MicroRNA-21 (miR-21) in breast cancer: From apoptosis dysregulation to therapeutic opportunities.

Breast cancer, a pervasive and complex disease, continues to pose significant challenges in the field of oncology. Its heterogeneous nature and diverse molecular profiles necessitate a nuanced understanding of the underlying mechanisms driving tumorigenesis and progression. MicroRNA-21 (miR-21) has emerged as a crucial player in breast cancer development and progression by modulating apoptosis, a programmed cell death mechanism that eliminates aberrant cells. MiR-21 overexpression is a hallmark of breast cancer, and it is associated with poor prognosis and resistance to conventional therapies. This miRNA exerts its oncogenic effects by targeting various pro-apoptotic genes, including Fas ligand (FasL), programmed cell death protein 4 (PDCD4), and phosphatase and tensin homolog (PTEN). By suppressing these genes, miR-21 promotes breast cancer cell survival, proliferation, invasion, and metastasis. The identification of miR-21 as a critical regulator of apoptosis in breast cancer has opened new avenues for therapeutic intervention. This review investigates the intricate mechanisms through which miR-21 influences apoptosis, offering insights into the molecular pathways and signaling cascades involved. The dysregulation of apoptosis is a hallmark of cancer, and understanding the role of miR-21 in this context holds immense therapeutic potential. Additionally, the review highlights the clinical significance of miR-21 as a diagnostic and prognostic biomarker in breast cancer, underscoring its potential as a therapeutic target.

Felty Syndrome Presented With Candida albicans Lung Abscess Without Arthritis: A Case Report.

Felty syndrome (FS) is a late manifestation of severe active rheumatoid arthritis (RA). A high index of suspicion or FS is needed in patients who present with neutropaenia and splenomegaly with no initial or obvious identifiable cause. We present the case of a 52-year-old who presented with a one-week history of haemoptysis, fever, and night sweats. The patient was hypotensive, tachycardia, and febrile (38 °C). On examination, bilateral crackles and reduced air entry were identified on the right basal and middle zones. The patient was diagnosed with RA two years prior to this presentation and was not on a disease-modifying antirheumatic drug (DMARD). Haematology showed high inflammatory markers and pancytopenia. Chest X-ray showed a right upper lobe abscess. CT-thorax, abdomen, and pelvis confirmed lung abscesses and hepatosplenomegaly. Candida albicans was detected on the broncho-alveolar lavage. He responded well to antifungal medication and corticosteroids with normalisation of the pancytopenia and inflammatory markers and reduction of the spleen size. This case report details the unusual and early presentation of FS in a patient newly diagnosed with RA and who had no active arthritis. We wish to emphasize the importance of a high index of suspicion in patients with RA regardless of the length of their illness.

Vaccination status, awareness, and its correlates among healthcare workers in the Delhi-National Capital Region (NCR): a mixed-method study.

Introduction: Healthcare workers (HCWs) are on the frontline of infections. To safeguard HCWs from occupational exposure to infections and to curb nosocomial infection a set of vaccines has been recommended for them by the WHO. Hence, we aimed to assess the vaccination status, awareness, and its correlates amongst HCWs in the Delhi-NCR. Method: The study used a cross-sectional mixed-method approach from January to April 2023. For the quantitative arm, a structured questionnaire was circulated to the participants in conveniently-selected private and government tertiary care hospitals of the Delhi-NCR, both through e-survey using Google form, and in person, data were collected on socio-demographics, vaccination status, and awareness. SPSS version 25 was used for the analysis. For the qualitative arm, in-depth interviews were conducted and data were analyzed manually. Results: Out of 387 participants (62.8% males, 37.2% females), the awareness about the vaccines recommended for HCWs was 64.1%. However, only 15.3% of HCWs were completely aware of all the recommended vaccines. SARS CoV-2, Polio, Hepatitis B, and BCG had the highest vaccination coverage, 97.4%, 87.9%, 83.7%, and 50.9%, respectively. It was found that gender, education, type (private or governmental) of tertiary care hospital, and profession had a significance (p<0.05) on the vaccination status score and awareness of all WHO-recommended vaccines (AOR=7.6, 95% CI, 3.24-18.0). The qualitative arm further augmented the findings. Conclusion: The study reveals insufficient awareness and vaccination status regarding recommended vaccines. Prioritizing the preparation of unified standard guidelines for Indian HCWs and involving concerned stakeholders is crucial.

Barriers to a Healthy Lifestyle Among Obese Patients Attending Primary Care Clinics in Al-Ahsa, Saudi Arabia.

Obesity is a significant public health issue in Saudi Arabia, contributing to high morbidity and mortality rates. This study aimed to identify the barriers preventing obese patients from adhering to healthy diets and regular exercise while following a health coach in primary healthcare centers in Al-Ahsa. A cross-sectional study of 283 obese adults revealed that major barriers included lack of energy, willpower, and time for exercise, as well as lack of willpower, social influence, and time for maintaining a healthy diet. These barriers were significantly associated with demographic factors such as obesity grade, comorbidities, and educational level. Addressing these barriers is essential for developing effective interventions to support lifestyle changes in obese patients.

Antibacterial Dental Adhesive Containing Cetylpyridinium Chloride Montmorillonite.

Oral bacteria cause tooth caries and periodontal disease. Much research is being conducted to prevent both major oral diseases by rendering dental materials' antimicrobial potential. However, such antimicrobial materials are regarded as 'combination' products and face high hurdles for regulatory approval. We loaded inorganic montmorillonite with the antimicrobial agent cetylpyridinium chloride, referred to below as 'CPC-Mont'. CPC-Mont particles in a 1, 3 and 5 wt% concentration were added to the considered gold-standard self-etch adhesive Clearfil SE Bond 2 ('CSE2'; Kuraray Noritake) to render its antibacterial potential (CSE2 without CPC-Mont served as control). Besides measuring (immediate) bonding effectiveness and (aged) bond durability to dentin, the antibacterial activity against S. mutans and the polymerization-conversion rate was assessed. Immediate and aged bond strength was not affected by 1 and 3 wt% CPC-Mont addition, while 5 wt% CPC-Mont significantly lowered bond strength and bond durability. The higher the concentration of the antimicrobial material added, the stronger the antimicrobial activity. Polymerization conversion was not affected by the CPC-Mont addition in any of the three concentrations. Hence, adding 3 wt% CPC-Mont to the two-step self-etch adhesive rendered additional antimicrobial potential on top of its primary bonding function.

Using Repeated Lysis Steps Fractionates Between Heterotrophic and Cyanobacterial DNA Extracted from Xenic Cyanobacterial Cultures.

Extracting DNA from cyanobacteria can be a challenge because of their diverse morphologies, challenging cellular structure, and the heterotrophic microbiome often present within cyanobacterial cultures. As such, even when our DNA yields are sufficient for sequencing, the percentage of reads coming from the cyanobacterial host can be low, leading to incomplete genomes spread across several scaffolds. In this research, we optimized a DNA isolation protocol using three iterative cell lysis steps to enrich the portion of DNA isolated coming from the cyanobacterial host rather than the heterotrophic microbiome. In order to utilize in-house nanopore sequencing, we faced a challenge in that our lysis protocol led to DNA shearing and a lower molecular weight DNA extract than is suitable for this sequencing technology. As such we used two bead-based size selection steps to remove shorter molecules of DNA before nanopore sequencing. EPI2ME analysis of the processed reads from the iterative lysis steps showed that in the first lysis the heterotrophic microbiome could make up more than half of all reads, but with each lysis the proportion of reads coming from these other species decreased. Using our iterative lysis protocol, we were able to sequence the genomes of two cyanobacteria isolated from fresh water sources around northern Mississippi, namely Leptolyngbya sp. BL-A-14 and Limnothrix sp. BL-A-16. The genomes of these isolates were assembled as closed chromosomes of 7.2 and 4.5 Mb for Leptolyngbya sp. BL-A-14 and Limnothrix sp. BL-A-16, respectively. Because some cyanobacteria have symbioses with their heterotrophic microbiome it is not always possible to prepare axenic cultures of these organisms, we hope our approach will be useful for sequencing xenic cultures of cyanobacteria, but we can also imagine applications in studying this microbiome specifically by focusing sequencing efforts on the first fraction.

Femoral neck fracture in sickle cell anemia: A comprehensive case study.

Key Clinical Message: The significance of taking femoral neck stress fractures into account as a possible consequence in sickle cell anemia patients is underscored by this case report. In this high-risk group, early identification, timely diagnosis, and suitable care are crucial for averting major problems and improving results. When sickle cell anemia patients complain with hip or groin discomfort, healthcare practitioners should keep a high index of suspicion for femoral neck stress fractures to assure prompt management and prevent long-term impairment. Abstract: Sickle cell disease (SCD) is a prevalent genetic hemoglobinopathy with significant global implications, affecting a substantial portion of the population. Avascular necrosis of the femoral head is a common complication in SCD, leading to severe joint damage and immobility. This case report is of a 20-year-old male who presented with severe hip pain due to a femoral neck stress fracture, which progressed to a complete fracture. This patient had a past medical history of sickle cell anemia and a malunited subtrochanteric fracture that resulted in shortening, external rotation, and a limping gait. Surgical treatment via subtrochanteric osteotomy with fixation using a dynamic hip screw with or without iliac crest bone graft was planned, with a satisfactory reduction and closure of the fracture gap, postoperatively. In cases of sickle cell anemia patients, bone complications such as both osteonecrosis and stress fractures are common. As a healthcare provider, it is important to manage and address these not only through medical interventions, but also through counseling and patient education. Patients must be reminded about the importance of compliance with medical advice to avoid progression or recurrence of complications.

An architecture for COVID-19 analysis and detection using big data, AI, and data architectures.

The COVID-19 epidemic is affecting individuals in many ways and continues to spread all over the world. Vaccines and traditional medical techniques are still being researched. In diagnosis and therapy, biological and digital technology is used to overcome the fear of this disease. Despite recovery in many patients, COVID-19 does not have a definite cure or a vaccine that provides permanent protection for a large number of people. Current methods focus on prevention, monitoring, and management of the spread of the disease. As a result, new technologies for combating COVID-19 are being developed. Though unreliable due to a lack of sufficient COVID-19 datasets, inconsistencies in the datasets availability, non-aggregation of the database because of conflicting data formats, incomplete information, and distortion, they are a step in the right direction. Furthermore, the privacy and confidentiality of people's medical data are only partially ensured. As a result, this research study proposes a novel, cooperative approach that combines big data analytics with relevant Artificial Intelligence (AI) techniques and blockchain to create a system for analyzing and detecting COVID-19 instances. Based on these technologies, the reliability, affordability, and prominence of dealing with the above problems required time. The architecture of the proposed model will analyze different data sources for preliminary diagnosis, detect the affected area, and localize the abnormalities. Furthermore, the blockchain approach supports the decentralization of the central repository so that it is accessible to every stakeholder. The model proposed in this study describes the four-layered architecture. The purpose of the proposed architecture is to utilize the latest technologies to provide a reliable solution during the pandemic; the proposed architecture was sufficient to cover all the current issues, including data security. The layers are unique and individually responsible for handling steps required for data acquisition, storage, analysis, and reporting using blockchain principles in a decentralized P2P network. A systematic review of the technologies to use in the pandemic covers all possible solutions that can cover the issue best and provide a secure solution to the pandemic.

Role of systemic immune-inflammatory index and systemic inflammatory response index in predicting the diagnosis of necrotizing pneumonia in children.

BACKGROUND: Necrotizing pneumonia (NP) is a rare serious complication of community-acquired pneumonia (CAP) in children, which is characterized by a protracted course of the disease and a prolonged hospital stay. This study aimed to assess the role of systemic immune-inflammatory index and systemic inflammatory response index in predicting early lung necrotization in children with CAP. METHODS: This study included all children hospitalized in Pediatric Pulmonology Unit, Tanta University, Egypt, with CAP between the ages of two months and 18 years. Systemic inflammatory indices, including the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), systemic immune-inflammatory index (SII), and systemic inflammation response index (SIRI), were calculated on patients' admission. RESULTS: The study involved a total of 228 children, 42 patients had NP, 46 patients had parapneumonic effusion, and 140 patients had non-complicated CAP. Patients with NP were substantially younger (p = 0.002), stayed in the hospital longer (p < 0.001), had a longer duration of symptoms before hospital admission (p < 0.001), and had fever for a longer duration than those in the other groups (p < 0.001). Regarding the inflammatory ratios, patients with NP had significantly higher MLR, PLR, SII, and SIRI than those in the other groups (p = 0.020, p = 0.007, p = 0.001, p = 0.037, respectively). ROC curve analysis showed that the combined SII + SIRI + D-dimer showed the highest AUC with a good specificity in predicting the diagnosis of NP. CONCLUSIONS: SII, SIRI, and D-dimer may be beneficial biomarkers for predicting the occurrence of NP in children when performed on patients' admission. In addition, it was found for the first time that combined SII + SIRI + D-dimer had a good sensitivity and specificity in the diagnosis of NP.

Non-coding RNAs in BRAF-mutant melanoma: targets, indicators, and therapeutic potential.

Melanoma, a highly aggressive skin cancer, is often driven by BRAF mutations, such as the V600E mutation, which promotes cancer growth through the MAPK pathway and contributes to treatment resistance. Understanding the role of non-coding RNAs (ncRNAs) in these processes is crucial for developing new therapeutic strategies. This review aims to elucidate the relationship between ncRNAs and BRAF mutations in melanoma, focusing on their regulatory roles and impact on treatment resistance. We comprehensively reviewed current literature to synthesize evidence on ncRNA-mediated regulation of BRAF-mutant melanoma and their influence on therapeutic responses. Key ncRNAs, including microRNAs and long ncRNAs, were identified as significant regulators of melanoma development and therapy resistance. MicroRNAs such as miR-15/16 and miR-200 families modulate critical pathways like Wnt signaling and melanogenesis. Long ncRNAs like ANRIL and SAMMSON play roles in cell growth, invasion, and drug susceptibility. Specific ncRNAs, such as BANCR and RMEL3, intersect with the MAPK pathway, highlighting their potential as therapeutic targets or biomarkers in BRAF-mutant melanoma. Additionally, ncRNAs involved in drug resistance, such as miR-579-3p and miR-1246, target processes like autophagy and immune checkpoint regulation. This review highlights the pivotal roles of ncRNAs in regulating BRAF-mutant melanoma and their contribution to drug resistance. These findings underscore the potential of ncRNAs as biomarkers and therapeutic targets, paving the way for innovative treatments to improve outcomes for melanoma patients.

Evaluation of hepcidin-25/erythroferrone ratio as a potential biomarker for iron utility and erythropoiesis responsiveness to erythropoiesis-stimulating therapy in comparison to immature erythrocyte/reticulocyte parameters in hemodialysis patients.

BACKGROUND: Anemia-associated chronic kidney disease increases in more advanced stages with a subsequent acceleration in renal impairment progressing to end-stage renal disease. Although hepcidin and erythroferrone have been described as novel biomarkers of iron metabolism, there is still an area of ambiguity regarding iron utility in anemia-associated end-stage renal disease. OBJECTIVES: This study aims to determine the correlations between erythropoietin, erythroferrone, and hepcidin-25 in hemodialysis, and to evaluate the clinical utility of the hepcidin-25/erythroferrone ratio as a biomarker of erythropoiesis-stimulating agent effectiveness compared to reticulocyte maturation parameters. METHODS: Serum erythropoietin, erythroferrone, and hepcidin-25 levels in 35 dialysis-dependent patients on a maintenance dose of a short-acting erythropoiesis-stimulating agent were consequently assessed on Days 0, 5, and 7. The erythropoiesis activity was monitored by measuring the increment in reticulocyte maturation parameters. RESULTS: Though the effectiveness of erythropoiesis in these patients was not associated with the hepcidin-25/erythroferrone ratio, it was lower among those with effective erythropoiesis than those with ineffective erythropoiesis. The effective group showed a statistically significant increase in reticulocyte maturation parameters compared to the ineffective group. CONCLUSIONS: The findings show the pathogenesis of iron homeostasis in hemodialysis, the validity of hepcidin-25/erythroferrone ratio as a biomarker of erythropoiesis-stimulating agent effectiveness, and the advantageous monitoring of reticulocyte maturation measures to improve management of anemia-associated chronic kidney disease.

Consensus Recommendations for the Management of Atopic Dermatitis in the United Arab Emirates.

Atopic dermatitis often begins in infancy and follows a chronic course of exacerbations and remissions. The etiology is complex and involves numerous factors that contribute to skin barrier defect and inflammation. In the Middle East, the burden of atopic dermatitis is understudied. Epidemiological data specific to the Gulf region are scarce but reveal a prevalence of up to about 40% in the United Arab Emirates. Region-specific factors, such as the climate and the frequency of consanguineous marriages, may affect atopic dermatitis incidence, prevalence, and evolution over time. A panel of experts predominantly from the United Arab Emirates analyzed the evidence from published guidelines, and considered expert guidance and local treatment practices to develop clear recommendations for the management of atopic dermatitis in the United Arab Emirates. They encourage a systematic approach for the diagnosis and treatment, using disease severity scores and quality-of-life measurement tools. Treatment recommendations take into consideration both established therapies and the approved systemic biologics dupilumab and tralokinumab, and the Janus kinase inhibitors baricitinib, upadacitinib, and abrocitinib.

Thrombus in transit associated with fatal pulmonary thromboembolism in an elderly Ethiopian man following a surgical procedure: A case report.

Key Clinical Message: Early detection, timely management, and exploration of alternative treatment options are crucial for patients with high-risk pulmonary thromboembolism, particularly those with thrombus in transit. Furthermore, prophylactic measures against thromboembolic events should be highly considered for patients with predisposing conditions for venous thromboembolism, including surgical procedures. Abstract: A thrombus in transit refers to a thrombus that is temporarily lodged in the right-side chambers of the heart with a high risk of embolization to the pulmonary artery. A 75-year-old man presented to the emergency department with a sudden onset of retrosternal chest pain for an hour associated with shortness of breath, which developed a week after transurethral resection of the prostate was done for the indication of benign prostatic hyperplasia. The physical examination was remarkable for tachycardia, tachypnea, hypoxia, and raised jugular venous pressure. Echocardiography revealed a serpiginous echogenic density in the right atrium, protruding through the tricuspid valve and extending to the right ventricle. He was put on facemask oxygen, and he received anticoagulation with unfractionated heparin, followed by thrombolytic therapy with streptokinase. However, the patient experienced cardiac arrest during the administration of thrombolytic therapy, and he died despite all the efforts, most likely due to a massive pulmonary thromboembolism resulting from the thrombus in transit. This case report has brought attention to the rare occurrence of a thrombus in transit complicated by fatal pulmonary thromboembolism. It has also highlighted the significant mortality risk that this condition carries, even with thrombolytic therapy.

Spirulina platensis shields the submandibular gland from cadmium toxicity by bolstering antioxidant defenses and maintaining its structural integrity.

Cadmium (Cd), an element categorized as a non-essential transitional metal, has potential hazards to the health of both human beings and animals. Spirulina platensis (SP), a type of blue-green algae, possesses a high concentration of essential antioxidants. The present study aimed to explore the possible defensive role of SP against Cd-induced submandibular gland injury in rats by assessment of biomarkers related to both oxidative stress and inflammatory processes, which were further explored through histopathological examination of submandibular gland tissue. Consequently, the study included 32 mature rats, subdivided into four different groups as follows: control, SP, Cadmium chloride (CdCl2), and CdCl2/SP. The duration of the study was 24days. The results revealed that CdCl2 induced submandibular gland injury as shown by the oxidant/antioxidant imbalance and increased inflammatory reactions, in addition to, histopathological changes and overexpression of BAX immunostaining. Concurrent SP administration to CdCl2-treated rats significantly improved all these effects. We concluded that concurrent SP supplement improved the submandibular gland injury provoked by CdCl2.

Formulation and Evaluation of pH-Modulated Amorphous Solid Dispersion-Based Orodispersible Tablets of Cefdinir.

Cefdinir (CEF) is a semi-synthetic third-generation broad-spectrum oral cephalosporin that exhibits poor solubility at lower pH values. Considering this, pH-modulated CEF solid dispersions (ASDs) were produced by solvent evaporation method employing various hydrophilic carriers and alkalizers. Among different carriers, ASDs produced using PEG 6000 with meglumine as alkalizer were found to significantly increase (p < 0.005) the drug solubility (4.50 ± 0.32 mg/mL) in pH 1.2. Fourier transform infrared spectrophotometry confirmed chemical integrity of CEF while differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) indicated CEF was reduced to an amorphous state in ASD8. Antimicrobial assay performed by well diffusion method against Staphylococcus aureus (MTCC96) and Escherichia coli (MTCC118) demonstrated significantly superior (p < 0.001) efficacy of CEFSD compared to CEF. The porous orodispersible tablets (ODTs) of ASD8 (batch F5) were developed by incorporating ammonium bicarbonate as a subliming agent by direct compression, followed by vacuum drying displayed quick disintegration (27.11 ± 1.96 s) that met compendial norms and near-complete dissolution (93.85 ± 1.27%) in 30 min. The ODTs of ASD8 appear to be a promising platform to mitigate the pH-dependent solubility and dissolution issues associated with CEF in challenging physiological pH conditions prevalent in stomach. Thus, ODTs of ASD8 are likely to effectively manage various infections and avoid development of drug-resistant strains, thereby improving the curing rates.

Using Quality by Design Tools to Study Gel Formulation from Brassica juncea Leaves and Conducting its In vitro, In vivo, Molecular Docking, and ADMET Analyses.

INTRODUCTION: This research aims to create a gel formulation of Brassica juncea leaf extract and assess its anti-inflammatory properties using an in silico study. The anti-inflamma-tory activity has been compared with Diclofenac molecules in PDB id: 4Z69. Further, the Ab-sorption, Distribution, Metabolism, Excretion, and Toxicity analysis has been performed to en-sure the therapeutic potential and safety of the drug development process. The Quality by De-sign tool has been applied to optimize formulation development. METHODS: The extracted gel is characterized by performing Fourier transformer infrared, zeta potential, particle size, Scanning Electron Microscope, and entrapment efficiency. Further, the formulation is evaluated by examining its viscosity, spreadability, and pH measurement. An In-vitro study of all nine extract suspensions was conducted to determine the drug contents at 276 nm. RESULTS: The optimized suspension has shown the maximum percentage of drug release (82%) in 10 hours of study. Animal study for anti-inflammatory activity was performed, and results of all five groups of animals compared the % inhibition of paw edema at three hours; gel (56.70 %), standard (47.86 %), and (39.72 %) were found. CONCLUSION: The research could conclude that the anti-inflammatory activity of gel formulation is high compared to extract, and a molecular docking study validates the anti-inflammatory ther-apeutic effects. ADMET analysis ensures the therapeutic effects and their safety.