Longitudinal cytokine and multi-modal health data of an extremely severe ME/CFS patient with HSD reveals insights into immunopathology, and disease severity.

Introduction: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) presents substantial challenges in patient care due to its intricate multisystem nature, comorbidities, and global prevalence. The heterogeneity among patient populations, coupled with the absence of FDA-approved diagnostics and therapeutics, further complicates research into disease etiology and patient managment. Integrating longitudinal multi-omics data with clinical, health,textual, pharmaceutical, and nutraceutical data offers a promising avenue to address these complexities, aiding in the identification of underlying causes and providing insights into effective therapeutics and diagnostic strategies. Methods: This study focused on an exceptionally severe ME/CFS patient with hypermobility spectrum disorder (HSD) during a period of marginal symptom improvements. Longitudinal cytokine profiling was conducted alongside the collection of extensive multi-modal health data to explore the dynamic nature of symptoms, severity, triggers, and modifying factors. Additionally, an updated severity assessment platform and two applications, ME-CFSTrackerApp and LexiTime, were introduced to facilitate real-time symptom tracking and enhance patient-physician/researcher communication, and evaluate response to medical intervention. Results: Longitudinal cytokine profiling revealed the significance of Th2-type cytokines and highlighted synergistic activities between mast cells and eosinophils, skewing Th1 toward Th2 immune responses in ME/CFS pathogenesis, particularly in cognitive impairment and sensorial intolerance. This suggests a potentially shared underlying mechanism with major ME/CFS comorbidities such as HSD, Mast cell activation syndrome, postural orthostatic tachycardia syndrome (POTS), and small fiber neuropathy. Additionally, the data identified potential roles of BCL6 and TP53 pathways in ME/CFS etiology and emphasized the importance of investigating adverse reactions to medication and supplements and drug interactions in ME/CFS severity and progression. Discussion: Our study advocates for the integration of longitudinal multi-omics with multi-modal health data and artificial intelligence (AI) techniques to better understand ME/CFS and its major comorbidities. These findings highlight the significance of dysregulated Th2-type cytokines in patient stratification and precision medicine strategies. Additionally, our results suggest exploring the use of low-dose drugs with partial agonist activity as a potential avenue for ME/CFS treatment. This comprehensive approach emphasizes the importance of adopting a patient-centered care approach to improve ME/CFS healthcare management, disease severity assessment, and personalized medicine. Overall, these findings contribute to our understanding of ME/CFS and offer avenues for future research and clinical practice.

Expanding Education Researchers' Access to Classroom Observation Data With a Remote and Cost-Effective Video Data Collection Protocol.

The onset of the COVID-19 pandemic and associated long-term shifts to virtual instruction among most US schools presented notable challenges among education researchers. Ongoing projects conducted in school settings experienced sudden losses of access to teacher and student participants, in many cases leading to severe interruptions to data collection efforts. Perhaps most notably, upon returns to in-person instruction in the 2021/22 academic year most schools instigated strict policies limiting the number of non-school personnel who could enter school buildings, including researchers conducting in-person data collections. As such, many researchers had to find alternative means to gather data. In this paper, we offer a new protocol that we created in response to these challenges that allows for the secure and fully remote collection of video data in school settings. This new protocol not only addressed the immediate needs of the focal study but also addresses some of the most notable barriers to collecting classroom video data in the field of education research at large. In this paper, we describe the initial development and application of this protocol among a local study of elementary teachers, as well as the scaling of this protocol in a study of elementary teachers in multiple states. It is our hope that this protocol can expand education researchers', practitioners', and policymakers' access to classroom video data.

Complete genome sequences of Streptomyces griseus phages Spelly and Phredrick.

We present the complete genome sequences of two viruses with siphovirus morphology, isolated from soils collected in Southwestern Indiana using the host Streptomyces griseus. Spelly is a BE2 cluster phage with a 131,347-bp genome. Phredrick is a BK1 cluster phage with a 128,873-bp genome.

Transient Elevation of Plasma Glucocorticoids Supports Psilocybin-Induced Anxiolysis in Mice.

While correlations between drug-induced cortisol elevation, self-reported anxiety, and treatment outcomes have been reported for human studies during psilocybin-assisted psychotherapy, the mechanistic relationship between psychedelic-associated alterations in plasma glucocorticoid responses and the time course of anxious responsiveness remains unclear. Using rodents, both time-bound manipulation of glucocorticoid concentrations and assessment of anxiety-like behaviors can be achieved. Here, 3 mg/kg IP psilocybin was found to have anxiolytic-like effects in C57BL/6 male mice at 4 h after treatment. These effects were not altered by pretreatment with a 5-HT2A antagonist but were blunted by pretreatment with a glucocorticoid receptor antagonist or suppression of psilocybin-induced corticosterone elevations. Anxiolytic-like effects were also observed at 4 h following treatment with the nonpsychedelic 5-HT2A agonist lisuride at a dose causing a similar increase in plasma glucocorticoids as that seen with psilocybin, as well as following stress-induced (via repeated injection) glucocorticoid release alone. Psilocybin's anxiolytic-like effects persisted at 7 days following administration. The long-term anxiolytic effects of psilocybin were lost when psilocybin was administered to animals with ongoing chronic elevations in plasma corticosterone concentrations. Overall, these experiments indicate that acute, resolvable psilocybin-induced glucocorticoid release drives the postacute anxiolytic-like effects of psilocybin in mice and that its long-term anxiolytic-like effects can be abolished in the presence of chronically elevated plasma glucocorticoid elevations.

Factors that sustain indigenous youth mentoring programs: a qualitative systematic review.

BACKGROUND: Indigenous youth worldwide continue to experience disproportional rates of poorer mental health and well-being compared to non-Indigenous youth. Mentoring has been known to establish favorable outcomes in many areas of health but is still in its early phases of research within Indigenous contexts. This paper explores the barriers and facilitators of Indigenous youth mentoring programs to improve mental health outcomes and provides evidence for governments' response to the United Nations Declaration on the Rights of Indigenous Peoples. METHODS: A systematic search for published studies was conducted on PubMed, Embase, Scopus, CINAHL, and grey literature through Trove, OpenGrey, Indigenous HealthInfoNet, and Informit Indigenous Collection. All papers included in the search were peer-reviewed and published from 2007 to 2021. The Joanna Briggs Institute approaches to critical appraisal, data extraction, data synthesis, and confidence of findings were used. RESULTS: A total of eight papers describing six mentoring programs were included in this review; six papers were from Canada, and two originated from Australia. Studies included mentor perspectives (n = 4) (incorporating views of parents, carers, Aboriginal assistant teachers, Indigenous program facilitators, young adult health leaders, and community Elders), mentee perspectives (n = 1), and both mentor and mentee perspectives (n = 3). Programs were conducted nationally (n = 3) or within specific local Indigenous communities (n = 3) with varying mentor styles and program focus. Five synthesized findings were identified from the data extraction process, each consisting of four categories. These synthesized findings were: establishing cultural relevancy, facilitating environments, building relationships, facilitating community engagement, and leadership responsibilities, which were discussed in the context of extant mentoring theoretical frameworks. CONCLUSION: Mentoring is an appropriate strategy for improving general well-being. However, more research is needed to explore program sustainability and maintaining outcomes in the long term.

Clinical application of a previously validated pregnancy-specific screening tool for sleep apnea in a cohort with a high prevalence of obesity.

Objective: The purpose of this project was to determine the positive predictive value of existing obstructive sleep apnea (OSA) screening tools in clinical use, in a real-world clinical population of gravidae, and to explore the development of a new questionnaire for screening for OSA during pregnancy. Methods: Pregnant people were administered sleep screening questionnaires as part of routine clinical care. These included Facco's four variable OSA screening tool, the STOP-BANG, and the Epworth Sleepiness Scale. Those who screened positive were referred for diagnostic sleep testing, typically with a type III home monitoring device. Here we analyzed the screening responses used by those who completed diagnostic testing to determine the positive predictive value of the existing tools. Results: 159 pregnant people completed diagnostic OSA testing and were included in this analysis. The positive predictive value of Facco's four variable sleep screening tool was 74.3%, STOP-BANG was 75.3%, and the Epworth Sleepiness Scale was 69.8%. Our sample size was insufficient to create a new screening tool. Conclusions: Here we calculated the positive predictive value of Facco's 4 variable screening tool for screening for OSA in pregnancy in a real-world pregnant population. While we were not able to generate a new screening tool for screening for OSA during pregnancy, both STOP-BANG and Facco's four variable tool had positive predictive values over 70% in our population which was characterized by high BMI and advanced maternal age. Increased clinical use of the pregnancy-specific tool may be warranted.

A consensus viewpoint on the role of direct factor Xa inhibitors in the management of cancer-associated venous thromboembolism in the UK.

OBJECTIVE: Cancer patients are at high risk of venous thromboembolism (VTE), a significant cause of cancer-related death. Historically, low molecular weight heparins (LMWH) were the gold standard therapy for cancer-associated VTE, but recent evidence supports the use of direct factor Xa inhibitors in cancer-associated VTE and this is now reflected in many guidelines. However, uptake of direct factor Xa inhibitors varies and guidance on the use of direct factor Xa inhibitors in specific cancer sub-populations and clinical situations is lacking. This review presents consensus expert opinion alongside evaluation of evidence to support healthcare professionals in the use of direct factor Xa inhibitors in cancer-associated VTE. METHODS: Recent guidelines, meta-analyses, reviews and clinical studies on anticoagulation therapy for cancer-associated VTE were used to direct clinically relevant topics and evidence to be systematically discussed using nominal group technique. The consensus manuscript and recommendations were developed based on these discussions. RESULTS: Considerations when prescribing anticoagulant therapy for cancer-associated VTE include cancer site and stage, systemic anti-cancer therapy (including vascular access), drug-drug interactions, length of anticoagulation, quality of life and needs during palliative care. Treatment of patients with kidney or liver impairment, gastrointestinal disorders, extremes of bodyweight, elevated bleeding or recurrence risk, VTE recurrence and COVID-19 is discussed. CONCLUSION: Anticoagulant therapy for cancer-associated VTE patients should be carefully selected with consideration given to the relative benefits of specific drugs when individualizing care. Direct factor Xa inhibitors are typically the treatment of choice for preventing VTE recurrence in non-cancer patients and should also be considered as such for cancer-associated VTE in most situations.

Measurement Equality of Frequency and Severity Item Response Options on Depression and Generalized Anxiety Scales.

Rating scales are commonly used in psychological research and practice. It is important to consider how different item response options used on rating scales, such as those based on frequency or severity, may affect how they measure psychological constructs. In this study, participants were randomly assigned to conditions where they completed two depression and two generalized anxiety rating scales that used either frequency or severity item response options. Descriptive statistics and reliability estimates across depression and generalized anxiety scales using different item response options were similar. Measurement invariance tests indicated that depression and generalized anxiety scales with different item response options could be considered practically invariant. Finally, depression and generalized anxiety scales with different item response options had similar correlations with measures of impairment and other psychological constructs. There were essentially no differences in psychometric and measurement properties of these depression and generalized anxiety scales when using different item response options, suggesting this may not substantially affect the measurement of these constructs.

In vivo validation of psilacetin as a prodrug yielding modestly lower peripheral psilocin exposure than psilocybin.

Introduction: The use of the psychedelic compound psilocybin in conjunction with psychotherapy has shown promising results in the treatment of psychiatric disorders, though the underlying mechanisms supporting these effects remain unclear. Psilocybin is a Schedule I substance that is dephosphorylated in vivo to form an active metabolite, psilocin. Psilacetin, also known as O-acetylpsilocin or 4-acetoxy-N,N-dimethyltryptamine (4-AcO-DMT), is an unscheduled compound that has long been suggested as an alternative psilocin prodrug, though direct in vivo support for this hypothesis has thus far been lacking. Methods: This study employed liquid chromatography-tandem mass spectrometry (LC-MS/MS) to assess the time-course and plasma concentrations of psilocin following the intraperitoneal (IP) administration of psilacetin fumarate or psilocybin to male and female C57Bl6/J mice. Results: Direct comparisons of the time courses for psilocin exposure arising from psilocybin and psilacetin found that psilocybin led to 10-25% higher psilocin concentrations than psilacetin at 15-min post-injection. The half-life of psilocin remained approximately 30 min, irrespective of whether it came from psilocybin or psilacetin. Overall, the relative amount of psilocin exposure from psilacetin fumarate was found to be approximately 70% of that from psilocybin. Discussion: These findings provide the first direct support for the long-standing assumption in the field that psilacetin functions as a prodrug for psilocin in vivo. In addition, these results indicate that psilacetin fumarate results in lower peripheral psilocin exposure than psilocybin when dosed on an equimolar basis. Thoughtful substitution of psilocybin with psilacetin fumarate appears to be a viable approach for conducting mechanistic psychedelic research in C57Bl6/J mice.

Thrombosis and thrombocytopenia after vaccination against and infection with SARS-CoV-2 in the United Kingdom.

Population-based studies can provide important evidence on the safety of COVID-19 vaccines. Using data from the United Kingdom, here we compare observed rates of thrombosis and thrombocytopenia following vaccination against SARS-CoV-2 and infection with SARS-CoV-2 with background (expected) rates in the general population. First and second dose cohorts for ChAdOx1 or BNT162b2 between 8 December 2020 and 2 May 2021 in the United Kingdom were identified. A further cohort consisted of people with no prior COVID-19 vaccination who were infected with SARS-Cov-2 identified by a first positive PCR test between 1 September 2020 and 2 May 2021. The fourth general population cohort for background rates included those people in the database as of 1 January 2017. In total, we included 3,768,517 ChAdOx1 and 1,832,841 BNT162b2 vaccinees, 401,691 people infected with SARS-CoV-2, and 9,414,403 people from the general population. An increased risk of venous thromboembolism was seen after first dose of ChAdOx1 (standardized incidence ratio: 1.12 [95% CI: 1.05 to 1.20]), BNT162b2 (1.12 [1.03 to 1.21]), and positive PCR test (7.27 [6.86 to 7.72]). Rates of cerebral venous sinus thrombosis were higher than otherwise expected after first dose of ChAdOx1 (4.14 [2.54 to 6.76]) and a SARS-CoV-2 PCR positive test (3.74 [1.56 to 8.98]). Rates of arterial thromboembolism after vaccination were no higher than expected but were increased after a SARS-CoV-2 PCR positive test (1.39 [1.21 to 1.61]). Rates of venous thromboembolism with thrombocytopenia were higher than expected after a SARS-CoV-2 PCR positive test (5.76 [3.19 to 10.40]).

Convolution Neural Networks and Targeted Fluorescent Nanoparticles to Detect and ICDAS Score Caries.

Previous work has shown targeted fluorescent starch nanoparticles (TFSNs) can label the subsurface of carious lesions and assist dental professionals in the diagnostic process. In this study, we aimed to evaluate the potential of using artificial intelligence (AI) to detect and score carious lesions using ICDAS in combination with fluorescent imaging following application of TFSNs on teeth with a range of lesion severities, using ICDAS-labeled images as the reference standard. A total of 130 extracted human teeth with ICDAS scores from 0 to 6 were selected by a calibrated cariologist. Then, the same surface was imaged with a stereomicroscope under white light illumination, without visible fluorescence, and blue light illumination with an orange filter following application of the TFSNs. Both sets of images were labeled by another blinded ICDAS-calibrated cariologist to demarcate lesion position and severity. Convolutional neural networks, state-of-the-art models in imaging AI, were trained to determine the presence, location, ICDAS score (severity), and lesion surface porosity (as an indicator of activity) of carious lesions, and tested by 30 k-fold validation for white light, blue light, and the combined image sets. The best models showed high performance for the detection of carious lesions (sensitivity 80.26%, PPV 76.36%), potential for determining the severity via ICDAS scoring (accuracy 72%, SD 5.67%), and the detection of surface porosity as an indicator of the activity of the lesions (accuracy 90%, SD 7.00%). More broadly, the combination of targeted biopolymer nanoparticles with imaging AI is a promising combination of novel technologies that could be applied to many other applications.

Exploiting the distinctive properties of the bacterial and human MutS homolog sliding clamps on mismatched DNA.

MutS homologs (MSHs) are highly conserved core components of DNA mismatch repair. Mismatch recognition provokes ATP-binding by MSH proteins that drives a conformational transition from a short-lived lesion-searching clamp to an extremely stable sliding clamp on the DNA. Here, we have expanded on previous bulk biochemical studies to examine the stability, lifetime, and kinetics of bacterial and human MSH sliding clamps on mismatched DNA using surface plasmon resonance and single-molecule analysis of fluorescently labeled proteins. We found that ATP-bound MSH complexes bound to blocked-end or very long mismatched DNAs were extremely stable over a range of ionic conditions. These observations underpinned the development of a high-throughput Förster resonance energy transfer system that specifically detects the formation of MSH sliding clamps on mismatched DNA. The Förster resonance energy transfer system is capable of distinguishing between HsMSH2-HsMSH3 and HsMSH2-HsMSH6 and appears suitable for chemical inhibitor screens. Taken together, our results provide additional insight into MSH sliding clamps as well as methods to distinguish their functions in mismatch repair.

Early occlusal caries detection using targeted fluorescent starch nanoparticles.

OBJECTIVES: We have previously shown fluorescent cationic starch nanoparticles (FCSNs) penetrate enamel surface porosity of active carious lesions, potentially aiding their detection. Here, we evaluate the in vitro diagnostic accuracy of FCSNs in detecting occlusal caries compared to histologic reference standard. METHODS: 100 extracted human teeth were selected with sound (50), or either non-cavitated (25) or cavitated (25) lesions. A region of interest (ROI) on the occlusal surface was assessed for fluorescence by two independent examiners, after immersion in FCSN solution, water rinse, and illumination by dental curing lamp viewed through orange UV-filter glasses. ROIs were sectioned and evaluated by histology (Downer Criteria) as a gold standard for caries presence. Cohen's Kappa was determined for inter- and intra-examiner agreement, and sensitivity, specificity, and area under the curve of Receiver Operator Curves (ROCAUC) were calculated. The analysis was repeated for the subset of "early" lesions, defined as being limited to enamel. RESULTS: FCSN use resulted in substantial inter-user (k=0.74±0.07), and high intra-user agreement (k=0.80±0.06; 0.94±0.03, by examiner). Sensitivity, specificity and ROCAUC for FCSNs were 88.9%; 94.6%; 0.92±0.06 for all, and 76.9%, 94.6%, and 0.86±0.10 for early lesions. In post hoc analysis, sensitivity seemed to be greater with the FCSN than the expert visual exam, particularly for early lesions. CONCLUSIONS/CLINICAL SIGNIFICANCE: FCSNs are a reproducible and accurate novel technology for occlusal caries detection, with high sensitivity and specificity compared to histology. Future clinical validation is necessary. FCSNs can improve early caries detection and shift treatment towards non-invasive approaches, improving oral health.

Reversible Dissociation for Effective Storage of Diborane Gas within the UiO-66-NH2 Metal-Organic Framework.

There is an acute need for materials that can store the toxic and highly reactive diborane gas at room temperature. In this work, the interfacial chemistry leading to safe and reversible storage of diborane (B2H6) in the UiO-66-NH2 metal-organic framework (MOF) was investigated via in situ transmission infrared (IR) spectroscopy, temperature-programmed desorption (TPD), and electronic structure calculations. The infrared spectrum of B2H6 adsorbed within UiO-66-NH2 indicates hydrogen bonding with the µ3-OH groups of the MOF nodes and chemisorption at the -NH2 groups of the MOF linkers. The conversion of physisorbed to chemisorbed diborane, as observed through a spectroscopically unique intermediate species, occurred over a broad temperature regime from 80 to 410 K. During B2H6-TPD studies, both the weakly and strongly bound species were found to desorb exclusively as molecular B2H6. Infrared spectroscopic studies, performed during diborane adsorption and reaction, combined with electronic structure calculations, revealed that chemisorption occurred via a reversible dissociation reaction involving a "half-open" B2H6 intermediate and resulted in the formation of two NH2-bound BH3 units, which leave the MOF as B2H6 via recombinative desorption. The close spacing of -NH2 groups in the UiO-66-NH2 MOF is key to enabling high-temperature chemisorptive storage of B2H6, and the spatial arrangement of the amine groups has a significant effect on the dissociation energy profile. This work demonstrates that reversible dissociation of B2H6 on precisely engineered, nucleophile-rich materials represents a promising pathway to diborane stabilization and long-term storage.

Efficacy and safety of leadless pacemaker: A systematic review, pooled analysis and meta-analysis.

BACKGROUND: Leadless pacemakers have been designed as an alternative to transvenous systems which avoid some of the complications associated with transvenous devices. We aim to perform a systematic review of the literature to report the safety and efficacy findings of leadless pacemakers. METHODS: We searched MEDLINE and EMBASE to identify studies reporting the safety, efficacy and outcomes of patients implanted with a leadless pacemaker. The pooled rate of adverse events was determined and random-effects meta-analysis was performed to compare rates of adverse outcomes for leadless compared to transvenous pacemakers. RESULTS: A total of 18 studies were included with 2496 patients implanted with a leadless pacemaker and success rates range between 95.5 and 100%. The device or procedure related death rate was 0.3% while any complication and pericardial tamponade occurred in 3.1% and 1.4% of patients, respectively. Other complications such as pericardial effusion, device dislodgement, device revision, device malfunction, access site complications and infection occurred in less than 1% of patients. Meta-analysis of four studies suggests that there was no difference in hematoma (RR 0.67 95%CI 0.21-2.18, 3 studies), pericardial effusion (RR 0.59 95%CI 0.15-2.25, 3 studies), device dislocation (RR 0.33 95%CI 0.06-1.74, 3 studies), any complication (RR 0.44 95%CI 0.17-1.09, 4 studies) and death (RR 0.45 95%CI 0.15-1.35, 2 studies) comparing patients who received leadless and transvenous pacemakers. CONCLUSION: Leadless pacemakers are safe and effective for patients who have an indication for single chamber ventricular pacing and the findings appear to be comparable to transvenous pacemakers.

Aboriginal Health Workers Promoting Oral Health among Aboriginal and Torres Strait Islander Women during Pregnancy: Development and Pilot Testing of the Grinnin' Up Mums & Bubs Program.

BACKGROUND: this study aimed to develop and pilot test the model of care, Grinnin' Up Mums & Bubs, to train Aboriginal Health Workers to promote oral health among Aboriginal and Torres Strait Islander pregnant women. METHODS: Participatory Action Research was employed to develop the different components of the model (oral health promotion resources, training workshop, and a culturally safe referral pathway to dental services). The model was piloted (pre-post), using an embedded mixed-methods design, to determine the acceptability, satisfaction, and any recommendations made by seven Aboriginal Health Workers at an antenatal service in Western Sydney, Australia. RESULTS: there was a high level of satisfaction with the components of the model of care among the participants, who believed that the model could be integrated into practice. The training showed some improvement in oral health knowledge and confidence. The participants recommended strategies for discussing oral health with Aboriginal and Torres Strait Islander pregnant women, and changes in public health dental policy to ensure that all women would be able to access affordable dental services through the referral pathway. CONCLUSION: the findings suggest a high level of satisfaction with the model of care among the Aboriginal Health Workers. Further evaluation is needed to confirm the short and long-term impact of the model.

"You Can't Work with My People If You Don't Know How to": Enhancing Transfer of Care from Hospital to Primary Care for Aboriginal Australians with Chronic Disease.

Indigenous Australians experience significantly poorer health compared to other Australians, with chronic disease contributing to two-thirds of the health gap. We report on an evaluation of an innovative model that leverages mainstream and Aboriginal health resources to enable safe, supported transfer of care for Aboriginal adults with chronic conditions leaving hospital. The multisite evaluation was Aboriginal-led and underpinned by the principles of self-determination and equity and Indigenous research protocols. The qualitative study documented processes and captured service user and provider experiences. We found benefits for patients and their families, the hospital and the health system. The new model enhanced the patient journey and trust in the health service and was a source of staff satisfaction. Challenges included staff availability, patient identification and complexity and the broader issue of cultural safety. Critical success factors included strong governance with joint cultural and clinical leadership and enduring relationships and partnerships at the service delivery, organisation and system levels. A holistic model of care, bringing together cultural and clinical expertise and partnering with Indigenous community organisations, can enhance care coordination and safety across the hospital-community interface. It is important to consider context as well as specific program elements in design, implementation and evaluation.

Deletion of muscle Igf1 exacerbates disuse atrophy weakness in mice.

Muscle atrophy occurs as a result of prolonged periods of reduced mechanical stimulation associated with injury or disease. The growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and load sensing pathways can both aid in recovery from disuse through their shared downstream signaling, but their relative contributions to these processes are not fully understood. The goal of this study was to determine whether reduced muscle IGF-1 altered the response to disuse and reloading. Adult male mice with inducible muscle-specific IGF-1 deletion (MID) induced 1 wk before suspension and age-matched controls (CON) were subjected to hindlimb suspension and reloading. Analysis of muscle force, morphology, gene expression, signaling, and tissue weights was performed in nonsuspended (NS) mice, and those suspended for 7 days or reloaded following suspension for 3, 7, and 14 days. MID mice displayed diminished IGF-1 protein levels and muscle atrophy before suspension. Muscles from suspended CON mice displayed a similar extent of atrophy and depletion of IGF-1, yet combined loss of load and IGF-1 was not additive with respect to muscle mass. In contrast, soleus force generation capacity was diminished to the greatest extent when both suspension and IGF-1 deletion occurred. Recovery of mass, force, and gene expression patterns following suspension were similar in CON and MID mice, even though IGF-1 levels increased only in muscles from CON mice. Diminished strength in disuse atrophy is exacerbated with the loss of muscle IGF-1 production, whereas recovery of mass and strength upon reloading can occur even IGF-1 is low.NEW & NOTEWORTHY A mouse model with skeletal muscle-specific inducible deletion of Igf1 was used to address the importance of this growth factor for the consequences of disuse atrophy. Rapid and equivalent loss of IGF-I and mass occurred with deletion or disuse. Decrements in strength were most severe with combined loss of load and IGF-1. Return of mass and strength upon reloading was independent of IGF-1.

Digital mHealth Interventions for Employees: Systematic Review and Meta-Analysis of Their Effects on Workplace Outcomes.

OBJECTIVES: To justify the capital investment, employers require proof of benefit of digital mHealth beyond symptomatic improvement. METHODS: A systematic review and meta-analysis were conducted to identify studies investigating digital mHealth interventions for employees and their effects on workplace outcomes. RESULTS: We identified 28 eligible studies, (8023 employees) comparing digital mHealth interventions to controls. Small significant effects at postintervention in engagement (g = 0.19), and productivity (g = 0.16) were found. Sustained effects were observed, engagement (g = 0.24) and productivity (g = 0.20). There was a wide range of study heterogeneity (I2 = 16% to 94%). CONCLUSION: In RCTs digital mHealth interventions demonstrate small, potentially sustained efficacy on employee's engagement and productivity. Similar small yet non-significant effect sizes were seen for absenteeism and presenteeism. This supports the need to find ways of enabling employers to deliver these low-cost digital mHealth interventions that can help improve employee's mental health.