A systematic review of the clinical characteristics and course of atrioventricular blocks in hyperthyroidism.

BACKGROUND: Atrioventricular block (AVB) is rare in hyperthyroidism (HTH). Little is known about the true prevalence, clinical course, optimal management, and outcomes of different types of AVBs in patients with HTH. To address these uncertainties, we aimed to conduct a systematic review by combining the available literature to provide more meaningful data regarding AVBs in HTH. METHODS: We systematically searched PubMed, Scopus, Embase, and Google Scholar for articles reporting patients who developed AVB in the context of HTH. Data were analysed in STATA 16. The main outcomes included types of AVB, frequency of pacemaker insertion, and resolution of AVB. The systematic review is registered with the International Prospective Register of Systematic Reviews (PROSPERO) with the identification number CRD42022335598. RESULTS: A total of 56 studies (39 case reports, 12 case series, 3 conference abstracts, 1 retrospective study, and 1 prospective observational study) with 87 patients were included in the analysis, with a mean age of 39.1 ± 17.6 years. Females constituted 65.7% (n = 48) of the cohort. Complete heart block (CHB) was the most commonly reported AVB (N = 45, 51.7%), followed by first-degree AVB (16.1%) and second-degree AVB (14.9%). Overall, 21 patients underwent pacing. A permanent pacemaker was inserted in one patient with second-degree AVB and six patients with CHB. Mortality was reported in one patient with CHB. The clinical course and management of HTH and AVBs did not differ in patients with CHB or lower-degree blocks. Apart from lower rates of goitre and more use of carbimazole in those who underwent pacing, no differences were found when compared to the patients managed without pacing. CONCLUSION: Current data suggest that CHB is the most common type of AVB in patients with HTH. Most patients can be managed with anti-thyroid management alone. Additionally, whether pacemaker insertion alters the clinical outcomes needs further exploration.

Women and Cardiovascular Health: Unraveling Gender-Specific Factors, Risks, and Therapeutic Approaches in Contemporary Medicine.

Background and objective Cardiovascular diseases (CVDs) constitute a significant global health challenge, causing millions of deaths annually and straining healthcare systems worldwide. This study aimed to investigate and elucidate gender-specific factors, risks, and therapeutic approaches related to cardiovascular health in women within the context of contemporary medicine. Methodology We conducted a prospective observational study spanning one year (November 2022 to October 2023) at the Peshawar Medical Complex Hospital, to meticulously explore the field of women's cardiovascular health. With a diverse cohort of 435 women (age range: 18-55 years), representing various socioeconomic backgrounds and geographic locations, our study aimed to elicit comprehensive insights. Through structured interviews covering reproductive history, lifestyle, and psychosocial aspects, coupled with clinical assessments, we gathered multifaceted data. Statistical analysis was done using SPSS Statistics version 23.0 (IBM Corp., Armonk, NY). By employing descriptive and t-tests for quantitative analysis and by thematically analyzing qualitative insights, our approach ultimately sought to provide a nuanced understanding of gender-specific factors impacting women's cardiovascular health. Results The study, involving 435 women, revealed various prevalent cardiovascular risk factors. Notable findings include a high incidence of a family history of CVD (n=213, 48.96%, p=0.013), hypertension (n=207, 47.58%), hypercholesterolemia (n=114, 26.21%), elevated triglycerides (n=162, 37.24%), and diabetes (n=64, 14.71%). Physical inactivity was also significantly more common (53.56%, p=0.004) compared to those engaging in regular activity. Women-specific risk factors comprised miscarriage (n=191, 43.91%). Therapeutic preferences varied, with a majority opting for lifestyle modifications (n=263, 60.39%) and pharmacological interventions (n=331, 76.33%). Conclusions This study provides a comprehensive understanding of prevalent cardiovascular risk factors, distinctive women-specific contributors, and diverse therapeutic preferences, highlighting the importance of personalized and targeted interventions to optimize women's cardiovascular health outcomes in contemporary medicine.

Association of Red Cell Distribution Width and Mean Platelet Volume With Disease Activity in Rheumatoid Arthritis Patients.

BACKGROUND: The inner layer of the synovial joints is the primary target of rheumatoid arthritis, or RA, a chronic systemic inflammatory disorder that is linked to increasing disability, early mortality, and economic hardships. The objective is to determine the association of red cell distribution width (RDW) and mean platelet volume (MPV) with disease activity in RA. MATERIAL AND METHODS: A retrospective study was conducted between July 2021 and January 2022 in the outpatient rheumatology clinics at Gulab Devi Teaching Hospital. In this study, 100 consecutive participants with a diagnosis of RA fulfilling the ACR/EULAR 2010 classification criteria were enrolled. Patient's records were reviewed for age, gender, length of illness, smoking status, treatment history, current treatment regimen, concomitant medications, rheumatoid factor (RF), anti-cyclic citrulline peptide (anti-CCP) antibodies, and extra-articular manifestations. Laboratory investigations were reviewed for complete blood count including RDW and MPV, ESR, CRP, liver, and renal functions. Disease activity score DAS 28-ESR was used to quantify disease activity. To determine the relationship between different parameters and the RDW and MPV, linear regression research was conducted. RESULTS: According to the DAS28 score, 12% of patients were in remission, 9% had low, 34% had moderate, and 45% had high disease activity. DAS28 score was 5.01±1.72 (2.45-9.32) and RDW was 16.18±4.42. There was a strong positive correlation (r = 0.653) of RDW with the DAS28 score and it was statistically significant (p<0.001). MPV was 11.30±2.09 fL. There was a moderately positive correlation (r = 0.366) of MPV with the DAS28 score and it was statistically significant (p<0.001). CONCLUSION: Conclusively, both RDW and MPV are positively related to disease activity in patients with RA. These can be used as a simple tool for assessing disease activity and guiding the treatment.

Preoperative factors that predict pathologic nodal involvement in early-stage HER2+ breast cancer: selecting cT1cN0 patients for treatment with neoadjuvant chemotherapy versus upfront surgery.

PURPOSE: The goal of this study was to identify the preoperative predictors of pathologic nodal metastases (pN+) in cT1cN0 HER2+ breast cancer undergoing upfront surgery. METHODS: We retrospectively reviewed data from women with cT1-T2N0 HER2+ breast cancer treated with neoadjuvant therapy (NAC) or upfront surgery at our institution between 2012 and 2023. Factors associated with management strategy were evaluated, and in those undergoing upfront surgery, univariate analyses were performed to identify the clinicopathologic factors associated with nodal metastases. RESULTS: Overall, 255 women with cT1-T2N0 HER2+ breast cancer met inclusion criteria, including 170 (68.6%) upfront surgery patients and 85 (31.4%) who underwent NAC. The median age at diagnosis was 59 years (range, 27-90 years). Younger age, larger clinical tumor size, high-grade disease, ER-PR-HER2+ subtype, and year of diagnosis after 2019 were significantly associated with receipt of NAC (p < 0.05). In those undergoing upfront surgery, 25.3% were pN+ , including 32.5% of cT1cN0 tumors. Factors associated with nodal involvement included age under 50, larger clinical tumor size, lymphovascular invasion (LVI), multifocality/multicentricity, and abnormal lymph nodes on axillary ultrasound (p < 0.05). In subset analysis of cT1cN0 HER2+ cases, LVI remained the strongest predictor of pN + disease (73.3% vs. 22.6%, p < 0.001). Patients with cT1cN0 HER2+ breast cancer under 50 years had a 47.1% likelihood of pN+ disease. CONCLUSION: Patients with cT1cN0 breast cancer have a 32.5% likelihood of nodal metastases, with higher incidence with younger age, LVI, multifocality/multicentricity, and abnormal axillary ultrasound. The presence of these factors may identify the patients who would benefit from treatment with neoadjuvant chemotherapy.

Synthesis of a Novel Gold(I) Complex and Evaluation of Its Anticancer Properties in Breast Cancer Cells.

BACKGROUND: Platinum complexes are commonly used for cancer chemotherapy; however, they are not only highly-priced but also have various side effects. It is, therefore, important to design affordable anticancer drugs with minimal side effects. METHODS: We synthesized a new gold(I) complex, PF6{(BDPEA)(TPPMS) digold(I)} (abbreviated as PBTDG) and tested its cytotoxicity in MCF-7 breast cancer cells. We also evaluated the effects of PBTDG on mitochondrial membrane potential, generation of reactive oxygen species (ROS) and apoptosis in breast cancer cells. RESULTS: The IC50 values for PBTDG and sorafenib were found to be 1.48 µM and 4.45 µM, respectively. Exposure to PBTDG caused significant and concentration-dependent depletion of ATP and disruption of mitochondrial membrane potential. PBTDG induced 2.6, 3.6, and 5.7-fold apoptosis for 1 µM, 3 µM, and 10 µM concentrations, respectively. The induction of apoptosis by the same concentrations of sorafenib was 1.2, 1.3, and 1.6-fold, respectively. The low concentration of PBTDG (1 µM) induced the generation of ROS by 99.83%, which was significantly higher than the ROS generation caused by the same concentration of sorafenib (73.76%). The ROS induction caused by higher concentrations (5 µM) of PBTDG and sorafenib were 104.95% and 122.11%, respectively. CONCLUSION: The lower concentration of PBTDG produced similar cytotoxicity and apoptotic effects that were caused by a comparatively higher concentration of known anticancer drug (sorafenib). The anticancer effects of PBTDG are attributed to its tendency to disrupt mitochondrial membrane potential, induction of apoptosis and generation of ROS. Further studies are warranted to test the anticancer effects of PBTDG in animal models of cancer.

Undiagnosed Depression and Its Effects on Patients With Systemic Lupus Erythematosus.

Introduction Different organs and organ systems are affected by a well-known chronic immune disorder called systemic lupus erythematosus (SLE). Besides the physical harm caused by this disorder, it affects the mental health of patients in a greater ratio by causing depression and anxiety. The objective of this study is to assess the prevalence of undiagnosed depression and its effects on patients with systemic lupus erythematosus. Material and methods This prospective cross-sectional study was carried out in the Rheumatology outpatient department of Fatima Memorial Hospital (FMH), Lahore, from November 2022 to February 2023. All study subjects had been given a prior diagnosis of SLE based on the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria. Three sections comprised the survey form: section I asked questions about socio-demographic information (gender and age); section II assessed the degree of mental illness activity; and section III assessed the degree of SLE disease activity. The nine-item PHQ-9 (Patient Health Questionnaire 9) scale, which is used to diagnose severe depressive disorder, was utilized to measure depression. To compare categorical variables, we applied Fisher's exact tests and chi-square; for continuous variables, we utilized the student's t-test. The statistical analysis was conducted using SPSS software for Windows Version 21.0 (IBM Corp., Armonk, NY, USA), with a significance threshold of p-value <0.05. Results Mild, moderate, and severe depression were present in 20%, 37.5%, and 37.5% of the patients, respectively. Pearson correlation of disease severity was strongly positive with depression (R2=0.634, p=0.01). The correlation was statistically significant. Conclusion Our research indicates that depression is a real problem for SLE patients. There is a positive correlation between the activity of the disease and the intensity of depression.

Antiproliferative effect of Solanum nigrum L. water extract on breast can-cer cells: potential roles of apoptosis and oxidative stress.

Breast cancer is the most progressive cancer among women worldwide. The currently available chemotherapeutic agents induce severe unacceptable adverse effects in breast cancer patients. In this context, natural medicinal herbs are gaining importance to find non-toxic effective anticancer drugs. Solanum nigrum is one of the major traditional medicinal plants widely used in Ayurveda for the treatment of various diseases. This study investigated the anticancer effect of Solanum nigrum water extract (SNWE) against MCF-7 and triple-negative MDA-MB-231 breast cancer cell lines. SNWE significantly induced oxidative stress-mediated apoptotic cell death in a concentration-dependent manner. Real-time PCR results illustrated the upregulation of proapoptotic genes and downregulation of antiapoptotic genes after SNWE treatment in MCF-7 and MDA-MB-231 cell lines. Immunofluorescence analysis showed increased expressions of apoptotic markers like p53, Caspase3 and BAX by SNWE treatment. In conclusion, the findings of this study indicate the antiproliferative effect and apoptosis-inducing property of SNWE in both cell lines. Further studies are warranted on testing the anticancer activity of S. nigrum L. using animal models of cancer.

The Role of Mitochondrial Dysfunction in Cytotoxic Effects of Solanum nigrum Water Extract on MCF-7 and MDA-MB-231 Breast Cancer Cells.

BACKGROUND: Recent studies suggest that numerous naturally occurring agents have the potential to kill cancer cells via mitochondrial dysfunction. Solanum nigrum is a herb widely used in alternative medical systems. This study aimed to investigate the cytotoxic effect of Solanum nigrum water extract (SNWE) against Michigan Cancer Foundation-7 (MCF-7) and MD Anderson-Metastatic Breast Cancer-231 (MDA-MB-231) cells. METHODS: We used an MTT reduction assay for cytotoxicity analysis. To explore the mode of action, the cellular adenosine triphosphate (ATP) levels and mitochondrial membrane potential were analyzed using a colorimetric ATP assay and Rhodamine-123 fluorescent staining, respectively, during SNWE treatment for 72 h. RESULTS: The cytotoxic effect was significant in both cell lines, with IC50 values of 4.26 µg/mL and 5.30 µg/mL in MCF-7 and MDA-MB-231 cells, respectively. The 24, 48, and 72 h treatments of 100 µg/mL SNWE showed 0.85 ± 0.07, 0.38 ± 0.1, and 0.20 ± 0.1 nM ATP in MCF-7 cells and 0.94 ± 0.07, 0.84 ± 0.2 and 0.46 ± 0.2 nM in MDA-MB-231 cells, respectively. The SNWE treatment altered the mitochondrial membrane potential (ΔΨm) in a concentration-dependent manner in both the breast cancer cell lines, to 29.6 ± 4.1% in MCF-7 and 28.7 ± 4.17% in MDA-MB-231 cells, when compared with healthy mitochondria (100% ΔΨm). CONCLUSIONS: The cytotoxic effects of Solanum nigrum against breast cancer cells are associated with energy metabolism. Additional studies are warranted to test the anticancer effect of Solanum nigrum using an animal model of breast cancer.

Fault Classification for Cooling System of Hydraulic Machinery Using AI.

Hydraulic systems are used in all kinds of industries. Mills, manufacturing, robotics, and Ports require the use of Hydraulic Equipment. Many industries prefer to use hydraulic systems due to their numerous advantages over electrical and mechanical systems. Hence, the growth in demand for hydraulic systems has been increasing over time. Due to its vast variety of applications, the faults in hydraulic systems can cause a breakdown. Using Artificial-Intelligence (AI)-based approaches, faults can be classified and predicted to avoid downtime and ensure sustainable operations. This research work proposes a novel approach for the classification of the cooling behavior of a hydraulic test rig. Three fault conditions for the cooling system of the hydraulic test rig were used. The spectrograms were generated using the time series data for three fault conditions. The CNN variant, the Residual Network, was used for the classification of the fault conditions. Various features were extracted from the data including the F-score, precision, accuracy, and recall using a Confusion Matrix. The data contained 43,680 attributes and 2205 instances. After testing, validating, and training, the model accuracy of the ResNet-18 architecture was found to be close to 95%.

Complement Activation-Independent Attenuation of SARS-CoV-2 Infection by C1q and C4b-Binding Protein.

The complement system is a key component of the innate immune response to viruses and proinflammatory events. Exaggerated complement activation has been attributed to the induction of a cytokine storm in severe SARS-CoV-2 infection. However, there is also an argument for the protective role of complement proteins, given their local synthesis or activation at the site of viral infection. This study investigated the complement activation-independent role of C1q and C4b-binding protein (C4BP) against SARS-CoV-2 infection. The interactions of C1q, its recombinant globular heads, and C4BP with the SARS-CoV-2 spike and receptor binding domain (RBD) were examined using direct ELISA. In addition, RT-qPCR was used to evaluate the modulatory effect of these complement proteins on the SARS-CoV-2-mediated immune response. Cell binding and luciferase-based viral entry assays were utilised to assess the effects of C1q, its recombinant globular heads, and C4BP on SARS-CoV-2 cell entry. C1q and C4BP bound directly to SARS-CoV-2 pseudotype particles via the RBD domain of the spike protein. C1q via its globular heads and C4BP were found to reduce binding as well as viral transduction of SARS-CoV-2 spike protein expressing lentiviral pseudotypes into transfected A549 cells expressing human ACE2 and TMPRSS2. Furthermore, the treatment of the SARS-CoV-2 spike, envelope, nucleoprotein, and membrane protein expressing alphaviral pseudotypes with C1q, its recombinant globular heads, or C4BP triggered a reduction in mRNA levels of proinflammatory cytokines and chemokines such as IL-1ß, IL-8, IL-6, TNF-α, IFN-α, and RANTES (as well as NF-κB) in A549 cells expressing human ACE2 and TMPRSS2. In addition, C1q and C4BP treatment also reduced SARS-CoV-2 pseudotype infection-mediated NF-κB activation in A549 cells expressing human ACE2 and TMPRSS2. C1q and C4BP are synthesised primarily by hepatocytes; however, they are also produced by macrophages, and alveolar type II cells, respectively, locally at the pulmonary site. These findings support the notion that the locally produced C1q and C4BP can be protective against SARS-CoV-2 infection in a complement activation-independent manner, offering immune resistance by inhibiting virus binding to target host cells and attenuating the infection-associated inflammatory response.

Serum Levels of Proinflammatory Biomarkers in Military Recruits with and without Metabolic Syndrome.

Objectives: Inflammatory mediators are associated with many chronic diseases; however, their role in metabolic syndrome (Met-S) is not well documented. We therefore aimed to compare the serum markers of inflammation including C-reactive protein (CRP), myeloperoxidase (MPO), interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-α), and TNF-ß in young military recruits with and without Met-S. We hypothesized that any significant change in inflammatory markers between the two groups would indicate the role of inflammation in Met-S that would help in future directions for screening and treatment of Met-S. Design and Methods. A total of 2010 adult men, aged 18-30 years, were divided into two groups: with Met-S (N = 488) and without Met-S (N = 1522), according to the International Diabetes Federation definition. We compared the serum levels of inflammatory biomarkers between the two groups. We also studied the correlations between the inflammatory markers and the components of Met-S to explore the biomarker potential of inflammatory markers for screening of Met-S. Logistic regression analysis was performed to test the association between inflammatory markers and Met-S. Results: A large number of subjects in the Met-S group were suffering from obesity. Out of the 2010 total subjects, only 731 (36.4%) had normal fasting blood sugar (FBS), while the prevalence of prediabetes and diabetes was significantly higher in subjects with Met-S. We observed significant increases in serum levels of CRP, MPO, IL-6, and TNF-ß but not TNF-α in subjects with Met-S as compared to subjects without Met-S. All the markers of inflammation showed significant correlations with Met-S, triglycerides (TG), blood pressure, body mass index (BMI), and age; however, none of these markers were correlated with HDL. Logistic regression analysis showed a significant association between Met-S and inflammatory markers. Conclusions: Serum levels of CRP, MPO, IL-6, and TNF-ß are significantly increased in young adults with Met-S. This is probably the first study reporting TNF-ß levels in Met-S. Since a proinflammatory cascade precedes many years before the onset of cardiovascular disease, these inflammatory biomarkers could help in the monitoring of high-risk individuals with Met-S who will be requiring therapeutic intervention.

Laparoscopic sleeve gastrectomy for obesity treatment in adolescents and young adults: a systematic review and meta-analysis.

BACKGROUND: The incidence of obesity has been increasing in younger population, posing a significant impact on adolescents' life and health care system worldwide. METHODS: We critically analyzed the existing literature on the use of laparoscopic sleeve gastrectomy (LSG) for the treatment of obesity. We performed an in-depth evaluation of 37 studies and analyzed the effect of LSG in 2300 patients, aged ≤ 22 years. RESULTS: Mean body mass index (BMI) loss after LSG was 17.81 kg/m2. Gastroesophageal reflux was the most common complication. Most of the patients showed remission of comorbidities including hypertension, diabetes, and obstructive sleep apnea after LSG. CONCLUSIONS: These findings suggest that surgical intervention is highly beneficial for reducing BMI in appropriately selected adolescents and young adults suffering from obesity and comorbidities such as life-threatening obstructive sleep apnea.

Smartphone addiction in medical students: Association with perceived stress, personality factors and loneliness.

Background: Smartphone addiction (SMA) is an emerging concept. It has been associated with high perceived stress. There is a dearth of data on its association with loneliness and personality in the Indian context. Objectives: We planned this study to estimate the prevalence of SMA in medical students, verify its reported association with perceived stress, and determine its association with personality factors and loneliness. Methods: Four hundred and two medical students participated in this cross-sectional study. We used the SMA scale-short version to divide students into those having an addiction and not having an addiction. The Perceived Stress Scale, ten-item personality inventory, and University of California, Los Angeles Loneliness Scale were used to assess perceived stress, personality, and loneliness. Ninety-five percent confidence intervals were reported for all comparisons. Results: The prevalence of SMA in medical students was 34.8%. SMA was associated with higher perceived stress and loneliness. Students having SMA scored lower on personality domains of extraversion, agreeableness, conscientiousness, emotional stability, and openness to experience. Moreover, SMA interfered with students' social life and academic performance. Conclusions: SMA is a cause for concern. We need to plan the awareness campaigns focusing on SMA and its association with social life and academic performance. Researchers need to explore this concept in larger samples and diverse population groups to know its actual magnitude and impact. Moreover, dedicated psychiatric committees need to recommend the guidelines for the judicious use of smartphones.

Early Identification of Crop Type for Smallholder Farming Systems Using Deep Learning on Time-Series Sentinel-2 Imagery.

Climate change and the COVID-19 pandemic have disrupted the food supply chain across the globe and adversely affected food security. Early estimation of staple crops can assist relevant government agencies to take timely actions for ensuring food security. Reliable crop type maps can play an essential role in monitoring crops, estimating yields, and maintaining smooth food supplies. However, these maps are not available for developing countries until crops have matured and are about to be harvested. The use of remote sensing for accurate crop-type mapping in the first few weeks of sowing remains challenging. Smallholder farming systems and diverse crop types further complicate the challenge. For this study, a ground-based survey is carried out to map fields by recording the coordinates and planted crops in respective fields. The time-series images of the mapped fields are acquired from the Sentinel-2 satellite. A deep learning-based long short-term memory network is used for the accurate mapping of crops at an early growth stage. Results show that staple crops, including rice, wheat, and sugarcane, are classified with 93.77% accuracy as early as the first four weeks of sowing. The proposed method can be applied on a large scale to effectively map crop types for smallholder farms at an early stage, allowing the authorities to plan a seamless availability of food.

Hybrid Nanoparticles of Manganese Oxide and Highly Reduced Graphene Oxide for Photodynamic Therapy.

BACKGROUND: Graphene-based nanomaterials possess unique optical, physicochemical and biomedical properties which make them potential tools for imaging and therapy. Manganese oxide nanoparticles are attractive candidates for contrast agents in magnetic resonance imagint (MRI). We used manganese oxide (Mn3O4) and highly reduced graphene oxide (HRG) to synthesize hybrid nanoparticles (HRG-Mn3O4) and tested their efficacy for photodynamic therapy (PDT) in breast cancer cells. METHODS: The newly synthesized nanoparticles were characterized by transmission electron microscopy (TEM), energy-dispersive X-ray (EDX) spectroscopy, UV-visible spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy, thermogravimetry, and X-ray diffraction (XRD) analyses. We used standard protocols of cytotoxicity and PDT after exposing A549 cells to various concentrations of hybrid nanoparticles (HRG-Mn3O4). We also performed fluorescence microscopy for live/dead cellular analysis. A549 cells were incubated with nanoparticles for 24 h and stained with fluorescein diacetate (green emission for live cells) and propidium iodide (red emission for dead cells) to visualize live and dead cells, respectively. RESULTS: The cell viability analysis showed that more than 98% of A549 cells survived even after the exposure of a high concentration (100 µg/mL) of nanomaterials. These results confirmed that the HRG-Mn3O4 nanoparticles are nontoxic and biocompatible at physiological conditions. When the cell viability analysis was performed after laser irradiation, we observed significant and concentration-dependent cytotoxicity of HRG-Mn3O4 as compared to Mn3O4 nanoparticles. Fluorescence microscopy showed that almost 100% cells were viable when treated with phosphate buffered saline or Mn3O4 while only few dead cells were detected after exposure of HRG-Mn3O4 nanoparticles. However, laser irradiation resulted in massive cellular damage by HRG-Mn3O4 nanoparticles which was directly related to the generation of reactive oxygen species (ROS). CONCLUSIONS: HRG-Mn3O4 hybrid nanoparticles are stable, biocompatible, nontoxic, and possess therapeutic potential for photodynamic therapy of cancer. Further studies are warranted to explore the MRI imaging ability of these nanomaterials using animal models of cancer.

Evaluation of use of hyperbaric oxygen in suppression of hyper-proliferation in hypoxic NSCLC cells.

Hyperbaric oxygen therapy (HBO) is being researched as a potential adjuvant treatment for solid malignancies, such as NSCLC. It can reduce tumour hypoxia and has been found to slow tumour growth, stop dedifferentiation, and reduce apoptosis resistance in hypoxic NSCLC cells. Though HBO has shown promise in treating various cancers, more study is required to determine its precise mechanism of action in NSCLC. Analyze the effect of hyperbaric oxygen on the growth of hypoxic non-small cell lung cancer cells. We used the NSCLC cell lines A549 and H1299 to analyze aerobic glycolysis in vitro. Warburg effect testing included glucose absorption, lactate, adenosine triphosphate (ATP), and pyruvate measurements. Using a quantitative glycolytic flow model, we also analyzed the effect of HIF-1-induced genes on the flux of glucose metabolism. Lewis lung carcinoma (LLC) animal models in C57BL/6J mice were used to examine the development of lung tumours. The effects of pcDNA and HIF1A on glucose uptake, lactate production, pyruvate, and ATP levels were studied in A549 and H1299 NSCLC cells. While A549's glucose absorption increased over time, H1299's was dramatically decreased by HBO treatment. The pyruvate levels were more significant in H1299, particularly in hypoxia, and were lowered by HBO. In A549, the lactate content was more effective. After HBO treatment, glucose absorption was reduced while intracellular ATP levels were maintained. Overexpression of HIF-1a was able to counteract the effect of HBO on glycolytic gene expression. PFKP is a possible therapeutic target because HBO reduces the Warburg effect in NSCLC cells by downregulating HIF-1.

Nanocomposites of Nitrogen-Doped Graphene Oxide and Manganese Oxide for Photodynamic Therapy and Magnetic Resonance Imaging.

Cancer is a leading cause of death worldwide. Conventional methods of cancer treatment, including chemotherapy and radiotherapy, are associated with multiple side effects. Recently, photodynamic therapy (PDT) has emerged as an effective therapeutic modality for cancer treatment without adversely affecting normal tissue. In this study, we synthesized nitrogen doped graphene (NDG) and conjugated it with Mn3O4 nanoparticles to produce NDG-Mn3O4 nanocomposite with the aim of testing its bimodal performance including PDT and magnetic resonance imaging (MRI). We did not use any linker or binder for conjugation between NDG and Mn3O4, rather they were anchored by a milling process. The results of cell viability analysis showed that NDG-Mn3O4 nanocomposites caused significant cell death under laser irradiation, while control and Mn3O4 nanoparticles showed negligible cell death. We observed increased generation of singlet oxygen after exposure of NDG-Mn3O4 nanocomposites, which was directly proportional to the duration of laser irradiation. The results of MRI showed concentration dependent enhancement of signal intensity with an increasing concentration of NDG-Mn3O4 nanocomposites. In conclusion, NDG-Mn3O4 nanocomposites did not cause any cytotoxicity under physiological conditions. However, they produced significant and dose-dependent cytotoxicity in cancer cells after laser irradiation. NDG-Mn3O4 nanocomposites also exhibited concentration-dependent MRI contrast property, suggesting their possible application for cancer imaging. Further studies are warranted to test the theranostic potential of NDG-Mn3O4 nanocomposites using animal models of cancer.

Detecting fake news and disinformation using artificial intelligence and machine learning to avoid supply chain disruptions.

Fake news and disinformation (FNaD) are increasingly being circulated through various online and social networking platforms, causing widespread disruptions and influencing decision-making perceptions. Despite the growing importance of detecting fake news in politics, relatively limited research efforts have been made to develop artificial intelligence (AI) and machine learning (ML) oriented FNaD detection models suited to minimize supply chain disruptions (SCDs). Using a combination of AI and ML, and case studies based on data collected from Indonesia, Malaysia, and Pakistan, we developed a FNaD detection model aimed at preventing SCDs. This model based on multiple data sources has shown evidence of its effectiveness in managerial decision-making. Our study further contributes to the supply chain and AI-ML literature, provides practical insights, and points to future research directions.

Role of Ondansetron in Reducing Methotrexate Intolerance in Patients with Inflammatory Arthritis.

OBJECTIVE: To determine the frequency of intolerance to Methotrexate (MTX) in patients with inflammatory arthritis by using MTX intolerance severity score, and evaluate the effects of Ondansetron in reducing MTX intolerance. STUDY DESIGN: Interventional study. PLACE AND DURATION OF STUDY: Rheumatology clinic, Combined Military Hospital (CMH), Lahore, from 1st November 2021 to 30th April 2022. METHODOLOGY: Patients with inflammatory arthritis taking methotrexate regularly for >3 months participated in the study. The patients' age, gender, education level, marital status and smoking history were documented. The disease duration and disease activity was also recorded. Dose/duration/route/frequency and timing of MTX were noted. MTX intolerance was calculated with the use of the Methotrexate intolerance severity score (MISS) questionnaire. Those MTX intolerant patients who reported nausea and vomiting were prescribed ondansetron along with MTX and were followed up for the next 3 consecutive months. RESULTS: Out of 181 patients, 48(26.5%) showed methotrexate intolerance. The predominant symptom was nausea after taking MTX reported in 93.8% of the MTX intolerant patients followed by behavioural symptoms including restlessness and irritability reported among 79% and 77% of intolerant patients respectively. Those methotrexate intolerant patients who mainly had complaints of nausea and vomiting were started on ondansetron on the day of methotrexate and showed a significant reduction in the median of MISS score in the following two consecutive months (p <0.05) while at 3 months the median did not show further reduction as compared to second month (p=0.12). CONCLUSION: Ondansetron prescribed along with methotrexate in patients having complaints of nausea and vomiting with MTX, reduces the intolerance significantly. KEY WORDS: Rheumatoid arthritis, Methotrexate, Ondansetron, Nausea, Arthritis juvenile.

Safety and outcomes of thrombolytic therapy in patients with pulmonary embolism and thrombocytopenia: A systematic review.

Thrombolysis is an established therapeutic modality for patients with high-risk (and some selected intermediate-risk) pulmonary embolism (PE) with hemodynamic instability. Physicians sometimes experience cases where both a high-risk PE and thrombocytopenia coexist. Although thrombocytopenia of <  100 × 103/mm3 is considered a contraindication in patients with ischemic stroke, the safety and outcomes of thrombolysis in patients with acute PE and thrombocytopenia are unknown. This systemic review aimed to pool data on the safety and outcomes of thrombolysis use in patients with PE and platelet count less than 150 × 103/mm3. Patients' demographics, clinical characteristics, management, type of thrombolytic therapy, and outcomes were extracted and analyzed. Of 283 articles identified through the systematic search, 11 case reports fulfilled the inclusion criteria. The mean age of the patients was 52.27 years, and 54.5% were women. The median platelet level before thrombolysis was 65.50 × 103/mm3. Before thrombolysis was initiated, the lowest and highest platelet levels were 29 × 103/mm3 and 105 × 103/mm3, respectively. Alteplase was used in 10 patients and urokinase in one patient. One patient who had a massive PE died of aspiration pneumonia. Interestingly, no thrombocytopenia-related complications were reported. This systematic review highlights the potential benefits and safety of thrombolysis in patients with acute PE in the context of thrombocytopenia. Nevertheless, data available in the literature concerning this topic are scarce and limited to case reports. More extensive studies on the use of thrombolysis in patients with PE and thrombocytopenia are desperately needed. Systematic review registration: The protocol has been registered in the International Prospective Register of Systematic Reviews (PROSPERO): CRD42021286415.