Azafuramidines as potential anticancer Agents: Pro-apoptotic profile and cell cycle arrest.

The current study aimed to test the antiproliferative activity of three azafuramidines (X, Y, and Z) against three different human cell lines; liver HepG2, breast MCF-7, and bone U2OS. And to explore the molecular mechanism(s) of the antiproliferative activity of these derivatives. The three new azafuramidines demonstrated a potent cytotoxicity at < 2 µM against the three cell lines investigated. The azafuramidines were highly selective with selectivity index âˆ¼ 47 - 61 folds indicating safety to the normal cells. In the scratch assay, azafuramidines significantly reduced the percentage of wound healing indicating ability to prevent or reduce metastasis. Derivatives X and Z arrested the HepG2 cells at S and G2/M phases detected by the flow cytometry. Derivatives X, Y, and Z elevated the apoptosis of HepG2 cells by âˆ¼ 71 %, 66 %, and 59 %, respectively. Derivatives X and Z were superior to derivative Y. The potent antiproliferative, cell cycle arrest, and pro-apoptotic efficacy of these chlorophenyl derivatives could be attributed to their ability of inducing the overexpression of p53, p21, and p27. These derivatives had the potential to act as anticancer agents and merit further investigations.

Enhancing metabolic efficiency via novel constitutive promoters to produce protocatechuic acid in Escherichia coli.

The antioxidant molecule protocatechuic acid (PCA) can also serve as a precursor for polymer building blocks. PCA can be produced in Escherichia coli overexpressing 3-dehydroshikimate dehydratase (DSD), an enzyme that catalyses the transformation of 3-dehydroshikimate to PCA. Nevertheless, optimizing the expression rate of recombinant enzymes is a key factor in metabolic engineering when producing biobased chemicals. In this study, a degenerate synthetic promoter approach was investigated to improve further the production of PCA. By limited screening of a randomized promoter library made using pSEVA221 plasmid in E. coli, three novel synthetic constitutive promoters were selected that increased the PCA yield from glucose by 10-21% compared to the inducible T7-promoter. RT-qPCR analysis showed that the DSD gene, regulated by the synthetic promoters, had high expression during the exponential phase, albeit the gene expression level dropped 250-fold during stationary phase. Besides the increased product yield, the synthetic promoters avoided the need for a costly inducer for gene expression. Screening of the entire promoter library is likely to provide more positive hits. The study also shows that E. coli transformed with the DSD gene on either pSEVA221 or pCDFDuet plasmids exhibit background PCA levels (~ 0.04 g/L) in the absence of a transcriptional regulatory element. KEY POINTS: • Degenerate synthetic promoters are remarkable tools to produce protocatechuic acid. • The constitutive synthetic promoters did not affect the growth rate of the bacterial host. • The use of constitutive synthetic promoters avoids the need for the costly inducer.

RobEns: Robust Ensemble Adversarial Machine Learning Framework for Securing IoT Traffic.

Recently, Machine Learning (ML)-based solutions have been widely adopted to tackle the wide range of security challenges that have affected the progress of the Internet of Things (IoT) in various domains. Despite the reported promising results, the ML-based Intrusion Detection System (IDS) proved to be vulnerable to adversarial examples, which pose an increasing threat. In fact, attackers employ Adversarial Machine Learning (AML) to cause severe performance degradation and thereby evade detection systems. This promoted the need for reliable defense strategies to handle performance and ensure secure networks. This work introduces RobEns, a robust ensemble framework that aims at: (i) exploiting state-of-the-art ML-based models alongside ensemble models for IDSs in the IoT network; (ii) investigating the impact of evasion AML attacks against the provided models within a black-box scenario; and (iii) evaluating the robustness of the considered models after deploying relevant defense methods. In particular, four typical AML attacks are considered to investigate six ML-based IDSs using three benchmarking datasets. Moreover, multi-class classification scenarios are designed to assess the performance of each attack type. The experiments indicated a drastic drop in detection accuracy for some attempts. To harden the IDS even further, two defense mechanisms were derived from both data-based and model-based methods. Specifically, these methods relied on feature squeezing as well as adversarial training defense strategies. They yielded promising results, enhanced robustness, and maintained standard accuracy in the presence or absence of adversaries. The obtained results proved the efficiency of the proposed framework in robustifying IDS performance within the IoT context. In particular, the accuracy reached 100% for black-box attack scenarios while preserving the accuracy in the absence of attacks as well.

Design, Analysis, and Development of Low-Cost State-of-the-Art Magnetorheological-Based Microprocessor Prosthetic Knee.

For amputees, amputation is a devastating experience. Transfemoral amputees require an artificial lower limb prosthesis as a replacement for regaining their gait functions after amputation. Microprocessor-based transfemoral prosthesis has gained significant importance in the last two decades for the rehabilitation of lower limb amputees by assisting them in performing activities of daily living. Commercially available microprocessor-based knee joints have the needed features but are costly, making them beyond the reach of most amputees. The excessive cost of these devices can be attributed to custom sensing and actuating mechanisms, which require significant development cost, making them beyond the reach of most amputees. This research contributes to developing a cost-effective microprocessor-based transfemoral prosthesis by integrating off-the-shelf sensing and actuating mechanisms. Accordingly, a three-level control architecture consisting of top, middle, and low-level controllers was developed for the proposed prosthesis. The top-level controller is responsible for identifying the amputee intent and mode of activity. The mid-level controller determines distinct phases in the activity mode, and the low-level controller was designed to modulate the damping across distinct phases. The developed prosthesis was evaluated on unilateral transfemoral amputees. Since off-the-shelf sensors and actuators are used in i-Inspire, various trials were conducted to evaluate the repeatability of the sensory data. Accordingly, the mean coefficients of correlation for knee angle, force, and inclination were computed at slow and medium walking speeds. The obtained values were, respectively, 0.982 and 0.946 for knee angle, 0.942 and 0.928 for knee force, and 0.825 and 0.758 for knee inclination. These results confirmed that the data are highly correlated with minimum covariance. Accordingly, the sensors provide reliable and repeatable data to the controller for mode detection and intent recognition. Furthermore, the knee angles at self-selected walking speeds were recorded, and it was observed that the i-Inspire Knee maintains a maximum flexion angle between 50° and 60°, which is in accordance with state-of-the-art microprocessor-based transfemoral prosthesis.

Visnagin: A novel cardioprotective agent against anthracycline toxicity (Review).

Doxorubicin (DOX), a cornerstone of cancer chemotherapy, is marred by its dose-dependent cardiotoxicity, leading to cardiomyopathy and heart failure. The epidemiology of DOX-related cardiotoxicity highlights its cumulative, progressive nature, with a significant impact on the health of patients. The pathophysiological mechanisms involve mitochondrial dysfunction, oxidative stress and disrupted calcium homeostasis in cardiomyocytes. Despite the search for effective cardioprotective strategies, current treatments offer limited efficacy. Visnagin emerges as a potential solution, known for its vasodilatory and anti-inflammatory properties, and recent studies suggest its cardioprotective efficacy against DOX-induced cardiotoxicity through mitochondrial protection, the modulation of key signaling pathways and the inhibition of apoptosis. The present review aimed to provide a comprehensive overview of the mechanisms of action of visnagin, as well as to provide experimental evidence, and potential integration into cancer treatment regimens, highlighting its promise as a novel therapeutic agent for managing cardiotoxicity in patients undergoing anthracycline chemotherapy.

Selective Immunoglobulin M Deficiency in Patients with Autoimmune Liver Diseases.

Cite this article as: Balaban YH, Ismail M, Nur Ayar S. Selective immunoglobulin M deficiency in patients with autoimmune liver diseases. Turk J Gastroenterol. 2024;35(6):505-508.

Skin Cancer Recognition Using Unified Deep Convolutional Neural Networks.

The incidence of skin cancer is rising globally, posing a significant public health threat. An early and accurate diagnosis is crucial for patient prognoses. However, discriminating between malignant melanoma and benign lesions, such as nevi and keratoses, remains a challenging task due to their visual similarities. Image-based recognition systems offer a promising solution to aid dermatologists and potentially reduce unnecessary biopsies. This research investigated the performance of four unified convolutional neural networks, namely, YOLOv3, YOLOv4, YOLOv5, and YOLOv7, in classifying skin lesions. Each model was trained on a benchmark dataset, and the obtained performances were compared based on lesion localization, classification accuracy, and inference time. In particular, YOLOv7 achieved superior performance with an Intersection over Union (IoU) of 86.3%, a mean Average Precision (mAP) of 75.4%, an F1-measure of 80%, and an inference time of 0.32 s per image. These findings demonstrated the potential of YOLOv7 as a valuable tool for aiding dermatologists in early skin cancer diagnosis and potentially reducing unnecessary biopsies.

Population Pharmacokinetics of Bepirovirsen in Healthy Participants and Participants with Chronic Hepatitis B Virus Infection: Results from Phase 1, 2a, and 2b Studies.

INTRODUCTION: Bepirovirsen is a novel antisense oligonucleotide in development for chronic hepatitis B virus (HBV) infection therapy. Understanding the impact that clinical characteristics may have on bepirovirsen exposure is important for determining efficacious and well-tolerated dosing regimens. This analysis evaluated demographics and clinical characteristics associated with bepirovirsen exposure using a population pharmacokinetic (PK) analysis. METHODS: Population PK analyses were conducted using pooled data from three phase 1/2 clinical studies (NCT03020745/NCT02981602/NCT04449029) to construct a structural PK model for bepirovirsen that adequately described plasma concentration-time profiles and identify covariates that affect systemic exposure. The final population PK model was used to simulate bepirovirsen exposure measures to inform exposures at different dose levels and within different subpopulations. RESULTS: Bepirovirsen PK data were well-described by a linear, three-compartment model with first-order absorption and absorption delay. Chronic HBV infection status, body weight, and Asian versus non-Asian race were key covariates included in the final model. Visual inspection of correlation scatter plots confirmed general agreement between observed and predicted data from the studies. In simulations, bepirovirsen systemic exposure was dosed proportionally and predicted to be almost completely washed out by 12 weeks following the final 300-mg dose. Differences in body weight, Asian race, or disease status did not result in clinically relevant differences in exposure. CONCLUSIONS: This analysis demonstrated that the linear three-compartmental model accurately described bepirovirsen PK data. The lack of clinically relevant differences seen in exposure indicate that dose adjustments are not recommended for bepirovirsen based on demographics or clinical characteristics.

Treatment-Resistant Immunoproliferative Small Intestinal Disease (IPSID) Leading to Lymphoma.

Immunoproliferative small intestinal disease (IPSID) is a distinct variant of mucosa-associated lymphoid tissue (MALT) lymphoma, often linked to chronic Campylobacter jejuni infection. Characterized as an extra-nodal marginal zone B-cell lymphoma, IPSID predominantly affects the proximal small intestine. It features lymphoplasmacytic infiltration and deposition of monotypic α-heavy chains in the lamina propria, leading to blunted intestinal villi, malabsorption, and protein-losing enteropathy. IPSID's clinical spectrum ranges from lymphoid infiltration to malignant diffuse large B-cell lymphoma. Similar to MALT lymphoma, early-stage IPSID can be resolved with antibiotic therapy. This case study documents a 50-year-old Nigerian woman presenting with recurrent watery diarrhea, abdominal pain, and weight loss, unresponsive to antibiotics. A 50-year-old female immigrant from Nigeria presented with recurrent watery diarrhea, abdominal pain, and significant weight loss, all refractory to antibiotic treatment. Initial diagnostic investigations revealed a positive Campylobacter stool antigen, mesenteric lymphadenopathy on CT and gallium scans, and diffuse mucosal lymphoplasmacytic infiltration with villi flattening on small bowel biopsies. An octreotide scan identified a reactive mesenteric lymph node, confirmed by surgical biopsy as reactive lymphadenitis. The patient was diagnosed with IPSID and commenced antibiotic therapy, which initially resolved her symptoms. However, she experienced frequent recurrences requiring multiple hospitalizations and repeated courses of intravenous antibiotics. Eventually, the disease progressed to lymphoma, necessitating chemotherapy initiation. This case underscores the diagnostic complexities of IPSID, particularly in distinguishing it from other causes of mesenteric lymphadenopathy. It also highlights the challenges in preventing disease progression from a benign to a malignant state despite appropriate antibiotic treatment. Given IPSID's prevalence in endemic regions, it should be considered in differential diagnoses for similar presentations. Continuous monitoring is crucial to evaluate therapeutic response and mitigate the risk of progression to lymphoma. IPSID presents a significant diagnostic and therapeutic challenge. This case exemplifies the necessity for heightened clinical awareness, especially in patients from endemic regions, and the importance of rigorous monitoring to prevent malignant transformation. Further research is warranted to elucidate the mechanisms behind IPSID progression in certain patients despite repeated antibiotic interventions.

A Novel Case of a Massive Amebic Liver Abscess in the Setting of Uncontrolled Diabetes Mellitus and Concurrent Pulmonary Embolism.

Amebic liver abscesses (ALAs), one of the most common extraintestinal manifestations of invasive amebiasis, pose diagnostic challenges due to their various clinical presentations and difficulty in distinguishing them from pyogenic abscesses. This case presentation highlights the intricacy of determining the source of an unusually large liver abscess that had an even rare occurrence of a coinciding pulmonary embolus without any evidence of a deep vein thrombosis. This unusual combination underscores the challenges in identifying and managing atypical cases of ALA and emphasizes the need for more comprehensive data to enhance our understanding of such occurrences.

Prevalence and associated factors of acute diarrhea among under-five children living in Hargeisa Internally Displaced Persons, Somaliland: a community-based cross-sectional study.

Introduction: in developing countries, diarrhea is a major cause of child death among those under five years old. Dehydration, malnutrition, delayed physical development and early childhood mortality are the major consequences of diarrheal diseases. In Somaliland, diarrheal diseases have been endemic and a major problem since 1994, with epidemics occurring annually. This study aimed to assess the prevalence and risk factors of acute diarrhea among children under five years old living in Hargeisa Internally Displaced Persons (IDPs), Somaliland. Methods: a community-based cross-sectional study was conducted among mothers of children under five from August to September 2020 in Hargeisa IDPs. A total of 383 mothers were selected using single population proportional formula. Data was entered, cleaned, and analyzed using SPSS version 22. To explore the association between variables, bivariate logistic regression was performed for each independent variable with the dependent variable. Variables with a p-value of < 0.05 were adjusted in multivariate logistic regression. Finally, variables with a p-value < 0.05 were recognized as determinants of acute diarrheal disease. Results: the prevalence of diarrhea among children under five living in Hargeisa IDPs was 51% (95% CI: 46%-56%). Children older than one year (AOR= 3.59, 95% CI: 2.05-5.20), those not exclusively breastfed (AOR= 4.01, 95% CI: 3.27-4.60), those not given colostrum milk (AOR= 36.41, 95% CI: 25.76-47.90), those drinking water stored in jerry-cans (AOR = 4.90, 95% CI: 1.31-8.39), and those with poor hand washing practices (AOR = 5.74, 95% CI: 1.38-7.82) were more likely to develop diarrhea than their counterparts. Conclusion: this study concludes that the prevalence of diarrhea was very high (51%). Lack of awareness of exclusive breastfeeding and colostrum feeding, storing drinking water in unprotected containers, and poor hand-washing practices were identified as significant predictors for childhood diarrhea (p-value < 0.05).

Atypical Clostridium difficile Infection in a Pregnant Patient: A Case Study on Non-Diarrheal Presentation and Syndrome of Inappropriate Antidiuretic Hormone (SIADH) Complication.

Clostridium difficile (C. difficile) is a Gram-positive, spore-producing bacterium that often leads to pseudomembranous colitis, typically manifesting as watery diarrhea. The risk factors for C. difficile infection (CDI) include exposure to broad-spectrum antibiotics, immunocompromised states, advanced age, usage of proton pump inhibitors (PPI), and comorbid conditions such as chronic kidney disease (CKD). This report details a case involving a 23-year-old pregnant woman who presented with symptoms of abdominal pain and constipation. She was diagnosed with a urinary tract infection (UTI) and treated with ceftriaxone. During her hospitalization, she was administered opioid pain relievers and underwent an intensive bowel regimen. Despite these measures, her constipation and abdominal discomfort persisted, and magnetic resonance imaging (MRI) of the abdomen revealed significant dilatation of the large bowel. The patient, discovered to have hyponatremia, underwent further evaluation. This revealed elevated urine osmolality and decreased blood plasma osmolality, indicative of a syndrome of inappropriate antidiuretic hormone secretion (SIADH). The patient received treatment with hypertonic saline. Later in her hospital stay, she tested positive for CDI through stool analysis and was treated with oral vancomycin. This case underscores the importance of considering CDI as a differential diagnosis in cases of ileus, abdominal pain, and constipation, especially in patients with notable risk factors for CDI. It highlights that the presence of diarrhea or watery bowel movements is not a necessary symptom for CDI testing.

Burden of Ischemic Heart Diseases among US States from 1990-2019.

BACKGROUND: Ischemic Heart Disease (IHD) is a leading cause of global mortality, including in the United States. Understanding the burden of IHD in the United States is crucial for informed decision-making and targeted interventions aimed at reducing morbidity and mortality associated with this leading cause of death. This study aimed to understand the burden of IHD, identify gender disparities and risk factors, explore the relationship between socioeconomic growth and IHD, and analyze risk factor distribution across the states of the United States. METHODS: This study utilized data from the Global Burden of Diseases Study 2019, which provided comprehensive information on IHD from 1990 to 2019. Data related to IHD from these years were extracted using a query tool from the Institute for Health Metrics and Evaluation (IHME) website. The study assessed the relationship between IHD and socioeconomic development using the Socio-demographic Index (SDI) and measured the overall impact of IHD using Disability-adjusted Life Years (DALYs), considering premature death and disability. Additionally, the study analyzed the burden of IHD attributed to six main risk factors. Data analysis involved comparing prevalence, mortality, SDI, DALYs, attributable burden, and risk estimation among the states. RESULTS: Between 1990 and 2019, there was an improvement in socioeconomic development in all states. Age-standardized rates of disease burden for IHD decreased by 50% [ASDR 3278.3 to 1629.4 (95% UI: 1539.9-1712.3) per 100,000] with the most significant decline observed in Minnesota. Males had higher burden rates than females in all states, and the southeast region had the highest mortality rates. The prevalence of IHD showed a declining trend, with approximately 8.9 million cases (95% UI: 8.0 million to 9.8 million) in 2019, representing a 37.1% decrease in the Age-standardized Prevalence Rate (ASPR) from 1990. Metabolic risks were the leading contributors to the disease burden, accounting for 50% of cases, with Mississippi having the highest attributable risk. Arkansas had the highest attributable risk for high cholesterol and smoking. Conversely, Minnesota had the lowest burden of IHD among all the states. CONCLUSION: This study highlights variations in the burden of IHD across US states and emphasizes the need for tailored prevention programs to address specific risk factors and gender differences. Understanding the trend in IHD may inform policymakers and healthcare professionals in effectively allocating resources to reduce the burden of IHD and improve national health outcomes.

Shifting tides in cardiology fellowship: an analysis of trends and the virtual interview revolution, 2017 to 2021.

Introduction: This investigation aimed to delineate the trends in cardiology fellowship applications and match rates between 2017 and 2021, with a particular focus on the effect of the COVID-19 pandemic. Methods: Utilizing data from the National Resident Matching Program and the American Board of Internal Medicine covering 6693 applicants, we conducted chi-square tests to assess match rate variations. IBM SPSS version 23 was used for statistical analysis. Results: The study noted an increase in matched US MD applicants (from 482 in 2017 to 549 in 2021, P = 0.0001) but a decrease in their match rate (from 89.8% to 83.1%). Matched US DO applicants rose significantly from 60 in 2017 to 103 in 2021 (P = 0.0001). A decline in first-choice matches and an increase in matches beyond the third choice were observed after the shift to virtual interviews. Conclusions: The study's analysis of cardiology fellowship trends from 2017 to 2021 underscores the escalating competitiveness in this field and signals a critical need for further research.

Primary Hepatic EBV-DLBCL Lymphoma in the Setting of COVID-19 Infection.

This case study describes an instance of primary hepatic diffuse large B cell lymphoma (DLBCL) in a patient who had prolonged coronavirus disease 2019 (COVID-19). DLBCL rarely presents as a primary hepatic mass. The 53-year-old man sought emergency care because of fatigue and weight loss. Diagnostic tests showed mildly elevated liver enzymes and imaging pointed to several low-density liver lesions. A liver biopsy paired with immunohistochemical testing verified the DLBCL diagnosis. Notably, the patient had COVID-19 4 months before the liver-related symptoms. The link between COVID-19 and the emergence of solid tumor cancers is unclear, but this case underscores its potential significance and the need for further research. This report stresses the importance of recognizing and documenting instances where COVID-19 might influence the onset of solid tumor cancers, including primary hepatic DLBCL.

Hepatocellular Carcinoma Incidence and Mortality in the USA by Sex, Age, and Race: A Nationwide Analysis of Two Decades.

Background and Aims: While the incidence rates of hepatocellular carcinoma (HCC) are increasing, there are limited comprehensive data on demographic-specific incidence and mortality trends in the USA. We aimed to evaluate recent trends in HCC incidence and mortality among different demographic groups in the USA. Methods: Age-adjusted HCC incidence rates were calculated from the Centers for Disease Control's United States Cancer Statistics database, which combines incidence data on newly diagnosed cancer cases and covers approximately 98% of the population in the USA. Additionally, age-adjusted HCC mortality rates were obtained from the Centers for Disease Control's National Center for Health Statistics database, which offers comprehensive coverage spanning nearly 100% of deaths attributed to HCC in the USA. Rates were stratified by sex, age (older [≥55 years] and younger [<55 years] adults), race and ethnicity (Non-Hispanic White, Non-Hispanic Black, Hispanic, Non-Hispanic Asian/Pacific Islander, and Non-Hispanic American Indian/Alaska Native), and tumor stage at diagnosis (early and late). Annual and average annual percentage change (AAPC) were calculated using joinpoint regression. A sex-specific pairwise comparison was conducted. Results: Between 2001 and 2020, there were 467,346 patients diagnosed with HCC (26.0% women), with increasing incidence in both sexes without significant difference (p=0.65). In younger adults (78,169 patients), the incidence decreased in men but not in women (AAPC difference=-2.39, p=0.002). This was seen in various racial and ethnic groups, mostly driven by early-stage tumors (AAPC difference=-2.65, p=0.02). There were 329,973 deaths attributed to HCC between 2000 and 2020 (28.4% women). In younger adults (43,093 deaths), mortality decreased in men at a greater rate than in women (AAPC difference=1.61, p=0.007). This was seen in various racial and ethnic groups, most notably in non-Hispanic American Indian/Alaska Natives (AAPC difference=-4.51, p=0.01). Conclusions: Nationwide USA data, covering nearly all HCC cases, show an increasing incidence and mortality over the last two decades. In younger adults, there was a decreasing incidence in men but not in women, due to early-stage tumors. Mortality improved in younger men at a greater rate than in women, especially in Non-Hispanic American Indian/Alaska Natives. Future studies are warranted to identify the risk factors associated with the occurrence and outcomes of HCC in demographic-specific populations, especially younger women.

Unique structural effect on the fluorosolvatochromism and dual fluorescence emission of D-π-A+ cationic chromophores with furyl bridge. An approach to white light emitters.

Photophysical behavior of two D - π - A+ cationic compounds with the same furyl bridge and nicotinamidine group as an electron acceptor moiety and two electron donating groups, namely methoxy (I) and N,N-dimethylamino (II) groups was examined using steady-state and time-resolved techniques in variety of solvents. Time-dependent density functional theory (TDDFT) calculations were performed in some representative solvents and compared with the experimental results. Steady state and time-resolved studies in different solvents reveal that fluorescence emission of (I) is ascribed to an emission from an excited state (ICT) with higher dipole moment than the ground state while the emission of (II) is a dual emission from a state with high charge transfer nature (ICT) in addition to the locally excited state (LE). The fluorescence emission spectra of (II) were found to depend on the excitation wavelength and an increase in the excitation wavelength led to the formation of a longer wavelength emission band with lower quantum yield. It has also been found that the fluorescence excitation spectra were dependent on the emission wavelength. The effect of solvent on the nature of dual emission was examined. Correlation of the photophysical properties of the excited states of (I) and (II) with the solvent polarity, ε, reveals the charge transfer nature of (I) and the long wavelength emission band of (II), while their correlation with the solvent polarity parameter (ETN) shows two different trends when the solvents are divided to aprotic and protic solvents. For precise investigation of the impact of each solvent parameter on each photophysical property, Catalán's and Laurence's four parametric linear solvation energy relationships were studied. We have found that the non-specific interactions of the solvent are primarily responsible for controlling the photophysical properties, as demonstrated by Catalán's and Laurence's treatments. DFT and TDDFT calculations were used to anticipate the dipole moments in the ground and excited states and geometry of both states.

Fibrolamellar Hepatocellular Carcinoma (FLHCC) in a Young Patient Presenting With Nausea and Vomiting After a Greasy Meal.

Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare and distinct subtype of liver cancer, predominantly affecting younger patients without underlying liver diseases. This case report discusses a unique presentation of FLHCC in a 38-year-old male with a past medical history of a well-controlled seizure disorder. The patient presented with nausea, vomiting, and abdominal pain following a fatty meal. Laboratory tests revealed elevated liver enzymes and anemia, and imaging showed a large hepatic lesion. Initial management included a septic workup and broad-spectrum antibiotics. However, a liver biopsy performed subsequently revealed the presence of FLHCC. The patient underwent a successful open right hepatectomy and was managed postoperatively with consideration of his seizure disorder. Follow-up at six months showed a stable postoperative condition without any evidence of recurrence. The diagnosis of FLHCC is challenging due to its rarity and nonspecific presentation. The case emphasizes the importance of considering FLHCC in the differential diagnosis of hepatic lesions, particularly in young patients. Surgical resection remains the primary treatment modality. This case underscores the importance of a thorough evaluation of hepatic lesions, especially in younger patients. It also illustrates the complexities in managing patients with FLHCC, requiring a multidisciplinary approach for optimal outcomes. Further research is necessary to better understand the pathogenesis of FLHCC and to develop more effective treatment strategies.

Gender-specific responses in gene expression of Nile tilapia (Oreochromis niloticus) to heavy metal pollution in different aquatic habitats.

Monitoring heavy metal accumulation is essential for assessing the viability of aquatic ecosystems. Our methodology involved integrating analysis of immunological, stress, inflammatory, and growth-related gene expression in male and female Nile tilapia with on-site recordings of physicochemical parameters. Additionally, we assessed the effect of different physicochemical parameters on heavy metal bioavailability and residual concentration in fish and water. Samples of fish and water were gathered from three different localities: Lake Brullus, a brackish lake sited in northern Egypt; Lake Nasser, an artificial freshwater reservoir located in southern Egypt; and El-Qanater El-Khayria, a middle-freshwater location belonging to the Rashid branch of the river Nile. The assessment of heavy metal residues (Fe, Cu, Zn, Mn, and Ni) revealed that their concentrations were higher in fish specimens compared to their counterparts in water (except for Ni). In addition, Lake Brullus emerges as the most polluted area, exhibiting elevated levels of heavy metals concentrations in water and fish specimens. In contrast, Lake Nasser showed the least degree of heavy metals pollution. Gene expression analysis revealed gender-specific responses to heavy metal exposure at the three investigated water bodies. The expression of hepatic antioxidant genes (GST and MT) and inflammatory-related genes (CC-chemokine and TNFα) increased in males compared to females. In females, the immune and pro-inflammatory-related genes (IgM and CXC2-chemokine) transcripts were upregulated. Additionally, growth-related genes were downregulated in both Lake Brullus and El-Qanater; on the contrary, fish samples from Lake Nasser exhibited a normal expression pattern of growth-related genes. Stress-related genes (HSP70 and HSP27) showed significant downregulation in gills of both genders from Lake Brullus. The minimal presence of heavy metal contaminants in Lake Nasser seems to endorse the normal patterns of gene expression across all gene categories. A potential gender-specific gene expression response towards pollution was noticed in genes associated with inflammation and antioxidant activities. This highlights the importance of considering gender-related responses in future environmental assessments.

An Unidentified Infiltrative Etiology of Spinal Cord Compression: A Case Report and Literature Review.

Spinal cord compression is a neurosurgical emergency. Symptoms of this disorder are highlighted as back pain, ambulatory difficulties, and bladder/bowel incontinence. Diagnostic imaging is not indicated in many circumstances of nonspecific back pain; however, the addition of neurologic deficits in the setting of back pain justifies radiologic imaging. Various pathologies can cause constriction of the spinal cord due to the delicate nature of spinal cord anatomy. Etiologies may include trauma, neoplasms, and infections. In this report, we present an unusual case of a 31-year-old male who presented to the emergency department with a history of chronic back pain accompanied by neurological deficits, ataxia, and bladder dysfunction. Contrast-enhanced MRI imaging heightened the suspicion of a neoplastic etiology; however, neuropathology revealed a non-neoplastic nature with abnormal lymphohistiocytic infiltrate suspicious for Langerhans cell histiocytosis or infectious etiology. A second opinion was provided by Mayo Clinic Laboratories, resulting in the definitive conclusion that the mass was non-neoplastic and tested negative for SD1a and Langerhin, biomarkers used to diagnose Langerhans cell histiocytosis. This unusual non-neoplastic lesion exemplifies one of many diverse and multifaceted pathologies that can precipitate spinal cord compression. Additionally, these findings underscore the importance of considering both neoplastic and non-neoplastic causes in the differential diagnosis of spinal cord compression, thereby enhancing clinical vigilance and improving patient outcomes for underlying spinal conditions.