Life-threatening Disease Research Articles

Reporting three rare pathogenic variants at the CFTR gene in two unrelated Iranian Azeri children with cystic fibrosis

BackgroundCystic fibrosis (CF) is an autosomal recessive inherited life-threatening disease that causes changes in the electrolyte transport system, leading to high absorption of sodium and water. Disease-causing variants of the CFTR gene are responsible for this disease. In the present study, three rare pathogenic variants were identified in two unrelated Iranian Azeri children with CF.Case presentationOne child affected with CF was found to have two rare variants, c.1545_1546delTA and c.3196C > T, detected through Sanger sequencing of the entire coding region and promoter of the CFTR gene. Another patient was identified as compound heterozygous for the variant c.1545_1546delTA and a rare variant, c.2998delA, which has not been previously reported. The variants were found to be in trans, as both parents were heterozygous for the variants.ConclusionThe rare variant c.1545_1546delTA has been previously reported as a known variant in certain populations, including Azeris in northwest Iran. Our results, along with previous findings, suggest that this variant may be considered a founder mutation in specific geographical regions. The variant c.2998delA has not been previously reported as pathogenic. Following the guidelines of the American College of Genetics and Genomics and considering the proband's symptoms, we classified this variant as pathogenic based on criteria PVS1, PS4, PM3, PP1, and PM2. The identified variants in the CFTR gene as well as the previously reported variants could serve as a basis for future genetic counseling and prenatal diagnosis in Iran.

Neonatal tetanus in South Sudan: a case series

Introduction: Neonatal tetanus is a life-threatening disease of public health importance; it is yet to be eliminated and is still occurring in South Sudan. It is caused by a neurotoxin from a bacterium Clostridium tetani whose spores exist in the environment. Compared to high-income countries, most low-income countries lack intensive care units, and magnesium sulfate shown to improve neonatal tetanus outcomes. Objectives: We aimed to determine the outcome of neonatal tetanus in Al Sabah Children’s Hospital, Juba, South Sudan. Methods: We conducted a case series study in Al Sabah Children’s Hospital in Juba, South Sudan. It described three neonates who presented within the first seven days of life with a history of excessive crying, inability to breastfeed, and tetanic muscle spasms when stimulated. They had signs of respiratory distress, fever, and labile heart rates. We made a diagnosis of neonatal tetanus with autonomic dysfunction, and started them on phenobarbitone because diazepam was not available, oxygen, and antibiotics. However, tetanus immune globulin and anti-tetanus serum were not available. Results: Unfortunately, all three neonates died within 24 hours of admission. Conclusion: Our primary focus as a nation is to improve access to quality health services and the prevention of neonatal tetanus through encouraging appropriate antenatal care, facility delivery, clean delivery and healthy umblical cord care practices, and tetanus vaccinations in teenage girls and young adults. When prevention fails, there is a need for neonatal intensive care with recommended medicines to significantly decrease mortality in this preventable tragic illness. Keywords: Neonatal tetanus; low-income countries; neonates; Al sabah children hospital; South Sudan.

7564 Adrenal Pheochromocytoma In A Clinically Inapparent Adrenal Mass

Abstract Disclosure: L. Medina Mora: None. S. Htoo: None. A. Sanchez Ruiz: None. M. Harshan: None. A. Busta: None. Introduction: Pheochromocytomas (PCC) are rare tumors that arise from the adrenal medulla, with an estimated annual incidence of 0.8 per 100,000 person-years. These tumors have been associated with significant morbidity and mortality and are considered among the most life-threatening endocrine diseases, particularly if left undiagnosed. Its symptoms can be related to the tumor's mass effect or catecholamine excess. As a result, they can mimic other conditions, often leading to delayed or incorrect diagnosis. A study conducted on 296 patients with PCC treated from 2005 to 2016 found that 61% were discovered incidentally through cross-sectional imaging (CSI). The widespread use of CSI in recent years has led to the identification of asymptomatic cases that would have otherwise gone undetected. In this case, we present a middle-aged female who was incidentally found to have a PCC. Case Report: A 59-year-old female with a history of hypertension, cerebrovascular accident, pulmonary hypertension, systolic heart failure, mitral valve replacement, and asthma presented to the clinic for evaluation of a right adrenal lesion measuring 4.2 x 3.5 cm found during an emergency room visit during the evaluation of chest pain. She had no known family history of brain or endocrine disorders. Her lab results showed elevated plasma metanephrine and normetanephrine to 578.4 (reference range: 0-88) and 459.9 (reference: 0-244), respectively. Additionally, her 24-hour urine metanephrine was elevated to 984 mcg (normal range: 36-209), and Chromogranin A was 164.3 (reference range: 0-101). The rest of her labs, including cortisol, renin, aldosterone, and DHEA-S were unremarkable. A CT with and without contrast revealed a 3.0 x 3.5 x 5.1 cm solid non-calcified right adrenal mass measuring 39 Hounsfield units (HU). In addition, it measured 53 HU in the venous phase and 61 HU in the 15-minute delayed phase (relative washout of <1%; absolute washout of <7%). The patient was treated with alpha-blockers and underwent a robotic-assisted right adrenalectomy. The pathology was significant for a 5.4 cm well-differentiated PCC. The tumor had extended into but not beyond the adrenal capsule. The postoperative course of the patient was uncomplicated. Discussion: After a PCC is detected, the most effective treatment option is to surgically remove it. This procedure necessitates a combination of alpha and beta-blockade to regulate blood pressure and prevent a hypertensive crisis. Despite the success of surgery, there is still uncertainty about the optimal follow-up after the procedure, which often leads to many patients being lost during the process. Furthermore, even a decade after the initial surgery, there remains a substantial likelihood of illness reoccurrence or metastasis, making the situation even more complex. Therefore, it is crucial to adhere to a lifelong follow-up plan that includes annual biochemical testing. Presentation: 6/2/2024

6575 From Tonsils to the Thyroid: A Rare Case of Acute Suppurative Thyroiditis in an Immunocompetent Adult

Abstract Disclosure: F. Sajid: None. A. Mubashir: None. F. Mohsin: None. M. Sattar: None. Introduction: Acute suppurative thyroiditis (AST) is a rare infection of the thyroid gland due to its high vascularity, protective encapsulation, and high iodine content. Most AST cases occur in children with anatomical aberrations or in immunosuppressed adults. Here, we describe a case of AST in an immunocompetent woman. Case: A 54-year-old woman with no medical history presented to the emergency department due to dyspnea, dysphagia, and odynophagia for two days. She reported a four-day history of sore throat, fever, and chills. She was saturating well on room air but was sitting in a tripod position. She had erythema, swelling, tenderness to palpation in the anterior neck with a hoarse voice, and moderate trismus. Nasopharyngoscopy revealed no mass, but the scope could not pass beyond the velum due to edema. The patient’s condition quickly deteriorated, necessitating emergent intubation for acute hypoxic respiratory failure. After intubation, the patient had cardiac arrest with asystole requiring resuscitation and successful ROSC. The initial CT scan showed extensive soft tissue abnormalities in the nasopharynx and parapharyngeal tissues, extending to the thyroid gland and mediastinum with the possibility of developing abscesses. A thyroid ultrasound showed a heterogeneous thyroid gland without nodules or increased vascularity. Treatment commenced with ampicillin-sulbactam. Laboratory results showed Free T4 of 4.74 ng/dL (0.58-1.64), TSH 0.03 MCIU/mL (0.39-4.08), Total T3 1.56 ng/dL (0.72-1.35), WBC 19.3 K/UL (4.8-10.8), and elevated ESR and CRP levels. Thyroid-stimulating Immunoglobulin (TSI), Thyroid Peroxidase (TPO) Antibody, and Thyrotropin Binding Inhibitory Immunoglobulin (TBII) were negative, making AST the top differential. Methimazole was initiated due to concerns of thyroid storm, but it was quickly tapered due to a significant decrease in Free T4 levels and suspicion of AST. A repeat CT scan revealed more defined abscesses along the bilateral pharyngeal walls extending to the thyroid bed. The patient underwent bilateral tonsillectomy and drainage of the abscesses. She was extubated the following day. Cultures from the abscesses grew rare Klebsiella pneumoniae, susceptible to Ampicillin-sulbactam. A barium swallow on day 14 showed no evidence of a pyriform sinus fistula. She was discharged on day 15 with Augmentin for 7 days. On discharge, free T4 decreased to half (2.39 ng/dL), and Total T3 normalized (1.08ng/dL). Conclusion: This case presents a rare instance of AST in an immunocompetent patient without anatomical anomalies, stemming from the spread of peritonsillar and parapharyngeal abscesses into the thyroid bed. AST should be considered in cases of deep neck infections, as it is a potentially life-threatening disease. It is crucial to identify and treat AST early to prevent complications. The primary treatment involves antibiotics, incision, and drainage. Presentation: 6/1/2024

Copeptin as an inflammatory marker in diagnosis and prognosis of neonatal sepsis

BackgroundCopeptin is an immediate biomarker of individual stress response; many life-threatening diseases are causing a high elevation of its concentration in plasma, such as myocardial infarction and cardiovascular shock. Moreover, copeptin is a promising marker in sepsis. We aimed to evaluate copeptin as a diagnostic and prognostic marker in neonatal sepsis for the early initiation of appropriate therapy and the prediction of mortality. A prospective case-control study involved 237 neonates (165 cases had neonatal sepsis, and 72 served as controls). Cases were admitted to the neonatal intensive care unit (NICU) and followed up for symptoms and signs of sepsis confirmed by laboratory data: complete blood count (CBC), c-reactive protein (CRP), and cultures. Serum copeptin level by the enzyme-linked immunosorbent assay (ELISA) was measured for all included neonates. We observed that the copeptin level was significantly higher in cases than control (3.51 ± 1.4, 1.61 ± 0.51 pmol/liter, respectively). The cut-off value of copeptin at which we can discriminate between cases and controls was above 2.065 pmol/liter. Among cases, copeptin was higher in early-onset sepsis (EOS) than late-onset sepsis (LOS) neonates, and there was a significant correlation between its level and all the following: age at admission, birth weight, gestational age, history of perinatal asphyxia, maternal chorioamnionitis, and premature rupture of membrane (PROM). Also, copeptin was strongly associated with CRP level and the poor prognosis of patients. Copeptin can predict the death of cases at a cut-off value above 2.995 pmol/liter.ConclusionSerum copeptin level can be used as a diagnostic and prognostic marker in neonatal sepsis.

Enforced HCELL Expression Enhances Bone Marrow Stromal Cells Homing and Amelioration of Cerebral Ischemia-Reperfusion Injury via induction of PGE2.

Ischemic stroke (IS) is a significant and potentially life-threatening disease with limited treatment options, often resulting in severe disability. Bone marrow stromal cells (BMSCs) transplantation has exhibited promising neuroprotection following cerebral ischemia-reperfusion injury (CIRI). However, the effectiveness is hindered by their low homing rate when administered through the vein. In this study, we aimed to enhance the homing ability of BMSCs through lentivirus transfection to express fucosyltransferase 7. This glycosylation engineered CD44 on BMSCs to express hematopoietic cell E-selectin/L-selectin ligand (HCELL), which is the most potent E-selectin ligand. Following enforced HCELL expression, the transplantation of BMSCs was then evaluated in a middle cerebral artery occlusion (MCAO) model. Results showed that HCELL+BMSCs significantly ameliorated neurological deficits and reduced the volume of cerebral infarction. Furthermore, the transplantation led to a decrease in apoptosis by up-regulating BCL-2 and down-regulating BAX, also reduced the mRNA levels of inflammatory factors, such as interleukin-1β (IL-1β), IL-2, IL-6 and tumor necrosis factor-alpha (TNF-α) in the ischemic brain tissue. Notably, enforced HCELL expression facilitated the migration of BMSCs towards cerebral ischemic lesions and their subsequent transendothelial migration through the up-regulation of PTGS-2, increased production of PGE2 and activation of VLA-4. In summary, our study demonstrates that transplantation of HCELL+BMSCs effectively alleviates CIRI, and that enforced HCELL expression enhances the homing of BMSCs to cerebral ischemic lesions and their transendothelial migration via PTGS-2/PGE2/VLA-4. These findings indicate that enforced expression of HCELL on BMSCs could serve as a promising therapeutic strategy for the treatment of ischemic stroke.

Surcharges cutanées endogènes

As in other organs, the diagnosis of endogenous cutaneous overload diseases is based on histopathological analysis of the lesions using special stainings, even if the clinical appearance is sometimes very suggestive. The lesions are sometimes very subtle and can be included in the group of "invisible" dermatoses, such as primary macular cutaneous amyloidosis or calciphylaxis. Superficial dermal melanosis or pigmentary incontinence generally reflects the post-inflammatory stage of a chronic or recurrent interface dermatitis. Section levels should be systematically performed to look for active lesions of diagnostic interest: Alcian blue staining to identify dermal mucinosis (connectivitis) and pan-T markers (fixed pigmented erythema, lichenoid mycosis fungoides, and vitiligo). Some pathologies have a prognostic impact, either because they reflect an underlying disease, monoclonal gammopathies, in particular myeloma, being one of the most common conditions in this context (AL amyloidosis, xanthoma and xanthogranuloma, scleromyxedema), or because they can be associated with visceral damage (AL amyloidosis, scleromyxedema). The clinical-pathological comparison is mandatory to rule out differential diagnoses, especially for life-threatening diseases: nodular amyloidosis and primary cutaneous amyloidosis versus systemic AL amyloidosis, papular mucinosis versus scleromyxedema and calcific panniculitis versus calciphylaxis.

Delineating, Imaging, and Assessing Pulmonary Fibrosis Remodeling via Collagen Hybridization.

Idiopathic pulmonary fibrosis (IPF) is a progressive, life-threatening disease with no early detection, few treatments, and dismal outcomes. Although collagen overdeposition is a hallmark of lung fibrosis, current research mostly focuses on the cellular aspect, leaving collagen, particularly its dynamic remodeling (i.e., degradation and turnover), largely unexplored. Here, using a collagen hybridizing peptide (CHP) that specifically binds unfolded collagen chains, we reveal vast collagen denaturation in human IPF lungs and delineate the spatiotemporal progression of collagen denaturation three-dimensionally within fibrotic lungs in mice. Transcriptomic analyses support that lung collagen denaturation is strongly associated with up-regulated collagen catabolism in mice and patients. We thus show that CHP probing differentiates remodeling responses to antifibrotics and highlights the resolution of established fibrosis by agents up-regulating collagen catabolism. We further develop a radioactive CHP that detects fibrosis in vivo in mice as early as 7 days postlung-injury (Ashcroft score: 2-3) by positron emission tomography (PET) imaging and ex vivo in clinical lung specimens. These findings establish collagen denaturation as a promising marker of fibrotic remodeling for the investigation, diagnosis, and therapeutic development of pulmonary fibrosis.

Optimal medical therapy, clinical outcome and its predictors in patients with acute coronary syndrome after discharge with secondary prevention medications at University of Gondar Comprehensive Specialized Hospital, North West Ethiopia, 2023: A retrospective follow-up study

BackgroundThe life-threatening diseases known as ACS (acute coronary syndrome) continue to produce considerable rates of morbidity and mortality despite breakthroughs in therapy. The study determined clinical outcome and its predictors in patients at the University of Gondar Comprehensive and Specialized Hospital (UOGCSH), North West Ethiopia.Design, setting, and participantsA retrospective cohort study design was employed at UOGCSH from January 31, 2018 to February 1, 2023. The hospital used a systematic random sampling procedure to select study participants from the medical records of patients in chronic cardiac follow-up clinics.Main outcome measuresExposures were optimal medical therapy (OMT) versus non-optimal medical therapy collected from May to August 2023. Descriptive and analytical statistics were employed to compare study groups. A binary logistic regression model was employed to identify candidate variables for further analysis. Cox's proportional hazard model and log-rank test were employed, with a P-value < 0.05 used to evaluate statistical significance. A five-year all-cause mortality after discharge estimate was displayed by using Kaplan–Meier curves.ResultsAmong 422 patients with ACS [mean age, 61.56 (SD = 9.686) years; 54.7% male], of whom only 59.2% (250) received optimal medical therapy at discharge. Age ≥ 65, atrial fibrillation, chronic kidney diseases, and cardiogenic shock were negative independent predictors of optimal medical therapy. On the other hand, male sex was independently associated with the use of optimal medical therapy. All-cause mortality occurred in 16.6% (n = 70) and major adverse cardiac events occurred in 30.8% (n = 130) of patients with a 95% CI of 0.132–0.205 and 0.264–0.355, respectively. Multivariate analyses indicated that OMT was significantly associated with reduced all-cause mortality (aHR: 0.431, 95% CI: 0.222–0.835; P = 0.013).ConclusionThis study revealed that the use of preventive OMT in patients discharged with acute coronary syndrome was associated with a reduction in all-cause mortality. However, the use of this OMT is suboptimal.

What do family caregivers of patients with life-threatening diseases need from healthcare professionals? A qualitative study

ObjectivesTo explore the common ground of what family caregivers need in their various roles (caregiver, care recipient and patient’s partner, child or friend) from healthcare professionals across healthcare settings and...

Incontinentia pigmenti underlies thymic dysplasia, autoantibodies to type I IFNs, and viral diseases.

Human inborn errors of thymic T cell tolerance underlie the production of autoantibodies (auto-Abs) neutralizing type I IFNs, which predispose to severe viral diseases. We analyze 131 female patients with X-linked dominant incontinentia pigmenti (IP), heterozygous for loss-of-function (LOF) NEMO variants, from 99 kindreds in 10 countries. Forty-seven of these patients (36%) have auto-Abs neutralizing IFN-α and/or IFN-ω, a proportion 23 times higher than that for age-matched female controls. This proportion remains stable from the age of 6 years onward. On imaging, female patients with IP have a small, abnormally structured thymus. Auto-Abs against type I IFNs confer a predisposition to life-threatening viral diseases. By contrast, patients with IP lacking auto-Abs against type I IFNs are at no particular risk of viral disease. These results suggest that IP accelerates thymic involution, thereby underlying the production of auto-Abs neutralizing type I IFNs in at least a third of female patients with IP, predisposing them to life-threatening viral diseases.

Ameliorative effects of Turbinaria ornata extract on hepatocellular carcinoma induced by diethylnitrosamine in-vivo.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths and the fifth most common cancer worldwide. Brown algae appeared to be a rich source of efficient and safe agents against many life-threatening diseases like cancer. Thus, the scope of this study was to investigate the therapeutic effects of Turbinaria ornata against experimentally induced HCC in a rat model. Accordingly, forty male albino rats were divided into four groups. HCC was induced by intraperitoneal injection with diethylnitrosamine (DENA) followed by carbon tetrachloride (CCL4). After four weeks of DENA + CCL4 injection and two weeks of treatment with Turbinaria ornata, rats were sacrificed to collect hepatic tissue and blood samples for histopathological observations and various biochemical markers such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alpha-fetoprotein (AFP), urea, creatinine, albumin (ALB), and alkaline phosphatase (ALP). Rats that were injected for four weeks with DENA + CCL4 showed a significant increase in AFP levels, transforming growth factor-beta (TGF-β) and tumor necrosis factor-alpha (TNF-α), as well as a high percentage of malignant changes in hepatic tissues. The extension of malignant changes in the rat liver tissues was markedly reduced using Turbinaria ornata, as the treatment displayed liver patterns similar to that of the normal control rats. Furthermore, rats with HCC fed with Turbinaria ornata extract for two weeks showed decreasing levels of TGF-β and TNF-α. These findings demonstrate that Turbinaria ornata supplement can prevent HCC development in hepatic rats; however, the exact mechanism requires further investigation.

A rare case of tetanus with early manifestation of apnea but without trismus

BackgroundTetanus is a life-threatening disease caused by tetanus neurotoxin (TeNT) produced by Clostridium tetani. Early symptoms of tetanus are trismus and muscle stiffness, both caused by spasticity. TeNT mainly exerts its effect by impairment of inhibitory neurons in the spine and brainstem, resulting in the hyperactivity of motor neurons, which causes spasticity and muscle spasms. Apnea is not a symptom that is predicted to occur in the early stages. Case ReportWe present a rare case of severe tetanus with an early manifestation of apnea but without trismus. We believe that apnea was caused by spasms of the intercostal muscles and its early manifestation was due to a high load of TeNT, considering that the speed of disease progression is related to disease severity. We hypothesize that the absence of trismus was also due to a high load of TeNT, exerting toxic effect at the neuromuscular junction and causing flaccid paralysis of the massetersWhy Should an Emergency Physician Be Aware of This?:Since there is no diagnostic laboratory test for tetanus, emergency physicians must be well aware of symptoms that may or may not appear in tetanus. Tetanus should be considered as a differential diagnosis for patients arriving at the emergency department with apnea as an early symptom. The absence of trismus should not rule out the possibility of tetanus.

FocalNeXt: A ConvNeXt augmented FocalNet architecture for lung cancer classification from CT-scan images

Early and accurate diagnosis of lung cancer, a life-threatening disease, is critical to the successful treatment of patients with the disease. On the other hand, it is well known that the integration of computer-aided diagnosis (CAD) systems into the diagnostic workflow facilitates the process and improves the diagnostic results of automated systems by reducing the difficulties associated with human observation. In this paper, we present FocalNeXt, a new ConvNeXt-augmented FocalNet architecture specifically designed for automated lung cancer detection from computed tomography (CT) scan images. By combining the strong attention mechanism of FocalNet and the feature extraction mechanism of ConvNeXt within the vision transformer paradigm, FocalNeXt aims to improve diagnostic accuracy. Our comprehensive evaluation of a publicly available Iraq-Oncology Teaching Hospital/National Center for Cancer Diseases (IQ-OTH/NCCD) CT-scan dataset includes rigorous comparisons and an ablation study. FocalNeXt achieved an accuracy of 99.81%, outperforming the state-of-the-art methods. The model also excelled in sensitivity (99.78%), recall (99.36%), and F1-score (99.56%), positioning FocalNeXt as a leading model for lung cancer detection. The ablation study further demonstrated its efficacy and underscored the robustness of FocalNeXt in different configurations. The results underline its potential to contribute to advances in medical imaging and personalized healthcare.

Conformational Differences in the Light Chain Constant Domain of Immunoglobulin G and Free Light Chain May Influence Proteolysis in AL Amyloidosis

Immunoglobulin light chain amyloidosis (AL) is a life-threatening disease caused by the deposition of light chain (LC) and its fragments containing variable (VL) and portions of constant (CL) domains. AL patients feature either monoclonal free LCs (FLCs) circulating as covalent and noncovalent homodimers, or monoclonal immunoglobulin (Ig) wherein the LC and heavy chain (HC) form disulfide-linked heterodimers, or both. The role of full-length Ig in AL amyloidosis is unclear as prior studies focused on FLC or VL domain. We used a mammalian cell-based expression system to generate four AL patient-derived full-length IgGs, two non-AL IgG controls, and six corresponding FLC proteins derived from an IGLV6-57 germline precursor. Comparison of proteins’ secondary structure, thermal stability, proteolytic susceptibility, and disulfide link reduction suggested the importance of local vs. global conformational stability. Analysis of IgGs vs. corresponding FLCs using hydrogen–deuterium exchange mass spectrometry revealed major differences in the local conformation/dynamics of the CL domain. In all IgGs vs. FLCs, segments containing β-strand and α-helix βAC-αACBC were more dynamic/exposed while segment βDC-βEC was less dynamic/exposed. Notably, these segments overlapped proteolysis-prone regions whose in vivo cleavage generates LC fragments found in AL deposits. Altogether, the results suggest that preferential cleavage in segments βAC-αACBC of FLC or βDC-βEC of LC in IgG helps generate amyloid protein precursors. We propose that protecting these segments using small-molecule stabilizers, which bind to the interfacial cavities CL-CL in FLC and/or CL-CH1 in IgG, is a potential therapeutic strategy to complement current approaches targeting VL-VL or VL-CL stabilization of LC dimer.

The Antiviral Potential of a Natural Compound for COVID-19: A Review of the Current Findings

Objective Coronavirus disease 2019 (COVID-19), a novel viral disease originating from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a life-threatening disease with dramatic morbidity and mortality globally. In this review, we aim to discuss the current evidence showing that the Imam Kazem drug, a natural compound that comprises Foeniculum vulgare, Terminalia chebula, Pistacia lentiscus, and red sugar, may be a therapeutic candidate in the fight against COVID-19 infection. Methods This literature review was performed by searching related words, including “ Imam Kazem drug,” “ Foeniculum vulgare,” “ Terminalia chebula,” “ Pistacia lentiscus,” “ Red sugar,” “Natural compounds,” “Traditional medicine,” “Coronaviruses,” “Antiviral,” “COVID-19,” “SARS-CoV-2,” in different databases like Google Scholar, Scopus, PubMed, Web of Science, and Scientific Information Databases until 2023. Results The current documents underscore that the Imam Kazem drug may be safe and effective against COVID-19. This natural compound, thanks to its constituents, may affect the pathogenic occurrence related to the disease, such as attenuating oxidative stress and inflammation-associated occurrences by different mechanisms, like scavenging free radicals, enhancing the function of antioxidant enzymes, and attenuating cytokine storm. Moreover, the Imam Kazem drug can exert its antiviral ability mainly by suppressing viral replication and blocking glycosaminoglycan binding sites. However, more preclinical and clinical evidence is required to support these results. Conclusion Imam Kazem drug may have a therapeutic capacity for patients with COVID-19 infection.

NEURO DEEP FUZZY GENETIC ALGORITHM APPROACH FOR CLASSIFICATION AND DETECTION OF BRAIN TUMOR FROM LARGE DATASETS

Brain tumors represent one of the most critical and life-threatening diseases. Early detection and accurate classification are essential for effective treatment planning and survival rate improvement. With the exponential growth of medical data, particularly in imaging and diagnostic datasets, traditional algorithms face limitations in handling large-scale, high-dimensional data efficiently. Conventional machine learning and diagnostic methods often struggle with classification accuracy, computational complexity, and overfitting in large, noisy datasets. Addressing these issues is crucial for the development of robust diagnostic tools capable of handling real-world clinical data. This paper presents a novel hybrid approach combining Neural Networks, Deep Learning, Fuzzy Logic, and Genetic Algorithms, termed Neuro Deep Fuzzy Genetic Algorithm (NDFGA), for the classification and detection of brain tumors from large datasets. Neural Networks and Deep Learning architectures are leveraged for feature extraction and hierarchical learning. Fuzzy Logic improves interpretability and manages uncertainty in medical data, while Genetic Algorithms optimize feature selection and model parameters. This hybrid method is designed to maximize classification accuracy while minimizing false positives and computational overhead. The proposed approach was tested on a large brain tumor dataset comprising over 10,000 MRI scans. The NDFGA approach demonstrated superior performance compared to standalone methods. It achieved a classification accuracy of 97.8%, a sensitivity of 96.5%, and a specificity of 98.1%. The model also showed improved robustness in handling large datasets, reducing false positives by 12% and computational time by 15% compared to traditional methods. This hybrid model presents a scalable and efficient solution for brain tumor detection, especially in clinical environments.

A scenario for heart failure during the filling phase

Heart failure (HF) is a life-threating cardiac disease that develops progressively for the reduced ability of the left ventricle (LV) to pump blood into the circulation during systole. HF can also develop in patients with a preserved systolic function, typically in presence of hypertrophic cardiomyopathy (HCM). This type of HF is sometimes termed as diastolic HF, but its biomechanical origin is still unclear. This study employs a physics-based analysis of both the LV and left atrium (LA) in selected HCM patients and matched healthy subjects using 3D echocardiography and demonstrates that alteration on the LV side (stiffening) reduces the elastic recovery of the LA. Moreover, the analysis of the forces exchanged between the two chambers demonstrates that they result unbalanced, keeping the LA in a sustained stretched condition that leads to dilation. This scenario clarifies the diastolic root of the dysfunction that may likely be the cause of the spiraling of events progressing toward failure of both LA emptying and LV filling. This deeply interdisciplinary study provides a physics-based basis for both physics/engineering modeling of heart function and to cardiologists for the design of clinical studies.

Recent Insight into Herbal Bioactives-based Novel Approaches for Chronic Intestinal Inflammatory Disorders Therapy.

Inflammatory bowel disease (IBD) is a life-threatening complex disease. It causes chronic intestinal inflammation in GIT. IBD significantly affects people's lifestyles and carries a high risk of colon cancer. IBD involves the rectum, ileum, and colon, with clinical manifestations of bloody stools, weight loss, diarrhea, and abdominal pain. The prevalence of inflammatory disease is increasing dramatically worldwide. Over 16 million people are affected annually in India, with an economic burden of $6.8- $8.8 billion for treatment. Modern medicine can manage IBD as immunosuppressive agents, corticosteroids, tumor necrosis factor antagonists, integrin blockers, and amino-salicylates. However, these approaches are allied with limitations such as limited efficacy, drug resistance, undesired side effects, and overall cost, which cannot be ignored. Hence, the herbal bioactives derived from various plant resources can be employed in managing IBD. Science Direct, PubMed, Google, and Scopus databases have been searched for conclusively relevant herbal plant-based anti-inflammatory agent compositions. Studies were screened through analysis of previously published review articles. Eminent herbal bioactives, namely curcumin, resveratrol, ellagic acid, silybin, catechin, kaempferol, icariin, glycyrrhizin acid, berberine, quercetin, rutin, and thymol are reported to be effective against IBD. Herbal leads are promising treatment options for IBD; they have been shown to display antiinflammatory and antioxidant properties by targeting enzymes and regulating the expressions of various inflammatory mediators. Natural products have been reported to have anti-inflammatory properties in various clinical and preclinical studies, and some are available as herbal preparations. Herbal medicine would be promising in association with the implication of a novel drug delivery system for managing IBD.

Pyometra alters uterine aquaporins related with lipopolysaccharide concentrations and antioxidant enzyme activities in bitches

Pyometra is a common life-threatening inflammatory disease with a complex etiopathogenesis that develops during the diestrus stage and can be observed in elderly intact bitches. The present study evaluated five aquaporin (AQP1, AQP2, AQP3, AQP5, and AQP9) transcript abundances and immunolocalization in the uterine tissue, and investigated their relationship with uterine tissue and blood lipopolysaccharide (LPS) concentration, superoxide dismutase (SOD) and glutathione peroxidase (GPX) activity, and nitric oxide (NO) production in dogs suffering from pyometra. The study sampled 36 client-owned intact bitches from different breeds, of which 24 cases were diagnosed with pyometra. Twelve of these bitches in the diestrus stage that presented for elective ovariohysterectomy were used as the control group. Blood samples were collected into tubes without anticoagulant for serum progesterone, LPS concentration, and antioxidant activities at the time of diagnosis. Bacteriological and tissue samples from the uteri were collected after the ovariohysterectomy. The tissue samples were used to determine antioxidant activity, and hormone and toxin concentrations. Transcript abundance of uterine AQPs were determined by qPCR, and their presence and localization were determined by by immunohistochemistry. For all pyometra samples, the bacteria isolated from the uterine swabs were Escherichia coli. Compared to the control group, AQP1, AQP2, and AQP5 were downregulated more than 2-fold, whereas AQP9 was upregulated nearly 3-fold and AQP3 was upregulated more than 4-fold in the pyometra affected uteri (P<0.05). Uterine AQP1 was moderately negatively correlated with serum LPS concentration (r=-0.568, P<0.01) and tissue NO production (r=-0.407, P<0.05). AQP5 was positively correlated with serum SOD activity (r=0.485, P<0.05) and negatively correlated with serum LPS concentration (r=-0.512, P<0.05). AQP9 was negatively correlated with tissue SOD and serum GPx activity. This is the first study to identify AQP9 transcript abundance and immunolocalization in canine uterine tissue. Uterine AQP1, AQP2, AQP3, AQP5, and AQP9 transcript abundances were altered in spontaneously developed canine pyometra while AQP transcript abundance was negatively related to serum toxin concentration, NO production, and antioxidant enzyme activity. Further studies should be conducted to determine the role of altered abundances of AQPs transcripts in pyometra pathogenesis.