Serum neurofilament light chain level as a predictor of cognitive stage transition

Background Neurofilament light chain (NFL) level has been suggested as a blood-based biomarker for neurodegeneration in dementia. However, the association between baseline NFL levels and cognitive stage transition or cortical thickness is unclear. This study aimed to investigate whether baseline NFL levels are associated with cognitive stage transition or cortical thickness in mild cognitive impairment (MCI) and cognitively unimpaired (CU) participants. Methods This study analyzed data on participants from the independent validation cohort of the Korea Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s disease (KBASE-V) study. Among the participants of KBASE-V study, 53 MCI and 146 CU participants who were followed up for ≥ 2 years and had data on the serum NFL levels were eligible for inclusion in this study. Participants were classified into three groups according to baseline serum NFL levels of low, middle, or high. Results The Kaplan–Meier analysis showed association between the serum NFL tertiles and risk of cognitive stage transition in MCI (P = 0.002) and CU (P = 0.028) participants, analyzed separately. The same is true upon analysis of MCI and CU participants together (P < 0.001). In MCI participants, the highest serum NFL tertile and amyloid-beta positivity were independent predictors for cognitive stage transition after adjusting for covariates. For CU participants, only amyloid-beta positivity was identified to be an independent predictor. Conclusion The study shows that higher serum NFL tertile levels correlate with increased risk of cognitive stage transition in both MCI and CU participants. Serum NFL levels were negatively correlated with the mean cortical thickness of the whole-brain and specific brain regions.

Effects of Cued and Uncued Swallowing in Patients With Dementia

Purpose: Parameters such as bolus location at swallow onset (BLSO), stage transition duration (STD), pharyngeal transition duration (PTD), pharyngeal response duration (PRD), and pharyngeal phase duration (PPD) often vary between cued and uncued swallowing conditions. Research has demonstrated that cued swallows may offer functional benefits that mitigate pathophysiological processes. However, there are limited data assessing differences between cued and uncued swallows in disordered populations, such as dementia. The purpose of this study was to evaluate if cued swallowing alters swallowing biomechanics in patients living with dementia. Method: Through a retrospective analysis of videofluoroscopic swallow studies (VFSS), 105 swallows from 26 participants living with dementia ( M age = 81 years; 14 women) were analyzed in duplicate by blinded raters using the Analysis of Swallowing Physiology, Events, Kinematics, and Timing method. Only VFSS with at least one cued and one uncued swallow were included in the analysis. Chi-square tests were used to explore differences in BLSO. Repeated-measures analyses of variance (ANOVAs) were used to explore differences in STD, PTD, PRD, and PPD. Results: Results revealed no significant differences in BLSO between cued and uncued swallows for patients living with dementia ( p = .934). Repeated-measures ANOVAs revealed no significant differences between the two types of swallows for STD ( p = .995), PTD ( p = .864), PRD ( p = .807), or PPD ( p = .660). Conclusions: This study suggests that there may be limited benefit to providing cued swallows to individuals living with dementia. Further research should investigate if this is due to impaired cognition and/or changes in motor control to volitionally complete the cued swallow.

Firsthand Experience in Graduating Three Cohorts of Forensic Pathologists Trained With Competency by Design (CBD) Curriculum

Introduction: The University of Toronto experienced graduating three cohorts of forensic pathologists trained with Competency by Design (CBD) curriculum. We achieved this as a result of multiyear development of Entrustable Professional Activities (EPAs), Required Training Experience (RTEs), and Specialty Competency Requirements (SCRs) by the Royal College of Physicians and Surgeons of Canada’s Forensic Pathology Speciality Committee, the Ontario Forensic Pathology Service, and the University of Toronto. Method: Our academic year is comprised of 13 blocks. We divided the 13-block period into 4 stages to map all the EPAs and RTEs. The first stage, Transition to Discipline, is 1 block, the second stage, Foundation of Discipline, consists of 3 blocks; the third stage, Core of Discipline, consists of 6 blocks, and the final fourth stage, Transition to Practice, consists of 3 blocks. Board-certified faculty members in Forensic Pathology with more than five years of experience supervised the trainees. We graduated 5 Canadian and 4 international trainees at the end of the third cycle of CBD-based training program. Conclusion: Using the Royal College Speciality Committee blueprint, the University of Toronto started in 2016 planning the CBD curriculum in the forensic pathology training program. By the end of June 2021, we graduated nine trainees from our CBD-based Forensic Pathology training program. We are training the fourth cohort, and they will be graduating at the end of June 2022. This article aims to share our firsthand experiencing in CBD training in forensic pathology.

Unexpected plasticity in the life cycle of Trypanosoma brucei

African trypanosomes cause sleeping sickness in humans and nagana in cattle. These unicellular parasites are transmitted by the bloodsucking tsetse fly. In the mammalian host's circulation, proliferating slender stage cells differentiate into cell cycle-arrested stumpy stage cells when they reach high population densities. This stage transition is thought to fulfil two main functions: first, it auto-regulates the parasite load in the host; second, the stumpy stage is regarded as the only stage capable of successful vector transmission. Here, we show that proliferating slender stage trypanosomes express the mRNA and protein of a known stumpy stage marker, complete the complex life cycle in the fly as successfully as the stumpy stage, and require only a single parasite for productive infection. These findings suggest a reassessment of the traditional view of the trypanosome life cycle. They may also provide a solution to a long-lasting paradox, namely the successful transmission of parasites in chronic infections, despite low parasitemia.

Single-Cell RNA Sequencing Reveals Cellular Heterogeneity and Stage Transition under Temperature Stress in Synchronized Plasmodium falciparum Cells

The malaria parasite has a complex life cycle exhibiting phenotypic variations in two different hosts accompanied by cell-to-cell variability that is important for stress tolerance, immune evasion, and drug resistance. To investigate cellular heterogeneity determined by gene expression, we performed single-cell RNA sequencing (scRNA-seq) of about 12,000 synchronized Plasmodium cells under physiologically relevant normal (37°C) and temperature stress (40°C) conditions phenocopying the cyclic bouts of fever experienced during malarial infection.

Heterogeneity in spontaneous sleep arousals: positive and negative links with early amyloid-beta and cognition

Recent literature is pointing towards a tight relationship between sleep quality and amyloid-beta (Aβ) accumulation, a hallmark of Alzheimer’s disease (AD). Sleep arousals are considered to induce sleep disruption, and though their heterogeneity has been suggested, their correlates remain to be established. We classified arousals in sleep of 100 healthy older individuals according to their association with muscular tone increase (E+/E-) and sleep stage transition (T+/T-), and show differences in EEG oscillatory compositions across arousal types. We found that T + E- arousals, which interrupt sleep stability, were positively correlated with Aβ burden in brain regions earliest affected by AD neuropathology. By contrast, more prevalent T-E + arousals, upholding sleep continuity, were associated with lower cortical Aβ burden, and better cognition. We provide empirical evidence that spontaneous arousals are diverse and differently associated with brain integrity and cognition. Sleep arousals may offer opportunities to transiently synchronise distant brain areas, akin to sleep spindles.

Schizophrenia polygenic risk scores in youth mental health: preliminary associations with diagnosis, clinical stage and functioning

Background The schizophrenia polygenic risk score (SCZ-PRS) is an emerging tool in psychiatry. Aims We aimed to evaluate the utility of SCZ-PRS in a young, transdiagnostic, clinical cohort. Method SCZ-PRSs were calculated for young people who presented to early-intervention youth mental health clinics, including 158 patients of European ancestry, 113 of whom had longitudinal outcome data. We examined associations between SCZ-PRS and diagnosis, clinical stage and functioning at initial assessment, and new-onset psychotic disorder, clinical stage transition and functional course over time in contact with services. Results Compared with a control group, patients had elevated PRSs for schizophrenia, bipolar disorder and depression, but not for any non-psychiatric phenotype (for example cardiovascular disease). Higher SCZ-PRSs were elevated in participants with psychotic, bipolar, depressive, anxiety and other disorders. At initial assessment, overall SCZ-PRSs were associated with psychotic disorder (odds ratio (OR) per s.d. increase in SCZ-PRS was 1.68, 95% CI 1.08–2.59, P = 0.020), but not assignment as clinical stage 2+ (i.e. discrete, persistent or recurrent disorder) (OR = 0.90, 95% CI 0.64–1.26, P = 0.53) or functioning (R = 0.03, P = 0.76). Longitudinally, overall SCZ-PRSs were not significantly associated with new-onset psychotic disorder (OR = 0.84, 95% CI 0.34–2.03, P = 0.69), clinical stage transition (OR = 1.02, 95% CI 0.70–1.48, P = 0.92) or persistent functional impairment (OR = 0.84, 95% CI 0.52–1.38, P = 0.50). Conclusions In this preliminary study, SCZ-PRSs were associated with psychotic disorder at initial assessment in a young, transdiagnostic, clinical cohort accessing early-intervention services. Larger clinical studies are needed to further evaluate the clinical utility of SCZ-PRSs, especially among individuals with high SCZ-PRS burden.

Sleep Stage Classification based on Two-Cycle Sleep Model Recognition using Continuous Heart Rate Variability

：Sleep stage on the whole night is not steady. Sleepers generally pass through three to five cycles. In each cycle, there are occur four typical sleep stages, such as wake stage (WS), light stage (LS), deep sleep (DS), rapid eye movement sleep stage (REM). According to the natural routine, in this paper, we investigate the stage transition and analyze the feature of stage transition using the local cluster Algorithm (LCA). Two-cycle sleep model (TCSM) is proposed to automatically classify sleep stages using over-night continuous heart rate variability (HRV) data. The generated model is based on the characteristics of the nested cycle's sleep stage distribution and the transition probabilities of sleep stages. Experiments were conducted using a public data set including 400 healthy subjects (female 239, male 161) and the model&rsquo;s classification accuracy was evaluated for four sleep stages: WS, LS, DS, REM. The experimental results showed that based on the TCSM model, the segmentation classification of pure sleep is 5.2% higher than that of the traditional method, and the accuracy of segmentation classification is 11.2% higher than the traditional sleep staging accuracy. The experimental performance is promising in terms of the accuracy, sensitivity, and specificity rates compared with the ones of the state-of-the-art methods. The study contributes to improve the quality of sleep monitoring in daily life using easy-to-wear HRV sensors.