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.

Polymyalgia Rheumatica Following Respiratory Syncytial Virus (RSV) Vaccination.

Introduction: Polymyalgia rheumatica (PMR) is a chronic inflammatory disorder that causes stiffness and pain in the proximal joints, including the shoulders, hips and neck. The exact cause of polymyalgia rheumatica is yet to be fully understood, but research suggests that both genetic and environmental factors may contribute to it. Studies have previously linked the onset and relapse of polymyalgia rheumatica symptoms to the influenza and COVID-19 vaccines. The Food and Drug Administration approved the respiratory syncytial virus (RSV) vaccine, which is a recombinant protein vaccine for adults over 60, in May 2023. No previous reports of polymyalgia rheumatica onset or relapse have been linked to the RSV vaccine. The human proteome shares some peptides with the RSV F antigen, suggesting a high risk of cross-reactivity when using that antigen in vaccination formulations. Case description: A 72-year-old man experienced a new onset of bilateral shoulder pain and stiffness three days after receiving the Abrysvo® RSV vaccine. The symptoms lasted more than an hour (up until noon) and interfered with his activities of daily living. Inflammatory markers such as C-reactive protein were elevated. The patient's symptoms and inflammatory marker levels significantly improved with prednisone therapy. Conclusion: In patients with typical PMR symptoms, it is important for clinicians to carefully review immunisation history to rule out any potentially related adverse effects. LEARNING POINTS: Vaccines can trigger autoimmune diseases in some individuals.This case report suggests respiratory syncytial virus (RSV) vaccine is among the possible triggers for polymyalgia rheumatica.

A Comparative In Vitro Physicochemical Analysis of Resin Infiltrants Doped With Bioactive Glasses.

Objective This study aimed to investigate the longevity and effectiveness of bioactive glass (BAG)-based dental resin infiltrants. Materials and methods The three types of BAG - 45S5 bioglass (RIS), boron-substituted (RIB), and fluoride-substituted (RIF) - were incorporated with photoinitiated dimethacrylate monomers to create experimental resin infiltrants. ICON® (CN; DMG-America, Ridgefield Park, NJ) and pure resin (PR) were used as control groups in this study. Disc-shaped samples were prepared for the experimental and control groups. The samples were challenged with the pH cycle and immersed in the artificial saliva for 30 days. On Day 0 and Day 30, the pH cycle and artificial saliva immersion, Vicker's microhardness, surface roughness, and surface morphology were investigated. Results The RIF group's disc samples showed the highest Vicker's microhardness values (78.20 ±0.06) on Day 30 of artificial saliva immersion, whereas the CN group's values were the lowest (55.99 ±0.24). Following the pH cycling, the RIF displayed the highest hardness (64.15 ±1.89) whereas the CN group's values were the lowest (33.47 ±1.28). Regarding surface roughness, on Day 30, the RIB resin group exhibited the highest (1.14 ±0.001 µm). In contrast, the CN resin showed the lowest (1.07 ±0.06 µm) values, while immersed in the artificial saliva solution. In the same duration of time, in the pH cycling solution, PR showed the least (0.85 ±0.89 µm), while RIF showed the highest roughness value (0.94 ±0.54 µm). Morphological analysis revealed that following the artificial saliva immersion, the RIB, CN, and PR exhibited smoother surfaces compared to the RIS and RIF groups. However, when immersed in the pH cycling solution, RIB and RIF showed more resistance against acid attack. Conclusions Our results revealed that the experimental resin groups performed much better than the commercial resin infiltrants following artificial saliva and pH cycling challenges.

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.

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.

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.

Inflammatory Markers and Aortic Aneurysms: Exploring the Role of Hs-CRP and MHR in Ascending Aortic Aneurysm Development.

Background: Aortic aneurysms, particularly those affecting the ascending aorta, pose significant health risks due to their potential to cause life-threatening complications such as rupture and dissection. While the etiology of ascending aortic aneurysms has traditionally been associated with non-inflammatory processes, emerging evidence suggests a potential role of inflammation in their development. Methods: This study investigates the relationship between inflammatory markers and ascending aortic aneurysms, focusing on high-sensitivity C-reactive protein (hs-CRP) and the monocyte-to-HDL ratio (MHR). A total of 135 patients with ascending aortic aneurysms and 40 control subjects underwent comprehensive evaluations, including echocardiography, computed tomography imaging, and serum biomarker measurements. Results: The results indicate significantly elevated levels of hs-CRP and MHR in patients with ascending aortic aneurysms compared to the control group, suggesting a potential inflammatory component in the pathogenesis of these aneurysms. However, the precise mechanisms underlying this association remain to be elucidated. Conclusion: Despite limitations such as the cross-sectional study design and relatively small sample size, this study provides valuable insights into the potential involvement of inflammation in ascending aortic aneurysms. Further research, including longitudinal studies and histopathological analysis of aortic tissue, is warranted to confirm these findings and explore the utility of inflammatory markers as diagnostic and prognostic indicators in this patient population.

Evaluating the properties that affect the quality of the charcoal product, determining the limits of toxic emissions during combustion, and studying their impact on human health.

This research focuses on examining the potential impact of charcoal briquettes and lumps on human health due to the emissions they release, and verifying their quality standards. Quality assessment was conducted using a device capable of measuring toxic gases to identify contaminants from various sources such as biomass, synthetic resins, coal, metals, and mineral matter. Toxicity assessments were carried out on five types of briquettes and two varieties of lump charcoal. All charcoal samples were subjected to elemental analysis (SEM/EDAX), including the examination of Ca, Al, Cr, V, Cu, Fe, S, Sr, Si, Ba, Pb, P, Mn, Rb, K, Ti, and Zn. The results showed that burning lump charcoal had toxicity indexes ranging from 2.5 to 5, primarily due to NOx emissions. Briquettes, on the other hand, exhibited higher toxicity indices between 3.5 and 6.0, with CO2 being the main contributor to toxicity. The average 24-h CO content of all charcoal samples exceeded the World Health Organization's 24-h Air Quality Guideline of 6.34 ppm, with a measurement of 37 ppm. The data indicates that most of the products tested did not meet the prevailing quality standard (EN 1860-2:2005 (E) in Appliances, solid fuels and firelighters for barbecuing-Part 2: Barbecue charcoal and barbecue charcoal briquettes-Requirements and test method, 2005), which specifies a maximum of 1% contaminants, with some products containing as much as 21% impurities. The SEM analysis revealed irregularly shaped grains with an uneven distribution of particles, and the average particle size distribution is quite broad at 5 µm. Malaysia Charcoal had the highest calorific value at 32.80 MJ/Kg, with the value being influenced by the fixed carbon content-higher carbon content resulting in a higher calorific value.

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.

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.

CONSORT statement adherence and risk of bias in randomized controlled trials on deep caries management: a meta-research.

BACKGROUND: Recently, trials have supported changes in deep caries management. However, reporting might lack details, affecting interpretation and implementation. Thus, we aimed to evaluate the adherence to the CONSORT statement and the risk of bias of randomized controlled trials (RCTs) on deep caries management published in pediatric dental journals. METHODS: We searched PubMed for RCTs in six pediatric dental journals between 2010 and 2022, focusing on deep caries lesion management. Adherence to the CONSORT guideline and the risk of bias were assessed using a modified tool with 19 items; each scored from 0 to 2 (maximum of 38 points), and the Cochrane risk-of-bias (RoB 2) tool. We performed descriptive and regression analyses (α = 5%). RESULTS: We analyzed 127 RCTs. The mean (standard deviation) CONSORT adherence score was 21.1 (6.7). Notably, 96.1% of the studies received a score of 2 for the "intervention" item, whereas 83.5% scored 0 for the "estimated effect size". The risk of bias assessment revealed that 40.2% of the RCTs were at high risk, 59% were at low risk, and 0.8% were at low risk. RCTs with a high risk of bias had lower CONSORT scores (p<0.001) than those with low or some concerns. RCTs published in journals without the endorsement of the CONSORT statement had lower scores than those in journals with the endorsement of the CONSORT statement. Older RCTs (6-10 years old and more than 10 years old) showed significantly lower CONSORT statement compliance than trials published recently within 5 years. CONCLUSION: Adherence to the CONSORT was relatively low among the investigated RCTs. Moreover, lower adherence to the CONSORT was associated with a higher risk of bias. TRIAL REGISTRATION: This study protocol was prospectively registered on the Open Science Framework - DOI ( 10.17605/OSF.IO/V6SYZ ).

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.

Long-pulsed nd: YAG laser treatment of nail psoriasis: clinical and ultrasonographic assessment.

Nail psoriasis is a chronic, inflammatory condition which is difficult to treat, linked with greater psoriasis severity, and may be associated with anxiety and significant functional impairment of the quality of life. The 1064 nm Nd: YAG laser was reported to yield satisfactory results in the treatment of nail psoriasis.The aim of the study was to assess the clinical and ultrasonographic efficacy of long-pulsed 1064 nm Nd: YAG laser in the treatment of fingernail psoriasis and compare its effect to control fingernails.This intra-patient randomized controlled trial analyzed 86 fingernails collected from 13 patients suffering from cutaneous and nail psoriasis. The nails were randomized into two groups. Group A was treated with Nd: YAG laser once monthly for three sessions while group B served as control. Assessment took place at baseline, 1 and 3 months after the last treatment session. For scoring, the 32-points target NAPSI scoring systems was used. Additionally, two blinded dermatologists' score of improvement, patients' pain assessment by visual analogue score and ultrasonographic assessment were all performed.At the end of follow up, the medians of tNAPSI score, plate definition, matrix thickness, bed thickness and bed vascularity decreased significantly in the Nd: YAG laser treated group in comparison to baseline (p = 0.001, 0.006, 0.039, < 0.001 and 0.010, respectively). While, there was a non-significant reduction in median tNAPSI score in the control group at last follow up, however, ultrasonography recorded a significant reduction in the medians of plate definition, bed thickness and vascularity (p = 0.002, 0.011 and 0.033, respectively) from the baseline. Comparison of the Nd: YAG laser and the control groups showed no significant difference from baseline regarding the medians of tNAPSI, tNAPSI percentile improvement, pits count, blinded evaluation of photographs and ultrasonographic assessments.In conclusion, Nd: YAG laser showed clinical and ultrasonographic improvement in fingernail psoriasis. Ultrasonography is a useful noninvasive tool in diagnosing and monitoring the clinical and even the subclinical changes in nail psoriasis. Nail psoriasis although difficult to treat, may show spontaneous improvement.

Benefit and potential risk: Effects of in ovo copper oxide nanoparticles supplementation on hatchability traits, organ weights and histological features of newly hatched chicks.

This investigation was directed to examine the influence of copper oxide nanoparticles (CuO-NPs) on the hatchability traits, and chick quality of newly hatched broiler chicks. A total of 480 eggs were randomly divided into four treatment groups, each consisting of three duplicates. As a negative control (NC), the first group was not injected; the second group was injected with saline and served as a positive control (PC), the third and fourth groups were injected with 30 and 60 ppm of (CuO-NPs)/egg. Eggs were injected into the amniotic fluid on the eighteenth day of the incubation period. Results showed that the hatchability, chick yield %, yolk free-body mass (YFBM), chick length, shank length (SL), and relative weight of the heart, gizzard and intestine of day-old broiler chicks were all unaffected by the in ovo injection of CuO-NPs. The Pasgar Score was slightly improved compared to the NC and PC groups. Also, the in ovo administration of CuO-NPs (60 ppm/egg) significantly increased the intestine length. Both levels of CuO-NPs significantly increased the concentration of Cu ions in the hepatic tissue. Additionally, different levels of tissue damage were seen in the liver of the birds that were given low or high dosages of CuO-NPs. Conclusively, the in ovo injection of CuO-NPs has a good result on the appearance of the chicks (Pasgar score). However, negative effect of CuO-NPs on liver tissue may raise concerns about the potential risks of applying CuO-NPs in ovo administration.

Association of aerobic fitness and grip strength with cognitive and academic performance in Arab children.

This study investigated the association between aerobic and muscular fitness with the cognitive control and academic performance of preadolescent Arab children. Ninety-three children aged 10-13years (mean=11.5, SD=0.5) representing eight Arab nations (Egypt, Saudi Arabia, Sudan, Syria, Jordan, Lebanon, Yemen, and Morocco) participated in this cross-sectional study. The participants completed tests for aerobic (progressive aerobic cardiovascular endurance run) and muscular (maximum grip strength) fitness, and cognitive control (flanker task). We assessed their academic performance based on their overall grade point average (GPA). Our analyses revealed that greater aerobic fitness was associated with higher GPA scores and greater muscular fitness was associated with a shorter response time in a task condition requiring extensive cognitive control (incongruent condition). No association was found between aerobic fitness and flanker task performance nor between muscular fitness and GPA. These results bridge the knowledge gap on the associations of physical fitness to the cognitive control and academic performance of Arab children, suggesting that the positive associations found in Western and Asian literature can be generalized to the Arab context.

Dissecting Acute Drug-Induced Hepatotoxicity and Therapeutic Responses of Steatotic Liver Disease Using Primary Mouse Liver and Blood Cells in a Liver-On-A-Chip Model.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is hallmarked by hepatic steatosis, cell injury, inflammation, and fibrosis. This study elaborates on a multicellular biochip-based liver sinusoid model to mimic MASLD pathomechanisms and investigate the therapeutic effects of drug candidates lanifibranor and resmetirom. Mouse liver primary hepatocytes, hepatic stellate cells, Kupffer cells, and endothelial cells are seeded in a dual-chamber biocompatible liver-on-a-chip (LoC). The LoC is then perfused with circulating immune cells (CICs). Acetaminophen (APAP) and free fatty acids (FFAs) treatment recapitulate acute drug-induced liver injury and MASLD, respectively. As a benchmark for the LoC, multiplex immunofluorescence on livers from APAP-injected and dietary MASLD-induced mice reveals characteristic changes on parenchymal and immune cell populations. APAP exposure induces cell death in the LoC, and increased inflammatory cytokine levels in the circulating perfusate. Under FFA stimulation, lipid accumulation, cellular damage, inflammatory secretome, and fibrogenesis are increased in the LoC, reflecting MASLD. Both injury conditions potentiate CIC migration from the perfusate to the LoC cellular layers. Lanifibranor prevents the onset of inflammation, while resmetirom decreases lipid accumulation in hepatocytes and increases the generation of FFA metabolites in the LoC. This study demonstrates the LoC potential for functional and molecular evaluation of liver disease drug candidates.

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.

Prevalence and characteristics of patent foramen ovale in a sample of Egyptian population: a computed tomography study.

BACKGROUND: The reported prevalence of patent foramen ovale (PFO) in the general population is variable. It ranges between 8.6 and 42% according to the population studied and the imaging technique used. We aim to prospectively assess the prevalence and characteristics of PFO and interatrial septum (IAS) abnormalities as well as the related clinical manifestations in a sample of Egyptian population. RESULTS: This study comprised 1000 patients who were referred for CT coronary angiography (CTCA). Mean age was 52.5 ± 10.9 years. The prevalence of PFO among the studied population was 16.3%; closed PFO (grade I) 44.2%, open PFO (grade II) 50.9%, and open PFO with jet (grade III) 4.9%. Anatomical high-risk PFO features-defined as the presence of at least 2 or more of the following (diameter ≥ 2 mm, length ≥ 10 mm, septal aneurysm "ASA", or redundant septum)-were found in 51.5% of PFOs' population. Other IAS abnormalities as redundant septum (8.6%), ASA (5.3%), Bachmann's bundle (4.5%), microaneurysm (2.6%), and atrial septal defect (ASD) (0.4%) were detected. There was a lower rate of coexistence of ASA with PFO (p = 0.031). Syncope was significantly higher in patients with PFO compared to those without PFO (6.7% vs. 1.6%, p = 0.001). Stroke, transient ischaemic attacks (TIA), and dizziness were similar in both groups. TIA, dizziness, and syncope were significantly higher in patients with IAS abnormalities including PFO compared to those without IAS abnormalities. Syncope was also significantly higher in PFO with high-risk anatomical features compared to those with non-high-risk PFO population (p = 0.02). CONCLUSION: The prevalence of PFO in our study was approximately 16.3%, almost half of them showed anatomical high-risk features for stroke. Dizziness, syncope and TIA were significantly higher in patients with IAS abnormalities including PFO.

Two decades of ceria nanoparticle research: structure, properties and emerging applications.

Cerium oxide nanoparticles (CeNPs) are versatile materials with unique and unusual properties that vary depending on their surface chemistry, size, shape, coating, oxidation states, crystallinity, dopant, and structural and surface defects. This review encompasses advances made over the past twenty years in the development of CeNPs and ceria-based nanostructures, the structural determinants affecting their activity, and translation of these distinct features into applications. The two oxidation states of nanosized CeNPs (Ce3+/Ce4+) coexisting at the nanoscale level facilitate the formation of oxygen vacancies and defect states, which confer extremely high reactivity and oxygen buffering capacity and the ability to act as catalysts for oxidation and reduction reactions. However, the method of synthesis, surface functionalization, surface coating and defects are important factors in determining their properties. This review highlights key properties of CeNPs, their synthesis, interactions, and reaction pathways and provides examples of emerging applications. Due to their unique properties, CeNPs have become quintessential candidates for catalysis, chemical mechanical planarization (CMP), sensing, biomedical applications, and environmental remediation, with tremendous potential to create novel products and translational innovations in a wide range of industries. This review highlights the timely relevance and the transformative potential of these materials in addressing societal challenges and driving technological advancements across these fields.

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.