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NPJ Parkinson's Disease Jun 2024In Parkinson's disease (PD), GBA1- and LRRK2-mutations are associated with different clinical phenotypes which might be related to differential involvement of the...
In Parkinson's disease (PD), GBA1- and LRRK2-mutations are associated with different clinical phenotypes which might be related to differential involvement of the cholinergic system. We investigated cholinergic integrity in 149 asymptomatic GBA1 and 169 asymptomatic LRRK2 mutation carriers, 112 LRRK2 and 60 GBA1 carriers with PD, 492 idiopathic PD, and 180 controls from the PPMI cohort. Basal forebrain volumes were extracted and white matter pathways from nucleus basalis of Meynert (NBM) to cortex and from pedunculopontine nucleus (PPN) to thalamus were assessed with a free water-corrected DTI model. Bayesian ANCOVAs were conducted for group comparisons and Bayesian linear mixed models to assess associations with cognitive decline. Basal forebrain volumes were increased in asymptomatic GBA1 (Bayes Factor against the null hypothesis (BF) = 75.2) and asymptomatic LRRK2 (BF = 57.0) compared to controls. Basal forebrain volumes were increased in LRRK2- compared to GBA1-PD (BF = 14.5) and idiopathic PD (BF = 3.6*10), with no difference between idiopathic PD and PD-GBA1 (BF = 0.25). Mean diffusivity along the medial NBM pathway was decreased in asymptomatic GBA1 compared to controls (BF = 30.3). Over 5 years, idiopathic PD and PD-GBA1 declined across all cognitive domains whereas PD-LRRK2 patients only declined in processing speed. We found an interaction between basal forebrain volume and time in predicting multiple cognitive domains in idiopathic PD and PD-GBA1, but not in PD-LRRK2. While LRRK2 and GBA1 mutations are both associated with increased basal forebrain volume at asymptomatic stages, this increase persists at the symptomatic PD stage only in LRRK2 and might be related to slower cognitive decline in these patients.
PubMed: 38951174
DOI: 10.1038/s41531-024-00743-w -
Mathematical Biosciences Jun 2024We construct, analyze and interpret a mathematical model for an environmental transmitted disease characterized for the existence of three disease stages: acute, severe...
We construct, analyze and interpret a mathematical model for an environmental transmitted disease characterized for the existence of three disease stages: acute, severe and asymptomatic. Besides, we consider that severe and asymptomatic cases may present relapse between them. Transmission dynamics driven by the contact rates only occurs when a parameter R>1, as normally occur in directly-transmitted or vector-transmitted diseases, but it will not adequately correspond to a basic reproductive number as it depends on environmental parameters. In this case, the forward transcritical bifurcation that exists for R<1, becomes a backward bifurcation, producing multiple steady-states, a hysteresis effect and dependence on initial conditions. A threshold parameter for an epidemic outbreak, independent of R is only the ratio of the external contamination inflow shedding rate to the environmental clearance rate. R describes the strength of the transmission to infectious classes other than the I-(acute) type infections. The epidemic outbreak conditions and the structure of R appearing in this model are both responsible for the existence of endemic states.
PubMed: 38950818
DOI: 10.1016/j.mbs.2024.109244 -
The Journal of Experimental Medicine Sep 2024Children resist COVID-19, and previous studies reported increased innate immunity in their upper airways. A new paper by Watkins et al....
Children resist COVID-19, and previous studies reported increased innate immunity in their upper airways. A new paper by Watkins et al. (https://doi.org/10.1084/jem.20230911) shows that the nasal mucosa of children is characterized by often asymptomatic viral and/or bacterial infections that dynamically regulate distinct innate immune programs.
Topics: Humans; COVID-19; Child; Immunity, Innate; SARS-CoV-2; Nasal Mucosa
PubMed: 38949639
DOI: 10.1084/jem.20241027 -
The Journal of Experimental Medicine Sep 2024Studies during the COVID-19 pandemic showed that children had heightened nasal innate immune responses compared with adults. To evaluate the role of nasal viruses and...
Studies during the COVID-19 pandemic showed that children had heightened nasal innate immune responses compared with adults. To evaluate the role of nasal viruses and bacteria in driving these responses, we performed cytokine profiling and comprehensive, symptom-agnostic testing for respiratory viruses and bacterial pathobionts in nasopharyngeal samples from children tested for SARS-CoV-2 in 2021-22 (n = 467). Respiratory viruses and/or pathobionts were highly prevalent (82% of symptomatic and 30% asymptomatic children; 90 and 49% for children <5 years). Virus detection and load correlated with the nasal interferon response biomarker CXCL10, and the previously reported discrepancy between SARS-CoV-2 viral load and nasal interferon response was explained by viral coinfections. Bacterial pathobionts correlated with a distinct proinflammatory response with elevated IL-1β and TNF but not CXCL10. Furthermore, paired samples from healthy 1-year-olds collected 1-2 wk apart revealed frequent respiratory virus acquisition or clearance, with mucosal immunophenotype changing in parallel. These findings reveal that frequent, dynamic host-pathogen interactions drive nasal innate immune activation in children.
Topics: Humans; Immunity, Innate; Child, Preschool; Infant; COVID-19; Child; SARS-CoV-2; Female; Male; Nasopharynx; Viral Load; Nasal Mucosa; Cytokines; Host-Pathogen Interactions; Adolescent; Nose; Coinfection
PubMed: 38949638
DOI: 10.1084/jem.20230911 -
African Journal of Primary Health Care... Jun 2024No abstract vailable.
No abstract vailable.
Topics: Humans; Male; Sexually Transmitted Diseases; Risk Factors; Homosexuality, Male
PubMed: 38949445
DOI: 10.4102/phcfm.v16i1.4660 -
Journal of Medical Virology Jul 2024Dengue fever is a mosquito-borne viral disease caused by the dengue virus (DENV). It poses a public health threat globally and, while most people with dengue have mild...
Dengue fever is a mosquito-borne viral disease caused by the dengue virus (DENV). It poses a public health threat globally and, while most people with dengue have mild symptoms or are asymptomatic, approximately 5% of affected individuals develop severe disease and need hospital care. However, knowledge of the molecular mechanisms underlying dengue infection and the interaction between the virus and its host remains limited. In the present study, we performed a quantitative proteomic and N-glycoproteomic analysis of serum from 19 patients with dengue and 11 healthy people. The results revealed distinct proteomic and N-glycoproteomic landscapes between the two groups. Notably, we report for the first time the changes in the serum N glycosylation pattern following dengue infection and provide abundant information on glycoproteins, glycosylation sites, and intact N-glycopeptides using recently developed site-specific glycoproteomic approaches. Furthermore, a series of key functional pathways in proteomic and N-glycoproteomic were identified. Collectively, our findings significantly improve understanding of host and DENV interactions and the general pathogenesis and pathology of DENV, laying a foundation for functional studies of glycosylation and glycan structures in dengue infection.
Topics: Humans; Dengue; Proteomics; Glycoproteins; Glycosylation; Dengue Virus; Male; Female; Adult; Proteome; Middle Aged
PubMed: 38949184
DOI: 10.1002/jmv.29775 -
EFORT Open Reviews Jul 2024Adolescent idiopathic scoliosis (AIS) is an abnormal coronal curvature of the spine that most commonly presents in adolescence. While it may be asymptomatic, AIS can... (Review)
Review
Adolescent idiopathic scoliosis (AIS) is an abnormal coronal curvature of the spine that most commonly presents in adolescence. While it may be asymptomatic, AIS can cause pain, cosmetic deformity, and physical and psychological disability with curve progression. As adolescents with AIS enter adulthood, condition outcomes vary with some experiencing curve stabilization and others noting further curve progression, chronic pain, osteoporosis/fractures, declines in pulmonary and functional capacity, among others. Regular monitoring and individualized management by healthcare professionals are crucial to address the diverse challenges and provide appropriate support for a fulfilling adult life with AIS. This review examines the prevalence, risk factors, presenting symptoms, diagnosis, management, and complications of AIS in the adult population, informing targeted interventions by clinicians caring for adult patients with AIS.
PubMed: 38949156
DOI: 10.1530/EOR-23-0162 -
Influenza and Other Respiratory Viruses Jul 2024Understanding the clinical spectrum of SARS-CoV-2 infection, including the asymptomatic fraction, is important as asymptomatic individuals are still able to infect other... (Meta-Analysis)
Meta-Analysis
Understanding the clinical spectrum of SARS-CoV-2 infection, including the asymptomatic fraction, is important as asymptomatic individuals are still able to infect other individuals and contribute to ongoing transmission. The WHO Unity Household transmission investigation (HHTI) protocol provides a platform for the prospective and systematic collection of high-quality clinical, epidemiological, serological and virological data from SARS-CoV-2 confirmed cases and their household contacts. These data can be used to understand key severity and transmissibility parameters-including the asymptomatic proportion-in relation to local epidemic context and help inform public health response. We aimed to estimate the asymptomatic proportion of SARS-CoV-2 Omicron variant infections in Unity-aligned HHTIs. We conducted a systematic review and meta-analysis in alignment with the PRISMA 2020 guidelines and registered our systematic review on PROSPERO (CRD42022378648). We searched EMBASE, Web of Science, MEDLINE and bioRxiv and medRxiv from 1 November 2021 to 22 August 2023. We identified 8368 records, of which 98 underwent full text review. We identified only three studies for data extraction, with substantial variation in study design and corresponding estimates of the asymptomatic proportion. As a result, we did not generate a pooled estimate or I metric. The limited number of quality studies that we identified highlights the need for improved preparedness and response capabilities to facilitate robust HHTI implementation, analysis and reporting, to better inform national, regional and global risk assessments and policymaking.
Topics: Humans; Asymptomatic Infections; COVID-19; Family Characteristics; SARS-CoV-2
PubMed: 38949103
DOI: 10.1111/irv.13348 -
BioRxiv : the Preprint Server For... Jun 2024Cirrhosis, advanced liver disease, affects 2-5 million Americans. While most patients have compensated cirrhosis and may be fairly asymptomatic, many decompensate and...
UNLABELLED
Cirrhosis, advanced liver disease, affects 2-5 million Americans. While most patients have compensated cirrhosis and may be fairly asymptomatic, many decompensate and experience life-threatening complications such as gastrointestinal bleeding, confusion (hepatic encephalopathy), and ascites, reducing life expectancy from 12 to less than 2 years. Among patients with compensated cirrhosis, identifying patients at high risk of decompensation is critical to optimize care and reduce morbidity and mortality. Therefore, it is important to preferentially direct them towards specialty care which cannot be provided to all patients with cirrhosis. We used discovery Top-down Proteomics (TDP) to identify differentially expressed proteoforms (DEPs) in the plasma of patients with progressive stages of liver cirrhosis with the ultimate goal to identify candidate biomarkers of disease progression. In this pilot study, we identified 209 DEPs across three stages of cirrhosis (compensated, compensated with portal hypertension, and decompensated), of which 115 derived from proteins enriched in the liver at a transcriptional level and discriminated the three stages of cirrhosis. Enrichment analyses demonstrated DEPs are involved in several metabolic and immunological processes known to be impacted by cirrhosis progression. We have preliminarily defined the plasma proteoform signatures of cirrhosis patients, setting the stage for ongoing discovery and validation of biomarkers for early diagnosis, risk stratification, and disease monitoring.
HIGHLIGHTS
Performed a pilot top-down LC-MS/MS analysis to identify proteoforms (PFRs) in the plasma of patients with 3 progressive stages of liver cirrhosis.Identified 2867 proteoforms (PFRs) and 209 differentially regulated proteoforms (DRPs) in the different stages of the disease.Identified DRP profiles able to potentially distinguish early from late stages of the disease, including 115 liver-derived DRPs.Fibrinogen alpha chain, haptoglobin, and Apo A-I are the proteins with the highest number of DRPs and represent potential candidate biomarkers of liver cirrhosis progression.
PubMed: 38948836
DOI: 10.1101/2024.06.19.599662 -
Journal of Family Medicine and Primary... May 2024The coronavirus disease 2019 (COVID-19) is a viral infection characterized by respiratory and gastrointestinal symptoms. The causative agent of this infection is the...
INTRODUCTION
The coronavirus disease 2019 (COVID-19) is a viral infection characterized by respiratory and gastrointestinal symptoms. The causative agent of this infection is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The genomic study helps in understanding the pathogenesis, epidemiology, and the development of therapeutic and preventive strategies in the combat against COVID-19.
MATERIALS AND METHODS
Nasopharyngeal and oropharyngeal swab samples were collected from asymptomatic and symptomatic patients during the time period of 2021-2022 for the detection of SARS-CoV-2 by employing real-time reverse transcriptase, cDNA synthesis, whole-genome sequencing by next-genome sequencing, analysis of SARS-CoV-2 sequence data and lineage and variant of concern assignment along with phylogenetic analysis.
RESULTS
Lineages BA.2.10 and BA.4.1.1 clustered with genomes from Senegal suggested the spread of infections. Similarly, high clustering among delta samples during the second wave showed possible importation and subsequent spread via local transmission.
CONCLUSIONS
Studies like these are important to understand the characteristics and origins of locally circulating SARS-CoV-2 diversity in order to prevent further spread.
PubMed: 38948575
DOI: 10.4103/jfmpc.jfmpc_1698_23