Correlation between forkhead box P3 (rs3761548) gene polymorphism and serum interleukin13 as biomarkers of severity in Egyptian allergic conjunctivitis: a retrospective study.

Introduction: The genetic variants that alter human Forkhead Box P3 (FOXP3) function may have a part in the establishment of allergic conjunctivitis. Our study aimed to evaluate the FOXP3 polymorphism, serum interleukin13 (IL13) and total immunoglobulin E (IgE) levels in allergic conjunctivitis and assess their role as biomarkers for allergic conjunctivitis risk and severity. Methods: This study included 52 cases and 52 controls. Blood samples were taken from allergic conjunctivitis patients and controls for total IgE, IL13 measurement and detection of FOXP3 (rs3761548) gene polymorphism. Results: There was a statistically significant difference between the allergic conjunctivitis group and healthy control group regarding FOXP3 (rs3761548) polymorphism with those have AA genotype are 12 times at risk for allergic conjunctivitis and A allele increases the risk of allergic conjunctivitis by about 4 times. There was statistically significant difference between mild/moderate and severe allergic conjunctivitis regarding FOXP3 (rs3761548) polymorphism with those have AA genotype are 53 times at risk for severe allergic conjunctivitis and A allele increases the risk of severe allergic conjunctivitis by about 6 times. Also, there was a significantly higher value of total IgE IU/ml, IL13 Pg/ml value in severe allergic conjunctivitis compared to moderate/mild allergic conjunctivitis. The best cutoff values of total IgE and serum IL13 for detecting the severity of allergic conjunctivitis were ≥320 IU/ml and ≥40 Pg/ml and the area under the curve were 0.89 and 0.95 respectively. Conclusion: The research significantly contributes to find correlation of FOXP3 polymorphism, total IgE and IL13 with risk and severity of allergic conjunctivitis which are limited in the literature on the perceived value relevance of FOXP3 polymorphism in allergic conjunctivitis risk and severity.

Analysis of Pancreatic Cancer Genetic Risk Factors in a Multi-Ethnic Population Sample.

Background: Pancreatic cancer (PC) has one of the highest mortality to incidence ratio of all cancers. Early identification of at-risk individuals should permit early diagnosis. Genome-wide association studies showed the association of several genetic variants with PC risk in multi-ethnic populations. Our objective was to examine the association of these genetic variants with PC in a population sample from Kuwait. Methods: DNA samples from 103 pancreatic ductal adenocarcinoma (PDAC) specimens and 132 healthy controls were used for genotyping ABO rs505922, BCAR1 rs7190458, LINC-PINT rs6971499, HNF1B rs4795218, VDR rs2228570 rs731236, and PRSS1 rs111033565 rs111033568 rs387906698 and rs267606982 using TaqMan genotyping assays, and VDR expression was performed by immunocytochemistry. Results: ABO rs505922C and VDR rs2228570A were associated with PDAC risk (odds ratio (OR): 1.55, 95% confidence interval (CI): 1.07 - 2.24, P = 0.027; OR: 1.64, 95% CI: 1.09 - 2.48, P = 0.024; respectively). An unweighted polygenic risk score (ABO rs505922, BCAR1 rs7190458, LINC-PINT rs6971499, and HNF1B rs4795218) was significantly associated with PDAC risk (ß: -0.11, 95% CI: -0.15 to -0.05, P < 0.001). VDR expression was downregulated or absent in most PDAC specimens regardless of VDR haplotype. Conclusion: ABO rs505922C and VDR rs2228570A are PDAC genetic risk factors in our population. Ethnicity influences the association of reported genetic PDAC risk factors and should be adjusted for when performing PDAC genetic risk estimations. Investigation of these genetic risk factors in other ethnic populations is a necessity to evaluate their PDAC risk prediction potential.

Involvement of a battery of investigated genes in lipid droplet pathophysiology and associated comorbidities.

Lipid droplets (LDs) are highly specialized energy storage organelles involved in the maintenance of lipid homoeostasis by regulating lipid flux within white adipose tissue (WAT). The physiological function of adipocytes and LDs can be compromised by mutations in several genes, leading to NEFA-induced lipotoxicity, which ultimately manifests as metabolic complications, predominantly in the form of dyslipidemia, ectopic fat accumulation, and insulin resistance. In this review, we delineate the effects of mutations and deficiencies in genes - CIDEC, PPARG, BSCL2, AGPAT2, PLIN1, LIPE, LMNA, CAV1, CEACAM1, and INSR - involved in lipid droplet metabolism and their associated pathophysiological impairments, highlighting their roles in the development of lipodystrophies and metabolic dysfunction.

Oncology Nurses' Communication Practices and Challenges Towards Advance Care Planning: A Sequential Explanatory Mixed-Method Study.

AIMS: This study aims to explore the practice of advance care planning (ACP) among Chinese oncology nurses and identify challenges influencing care provision. DESIGN: A sequential explanatory mixed-method design was employed, comprising a quantitative phase to assess communication practices, followed by a qualitative phase to explore the challenges faced in ACP. METHODS: The study employed convenience sampling, including 532 oncology nurses from seven hospitals in northern China. Quantitative data were collected through a cross-sectional survey and the ACP communication index from December 2021 to January 2022. The qualitative phase consisted of 19 interviews conducted between May and July 2022, which were thematically analysed to elucidate the challenges in ACP practices. RESULTS: Quantitative findings revealed a low frequency of ACP communication among Chinese oncology nurses. Qualitative analysis identified four themes: lack of optimal timing, passive engagement of patients or families, reluctance of healthcare professionals and unsupported policies. CONCLUSION: The study concluded that identified challenges compromise the effectiveness of ACP practices among Chinese oncology nurses. Inadequate communication, limited interdisciplinary collaboration and policy gaps contribute to nonstandardised ACP processes. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: The findings underscore the need for targeted interventions to enhance nurses' communication skills, foster interdisciplinary collaboration and provide policy support. Such interventions are pivotal to optimising end-of-life care in oncology settings and facilitating the integration of ACP into routine nursing practices. REPORTING METHODS: This study adhered to the Mixed Methods Article Reporting Standards. PATIENT OR PUBLIC CONTRIBUTION: No contributions from patients or the public were involved in this study.

Design and evaluation of sulfadiazine derivatives as potent dual inhibitors of EGFRWT and EGFRT790M: integrating biological, molecular docking, and ADMET analysis.

A series of derivatives (5-14) were synthesized through the diazotization of sulfadiazine with active methylene compounds. The chemical structures of these newly designed compounds were validated through spectral and elemental analysis techniques. The antiproliferative potential of derivatives 5-14 was assessed against three distinct cancer cell lines (A431, A549, and H1975) using the MTT assay. The results revealed that compounds 8, 12, and 14 exhibited the most potent antiproliferative activity, with IC50 values ranging from 2.31 to 7.56 µM. Notably, these values were significantly lower than those of known EGFR inhibitors, including erlotinib, gefitinib, and osimertinib, suggesting the potential of these derivatives as novel antiproliferative agents. Furthermore, compound 12 was identified as the most potent inhibitor of both EGFRWT and EGFRT790M protein kinases, with IC50 values of 14.5 and 35.4 nM, respectively. These results outperformed those of gefitinib and osimertinib, which exhibited IC50 values of 18.2 and 368.2 nM, and 57.8 and 8.5 nM, respectively. Molecular docking studies of compounds 8, 12, and 14 within the ATP-binding sites of both EGFRWT and EGFRT790M corroborated the in vitro results when compared to erlotinib, gefitinib, and osimertinib. The docking results indicated that compound 8 exhibited a favorable binding affinity for both EGFRWT and EGFRT790M, with binding scores of -6.40 kcal mol-1 and -7.53 kcal mol-1, respectively, which were comparable to those of gefitinib and osimertinib, with binding scores of -8.01 and -8.72 kcal mol-1, respectively. Furthermore, an assessment of the most promising EGFR inhibitors (8, 12, and 14) using the egg-boiled method for their in silico ADME properties revealed significant lipophilicity, blood-brain barrier (BBB) penetration, and gastrointestinal (GIT) absorption. Collectively, our designed analogs, particularly compounds 8, 12, and 14, exhibit promising dual antiproliferative and EGFRWT and EGFRT790M kinase inhibitory properties, positioning them as efficient candidates for further therapeutic development.

The influence of arch shape on the incidence of third molar impaction: A cross-sectional study.

Introduction: Impaction of third molar is a pathological problem that reduces the chance of normal eruption of tooth. The main reason for impaction is inadequate space in the maxillary and mandibular arch. The aim of this study is to investigate the relationship between arch shape and the prevalence of third molar impaction. Methods: This cross­sectional study was performed on patients referring to the Department of Oral and Maxillofacial Surgery between December 2023 and February 2024 to obtain an orthopantomogram (OPG). Convenience sampling was employed, and orthopantomograms were analyzed to determine impaction types. Dental arch shape variables were assessed using Budiman's analysis, with a Chi-square test employed to evaluate any significant association between arch shape and impaction type at a significance level of 0.05. Results: Among the 185 maxilla and 185 mandibles studied, 154 were male patients, and 216 were female patients, with a mean age of 26.75 years. A statistically significant difference was found in impacted teeth, among females having more impacted molars than males (p-value = 0.002*). However, no significant differences were found in the type of impaction, Gregory classification, or position based on the shape of the mandible on both the right and left sides (p-value > 0.05). Similarly, no significant differences were observed in Gregory's classification based on the shape of the maxilla on both the right and left sides. However, there is a statistically significant difference in the occurrence impaction based on the maxilla's shape (p-value < 0.05). Conclusion: The study suggests a significant correlation between maxillary arch shape and the occurrence of third molar impaction, with a higher prevalence among females.

A Hypercalcemic Crisis Complicating Subcutaneous Fat Necrosis of the Newborn: A Case Report and Literature Review.

Subcutaneous fat necrosis of the newborn (SFNN) is a rare panniculitis that is characterized by the presence of skin nodules. Although SFNN is a self-limited benign disease, effective follow-up is highly recommended to detect hypercalcemia and other complications early on. A male newborn was admitted twice to the neonatal intensive care unit (NICU). The first NICU admission was for hypoglycemia, and the second was due to late-onset sepsis, in which reddish nodules were detected on the back, flanks, shoulders, and posterior aspects of the legs. At 44 days old, the infant was referred to the emergency department due to a hypercalcemic crisis. Screening for other SFNN complications revealed eosinophilia, hypoglycemia, and nephrocalcinosis. The hospitalization was further complicated by a rare occurrence of deep venous thrombosis. The calcium level was followed up to ensure the patient's recovery. This case highlights the complications that might follow SFNN and emphasizes the importance of its surveillance.

Temporary Conjunctival Flap Plus Medical Treatment Versus Medical Treatment Only for High-Risk Fungal Keratitis: A Randomized Controlled Trial.

PURPOSE: The purpose of this study was to evaluate the efficacy of temporary conjunctival flap with topical natamycin and oral voriconazole compared with medical treatment only in reducing the rate of perforation in high-risk fungal keratitis. METHODS: Sixty-two eyes of 62 patients with severe fungal keratitis were examined; only 54 patients were enrolled and divided randomly into 2 groups. The first group received medical treatment only in the form of topical natamycin 5% together with oral voriconazole 200 mg, while the second group received the same medical treatment plus a temporary conjunctival flap that was removed after 2 weeks. Five patients were lost during the follow-up, and only 49 patients were statistically analyzed. All patients were examined frequently until reepithelialization or the development of perforation. RESULTS: Fifteen perforations were reported, with a higher rate among the medical group (48%) compared with the conjunctival flap group (12.5%), with P value <0.05. A significant delay was noted in reepithelialization time in the medical group compared with the conjunctival flap group (mean time was 21.69 ± 5.41 and 15.36 ± 2.2 days, respectively), with P value = 0.001. Significant improvement in visual acuity was reported over time when comparing baseline versus 3-month visual acuity in the same group using paired t sample test (P value was 0.003 and <0.001 in the first and second group, respectively). CONCLUSIONS: Temporary conjunctival flap is associated with a lower perforation rate compared with medical treatment only in severe fungal keratitis, which can provide a cheap and available alternative to therapeutic penetrating keratoplasty.

Bilateral simultaneous acute angle closure glaucoma triggered by an over-the-counter cold and influenza medication.

A woman in her mid-60s who is a high hypermetrope presented with bilateral eye pain and headache approximately 1 hour after taking a single dose of a widely available decongestant containing paracetamol, guaifenesin and phenylephrine hydrochloride for coryzal symptoms. She had previous successful bilateral peripheral iridotomies performed for narrow angles. At presentation, her intraocular pressures (IOPs) were significantly raised at 72 mm Hg and 66 mm Hg in the right and left eye, respectively, with bilateral corneal oedema. Her IOP was normalised with urgent treatment using 500 mg intravenous acetazolamide, pilocarpine 2%, dexamethasone 0.1% and IOP-lowering drops. She was listed for cataract surgery and was advised to avoid the precipitating agent and other over-the-counter decongestants. This is the first reported case of bilateral angle closure triggered by a decongestant with such a combination of ingredients. Clinicians should be aware of this rare side effect for prompt diagnosis and management.

Super-response to renal denervation in treatment-resistant essential hypertension.

Renal denervation may be indicated in patients with treatment-resistant essential hypertension to decrease sympathetic nervous activity and optimise blood pressure. We present the case of a woman in her 50s with long-standing essential hypertension, a previous transient ischaemic attack, obesity and a family history of cardiovascular disease, who presented with persistent 24-hour ambulatory hypertension despite ongoing lifestyle modifications and being on five antihypertensive agents with no evidence of an alternative primary aetiology. She had intermittent palpitations and blurring of vision alongside evidence of left ventricular hypertrophy on a CT scan. She underwent renal denervation, following which, not only was she able to cease all antihypertensive therapy but managed to maintain optimised blood pressure with subsequent reversal of left ventricular hypertrophy. Trials have demonstrated modest but inconsistent reductions in blood pressure whereas our case represents a 'super-response' likely due to a higher number of circumferential ablations in comparison to previous studies.

Multicomponent reaction for synthesis, molecular docking, and anti-inflammatory evaluation of novel indole-thiazole hybrid derivatives.

In this article, novel thiazol-indolin-2-one derivatives 4a-f have been synthesized via treatment of thiosemicarbazide (1) with some isatin derivative 2a-f and N-(4-(2-bromoacetyl)phenyl)-4-tolyl-sulfonamide (3) under reflux in ethanol in the presence of triethyl amine (TEA). The structures of new products were elucidated by elemental and spectral analyses. Moreover, all compounds were investigated for their in vivo anti-inflammatory activity using celecoxib as a reference drug. The target compound 4b was the most active anti-inflammatory candidate and exhibited higher edema inhibition (EI = 38.50%) than that recorded by celecoxib (EI = 34.58%) after 3 h. Furthermore, the most active compounds 4b and 4f were subjected to a molecular docking study inside COX-2 enzyme to show their binding interactions. Both compounds 4b and 4f showed good fitting into COX-2 binding site with docking energy scores - 11.45 kcal/mol and - 10.48 kcal/mol, respectively which indicated that compound 4b revealed the most promising and effective anti-inflammatory potential.

Catalyzed syntheses of novel series of spiro thiazolidinone derivatives with nano Fe2O3: spectroscopic, X-ray, Hirshfeld surface, DFT, biological and docking evaluations.

Twelve spiro thiazolidinone compounds (A-L) were synthesized via either conventional thermal or ultrasonication techniques using Fe2O3 nanoparticles. The modification of the traditional procedure by using Fe2O3 nanoparticles led to enhancement of the yield of the desired candidates to 78-93% in approximately half reaction time compared with 58-79% without catalyst. The products were fully characterized using different analytical and spectroscopic techniques. The structure of the two derivatives 4-phenyl-1-thia-4-azaspirodecan-3-one (A) and 4-(p-tolyl)-1-thia-4-azaspirodecan-3-one (B) were also determined using single crystal X-ray diffraction and Hirshfeld surface analysis. The two compounds (A and B) were crystallized in the orthorhombic system with Pbca and P212121 space groups, respectively. In addition, the crystal packing of compounds revealed the formation of supramolecular array with a net of intermolecular hydrogen bonding interactions. The energy optimized geometries of some selected derivatives were performed by density functional theory (DFT/B3LYP). The reactivity descriptors were also calculated and correlated with their biological properties. All the reported compounds were screened for antimicrobial inhibitions. The two derivatives, F and J, exhibited the highest levels of bacterial inhibition with an inhibition zone of 10-17 mm. Also, the two derivatives, F and J, displayed the most potent fungal inhibition with an inhibition zone of 15-23 mm. Molecular docking investigations of some selected derivatives were performed using a B-DNA (PDB: 1BNA) as a macromolecular target. Structure and activity relationship of the reported compounds were correlated with the data of antimicrobial activities and the computed reactivity parameters.

Contraindications to tissue plasminogen activator thrombolysis for acute lower extremity ischemia.

OBJECTIVE: Previous randomized prospective trials have demonstrated the effectiveness of transcatheter tissue plasminogen activator (tPA) thrombolysis in treating acute limb ischemia (ALI) compared to conventional surgery. These pivotal trials have also highlighted contraindications for these procedures. Given recent advancements in techniques and technology, our aim is to reassess the relevance of these contraindications in contemporary practice. METHODS: A retrospective chart analysis was performed utilizing the inpatient medical records of consecutive individuals who underwent tPA treatment for acute limb ischemia (ALI) from September 2016 to April 2022. Inclusion criteria encompassed patients aged 18 and above displaying clinical symptoms and imaging evidence of ALI within 14 days. All patients received tPA with suction thrombectomy following the fast-track thrombolysis protocol. In cases where a persistent thrombus or stenosis was detected, catheter-directed thrombolysis was considered overnight, and patients underwent angiography and reassessment in the operating room subsequently. RESULTS: Patients were classified into two groups based on the STILE trial's established contraindications for endovascular treatment in acute limb ischemia (ALI). If a patient had any of these contraindications, they were placed in the contraindicated group. This resulted in 24 patients (32%) in the contraindicated group and 52 patients (68%) in the non-contraindicated group. No statistically significant demographic variations were observed between these groups. Contraindications in our study included uncontrolled hypertension (12/24, 50%), recent invasive procedures (7/27, 29%), history of cerebrovascular accident (CVA) within 6 months (3/24, 12%), and intracranial malformation/neoplasms (2/24, 8%). Three patients within the non-contraindicated group experienced bleeding complications: two with puncture site bleeds and one with nasal bleeding. In contrast, one patient in the contraindicated group had transient postoperative hematuria. There were no significant differences in bleeding complications observed between the two groups (p = .771). Additionally, no amputations were observed within our population. CONCLUSIONS: In light of our study results and advancements in endovascular therapies, we can now safely and efficiently treat patients who were previously considered contraindicated for such treatments. It is essential to individualize treatments and carefully balance the risks and benefits of endovascular versus open surgical revascularization for these patients. Additionally, we believe that the nearly 30-year-old guidelines for endovascular therapies need to be revisited and updated to align with modern technology.

Methods for Bioinformatic Prediction of Genuine sRNAs from Outer Membrane Vesicles.

The molecular pathogenesis of Gram-negative bacteria remains a complex and incompletely understood phenomenon. Various factors are believed to contribute to the pathogenicity of these bacteria. One key mechanism utilized by Gram-negative bacteria is the production of outer membrane vesicles (OMVs), which are small spherical particles derived from the bacterial outer membrane. These OMVs are crucial in delivering virulence factors to the host, facilitating host-pathogen interactions. Within these OMVs, small regulatory RNAs (sRNAs) have been identified as important players in modulating the host immune response. One of the main challenges in studying OMVs and their cargo of sRNAs is the difficulty in isolating and purifying sufficient quantities of OMVs, as well as accurately predicting genuine sRNAs computationally. In this chapter, we present protocols aimed at overcoming these obstacles.

Headache attributed to ischemic stroke - a new scope for management: a case study.

Acute ischemic stroke may present with serious clinical manifestations. Headache attributed to ischemic stroke is one of these clinical manifestations which may be neglected and affect the functional outcome of the patients. Understanding the exact pathophysiology, and recognition of the most clinical and radiological predictors can help to provide good management and open scope for prophylactic approaches. Here, we report a case presented with acute onset of ischemic stroke and developed a new onset headache on the first day of stroke onset. According to the International Classification of Headache Disorders third edition (ICHD-3), the patient has a post-stroke headache. Using transcranial duplex ultrasound, activation of the trigeminovascular pathway could be attributed to the opening of more pain-sensitive collateral channels as the left posterior communicating artery (P Com A). In conclusion, we can predict the development of acute headache at stroke onset based on different clinical and radiological factors. Opening of the collateral channels is strongly implicated in the production of post-stroke headache.

Association of postoperative delirium with hypotension in critically ill patients after cardiac surgery: a prospective observational study.

BACKGROUND: Postoperative delirium (POD), an acute and variable disturbance in cognitive function, is an intricate and elusive phenomenon that occurs after cardiac surgery. Despite progress in surgical techniques and perioperative management, POD remains a formidable challenge, imposing a significant burden on patients, caregivers, and healthcare systems. METHODS: This prospective observational study involved 307 patients who underwent cardiac surgery. Data on the occurrence of delirium, clinical parameters, and postoperative characteristics were collected. A multivariate analysis was performed to assess the relationship between POH and POD. RESULTS: Sixty-one patients (21%) developed delirium, with an average onset of approximately 5 days postoperatively and a duration of approximately 6 days. On multivariate analysis, POH was significantly associated with POD, and the adjusted odds ratios indicated that patients with POH were more likely to develop delirium (OR, 5.61; p = 0.006). Advanced age (OR, 1.11; p = 0.002), emergency surgery (OR, 8.31; p = 0.001), and on-pump coronary artery bypass grafting were identified as risk factors of POD. Patients who developed delirium were typically older, more likely to be male, and had higher morbidity rates than those who did not. CONCLUSION: POH is significantly associated with delirium in critically ill patients after cardiac surgery. Surgical complexity and advanced age contribute to the risk of developing POD and poor postoperative outcomes.

Production of Fucoxanthin from Microalgae Isochrysis galbana of Djibouti: Optimization, Correlation with Antioxidant Potential, and Bioinformatics Approaches.

Fucoxanthin, a carotenoid with remarkable antioxidant properties, has considerable potential for high-value biotechnological applications in the pharmaceutical, nutraceutical, and cosmeceutical fields. However, conventional extraction methods of this molecule from microalgae are limited in terms of cost-effectiveness. This study focused on optimizing biomass and fucoxanthin production from Isochrysis galbana, isolated from the coast of Tadjoura (Djibouti), by testing various culture media. The antioxidant potential of the cultures was evaluated based on the concentrations of fucoxanthin, carotenoids, and total phenols. Different nutrient formulations were tested to determine the optimal combination for a maximum biomass yield. Using the statistical methodology of principal component analysis, Walne and Guillard F/2 media were identified as the most promising, reaching a maximum fucoxanthin yield of 7.8 mg/g. Multiple regression models showed a strong correlation between antioxidant activity and the concentration of fucoxanthin produced. A thorough study of the optimization of I. galbana growth conditions, using a design of experiments, revealed that air flow rate and CO2 flow rate were the most influential factors on fucoxanthin production, reaching a value of 13.4 mg/g. Finally, to validate the antioxidant potential of fucoxanthin, an in silico analysis based on molecular docking was performed, showing that fucoxanthin interacts with antioxidant proteins (3FS1, 3L2C, and 8BBK). This research not only confirmed the positive results of I. galbana cultivation in terms of antioxidant activity, but also provided essential information for the optimization of fucoxanthin production, opening up promising prospects for industrial applications and future research.