Search Results (200)

Cancer disparities in low- and middle-income countries (LMICs) arise from multifaceted interactions between environmental exposures, infectious agents, and systemic inequities, such as limited access to care. The exposome, a framework encompassing the totality of non-genetic exposures throughout life, offers a powerful lens for understanding these disparities. In LMICs, populations are disproportionately affected by air and water pollution, occupational hazards, and oncogenic infections, including human papillomavirus (HPV), hepatitis B virus (HBV), Helicobacter pylori (H. pylori), human immunodeficiency virus (HIV), and neglected tropical diseases, such as schistosomiasis. These infectious agents contribute to increased cancer susceptibility and poor outcomes, particularly in immunocompromised individuals. Moreover, climate change, food insecurity, and barriers to healthcare access exacerbate these risks. This review adopts a population-level exposome approach to explore how environmental and infectious exposures intersect with genetic, epigenetic, and immune mechanisms to influence cancer incidence and progression in LMICs. We highlight the critical pathways linking chronic exposure and inflammation to tumor development and evaluate strategies such as HPV and HBV vaccination, antiretroviral therapy, and environmental regulation. Special attention is given to tools such as exposome-wide association studies (ExWASs), which offer promise for exposure surveillance, early detection, and public health policy. By integrating exposomic insights into national health systems, especially in regions such as sub-Saharan Africa (SSA) and South Asia, LMICs can advance equitable cancer prevention and control strategies. A holistic, exposome-informed strategy is essential for reducing global cancer disparities and improving outcomes in vulnerable populations. Full article

RNA viruses pose significant threats to global health, causing diseases such as COVID-19, HIV/AIDS, influenza, and dengue. These viruses are characterized by high mutation rates, rapid evolution, and the ability to evade traditional antiviral therapies, making effective treatment and prevention particularly challenging. In recent years, CRISPR/Cas13 has emerged as a promising antiviral tool due to its ability to specifically target and degrade viral RNA. Unlike conventional antiviral strategies, Cas13 functions at the RNA level, providing a broad-spectrum and programmable approach to combating RNA viruses. Its flexibility allows for rapid adaptation of guide RNAs to counteract emerging viral variants, making it particularly suitable for highly diverse viruses such as SARS-CoV-2 and HIV. This review discusses up-to-date applications of Cas13 in targeting a wide range of RNA viruses, including SARS-CoV-2, HIV, dengue, influenza, and other RNA viruses, focusing on its therapeutic potential. Preclinical studies have demonstrated Cas13’s efficacy in degrading viral RNA and inhibiting replication, with applications spanning prophylactic interventions to post-infection treatments. However, challenges such as collateral cleavage, inefficient delivery, potential immunogenicity, and the development of an appropriate ethical framework must be addressed before clinical translation. Future research should focus on optimizing crRNA design, improving delivery systems, and conducting rigorous preclinical evaluations to enhance specificity, safety, and therapeutic efficacy. With continued advancements, Cas13 holds great promise as a revolutionary antiviral strategy, offering novel solutions to combat some of the world’s most persistent viral threats. Full article

Background/Objectives: Despite medical advances, stigma remains a major challenge for people living with HIV (PLWH). This study examined clinical, sociodemographic, and psychological predictors of HIV-related stigma, and explored whether affective temperament moderates the impact of depression on stigma. Methods: This cross-sectional observational study included 97 PLWH attending a tertiary infectious disease unit in Rome, Italy. Participants completed a battery of validated psychometric instruments assessing depressive symptoms, anxiety, manic symptoms, mixed affective states, general psychopathology, impulsivity, and affective temperament. HIV-related stigma was evaluated using the Berger HIV Stigma Scale, which measures personalized stigma, disclosure concerns, negative self-image, and concerns with public attitudes. Descriptive statistics were used to characterize the sample. Univariate linear regressions were conducted to explore associations between clinical, psychometric, and sociodemographic variables and each stigma subdimension, as well as the total stigma score. Variables significant at p < 0.05 were included in five multivariate linear regression models. Moderation analyses were subsequently performed to assess whether affective temperaments moderated the relationship between significant psychopathological predictors and stigma. Bonferroni correction was applied where appropriate. Results: Higher depressive symptom scores are significantly associated with greater internalized stigma (B = 0.902, p = 0.006) and total stigma (B = 2.603, p = 0.008). Furthermore, moderation analyses showed that anxious temperament significantly intensified the relationship between depressive symptoms and both negative self-image (interaction term B = 0.125, p = 0.001) and total stigma (B = 0.336, p = 0.002). Conclusions: Depressive symptoms and anxious temperament are associated with HIV-related stigma. Integrating psychological screening and targeted interventions for mood and temperament vulnerabilities may help reduce stigma burden in PLWH and improve psychosocial outcomes. Full article

Acute myocardial infarction (AMI) in young adults, though less common than in older populations, is an emerging clinical concern with increasing incidence and diverse etiologies. Unlike classic atherosclerotic presentations, a significant proportion of AMI cases in individuals under 45 years are due to nonatherothrombotic mechanisms such as coronary vasospasm, spontaneous coronary artery dissection (SCAD), vasculitis, hypercoagulable states, and drug-induced coronary injury. This manuscript aims to explore the multifactorial nature of AMI in young adults through a focused review of current evidence and a series of illustrative clinical cases. We present and analyze four distinct cases of young patients with AMI, each demonstrating different pathophysiological mechanisms and risk profiles—including premature atherosclerosis, substance use, human immunodeficiency virus (HIV)-related coronary disease, and SCAD. Despite the heterogeneity of underlying causes, early diagnosis, individualized management, and aggressive secondary prevention were key to favorable outcomes. Advanced imaging, lipid profiling, and risk factor modification played a central role in guiding therapy. AMI in young adults requires heightened clinical suspicion and a comprehensive, multidisciplinary approach. Early intervention and recognition of nontraditional risk factors are essential to improving outcomes and preventing recurrent events in this vulnerable population. Full article

Anticytokine autoantibodies (AAbs), particularly anti-interferon-gamma (anti-IFN-γ) AAbs, disrupt cytokine functions, leading to infections, autoimmune-like diseases, and conditions resembling interleukin-12 (IL-12)/IFN-γ pathway defects. Advances in genetic testing have clarified overlaps between autoinflammatory, autoimmune disorders, and primary immunodeficiencies but reveal complex phenotypes and pathways. While these insights deepen our understanding of immune mechanisms, they also complicate diagnosis and treatment, with limited options for IFN-γ deficiencies caused by genetic mutations. The adult-onset immunodeficiency with disseminated lymphadenitis due to nontuberculous mycobacteria (NTM) and other opportunistic infections has been linked to high levels of anti-IFN-γ AAbs. This syndrome, initially identified in HIV-negative Asian patients, frequently affects individuals of Asian descent and may be associated with specific human leukocyte antigen (HLA) alleles. The presence of neutralizing anti-IFN-γ AAbs impairs the IFN-γ-dependent immune response, likely contributing to the persistent NTM infection. This study underscores the potential for late-onset anti-IFN-γ AAb syndrome to manifest with disseminated NTM (dNTM) infections, highlights the importance of timely diagnosis and considers rituximab as a potential therapeutic option. Full article

Background and Aim: Syphilis, caused by Treponema pallidum, classically presents with genital or anal chancres; rectal involvement is rare and frequently misdiagnosed as inflammatory bowel disease or malignancy. We describe an unusually severe case of syphilitic proctitis in the setting of advanced HIV-related immunosuppression (CD4 39 cells/µL), in which targeted immunophenotyping (ERG and CD38) was a valuable adjunctive tool in the differential diagnosis. Case Presentation: A 46-year-old man with a recent history of erosive gastritis and esophageal candidiasis presented after six months of unintentional 20 kg weight loss, profound fatigue, intermittent fevers, profuse diarrhea, and two episodes of hematemesis. Workup revealed a new diagnosis of HIV infection (CD4: 39 cells/µL; viral load: 87,837 copies/mL). Contrast-enhanced CT demonstrated uniform, concentric rectal wall thickening (“target sign”). Colonoscopic biopsy showed exuberant granulation tissue and dense plasma cell infiltrates. Immunohistochemistry revealed a dense infiltrate of CD38-positive plasma cells and ERG-positive endothelial proliferation. These findings, in the context of positive serology, were highly supportive of a spirochetal etiology and helped differentiate it from potential mimics. Serology was positive for latent late syphilis (VDRL 1:64). The patient received three weekly doses of intramuscular benzathine penicillin; lumbar puncture excluded neurosyphilis. Discussion: This is among the first reported cases of syphilitic proctitis in a patient with CD4 < 50 cells/µL, where advanced immunophenotyping differentiated syphilitic inflammation from neoplastic or inflammatory mimics. Profound immunosuppression accelerates disease progression and yields atypical clinical features. Conclusion: In HIV-infected patients with chronic rectal symptoms, especially those with CD4 < 50 cells/µL, syphilitic proctitis must be considered. Integration of radiologic assessment, histopathology with ERG/CD38 staining, and serologic testing permits prompt diagnosis. Early benzathine penicillin therapy and rigorous clinical and serologic follow-up are essential to prevent complications, including neurosyphilis. Full article

Treatment for HIV infection has become more manageable due to advances in combination antiretroviral therapy (cART). However, HIV still significantly affects the central nervous system (CNS) in infected individuals, even with effective plasma viral suppression, due to persistent viral reservoirs and chronic neuroinflammation. This ongoing inflammation contributes to the development of HIV-associated neurocognitive disorders (HANDs), including dementia and Alzheimer’s disease-like pathology. These complications are particularly prevalent among the aging population with HIV. This review aims to provide a comprehensive overview of HAND, with a focus on the contribution of oxidative stress induced by HIV-mediated reactive oxygen species (ROS) production through viral proteins such as gp120, Tat, Nef, Vpr, and reverse transcriptase. In addition, we discuss current and emerging therapeutic interventions targeting HAND, including antioxidant strategies and poly (ADP-ribose) polymerase (PARP) inhibitors. These are potential adjunctive approaches to mitigate neuroinflammation and oxidative damage in the CNS. Full article

The COVID-19 pandemic has illuminated and intensified pre-existing structural vulnerabilities among older adults living with HIV/AIDS in sub-Saharan Africa, particularly Nigeria. Within already overstretched healthcare infrastructures, these individuals faced heightened economic precarity, disrupted HIV care, and pronounced psychosocial distress. Exploring their lived experiences critically advances an understanding of resilience and informs contextually responsive interventions that can mitigate future health crises. This study employed a narrative qualitative approach to explore the lived experiences of older adults (aged 50 and above) attending the Infectious Diseases Institute (IDI) clinic in Ibadan, Nigeria, during the pandemic lockdown. Purposive sampling guided by maximum variation principles enabled the selection of 26 participants who provided detailed accounts through in-depth interviews. Reflective thematic analysis identified complex narratives illustrating intensified financial hardships, disrupted access to antiretroviral therapy (ART), and heightened psychological distress, including anxiety, depression, and profound isolation. Conversely, participants also articulated experiences of resilience, manifesting in improved medication adherence, strengthened family bonds, and introspective growth fostered by enforced isolation. These nuanced findings highlights the necessity of developing an adaptive, integrated healthcare interventions that addresses economic vulnerabilities, psychosocial wellbeing, and ART continuity, thereby better preparing resource-constrained health systems to support older adults with HIV/AIDS in future public health crises. Full article

The global impact of HIV is especially significant when diagnoses are made in advanced stages. While strategies exist to mitigate late presentations, Ecuador’s 2018–2022 strategic plan has not yet been evaluated. This study assesses the prevalence and implications of late and advanced HIV presentations in Ecuador, using data from a reference hospital in Quito. A cross-sectional analysis of 436 medical records of people living with HIV from the “Hospital de Especialidades Eugenio Espejo” was conducted between November 2015 and February 2020. The data were divided into “Pre-Plan” and “Post-Plan” periods for comparative analysis. The mean CD4 T count showed a non-statistically significant increase in the post-plan period (January 2018–February 2020). Notably, 65.1% of patients presented late, and 39.4% had advanced disease. Demographic data indicated that 89.9% were men, and 54.1% were under 30 years of age. No characteristics were identified that were associated with advanced late presentation of HIV infection. Sexual orientation data revealed that 69.1% identified as homosexual or bisexual. A predominance of late and advanced presenters was identified in the post-plan period, associated with being employed (p < 0.05) and being drug users (p < 0.001). There was also a greater incidence of late presenters among immigrants in the post-plan period (p = 0.045). Despite the implementation of Ecuador’s 2018–2022 strategic plan for HIV, substantial challenges in reducing late presentations remain. This study suggests that early diagnoses have not significantly improved. Employed patients and drug users were more likely to present late, with drug users also accounting for many advanced cases. This study highlights the need for more focused and targeted strategies to supplement the existing plan. Full article

Cardiac glycosides (CGs), a class of plant- and animal-derived compounds historically used to treat heart failure, have garnered renewed interest for their diverse pharmacological properties beyond Na⁺/K⁺-ATPase (NKA) inhibition. Recent studies reveal that CGs modulate key signaling pathways—such as NF-κB, PI3K/Akt, JAK/STAT, and MAPK—affecting processes central to cancer, viral infections, immune regulation, and neurodegeneration. In cancer, CGs induce multiple forms of regulated cell death, including apoptosis, ferroptosis, pyroptosis, and immunogenic cell death, while also inhibiting angiogenesis, epithelial–mesenchymal transition, and cell cycle progression. They demonstrate broad-spectrum antiviral activity by disrupting viral entry, replication, and mRNA processing in viruses such as HSV, HIV, influenza, and SARS-CoV-2. Immunologically, CGs regulate Th17 differentiation via RORγ signaling, although both inhibitory and agonistic effects have been reported. In the nervous system, CGs modulate neuroinflammation, support synaptic plasticity, and improve cognitive function in models of Alzheimer’s disease, epilepsy, and multiple sclerosis. Despite their therapeutic potential, clinical translation is hindered by narrow therapeutic indices and systemic toxicity. Advances in drug design and nanocarrier-based delivery are critical to unlocking CGs’ full potential as multi-target agents for complex diseases. This review synthesizes the current knowledge on the emerging roles of CGs and highlights strategies for their safe and effective repurposing. Full article

HIV, primarily targeting CD4 cells, infiltrates the CNS through various mechanisms, including chemokine-mediated signaling and blood–brain barrier disruption, leading to neuroinflammation and neuronal dysfunction. Viral proteins such as gp120, Tat, and Vpr directly induce neurotoxicity, oxidative stress, and mitochondrial dysfunction, exacerbating cognitive deficits and motor impairments observed in HIV-associated neurocognitive disorders (HANDs). Host genetic factors, including CCR5 mutations and HLA alleles, influence susceptibility to HIV-related neurologic complications, shaping disease progression and treatment responses. Advanced molecular and bioinformatics techniques, from genome sequencing to structural modeling and network analysis, provide insights into viral pathogenesis and identify potential therapeutic targets. These findings underscore the future potential of precision medicine approaches tailored to individual genetic profiles to mitigate neurologic complications and improve outcomes in HIV-infected populations. This comprehensive review explores the intricate interplay between HIV infection and neurogenetics, focusing on how the virus impacts the central nervous system (CNS) and contributes to neurocognitive disorders. This report delves into how the virus influences genetic expression, neuroinflammation, and neurodegeneration, offering insights into molecular mechanisms behind HAND. Full article

Monitoring CD4 count levels is essential for tracking the progression of HIV in patients. This study aimed to identify the key factors influencing HIV progression by incorporating time-varying factors and transition probabilities. The data for this study were obtained from the Centre for the AIDS Programme of Research in South Africa (CAPRISA), which enrolled 3325 patients aged 14 to 76 who initiated antiretroviral therapy (ART) and were followed up with between June 2004 and August 2013. The dataset included clinical, demographic, and treatment information to capture a comprehensive picture of HIV progression. To analyze the factors associated with HIV progression, this study employed time-inhomogeneous Markov models, which allow for incorporating covariates that change over time and transition probabilities. These models provided a robust framework to assess how various factors, such as CD4 count, viral load, and treatment adherence, evolve and influence disease progression. The results indicated that males had a significantly higher risk of moving from a normal (more than 500 cells/mm³) to mild state (351–500 cells/mm³) than females [HR: 1.614, 95% CI (1.281, 2.034)]. Rural patients had a significantly higher risk compared to urban patients of transiting from a mild state (351–500 cells/mm³) to an advanced state (200–350 cells/mm³) with a 95% confidence interval of (0.641, 1.009) [HR: 0.805, 95% CI (0.641, 1.009)]. The multistate model identified regimen, location, gender, and age as significant clinical variables influencing HIV progression. Rural patients and males showed slower transitions to CD4 count recovery. These findings provide valuable insights for disease management, treatment planning, and understanding the long-term prognosis for individuals living with HIV. Improving healthcare access, increasing educational efforts targeting men, reducing stigma, and fostering supportive environments can play a crucial role in enhancing CD4 count recovery and overall health outcomes for people living with HIV. Full article

Background: Vasculonecrotic reactions in leprosy are typically associated with type 2 reactions. Differentiating between necrotizing erythema nodosum leprosum (nENL) and Lucio’s phenomenon (LP) can be difficult, as overlapping clinical and histopathological features have been reported. Mycobacterium lepromatosis, a recently identified species causing leprosy, has been sporadically linked to LP. While type 1 reactions are more commonly observed in HIV-coinfected individuals, reports of LP or ENL occurring outside the context of immune reconstitution inflammatory syndrome (IRIS) remain rare. Methods: We report a case of a vasculonecrotic leprosy reaction due to M. lepromatosis in an antiretroviral-naive patient with advanced HIV infection. Results: The patient presented with a two-month history of papules and nodules that progressed to painful necrotic ulcers, accompanied by systemic symptoms. Clinically, the presentation was consistent with nENL; however, histopathological analysis supported a diagnosis of LP. The patient rapidly deteriorated, developing septic shock and dying shortly thereafter. To our knowledge, this is the first reported case of a leprosy-associated vasculonecrotic reaction caused by M. lepromatosis in an HIV-infected individual not associated with IRIS. Conclusions: Vasculonecrotic reactions in leprosy are life-threatening emergencies due to their potential for rapid clinical deterioration and sepsis. In individuals with advanced HIV infection, recognition of these reactions may be challenging, as they can mimic other opportunistic infections, including fungal diseases, malignant syphilis, and disseminated mycobacterial infections. Early identification and prompt treatment are critical to improving outcomes. Full article

Over the past several decades, viral vector-based vaccines have emerged as some of the most versatile and potent platforms in modern vaccinology. Their capacity to deliver genetic material encoding target antigens directly into host cells enables strong cellular and humoral immune responses, often superior to what traditional inactivated or subunit vaccines can achieve. This has accelerated their application to a wide array of pathogens and disease targets, from well-established threats like HIV and malaria to emerging infections such as Ebola, Zika, and SARS-CoV-2. The COVID-19 pandemic further highlighted the agility of viral vector platforms, with several adenovirus-based vaccines quickly authorized and deployed on a global scale. Despite these advances, significant challenges remain. One major hurdle is pre-existing immunity against commonly used vector backbones, which can blunt vaccine immunogenicity. Rare but serious adverse events, including vector-associated inflammatory responses and conditions like vaccine-induced immune thrombotic thrombocytopenia (VITT), have raised important safety considerations. Additionally, scaling up manufacturing, ensuring consistency in large-scale production, meeting rigorous regulatory standards, and maintaining equitable global access to these vaccines present profound logistical and ethical dilemmas. In response to these challenges, the field is evolving rapidly. Sophisticated engineering strategies, such as integrase-defective lentiviral vectors, insect-specific flaviviruses, chimeric capsids to evade neutralizing antibodies, and plug-and-play self-amplifying RNA approaches, seek to bolster safety, enhance immunogenicity, circumvent pre-existing immunity, and streamline production. Lessons learned from the COVID-19 pandemic and prior outbreaks are guiding the development of platform-based approaches designed for rapid deployment during future public health emergencies. This review provides an exhaustive, in-depth examination of the historical evolution, immunobiological principles, current platforms, manufacturing complexities, regulatory frameworks, known safety issues, and future directions for viral vector-based vaccines. Full article

The publication focuses on the innovative applications of PROTAC (proteolysis-targeting chimera) technology in modern pharmacotherapy, with particular emphasis on cancer treatment. PROTACs represent an advanced therapeutic strategy that enables selective protein degradation, opening new possibilities in drug design. This technology shows potential in the treatment of cancers, viral infections (such as HIV and COVID-19), and chronic diseases including atherosclerosis, Alzheimer’s disease, atopic dermatitis, and Huntington’s disease. Promising results from clinical studies on the compound ARV-471 confirm the effectiveness of this approach. New types of PROTACs, like TF-PROTAC and PhosphoTAC, are designed to enhance the effectiveness, stability, and absorption of treatment drugs. The conclusions of the review highlight the broad therapeutic potential of PROTACs in various diseases and their relevance for the future of therapies, particularly in oncology. Full article