Test Group Differences Research Articles

Identifying Risk Factors for Disease Progression in Developmental Dysplasia of the Hip Using a Contralateral Hip Model

Background: Developmental dysplasia of the hip (DDH) can cause pain and premature osteoarthritis. The risk factors and timing for disease progression in adolescents and young adults have not been fully defined. This study aimed to determine the prevalence of and risk factors for contralateral hip pain and surgery after periacetabular osteotomy (PAO) on a dysplastic hip. Methods: Patients undergoing unilateral PAO for DDH were followed for at least 2 years and categorized into contralateral pain and no-pain groups and contralateral surgery and no-surgery groups. Pain was defined with the modified Harris hip score. Univariate analysis tested group differences in demographics, radiographic measures, and range of motion. Kaplan-Meier survival analysis was used to assess pain development and surgery in the contralateral hip over time. Multivariable regression identified risk factors for contralateral pain and surgery. Contralateral pain and surgery predictors were secondarily assessed after categorization of the contralateral hips as dysplastic, borderline, and non-dysplastic and in subgroups based on the lateral center-edge angle (LCEA) and acetabular inclination (AI) in 5° increments. Results: One hundred and eighty-four patients were followed for a mean of 4.6 ± 1.6 years (range, 2.0 to 8.8 years), during which 51% (93) reported contralateral hip pain and 33% (60) underwent contralateral surgery. Kaplan-Meier analysis predicted 5-year survivorship of 49% with contralateral pain development as the end point and 66% with contralateral surgery as the end point. Painful hips exhibited more severe dysplasia compared with no-pain hips (LCEA = 16.5° versus 20.3°, p < 0.001; AI = 13.2° versus 10.0°, p < 0.001). AI was the sole predictor of pain, with every 1° increase in the AI raising the risk by 11%. Surgically treated hips also had more severe dysplasia (LCEA = 14.9° versus 20.0°, p < 0.001; AI = 14.7° versus 10.2°, p < 0.001) and were in younger patients (21.6 versus 24.1 years, p = 0.022). AI and a maximum alpha angle of ≥55° were predictors of contralateral surgery. Conclusions: At 5 years after hip PAO, approximately 50% of contralateral hips will have pain and approximately 35% can be expected to need surgery. More severe dysplasia, based on the LCEA and AI, increases the risk of contralateral hip pain and surgery, with AI being a predictor of both outcomes. Knowing these risks can inform patient counseling and treatment planning. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Comparing approaches for chemoprevention for school-based malaria control in Malawi: an open label, randomized, controlled clinical trial

School-age children in sub-Saharan Africa suffer an underappreciated burden of malaria which threatens their health and education. To address this problem, we compared the efficacy of two school-based chemoprevention approaches: giving all students intermittent preventive treatment (IPT) or screening and treating only students with detected infections (IST). In a three-arm, open-label, randomized, controlled trial (NCT05244954) in Malawi, 746 primary school students, aged 5-19 years, were individually randomized within each grade-level to IPT (n=249), IST with a high-sensitivity rapid diagnostic test (hs-RDT, n=248), or control (n=249). At six-week intervals three times within the peak malaria transmission season (February-June 2022) treatment with dihydroartemisinin-piperaquine (DP) was administered to girls <10 years and all boys, and chloroquine to older girls. The primary outcome was Plasmodium falciparum (Pf) infection detected by PCR 6-8 weeks after the final intervention. Secondary outcomes included anaemia, clinical malaria, and scores on tests of attention, literacy, and math. Analysis was by modified intention-to-treat. Outcomes analyses included 727 (97%) participants. At the end of the study, prevalence of Pf infection was 17% (41/243) in the IPT arm, 24% (58/244) in the IST arm, and 53% (127/240) in the control arm. Compared to controls, IPT and IST reduced the odds of Pf infection (IPT adjusted odds ratio [aOR]: 0.18 (95% CI: 0.11, 0.27); p<0.0001; IST aOR: 0.27 (95% CI: 0.18, 0.40); p<0.0001). However, only participants receiving IPT had a lower incidence of clinical malaria (0.19 cases per person per six months (95% CI: 0.14, 0.27) vs 0.56 (95% CI: 0.46, 0.68); incidence rate ratio: 0.38 (95% CI: 0.26, 0.55); p<0.0001)) and prevalence of anaemia (8% [20/243] vs 15% [36/240]; aOR: 0.49 (95% CI: 0.27, 0.91); p=0.023) compared to controls. Literacy scores were higher in both intervention arms. No between group differences in tests of attention or math or number of serious adverse events were found. Results support implementation of IST with hs-RDTs or IPT for reduction in the prevalence of infection. Based on reductions in clinical malaria, IPT may provide additional benefits warranting further consideration by school-based malaria chemoprevention programs. Doris Duke Charitable Foundation Clinical Scientist Development Award 2021191, U.S. NIH K24AI114996 & K23AI135076.

IDENTIFYING RISK FACTORS FOR DISEASE PROGRESSION IN DEVELOPMENTAL DYSPLASIA OF THE HIP USING A CONTRALATERAL HIP MODEL

Developmental dysplasia of the hip can cause pain and premature osteoarthritis. However, the risk factors and timing for disease progression in young adults are not fully defined. This study identified the incidence and risk factors for contralateral hip pain and surgery after periacetabular osteotomy (PAO) on an index dysplastic hip.Patients followed for 2+ years after unilateral PAO were grouped by eventual contralateral pain or no-pain, based on modified Harris Hip Score, and surgery or no-surgery. Univariate analysis tested group differences in demographics, radiographic measures, and range-of-motion. Kaplan-Meier survival analysis assessed pain development and contralateral hip surgery over time. Multivariate regression identified pain and surgery risk factors. Pain and surgery predictors were further analyzed in Dysplastic, Borderline, and Non-dysplastic subcategories, and in five-degree increments of lateral center edge angle (LCEA) and acetabular inclination (AI).184 patients were followed for 4.6±1.6 years, during which 51% (93/184) reported hip pain and 33% (60/184) underwent contralateral surgery. Kaplan-Meier analysis predicted 5-year survivorship of 49% for pain development and 66% for contralateral surgery. Painful hips exhibited more severe dysplasia than no-pain hips (LCEA 16.5º vs 20.3º, p&lt;0.001; AI 13.2º vs 10.0º p&lt;0.001). AI was the sole predictor of pain, with every 1° AI increase raising the risk by 11%. Surgical hips also had more severe dysplasia (LCEA 14.9º vs 20.0º, p&lt;0.001; AI 14.7º vs 10.2º p&lt;0.001) and were younger (21.6 vs 24.1 years, p=0.022). AI and a maximum alpha angle ≥55° predicted contralateral surgery.5 years after index hip PAO, 51% of contralateral hips experience pain and 34% percent are expected to need surgery. More severe dysplasia, based on LCEA and AI, increases the risk of contralateral hip pain and surgery, with AI being a predictor of both outcomes. Knowing these risks can inform patient counseling and treatment planning.

Sex Differences in Colonic Mucosal Microbiome of Irritable Bowel Syndrome Patients Compared to Healthy Controls.

Irritable bowel syndrome (IBS) is a female-predominant disorder of brain-gut interactions. Our previous study on colonic mucosal microbiota demonstrated significant differences between IBS bowel habit subtypes and showed that gut microbiota is associated with abdominal pain in IBS patients. However, there is no consensus on sex-related differences in mucosal microbiota in IBS compared to healthy controls (HC). We aimed to identify sex-related differences in the mucosal microbes associated with IBS. Sigmoid mucosal biopsies were obtained from 97 Rome+ IBS patients and 54 healthy controls (HC). Mucosal microbiome was characterized using 16S rRNA sequencing and analyzed and general linear models were used to test group differences between IBS diagnosis and sex. Sex-specific relationships between mucosal microbiome and IBS symptoms were assessed using sparse partial least squares (sPLS) regression. Beta diversity was significantly different between men and women overall (p=.03) but not within IBS or HC. IBS women showed lower abundance of Catenibacterium and Ruminoclstridium_9 and increased abundance of Bacteroides, Escherichia/Shigella, Lachnoclostridium and Ruminococcaceae compared to men with IBS (p<0.05). However, healthy women had a lower abundance of six distinct genera compared to healthy men. In women, higher IBS symptoms were associated with an increased abundance of bacteria including prevotella_9, and paraprevotella, however, in men, IBS symptoms were associated with increased abundances of genera such as Dialister. Interestingly, increased abundance of Desulfovibrio was associated with higher symptoms in women but lower symptoms in men. There are distinct sex-related differences in the mucosal microbiome between IBS and healthy participants supporting the importance of studying sex-specific mechanisms in IBS pathophysiology.

A Randomized Controlled Trial Testing the Effects of a Social Needs Navigation Intervention on Health Outcomes and Healthcare Utilization among Medicaid Members with Type 2 Diabetes.

Health systems are increasingly assessing and addressing social needs with referrals to community resources. The objective of this randomized controlled trial was to randomize adult Medicaid members with type 2 diabetes to receive usual care (n = 239) or social needs navigation (n = 234) for 6 months and compare HbA1c (primary outcome), quality of life (secondary outcome), and other exploratory outcomes with t-tests and mixed-effects regression. Eligible participants had an HbA1c test in claims in the past 120 days and reported 1+ social needs. Data were collected from November 2019 to July 2023. Surveys were completed at baseline and at 3-, 6-, and 12-month follow-up. Health plan data included care management records and medical and pharmacy claims. The sample was from Louisiana, USA, M = 51.6 (SD = 9.5) years old, 76.1% female, 66.5% Black, 29.4% White, and 3.0% Hispanic. By design, more navigation (91.5%) vs. usual care (6.7%) participants had a care plan. Social needs persisted for both groups. No group differences in HbA1c tests and values were observed, though the large amount of missing HbA1c lab values reduced statistical power. No group differences were observed for other outcomes. Proactively eliciting and attempting to provide referrals and resources for social needs did not demonstrate significant health benefits or decrease healthcare utilization in this sample.

Negative emotional eating patterns in general Chinese adults: A replication and expansion study examining group differences in eating disorder symptomatology, psychosocial impairment, and emotion regulation difficulties

Previous research identified four patterns of negative emotional eating in American and Chinese university students and proposed future directions (e.g., exploring potential differences in emotion regulation across patterns and replicating the patterns in a general, non-student population). Furthermore, prior research has not explored group differences in muscularity-oriented eating disorder symptomatology or psychosocial impairment. Therefore, the present study addressed these gaps in a sample of general Chinese adults, further testing group differences in typical and muscularity-oriented eating disorder symptomatology, psychosocial impairment, and emotion regulation difficulties across patterns of negative emotional eating. A total of 600 Chinese adults were recruited. Latent class analysis (LCA) was used. Results replicated the four patterns of negative emotional eating in previous research, including non-emotional eating (non-EE), emotional over- and under-eating (EOE-EUE), emotional over-eating (EOE), and emotional under-eating (EUE). Significant class differences were identified in eating disorder symptomatology, psychosocial impairment, and emotion regulation difficulties. Specifically, individuals with EOE and EOE-EUE patterns exhibited higher eating disorder symptomatology, higher psychosocial impairment, and more emotion regulation difficulties than those with non-EE and EUE patterns. Therefore, these two classes (i.e., EOE and EOE-EUE), especially the poorly researched EOE-EUE group, should be further examined to elucidate research and clinical applications. Furthermore, findings underscore the role of emotion regulation difficulties in further describing the differences across these negative emotional eating patterns, which can be considered in future interventions for reducing negative emotional eating.

Unrefreshing naps and sleep architecture during the multiple sleep latency test in idiopathic hypersomnia

SummaryPatients with idiopathic hypersomnia frequently report having unrefreshing naps. However, whether they have abnormal sleep architecture during naps that may explain their unrefreshing aspect is unknown. We compared sleep architecture during short daytime naps in patients with idiopathic hypersomnia reporting unrefreshing and refreshing naps. One‐hundred and thirty‐four patients tested with one‐night polysomnography, followed by an adapted version of the Multiple Sleep Latency Test with four naps, were included. They were asked about the refreshing aspect of their habitual naps during a clinical interview. They were classified as having objective (Multiple Sleep Latency Test ≤ 8 min) or subjective idiopathic hypersomnia (Multiple Sleep Latency Test &gt; 8 min), and as presenting refreshing or unrefreshing naps. We tested Group differences (refreshing versus unrefreshing naps) on nap sleep architecture in the whole sample and for subjective and objective idiopathic hypersomnia subgroups separately using ANCOVAs. No Group effects were observed in the Multiple Sleep Latency Test architecture in the whole sample and in objective and subjective idiopathic hypersomnia subgroups. This study provides preliminary evidence that reporting unrefreshing naps is not associated with clinically significant findings in Multiple Sleep Latency Test sleep architecture in patients with idiopathic hypersomnia. Given that naps taken by patients with idiopathic hypersomnia are typically long, future studies should investigate longer daytime sleep episodes.

Measuring self and informant perspectives of Restricted and Repetitive Behaviours (RRBs): psychometric evaluation of the Repetitive Behaviours Questionnaire-3 (RBQ-3) in adult clinical practice and research settings

BackgroundBrief questionnaires that comprehensively capture key restricted and repetitive behaviours (RRBs) across different informants have potential to support autism diagnostic services. We tested the psychometric properties of the 20-item Repetitive Behaviours Questionnaire-3 (RBQ-3), a questionnaire that includes self-report and informant-report versions enabling use across the lifespan.MethodIn Study 1, adults referred to a specialised adult autism diagnostic service (N = 110) completed the RBQ-3 self-report version, and a relative or long-term friend completed the RBQ-3 informant-report version. Clinicians completed the abbreviated version of the Diagnostic Interview for Social and Communication Disorders (DISCO-Abbreviated) with the same adults as part of the diagnostic process. For half of the assessments, clinicians were blind to the RBQ-3 ratings. We tested internal consistency, cross-informant reliability and convergent validity of the RBQ-3. In Study 2, a follow-up online study with autistic (N = 151) and non-autistic (N = 151) adults, we further tested internal consistency of the RBQ-3 self-report version. We also tested group differences and response patterns in this sample.ResultsStudy 1 showed good to excellent internal consistency for both self- and informant-report versions of the RBQ-3 (total score, α = 0.90, ω = 0.90, subscales, α = 0.76-0.89, ω = 0.77-0.88). Study 1 also showed cross-informant reliability as the RBQ-3 self-report scores significantly correlated with RBQ-3 informant-report scores for the total score (rs = 0.71) and subscales (rs= 0.69-0.72). Convergent validity was found for both self and informant versions of the RBQ-3, which significantly correlated with DISCO-Abbreviated RRB domain scores (rs = 0.45-0.54). Moreover, the RBQ-3 scores showed significantly weaker association with DISCO -Abbreviated scores for the Social Communication domain, demonstrating divergent validity. Importantly, these patterns of validity were found even when clinicians were blind to RBQ-3 items. In Study 2, for both autistic and non-autistic groups, internal consistency was found for the total score (α = 0.82-0.89, ω = 0.81-0.81) and for subscales (α = 0.68-0.85, ω = 0.69-0.85). A group difference was found between groups.LimitationsDue to the characteristics and scope of the specialist autism diagnostic service, further testing is needed to include representative samples of age (including children) and intellectual ability, and those with a non-autistic diagnostic outcome.ConclusionsThe RBQ-3 is a questionnaire of RRBs that can be used across the lifespan. The current study tested its psychometric properties with autistic adults without intellectual disability and supported its utility for both clinical diagnostic and research settings.

Protocol of the HARMONY study: A culturally relevant, randomized-controlled, stress management intervention to reduce cardiometabolic risk in African American women

BackgroundAfrican American Women (AAW) are at high risk for stress-related cardiometabolic (CM) conditions including obesity, heart disease, and diabetes. Prior interventions lack attention to culturally-nuanced stress phenomena (Superwoman Schema [SWS], contextualized stress, and network stress), which are positively and significantly associated with unhealthy eating and sedentary behavior. PurposeThe HARMONY Study is designed to test a culturally tailored mindfulness-based stress management intervention to address SWS, contextualized stress, and network stress as potential barriers to adherence to healthy exercise and eating goals. The study will help AAW build on their strengths to promote cardiometabolic health by enhancing positive reappraisal, self-regulation, and self-efficacy as protective factors against chronic stress-inducing biobehavioral morbidity and mortality risk. MethodsThis two-arm, randomized-controlled trial will test the effects of two group-based, online interventions. HARMONY 1 includes culturally-tailored exercise and nutrition education. HARMONY 2 includes mindfulness-based stress reduction, exercise, and nutrition education. We aim to recruit 200 AAW ≥ 18 years old with CM risk. ResultsPrimary outcomes (actigraphy and carotenoid levels) and secondary outcomes (body composition, inflammatory markers, glucose metabolism, and stress) are being collected at baseline and 4-, 8-, and 12-months post-intervention. Intent-to-treat, data analytic approaches will be used to test group differences for the primary outcomes. DiscussionThis study is the first to address culturally-nuanced stress phenomena in AAW (SWS, network stress, and contextualized stress) using culturally-tailored stress management, exercise, and nutrition educational approaches to reduce biobehavioral CM risk among AAW. Quantitative and qualitative results will inform the development of scalable and sustainable CM risk-reduction programming for AAW. Trial registrationThe Multiple PIs registered the clinical trial (Identifier: NCT04705779) and reporting of summary results in ClinicalTrials.gov in accordance with the NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information, within the required timelines.

Differential impact of prenatal PTSD symptoms and preconception trauma exposure on placental NR3C1 and FKBP5 methylation

Perinatal stress is associated with altered placental methylation, which plays a critical role in fetal development and infant outcomes. This proof-of-concept pilot study investigated the impact of lifetime trauma exposure and perinatal PTSD symptoms on epigenetic regulation of placenta glucocorticoid signaling genes (NR3C1 and FKBP5). Lifetime trauma exposure and PTSD symptoms during pregnancy were assessed in a racially/ethnically diverse sample of pregnant women (N = 198). Participants were categorized into three groups: (1) No Trauma (−T); (2) Trauma, No Symptoms (T − S); and (3) Trauma and Symptoms (T + S). Placental tissue was analyzed via bisulfite pyrosequencing for degree of methylation at the NR3C1 promoter and FKBP5 regulatory regions. Analyses of covariance were used to test group differences in percentages of NR3C1 and FKBP5 methylation overall and at each CpG site. We found a significant impact of PTSD symptoms on placental NR3C1 methylation. Compared to the −T group, the T + S group had greater NR3C1 methylation overall and at CpG6, CpG8, CpG9, and CpG13, but lower methylation at CpG5. The T + S group had significantly higher NR3C1 methylation overall and at CpG8 compared to the T − S group. There were no differences between the T − S group and − T group. Additionally, no group differences emerged for FKBP5 methylation. Pregnant trauma survivors with PTSD symptoms exhibited differential patterns of placental NR3C1 methylation compared to trauma survivors without PTSD symptoms and pregnant women unexposed to trauma. Results highlight the critical importance of interventions to address the mental health of pregnant trauma survivors.

Examining the Early Academic Performance of Doctor of Physical Therapy Students After Holistic Review: A Retrospective Cohort Study.

A diverse health care workforce can help to address systemic health disparities. Holistic review and use of an expanded definition of underrepresented minority (URM) that includes factors beyond race and ethnicity are suggested methods to promote diversity in the physical therapist (PT) workforce and ultimately address societal health disparities. Evidence suggests that holistic review can promote PT student diversity; however, limited evidence exists that describes the academic outcomes of holistic review that consider social determinants of learning (SDOL) factors in the review process. The purpose of this study was to examine the early academic outcomes of students after a holistic review and to examine relationships between SDOL factors and academic performance. A convenience sample of 160 students admitted to a doctor of physical therapy (DPT) program from June 2020 to June 2022 was used. A secondary analysis of students' self-reported responses from their admissions application was used to categorize response data into SDOL groups. An independent-sample t-test was used to test group differences in academic performance, and regression modeling was used to test relationships between SDOL factors and academic performance. The mean 6-month DPT program grade point average (GPA) of the sample was 3.32 ± .43. Nonstatistically significant differences appeared in early DPT GPA between URM and non-URM student groups. However, after controlling for undergraduate GPA, a history of educational disadvantage was the only SDOL factor that contributed to early DPT GPA variance (2.6%), P < .05. The similar academic performance of URM and non-URM students provides support for using an expanded URM definition in holistic review. Most of the educationally disadvantaged group were first-generation college students, which was associated with lower early GPA. These results provide emerging evidence that first-generation students in DPT programs may benefit from additional academic support.

The relationship between pathological brain activity and functional network connectivity in glioma patients

PurposeGlioma is associated with pathologically high (peri)tumoral brain activity, which relates to faster progression. Functional connectivity is disturbed locally and throughout the entire brain, associating with symptomatology. We, therefore, investigated how local activity and network measures relate to better understand how the intricate relationship between the tumor and the rest of the brain may impact disease and symptom progression.MethodsWe obtained magnetoencephalography in 84 de novo glioma patients and 61 matched healthy controls. The offset of the power spectrum, a proxy of neuronal activity, was calculated for 210 cortical regions. We calculated patients’ regional deviations in delta, theta and lower alpha network connectivity as compared to controls, using two network measures: clustering coefficient (local connectivity) and eigenvector centrality (integrative connectivity). We then tested group differences in activity and connectivity between (peri)tumoral, contralateral homologue regions, and the rest of the brain. We also correlated regional offset to connectivity.ResultsAs expected, patients’ (peri)tumoral activity was pathologically high, and patients showed higher clustering and lower centrality than controls. At the group-level, regionally high activity related to high clustering in controls and patients alike. However, within-patient analyses revealed negative associations between regional deviations in brain activity and clustering, such that pathologically high activity coincided with low network clustering, while regions with ‘normal’ activity levels showed high network clustering.ConclusionOur results indicate that pathological activity and connectivity co-localize in a complex manner in glioma. This insight is relevant to our understanding of disease progression and cognitive symptomatology.

RACIAL/ETHNIC DIFFERENCES IN NEUROCOGNITIVE PROFILES OF OLDER ADULTS WITH 6-YEAR INCIDENT DEMENTIA

Abstract Hispanic and non-Hispanic Black (NHB) older adults have higher dementia rates than non-Hispanic Whites (NHWs). Estimates of dementia prevalence and incidence in community-based cohorts are mostly based on threshold value performance on cognitive assessment batteries. We used longitudinal data from the HRS Harmonized Cognitive Assessment Protocol (HCAP) to (1) generate and compare, across race/ethnicity, neurocognitive profiles for older adults (&amp;gt;65 years) not meeting research criteria for dementia in 2010 and developing dementia by 2016 (using Langa-Weir’s dementia classification), (2) assess racial/ethnic differences in these profiles, and (3) test socio-demographic effects on dementia-specific differences in neurocognitive performance. Performance on all HCAP measures was highly sensitive to 6-year incident dementia classification. However, we found notable domain-specific differences in test sensitivity, whereby performance on general screeners (e.g., MMSE) and memory-based tests (e.g., CERAD word list recognition) were significantly lower (≤2 SDs from normed population means). Hispanics and NHBs generally performed lower than NHWs, with more pronounced group differences in general screeners and executive function tests. Sociodemographic characteristics significantly attenuated Hispanic differences, but less so for NHBs, relative to NHWs. Despite these group differences, NHWs with incident dementia had worse neurocognitive profiles than their NHB and Hispanic counterparts. Dementia classification algorithms (e.g., Langa-Weir) sensitively detect cognitive impairment. However, these algorithms more accurately identify higher severity cognitive impairment in NHWs compared to NHBs and Hispanics. Such methods can yield dementia estimates biased by sociocultural factors. Further research is needed to identify culturally appropriate neurocognitive tests that enhance precise dementia diagnosis, using population-level epidemiological data.

DOES INTERNET USE PROMOTE OLDER ADULTS’ SELF-PERCEPTION OF AGING: SEPARATING WITHIN- AND BETWEEN-PERSON EFFECTS

Abstract Previous longitudinal studies indicate a positive causal association between older adults’ Internet use and self-perception of aging (SPA). However, it is unclear whether this positive effect is truly due to the lagged within-person changes in Internet use or due to some stable, trait-like between-person differences. Thus, with between-person differences controlled, this study aimed to 1) examine reciprocal associations of within-person SPA and Internet use and 2) investigate the potential age, gender, race/ethnicity, and education group differences. Data used in this study were from the Health and Retirement Study (T1: 2008; T2: 2012; T3: 2016). Older adults aged 65 and older with normal cognition were included in the analysis (n = 6,666). Random-intercept cross-lagged panel models (RI-CLPM) were applied to separate the within- and between-person effects regarding the associations between SPA and Internet use. Multiple-group analyses were used for testing group differences. Results showed positive carry-over stability of both Internet use and SPA across time. At the within-person level, only one cross-lagged path, Internet use (T1) ♢ SPA (T2), was significant (b = .08, p &amp;lt; .05), indicating that the within-person Internet use change was predictive of within-person SPA change at T2. At the between-person level, SPA and ICT use were positively correlated (r = .16, p &amp;lt; .001). No group differences were identified. This study indicates that the positive effects of Internet use on SPA may be largely due to between-person differences. Internet use may promote SPA to some extent, but effects may plateau after a certain period of time.

Reduced GABA concentration in patients with white matter hyperintensities.

To investigate potential alterations of white matter hyperintensities (WMHs) on J-edited MR spectroscopy (MRS) measures of the primary inhibitory neurotransmitter γ-aminobutyric acid (GABA). Twenty-four WMHs patients and 20 healthy controls (HCs) were recruited to undergo magnetic resonance spectroscopy (MRS) scan at 3T from voxels in left centrum semiovale white matter, using the MEGA point resolved spectroscopy (MEGA-PRESS) technique with the MATLAB-based Gannet tool to estimate GABA+ co-edited macromolecule (GABA+) levels and using Tarquin software to estimate levels of glutamate + glutamine (Glx), total N-acetylaspartate (tNAA), total choline (tCho), and total creatine (tCr). Independent t-tests or Mann-Whitney U-tests were used to test group differences between WMHs and HCs. Additionally, WMHs patients were divided into mild and moderate-severe WMHs subgroup according to the Fazekas scale. Analysis of variance (ANOVA) and post-hoc tests were used among WMHs subgroups and HCs. We found there was a significant reduction in GABA+ levels (p = 0.018) in WMHs patients compared with healthy controls. In subgroup analyses, there was also a significant reduction of GABA+ levels in moderate-severe WMHs subgroup (p = 0.037) and mild WMHs subgroup (p = 0.047) when compared to HCs. Besides, the moderate-severe WMHs subgroup had significantly higher levels of tCho compared with healthy controls (p = 0.019). In conclusion, reduced GABA+ levels in WMHs patients and elevated tCho levels in moderate-severe WMHs were observed when compared with HCs. These results demonstrate that abnormalities of the GABAergic system and choline metabolism may contribute to the pathogenesis of WMHs.

Synaptic dysfunction, Tau pathology and Neurodegeneration

AbstractBackgroundTau plays a prominent role in the synapse and has been shown to be closely related to neurodegeneration. Recent evidence show that cerebrospinal fluid (CSF) synaptic markers are related to CSF tau and degeneration. However, it is not clear whether synaptic dysfunction in combination with tau tangles is associated with neurodegeneration in the same brain regions. Our study aims to map in the brain the association of synaptic markers with tau and degeneration.MethodWe evaluated 147 individuals from the TRIAD cohort with CSF GAP43, SYT1, SNAP25, neurogranin (Ng), ptau217, neurofilament light protein (NfL) quantification, as well as tau positron emission tomography (PET), magnetic resonance imaging, and clinical assessments. One‐way ANOVA tested group differences on synaptic levels. Spearman correlation tested the association among synaptic proteins. Linear regressions tested the association between biomarkers. Voxel‐based morphometry (VBM) was considered as an index of neurodegeneration.ResultWe observed an increase in synaptic markers across age and the AD spectrum, reaching a plateau when cognition is affected (Figure 1A). Among the synaptic markers, SNAP25 showed the greatest magnitude of change, on average, between young, aged cognitively unimpaired, mild cognitive impaired, and AD individuals (mean 62.44%). (Figure 1B‐C). In addition, we found that all synaptic markers are significantly intercorrelated (Figure 1D). Moreover, CSF ptau217 correlated with all synaptic biomarkers, GAP43 (β = ‐044), SYT1 (β = ‐0.41), SNAP25 (β = ‐0.59) and Ng (β = ‐0.25). Conversely, CSF NfL was strongly but only correlated with GAP43 (β = 0.62) (Figure 2). Voxel‐wise correlation revealed that tau tangles measured by [18F]‐MK6240 PET, was positively associated with SNAP25 in AD‐related regions, and VBM was associated with all synaptic markers, but more closely with GAP43. Furthermore, the interaction between synaptic markers and temporal meta‐ROI [18F]‐MK6240 on VBM was significant for Ng and GAP43 (Figure 3).ConclusionOur results support a heterogenous role of synaptic markers in the AD continuum and suggest that synaptic dysfunction in the presence of tau pathology may not be driving atrophy.

A multivariate MRI model of Alzheimer’s disease risk is associated with clinical diagnosis, PET imaging, and plasma biomarkers in a mixed dementia sample

AbstractBackgroundWe sought to validate two structural MRI‐based brain health models: Spatial Pattern of Atrophy for REcognition of Alzheimer’s disease (SPARE‐AD) and SPARE‐Brain Age Gap (SPARE‐BAG), which estimates the discrepancy between biological brain age and chronological age. These models' generalization to non‐amnestic AD (naAD) syndromes and associations with positron emission tomography (PET) and plasma biomarkers remain underinvestigated. We hypothesized that SPARE‐AD scores in naAD would be lower (less abnormal) than in amnestic AD (aAD) but elevated (more abnormal) relative to controls; and that SPARE‐AD but not SPARE‐BAG scores would be associated with PET and plasma biomarkers of AD.MethodSPARE‐AD and SPARE‐BAG scores were estimated for each of 1607 MRI scans from 277 cognitively normal adults (62.8% female; mean age = 69.5 years) and 902 clinical participants (54.2% female; mean age = 73.1 years), including 585 with amnestic mild cognitive impairment (aMCI) or aAD; 56 with naAD syndromes; 28 with vascular disease; 28 with Lewy body disorders (LBD); 18 with suspected frontotemporal lobar degeneration (FTLD); 56 with non‐amnestic MCI of uncertain etiology; and 131 with other clinical diagnoses. We used mixed effects models adjusting for age, sex, and global cognition to test group differences in SPARE‐AD and SPARE‐BAG. Additionally, we assessed associations with tau (n = 122) and amyloid‐beta (n = 199) PET imaging and plasma‐based phosphorylated tau‐181 (p‐tau181) and glial fibrillary acidic protein (GFAP) (n = 358).ResultSPARE‐AD scores were elevated vs. controls in aMCI/aAD, naAD, vascular disease, FTLD, and naMCI (all p&lt;0.003) but not in LBD or other diagnoses (p&gt;0.1). NaAD patients had lower SPARE‐AD (p&lt;0.02) but higher SPARE‐BAG scores (p&lt;0.02) than aMCI/aAD patients. SPARE‐AD scores were positively associated with mean cortical tau PET uptake, amyloid PET positivity, and plasma p‐tau181 and GFAP (all p&lt;0.001). In contrast, SPARE‐BAG scores were not associated with PET or plasma biomarkers (all p&gt;0.05).ConclusionSPARE‐AD values for naAD syndromes were intermediate between those of controls and aMCI/AD patients, likely reflecting divergent, partially overlapping cortical atrophy relative to aAD. PET and plasma biomarkers of AD neuropathologic change were associated with SPARE‐AD but not with SPARE‐BAG scores, suggesting SPARE‐BAG reflects age‐related atrophy that is largely independent of AD.

Synaptic dysfunction in the presence of tau tangles is not a strong predictor of atrophy

AbstractBackgroundTau plays a prominent role in the synapse and has been shown to be closely related to neurodegeneration. Recent evidence show that cerebrospinal fluid (CSF) synaptic markers are related to CSF tau and degeneration. However, it is not clear whether synaptic dysfunction in combination with tau tangles is associated with neurodegeneration in the same brain regions. Our study aims to map in the brain the association of synaptic markers with tau and degeneration.MethodWe evaluated 147 individuals from the TRIAD cohort with CSF GAP43, SYT1, SNAP25, neurogranin (Ng), ptau217, neurofilament light protein (NfL) quantification, as well as tau positron emission tomography (PET), magnetic resonance imaging, and clinical assessments. One‐way ANOVA tested group differences on synaptic levels. Spearman correlation tested the association among synaptic proteins. Linear regressions tested the association between biomarkers. Voxel‐based morphometry (VBM) was considered as an index of neurodegeneration.ResultWe observed an increase in synaptic markers across age and the AD spectrum, reaching a plateau when cognition is affected (Figure 1A). Among the synaptic markers, SNAP25 showed the greatest magnitude of change, on average, between young, aged cognitively unimpaired, mild cognitive impaired, and AD individuals (mean 62.44%). (Figure 1B‐C). In addition, we found that all synaptic markers are significantly intercorrelated (Figure 1D). Moreover, CSF ptau217 correlated with all synaptic biomarkers, GAP43 (ß = ‐044), SYT1 (ß = ‐0.41), SNAP25 (ß = ‐0.59) and Ng (ß = ‐0.25). Conversely, CSF NfL was strongly but only correlated with GAP43 (ß = 0.62) (Figure 2). Voxel‐wise correlation revealed that tau tangles measured by [18F]‐MK6240 PET, was positively associated with SNAP25 in AD‐related regions, and VBM was associated with all synaptic markers, but more closely with GAP43. Furthermore, the interaction between synaptic markers and temporal meta‐ROI [18F]‐MK6240 on VBM was significant for Ng and GAP43 (Figure 3).ConclusionOur results support a heterogenous role of synaptic markers in the AD continuum and suggest that synaptic dysfunction in the presence of tau pathology may not be driving atrophy.

Are There Racial Differences in the Rate of Surgical Site Infection Based on Surgical Subspecialty?

Background: Surgical site infection (SSI) is a common, morbid post-operative complication. We hypothesized the presence of racial differences in SSI rates, comparing black/African American (BAA) to white non-Hispanic (WNH) patients. Patients and Methods: Using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database (2017), BAA and WNH surgery patients across 10 surgical specialties were identified: general surgery (GS), vascular surgery (VS), cardiac surgery (CS), thoracic surgery (TS), orthopedics (OS), neurosurgery (NS), urology (US), otolaryngology (ENT), plastic surgery (PS), and gynecology (GYN). The primary outcome was SSI rate (superficial, deep incisional, or organ/space). The secondary outcome was rate of non-surgical infection. Pearson χ2 and Fisher exact tests were used to test group differences of categorical variables. Continuous variables were tested with the Student t-test, or Mann-Whitney U test, with statistical significance set at a value of p < 0.05. Multivariable logistic regression models were conducted to analyze the association between race/ethnicity and the infection outcomes. Results: A total of 740,144 patients were included: 99,425 (13.4%) BAA and 640,749 (86.6%) WNH, distributed as follows; 32,2976 GS, 17,6175 OS, 44,383 VS, 2,227 CS, 9,645 TS, 42,298 NS, 42,726 US, 18,518 ENT, 20,709 PS, and 60,517 GYN cases. Surgical site infection rates were higher among WNH in GS (4.4% vs. 4.1%; p = 0.003) and TS (3.1% vs. 1.7%; p = 0.015); lower in VS (3.2% vs. 4.4%; p < 0.001), OS (1.2% vs.1.6%; p < 0.001), and GYN (2.4% vs. 3%; p < 0.001); and similar between WNH and BAA in ENT (1.8% vs 1.8%; p = 0.76), and US (1.9% vs. 1.9%; p = 0.90). Non-surgical infection was higher in BAA in NS (3.2% vs. 2.5%; p = 0.003), and higher in WNH in GYN (2.6% vs. 2%; p < 0.001), OS (1.7% vs. 1.1%; p < 0.001), US (4.4% vs. 3.6%; p = 0.014), and VS (3.4% vs. 2.6%; p < 0.001). Conclusions: Variation exists in SSI rates between WNH and BAA patients among surgical subspecialties. Further research is required to understand these differences and address racial disparities in outcomes.

Variation and covariation of external shape and cross-sectional geometry in the human metacarpus.

Analyses of external bone shape using geometric morphometrics (GM) and cross-sectional geometry (CSG) are frequently employed to investigate bone structural variation and reconstruct activity in the past. However, the association between these methods has not been thoroughly investigated. Here, we analyze whole bone shape and CSG variation of metacarpals 1-5 and test covariation between them. We analyzed external metacarpal shape using GM and CSG of the diaphysis at three locations in metacarpals 1-5. The study sample includes three modern human groups: crew from the shipwrecked Mary Rose (n = 35 metacarpals), a Pre-industrial group (n = 50), and a Post-industrial group (n = 31). We tested group differences in metacarpal shape and CSG, as well as correlations between these two aspects of metacarpal bone structure. GM analysis demonstrated metacarpus external shape variation is predominately related to changes in diaphyseal width and articular surface size. Differences in external shape were found between the non-pollical metacarpals of the Mary Rose and Pre-industrial groups and between the third metacarpals of the Pre- and Post-industrial groups. CSG results suggest the Mary Rose and Post-industrial groups have stronger metacarpals than the Pre-industrial group. Correlating CSG and external shape showed significant relationships between increasing external robusticity and biomechanical strength across non-pollical metacarpals (r: 0.815-0.535; p ≤ 0.05). Differences in metacarpal cortical structure and external shape between human groups suggest differences in the type and frequency of manual activities. Combining these results with studies of entheses and kinematics of the hand will improve reconstructions of manual behavior in the past.