Polyvinyl alcohol-chitosan-polyethylene glycol-glycerol incorporated with Peganum harmala loaded in lipid nanocapsules as an elastic nanocomposite surgical sealant to control bleeding.

Uncontrolled hemorrhage remains a critical threat in trauma and surgery. This study developed a novel hemostatic composite by encapsulating Peganum harmala L. seed extract (PH) with known hemostatic properties into lipid nanocapsules (PH-LNCs) and then embedding them within a polyvinyl alcohol-chitosan-polyethylene glycol-glycerol (PVA-CS-PEG-G) matrix. The composite was physically crosslinked via the dual processes of freezing-thawing and thermally crosslinking for robust mechanical properties reaching 0.434 ±â€¯0.014 MPa and elasticity of 40.685 % ±â€¯4.04. It also demonstrated excellent biocompatibility, surface morphology, physical stability, and ex-vivo skin deposition/permeation were assessed. The characterization of PH-LNCs revealed optimal PH-LNC formation and successful integration into the composite with particle size, zeta potential, and PDI were approximately 45.45 ±â€¯24 nm, -16.3 ±â€¯1.4 mV, and 0.374 ±â€¯0.1, respectively. In vitro studies highlighted enhanced blood clotting and platelet adhesion, while in vivo experiments confirmed superior hemostatic efficacy in a mouse tail amputation model. The composite's soft texture, conformability, and mechanical strength make it a promising candidate for effective traumatic wound management.

Early Detection of Lymph Node Metastasis Using Primary Head and Neck Cancer Computed Tomography and Fluorescence Lifetime Imaging.

Objectives: Early detection and accurate diagnosis of lymph node metastasis (LNM) in head and neck cancer (HNC) are crucial for enhancing patient prognosis and survival rates. Current imaging methods have limitations, necessitating new evaluation of new diagnostic techniques. This study investigates the potential of combining pre-operative CT and intra-operative fluorescence lifetime imaging (FLIm) to enhance LNM prediction in HNC using primary tumor signatures. Methods: CT and FLIm data were collected from 46 HNC patients. A total of 42 FLIm features and 924 CT radiomic features were extracted from the primary tumor site and fused. A support vector machine (SVM) model with a radial basis function kernel was trained to predict LNM. Hyperparameter tuning was conducted using 10-fold nested cross-validation. Prediction performance was evaluated using balanced accuracy (bACC) and the area under the ROC curve (AUC). Results: The model, leveraging combined CT and FLIm features, demonstrated improved testing accuracy (bACC: 0.71, AUC: 0.79) over the CT-only (bACC: 0.58, AUC: 0.67) and FLIm-only (bACC: 0.61, AUC: 0.72) models. Feature selection identified that a subset of 10 FLIm and 10 CT features provided optimal predictive capability. Feature contribution analysis identified high-pass and low-pass wavelet-filtered CT images as well as Laguerre coefficients from FLIm as key predictors. Conclusions: Combining CT and FLIm of the primary tumor improves the prediction of HNC LNM compared to either modality alone. Significance: This study underscores the potential of combining pre-operative radiomics with intra-operative FLIm for more accurate LNM prediction in HNC, offering promise to enhance patient outcomes.

A Contemporary Review of Blood Transfusion in Critically Ill Patients.

Blood transfusion is a common therapeutic intervention in hospitalized patients. There are numerous indications for transfusion, including anemia and coagulopathy with deficiency of single or multiple coagulation components such as platelets or coagulation factors. Nevertheless, the practice of transfusion in critically ill patients has been controversial mainly due to a lack of evidence and the need to consider the appropriate clinical context for transfusion. Further, transfusion carries many risk factors that must be balanced with benefits. Therefore, transfusion practice in ICU patients has constantly evolved, and we endeavor to present a contemporary review of transfusion practices in this population guided by clinical trials and expert guidelines.

Cleft Lip Surgery in Sudan: Clinical Presentations, Early Outcomes, and Patient and Professional Satisfaction: A sub-Saharan African experience.

Background: Cleft lip and palate are the most common congenital craniofacial anomalies. They account for approximately 13% of all congenital anomalies. Objectives: To study the presentation of cleft lip and the early results of surgical repair among patients who presented to our centers. Methods: This was a hospital-based prospective cohort study of 72 patients who underwent cleft lip repair in Sudan. Results: The commonest age group was between 10-18 months. The male-to-female ratio was 2:1, and a family history of cleft lip was found in 2.8% of patients. The cleft lip was complete in 81.9%, incomplete in 12.5%, and hybrid in 5.6% of patients. Associated cleft palate was observed in 54 patients. Associated syndromes were found in 10 patients. The surgery was carried out in most patients at 9 months or less; in 4 patients, it was more than 18 months. Achievement of reasonable lip repair was moderate (50% collectively). High achievement was observed for criteria, such as accurate union (90.3%), and sub-moderate achievement in even vermillion border and cupid's bow (44%), low nose symmetry (30.6%), and quality of scar (18.1%). Early complications were reported at the rate of 13.9%. Patient satisfaction was 59.7%; however, the professionals showed higher satisfaction levels (66.7%). The anthropometric measurements of normal infants were moderately similar to those of the infants who underwent surgery. Conclusion: The patients with cleft lip showed early presentation, with a predominance of the male gender and left side pattern. The preliminary outcome of cleft lip repair was moderate, with variations in different criteria. Patient and professional satisfaction were above average.

Efficacy of propolis and royal jelly in attenuating cadmium-induced spermatogenesis and steroidogenesis dysregulation, causing infertility in rats.

Bee-derived pharmaceutical products, including propolis (PRO) and royal jelly (ROJ), possess outstanding pharmacological properties. However, their efficiency in counteracting the deleterious influences of cadmium (Cd) in testes and the relevant mechanisms entail further investigations. Therefore, this study sheds light on the therapeutic efficacy of PRO and ROJ against testicular dysfunction and infertility induced by Cd. Toward this end, 30 mature male Wistar albino rats were randomly divided into six groups (5 animals/group), including (I) control, (II) Cd, (III) PRO, (IV) ROJ, (V) PRO + Cd, and (VI) ROJ + Cd groups. Furthermore, antioxidant factors, semen quality, hormonal levels, steroidogenic enzymes, and genotoxicity were assessed. Moreover, histopathological and ultrastructural attributes and offspring rates were investigated. The Cd-treated group revealed marked reductions in reduced glutathione (GSH), total antioxidant capacity (TAC), and superoxide dismutase (SOD) with an amplification of lipid peroxidation in testes, indicating disruption of the antioxidant defense system. Furthermore, myeloperoxidase (MPO) activity and DNA damage were significantly heightened, implying inflammation and genotoxicity, respectively. Moreover, steroidogenic enzymes, including 17ß-Hydroxy Steroid Dehydrogenase 3 (HSD17b3), 3ß-Hydroxy Steroid Dehydrogenase 2 (HSD3b2), 17α-hydroxylase/17,20-lyase (CYP17A1), and steroid 5α-reductase 2 (SRD5A2) were markedly diminished accompanied with disorders in luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. Besides, spermatozoa quality was reduced, associated with a diminution in the diameter of seminiferous tubules. By contrast, PRO or ROJ significantly protected and/or counteracted the Cd-induced pathophysiological consequences, ameliorating antioxidant and inflammatory biomarkers, steroidogenic enzymes, hormonal levels, and sperm properties, along with lessening DNA impairments. Critically, histological and ultrastructural analyses manifested several anomalies in the testicular tissues of the Cd-administered group, including the Leydig and Sertoli cells and spermatozoa. Conversely, PRO or ROJ sustained testicular tissues' structure, enhancing spermatozoa integrity and productivity. Interestingly, treatment with PRO or ROJ improved fertility indices through offspring rates compared to the Cd-animal group. Our data suggest that PRO is a more effective countermeasure than ROJ against Cd toxicity for securing the delicate testicular microenvironment for spermatogenesis and steroidogenesis.

Non-Receptor Tyrosine Kinases: Their Structure and Mechanistic Role in Tumor Progression and Resistance.

Protein tyrosine kinases (PTKs) function as key molecules in the signaling pathways in addition to their impact as a therapeutic target for the treatment of many human diseases, including cancer. PTKs are characterized by their ability to phosphorylate serine, threonine, or tyrosine residues and can thereby rapidly and reversibly alter the function of their protein substrates in the form of significant changes in protein confirmation and affinity for their interaction with protein partners to drive cellular functions under normal and pathological conditions. PTKs are classified into two groups: one of which represents tyrosine kinases, while the other one includes the members of the serine/threonine kinases. The group of tyrosine kinases is subdivided into subgroups: one of them includes the member of receptor tyrosine kinases (RTKs), while the other subgroup includes the member of non-receptor tyrosine kinases (NRTKs). Both these kinase groups function as an "on" or "off" switch in many cellular functions. NRTKs are enzymes which are overexpressed and activated in many cancer types and regulate variable cellular functions in response to extracellular signaling-dependent mechanisms. NRTK-mediated different cellular functions are regulated by kinase-dependent and kinase-independent mechanisms either in the cytoplasm or in the nucleus. Thus, targeting NRTKs is of great interest to improve the treatment strategy of different tumor types. This review deals with the structure and mechanistic role of NRTKs in tumor progression and resistance and their importance as therapeutic targets in tumor therapy.

The role of surgery for invasive pulmonary aspergillosis in paediatric hemato-oncology patients-Can we better define it?

BACKGROUND: Invasive pulmonary aspergillosis (IPA) is a serious condition with high morbidity and mortality in paediatric patients with cancer, haematological diseases or immunodeficiencies with or without allogeneic haematopoietic stem cell transplantation (HSCT). The role of surgical intervention for the management of IPA has scarcely been investigated. OBJECTIVES: The aim of this study was to present a single center experience of management of IPA in paediatric patients of an oncological ward, to determine the short and long-term outcomes after thoracic surgical interventions, and to outline the indications of surgical interventions in selected patients. PATIENTS/METHODS: We conducted a retrospective study of 44 paediatric patients with proven and probable IPA treated in our institution between January 2003 and December 2021. The primary endpoint was the overall survival after surgical interventions. Secondary endpoints included post-operative morbidity and mortality. RESULTS: The median age at diagnosis of IPA in our cohort was 11.79 years (range 0.11-19.6). The underlying conditions were malignancies in 34 (77%) patients and haematological or immunological disorders with allogeneic HSCT in 9 (23%) patients. We performed thoracic surgical interventions in 10 (22.7%) patients. Most patients received a video assisted thoracic surgery. Only one patient died within 90 days after surgery with a median follow-up time of 50 months. No other major post-operative complications occurred. The calculated 5-year survival rate from IPA for patients after surgical intervention with curative intention was 57% and 56% for patients without (p = .8216). CONCLUSIONS: IPA resulted in relevant morbidity and mortality in our paediatric patient cohort. Thoracic surgical interventions are feasible and may be associated with prolonged survival as a part of multidisciplinary approach in selected paediatric patients with IPA. Larger scale studies are necessary to investigate the variables associated with the necessity of surgery.

hTERT Epigenetics Provides New Perspectives for Diagnosis and Evidence-Based Guidance of Chemotherapy in Cancer.

Strong epigenetic pan-cancer biomarkers are required to meet several current, urgent clinical needs and to further improve the present chemotherapeutic standard. We have concentrated on the investigation of epigenetic alteration of the hTERT gene, which is frequently epigenetically dysregulated in a number of cancers in specific developmental stages. Distinct DNA methylation profiles were identified in our data on early urothelial cancer. An efficient EpihTERT assay could be developed utilizing suitable combinations with sequence-dependent thermodynamic parameters to distinguish between differentially methylated states. We infer from this data set, the epigenetic context, and the related literature that a CpG-rich, 2800 bp region, a prominent CpG island, surrounding the transcription start of the hTERT gene is the crucial epigenetic zone for the development of a potent biomarker. In order to accurately describe this region, we have named it "Acheron" (Ἀχέρων). In Greek mythology, this is the river of woe and misery and the path to the underworld. Exploitation of the DNA methylation profiles focused on this region, e.g., idiolocal normalized Methylation Specific PCR (IDLN-MSP), opens up a wide range of new possibilities for diagnosis, determination of prognosis, follow-up, and detection of residual disease. It may also have broad implications for the choice of chemotherapy.

Corneal densitometry changes after femtosecond laser-assisted intracorneal ring segments implantation in keratoconus.

Background: Intrastromal corneal ring segments are commonly implanted in the corneas of eyes with mild-to-moderate keratoconus; however, changes in corneal densitometry (CD) after implantation are a matter of debate in the current literature. We evaluated the changes in CD 1 and 3 months after femtosecond laser-assisted Keraring implantation. Methods: This retrospective, non-comparative, multicenter, case series study included patients with keratoconus who underwent femtosecond laser-assisted implantation of double segments with 90° and 160° arc lengths or two 160° arc length Keraring segments. Demographic and baseline clinical ophthalmic data were recorded. Corneal topography and tomography data acquired using a Pentacam HR Scheimpflug tomography system (Pentacam High Resolution; Oculus, Wetzlar, Germany) with a best-fit sphere were used as a reference surface. Using the Pentacam HR, CD measurements were acquired over a corneal area of 12 mm in total and at four concentric zones (0-2, 2-6, 6-10, and 10-12 mm) of three corneal stromal depths: 120 µm of the anterior corneal stromal layer, 60 µm of the posterior corneal stromal layer, and the central layer of stroma lying between these two layers. Results: We included 40 eyes of 40 patients, including 8 (20%) male and 32 (80%) female individuals, with a mean (standard deviation) age of 21.0 (6.4) years. We observed a significant improvement in the topographic values of steep keratometry (K), flat K, maximum K, and corneal astigmatism (all P < 0.05), but not in the mean K, thinnest corneal pachymetry, corneal thickness at the apex, back elevation, or front elevation (all P > 0.05). The mean total anterior, central, and posterior CD differed significantly among the time points, with a significant increase from the preoperative to the 1-month and 3-month postoperative visits (all P < 0.05) and no difference between those of the 1-month and 3-month postoperative visits (all P > 0.05). The mean CD for the anterior layer in the central, paracentral, and mid-peripheral zones, and the central layer in all four zones, differed significantly among time points, with a significant increase from the preoperative to the 1-month and 3-month postoperative visits (all P < 0.05), which remained unchanged from the 1-month to the 3-month postoperative visit (all P < 0.05), except for the central 2-6-mm zone, which decreased significantly from the 1-month to the 3-month postoperative visit (P < 0.001). The CD of the central 10-12-mm zone did not differ significantly in each pairwise comparison (all P > 0.05). In contrast, CD for the posterior layer in the paracentral zone decreased significantly from the preoperative to the 1-month and 3-month postoperative visits but increased, to a lesser extent, from the 1-month to the 3-month postoperative visit (all P < 0.05). Conclusions: Femtosecond laser-assisted Keraring implantation significantly changes CD, with improvement in most topography parameters. Further longitudinal studies with larger sample sizes are required to verify these preliminary findings.

miRNAs: possible regulators of toll like receptors and inflammatory tumor microenvironment in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is ranked as the third most commonly diagnosed cancer and the third cause of cancer related deaths. CRC is greatly attributed to genetic and epigenetic mutations and immune dysregulation. Tumor aberrant expression of Toll-like Receptors (TLRs) can contribute to tumorigenesis. Recent studies suggested that microRNAs act as direct ligands of TLRs altering their expression and signaling pathways. AIM: To prove our concept that specific miRNA mimics may act as antagonists of their specific toll like receptors inhibiting their expression that could limit the release of pro-inflammatory and pro-tumorigenic cytokines leading to apoptosis of tumor cells. METHODS: From public microarray databases, we retrieved TLRs and miRNAs related to CRC followed by in silico docking of the selected miRNA ligands into the TLRs. Clinical validation after co-immunoprecipitation of TLRs and their interacting miRNA ligands was done. Expression of TLRs 1, 7,8 was determined by ELISA while miRNAs was measured by RT-qPCR. In addition, microRNA mimics of the down regulated miRNAs were transfected into human CRC cell lines. RESULTS: Our data demonstrate that TLRs 1, 7, 8 are up regulated in CRC compared to controls. Further, three miRNAs (-122, -29b and -15b) are relatively downregulated, while 4 miRNAs (-202, miRNA-98, -21 and -let7i) are upregulated in CRC patients compared to those with benign tumor and healthy controls. Transfection of down regulated miRNA mimics into CRC cell lines resulted in a significant reduction of the number and viability of cells as well as down regulating the expression of TLRs 1, 7 and 8 with ultimate reduction of downstream effector IL6 protein, suggesting that these miRNAs are negative regulators of carcinogenesis. CONCLUSION: MicroRNAs could act as antagonistic ligands of TLRs limiting the inflammatory tumor microenvironment.

Etiology, Risk Factors and Outcome of Spontaneous Intracerebral Hemorrhage in Young Adults Admitted to Tertiary Care Hospital in Mogadishu, Somalia.

Introduction: Spontaneous Intracerebral hemorrhage (ICH) in young patients is less common and not well studied compared to ICH in older patients. The etiology, risk factors and outcome of ICH in young patients may have regional and ethnic differences. The study aims to investigate the clinical characteristics, risk factors, etiology and outcome of spontaneous intracerebral hemorrhage in young adults in Somalia. Methods: The study enrolled 168 young patients with ICH (16-50 years) admitted to the neurology department of a tertiary hospital from 2019 to 2022. The information about the demographic details, documented ICH risk factors, etiology and patients' clinical status were retrieved. The etiology of ICH was determined based on clinical, laboratory and radiological findings. Intra-hospital survival status and associated factors were assessed. Results: The mean age of the patients was 35±8.6 years. 99 (59%) of patients were male while 69 (41%) were females. Hypertension 48 (29%) was the most common risk factor, followed by substance abuse. Hypertensive hemorrhage was the most common etiology of ICH 60 (35.7%), followed by cerebral venous thrombosis (CVT) 5(15%), substance abuse 23 (13.7%) and arteriovenous malformation (AVM) in 10 (6%). AVM, CVT, cavernoma, eclampsia, substance abuse and cryptogenic etiology were more common in the 2nd and 3rd decades whereas hypertension was more common in the 4th and 5th decade. Intrahospital mortality was 28% in this study. Factors predicting intrahospital mortality were hematoma volume of greater than 30mL, thrombolytic etiology, brainstem ICH location, substance abuse related etiology, presence of associated mass effect, low GCS score on admission, high systolic blood pressure on admission, and the presence of chronic renal failure. Conclusion: In this study, hypertension, substance abuse, CVT and vascular malformation are the leading causes of ICH in young adults. Intracerebral hemorrhage in the young has different spectrum of etiologies and factors associated with short-term mortality compared to older patients.

Undiagnosed Epileptic Case Since Childhood of Sturge-Weber Syndrome: First Case Report from Somalia.

Sturge-Weber syndrome is a rare, sporadic, progressive neurocutaneous condition that presents with congenital hamartomatous malformations, epilepsy, and a variety of facial symptoms. We discussed a rare case of an eighteen-year-old female child who came to our neurology department with status epilepticus, mental impairment, and a port-wine in the lateral left side of her face. We diagnosed Sturge-Weber syndrome after a thorough neurological and radiological evaluation. The purpose of presenting this case is to illustrate both the characteristic presentation and the complications associated with managing Sturge-Weber syndrome.

Advancements in silk fibroin and silk sericin-based biomaterial applications for cancer therapy and wound dressing formulation: A comprehensive review.

Silks are a class of proteins generated naturally by different arthropods, including silkworms, spiders, scorpions, mites, wasps, and bees. This review discusses the silk fibroin and silk sericin fabricated by Bombyx mori silkworm as versatile fibers. This silk fiber is predominantly composed of hydrophobic silk fibroin and hydrophilic silk sericin. Fibroin is defined as a structural protein that bestows silk with strength, while sericin is characterized as a gum-like protein, tying the two fibrous proteins together and endowing silk proteins with elasticity. Due to their versatile structures, biocompatibility, and biodegradability, they could be tailored into intricate structures to warrant particular demands. The intrinsic functional groups of both proteins enable their functionalization and cross-linking with various biomaterials to endow the matrix with favorable antioxidant and antibacterial properties. Depending on the target applications, they can be integrated with other materials to formulate nanofibrous, hydrogels, films, and micro-nanoparticles. Given the outstanding biological and controllable physicochemical features of fibroin and sericin, they could be exploited in pharmaceutical applications involving tissue engineering, wound repair, drug delivery, and cancer therapy. This review comprehensively discusses the advancements in the implementation of different formulations of silk fibroin and sericin in wound healing and drug delivery systems, particularly for cancer treatment.

Acetamiprid induces cardiotoxicity in rats by dysregulating α7 nAChR and its downstream targets: The ameliorative role of resveratrol.

Acetamiprid (ACP) is a novel neonicotinoid insecticide used for controlling insect pests. Resveratrol (RSV) is a natural polyphenol that possesses anti-oxidant, anti-inflammatory and anti-apoptotic actions. The current research explores the mechanism of ACP-induced cardiotoxicity and the alleviative effects of RSV. Male rats were allocated to four groups of ten each. Rats were treated daily for 90 days via oral route. Control rats received distilled water, ACP rats received 25 mg acetamiprid/kg, RSV rats received 20 mg resveratrol/kg and ACP + RSV rats received both ACP and RSV. ACP exposure increased serum creatine phosphokinase activity and cardiac troponin level. It also induced oxidative stress, as evidenced by the glutathione reduction, and malondialdehyde elevation, as well as the detrimental histopathological and immunohistochemical changes in the myocardium. Gene expression analysis revealed down-regulation in the mRNA expression of the survival-related genes α7 nAChR, Erk and Bcl-2, and up-regulation in the apoptosis-related genes Jnk, Bax and Caspase-3. Conversely, the concomitant administration of ACP with RSV alleviated most of the aforementioned toxic impacts. It can be concluded that ACP induces cardiotoxicity by dysregulating the mRNA expression of α7 nAChR and its downstream targets. Additionally, RSV is proved to be a promising ameliorative agent against ACP-induced cardiotoxicity.

Prediction of the most deleterious non-synonymous SNPs in the human IL1B gene: evidence from bioinformatics analyses.

BACKGROUND: Polymorphisms in IL1B play a significant role in depression, multiple inflammatory-associated disorders, and susceptibility to infection. Functional non-synonymous SNPs (nsSNPs) result in changes in the encoded amino acids, potentially leading to structural and functional alterations in the mutant proteins. So far, most genetic studies have concentrated on SNPs located in the IL1B promoter region, without addressing nsSNPs and their association with multifactorial diseases. Therefore, this study aimed to explore the impact of deleterious nsSNPs retrieved from the dbSNP database on the structure and functions of the IL1B protein. RESULTS: Six web servers (SIFT, PolyPhen-2, PROVEAN, SNPs&GO, PHD-SNP, PANTHER) were used to analyze the impact of 222 missense SNPs on the function and structure of IL1B protein. Five novel nsSNPs (E100K, T240I, S53Y, D128Y, and F228S) were found to be deleterious and had a mutational impact on the structure and function of the IL1B protein. The I-mutant v2.0 and MUPro servers predicted that these mutations decreased the stability of the IL1B protein. Additionally, these five mutations were found to be conserved, underscoring their significance in protein structure and function. Three of them (T240I, D128Y, and F228S) were predicted to be cancer-causing nsSNPs. To analyze the behavior of the mutant structures under physiological conditions, we conducted a 50 ns molecular dynamics simulation using the WebGro online tool. Our findings indicate that the mutant values differ from those of the IL1B wild type in terms of RMSD, RMSF, Rg, SASA, and the number of hydrogen bonds. CONCLUSIONS: This study provides valuable insights into nsSNPs located in the coding regions of IL1B, which lead to direct deleterious effects on the functional and structural aspects of the IL1B protein. Thus, these nsSNPs could be considered significant candidates in the pathogenesis of disorders caused by IL1B dysfunction, contributing to effective drug discovery and the development of precision medications. Thorough research and wet lab experiments are required to verify our findings. Moreover, bioinformatic tools were found valuable in the prediction of deleterious nsSNPs.

Heterologous maternal antibodies derived from infectious bronchitis vaccines prevent the development of lesions associated with false layer syndrome.

Infectious bronchitis virus (IBV) strains of the Delmarva (DMV)/1639 genotype have been causing false layer syndrome (FLS) in the Eastern Canadian layer operations since the end of 2015. FLS is characterized by the development of cystic oviducts in layer pullets infected at an early age. Currently, there are no homologous vaccines for the control of this IBV genotype. Our previous research showed that a heterologous vaccination regimen incorporating Massachusetts (Mass) and Connecticut (Conn) IBV types protects layers against DMV/1639 genotype IBV. The aim of this study was to investigate the role of maternal antibodies conferred by breeders received the same vaccination regimen in the protection against the development of DMV/1639-induced FLS in pullets. Maternal antibody-positive (MA+) and maternal antibody-negative (MA-) female progeny chicks were challenged at 1 day of age and kept under observation for 16 weeks. Oviductal cystic formations were observed in 3 of 14 birds (21.4 %) in the MA- pullets, while the lesions were notably absent in the MA+ pullets. Milder histopathological lesions were observed in the examined tissues of the MA+ pullets. However, the maternal derived immunity failed to demonstrate protection against the damage to the tracheal ciliary activity, viral shedding, and viral tissue distribution. Overall, this study underscores the limitations of maternal derived immunity in preventing certain aspects of viral pathogenesis, emphasizing the need for comprehensive strategies to address different aspects of IBV infection.

Decision-making on peri-implant mucositis management and treatment approaches.

Peri-implant mucositis is characterised by inflammation of soft tissues surrounding a dental implant without associated bone loss beyond initial remodelling. Early detection and timely intervention are critical to prevent its progression to peri-implantitis. This paper focuses on various treatment options for treating peri-implant mucositis. The cornerstone of professional treatment lies in the mechanical disruption and removal of microbial biofilms around the implant. This can be achieved through careful use of manual or powered instruments, such as ultrasonic scalers or air polishing devices. However, there is a need for further research to determine the most effective single approach for treating peri-implant mucositis. Current evidence does not support the combination of mechanical debridement with locally administered antibiotics. Contrarily, evidence strongly supports the removal, cleaning, and modifications of prostheses to improve both self-performance and professional cleanability. The use of adjunctive therapies like photodynamic therapy and diode laser, in conjunction with mechanical instrumentation, is not currently recommended due to the limited strength of available evidence. Preventive measures emphasise the importance of comprehensive oral hygiene care, encompassing professional guidance and at-home practices, to manage biofilms effectively. This encompasses oral hygiene instruction, regular debridement, and maintenance care. Supporting peri-implant therapy is also vital for ongoing implant monitoring, preventing the recurrence of mucositis, and halting its progression to peri-implantitis. This multifaceted approach is key to effectively managing and treating peri-implant mucositis.

The effect of NHFOV on hemodynamics in mild and moderately preterm neonates: a randomized clinical trial.

The aim of this study is to study cardio-respiratory effects of nasal high-frequency oscillatory ventilation (NHFOV) vs. NCPAP as an initial mode of ventilation in moderate-late-preterm infants. A randomized controlled trial was conducted in NICU of Alexandria University Maternity Hospital (AUMH). One-hundred late-moderate-preterm infants were randomly assigned to either NHFOV-group (n = 50) or NCPAP-group (n = 50). For both groups, functional echocardiography was performed in the first 24 h to detect hemodynamic changes and respiratory outcome was monitored throughout the hospital stay. The main outcomes were hemodynamic measurements and myocardial function using functional echocardiography of those infants along with the respiratory outcome and complications. Kaplan-Meier survival plot was used representing time course of NCPAP and NHFOV failure. Left ventricular output values were not significantly different in both groups with median 202 ml/kg /min and IQR (176-275) in NCPAP-group and 226 ml/kg/min with IQR (181-286) in NHFOV group. Nevertheless, ejection fraction and fractional shortening were significantly higher in NHFOV-group with P 0.001. The time to weaning, the time to reach 30%-FIO2, the need for invasive ventilation, oxygen support duration, and maximal-FIO2 were significantly more in NCAPAP group.     Conclusion: NHFOV is an effective and promising tool of non-invasive-ventilation which can be used as a primary modality of respiratory support in preterm infants with variable forms of respiratory distress syndrome without causing detrimental effect on hemodynamics or significant respiratory complications.     Trial registration: NCT05706428 (registered on January 21, 2023). What is Known: • NHFOV might be beneficial as a secondary mode of ventilation and might have an impact on hemodynamics. What is New: • NHFOV can be used as an initial mode of ventilation with CDP beyond the reported pressure limits of CPAP without causing neither CO2 retention nor adverse hemodynamic consequences.

Combination of metronomic capecitabine and letrozole in metastatic hormone receptor positive, HER2 negative breast cancer: a randomized phase II trial.

First line endocrine therapy is the gold standard for advanced estrogen receptor positive, human epidermal growth factor receptor 2 negative breast cancer. Adding CDK4/6 inhibitors has improved progression free survival. Metronomic Capecitabine has proven to be safe to combine with endocrine therapy with promising efficacy. We conducted a phase II randomized, open label, single centre clinical trial on patients with metastatic ER positive and HER 2 negative breast cancer. Eligible patients were randomized (1:1) to arm A: metronomic dose of capecitabine (500 mg/m2 BID) combined with letrozole (2.5 mg OD) or arm B: letrozole single agent. The primary endpoint was progression free survival. The study was terminated early due to poor accrual and 60 eligible patients out of the planned 204 were randomized. This clinical trial is registered on ClinicalTrials.gov (MD-127-2019, NCT04571437). Between February 2019 and April 2022, 60 patients were randomized. This is the first report of the study, after a median follow-up of 18.6 months. The median age at diagnosis was 47 years with only 41.7% of patients post-menopausal. Half of our patients had bone-only disease, 45% had visceral metastasis (liver and lung) and 63% presented with endocrine sensitive disease. The estimated median PFS for the whole population was 16.2 months. Median PFS for capecitabine arm was 17.7 months versus 14.6 months for letrozole alone (p = 0.078). Overall response rate was 70% for capecitabine/letrozole arm and 56.6% for letrozole only. Clinical benefit rate was 90% in the capecitabine/letrozole arm versus 73.3% in the letrozole arm. Overall survival data is still immature after this short follow up duration. Adverse event assessment showed acceptable all grade and high grade toxicity profile consistent with the established adverse events of both capecitabine and letrozole. Anaemia (28.3%) and hand & foot syndrome (43.8%) were significantly more common in the capecitabine/letrozole arm. Capecitabine combined with letrozole have showed a trend towards improvement in progression free survival with potential more benefit to certain sub-groups and the combination showed acceptable safety profile consistent with the established known safety profile of both letrozole and capecitabine.

Adipokine (adiponectin-rs1501299) Gene Variant and Patient Characteristics in Relation to Metabolic-associated Fatty Liver Disease.

Background: Several genetic and metabolic variables, most notably the variation in the adipokine gene rs1501298, have been linked to metabolic-associated fatty liver disease etiopathogenesis (MAFLD). Liver biopsy, the gold standard for diagnosing MAFLD, is an invasive procedure; therefore, alternative diagnostic methods are required. Consequently, the integration of these metabolic variables with some of the patients' characteristics may facilitate the development of noninvasive diagnostic methods that aid in the early detection of MAFLD, identification of at-risk individuals and planning of management strategies. Methods: This study included 224 Egyptians (107 healthy individuals and 117 MAFLD patients). Age, sex, BMI, clinical and laboratory characteristics, and rs1501299 adipokine gene polymorphisms were examined. The rs1501299 variant, insulin resistance, hypertension, obesity, blood pressure, lipid profile, hemoglobin A1C level, and hepatic fibrosis predictors were evaluated for MAFLD risk. The feasibility and effectiveness of developing non-invasive MAFLD diagnostic models will be investigated. Results: The +276G/T (rs1501299) polymorphism (GG vs GT/TT) was linked with MAFLD (OR: 0.43, CI: 0.26-0.69, P = 0.002). The GG variants had lower MAFLD rates than those of the GT and TT variants. In addition to altered lipid profiles, patients with MAFLD showed increased gamma-glutamyl transferase levels (GGT: 56 IU/L vs. 36 IU/L). Genetic diversity also affects the accuracy of hepatic fibrosis and steatosis prediction. Hepatic fibrosis and steatosis predictors had receiver operating characteristic (ROC) AUCs of 0.529%, 0.846%, and 0.700-0.825%, respectively. We examined a diagnostic model based on these variables and demonstrated its effectiveness. Conclusion: The Adipokine variant rs1501299 increased the risk of MAFLD. Identifying and genotyping this variation and other metabolic variables allow for a noninvasive diagnostic model for early MAFLD diagnosis and identification of those at risk. This study illuminates the prevention and management of MAFLD. Further research with more participants is needed to verify these models and to prove their MAFLD diagnostic efficacy.