VCP/p97 Extracts Sterically Trapped Ku70/80 Rings from DNA in Double-Strand Break Repair.

During DNA double-strand break (DSB) repair, the ring-shaped Ku70/80 complex becomes trapped on DNA and needs to be actively extracted, but it has remained unclear what provides the required energy. By means of reconstitution of DSB repair on beads, we demonstrate here that DNA-locked Ku rings are released by the AAA-ATPase p97. To achieve this, p97 requires ATP hydrolysis, cooperates with the Ufd1-Npl4 ubiquitin-adaptor complex, and specifically targets Ku80 that is modified by K48-linked ubiquitin chains. In U2OS cells, chemical inhibition of p97 or siRNA-mediated depletion of p97 or its adapters impairs Ku80 removal after non-homologous end joining of DSBs. Moreover, this inhibition attenuates early steps in homologous recombination, consistent with p97-driven Ku release also affecting repair pathway choice. Thus, our data answer a central question regarding regulation of Ku in DSB repair and illustrate the ability of p97 to segregate even tightly bound protein complexes for release from DNA.

Psycholinguistic changes in the communication of adolescent users in a suicidal ideation online community during the COVID-19 pandemic.

Since the outbreak of the COVID-19 pandemic, increases in suicidal ideation and suicide attempts in adolescents have been registered. Many adolescents experiencing suicidal ideation turn to online communities for social support. In this retrospective observational study, we investigated the communication-language style, contents and user activity-in 7975 unique posts and 51,119 comments by N = 2862 active adolescent users in a large suicidal ideation support community (SISC) on the social media website reddit.com in the onset period of the COVID-19 pandemic. We found significant relative changes in language style markers for hopelessness such as negative emotion words (+ 10.00%) and positive emotion words (- 3.45%) as well as for social disengagement such as social references (- 8.63%) and 2nd person pronouns (- 33.97%) since the outbreak of the pandemic. Using topic modeling with Latent Dirichlet Allocation (LDA), we identified significant changes in content for the topics Hopelessness (+ 23.98%), Suicide Methods (+ 17.11%), Social Support (- 14.91%), and Reaching Out to users (- 28.97%). Changes in user activity point to an increased expression of mental health issues and decreased engagement with other users. The results indicate a potential shift in communication patterns with more adolescent users expressing their suicidal ideation rather than relating with or supporting other users during the COVID-19 pandemic.

Intensity of Treatment as Usual and Its Impact on the Effects of Face-to-Face and Internet-Based Psychotherapy for Depression: A Preregistered Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Treatment as usual (TAU) is the most frequently used control group in randomized trials of psychotherapy for depression. Concerns have been raised that the heterogeneity of treatments in TAU leads to biased estimates of psychotherapy efficacy and to an unclear difference between TAU and control groups like waiting list (WL). OBJECTIVE: We investigated the impact of control group intensity (i.e., amount and degree to which elements of common depression treatments are provided) on the effects of face-to-face and internet-based psychotherapy for depression. METHODS: We conducted a preregistered meta-analysis (www.osf.io/4mzyd). We included trials comparing psychotherapy with TAU or WL in patients with symptoms of unipolar depression. Six indicators were used to assess control group intensity. PRIMARY OUTCOME: Standardized mean difference (SMD) of psychotherapy and control in depressive symptoms at treatment termination. RESULTS: We included 89 trials randomizing 14,474 patients to 113 psychotherapy conditions and 89 control groups (TAU in 42 trials, WL in 47 trials). Control group intensity predicted trial results in preregistered (one-sided ps < 0.042) and exploratory analyses. Psychotherapy effects were significantly smaller (one-sided p = 0.002) in trials with higher intensity TAU (SMD = 0.324, CI 0.209 to 0.439) than in trials with lower intensity TAU (SMD = 0.628, CI 0.455 to 0.801). Psychotherapy effects against lower intensity TAU did not differ from effects against WL (two-sided p = 0.663). CONCLUSIONS: Our results suggest that variation in TAU intensity impacts the outcome of trials. More scrutiny in the design of control groups for clinical trials is recommended.

Digital Platform Uses for Help and Support Seeking of Parents With Children Affected by Disabilities: Scoping Review.

BACKGROUND: Receiving a diagnosis that leads to severe disability in childhood can cause a traumatic experience with long-lasting emotional stress for patients and family members. In recent decades, emerging digital technologies have transformed how patients or caregivers of persons with disabilities manage their health conditions. As a result, information (eg, on treatment and resources) has become widely available to patients and their families. Parents and other caregivers can use digital platforms such as websites or social media to derive social support, usually from other patients and caregivers who share their lived experiences, challenges, and successes on these platforms. However, gaps remain in our understanding of platforms that are most frequently used or preferred among parents and caregivers of children with disabilities. In particular, it is not clear what factors primarily drive or discourage engagement with these digital tools and what the main ethical considerations are in relation to these tools. OBJECTIVE: We aimed to (1) identify prominent digital platforms used by parents or caregivers of children with disabilities; (2) explore the theoretical contexts and reasons for digital platform use, as well as the experiences made with using these platforms reported in the included studies; and (3) identify any privacy and ethical concerns emerging in the available literature in relation to the use of these platforms. METHODS: We conducted a scoping review of 5 academic databases of English-language articles published within the last 10 years for diseases with childhood onset disability and self-help or parent/caregiver-led digital platforms. RESULTS: We identified 17 papers in which digital platforms used by parents of affected children predominantly included social media elements but also search engines, health-related apps, and medical websites. Information retrieval and social support were the main reasons for their utilization. Nearly all studies were exploratory and applied either quantitative, qualitative, or mixed methods. The main ethical concerns for digital platform users included hampered access due to language barriers, privacy issues, and perceived suboptimal advice (eg, due to missing empathy of medical professionals). Older and non-college-educated individuals and ethnic minorities appeared less likely to access information online. CONCLUSIONS: This review showed that limited scientifically sound knowledge exists on digital platform use and needs in the context of disabling conditions in children, as the evidence consists mostly of exploratory studies. We could highlight that affected families seek information and support from digital platforms, as health care systems seem to be insufficient for satisfying knowledge and support needs through traditional channels.

Changes in Language Style and Topics in an Online Eating Disorder Community at the Beginning of the COVID-19 Pandemic: Observational Study.

BACKGROUND: COVID-19 has affected individuals with lived experience of eating disorders (EDs), with many reporting higher psychological distress, higher prevalence of ED symptoms, and compensatory behaviors. The COVID-19 pandemic and the health and safety measures taken to contain its spread also disrupted routines and reduced access to familiar coping mechanisms, social support networks, and health care services. Social media and the ED communities on social media platforms have been an important source of support for individuals with EDs in the past. So far, it is unknown how discussions in online ED communities changed as offline support networks were disrupted and people spent more time at home in the first months of the COVID-19 pandemic. OBJECTIVE: The aim of this study is to identify changes in language content and style in an online ED community during the initial onset of the COVID-19 pandemic. METHODS: We extracted posts and their comments from the ED community on the social media website Reddit and concatenated them to comment threads. To analyze these threads, we applied top-down and bottom-up language analysis methods based on topic modeling with latent Dirichlet allocation and 13 indicators from the Linguistic Inquiry and Word Count program, respectively. Threads were split into prepandemic (before March 11, 2020) and midpandemic (after March 11, 2020) groups. Standardized mean differences were calculated to estimate change between pre- and midpandemic threads. RESULTS: A total of 17,715 threads (n=8772, 49.5% prepandemic threads; n=8943, 50.5% midpandemic threads) were extracted from the ED community and analyzed. The final topic model contained 21 topics. CIs excluding zero were found for standardized mean differences of 15 topics and 9 Linguistic Inquiry and Word Count categories covering themes such as ED symptoms, mental health, treatment for EDs, cognitive processing, social life, and emotions. CONCLUSIONS: Although we observed a reduction in discussions about ED symptoms, an increase in mental health and treatment-related topics was observed at the same time. This points to a change in the focus of the ED community from promoting potentially harmful weight loss methods to bringing attention to mental health and treatments for EDs. These results together with heightened cognitive processing, increased social references, and reduced inhibition of negative emotions detected in discussions indicate a shift in the ED community toward a pro-recovery orientation.

High-Throughput Screening for CEBPD-Modulating Compounds in THP-1-Derived Reporter Macrophages Identifies Anti-Inflammatory HDAC and BET Inhibitors.

This study aimed to identify alternative anti-inflammatory compounds that modulate the activity of a relevant transcription factor, CCAAT/enhancer binding protein delta (C/EBPδ). C/EBPδ is a master regulator of inflammatory responses in macrophages (Mϕ) and is mainly regulated at the level of CEBPD gene transcription initiation. To screen for CEBPD-modulating compounds, we generated a THP-1-derived reporter cell line stably expressing secreted alkaline phosphatase (SEAP) under control of the defined CEBPD promoter (CEBPD::SEAP). A high-throughput screening of LOPAC®1280 and ENZO®774 libraries on LPS- and IFN-γ-activated THP-1 reporter Mϕ identified four epigenetically active hits: two bromodomain and extraterminal domain (BET) inhibitors, I-BET151 and Ro 11-1464, as well as two histone deacetylase (HDAC) inhibitors, SAHA and TSA. All four hits markedly and reproducibly upregulated SEAP secretion and CEBPD::SEAP mRNA expression, confirming screening assay reliability. Whereas BET inhibitors also upregulated the mRNA expression of the endogenous CEBPD, HDAC inhibitors completely abolished it. All hits displayed anti-inflammatory activity through the suppression of IL-6 and CCL2 gene expression. However, I-BET151 and HDAC inhibitors simultaneously upregulated the mRNA expression of pro-inflammatory IL-1ß. The modulation of CEBPD gene expression shown in this study contributes to our understanding of inflammatory responses in Mϕ and may offer an approach to therapy for inflammation-driven disorders.

{FeNO}7 -Type Halogenido Nitrosyl Ferrates: Syntheses, Bonding, and Photoinduced Linkage Isomerism.

Mononitrosyl-iron compounds (MNICs) of the Enemark-Feltham {FeNO}7 type can be divided into a doublet (S=1/2) and a quartet (S=3/2) spin variant. The latter relies on weak-field co-ligands such as amine carboxylates. Aqua-only co-ligation appears to exist in the long-known "brown-ring" [Fe(H2 O)5 (NO)]2+ cation, which was prepared originally from ferrous salts and NO in sulfuric acid. A chloride variant of this species, the green [FeCl3 (NO)]- ion, was first prepared analoguosly by using hydrochloric instead of sulfuric acid. As a tetrahedral species, it is the simple prototype of sulfur-bonded {FeNO}7 (S=3/2) MNICs of biological significance. Although it has been investigated for more than a century, neither clean preparative routes nor reliable structural parameters were available for the [FeCl3 (NO)]- ion and related species such as the [FeCl2 (NO)2 ]- ion, a prototypical dinitrosyliron species (a "DNIC"). In this work, both issues have been resolved. In addition, we report on a computational study on the ground- and excited-state properties including an assignment of the chromophoric transitions. Photoinduced metastable isomers were characterised in a combined experimental and computational approach that resulted in the confirmation of a single photoinduced linkage isomer of the paramagnetic nitrosyl-metal coordination entity.

Two-Year Follow-Up after Treatment with the Cognitive Behavioral Analysis System of Psychotherapy versus Supportive Psychotherapy for Early-Onset Chronic Depression.

BACKGROUND: Evidence on the long-term efficacy of psychotherapeutic approaches for chronic depression is scarce. OBJECTIVE: To evaluate the effects of the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) compared to Supportive Psychotherapy (SP) 1 year and 2 years after treatment termination. METHODS: In this study, we present 1- and 2-year follow-up assessments of a prospective, multicenter, evaluator-blinded, randomized clinical trial of outpatients with early-onset chronic major depression (n = 268). The initial treatment included 32 sessions of CBASP or SP over 48 weeks. The primary outcome was the rate of "well weeks" (Longitudinal Interval Follow-Up Evaluation; no/minimal symptoms) after 1 year and 2 years. The secondary outcomes were, among others, clinician- and self-rated depressive symptoms, response/remission rates, and quality of life. RESULTS: Of the 268 randomized patients, 207 (77%) participated in the follow-up. In the intention-to-treat analysis, there was no statistically significant difference between CBASP and SP patients in experiencing well weeks (CBASP: mean [SD] of 48.6 [36.9] weeks; SP: 39.0 [34.8]; rate ratio 1.26, 95% CI 0.99-1.59, p = 0.057, d = 0.18) and in remission rates (CBASP: 1 year 40%, 2 years 40.2%; SP: 1 year 28.9%, 2 years 33%) in the 2 years after treatment. Statistically significant effects were found in favor of CBASP 1 year after treatment termination regarding the rate of well weeks, self-rated depressive symptoms, and depression-related quality of life. CONCLUSIONS: CBASP lost its superiority over SP at some point between the first and the second year. This suggests the necessity of maintenance treatment for early-onset chronically depressed patients remitted with CBASP during the acute therapy phase, as well as the sequential integration of other treatment strategies, including medication for those who did not reach remission.

Antidepressant prescription practice and related factors in Switzerland: a cross-sectional analysis of health claims data.

BACKGROUND: The aim of the study was to examine the prevalence of and factors associated with antidepressant (AD) prescriptions in order to draw a comprehensive picture of prescribing practices in Switzerland. METHOD: We conducted a population-based, cross-sectional descriptive study using a large Swiss healthcare claims database, covering approximately 13% of the Swiss population. AD prescription was determined by identifying patients (N = 105,663) with health claims data of at least 1 AD prescription in the year 2016. AD medication was identified using ATC-codes classified by the World Health Organisation. Univariate, bivariate and multivariate analyses using logistic regression were performed. RESULTS: The extrapolated 1-year prevalence of AD prescription was 8.7% (95% CI, 8.7-8.8) with two thirds of AD recipients being female and the average age being 59 years (SD = 19.1). The regional distribution of prescription rates varied between cantons and ranged from 6.5 to 11.7%. Logistic regression revealed higher prescription rates among females compared to males (OR: 1.52) and an increased probability of AD prescription by age up until 54 years (OR: 2.25) and ≥ 85 years (OR: 2.32). Comorbidity is associated with higher odds (OR: 3.26 with 1-2 comorbidities) and enrollment in a managed care plan (compared to standard care) with lower odds for an AD prescription (OR: 0.85). CONCLUSION: This study is the first in Switzerland to describe the prevalence of and factors associated with AD prescription based on a large health claims database reflecting routine care. The results provide important information about regional variation, prescription source, and potential over-prescription in the treatment of depressive disorders.

Analyzing big data in social media: Text and network analyses of an eating disorder forum.

OBJECTIVE: Social media plays an important role in everyday life of young people. Numerous studies claim negative effects of social media and media in general on eating disorder risk factors. Despite the availability of big data, only few studies have exploited the possibilities so far in the field of eating disorders. METHOD: Methods for data extraction, computerized content analysis, and network analysis will be introduced. Strategies and methods will be exemplified for an ad-hoc dataset of 4,247 posts and 34,118 comments by 3,029 users of the proed forum on Reddit. RESULTS: Text analysis with latent Dirichlet allocation identified nine topics related to social support and eating disorder specific content. Social network analysis describes the overall communication patterns, and could identify community structures and most influential users. A linear network autocorrelation model was applied to estimate associations in language among network neighbors. The supplement contains R code for data extraction and analyses. DISCUSSION: This paper provides an introduction to investigating social media data, and will hopefully stimulate big data social media research in eating disorders. When applied in real-time, the methods presented in this manuscript could contribute to improving the safety of ED-related online communication.

Patent Foramen Ovale and Cryptogenic Strokes in the Stroke in Young Fabry Patients Study.

BACKGROUND AND PURPOSE: A patent foramen ovale (PFO) is disproportionately prevalent in patients with cryptogenic stroke. Without alternative explanations, it is frequently considered to be causative. A detailed stratification of these patients may improve the identification of incidental PFO. METHODS: We investigated the PFO prevalence in 3497 transient ischemic attack and ischemic stroke patients aged 18 to 55 years in the prospective multicenter SIFAP1 study (Stroke in Young Fabry Patients 1) using the ASCO classification. Patients without an obvious cause for transient ischemic attack/stroke (ASCO 0) were divided into subgroups with and without vascular risk factors (ASCO 0+ and 0-). In addition, we looked for PFO-related magnetic resonance imaging lesion patterns. RESULTS: PFO was identified in 25% of patients. Twenty percent of patients with a definite or probable cause of transient ischemic attack/stroke (≥1 grade 1 or 2 ASCO criterion; n=1769) had a PFO compared with 29% of cryptogenic stroke patients (ASCO 0 and 3; n=1728; P<0,001); subdivision of cryptogenic strokes revealed a PFO in 24% of 978 ASCO 3 patients (n.s. versus ASCO 1 and 2) and a higher prevalence of 36% in 750 ASCO 0 cases (P<0.001 versus ASCO 3 and versus ASCO 1 and 2). PFO was more commonly observed in ASCO 0- (n=271) than in ASCO 0+ patients (n=479; 48 versus 29%; P<0.001). There was no PFO-associated magnetic resonance imaging lesion pattern. CONCLUSIONS: Cryptogenic stroke patients demonstrate a heterogeneous PFO prevalence. Even in case of less conclusive diseases like nonstenotic arteriosclerosis, patients should preferentially be considered to have a non-PFO-mediated stroke. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00414583.

Establishing the Secondary Metabolite Profile of the Marine Fungus: Tolypocladium geodes sp. MF458 and Subsequent Optimisation of Bioactive Secondary Metabolite Production.

As part of an international research project, the marine fungal strain collection of the Helmholtz Centre for Ocean Research (GEOMAR) research centre was analysed for secondary metabolite profiles associated with anticancer activity. Strain MF458 was identified as Tolypocladium geodes, by internal transcribed spacer region (ITS) sequence similarity and its natural product production profile. By using five different media in two conditions and two time points, we were able to identify eight natural products produced by MF458. As well as cyclosporin A (1), efrapeptin D (2), pyridoxatin (3), terricolin A (4), malettinins B and E (5 and 6), and tolypocladenols A1/A2 (8), we identified a new secondary metabolite which we termed tolypocladenol C (7). All compounds were analysed for their anticancer potential using a selection of the NCI60 cancer cell line panel, with malettinins B and E (5 and 6) being the most promising candidates. In order to obtain sufficient quantities of these compounds to start preclinical development, their production was transferred from a static flask culture to a stirred tank reactor, and fermentation medium development resulted in a nearly eight-fold increase in compound production. The strain MF458 is therefore a producer of a number of interesting and new secondary metabolites and their production levels can be readily improved to achieve higher yields.

First-person Pronoun Use in Spoken Language as a Predictor of Future Depressive Symptoms: Preliminary Evidence from a Clinical Sample of Depressed Patients.

Several theories suggest that self-focused attention plays an important role in the maintenance of depression. However, previous studies have predominantly relied on self-report and laboratory-based measures such as sentence completion tasks to assess individual differences in self-focus. We present a prospective, longitudinal study based on a sample of 29 inpatients with clinical depression, investigating whether an implicit, behavioural measure of self-focused attention, i.e., the relative frequency of first-person singular pronouns in naturally spoken language, predicts depressive symptoms at follow-up over and above initial depression. We did not find a significant cross-sectional association between depressive symptoms and first-person singular pronoun use. However, first-person singular pronoun use significantly predicted depressive symptoms approximately 8 months later, even after controlling for depressive symptoms at baseline or discharge. Exploratory analyses revealed that this effect was mainly driven by the use of objective and possessive self-references such as 'me' or 'my'. Our findings are in line with theories that highlight individual differences in self-focused attention as a predictor of the course of depression. Moreover, our findings extend previous work in this field by adopting an unobtrusive approach of non-reactive assessment, capturing naturally occurring differences in self-focused attention. We discuss possible clinical applications of language-based assessments and interventions with regard to self-focus. Copyright © 2016 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: Naturally occurring individual differences in first-person singular pronoun use provide an unobtrusive way to assess patients' automatic self-focused attention. Frequent use of first-person singular pronouns predicts an unfavourable course of depression. Self-focused language might offer innovative ways of tracking and targeting therapeutic change.

Internet-Delivered Disease Management for Recurrent Depression: A Multicenter Randomized Controlled Trial.

BACKGROUND: Strategies to improve the life of patients suffering from recurrent major depression have a high relevance. This study examined the efficacy of 2 Internet-delivered augmentation strategies that aim to prolong symptom-free intervals. METHODS: Efficacy was tested in a 3-arm, multicenter, open-label, evaluator-blind, randomized controlled trial. Upon discharge from inpatient mental health care, 232 adults with 3 or more major depressive episodes were randomized to 1 of 2 intervention groups (SUMMIT or SUMMIT-PERSON) or to treatment as usual (TAU) alone. Over 12 months, participants in both intervention arms received, in addition to TAU, intense monitoring via e-mail or a smartphone, including signaling of upcoming crises, assistance with personal crisis management, and facilitation of early intervention. SUMMIT-PERSON additionally offered regular expert chats. The primary outcome was 'well weeks', i.e. weeks with at most mild symptoms assessed by the Longitudinal Interval Follow-Up Evaluation, during 24 months after the index treatment. RESULTS: SUMMIT compared to TAU reduced the time with an unwell status (OR 0.48; 95% CI 0.23-0.98) through faster transitions from unwell to well (OR 1.44; 95% CI 0.83-2.50) and slower transitions from well to unwell (OR 0.69; 95% CI 0.44-1.09). Contrary to the hypothesis, SUMMIT-PERSON was not superior to either SUMMIT (OR 0.77; 95% CI 0.38-1.56) or TAU (OR 0.62; 95% CI 0.31-1.24). The efficacy of SUMMIT was strongest 8 months after the intervention. CONCLUSIONS: The fully automated Internet-delivered augmentation strategy SUMMIT has the potential to improve TAU by reducing the lifelong burden of patients with recurrent depression. The fact that the effects wear off suggests a time-unlimited extension.

NaV1.4 mutations cause hypokalaemic periodic paralysis by disrupting IIIS4 movement during recovery.

Hypokalaemic periodic paralysis is typically associated with mutations of voltage sensor residues in calcium or sodium channels of skeletal muscle. To date, causative sodium channel mutations have been studied only for the two outermost arginine residues in S4 voltage sensor segments of domains I to III. These mutations produce depolarization of skeletal muscle fibres in response to reduced extracellular potassium, owing to an inward cation-selective gating pore current activated by hyperpolarization. Here, we describe mutations of the third arginine, R3, in the domain III voltage sensor i.e. an R1135H mutation which was found in two patients in separate families and a novel R1135C mutation identified in a third patient in another family. Muscle fibres from a patient harbouring the R1135H mutation showed increased depolarization tendency at normal and reduced extracellular potassium compatible with the diagnosis. Additionally, amplitude and rise time of action potentials were reduced compared with controls, even for holding potentials at which all NaV1.4 are fully recovered from inactivation. These findings may be because of an outward omega current activated at positive potentials. Expression of R1135H/C in mammalian cells indicates further gating defects that include significantly enhanced entry into inactivation and prolonged recovery that may additionally contribute to action potential inhibition at the physiological resting potential. After S4 immobilization in the outward position, mutant channels produce an inward omega current that most likely depolarizes the resting potential and produces the hypokalaemia-induced weakness. Gating current recordings reveal that mutations at R3 inhibit S4 deactivation before recovery, and molecular dynamics simulations suggest that this defect is caused by disrupted interactions of domain III S2 countercharges with S4 arginines R2 to R4 during repolarization of the membrane. This work reveals a novel mechanism of disrupted S4 translocation for hypokalaemic periodic paralysis mutations at arginine residues located below the gating pore constriction of the voltage sensor module.

Age and gender related neuromuscular changes in trunk flexion-extension.

BACKGROUND: The root mean square surface electromyographic activity of lumbar extensor muscles during dynamic trunk flexion and extension from a standing position and task specific spine ranges of motion objectively assess muscle function in healthy young and middle age individuals. However, literature on neuromuscular activation and associated spine and hip kinematics in older individuals is sparse. This cross sectional study sought to examine the sex and age (<40 versus >60 years) related differences in the neuromuscular activation profiles of the lumbar extensors and the related spine and hip kinematics from healthy individuals during a standardized trunk flexion-extension task. METHODS: Twenty five older (13 females, 60-90 years) and 24 younger (12 females, 18-40 years) healthy individuals performed trunk flexion-extension testing by holding static positions at half-flexion way and full range of motion between standing and maximum trunk flexion. The associated lumbar extensor muscle activity was derived from measurements at standing, half, and maximum flexion positions. The range of motion at the hip and lumbar spine was recorded using 3d accelerometers attached to the skin overlying the multifidus and semispinalis thoracis muscles lateral to the L5 and T4 spinous processes, respectively. Statistical calculations were performed using a permutation ANOVA with bootstrap confidence intervals. RESULTS: The muscle activity in the half related to the maximum flexion position (half flexion relaxation ratio) was significantly smaller in older males when compared with younger males. Moreover, measurements revealed smaller activity changes from standing to the half and from half to the maximum flexion position in older compared to younger individuals. Older males displayed smaller gross trunk range of motion from standing to maximum flexion than any other group. CONCLUSIONS: Gender and normal aging significantly affect both the activation patterns of the lumbar extensor muscles and the kinematics of the trunk during a standardized trunk flexion-extension task. Measurement results from healthy young and middle age individuals should not be used for the assessment of individuals older than 60 years of age.

The potential use of spectral electromyographic fatigue as a screening and outcome monitoring tool of sarcopenic back muscle alterations.

BACKGROUND: To examine whether or not median frequency surface electromyographic (MF-EMG) back muscle fatigue monitoring would be able to identify alterations in back muscle function in elderly muscles, if a protocol was used that allowed optimum standardization of the processes underlying electromyographic fatigue, and whether these tests were reliable from day to day. METHODS: A total of 42 older (21 females; 67 (±10.5) years old) and 44 younger persons (19 females; 33 (±10) years) performed maximum isometric back extensions which were followed by one 30 s lasting 80% submaximum extension. Participants were seated on a dynamometer with their trunks 30° anteflexed, and they repeated all tests after 1-2 days and 6 weeks. SEMG was recorded bilaterally from the L1 (iliocostalis lumborum), L2 (longissimus), and L5 (multifidus) recording sites. Outcome variables included maximum back extension torque, initial MF-EMG (IMF-EMG), MF-EMG slope declines, and individual MF-EMG muscular imbalance scores. Two-factorial ANOVAs served to examine the age and gender-specific effects, and models from Generalizability Theory (G-Theory) were used for assessing retest-reliability. RESULTS: Maximum back extension moment was non-significantly smaller in elders. IMF-EMG was overall higher in elders, with significant differences at the L5 recordings sites. In the elderly, MF-EMG fatigue declines were significantly smaller in L5, in the recording with the most negative slope, or if the slope of all electrodes was considered. Retest reliability was unanimous in young and older persons. ICC-type measurements from G-Theory of both the IMF and the fatigue slopes ranged from 0.7 to 0.85. Absolute SEM values were found clinically acceptable for the IMF-EMG, but relatively high for the fatigue slope declines. CONCLUSIONS: The MF-EMG fatigue method is able to elucidate alterations of aging back muscles. This method, thus, might be suggested as a potential biomarker to objectively identify persons at risk for sarcopenia. Considering the clinical relevance of the IMF-EMG relative to the MF-EMG slope declines, spectral EMG may also be used as an outcome monitoring tool in elderly populations.

Cost-effectiveness of an internet-based aftercare intervention after inpatient treatment in a psychosomatic hospital.

OBJECTIVE: The implementation of new interventions into routine care requires the demonstration of both their effectiveness and cost-effectiveness. METHOD: We explored the cost-effectiveness of an Internet-based aftercare program in addition to treatment as usual (CHAT) which was compared to treatment as usual (TAU) following inpatient treatment. Incremental cost-effectiveness ratios were calculated based on cost of the intervention, cost of outpatient treatment, and remission rates within 1 year after discharge from hospital. RESULTS: Assuming a willingness-to-pay of an additional 14.87 € per treatment for every additional percent of remission, CHAT was cost-effective against TAU at a 95% level of certainty. Cost per remission equaled 2664.84 € in TAU and 1752.75 € in CHAT (34.2% savings). CONCLUSIONS: This is the first evidence that Internet-based aftercare may enhance long-term treatment outcome in a cost-effective way.

Prognostic Risk Factors in Randomized Clinical Trials of Face-to-Face and Internet-Based Psychotherapy for Depression: A Systematic Review and Meta-Regression Analysis.

Importance: Variables such as severe symptoms, comorbidity, and sociodemographic characteristics (eg, low educational attainment or unemployment) are associated with a poorer prognosis in adults treated for depressive symptoms. The exclusion of patients with a poor prognosis from RCTs is negatively associated with the generalizability of research findings. Objective: To compare the prognostic risk factors (PRFs) in patient samples of RCTs of face-to-face therapy (FTF) and internet-based therapy (IBT) for depression. Data Sources: PsycINFO, Cochrane CENTRAL, and reference lists of published meta-analyses were searched from January 1, 2000, to December 31, 2021. Study Selection: RCTs that compared FTF (individual or group therapy) and IBT (guided or self-guided interventions) against a control (waitlist or treatment as usual) in adults with symptoms of depression were included. Data Extraction and Synthesis: Data were extracted by 2 independent observers. The Cochrane revised risk-of-bias tool was used to assess the risk of bias. The study was preregistered with OSF Registries and followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Main Outcomes and Measures: The primary outcome was the standardized mean difference (Hedges g effect size) in depressive symptoms at treatment termination (assessed with standard patient self-report questionnaires), with a positive standardized mean difference indicating larger improvements in the intervention compared with those in the control group. Meta-regression analyses were adjusted for the type of control group. Three preregistered and 2 exploratory sensitivity analyses were conducted. A prognostic risk index (PROG) was created that calculated the sum of 12 predefined individual indicators, with scores ranging from 0 to 12 and higher scores indicating that a sample comprised patients with poorer prognoses. Results: This systematic review and meta-regression analysis identified 105 eligible RCTs that comprised 18 363 patients. In total, 48 studies (46%) examined FTF, and 57 studies (54%) examined IBT. The PROG was significantly higher in the RCTs of FTF than in the RCTs of IBT (FTF: mean [SD], 3.55 [1.75]; median [IQR], 3.5 [2.0-4.5]; IBT: mean [SD], 2.27 [1.66]; median [IQR], 2.0 [1.0-3.5]; z = -3.68, P < .001; Hedges g = 0.75; 95% CI, 0.36-1.15). A random-effects meta-regression analysis found no association of the PROG with the effect size. Sensitivity analyses with outliers excluded and accounting for risk of bias or small-study effects yielded mixed results on the association between the PROG and effect size. Conclusions and Relevance: The findings of this systematic review and meta-regression analysis suggest that samples of RCTs of FTF vs IBT differ with regard to PRFs. These findings have implications for the generalizability of the current evidence on IBT for depression. More RCTs of internet-based interventions with clinically representative samples are needed, and the reporting of PRFs must be improved.