Life-threatening Disease Research Articles

Practical Management of ANCA-associated Vasculitis – A Clinician’s Perspective

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis can be a life-threatening condition, characterised by necrotising inflammation of small blood vessels. Major organ involvement, most commonly kidney and lung disease, is associated with significant morbidity and mortality. Intensive early immunosuppressive therapy is the cornerstone of management and has transformed ANCA-associated vasculitis (AAV) into a chronic relapsing condition. Remission induction with tapering glucocorticoids in combination with cyclophosphamide or rituximab is the standard of care for severe disease. Avacopan, an oral C5aR1 antagonist, has been approved for remission induction and helps minimise glucocorticoid exposure. Plasma exchange should be considered for severe kidney or life-threatening disease. Lower dose glucocorticoid induction regimens can be used without compromising remission rates. Remission maintenance therapy is recommended, and rituximab is usually first line over azathioprine. Mycophenolate mofetil (MMF) or methotrexate with low dose glucocorticoids are third line options. Immunosuppression associated infection risk remains a concern; both during acute presentations and in the long term; highlighted by the impact of rituximab on humoral immunity and vaccine response during the COVID-19 pandemic. There remains an ongoing need for therapies which induce rapid remission and optimise kidney recovery whilst minimising infection risk. Clinical trials are evaluating newer therapeutic options. Due to increasing treatment options, management should be individualised, balancing effective immunosuppression against co-morbidities and frailty. Summary: This review focuses on the treatment decision pathways for clinicians and patients in the management of severe AAV (granulomatosis with polyangiitis and microscopic polyangiitis). Key clinical trials, predictors of outcome, novel therapeutics and practical steps to mitigate infection risk are discussed. Key messages: Immunosuppression regimens have been refined due to emerging evidence from clinical trials. Rituximab, avacopan and reduced-dose glucocorticoid schedules have been the focus of recent studies. Infections and immunosuppression-induced immunodeficiency must be considered when determining individualised treatment.

An outbreak of dengue virus type 3 on Mer Island in the Torres Strait, Australia in 2024.

In early 2024, there were eight confirmed cases of locally acquired dengue on Mer Island in the Torres Strait. This dengue outbreak prompted an in-community public health response which included active case finding, health promotion and vector control. This was the first detected dengue outbreak in the Torres Strait since 2017. It highlights the importance of testing in primary healthcare, vector control and ongoing public health surveillance to minimise the risk of local transmission and establishment of endemic viruses which may cause significant and potentially life-threatening disease within populations in northern Australia.

Retrospective analysis of health and economic burden among commercially-insured individuals diagnosed with invasive meningococcal disease in the United States

ABSTRACT Invasive meningococcal disease (IMD) is a life-threatening yet vaccine-preventable disease, with vaccines approved and recommended in the United States by the Centers for Disease Control and Prevention. This study assessed complications, mortality, healthcare resource utilization (HCRU), and healthcare costs among a sample of commercially-insured individuals living in the United States who experienced IMD. We used retrospective data from large claims databases limited to individuals with IMD covered by commercial health plans between January 2010–March 2022. Health outcomes, HCRU, and healthcare costs were analyzed during the acute (index date to 30 days post-hospital discharge) and post-acute (end of acute phase to end of follow-up period) phases. Among 618 IMD cases identified, the most common acute phase complications were severe brain damage, renal failure, and autoimmune disease. The most common post-acute phase complications were autoimmune disease, arthralgia, and renal failure. Acute phase HCRU ranged from 72.7 (95% confidence interval [CI] 19.81–186.12) intensive care unit (ICU) stays to 12,102.9 (95% CI 11,201.07–13,058.00) surgeries per 1,000 patient-years. Post-acute phase HCRU ranged from 3.6 (95% CI 1.18–8.50) ICU stays to 7,808.3 (95% CI 7,661.22–7,957.54) specialty physician visits per 1,000 patient-years. Patients with IMD incurred average healthcare costs of $60,866.23 and $145,883.65 during the acute and post-acute phases, respectively. Negative health outcomes and high HCRU and costs were observed among commercially-insured patients with IMD. Our findings suggest that IMD immunization efforts and healthcare interventions targeting education on vaccine recommendations to healthcare providers and patients could help prevent IMD and reduce disease burden.

Nuclear lipid droplets: a novel regulator of nuclear homeostasis and ageing.

Aging is a fundamental driver of numerous life-threatening diseases, significantly compromising cellular structures and functions, including the integrity of the nucleus. A consistent feature of aging across diverse species is the progressive accumulation of lipid droplets (nLDs) within the nuclear compartment, which disrupts nuclear architecture and functionality. Notably, aging is accompanied by a marked increase in nLD accumulation at the nuclear envelope. Interventions known to extend lifespan, such as caloric restriction and reduced insulin signaling, significantly reduce both the rate of accumulation and the size of nLDs. The triglyceride lipase ATGL-1, which localizes to the nuclear envelope, plays a critical role in limiting nLD buildup and maintaining nuclear lipid balance, especially in long-lived mutant worms. These findings establish excessive nuclear lipid deposition as a key hallmark of aging, with profound implications for nuclear processes such as chromatin organization, DNA repair, and gene regulation. In addition, ATGL-1 emerges as a promising therapeutic target for preserving nuclear health, extending organismal healthspan, and combating age-related disorders driven by lipid dysregulation.

Infant feces-derived Lactobacillus gasseri FWJL-4 mitigates experimental necrotizing enterocolitis via acetate production

ABSTRACT Necrotizing enterocolitis (NEC) is a life-threatening disease in premature infants, characterized by high mortality. Recent studies increasingly highlight the role of gut dysbiosis in NEC pathogenesis. Although probiotics have shown some efficacy in preventing NEC, further research is needed to determine potential strains and approaches. In this study, we demonstrated that the novel probiotic strain Lactobacillus gasseri (L. gasseri) FWJL-4, isolated from the feces of healthy infants, significantly enhanced intestinal barrier function, providing substantial protection against NEC. This protective effect was attributed to elevated intestinal acetate levels. Notably, acetate supplementation alone was sufficient to mitigate NEC, mimicking the protective effects of L. gasseri FWJL-4. Mechanistically, we revealed that L. gasseri FWJL-4 inhibited necroptosis and preserved the number of the goblet cells and enterocytes through the production of the short-chain fatty acid acetate, via activation of the acetate receptors G protein-coupled receptor (GPR) 41 and GPR43. Our findings suggest that L. gasseri FWJL-4 enhances intestinal barrier function to protect against NEC, underscoring the potential of probiotic manipulation as a promising strategy for NEC prevention.

Using Deep Learning Techniques to Enhance Blood Cell Detection in Patients with Leukemia

Medical diagnosis plays a critical role in the early detection and treatment of diseases by examining symptoms and supporting findings through advanced laboratory testing. Early and accurate diagnosis is essential for detecting medical problems and then prescribing the most effective treatment strategies, especially in life-threatening diseases such as leukemia. Leukemia, a blood malignancy, is one of the most prevalent cancer types affecting both adults and children. It is caused by the rapid and uncontrolled growth of abnormal white blood cells in the bone marrow. This accumulation interferes with the production of normal blood cells, leading to a weakened immune deficiency, anemia, and bleeding disorders. Conventional leukemia diagnostic methods are time-consuming, manually intensive, and inefficient. This research study proposes an automatic diagnostics prediction of leukemia by analyzing blood images according to the shape of the blast cells using digital image processing and machine learning. The purpose of blood cell detection is to precisely identify and classify diverse blood cells, detecting anomalies associated with blood cancers like leukemia. This supports early diagnosis and monitoring, which leads to more effective treatments and improved results for cancer patients. To accomplish this task, we use digital image processing techniques and then apply the convolutional neural network (CNN) deep learning algorithm to blood sample images. This research employs a multi-stage methodology, including data preparation, data preprocessing, feature extraction, and then classification. While our model is built on a typical CNN architecture, we make significant advances by using preprocessing techniques and hyperparameter tuning. We have modified its layers combination to include convolutional, pooling, and fully connected layers that are optimized for image characteristics. These layers are fine-tuned for better feature extraction and classification accuracy. This study showed that blood cell detection for diagnosing acute leukemia based on images had 99% accuracy and outperformed other advanced models, including DenseNet121, ResNet-50, Incep-tionv3, MobileNet, and EfficientNet. The comprehensive analysis of the results reveals the highest accuracy of leukemia detection as compared to existing studies in the relevant literature.

Targeted dual-receptor phage cocktail against Cronobacter sakazakii: insights into phage-host interactions and resistance mechanisms

IntroductionCronobacter sakazakii is a notorious foodborne pathogen, frequently contaminating powdered infant formula and causing life-threatening diseases in infants. The escalating emergence of antibiotics-resistant mutants has led to increased interest in using bacteriophage as an alternative antimicrobial agent.MethodsTwo phages, CR8 and S13, were isolated from feces and soil samples and their morphology, physiology, and genomics were characterized. Phage receptor was determined using deletion mutants lacking flgK, rfaC, fhuA, btuB, lamb, or ompC genes, followed by complementation. Phage-resistant mutants were analyzed for phenotypic changes and fitness trade-offs using motility assays and Caco-2 cell invasion models.ResultsCR8 and S13 were identified as members of Caudoviricetes. Phage CR8 and phage S13 utilize flagella and LPS, respectively, to adhere to host cells. Bacterial challenge assay demonstrated delayed emergence of the resistant mutant as well as stronger lytic activity of a phage cocktail consisting of CR8 and S13 than the single phage treatment. Phenotypic analysis of the phage cocktail resistant strain, designated as CSR strain, revealed that the resistance resulted from the impaired receptor proteins for phage, such as defects in motility and alteration in LPS structure. CSR strain exhibited significant attenuation in invading human intestinal epithelial Caco-2 cells compared to WT cells.ConclusionThis study demonstrates that the development of the phage cocktail targeting distinct host receptors can serve as a promising antimicrobial strategy to effectively control C. sakazakii.

Topical dutasteride for androgenic alopecia: current state and prospects.

Androgenic alopecia has a high incidence, affecting 80% of men and 50% of women in their lifetimes. Although not a life-threatening disease, it can be a deep psychological burden to patients and still lacks an effective and safe treatment. Dutasteride is a5-alpha-reductase inhibitor approved to treat benign prostatic hyperplasia that is also commonly prescribed off-label to treat androgenic alopecia. However, oral dutasteride may cause several severe sexual and neurological sideeffects. Therefore, an effective, localized dutasteride treatment that can reduce the effects of systemic uptake is of great interest. Here, we review available therapies to treat androgenic alopecia focusing on topicalformulations developed thus far-including minoxidil, finasteride, and cosmetics-and on dutasteride-loaded nanocarriers targeting hair follicles.

Isolation and characterization of bacteriophages targeting methicillin-resistant Staphylococcus aureus (MRSA) from burn patients and sewage water: a genomic and proteomic study.

The spectrum of infections caused by methicillin-resistant Staphylococcus aureus (MRSA) ranges from minor conditions to potentially life-threatening diseases. The rising antibiotic resistance in MRSA often leads to treatment failures, underscoring the urgent need for novel eradication strategies. This study focuses on isolating MRSA from burn patients, determining its antibiogram profile, and isolating and characterizing bacteriophages from sewage water that target MRSA, alongside conducting genomic analysis of the phages. A total of 70 samples were collected from burn patients, with MRSA identification and characterization performed using a combination of biochemical and molecular techniques, as well as antibiotic sensitivity testing. Based on host range analysis, a specific phage (phage-3) was selected for detailed characterization, including proteomic analysis, genetic mapping, phylogenetic studies, and analysis of open reading frames (ORFs) and motifs. The prevalence of MRSA in the samples was found to be 28.6%. Antibiotic susceptibility tests indicated that 94% of the MRSA isolates were sensitive to tobramycin and gentamicin, while vancomycin exhibited the lowest sensitivity, with only 2% effectiveness. Using the soft agar overlay method, three bacteriophages (phage-1, phage-2, and phage-3) were successfully isolated from sewage water. Among these, phage-3 exhibited the broadest host range. Further analysis showed that phage-3 demonstrated optimal activity at pH levels between 6 and 8, and within a temperature range of 20-40°C. Phage-3 also displayed a rapid adsorption phase within the first 0-5min, and its one-step growth curve revealed a latent period lasting up to 30min, followed by a significant increase in titer from 30 to 50min. Proteomic analysis of phage-3 identified the presence of 33kDa and 65kDa proteins. Phylogenetic analysis showed that phage-3 shares 96.6% similarity with Mammallicoccus phage vB_MscM-PMS3. The ORF analysis identified 80 potential ORFs within the phage's entire genome.

The Prevalence and Comparative Analysis of Adhesion and Biofilm-Related Genes in Staphylococcus aureus Isolates: A Network Meta-Analysis.

Staphylococcus aureus is a versatile pathogen capable of causing a wide range of infections, from minor skin infections to life-threatening invasive diseases. The pathogenicity of S. aureus is attributed to its ability to produce various virulence factors, including adhesion and biofilm-related proteins. Understanding the prevalence and distribution of these genes among S. aureus isolates from different sources is crucial for devising effective strategies to combat biofilm-associated contamination. In this study, we conducted a comprehensive network meta-analysis to assess the prevalence of adhesion and biofilm-related genes in S. aureus isolates and investigate the impact of the isolate source on their occurrence. A systematic search of multiple databases was performed, and a total of 53 relevant studies were included. The prevalence of adhesion and biofilm-related genes in S. aureus isolates was determined, with the highest prevalence observed for clfB (p-estimate = 85.4, 95% confidence interval [CI] 78-90.6), followed by eno (p-estimate = 81.1, 95% CI 61.7-91.9), and icaD (p-estimate = 77, 95% CI 68.6-83.6). Conversely, bap and bbp genes exhibited the lowest prevalence rates (p-estimate = 6.7 and 18.7, respectively). The network meta-analysis allowed us to examine the pairwise co-study of adhesion and biofilm-related genes in S. aureus isolates. The most frequently co-studied gene pairs were icaA-icaD (30 times) and fnbA-fnbB (25 times). Subgroup analysis showed that the occurrence of icaC and icaB genes was significantly lower in animal isolates compared to human and food isolates (p < 0.05). It is worth noting that there was limited data available for the analysis of sasG, bbp, bap, eno, and fib genes. In conclusion, the study revealed varying prevalence rates of adhesion and biofilm-related genes in S. aureus isolates. Genes such as clfB, eno, and icaD were found to be highly prevalent, while bap and bbp were less common. Limited existing data on the prevalence of genes like sasG, bbp, bap, eno, and fib highlights the need for further research to determine their exact prevalence rates. Our results contribute to a better understanding of S. aureus pathogenesis and can facilitate the development of effective strategies for the prevention and treatment of S. aureus infections.

Prequalification of genome-based newborn screening for severe childhood genetic diseases through federated training based on purifying hyperselection

Genome-sequence-based newborn screening (gNBS) has substantial potential to improve outcomes in hundreds of severe childhood genetic disorders (SCGDs). However, a major impediment to gNBS is imprecision due to variants classified as pathogenic (P)or likely pathogenic (LP) that are not SCGD causal. gNBS with 53,855 P/LP variants, 342 genes, 412 SCGDs, and 1,603 therapies was positive in 74% of UK Biobank (UKB470K) adults, suggesting 97% false positives. We used the phenomenon of purifying hyperselection, which acts to decrease the frequency of SCGD causal diplotypes, to reduce false positives. Training of gene-disease-inheritance mode-diplotype tetrads in 618,290 control and affected subjects identified 293 variants or haplotypes and seven genes with variable inheritance contributing higher positive diplotype counts than consistent with purifying hyperselection and with little or no evidence of SCGD causality. With these changes, 2.0% of UKB470K adults were positive. In contrast, gNBS was positive in 7.2% of 3,118 critically ill children with suspected SCGDs and 7.9% of 705 infant deaths. When compared with rapid diagnostic genome sequencing (RDGS), gNBS had 99.1% recall. In eight true-positive children, gNBS was projected to decrease time to diagnosis by a median of 121days and avoid life-threatening disease presentations in four children, organ damage in six children, ∼$1.25 million in healthcare cost, and ten (1.4%) infant deaths. Federated training predicated on purifying hyperselection provides a general framework to attain high precision in population screening. Federated training across many biobanks and clinical trials can provide a privacy-preserving mechanism for qualification of gNBS in diverse genetic ancestries.

Presence of Gut Microbiota Worsens D-Galactosamine and Lipopolysaccharide-Induced Hepatic Injury in Mice.

Acute liver failure is a serious, life-threatening disease. Although the gut microbiota has been considered to play a role in liver failure, the extent to which it is involved in the pathogenesis of this disease has not been fully elucidated to date. Therefore, we here analyzed the importance of the presence of intestinal microbiota in the pathogenesis of acute liver injury, using D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-treated mice, which is a widely used experimental model of acute liver injury. First, administration of the antibiotic polymyxin B markedly alleviated liver injury. Liver injury was also reduced in germ-free mice, leading to the conclusion that the presence of intestinal microbiota aggravates D-GalN/LPS-induced liver injury. The amount of bacteria and LPS transferred from the gut to the blood was not increased by D-GalN/LPS, suggesting that the worsening of liver injury was not simply owing to the entry of bacteria into the circulation. In conclusion, acute liver injury in polymyxin B-pretreated or germ-free mice was ameliorated by modulation of the gut microbiota. Modification of the gut microbiota using polymyxin B may hence have the potential to alleviate acute liver injury in human patients.

Epstein-Barr virus and immunity.

The Epstein-Barr virus has infected the vast majority of the world's population. EBV is the most common herpes virus in the human population. In childhood, viral infection is either asymptomatic or can lead to infectious mononucleosis. In a small proportion of latently infected people, especially in immunosuppressed patients, EBV causes lymphoid and epithelial malignancies and a number of autoimmune diseases, including one of the causes of the development of multiple sclerosis. Innate immunity is the first line of antiviral defense, which EBV evades using a number of strategies to achieve successful infection. EBV disrupts the innate immune signaling pathways activated by Toll-like, RIG-I-like, NOD-like and AIM2-like receptors, as well as cyclic GMP-AMP synthetase. EBV also antagonizes interferon production and signaling, including the TBK1-IRF3 and JAK-STAT pathways. Through differential modulation of proviral and antiviral mechanisms of action of caspases and other cellular life cycle regulators at different stages of infection, EBV actively interferes with apoptotic and inflammatory pathways to continue effective infection. By turning the activation of innate immunity to its advantage by triggering a pro-inflammatory reaction and proteolytic cleavage of caspases that exhibit proviral activity, the virus establishes latency or enters the lytic reactivation phase, which contributes to the development of serious life-threatening diseases, including oncogenesis. The outcome of EBV infection is regulated by a subtle interaction between innate, adaptive immunity, and viral replication. In the absence of licensed preventive vaccines, immunocorrection and antiviral therapy are the only possible ways to combat the virus and prevent diseases associated with it. Understanding the mechanisms of action of certain EBV genes involved in the life cycle at different stages of infection will help in the future to find the right approach to the development of preventive and therapeutic drugs against EBV.

An innovative cellular medicine approach via the utilization of novel nanotechnology-based biomechatronic platforms as a label-free biomarker for early melanoma diagnosis

Innovative cellular medicine (ICM) is an exponentially emerging field with a promising approach to combating complex and ubiquitous life-threatening diseases such as multiple sclerosis (MS), arthritis, Parkinson’s disease, Alzheimer’s, heart disease, and cancer. Together with the advancement of nanotechnology and bio-mechatronics, ICM revolutionizes cellular therapy in understanding the essence and nature of the disease initiated at a single-cell level. This paper focuses on the intricate nature of cancer that requires multi-disciplinary efforts to characterize it well in order to achieve the objectives of modern world contemporary medicine in the early detection of the disease at a cellular level and potentially arrest its proliferation mechanism. This justifies the multidisciplinary research backgrounds of the authors of this paper in advancing cellular medicine by bridging the gap between experimental biology and the engineering field. Thus, in pursuing this approach, two novel miniaturized and highly versatile biomechatronic platforms with dedicated operating software and microelectronics are designed, modeled, nanofabricated, and tested in numerous in vitro experiments to investigate a hypothesis and arrive at a proven theorem in carcinogenesis by interrelating cellular contractile force, membrane potential, and cellular morphology for early detection and characterization of melanoma cancer cells. The novelties that flourished within this work are manifested in sixfold: (1) developing a mathematical model that utilizes a Heaviside step function, as well as a pin-force model to compute the contractile force of a living cell, (2) deriving an expression of cell-membrane potential based on Laplace and Fourier Transform and their Inverse Transform functions by encountering Warburg diffusion impedance factor, (3) nano-fabricating novel biomechatronic platforms with associated microelectronics and customized software that extract cellular physics and mechanics, (4) developing a label-free biomarker, (5) arrive at a proved theorem in developing a mathematical expression in relating cancer cell mechanobiology to its biophysics in connection to the stage of the disease, and (6) to the first time in literature, and to the best of the authors’ knowledge, discriminating different stages and morphology of cancer cell melanoma based on their cell-membrane potentials, and associated contractile forces that could introduce a new venue of cellular therapeutic modalities, preclinical early cancer diagnosis, and a novel approach in immunotherapy drug development. The proposed innovative technology-based versatile bio-mechatronic platforms shall be extended for future studies, investigating the role of electrochemical signaling of the nervous system in cancer formation that will significantly impact modern oncology by pursuing a targeted immunotherapy approach. This work also provides a robust platform for immunotherapy practitioners in extending the study of cellular biophysics in stalling neural-cancer interactions, of which the FDA-approved chimeric antigen receptor (CAR)-T cell therapies can be enhanced (genetically engineered) in a lab by improving its receptors to capture cancer antigens. This work amplifies the importance of studying neurotransmitters and electrochemical signaling molecules in shaping the immune T-cell function and its effectiveness in arresting cancer proliferation rate (mechanobiology mechanism).

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

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

A mini-review on clinical and epidemiological assessment of PAHs toxicity: Process of policy-making on a global scale

Growing anthropological inhabitants and unorganized cleaning and disposal leads to the widespread garbage and usable residues witnessed every here and there in the ecosystem, especially Polycyclic Aromatic Hydrocarbons (PAHs). This waste of PAHs and its various forms is a great disaster that is been mixed in right from the air all respirate into the water organisms drink plus food intake is also contaminated. The pollution made by this bio-cumulative pollutant not only cause damage to land and water but directly alter the metabolisms of living beings and causes life-threatening disease and sometimes takes the life of immune defective groups. Whereas short communication sharply and crisply explains the PAHs in society and their worsening body impacts other than it this brief about the degradation techniques with latest techno advancements. Differently, this paper concentrates on the cleaning up or removal methods, policy discussion and making by governmental organizations.

Doctors’ knowledge, practices, challenges, and limitations regarding disclosure of bad news: A multicentre study from Pakistan

ABSTRACT Background: Breaking bad news is one of the most difficult tasks for practicing doctors, especially for those working in health care specialties where life-threatening diseases are diagnosed and managed routinely. Our aim was to elicit the knowledge and practices of doctors and identify barriers faced by them in disclosure of bad news across the provinces of Pakistan. Methods: Cross-sectional, multi-centered study supported by an external grant in 15 Government and Private Hospitals across Pakistan. A total of 1185 doctors were surveyed. Responses were compared across provinces. Results: 80% of doctors across all specialties considered life-threatening diagnoses like cancer and stroke as equivalent to bad news, whereas less than 50% perceived conditions like malaria and typhoid as bad news. Regarding the level of difficulty encountered in giving bad news on a scale of 0 to 6, over 57% doctors rated it 4 and above. The reasons identified were lack of confidentiality, lack of privacy, lack of time, lack of training, fear of patients’ and family reactions, not wanting to hurt the patient or causing more distress, concern of having failed the patient, and their own reactions among others. Conclusions: Technical proficiency, training, good patient-centered communication, and incorporating socio-cultural aspects are essential for effective disclosure of bad news.

Anti-viral Application of Ganoderma lucidum in COVID-19

Abstract: Ganoderma lucidum (Lingzhi), a common medicinal fungus, has been utilized in China since ancient times for health promotion and longevity. It has anti-inflammatory, antiviral, antitumor, antioxidant, and antiallergic activities. The antioxidant and immunomodulatory effects of this mushroom have shown promising impacts in the treatment of some viral diseases. COVID-19 is a life-threatening disease caused by SARS-CoV-2 that has recently been pandemic. Modern medicines have not been very efficient in the direct treatment of these viral infections, and although vaccination is effective in preventing viral infections, the incidence of acute respiratory infection can be reduced only slightly. Thus, alternative therapies are required, and in this regard, stimulating the immune system can be an effective way to prevent these infections. This study reports the potential of natural fungus-derived compounds that can possibly be used to fight SARS-CoV-2 infections.

Intranasal delivery of macrophage cell membrane cloaked biomimetic drug-nanoparticle system attenuates acute lung injury

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), a life-threatening disease, is typically induced by uncontrolled inflammatory responses and excessive production of reactive oxygen species (ROS). Astaxanthin (Ast) is known for its powerful natural antioxidant properties, showcasing excellent antioxidant, anti-inflammatory, and immunomodulatory effects. However, its poor water solubility and bioavailability significantly limit its efficacy. Taking inspiration from biomimetic biology, this study developed a nasal drug delivery system comprising macrophage membrane (Mϕ)-encapsulated Ast-loaded nanoparticles (Mϕ@Ast-NPs) for the treatment of ALI. Mϕ@Ast-NPs retain the original homing properties of Mϕ, enabling targeted delivery to inflamed lungs and enhancing the anti-inflammatory effects of Astaxanthin (Ast). In vitro and in vivo, Mϕ@Ast-NPs demonstrated excellent biocompatibility and safety, as evidenced by no hemolysis of red blood cells and no significant toxic effects on cells and major organs. To determine the inflammation-targeting of Mϕ@Ast-NPs, both healthy and ALI mice were intranasally administered with Mϕ@Ast-NPs, the results demonstrated that highly targeting to inflamed lungs and endothelia, while with minimal accumulation in healthy lungs and endothelia. Mϕ@Ast-NPs effectively inhibited ROS production, enhanced Nrf2 expression and nucleus translocation, and reduced the levels of pro-inflammatory factors such as IL-1β, IL-6, and tumor necrosis factor-α (TNF-α) in LPS-induced RAW264.7 cells and ALI mice. Our study provided a safe and effective nasal delivery platform for pulmonary diseases, and this biomimetic nano-formulation of Ast could be as functional foods in the future.

Efficient management of pulmonary embolism diagnosis using a two-step interconnected machine learning model based on electronic health records data.

Pulmonary Embolism (PE) is a life-threatening clinical disease with no specific clinical symptoms and Computed Tomography Angiography (CTA) is used for diagnosis. Clinical decision support scoring systems like Wells and rGeneva based on PE risk factors have been developed to estimate the pre-test probability but are underused, leading to continuous overuse of CTA imaging. This diagnostic study aimed to propose a novel approach for efficient management of PE diagnosis using a two-step interconnected machine learning framework directly by analyzing patients' Electronic Health Records data. First, we performed feature importance analysis according to the result of LightGBM superiority for PE prediction, then four state-of-the-art machine learning methods were applied for PE prediction based on the feature importance results, enabling swift and accurate pre-test diagnosis. Throughout the study patients' data from different departments were collected from Sina educational hospital, affiliated with the Tehran University of medical sciences in Iran. Generally, the Ridge classification method obtained the best performance with an F1 score of 0.96. Extensive experimental findings showed the effectiveness and simplicity of this diagnostic process of PE in comparison with the existing scoring systems. The main strength of this approach centered on PE disease management procedures, which would reduce avoidable invasive CTA imaging and be applied as a primary prognosis of PE, hence assisting the healthcare system, clinicians, and patients by reducing costs and promoting treatment quality and patient satisfaction.