Search Results (1,784)

The present study aimed to identify a safe and novel approach using zinc oxide/copper oxide nanocomposites (AZ) to enhance growth parameters, immunity, and fight Sarcoptic mange in vitro and in vivo in rabbits. In vitro: the acaricidal activity of AZ was assessed at concentrations of AZ-25: 2.5% w/w AZ/molasses, AZ-125: 12.5% w/w AZ/molasses, and controls (normal saline, molasses, and Ivermectin) every hour for seven hours under a stereoscopic microscope. In vivo: involved 40 rabbits (10 replicates/group). G1 served as the control negative group (normal un-infected rabbits), G2 served as the control negative group (infected rabbits), the animals in the G3 group were given a combination of AZ (40 mg/kg body weight (BW)) and molasses (5 mg/mL), and G4 served as the control to the vehicle; receiving molasses 8 mL/kg BW twice weekly for 6 weeks. Blood, serum, and tissue samples were collected at the middle and the end of the trial. AZ was made using the sonication sol–gel method. X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) were performed to confirm the crystal structure, purity, particle size, and oxidation states. AZ showed immunostimulant, acaricidal, and antioxidant effects with normal tissue histological structure and low tissue residual levels. Additionally, there were improvements in blood interferon-gamma, immunoglobulin (Ig) M, IgG, phagocytic activity, phagocytic index, globulin, and total protein in the AZ group. The XRD patterns of AZ were coordinated by XRD reference codes Crystallography Open Database (COD): 9016326 for Tenorite (CuO) and by XRD reference COD: 9004179 for Zincite (ZnO). The CuO and ZnO crystal sizes were 21.87 Å and 24.89 Å, respectively. The XPS spectra indicated the presence of Cu as Cu (II) and Zn as ZnO.OH and ZnO. In conclusion, AZ exhibited antioxidant, acaricidal, and immunostimulant effects, with mild residues in the brain, liver, and kidney tissues, while maintaining a normal histological structure of tissues. Full article

The human gut microbiota—an intricate and dynamic ecosystem—plays a pivotal role in metabolic regulation, immune modulation, and the maintenance of intestinal barrier integrity. Although antibiotic therapy is indispensable for managing bacterial infections, it profoundly disrupts gut microbial communities. Such dysbiosis is typified by diminished diversity and shifts in community structure, especially among beneficial bacterial genera (e.g., Bifidobacterium and Eubacterium), and fosters antibiotic-resistant strains and the horizontal transfer of resistance genes. These alterations compromise colonization resistance, increase intestinal permeability, and amplify susceptibility to opportunistic pathogens like Clostridioides difficile. Beyond gastrointestinal disorders, emerging evidence associates dysbiosis with systemic conditions, including chronic inflammation, metabolic syndrome, and neurodegenerative diseases, underscoring the relevance of the microbiota–gut–brain axis. The recovery of pre-existing gut communities post-antibiotic therapy is highly variable, influenced by drug spectrum, dosage, and treatment duration. Innovative interventions—such as fecal microbiota transplantation (FMT), probiotics, synbiotics, and precision microbiome therapeutics—have shown promise in counteracting dysbiosis and mitigating its adverse effects. These therapies align closely with antibiotic stewardship programs aimed at minimizing unnecessary antibiotic use to preserve microbial diversity and curtail the spread of multidrug-resistant organisms. This review emphasizes the pressing need for microbiota-centered strategies to optimize antibiotic administration, promote long-term health resilience, and alleviate the disease burden associated with antibiotic-induced dysbiosis. Full article

Background/Objectives: Patients with central nervous system injuries who are hospitalized in intensive care units (ICUs) are at high risk for nosocomial infections. Limited data are available on the incidence and patterns of microbial colonization and infection in this patient population. Methods: To fill this gap, we performed an electronic health record-based study of 1614 chronic patients with brain injury admitted to the ICU from 2017 to 2023. Results: Among the infectious complications, pneumonia was the most common (n = 879; 54.46%). Sepsis was diagnosed in 54 patients, of whom 46 (85%) were diagnosed with pneumonia. The only pathogen that showed an association with the development of pneumonia and sepsis in colonized patients was Pseudomonas aeruginosa (pneumonia: p = 7.2 × 10⁻⁹; sepsis: p = 1.7 × 10⁻⁵). Bacterial isolates from patients with and without pneumonia did not differ in pathogen titer or dynamics, but patients with monomicrobial culture were more likely to develop pneumonia than patients with polymicrobial culture (1 vs. 2 pathogens, p = 0.014; 1 + 2 pathogens vs. 3 + 4 pathogens, p = 2.8 × 10⁻⁶), although the pathogen titer was lower in monoculture than in polyculture. Bacterial isolates from all patients and all culture sites showed high levels of multidrug resistance (Gram-negative bacteria: 88–100%; Gram-positive bacteria: 48–97%), with no differences in multidrug-resistant organism (MDRO) colonization and infection rates. Conclusions: Our results highlight the high burden of MDROs in neurological ICUs and provide novel ecosystem-based insights into mono- and polymicrobial colonization and infection development. These findings may be useful for developing strategies to protect against infections. Full article

One of the main threats for the survival of the Iberian lynx is infectious disease. Feline parvoviruses cause often fatal diseases in cats and have been isolated from different species of Felidae and other carnivores. The present study is the first description of a parvoviral sequence isolated from the brain of an Iberian lynx which died four weeks after being transferred to a quarantine centre from a hunting estate in Castilla-La-Mancha (southern border of the Iberian plateau). Four days prior to death, it had developed anorexia and muscle weakness. The nucleotide sequence, at 4589 nt long (GenBank PP781551), was most proximal to that isolated from a Eurasian badger in Italy but also showed great homology with others from cats and other carnivores isolated in Spain and Italy, including that from a cat sequenced by us to elucidate the origin of the infection, which has not been clarified. The phylogenetic analysis of the capsid protein, VP2, which determines tropism and host range, confirmed that the lynx sequence was most proximal to feline than to canine parvoviruses, and was thus typed as Protoparvovirus carnivoran1. More studies, including serology, are needed to understand the pathogenesis of this infection. Full article

Background: COVID-19 is linked to multiple adverse pregnancy outcomes but with inconsistent evidence associating the disease with fetal growth restriction (FGR) and small for gestational age (SGA). There are limited data on the impact of COVID-19 on neonatal growth measurements, specifically microcephaly without SGA or low birth weight. We hypothesize that COVID-19 is associated with smaller neonatal head measurements without increasing the risk of small for gestational age. This relationship may be related to the timing of COVID-19 exposure in pregnancy. Methods: An Institutional Review Board (IRB) approved retrospective cohort study enrolled 140 COVID-19-infected and 136 COVID-19-uninfected patients. Inclusion criteria: (a) singleton birth between 28 April 2020 and 31 December 2022; and (b) maternal COVID-19 infection diagnosed via polymerase chain reaction (PCR). Exclusion criteria: Less than 12 years of maternal age, major fetal anomalies, and fetal loss < 15 weeks. The outcomes were a comparison of newborn growth measurements (length, weight, and head circumference (HC) at birth), Ponderal Index (PI), and development of SGA between SARS-CoV-2-infected and uninfected patients. Maternal and neonatal characteristics were descriptively summarized, and multivariate analyses and linear regression models were performed. Baseline maternal demographics did not differ amongst cohorts. Results: Compared to the uninfected cohort, COVID-19 diagnosed in the third trimester was associated with a lower neonatal HC compared to newborns of uninfected patients (β = −0.38 [0.38 SD lower], 95% CI −0.65 to −0.10, p = 0.024). There was no significant difference among cohorts in birth length, weight, or diagnosis of small for gestational age. Conclusions: We found that COVID-19 infection in the third trimester was associated with a lower neonatal head circumference without associated SGA. The cause underlying this association is unknown. Further research to determine the risk of neurotropic fetal infection by SARS-CoV-2, like ZIKA’s effect on the fetal immune system leading to microcephaly, is urgently needed. Full article

Sepsis is a syndrome of life-threatening acute organ dysfunction caused by a dysregulated host response to infection. Sepsis-associated encephalopathy (SAE) refers to the diffuse brain dysfunction observed in sepsis cases, clinically characterized by a spectrum of neuropsychiatric manifestations ranging from delirium to coma. SAE is independently associated with increased short-term mortality and long-term neurological abnormalities, with currently no effective preventive or treatment strategies. The pathogenesis is intricate, involving disruptions in neurotransmitters, blood–brain barrier (BBB) breakdown, abnormal brain signal transmission, and oxidative stress, among others. These mechanisms interact or act in conjunction, contributing to the complexity of SAE. Scholars worldwide have made significant strides in understanding the pathogenesis of SAE, offering new perspectives for diagnosis and treatment. This review synthesizes recent mechanistic breakthroughs and clinical evidence to guide future research directions, particularly in targeting BBB restoration and oxidative stress. Full article

The global impact of the COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), persists in part due to the emergence of new variants. Understanding variant-specific infection dynamics and pathogenesis in murine models is crucial for identifying phenotypic changes and guiding the development of countermeasures. To address the limitations of earlier studies that investigated only a few variants or used small sample sizes, we evaluated clinical disease, infection kinetics, viral titers, cellular localization, and histopathologic changes in the lungs and brains of transgenic B6.Cg-Tg(K18-ACE2)2Prlmn/J (“K18”) and corresponding genetic control (C57BL/6J) mice expressing human angiotensin-converting enzyme 2 (hACE2). Six SARS-CoV-2 variants were assessed: B.1 (WA1-like), alpha, beta, delta, omicron, and omicron XBB.1.5, using cohorts of ≥18 mice. Following intranasal inoculation with B.1, alpha, beta, or delta variants, K18 mice experienced rapid weight loss and reached euthanasia criteria by 5–6 days post-inoculation (dpi). In contrast, K18 mice inoculated with both omicron variants recovered to their starting weight within 4–6 dpi. Infectious SARS-CoV-2 was detected in the oropharynx at 1 and2 dpi, in the lungs at 2, 4, and 6 dpi, and in the brain at 4 and 6 dpi for all variants except omicron. SARS-CoV-2 nucleoprotein was detected, and interstitial pneumonia of varying severity was observed in K18 mice infected with all variants. Brain lesions were identified in mice infected with the B.1, beta, and delta variants 6 dpi. As K18 mice express hACE2 in the brain—a feature not present in humans—we also compared infection dynamics of three variants to those of a mouse-adapted WA1 strain in C57BL/6J mice lacking the human ACE2 gene. C57BL/6J mice did not experience lethal disease, exhibited milder pneumonia, and had no evidence of neuroinvasion despite similar infection kinetics to K18 mice. These findings demonstrate contrasting phenotypes across the two models and reduced tropism and pathology of omicron compared to earlier variants in both models. This comprehensive analysis of SARS-CoV-2 variants in two mouse models provides valuable insights for model and variant selection for future studies. Full article

Neurological symptoms such as impaired smell and taste have been recognized as hallmark manifestations of severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. This study investigates and quantifies microstructural changes in the white matter of the olfactory bulb and taste-related brain regions (frontal operculum, insular cortex and parietal operculum) using diffusion-weighted magnetic resonance imaging (DW-MRI). Apparent diffusion coefficient (ADC) values were measured in patients with confirmed coronavirus disease of 2019 (COVID-19) at the onset of anosmia and ageusia (24 patients, scanned between March and December 2020), 1 month post-infection (20 subjects) and 36 months post-infection (20 participants). ADC values were analyzed over time and compared to normal white matter ADC ranges (calculated retrospectively from 979 pre-pandemic patients) and to those from patients infected with the 2024 strain of SARS-CoV-2 (27 patients). The results revealed significantly elevated ADC values in the white matter of the targeted brain regions, with a peak at the time of infection, followed by a decline 1 month post-infection, and a return to near-normal levels 3 years later. In contrast, the 2024 COVID-19 variant demonstrated reduced virus-related alterations in brain microstructure compared to the 2020 strain. These findings highlight the potential of DWI as a non-invasive tool for elucidating the molecular mechanisms underlying olfactory and taste dysfunction in COVID-19 patients. Full article

Bergamot [Citrus × limon (L.) Osbeck, syn. C. × bergamia (Risso) Risso & Poit.] is primarily cultivated in the Calabria region of Italy and exploited in the food and perfumery industry. The epicarp of its fruit is a rich source of essential oil (BEO) containing mainly monoterpenes, which are known for their diverse biological activities, including antimicrobial, anti-inflammatory, antiproliferative, and neuromodulatory effects. Emerging evidence suggests that oxidative stress plays a central role in the pathogenesis of neurodegenerative diseases, particularly Alzheimer’s disease (AD), where it contributes to neuronal dysfunction and cell death. Moreover, heavy metal exposure has been identified as a key environmental factor exacerbating oxidative stress and neurodegeneration in AD. This study aimed to explore whether BEO could mitigate heavy metal (Cd²⁺, Hg²⁺, and Pb²⁺)-induced neurotoxicity in SH-SY5Y cells, a model system for brain cells. MTT and calcein-AM assays were performed to examine the viability of the SH-SY5Y cells after exposure to each heavy metal itself, or in combination with BEO, whereas the LDH assay was carried out to determine the effects of BEO towards necrotic cell death induced by heavy metals. Furthermore, DCFH-DA was performed to determine whether BEO could protect SH-SY5Y from heavy metal-induced oxidative stress. This study also investigated the antibacterial properties of BEO on different Gram-positive and Gram-negative bacterial strains belonging to the ATCC collection. These results suggest that BEO may help counteract heavy metal-induced neuronal damage, particularly Cd²⁺ toxicity, potentially reducing one of the environmental risk factors associated with AD. Additionally, its antimicrobial properties reinforce its relevance in preventing infections that may contribute to neuroinflammation in AD. Full article

Background/Objectives: The COVID-19 pandemic increased psychiatric symptoms in patients with pre-pandemic mental health conditions. However, the effects of pandemic on the brain, stress, and mental illness remain largely conjectural. Our objective was to examine how the pandemic affected prefrontal cortical thicknesses (CTs), stress, and PTSD symptoms in people with pre-pandemic trauma histories. Methods: Fifty-one survivors from a pre-pandemic trauma study who had completed a pre-pandemic PTSD Checklist-5 (PCL) to assess PTSD symptoms and a sMRI scan to measure prefrontal CTs were re-recruited after the pandemic. They subsequently completed the COVID Stress Scale (CSS) to assess stress, the Clinician Administered PTSD Scale-5 (CAPS) to diagnose PTSD, and a second sMRI scan. COVID-19 infection was self-reported. Associations between stress and symptom assessments and post-pandemic CTs, differences in CTs in PTSD vs. non-PTSD groups, and changes in pre- to post-pandemic CTs were examined. Results: Pre-pandemic PCL scores were positively associated with CSS scores which, in turn, were higher in the PTSD group. Thicker IFG-opercularis CTs were associated with COVID-19 infection. Post-pandemic rMFG and IFG-orbitalis CTs were positively associated with CAPS scores. rACC CTs were negatively associated with CSS scores. Pre- to post-pandemic rMFG and frontal pole CTs thickened in the PTSD group but thinned in the non-PTSD group, whereas rACC CTs thinned in the PTSD group but thickened in the non-PTSD group. Conclusions: These findings provide novel evidence that the COVID-19 pandemic had diverse effects involving prefrontal cortex structure, stress, and PTSD symptoms in subjects with pre-pandemic trauma history and suggest that treatments are needed to counter these diverse effects. Full article

Background/Objectives: Headache is one of the most common neurological symptoms associated with COVID-19, affecting approximately 25% of patients. While most headaches resolve within weeks, some persist for months, suggesting underlying structural brain changes. This study aimed to identify brain MRI abnormalities associated with chronic headaches in patients with a history of COVID-19 infection. Methods: This retrospective study included 30 patients with post-COVID-19 headaches and 30 control patients with no history of COVID-19. Demographic characteristics were analyzed using t-tests and chi-square tests. MRI findings were categorized into six types: cortical atrophy, white matter lesions, vascular lesions, lacunar lesions, vascular encephalopathy, and sinusitis. Differences in MRI findings between the two groups were evaluated using chi-square tests. Secondary outcomes included the analysis of symptoms accompanying headaches, diagnoses following MRI, and treatments applied. Results: White matter lesions were significantly more frequent in the post-COVID-19 group (50%) compared to controls (20%) (p = 0.015). Conversely, sinusitis was more prevalent in the control group (36.7%) than in the post-COVID-19 group (6.7%) (p = 0.005). Other MRI abnormalities showed no significant differences. Cognitive dysfunction (30%) and dizziness (33.3%) were the most common associated symptoms. The most frequent diagnoses after MRI in the post-COVID-19 group were headaches/migraines (23.3%), post-COVID-19 headache (20%), and vestibular syndrome (13.3%). Conclusions: Persistent post-COVID-19 headaches may be linked to structural white matter changes observed in MRI. Further research, ideally including pre-infection imaging data, is needed to determine the causal relationship between these lesions and chronic headache symptoms. Trial Registration: This study was registered in ClinicalTrials with the trial registration number NCT06825741 on 13 February 2025. Full article

A proviral reservoir persists within the central nervous system (CNS) of people with HIV, but its characteristics remain poorly understood. Research has primarily focused on cerebrospinal fluid (CSF), as acquiring brain tissue is challenging. We examined size, cellular tropism, and infection-dynamics of the viral reservoir in post-mortem brain tissue from five individuals on and off antiretroviral therapy (ART) across three brain regions. Microglia-enriched fractions (CD11b⁺) were isolated and levels of intact proviral DNA were quantified (IPDA). Full-length envelope reporter viruses were generated and characterized in CD4⁺ T cells and monocyte-derived microglia. HIV DNA was observed in microglia-enriched fractions of all individuals, but intact proviruses were identified only in one ART-treated individual, representing 15% of the total proviruses. Phenotypic analyses of clones from this individual showed that 80% replicated efficiently in microglia and CD4⁺ T cells, while the remaining viruses replicated only in CD4⁺ T cells. No region-specific effects were observed. These results indicate a distinct HIV brain reservoir in microglia for all individuals, although intact proviruses were detected in only one. Given the unique immune environment of the CNS, the characteristics of microglia, and the challenges associated with targeting these cells, the CNS reservoir should be considered in cure strategies. Full article

The trigeminal nerve is the primary gateway through which the rabies virus enters the brain. Viral infection-related trigeminal neuritis is associated with certain clinical signs. This study investigated trigeminal ganglion histopathology in 92 rabid dogs. Trigeminal ganglionitis was classified into three pathological grades: mild, moderate, and severe. Immunostaining of selected sections was performed using antibodies against lymphocytes (CD3, CD20), stellate cells (glial fibrillary acidic protein, GFAP), macrophages (Iba-1, HLA-DR), ganglion cells (neurofilament, NF), and Schwann cells (S-100) to identify lesion cell types. In moderate and severe cases, double-immunofluorescence staining was performed to determine neuronophagia and Nageotte nodule cell types. Mild (13.0%) cases had minimal morphological changes in ganglion cells; moderate (56.5%) and severe (30.4%) cases showed infected ganglion cells and axons with degenerative necrosis, which were replaced by inflammatory cells. Immunohistochemically, viral antigens were detected in most ganglion cells in mild cases and were significantly reduced in severe cases. The number of CD3-, CD20-, GFAP-, and Iba-1-positive cells increased as the severity progressed, and neuronophagia and Nageotte nodules primarily comprised HLA-DR-positive cells. These findings suggest that the rabies virus reaches the trigeminal ganglion via ascending or descending routes and induces trigeminal neuropathological changes, contributing to neurological symptoms in rabid dogs. Full article

Background/Objectives: HIV persists in central nervous system (CNS) reservoirs, where infected microglia and macrophages drive neuroinflammation, oxidative stress, and neuronal damage, contributing to HIV-associated neurocognitive disorder (HAND). Nanoparticle-based drug delivery systems, particularly poly(lactic-co-glycolic acid) (PLGA) nanoparticles, offer a promising strategy to improve CNS antiretroviral therapy (ART) delivery. This study aimed to evaluate the efficacy of co-administration of PLGA nanoparticles (NPs) encapsulating elvitegravir (EVG) and curcumin (CUR) in targeting CNS reservoirs, reducing neuroinflammation, and mitigating oxidative stress. Methods: PLGA NPs encapsulating EVG and CUR (PLGA-EVG and PLGA-CUR) were prepared via the nanoprecipitation method. The NPs were characterized for size, zeta potential, and encapsulation efficiency (EE). Their therapeutic efficacy was evaluated in vitro using U1 macrophages and in vivo in Balb/c mice. Key parameters, including cytokine levels, oxidative stress markers, and neuronal marker expression, were analyzed. Results: The PLGA-EVG and PLGA-CUR NPs demonstrated high EE% (~90.63 ± 4.21 for EVG and 87.59 ± 3.42 for CUR) and sizes under 140 nm, ensuring blood–brain barrier (BBB) permeability. In vitro studies showed enhanced intracellular EVG concentrations and reductions in proinflammatory cytokines (IL-1β, TNFα, and IL-18) and improved antioxidant capacity in U1 macrophages. In vivo, the co-administration of NPs improved CNS drug delivery, reduced neuroinflammation and oxidative stress, and preserved neuronal markers (L1CAM, synaptophysin, NeuN, GFAP). Conclusions: PLGA-based co-delivery of EVG and CUR enhances ART CNS drug delivery, mitigating neuroinflammation and reducing oxidative stress. These findings highlight the potential of nanoparticle-based ART strategies to address limitations in current regimens and pave the way for more effective HAND therapies. Future studies should focus on optimizing formulations and evaluating safety in chronic HIV settings. Full article

Background: Fungal pericarditis is a rare disease but its incidence has risen in parallel with the global increase in invasive fungal infections. This systematic review analyzes data from previously reported cases of fungal pericarditis to provide an improved understanding of the etiology, clinical presentation, management, and outcomes of this rare disease. Methodology: We reviewed Medline and Scopus databases from 1 January 1990 to 29 January 2024 for case reports that documented the isolation of a fungal pathogen from pericardial fluid or tissue. Results: Of the 2330 articles screened, 101 cases met the inclusion criteria. Patients with fungal pericarditis and the involvement of at least one other organ—usually the lungs, brain, or kidney—had worse outcomes than patients with isolated pericardial disease. Immunosuppression was reported in 50% of cases and was associated with worse outcomes in adults. Patients who presented with chest pain, received adequate empiric antifungal therapy, and underwent pericardiocentesis and pericardiectomy had improved survival. The most common isolated pathogens were Candida spp., followed by Aspergillus spp. and Mucor spp., with the latter two linked to worse outcomes. Only 35% of patients received empiric antifungal medications before the causative pathogen was identified, and mortality was associated with a delay in appropriate therapy. Immunosuppression, disseminated disease, and presence of shock/multiorgan failure were additional risk factors associated with death. Conclusions: Fungal pericarditis carries a mortality rate of up to 50%, with nearly half of patients being immunocompromised. Clinicians frequently do not consider fungal pericarditis in the differential diagnoses, which leads to delays in treatment and poorer outcomes. Further prospective multicenter studies are urgently needed to better understand the epidemiology, improve diagnostic testing and management, and decrease unacceptably high mortality in patients with fungal pericarditis. Full article