Search Results (494)

Chronic kidney disease (CKD) has now reached epidemic proportions in many parts of the world, primarily due to the high incidence of diabetes and hypertension. By 2040, CKD is predicted to be the fifth-leading cause of years of life lost. Developing strategies to prevent CKD and to reduce its progression to kidney failure is thus of great public health significance. Hypertension is known to be both a cause and a consequence of kidney damage and an eminently modifiable risk factor. An increased risk of hypertension, especially among women, has been linked to chronic exposure to the ubiquitous food contaminant cadmium (Cd). The mechanism is unclear but is likely to involve its action on the proximal tubular cells (PTCs) of the kidney, where Cd accumulates. Here, it leads to chronic tubular injury and a sustained drop in the estimated glomerular filtration rate (eGFR), a common sequela of ischemic acute tubular necrosis and acute and chronic tubulointerstitial inflammation, all of which hinder glomerular filtration. The present review discusses exposure levels of Cd that have been associated with an increased risk of hypertension, albuminuria, and eGFR ≤ 60 mL/min/1.73 m² (low eGFR) in environmentally exposed people. It highlights the potential role of 20-hydroxyeicosatetraenoic acid (20-HETE), the second messenger produced in the kidneys, as the contributing factor to gender-differentiated effects of Cd-induced hypertension. Use of GFR loss and albumin excretion in toxicological risk calculation, and derivation of Cd exposure limits, instead of β₂-microglobulin (β₂M) excretion at a rate of 300 µg/g creatinine, are recommended. Full article

Inherited epidermolysis bullosa (EB) is a heterogeneous clinical entity that includes over 30 phenotypically and/or genotypically distinct inherited disorders, characterized by mechanical skin fragility and bullae formation. Junctional EB (JEB) is an autosomal recessive disease characterized by an intermediated cleavage level within the skin layers, commonly at the “lamina lucida”. Laryngo-onycho-cutaneous syndrome (LOC) is an extremely rare variant of JEB, characterized by granulation tissue formation in specific body sites (skin, larynx, and nails). Although most cases of JEB are caused by pathogenic variants occurring in the genes encoding for classical components of the lamina lucida, such as laminin 332 (LAMA3, LAMB3, LAMC2), integrin α6β4 (ITGA6, ITGB4), and collagen XVII (COL17A1), other variants have also been described. We report the case of a 4-month-old male infant who presented with recurrent bullous and erosive lesions from the first month of life. At the first dermatological evaluation, the patient was agitated and exhibited hoarse breathing, a clinical sign suggestive of laryngeal involvement. Multiple polygonal skin erosions were observed on the cheeks, along with similar isolated, roundish lesions on the scalp and legs. Notably, nail dystrophy and near-complete anonychia were evident on the left first and fifth toes. Due to the coexistence of skin erosions and nail dystrophy in such a young infant, a congenital bullous disorder was suspected, prompting molecular analysis of all potentially involved genes. In the patient’s DNA, clinical exome sequencing (CES) identified a pathogenic variant, apparently in homozygosity, in the exon 1 of the LAMA3 gene (18q11.2; NM_000227.6): c.47G > A;p.Trp16*. The presence of this variant was confirmed, in heterozygosity, in the genomic DNA of the patient’s mother, while it was absent in the father’s DNA. Subsequently, trio-based SNP array analysis was performed, revealing a paternally derived pathogenic microdeletion encompassing the LAMA3 locus (18q11.2). To our knowledge, this is the first reported case of JEB with a LOC-like phenotype caused by a maternally inherited monoallelic nonsense mutation in LAMA3, unmasked by an almost complete deletion of the paternal allele. The combined use of exome sequencing and SNP array is proving essential for elucidating autosomal recessive diseases with a discordant segregation. This is pivotal for providing accurate genetic counseling to parents regarding future pregnancies. Full article

Background: The development of antimicrobial resistance is a major public health issue, in which dentists play a significant role by prescribing 7–11% of worldwide antibiotics. The aim of this study is to evaluate the self-perception and knowledge of antibiotic therapy in fifth-year undergraduate dental students. Methods: This is a cross-sectional observational study based on the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines. An electronic survey consisting of 18 questions was conducted with fifth-year students enrolled in the 2022/23 and 2023/24 academic years. The data were analyzed using descriptive and inferential statistical methods. Results: A total of 139 students (76.4%) completed the questionnaire. A total of 71.9% of students considered that they had received adequate education in antibiotic therapy, particularly in Oral Surgery (89.2%) and Periodontics (86.3%). The theoretical classes (3.50 ± 0.98) and practical sessions (3.18 ± 1.29) provided the knowledge that had the greatest influence on their education. They showed high self-confidence in diagnosing an infection (3.49 ± 0.73) and in choosing the appropriate antibiotic and dosage (3.26 ± 0.73). Over 76% of students answered correctly regarding the need for antibiotic prescriptions in various practical scenarios, except in the replantation of avulsed permanent teeth (54%). Conclusions: Dental students’ knowledge of antibiotics should be reinforced, as a high percentage answered correctly regarding the indications for antibiotics in pulpal and periapical diseases, but students performed less well regarding the choice of antibiotic and dosage in patients without sensitivity to β-lactams. Full article

Polyunsaturated fatty acids are vital for brain health, supporting cognitive development and helping to prevent neurodegenerative diseases. Since the body cannot produce them, they must be obtained through food. This study aimed to assess the effects of corn oil on the behavior and biochemical parameters of Drosophila melanogaster. The flies were fed a diet supplemented with different concentrations of corn oil from the larval stage until the fifth day of adulthood. A diet containing corn oil (37.8 mg/mL of linoleic acid) reduced mortality under starvation conditions and enhanced locomotor performance (p < 0.01). Biochemical analyses revealed increased levels of glutathione (p < 0.001), citrate synthase activity (p < 0.05), and mitochondrial phosphorylation (p < 0.05), indicating a potential boost in energy metabolism. Conversely, a decrease in acetylcholinesterase activity (p < 0.05) was observed, suggesting cholinergic modulation. These results demonstrate that corn oil supplementation supports neural health in this animal model, opening pathways for further research into non-pharmacological treatments for neurodegenerative diseases such as Alzheimer’s disease. Full article

Background: Human herpesviruses are double-stranded DNA viruses of which eight types have been identified at present. Herpesvirus infection comprises an active lytic phase and a lifelong latency phase with the possibility of reactivation. These infections are highly prevalent worldwide and can lead to a broad spectrum of clinical manifestations, ranging from mild symptoms to severe disease, particularly in immunocompromised individuals. Clustered regularly interspaced palindromic repeats (CRISPR)-based therapy is an interesting alternative to current antiviral drugs, which fail to cure latent infections and are increasingly challenged by viral resistance. Objective: This scoping review aimed to summarize the current state of CRISPR-based antiviral strategies against herpesvirus infections, highlighting the underlying mechanisms, study design and outcomes, and challenges for clinical implementation. Design: A literature search was conducted in the databases PubMed and Web of Science, using both a general and an individual approach for each herpesvirus. Results: This scoping review identified five main mechanisms of CRISPR-based antiviral therapy against herpesvirus infections in vitro and/or in vivo. First, CRISPR systems can inhibit the active lytic replication cycle upon targeting viral lytic genes or host genes. Second, CRISPR technologies can remove latent viral genomes from infected cells by targeting viral genes essential for latency maintenance or destabilizing the viral genome. Third, reactivation of multiple latent herpesvirus infections can be inhibited by CRISPR-Cas-mediated editing of lytic viral genes, preventing a flare-up of clinical symptoms and reducing the risk of viral transmission. Fourth, CRISPR systems can purposefully induce viral reactivation to enhance recognition by the host immune system or improve the efficacy of existing antiviral therapies. Fifth, CRISPR technology can be applied to develop or enhance the efficiency of cellular immunotherapy. Conclusions: Multiple studies demonstrate the potential of CRISPR-based antiviral strategies to target herpesvirus infections through various mechanisms in vitro and in vivo. However, aspects regarding the delivery and biosafety of CRISPR systems, along with the time window for treatment, require further investigation before broad clinical implementation can be realized. Full article

Road traffic accidents (RTAs) are a leading cause of physical injury worldwide, but they also frequently result in post-traumatic stress disorder (PTSD). This systematic review examines the prevalence, predictors, comorbidity, and treatment of PTSD among RTA survivors. Four electronic databases (PubMed, Scopus, EBSCO, and ProQuest) were searched following PRISMA 2020 guidelines. Articles were included if reporting on the presence of post-traumatic stress disorder as a result of a road traffic accident in adults aged 18 years and older. Including peer-reviewed journal articles and awarded doctoral theses across all publication years, and written in English, Macedonian, Serbian, Bosnian, Croatian, and Bulgarian, identified 259 articles, and using Literature Evaluation and Grading of Evidence (LEGEND) assessment of evidence 96 were included in the final review, involving 50,275 participants. Due to the heterogeneity of findings, quantitative data were synthesized thematically rather than through meta-analytic techniques. Findings are reported from Random Control Trial (RCT) and non-RCT studies. PTSD prevalence following RTAs ranged widely across studies, from 20% (using Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, DSM-5 criteria) to over 45% (using International Classification of Diseases, 10th Revision, ICD-10 criteria) within six weeks post-accident (non-RCT). One-year prevalence rates ranged from 17.9% to 29.8%, with persistence of PTSD symptoms found in more than half of those initially diagnosed up to three years post-RTA (non-RCTs). Mild or severe PTSD symptoms were reported by 40% of survivors one month after the event, and comorbid depression and anxiety were also frequently observed (non-RCTs). The review found that nearly half of RTA survivors experience PTSD within six weeks, with recovery occurring over 1 to 3 years (non-RCTs). Even minor traffic accidents lead to significant psychological impacts, with 25% of survivors avoiding vehicle use for up to four months (non-RCT). Evidence-supported treatments identified include Cognitive Behavioural Therapy (CBT) (RCTs and non-RCTs), Virtual Reality (VR) treatment (RCTs and non-RCTs), and Memory Flexibility training (Mem-Flex) (pilot RCT), all of which demonstrated statistically significant reductions in PTSD symptoms across validated scales. There is evidence for policy actions including mandatory and regular psychological screening post RTAs using improved assessment tools, sharing health data to better align early and ongoing treatment with additional funding and access, and support and interventions for the family for RTA comorbidities. The findings underscore the importance of prioritizing research on the psychological impacts of RTAs, particularly in regions with high incident rates, to understand better and address the global burden of post-accident trauma. Full article

Background: High-grade glioma (HGG) is the most common primary malignant brain tumor, with peak incidence in the fifth and sixth decades of life. Although HGG is rare in children, the prognosis remains poor, with a median overall survival (OS) of less than two years. Recently, TRK inhibitors have been approved for the treatment of tumors harboring NTRK gene fusions. In this review, we analyzed data from early clinical trials investigating the use of these agents in patients with HGG. Methods: A systematic literature search was performed in the PubMed database. Studies involving patients with HGG treated with TRK inhibitors were included. We analyzed progression-free survival (PFS), 24-week disease control rate, and complete or partial radiological responses according to the Response Assessment in Neuro-Oncology (RANO) criteria. Results: Sixteen studies comprising 55 patients with HGG harboring NTRK gene fusions (19 adults and 36 children) were included. A statistically significant difference in PFS was observed between pediatric and adult patients treated with TRK inhibitors (17 vs. 8.5 months; p < 0.001). Pediatric patients also exhibited a higher rate of complete or partial radiological response compared to adults (94% vs. 57%). Discussion: Although the available evidence on TRK inhibitors in HGG is limited, the findings of this review highlight a potentially promising role for these agents, particularly in the treatment of pediatric HGGs. Full article

Polyomaviruses have the potential to cause significant morbidity not only in transplant medicine, but also in other forms of disease or variants of immunosuppression. In kidney transplant recipients or recipients of human stem cell transplants, the BK-Virus is the major proponent of manifestations such as BKPyV-associated nephropathy or hemorrhagic cystitis. As no polyomavirus-specific drug with proven in vivo effects has been developed so far, methods to screen for such drugs are important. This work describes the establishment of a virus-secreting cell line. By infecting a pre-established monkey kidney cell line (COS-1) with a non-rearranged human BK polyomavirus isolated from a kidney transplant patient suffering from BKPyV-associated nephropathy, a continuously replicating cell type with consistent virus secretion could be established and was termed COSSA. Measurements of BKPyV replication, virion production, and secretion were performed both intracellularly and in the cell supernatant. Viral proteins such as VP1 and LTAg were accurately tracked by confocal microscopy, as well as by immunoblot and qPCR. An intracellular flow cytometry (FACS) assay detecting VP1 protein was established and revealed an expanded range of positive intracellular signals. The viruses produced proved to be infectious in human tubular epithelial cell lines. Long-range sequencing of the COSSA genome using Oxford Nanopore Technology revealed a total of five distinct BKPyV integration events. One integration of a partial BKPyV genome was located upstream of the epidermal growth factor receptor gene. The second and third, both truncated forms of integration, were close to histocompatibility gene locuses, while the fourth was characterized by a ninefold and the fifth by a fourfold tandem repeat of the BKPyV genome. From both of the repeat forms, virus replicates were derived showing deletions/duplications on early and late genes and inversions within the non-coding control region (NCCR). This pattern of repetitive viral genome integration is a potential key driver of enhanced viral replication and increased virion assembly, ultimately supporting efficient virus egress. Quantitative PCR analysis confirmed the release of approximately 10⁸/mL viral units per 48 h from 2 × 10⁵ COSSA cells into the culture supernatant. Notably, the NCCR region of the most frequent copies of circular virus and the integrated tetrameric tandem repeat exhibited a rearranged configuration, which may contribute to the observed high replication dynamics. The establishment of a consistent methodology to generate and secrete BKPyV from a cell line is expected to significantly facilitate antiviral drug development. Full article

Alzheimer’s Disease (AD) is a global issue, with increasing incidence and prevalence as the world’s population ages and life expectancy increases. Projections indicate that by 2050, over 150 million individuals worldwide will be personally living with AD, an impending crisis made worse by the absence of cure therapies. Moreover, the risk factor relationship of dementia with rising global temperatures and air pollution further necessitates the urgency of a coordinated international response. With an extensive economic and emotional burden, AD is no longer just a disease; it is a worldwide societal crisis. This review presents five calls to action to address the AD global health emergency. First, AD research must be approached as an internationally performed activity, involving standardized data sharing, collaborative innovation, and improved access to pharmaceutical studies in low- and middle-income countries (LMICs), alongside increased diversity, inclusion, and equity in research. Second, there must be a commitment to develop universally accessible, affordable, and non-invasive diagnostic tools for AD. Third, advancements in AD therapeutics should prioritize the development of affordable agents, allowing for widespread geographic distribution. Fourth, we identify focus areas for global dementia risk reduction: sleep, head injury prevention, exercise, learning, and diet (SHIELD risk reduction strategy). Fifth, improving care for individuals with AD requires eliminating stigma through educational programs for both the public and caregivers. The escalating AD crisis demands an unprecedented global coalition in research, diagnostics, therapeutics, prevention, and education to avoid a future where the disease becomes the defining crisis of our era. Full article

The clinical efficacy of inhalation therapy in chronic respiratory diseases is fundamentally constrained by particle deposition patterns. This study employs computational fluid dynamics (CFD) and response surface methodology (RSM) to elucidate the mechanistic interplay of deposition determinants through multifactorial sensitivity mapping. The study comprises two key components: (i) the development of an accurate three-dimensional respiratory airway model spanning from the oral cavity to the fifth-generation bronchi and (ii) the integration of a Box–Behnken Design (BBD) experimental framework with computational fluid dynamics simulations. Furthermore, we developed a multifactorial regression model to analyze the synergistic interactions among deposition determinants. The study demonstrated a positive correlation between breath-holding time and drug deposition efficiency, revealing a hierarchical order of critical parameters: peak flow rate > breath-holding time > particle diameter. These findings have important implications for optimizing respiratory drug delivery strategies in clinical settings. Full article

This narrative review introduces key concepts in artificial intelligence (AI), data science, and wearable devices aimed at headache clinicians and researchers. PubMed and IEEEXplore were searched to identify relevant studies, and these were reviewed systematically. We identified six primary research topics. First, the most common application of AI and data science is in the diagnosis of headache disorders, with reported accuracies of up to 90%. Second, AI and data science are used for predicting headache disease trajectories and forecasting attacks. Third, prediction of treatment effects and data-driven individualization of treatment prescription demonstrate promising results, with accuracies ranging from 40% to 83%. Fourth, AI and data science can uncover hidden information within headache datasets, offering clinicians deeper insights. Fifth, wearables, combined with AI and data science, can improve remote monitoring and migraine management. Lastly, user experience studies indicate strong interest from both clinicians and patients in adopting these technologies. The potential applications of AI, data science, and wearable device technologies in headache research are vast. However, many studies are small pilot studies, and models often suffer from poor performance, limited reporting, and lack of external validation, which impede generalizability and clinical implementation. Full article

In 2024, Europe experienced a significant upsurge in cases of Parvovirus B19 (B19V), the etiological agent of erythema infectiosum, also known as fifth disease. The prevalence of B19V in pregnant women, a particularly vulnerable population, holds critical clinical significance. Typically, B19V follows a well-documented seasonal pattern, with annual epidemics peaking in the spring and larger outbreaks occurring approximately every four years. B19V exhibits a tropism for erythroid precursor cells, potentially resulting in fetal anemia and, in the most severe scenarios, intrauterine demise. Severe in utero infections necessitate intrauterine erythrocyte transfusion (IUT), a highly specialized and technically demanding procedure that is exclusively performed in tertiary-level prenatal care units. This study delineates how the notable increase in B19V infections is also reflected in our prenatal diagnosis unit at Fondazione Policlinico Agostino Gemelli (FPG) IRCCS, Rome, Italy. According to our case series, since 2018, B19V has been identified as the second most common cause of fetal anemia during the study period (29%, 6 patients), yet it accounted for the majority of IUT procedures performed in 2024 (16 out of 19 cases, 84.2%). Given the rising incidence of severe intrauterine infections in recent epidemic cycles, healthcare professionals should maintain a high index of suspicion regarding the clinical manifestations of maternal B19V infection and its potential obstetric complications. Further research is imperative to evaluate the cost-effectiveness of routine screening for B19V immunity in pregnant women and to investigate the long-term neurodevelopmental and clinical outcomes of neonates affected by intrauterine B19V infection. Full article

Endometrial cancer is the fifth most common cancer worldwide, with one of the highest incidence and mortality rates. Its incidence is projected to increase 55% by 2030. Currently, the techniques used for its detection are heterogeneous and can be invasive and nonspecific. In this context, omics studies have gained relevance, providing solutions that have improved patient diagnosis and prognosis. In this study, we used data from the GSE268888 study as discovery cohort and data from the TCGA consortium as a validation cohort. Expression analyses were performed to identify miRNAs overexpressed in endometrial cancer. These miRNAs were then analyzed in relation to diagnostic and prognostic clinical variables. The target genes of these miRNAs were identified using bioinformatic tools, and functional enrichment analyses were conducted with this gene set to explore their involvement in relevant oncogenic signaling pathways. We also calculated the structural topology of the miRNA–target complexes and computed their correlation coefficients. We found that hsa-miR-182 and hsa-miR-760 had diagnostic and prognostic relevance and interacted with the p53 signaling pathway. Specifically, hsa-miR-449a was associated with diagnosis, but not with prognosis. Furthermore, we found that these miRNAs share TP53INP1 as a common target gene and estimated a high probability of complex formation, along with a positive correlation between these miRNAs and TP53INP1 in more advanced stages of the disease. These findings suggest that this miRNA signature has potential to be used as a diagnostic and prognostic biomarker and could serve as a foundation for future therapeutic strategies for endometrial cancer. However, further experimental validation is needed to confirm its clinical applicability. Full article

Waste from livestock farms contains various pathogens, including eggs and larvae of helminths—pathogens of parasitic diseases harmful to animals and humans. One of the methods for their effective processing to obtain biofertilizer and biofuel is anaerobic digestion, which requires further improvement to completely suppress the viability of pathogenic microorganisms in mesophilic conditions. To this end, the use of anaerobic digestion under sulfate reduction conditions to suppress pathogens using biogenic hydrogen sulfide is promising. Consequently, this study aims to study the effect of a sulfur-containing additive such as phosphogypsum on the disinfection of pig manure during anaerobic digestion. Egg mortality was already found to increase significantly compared to the control (80% and more), even at a minimum concentration of phosphogypsum (5%), on the fifth day of the experiment. At the same time, the maximum effect (100% mortality of Trichuris suis eggs) was recorded at a 10% concentration of phosphogypsum, starting from the 10th day of the study. Our experiment showed that changes in anaerobic digestion conditions using phosphogypsum could positively affect digestate disinfection. However, further research is needed to optimize the conditions of the process for an effective combination of disinfection with the production of environmentally safe organic fertilizers and high-quality biogas with a high level of methane. Full article

Aim: To identify ultrasound (US) predictors of persistence or change in the diagnosis of rheumatoid arthritis (RA) after five years in a cohort of patients with early RA. Patients and Methods: One hundred and twenty patients with early arthritis who met the 2010 ACR/EULAR classification criteria for RA were followed for a period of five years. The US assessment at baseline included a bilateral evaluation of the wrists, second to fifth metacarpophalangeal (MCP) joints, second to fifth proximal interphalangeal (PIP) joints, the IV and VI extensor compartments of the wrists, and the flexor tendons of the second to fifth fingers. This evaluation was conducted using both grayscale ultrasound (GSUS) and power Doppler ultrasound (PDUS). The following scores were recorded for each patient: synovitis score, mini-enthesitis score (including paratenonitis of the finger extensor tendon at the MCP joint, central slip enthesitis at the PIP joint, pseudotenosynovitis, and the A1 pulley of the second finger), finger flexor tenosynovitis score, and tenosynovitis score for the IV and VI wrist extensor compartments. The receiver operating characteristic (ROC) curve was utilized to identify the ultrasound predictors for either maintaining or revising an initial diagnosis of RA. Results: At month 6, 82 (68%) patients were classified as having RA according to 1987 ACR RA criteria, 23 (19.2%) were diagnosed with psoriatic arthritis (PsA), 10 (8.3%) with systemic connective tissue disease (SCTD)–8 (6.7%) patients with Sjogren Syndrome and 2 (1.7%) patients with systemic lupus erythematosus (SLE)–and 5 (4.2%) patients with calcium pyrophosphate deposition disease (CPPD). The most significant predictor of RA in the fifth year was the VI extensor compartment tenosynovitis score, with an AUC of 0.915 and a criterion value > 0, associated with a sensitivity of 82.93% and a specificity of 100% (p < 0.001). The PDUS synovitis score demonstrated the second-best prognostic ability with an AUC of 0.823, a criterion value > 2, a sensitivity of 82.93%, and a specificity of 73.68% (p < 0.001). The mini-enthesitis score showed the best prognostic ability of a PsA diagnosis with an AUC of 0.998, a criterion value > 1, a sensitivity of 95.65%, and a specificity of 100% (p < 0.001). The paratenonitis score, pseudotenosynovitis score, and thickened A1 pulley were also predictive of PsA diagnosis with AUCs of 0.977, 0.955, and 0.919, respectively (p < 0.001 for all). Conclusions: Nearly one-third of the patients who were initially classified as having RA had their diagnosis revised at the end of the fifth year. Ultrasound of joints, tendons, and mini-entheses at baseline may serve as potential imaging predictive biomarkers for persistence or change in diagnosis after 5 years. Full article