Multivariate General Linear Model Research Articles

Implementing an osteoarthritis management program to deliver guideline-driven care for knee and hip osteoarthritis in a U.S. academic health system

ObjectiveAssess implementation feasibility and outcomes for an Osteoarthritis Management Program (OAMP) at an academic center. DesignThis open study assessed an OAMP designed to deliver care in 1–5 individual or group visits across ≤12 months. Eligibility included adults with knee or hip osteoarthritis with ≥1 visit from 7/1/2017–1/15/2021. A multidisciplinary care team provided: education on osteoarthritis, self-management, exercise, weight loss; pharmacologic management; assessments of mood, sleep, quality of life, and diet. Clinic utilization and growth are reported through 2022. Patient outcomes of body mass index (BMI), pain, and function were analyzed using multivariable general linear models. OAMP outcomes were feasibility and sustainability. ResultsMost patients were locally referred by primary care. 953 patients attended 2531 visits (average visits 2.16, treatment duration 187.9 days). Most were female (72.6%), older (62.1), white (91.1%), and had medical insurance (95.4%). Obesity was prevalent (84.7% BMI ≥30, average BMI 40.9), mean Charlson Comorbidity Index was 1.89, and functional testing was below average. Longitudinal modeling revealed statistically but not clinically significant pain reduction (4.4–3.9 on 0–10 scale, p ​= ​0.002). BMI did not significantly change (p ​= ​0.87). Higher baseline pain and BMI correlated with greater reductions in each posttreatment. Uninsured patients had shorter treatment duration. Increasing clinic hours (4–24 ​h weekly) and serving 953 patients over four years demonstrated OAMP sustainability. ConclusionsOAMP implementation was feasible and sustainable. Patients with high baseline pain and BMI were more likely to improve. Noninsurance was a barrier. These results contribute to understanding OAMP outcomes in U.S. healthcare.

Small dense low-density lipoprotein cholesterol and coronary artery calcification in the Multi-Ethnic Study of Atherosclerosis.

Elevated small dense LDL cholesterol (sd-LDL-C) increases atherosclerotic cardiovascular disease (CVD) risk. Although coronary artery calcification (CAC) is widely used for predicting CVD events, few studies have examined the relationship between sd-LDL-C and CAC. This study included 4672 individuals with directly measured baseline sd-LDL-C and CAC from the Multi-Ethnic Study of Atherosclerosis [mean (standard deviation) age: 61.9 (10.4) years; 52.5% women; 47.3% with baseline CAC (mean score >0)]. We used multi-variable general linear models and restricted cubic splines with the goodness of fit testing to evaluate the association of sd-LDL-C with the presence of CAC. Odds ratios [OR (95% confidence interval)] were adjusted for demographics and cardiovascular risk factors, including estimated total LDL-C. Higher quartiles of sd-LDL-C were associated with the presence of CAC, even after accounting for total LDL-C. Compared with the lowest quartile of sd-LDL-C, participants in Quartiles 2, 3, and 4 had higher odds for the presence of baseline CAC [Quartile 2 OR: 1.24 (1.00, 1.53); Quartile 3 OR: 1.51 (1.19, 1.93); and Quartile 4 OR 1.59 (1.17, 2.16)]. Splines suggested a quadratic curvilinear relationship of continuous sd-LDL-C with CAC after adjustment for demographics and CVD risk factors (quadratic vs. first-order sd-LDL-C terms likelihood ratio test: P = 0.015), but not after accounting for total LDL-C (quadratic vs. first-order terms: P = 0.156). In a large, multi-ethnic sample without known CVD, higher sd-LDL-C was associated with the presence of CAC, above and beyond total LDL-C. Whether selective direct measurement of sd-LDL-C is indicated to refine cardiovascular risk assessment in primary prevention warrants further investigation.

Association of Metabolic Syndrome with Macular Thickness and Volume in Older Adults: A Population-Based Optical Coherence Tomography Study.

Background: To explore the associations of the metabolic syndrome (MetS) and individual components with macular thickness and volume among rural-dwelling Chinese older adults. Methods: This population-based cross-sectional study included 705 participants (age ≥60 years) derived from the MIND-China study. In 2018-2019, we collected data through face-to-face interview, clinical examination, optical coherence tomography (OCT) examination, and blood test. We measured macular thickness and volume using spectral-domain OCT. MetS was defined following the International Diabetes Federation (IDF) criteria, the IDF/American Heart Association (AHA) criteria, the National Cholesterol Education Program-Adult Treatment Panel III criteria, and the Chinese Diabetes Society (CDS) criteria. Data were analyzed with multivariable general linear models. Results: MetS was significantly associated with thinner macula in central (multivariable-adjusted β = -5.29; 95% confidence interval: -9.31 to -1.26), parafoveal (-2.85; -5.73 to 0.04) and perifoveal regions (-4.37; -6.79 to -1.95) when using the IDF criteria, in the perifoveal regions (-3.82; -6.18 to -1.47) when using the IDF/AHA criteria, and in the central region (-5.63; -10.25 to -1.02) when using the CDS criteria, and with reduced macular volume when using the IDF (-0.16; -0.26 to -0.07) and IDF/AHA (-0.13; -0.22 to -0.04) criteria. In the parafoveal region, the IDF-defined MetS was significantly associated with thinner retina in men (β = -6.25; -10.94 to -1.56) but not in women. Abdominal obesity (-2.83; -5.41 to -0.25) and elevated fasting blood glucose (-2.65; -5.08 to -0.21) were associated with thinner macular thickness in the perifoveal region. Conclusion: MetS is associated with macular thinning and reduced macular volume among rural-dwelling older adults, and the associations vary by the defining criteria of MetS.

Factors associated with blood mercury concentrations and their interactions with three glutathione S-transferase genes (GSTT1, GSTM1, and GSTP1): an exposure assessment study of typically developing Jamaican children

BackgroundJamaican soil is abundant in heavy metals including mercury (Hg). Due to availability and ease of access, fish is a traditional dietary component in Jamaica and a significant source of Hg exposure. Mercury is a xenobiotic and known neuro-toxicant that affects children's neurodevelopment. Human glutathione S-transferase (GST) genes, including GSTT1, GSTM1, and GSTP1, affect Hg conjugation and elimination mechanisms.MethodsIn this exposure assessment study we used data from 375 typically developing (TD) 2–8-year-old Jamaican children to explore the association between environmental Hg exposure, GST genes, and their interaction effects on blood Hg concentrations (BHgCs). We used multivariable general linear models (GLMs).ResultsWe identified the child’s age, consumption of saltwater fish, canned fish (sardine, mackerel), string beans, grain, and starches (pasta, macaroni, noodles) as the environmental factors significantly associated with BHgCs (all P < 0.05). A significant interaction between consumption of canned fish (sardine, mackerel) and GSTP1 in relation to BHgC using either a co-dominant or recessive genetic model (overall interaction P = 0.01 and P < 0.01, respectively) indicated that consumption of canned fish (sardine, mackerel) was significantly associated with higher mean BHgC only among children with the GSTP1 Ile105Val, Ile/Ile [Ratio of mean Hg (95% CI) = 1.59 (1.09, 2.32), P = 0.02] and Ile/Val [Ratio of mean Hg (95% CI) = 1.46 (1.12, 1.91), P = 0.01] genotypes.ConclusionsSince this is the first study from Jamaica to report these findings, replication in other populations is recommended.

Blood Markers in Relation to a History of Traumatic Brain Injury Across Stages of Cognitive Impairment in a Diverse Cohort.

Traumatic brain injury (TBI) has been linked to multiple pathophysiological processes that could increase risk for Alzheimer's disease and related dementias (ADRD). However, the impact of prior TBI on blood biomarkers for ADRD remains unknown. Using cross-sectional data, we assessed whether a history of TBI influences serum biomarkers in a diverse cohort (approximately 50% Hispanic) with normal cognition, mild cognitive impairment, or dementia. Levels of glial fibrillary acidic protein (GFAP), neurofilament light (NFL), total tau (T-tau), and ubiquitin carboxy-terminal hydrolase-L1 (UCHL1) were measured for participants across the cognitive spectrum. Participants were categorized based on presence and absence of a history of TBI with loss of consciousness, and study samples were derived through case-control matching. Multivariable general linear models compared concentrations of biomarkers in relation to a history of TBI and smoothing splines modelled biomarkers non-linearly in the cognitively impaired groups as a function of time since symptom onset. Each biomarker was higher across stages of cognitive impairment, characterized by clinical diagnosis and Mini-Mental State Examination performance, but these associations were not influenced by a history of TBI. However, modelling biomarkers in relation to duration of cognitive symptoms for ADRD showed differences by history of TBI, with only GFAP and UCHL1 being elevated. Serum GFAP, NFL, T-tau, and UCHL1 were higher across stages of cognitive impairment in this diverse clinical cohort, regardless of TBI history, though longitudinal investigation of the timing, order, and trajectory of the biomarkers in relation to prior TBI is warranted.

Common Wrist-Extensor Tendon and Pectoralis Muscle Stiffness in Healthy Recreational Tennis Players.

Imbalances in upper-extremity soft tissue stiffness may play a role in the development of shoulder and elbow musculoskeletal injuries in tennis players. Ultrasound shear wave elastography provides quantifiable and specific data regarding muscle stiffness. The purpose of this study was to compare tendon and muscle stiffness in healthy tennis players to nontennis players. Cross-sectional study. The shear wave modulus, measured in kilopascals, was obtained for the dominant pectoralis major, pectoralis minor, and common wrist-extensor tendon using 2-dimensional shear wave elastography ultrasound imaging (GE Logiq S8, L9 linear transducer). Independent t test was run to compare age, body mass index, and the activity index score between both groups. Within-day intrarater reliability was assessed using a within-examiner intraclass correlation coefficients (ICC [3, 1]) with 95% confidence intervals. A multivariate general linear model was run to compare the mean differences between the tennis and nontennis players for each of the soft tissues. Twenty-six individuals (13 tennis players and 13 nontennis players) were recruited. Within-day ICCs were very good (ICC > .78 for the pectoralis musculature) and excellent (ICC > .94 for the common wrist extensor). Common extensor tendon stiffness was significantly higher in tennis players compared to nontennis players (mean difference = 114.8 [61.8], confidence interval, -22.8 to 252.5kPa for the dominant arm [P = .039]). Mean pectoralis major and minor stiffness differences were not significant (P > .214). Common wrist-extensor stiffness in healthy recreational tennis players is higher than those who do not play tennis. Therefore, clinicians may need to facilitate a greater soft tissue stiffness response with resistance training when rehabilitating recreational tennis players as compared to those not playing tennis. Additional normative data on a larger sample of recreational tennis players should be collected.

Effectiveness of sponsorship type, sport team identification, team support and congruence

PurposeThe aim of this paper is to investigate the interaction effect that sponsor-team congruence and team fan (home/rival team) have on the influence of different types of sports sponsorship (joint, corporate social responsibility [CSR]-linked and conventional sponsorship) on fans' attitudes and purchase intentions toward the sponsor.Design/methodology/approachTwo experimental studies were conducted on 391 and 297 participants. The data gathered underwent analysis through five multivariate general linear model analyses.FindingsThe study found that CSR-linked sponsorship had the strongest positive impact and the weakest negative impact on the attitude and purchase intention of home team supporters and the attitude of rival team supporters. Nonetheless, the sponsor-team congruence did not significantly moderate the relationship. Additionally, the research demonstrated that the fan identity of both home and rival teams moderates the impact of sports sponsorships on attitude and purchase intention.Originality/valuePrevious research has studied the effectiveness of sponsorship format types independently. This is the first research comparing sponsorship formats regarding fan type and congruence.

Examining the impact of time management and resilience training on work-family conflict among Iranian female nurses: a randomized controlled trial

BackgroundFemale nurses confronting work-family conflict may endure adverse consequences for themselves and their families, leading to a decline in job performance and intentions to quit. Investigating the effects of interventions based on factors contributing to work-family conflict can aid in identifying optimal strategies for conflict reduction and mitigating its negative repercussions. This study aimed to examine the impact of time management and resilience training on work-family conflict among Iranian female Nurses in 2022.MethodsIn this randomized controlled trial employing pre, post, and follow-up measures, 132 female nurses employed in the hospitals of Bushehr University of Medical Sciences (Bushehr, Iran) were selected and subsequently categorized into three groups—time management, resilience training, and control groups—using simple random sampling method. 10 online training sessions were conducted for each intervention group. A demographic form and a work-family conflict questionnaire were used for data collection. Repeated measures ANOVA, one-way ANOVA and multivariate general linear model were used to examine the hypotheses.ResultsRegarding total work-family conflict, posttest mean scores were significantly lower than the pretest in both time management (p < 0.001) and resilience (p < 0.001) training groups, but follow-up mean scores were significantly higher than posttests in both time management (p < 0.001) and resilience (p < 0.001) training groups. In the control group, the mean scores at three time points were not statistically different (P = 0.058). The post-test mean score of work-family conflict was comparable in the two intervention groups (P > 0.05) and lower than the control group (P < 0.001) The follow-up mean score was comparable in the two intervention groups (P > 0.05) and lower than the control group (P < 0.001).ConclusionTime management and resilience training effectively reduced the work-family conflict experienced by female nurses. Therefore, it is recommended that training programs such as time management and resilience training be incorporated into the ongoing education of nurses to alleviate their work-family conflict. Considering the diminishing impact of these interventions over time, training should be reiterated based on the evolving needs of the nurses.Trial registrationNumber (IRCT20190122042453N2),01/27/2022.

College Students' Trust, Betrayal, and Needs During and After Their Worst Nonassault-Related Healthcare Experiences Differ Based on Sexual Violence Exposure.

The BITTEN theoretical framework conceptually links patient's past healthcare betrayal and trauma experiences with their current and future healthcare interactions. BITTEN was used to examine whether healthcare experiences, behaviors, and needs differ between those with and without a history of sexual violence exposure. College students at two public universities in the southeastern United States (n = 1,381; 59.5% White, 61.0% women) completed measures about their self-selected worst or most frightening but nonassault-related healthcare experience. Multivariate general linear and mediation models were used to test theory-derived hypotheses. Participants exposed to sexual violence reported greater healthcare institutional betrayal, lower trust, and greater need for tangible aid and trauma-informed care during their worst nonassault-related healthcare experience. They also reported greater current healthcare avoidance alongside increased utilization of more physical and mental healthcare appointments, even after accounting for gender and race differences. These results suggest that, with minimal information about past sexual violence exposure, healthcare providers could be better poised to predict and address vulnerable patients' healthcare needs.

Reduced grey matter volume in adolescents with conduct disorder: a region-of-interest analysis using multivariate generalized linear modeling

BackgroundConduct disorder (CD) involves a group of behavioral and emotional problems that usually begins during childhood or adolescence. Structural brain alterations have been observed in CD, including the amygdala, insula, ventrolateral and medial prefrontal cortex, anterior cingulate cortex, and fusiform gyrus. The current study developed a multivariate generalized linear model (GLM) to differentiate adolescents with CD from typically developing (TD) adolescents in terms of grey matter volume (GMV).MethodsThe whole‐brain structural MRI data were collected from 96 adolescents with CD (mean age = 16.188pm 1.259 years; mean IQ = 104.292pm 8.107; 63 males) and 90 TD individuals (mean age = 15.956pm 1.506 years; mean IQ = 106.622pm 9.076; 59 males) matched on age, IQ, and sex. Region-wise GMV was extracted following whole-brain parcellation into 68 cortical and 14 subcortical regions for each participant. A multivariate GLM was developed to predict the GMV of the pre-hypothesized regions-of-interest (ROIs) based on CD diagnosis, with intracranial volume, age, sex, and IQ serving as the covariate.ResultsA diagnosis of CD was a significant predictor for GMV in the right pars orbitalis, right insula, right superior temporal gyrus, left fusiform gyrus, and left amygdala (F(1, 180) = 5.460–10.317, p < 0.05, partial eta squared = 0.029–0.054). The CD participants had smaller GMV in these regions than the TD participants (MCD–MTD = [− 614.898] mm3–[− 53.461] mm3).ConclusionsAltered GMV within specific regions may serve as a biomarker for the development of CD in adolescents. Clinical work can potentially target these biomarkers to treat adolescents with CD.

Fear of birth among Iranian fathers of full-term and preterm neonates: A cross-sectional study

BackgroundPregnancy, childbirth, and parenting can cause different emotional reactions in fathers, in addition to mothers, including fear of childbirth. PurposeTo compares the fear of childbirth among fathers of preterm and term infants. Study designThis cross-sectional study included 157 fathers with preterm neonates (below 37 weeks) and 314 with term neonates (above 37 weeks) in Tabriz, Iran. The instruments used for data collection included socio-demographic and obstetric characteristics and paternal fear of childbirth questionnaires. The data were analyzed using a general linear model. ResultsThere was a statistically significant difference between the two groups regarding the total score of fear of childbirth (p < 0.001). Also, a multivariate general linear model with adjusted socio-demographic and obstetric characteristics found no significant difference in the fear of childbirth between the fathers of term and preterm neonates. There was a statistically significant association between a father's fear of birthing and his wife's gestational age and parity, with men who had primiparous women and premature infants reporting the greatest levels of anxiety. ConclusionThis study found that first-time fathers whose spouses are primiparous and whose gestational ages are short tend to fear childbirth more. Providing support and interventions during the prenatal period is essential for reducing this anxiety.

87 The Cumulative and Unique Effect of Competitive Youth Participation in the United States’ Most Popular Sports on Executive Function

Objective:Engagement in sporting activities has shown improvement in executive function among youth (Contreras-Osorio et al., 2021). Additionally, participation in specific sports such as soccer has been shown to enhance executive function in youth athletes compared to same-aged non-athletes (Yongtawee et al., 2021). The present study aimed to examine the effects of competitive participation in the United States’ four most popular sports on executive function among youth athletes. The most popular sports, as defined by viewership, revenue, and youth participation in the U.S. are American football, basketball, baseball, and soccer (Injai, 2022; Aspen Institute, 2020).Participants and Methods:Data from the following three executive functioning subtests were analyzed in a sample of youth athletes (n=76), aged 8-18 years (mean age=11.94): Delis-Kaplan Executive Function System Trail Making Letter-Number Sequencing (cognitive flexibility), Wechsler Intelligence Scale for Children Fourth Edition Working Memory Index, and Golden Stroop Color-Word Inhibition. Participants completed these measures as part of a larger neuropsychological baseline assessment. Multivariate General Linear Model (GLM) regression was used to examine the influence of total cumulative years playing in one or more of the four most popular sports on executive functioning. A multivariate GLM regression also investigated the unique contributions of total years playing soccer (n=40; mean age=12.40) and total years playing American football (n=32; mean age=12.03) on subtest performance. The unique contributions of basketball (n=14) and baseball (n=21) were not analyzed due to small sample size.Results:Total cumulative years playing &gt; one of the four most popular sports significantly predicted cognitive flexibility (p=.007) and working memory (p=.002), but not inhibition (p=0.639). Total years playing soccer also significantly predicted cognitive flexibility (p=.029) and working memory (p=0.05), but not inhibition (p=.310). Total years playing American football did not significantly predict performance on tasks requiring cognitive flexibility (p=.186), working memory (p=0.150), or inhibition (p=0.277).Conclusions:In congruence with previous research, sports participation predicted enhanced cognitive flexibility and working memory on certain executive tasks. Among youth athletes, prolonged competitive participation in one or more of the four most popular sports in the U.S. predicted better performance on measures of cognitive flexibility and working memory. Furthermore, protracted participation in soccer predicted enhanced performance on measures of cognitive flexibility and working memory, whereas extended participation in American football did not. Future research should examine this effect in larger samples within all four sports. Examining the cumulative length of competitive participation in these popular sports on executive function could present a favorable developmental outcome of youth participation if competitive participation is sustained. Additionally, the present data on executive function performance between lasting soccer participation and lasting American football participation suggests that executive function development and performance may be influenced by the sport played. The direction of this possible influence is unclear. More research is needed to establish this observed difference, and to better understand its existence and directionality.

Exploring Verbal Fluency Strategies among Individuals with Normal Cognition, Amnestic and Non-Amnestic Mild Cognitive Impairment, and Alzheimer's Disease.

Background and Objectives: The present study explored the utilization of verbal fluency (VF) cognitive strategies, including clustering, switching, intrusions, and perseverations, within both semantic (SVF) and phonemic (PVF) conditions, across a continuum of neurocognitive decline, spanning from normal cognitive ageing (NC) to mild cognitive impairment (MCI) and its subtypes, amnestic (aMCI) and non-amnestic (naMCI), as well as AD. Materials and Methods: The study sample was derived from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) cohort. The sample included 1607 NC individuals, 146 with aMCI (46 single-domain and 100 multi-domain), 92 with naMCI (41 single-domain and 51 multi-domain), and 79 with AD. Statistical analyses, adjusting for sex, age, and education, employed multivariate general linear models to probe differences among these groups. Results: Results showed that AD patients exhibited poorer performance in switching in both VF tasks and SVF clustering compared to NC. Similarly, the aMCI group performed worse than the NC in switching and clustering in both tasks, with aMCI performing similarly to AD, except for SVF switching. In contrast, the naMCI subgroup performed similarly to those with NC across most strategies, surpassing AD patients. Notably, the aMCI subgroup's poor performance in SVF switching was mainly due to the subpar performance of the multi-domain aMCI subgroup. This subgroup was outperformed in switching in both VF tasks by the single-domain naMCI, who also performed better than the multi-domain naMCI in SVF switching. No significant differences emerged in terms of perseverations and intrusions. Conclusions: Overall, these findings suggest a continuum of declining switching ability in the SVF task, with NC surpassing both aMCI and AD, and aMCI outperforming those with AD. The challenges in SVF switching suggest executive function impairment associated with multi-domain MCI, particularly driven by the multi-domain aMCI.

Association of Triglyceride-Glucose Index With Cognitive Function and Brain Atrophy: A Population-Based Study

ObjectiveTo investigate the associations of triglyceride-glucose (TyG) index, a reliable surrogate marker for insulin resistance, with the function of various cognitive domains and brain structures among older adults. DesignA population-based cross-sectional study. SettingOlder adults living in the rural communities in China. ParticipantsAbout 4,541 rural-dwelling dementia-free participants (age ≥65 years; 56.37% women) undertook examinations in March–September 2018 for MIND-China. MeasurementsTyG index was calculated as ln[fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. A neuropsychological test battery was used to assess memory, attention, verbal fluency, and executive function. Volumetric brain measures were assessed on magnetic resonance imaging (MRI) in a subsample (n = 1,019). Data were analyzed with restricted cubic spline and multivariable general linear models. ResultsAn inverted J-shaped association was observed between TyG index and z-scores of multiple cognitive domains, such that among individuals with TyG index ≥8.57 (median), a higher TyG index was significantly associated with lower z-scores of memory, attention, verbal fluency, executive function, and global cognition (all p < 0.05); among people with TyG index <8.57, a higher TyG index was significantly associated with a higher executive function z-score (p < 0.05), but not with any of the other examined cognitive domains. In the MRI subsample, a higher TyG index was significantly associated with lower volumes of total brain tissue, gray matter, and white matter as well as greater cerebrospinal fluid volume (p < 0.05), but not with white matter hyperintensity volume. ConclusionsInsulin resistance, as indicated by a high TyG index, was associated with poor function in multiple cognitive domains and global brain atrophy.

Nociception assessment with videopupillometry in deeply sedated intensive care patients: Discriminative and criterion validations

BackgroundNociceptive assessment in deeply sedated patients is challenging. Validated instruments are lacking for this unresponsive population. Videopupillometry is a promising tool but has not been established in intensive care settings. Aim/ObjectiveTo test the discriminate validity of pupillary dilation reflex (PDR) between non-noxious and noxious procedures for assessing nociception in non-neurological intensive care unit (ICU) patients and to test the criterion validity of pupil dilation using recommended PDR cut-off points to determine nociception. MethodsA single-centre prospective observational study was conducted in medical–surgical ICU patients. Two independent investigators performed videopupillometer measurements during a non-noxious and a noxious procedure, once a day (up to 7 days), when the patient remained deeply sedated (Richmond Agitation–Sedation Scale score: −5 or −4). The non-noxious procedures consisted of a gentle touch on each shoulder and the noxious procedures were endotracheal suctioning or turning onto the side. Bivariable and multivariable general linear mixed models were used to account for multiple measurements in same patients. Sensitivity and specificity, and areas under the curve of the receiver operating characteristic curve were calculated. ResultsSixty patients were included, and 305 sets of 3 measurements (before, during, and after), were performed. PDR was higher during noxious procedures than before (mean difference between noxious and non-noxious procedures = 31.66%). After testing all variables of patient and stimulation characteristics in bivariable models, age and noxious procedures were kept in the multivariable model. Adjusting for age, noxious procedures (coefficient = −15.14 (95% confidence interval = −20.17 to −15.52, p < 0.001) remained the only predictive factor for higher pupil change. Testing recommended cut-offs, a PDR of >12% showed a sensitivity of 65%, and a specificity of 94% for nociception prediction, with an area under the receiver operating curve of 0.828 (95% confidence interval = 0.779–0.877). ConclusionsIn conclusion, PDR is a potentially appropriate measure to assess nociception in deeply sedated ICU patients, and we suggest considering its utility in daily practices. RegistrationThis study was not preregistered in a clinical registry. Tweetable abstractPupillometry may help clinicians to assess nociception in deeply sedated ICU patients.

Disentangling population genetic and climatic effects on skull size and shape of brown hares, Lepus europaeus (Lagomorpha: Leporidae), from Türkiye

Brown hares (Lepus europaeus) from Türkiye exhibit substantial phenotypic variation, assumingly connected to regional climate differences. We used general linear models (GLMs) of linear measurements and geometric morphometric data of dorsal and ventral skull and lateral mandible landmarks of 160 adult individuals from 75 locations across Türkiye, to specifically test for climate-related effects on skull size and shape, while accounting for potentially confounding effects of sex, geographic location, and population genetic assignment. We found a moderate positive correlation between individual condylobasal lengths (CBL) and centroid size scores (CSS) and used them separately as dependent skull size variables in our GLMs. Skull shape factors were obtained from principal component analyses (PCAs), separately for transformed linear morphometric and landmark data; they were also used as dependent variables in our GLMs, along with sex, geographic sampling coordinates, CBL or CSS, as well as temperature and precipitation factors from PCAs of local climate data as fixed factors. Our multivariate GLMs returned no climate effect on skull size and only one minor precipitation effect on geometric skull shape. Rather, skull size and shape were predominantly and significantly affected by the assignment of the hares to the genetic populations as determined by an earlier microsatellite study. Our results correspond to microphylogeographic differentiation of skull size and shape of the studied hares, largely indepedent of specific adaptation to local or regional climate.

Striatal Dopamine Transporter Uptake, Parkinsonism, and Cognition in Alzheimer's Disease.

The correlates of motor parkinsonism in Alzheimer's disease (AD) remains controversial. We evaluated the effects of nigrostriatal dopaminergic degeneration on parkinsonism and cognition in biomarker-validated patients with AD. This study recruited 116 patients with AD who underwent dual-phase 18 F-N-(3-fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) nortropane PET, 18 F-Florbetaben PET, 3-Tesla brain MRI, Unified Parkinson's Disease Rating Scale (UPDRS) and neuropsychological tests. The mean cortical thickness in the frontal, temporal, parietal, and occipital cortices, and the dopamine transporter (DAT) uptake in the caudate, anterior/posterior putamen, and substantia nigra were quantified. We investigated the relationship between DAT uptake, mean lobar cortical thickness, UPDRS motor score, and cognition using general linear models (GLMs) after controlling for age, sex, education, intracranial volume, and deep and periventricular white matter hyperintensities. A path analysis was performed for the UPDRS motor score with the same covariates. Path analysis and multivariable GLM for UPDRS motor score showed that lower caudate DAT uptake was directly associated with a higher UPDRS motor score, whereas caudate DAT uptake confounded the association between mean frontal/parietal thickness and UPDRS motor score. Multivariable GLMs for cognitive scores showed that lower caudate DAT uptake was associated with visuospatial/executive dysfunction independent of mean frontal or parietal thickness. Nigrostriatal dopaminergic dysfunction is associated with parkinsonism and visuospatial/executive dysfunction in patients with AD.

Do executive functions differentiate Iranian children with attention-deficit/hyperactivity disorder with and without comorbid obesity?

To compare multiple dimensions of executive function between children with attention-deficit/hyperactivity disorder (ADHD) with and without comorbid obesity. Participants were 90 Iranian children (ages 8-13, 50% female) who were equally dispersed across three study groups: typically developing (TD), ADHD with obesity (ADHD+O), and ADHD without obesity (ADHD-O). Study participants were administered a comprehensive battery of Iranian-adapted "cool" executive function tasks including Digit Span from the Wechsler Intelligence Scale for Children-Fifth Edition (WISC-V), Victoria Stroop Test (VST), Wisconsin Card Sorting Test (WCST), Tower of London, and dot-probe task (i.e., a task of attentional bias). Parents completed the Children's Scale for Future Thinking Questionnaire, which assesses future-oriented cognition (e.g., saving, planning, episodic foresight, delay of gratification), aligning more with "hot" executive functions. Groups were compared using multivariate and post-hoc univariate general linear models. Significant group effects were observed for all executive function variables, broadly with the gradient pattern of TD > ADHD-O > ADHD+O. ADHD+O had poorer performances than ADHD-O for WISC-V Digit Span (d = -0.84), WCST Categories Completed (d = -0.55) and Perseverative Responses (d = 1.15), VST Interference Errors (d = 0.83) and Interference Time (d = 1.38), and Dot-Probe Task (d = 0.84). Relative to the ADHD-O group, ADHD+O had also poorer parent-reported Prospective Memory (d = -0.62), Episodic Foresight (d = -0.63), and Delay of Gratification (d = -0.54). Children with ADHD-O have poorer executive functioning than those without obesity. We observed stronger effects for "cool" rather than "hot" domains of executive function, though this could be due to the former being performance-based and the latter parent-reported.

Association of the Severity of Hypertensive Disorders in Pregnancy with Birthweight, Childhood Obesity, and Blood Pressure at Age 7.

We aimed to examine the effects of various severities of hypertensive disorders in pregnancy on birthweight, blood pressure (BP), and body mass index in offspring at age 7. In the China Labor and Delivery Survey and the United States Collaborative Perinatal Project (CPP), the relationship of the severity of hypertensive disorders and nutritional and cardiovascular outcomes in offspring was assessed using a multivariable logistic and general linear regression model. In both datasets, those with gestational hypertension were more likely to deliver large for gestational age (LGA) and macrosomia (adjusted odds ratios (aOR) ranged from 1.29 to 1.91), as well as low birth weight (LBW) neonates (aOR ranged from 1.23 to 3.56), compared with normotensive mothers. In the CPP, when gestational hypertension was further stratified into mild and severe, only those with mild gestational hypertension (the mild group) were more likely to deliver macrosomia and LGA (aOR ranged from 1.25 to 1.32). Others (severe gestational hypertension and preeclampsia/eclampsia) were closely related to LBW and small for gestational age (aOR ranged from 1.27 to 2.77). Moreover, children of mothers in the mild group tended to be overweight/obese and had elevated diastolic BP. We concluded that the severity of hypertensive disorders had different effects on birthweight, childhood overweight, and BP.

Association of markers of inflammation on attention and neurobehavioral outcomes in survivors of childhood acute lymphoblastic leukemia.

Survivors of childhood acute lymphoblastic leukemia (ALL) are at-risk of developing cognitive impairment and neurobehavioral symptoms. Inflammation induced by a compromised health status during cancer survivorship is proposed as a pathophysiological mechanism underlying cognitive impairment in cancer survivors. To evaluate the associations of biomarkers of inflammation with attention and neurobehavioral outcomes in survivors of childhood ALL, and to identify clinical factors associated with biomarkers of inflammation in this cohort. We recruited patients who were diagnosed with ALL at ≤ 18 years old and were currently ≥5 years post-cancer diagnosis. The study outcomes were attention (Conners Continuous Performance Test) and self-reported behavioral symptoms (Adult Self-Report [ASR] checklist). Using a commercial screening kit, survivors' plasma (5ml) was assayed for 17 cytokines/chemokine cell-signaling molecules that are associated with neurodegenerative diseases. The final panel of the targeted markers included interleukin (IL)-8, IL-13, interferon-gamma (IFN-γ), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1β, and tumor necrosis factor-α. Biomarker levels were rank-ordered into tertiles based on the sample distribution. Multivariable general linear modeling was used to test for associations between biomarkers and study outcomes in the overall cohort and stratified by gender. This study included 102 survivors (55.9% males, mean[SD] age 26.2[5.9] years; 19.3[7.1] years post-diagnosis). Survivors within top tertiles of IFN-γ (Estimate =6.74, SE=2.26; P=0.0037) and IL-13 (Estimate =5.10, SE=2.27; P=0.027) demonstrated more inattentiveness. Adjusting for age, gender and treatment, more self-reported thought (Estimate=3.53, SE=1.78; P=0.050) and internalizing problems (Estimate =6.52, SE=2.91; P=0.027) correlated with higher IL-8. Higher levels of IL-13 (RR = 4.58, 95% CI: 1.01-11.10) and TNF-α (RR = 1.44, 95% CI: 1.03-4.07) were observed in survivors had developed chronic health conditions (n=26, 25.5%). The stratified analysis showed that association of IFN-γ with attention was stronger in male survivors than in female survivors. Inflammation due to cancer-related late effects may potentially be mechanistic mediators of neurobehavioral problems in pediatric ALL survivors. Markers of inflammation can potentially be applied to assess or monitor the effectiveness of interventions, particularly behavioral interventions, in improving cognitive outcomes in survivors. Future work includes understanding the underlying gender-specific pathophysiology behind functional outcomes in the population.