Linear Mixed-effects Regression Analysis Research Articles

#500 Monitoring relative blood volume and calf bioimpedance in hemodialysis patients

Abstract Background and Aims Measurements of relative blood volume (RBV, %) are used to monitor the relative change in blood plasm during hemodialysis (HD). Continuous measurement of calf extracellular volume (cECV) during HD allows the calculation of relative change in cECV (RCE). RCE was defined as the ratio of cECV to its initial value, cECV0 (RCE = 100 × cECV/cECV0, %). The aim of our study was to investigate the relationship between RBV, RCE and the occurrence of intradialytic hypotension (IDH). Method Fifty-five HD patients were studied. We reduced the HD target weight stepwise by 0.1 to 0.2 kg per HD session until clinically defined IDH symptoms occurred. RBV was monitored using the blood volume monitor (BVM, Fresenius Medical Care, Germany). Whole body bioimpedance spectroscopy (wBIS) provided whole body ECV (wECV) and intracellular volume (wICV) pre and post HD. Continuous calf bioimpedance (Hydra 4200, Xitron Technologies, San Diego, CA USA) provided cECV during HD. Pre HD overhydration (OH) was calculated according to whole body composition model (Chamney et al, Am J Clin Nutr 2007; 85:80). Total number of HD sessions in all patients were divided into three groups according to the pre HD OH: 1) normal OH (NOH, OH < 1 L), 2) moderate OH (MOH, 1 ≤ OH < 4 L) and 3) severe OH (SOH, OH ≥ 4 L). Furthermore, patients were stratified by the presence or absence of IDH in each hydration group. Ultrafiltration rate (UFR), pre HD body weight, body mass index (BMI) were measured. Minimal RBV (RBVMin) and minimal RCE (RCEMin) in each HD session were recorded. These measures represent maximum reduction of fluid in the intravascular and interstitial spaces, respectively. Reducing cECV can be considered as refilling fluid from interstitial transferring to intravascular space driving by ultrafiltration. The difference between RCEMin and RBVMin was defined as vascular refilling capacity. Linear mixed-effect logistic regression (LMELR) analysis was applied to explore relationships between IDH with RBVMin, RCEMin, wECV and BMI. Results We studied 621 HD sessions in 55 patients. MOH was present in 57%, SOH in 22% and NOH in 21% of total number of HD sessions respectively. There were significant differences in age, UFR, RBVMin, RCEMin, pre HD wECV, BMI between three groups, while the IDH rate did not differ significantly (Table 1). RBVMin was inversely correlated with UFR (Fig. 1) in all measurements. Pre HD wECV was the only factor associated with IDH in overall measurement. Pre HD wECV was significantly lower in IDH than in non-IDH patients in the NOH group (Fig. 2). In the MOH group, UFR and RCEMin-RBVMin were higher in IDH than in non-IDH patients (Fig. 3a and Fig. 3b). In the SOH group, Pre HD OH is the major factor associated with IDH (Fig. 4). Conclusion This study found that the major factors leading to IDH are 1) lower hydration status; 2) relative higher UFR; and 3) the limited refilling capacity. RBVMin correlated with UFR, but it did not predict IDH. Combined analysis of RBV and calf bioimpedance may provide a means to quantitate the fluid transport between intravascular and interstitial compartments and could add to an early IDH warning system.

What relationships exist between nouns and verbs and the use of prepositions, adverbs, and adjectives in children and adolescents who use speech generating devices?

The relationships between the use of nouns and verbs, and other word classes have been well established in the typical language development literature. However, questions remain as to whether the same relationships are seen in the language use of individuals who use graphic symbol-based augmentative and alternative communication (AAC). The aim of the study was to examine relationships between the use of verbs and nouns, and the use of prepositions, adverbs, and adjectives through a secondary analysis of language transcripts taken from 12 children and adolescents who used aided AAC in conversation with an adult. A series of multiple linear mixed-effect regression analyses showed a positive predictive association between the use of verbs and the use of prepositions and adverbs, as well as a positive predictive relationship between the use of nouns and the use of adjectives. The theoretical and practical implications of these findings are discussed.

Resilience in the first year of surviving a stroke in Nigeria

Objectives There is a knowledge gap on resilience and its impact on mental health of Africans who survive a stroke. We describe the trajectory of psychological resilience and its association with depression and quality of life (QoL) across the first poststroke year in Nigeria. Method Prospective observational study of 150 survivors of a first ever stroke. Resilience was ascertained at 3 time-points prospectively over 12 months using the 25-items Resilience Scale (RS). Depression and QoL were also assessed at baseline and follow-up, respectively using the centre for epidemiologic studies depression scale (CES-D 10) and health related quality of life in stroke patients (HRQOLISP-26). Associations were investigated using regression models and presented as adjusted odds ratios (OR) and Wald test coefficients within 95% confidence intervals (CI). Results Resilience improved across time points of measurement (p < 0.001). In multivariate logistic regression analyses adjusted for the effect of age, education, alcohol use, and hypertension, higher resilience was associated with male sex (OR = 5.3, 95% CI= 1.7, 17.2), younger age (OR = 4.8, 95% CI = 1.5,15.7), and baseline hypertension (OR= 0.2, 95% CI ≤ 0.1,0.8). In similarly adjusted mixed effect linear regression analyses, higher resilience was associated with improvement in depression (months 12= −4.2, 95% CI= −5.6, −2.8) and quality of life (months twelve = 5.2, 95% CI = 2.2, 8.2) overtime. Conclusion Resilience, which was associated with better mental health and wellbeing of stroke survivors, was less likely with hypertension. Results suggest an important role for control of vascular risk factors as part of resilience interventions to promote poststroke recovery.

Glycemic control in children with type 1 diabetes: Insulin pump therapy versus multiple daily injections

While many studies compared multiple daily injections (MDI) and insulin pump therapy on various clinical outcomes, the results remain inconclusive. This multicenter retrospective cohort study included 175 patients and aimed to evaluate the effects of different insulin therapy methods on various clinical outcomes, including hemoglobin A1c (HbA1c), total daily insulin dosage, body mass index, glomerular filtration rate, in pediatric patients with type 1 diabetes. In a linear mixed-effects regression analysis, a statistically significant interaction between time and treatment type on HbA1c was found. It suggested significantly higher reduction of HbA1c values between 12-month visit and baseline in the group receiving MDIs compared to insulin pump therapy. Patients using MDIs observed higher reduction of HbA1c levels and lower total daily insulin dose relative to insulin pump therapy group. Other changes of clinical indicators were the same for group of patients. Various studies report controversial results on long term effects of these treatments on HbA1c values necessitating large population-based cohort studies in this field.

Associations between school-based fluoride mouth-rinse program, medical-dental expense subsidy policy, and children's oral health in Japan: an ecological study.

Dental caries are a common non-communicable disease among children. As a public health measure at the prefectural level, school-based fluoride mouth-rinse (S-FMR) program, medical/dental expense subsidy policies, and other factors may reduce the incidence of dental caries and tooth loss. Prefectures focusing on promoting oral health policies may promote both, but the interaction effect of implementing both subsidy policies and S-FMR at the prefectural level on caries prevention has not yet been examined. We conducted an ecological study using two-wave panel data, prefecture-level aggregated data in Japan for 2016 and 2018. Coefficient and 95% confidence intervals (CI) were calculated for the dependent variables for oral health using mixed-effects linear regression analysis adjusted for possible confounders. Two dependent variables were used; the standardized claim ratio (SCR) of deciduous tooth extraction and 12-year-olds' decayed, missing, or filled permanent teeth (DMFT). Four independent variables were S-FMR, the SCR of dental sealants, prefectural income per person, and subsidy policy in three models: co-payment until children enter elementary school (n = 23), no co-payment until children enter elementary school (n = 7), and co-payment continuing beyond elementary school (n = 17). The effects of six interaction terms, each representing a unique pairing from the four independent variables, were individually calculated. S-FMR was negatively associated with the SCR of deciduous tooth extractions and DMFT (coefficient = -0.11, 95% CI -0.20; -0.01 and coefficient = -0.003, 95% CI -0.005; -0.001, respectively). No co-payment until children enter elementary school was positively associated with the SCR of deciduous tooth extraction compared to co-payment until children enter elementary school(coefficient = 11.42, 95% CI 3.29; 19.55). SCR of dental sealants was positively associated with the SCR of deciduous tooth extractions (coefficient = 0.12, 95% CI 0.06; 0.19) but negatively associated with DMFT (coefficient = -0.001, 95% CI -0.003; -0.0001). Per capita prefectural income was positively associated with the SCR of deciduous tooth extractions(coefficient = 0.01, 95% CI 0.001; 0.02). No interaction was found between S-FMR and the subsidy policy at both outcomes. High S-FMR utilization and no co-payment until children enter elementary school were associated with fewer deciduous tooth extractions. Also, S-FMR and dental sealant were associated with decreased DMFT.

No Effect of Serum Electrolyte Levels on Electroconvulsive Therapy Seizure Quality Parameters.

Seizure quality is considered to be associated with treatment outcomes of electroconvulsive therapy (ECT). A wide range of treatment parameters and patient characteristics are known to influence seizure quality. However, conflicting results exist for the role of serum electrolyte levels and seizure quality. We retrospectively analyzed a total of 454 patients and a total of 2119 individual acute ECT sessions irrespective of diagnosis where a clinical evaluation of serum levels of sodium, potassium, and calcium took place routinely up to 2 days before the ECT session. To assess the impact of serum electrolyte levels on seizure quality parameters, we used mixed-effects linear regression analysis with Bonferroni correction for multiple testing. Serum sodium, potassium, and calcium levels were not associated with seizure quality markers after correcting the significance level for multiple testing. Younger age was consistently associated with higher postictal suppression, interhemispheric coherence, midictal amplitude, and peak heart rate. Lower dose was consistently associated with longer electroencephalogram and motor seizure duration. Our results suggest that there is no clinically relevant effect of serum electrolyte levels on seizure quality, at least within clinically commonly observed ranges of serum electrolyte concentrations.

Impact of motor task conditions on end-point kinematics and trunk movements during goal-directed arm reach

Task conditions significantly impact human motor control. We investigated how task type, difficulty, and constraints influence the kinematics of goal-directed arm reaching. Non-disabled young adults performed two distinct goal-directed arm reaching tasks: pointing and picking up an object with chopsticks. These tasks were carried out under various conditions, including constrained and unconstrained elbow extension and two different task difficulties. We collected kinematic data using a 3-D motion capture system and analyzed the effects of different task conditions on kinematic variables using linear mixed-effects regression analysis. Our findings revealed statistically significant differences in kinematics between the two tasks. Arm reaching during the picking-up task was slower and exhibited jerkier movements compared to the pointing task. Additionally, when arm reaching was performed with constrained elbow extension, it led to slower and jerkier movements, with an increased involvement of trunk movements compared to the unconstrained condition. These findings show that complex manipulative motor tasks requiring higher hand dexterity necessitate feedback-based control of arm reaching, but simple pointing tasks requiring less hand dexterity do not. In conclusion, our study sheds light on the influence of task conditions on goal-directed arm reaching kinematics and provides valuable insights into the motor control strategies involved in different tasks.

Revised Temperament and Character Inventory factors predict neuropsychiatric symptoms and aging-related cognitive decline across 25 years.

Personality traits and neuropsychiatric symptoms such as neuroticism and depression share genetic overlap and have both been identified as risks factors for development of aging-related neurocognitive decline and Alzheimer's disease (AD). This study aimed to examine revised personality factors derived from the Temperament and Character Inventory, previously shown to be associated with psychiatric disorders, as predictors of neuropsychiatric, cognitive, and brain trajectories of participants from a population-based aging study. Mixed-effect linear regression analyses were conducted on data for the full sample (Nmax = 1,286), and a healthy subsample not converting to AD-dementia during 25-year follow-up (Nmax = 1,145), complemented with Cox proportional regression models to determine risk factors for conversion to clinical AD. Two personality factors, Closeness to Experience (CE: avoidance of new stimuli, high anxiety, pessimistic anticipation, low reward seeking) and Tendence to Liabilities (TL: inability to change, low autonomy, unaware of the value of their existence) were associated with higher levels of depressive symptoms, stress (CE), sleep disturbance (TL), as well as greater decline in memory, vocabulary and verbal fluency in the full sample. Higher CE was additionally associated with greater memory decline across 25 years in the healthy subsample, and faster right hippocampal volume reduction across 8 years in a neuroimaging subsample (N = 216). Most, but not all, personality-cognition associations persisted after controlling for diabetes, hypertension and cardiovascular disease. Concerning risks for conversion to AD, higher age, and APOE-ε4, but none of the personality measures, were significant predictors. The results indicate that personality traits associated with psychiatric symptoms predict accelerated age-related neurocognitive declines even in the absence of neurodegenerative disease. The attenuation of some personality effects on cognition after adjustment for health indicators suggests that those effects may be partly mediated by somatic health. Taken together, the results further emphasize the importance of personality traits in neurocognitive aging and underscore the need for an integrative (biopsychosocial) perspective of normal and pathological age-related cognitive decline.

The DizzyQuest Combined with Accelerometry: Daily Physical Activities and Limitations among Patients with Bilateral Vestibulopathy Due to DFNA9.

DFNA9 is a genetic disease of the inner ear, causing progressive bilateral sensorineural deafness and bilateral vestibulopathy (BV). In this study, DizzyQuest, a mobile vestibular diary, and the MOX accelerometer were combined to assess the daily life functional limitations and physical activity of patients with DFNA9 suffering from BV. These parameters might be appropriate as potential candidacy criteria and outcome measures for new therapeutic interventions for BV. Fifteen DFNA9 patients with BV and twelve age-matched healthy controls were included. The DizzyQuest was applied for six consecutive days, which assessed the participants' extent of functional limitations, tiredness, types of activities performed during the day, and type of activity during which the participant felt most limited. The MOX accelerometer was worn during the same six days of DizzyQuest use, measuring the participants intensity and type of physical activity. Mixed-effects linear and logistic regression analyses were performed to compare the DFNA9 patients and control group. DFNA9 patients with BV felt significantly more limited in activities during the day compared to the age-matched controls, especially in social participation (p < 0.005). However, these reported limitations did not cause adjustment in the types of activities and did not reduce the intensity or type of physical activity measured with accelerometry. In addition, no relationships were found between self-reported functional limitations and physical activity. This study demonstrated that self-reported functional limitations are significantly higher among DFNA9 patients with BV. As a result, these limitations might be considered as part of the candidacy criteria or outcome measures for therapeutic interventions. In addition, the intensity or type of physical activity performed during the day need to be addressed more specifically in future research.

The impact of parental overprotection on the emotions and behaviors of pediatric hematologic cancer patients: a multicenter cross-sectional study.

Parental overprotection may have an impact on children's emotional and behavioral problems (EBPs). As pediatric hematologic cancer patients have compromised immune systems, parents of such children often worry excessively, interfering with their daily lives. Therefore, avoiding overprotection is crucial for the overall physical and mental health of pediatric hematologic cancer patients. The aim of this study was to examine the current status of EBPs in pediatric hematologic cancer patients and analyze their associated risk factors. This work was a multicenter cross-sectional observational and correlational study. We collected data anonymously through parental questionnaires from three pediatric hematologic oncology hospitals in China. The Strengths and Difficulties Questionnaire, the Parental Overprotection Measure (POM) scale, and a general information survey designed by the research team were employed to assess children's EBPs, the degree of parental overprotection, as well as basic demographic and disease-related information. Chi-square tests and generalized linear mixed-effects regression analysis were used to analyze the factors influencing EBPs among the pediatric hematologic cancer patients. Using a convenience sampling method, a total of 202 participants' parents were selected. All participants were invited to complete the questionnaire through one-on-one guidance. Emotional symptoms accounted for the highest proportion of abnormal EBPs in children (27.72%), followed by peer problems (26.24%), prosocial behavior (25.74%), behavioral problems (14.36%), and total difficulties (13.86%). A minority of children had abnormal hyperactivity scores (4.95%). The results of a generalized linear mixed regression analysis showed that age, duration of illness, and parental overprotection were significant factors influencing abnormal EBPs in children (p < 0.05). A POM score threshold of 37 exhibited good sensitivity (74%) and specificity (90%) in predicting abnormal EBPs in children. Pediatric hematologic cancer patients under excessive parental protection are more prone to experiencing EBPs. Healthcare professionals should guide parents to reduce this excessive protection, thus mitigating the occurrence of EBPs in children.

Implementation and engagement of the SMART Work & Life sitting reduction intervention: an exploratory analysis on intervention effectiveness

BackgroundTo enhance the impact of interventions, it is important to understand how intervention engagement relates to study outcomes. We report on the level of implementation and engagement with the SMART Work & Life (SWAL) programme (delivered with (SWAL plus desk) and without a height-adjustable desk (SWAL)) and explore the effects of different levels of this on change in daily sitting time in comparison to the control group.MethodsThe extent of intervention delivery by workplace champions and the extent of engagement by champions and participants (staff) with each intervention activity was assessed by training attendance logs, workplace champion withdrawal dates, intervention activities logs and questionnaires. These data were used to assess whether a cluster met defined criteria for low, medium, or high implementation and engagement or none of these. Mixed effects linear regression analyses tested whether change in sitting time varied by: (i) the number of intervention activities implemented and engaged with, and (ii) the percentage of implementation and engagement with all intervention strategies.ResultsWorkplace champions were recruited for all clusters, with 51/52 (98%) attending training. Overall, 12/27 (44.4%) SWAL and 9/25 (36.0%) SWAL plus desk clusters implemented all main intervention strategies. Across remaining clusters, the level of intervention implementation varied. Those in the SWAL (n = 8 (29.6%) clusters, 80 (32.1%) participants) and SWAL plus desk (n = 5 (20.0%) clusters, 41 (17.1%) participants) intervention groups who implemented and engaged with the most intervention strategies and had the highest percentage of cluster implementation and engagement with all intervention strategies sat for 30.9 (95% CI -53.9 to -7.9, p = 0.01) and 75.6 (95% CI -103.6 to -47.7, p < 0.001) fewer minutes/day respectively compared to the control group at 12 month follow up. These differences were larger than the complete case analysis. The differences in sitting time observed for the medium and low levels were similar to the complete case analysis.ConclusionsMost intervention strategies were delivered to some extent across the clusters although there was large variation. Superior effects for sitting reduction were seen for those intervention groups who implemented and engaged with the most intervention components and had the highest level of cluster implementation and engagement.Trial RegistrationISRCTN11618007. Registered on 24 January 2018. https://www.isrctn.com/ISRCTNISRCTN11618007.

Final Analysis of the Daliah Trial: A Randomized Phase III Trial of Interferon-α Versus Hydroxyurea in Patients with MPN

Background: Hydroxyurea (HU) is the most commonly used first-line cytoreductive treatment option for patients with myeloproliferative neoplasms (MPN) worldwide. However, increasing evidence on the efficacy and safety of pegylated interferon-alpha2 (IFNα) is emerging, and optimal first-line treatment is to be established. Aims: To compare the efficacy and safety of HU vs. low-dose IFNα in patients with MPN over five years. Methods: DALIAH (NCT01387763) was a randomized phase III trial of HU vs. IFNα in newly diagnosed or untreated patients with MPN (essential thrombocythemia (ET), polycythemia vera (PV), prefibrotic myelofibrosis (PreMF), and primary myelofibrosis (PMF)). Patients &amp;gt; age 60 were randomized (1:1:1) to HU, IFNα-2a, or IFNα-2b whereas patients ≤ age 60 were randomized to IFNα-2a or IFNα-2b. The primary outcome was the JAK2V617F molecular response (MR) rate at 18, 36, and 60 months per 2009 European LeukemiaNetwork (ELN) (ET, PV, PreMF) or 2005 European Myelofibrosis Network (EUMNET) (PMF) criteria. Secondary outcomes included the complete clinicohematologic response (CHR) rate at 12 months. The JAK2V617F allele burden was measured using quantitative polymerase chain reaction (qPCR) on peripheral blood (assay sensitivity: 0.1%). Primary and secondary outcomes were compared between groups (HU vs. IFNα or HU vs. IFNα &amp;gt; 60 years) using Fisher's exact test (categorical variables) or Wilcoxon rank-sum test (continuous variables). Paired comparisons (within groups) were made using Wilcoxon signed-rank test. Serial JAK2V617F measurements were compared by unadjusted mixed-effects linear regression analysis. Results: We included 203 patients (ET: 73 (36%), PV: 89 (44%), PreMF: 16 (8%), and PMF: 25 (12%)) in the modified intention-to-treat (ITT) population. Baseline characteristics were well balanced except for median age (HU: 68 years vs. IFNα: 59 years, p&amp;lt;0.0001) ( Table 1). The MR rate by ITT analysis was similar between HU and IFNα (18 months: 19% vs. 21%, p=1.00; 36 months: 19% vs. 26%, p=0.64; 60 months: 23% vs. 24%, p=1.00) (Figure 1A). However, the JAK2V617F allele burden was significantly lower in the IFNα group at month 36 and beyond (Figure 1B) and the absolute median (IQR) change in JAK2V617F allele burden (baseline to 60 months) was greater with IFNα (-20% (-9;-49) vs. -7% (3;-15), p=0.0053) (Figure 1C). Two patients (IFNα: n=2) were in complete molecular remission (undetectable JAK2V617F) at 60 months. The CHR rate by ITT analysis was higher with HU at 18 months (58% vs. 38%, p=0.03) but similar at all other time points (12 months: 50% vs. 36%, p=0.21; 60 months: 24% vs. 22%, p=0.83) ( Figure 1D). A post hoc subgroup analysis comparing HU with IFNα &amp;gt; age 60 showed comparable efficacy results. Among patients remaining on treatment (per-protocol analysis), the MR and CHR rates were superior in the IFNα group compared to the HU group at 36 months and beyond. The MR and CHR rates (HU vs. IFNα) by per-protocol analysis were: MR at 36 months: 23% vs. 56%, p=0.01; MR at 48 months: 27% vs. 59%, p=0.02; MR at 60 months: 35% vs. 67%, p=0.03; CHR at 36 months: 33% vs. 67%, p=0.002; CHR at 60 months: 38% vs. 62%, p=0.05. Overall treatment discontinuation at 60 months was 60% (HU: 37% vs. IFNα: 65%, p=0.0019). The most common cause of treatment discontinuation was adverse events (HU: 6/38 (16%); IFNα: 71/165 (43%)). Adverse events ≥ grade 3 occurred in 46% (HU: 58% vs. IFNα: 45%, p=0.15). Nineteen major thrombotic events were reported in 16 patients (HU: 4 events in 4 patients; IFNα&amp;gt;60: 12 events in 10 patients; IFNα≤60: 3 events in 2 patients), corresponding to an incidence rate of 2.6 per 100 person-years for HU and 3.4 per 100 person-years for IFNα (IFNα&amp;gt;60: 6.2; IFNα≤60: 1.2). None of the patients transformed into secondary acute myeloid leukemia. Five patients died during follow-up (HU: 2; IFNα: 3). Bone marrow histologic remission rates at 36 and 60 months will be presented at the meeting. Conclusion: ITT analysis detected no significant difference in the MR or CHR rates between HU and IFNα with long-term treatment (5 years) among patients with MPN, reflecting a higher treatment discontinuation rate in the IFNα group (65%). Thus, using the per-protocol principle, the MR and CHR rates were superior in the IFNα group at 36 months and beyond.

Association of red cell omega-3 fatty acids, particularly EPA, with cognitive performance in atrial fibrillation

Abstract Introduction Atrial fibrillation (AF) is associated with cognitive impairment and dementia. Whether or not omega-3 Fatty Acids (n-3 FAs) have neuroprotective effects is controversial. We therefore aimed to determine the correlation of n-3 FAs with cognitive function in a large cohort of AF patients. Methods Red cell n-3 FAs levels were determined by gas chromatography and mass spectrometry in 2359 patients from the prospective ongoing multicenter Swiss Atrial Fibrillation study (Swiss-AF). To assess the overall cognitive performance of patients, we used several validated neurocognitive assessment tools, including the Montreal Cognitive Assessment (MoCA), Semantic Fluency Tests (SF), Trail Making Test (TMT A&amp;B), and the Digit Symbol Substitution Test (DST). We also used a summary score that we have previously developed (the cognitive construct (CoCo) score). We performed mixed-effect linear regression analyses. Two adjustment models were applied; model 1 (adjusted for age, sex, and educational level) and model 2 (adjusted for age, sex, educational level, history of stroke/TIA, AF type, heart rate, arterial hypertension, diabetes, coronary artery disease, BMI, chronic kidney disease, smoking status, alcohol consumption, geriatric depression scale, use of oral anticoagulation and antiplatelet medication). We also included a random intercept to control for center-effect in both models. Results The mean age of our study population was 73 years (standard deviation [SD] 8.4), and 662 patients were females (28%), 318 had a history of stroke (13%), and 716 suffered from coronary artery disease (30%). We observed statistically significant associations of total n-3 FAs levels (EPA + DHA + DPA + ALA) with all neurocognitive assessments, as seen in figure a. Individual n-3 FAs levels (EPA and ALA) were positively associated with MoCA score in both models. EPA was significantly associated with multiple neurocognitive assessments including MoCA, SF, TMT-B, DST, and overall CoCo score in both models (figure b). We found that a 1% red cell EPA level increase was associated with 0.19 (Model 1, 95%CI 0.06-0.31, p=0.003) and 0.14 (Model 2, 95% CI 0.01-0.26, p=0.02) units increase in the standardized MoCA score. Conclusions Red cell n-3 FAs levels are associated with better cognitive performance in AF patients. We observed a particularly strong association of EPA levels with all neurocognitive assessments.

Associations between nutritional intake, stress and hunger biomarkers, and anxiety and depression during the treatment of anorexia nervosa in adolescents and young adults

Adolescents and young adults (AYA) with anorexia nervosa (AN) frequently have co-occurring anxiety and depression, which can negatively impact prognosis. To inform treatment of co-occurring anxiety and depression, we assessed the association of nutritional intake and hunger/stress hormones on anxiety and depression using a six-month longitudinal study of 50 AYA females receiving care for AN. At baseline and six months, we measured anxiety (Spielberger State/Trait Anxiety Inventory [STAI]), depression (Beck Depression Inventory [BDI]), body mass index (BMI), 3-day dietary intake (total calories and proportion of fat, carbohydrate, protein), and serum cortisol, leptin, and adiponectin. We performed mixed effects linear regression analyses, adjusting for age, duration of AN, and percentage of median BMI (%mBMI). At baseline, median age was 16.3 (interquartile range [IQR] = 2.5) years, duration of AN was 6 (IQR = 8.8) months and %mBMI was 87.2 (IQR = 10.5)%. Fifty-six percent had clinically significant anxiety; 30 % had depression. Over 6 months, participants had significant improvements in %mBMI (+2.2[IQR = 9.2]%, p < .01), STAI (−9.0[IQR = 25.0], p < .01), and BDI (−5.0[IQR = 13.8], p < .01) scores. Participants with larger improvements in caloric intake had greater improvements in STAI (p = .03) and BDI scores (p = .04). Larger improvement in BDI was significantly associated with increased fat intake (p < .01), but not carbohydrate or protein intake. Change in STAI was not associated with changes in fat, carbohydrate, or protein intake. Changes in STAI or BDI scores were not associated with changes in cortisol, leptin, or adiponectin. Increased caloric intake may augment treatment of co-occurring anxiety and depression, and increased fat intake may improve depression for AYA with AN.

Circulating Metabolomic Associations with Neurocognitive Outcomes in Pediatric CKD.

Children with CKD are at risk for impaired neurocognitive functioning. We investigated metabolomic associations with neurocognition in children with CKD. We leveraged data from the Chronic Kidney Disease in Children (CKiD) study and the Neurocognitive Assessment and Magnetic Resonance Imaging Analysis of Children and Young Adults with Chronic Kidney Disease (NiCK) study. CKiD is a multi-institutional cohort that enrolled children aged 6 months to 16 years with eGFR 30-90 ml/min per 1.73 m 2 ( n =569). NiCK is a single-center cross-sectional study of participants aged 8-25 years with eGFR<90 ml/min per 1.73 m 2 ( n =60) and matched healthy controls ( n =67). Untargeted metabolomic quantification was performed on plasma (CKiD, 622 metabolites) and serum (NiCK, 825 metabolites) samples. Four neurocognitive domains were assessed: intelligence, attention regulation, working memory, and parent ratings of executive function. Repeat assessments were performed in CKiD at 2-year intervals. Linear regression and linear mixed-effects regression analyses adjusting for age, sex, delivery history, hypertension, proteinuria, CKD duration, and glomerular versus nonglomerular diagnosis were used to identify metabolites associated with neurocognitive z-scores. Analyses were performed with and without adjustment for eGFR. There were multiple metabolite associations with neurocognition observed in at least two of the analytic samples (CKiD baseline, CKiD follow-up, and NiCK CKD). Most of these metabolites were significantly elevated in children with CKD compared with healthy controls in NiCK. Notable signals included associations with parental ratings of executive function: phenylacetylglutamine, indoleacetylglutamine, and trimethylamine N-oxide-and with intelligence: γ -glutamyl amino acids and aconitate. Several metabolites were associated with neurocognitive dysfunction in pediatric CKD, implicating gut microbiome-derived substances, mitochondrial dysfunction, and altered energy metabolism, circulating toxins, and redox homeostasis.

Independent effect of Aβ burden on cognitive impairment in patients with small subcortical infarction

BackgroundThe effect of amyloid-β (Aβ) on cognitive impairment in patients with small subcortical infarction remains controversial, although a growing body of evidence shows a substantial overlap between Alzheimer’s disease (AD) and subcortical ischemic vascular dementia, another form of cerebral small vessel disease (cSVD). Therefore, we investigated the relationships between Aβ positivity and the development of post-stroke cognitive impairment (PSCI) in patients with small subcortical infarction.MethodsWe prospectively recruited 37 patients aged ≥ 50 years, with first-ever small subcortical infarction, who underwent amyloid positron emission tomography, 3 months after stroke at Korea University Guro Hospital. We also enrolled CU participants matched for age and sex with stroke patients for comparison of Aβ positivity. Patients were followed up at 3 and 12 months after the stroke to assess cognitive decline. Logistic and linear mixed-effect regression analyses were performed to identify the effect of Aβ positivity on PSCI development and long-term cognitive trajectories.ResultsAt 3 months after stroke, 12/37 (32.4%) patients developed PSCI, and 11/37 (29.7%) patients had Aβ deposition. Aβ positivity (odds ratio [OR] = 72.2, p = 0.024) was predictive of PSCI development regardless of cSVD burden. Aβ positivity (β = 0.846, p = 0.014) was also associated with poor cognitive trajectory, assessed by the Clinical Dementia Rating-Sum of Box, for 1 year after stroke.ConclusionsOur findings highlight that Aβ positivity is an important predictor for PSCI development and cognitive decline over 1 year. Furthermore, our results provide evidence that anti-AD medications may be a strategy for preventing cognitive decline in patients with small subcortical infarctions.

Effect of speed and water depth on limb and back kinematics in Thoroughbred horses walking on a water treadmill

Water treadmill (WT) exercise may induce limb and back kinematics that meet specific training and rehabilitation goals. The study aimed to investigate the effects of walk speed, at different water depths (WDs), on limb and back kinematics of six Thoroughbreds exercising on a WT. Horses walked at 2.8/4.3/5.5/6.0 km/h (i.e. 0.8/1.2/1.5/1.7 m/s) at dry, metacarpophalangeal and carpal WD. Videography captured limb movement in the sagittal plane. Motion-capture measured thoracolumbosacral flexion-extension (FE), and lateral bend (LB) ranges of movement (ROM) using skin surface markers on the sixth, tenth, thirteenth, eighteenth thoracic, third and fifth lumbar, and third sacral spinous processes. Inertial-motion-sensors measured poll, withers and pelvic displacements. Following preliminary univariable analyses, multivariable mixed-effects linear-regression analyses were used to examine the relationship between speed, WD and each outcome variable (P < 0.05). Peak metacarpophalangeal, carpal and tarsal joint flexion increased with speed (P ≤ 0.002) and depth combined (P 0.001) while peak metatarsophalangeal flexion increased with WD only (P 0.001). Thoracolumbar FE-ROM between T10 and L3 and hindlimb retraction was increased by speed and WD combined (P 0.001). Hindlimb protraction was increased by speed (P 0.001) while hindlimb retraction was increased by speed and WD combined (P 0.001). Dorsoventral poll displacement was increased by speed (P 0.001) and carpal WD (P = 0.013), craniocaudal poll displacement was increased by speed and WD combined (P 0.001). Pelvic (tubera coxae and sacrum) dorsoventral displacements increased with speed and WD combined (P 0.001). Understanding the effects of speed and WD on limb, back and pelvic kinematics will improve decision making relating to dry and WT exercise within training.

Relationship between lexicon and grammar in children and youth who use augmentative and alternative communication

The present study investigated the relationship between lexicon and grammar in individuals who use graphic symbol-based aided augmentative and alternative communication (AAC). Data came from 60 transcripts of generalization sessions that were part of two previous intervention studies, aimed at improving the expressive vocabulary and grammar of 12 children and youth who used graphic symbol-based AAC. The specific aims of the current study were to (a) describe vocabulary composition across different levels of expressive vocabulary and (b) analyze the relationship between global measures of expressive vocabulary and the use of grammar in individuals who use aided AAC. A series of multiple linear mixed effect regression analyses showed a positive predictive association between overall vocabulary size and the use of closed-class words, and a positive relationship between the use of verbs and the use of closed-class words. Additionally, the use of verbs had a significant positive association with the use of inflectional morphology, while the use of nouns did not. Theoretical and practical implications of these findings are discussed.

CSF metabolites associated with biomarkers of Alzheimer's disease pathology.

Metabolomics technology facilitates studying associations between small molecules and disease processes. Correlating metabolites in cerebrospinal fluid (CSF) with Alzheimer's disease (AD) CSF biomarkers may elucidate additional changes that are associated with early AD pathology and enhance our knowledge of the disease. The relative abundance of untargeted metabolites was assessed in 161 individuals from the Wisconsin Registry for Alzheimer's Prevention. A metabolome-wide association study (MWAS) was conducted between 269 CSF metabolites and protein biomarkers reflecting brain amyloidosis, tau pathology, neuronal and synaptic degeneration, and astrocyte or microglial activation and neuroinflammation. Linear mixed-effects regression analyses were performed with random intercepts for sample relatedness and repeated measurements and fixed effects for age, sex, and years of education. The metabolome-wide significance was determined by a false discovery rate threshold of 0.05. The significant metabolites were replicated in 154 independent individuals from then Wisconsin Alzheimer's Disease Research Center. Mendelian randomization was performed using genome-wide significant single nucleotide polymorphisms from a CSF metabolites genome-wide association study. Metabolome-wide association study results showed several significantly associated metabolites for all the biomarkers except Aβ42/40 and IL-6. Genetic variants associated with metabolites and Mendelian randomization analysis provided evidence for a causal association of metabolites for soluble triggering receptor expressed on myeloid cells 2 (sTREM2), amyloid β (Aβ40), α-synuclein, total tau, phosphorylated tau, and neurogranin, for example, palmitoyl sphingomyelin (d18:1/16:0) for sTREM2, and erythritol for Aβ40 and α-synuclein. This study provides evidence that CSF metabolites are associated with AD-related pathology, and many of these associations may be causal.

Immediate versus conventional loading of mandibular implant-retained overdentures: a 3-year follow-up of a randomized controlled trial.

There is a scarcity of randomized clinical trials (RCT) that report medium- and long-term results and a lack of consensus in the literature on the predictability of immediately loaded unsplinted narrow diameter implants supporting mandibular overdentures. This RCT compared the performance of conventional (CL) and immediate loading (IL) of mandibular overdentures retained by two narrow-diameter implants for 3years. Patients from an RCT treated with CL or IL were invited to attend to 2- and 3-year follow-ups. Clinical, radiographic, functional, and oral health-related quality of life parameters were evaluated. Prosthetic maintenance events, biological complications, and success and survival rates were also recorded. The data were tested by multilevel mixed-effects linear regression analysis and chi-squared tests. The 1-year survival rates of 90% in the CL group and 85% in the IL group were maintained as no implants were lost between 1 and 3years. The marginal bone loss (MBL) in the IL group was significantly lower after year 3 (-0.04; p < 0.01). Significant changes were found only for the intra-group comparisons in the third year of function: (i) CL and IL presented similar progression of implant stability, MBL, and posterior bone area resorption; (ii) while CL started deteriorating of masticatory function, IL still exhibited functional evolution and (iii) oral comfort domain in the CL and pain domain in the IL were improved. Although IL experienced the lowest MBL after 3years, the outcomes showed that both loading protocols result in predictable medium-term rehabilitation when monitored annually. It can be expected that in the third year of function, patients with immediate loading may present more complaints related to general performance even with acceptable masticatory function and self-reported improvements in oral comfort.