Longitudinal Analysis Research Articles

Central Vein Sign, Cortical Lesions, and Paramagnetic Rim Lesions for the Diagnostic and Prognostic Workup of Multiple Sclerosis.

The diagnosis of multiple sclerosis (MS) can be challenging in clinical practice because MS presentation can be atypical and mimicked by other diseases. We evaluated the diagnostic performance, alone or in combination, of the central vein sign (CVS), paramagnetic rim lesion (PRL), and cortical lesion (CL), as well as their association with clinical outcomes. In this multicenter observational study, we first conducted a cross-sectional analysis of the CVS (proportion of CVS-positive lesions or simplified determination of CVS in 3/6 lesions-Select3*/Select6*), PRL, and CL in MS and non-MS cases on 3T-MRI brain images, including 3D T2-FLAIR, T2*-echo-planar imaging magnitude and phase, double inversion recovery, and magnetization prepared rapid gradient echo image sequences. Then, we longitudinally analyzed the progression independent of relapse and MRI activity (PIRA) in MS cases over the 2 years after study entry. Receiver operating characteristic curves were used to test diagnostic performance and regression models to predict diagnosis and clinical outcomes. The presence of ≥41% CVS-positive lesions/≥1 CL/≥1 PRL (optimal cutoffs) had 96%/90%/93% specificity, 97%/84%/60% sensitivity, and 0.99/0.90/0.77 area under the curve (AUC), respectively, to distinguish MS (n = 185) from non-MS (n = 100) cases. The Select3*/Select6* algorithms showed 93%/95% specificity, 97%/89% sensitivity, and 0.95/0.92 AUC. The combination of CVS, CL, and PRL improved the diagnostic performance, especially when Select3*/Select6* were used (93%/94% specificity, 98%/96% sensitivity, 0.99/0.98 AUC; p = 0.002/p < 0.001). In MS cases (n = 185), both CL and PRL were associated with higher MS disability and severity. Longitudinal analysis (n = 61) showed that MS cases with >4 PRL at baseline were more likely to experience PIRA at 2-year follow-up (odds ratio 17.0, 95% confidence interval: 2.1-138.5; p = 0.008), whereas no association was observed between other baseline MRI measures and PIRA, including the number of CL. The combination of CVS, CL, and PRL can improve MS differential diagnosis. CL and PRL also correlated with clinical measures of poor prognosis, with PRL being a predictor of disability accrual independent of clinical/MRI activity.

The Role of Physical Literacy in the Association Between Weather and Physical Activity: A Longitudinal Multilevel Analysis With 951 Children.

Numerous studies showed an effect of weather on physical activity (PA) levels in children. However, no study has yet examined the relevance of personal factors in this relationship. Therefore, this study analyzes (1) whether there are systematic interindividual differences in the extent to which weather affects the PA behavior and (2) whether physical literacy (PL) moderates the weather-PA association in children. A total of 951 children in 12 Danish schools (age 9.76 [1.59]y; 54.3% girls) completed objective PA assessments via accelerometry (moderate to vigorous PA, light PA, and sedentary behavior). Local weather data (precipitation, wind speed, temperature, and sunshine duration) were provided by the Danish Meteorological Institute. Participants' PL was measured employing the Danish version of the Canadian Assessment of Physical Literacy-2. The 4116 accelerometer days underwent longitudinal multilevel analyses while considering their nesting into pupils and school classes (n = 51). Fluctuations in all PA indicators were significantly explained by variations in weather conditions, especially precipitation (P ≤ .035). Significant interindividual differences were found for 9 of 12 analytical dimensions, suggesting that weather changes influence PA behavior differently across individuals (especially moderate to vigorous PA, χ2[4] ≥ 11.5, P ≤ .021). However, PL moderated the relationship between weather and PA in only 2 of the 48 analytical constellations. Despite the varying impact of weather on PA across individuals, the present study favors a main effect model in which weather and PL exert independent effects on children's PA. The insufficient support for PL as a moderating factor calls for future studies to test alternative mechanisms in the weather-PA association.

Impact of hypertensive disorders of pregnancy on offspring cardiovascular function. Study from fetal life to early childhood.

Epidemiological studies suggest that children following in utero exposure to hypertensive disorders of pregnancy (HDP) may be at increased long term cardiovascular risk. However, data in early childhood are lacking. We aimed to investigate the independent influence of HDP on childhood heart after accounting for differences in childhood risk factor profile. We performed detailed cardiovascular assessment in fetuses at mid-gestation and at a median of 2.3 years (IQR: 2.1, 2.4 years) postnatally in 71 cases where the mothers had HDP and 304 who did not have HDP. There were no differences in demographic characteristics between groups but in the HDP group delivery was earlier and birthweight was lower. In fetal life, there were no significant differences in cardiac function or structure between the HDP and non-HDP groups. In early childhood, in the HDP compared to the non-HDP group, there was greater relative wall thickness (0.7 SD 0.3 vs. 0.6 SD 0.3 mm, p=0.047) and increased left ventricular mass (80.9 SD 20.4 vs. 75.7 SD 16.5, p=0.024); however, these differences were abolished following multivariable analysis. Longitudinal analysis revealed that in HDP, compared to the non-HDP group, there was no difference in the change of cardiac functional indices from fetal life to early childhood. Epidemiological studies suggest that HDP have an adverse impact on offspring cardiovascular health, but such an effect is not apparent in fetal life or in early childhood. This article is protected by copyright. All rights reserved.

Enhancing Cardiorespiratory Fitness Through Sauna Bathing: Insights From the Kuopio Ischemic Heart Disease Prospective Study.

The physiological adaptations stimulated by a sauna bath(SB) are similar to those produced by moderate- or high-intensity physical activity (PA), but the relationship between SB and cardiorespiratory fitness (CRF) is not clear. The objective of this study was to evaluate the cross-sectional and longitudinal associations between frequency and duration of SB with CRF. Baseline SB habits were assessed in 2012 men aged 42 -61yr. CRF was directly measured using a respiratory gas exchange analyzer during cardiopulmonary exercise testing at baseline and 11yr later. The associations of SB frequency and duration with baseline and 11-yr levels of CRF were examined using robust regression analyses adjusted for several confounders, including lifestyle factors such as PA. In baseline analysis, a unit increase in sauna sessions/wk was associated with an increase in CRF 0.30 mL/kg/min (standard error [SE]: 0.14; P=.034). Alternatively, compared with a single sauna sessions/wk, 2-3 and 4-7 sauna sessions/wk was each associated with significant increases in levels of CRF: 0.84 mL/kg/min (SE: 0.32; P=.008) and 1.17 mL/kg/min (SE: 0.57; P=.041), respectively. In longitudinal analysis, frequent SB was associated with increases in 11-yr CRF levels, but this was only significant for 2-3 sauna sessions/wk compared with a single sauna sessions/wk: 1.22 mL/kg/min (SE: 0.59; P=.038). Duration of SB was not significantly associated with CRF levels in cross-sectional and longitudinal analyses. Frequent SB may improve levels of CRF independently of PA. These results warrant replication in robust definitive randomized controlled trials.

Why circadian rhythmicity matters: Associations between sleep irregularity and mental health conditions during the Covid-19 health crisis

Objective To assess the association between sleep irregularity, anxiety, and depression while controlling for other sleep dimensions and using a longitudinal design. Methods Longitudinal cohort study which started in April 2020 during the first French lockdown in the general population. Follow-up questionnaires were completed in June 2020, a period without lockdown measures. Participants were asked about their sleep (regularity, duration, timing, complaints) and their anxiety (General Anxiety Disorder-7) and depressive (Patient Health Questionnaire-9) symptoms. Results A total of 3745 participants were included (mean age: 28.9 years) with 2945 women (78.6%). At baseline, 38.1% (1428) of participants reported irregular sleep timing, 23.8% (891) anxiety and 28.9% (1081) depressive symptoms. In cross-sectional analyses, irregular sleep timing was associated with a 2.5-fold higher likelihood of anxiety and a 4-fold higher likelihood of depressive symptoms compared to regular sleepers. Associations were not explained by the other sleep dimensions and persisted in a longitudinal analysis, with irregular sleep timing at baseline being associated with anxiety (OR = 3.27[1.58–6.76]) and depressive symptoms (OR = 3.45[1.66–7.19]) during follow-up. Conclusion The results show a strong association between sleep irregularity and mental health. Furthers studies are needed to explore how sleep regularity could promote good mental health in non-clinical populations.

Health-related quality scores in childhood interstitial lung disease: Good agreement between patient and caregiver reports.

Childhood interstitial lung disease (chILD) is a heterogeneous group of mostly chronic respiratory disorders. Assessment of health-related quality of life (HrQoL) in chILD has become increasingly important in clinical care and research. The aim of this study was to assess differences between patient-reported (self) and caregiver-reported (proxy) HrQoL scores. This study used data obtained from the chILD-EU Register. After inclusion (baseline), the patient's health status was followed up at predefined study visits. At each study visit, caregivers and patients were handed validated, age-specific HrQoL questionnaires. HrQoL data entered at baseline were used to compare self- and proxy-reported HrQoL scores. For the longitudinal analysis, we compared HrQoL scores between the baseline and the next follow-up visit. No differences between patient- and caregiver-reported HrQoL scores were found for school functioning, chILD-specific questionnaire score, and physical health summary score. Self-reported HrQoL scores were higher for the subscales emotional functioning (77.4 vs. 70.7; p < .001), social functioning (81.9 vs. 76.2; p < .001), as well as psycho-social summary score (76.5 vs. 71.8; p < .001) and total score (74.7 vs. 70.8; <.001). The longitudinal analysis showed that a significant change in a patient-reported HrQoL score resulted in a significant change in a caregiver-reported HrQoL score after a mean time of 11.0 months (SD 9.4). We found a good agreement between children- and caregiver-related HrQoL scores. In chILD, caregivers are able to sense changes in children's HrQoL scores over time and may be used as a proxy for children unable to complete HrQoL questionnaires.

Unpacking the multispatial configurations of metagoverning tourism development: a longitudinal application of the TPSNE framework

ABSTRACT This paper advances the study of metagovernance by examining its spatial horizons in the empirical case of tourism development. Drawing upon Jessop et al.’s (2008) TPSNE framework on territory, place, scale, network and environment for a longitudinal qualitative analysis, the article traces the evolution of tourism metagovernance in northernmost Finland and Sweden over the past 150 years. The shifts from pre-Fordism over welfare state Fordism to the competition state manifest themselves in tourism metagovernance through distinct socio-spatial relationships between the state, tourism stakeholders and society at large. Applying the TPSNE framework provides crucial explanatory insights into processes and drivers of change and continuity in tourism’s sectoral development as part of wider societal and political transformations.

Leadership Matters: Investigating the Association between Nursing Home Administrator Turnover and Quality.

Existing research has associated nursing home (NH) staff turnover with poor performance, yet the impact of nursing home administrator (NHA) turnover remains relatively understudied. This study aimed to explore the relationship between NHA turnover and NH quality, and to determine if this relationship was mediated by registered nurse (RN) turnover. Utilizing data from multiple secondary sources, including the Care Compare: Skilled Nursing Facility Quality Reporting Program (SNF QRP) and LTCFocus.org, this study employed a longitudinal analysis covering the period 2021-2022 (n=19,645). The dependent variable was quality star ratings from SNF QRP, while the independent variable was NHA turnover, reflecting the number of administrators who left each facility annually. We used Baron and Kenny's mediation testing method, incorporating two-way fixed effects (state and year level) with appropriate organizational and market level control variables. The results affirmed that NHA turnover negatively affected quality, decreasing the likelihood of a higher star rating by 14% with one departure and 25% with multiple departures (p=0.001). Additionally, NHA turnover correlated with an increase in RN turnover by 7% and 11%, respectively, for one and multiple departures (p=0.001). RN turnover fully mediated the impact of NHA turnover on quality, nullifying the direct effect of NHA turnover. The results of this study highlight the synergistic relationship between administrators and caregivers in NHs. To enhance NHA retention, NHs should improve compensation and benefits. Nonetheless, broader governmental support and interventions might be necessary to sustain these improvements.

Clinical and molecular features of patients with IDH1 wild-type primary glioblastoma presenting unexpected short-term survival after gross total resection.

This study investigated the factors influencing short-term survivors (STS) after gross total resection (GTR) in patients with IDH1 wild-type primary glioblastoma. We analyzed five independent cohorts who underwent GTR, including 83 patients from Kitasato University (K-cohort), and four validation cohorts of 148 patients from co-investigators (V-cohort), 66 patients from the Kansai Molecular Diagnosis Network for the Central Nervous System tumors, 109 patients from the Cancer Genome Atlas, and 40 patients from the Glioma Longitudinal AnalySiS. The study defined STS as those who had an overall survival ≤ 12months after GTR with subsequent radiation therapy, and concurrent and adjuvant temozolomide (TMZ). The study included 446 patients with glioblastoma. All cohorts experienced unexpected STS after GTR, with a range of 15.0-23.9% of the cases. Molecular profiling revealed no significant difference in major genetic alterations between the STS and non-STS groups, including MGMT, TERT, EGFR, PTEN, and CDKN2A. Clinically, the STS group had a higher incidence of non-local recurrence early in their treatment course, with 60.0% of non-local recurrence in the K-cohort and 43.5% in the V-cohort. The study revealed that unexpected STS after GTR in patients with glioblastoma is not uncommon and such tumors tend to present early non-local recurrence. Interestingly, we did not find any significant genetic alterations in the STS group, indicating that such major alterations are characteristics of GB rather than being reliable predictors for recurrence patterns or development of unexpected STS.

Joint modeling of monocyte HLA-DR expression trajectories predicts 28-day mortality in severe SARS-CoV-2 patients.

The recent SarsCov2 pandemic has disrupted healthcare system notably impacting intensive care units (ICU). In severe cases, the immune system is dysregulated, associating signs of hyperinflammation and immunosuppression. In the present work, we investigated, using a joint modeling approach, whether the trajectories of cellular immunological parameters were associated with survival of COVID-19 ICU patients. This study is based on the REA-IMMUNO-COVID cohort including 538 COVID-19 patients admitted to ICU between March 2020 and May 2022. Measurements of monocyte HLA-DR expression (mHLA-DR), counts of neutrophils, of total lymphocytes, and of CD4+ and CD8+ subsets were performed five times during the first month after ICU admission. Univariate joint models combining survival at day 28 (D28), hospital discharge and longitudinal analysis of those biomarkers' kinetics with mixed-effects models were performed prior to the building of a multivariate joint model. We showed that a higher mHLA-DR value was associated with a lower risk of death. Predicted mHLA-DR nadir cutoff value that maximized the Youden index was 5414 Ab/C and led to an AUC = 0.70 confidence interval (95%CI) = [0.65; 0.75] regarding association with D28 mortality while dynamic predictions using mHLA-DR kinetics until D7, D12 and D20 showed AUCs of 0.82 [0.77; 0.87], 0.81 [0.75; 0.87] and 0.84 [0.75; 0.93]. Therefore, the final joint model provided adequate discrimination performances at D28 after collection of biomarker samples until D7, which improved as more samples were collected. After severe COVID-19, decreased mHLA-DR expression is associated with a greater risk of death at D28 independently of usual clinical confounders.

Changing Dermatologic Procedural Patterns in the Medicare Population: A National Trend Analysis.

Dermatologists are trained in diagnostic and therapeutic procedures for cutaneous lesions, yet comparative trends for basic dermatologic procedures across dermatology providers are lacking at the national level. To trend common dermatologic procedures among general dermatologists, Mohs surgeons, primary care providers or primary care physicians (PCPs), and nonphysician clinicians (NPCs). Longitudinal analysis of 2016 to 2021 Medicare Public Use Files. Aggregate dermatologic procedural volume decreased 3.0%. Procedural volume declined among general dermatologists (-11.7%), Mohs surgeons (-16.7%), and PCPs (-41.7%) but increased among NPCs (+57.5%). The proportion of procedures by general dermatologists decreased substantially for premalignant destructions (-6.2%), skin biopsies and shave removals (-4.7%), and malignant excisions (-4.1%) and more notably in counties that were nonmetro (-7.1%), low in income (-6.1%), and with <4.0 dermatologists per 100,000 population (-7.0%). Aggregate procedural volume decreased across the study period with general dermatologists, Mohs surgeons, and PCPs performing a progressively smaller proportion. The increase in procedures by NPCs may help to address demand but underscores the value of formalized procedural training. The procedural decline by general dermatologists in rural and low-income counties and those with baseline dermatologist shortages may exacerbate existing unmet need. Primary limitation included lack of commercial data.

Investigating the Role of Social Determinants in Child Mortality and Life Expectancy: Longitudinal Analysis of 200 Countries from 1990 to 2021

Investigating the Role of Social Determinants in Child Mortality and Life Expectancy: Longitudinal Analysis of 200 Countries from 1990 to 2021

Social contact and the perceived impact of social distancing on health outcomes during the COVID-19 pandemic among community dwelling older adults taking part in the OPAL cohort study

BackgroundDuring the COVID-19 pandemic, social distancing and reduced social contact may have affected older adults’ health.ObjectivesTo evaluate the perceived impact of social distancing on older adults’ health and explore the association between social contact and health outcomes.DesignCross-sectional and longitudinal analyses of the OPAL cohort study.SubjectsCommunity dwelling older adults.MethodsWe sent questionnaires to participants of an existing cohort study (n = 4328). Questions included the amount and type of social contact, and how often they went outside. Participants rated the impact of social distancing on their health. Sociodemographic factors and quality of life were available from previous questionnaires. We examined quality of life prior to and during the pandemic and explored the cross-sectional relationship between social contact and health using logistic regression.ResultsThere were 3856/4328 (89%) questionnaires returned. EQ-5D scores changed little compared to pre-pandemic scores but 25% of participants reported their overall health had worsened. The telephone was the most used method of contact (78%). Video calls were used least with 35% of participants not using them or having no access to them. 13% of respondents never went outside. Lower levels of contact were associated with increased risk of reporting worse health (Odds ratio (OR) 1.04 (95% CI 1.01–1.08)). Those experiencing financial strain and who spent less time outside experienced the largest increase in risk of reporting perceived worsened overall health. Those reporting a strain to get by financially were 4 times more likely to report worsened health than those who described themselves as quite comfortably off (OR 4.00 (95% CI 1.86–8.16)). Participants who reported never going outside were twice as likely to report worsened health compared to those who went outside daily (OR 2.00 (95% CI 1.57–2.54)).ConclusionsLess contact with other people was associated with perceived worsening in overall health. Although many older people reported using online technology, such as video calls, a substantial proportion were not using them. Older people facing financial strain were more likely to report worsened health, highlighting the impact of social inequalities during the pandemic. Going outside less was also associated with perceived worsened health.

Anti-FHL1 autoantibodies in adult patients with myositis: a longitudinal follow-up analysis.

To determine prevalence and clinical associations of anti-FHL1 autoantibodies in patients with idiopathic inflammatory myopathies (IIM), and to evaluate autoantibody levels over time. Sera at the time of diagnosis from patients with IIM (n = 449), autoimmune disease controls (DC, n = 130), neuromuscular diseases (NMD, n = 16) and healthy controls (HC, n = 100) were analyzed for anti-FHL1 autoantibodies by Enzyme-Linked ImmunoSorbent Assay (ELISA). Patients with IIM FHL1+ and FHL1- were included in a longitudinal analysis. Serum levels were correlated to disease activity. Autoantibodies to FHL1 were more frequent in patients with IIM (122/449, 27%) compared with DC (Autoimmune DC and NMD, 13/146, 9%, p< 0.001) and HC (3/100,3%, p< 0.001). Anti-FHL1 levels were higher in IIM [median (IQR)=0.62 (0.15-1.04)] in comparison with DC [0.22 (0.08-0.58)], HC [0.35 (0.23-0.47)] and NMD [0.48 (0.36-0.80)] p< 0.001. Anti-FHL1+ patients with IIM were younger at time of diagnosis compared with the anti-FHL1- group (p= 0.05) and were seronegative for other autoantibodies in 25%.In the first follow-up anti-FHL1+ sample 20/33 (60%) positive at baseline had turned negative for anti-FHL1 autoantibodies. Anti-FHL1 autoantibodies rarely appeared after initiating treatment. Anti-FHL1 autoantibody levels correlated with CK (r = 0.62, p= 0.01), disease activity measure MYOACT (n = 14, p= 0.004) and inversely with manual muscle test-8 (r=-0.59, p= 0.02) at baseline. Anti-FHL1 autoantibodies were present in 27% of patients with IIM, of these 25% were negative for other autoantibodies. Other autoimmune diseases had lower frequencies and levels. Anti-FHL1 levels often decreased with immunosuppressive treatment, correlated with disease activity measures at diagnosis and rarely appeared after start of treatment.

Losing sleep influences dietary intake in children: a longitudinal compositional analysis of a randomised crossover trial

BackgroundAlthough inadequate sleep increases the risk of obesity in children, the mechanisms remain unclear. The aims of this study were to assess how sleep loss influenced dietary intake in children while accounting for corresponding changes in sedentary time and physical activity; and to investigate how changes in time use related to dietary intake.MethodsA randomized crossover trial in 105 healthy children (8–12 years) with normal sleep (~ 8–11 h/night) compared sleep extension (asked to turn lights off one hour earlier than usual for one week) and sleep restriction (turn lights off one hour later) conditions, separated by a washout week. 24-h time-use behaviors (sleep, wake after sleep onset, physical activity, sedentary time) were assessed using waist-worn actigraphy and dietary intake using two multiple-pass diet recalls during each intervention week. Longitudinal compositional analysis was undertaken with mixed effects regression models using isometric log ratios of time use variables as exposures and dietary variables as outcomes, and participant as a random effect.ResultsEighty three children (10.2 years, 53% female, 62% healthy weight) had 47.9 (SD 30.1) minutes less sleep during the restriction week but were also awake for 8.5 (21.4) minutes less at night. They spent this extra time awake in the day being more sedentary (+ 31 min) and more active (+ 21 min light physical activity, + 4 min MVPA). After adjusting for all changes in 24-h time use, losing 48 min of sleep was associated with consuming significantly more energy (262 kJ, 95% CI:55,470), all of which was from non-core foods (314 kJ; 43, 638). Increases in sedentary time were related to increased energy intake from non-core foods (177 kJ; 25, 329) whereas increases in MVPA were associated with higher intake from core foods (72 kJ; 7,136). Changes in diet were greater in female participants.ConclusionLoss of sleep was associated with increased energy intake, especially of non-core foods, independent of changes in sedentary time and physical activity. Interventions focusing on improving sleep may be beneficial for improving dietary intake and weight status in children.Trial RegistrationAustralian New Zealand Clinical Trials Registry ANZCTR ACTRN12618001671257, Registered 10th Oct 2018, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=367587&isReview=true

Association of Misfolded α-Synuclein Derived from Neuronal Exosomes in Blood with Parkinson's Disease Diagnosis and Duration.

Misfolded α-synuclein can be detected in blood samples of Parkinson's disease (PD) patients by a seed amplification assay (SAA), but the association with disease duration is not clear, yet. In the present study we aimed to elucidate whether seeding activity of misfolded α-synuclein derived from neuronal exosomes in blood is associated with PD diagnosis and disease duration. Cross-sectional samples of PD patients were analyzed and compared to samples of age- and gender-matched healthy controls using a blood-based SAA. Presence of α-synuclein seeding activity and differences in seeding parameters, including fluorescence response (in arbitrary units) at the end of the amplification assay (F60) were analyzed. Additionally, available PD samples collected longitudinally over 5-9 years were included. In the cross-sectional dataset, 79 of 80 PD patients (mean age 69 years, SD = 8; 56% male) and none of the healthy controls (n = 20, mean age 70 years, SD = 10; 55% male) showed seeding activity (sensitivity 98.8%). When comparing subgroups divided by disease duration, longer disease duration was associated with lower α-synuclein seeding activity (F60: p < 0.001). In the longitudinal analysis 10/11 patients showed a gradual decrease of α-synuclein seeding activity over time. This study confirms the high sensitivity of the blood-based α-synuclein SAA applied here. The negative association of α-synuclein seeding activity in blood with disease duration makes this parameter potentially interesting as biomarker for future studies on the pathophysiology of disease progression in PD, and for biologically oriented trials in this field.

A longitudinal qualitative study on physician experience in managing multimorbidity across the COVID-19 pandemic in Odisha, India

While many studies have documented adverse impact of multiple chronic conditions or multimorbidity on COVID-19 outcomes in patients, there is scarcity of report on how physicians managed these patients. We investigated the experiences and challenges of clinicians in managing patients with multimorbidity throughout the COVID-19 pandemic in Odisha state, India. To understand the factors influencing illness management and the adaptive responses of physicians alongside the evolving pandemic, we followed a longitudinal qualitative study design. Twenty-three physicians comprising general practitioners, specialists, and intensivists, were telephonically interviewed in-depth. Saldana’s longitudinal qualitative data analysis method was employed for data analysis. COVID-19 pandemic initially diverted the attention of health systems, resulting in reduced care. With time, the physicians overcame fear, anxiety, and feelings of vulnerability to COVID-19 and started prioritising patients with multimorbidity for treatment and vaccination. All physicians recommended teleconsultation and digital health records to benefit chronic illness care during future public health crises. The findings underscore the transformative potential of physician resilience and adaptation during the COVID-19 pandemic, emphasizing the importance of prioritizing patients with multimorbidity, incorporating teleconsultation, and implementing digital health records in healthcare systems to enhance chronic illness care and preparedness for future public health crises.

Effect of retirement on loneliness: a longitudinal comparative analysis across Australia, China and the USA

BackgroundThere is evidence that the transition to retirement can bring social challenges and may increase loneliness. Few studies have examined the impact of retirement on loneliness; most have been conducted...

Longitudinal Analysis of Mitochondrial Function in a Choline-Deficient L-Amino Acid-Defined High-Fat Diet-Induced Metabolic Dysfunction-Associated Steatohepatitis Mouse Model.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is one of the most common chronic liver diseases worldwide. Some patients with MAFLD develop metabolic dysfunction-associated steatohepatitis (MASH), which can lead to severe liver fibrosis. However, the molecular mechanisms underlying this progression remain unknown, and no effective treatment for MASH has been developed so far. In this study, we performed a longitudinal detailed analysis of mitochondria in the livers of choline-deficient, methionine-defined, high-fat-diet (CDAHFD)-fed mice, which exhibited a MASH-like pathology. We found that FoF1-ATPase activity began to decrease in the mitochondria of CDAHFD-fed mice prior to alterations in the activity of mitochondrial respiratory chain complex, almost at the time of onset of liver fibrosis. In addition, the decrease in FoF1-ATPase activity coincided with the accelerated opening of the mitochondrial permeability transition pore (PTP), for which FoF1-ATPase might be a major component or regulator. As fibrosis progressed, mitochondrial permeability transition (PT) induced in CDAHFD-fed mice became less sensitive to cyclosporine A, a specific PT inhibitor. These results suggest that episodes of fibrosis might be related to the disruption of mitochondrial function via PTP opening, which is triggered by functional changes in FoF1-ATPase. These novel findings could help elucidate the pathogenesis of MASH and lead to the development of new therapeutic strategies.

The impact of orthographic knowledge on reading development in German third graders

AbstractOrthographic knowledge (i.e., the knowledge of conventions of a written language) has been identified as a predictor of both basic and higher-level reading processes, however, mostly examined in a cross-sectional design. It remains unclear, whether and how orthographic knowledge contributes uniquely in explaining differences in the acquisition of reading skills. The aim of this study was therefore to examine the effects of orthographic knowledge on basic (word-reading) and higher level (sentence- and text-comprehension) reading development in German third graders over the course of a schoolyear. 325 German speaking children (mean age = 8.35 years, standard deviation = 0.57; 49% girls) participated in the study, 100 of whom also provided data on vocabulary and naming speed. Data were analyzed via multiple regression in hierarchical models with random intercepts, since the children were nested in classes. The longitudinal analyses showed that orthographic knowledge contributes to the development of reading on the word- and text-level, over and above vocabulary knowledge and naming speed. These findings support and extend previous results, showing that orthographic knowledge not only supports reading processes, but also plays an important role in reading development over the course of a schoolyear. The fact that no significant interaction between orthographic knowledge and reading comprehension could be found implies that orthographic knowledge is relevant for reading development in German third graders, independent of the level of reading proficiency. The present findings suggest that orthographic knowledge should be considered in reading instruction at school as well as during reading related interventions.