Associations of strabismus surgery timing in childhood with mental health: a retrospective cohort study.

PURPOSE: To investigate the incidence of psychiatric diagnoses in relation to strabismus surgery timing among children with an early strabismus diagnosis who underwent surgery in childhood. METHODS: We conducted a retrospective cohort study using TriNetX network data from 2003-2023 on patients diagnosed with strabismus at ≤5 years of age and having strabismus surgery before 18 years of age. Cohort 1 comprised patients who underwent initial strabismus surgery at ≤6 years of age; cohort 2, patients with initial surgical intervention at ≥7 years of age. Incidence of mental health diagnoses from 7 until 18 years of age were compared between cohorts. RESULTS: In cohort 1, 59 of 688 patients (8.6%) of patients were diagnosed with at least 1 mental health disorder versus 123 of 693 patients (17.7%) in cohort 2 (risk ratio [RR] = 2.07; 95% CI, 1.546 to 2.77; P < 0.0001). Gender analysis showed that only males had a statistically significant increased rate of mental health diagnoses in cohort 2 versus cohort 1 (RR = 1.82; 95% CI, 1.284 to 2.577; P = 0.006). An increased risk for specific psychiatric diagnoses was found in cohort 2 versus cohort 1; anxiety disorders (RR = 2.19; 95% CI, 1.225-3.922; P = 0.0065), attention-deficit / hyperactivity disorder (RR = 2.18; 95% CI, 1.499-3.175; P < 0.0001), conduct disorders (RR = 2.81; 95% CI, 1.425-5.556; P = 0.0018), and adjustment disorders (RR = 2.07; 955% CI, 1.103-3.876; P = 0.0204). Depressive disorders showed no statistically significant difference between cohorts (RR = 1.00; 95% CI, 0.419-2.392; P = 0.9974). CONCLUSIONS: Compared with children having early strabismus surgery, those having surgery at a later age after an early strabismus diagnosis at ≤5 years of age may be more likely to experience a mental health disorder during childhood, although it is unclear whether such disorders are a result of delayed surgery or a driver of the decision to opt for surgery rather than continued conservative management.

Novel Quality Control Metric for the Pharmacotherapy of Major Depressive Disorder: Measuring Guideline Concordance and Its Impact on Symptom Severity.

Objective: Studies suggest that people with major depressive disorder (MDD) often receive treatment that is not concordant with practice guidelines. To evaluate this, we (1) developed a guideline concordance algorithm for MDD pharmacotherapy (GCA-8), (2) scored it using clinical data, and (3) compared its explanation of patient-reported symptom severity to a traditional concordance measure.Methods: This study evaluated 1,403 adults (67% female, 85% non-Hispanic/Latino White, mean age 43 years) with non-psychotic MDD (per ICD-10 codes), from the Penn State Psychiatry Clinical Assessment and Rating Evaluation System (PCARES) registry (visits from February 1, 2015, to April 13, 2021). We (1) scored 1-year concordance using the Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines and deviation from 8 pharmacotherapy-related criteria and (2) examined associations between concordance and Patient Health Questionnaire depression module (PHQ-9) scores.Results: The mean GCA-8 score was 6.37 (standard deviation [SD] = 1.30; 8.00 = perfect concordance). Among those who switched drugs (n = 671), 81% (n = 542) did not have their dose increased to the recommended maximum before switching. In our adjusted analyses, we found that a 1 SD increase in the GCA-8 was associated with a 0.78 improvement in the mean PHQ-9 score (P < .001). The comparison concordance measure was not associated with the mean PHQ-9 score (ß = -0.20; P = .20; R2 = 0.53), and adding the GCA-8 score significantly improved the model (R2 = 0.54; Vuong test P = .008).Conclusions: By measuring naturalistic MDD pharmacotherapy guideline concordance with the GCA-8, we revealed potential treatment gaps and an inverse association between guideline concordance and MDD symptom severity.

Effects of mixed metal exposures on MRI diffusion features in the medial temporal lobe.

Background: Environmental exposure to metal mixtures is common and may be associated with increased risk for neurodegenerative disorders including Alzheimer's disease. Objective: This study examined associations of mixed metal exposures with medial temporal lobe (MTL) MRI structural metrics and neuropsychological performance. Methods: Metal exposure history, whole blood metal, and neuropsychological tests were obtained from subjects with/without a history of mixed metal exposure from welding fumes (42 exposed subjects; 31 controls). MTL structures (hippocampus, entorhinal and parahippocampal cortices) were assessed by morphologic (volume, cortical thickness) and diffusion tensor imaging [mean (MD), axial (AD), radial diffusivity (RD), and fractional anisotropy (FA)] metrics. In exposed subjects, correlation, multiple linear, Bayesian kernel machine regression, and mediation analyses were employed to examine effects of single- or mixed-metal predictor(s) and their interactions on MTL structural and neuropsychological metrics; and on the path from metal exposure to neuropsychological consequences. Results: Compared to controls, exposed subjects had higher blood Cu, Fe, K, Mn, Pb, Se, and Zn levels (p's<0.026) and poorer performance in processing/psychomotor speed, executive, and visuospatial domains (p's<0.046). Exposed subjects displayed higher MD, AD, and RD in all MTL ROIs (p's<0.040) and lower FA in entorhinal and parahippocampal cortices (p's<0.033), but not morphological differences. Long-term mixed-metal exposure history indirectly predicted lower processing speed performance via lower parahippocampal FA (p=0.023). Higher whole blood Mn and Cu predicted higher entorhinal diffusivity (p's<0.043) and lower Delayed Story Recall performance (p=0.007) without overall metal mixture or interaction effects. Discussion: Mixed metal exposure predicted MTL structural and neuropsychological features that are similar to Alzheimer's disease at-risk populations. These data warrant follow-up as they may illuminate the path for environmental exposure to Alzheimer's disease-related health outcomes.

Underuse of SARS-CoV-2-Neutralizing Monoclonal Antibodies in Skilled Nursing Facilities.

OBJECTIVE: Little is known about deployment of SARS-CoV-2-neutralizing monoclonal antibodies (mab) in skilled nursing facilities (SNFs), a high-risk population for COVID-19-related complications. We assessed the utilization of mabs in SNFs and identified facility characteristics associated with effective use. DESIGN: Retrospective cohort study assessing the correlation of SNF characteristics with increasing mab use. SETTING AND PARTICIPANTS: United States SNFs participating in Project ECHO (Extensions for Community Health Outcomes). METHODS: The primary outcome was percentage of total mabs per COVID-19 cases in SNFs. Facilities were divided into 3 groups based on the percentage of the administration of mabs per number of cases: 0%, >0% to 20%, >20%. Ordinal logistic regression was applied to assess whether facility characteristics-study group, state, location, type, size, rating at baseline, weekly average of residents vaccinated, weekly average of staff vaccinated, and total weeks short staffed-correlated with the primary outcome. A multivariable model was used to evaluate the independent effect of predictors. RESULTS: A total of 130 facilities were included. Between the weeks ending on May 30, 2021, and on May 29, 2022, mean mab use when accounting for the number of COVID-19 cases was 12.96% (±26.71%) and >50% of facilities administered 0 doses of mabs. Facility location was associated with mab use (P value .030), with micropolitan facilities having the highest percentage of facilities administering mabs (30.4% in >0% to 20%, and 39.1% in >20%, respectively). There was a nonsignificant trend toward increased mab use in facilities reporting fewer staffing shortages. When the multivariable ordinal logistic regression model was applied, location in a micropolitan vs metropolitan area was associated with higher odds [3.29 (1.30, 8.32), P value .012] of increasing percentage total mabs per cases. CONCLUSIONS AND IMPLICATIONS: COVID-19 mabs were underutilized in a high-risk population for COVID-19 hospitalization and death. Understanding the barriers to effective distribution is critical in shaping pandemic preparedness efforts for the future.

Ultrasound versus computed tomography-guided transthoracic biopsy for pleural and peripheral lung lesions: a systematic review and meta-analysis.

BACKGROUND: An accurate diagnosis of peripheral lung and pleural lesions using image-guided transthoracic biopsy procedure becomes a good diagnostic performance protocol. PURPOSE: To examine the difference between ultrasonography (USG)-guided versus computed tomography (CT)-guided transthoracic biopsy for pleural and peripheral lung lesions by pooling data from published studies. MATERIAL AND METHODS: PubMed, CENTRAL, Scopus, Web of Science, and Embase were searched for comparative studies up to 20 February 2023 irrespective of the language of publication. The outcomes were adequacy of the sample and complications (pneumothorax and hemothorax). RESULTS: Two randomized controlled trials (RCTs) and eight non-RCTs were eligible. The total sample size was 1618. Meta-analysis showed that there was no difference in the adequacy of the sample obtained by USG- or CT-guided biopsies; however, an analysis of only non-RCTs indicated better adequacy with USG. On pooled analysis of any pneumothorax, there was a lower risk associated with USG-guided biopsies, but the risk of pneumothorax requiring interventional treatment was not different in the two groups. Similarly, the pooled analysis also demonstrated a reduced risk of hemothorax with USG-guided biopsies. CONCLUSION: While there seems to be no difference in the adequacy of the sample obtained with either imaging modality, retrospective data show that USG guidance offers better diagnostic yield compared to CT guidance for peripheral lung and pleural biopsies. The risk of pneumothorax and hemothorax is also significantly lower with USG-guided biopsies. Results should be interpreted with caution owing to selection bias among studies. There is a need for large-scale RCTs to enhance current evidence.

Atmospheric oxidation capacity and secondary pollutant formation potentials based on photochemical loss of VOCs in a megacity of the Sichuan Basin, China.

Volatile organic compounds (VOCs) are significant precursors to photochemical pollution. However, reactive VOC species are easily oxidized during transportation, resulting in a systematic underestimate of the measured concentrations. To address this, we applied an improved calculation method to correct the measured VOC concentrations into photochemical initial concentrations (PICs) in Chengdu, a megacity in the Sichuan Basin, China, which is highly vulnerable to complex pollution. In this study, 56 VOC species on the Photochemical Assessment Monitor Station (PAMS) target list were quantitatively monitored throughout all four seasons. Comparing to directly measured values, photochemically initialized total mixing ratios of VOCs increased by 18.6 % in general. The photochemical loss percentages of alkenes and aromatics were prominent in summer (68.6 %, 28.7 %) and spring (65.9 %, 24.7 %), respectively. Furthermore, we examined contributions of VOCs to atmospheric oxidation capacity (AOC) depending on PICs and found that maximum daily total AOC showed a surge in spring and summer. Besides hydroxyl radicals, daytime O3 in spring and late-afternoon nitrate radicals in summer were essential for AOC with PICs. As expected, alkenes and aromatics dominated PIC-based ozone formation potentials (OFPs). Furthermore, contribution of alkenes to secondary organic aerosol formation potentials reached 15.5 % and 7.6 % in spring and summer, respectively. Using positive matrix factorization model, we identified five VOC sources including vehicular exhaust, industrial emissions, solvent usage, biogenic sources, and liquefied petroleum gas/natural gas use. Based on PICs, biogenic sources were significantly underestimated in spring and summer. Meanwhile, m,p-xylene from solvent usage and isoprene from biogenic sources were the primary contributors to OFPs. Consequently, these results emphasize the significance of photochemically oxidized VOC concentrations, especially for reactive species in typical seasons.

Accelerating guideline dissemination in nursing homes during the COVID-19 pandemic: A patient-centered randomized controlled trial.

BACKGROUND: Nursing homes were ill-equipped for the pandemic; though facilities are required to have infection control staff, only 3% have taken a basic infection control course. Little is known about the implementation of effective practices outside of the acute care setting. We proposed an intervention utilizing Project ECHO, to connect Penn State University experts with nursing home staff and administrators to explore how infection control guidelines can be implemented effectively. METHODS: A stratified cluster randomized design was used to assign nursing homes to either AHRQ-funded COVID-19 ECHO or AHRQ-funded COVID-19 ECHO+. RESULTS: 136 nursing homes participated. There were no significant differences in COVID-19 infection rate, hospitalization, deaths, or influenza, between ECHO or ECHO+. DISCUSSION: The ECHO model has significant strengths when compared to traditional training, as it allows for remote learning delivered by a multidisciplinary team of experts and utilizes case discussions that match the context of nursing homes.

Imaging features of small vessel disease in cerebral amyloid angiopathy among patients with Alzheimer's disease.

BACKGROUND AND PURPOSE: Cerebral small vessel disease biomarkers including white matter hyperintensities (WMH), lacunes, and enlarged perivascular spaces (ePVS) are under investigation to identify those specific to cerebral amyloid angiopathy (CAA). In subjects with Alzheimer's disease (AD), we assessed characteristic features and amounts of WMH, lacunes, and ePVS in four CAA categories (no, mild, moderate and severe CAA) and correlated these with Clinical Dementia Rating sum of boxes (CDRsb) score, ApoE genotype, and neuropathological changes at autopsy. METHODS: The study included patients with a clinical diagnosis of dementia due to AD and neuropathological confirmation of AD and CAA in the National Alzheimer's Coordinating Center (NACC) database. The WMH, lacunes, and ePVS were evaluated using semi-quantitative scales. Statistical analyses compared the WMH, lacunes, and ePVS values in the four CAA groups with vascular risk factors and AD severity treated as covariates, and to correlate the imaging features with CDRsb score, ApoE genotype, and neuropathological findings. RESULTS: The study consisted of 232 patients, of which 222 patients had FLAIR data available and 105 patients had T2-MRI. Occipital predominant WMH were significantly associated with the presence of CAA (p = 0.007). Among the CAA groups, occipital predominant WMH was associated with severe CAA (ß = 1.22, p = 0.0001) compared with no CAA. Occipital predominant WMH were not associated with the CDRsb score performed at baseline (p = 0.68) or at follow-up 2-4 years after the MRI (p = 0.92). There was no significant difference in high grade ePVS in the basal ganglia (p = 0.63) and centrum semiovale (p = 0.95) among the four CAA groups. The WMH and ePVS on imaging did not correlate with the number of ApoE ε4 alleles but the WMH (periventricular and deep) correlated with the presence of infarcts, lacunes and microinfarcts on neuropathology. CONCLUSION: Among patients with AD, occipital predominant WMH is more likely to be found in patients with severe CAA than in those without CAA. The high-grade ePVS in centrum semiovale were common in all AD patients regardless of CAA severity.

Dopamine D1 Agonists: First Potential Treatment for Late-Stage Parkinson's Disease.

Current pharmacotherapy has limited efficacy and/or intolerable side effects in late-stage Parkinson's disease (LsPD) patients whose daily life depends primarily on caregivers and palliative care. Clinical metrics inadequately gauge efficacy in LsPD patients. We explored if a D1/5 dopamine agonist would have efficacy in LsPD using a double-blind placebo-controlled crossover phase Ia/b study comparing the D1/5 agonist PF-06412562 to levodopa/carbidopa in six LsPD patients. Caregiver assessment was the primary efficacy measure because caregivers were with patients throughout the study, and standard clinical metrics inadequately gauge efficacy in LsPD. Assessments included standard quantitative scales of motor function (MDS-UPDRS-III), alertness (Glasgow Coma and Stanford Sleepiness Scales), and cognition (Severe Impairment and Frontal Assessment Batteries) at baseline (Day 1) and thrice daily during drug testing (Days 2-3). Clinicians and caregivers completed the clinical impression of change questionnaires, and caregivers participated in a qualitative exit interview. Blinded triangulation of quantitative and qualitative data was used to integrate findings. Neither traditional scales nor clinician impression of change detected consistent differences between treatments in the five participants who completed the study. Conversely, the overall caregiver data strongly favored PF-06412562 over levodopa in four of five patients. The most meaningful improvements converged on motor, alertness, and functional engagement. These data suggest for the first time that there can be useful pharmacological intervention in LsPD patients using D1/5 agonists and also that caregiver perspectives with mixed method analyses may overcome limitations using methods common in early-stage patients. The results encourage future clinical studies and understanding of the most efficacious signaling properties of a D1 agonist for this population.

Higher hippocampal diffusivity values in welders are associated with greater R2* in the red nucleus and lower psychomotor performance.

INTRODUCTION: Chronic excessive welding exposure may be related to higher metal accumulation and structural differences in different subcortical structures. We examined how welding affected brain structures and their associations with metal exposure and neurobehavioral consequences. METHODS: Study includes 42 welders and 31 controls without a welding history. Welding-related structural differences were assessed by volume and diffusion tensor imaging (DTI) metrics in basal ganglia, red nucleus (RN), and hippocampus. Metal exposure was estimated by both exposure questionnaires and whole blood metal levels. Brain metal accumulations were estimated by R1 (for Mn) and R2* (for Fe). Neurobehavioral status was assessed by standard neuropsychological tests. RESULTS: Compared to controls, welders displayed higher hippocampal mean (MD), axial (AD), and radial diffusivity (RD) (p's < 0.036), but similar DTI or volume in other ROIs (p's > 0.117). Welders had higher blood metal levels (p's < 0.004), higher caudate and RN R2* (p's < 0.014), and lower performance on processing/psychomotor speed, executive function, and visuospatial processing tasks (p's < 0.046). Higher caudate and RN R2* were associated with higher blood Fe and Pb (p's < 0.043), respectively. RN R2* was a significant predictor of all hippocampal diffusivity metrics (p's < 0.006). Higher hippocampal MD and RD values were associated with lower Trail Making Test-A scores (p's < 0.025). A mediation analysis of both groups revealed blood Pb indirectly affected hippocampal diffusivity via RN R2* (p's < 0.041). DISCUSSION: Welding-related higher hippocampal diffusivity metrics may be associated with higher RN R2* and lower psychomotor speed performance. Future studies are warranted to test the role of Pb exposure in these findings.

Short-term Air Pollution Levels and Blood Pressure in Older Women.

BACKGROUND: Evidence of associations between daily variation in air pollution and blood pressure (BP) is varied and few prior longitudinal studies adjusted for calendar time. METHODS: We studied 143,658 postmenopausal women 50 to 79 years of age from the Women's Health Initiative (1993-2005). We estimated daily atmospheric particulate matter (PM) (in three size fractions: PM2.5, PM2.5-10, and PM10) and nitrogen dioxide (NO2) concentrations at participants' residential addresses using validated lognormal kriging models. We used linear mixed-effects models to estimate the association between air pollution concentrations and repeated measures of systolic and diastolic BP (SBP, DBP) adjusting for confounders and calendar time. RESULTS: Short-term PM2.5 and NO2 were each positively associated with DBP {0.10 mmHg [95% confidence interval (CI): 0.04, 0.15]; 0.13 mmHg (95% CI: 0.09, 0.18), respectively} for interquartile range changes in lag 3-5 day PM2.5 and NO2. Short-term NO2 was negatively associated with SBP [-0.21 mmHg (95%CI: -0.30, -0.13)]. In two-pollutant models, the NO2-DBP association was slightly stronger, but for PM2.5 was attenuated to null, compared with single-pollutant models. Associations between short-term NO2 and DBP were more pronounced among those with higher body mass index, lower neighborhood socioeconomic position, and diabetes. When long-term (annual) and lag 3-5 day PM2.5 were in the same model, associations with long-term PM2.5 were stronger than for lag 3-5 day. CONCLUSIONS: We observed that short-term PM2.5 and NO2 levels were associated with increased DBP, although two-pollutant model results suggest NO2 was more likely responsible for observed associations. Long-term PM2.5 effects were larger than short-term.

Intensive behavioral Therapy for weight loss in patients with, or At-Risk of, type 2 Diabetes: Results from the PaTH to health diabetes study.

Intensive behavioral therapy (IBT) is an important component of obesity treatment and can reduce the risk of type 2 diabetes (T2DM). Objective was to compare the effectiveness of IBT to usual care in achieving weight loss in two study cohorts within PaTH Network: T2DM and At-Risk of T2DM. The TD2M cohort was defined as age 18 years and older with an indication of T2DM in the EHR based on a validated algorithm and at least 2 outpatient primary care visits. The At-Risk of T2DM cohort was defined by a BMI ≥ 25 kg/m2. The primary outcome was weight change within 1-year of index date. Mixed-effects models assessed the effectiveness of IBT by comparing the changes between study groups. Between 2009 and 2020, a total of 567,908 patients were identified in the T2DM cohort and2,054,256 patients in the At-Risk of T2DM cohort. Both IBT patients and matched non-IBT patients in the T2DM cohort had decreased mean weight (primary outcome) (-1.56 lbs, 95 %CI: -1.88, -1.24 vs -1.70 lbs, 95 %CI: -1.95, -1.44) in 1-year after index date. In the At-Risk of T2DM cohort, both IBT and non-IBT patients experienced weight gain and resultant increased BMI. Patients with more than one IBT visit gained less weight than those with only one visit (1.22 lbs, 95 %CI: 0.82, 1.62 vs 6.72 lbs, 95 %CI: 6.48, 6.97; p < 0.001). IBT was unlikely to result in clinically significant weight loss. Barriers to utilizing IBT require further research to ensure broader adoption of obesity management in primary care.

Susceptibility Magnetic Resonance Imaging Correlates with Glial Density and Tau in the Substantia Nigra Pars Compacta.

BACKGROUND: Susceptibility magnetic resonance imaging (MRI) is sensitive to iron-related changes in the substantia nigra pars compacta (SNc), the key pathologic locus of parkinsonisms. It is unclear, however, if iron deposition in the SNc is associated with its neurodegeneration. OBJECTIVE: The objective of this study was to test whether susceptibility MRI metrics in parkinsonisms are associated with SNc neuropathologic features of dopaminergic neuron loss, gliosis, and α-synuclein and tau burden. METHODS: This retrospective study included 27 subjects with both in vivo MRI and postmortem data. Multigradient echo imaging was used to derive the apparent transverse relaxation rate (R2*) and quantitative susceptibility mapping (QSM) in the SNc. Archived midbrain slides that were stained with hematoxylin and eosin, anti-α-synuclein, and anti-tau were digitized to quantify neuromelanin-positive neuron density, glial density, and the percentages of area occupied by positive α-synuclein and tau staining. MRI-histology associations were examined using Pearson correlations and regression. RESULTS: Twenty-four subjects had postmortem parkinsonism diagnoses (Lewy body disorder, progressive supranuclear palsy, multiple system atrophy, and corticobasal degeneration), two had only Alzheimer's neuropathology, and one exhibited only mild atrophy. Among all subjects, both R2* and QSM were associated with glial density (r ≥ 0.67; P < 0.001) and log-transformed tau burden (r ≥ 0.53; P ≤ 0.007). Multiple linear regression identified glial density and log-transformed tau as determinants for both MRI metrics (R2 ≥ 0.580; P < 0.0001). Neither MRI metric was associated with neuron density or α-synuclein burden. CONCLUSIONS: R2* and QSM are associated with both glial density and tau burden, key neuropathologic features in the parkinsonism SNc. © 2023 International Parkinson and Movement Disorder Society.

Thermo-Sensitive Spikelet Defects 1 acclimatizes rice spikelet initiation and development to high temperature.

Crop reproductive development is vulnerable to heat stress, and the genetic modulation of thermotolerance during the reproductive phase, especially the early stage, remains poorly understood. We isolated a Poaceae-specific FAR-RED ELONGATED HYPOCOTYLS3 (FHY3)/FAR-RED IMPAIRED RESPONSE1 (FAR1)family transcription factor, Thermo-sensitive Spikelet Defects 1 (TSD1), derived from transposase in rice (Oryza sativa) TSD1 was highly expressed in spikelets, induced by heat, and specifically enhanced the thermotolerance of spikelet morphogenesis. Disrupting TSD1 did not affect vegetative growth but markedly retarded spikelet initiation and development, as well as caused varying degrees of spikelet degeneration, depending on the temperature. Most tsd1 spikelets were normal at low temperature but gradually degenerated as temperature increased, and all disappeared at high temperature, leading to naked branches. TSD1 directly promoted the transcription of YABBY1 and YABBY3 and could physically interact with YABBY1 and three TOB proteins, YABBY5, YABBY4, and YABBY3. These YABBY proteins can form either homodimers or heterodimers and play an important role in spikelet morphogenesis, similar to TSD1. Notably, the knockout mutant yab5-ko and double mutant tsd1 yab5-ko resembled tsd1 in spikelet appearance and response to temperature, indicating that these genes likely participate in spikelet development through the cooperative TSD1-YABBY module. These findings reveal a distinctive function of FHY3/FAR1 family genes and a unique TSD1-YABBY complex to acclimate spikelet development to high temperature in rice, providing insight into the regulating pathway of enhancing thermotolerance in plant reproductive development.

Frontostriatal and limbic contributions to cognitive decline in Parkinson's disease.

BACKGROUND AND PURPOSE: The circuitry underlying heterogenous cognitive profiles in Parkinson's disease (PD) remains unclear. The purpose of this study is to investigate whether structural changes in frontostriatal and limbic pathways contribute to different cognitive trajectories in PD. METHODS: We obtained clinical and multimodal MRI data from 120 control and 122 PD subjects without dementia or severe motor disability. T1/T2-weighted images estimated volume, and diffusion imaging evaluated fractional anisotropy (FA) of frontostriatal (striatum and frontostriatal white matter [FSWM]) and limbic (hippocampus and fornix) structures. Montreal Cognitive Assessment (MoCA) gauged total and domain-specific (attention/executive and memory) cognitive function. Linear mixed-effects models were used to compare MRI and cognitive progression over 4.5 years between controls and PD and evaluate associations between baseline MRI and cognitive changes in PD. RESULTS: At baseline, control and PD groups were comparable, except PD participants had smaller striatal volume (p < 0.001). Longitudinally, PD showed faster decline in hippocampal volume, FSWM FA, and fornix FA (ps < .016), but not striatal volume (p = .218). Total and domain-specific MoCA scores declined faster in PD (ps < .030). In PD, lower baseline hippocampal volume (p = .005) and fornix FA (p = .032), but not striatal volume (p = .662) or FSWM FA (p = .143), were associated with faster total MoCA decline. Baseline frontostriatal metrics of striatal volume and FSWM FA were associated with faster attention/executive decline (p < .038), whereas lower baseline hippocampal volume was associated with faster memory decline (p = .005). CONCLUSION: In PD, frontostriatal structural metrics are associated with attention/executive tasks, whereas limbic changes correlated with faster global cognitive decline, particularly in memory tasks.

Effects of Desk Pedaling Work Rate on Concurrent Work Performance among Physically Inactive Adults: A Randomized Experiment.

PURPOSE: Under-desk pedaling devices could help reduce health risks associated with the global decline in work-related energy expenditure. However, the optimal pedaling work rate to facilitate concurrent work performance among physically inactive adults is unclear. We examined the effects of two light-intensity pedaling work rates on physically inactive adults' work performance. METHODS: We recruited equal numbers of older (45-65 yr) versus younger (20-44 yr), male versus female, and overweight/obese (body mass index [BMI], 25-35 kg·m -2 ) versus normal weight (BMI, 18.5-24.9 kg·m -2 ) participants. Using a Graeco-Latin square design, participants ( n = 96) completed a laboratory experiment to evaluate the effects of using an under-desk pedaling device at two seated light-intensity work rates (17 and 25 W), relative to a seated nonpedaling condition on objectively measured typing, reading, logical reasoning, and phone task performance. Ergonomic comfort under each pedaling work rate was also assessed. Equivalence tests were used to compare work performance under the pedaling versus nonpedaling conditions. RESULTS: Treatment fidelity to the 17- and 25-W pedaling work rates exceeded 95%. Mean work performance scores for each pedaling and nonpedaling condition were equivalent under alpha = 0.025. Age, sex, and BMI did not significantly moderate the effect of pedaling on work performance. Participants reported greater ergonomic comfort while completing work tasks at the 17-W relative to the 25-W work rate. CONCLUSIONS: Physically inactive adults obtained similar work performance scores under the 17- and 25-W pedaling and the nonpedaling conditions, suggesting that either pedaling work rate could help reduce health risks of sedentary work time. The 17-W work rate yielded greater ergonomic comfort and may be an appropriate starting point for introducing diverse inactive workers to under-desk pedaling.

A Novel Multi-view Bi-clustering method for identifying abnormal Co-occurrence medical visit behaviors.

Abnormal co-occurrence medical visit behavior is a form of medical insurance fraud. Specifically, an organized gang of fraudsters hold multiple medical insurance cards and purchase similar drugs frequently at the same time and the same location in order to siphon off medical insurance funds. Conventional identification methods to identify such behaviors rely mainly on manual auditing, making it difficult to satisfy the needs of identifying the small number of fraudulent behaviors in the large-scale medical data. On the other hand, the existing single-view bi-clustering algorithms only consider the features of the time-location dimension while neglecting the similarities in prescriptions and neglecting the fact that fraudsters may belong to multiple gangs. Therefore, in this paper, we present a multi-view bi-clustering method for identifying abnormal co-occurrence medical visit behavioral patterns, which performs cluster analysis simultaneously on the large-scale, complex and diverse visiting record dimension and prescription dimension to identify bi-clusters with similar time-location features. The proposed method constructs a matrix view of patients and visit records as well as a matrix view of patients and prescriptions, while decomposing multiple data matrices into sparse row and column vectors to obtain a consistent patient population across views. Subsequently the proposed method identifies the corresponding abnormal co-occurrence medical visit behavior and may greatly facilitate the safe operations and the sustainability of medical insurance funds. The experimental results show that our proposed method leads to more efficient and more accurate identifications of abnormal co-occurrence medical visit behavior, demonstrating its high efficiency and effectiveness.

Hospitalization and mortality in patients with COVID-19 with or at risk of type 2 diabetes: data from five health systems in Pennsylvania and Maryland.

OBJECTIVE: To identify the demographic and clinical characteristics associated with adverse COVID-19 outcomes across a 12-month period in 2020 and 2021. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study using electronic health records from five academic health systems in Pennsylvania and Maryland, including patients with COVID-19 with type 2 diabetes or at risk of type 2 diabetes. Patients were classified based on 30-day outcomes: (1) no hospitalization; (2) hospitalization only; or (3) a composite measure including admission to the intensive care unit (ICU), intubation, or death. Analyses were conducted in patients with type 2 diabetes and patients at risk of type 2 diabetes separately. RESULTS: We included 15 725 patients with COVID-19 diagnoses between March 2020 and February 2021. Older age and higher Charlson Comorbidity Index scores were associated with higher odds of adverse outcomes, while COVID-19 diagnoses later in the study period were associated with lower odds of severe outcomes. In patients with type 2 diabetes, individuals on insulin treatment had higher odds for ICU/intubation/death (OR=1.59, 95% CI 1.27 to 1.99), whereas those on metformin had lower odds (OR=0.56, 95% CI 0.45 to 0.71). Compared with non-Hispanic White patients, Hispanic patients had higher odds of hospitalization in patients with type 2 diabetes (OR=1.73, 95% CI 1.36 to 2.19) or at risk of type 2 diabetes (OR=1.77, 95% CI 1.43 to 2.18.) CONCLUSIONS: Adults who were older, in racial minority groups, had multiple chronic conditions or were on insulin treatment had higher risks for severe COVID-19 outcomes. This study reinforced the urgency of preventing COVID-19 and its complications in vulnerable populations. TRIAL REGISTRATION NUMBER: NCT02788903.

A Dopamine D1 Agonist Versus Methylphenidate in Modulating Prefrontal Cortical Working Memory.

Methylphenidate is used widely to treat symptoms of attention-deficit/hyperactivity disorder (ADHD), but like other stimulants has significant side effects. This study used a rodent model (spontaneously hypertensive rat) of spatial working memory (sWM) to compare the effects of methylphenidate with the novel dopamine D1-like receptor agonist 2-methyldihydrexidine. Acute oral administration of methylphenidate (1.5 mg/kg) caused sWM improvement in half of the tested rats, but impairment in the others. Both improvement or impairment were eliminated by administration of the D1 antagonist SCH39266 directly into the prefrontal cortex (PFC). Conversely, 2-methyldihydrexidine showed greater sWM improvement compared with methylphenidate without significant impairment in any subject. Its effects correlated negatively with vehicle-treated baseline performance (i.e., rats with lower baseline performance improved more than rats with higher baseline performance). These behavioral effects were associated with neural activities in the PFC. Single neuron firing rate was changed, leading to the alteration in neuronal preference to correct or error behavioral responses. Overall, 2-methyldihydrexidine was superior to methylphenidate in decreasing the neuronal preference, prospectively, in the animals whose behavior was improved. In contrast, methylphenidate, but not 2-methyldihydrexidine, significantly decreased neuronal preference, retrospectively, in those animals who had impaired performance. These results suggest that a D1 agonist may be more effective than methylphenidate in regulating sWM-related behavior through neural modulation of the PFC, and thus may be superior to methylphenidate or other stimulants as ADHD pharmacotherapy. SIGNIFICANCE STATEMENT: Methylphenidate is effective in ADHD by its indirect agonist stimulation of dopamine and/or adrenergic receptors, but the precise effects on specific targets are unclear. This study compared methylphenidate to a dopamine D1 receptor-selective agonist by investigating effects on working memory occurring via neural modulation in the prefrontal cortex. The data suggest that pharmacological treatment selectively targeting the dopamine D1 may offer a superior approach to ADHD pharmacotherapy.

Tyrosine hydroxylase involved in cuticle tanning and reproduction in the 28-spotted potato ladybeetle, Henosepilachna vigintioctopunctata.

BACKGROUND: Tyrosine hydroxylase (TH), a melanin synthesis pathway enzyme hydroxylating tyrosine into 3,4-dihydroxyphenylalanine, is involved in the pigmentation and sclerotization of insect cuticles. However, the role of TH in 28-spotted potato ladybeetle (Henosepilachna vigintioctopunctata), an emerging pest of the solanaceous crops has been explored to a limited extent. In this study, we integrated dietary RNA interference (RNAi) and hematoxylin and eosin (H&E) staining with various bioassays to analyze the role of tyrosine hydroxylase (HvTH) throughout the developmental processes of Henosepilachna vigintioctopunctata. RESULTS: The results revealed that ingestion of dsHvTH led to cuticle tanning impairment, arrested larval feeding in the first and second instars of Henosepilachna vigintioctopunctata, and subsequently resulted in 100% mortality. The H&E staining assays revealed that dsHvTH prevented new abdominal cuticle formation. A pharmacological study using 3-iodo-tyrosine (3-IT), a HvTH inhibitor, disrupted larval-larval-pupal cuticle tanning during the third-fourth instar larval development and eventually failed to pupate. Similarly, dsHvTH fed to fourth instars hindered larval-pupal-adult cuticle tanning, and the eclose adults were 100% malformed. Ingestion of dsHvTH or 3-IT significantly down-regulated HvTH, HvDDC, Hvebony, and Hvlaccase2 expression and reduced dopamine levels. Finally, HvTH silencing in adult females substantially reduced the offspring hatching rates. CONCLUSIONS: The collective results of the study suggested that HvTH plays conserved roles in larval-pupal-adult cuticle melanization and sclerotization while exhibiting a novel function in Henosepilachna vigintioctopunctata reproduction. © 2022 Society of Chemical Industry.