Depression readmission risk is elevated in multiple sclerosis compared to other chronic illnesses.

OBJECTIVE: Assess readmissions for depression or suicide attempt (SA) after MS admission versus other chronic inflammatory illnesses. METHODS: This retrospective cohort study identified MS, asthma, rheumatoid arthritis (RA), depression, and SA in the 2013 National Readmissions Database by International Classification of Diseases codes. Index admissions (MS, n = 7698; asthma, n = 93,590; RA, n = 3685) and depression or SA readmission rates were analyzed. Hazard ratios (HRs) estimated 1-year depression/SA readmission hazard, comparing MS to asthma or RA, adjusting for age, sex, psychiatric comorbidity, substance abuse, tobacco use, income, and index hospitalization characteristics. RESULTS: MS had more baseline depression (24.7%) versus asthma (15.6%) and RA (14.6%). Ninety-day depression readmission rate was higher in MS (0.5%) than asthma (0.3%) and RA (0.03%). Depression readmission HR was higher after MS admission versus asthma (HR = 1.37, 95% confidence interval (CI) = 1.00-1.86, p = 0.0485) and RA (HR = 4.68, 95% CI = 1.60-13.62, p = 0.0047). HR was not different for SA readmission across groups. Depression readmission HR was more than double in MS patients with psychiatric disease or substance abuse versus RA or asthma patients with either comorbidity. CONCLUSION: Depression readmission risk after MS hospitalization was elevated versus asthma/RA. Substance use and baseline psychiatric comorbidity were more strongly associated with depression readmission in MS patients.

Depression and cognitive function in early multiple sclerosis: Multitasking is more sensitive than traditional assessments.

BACKGROUND: Persons with multiple sclerosis (MS) and depression symptoms report real-world cognitive difficulties that may be missed by laboratory cognitive tests. OBJECTIVE: To examine the relationship of depressive symptoms to cognitive monotasking versus multitasking in early MS. METHOD: Persons with early MS (n = 185; ⩽5 years diagnosed) reported mood, completed monotasking and multitasking cognitive tests, and received high-resolution 3.0 T magnetic resonance imaging (MRI). Partial correlations analyzed associations between mood and cognition, controlling for age, sex, estimated premorbid IQ, T2 lesion volume, and normalized gray matter volume. RESULTS: Depression symptoms were more related to worse cognitive multitasking (-0.353, p < 0.001) than monotasking (r = -0.189, p = 0.011). There was a significant albeit weaker link to cognitive efficiency composite score (r = -0.281, p < 0.001), but not composite memory (r = -0.036, p > 0.50). Findings were replicated with a second depression measure. Multitasking was worse in patients with at least mild depression than both patients with no/minimal depression and healthy controls. Multitasking was not related to mood in healthy controls. CONCLUSIONS: Depression symptoms are linked to cognitive multitasking in early MS; standard monotasking cognitive assessments appear less sensitive to depression-related cognition. Further investigation should determine directionality and mechanisms of this relationship, with the goal of enhancing treatment for cognitive dysfunction and depression in MS.

Transient N-glycosylation abnormalities likely due to a de novo loss-of-function mutation in the delta subunit of coat protein I.

Accurate glycosylation of proteins is essential for their function and their intracellular transport. Numerous diseases have been described, where either glycosylation or intracellular transport of proteins is impaired. Coat protein I (COPI) is involved in anterograde and retrograde transport of proteins between endoplasmic reticulum and Golgi, where glycosylation takes place, but no association of defective COPI proteins and glycosylation defects has been described so far. We identified a patient whose phenotype at a first glance was reminiscent of PGM1 deficiency, a disease that also affects N-glycosylation of proteins. More detailed analyses revealed a different disease with a glycosylation deficiency that was only detectable during episodes of acute illness of the patient. Trio-exome analysis revealed a de novo loss-of-function mutation in ARCN1, coding for the delta-COP subunit of COPI. We hypothesize that the capacity of flow through Golgi is reduced by this defect and at high protein synthesis rates, this bottleneck also manifests as transient glycosylation deficiency.

Testing the Efficacy of OurSpace, a Brief, Group Dynamics-Based Physical Activity Intervention: A Randomized Controlled Trial.

BACKGROUND: Emerging technologies (ie, mobile phones, Internet) may be effective tools for promoting physical activity (PA). However, few interventions have provided effective means to enhance social support through these platforms. Face-to-face programs that use group dynamics-based principles of behavior change have been shown to be highly effective in enhancing social support through promoting group cohesion and PA, but to date, no studies have examined their effects in Web-based programs. OBJECTIVE: The aim was to explore proof of concept and test the efficacy of a brief, online group dynamics-based intervention on PA in a controlled experiment. We expected that the impact of the intervention on PA would be moderated by perceptions of cohesion and the partner's degree of presence in the online media. METHODS: Participants (n=135) were randomized into same-sex dyads and randomly assigned to one of four experimental conditions: standard social support (standard), group dynamics-based-high presence, group dynamics-based-low presence, or individual control. Participants performed two sets of planking exercises (pre-post). Between sets, participants in partnered conditions interacted with a virtual partner using either a standard social support app or a group dynamics-based app (group dynamics-based-low presence and group dynamics-based-high presence), the latter of which they participated in a series of online team-building exercises. Individual participants were given an equivalent rest period between sets. To increase presence during the second set, participants in the group dynamics-based-high presence group saw a live video stream of their partner exercising. Perceptions of cohesion were measured using a modified PA Group Environment Questionnaire. Physical activity was calculated as the time persisted during set 2 after controlling for persistence in set 1. RESULTS: Perceptions of cohesion were higher in the group dynamics-based-low presence (overall mean 5.81, SD 1.04) condition compared to the standard (overall mean 5.04, SD 0.81) conditions ( P=.006), but did not differ between group dynamics-based-low presence and group dynamics-based-high presence (overall mean 5.42, SD 1.07) conditions ( P=.25). Physical activity was higher in the high presence condition (mean 64.48, SD 20.19, P=.01) than all other conditions (mean 53.3, SD 17.35). CONCLUSIONS: A brief, online group dynamics-based intervention may be an effective method of improving group cohesion in virtual PA groups. However, it may be insufficient on its own to improve PA.

Comparative gene identification 58/α/ß hydrolase domain 5 lacks lysophosphatidic acid acyltransferase activity.

Mutations in the gene encoding comparative gene identification 58 (CGI-58)/α/ß hydrolase domain 5 (ABHD5) cause Chanarin-Dorfman syndrome, characterized by excessive triacylglycerol storage in cells and tissues. CGI-58 has been identified as a coactivator of adipose TG lipase (ATGL) and a lysophosphatidic acid acyltransferase (LPAAT). We developed a molecular model of CGI-58 structure and then mutated predicted active site residues and performed LPAAT activity assays of recombinant WT and mutated CGI-58. When mutations of predicted catalytic residues failed to reduce LPAAT activity, we determined that LPAAT activity was due to a bacterial contaminant of affinity purification procedures, plsC, the sole LPAAT in Escherichia coli Purification protocols were optimized to reduce plsC contamination, in turn reducing LPAAT activity. When CGI-58 was expressed in SM2-1(DE3) cells that lack plsC, lysates lacked LPAAT activity. Additionally, mouse CGI-58 expressed in bacteria as a glutathione-S-transferase fusion protein and human CGI-58 expressed in yeast lacked LPAAT activity. Previously reported lipid binding activity of CGI-58 was revisited using protein-lipid overlays. Recombinant CGI-58 failed to bind lysophosphatidic acid, but interestingly, bound phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 5-phosphate [PI(5)P]. Prebinding CGI-58 with PI(3)P or PI(5)P did not alter its coactivation of ATGL in vitro. In summary, purified recombinant CGI-58 that is functional as an ATGL coactivator lacks LPAAT activity.

Disability outcomes in early-stage African American and White people with multiple sclerosis.

BACKGROUND: Factors driving differences in disease burden between African American and White people with multiple sclerosis (pwMS) remain unclear. Here, we explored whether differences in disability outcomes could be observed after controlling for major sociodemographic factors and comorbidities, and assessed the presence of a possible interaction between MS and race. METHODS: In this cross-sectional study, 120 pwMS within 6 years from disease onset and 82 healthy controls between 18 and 70 years of age, self-identified as either African American or White, were prospectively enrolled. Inclusion criteria for pwMS were: diagnosis of MS according to the revised McDonald criteria, relapsing-remitting phenotype and Expanded Disability Status Scale (EDSS) < 6.5. Study outcomes included: (i) global disability (EDSS); (ii) quantitative mobility and leg function (Timed 25 Foot Walk Test-T25FWT); (iii) quantitative finger dexterity (9-Hole Peg Test-9HPT); (iv) cognitive efficiency and speed performance (Symbol Digit Modalities Test-SDMT). Differences in disability outcomes were assessed employing multivariable linear regression models. Based on their association with MS or disability, covariates included age, gender, race, years of education, total income, body mass index, comorbidities. The interaction between MS and race on disability outcomes was estimated via relative excess risk of interaction and attributable proportion. RESULTS: Accounting for age, gender, total income, education, body mass index and comorbidities, African American pwMS showed significantly worse performances in manual dexterity and cognition than White pwMS (White pwMS coeff. 3.24, 95% CI 1.55, 4.92 vs African American pwMS coeff. 5.52, 95% CI 3.55, 7.48 and White pwMS coeff. -5.87, 95% CI -8.86, -2.87 vs African American pwMS coeff. -7.99, 95% CI -11.58,-4.38). MS and race independently contributed to the observed gradient in disability severity. CONCLUSIONS: Complex social disparities and systemic racism might contribute to clinical heterogeneity in MS.

Weight change and mental health status in a behavioral weight loss trial.

BACKGROUND: Obesity, depression, and anxiety often co-occur, but research on weight change and mental health status is limited. This analysis examined how the mental component score (MCS-12) from the Short Form health survey changed over 24 months in weight loss trial participants with vs. without treatment seeking for affective symptoms (TxASx) and by weight change quintiles. METHODS: Participants with complete data (n = 1163) were analyzed from enrollees in a cluster-randomized, behavioral weight loss trial in rural U.S. Midwestern primary care practices. Participants received a lifestyle intervention with different delivery models, including in-clinic individual, in-clinic group, or telephone group counseling visits. Participants were stratified by baseline TxASx status and 24-month weight change quintiles. Mixed models were used to estimate MCS-12 scores. RESULTS: There was a significant group-by-time interaction at the 24-month follow-up. The largest 0-24 month increase in MCS-12 scores (+5.3 points [12 %]) was observed in participants with TxASx who lost the most weight during the trial, while the largest decrease in MCS-12 scores (-1.8 points [-3 %]) was observed in participants without TxASx who gained the most weight (p < 0.001). LIMITATIONS: Notable limitations included self-reported mental health, the observational analytical design, and a largely homogenous source population, as well as the possibility of reverse causation biasing some findings. CONCLUSIONS: Mental health status generally improved, particularly among participants with TxASx who experienced significant weight loss. Those without TxASx who gained weight, however, had a decline in mental health status over 24 months. Replication of these findings is warranted.

Travel burden in a rural primary care behavioral weight loss randomized trial: Impact on visit attendance and weight loss.

PURPOSE: Rural residents have higher obesity rates and need access to treatment. Travel burden may limit use and effectiveness of clinic-based behavioral weight loss treatment, which includes frequent visits. This paper examines the impact of travel distance and time on visit attendance and weight loss during a 2-year cluster randomized trial. METHODS: Thirty-six primary care practices were randomized to 1 of 3 methods of providing behavioral weight loss counseling: individual clinic visits, group clinic visits, or group phone visits. Participants in the clinic visit conditions were included in this secondary analysis (n = 875). Travel distance and time was measured using ArcGIS and categorized as <15 miles (and minutes) or ≥15 miles (and minutes). Percent visit attendance and percent weight loss were measured 6 and 24 months. FINDINGS: Participants traveling ≥15 miles (n = 211) had lower attendance than those traveling <15 miles (n = 664) for individual clinic visits, both in the first 6 months (81.4% vs 89.1%, respectively; P = .005) and between 7 and 24 months (52.8% vs 61.6%, respectively; P = .02). Travel time revealed similar findings. Neither travel distance nor time had an effect on attendance to group clinic visits. Travel distance and time were not significantly associated with weight loss for either individual or group visits. CONCLUSION: Travel burden to clinics was associated with visit attendance for individual visits but not for group visits and was not significantly associated with weight loss. Assessment of travel burden as a potential barrier to clinic-based weight loss interventions should be based on local empirical data.

Rural engagement in primary care for optimizing weight reduction (REPOWER): A mixed methods study of patient perceptions.

OBJECTIVE: To report on patients' satisfaction and experience of care across three different modes of weight loss counseling. METHODS: 1407 patients with obesity in the rural Midwest were enrolled to a 2-year weight management trial through their primary care practice and assigned to one of three treatment conditions: in-clinic individual, in-clinic group, phone group counseling. Patients completed surveys assessing seven domains of satisfaction and experience of care at 6 and 24-months. Post-treatment interviews were conducted to add context to survey responses. RESULTS: 1295 (92.0%) and 1230 (87.4%) completed surveys at 6 and 24-months, respectively. Patients in phone group counseling reported lower satisfaction than patients who received in-clinic group or in-clinic individual counseling across all domains at 6-months and five out of seven domains at 24-months. Interviews revealed that patients were more satisfied when they received face-to-face counseling and had meaningful interactions with their primary care provider (PCP) about their weight. CONCLUSION: Rural patients with obesity have higher satisfaction and experience of care when weight loss counseling is delivered in a face-to-face environment and when their PCP is involved with their treatment. PRACTICE IMPLICATIONS: Primary care practices looking to offer weight loss treatment should consider incorporating some level of face-to-face treatment plans that involves meaningful interaction with the PCP.

Pediatric ICU Admissions After Adolescent Suicide Attempts During the Pandemic.

BACKGROUND AND OBJECTIVES: The worldwide severe acute respiratory syndrome coronavirus 2 pandemic challenges adolescents' mental health. In this study, we aim to compare the number of pediatric ICU (PICU) admissions after suicide attempts during the first German lockdown and one year later during a second, prolonged lockdown with prepandemic years. METHODS: A retrospective multicenter study was conducted among 27 German PICUs. Cases <18 years admitted to the PICU because of accidents or injuries between March 16 and May 31 of 2017 to 2021 were identified based on International Classification of Diseases, 10th Revision codes (German modification) and patient data entered into a database. This study is a subset analysis on suicide attempts in adolescents aged 12 to 17.9 years. The Federal Statistics Office was queried for data on fatal suicides, which were available only for 2020 in adolescents aged 10 to 17.9 years. RESULTS: Total admissions and suicide attempts declined during the first lockdown in 2020 (standardized morbidity ratio 0.74 (95% confidence interval; 0.58-0.92) and 0.69 (0.43-1.04), respectively) and increased in 2021 (standardized morbidity ratio 2.14 [1.86-2.45] and 2.84 [2.29-3.49], respectively). Fatal suicide rates remained stable between 2017 to 2019 and 2020 (1.57 vs 1.48 per 100 000 adolescent years) with monthly numbers showing no clear trend during the course of 2020. CONCLUSIONS: This study shows a strong increase in serious suicide attempts among adolescents during the course of the pandemic in Germany. More research is needed to understand the relation between pandemic prevention measures and suicidal ideation to help implement mental health support for adolescents.

Impact of the First COVID Lockdown on Accident- and Injury-Related Pediatric Intensive Care Admissions in Germany-A Multicenter Study.

Children's and adolescents' lives drastically changed during COVID lockdowns worldwide. To compare accident- and injury-related admissions to pediatric intensive care units (PICU) during the first German COVID lockdown with previous years, we conducted a retrospective multicenter study among 37 PICUs (21.5% of German PICU capacities). A total of 1444 admissions after accidents or injuries during the first lockdown period and matched periods of 2017-2019 were reported and standardized morbidity ratios (SMR) were calculated. Total PICU admissions due to accidents/injuries declined from an average of 366 to 346 (SMR 0.95 (CI 0.85-1.05)). Admissions with trauma increased from 196 to 212 (1.07 (0.93-1.23). Traffic accidents and school/kindergarten accidents decreased (0.77 (0.57-1.02 and 0.26 (0.05-0.75)), whereas household and leisure accidents increased (1.33 (1.06-1.66) and 1.34 (1.06-1.67)). Less neurosurgeries and more visceral surgeries were performed (0.69 (0.38-1.16) and 2.09 (1.19-3.39)). Non-accidental non-suicidal injuries declined (0.73 (0.42-1.17)). Suicide attempts increased in adolescent boys (1.38 (0.51-3.02)), but decreased in adolescent girls (0.56 (0.32-0.79)). In summary, changed trauma mechanisms entailed different surgeries compared to previous years. We found no evidence for an increase in child abuse cases requiring intensive care. The increase in suicide attempts among boys demands investigation.

Recruitment of Men Into a Pragmatic Rural Primary Care Weight Loss Trial.

Men remain underrepresented in behavioral weight loss trials and are more difficult to recruit compared to women. We describe recruitment response of men and women into a mixed-gender behavioral weight loss trial conducted within 36 rural primary care clinics. Participants were recruited through primary care clinics via direct mailings (n = 15,076) and in-clinic referrals by their primary care provider (PCP). Gender differences were examined in response rate to direct mailings, study referral source, and rates of proceeding to study screening, being eligible, and enrolling. Men had a lower response rate to direct mailings than women (7.8% vs. 17.7%, p < .001). Men (vs. women) responding to the mailing were more likely to respond by opt-in postcard (64.6% vs. 56.8%) and less likely to respond by phone (33.9% vs. 39.6%), p = .002. Among potential participants contacting the study (n = 2413), men were less likely to report being referred by PCPs (15.2% vs. 21.6%; p < .001), but were just as likely to proceed to screening, be eligible, and enroll. Men and women were more likely to proceed to screening when referred by PCPs (93.3% vs. 95.4%) compared to direct mailings (74.2% vs. 73.9%). Enrolled men were older (p < .001), more likely to be married (p = .04), and had higher levels of education (p = .01). Men were less likely than women to respond to direct mailings and to be referred by their PCP, but after contacting the study, had similar screening, eligibility, and enrollment rates. Encouraging and training providers to refer men during clinic visits may help recruit more men into primary care-based weight loss trials.

An electrochemical calibration unit for hydrogen analysers.

Determination of hydrogen in solids such as high strength steels or other metals in the ppb or ppm range requires hot-extraction or melt-extraction. Calibration of commercially available hydrogen analysers is performed either by certified reference materials CRMs, often having limited availability and reliability or by gas dosing for which the determined value significantly depends on atmospheric pressure and the construction of the gas dosing valve. The sharp and sudden appearance of very high gas concentrations from gas dosing is very different from real effusion transients and is therefore another source of errors. To overcome these limitations, an electrochemical calibration method for hydrogen analysers was developed and employed in this work. Exactly quantifiable, faradaic amounts of hydrogen can be produced in an electrochemical reaction and detected by the hydrogen analyser. The amount of hydrogen is exactly known from the transferred charge in the reaction following Faradays law; and the current time program determines the apparent hydrogen effusion transient. Random effusion transient shaping becomes possible to fully comply with real samples. Evolution time and current were varied for determining a quantitative relationship. The device was used to produce either diprotium (H2) or dideuterium (D2) from the corresponding electrolytes. The functional principle is electrochemical in nature and thus an automation is straightforward, can be easily implemented at an affordable price of 1-5% of the hydrogen analysers price.

Closed-Loop Feedback Illumination for Optical Inverse Tone-Mapping in Light Microscopy.

In this paper, we show that optical inverse tone-mapping (OITM) in light microscopy can improve the visibility of specimens, both when observed directly through the oculars and when imaged with a camera. In contrast to previous microscopy techniques, we premodulate the illumination based on the local modulation properties of the specimen itself. We explain how the modulation of uniform white light by a specimen can be estimated in real time, even though the specimen is continuously but not uniformly illuminated. This information is processed and back-projected constantly, allowing the illumination to be adjusted on the fly if the specimen is moved or the focus or magnification of the microscope is changed. The contrast of the specimen's optical image can be enhanced, and high-intensity highlights can be suppressed. A formal pilot study with users indicates that this optimizes the visibility of spatial structures when observed through the oculars. We also demonstrate that the signal-to-noise (S/N) ratio in digital images of the specimen is higher if captured under an optimized rather than a uniform illumination. In contrast to advanced scanning techniques that maximize the S/N ratio using multiple measurements, our approach is fast because it requires only two images. This can improve image analysis in digital microscopy applications with real-time capturing requirements.