Are We Providing Enough Information to the Pathologists? An Audit of Filling of Histopathology Request Forms for Surgically Resected Tumours.

OBJECTIVE: To analyse quantitatively the adequacy of demographics of clinical information and highlight specific areas of neglect, by assessing the adequacy of filling out histopathology request forms. STUDY DESIGN: Clinical Audit. Place and Duration of the Study: Department of Pathology, Dow University of Health Sciences (DUHS), Karachi, Pakistan, from January to September 2021. METHODOLOGY: A retrospective audit was carried out on the request forms of surgically resected tumours and biopsies. The recorded details of the patients' demographics and biopsy, clinical history and examination, and intraoperative findings were analysed. RESULTS: Out of 175 forms, patients' names were written in 174 (99.4%) while medical record numbers were written in 113 (64.6%). The doctors' names were given in 172 (98.3%) forms and phone numbers in 34 (19.4%). A clinical diagnosis was provided in 164 (93.7%) forms, while 152 (86.9%) forms correctly entered the biopsy site. Sixty-seven (38.3%) forms included the correct nature of the biopsy. Relevant operative details were provided in half of the forms. Symptoms and their duration were mentioned in 144 (82.3%) and 100 (57.1%), respectively. The form-filling rate was the same for both benign and malignant tumours. CONCLUSION: This study shows that in a significant proportion of cases, complete relevant information is not provided to the histopathologists on request forms for logistics. KEY WORDS: Histopathology, Request forms, Tumours, Audit.

Europinidin Mitigates 3-NPA-Induced Huntington's Disease Symptoms in Rats: A Comprehensive Analysis of Oxidative Stress, Mitochondrial Enzyme Complex Activity, Pro-Inflammatory Markers and Neurotransmitter Alterations.

Huntington's disease (HD) is a neurodegenerative disease that causes progressive motor and cognitive dysfunction. There is no cure for HD, and current therapeutics can only manage the signs and symptoms as well as slowing disease progression. This investigation examines the possible therapeutic advantages of europinidin in 3-nitropropionic acid (3-NPA) injected HD in rats. Wistar rats were randomly assigned to five groups (n = 6): normal control, 3-NPA (10 mg/kg, i.p.), 3-NPA + europinidin-10 (10 mg/kg, p.o.), 3-NPA + europinidin-20 (20 mg/kg, p.o.), and europinidin alone (20 mg/kg, p.o.) for 15-day. Various behavioral and biochemical parameters including antioxidant levels, oxidative stress, pro-inflammatory markers, mitochondrial enzyme complex, and neurotransmitters were assessed. Europinidin restored biochemical, mitochondrial dysfunction, oxidative stress, neurotransmitter, and pro-inflammatory parameters disrupted by 3-NPA. Here we show that europinidin attenuates 3-NPA-induced neurodegeneration in rat models of HD. Europinidin modulates oxidative stress, enhances antioxidants, restores mitochondrial enzyme complex activity, reduces neuroinflammation, and modulates neurotransmitter levels. Our findings reveal the potential of europinidin as a novel therapeutic agent for the treatment of HD. This study also provides new insights into the molecular mechanisms of europinidin-mediated neuroprotection and may have a beneficial role in the management of neurological diseases.

Noncoding RNAs in hepatitis: Unraveling the apoptotic pathways.

Hepatitis is a worldwide health issue that causes inflammation of the liver and is frequently brought on by viral infections, specifically those caused by the hepatitis B and C viruses. Although the pathophysiological causes of hepatitis are complex, recent research indicates that noncoding RNAs (ncRNAs) play a crucial role in regulating apoptosis, an essential process for maintaining liver homeostasis and advancing the illness. Noncoding RNAs have been linked to several biological processes, including apoptosis. These RNAs include microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). Distinct expression patterns characterising different stages of the disease have been discovered, indicating dysregulation of these non-coding RNAs in liver tissues infected with hepatitis. The complex interplay that exists between these noncoding RNAs and apoptotic effectors, including caspases and members of the Bcl-2 family, plays a role in the precarious equilibrium that regulates cell survival and death during hepatitis. The purpose of this review is to provide an overview of ncRNA-mediated apoptosis in hepatitis, as well as insights into possible therapeutic targets and diagnostic indicators.

Apoptosis-driven synergistic anti-cancer efficacy of ethyl acetate extract of Memecylon sisparense Gamble leaves and doxorubicin in in-vitro and in-vivo models of triple-negative breast cancer.

In the spectrum of breast neoplasms, approximately 15 to 20% of all diagnosed cases are triple-negative breast carcinoma. TNBC grows and spreads faster than other invasive breast cancers and has a worse prognosis. The existing therapies and chemotherapeutic drugs have several limitations, so the development of safe and affordable treatment options is currently in demand. Hence, this research focuses on scientifically evaluating the therapeutic anticancer effect of ethyl acetate extract of MSG and its combined efficacy with doxorubicin against TNBC. MSG has shown an IC50 value of 48.40 ± 1.68 µg/ml on the MDA-MB-231 cell line, and the combination of MSG with Dox demonstrated the synergistic effect. Apoptotic changes such as membrane blebbing chromatin condensation were observed in MSG alone and in combination with doxorubicin treatments. Apoptosis was confirmed with Annexin V-FITC/PI staining and increased apoptotic markers such as Cleaved caspase-3 Bax and decreased anti-apoptotic markers Bcl-2 by western blotting. The tumor burden significantly decreased in MSG and combination treatment groups while restoring their body weights. Meanwhile, the Dox-treated group indicated a decreased tumor burden combined with weight loss. The present investigation revealed that MSG and doxorubicin have a synergistic anticancer effect in TNBC.

Multidisciplinary management of high-grade pediatric liver injuries.

OBJECTIVE: To present our experience of multidisciplinary management of high-grade pediatric liver injuries. INTRODUCTION: Pediatric high-grade liver injuries pose significant challenge to management due to associated morbidity and mortality. Emergency surgical intervention to control hemorrhage and biliary leak in these patients is usually suboptimal. Conservative management in selected high-grade liver injuries is now becoming standard of care. Management of hemobilia due to pseudoaneurysm formation and traumatic bile leaks requires multidisciplinary management. METHODS: A retrospective review was undertaken for patients presenting with blunt liver injuries at two tertiary care centers in Karachi, Pakistan, from March 2021 to December 2022. Twenty-eight patients were identified, and four patients fulfilled the criteria for grade 4 and above blunt liver injury during this period. RESULTS: One case with grade 4 liver injury developed hemobilia on 7th day of injury. He required two settings of angioembolization but had recurrent leak from pseudoaneurysm. He ultimately needed right hepatic artery ligation. Second patient presented with massive biliary peritonitis 2 days following injury. He was managed initially with tube laparostomy followed by ERCP and stent placement. The third patient developed large hemoperitoneum managed conservatively. One case with grade 5 injury expired during emergency surgery. CONCLUSION: Conservative management of advanced liver injuries can result in significant morbidity and mortality due to high risk of complications. Trauma surgeons need to have multidisciplinary team for management of these patients to gain optimal outcome.

Comparative effectiveness of intra-articular therapies in knee osteoarthritis: a meta-analysis comparing platelet-rich plasma (PRP) with other treatment modalities.

Introduction: Knee osteoarthritis (KOA) is a progressive joint disease commonly treated with intra-articular injections, including platelet-rich plasma (PRP), hyaluronic acid (HA), or corticosteroids (CS). This updated meta-analysis aims to enhance the statistical power of the results and provide comprehensive clinical evidence that reflects the most current research. By doing so, the authors aim to suggest a reliable estimate for the development of guidelines, addressing the pressing need for effective and minimally invasive treatment options. Methods: PubMed, Scopus, clinicaltrials.gov, Cochrane Central were searched until March 2023, for randomized controlled trials (RCTs) comparing the effectiveness of intra-articular injectable therapies, including PRP, HA, CS, and placebo, in KOA. Data extraction involved baseline characteristics and outcome measures [Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores, Visual Analog Scale (VAS) pain scores, KOOS, and IKDC scores] at 1, 3, 6 and 12 months. Statistical analysis, including subgroup analysis, assessment of heterogeneity, and publication bias, was conducted using Review Manager. Results: Our meta-analysis of 42 studies involving 3696 patients demonstrated that PRP treatment resulted in significant pain relief compared to HA injections, as evidenced by improved WOMAC pain (MD: -0.74; 95% CI: -1.02 to -0.46; P≤0.00001; I 2=94%) and VAS pain (MD: -0.65; 95% CI: -1.24 to -0.06; P=0.03; I2=97%) outcomes. Similarly, PRP showed greater efficacy in reducing WOMAC pain (MD: -8.06; 95% CI: -13.62 to -2.51: P=0.004; I 2=96%) and VAS pain (MD: -1.11; 95% CI: -1.64 to -0.59; P≤0.0001; I 2=68%) compared to CS injections, with the most significant improvement observed at 6 months. Conclusions: PRP is an effective treatment for KOA. It provides symptomatic relief, has the potential to reduce disease progression, and has sustained effects up to 12 months. PRP offers superior pain relief and functional enhancement compared to CS and HA injections.

The ncRNA-TGF-ß axis: Unveiling new frontiers in colorectal cancer research.

Colorectal cancer (CRC) poses a substantial global challenge, necessitating a deeper understanding of the molecular underpinnings governing its onset and progression. The transforming growth factor beta (TGF-ß) network has been a well-recognized cornerstone in advancing CRC. Nevertheless, a recent study has highlighted the growing importance of non-coding RNAs (ncRNAs) in this context. This comprehensive review aims to present an extensive examination of the interaction between ncRNAs and TGF-signaling. Noncoding RNAs (ncRNAs), encompassing circular RNAs (circRNAs), long-ncRNAs (lncRNAs), and microRNAs (miRNAs), have surfaced as pivotal modulators governing various aspects of TGF-ß signaling. MiRNAs have been discovered to target elements within the TGF-ß signaling, either enhancing or inhibiting signaling, depending on the context. LncRNAs have been associated with CRC progression, functioning as miRNA sponges or directly influencing TGF-ß pathway elements. Even circRNAs, a relatively recent addition to the ncRNA family, have impacted CRC, affecting TGF-ß signaling through diverse mechanisms. This review encompasses recent progress in comprehending specific ncRNAs involved in TGF-ß signaling, their functional roles, and their clinical relevance in CRC. We investigate the possibility of ncRNAs as targets for detection, prognosis, and therapy. Additionally, we explore the interaction of TGF-ß and other pathways in CRC and the role of ncRNAs within this intricate network. As we unveil the intricate regulatory function of ncRNAs in the TGF-ß signaling in CRC, we gain valuable insights into the disease's pathogenesis. Incorporating these discoveries into clinical settings holds promise for more precise diagnosis, prognosis, and targeted therapeutic approaches, ultimately enhancing the care of CRC patients. This comprehensive review underscores the ever-evolving landscape of ncRNA research in CRC and the potential for novel interventions in the battle against this formidable disease.

Anaesthesia-induced Changes in Genomic Expression Leading to Neurodegeneration.

General anaesthetics (GA) have been in continuous clinical use for more than 170 years, with millions of young and elderly populations exposed to GA to relieve perioperative discomfort and carry out invasive examinations. Preclinical studies have shown that neonatal rodents with acute and chronic exposure to GA suffer from memory and learning deficits, likely due to an imbalance between excitatory and inhibitory neurotransmitters, which has been linked to neurodevelopmental disorders. However, the mechanisms behind anaesthesia-induced alterations in late postnatal mice have yet to be established. In this narrative review, we present the current state of knowledge on early life anaesthesia exposure-mediated alterations of genetic expression, focusing on insights gathered on propofol, ketamine, and isoflurane, as well as the relationship between network effects and subsequent biochemical changes that lead to long-term neurocognitive abnormalities. Our review provides strong evidence and a clear picture of anaesthetic agents' pathological events and associated transcriptional changes, which will provide new insights for researchers to elucidate the core ideas and gain an in-depth understanding of molecular and genetic mechanisms. These findings are also helpful in generating more evidence for understanding the exacerbated neuropathology, impaired cognition, and LTP due to acute and chronic exposure to anaesthetics, which will be beneficial for the prevention and treatment of many diseases, such as Alzheimer's disease. Given the many procedures in medical practice that require continuous or multiple exposures to anaesthetics, our review will provide great insight into the possible adverse impact of these substances on the human brain and cognition.

GAS5: A pivotal lncRNA in diabetes mellitus pathogenesis and management.

The long non-coding RNA (lncRNA), GAS5, has garnered significant attention recently for its multifaceted involvement in cellular processes, particularly within the context of diabetes. This comprehensive review delves into the intricate molecular interactions associated with GAS5 and their profound implications for understanding, diagnosing, and effectively managing diabetes mellitus. The article begins by highlighting the global prevalence of diabetes and the urgent need for innovative insights into its underlying mechanisms and therapeutic approaches. It introduces GAS5 as a crucial regulator of gene expression, with emerging significance in the context of diabetes-related processes. The core of this review unravels the regulatory network of GAS5 in diabetes, elucidating its impact on various aspects of the disease. It explores how GAS5 influences insulin signaling pathways, glucose metabolism, and the function of ß-cells, shedding light on its role in hyperglycemia and insulin resistance. Moreover, the article underscores the clinical relevance of GAS5's interactions by discussing their associations with different diabetes subtypes, predictive value, and potential applications as both diagnostic tools and therapeutic targets. It provides insights into ongoing research endeavours aimed at harnessing the potential of GAS5 for innovative disease management strategies, including the development of RNA-based therapeutics. Concluding with a forward-looking perspective, the abstract highlights the broader implications of GAS5 in the field of diabetes, such as its connection to diabetic complications and its potential for personalized approaches in disease management.

Efficacy of Atezolizumab Plus Bevacizumab Versus Lenvatinib in Patients with Unresectable Hepatocellular Carcinoma: a Meta-analysis.

INTRODUCTION: Hepatocellular carcinoma is a lethal disease and there has been a debate regarding the first-line treatment of its advanced and unresectable form. Observational studies have explored atezolizumab plus bevacizumab versus lenvatinib, yielding mixed results. This systematic review and meta-analysis aim to compare efficacy and safety of both treatment arms. METHODS: A systematic literature review was conducted in accordance with PRISMA guidelines. Randomized control trials, cohort studies, or case-control that included patients above age 60 with unresectable hepatocellular carcinoma confirmed by radiological imaging were included. At least one of the outcomes: overall survival (OS), progression-free survival (PFS), objective response rate (ORR), duration of response, or adverse events was included in the selected studies. RESULTS: Ten cohorts were included in the analysis with a total of 6493 patients. Nine of the included studies had patients with advanced HCC (BCLC-C) or intermediate HCC (BCLC-B) and 1 study included patients with all three stages (BCLC-A, BCLC-B, and BCLC-C). Of these patients, 2524 patients received atezolizumab plus bevacizumab (A + B) combination while 3969 received lenvatinib. The overall survival was better statistically in the A + B group then the lenvatinib group (MD: - 5.06; 95% CI: - 7.79 to - 2.33; p = 0.0003, I2 = 0%). The progression-free survival was significantly improved in A + B arm as well group (MD: - 4.96; 95% CI: - 7.67 to - 2.26; I2 = 0%, p = 0. 0003). There was no significant difference in objective response rate, disease control rate, and frequency of adverse events in either of the group. CONCLUSION: Our study concluded that combination therapy with atezolizumab plus bevacizumab could increase the survival duration without affecting the disease course. Moreover, while the severity of adverse events was greater in the A + B group, their frequency was comparable to the lenvatinib group.

Autologous Stem Cell Transplant in Hodgkin's and Non-Hodgkin's Lymphoma, Multiple Myeloma, and AL Amyloidosis.

Human body cells are stem cell (SC) derivatives originating from bone marrow. Their special characteristics include their capacity to support the formation and self-repair of the cells. Cancer cells multiply uncontrollably and invade healthy tissues, making stem cell transplants a viable option for cancer patients undergoing high-dose chemotherapy (HDC). When chemotherapy is used at very high doses to eradicate all cancer cells from aggressive tumors, blood-forming cells and leukocytes are either completely or partially destroyed. Autologous stem cell transplantation (ASCT) is necessary for patients in those circumstances. The patients who undergo autologous transplants receive their own stem cells (SCs). The transplanted stem cells first come into contact with the bone marrow and then undergo engraftment, before differentiating into blood cells. ASCT is one of the most significant and innovative strategies for treating diseases. Here we focus on the treatment of Hodgkin's lymphoma, non-Hodgkin's lymphoma, multiple myeloma, and AL amyloidosis, using ASCT. This review provides a comprehensive picture of the effectiveness and the safety of ASCT as a therapeutic approach for these diseases, based on the currently available evidence.

Cardiac papillary fibroelastoma: a rare cause of ST-segment elevation myocardial infarction: a case report.

Introduction and importance: Primary tumors of the heart are extremely rare occurrences. Among them, cardiac papillary fibroelastoma (CPF) is the second most common type. Although these tumors are usually benign, they can pose a risk of embolization, which may lead to severe complications like sudden death or embolization affecting the neurological, systemic, or coronary vasculature. Such complications can be life-threatening. Case presentation: In this report, the authors present the case of a 68-year-old woman who experienced ST-segment elevation myocardial infarction due to embolization from a large papillary fibroelastoma. To address the issue, the authors performed a minimally invasive surgical removal and resection of the aortic valve, followed by a histological examination to confirm the diagnosis. Clinical discussion: This case report discusses a rare occurrence of myocardial infarction caused by tumor embolization from a CPF. The patient presented with complete blockage of a coronary artery in the absence of atherosclerotic disease. Through a comprehensive workup, including transesophageal echocardiography, the CPF was identified as the source of embolization. Surgical resection of CPFs is curative, and recurrence has not been documented. Clinicians should consider CPFs in cases of coronary artery occlusion without atherosclerotic disease and employ transesophageal echocardiography for diagnosis. Prompt surgical intervention leads to an excellent prognosis and prevents recurrent embolization. Conclusion: This report emphasizes the importance of recognizing the potential complications associated with papillary fibroelastoma-induced embolization to the coronary arteries and highlights the need to mitigate the risk of such complications occurring.

Public Awareness Regarding Corticosteroid Use and Side Effects: A Cross-Sectional Study in Riyadh, Saudi Arabia.

The administration of corticosteroids may have possible hazards, ranging from minor adverse medication reactions to more serious considerations. We aimed to assess levels of public awareness concerning corticosteroid use, side effects, and predictors of its use. A cross-sectional study was conducted online throughout the period of May to July 2023. The present investigation utilized a previously developed questionnaire tool. The study encompassed a cohort of 732 individuals. Upon inquiry regarding the adverse effects of corticosteroid treatment, the participants predominantly reported weight gain, skin alterations, and fluid retention leading to breathing difficulties, constituting 44.4%, 30.3%, and 27.7% of the responses, respectively. The prevailing adverse effects observed in individuals using corticosteroids were weight gain, alterations in mood, and changes in skin characteristics, which accounted for 38.1%, 25.7%, and 21.8% of reported cases, respectively. Individuals within the age range of 41-50 years and those who are currently not working show a higher propensity for utilizing corticosteroids in comparison to other demographic groups (p < 0.05). The level of general public knowledge about corticosteroids and the side effects connected with them in Saudi Arabia was adequate. Demographic factors, such as age, gender, and education, have an impact on the use of corticosteroids.

Phytochemical profiling and anti-inflammatory, analgesic activity of Ficus religiosa L. and molecular docking study against iNOS, TNF-α enzyme.

Ficus religiosa L., a member of the Moraceae family, is a medicinal plant having a number of pharmacological properties. The anti-inflammatory and analgesic actions of an ethanolic extract of F. religiosa bark FRE (at 100 and 200mg/kg dosages) and the biomarker component quercetin QC (at 5 and 10mg/kg doses) were investigated. The estimate of quercetin was carried by using an HPTLC analysis of FRE. Additionally, qualitative and quantitative screening for key important phytocomponents was done using dried, ground plant stem barks. By using molecular docking, the molecular interaction profile with several anti-inflammatory drug targets was examined. Both the FRE as well as QC showed a substantial decline in paw volume when compared with the relevant control groups (p<0.01 & p<0.001). Following the administration of acetic acid to mice, the FRE and QC both demonstrate a substantial lengthening of the paw licking or leaping towards Eddy's hot plate as well as a decrease in the number of writhes (p<0.01 & p<0.001). This study supports the use of these herbs in conventional medicine to treat pain and inflammation by through similar mechanism as compound quercetin (QC).

Exploring GAS5's impact on prostate cancer: Recent discoveries and emerging paradigms.

Novel treatment targets must be discovered to improve the results for patients with prostate cancer, which continues to be a significant worldwide health problem. Growth Arrest-Specific 5 (GAS5) is a long non-coding RNA (lncRNA) that has emerged as a promising target. GAS5 is a non-coding RNA that is a tumour suppressor in many different cancers by reducing cell proliferation and increasing apoptosis. GAS5 influences cell cycle control and apoptosis via interactions with important signalling pathways and microRNAs, as has been shown by recent studies. Furthermore, GAS5 has attracted interest for its diagnostic and prognostic potential in prostate cancer. GAS5 expression is a promising biomarker for disease classification and individualized treatment approaches because of its association with clinicopathological characteristics such as tumour stage, Gleason score, and metastatic potential. Preclinical models have revealed encouraging anticancer benefits from experimental techniques employing GAS5 overexpression or synthetic analogues, indicating the possibility of translational treatments. Whether GAS5 can be used as a diagnostic biomarker and therapeutic target might lead to more effective and individualized ways to fight prostate cancer, improving patient outcomes and quality of life. To utilize its potential for therapy and establish it as a useful addition to the clinical arsenal against this pervasive malignancy, more investigation into the complex molecular pathways of GAS5 in prostate cancer is essential. This review highlights the recent advancements and insights into the role of GAS5 in prostate cancer pathogenesis and progression.

Evaluation of anti-cancer effects of carnosine and melittin-loaded niosomes in MCF-7 and MDA-MB-231 breast cancer cells.

Background: We investigated the anti-cancer effect of carnosine-loaded niosomes (Car-NIO) and melittin-loaded niosomes (Mel-NIO) with olaparib in breast cancer cell lines (MCF-7 and MDA-MB-231). Methods: The thin film method was used for preparing the niosomes and characterized in terms of morphology, size, and polydispersity index (PDI). We further evaluated the impact of these peptides on breast cancer cells viability, RT-qPCR assays, malondialdehyde (MDA) activity, and cell cycle progression, to determine if these are linked to carnosine and melittin's anti-proliferative properties. Results: Car-NIO and Mel-NIO in vitro study inhibited cancer cell viability. They have also upregulated the expression of protein 53 (P53), BCL2-Associated X Protein (Bax), caspase-9, caspase-3, programmed cell death 4 (PDCD4), and Forkhead box O3 (FOXO3), while downregulated the expression of B-cell lymphoma 2 (Bcl2), poly (ADP-ribose) polymerase (PARP 1), and MicroRNA-183 (miRNA-183). The MCF-7 cells were arrested at the G2/M phase in Car-NIO, on the other hand, the MDA-MB-231 cells were arrested at the S phase. While the Mel-NIO and olaparib arrested the MCF-7 and MDA-MB-231 cells at the G0/1 phase. Conclusion: Our study successfully declared that Mel-NIO had more anti-cancer effects than Car-NIO in both MCF-7 and MDA-MB-231 breast cancer cells.

The Prevalence of Multidrug-Resistant Acinetobacter baumannii and Its Vaccination Status among Healthcare Providers.

There is growing concern among healthcare providers worldwide regarding the prevalence of multidrug-resistant Acinetobacter baumannii (A. baumannii). Some of the worst hospital-acquired infections, often in intensive care units (ICUs), are caused by this bacterial pathogen. In recent years, the rise in multidrug-resistant A. baumannii has been linked to the overuse of antimicrobial drugs and the lack of adequate infection control measures. Infections caused by this bacterial pathogen are the result of prolonged hospitalization and ICU stays, and they are associated with increased morbidity and mortality. This review outlines the epidemiology, risk factors, and antimicrobial resistance associated with A. baumannii in various countries, with a special focus on the Kingdom of Saudi Arabia. In response to the growing concern regarding this drug-resistant bacteria, fundamental information about its pathology has been incorporated into the development of vaccines. Although these vaccines have been successful in animal models, their effectiveness in humans remains unproven. The review will discuss the development of A. baumannii vaccines, potential related obstacles, and efforts to find an effective strategy against this pathogen.

Neurotoxoplasmosis in the Immunocompetent: A Rare Occurrence.

Cerebral toxoplasmosis is a rare condition that predominantly affects immunocompromised people and is relatively uncommon in immunocompetent individuals. Acute toxoplasmosis primarily presents with focal and diffuse neurological signs and symptoms depending on the site of the lesion, the degree of local damage, and the severity of inflammation. In this report, we present a case of cerebral toxoplasmosis in an immunocompetent adult female who presented with an altered level of consciousness, fever, headache, and shortness of breath. This case highlights the diagnostic challenges that may arise when dealing with patients who have a wide range of clinical manifestations.

Detection of Circulating Tumor Cells and Epithelial Progenitor Cells: A Comprehensive Study.

Technological advancement to enhance tumor cells (TC) has allowed discovery of various cellular bio-markers: cancer stem cells (CSC), circulating tumor cells (CTC), and endothelial progenitor cells (EPC). These are responsible for resistance, metastasis, and premetastatic conditions of cancer. Detection of CSC, CTC, and EPC assists in early diagnosis, recurrence prediction, and treatment efficacy. This review describes various methods to detect TC subpopulations such as in vivo assays (sphere-forming, serial dilution, and serial transplantation), in vitro assays (colony-forming cells, microsphere, side-population, surface antigen staining, aldehyde dehydrogenase activity, and Paul Karl Horan label-retaining cells, surface markers, nonenriched and enriched detection), reporter systems, and other analytical methods (flow cytometry, fluorescence microscopy/spectroscopy, etc.). The detailed information on methods to detect CSC, CTC, and EPC in this review will assist investigators in successful prognosis, diagnosis, and cancer treatment with greater ease.

The anticancer and EGFR-TK/CDK-9 dual inhibitory potentials of new synthetic pyranopyrazole and pyrazolone derivatives: X-ray crystallography, in vitro, and in silico mechanistic investigations.

Treatment options for the management of breast cancer are still inadequate. This inadequacy is attributed to the lack of effective targeted medications, often resulting in the recurrence of metastatic disorders. Cumulative evidence suggests that epidermal growth factor receptor (EGFR-TK) and cyclin-dependent kinases-9 (CDK-9) overexpression correlates with worse overall survival in breast cancer patients. Pyranopyrazole and pyrazolone are privileged options for the development of anticancer agents. Inspired by this proven scientific fact, we report here the synthesis of two new series of suggested anticancer molecules incorporating both heterocycles together with their characterization by IR, 1H NMR, 13C NMR, 13C NMR-DEPT, and X-ray diffraction methods. An attempt to get the pyranopyrazole-gold complexes was conducted but unexpectedly yielded benzylidene-2,4-dihydro-3H-pyrazol-3-one instead. This unexpected result was confirmed by X-ray crystallographic analysis. All newly synthesized compounds were assessed for their anti-proliferative activity against two different human breast cancer cells, and the obtained results were compared with the reference drug Staurosporine. The target compounds revealed variable cytotoxicity with IC50 at a low micromolar range with superior selectivity indices. Target enzyme EGFR-TK and CDK-9 assays showed that compounds 22 and 23 effectively inhibited both biological targets with IC50 values of 0.143 and 0.121 µM, respectively. Molecular docking experiments and molecular dynamics simulation were also conducted to further rationalize the in vitro obtained results.Communicated by Ramaswamy H. Sarma.