The effect of first-wave COVID-19 restrictions on HCV testing in Alberta, Canada: A trend analysis from 2019 to 2022.

Background: Prior to the COVID-19 pandemic, Alberta was on track to meet national HCV elimination targets by 2030. However, it is unclear how the pandemic has affected progress. Here, we aim to assess the impact of first-wave COVID-19 restrictions on Alberta HCV testing trends. Methods: HCV testing information was extracted from the provincial public health laboratory from 2019 to 2022. HCV antibody and RNA testing were categorized into (1) number ordered, (2) number positive, and (3) percent positivity, and stratified by HCV history status. Testing trends were evaluated across locations engaging high-risk individuals and priority demographics. An interrupted time-series analysis was used to identify average monthly testing rates before, during, and after first-wave COVID-19 restrictions. Results: Overall, HCV testing trends were significantly affected by COVID-19 restrictions in April 2020. Average monthly rates decreased by 98.39 antibody tests ordered per 100,000 among individuals without an HCV history and by 1.78 RNA tests ordered per 100,000 among those with an HCV history. While antibody and RNA testing trends started to rebound in the follow-up period relative to pre-restriction period, testing levels in the follow-up period remained below pre-restriction levels for all groups, except for addiction/recovery centres and emergency room/acute care facilities, which increased. Conclusions: If rates are to return to pre-restriction levels and elimination goals are to be met, more work is needed to engage individuals in HCV testing. As antibody testing rates are rebounding, reengaging those with a history of HCV for viral load monitoring and treatment should be prioritized.

Digital Clock Drawing as an Alzheimer's Disease Susceptibility Biomarker: Associations with Genetic Risk Score and APOE in Older Adults.

BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia in older adults, but most people are not diagnosed until significant neuronal loss has likely occurred along with a decline in cognition. Non-invasive and cost-effective digital biomarkers for AD have the potential to improve early detection. OBJECTIVE: We examined the validity of DCTclockTM (a digitized clock drawing task) as an AD susceptibility biomarker. DESIGN: We used two primary independent variables, Apolipoprotein E (APOE) ε4 allele carrier status and polygenic risk score (PRS). We examined APOE and PRS associations with DCTclockTM composite scores as dependent measures. SETTING: We used existing data from the Framingham Heart Study (FHS), a community-based study with the largest dataset of digital clock drawing data to date. PARTICIPANTS: The sample consisted of 2,398 older adults ages 60-94 with DCTclockTM data (mean age of 72.3, 55% female and 92% White). MEASUREMENTS: PRS was calculated using 38 variants identified in a recent large genome-wide association study (GWAS) and meta-analysis of late-onset AD (LOAD). RESULTS: Results showed that DCTclockTM performance decreased with advancing age, lower education, and the presence of one or more copies of APOE ε4. Lower DCTclockTM Total Score as well as lower composite scores for Information Processing Speed (both command and copy conditions) and Drawing Efficiency (command condition) were significantly associated with higher PRS levels and more copies of APOE ε4. APOE and PRS associations displayed similar effect sizes in both men and women. CONCLUSIONS: Our results indicate that higher AD genetic risk is associated with poorer DCTclockTM performance in older adults without dementia. This is the first study to demonstrate significant differences in clock drawing performance on the basis of APOE status or PRS.

Primary care outreach and decision counseling for lung cancer screening.

INTRODUCTION: Lung cancer screening rates are very low despite a level B recommendation from the United States Preventive Services Task Force since 2013 and clear evidence that lung cancer screening reduces mortality. The Center for Medicare and Medicaid Services requires shared decision-making (SDM) for lung cancer screening reimbursement. The objective of this study was to determine the effect of an SDM intervention on lung cancer screening in primary care. METHODS: The study design was a single-arm clinical trial design. The intervention included phone contact outside of a primary care visit and the use of the Decision Counseling Program ®, an online interactive decision aid focused on determining the factors which influence patients to screen or not screen, prioritizing those factors, and determining a decision preference score. The primary outcome was the completion of low-dose computed tomography scan (LDCT) 1 year after the SDM session compared in participants versus nonparticipants. RESULTS: From six practices, there were 1359 potentially eligible patients in electronic medical record data, and 336 were reached to assess eligibility criteria. A total of 80 patients consented to be in the study, 64 completed a decision counseling session and 16 did not complete a session. Among the 64 people who agreed to have decision counseling, 45% had LDCT, higher than typically seen in routine clinical practice. Although not a comparable group, among the 16 people who declined decision counseling, none had LDCT. CONCLUSIONS: Decision counseling is a promising intervention that might support SDM in the context of improving uptake of lung cancer screening in primary care. However, further, larger studies are needed.

Outcomes and cost analysis of patients with dementia in the intensive care unit: a population-based cohort study.

BACKGROUND: Dementia is a neurological syndrome affecting the growing elderly population. While patients with dementia are known to require significant hospital resources, little is known regarding the outcomes and costs of patients admitted to the intensive care unit (ICU) with dementia. METHODS: We conducted a population-based retrospective cohort study of patients with dementia admitted to the ICU in Ontario, Canada from 2016 to 2019. We described the characteristics and outcomes of these patients alongside those with dementia admitted to non-ICU hospital settings. The primary outcome was hospital mortality but we also assessed length of stay (LOS), discharge disposition, and costs. RESULTS: Among 114,844 patients with dementia, 11,341 (9.9%) were admitted to the ICU. ICU patients were younger, more comorbid, and had less cognitive impairment (81.8 years, 22.8% had ≥ 3 comorbidities, 47.5% with moderate-severe dementia), compared to those in non-ICU settings (84.2 years, 15.0% had ≥ 3 comorbidities, 54.1% with moderate-severe dementia). Total mean LOS for patients in the ICU group was nearly 20 days, compared to nearly 14 days for the acute care group. Mortality in hospital was nearly three-fold greater in the ICU group compared to non-ICU group (22.2% vs. 8.8%). Total healthcare costs were increased for patients admitted to ICU vs. those in the non-ICU group ($67,201 vs. $54,080). CONCLUSIONS: We find that patients with dementia admitted to the ICU have longer length of stay, higher in-hospital mortality, and higher total healthcare costs. As our study is primarily descriptive, future studies should investigate comprehensive goals of care planning, severity of illness, preventable costs, and optimizing quality of life in this high risk and vulnerable population.

Generation of the iPSC line FINi002-A from a male Parkinson's disease patient carrying compound heterozygous mutations in the PRKN gene.

The most common cause of autosomal recessive familial Parkinson's disease (PD) are mutations in the PRKN/PARK2 gene encoding an E3 ubiquitin protein-ligase PARKIN. We report the generation of an iPSC cell line from the fibroblasts of a male PD patient carrying a common missense variant in exon 7 (p.Arg275Trp), and a 133 kb deletion encompassing exon 8, using transiently-present Sendai virus. The established line displays typical human primed iPSC morphology and expression of pluripotency-associated markers, normal karyotype without SNP array-detectable copy number variations and can give rise to derivatives of all three embryonic germ layers. We envisage the usefulness of this iPSC line, carrying a common and well-studied missense mutation in the RING1 domain of the PARKIN protein, for the elucidation of PARKIN-dependent mechanisms of PD using in vitro and in vivo models.

One high quality genome and two transcriptome datasets for new species of Mantamonas, a deep-branching eukaryote clade.

Mantamonads were long considered to represent an "orphan" lineage in the tree of eukaryotes, likely branching near the most frequently assumed position for the root of eukaryotes. Recent phylogenomic analyses have placed them as part of the "CRuMs" supergroup, along with collodictyonids and rigifilids. This supergroup appears to branch at the base of Amorphea, making it of special importance for understanding the deep evolutionary history of eukaryotes. However, the lack of representative species and complete genomic data associated with them has hampered the investigation of their biology and evolution. Here, we isolated and described two new species of mantamonads, Mantamonas vickermani sp. nov. and Mantamonas sphyraenae sp. nov., for each of which we generated transcriptomic sequence data, as well as a high-quality genome for the latter. The estimated size of the M. sphyraenae genome is 25 Mb; our de novo assembly appears to be highly contiguous and complete with 9,416 predicted protein-coding genes. This near-chromosome-scale genome assembly is the first described for the CRuMs supergroup.

Sustained wet-dry cycling on early Mars.

The presence of perennially wet surface environments on early Mars is well documented1,2, but little is known about short-term episodicity in the early hydroclimate3. Post-depositional processes driven by such short-term fluctuations may produce distinct structures, yet these are rarely preserved in the sedimentary record4. Incomplete geological constraints have led global models of the early Mars water cycle and climate to produce diverging results5,6. Here we report observations by the Curiosity rover at Gale Crater indicating that high-frequency wet-dry cycling occurred in early Martian surface environments. We observe exhumed centimetric polygonal ridges with sulfate enrichments, joined at Y-junctions, that record cracks formed in fresh mud owing to repeated wet-dry cycles of regular intensity. Instead of sporadic hydrological activity induced by impacts or volcanoes5, our findings point to a sustained, cyclic, possibly seasonal, climate on early Mars. Furthermore, as wet-dry cycling can promote prebiotic polymerization7,8, the Gale evaporitic basin may have been particularly conducive to these processes. The observed polygonal patterns are physically and temporally associated with the transition from smectite clays to sulfate-bearing strata, a globally distributed mineral transition1. This indicates that the Noachian-Hesperian transition (3.8-3.6 billion years ago) may have sustained an Earth-like climate regime and surface environments favourable to prebiotic evolution.

Evaluation and comparison of risk-based and universal prenatal HCV screening programs in Alberta, Canada.

BACKGROUND & AIMS: Canadian clinical practice guidelines currently recommend risk-based screening for HCV in pregnant individuals. However, no provinces or territories have ever compared the effectiveness of risk-based vs. universal screening for the prenatal diagnosis of HCV. We aimed to evaluate and compare HCV screening programs after implementing a universal population-level pilot program among prenatal patients in Alberta, Canada. METHODS: The Alberta Prenatal Screening Program for Select Communicable Diseases was amended to include universal HCV antibody screening. Cohorts of pregnant individuals screened for HCV through risk-based or universal programs were generated over 1-year periods. HCV screening rates and prevalence were analyzed and compared between cohorts to evaluate the effectiveness of screening methods. Social and demographic risk factors for HCV-positive individuals were compared between screening cohorts to identify which populations may be overlooked with risk-based guidelines. RESULTS: HCV antibody screening rates were 11.9% and 99.9% among pregnant individuals in the risk-based and universal cohorts, respectively. HCV prevalence among the cohorts was 0.07% and 0.11% (difference = 0.04%, p = 0.032), with an average of 21 additional HCV-positive pregnant individuals identified annually with universal screening. HCV-positive pregnant patients diagnosed through universal screening were more likely to engage in high-risk sexual behaviours/sex work compared to those diagnosed through risk-based screening (47.6% vs. 12.5%, respectively p = 0.035), suggesting that these high-risk cases are being missed by risk-based screening. CONCLUSIONS: Universal HCV screening diagnoses significantly higher numbers of pregnant individuals infected with HCV compared to risk-based screening. Universal HCV screening or amending risk-based guidelines to incorporate more proxy variables for risk factors should be considered to improve prenatal HCV screening guidelines in Canada and help achieve HCV elimination in the next decade. IMPACT AND IMPLICATIONS: HCV is a bloodborne pathogen that can cause severe liver disease and be vertically transmitted from a mother to her baby during pregnancy. Pregnant individuals in Alberta are currently only tested for HCV if they disclose engaging in activities that put them at risk of acquiring the infection (risk-based screening). Using a population-wide universal prenatal HCV screening program, our work shows that testing based on patient disclosed risk alone leads to the significant underdiagnosis of HCV in pregnant individuals and suggests individuals engaging in sex work or risky sexual behaviours are being overlooked by the current risk-based program. Our outcomes represent the first province-wide study to evaluate and compare prenatal HCV risk-based and universal screening programs in Canada and provide evidence to support the update of prenatal HCV screening policies across the country and in similar jurisdictions.

Wildlife health surveillance: gaps, needs and opportunities.

Disease emergence represents a global threat to public health, economy and biological conservation. Most emerging zoonotic diseases have an animal origin, most commonly from wildlife. To prevent their spread and to support the implementation of control measures, disease surveillance and reporting systems are needed, and due to globalisation, these activities should be carried out at the global level. To define the main gaps affecting the performance of wildlife health surveillance and reporting systems globally, the authors analysed data from a questionnaire sent to National Focal Points of the World Organisation for Animal Health that inquired on structure and limits of wildlife surveillance and reporting systems in their territories. Responses from 103 Members, covering all areas of the globe, revealed that 54.4% have a wildlife disease surveillance programme and 66% have implemented a strategy to manage disease spread. The lack of dedicated budget affected the possibility of outbreak investigations, sample collection and diagnostic testing. Although most Members maintain records relating to wildlife mortality or morbidity events in centralised databases, data analysis and disease risk assessment are reported as priority needs. The authors' evaluation of surveillance capacity found an overall low level, with marked variability among Members that was not restricted to a specific geographical area. Increased wildlife disease surveillance globally would help in understanding and managing risks to animal and public health. Moreover, consideration of the influence of socio-economic, cultural and biodiversity aspects could improve disease surveillance under a One Health approach.

L'émergence de maladies représente une menace pour la santé publique, l'économie et la conservation de la biodiversité au niveau mondial. La plupart des maladies émergentes sont d'origine animale et proviennent de la faune sauvage. Afin de prévenir leur propagation et de soutenir la mise en oeuvre de mesures de contrôle, une surveillance des maladies et des systèmes de notification sont nécessaires - et ce à l'échelle internationale, en raison de la mondialisation. En vue de définir les lacunes principales affectant les performances de la surveillance et de la notification sanitaire relative à la faune sauvage au niveau mondial, les auteurs ont analysé les données d'un questionnaire envoyé aux Points focaux nationaux de l'Organisation mondiale de la santé animale et traitant de la structure et des limites des systèmes de surveillance et de notification applicables à la faune sauvage sur leur territoire. Selon les réponses des 103 Membres, qui représentaient toutes les régions du monde, 54,4 % disposent d'un programme de surveillance et 66 % ont mis en oeuvre une stratégie visant à gérer la propagation de maladies. L'absence de budgets dédiés affecte la possibilité d'enquêter sur l'apparition d'épidémies, de prélever des échantillons et d'effectuer des tests diagnostiques. Bien que la majorité des Membres consignent dans des bases de données centralisées les événements de mortalité et de morbidité affectant la faune sauvage, l'analyse des données et l'évaluation des risques sanitaires ont été mentionnées comme étant des besoins prioritaires. Les auteurs ont évalué les capacités de surveillance qui se situent, selon eux, à un niveau faible et se caractérisent par une grande variabilité entre les Membres, indépendamment des zones géographiques dont il s'agit. Une meilleure surveillance sanitaire de la faune sauvage au niveau mondial permettrait d'améliorer la compréhension et la gestion des risques pour la santé animale et publique. Par ailleurs, une réflexion sur l'influence des aspects socio-économiques, culturels et liés à la biodiversité améliorerait la surveillance sanitaire mise en place dans le cadre de l'approche Une seule santé.

La aparición de enfermedades representa una amenaza de dimensión mundial para la salud pública, la economía y la conservación de los recursos biológicos. La mayor parte de las enfermedades zoonóticas tienen un origen animal, por lo general localizado en la fauna silvestre. Para evitar que estas enfermedades se propaguen y apoyar la aplicación de medidas de lucha hacen falta sistemas de vigilancia y notificación de enfermedades, sistemas que, teniendo en cuenta las dinámicas de la mundialización, deben declinarse a escala planetaria. Con objeto de determinar las principales carencias que lastran el buen funcionamiento de los sistemas de vigilancia y notificación de enfermedades de la fauna silvestre a escala mundial, los autores analizaron datos extraídos de un cuestionario distribuido entre los puntos focales nacionales de la Organización Mundial de Sanidad Animal, en el cual se les preguntaba por la estructura y los límites que presentaban en su territorio dichos sistemas. Las respuestas recibidas de 103 Miembros de todas las zonas del globo pusieron de relieve que un 54,4% de ellos cuenta con un programa de vigilancia sanitaria de la fauna silvestre y que un 66% tiene implantada una estrategia para contener la propagación de enfermedades. La falta de un presupuesto asignado específicamente a estas tareas limita la posibilidad de investigar eventuales brotes, obtener muestras y practicar pruebas de diagnóstico. Aunque la mayoría de los Miembros lleva un registro de los episodios de mortalidad y morbilidad de animales salvajes en bases de datos centralizadas, el análisis de datos y la determinación del riesgo de enfermedad son dos de los aspectos mencionados como necesidad prioritaria. La evaluación de la capacidad de vigilancia realizada por los autores puso de manifiesto un nivel en general bajo, con una marcada heterogeneidad entre los Miembros que no se circunscribía a una zona geográfica en particular. Una mayor vigilancia de las enfermedades de la fauna silvestre a escala mundial ayudaría a aprehender y manejar mejor los riesgos que estas presentan para la sanidad animal y la salud pública. Además, el hecho de tener en cuenta la influencia de factores socioeconómicos, culturales y ligados a la diversidad biológica podría traducirse en una más eficaz vigilancia sanitaria en clave de Una sola salud.

Prevalence of syphilis coinfection in hepatitis C virus positive prenatal patients from Alberta during a pilot routine screening program.

BACKGROUND: Alberta routinely screens pregnant patients for select communicable diseases. Hepatitis C virus (HCV) was added to the prenatal screening panel as part of a provincial pilot program in February 2020. This retrospective cross-sectional study aimed to characterize the prevalence of syphilis coinfections in prenatal patients infected with HCV following implementation of the pilot program.METHODS: Routine prenatal HCV and syphilis testing data were extracted from the Public Health Laboratory Information System over a 21-month period. HCV positivity was defined as HCV enzyme immunoassay (EIA) reactive with detected HCV ribonucleic acid (RNA) following molecular confirmation, and positive results were examined for syphilis coinfections. All patients reactive on a syphilis EIA and confirmatory Treponema pallidum particle agglutination (TPPA) or follow-up rapid plasma reagin (RPR) test were considered positive for syphilis. Descriptive statistics for coinfected patients were analyzed. RESULTS: Eighty-seven prenatal patients were identified to be positive for HCV. Of those, 19 (21.8%) were reactive on the syphilis EIA and 17 (19.5%) had confirmed infections with the TPPA or RPR tests. For HCV/syphilis coinfected patients, the majority resided in metropolitan regions (64.6%), were from the lowest income quintile neighbourhoods (47.1%) and had previously tested positive for HCV (82.4%) and syphilis (64.6%) at the public health laboratory. CONCLUSIONS: The prevalence of syphilis coinfections in prenatal patients infected with HCV is high in Alberta. HCV/syphilis coinfection prevalence should be further investigated in other jurisdictions and prenatal cohorts to better understand testing and treatment options for prevention of congenital transmission.

The Effects of Subjective Cognitive Decline on APOE Genotype Disclosure in the Butler Hospital Alzheimer's Prevention Registry.

BACKGROUND: Subjective cognitive decline (SCD) and APOE genotyping are both instrumental in identifying high-risk individuals for Alzheimer's disease (AD) prevention trials. OBJECTIVE: This study examined the relationship between SCD and the impact of APOE disclosure on the psychological and behavioral health of cognitively unimpaired individuals. Design/Setting/Participant: We recruited 189 trial volunteers (mean age 66, 65% female, 96% White), from the Butler Hospital Alzheimer's Prevention Registry. Participants completed screening for cognitive impairment and a psychological readiness assessment before learning their APOE genotype, and were followed for 6 months after. RESULTS: SCD had a modest, temporary impact on mood and event-related distress following APOE disclosure, specifically on those who were ε4 carriers. The presence of SCD (SCD+) did not compound the AD genetic test-specific distress related to learning that one was an ε4 carrier. SCD also did not moderate changes in perceived AD risk, with all non-carriers showing a more rapid decrease in perceived risk over time than carriers. Counterintuitively, those without SCD (SCD-) reported taking more steps in future-directives than the SCD+ group at baseline and after disclosure, potentially suggesting that those with SCD may have subtle executive declines that limit future-oriented actions or fear-avoidance behaviors. Further, the SCD- group was more accurate in recalling their APOE status and the recall accuracy correlated with their broad knowledge about APOE as a risk gene for AD. CONCLUSION: Our findings support the safety and tolerability of APOE disclosure in research volunteers regardless of their SCD statuses, but further studies are warranted to include diverse individuals and those pursuing testing through direct-to-consumer services outside of traditional research settings.

What's in a number? The value of titers as routine proof of immunity for medical students.

OBJECTIVES: To assess the guideline concordance of medical school requirements for students' proof-of-immunity in the United States (US) and Canada. METHODS: National guidelines for healthcare worker proof-of-immunity to measles, mumps, rubella, and varicella were compared to admission requirements for 62 US and 17 Canadian medical schools. RESULTS: All surveyed schools accepted at least one recommended form of proof-of-immunity, however, contrary to national guidelines, 16% of surveyed US schools asked for a serologic titer, and only 73-79% US schools accepted vaccination as the sole proof-of-immunity. CONCLUSIONS: The requirement of numerical, non-standardized serologic testing highlights an oversight in medical school admissions documentation. The requirement for quantitative values to demonstrate immunity is not practical from a laboratory standpoint, and is not needed to show individual immunity to these vaccine-preventable diseases. Until a more standardized process is adopted, laboratories will need to provide clear documentation and direction for quantitative titer requests.

Hydrogel oxygen reservoirs increase functional integration of neural stem cell grafts by meeting metabolic demands.

Injectable biomimetic hydrogels have great potential for use in regenerative medicine as cellular delivery vectors. However, they can suffer from issues relating to hypoxia, including poor cell survival, differentiation, and functional integration owing to the lack of an established vascular network. Here we engineer a hybrid myoglobin:peptide hydrogel that can concomitantly deliver stem cells and oxygen to the brain to support engraftment until vascularisation can occur naturally. We show that this hybrid hydrogel can modulate cell fate specification within progenitor cell grafts, resulting in a significant increase in neuronal differentiation. We find that the addition of myoglobin to the hydrogel results in more extensive innervation within the host tissue from the grafted cells, which is essential for neuronal replacement strategies to ensure functional synaptic connectivity. This approach could result in greater functional integration of stem cell-derived grafts for the treatment of neural injuries and diseases affecting the central and peripheral nervous systems.

Fast and slow skeletal myosin binding protein-C and aging.

Aging is associated with skeletal muscle strength decline and cardiac diastolic dysfunction. The structural arrangements of the sarcomeric proteins, such as myosin binding protein-C (MyBP-C) are shown to be pivotal in the pathogenesis of diastolic dysfunction. Yet, the role of fast (fMyBP-C) and slow (sMyBP-C) skeletal muscle MyBP-C remains to be elucidated. Herein, we aimed to characterize MyBP-C and its paralogs in the fast tibialis anterior (TA) muscle from adult and old mice. Immunoreactivity preparations showed that the relative abundance of the fMyBP-C paralog was greater in the TA of both adult and old, but no differences were noted between groups. We further found that the expression level of cardiac myosin binding protein-C (cMyBP-C), an important modulator of cardiac output, was lowered by age. Standard SDS-PAGE along with Pro-Q Diamond phosphoprotein staining did not identify age-related changes in phosphorylated MyBP-C proteins from TA and cardiac muscles; however, it revealed that MyBP-C paralogs in fast skeletal and cardiac muscle were highly phosphorylated. Mass spectrometry further identified glycogen phosphorylase, desmin, actin, troponin T, and myosin regulatory light chain 2 as phosphorylated myofilament proteins in both ages. MyBP-C protein-bound carbonyls were determined using anti-DNP immunostaining and found the carbonyl level of fMyBP-C, sMyBP-C, and cMyBP-C to be similar between old and adult animals. In summary, our data showed some differences regarding the MyBP-C paralog expression and identified an age-related reduction of cMyBP-C expression. Future studies are needed to elucidate which are the age-driven post-translational modifications in the MyBP-C paralogs.

HCV reflex testing: A single-sample, low-contamination method that improves the diagnostic efficiency of HCV testing among patients in Alberta, Canada.

BACKGROUND: Hepatitis C virus (HCV) can be cured with antiviral treatments. Diagnosis normally requires two blood samples, one for serology screening and one for molecular confirmation. This multi-step process creates barriers in patient care and decreases testing for hard-to-reach populations. We used the cobas® 6800 to detect HCV RNA after antibody testing to investigate whether a single-sample reflex testing method is effective and efficient for diagnosing HCV-positive patients. METHODS: HCV RNA-positive clinical samples (n = 152) were interchangeably loaded on the ARCHITECT i2000SR with negative samples (n = 152) in a checkerboard fashion, tested for HCV antibodies using fixed probes, and directly transferred to the cobas 6800 for molecular testing. Contamination rates, sensitivity, and specificity were determined by comparing Abbott m2000 and cobas 6800 viral loads. After implementing reflex testing, clinical data over a 6-month period were analyzed for diagnostic efficiency. RESULTS: Contamination was present in 5 of 152 pairs (3.29%) after reflex testing. Sensitivity and specificity were 99.3% (95% CI 95.1% to 99.9%) and 100% (95% CI 97.5% to 100%), respectively, using the cobas 6800 assay after serotesting. Approximately 97% of clinical patients received a conclusive test result with the reflex-testing algorithm. For HCV-positive patients, mean diagnostic turnaround times were significantly lower using reflex testing versus the two-sample method (4 versus 39 days; p < 0.0001). CONCLUSIONS: HCV reflex testing demonstrated low levels of contamination without compromising the integrity of the molecular assay. Implementation in clinical laboratories would increase the efficiency of diagnosis and decrease steps in the continuum of care for patients.

HISTORIQUE: Il est possible de vaincre le virus de l'hépatite C (VHC) par des traitements antirétroviraux. Pour poser un diagnostic, il faut normalement deux prélèvements de sang : l'un pour le dépistage sérologique et l'autre pour la confirmation moléculaire. Ce processus en plusieurs étapes crée des obstacles dans les soins aux patients et limite le dépistage auprès des populations difficiles à atteindre. Les auteurs ont utilisé la plateforme cobasMD 6800 pour déceler l'ARN du VHC après des tests de détection des anticorps et pour explorer si une méthode de dépistage réflexe à échantillon unique est efficace et efficiente lors du diagnostic des patients positifs au VHC. MÉTHODOLOGIE : Les chercheurs ont placé les échantillons cliniques positifs à l'ARN du VHC (n = 152) en échiquier avec des échantillons négatifs (n = 152) dans l'analyseur ARCHITECT i2000SR, ont dépisté les anticorps du VHC à l'aide de sondes fixes, puis ont transféré les échantillons directement sur la plateforme cobas 6800 en vue du test moléculaire. Ils ont établi les taux de contamination, la sensibilité et la spécificité en comparant les charges virales des plateformes Abbott m2000 et cobas 6800. Après le dépistage réflexe, ils ont analysé les données cliniques sur une période de six mois pour en établir l'efficience diagnostique. RÉSULTATS : Les chercheurs ont constaté une contamination dans cinq des 152 paires (3,29 %) après le dépistage réflexe. Après l'examen sérologique, ils ont obtenu une sensibilité de 99,3 % (IC à 95 %, de 95,1 % à 99,9 %) et une spécificité de 100 % (IC à 95 %, de 97,5 % à 100 %) au moyen de la plateforme cobas 6800. Environ 97 % des patients cliniques ont reçu un test concluant selon l'algorithme du dépistage réflexe. Chez les patients positifs au VHC, le délai diagnostique moyen était considérablement plus court après le dépistage réflexe qu'après la méthode à deux échantillons (quatre jours plutôt que 39; p < 0,0001). CONCLUSIONS : Le dépistage réflexe du VHC a démontré de faibles taux de contamination sans compromettre l'intégrité du dosage moléculaire. Son adoption en laboratoire clinique accroîtrait l'efficience du diagnostic et réduirait le nombre d'étapes dans le continuum des soins aux patients.

The introduction of competency-based medical education for postgraduate training in South Africa.

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Comparison of SARS-CoV-2 spike antibody quantitative titer reporting using the World Health Organization International Standard Units by four commercial assays.

The accurate measurement of serological response to SARS-CoV-2 vaccination is needed to correlate responses with effective protective immunity. The World Health Organization (WHO) has created an international standard to allow harmonization of immune response assessment to an arbitrary unit across different commercial assays; however, the accuracy of reporting of SARS-CoV-2 spike antibody titers in international standard units (BAU or IU/mL) from commercial assays is not well studied. Here, we report the performance comparison of four quantitative commercial assays testing for SARS-CoV-2 spike immunoglobins using the WHO's international standard. Sera, EDTA-plasma and heparinized plasma collected from individuals who are vaccine naïve or received BNT162b2 (Pfizer/BioNTech), mRNA-1273 (Moderna) or ChAdOx1-S (Oxford-AstraZeneca) were tested using Abbott Architect AdviseDx SARS-CoV-2 IgG II, DiaSorin LIAISON SARS-CoV-2 TrimericS IgG, Roche Elecsys Anti-SARS-CoV-2 S and GenScript cPass SARS-CoV-2 surrogate virus neutralization assays. The sensitivities ranged from 90% to 100%, and specificities from 88% to 100%. These four assays had excellent agreement (0.79-0.93) and correlation (0.87-0.97); however, Passing-Bablok regression analysis indicated that data generated by these assays were not comparable. Our data suggests that natural SARS-CoV-2 infection elicited a greater antibody response compared to vaccines, evident by a significantly higher neutralizing antibody titer in unvaccinated individuals who seroconverted.

Identifying the optimal developmental age of human pluripotent stem cell-derived midbrain dopaminergic progenitors for transplantation in a rodent model of Parkinson's disease.

Donor cell age can have a significant impact on transplantation outcomes. Despite the rapid advancement of human pluripotent stem cell (hPSC)-derived dopaminergic (DA) progenitors to the clinic for transplantation into Parkinson's Disease (PD), surprisingly limited data exists regarding the influence of cellular age on neural graft survival, composition, and integration. Here we examined the impact of transplanting ventral midbrain (VM) progenitors at varying days of differentiation (from day 13-30) into a rodent PD model, comparing two hPSC lines (an embryonic and an induced pluripotent cell line, hESC and hiPSC, respectively). Both hPSC lines expressed GFP under the promoter PITX3 enabling specific tracking of graft-derived DA neurons. Post-mortem analysis at 6 months revealed larger grafts from Day19 (D19), D22 and D25 progenitors, yet contained a higher proportion of non-DA and poorly specified (FOXA2-) cells. While D13 and D30 progenitors yielded smaller grafts. D13-derived grafts had the highest DA neuron proportion and proportionally more GIRK2+ DA neurons, the subpopulation critical for motor function. These younger progenitor grafts maintained their capacity to innervate developmentally relevant DA targets, with increased innervation capacity per DA neuron, collectively resulting in restoration of motor deficits with equal or greater proficiency than older donor cells. While donor age effects were reproducible for a given hPSC line and trends were similar between the two hPSC lines, grafts of D13 hiPSC-derived progenitors showed a 6-fold greater density of DA neurons compared to D13 hESC-derived grafts, highlighting between-line variability. These findings show that hPSC-derived VM donor age has a direct impact on graft survival, composition and maturation, and that careful assessment, on a line-to-line basis is required prior to translation.

Background shielding by dense samples in low-level gamma spectrometry.

In low activity gamma spectrometric measurements of large, dense samples, the bulk sample material shields the HPGe crystal from external background sources. If not accounted for in studies that utilise background-subtraction methods, this effect may result in systematic errors in the sample activity and detection limit estimation. We introduce a Monte Carlo based method to minimise the impact of this effect on sample gamma spectra. It is validated using simulated detector backgrounds and applied to a measurement of low-activity [Formula: see text] . One main prerequisite for the correct application of this method is to know in advance the nuclides which contribute to the detector background spectrum and their spatial distribution. With a thorough understanding of the detector backgrounds, the method improves the accuracy of sensitive low-background measurements of low-activity samples. Even without knowing the background sources and their distribution, conservative results may still be presented that account for the potential systematic errors introduced by this background shielding effect.