Immediate and Sustained Effects of Neurofeedback and Working Memory Training on Cognitive Functions in Children and Adolescents with ADHD: A Multi-Arm Pragmatic Randomized Controlled Trial

Objective: To evaluate the effects of neurocognitive training methods on targeted cognitive functions in children and adolescent with ADHD. Method: A pragmatic four-arm randomized controlled trial compared two types of neurofeedback (Slow Cortical Potential and Live Z-score) and Working-memory training (WMT) with treatment as usual. N = 202 participants with ADHD aged 9 to 17 years were included. A battery of cognitive function tests was completed pretreatment, posttreatment, and after 6-months. Results: The effects of WMT on spatial and verbal working-memory were superior to neurofeedback and treatment as usual at posttreatment, but only partially sustained at follow-up. No other consistent effects were observed. We found no clear indications that effects were moderated by ADHD presentation, ongoing medication, age, or sex. Conclusion: The sustained effects of neurocognitive training on cognitive functioning in children and adolescents with ADHD may be limited. Future research should focus on more personalized forms of neurocognitive training.

Evaluation of the Immediate Effects of Digital Intervention Modules for Goals, Planning and Coping Planning on Physical Activity: Secondary Analysis of a Randomized Controlled Trial (Preprint)

BACKGROUND The use of digital interventions can be accurately monitored via log files. However, monitoring engagement with intervention goals or enactment of the actual behaviors targeted by the intervention is more difficult and is usually evaluated based on pre-post measurements in a controlled trial. OBJECTIVE To evaluate if engaging with two digital intervention modules focusing on physical activity goals and action plans, and coping with barriers had immediate effects on the actual physical activity behavior. METHODS The NoHoW Toolkit (TK) was a digital intervention developed for supporting long-term weight loss maintenance, evaluated in a 2 x 2 factorial randomized controlled trial. The TK contained various modules based on behavioral self-regulation and motivation theories, and contextual emotion regulation approaches, and involved continuous tracking of weight and physical activity through connected commercial devices (Fitbit Aria TM and Charge 2 TM). Two of the four trial arms had access to two modules directly targeting physical activity, i.e. a module for goal setting and action planning (“Goal”) and a module for identifying barriers and coping planning (“Barriers”). Module visits and completion were determined based on TK log files and time spent in the module web page. Five physical activity metrics (steps; activity; energy expenditure; fairly active, very active and total active minutes; and distance) were compared before and after visiting and completing the modules to examine whether the modules had immediate or sustained effects on physical activity. Immediate effect was determined based on 7-day windows before and after the visit, and sustained effects were evaluated for weeks 1-8 after module completion. RESULTS Out of the 811 participants, 498 (61.4%) visited the Goal module and 406 (50.1%) visited the Barriers module. The Barriers module had an immediate effect on very active and total active minutes (before-median for very active minutes: 24.2min/day, interquartile range IQR 10.4–43.0min vs. after: 24.9min, IQR 10.0–46.3min; P=.047; before-median for total active minutes: 45.1min/day, interquartile range IQR 22.9–74.9min vs. after: 46.9min, IQR 22.4–78.4min; P=.029). The differences were larger when only completed Barriers modules were considered. Barriers module completion was also associated with sustained effects in fairly active and total active minutes for most of the eight weeks following module completion, and for three weeks in very active minutes. CONCLUSIONS The Barriers module had small significant immediate and sustained effects on active minutes measured by a wrist-worn activity tracker. Future interventions should pay attention to assessing barriers and planning coping mechanisms to overcome them. CLINICALTRIAL ISRTCN registry ISRCTN88405328; https://www.isrctn.com/ISRCTN88405328.

Characterization of the Ovine Vaginal Microbiome and Inflammation Patterns as an Improved Testing Model of Human Vaginal Irritation

The development of therapies targeted to improve the health of women has utilized direct vaginal delivery as a more effective and less toxic method of protection from HIV and other pathogens. Vaginal applicants and delivery devices that provide sustained effects have been met with increasing acceptability, but the efficacy and toxicity outcomes have not been successfully predicted by preclinical in vitro studies and animal modeling. We have explored the utilization of sheep as a model for testing the safety of vaginal applicants and devices based on spatial and structural similarities to the human vagina. As recently noted by the FDA, an additional safety measure is an impact on the vaginal microbiome (VMB) that is known to contribute to vaginal health and influence pathogen susceptibility and drug metabolism. To advance the utility of the sheep vaginal model, we completed a thorough molecular characterization of the ovine VMB utilizing both next-generation sequencing (NGS) and PCR methods. The process also created a custom PCR array to quantify ovine VMB community profiles in an affordable, higher throughput fashion. The results from vaginal swabs (>475 samples) collected from non-pregnant crossbred Dorset and Merino ewes treated with selected vaginal applicants or collected as sham samples established 16 VMB community types (VMB CTs). To associate VMB CTs with eubiosis or dysbiosis, we also completed custom ELISAs for six cytokines identifying IL1B, IL8, TNFa, and CXCL10 as useful markers to support the characterization of ovine vaginal inflammation. The results indicated that Pasteurella, Actinobacillus, Pseudomonas, Bacteroides, Leptotrichia, and E. coli were common markers of eubiosis (low inflammatory marker expression), and that Haemophilus, Ureaplasma, and Corynebacterium were associated with dysbiosis (high cytokine levels). Utilizing the optimized workflow, we also confirmed the utility of three commonly used vaginal applicants for impact on the VMB and inflammatory state, producing a dataset that supports the recommendation for the use of sheep for testing of vaginal applicants and devices as part of preclinical pipelines.

Effects of sub-threshold transcutaneous auricular vagus nerve stimulation on cerebral blood flow

Transcutaneous auricular vagus nerve stimulation (taVNS) has shown promise as a non-invasive alternative to vagus nerve stimulation (VNS) with implantable devices, which has been used to treat drug-resistant epilepsy and treatment-resistant depression. Prior work has used functional MRI to investigate the brain response to taVNS, and more recent work has also demonstrated potential therapeutic effects of high-frequency sub-threshold taVNS in rheumatoid arthritis. However, no studies to date have measured the effects of high-frequency sub-threshold taVNS on cerebral blood flow (CBF). The objective of this study was to determine whether high-frequency (20 kHz) sub-threshold taVNS induces significant changes in CBF, a promising metric for the assessment of the sustained effects of taVNS. Arterial spin labeling (ASL) MRI scans were performed on 20 healthy subjects in a single-blind placebo-controlled repeated measures experimental design. The ASL scans were performed before and after 15 min of either sub-threshold taVNS treatment or a sham control. taVNS induced significant changes in CBF in the superior posterior cerebellum that were largely localized to bilateral Crus I and Crus II. Post hoc analyses showed that the changes were driven by a treatment-related decrease in CBF. Fifteen minutes of high-frequency sub-threshold taVNS can induce sustained CBF decreases in the bilateral posterior cerebellum in a cohort of healthy subjects. This study lays the foundation for future studies in clinical populations, and also supports the use of ASL measures of CBF for the assessment of the sustained effects of taVNS.

Potential of Bacterial Strains Isolated from Coastal Water for Wastewater Treatment and as Aqua-Feed Additives

Bacteria have various and sustained effects on humans in various fields: molecular biology, biomedical science, environmental/food industry, etc. This study was conducted to evaluate the wastewater treatment capacity and feed-additive fish-growth effect of four strains of bacteria: Pseudoalteromonas mariniglutinosa, Psychrobacter celer, Bacillus albus, and Bacillus safensis. In a wastewater degradation experiment, (i) nitrate-N and nitrite-N were removed within 1 h in all of the 4 bacterial strains; (ii) the removal rates of TAN and TN were higher in all of the strains relative to the B. subtilis. In a feed-additive experiment (5% Kg−1), (i) the growth of fish was higher in all of the 4 bacterial strains with the B. subtilis relative to the commercial feed; (ii) there was no significant growth difference for B. albus and B. safensis relative to the B. subtilis, but growth was higher in P. mariniglutinosa and P. celer. The results indicated that the 4 bacterial strains can be effectively utilized for biological wastewater treatment processes and as aqua-feed.

Sustained Effects of Government Response on the COVID-19 Infection Rate in China: A Multiple Mediation Analysis

Many scholars have considered the relationship between the government response to COVID-19, an important social intervention strategy, and the COVID-19 infection rate. However, few have examined the sustained impact of an early government response on the COVID-19 infection rate. The current paper fills this gap by investigating a national survey performed in February 2020 and infection data from Chinese cities surveyed 1.5 years after the outbreak of COVID-19. The results suggest that the Chinese government’s early response to COVID-19 significantly and sustainedly reduced China’s COVID-19 infection rate, and that this impact worked through risk perception, the adoption of protective action recommendations (PARs), and the chain-mediating effects of risk perception and the adoption of PARs, respectively. These findings have important practical value. In demonstrating how government response and infection rate at the macro level are connected to the behaviour of individuals at the micro level, they suggest feasible directions for curbing the spread of diseases such as COVID-19. When facing such public health emergencies, the focus should be on increasing the public’s risk perception and adoption of PARs.

Psychotherapy for comorbid depression and somatic disorders: a systematic review and meta-analysis

Background The treatment of depression in patients with somatic disorders is crucial, given its negative impact on quality of life (QoL), functioning, and even on the somatic disease prognosis. We aimed to examine the most updated evidence on the effects of psychotherapy in patients with depression and somatic disorders, including HIV, oncological, cardiometabolic, and neurological disorders. Methods We conducted a meta-analysis of 75 randomized trials (8209 participants) of psychotherapy for adults with somatic disorders and a diagnosis or elevated symptoms of depression. Outcomes included depression, QoL, somatic health-related outcomes, and mortality. Results Psychotherapy significantly reduced the severity of depression at post-treatment across all categories of somatic disorders (Hedges'g = 0.65; 95% CI 0.52–0.79), with sustained effects at 6–11 months (g = 0.38; 95% CI 0.22–0.53) and at 12 months follow-up or longer (g = 0.13; 95% CI 0.04–0.21). Psychotherapy also showed significant effects on QoL (g = 0.26; 95% CI 0.17–0.35), maintained up to 11 months follow-up (g = 0.25; 95% CI 0.16–0.34). No significant effects were observed on the most frequently reported somatic health-related outcomes (glycemic control, pain), and neither on mortality. Heterogeneity in most analyses was very high, and only 29 (38%) trials were rated at low risk of bias (RoB). Conclusions Psychotherapy may be an effective treatment option for patients with depression and somatic disorders, with long-term effects on depression severity and QoL. However, these results should be interpreted with caution due to heterogeneity and RoB.

Sustained Effects of Muscle Calpain System Genotypes on Tenderness Phenotypes of South African Beef Bulls during Ageing up to 20 Days

The most important factor that determines beef tenderness is its proteolytic activity and the balance between calpain1 protease activity and calpastatin inhibition is especially important, while contributions could arise from calpain2 and possibly calpain3. These processes are however affected by the meat aging process itself. To determine whether genotypes in the calpaincalpastatin system can enhance tenderness throughout a 20 day aging period, South African purebred beef bulls (n=166) were genotyped using the Illumina BovineHD SNP BeadChip, through genebased association analysis targeting the cast, capn3, capn2 and capn1 genes. The WarnerBratzler shear force (WBSF) and myofibril fragment length (MFL) of Longissimus thoracis et lumborum (LTL) steaks were evaluated between d 3 d 20 of aging, with protease enzyme activity in the first 20 h postmortem. Although several of the 134 SNP associated with tenderness, only seven SNP in the cast, capn2 and capn1 genes sustained genetic associations, additive to agingassociated increases in tenderness for at least three of the four aging periods. While most genomic associations were relatively stable over time, some genotypes within SNP responded differently to aging, resulting in altered genomic effects over time. The level of aging at which genomic associations are performed is an important factor that determines whether SNP affect tenderness phenotypes.

P.037 Benefits of Treatment with OnabotulinumtoxinA in Naive and Non-naive Patients with Cervical Dystonia are Sustained over Time in CD PROBE

Background: The sustained effects of onabotulinumtoxinA in patients with cervical dystonia (CD) who were naïve or non-naïve to botulinum toxin at enrollment in CD PROBE (CD Patient Registry for Observation of BOTOX® Efficacy) were evaluated. Methods: Patients were included if they completed all three treatment cycles and had accompanying data in this prospective, observational study. Assessments included CD severity, Cervical Dystonia Impact Profile (CDIP-58), Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), treatment interval, total dose, and adverse events (AEs). Results: Changes in severity following each onabotulinumtoxinA treatment were generally similar between naïve (n=212) and non-naïve (n=138) patients. Severity scores were maintained or improved in most patients with mild/moderate symptoms, while 30.0-66.7% with the highest severity scores shifted to a lower score across treatments. Sustained improvements were seen in all CDIP-58 subscales and TWSTRS total scores irrespective of baseline CD severity and toxin status. The median time interval between injections was similar in naïve (93.0–98.0 days) and non-naïve patients (96.0–97.0 days); doses tended to be lower in naïve patients. The most common AEs (dysphagia, muscular weakness) were similar. Conclusions: CD severity was attenuated by repeat onabotulinumtoxinA treatments at consistent intervals regardless of prior botulinum toxin exposure. Treatments were well tolerated.