultry industry worldwide. METHODS: In Egypt, there is an unidentified disease associated with the runting-stunting syndrome with neoplasia, suspected to be REV, that has been continuously monitored in several breeder flocks. To diagnose and analyze REV by cell cultures, enzyme-linked immunosorbent assay (ELISA), histopathological investigation, the polymerase chain reaction (PCR) test, and sequencing analysis, 200 blood samples, and 50 tissue specimens were collected. The current study targets the occurrence and genetic characteristics of a viral neoplastic disease, resembling REV infection, circulating in breeder flocks from 2022 to 2023 in the Ismailia, El-Sharqia, and El-Dakahliya governorates. RESULT: Here, REV was isolated on chicken embryo fibroblast cell culture; exhibiting cell aggregation, rounding, and cell detachments. Collectively, only 70 serum samples were positive for anti-REV antibodies with seroprevalence rates of 35% based on the ELISA test. The histopathological observation demonstrated lymphoreticular tumors in the liver, spleen, and other examined organs. The immunohistochemical staining method confirmed the REV-positive signals in all examined organs (liver, kidney, spleen, bursa, ovaries) except for the heart. The PCR assay of the LTR gene assessed 370 base pairs with only 5 positive samples with a percentage of 16.6%. Three positive samples were further sequenced and submitted to the Genbank under accession numbers (PP763709, PP763710, PP763711). Phylogenetic analysis of the REV-LTR gene showed that our three isolates (Sharquia-1-REV, Ismilia-2-REV, Mansoura-3-REV) are REV subtype III which predominantly circulated in breeders in Egypt. These three isolates are highest similar to American, Chinese, and Taiwanese REV reference strains, and other Egyptian strains with nucleotide identity percentages of 100%, 99%, and 99%; respectively, and on the amino acid identity level were with (99-100%), (98%, 99%), (99%, 100%); respectively. CONCLUSIONS: This study established that REV infection was extensively distributed in the breeders and became one of the causes of the clinical outbreaks of tumors, raising awareness of REV as the causative agent of avian oncogenic disease in Egypt.

Suture closure AFtEr large bore vein access (SAFE-VEIN): A randomized, prospective study of the efficacy and safety of venous closure device.

BACKGROUND: Perclose ProGlide (PPG) Suture-Mediated Closure System™ is safe and can reduce time to hemostasis following procedures requiring arterial access. AIMS: We aimed to compare PPG to figure of 8 suture in patients who underwent interventional catheter procedures requiring large bore venous access (LBVA) (≥13 French). METHODS: In this physician-initiated, randomized, single-center study [clinicaltrials.gov ID: NCT04632641], single-stick venous access was obtained under ultrasound guidance. Eligible patients were randomized 1:1, and 100 subjects received allocated treatment to either PPG (n = 47) or figure of 8 suture (n = 53). No femoral arterial access was used in any patient. Primary outcomes were time to achieve hemostasis (TTH) and time to ambulation (TTA). Secondary outcomes were time to discharge (TTD) and vascular-related complications and mortality. Wilcoxon rank-sum test was used to compare TTH, TTA, and TTD. RESULTS: TTH (minutes) was significantly lower in PPG versus figure of 8 suture [median, (Q1, Q3)] [7 (2,10) vs. 11 (10,15) respectively, p < 0.001]. TTA (minutes) was significantly lower in PPG compared to figure of 8 suture [322 (246,452) vs. 403 (353, 633) respectively, p = 0.005]. TTD (minutes) was not significantly different between the PPG and figure of 8 suture arms [1257 (1081, 1544) vs. 1338 (1171,1435), p = 0.650]. There was no difference in minor bleeding or access site hematomas between both arms. No other vascular complications or mortality were reported. CONCLUSION: PPG use had lower TTH and TTA than figure of 8 suture in a population of patients receiving LBVA procedures. This may encourage same-day discharge in these patients.

L-2-hydroxyglutaric aciduria: a report of clinical, radiological, and genetic characteristics of two siblings from Egypt.

L-2-hydroxyglutaric aciduria (L-2-HGA) is a rare autosomal recessive disease characterized by elevated levels of hydroxyglutaric acid in the body fluids and brain with abnormal white matter. We present two siblings with psychomotor retardation and quadriparesis. Their brain imaging showed diffuse bilateral symmetrical involvement of the cerebral cortex, white matter, basal ganglia and cerebellum. The whole exome sequence studies revealed a homozygous likely pathogenic variant on chromosome 14q22.1 (NM_024884.2: c.178G > A; pGly60Arg) in the gene encoding for L-2-hydroxyglutarate dehydrogenase (L2HGDH) (OMIM #236792). Therefore, using the L2HGDH gene study is beneficial for L2HGA diagnosis.

Effects of long-term dehydration and quick rehydration on the camel kidney: pathological changes and modulation of the expression of solute carrier proteins and aquaporins.

BACKGROUND: Recurrent dehydration causes chronic kidney disease in humans and animal models. The dromedary camel kidney has remarkable capacity to preserve water and solute during long-term dehydration. In this study, we investigated the effects of dehydration and subsequent rehydration in the camel's kidney histology/ultrastructure and changes in aquaporin/solute carrier proteins along with gene expression. RESULTS: In light microscopy, dehydration induced few degenerative and necrotic changes in cells of the cortical tubules with unapparent or little effect on medullary cells. The ultrastructural changes encountered in the cortex were infrequent during dehydration and included nuclear chromatin condensation, cytoplasmic vacuolization, mitochondrial swelling, endoplasmic reticulum/ lysosomal degeneration and sometimes cell death. Some mRNA gene expressions involved in cell stability were upregulated by dehydration. Lesions in endothelial capillaries, glomerular membranes and podocyte tertiary processes in dehydrated camels indicated disruption of glomerular filtration barrier which were mostly corrected by rehydration. The changes in proximal tubules brush borders after dehydration, were accompanied by down regulation of ATP1A1 mRNA involved in Na + /K + pump that were corrected by rehydration. The increased serum Na, osmolality and vasopressin were paralleled by modulation in expression level for corresponding SLC genes with net Na retention in cortex which were corrected by rehydration. Medullary collecting ducts and interstitial connective tissue were mostly unaffected during dehydration. CKD, a chronic nephropathy induced by recurrent dehydration in human and animal models and characterized by interstitial fibrosis and glomerular sclerosis, were not observed in the dehydrated/rehydrated camel kidneys. The initiating factors, endogenous fructose, AVP/AVPR2 and uric acid levels were not much affected. TGF-ß1 protein and TGF-ß1gene expression showed no changes by dehydration in cortex/medulla to mediate fibrosis. KCNN4 gene expression level was hardly detected in the dehydrated camel's kidney; to encode for Ca + + -gated KCa3.1 channel for Ca + + influx to instigate TGF-ß1. Modulation of AQP 1, 2, 3, 4, 9 and SLC protein and/or mRNAs expression levels during dehydration/rehydration was reported. CONCLUSIONS: Long-term dehydration induces reversible or irreversible ultrastructural changes in kidney cortex with minor effects in medulla. Modulation of AQP channels, SLC and their mRNAs expression levels during dehydration/rehydration have a role in water conservation. Cortex and medulla respond differently to dehydration/rehydration.

Liver resection for hepatocellular carcinoma in elderly patients: does age matter?

BACKGROUND: Evaluation of the influence of the age of the patients upon the outcomes of liver resection (LR) for hepatocellular carcinoma (HCC). METHODS: HCC patients who underwent LR between 2010 and 2020 were analyzed. They were divided into 3 groups depending on the patient's age. Group I (patients less than 60 years), Group II (patients between 60 and 69 years), and Group III (patients equal to or more than 70 years). RESULTS: 364 patients were included. A significantly higher serum bilirubin and alpha feto-protein were noted in Group I and serum creatinine was noted in Group III. The study groups did not show any significant differences regarding HCC site, number, macrovascular invasion, the extent of LR, Pringle maneuver, and perioperative blood transfusions. Longer operation time was found in Groups II and III, while more blood loss was noted in Group (I) Group I patients had longer hospital stays. Higher postoperative morbidities were noted in both Group I and Group (II) Higher incidence of post-hepatectomy liver dysfunction was noted in Group I. More early mortalities were found in Group I, related to liver failure. We did not experience early mortality in Group (III) Late Mortalities occurred in 117 patients (32.1%). HCC recurrence occurred in 165 patients (45.3%). Regarding the overall- and tumor-free survival, we did not experience any significant differences among the 3 groups (Log Rank: p = 0.371 and 0.464 respectively). CONCLUSIONS: Curative LR can be safely performed in selected elderly patients with HCC. An advanced patient's age should not be considered as a contraindication for curative LR.

Morpho-Physiochemical Indices and Transcriptome Analysis Reveal the Role of Glucosinolate and Erucic Acid in Response to Drought Stress during Seed Germination of Rapeseed.

The global expansion of rapeseed seed quality has been focused on maintaining glucosinolate (GSL) and erucic acid (EA) contents. However, the influence of seed GSL and EA contents on the germination process under drought stress remains poorly understood. Herein, 114 rapeseed accessions were divided into four groups based on GSL and EA contents to investigate their performance during seed imbibition under drought stress. Our results revealed significant variations in seed germination-related traits, particularly with higher GSL and EA, which exhibited higher germination % (G%) and lower mean germination time (MGT) under drought stress conditions. Moreover, osmoregulation, enzymatic system and hormonal regulation were improved in high GSL and high EA (HGHE) versus low GSL and low EA (LGLE) seeds, indicating the essential protective role of GSL and EA during the germination process in response to drought stress. The transcriptional regulation mechanism for coordinating GSL-EA-related pathways in response to drought stress during seed imbibition was found to involve the differential expression of sugar metabolism-, antioxidant-, and hormone-related genes with higher enrichment in HGHE compared to LGLE seeds. GO enrichment analysis showed higher variations in transcription regulator activity and DNA-binding transcription factors, as well as ATP and microtubule motor activity in GSL-EA-related pathways. Furthermore, KEGG analysis identified cellular processes, environmental information processing, and metabolism categories, with varied gene participation between GSL, EA and GSL-EA-related pathways. For further clarification, QY7 (LGLE) seeds were primed with different concentrations of GSL and EA under drought stress conditions. The results showed that 200 µmol/L of GSL and 400 µmol/L of EA significantly improved G%, MGT, and seedling fresh weight, besides regulating stress and fatty acid responsive genes during the seed germination process under drought stress conditions. Conclusively, exogenous application of GSL and EA is considered a promising method for enhancing the drought tolerance of LGLE seeds. Furthermore, the current investigation could provide a theoretical basis of GSL and EA roles and their underlying mechanisms in stress tolerance during the germination process.

Screening of normal endoscopic large bowel biopsies with interpretable graph learning: a retrospective study.

OBJECTIVE: To develop an interpretable artificial intelligence algorithm to rule out normal large bowel endoscopic biopsies, saving pathologist resources and helping with early diagnosis. DESIGN: A graph neural network was developed incorporating pathologist domain knowledge to classify 6591 whole-slides images (WSIs) of endoscopic large bowel biopsies from 3291 patients (approximately 54% female, 46% male) as normal or abnormal (non-neoplastic and neoplastic) using clinically driven interpretable features. One UK National Health Service (NHS) site was used for model training and internal validation. External validation was conducted on data from two other NHS sites and one Portuguese site. RESULTS: Model training and internal validation were performed on 5054 WSIs of 2080 patients resulting in an area under the curve-receiver operating characteristic (AUC-ROC) of 0.98 (SD=0.004) and AUC-precision-recall (PR) of 0.98 (SD=0.003). The performance of the model, named Interpretable Gland-Graphs using a Neural Aggregator (IGUANA), was consistent in testing over 1537 WSIs of 1211 patients from three independent external datasets with mean AUC-ROC=0.97 (SD=0.007) and AUC-PR=0.97 (SD=0.005). At a high sensitivity threshold of 99%, the proposed model can reduce the number of normal slides to be reviewed by a pathologist by approximately 55%. IGUANA also provides an explainable output highlighting potential abnormalities in a WSI in the form of a heatmap as well as numerical values associating the model prediction with various histological features. CONCLUSION: The model achieved consistently high accuracy showing its potential in optimising increasingly scarce pathologist resources. Explainable predictions can guide pathologists in their diagnostic decision-making and help boost their confidence in the algorithm, paving the way for its future clinical adoption.

Acute kidney injury in infants diagnosed with congenital diaphragmatic hernia.

BACKGROUND: To assess the association and outcomes of acute kidney injury (AKI) in infants diagnosed with congenital diaphragmatic hernia (CDH). METHODS: We analyzed the National Inpatient Sample dataset for the years 2010 through 2018. We evaluated the prevalence and outcomes associated with AKI in infants diagnosed with CDH. Outcomes were assessed using regression analysis while controlling for variables. RESULTS: A total of 32,042,481 term infants were identified, of them 10,804 had CDH. Prevalence of AKI in infants with CDH was 6.5% compared to 0.05% in those without CDH (aOR = 14.7, CI: 13.0-16.6). ECMO was utilized at 62% of CDH infants that had AKI compared to 17% in infants without AKI (aOR = 4.22, CI: 3.38-5.27). Mortality was greater in CDH infants who developed AKI when compared to those without AKI (57.3 vs. 16.7%, aOR = 3.65, CI: 2.99-4.46). The trend of mortality in CDH infants who developed AKI decreased overtime, p < 0.001, while the trends for mortality in the overall CDH infants and in CDH infants without AKI did not change during the study period, p = 0.12. CONCLUSION: AKI is not uncommon in infants diagnosed with CDH. ECMO utilization and mortality are substantially increased in CDH infants when they develop AKI. IMPACT: Mortality in infants diagnosed with congenital diaphragmatic hernia (CDH) is relatively high despite advances in neonatal care. Infants with CDH are potentially at increased risk of acute kidney injury (AKI). Within CDH population, infants diagnosed with AKI are at increased risk for ECMO use and mortality. This is the largest study to address the association and outcomes of AKI in term infants diagnosed with CDH.

Impact of postnatal steroids on peripheral avascular retina and severity of retinopathy of prematurity.

BACKGROUND: We investigated the role of postnatal steroids on the severity of retinopathy of prematurity (ROP) and its impact on peripheral avascular retina (PAR). METHODS: A retrospective cohort study of infants born at ≤32 weeks gestation and/or birth weight ≤1500 g. Demographics, the dose and duration of steroid treatment, and age when full retinal vascularization occurred were collected. The primary outcomes were the severity of ROP and time to full vascularization of the retina. RESULTS: A total of 1695 patients were enrolled, 67% of whom received steroid therapy. Their birth weight was 1142 ± 396 g and gestational age was 28.6 ± 2.7 weeks. The total hydrocortisone-equivalent dose prescribed was 28.5 ± 74.3 mg/kg. The total days of steroid treatment were 8.9 ± 35.1 days. After correction for major demographic differences, infants who received a higher cumulative dose of steroids for a longer duration had a significantly increased incidence of severe ROP and PAR (P < 0.001). For each day of steroid treatment, there was a 3.2% increase in the hazard of the severe form of ROP (95% CI: 1.022-1.043) along with 5.7% delay in achieving full retinal vascularization (95% CI: 1.04-1.08) (P < 0.001). CONCLUSION: Cumulative dose and duration of postnatal steroid use were independently associated with the severity of ROP and PAR. Thus, postnatal steroids should be used very prudently. IMPACT: We report ROP outcomes in a large cohort of infants from two major healthcare systems where we have studied the impact of postnatal steroids on the severity of ROP, growth, and development of retinal vessels. After correcting our data for three major outcome measures, we show that high-dose postnatal steroids used for a prolonged duration of time are independently associated with severe ROP and delay in retinal vascularization. Postnatal steroids impact the visual outcomes of VLBW infants significantly, so their clinical use needs to be moderated.

A Pseudo-near isogenic F2 population strategy for rapid QTL cloning.

Near isogenic F2 (NIF2) population frequently developed by conventional backcross has dramatically contributed to QTL identification in plants. Developing such a NIF2 population is time-consuming. Thus, it is urgent to rapidly produce a NIF2 population for QTL cloning. Here, we proposed a rapid QTL cloning strategy by generating a Pseudo-near isogenic F2 population (Pseudo-NIF2), which segregates at the target QTL but is fixed at other QTLs for the target trait. Nineteen QTLs for GL, GW, and TGW were detected in the F2 population from the cross between Zhenshan 97 and Egy316. To verify the efficiency of Pseudo-NIF2 in QTL quick cloning, the novel moderate QTL qGL10.1 which explained 9.1% and 5.6% of grain length variation in F2 and F2:3 populations was taken as an example. An F2 plant (F2-120), which segregated at qGL10.1 but fixed at other 8 QTLs for grain length, was screened to generate a Pseudo-NIF2 population by selfing cross. In the Pseudo-NIF2 population, the segregation ratio of plants with long grains to short grains fits 3:1, indicating that one gene controlled the variation of grain length. Based on the Pseudo-NIF2 and its progeny, qGL10.1 was fine mapped to a 19.3-kb region, where a gene OsMADS56 was verified as the candidate by functional polymorphism between parental alleles. Pseudo-NIF2 strategy is a rapid way for QTL cloning, which saves 3 to 4 cropping seasons compared to the conventional way. Applying the method for cloning QTL with moderate or major effects is promising. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01408-x.

Early satisfactory results of percutaneous repair in neglected achilles tendon rupture.

PURPOSE: This investigation aimed to study the outcome of percutaneous repair of Achilles tendon ruptures regarding patient-reported and objective outcomes. METHODS: This is a retrospective review of a cohort of patients (n = 24) who underwent percutaneous repair of neglected Achilles rupture in the period between 2013 and 2019. Included patients were adults with closed injuries, presented 4-10 weeks after rupture, with intact deep sensation. All underwent clinical examination, X-rays to exclude bony injury and MRI for diagnosis confirmation. All underwent percutaneous repair by the same surgeon, using the same technique and rehabilitation protocol. The postoperative assessment was done subjectively using ATRS and AOFAS score and objectively using a percentage of heel rise comparison to the normal side and calf circumference difference. RESULTS: The mean follow-up period was 14.85 months ± 3 months. Average AOFAS scores at 6,12 months were 91 and 96, respectively, showing statistically significant improvement from pre-op level (P < 0.001). Percentage of heel rise on the affected side and calf circumference showed statistically significant improvement over the 12 month follow up period (P < 0.001). Superficial infection was reported in two patients (8.3%), and two cases reported transient sural nerve neuritis. CONCLUSION: Percutaneous repair of neglected Achilles rupture using the index technique proved a satisfactory patient-reported and objective measurement at a one-year follow-up. With only minor transient complications.

Association between IRS-1, PPAR-γ and LEP genes polymorphisms and growth traits in rabbits.

Single nucleotide polymorphisms are commonly associated with changes in quantitative traits, and have been considered useful markers for improving different traits in livestock. The current study aimed to explore the effect of three SNPs located in Insulin receptor substrate (IRS-1), Peroxisome proliferator-activated receptor γ (PPAR-γ), and Leptin (LEP) genes on the growth traits of rabbits. Individuals from three rabbit breeds were genotyped using RFLP-PCR. The IRS-1 variant (c.189T > G) was associated with post-weaning body weight, and body weight gains, However, the effect on growth rates was insignificant in Baladi Red and V-line rabbits. The PPAR-γ variant (c.207A > C) was significantly associated with 8-wk body weights in V-line rabbits, 10-wk body weights, and growth rates from 8 to 10 weeks of age in New Zealand rabbits. However, the differences between genotypes were insignificant for body weight gains and average daily gain. The LEP gene mutation (g.16079636C > G) had significant effects on body weights at 6 and 8 weeks of age in New Zealand White rabbits and 8 weeks of age in Baladi Red rabbits were associated with the presence of the C allele. Concludingly, the results stressed the importance of the IRS-1 gene in post-weaning growth and suggested the existence of breed-specific effects for PPAR-γ and LEP.

Comprehensive phytochemical characterization of Persea americana Mill. fruit via UPLC/HR-ESI-MS/MS and anti-arthritic evaluation using adjuvant-induced arthritis model.

Persea americana Mill. (avocado fruit) has many health benefits when added to our diet due to various pharmacological activities, such as preventing bone loss and inflammation, modulating immune response and acting as an antioxidant. In the current study, the total ethanol extract (TEE) of the fruit was investigated for in vitro antioxidant and anti-inflammatory activity via DPPH and cyclooxygenase enzyme inhibition. Biological evaluation of the antiarthritic effect of the fruit extract was further investigated in vivo using Complete Freund's Adjuvant (CFA) arthritis model, where the average percentages of body weight change, inhibition of paw edema, basal paw diameter/weight and spleen index were estimated for all animal groups. Inflammatory mediators such as serum IL-6 and TNF-α were also determined, in addition to histopathological examination of the dissected limbs isolated from all experimental animals. Eighty-one metabolites belonging to different chemical classes were detected in the TEE of P. americana fruit via UPLC/HR-ESI-MS/MS. Two classes of lyso-glycerophospholipids; lyso-glycerophosphoethanolamines and lysoglycerophosphocholines were detected for the first time in avocado fruit in the positive mode. The TEE of fruit exhibited significant antioxidant and anti-inflammatory activity in vitro. In vivo anti-arthritic activity of the fruit TEE improved paw parameters, inflammatory mediators and spleen index. Histopathological findings showed marked improvements in the arthritic condition of the excised limbs. Therefore, avocado fruit could be proposed to be a powerful antioxidant and antiarthritic natural product.

Cyanidin-3-Glucoside Modulates hsa_circ_0001345/miRNA106b/ATG16L1 Axis Expression as a Potential Protective Mechanism against Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common form of malignancy in the liver. Autophagy was found to have a significant effect in controlling HCC. Anthocyanins, which are naturally occurring pigments in a variety of fruits and vegetables, have been thoroughly documented to be involved in a variety of bioactive activities and are widely employed for their antioxidant capabilities. Cyanidin-3-glucoside (C3G) extracted from Morus alba L. has promising antioxidant and anti-tumour activities. The current study aims to examine the protective action of C3G against hepatocellular carcinoma through the investigation of the autophagy protein ATG16L1 expression along with its related RNA molecules (hsa_circ_0001345 and miRNA106b) in Wistar rats. In vivo precancerous lesions (PCL) were induced using diethylnitrosamine (DEN) and acetamidofluorene (2-AAF). Rats were treated with C3G (10, 15, and 20 mg/kg; 4 times weekly) for 112 days (16 weeks). Liver function tests, alfa fetoprotein, ATG16L1 expression, hsa_circ_0001345, and miRNA106b differential expression were examined. Liver sections were examined by histological and immunohistochemical approaches. The current study's findings indicated that C3G administration protects against the negative effects of DEN-2-AAF on liver functions and liver histopathological sections, which nominated C3G as a potential prophylactic agent against HCC.

Modulation of hepatic stellate cells by Mutaflor® probiotic in non-alcoholic fatty liver disease management.

BACKGROUND: NAFLD and NASH are emerging as primary causes of chronic liver disease, indicating a need for an effective treatment. Mutaflor® probiotic, a microbial treatment of interest, was effective in sustaining remission in ulcerative colitis patients. OBJECTIVE: To construct a genetic-epigenetic network linked to HSC signaling as a modulator of NAFLD/NASH pathogenesis, then assess the effects of Mutaflor® on this network. METHODS: First, in silico analysis was used to construct a genetic-epigenetic network linked to HSC signaling. Second, an investigation using rats, including HFHSD induced NASH and Mutaflor® treated animals, was designed. Experimental procedures included biochemical and histopathologic analysis of rat blood and liver samples. At the molecular level, the expression of genetic (FOXA2, TEAD2, and LATS2 mRNAs) and epigenetic (miR-650, RPARP AS-1 LncRNA) network was measured by real-time PCR. PCR results were validated with immunohistochemistry (α-SMA and LATS2). Target effector proteins, IL-6 and TGF-ß, were estimated by ELISA. RESULTS: Mutaflor® administration minimized biochemical and histopathologic alterations caused by NAFLD/NASH. HSC activation and expression of profibrogenic IL-6 and TGF-ß effector proteins were reduced via inhibition of hedgehog and hippo pathways. Pathways may have been inhibited through upregulation of RPARP AS-1 LncRNA which in turn downregulated the expression of miR-650, FOXA2 mRNA and TEAD2 mRNA and upregulated LATS2 mRNA expression. CONCLUSION: Mutaflor® may slow the progression of NAFLD/NASH by modulating a genetic-epigenetic network linked to HSC signaling. The probiotic may be a useful modality for the prevention and treatment of NAFLD/NASH.

Impact of Cotadutide drug on patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND: The food and drug administration approved many drugs to treat diabetes mellitus, but those drugs do not have a noticeable effect on weight management. Recently, glucagon-like peptide 1 agonist known as Cotadutide serve as a potent drug in treating type 2 diabetes by reducing blood glucose levels and body weight indices. This study aimed to explore the safety and efficacy of Cotadutide as a treatment for type 2 diabetes individuals. METHODS: A comprehensive literature search was done on different databases, including PubMed, Scopus, Web of Science, and Cochrane Library to capture all relevant articles using an established search strategy. The inclusion criteria were randomized controlled trials that assessed the safety and efficacy of Cotadutide versus placebo or any anti-diabetes drugs in patients with type 2 diabetes mellitus and a BMI between 22 kg/m2 and 40 kg/m2. We conducted the analysis using Revman software version 5.4. RESULTS: We found 663 relevant articles. From which nine studies were included and subjected to qualitative analysis and eight for quantitative analysis. The pooled effect showed that Cotadutide was better than placebo in reducing body weight (kg) (Mean difference (MD) = 3.31, p < 0.00001), glycated hemoglobin (HbA1c) (MD = 0.68, p > 0.00001), glucose area under the plasma concentration curve (AUC [0-4 h]) (MD = 30.15, p < 0.00001), and fasting plasma glucose over time (mg/dl) (MD = 31.31, p < 0.00001). CONCLUSION: Cotadutide is safe and effective in reducing plasma glucose levels, HbA1c and body weight in individuals with type 2 diabetes. TRIAL REGISTRATION: The study protocol was registered on PROSPERO (CRD: CRD42021257670 ).

Microneedling with topical vitamin C versus microneedling with topical insulin in the treatment of atrophic post-acne scars: A split-face study.

Post acne scars following sebaceous injury and abnormal wound healing during the course of acne is a prevalent and challenging to treat condition To evaluate microneedling by dermapen with topical vitamin C versus microneedling with topical insulin in treating atrophic post-acne scars. A split-face comparative study included 30 subjects with atrophic post-acne scars. Human insulin was topically applied to the left side of the face and on the right side, vitamin C serum was applied. Scars were assessed via the Acne Scar Assessment Scale (ASAS) and Scar quartile grading scale (SQGS). After 1 month of 4 treatments, a statistically significant mean improvement in ASAS value was reported on both split sides of the face (2.13 and 1.83) compared to baseline (3.03 and 2.93) (p = 0.005; p = 0.001 respectively). When compared to baseline, the mean ASAS value improved significantly with a slight more improvement on the vitamin c treated side. Topical insulin and vitamin c combined with microneedling, may both achieve comparable significant improvement for treating post acne scars. Insulin can be a promising novel anti-scarring therapy pending larger controlled studies to verify its efficacy.

Evaluation of memantine's efficacy and safety in the treatment of children with autism spectrum disorder: A systematic review and meta-analysis.

BACKGROUND: The United States Food and Drug Administration has approved drugs that address only autism-related symptoms rather than the underlying impairments. N-Methyl-D-Aspartate  receptor antagonists have recently emerged as a promising treatment option for a variety of neurologic and developmental problems, including autism. AIMS: To review (systematically), for the first time, the medical literature that explores the safety in and efficacy of memantine in autism. METHODS AND PROCEDURES: A comprehensive electronic search for relevant randomized controlled trials was conducted in four databases. Using RevMan software, we extracted and pooled data as a risk ratio (RR) or normalized mean differences in an inverse variance strategy. RESULTS: This systematic review and meta-analysis includes five trials. There was no difference in enhancing social responsiveness when compared to placebo, though memantine lowered the likelihood of anxiety (RR = 0.25; 95% Confidence interval: [0.07; 0.87], p = 0.03). However, memantine aggravated impulsive behaviors. Additionally, in another trial that compared memantine added to risperidone versus risperidone added to placebo, memantine was found to be effective and safe. CONCLUSION: Memantine showed safety in reducing acute symptoms of anxiety and other symptoms encountered in pediatric patients with autism spectrum disorders. However, memantine does not improve the core symptoms of autism. Nevertheless, further long-term trials are needed to explore its potential efficacy.

Comparative efficacy of bio-selenium nanoparticles and sodium selenite on morpho-physiochemical attributes under normal and salt stress conditions, besides selenium detoxification pathways in Brassica napus L.

Selenium nanoparticles (SeNPs) have attracted considerable attention globally due to their significant potential for alleviating abiotic stresses in plants. Accordingly, further research has been conducted to develop nanoparticles using chemical ways. However, our knowledge about the potential benefit or phytotoxicity of bioSeNPs in rapeseed is still unclear. Herein, we investigated the effect of bioSeNPs on growth and physiochemical attributes, and selenium detoxification pathways compared to sodium selenite (Se (IV)) during the early seedling stage under normal and salt stress conditions. Our findings showed that the range between optimal and toxic levels of bioSeNPs was wider than Se (IV), which increased the plant's ability to reduce salinity-induced oxidative stress. BioSeNPs improved the phenotypic characteristics of rapeseed seedlings without the sign of toxicity, markedly elevated germination, growth, photosynthetic efficiency and osmolyte accumulation versus Se (IV) under normal and salt stress conditions. In addition to modulation of Na+ and K+ uptake, bioSeNPs minimized the ROS level and MDA content by activating the antioxidant enzymes engaged in ROS detoxification by regulating these enzyme-related genes expression patterns. Importantly, the main effect of bioSeNPs and Se (IV) on plant growth appeared to be correlated with the change in the expression levels of Se-related genes. Our qRT-PCR results revealed that the genes involved in Se detoxification in root tissue were upregulated upon Se (IV) treated seedlings compared to NPs, indicating that bioSeNPs have a slightly toxic effect under higher concentrations. Furthermore, bioSeNPs might improve lateral root production by increasing the expression level of LBD16. Taken together, transamination and selenation were more functional methods of Se detoxification and proposed different degradation pathways that synthesized malformed or deformed selenoproteins, which provided essential mechanisms to increase Se tolerance at higher concentrations in rapeseed seedlings. Current findings could add more knowledge regarding the mechanisms underlying bioSeNPs induced plant growth.

Effect of modified genioglosuss advancement on hyoid bone position: Cephalometric study.

OBJECTIVE: To assess Hyoid bone position and retrolingual airway space after Modified Genioglossus Advancement Surgery by cephalometry in patients with obstructive sleep apnea (OSA). STUDY DESIGN: Prospective study. SETTING: Zagazig University Hospital. METHODS: Eighteen patients with moderate to severe OSA having multilevel airway obstruction confirmed by fiberoptic endoscopy during Muller's maneuver and DISE. All patients underwent modified genioglossus advancement surgery associated with antrolateral advancement pharyngoplasty. Beside Polysomnography and Drug induced sleep endoscopy, Cephalometry was done preoperatively and 6 months postoperative. RESULTS: Improved Polysomnography parameters as Postoperative mean ± SD apnea hypopnea index decreased from 52 ± 17.1 to 17 ± 3 (P < 0.001, 95% confidence interval 27.71 to 42.41). LOS increased from 79.89 ± 4.43% to 83 ± 4.05% (P 0.07, 95% confidence interval -0.31 to 6.97). Cephalometry analysis showed a significant difference between preoperative and postoperative findings, including: Retrolingual airway space at three levels significantly increased; Level 1 from 6.1 ± 1.6 to 8.5 ± 1.7, Level 2 from 10.5 ± 2.4 to 13.9 ± 2.1, Level 3 from 15.7 ± 3.1 to 21 ± 4, H-GN decreased from 51 ± 7 to 39 ± 8, H-MP decreased from 31.6 ± 7.7 to 24.9 ± 7.3, HS decreased from 121 ± 15 to 102 ± 12, H-PH increased from 29 ± 8 to 43 ± 9. With a success rate defined as AHI <20 and a 50% decrease in AHI of the preoperative value, the surgical success rate was 83.33%. CONCLUSION: This study showed that Modified genioglossus advancement procedures done for OSA patients significantly changed the position of hyoid bone into a more anterior and superior position and this was reflected in the postoperative Polysomnography.