NLRP3/1-mediated pyroptosis:beneficial clues for the development of novel therapies for Alzheimer’s disease

The inflammasome is a multiprotein complex involved in innate immunity that mediates the inflammatory response leading to pyroptosis,which is a lytic,inflammatory form of cell death.There is accumulating evidence that nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3(NLRP3)inflammasome-mediated microglial pyroptosis and NLRP1 inflammasome-mediated neuronal pyroptosis in the brain are closely associated with the pathogenesis of Alzheimer’s disease.In this review,we summarize the possible pathogenic mechanisms of Alzheimer’s disease,focusing on neuroinflammation.We also describe the structures of NLRP3 and NLRP1 and the role their activation plays in Alzheimer’s disease.Finally,we examine the neuroprotective activity of small-molecule inhibitors,endogenous inhibitor proteins,microRNAs,and natural bioactive molecules that target NLRP3 and NLRP1,based on the rationale that inhibiting NLRP3 and NLRP1 inflammasome-mediated pyroptosis can be an effective therapeutic strategy for Alzheimer’s disease.

The role of polymorphic cytochrome P450 gene(CYP2B6)in B-chronic lymphocytic leukemia(B-CLL)incidence and outcome among Egyptian patients

Cytochromes P450(CYPs)play a prominent role in catalyzing phase I xenobiotic biotransformation and account for about 75%of the total metabolism of commercially available drugs,including chemotherapeutics.The gene expression and enzyme activity of CYPs are variable between individuals,which subsequently leads to different patterns of susceptibility to carcinogenesis by genotoxic xenobiotics,as well as differences in the efficacy and toxicity of clinically used drugs.This research aimed to examine the presence of the CYP2B6*9 polymorphism and its possible association with the incidence of B-CLL in Egyptian patients,as well as the clinical outcome after receiving cyclophosphamide chemotherapy.DNA was isolated from whole blood samples of 100 de novo B-CLL cases and also from 100 sex-and age-matched healthy individuals.The presence of the CYP2B6*9(G516T)polymorphism was examined by PCR-based allele specific amplification(ASA).Patients were further indicated for receiving chemotherapy,and then they were followed up.The CYP2B6*9 variant indicated a statistically significant higher risk of B-CLL under different genetic models,comprising allelic(T-allele vs.G-allele,OR=4.8,p<0.001)and dominant(GT+TT vs.GG,OR=5.4,p<0.001)models.Following cyclophosphamide chemotherapy,we found that the patients with variant genotypes(GT+TT)were less likely to achieve remission compared to those with the wild-type genotype(GG),with a response percentage of(37.5%vs.83%,respectively).In conclusion,our findings showed that the CYP2B6*9(G516T)polymorphism is associated with B-CLL susceptibility among Egyptian patients.This variant greatly affected the clinical outcome and can serve as a good therapeutic marker in predicting response to cyclophosphamide treatment.

Establishment of a Multiplex Detection Method for Common Bacteria in Blood Based on Human Mannan-Binding Lectin Protein-Conjugated Magnetic Bead Enrichment Combined with Recombinase-Aided PCR Technology

Objective Recombinase-aided polymerase chain reaction(RAP)is a sensitive,single-tube,two-stage nucleic acid amplification method.This study aimed to develop an assay that can be used for the early diagnosis of three types of bacteremia caused by Staphylococcus aureus(SA),Pseudomonas aeruginosa(PA),and Acinetobacter baumannii(AB)in the bloodstream based on recombinant human mannanbinding lectin protein(M1 protein)-conjugated magnetic bead(M1 bead)enrichment of pathogens combined with RAP.Methods Recombinant plasmids were used to evaluate the assay sensitivity.Common blood influenza bacteria were used for the specific detection.Simulated and clinical plasma samples were enriched with M1 beads and then subjected to multiple recombinase-aided PCR(M-RAP)and quantitative PCR(qPCR)assays.Kappa analysis was used to evaluate the consistency between the two assays.Results The M-RAP method had sensitivity rates of 1,10,and 1 copies/μL for the detection of SA,PA,and AB plasmids,respectively,without cross-reaction to other bacterial species.The M-RAP assay obtained results for<10 CFU/mL pathogens in the blood within 4 h,with higher sensitivity than qPCR.M-RAP and qPCR for SA,PA,and AB yielded Kappa values of 0.839,0.815,and 0.856,respectively(P<0.05).Conclusion An M-RAP assay for SA,PA,and AB in blood samples utilizing M1 bead enrichment has been developed and can be potentially used for the early detection of bacteremia.

Clinical pathology analysis of esophageal sarcomatoid carcinoma

Objective： The purpose of this study was to study the clinical, imaging characters and pathological characteristics of esophageal sarcomatoid carcinoma. Methods： We reviewed 23 cases of esophageal sarcomatoid carcinoma from Janu ary 2006 to December 2013 in four hospitals. The data of patients who were esophageal sarcomatoid carcinoma operated were retrospectively analyzed. All cases had completed upper gastrointestinal barium images materials and 14 of these cases had completed CT images materials. Upper gastrointestinal barium images and CT imaging features include tumor location, size, shape, and strengthen, etc. The biological parameters of lesions including the express of cytokeratin AE1/AE3, 34E12,, Vimentin, desmin, Actin, S100 and Ki67 detected by immunhistochemical UltraSensitiveTM SP method （n = 23）, and the patients＇ data of contrastographic picture （n = 23）, imaging characters of CT scan （n = 14）, and their relationship were studied. Results： Upper gastrointestinal barium images, CT imaging and gastrointestinal fiberscopy revealed Iobulated intraluminal filling defect 0.4 cm to 5.7 cm x 3.5 cmx 1.3 cm （mean = 3. 7 cm） in the mid （n = 14）, lower （n = 7） and upper （n = 2） intrathoracic esophagus. Among 23 cases of esophageal sarcomatoid carcinoma, 19 patients were of mushroom type, 2 patients was of ulcer type, and 2 patients were of medulla type; 19 patients were pedunculated, and 4 patients were no pedunculated （2 patients was of ulcer type）. The tumor surface was relatively smooth and esophageal compliance was maintained. The pathological changes of esophagus such as lightly locked, rigid wall nomanifest partly, esophageal lumens expand partly, major filling sublobe defect could be shown through contrast medium. Normal esophagus was no unpack obviously over pathological changes. Enhanced computed tomography showed tumors in the intrathoracic esophagus and 8 lymph nodes metastases in 3 cases. Histologically, carcinomatous and sarcomatous components coexist. Microscopically, the tumor comprised poorly differentiated squamous cell carcinoma and spindleshaped cells resembling leiomyosarcoma. Immu nohistochemically, spindleshaped sarcomatous cells displayed weekly positive reaction to cytokeratin AE1/AE3. Transitional zone was seen between sarcomatous and carcinomatous elements in 5 cases. The 17 lymph nodes metastases in 5 cases （53 lymph nodes） among 23 cases esophageal sarcomatoid carcinoma （187 lymph nodes） were observed. Conclusion： The clinical and radiologic features of esophageal sarcomatoid carcinoma overlap with those of other esophageal neoplasms. There are the radiologic imaging changes such as a large, intraluminal, polypoid mass, major filling sublobe defect and pedicle skin flap tumor in esophageal lumen, esophageal lumen extension partly, dissepiment rigidity wall no obviously, etc. Histologically, carcinomatous and sarcomatous components coexist and the biphasic pattern is the key diagnostic feature. However, esophageal sarcomatoid carcinoma has a more favorable prognosis than other malignant esophageal neoplasms. Immunohistochemical staining seems necessary to distinguish these lesions from other esophageal neoplasms.

Prevalence and clinical significance of antiphospholipid antibodies among hospitalized COVID-19 patients

Objective:To describe the prevalence of antiphospholipid antibodies in coronavirus disease-19(COVID-19)and to find potential associations between antiphospholipid antibody positivity and clinical outcomes.Methods:From September to November 2020,clinical and laboratory data were collected from 50 COVID-19 patients hospitalized at Saiful Anwar General Hospital in Malang,Indonesia.Antiphospholipid antibodies were measured by finding Ig M anti-β2 glycoprotein,lupus anticoagulant,and Ig M/Ig G anticardiolipin.Clinical characteristics,thrombotic events,ICU admission,and mortality during hospitalization were recorded.Disease severity was defined by the Guidelines for the Prevention and Control of COVID-19,Indonesia.Results:Among 50 patients,5 patients(10.0%)were positive for antiphospholipid antibodies:4 patients(80.0%)had Ig M anti-β2 glycoprotein and 1 patient had Ig G anti-cardiolipin(20.0%)and Ig M anti-cardiolipin(20.0%),none of lupus anticoagulant was detected.Antiphospholipid antibodies were associated with anosmia(OR 8.1;95%CI 1.1-57.9;P=0.018),nausea and vomiting(OR 12.4;95%CI 1.2-122.6;P=0.010),diarrhea(OR 9.8;95%CI 1.3-70.9;P=0.010),cardiovascular disease(OR 1.4;95%CI 1.0-1.9;P=0.001),chronic kidney disease(OR 12.0;95%CI 1.6-90.1;P=0.05),acute coronary syndrome(OR 29.3;95%CI 2.0-423.7;P=0.001),moderate(OR 0.11;95%CI 0.01-1.10;P=0.031)and severe(OR 18.5;95%CI 1.8-188.4;P=0.002)disease severity,and in-hospital mortality(OR 8.1;95%CI 1.1-57.9;P=0.018).However,there is no correlation between the presence of antiphospholipid antibody and ICU admission.Conclusions:In summary,the prevalence of antiphospholipid antibodies in COVID-19 patients is low,mainly against Ig M anticardiolipin,and is associated with an acute coronary syndrome,gastrointestinal manifestations,moderate and severe disease severity,and increased risk of mortality.

Revaluation of clinical and histological criteria for diagnosis of dysmetabolic iron overload syndrome

AIM： To re-evaluate the diagnostic criteria of insulin resistance hepatic iron overload based on clinical, biochemical and histopathological findings. METHODS： We studied 81 patients with hepatic iron overload not explained by known genetic and acquired causes. The metabolic syndrome （MS） was defined according to ATPⅢ criteria. Iron overload was assessed by liver biopsy. Liver histology was evaluated by Ishak＇s score and iron accumulation by Deugnier＇s score; steatosis was diagnosed when present in ≥ 5% of hepatooltes. RESULTS： According to transferrin saturation levels, we observed significant differences in the amount of hepatic iron overload and iron distribution, as well as the number of metabolic abnormalities. Using Receiving Operating Curve analysis, we found that the presence of two components of the MS differentiated two groups with a statistically significant different hepatic iron overload （P 〈 0.0001）. Patients with ≥2 metabolic alterations and steatosis had lower amount of hepatic iron, lower transferrin saturation and higher sinusoidal iron than patients with 〈 2 MS components and absence of steatosis. CONCLUSION： In our patients, the presence of ≥ 2 alterations of the MS and hepatic steatosis was associated with a moderate form of iron overload with a prevalent sinusoidal distribution and a normal transferrin saturation, suggesting the existence of a peculiar pathogenetic mechanism of iron accumulation. These patients may have the typical dysmetabolic iron overload syndrome. By contrast, patients with transferrin saturation ≥ 60% had more severe iron overload, few or no metabolic abnormalities and a hemochromatosis-like pattern of iron overload.

Unfamiliar waveforms spanning from the ST to TP segments only observed in certain limb leads of the standard 12-lead electrocardiogram due to Aslanger’ s sign

Aslanger’s sign,also known as the arterial pulse tapping artifact or electromechanical association artifact,is an electrocardiographic artifact caused by arterial pulsation at the site where the limb leads of the standard 12-lead electrocardiogram near the radial or posterior tibial arteries are positioned,particularly in hyperdynamic states.[1–8]It occurs in every cardiac cycle with a constant coupling interval between the QRS complex and artifact.This synchronization with the underlying heart rhythm makes it less likely to be recognized as an artifact compared to unsynchronized artifacts,such as those caused by limb movement and inadequate contact between the electrode and skin.[1,2,7,8]Almost all reported cases of Aslanger’s sign exhibit an unusual waveform morphology in all 12 leads except one of the standard 12-lead electrocardiogram.This sign is often confused with an electrocardiographic finding commonly observed during acute coronary events.

Susceptibility patterns and virulence genotypes of Helicobacter pylori affecting eradication therapy outcomes among Egyptian patients with gastroduodenal diseases

BACKGROUND Helicobacter pylori(H.pylori)is a significant human pathogen that is responsible for a variety of illnesses,including mucosa-associated lymphoid tissue lymphoma,gastric cancer,peptic ulcers,and gastritis.AIM To investigate the frequency of H.pylori infection and its resistance patterns among Egyptian patients and to determine the influence of H.pylori virulence genetic determinants on the eradication success of 14-d triple therapy regimen.METHODS H.pylori infections were investigated in 72 patients with gastroduodenal complications suggestive of H.pylori infection.The cagA and vacA genotypes of cultured strains were studied using polymerase chain reaction.The patients underwent 14 d of triple-therapy treatment.The treatment response was examined using histology and a rapid urease test 6 wk after therapy discontinuation.RESULTS The intention-to-treat eradication rate was 59.2%(95%CI:48.2%-70.3%).Rates of H.pylori resistance to clarithromycin,amoxicillin,and metronidazole were 52.8%,81.9%,and 100%,respectively.Successful eradication of H.pylori was more significantly associated with vacA s1-positive strains[adjusted odds ratio(aOR)=0.507,95%CI:0.175-0.822].A significant association was found between failed eradication rate and H.pylori strains resistant to clarithromycin(aOR=0.204,95%CI:-0.005 to 0.412)and amoxicillin(aOR=0.223,95%CI:0.026-0.537).CONCLUSION This study’s low H.pylori eradication rate following 14-d triple therapy is concerning and worrying.H.pylori pan-resistance to metronidazole followed by the high resistance to ciprofloxacin,amoxicillin,and clarithromycin in this research is challenging and of great concern.

Clinical Significance of Serum Galectin-1 and Its Tissue Immunohistochemical Expression in Serous Ovarian Carcinoma Patients

Objectives: Serous ovarian carcinoma (SOC) is the commonest ovarian carcinoma type with poor prognosis due to early metastasis and first presentation with advanced stage. In this work, we investigated serum level of Galactin-1 (Gal-1) and its tissue immunohistochemical expression in SOC patients at different stages trying to find out its significance as a diagnostic and prognostic marker. Patients and methods: The study included 95 females I-Control group: Twenty five healthy females;II-Patients group: Seventy females diagnosed as SOC at different stages;Stage I: 8 cases, Stage II: 12 cases, Stage III: 32 cases and Stage VI:18 cases. Serum Galectin-1 and CA-125 were measured by ELIZA and tissue Galectin-1 was assessed by immunohistochemistry. All patients were followed for up to 3 years after surgery. Results: Serum Gal-1 and CA-125 levels were significantly higehr in SOC patients compared to controls (p 0.001). We found a direct positive statistically significant correlation between serum Gal-1 and CA125 levels (p 0.001). Serum Gal-1 at cut off value > 135 ng/ml was superior to CA-125 a cut off value > 49 u/ml with sensitivity, specificity of 100%, vs 88.57, 96% for CA-125. Serum Gal-1 was significantly associated with tumor stage (p 0.001). Immunohistochemistry showed that patients with strong Gal-1 expression had higher serum level (p = 0.002). Stromal and tumor Gal-1 expression were significantly correlated with tumor grade (p 0.001) and stage (p = 0.001). Serum Gal-1, CA-125 and IHC Gal-1 expression were associated with poor survival (p 0.001, p = 0.009 and p = 0.002) respectively. Conclusion: Serum Gal-1 and its tissue IHC expression are useful diagnostic and prognostic markers for SOC patients.

Overview of angiogenesis and oxidative stress in cancer

Neoplasms can be considered as a group of aberrant cells that need more vascular supply to fulfill all their functions.Therefore,they promote angiogenesis through the same neovascularization pathway used physiologically.Angiogenesis is a process characterized by a heterogeneous distribution of oxygen caused by the tumor and oxidative stress;the latter being one of the most powerful stimuli of angiogenesis.As a result of altered tumor metabolism due to hypoxia,acidosis occurs.The angiogenic process and oxidative stress can be detected by measuring serum and tissue biomarkers.The study of the mechanisms underlying angiogenesis and oxidative stress could lead to the identification of new biomarkers,ameliorating the selection of patients with neoplasms and the prediction of their response to possible anti-tumor therapies.In particular,in the treatment of patients with similar clinical tumor phenotypes but different prognoses,the new biomarkers could be useful.Moreover,they may lead to a better understanding of the mechanisms underlying drug resistance.Experimental studies show that blocking the vascular supply results in antiproliferative activity in vivo in neuroendocrine tumor cells,which require a high vascular supply.

Upper gastrointestinal bleeding as an unusual manifestation of localized Ménétrier’s disease with an underlying lipoma:A case report

BACKGROUND Ménétrier’s disease is a rare condition characterized by enlarged gastric folds,usually located in the whole body and fundus of the stomach.This report presents an unusual case of localized Ménétrier’s disease elevated by a submucosal lipoma and thus looking like a polypoid mass and causing an episode of upper gastrointestinal bleeding.The mass was successfully removed with endoscopic submucosal dissection.CASE SUMMARY Esophagogastroduodenoscopy was performed on a 76-year-old male patient after an episode of upper gastrointestinal bleeding,manifesting as fatigue and melena.A large polypoid mass(4 cm×1 cm)with enlarged mucosal folds was found in the body of the stomach,between the lesser curvature and posterior wall.A small ulcer at the distal end of the mass was identified as the source of the bleeding.Biopsy was negative for neoplasia.Computed tomography showed a submucosal lesion beneath the affected mucosa,most likely a lipoma.The mass was removed en bloc with tunneling endoscopic submucosal dissection.Final pathology determined that the mass included Ménétrier’s disease and a submucosal lipoma.The patient was scheduled for follow-up esophagogastroduodenoscopy.CONCLUSION Localized Ménétrier’s disease can coexist with a submucosal lipoma creating a polypoid mass with risk of bleeding.

Lamellar Bodies Count (LBC) as a Predictor of Fetal Lung Maturity in Preterm Premature Rupture of Membranes Compared to Neonatal Assessment

Background: Respiratory distress syndrome (RDS) is a major cause of neonatal morbidity and mortality, affecting approximately 1% of all live births and 10% of all preterm infants. Lamellar bodies represent a storage form of pulmonary surfactant within Type II pneumocytes, secretion of which increases with advancing gestational age, thus enabling prediction of the degree of FLM. Preterm premature rupture of membranes (PPROM) complicates approximately 1/3 of all preterm births. Birth within 1 week is the most likely outcome for any patient with PPROM in the absence of adjunctive treatments. Respiratory distress has been reported to be the most common complication of preterm birth. Sepsis, intraventricular haemorrhage, and necrotizing enterocolitis also are associated with prematurity, but these are less common near to term. Objective: To assess the efficacy of the amniotic fluid lamellar body counting from a vaginal pool in predicting fetal lung maturity in women with preterm premature rupture of membranes. Methods: This study was conducted at Ain Shams University Maternity Hospital in the emergency ward from January 2019 to September 2019. It included 106 women with singleton pregnancies, gestational age from 28 - 36 weeks with preterm premature rupture of membranes. This study is designed to assess the efficacy of the amniotic fluid lamellar body counting (LBC) from a vaginal pool in predicting fetal lung maturity in women with preterm premature rupture of membranes. Results: The current study revealed a highly significant increase in the lamellar body count in cases giving birth to neonates without RDS compared to that cases giving birth to neonates with RDS. Also, no statistically significant difference between LBC and age, parity and number of previous miscarriages in the mother was found. Gestational age at delivery was significantly lower among cases with respiratory distress. Steroid administration was significantly less frequent among cases with respiratory distress. However, lamellar bodies had high diagnostic performance in the prediction of respiratory distress. Conclusion: Lamellar body count (LBC) is an effective, safe, easy, and cost-effective method to assess fetal lung maturity (FLM). It does not need a highly equipped laboratory or specially trained personnel, it just needs the conventional blood count analyzer. Measurement of LBC is now replacing the conventional Lecithin/Sphyngomyelin L/S ratio. LBC cut-off value of ≤42.5 × 103/μL can be used safely to decide fetal lung maturity with sensitivity of 95.7% and specificity of 97.6%.

Proteomics of cell-free breast cancer scaffolds identify clinically relevant imprinted proteins and cancer-progressing properties

The composition of the extracellular tumor microenvironment(TME)has not been fully delineated,limiting the understanding of general cancer-progressing properties within the cancer niche.The interplay and dynamics between cancer cells and the surrounding structures and cells clearly differ between various subtypes of cancer,adding to the complexity of precision medicine[1].

Splenic hamartomas in children

Splenic hamartomas(SHs)are uncommon,benign vascular lesions of unclear etiology and are mostly found incidentally on abdominal images,at surgery,or at autopsy.Since the first case description,in 1861,less than 50 pediatric SH cases have been reported in the literature.In this article,we have performed an analysis of all SH cases in children published in the literature to date and presented our case of an 8-year-old male with SH.These lesions in children were shown to cause symptoms more often than in the adult population.The observed SH sizes in children ranged from a few millimeters to 18 cm,and the symptomatic lesions were mostly larger or multiple.The most common clinical finding was splenomegaly.Signs of hypersplenism were present in children with a single SH larger than 4.5 cm(diameter range:4.5-18.0 cm)and in those with multiple hamartomas,ranging from a few millimeters to 5 cm.Eighty percent of patients with available laboratory findings had hematological abnormalities such as anemia,thrombocytopenia,or pancytopenia.Other symptoms and signs included abdominal pain,recurrent infections,fever,night sweats,lethargy,growth retardation,and weight loss.The use of multiple imaging modalities may suggest the preoperative diagnosis of a splenic mass in children and determine the therapeutic approach.However,the final diagnosis of SH relies on histopathological evaluation.Surgery,including total or partial splenectomy(PS),is the mainstay of SH management.Milickovic M et al.Splenomas in children WJCC https://www.wjgnet.com 1910 April 16,2024 Volume 12 Issue 11 Although total splenectomy carries a greater risk of overwhelming post-splenectomy infection than PS it has remained the most performed surgical procedure in children with SH.In the majority of pediatric patients with symptomatic SH,resolution of symptoms and resolution or improvement of cytopenias occurred after surgical treatment.

Correlation between DKK-1 Level and Bone Density Status in Children on Maintenance Haemodialysis

Background: Renal osteodystrophy (ROD) is a bone disorder resulting from chronic kidney disease (CKD) and related metabolic diseases. Dickkopf-related protein-1 (DKK-1) is critical in regulating bone biology. This study aimed to evaluate the serum DKK-1 level as a bone marker in children with CKD who undergo regular hemodialysis (HD). Subjects and Methods: This case-control study involved 40 children with CKD on HD and 40 healthy children as controls. The study measured serum DKK-1 levels and performed a dual-energy X-ray absorptiometry scan (DEXA) in line with routine laboratory investigations. Results: There was a significant increase in the serum level of DKK-1 in the patient group compared to the control group. The DKK-1 levels were 2540.65 (2215.4 - 2909.2) pg/ml and 1110.45 (885.45 - 1527.65) pg/ml, respectively, with a p-value of less than 0.001. In the hemodialysis group, 25 patients (62.5%) had low bone mineral density (BMD) with a Z-score of under -2.0. Eighteen of these patients had low BMD in both the neck of the femur and lumbar spines. Additionally, there was a significant increase in serum DKK-1 level in patients with low BMD (2567.35 (2303.8 - 3108.1) pg/ml) compared to patients with normal BMD (2454 (1859 - 2820) pg/ml) (p = 0.041). There was also a significant positive correlation between DKK1 level and phosphorus, alkaline phosphatase, and Parathormone serum levels. In conclusion, the study indicates a clear correlation between DKK-1 and BMD in children undergoing maintenance hemodialysis. DKK1 is a promising biomarker for CKD-MBD.

Salivary C-reactive protein and mean platelet volume as possible diagnostic markers for late-onset neonatal pneumonia

BACKGROUND Neonatal sepsis,a formidable threat to newborns,is a leading cause of neonatal mortality,with late-onset sepsis manifesting after 72 hours post-birth being particularly concerning.Pneumonia,a prevalent sepsis presentation,poses a significant risk,especially during the neonatal phase when lung defenses are compromised.Accurate diagnosis of pneumonia is imperative for timely and effective interventions.Saliva,a minimally invasive diagnostic medium,holds great promise for evaluating infections,especially in infants.AIM To investigate the potential of serum C-reactive protein(CRP),salivary CRP(sCRP),and mean platelet volume(MPV)as diagnostic markers for late-onset neonatal pneumonia(LONP).METHODS Eighty full-term neonates were systematically examined,considering anthropometric measurements,clinical manifestations,radiology findings,and essential biomarkers,including serum CRP,sCRP,and MPV.RESULTS The study reveals noteworthy distinctions in serum CRP levels,MPV,and the serum CRP/MPV ratio between neonates with LONP and healthy controls.MPV exhibited a robust discriminatory ability[area under the curve(AUC)=0.87]with high sensitivity and specificity at a cutoff value of>8.8.Correlations between serum CRP,sCRP,and MPV were also identified.Notably,sCRP demonstrated excellent predictive value for serum CRP levels(AUC=0.89),underscoring its potential as a diagnostic tool.CONCLUSION This study underscores the diagnostic promise of salivary and serum biomarkers,specifically MPV and CRP,in identifying and predicting LONP among neonates.These findings advocate for further research to validate their clinical utility in larger neonatal cohorts.

Childhood asthma biomarkers including zinc: An exploratory crosssectional study

BACKGROUND Childhood bronchial asthma(BA)is a chronic inflammatory respiratory disease.Nutritional conditions,including zinc deficiency,can affect such allergic disorders.AIM To outline the difference in serum zinc levels between asthmatic children and healthy controls.METHODS A cross-sectional study was carried out at Children’s Hospital,Cairo University,investigating serum zinc levels in children with BA(n=40)and healthy children(n=21).Other markers included serum ferritin,iron,hemoglobin(Hb),and immunoglobulin E(IgE)levels.Independent t-tests and Mann-Whinny tests were used for comparisons.The Kruskal-Wallis test was applied to compare serum ferritin and IgE levels with regard to asthma severity.Spearman's rank correlation was performed to explore the relationship between serum ferritin levels and both iron and Hb levels in asthmatic children.RESULTS Children with BA had higher levels of zinc,yet the difference was not significant(P=0.115).Serum ferritin and IgE levels were significantly higher in asthmatic children(P=0.006 and 0.001,respectively),yet their levels did not differ significantly by severity(P=0.623 and 0.126,respectively).There was a nonsignificant weak correlation between serum ferritin levels and both serum iron and Hb levels.CONCLUSION Serum zinc levels do not seem to differ between asthmatic children and healthy children.Serum ferritin levels may be a marker of asthma control.Serum IgE levels are not markers of asthma severity.

Correlation between Wnt Signalling Inhibitors (Dickkopf-1 & Sclerostin) and the Intimal Medial Thickness in Children on Maintenance Hemodialysis

Background: Wnt signalling inhibitors (Dickkopf-1 and Sclerostin) signalling play a role in vascular development and may contribute to calcification. Aim: To investigate the association between Dickkopf-1 and sclerostin serum concentrations in children undergoing maintenance hemodialysis with intimal medial thickness and peak systolic velocity of the main arteries. Patients and Methods: A study was conducted on 40 children undergoing maintenance hemodialysis and controls of the same age and sex. The study measured the initial medial thickness (IMT) and peak systolic velocity (PSV) of the main vessels (carotid, ulnar, and femoral). Dickkopf-1 and sclerostin serum levels in both groups were assessed, and a routine investigation was performed. Results: The findings indicate that the levels of serum Dickkopf-1 and Sclerostin were significantly higher in the hemodialysis group 2540.65 (2215.4 - 2909.2 pg/ml) and 1.17 (0.85 - 2.03 ng/ml)respectively (P = 0.001), compared to their control group it was 1110.45 (885.45 - 1527.65 pg/ml) and 0.28 (0.25 - 0.32 ng/ml)) respectively P = 0.001. Additionally, there was a significant increase in intima-media thickness (IMT) with a decrease in peak systolic velocity (PSV) in the main blood vessels, including the carotid, ulnar, and femoral arteries. A significant correlation was also observed between Dickkopf-1 and sclerostin levels and IMT of the carotid, ulnar, and femoral arteries. Conclusion: Wnt signalling inhibitors (Dickkopf-1 and Sclerostin) exert effects beyond the bone and significantly contribute to early vascular calcification in pediatric patients undergoing maintenance hemodialysis.

Selenoprotein-p and insulin resistance in children and adolescents with obesity

BACKGROUND Insulin resistance and obesity present significant challenges in pediatric populations.Selenoprotein P1(SEPP1)serves as a biomarker for assessing selenium levels in the body.While its association with metabolic syndrome is established in adults,its relevance in children remains underexplored.AIM To ascertain SEPP1 blood levels in children and adolescents diagnosed with obesity and to assess its correlation with insulin resistance and adiposity indices.METHODS 170 children participated in this study,including 85 diagnosed with obesity and an equal number of healthy counterparts matched for age and sex.Each participant underwent a comprehensive medical evaluation,encompassing a detailed medical history,clinical examination,and anthropometric measurements like waist circumference and waist-to-height ratio.Furthermore,routine blood tests were conducted,including serum SEPP1,visceral adiposity index(VAI),and Homeostatic Model Assessment of Insulin Resistance(HOMA-IR)level.RESULTS Our findings revealed significantly lower serum SEPP1 levels in children with obesity compared to their healthy peers.Moreover,notable negative correlations were observed between serum SEPP1 levels and body mass index,VAI,and HOMA-IR.CONCLUSION The study suggests that SEPP1 could serve as a valuable predictor for insulin resistance among children and adolescents diagnosed with obesity.This highlights the potential utility of SEPP1 in pediatric metabolic health assessment and warrants further investigation.

Effect of alternative antibiotics in treatment of cefotaxime resistant spontaneous bacterial peritonitis

AIM:To evaluate effective alternative antibiotics in treatment of cefotaxime-resistant spontaneous bacterial peritonitis.METHODS:One hundred cirrhotic patients with spontaneous bacterial peritonitis [ascitic fluid polymorphonuclear cell count(PMNLs) ≥ 250 cells/mm 3 at admission] were empirically treated with cefotaxime sodium 2 g/12 h and volume expansion by intravenous human albumin.All patients were subjected to history taking,complete examination,laboratory tests(including a complete blood cell count,prothrombin time,biochemical tests of liver and kidney function,and fresh urine sediment),chest X-ray,a diagnostic abdominal paracentesis,and the sample subjected to total and differential cell count,chemical examination,aerobic and anaerobic cultures.Patients were divided after 2 d by a second ascitic PMNL count into group Ⅰ;patients sensitive to cefotaxime(n = 81),group Ⅱ(n = 19);cases resistant to cefotaxime(less than 25% decrease in ascitic PMNL count).Patients of group Ⅱ were randomly assigned into meropenem(n = 11) or levofloxacin(n = 8) subgroups.All patients performed an end of treatment ascitic PMNL count.Patients were considered improved when:PMNLs decreased to < 250 cells/mm 3,no growth in previously positive culture cases,and improved clinical manifestations with at least 5 d of antibiotic therapy.RESULTS:Age,sex,and Child classes showed no significant difference between group Ⅰ and group Ⅱ.Fever and abdominal pain were the most frequent manifestations and were reported in 82.7% and 80.2% of patients in group Ⅰ and in 94.7% and 84.2% of patients in group Ⅱ,respectively.Patients in group Ⅱ had a more severe ascitic inflammatory response than group Ⅰ and this was demonstrated by more ascitic lactate dehydrogenase(LDH) [median:540 IU/L(range:150-1200 IU/L) vs median:240 IU/L(range:180-500 IU/L),P = 0.000] and PMNL [median:15 000 cell/mm 3(range:957-23 822 cell/mm 3) vs 3400 cell/mm 3(range:695-26 400 cell/mm 3),P = 0.000] counts.Ascitic fluid culture was positive in 32% of cases.Cefotaxime failed in 19% of patients;of these patients,11(100%) responded to meropenem and 6(75%) responded to levofloxacin.Two patients with failed levofloxacin therapy were treated according to the in vitro culture and sensitivity(one case was treated with vancomycin and one case was treated with ampicillin/sulbactam).In group Ⅱ the meropenem subgroup had higher LDH(range:108-860 IU/L vs 120-491 IU/L,P = 0.042) and PMNL counts(range:957-23 822 cell/mm 3 vs 957-15 222 cell/mm 3,P = 0.000) at initiation of the alternative antibiotic therapy;there was no significant difference in the studied parameters between patients responsive to meropenem and patients responsive to levofloxacin at the end of therapy(mean ± SD:316.01 ± 104.03PMNLs/mm 3 vs 265.63 ± 69.61 PMNLs/mm 3,P = 0.307).The isolated organisms found in group Ⅱ were;enterococci,acinetobacter,expanded-spectrum β-lactamase producing Escherichia coli,β-lactamase producing Enterobacter and Staphylococcus aureus.CONCLUSION:Empirical treatment with cefotaxime is effective in 81% of cases;meropenem is effective in cefotaxime-resistant cases.