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Haematologica May 2024Not available.
Not available.
PubMed: 38752273
DOI: 10.3324/haematol.2024.285769 -
Frontiers in Medicine 2024Arboviruses pose a challenge in ensuring the supply of pathogen-free blood components because they are not routinely screened in blood banks, and blood components from...
OBJECTIVE
Arboviruses pose a challenge in ensuring the supply of pathogen-free blood components because they are not routinely screened in blood banks, and blood components from infected asymptomatic donors could be transfused. This study aimed to detect and characterize arboviral infections in Colombian blood donors.
METHODS
In a cross-sectional study, the prevalence of dengue (DENV), Zika (ZIKV), and chikungunya (CHIKV) viruses and co-infections of blood donors were compared between an epidemic period (November 2019-February 2020, = 462) and an endemic period (November 2021-August 2022, = 1,119). Viral RNA from each donor serum was purified, and the viruses were detected using a previously standardized multiplex hemi-nested RT-PCR protocol. Subsequently, donors who tested positive were surveyed 15 days after the detection of the virus to identify clinical characteristics related to the arboviral infection. The prevalences of each virus were presented as percentages and compared between epidemic and endemic periods.
RESULTS
Significantly higher prevalences were found in the epidemic period compared with the endemic period for DENV (14.5 vs. 1.9%), ZIKV (7.8 vs. 0.3%), CHIKV (8 vs. 3.3%), and co-infections (4.3 vs. 0.2%). The survey response rate of positive donors in the two periods was 83/175 (47%). In total, 57% of the donors surveyed were asymptomatic. Symptomatic donors most frequently reported headache (31%), malaise (13%), arthralgia (10%), and fever/chills (8%).
CONCLUSION
The prevalence observed in epidemic and endemic periods was higher than that reported in other studies in the Americas. The high proportion of asymptomatic cases found, in addition to the mild and nonspecific manifestations among the symptomatic, may limit the effectiveness of the donor selection criteria used to mitigate the risk of transfusion-transmitted arboviruses.
PubMed: 38751980
DOI: 10.3389/fmed.2024.1380129 -
Molecular Neurodegeneration May 2024Alzheimer's disease (AD), the most common form of dementia, remains challenging to understand and treat despite decades of research and clinical investigation. This... (Review)
Review
Alzheimer's disease (AD), the most common form of dementia, remains challenging to understand and treat despite decades of research and clinical investigation. This might be partly due to a lack of widely available and cost-effective modalities for diagnosis and prognosis. Recently, the blood-based AD biomarker field has seen significant progress driven by technological advances, mainly improved analytical sensitivity and precision of the assays and measurement platforms. Several blood-based biomarkers have shown high potential for accurately detecting AD pathophysiology. As a result, there has been considerable interest in applying these biomarkers for diagnosis and prognosis, as surrogate metrics to investigate the impact of various covariates on AD pathophysiology and to accelerate AD therapeutic trials and monitor treatment effects. However, the lack of standardization of how blood samples and collected, processed, stored analyzed and reported can affect the reproducibility of these biomarker measurements, potentially hindering progress toward their widespread use in clinical and research settings. To help address these issues, we provide fundamental guidelines developed according to recent research findings on the impact of sample handling on blood biomarker measurements. These guidelines cover important considerations including study design, blood collection, blood processing, biobanking, biomarker measurement, and result reporting. Furthermore, the proposed guidelines include best practices for appropriate blood handling procedures for genetic and ribonucleic acid analyses. While we focus on the key blood-based AD biomarkers for the AT(N) criteria (e.g., amyloid-beta [Aβ]40, Aβ42, Aβ42/40 ratio, total-tau, phosphorylated-tau, neurofilament light chain, brain-derived tau and glial fibrillary acidic protein), we anticipate that these guidelines will generally be applicable to other types of blood biomarkers. We also anticipate that these guidelines will assist investigators in planning and executing biomarker research, enabling harmonization of sample handling to improve comparability across studies.
Topics: Humans; Alzheimer Disease; Biomarkers; Biological Specimen Banks; Research Design; Amyloid beta-Peptides; Specimen Handling; tau Proteins
PubMed: 38750570
DOI: 10.1186/s13024-024-00711-1 -
Nature Communications May 2024The availability of protein measurements and whole exome sequence data in the UK Biobank enables investigation of potential observational and genetic protein-cancer risk...
The availability of protein measurements and whole exome sequence data in the UK Biobank enables investigation of potential observational and genetic protein-cancer risk associations. We investigated associations of 1463 plasma proteins with incidence of 19 cancers and 9 cancer subsites in UK Biobank participants (average 12 years follow-up). Emerging protein-cancer associations were further explored using two genetic approaches, cis-pQTL and exome-wide protein genetic scores (exGS). We identify 618 protein-cancer associations, of which 107 persist for cases diagnosed more than seven years after blood draw, 29 of 618 were associated in genetic analyses, and four had support from long time-to-diagnosis ( > 7 years) and both cis-pQTL and exGS analyses: CD74 and TNFRSF1B with NHL, ADAM8 with leukemia, and SFTPA2 with lung cancer. We present multiple blood protein-cancer risk associations, including many detectable more than seven years before cancer diagnosis and that had concordant evidence from genetic analyses, suggesting a possible role in cancer development.
Topics: Humans; United Kingdom; Neoplasms; Risk Factors; Biological Specimen Banks; Male; Female; Exome; Proteomics; Prospective Studies; Middle Aged; Blood Proteins; Aged; Exome Sequencing; Genetic Predisposition to Disease; Incidence; UK Biobank
PubMed: 38750076
DOI: 10.1038/s41467-024-48017-6 -
Science Advances May 2024Early and precise diagnosis of α-synucleinopathies is challenging but critical. In this study, we developed a molecular beacon-based assay to evaluate...
Early and precise diagnosis of α-synucleinopathies is challenging but critical. In this study, we developed a molecular beacon-based assay to evaluate microRNA-containing extracellular vesicles (EVs) in plasma. We recruited 1203 participants including healthy controls (HCs) and patients with isolated REM sleep behavior disorder (iRBD), α-synucleinopathies, or non-α-synucleinopathies from eight centers across China. Plasma miR-44438-containing EV levels were significantly increased in α-synucleinopathies, including those in the prodromal stage (e.g., iRBD), compared to both non-α-synucleinopathy patients and HCs. However, there are no significant differences between Parkinson's disease (PD) and multiple system atrophy. The miR-44438-containing EV levels negatively correlated with age and the Hoehn and Yahr stage of PD patients, suggesting a potential association with disease progression. Furthermore, a longitudinal analysis over 16.3 months demonstrated a significant decline in miR-44438-containing EV levels in patients with PD. These results highlight the potential of plasma miR-44438-containing EV as a biomarker for early detection and progress monitoring of α-synucleinopathies.
Topics: Humans; Extracellular Vesicles; Male; Biomarkers; Female; Middle Aged; Circulating MicroRNA; Parkinson Disease; Aged; Synucleinopathies; alpha-Synuclein; Case-Control Studies; MicroRNAs; Multiple System Atrophy
PubMed: 38748787
DOI: 10.1126/sciadv.adl6442 -
Transfusion May 2024The increasing demand for umbilical cord blood (UCB) used in stem cell transplantation led to the establishment of cord blood (CB) banks worldwide. These include public...
BACKGROUND
The increasing demand for umbilical cord blood (UCB) used in stem cell transplantation led to the establishment of cord blood (CB) banks worldwide. These include public foreign donor banks and private family-directed donor banks. Recently, our department has introduced a third banking model within a private-public-partnership. This hybrid banking allows for storage of family-directed CB units, while also getting Human leukocyte antigen (HLA)-typed and included in the national stem cell donor registry. So if the need arises, the HLA-compatible CB unit can be released to an unrelated recipient as a foreign donor stem cell graft.
OBJECTIVES
The aim of this study was to evaluate women's perspectives on the different CB banking options as well as retrospective satisfaction with their decisions.
METHODS
We performed a prospective survey study in postpartum women, using a validated questionnaire.
RESULTS
A total of 157 women were included in this survey study; 68% of them decided to have their UCB stored or donated. Among those women, 25% of them opted for hybrid storage, 72% of respondents stored UCB publicly, and 3% decided for private family-directed storage.
CONCLUSIONS
Our study shows the potential of hybrid banking as an attractive UCB storage option, as an alternative to family-directed banking rather than a substitute for public donation. Hybrid storage potentially combines advantages of family-directed banking as well as unrelated CB donation expanding the number of registered CB units available for transplantation and giving every pregnant woman the possibility to store UCB.
PubMed: 38746954
DOI: 10.1111/trf.17858 -
Peripheral GFAP and NfL as early biomarkers for dementia: longitudinal insights from the UK Biobank.BMC Medicine May 2024Peripheral glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are sensitive markers of neuroinflammation and neuronal damage. Previous studies...
BACKGROUND
Peripheral glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are sensitive markers of neuroinflammation and neuronal damage. Previous studies with highly selected participants have shown that peripheral GFAP and NfL levels are elevated in the pre-clinical phase of Alzheimer's disease (AD) and dementia. However, the predictive value of GFAP and NfL for dementia requires more evidence from population-based cohorts.
METHODS
This was a prospective cohort study to evaluate UK Biobank participants enrolled from 2006 to 2010 using plasma GFAP and NfL measurements measured by Olink Target Platform and prospectively followed up for dementia diagnosis. Primary outcome was the risk of clinical diagnosed dementia. Secondary outcomes were cognition. Linear regression was used to assess the associations between peripheral GFAP and NfL with cognition. Cox proportional hazard models with cross-validations were used to estimate associations between elevated GFAP and NfL with risk of dementia. All models were adjusted for covariates.
RESULTS
A subsample of 48,542 participants in the UK Biobank with peripheral GFAP and NfL measurements were evaluated. With an average follow-up of 13.18 ± 2.42 years, 1312 new all-cause dementia cases were identified. Peripheral GFAP and NfL increased up to 15 years before dementia diagnosis was made. After strictly adjusting for confounders, increment in NfL was found to be associated with decreased numeric memory and prolonged reaction time. A greater annualized rate of change in GFAP was significantly associated with faster global cognitive decline. Elevation of GFAP (hazard ratio (HR) ranges from 2.25 to 3.15) and NfL (HR ranges from 1.98 to 4.23) increased the risk for several types of dementia. GFAP and NfL significantly improved the predictive values for dementia using previous models (area under the curve (AUC) ranges from 0.80 to 0.89, C-index ranges from 0.86 to 0.91). The AD genetic risk score and number of APOE*E4 alleles strongly correlated with GFAP and NfL levels.
CONCLUSIONS
These results suggest that peripheral GFAP and NfL are potential biomarkers for the early diagnosis of dementia. In addition, anti-inflammatory therapies in the initial stages of dementia may have potential benefits.
Topics: Humans; Neurofilament Proteins; Glial Fibrillary Acidic Protein; Biomarkers; Female; Dementia; Male; United Kingdom; Prospective Studies; Aged; Middle Aged; Biological Specimen Banks; Longitudinal Studies; UK Biobank
PubMed: 38735950
DOI: 10.1186/s12916-024-03418-8 -
BMC Medicine May 2024The reason for higher incidence of atrial fibrillation (AF) in Europe compared with East Asia is unclear. We aimed to investigate the association between modifiable...
BACKGROUND
The reason for higher incidence of atrial fibrillation (AF) in Europe compared with East Asia is unclear. We aimed to investigate the association between modifiable lifestyle factors and lifetime risk of AF in Europe and East Asia, along with race/ethnic similarities and disparities.
METHODS
1:1 propensity score matched pairs of 242,763 East Asians and 242,763 White Europeans without AF were analyzed. Modifiable lifestyle factors considered were blood pressure, body mass index, cigarette smoking, diabetes, alcohol consumption, and physical activity, categorized as non-adverse or adverse levels. Lifetime risk of AF was estimated from the index age of 45 years to the attained age of 85 years, accounting for the competing risk of death.
RESULTS
The overall lifetime risk of AF was higher in White Europeans than East Asians (20.9% vs 15.4%, p < 0.001). The lifetime risk of AF was similar between the two races in individuals with non-adverse lifestyle factor profiles (13.4% vs 12.9%, p = 0.575), whereas it was higher in White Europeans with adverse lifestyle factor profiles (22.1% vs 15.8%, p < 0.001). The difference in the lifetime risk of AF between the two races increased as the burden of adverse lifestyle factors worsened (1 adverse lifestyle factor; 4.3% to ≥ 3 adverse lifestyle factors; 11.2%). Compared with East Asians, the relative risk of AF in White Europeans was 23% and 62% higher for one (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.16-1.29) and ≥ 3 adverse lifestyle factors (HR 1.62, 95% CI 1.51-1.75), respectively.
CONCLUSIONS
The overall higher lifetime risk of AF in White Europeans compared with East Asians might be attributable to adverse lifestyle factors. Adherence to healthy lifestyle factors was associated with the lifetime risk of AF of about 1 in 8 regardless of race/ethnicity.
Topics: Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Atrial Fibrillation; Biological Specimen Banks; Cohort Studies; Life Style; Longitudinal Studies; Republic of Korea; Risk Factors; UK Biobank; United Kingdom; White People; East Asian People
PubMed: 38735916
DOI: 10.1186/s12916-024-03400-4 -
Parasites & Vectors May 2024Animal African trypanosomiasis, which is caused by different species of African trypanosomes, is a deadly disease in livestock. Although African trypanosomes are often...
BACKGROUND
Animal African trypanosomiasis, which is caused by different species of African trypanosomes, is a deadly disease in livestock. Although African trypanosomes are often described as blood-borne parasites, there have been recent reappraisals of the ability of these parasites to reside in a wide range of tissues. However, the majority of those studies were conducted on non-natural hosts infected with only one species of trypanosome, and it is unclear whether a similar phenomenon occurs during natural animal infections, where multiple species of these parasites may be present.
METHODS
The infective trypanosome species in the blood and other tissues (adipose and skin) of a natural host (cows, goats and sheep) were determined using a polymerase chain reaction-based diagnostic.
RESULTS
The animals were found to harbour multiple species of trypanosomes. Different patterns of distribution were observed within the host tissues; for instance, in some animals, the blood was positive for the DNA of one species of trypanosome and the skin and adipose were positive for the DNA of another species. Moreover, the rate of detection of trypanosome DNA was highest for skin adipose and lowest for the blood.
CONCLUSIONS
The findings reported here emphasise the complexity of trypanosome infections in a natural setting, and may indicate different tissue tropisms between the different parasite species. The results also highlight the need to include adipose and skin tissues in future diagnostic and treatment strategies.
Topics: Animals; Goats; Trypanosomiasis, African; Adipose Tissue; Trypanosoma; Skin; Sheep; Goat Diseases; Cattle; Polymerase Chain Reaction; Sheep Diseases; DNA, Protozoan; Cattle Diseases
PubMed: 38734633
DOI: 10.1186/s13071-024-06277-7 -
The Lancet. Infectious Diseases May 2024The first licensed malaria vaccine, RTS,S/AS01, confers moderate protection against symptomatic disease. Because many malaria infections are asymptomatic, we conducted a...
Genotypic analysis of RTS,S/AS01 malaria vaccine efficacy against parasite infection as a function of dosage regimen and baseline malaria infection status in children aged 5-17 months in Ghana and Kenya: a longitudinal phase 2b randomised controlled trial.
BACKGROUND
The first licensed malaria vaccine, RTS,S/AS01, confers moderate protection against symptomatic disease. Because many malaria infections are asymptomatic, we conducted a large-scale longitudinal parasite genotyping study of samples from a clinical trial exploring how vaccine dosing regimen affects vaccine efficacy.
METHODS
Between Sept 28, 2017, and Sept 25, 2018, 1500 children aged 5-17 months were randomly assigned (1:1:1:1:1) to receive four different RTS,S/AS01 regimens or a rabies control vaccine in a phase 2b open-label clinical trial in Ghana and Kenya. Participants in the four RTS,S groups received two full doses at month 0 and month 1 and either full doses at month 2 and month 20 (group R012-20); full doses at month 2, month 14, month 26, and month 38 (group R012-14); fractional doses at month 2, month 14, month 26, and month 38 (group Fx012-14; early fourth dose); or fractional doses at month 7, month 20, and month 32 (group Fx017-20; delayed third dose). We evaluated the time to the first new genotypically detected infection and the total number of new infections during two follow-up periods (12 months and 20 months) in more than 36 000 dried blood spot specimens from 1500 participants. To study vaccine effects on time to the first new infection, we defined vaccine efficacy as one minus the hazard ratio (HR; RTS,S vs control) of the first new infection. We performed a post-hoc analysis of vaccine efficacy based on malaria infection status at first vaccination and force of infection by month 2. This trial (MAL-095) is registered with ClinicalTrials.gov, NCT03281291.
FINDINGS
We observed significant and similar vaccine efficacy (25-43%; 95% CI union 9-53) against first new infection for all four RTS,S/AS01 regimens across both follow-up periods (12 months and 20 months). Each RTS,S/AS01 regimen significantly reduced the mean number of new infections in the 20-month follow-up period by 1·1-1·6 infections (95% CI union 0·6-2·1). Vaccine efficacy against first new infection was significantly higher in participants who were infected with malaria (68%; 95% CI 50-80) than in those who were uninfected (37%; 23-48) at the first vaccination (p=0·0053).
INTERPRETATION
All tested dosing regimens blocked some infections to a similar degree. Improved vaccine efficacy in participants infected during vaccination could suggest new strategies for highly efficacious malaria vaccine development and implementation.
FUNDING
GlaxoSmithKline Biologicals SA, PATH, Bill & Melinda Gates Foundation, and the German Federal Ministry of Education and Research.
PubMed: 38723650
DOI: 10.1016/S1473-3099(24)00179-8