Epidemiology of Sjogren's syndrome in a sample of the Egyptian population: a cross-sectional study.

OBJECTIVE: To investigate the prevalence of Sjögren's syndrome (SS) and the associated factors in a sample of the Egyptian population. METHODS: This cross-sectional study obtained data by screening subjects from several hospitals in different governorates across Egypt. Demographic and health data were collected including symptoms and type of Sjögren's syndrome, associated autoimmune diseases, the presence of specific autoantibodies and associated malignancies. RESULTS: The study analysed 7960 participants and 64 (0.80%) had SS. Of these, 22 (34.38%) had primary SS and 42 patients (65.63%) had secondary SS. For the total study cohort, the prevalence of primary and secondary SS was 0.28% and 0.53%, respectively. There was a higher prevalence of SS in females compared with males and SS was more common in the fifth and sixth decades. All patients with SS complained of oral and ocular dryness. The most common concomitant autoimmune disease was rheumatoid arthritis. Anti-SSA (Ro) and anti-SSB (La) antibodies were the most frequently associated autoantibodies. Only two patients had non-Hodgkin's lymphoma. CONCLUSION: This was the first study to describe the prevalence of SS in Egypt. SS is not a rare disease in Egypt, so raising awareness of SS in both patients and healthcare professionals is very important.

Effect of web-based health education on nursing students' knowledge, adaptive healthy measures and attitudes regarding polycystic ovary syndrome: a randomized controlled trial.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder affecting women of reproductive age, and it has emerged as a significant global public health issue. This study aimed to investigate the effects of web-based health education on nursing students' knowledge, adaptive healthy measures, and attitudes toward PCOS. METHODS: A two-group randomized controlled trial (RCT) with pre-test and immediate post-test assessments was conducted. Study participants were recruited using a simple random sampling method from the Faculty of Nursing, Mansoura University, Egypt. A questionnaire consisting of six sections was developed to collect data, which was analyzed with the SPSS 23.0 using Student's t-test, Pearson's correlation test, and chi-square test analysis of variance. RESULTS: The analysis revealed a significant increase in knowledge scores post-intervention, with the web-based learning groups (32.2 ± 10.5) outperforming the traditional learning group (22.1 ± 10.2), with (p < 0.05). Similarly, there was a notable improvement in adaptive healthy measures scores post-intervention, with the web-based learning group (8.9 ± 2.4) showing better results than the traditional group (6.5 ± 2.9), with (p < 0.05). In terms of attitudes toward PCOS, the web-based group (18.2 ± 4.9) displayed a significant improvement compared to the traditional group (11.7 ± 5.2), with (p < 0.05). CONCLUSIONS: The findings suggest that web-based learning is more effective than traditional methods in enhancing nursing students' knowledge, adaptive healthy measures, and attitudes toward PCOS. TRIAL REGISTRATION: This study was registered by Clinical Trials.gov Identifier: (NCT06192381|| https://www. CLINICALTRIALS: gov/ ) on 5-1-2024.

Volumetric assessment of volume stable collagen matrix in maxillary single implant site development: A randomized controlled clinical trial.

INTRODUCTION: The stability of soft tissue volume around dental implants is an important factor for the final esthetic outcome. The main objective of this study was to compare volume stable collagen matrix (VCMX) versus connective tissue graft (CTG) in the augmentation of soft tissue profiles in single implant sites with a class I Siebert ridge defect. MATERIALS AND METHODS: Twenty patients (14 females and 6 males) were enrolled in the present study. After implant placement and augmentation of the buccal defect by VCMX or CTG, post-operative evaluation of the volumetric changes at the augmented implant site was carried out at 3, 6, and 9 months as primary outcome, clinical and radiographic soft tissue thickness were carried out at baseline and 9-month intervals, visual analog scale (VAS) and oral health impact profile-14 (OHIP14) were recorded 2 weeks after the surgery. RESULTS: A statistically significant difference in soft tissue volume was found between baseline and 3, 6, and 9 months postoperatively in both groups with the highest value at 9 months (136.33 ± 86.80) (mm3) in VCMX and (186.38 ± 57.52) (mm3) in CTG. Soft tissue thickness was significantly increased in both groups at 9 months in comparison to baseline. However, there was a significantly higher increase in soft tissue thickness at 9 months in CTG (3.87 ± 0.91) than in VCMX (2.94 ± 0.31). Regarding the radiographic soft tissue thickness, there was a statistically significant increase in both groups at 9 months in comparison to baseline. However, there was a statistically higher increase in the radiographic soft tissue thickness at 9 months in CTG (3.08 ± 0.97) than in VCMX (2.37 ± 0.29). VAS showed a statistically lower value in VCMX (0.4 ± 0.7) than CTG (2.8 ± 1.48). The OHIP recorded lower values in the VCMX group than the CTG group with no statistical significance. In addition, there was no difference in the PES between the two groups. CONCLUSION: The present study showed that CTG and VCMX were both effective in soft tissue augmentation around implants in the esthetic zone. However, CTG proved more efficient in increasing peri-implant soft tissue volume and mucosal thickness around single implants at a 9-month follow-up period. VCMX was associated with less pain or discomfort and reduced patient morbidity, as reflected by the significantly reduced VAS value in the VCMX group.

Treatment of class I Sibert alveolar ridge defects with volume stable collagen matrix. A case report.

INTRODUCTION AND IMPORTANCE: The soft tissue volume and its stability around dental implants are important for the final aesthetic outcome. CASE PRESENTATION: A 39-year-old female was referred for dental implant placement for her missing tooth. Following attachment of the cover screw VCMX was used to simultaneously augment buccal ridge defect. Patient was seen 2 weeks after surgery for follow up where sutures were removed. After 3 months, patient received her final crown and been on follow up for 9 months where a successful well-functioning restoration with clinically healthy soft tissue and optimal profilometric outcome were maintained. CLINICAL DISCUSSION: This approach is relatively simple, less invasive and time saving as it eliminates the need for another surgical donor site to manage the defect. CONCLUSIONS: The present report showed that VCMX was effective in soft tissue augmentation at implant sites in aesthetic zone. CLINICAL RELEVANCE: Within the limits of this study, the positive results suggest that the volume stable collagen matrix (VCMX) may be a reliable option in treatment of siebert class I ridge defects. VCMX was associated with less amount of pain or discomfort and reduced patient morbidity.

Neutrophil elastase as a versatile cleavage enzyme for activation of αvß3 integrin-targeted small molecule drug conjugates with different payload classes in the tumor microenvironment.

Introduction: The development of bioconjugates for the targeted delivery of anticancer agents is gaining momentum after recent success of antibody drug conjugates (ADCs) in the clinic. Smaller format conjugates may have several advantages including better tumor penetration; however, cellular uptake and trafficking may be substantially different from ADCs. To fully leverage the potential of small molecule drug conjugates (SMDCs) with potent binding molecules mediating tumor homing, novel linker chemistries susceptible for efficient extracellular activation and payload release in the tumor microenvironment (TME) need to be explored. Methods: We designed a novel class of SMDCs, which target αvß3 integrins for tumor homing and are cleaved by neutrophil elastase (NE), a serine protease active in the TME. A peptidomimetic αvß3 ligand was attached via optimized linkers composed of substrate peptide sequences of NE connected to different functional groups of various payload classes, such as camptothecins, monomethyl auristatin E, kinesin spindle protein inhibitors (KSPi) and cyclin-dependent kinase 9 inhibitors (CDK-9i). Results: NE-mediated cleavage was found compatible with the diverse linker attachments via hindered ester bonds, amide bonds and sulfoximide bonds. Efficient and traceless release of the respective payloads was demonstrated in biochemical assays. The newly designed SMDCs were highly stable in buffer as well as in rat and human plasma. Cytotoxicity of the SMDCs in cancer cell lines was clearly dependent on NE. IC50 values were in the nanomolar or sub-nanomolar range across several cancer cell lines reaching similar potencies as compared to the respective payloads only in the presence of NE. In vivo pharmacokinetics evaluating SMDC and free payload exposures in rat and particularly the robust efficacy with good tolerability in triple negative breast and small cell lung cancer murine models demonstrate the utility of this approach for selective delivery of payloads to the tumor. Discussion: These results highlight the broad scope of potential payloads and suitable conjugation chemistries paving the way for future SMDCs harnessing the safety features of targeted delivery approaches in combination with NE cleavage in the TME.

Impact of (nano ZnO/multi-wall CNTs) prepared by arc discharge method on the removal efficiency of stable iodine 127I and radioactive iodine 131I from water.

Radioactive iodine isotopes especially 131I are used for diagnosis and treatment of different types of cancer diseases. Due to the leak of radioactive iodine into the patient's urine in turn, the wastewater would be contaminated, so it is worth preparing a novel adsorption green material to remove the radioactive iodine from wastewater efficiently. The removal of 127I and 131I contaminants from aqueous solution is a problem of interest. Therefore, this work presents a new study for removing the stable iodine 127I- and radioactive iodine 131I from aqueous solutions by using the novel nano adsorbent (Nano ZnO/MWCNTs) which is synthesized by the arc discharge method. It is an economic method for treating contaminated water from undesired dissolved iodine isotopes. The optimal conditions for maximum removal are (5 mg/100 ml) as optimum dose with shacking (200 rpm) for contact time of (60 min), at (25 °C) in an acidic medium of (pH = 5). After the adsorption process, the solution is filtrated and the residual iodide (127I-) is measured at a maximum UV wavelength absorbance of 225 nm. The maximum adsorption capacity is (15.25 mg/g); therefore the prepared nano adsorbent (Nano ZnO/MWCNTs) is suitable for treating polluted water from low iodide concentrations. The adsorption mechanism of 127I- on to the surface of (Nano ZnO/MWCNTs) is multilayer physical adsorption according to Freundlich isotherm model and obeys the Pseudo-first order kinetic model. According to Temkin isotherm model the adsorption is exothermic. The removal efficiency of Nano ZnO/MWCNTs for stable iodine (127I-) from aqueous solutions has reached 97.23%, 89.75%, and 64.78% in case of initial concentrations; 0.1843 ppm, 0.5014 ppm and 1.0331 ppm, respectively. For the prepared radio iodine (131I-) solution of radioactivity (20 µCi), the dose of nano adsorbent was (10 mg/100 ml) and the contact time was (60 min) at (pH = 5) with shacking (200 rpm) at (25 °C). The filtration process was done by using a syringe filter of a pore size (450 nm) after 2 days to equilibrate. The removal efficiency reached (34.16%) after the first cycle of treatment and the percentage of residual radio iodine was (65.86%). The removal efficiency reached (94.76%) after five cycles of treatment and the percentage of residual radio iodine was (5.24%). This last percentage was less than (42.15%) which produces due to the natural decay during 10 days.

Rosuvastatin, but not atorvastatin, enhances the antihypertensive effect of cilostazol in an acute model of hypertension.

PURPOSE: Hypertensive emergency, a sudden and severe increase in blood pressure, necessitates immediate intervention to avoid end-organ damage. Cilostazol, a selective phosphodiesterase-III inhibitor, has vasodilator effect. Here, we investigated the effect of two commonly used statins, atorvastatin or rosuvastatin, on cilostazol antihypertensive activity in acute model of hypertension. METHODS: Hypertensive emergency was induced via angiotensin II intravenous infusion (120 ng.kg-1.min-1). Rats were subjected to real-time arterial hemodynamics and electrocardiogram recording while investigated drugs were injected slowly at cumulative doses 0.5, 1, and 2 mg.kg-1, individually or in combination, followed by baroreflex sensitivity (BRS) analysis and serum electrolytes (Na+ and K+) and vasomodulators (norepinephrine (NE), and nitric oxide (NO)) assessment. RESULTS: Cilostazol reduced systolic blood pressure (SBP), while co-injection with rosuvastatin augmented cilostazol SBP-reduction up to 30 mmHg. Compared to atorvastatin, rosuvastatin boosted the cilostazol-associated reduction in peripheral resistance, as evidenced by further decrease in diastolic, pulse, and dicrotic-notch pressures. Rosuvastatin co-injection prevented cilostazol-induced changes of ejection and non-ejection durations. Additionally, rosuvastatin coadministration produced better restoration of BRS, with an observed augmented increase in BRS indexes from spectral analysis. Greater reduction in sympathetic/parasympathetic ratio and serum NE upon rosuvastatin coadministration indicates further shift in sympathovagal balance towards parasympathetic dominance. Additionally, rosuvastatin coinjection caused a greater decrease in serum sodium, while more increase in NO indicating augmented reduction of extracellular volume and endothelial dysfunction. CONCLUSION: Rosuvastatin boosted cilostazol's antihypertensive actions through effects on peripheral resistance, BRS, sympathovagal balance, endothelial dysfunction, and electrolytes balance, while atorvastatin did not demonstrate a comparable impact.

The hepato- and neuroprotective effect of gold Casuarina equisetifolia bark nano-extract against Chlorpyrifos-induced toxicity in rats.

BACKGROUND: The bark of Casuarina equisetifolia contains several active phytoconstituents that are suitable for the biosynthesis of gold nanoparticles (Au-NPs). These nanoparticles were subsequently evaluated for their effectiveness in reducing the toxicity induced by Chlorpyrifos (CPF) in rats. RESULTS: Various hematological and biochemical measurements were conducted in this study. In addition, markers of oxidative stress and inflammatory reactions quantified in liver and brain tissues were evaluated. Histopathological examinations were performed on both liver and brain tissues. Furthermore, the native electrophoretic protein and isoenzyme patterns were analyzed, and the relative expression levels of apoptotic genes in these tissues were determined. The hematological and biochemical parameters were found to be severely altered in the group injected with CPF. However, the administration of Au-C. equisetifolia nano-extract normalized these levels in all treated groups. The antioxidant system markers showed a significant decrease (P ≤ 0.05) in conjunction with elevated levels of inflammatory and fibrotic markers in both liver and brain tissues of the CPF-injected group. In comparison, the pre-treated group exhibited a reduction in these markers when treated with the nano-extract, as opposed to the CPF-injected group. Additionally, the nano-extract mitigated the severity of histopathological lesions induced by CPF in both liver and brain tissues, with a higher ameliorative effect observed in the pre-treated group. Electrophoretic assays conducted on liver and brain tissues revealed that the nano-extract prevented the qualitative changes induced by CPF in the pre-treated group. Furthermore, the molecular assay demonstrated a significant increase in the relative expression of apoptotic genes in the CPF-injected rats. Although the nano-extract ameliorated the relative expression of these genes compared to the CPF-injected group, it was unable to restore their values to normal levels. CONCLUSION: Our results demonstrated that the nano-extract effectively reduced the toxicity induced by CPF in rats at hematological, biochemical, histopathological, physiological, and molecular levels, in the group pre-treated with the nano-extract.

Knowledge, attitudes, and practices of Female Genital Mutilation / Cutting among healthcare providers in two public hospitals in Egypt: A cross-sectional study.

Female Genital Mutilation / Cutting (FGM/C), also known as female circumcision, is a human rights violation and is still happening to date. Every woman or girl has the right to be protected from this harmful practice. Egypt has adopted a multi-layered strategy to end FGM/C nationwide. Even though considerable progress has been made throughout the country, the practice and inequality still exist. In 2021, The Egyptian Family Health Survey results showed a decrease in the prevalence of circumcision among ever-married women, reaching about 86%, compared to 92% in the latest public estimate of the Demographic Health Survey 2015, where 87% of all women between 15 and 49 years old are circumcised, of which 42.4% reported being circumcised by a healthcare professional (HCP) compared to a reported 47% in 2021. This study aimed to assess healthcare providers' knowledge, attitudes, and practices in two public hospitals in 2 governorates in Egypt using a validated questionnaire conducted among HCPs in Cairo (Urban) and Gharbia (Rural) governorates. A pre-tested questionnaire comprising 38 close-ended questions was used. The study population included 223 HCPs in Cairo and Gharbia governorates, of which 63.7% were women and 36.3% were men, with an average age of 42 years (42±5). 49.8% of the respondents are from an urban area. In the knowledge domain, the highest consequence identified was reduced sexual feelings. In attitudes, almost 63% believed that FGM/C should continue, while 65% agreed that the HCPs have a role in eliminating FGM/C. Almost 4% of our respondents have performed an FGM before, 45% had FGM in their household, and 62% would perform FGM on their daughters. HCPs' integration within the communities allows them to play a crucial role in preventing the practice. It is of utmost importance to compensate for the gap in the curricula of medical schools through informal learning activities and continuing medical education programs for sexual and reproductive health and rights and human rights, as legislation and law enforcement alone cannot eliminate FGM/C from society.

Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription.

Double-hit diffuse large B-cell lymphoma (DH-DLBCL) is an aggressive, and often refractory, type of B-cell non-Hodgkin lymphoma (NHL) characterized by rearrangements in MYC and BCL2. Cyclin-dependent kinase 9 (CDK9) regulates transcriptional elongation and activation of transcription factors, including MYC, making it a potential targeted approach for the treatment of MYC+ lymphomas. Enitociclib is a well-tolerated and clinically active CDK9 inhibitor leading to complete metabolic remissions in 2 of 7 patients with DH-DLBCL treated with once weekly 30 mg intravenous administration. Herein, we investigate the pharmacodynamic effect of CDK9 inhibition in preclinical models and in blood samples from patients [DH-DLBCL (n = 10) and MYC+ NHL (n = 5)] treated with 30 mg i.v. once weekly enitociclib. Enitociclib shows significant regulation of RNA polymerase II Ser2 phosphorylation in a MYC-amplified SU-DHL-4 cell line and depletion of MYC and antiapoptosis protein MCL1 in SU-DHL-4 and MYC-overexpressing SU-DHL-10 cell lines in vitro. Tumor growth inhibition reaching 0.5% of control treated SU-DHL-10 xenografts is achieved in vivo and MYC and MCL1 depletion as well as evidence of apoptosis activation after enitociclib treatment is demonstrated. An unbiased analysis of the genes affected by CDK9 inhibition in both cell lines demonstrates that RNA polymerase II and transcription pathways are primarily affected and novel enitociclib targets such as PHF23 and TP53RK are discovered. These findings are recapitulated in blood samples from enitociclib-treated patients; while MYC downregulation is most robust with enitociclib treatment, other CDK9-regulated targets may be MYC independent delivering a transcriptional downregulation via RNA polymerase II. SIGNIFICANCE: MYC+ lymphomas are refractory to standard of care and novel treatments that downregulate MYC are needed. The utility of enitociclib, a selective CDK9 inhibitor in this patient population, is demonstrated in preclinical models and patients. Enitociclib inhibits RNA polymerase II function conferring a transcriptional shift and depletion of MYC and MCL1. Enitociclib intermittent dosing downregulates transcription factors including MYC, providing a therapeutic window for durable responses in patients with MYC+ lymphoma.

Discovery of VIP236, an αvß3-Targeted Small-Molecule-Drug Conjugate with Neutrophil Elastase-Mediated Activation of 7-Ethyl Camptothecin Payload for Treatment of Solid Tumors.

The emerging field of small-molecule-drug conjugates (SMDCs) using small-molecule biomarker-targeted compounds for tumor homing may provide new perspectives for targeted delivery. Here, for the first time, we disclose the structure and the synthesis of VIP236, an SMDC designed for the treatment of metastatic solid tumors by targeting αvß3 integrins and extracellular cleavage of the 7-ethyl camptothecin payload by neutrophil elastase in the tumor microenvironment. Imaging studies in the Lewis lung mouse model using an elastase cleavable quenched substrate showed pronounced elastase activity in the tumor. Pharmacokinetics studies of VIP236 in tumor-bearing mice demonstrated high stability of the SMDC in plasma and high tumor accumulation of the cleaved payload. Studies in bile-duct-cannulated rats showed that biliary excretion of the unmodified conjugate is the primary route of elimination. Treatment- and time-dependent phosphorylation of H2AX, a marker of DNA damage downstream of topoisomerase 1 inhibition, verified the on-target activity of the payload cleaved from VIP236 in vivo. Treatment with VIP236 resulted in long-lasting tumor regression in subcutaneous patient-derived xenograft (PDX) models from patients with non-small-cell lung, colon, and renal cancer as well as in two orthotopic metastatic triple-negative breast cancer PDX models. In these models, a significant reduction of brain and lung metastases also was observed.

Intraoperative endomanometric laparoscopic Nissen fundoplication improves postoperative outcomes in large sliding hiatus hernias with severe gastroesophageal reflux disease: a retrospective cohort study.

BACKGROUND: Laparoscopic Nissen fundoplication (LNF) is the gold standard surgical intervention for gastroesophageal reflux disease (GERD). LNF can be followed by recurrent symptoms or complications affecting patient satisfaction. The aim of this study is to assess the value of the intraoperative endomanometric evaluation of esophagogastric competence and pressure combined with LNF in patients with large sliding hiatus hernia (>5 cm) with severe GERD (DeMeester score >100). MATERIALS AND METHODS: This is a retrospective, multicenter cohort study. Baseline characteristics, postoperative dysphagia and gas bloat syndrome, recurrent symptoms, and satisfaction were collected from a prospectively maintained database. Outcomes analyzed included recurrent reflux symptoms, postoperative side effects, and satisfaction with surgery. RESULTS: Three hundred sixty patients were stratified into endomanometric LNF (180 patients, LNF+) and LNF alone (180 patients, LNF). Recurrent heartburn (3.9 vs. 8.3%) and recurrent regurgitation (2.2 vs. 5%) showed a lower incidence in the LNF+ group ( P =0.012). Postoperative score III recurrent heartburn and score III regurgitations occurred in 0 vs. 3.3% and 0 vs. 2.8% cases in the LNF+ and LNF groups, respectively ( P =0.005). Postoperative persistent dysphagia and gas bloat syndrome occurred in 1.75 vs. 5.6% and 0 vs. 3.9% of patients ( P =0.001). Score III postoperative persistent dysphagia was 0 vs. 2.8% in the two groups ( P =0.007). There was no redo surgery for dysphagia after LNF+. Patient satisfaction at the end of the study was 93.3 vs. 86.7% in both cohorts, respectively ( P =0.05). CONCLUSIONS: Intraoperative high-resolution manometry and endoscopic were feasible in all patients, and the outcomes were favorable from an effectiveness and safety standpoint.

Frequency of rifampicin-resistant mycobacterium tuberculosis by GeneXpert MTB/RIF assay and its correlates among 2605 probable tuberculosis patients in upper Egypt.

RATIONALE: GeneXpert MTB/RIF (Mycobacterium tuberculosis/rifampicin) assay is a method for detecting rifampicin resistance (RR-MTB) in suspected samples in less than 2 hours with high sensitivity and specificity yield. This study aimed to use the GeneXpert MTB/RIF assay to determine the frequency of RR-MTB and to study the possible influencing correlates associated with positive results. SUBJECTS AND METHODS: This is a retrospective cross-sectional study of patients who visited TB clinic in 5 years (2016-2021). According to the data sheet of the patients, all the collected specimens were divided into 2 parts one for diagnosis by Ziehl-Neelsen stain and the other part for GeneXpert analysis. GeneXpert was also used to look for evidence of RR. RESULTS: Out of the 2605 total samples screened, 718 (27.6%) tested positive for MTB on GeneXpert assay; of them 633 (88.4%) were sensitive to Rifampicin, 83 (11.6%) were resistant to Rifampicin and 2 cases were undetermined. Factors contributing to RR-MTB were: smoker/ex-smoker, with 2.5 times more risk (p = 0.013.0, p = 0.001); recurrence cases had a 4-fold increased risk (p < 0.001); patients with very low M. tuberculosis detected on the GeneXpert MTB/RIF test were 8 times more likely to have RR-TB (P = 0.004). CONCLUSION: This study disclosed a high-rate MTB in Egyptian probable TB cases. Smoking, recurrence and cases with a very low M. tuberculosis burden noticed on the GeneXpert MTB/RIF test had augmented risk of RR-TB.

Hepatobiliary manifestations following two-stages elective laparoscopic restorative proctocolectomy for patients with ulcerative colitis: A prospective observational study.

BACKGROUND: Hepatobiliary manifestations occur in ulcerative colitis (UC) patients. The effect of laparoscopic restorative proctocolectomy (LRP) with ileal pouch anal anastomosis (IPAA) on hepatobiliary manifestations is debated. AIM: To evaluate hepatobiliary changes after two-stages elective laparoscopic restorative proctocolectomy for patients with UC. METHODS: Between June 2013 and June 2018, 167 patients with hepatobiliary symptoms underwent two-stage elective LRP for UC in a prospective observational study. Patients with UC and having at least one hepatobiliary manifestation who underwent LRP with IPAA were included in the study. The patients were followed up for four years to assess the outcomes of hepatobiliary manifestations. RESULTS: The patients' mean age was 36 ± 8 years, and males predominated (67.1%). The most common hepatobiliary diagnostic method was liver biopsy (85.6%), followed by Magnetic resonance cholangiopancreatography (63.5%), Antineutrophil cytoplasmic antibodies (62.5%), abdominal ultrasonography (35.9%), and Endoscopic retrograde cholangiopancreatography (6%). The most common hepatobiliary symptom was Primary sclerosing cholangitis (PSC) (62.3%), followed by fatty liver (16.8%) and gallbladder stone (10.2%). 66.4% of patients showed a stable course after surgery. Progressive or regressive courses occurred in 16.8% of each. Mortality was 6%, and recurrence or progression of symptoms required surgery for 15%. Most PSC patients (87.5%) had a stable course, and only 12.5% became worse. Two-thirds (64.3%) of fatty liver patients showed a regressive course, while one-third (35.7%) showed a stable course. Survival rates were 98.8%, 97%, 95.8%, and 94% at 12 mo, 24 mo, 36 mo, and at the end of the follow-up. CONCLUSION: In patients with UC who had LRP, there is a positive impact on hepatobiliary disease. It caused an improvement in PSC and fatty liver disease. The most prevalent unchanged course was PSC, while the most common improvement was fatty liver disease.

Urinary 20-HETE: A prospective Non-Invasive prognostic and diagnostic marker for diabetic kidney disease.

INTRODUCTION: The identification and validation of a non-invasive prognostic marker for early detection of diabetic kidney disease (DKD) can lead to substantial improvement in therapeutic decision-making. OBJECTIVES: The main objective of this study is to assess the potential role of the arachidonic acid (AA) metabolite 20-hydroxyeicosatetraenoic (20-HETE) in predicting the incidence and progression of DKD. METHODS: Healthy patients and patients with diabetes were recruited from the Hamad General Hospital in Qatar, and urinary 20-HETE levels were measured. Data analysis was done using the Statistical Package for Social Sciences (SPSS). RESULTS: Our results show that urinary 20-HETE-to-creatinine (20-HETE/Cr) ratios were significantly elevated in patients with DKD when compared to patients with diabetes who did not exhibit clinical signs of kidney injury (p < 0.001). This correlation was preserved in the multivariate linear regression accounting for age, diabetes, family history of kidney disease, hypertension, dyslipidemia, stroke and metabolic syndrome. Urinary 20-HETE/Cr ratios were also positively correlated with the severity of kidney injury as indicated by albuminuria levels (p < 0.001). A urinary 20-HETE/Cr ratio of 4.6 pmol/mg discriminated between the presence and absence of kidney disease with a sensitivity of 82.2 % and a specificity of 67.1%. More importantly, a 10-unit increase in urinary 20-HETE/Cr ratio was tied to a 10-fold increase in the risk of developing DKD, suggesting a 20-HETE prognostic efficiency. CONCLUSION: Taken together, our results suggest that urinary 20-HETE levels can potentially be used as non-invasive diagnostic and prognostic markers for DKD.

The role of rectal ultrasound in children with functional constipation.

AIM: The study aimed primarily to compare the transverse rectal diameter in children with functional constipation (FC) and children without constipation in different age groups, and between cases of constipation at baseline and after treatment. Secondary aim was to determine factors that could affect the transverse rectal diameter. METHODS: A controlled prospective study, including a total of 100 children between the ages of 2 and 11 years, who were divided into 50 patients suffering from constipation according to Rome IV criteria and 50 age- and sex-matched controls. Transverse rectal diameter was measured at presentation, and after 3 months of laxative therapy and behavioural modification. RESULTS: Initial rectal diameter was significantly different between cases (3.55 cm (interquartile range, IQR), 3.2-4) and controls (2.3 cm (IQR, 1.8-2.5)), P value < 0.001, and it was also significantly different between those above and below 4 years, so a separate cut-off point for diagnosis of constipation was suggested being >3 cm for the former and >2.5 cm for the latter. After 3 months of follow-up, rectal diameter significantly reduced to become 2.6 (IQR, 2-2.8), P value < 0.001. Duration of symptoms positively correlated with rectal diameter. CONCLUSIONS: Ultrasound measurement of rectal diameter is an important tool to diagnose and follow-up functional constipation in children. Different values of rectal diameter are found between those above and below 4 years of age.

Antifungal Effect of Metabolites from a New Strain Lactiplantibacillus Plantarum LPP703 Isolated from Naturally Fermented Yak Yogurt.

The antifungal effect of metabolites produced by a new strain of Lactiplantibacillus (Lpb.) plantarum LPP703, isolated from naturally fermented yak yogurt, was investigated. The results showed that Lpb. plantarum LPP703 significantly inhibited four fungal species, including Penicillium sp., Rhizopus delemar, Aspergillus flavus, and Aspergillus niger. The metabolites produced after 20 h of Lpb. plantarum LPP703 fermentation showed the highest antifungal activity against Penicillium sp. Compared with the control group, the Lpb. plantarum LPP703 metabolites-treated Penicillium sp. spores were stained red by propidium iodide, indicating that the cell membrane of the fungal spores was damaged. Moreover, the antifungal effect of the Lpb. plantarum LPP703 metabolites on Penicillium sp. was not changed after heating or treatment with various proteases, but showed a sharp decrease when the pH value was regulated to 5.0 or above. The oleamide, trans-cinnamic acid, and citric acid were the three most abundant in the Lpb. plantarum LPP703 metabolites. Molecular docking predicated that the oleamide interacted with the active site of lanosterol 14-alpha-demethylase (CYP51, a crucial enzyme for fungal membrane integrity) through hydrogen bonds and had the lowest docking score, representing the strongest binding affinity to CYP51. Taken together, the metabolites from a new strain of Lpb. plantarum, LPP703, had potent antifungal activity against Penicillium sp., which might be associated with the damage of the active ingredient to fungal membrane integrity. This study indicated that Lpb. plantarum LPP703 and its metabolites might act as biological control agents to prevent fungal growth in the food industry.

VIP152 is a selective CDK9 inhibitor with pre-clinical in vitro and in vivo efficacy in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is effectively treated with targeted therapies including Bruton tyrosine kinase inhibitors and BCL2 antagonists. When these become ineffective, treatment options are limited. Positive transcription elongation factor complex (P-TEFb), a heterodimeric protein complex composed of cyclin dependent kinase 9 (CDK9) and cyclin T1, functions to regulate short half-life transcripts by phosphorylation of RNA Polymerase II (POLII). These transcripts are frequently dysregulated in hematologic malignancies; however, therapies targeting inhibition of P-TEFb have not yet achieved approval for cancer treatment. VIP152 kinome profiling revealed CDK9 as the main enzyme inhibited at 100 nM, with over a 10-fold increase in potency compared with other inhibitors currently in development for this target. VIP152 induced cell death in CLL cell lines and primary patient samples. Transcriptome analysis revealed inhibition of RNA degradation through the AU-Rich Element (ARE) dysregulation. Mechanistically, VIP152 inhibits the assembly of P-TEFb onto the transcription machinery and disturbs binding partners. Finally, immune competent mice engrafted with CLL-like cells of Eµ-MTCP1 over-expressing mice and treated with VIP152 demonstrated reduced disease burden and improvement in overall survival compared to vehicle-treated mice. These data suggest that VIP152 is a highly selective inhibitor of CDK9 that represents an attractive new therapy for CLL.

The modulation and mechanism of probiotic-derived polysaccharide capsules on the immune response in allergic diseases.

Allergic diseases, derived from the dysregulation of immune tolerance mechanisms, have been rising in the last two decades. Recently, increasing evidence has shown that probiotic-derived polysaccharide capsules exhibit a protective effect against allergic diseases, involving regulation of Th1/Th2 balance, induction of differentiation of T regulatory cells and activation of dendritic cells (DCs). DCs have a central role in controlling the immune response through their interaction with gut microbiota via their pattern recognition receptors, including Toll-like receptors and C-type-lectin receptors. This review discusses the effects and critical mechanism of probiotic-derived polysaccharide capsules in regulating the immune system to alleviate allergic diseases. We first describe the development of immune response in allergic diseases and recent relevant findings. Particular emphasis is placed on the effects of probiotic-derived polysaccharide capsules on allergic immune response. Then, we discuss the underlying mechanism of the impact of probiotic-derived polysaccharide capsules on DCs-mediated immune tolerance induction.

New Insights into the Structural Requirements of Isatin-Derived Pro-Apoptotic Agents against Acute Myeloid Leukemia.

Searching for bioactive compounds within the huge chemical space is like trying to find a needle in a haystack. Isatin is a unique natural compound which is endowed with different bio-pertinent activities, especially in cancer therapy. Herein, we envisaged that adopting a hybrid strategy of isatin and α,ß-unsaturated ketone would afford new chemical entities with strong chemotherapeutic potential. Of interest, compounds 5b and 5g demonstrated significant antiproliferative activities against different cancer genotypes according to NCI-60 screening. Concomitantly, their IC50 against HL-60 cells were 0.38 ± 0.08 and 0.57 ± 0.05 µM, respectively, demonstrating remarkable apoptosis and moderate cell cycle arrest at G1 phase. Intriguingly, an impressive safety profile for 5b was reflected by a 37.2 times selectivity against HL-60 over PBMC from a healthy donor. This provoked us to further explore their mechanism of action by in vitro and in silico tools. Conclusively, 5b and 5g stand out as strong chemotherapeutic agents that hold clinical promise against acute myeloid leukemia.