Evaluation of the Centers for Disease Control and Prevention's Essentials for Parenting Toddlers and Preschoolers on parent behavioral outcomes.

BACKGROUND: The Centers for Disease Control and Prevention's web-based behavioral parent training (BPT) program, Essentials for Parenting Toddlers and Preschoolers (EfP), uses a psychoeducational approach to promote positive parenting and address common parenting challenges. The purpose of this study was to assess the effects of EfP on parenting behavior and whether implementation format impacted behavioral outcomes. METHODS: A sample of 200 parents of 2- to 4-year-old children were recruited via Internet advertising. Using a repeated single subject, multiple baseline design, parents were randomly assigned to guided navigation (GN; n = 100) or unguided navigation (UN; n = 100) study conditions. Parents were provided secure access to the EfP website and completed 18 weekly surveys. Latent growth curve modeling was used to determine intervention effectiveness on behavioral outcomes. RESULTS: Latent growth curve modeling indicated both GN and UN study conditions significantly increased use of praise (ß = 0.19, p = 0.038) and commands and consequences (ß = 0.17, p < 0.001), and decreased corporal punishment use (ß = -0.01, p = 0.017) and attitudes promoting corporal punishment (ß = -0.01, p < 0.001) over the study period. The UN condition exhibited a significant initial decrease in time-out use that increased over time to match the GN condition. CONCLUSIONS: This study provides evidence for the effectiveness of EfP in promoting non-violent parenting behavior and increasing positive parenting techniques. The format of EfP implementation made no difference in parenting behaviors over time. Digital BPT programs like EfP provide access to evidence-informed parenting resources and can enhance positive parenting.

Review of Policies and Practices to Prevent Technology-Facilitated Child Sexual Abuse Within Youth-Serving Organizations in the United States.

Technology-facilitated child sexual abuse (TF-CSA), or child sexual abuse that occurs online or through electronic communication, is a preventable public health problem that can be addressed within youth-serving organizations (YSOs). This study is a review of a purposive sample of organizational policies and practices designed to prevent TF-CSA collected from 13 national and local YSOs in the United States. Documents were coded to identify practices to prevent TF-CSA related to YSO activities or YSO staff, volunteers, or participants. Qualitative analysis indicated that YSOs included seven common practices to prevent TF-CSA in their documents. These practices included transparent electronic communication between youth and YSO staff; codes of conduct and online behavior agreements related to youth; monitoring the YSO's online presence; parental controls for youth online activity; safety behaviors for online activity for staff, parents, and youth; parent and youth trainings for youth online engagement and prevention of TF-CSA; and practices to address staff policy violations. Most prevention practices documented by YSOs identified in this study are consistent with emerging literature on TF-CSA prevention. Key gaps include protections for youth from groups inequitably burdened by TF-CSA and evaluation of the implementation and effectiveness of practices in preventing TF-CSA across settings and populations.

Enhanced anticancer effect of lysozyme-functionalized metformin-loaded shellac nanoparticles on a 3D cell model: role of the nanoparticle and payload concentrations.

Here we used a 3D human hepatic tumour cell culture model to assess the in vitro efficacy of "active" metformin-loaded nanoparticles (NPs) as anticancer therapeutics. The metformin nanocarrier design was repurposed from previous studies targeting bacterial and fungal biofilms with antimicrobials loaded in protease-coated nanoparticles. These active nanocarriers were constructed with shellac cores loaded with metformin as the anticancer agent and featured a surface coating of the cationic protease lysozyme. The lysozyme's role as a nanocarrier surface coating is to partially digest the extracellular matrix (ECM) of the 3D tumour cell culture which increases its porosity and the nanocarrier penetration. Hep-G2 hepatic 3D clusteroids were formed using a water-in-water (w/w) Pickering emulsion based on an aqueous two-phase system (ATPS). Our specific metformin nano-formulation, comprising 0.25 wt% lysozyme-coated, 0.4 wt% metformin-loaded, 0.2 wt% shellac NPs sterically stabilized with 0.25 wt% Poloxamer 407, demonstrated significantly enhanced anticancer efficiency on 3D hepatic tumour cell clusteroids. We examined the role of the lysozyme surface functionality of the metformin nanocarriers in their ability to kill both 2D and 3D hepatic tumour cell cultures. The anticancer efficiency at high metformin payloads was compared with that at a high concentration of nanocarriers with a lower metformin payload. It was discovered that the high metformin payload NPs were more efficient than the lower metformin payload NPs with a higher nanocarrier concentration. This study introduces a reliable in vitro model for potential targeting of solid tumours with smart nano-therapeutics, presenting a viable alternative to animal testing for evaluating anticancer nanotechnologies.

How (Cautious) Social Media Use May Improve Education and Pipeline Efforts of a Growing Postpandemic Forensic Pathologist Workforce Shortage.

ABSTRACT: Many subspecialties of pathology have initiated novel methods and strategies to connect with medical students and residents, stimulate interest, and offer mentorship. Emerging concern about the future of forensic pathology has been highlighted in contemporary literature as recruitment of new fellows has stagnated and workforce shortage concerns have blossomed. Amidst these challenges, the potential role of social networking platforms like social media (SoMe) in enhancing autopsy pathology/forensics education has garnered attention, yet literature focusing specifically on its application in autopsy and forensic pathology remains limited. This review aims to provide a comprehensive narrative overview of the current literature on the established uses of SoMe in forensic pathology. It seeks to build upon existing recommendations, introducing a contemporary compilation of online resources designed to facilitate virtual engagement among pathologists, learners, patients, and families. The review supports the idea that strategic, ethical, and conscientious use of SoMe has a place in addressing the growing workforce shortages and closing educational gaps in forensic pathology by enhancing exposure to the field and dispelling antiquated stereotypes.

Impact of acute kidney injury response on survival and liver transplant rates in hospitalized patients with cirrhosis awaiting liver transplantation: Results from the HRS-HARMONY consortium.

BACKGROUND & AIMS: Acute kidney injury (AKI) frequently complicates the course of hospitalized patients with cirrhosis and negatively affects their prognosis. How AKI response influences the timing of liver transplantation (LT) remains unclear. We sought to assess the impact of AKI response to treatment on survival and LT rates in cirrhosis patients awaiting LT. APPROACH & RESULTS: This was a retrospective multicenter study of cirrhosis patients waitlisted for LT and hospitalized with AKI in 2019. The exposure was AKI response versus no response during hospitalization. Outcomes were 90-day overall and transplant-free survival, and rates of LT with time to transplant. We adjusted for age, sex, race, cirrhosis etiology, site, and MELD-Na score. Among the 317 patients in this study, 170 had AKI response (53.6%), and 147 had no response (46.4%). Compared to non-responders, responders had better 90-day overall survival (89.4% vs. 76.2%, adjusted sHR for mortality 0.34, p=0.001), and transplant-free survival (63.5% vs. 25.2%, aHR for probability of death or transplant 0.35, p<0.001). The LT rate was lower in responders (45.9% vs. 61.2%, adjusted sHR 0.55, p=0.005). 79% of transplants in responders occurred after discharge, at a median of 103 days, while 62% of transplants in non-responders occurred during hospitalization, with the remainder occurring post-discharge at a median of 58 days. CONCLUSIONS: In patients with cirrhosis waitlisted for LT who are hospitalized with AKI, AKI response to therapy is associated with improved 90-day survival, despite a reduced LT rate and longer time to LT.

Pathogenic diversification of the gut commensal Providencia alcalifaciens via acquisition of a second type III secretion system.

Providencia alcalifaciens is a Gram-negative bacterium found in a wide variety of water and land environments and organisms. It has been isolated as part of the gut microbiome of animals and insects, as well as from stool samples of patients with diarrhea. Specific P. alcalifaciens strains encode gene homologs of virulence factors found in other pathogenic members of the same Enterobacterales order, such as Salmonella enterica serovar Typhimurium and Shigella flexneri. Whether these genes are also pathogenic determinants in P. alcalifaciens is not known. Here we have used P. alcalifaciens 205/92, a clinical isolate, with in vitro and in vivo infection models to investigate P. alcalifaciens -host interactions at the cellular level. Our particular focus was the role of two type III secretion systems (T3SS) belonging to the Inv-Mxi/Spa family. T3SS 1b is widespread in Providencia spp. and encoded on the chromosome. T3SS 1a is encoded on a large plasmid that is present in a subset of P. alcalifaciens strains, which are primarily isolates from diarrheal patients. Using a combination of electron and fluorescence microscopy and gentamicin protection assays we show that P. alcalifaciens 205/92 is internalized into eukaryotic cells, rapidly lyses its internalization vacuole and proliferates in the cytosol. This triggers caspase-4 dependent inflammasome responses in gut epithelial cells. The requirement for the T3SS 1a in entry, vacuole lysis and cytosolic proliferation is host-cell type specific, playing a more prominent role in human intestinal epithelial cells as compared to macrophages. In a bovine ligated intestinal loop model, P. alcalifaciens colonizes the intestinal mucosa, inducing mild epithelial damage with negligible fluid accumulation. No overt role for T3SS 1a or T3SS 1b was seen in the calf infection model. However, T3SS 1b was required for the rapid killing of Drosophila melanogaster . We propose that the acquisition of two T3SS by horizontal gene transfer has allowed P. alcalifaciens to diversify its host range, from a highly virulent pathogen of insects to an opportunistic gastrointestinal pathogen of animals.

Recovering high-quality fiber orientation distributions from a reduced number of diffusion-weighted images using a model-driven deep learning architecture.

PURPOSE: The aim of this study was to develop a model-based deep learning architecture to accurately reconstruct fiber orientation distributions (FODs) from a reduced number of diffusion-weighted images (DWIs), facilitating accurate analysis with reduced acquisition times. METHODS: Our proposed architecture, Spherical Deconvolution Network (SDNet), performed FOD reconstruction by mapping 30 DWIs to fully sampled FODs, which have been fit to 288 DWIs. SDNet included DWI-consistency blocks within the network architecture, and a fixel-classification penalty within the loss function. SDNet was trained on a subset of the Human Connectome Project, and its performance compared with FOD-Net, and multishell multitissue constrained spherical deconvolution. RESULTS: SDNet achieved the strongest results with respect to angular correlation coefficient and sum of squared errors. When the impact of the fixel-classification penalty was increased, we observed an improvement in performance metrics reliant on segmenting the FODs into the correct number of fixels. CONCLUSION: Inclusion of DWI-consistency blocks improved reconstruction performance, and the fixel-classification penalty term offered increased control over the angular separation of fixels in the reconstructed FODs.

TRIM71 mutations cause a neurodevelopmental syndrome featuring ventriculomegaly and hydrocephalus.

Congenital hydrocephalus (CH), characterized by cerebral ventriculomegaly, is one of the most common reasons for pediatric brain surgery. Recent studies have implicated lin-41 (lineage variant 41)/TRIM71 (tripartite motif 71) as a candidate CH risk gene, however, TRIM71 variants have not been systematically examined in a large patient cohort or conclusively linked with an OMIM syndrome. Through cross-sectional analysis of the largest assembled cohort of patients with cerebral ventriculomegaly, including neurosurgically-treated CH (totaling 2,697 parent-proband trios and 8,091 total exomes), we identified 13 protein-altering de novo variants (DNVs) in TRIM71 in unrelated children exhibiting variable ventriculomegaly, CH, developmental delay, dysmorphic features, and other structural brain defects including corpus callosum dysgenesis and white matter hypoplasia. Eight unrelated patients were found to harbor arginine variants, including two recurrent missense DNVs, at homologous positions in RPXGV motifs of different NHL domains. Seven additional patients with rare, damaging, unphased or transmitted variants of uncertain significance were also identified. NHL-domain variants of TRIM71 exhibited impaired binding to the canonical TRIM71 target CDKN1A; other variants failed to direct the subcellular localization of TRIM71 to processing bodies. Single-cell transcriptomic analysis of human embryos revealed expression of TRIM71 in early first-trimester neural stem cells of the brain. These data show TRIM71 is essential for human brain morphogenesis and that TRIM71 mutations cause a novel neurodevelopmental syndrome featuring ventriculomegaly and CH.

Next-generation neuropeptide Y receptor small-molecule agonists inhibit mosquito-biting behavior.

BACKGROUND: Female Aedes aegypti mosquitoes can spread disease-causing pathogens when they bite humans to obtain blood nutrients required for egg production. Following a complete blood meal, host-seeking is suppressed until eggs are laid. Neuropeptide Y-like receptor 7 (NPYLR7) plays a role in endogenous host-seeking suppression and previous work identified small-molecule NPYLR7 agonists that inhibit host-seeking and blood-feeding when fed to mosquitoes at high micromolar doses. METHODS: Using structure-activity relationship analysis and structure-guided design we synthesized 128 compounds with similarity to known NPYLR7 agonists. RESULTS: Although in vitro potency (EC50) was not strictly predictive of in vivo effect, we identified three compounds that reduced blood-feeding from a live host when fed to mosquitoes at a dose of 1 µM-a 100-fold improvement over the original reference compound. CONCLUSIONS: Exogenous activation of NPYLR7 represents an innovative vector control strategy to block mosquito biting behavior and prevent mosquito-human host interactions that lead to pathogen transmission.

'I'm a failure again, I can't do it': Attitudes towards, and experiences of, exercise participation in adults with class III obesity.

OBJECTIVES: Living within a larger body brings unique challenges to exercise participation, which are poorly understood. This qualitative study explored the attitudes towards, and experiences of, exercise participation in adults with class III obesity. DESIGN: Individual semi-structured qualitative interviews. METHODS: We recruited 30 adults with class III obesity (body mass index: 45.8 ± 8.6 kg/m2) from a specialist multidisciplinary weight management service. Participants took part in semi-structured interviews while participating in a 6-month home-based aerobic and resistance exercise intervention. Open-ended questions were used flexibly to explore their views and experiences of exercise, encompassing barriers, motives and perceived benefits. Transcripts were analysed using reflexive thematic analysis. RESULTS: Three themes were developed: (1) a web of barriers; (2) tailored exercise facilitates positive experiences; and (3) a desire to live a normal life. People with class III obesity perceived that they were unable to do exercise; a view that was attributed to perceived judgement, low physical function, pain during everyday activities and failed weight loss attempts. These complex physical and psychosocial barriers to exercise were described as contributing to exercise avoidance. High value was placed on tailored exercise that accommodates the unique needs of moving in a larger body. A desire to carry out everyday tasks underpinned motivations for exercise. CONCLUSIONS: Our findings suggest that multi-component obesity interventions should move away from generic exercise prescriptions designed to maximize energy expenditure, and instead move towards addressing the unique physical and psychosocial needs of people who have class III obesity with tailored person-centred and weight-neutral exercise prescriptions.

Implementation and evaluation of a fertility preservation telehealth counseling intervention for males with cystic fibrosis.

BACKGROUND: Most males with cystic fibrosis (MwCF) have congenital bilateral absence of the vas deferens and require assisted reproductive technology to conceive, yet many have limited knowledge about how CF affects sexual and reproductive health (SRH). This study evaluates the feasibility, acceptability, and potential effectiveness of telehealth fertility preservation (FP) counseling for MwCF. METHODS: Pre-lung transplant MwCF ≥18 years, recruited from U.S. CF centers, social media, and via snowball sampling, received individualized telehealth counseling. Participants completed intervention feasibility/acceptability one week post-counseling and FP knowledge, care satisfaction, and self-efficacy assessments at baseline and two months post-counseling. We completed acceptability interviews one-week post-counseling and audio-recorded, transcribed, and thematically analyzed results. We descriptively analyzed survey results and conducted pre/post comparisons using paired t-tests. RESULTS: Thirty MwCF (ages 22-49 years) completed counseling. Most were in a relationship (70 %) and White (86.7 %). Telehealth FP counseling was acceptable (M = 4.38/5 ± 0.60), appropriate (M = 4.37/5 ± 0.60), and feasible (M = 4.60/5 ± 0.45) to MwCF. FP knowledge (9.53 vs. 10.40/12; p = .010), care satisfaction (20.23 vs 26.67/32; p<.001), and self-efficacy (22.87 vs 25.20/30; p = .016) improved at two months post-counseling. Despite desiring provider-initiated SRH, wanting children (81 %), and perceiving the CF team as their primary care provider (97 %), 44 % report not receiving information about infertility by the CF team. CONCLUSIONS: Integrating FP counseling into CF care is feasible and acceptable to MwCF and can improve FP knowledge, self-efficacy, and care satisfaction. MwCF desire early and regular provider-initiated SRH education.

Understanding forms of childhood adversities and associations with adult health outcomes: A regression tree analysis.

BACKGROUND: Empirical studies have demonstrated associations between ten original adverse childhood experiences (ACEs) and multiple health outcomes. Identifying expanded ACEs can capture the burden of other childhood adversities that may have important health implications. OBJECTIVE: We sought to identify childhood adversities that warrant consideration as expanded ACEs. We hypothesized that experiencing expanded and original ACEs would be associated with poorer adult health outcomes compared to experiencing original ACEs alone. PARTICIPANTS: The 11,545 respondents of the National Longitudinal Surveys (NLS) and Child and Young Adult Survey were 48.9 % female, 22.7 % Black, 15.8 % Hispanic, 36.1 % White, 1.7 % Asian/Native Hawaiian/Pacific Islander/Native American/Native Alaskan, and 7.5 % Other. METHODS: This study used regression trees and generalized linear models to identify if/which expanded ACEs interacted with original ACEs in association with six health outcomes. RESULTS: Four expanded ACEs-basic needs instability, lack of parental love and affection, community stressors, and mother's experience with physical abuse during childhood -significantly interacted with general health, depressive symptom severity, anxiety symptom severity, and violent crime victimization in adulthood (all p-values <0.005). Basic needs instability and/or lack of parental love and affection emerged as correlates across multiple outcomes. Experiencing lack of parental love and affection and original ACEs was associated with greater anxiety symptoms (p = 0.022). CONCLUSIONS: This is the first study to use supervised machine learning to investigate interaction effects among original ACEs and expanded ACEs. Two expanded ACEs emerged as predictors for three adult health outcomes and warrant further consideration in ACEs assessments.

The microbiota-gut-brain-immune interface in the pathogenesis of neuroinflammatory diseases: a narrative review of the emerging literature.

Importance: Research is beginning to elucidate the sophisticated mechanisms underlying the microbiota-gut-brain-immune interface, moving from primarily animal models to human studies. Findings support the dynamic relationships between the gut microbiota as an ecosystem (microbiome) within an ecosystem (host) and its intersection with the host immune and nervous systems. Adding this to the effects on epigenetic regulation of gene expression further complicates and strengthens the response. At the heart is inflammation, which manifests in a variety of pathologies including neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Multiple Sclerosis (MS). Observations: Generally, the research to date is limited and has focused on bacteria, likely due to the simplicity and cost-effectiveness of 16s rRNA sequencing, despite its lower resolution and inability to determine functional ability/alterations. However, this omits all other microbiota including fungi, viruses, and phages, which are emerging as key members of the human microbiome. Much of the research has been done in pre-clinical models and/or in small human studies in more developed parts of the world. The relationships observed are promising but cannot be considered reliable or generalizable at this time. Specifically, causal relationships cannot be determined currently. More research has been done in Alzheimer's disease, followed by Parkinson's disease, and then little in MS. The data for MS is encouraging despite this. Conclusions and relevance: While the research is still nascent, the microbiota-gut-brain-immune interface may be a missing link, which has hampered our progress on understanding, let alone preventing, managing, or putting into remission neurodegenerative diseases. Relationships must first be established in humans, as animal models have been shown to poorly translate to complex human physiology and environments, especially when investigating the human gut microbiome and its relationships where animal models are often overly simplistic. Only then can robust research be conducted in humans and using mechanistic model systems.

Operative Time and Accrual of Postoperative Complications in Minimally Invasive Versus Open Myomectomy.

STUDY OBJECTIVE: To compare the prevalence and accrual of 30-day postoperative complications by operative time for open myomectomy (OM) and minimally invasive myomectomy (MIM). DESIGN: Retrospective cohort study SETTING: Hospitals participating in the National Surgical Quality Improvement Program database from January 2015 to December 2021. PATIENTS: Female patients aged ≥18 years undergoing OM or MIM. INTERVENTIONS: Patients were categorized into OM and MIM cohorts. Covariates associated with operative time and composite complications were identified using general linear model and chi-square or Fisher's exact test as appropriate. Adjusted spline regression was performed as a test of linearity between operative time and composite complications. Adjusted risk ratios of 30-day postoperative individual, minor, major, and composite complications by 60-minute operative time increments were estimated using Poisson regression with robust error variance. MEASUREMENTS AND MAIN RESULTS: Of 27 728 patients, 11 071 underwent MIM and 16 657 underwent OM. Mean operative times (SD) were 164.6 (82.0) for MIM and 129.2 (67.0) for OM. Raw composite complication rates were 5.5% for MIM and 15.8% for OM. Adjusted spline regression demonstrated linearity between operative time and relative risk of composite postoperative complications for both MIM and OM. MIM had higher adjusted relative risk (aRR, 95% CI) compared to OM of blood transfusion (1.55, 1.45-1.64 versus 1.29, 1.25-1.34), overall minor complications (1.13, 1.03-1.23 versus 1.01, 0.92-1.10), and overall major complications (1.43, 1.35-1.51 versus 1.27, 1.12-1.32). Operative time had greater impact on risk of composite complications for MIM than OM, reaching aRR 2.0 at 296 minutes versus 461 minutes for OM. CONCLUSION: OM has a higher overall rate of composite, minor, and major complications compared to MIM. While operative time is independently and linearly associated with postoperative complications with myomectomy regardless of approach, optimizing surgical efficiency for MIM may be more critical than for OM.

The novel adrenergic agonist ATR-127 targets skeletal muscle and brown adipose tissue to tackle diabesity and steatohepatitis.

OBJECTIVE: Simultaneous activation of ß2- and ß3-adrenoceptors (ARs) improves whole-body metabolism via beneficial effects in skeletal muscle and brown adipose tissue (BAT). Nevertheless, high-efficacy agonists simultaneously targeting these receptors whilst limiting activation of ß1-ARs - and thus inducing cardiovascular complications - are currently non-existent. Therefore, we here developed and evaluated the therapeutic potential of a novel ß2-and ß3-AR, named ATR-127, for the treatment of obesity and its associated metabolic perturbations in preclinical models. METHODS: In the developmental phase, we assessed the impact of ATR-127's on cAMP accumulation in relation to the non-selective ß-AR agonist isoprenaline across various rodent ß-AR subtypes, including neonatal rat cardiomyocytes. Following these experiments, L6 muscle cells were stimulated with ATR-127 to assess the impact on GLUT4-mediated glucose uptake and intramyocellular cAMP accumulation. Additionally, in vitro, and in vivo assessments are conducted to measure ATR-127's effects on BAT glucose uptake and thermogenesis. Finally, diet-induced obese mice were treated with 5 mg/kg ATR-127 for 21 days to investigate the effects on glucose homeostasis, body weight, fat mass, skeletal muscle glucose uptake, BAT thermogenesis and hepatic steatosis. RESULTS: Exposure of L6 muscle cells to ATR-127 robustly enhanced GLUT4-mediated glucose uptake despite low intramyocellular cAMP accumulation. Similarly, ATR-127 markedly increased BAT glucose uptake and thermogenesis both in vitro and in vivo. Prolonged treatment of diet-induced obese mice with ATR-127 dramatically improved glucose homeostasis, an effect accompanied by decreases in body weight and fat mass. These effects were paralleled by an enhanced skeletal muscle glucose uptake, BAT thermogenesis, and improvements in hepatic steatosis. CONCLUSIONS: Our results demonstrate that ATR-127 is a highly effective, novel ß2- and ß3-ARs agonist holding great therapeutic promise for the treatment of obesity and its comorbidities, whilst potentially limiting cardiovascular complications. As such, the therapeutic effects of ATR-127 should be investigated in more detail in clinical studies.

Dangers of the chronic stress response in the context of the microbiota-gut-immune-brain axis and mental health: a narrative review.

More than 20% of American adults live with a mental disorder, many of whom are treatment resistant or continue to experience symptoms. Other approaches are needed to improve mental health care, including prevention. The role of the microbiome has emerged as a central tenet in mental and physical health and their interconnectedness (well-being). Under normal conditions, a healthy microbiome promotes homeostasis within the host by maintaining intestinal and brain barrier integrity, thereby facilitating host well-being. Owing to the multidirectional crosstalk between the microbiome and neuro-endocrine-immune systems, dysbiosis within the microbiome is a main driver of immune-mediated systemic and neural inflammation that can promote disease progression and is detrimental to well-being broadly and mental health in particular. In predisposed individuals, immune dysregulation can shift to autoimmunity, especially in the presence of physical or psychological triggers. The chronic stress response involves the immune system, which is intimately involved with the gut microbiome, particularly in the process of immune education. This interconnection forms the microbiota-gut-immune-brain axis and promotes mental health or disorders. In this brief review, we aim to highlight the relationships between stress, mental health, and the gut microbiome, along with the ways in which dysbiosis and a dysregulated immune system can shift to an autoimmune response with concomitant neuropsychological consequences in the context of the microbiota-gut-immune-brain axis. Finally, we aim to review evidenced-based prevention strategies and potential therapeutic targets.

Axillary Surgery for Chemoresidual (ypN-Positive) Nodal Disease.

This cohort study using pooled data from 2 randomized clinical trials examines whether removing more lymph nodes with axillary lymph node dissection improved outcomes over sentinel lymph node biopsy when most patients received adjuvant radiation therapy or regional nodal irradiation.

The Association of Neighborhood Socioeconomic Status with Executive Function and Processing Speed in Cognitively Normal Mexican American Elders from the Health and Aging Brains Study: Health Disparities Cohort.

INTRODUCTION: Neighborhood socioeconomic status (NSES) has been linked with overall health, and this study will evaluate whether NSES is cross-sectionally associated with cognition in non-Hispanic whites (NHWs) and Mexican Americans (MAs) from the Health and Aging Brain: Health Disparities Study (HABS-HD). METHODS: The HABS-HD is a longitudinal study conducted at the University of North Texas Health Science Center. The final sample analyzed (n = 1,312) were 50 years or older, with unimpaired cognition, and underwent an interview, neuropsychological examination, imaging, and blood draw. NSES was measured using the national area deprivation index (ADI) percentile ranking, which considered socioeconomic variables. Executive function and processing speed were assessed by the trail making tests (A and B) and the digit-symbol substitution test, respectively. Linear regression was used to assess the association of ADI and cognitive measures. RESULTS: MAs were younger, more likely to be female, less educated, had higher ADI scores, performed worse on trails B (all p < 0.05), and had lower prevalence of APOE4 + when compared to NHWs (p < 0.0001). A higher percentage of MAs lived in the most deprived neighborhoods than NHWs. For NHWs, ADI did not predict trails B or DSS scores, after adjusting for demographic variables and APOE4. For MAs, ADI predicted trails A, trails B, and DSS after adjusting for demographic covariates and APOE4 status. CONCLUSION: Our study revealed that living in an area of higher deprivation was associated with lower cognitive function in MAs but not in NHWs, which is important to consider in future interventions to slow cognitive decline.

Impact of PET Reconstruction on Amyloid-ß Quantitation in Cross-Sectional and Longitudinal Analyses.

Amyloid-ß (Aß) accumulation in Alzheimer disease (AD) is typically measured using SUV ratio and the centiloid (CL) scale. The low spatial resolution of PET images is known to degrade quantitative metrics because of the partial-volume effect. This article examines the impact of spatial resolution, as determined by the reconstruction configuration, on the Aß PET quantitation in both cross-sectional and longitudinal data. Methods: The cross-sectional study involved 89 subjects with 20-min [18F]florbetapir scans generated on an mCT (44 Aß-negative [Aß-], 45 Aß-positive [Aß+]) using 69 reconstruction configurations, which varied in number of iteration updates, point-spread function, time-of-flight, and postreconstruction smoothing. The subjects were classified as Aß- or Aß+ visually. For each reconstruction, Aß CL was calculated using CapAIBL, and the spatial resolution was calculated as full width at half maximum (FWHM) using the barrel phantom method. The change in CLs and the effect size of the difference in CLs between Aß- and Aß+ groups with FWHM were examined. The longitudinal study involved 79 subjects (46 Aß-, 33 Aß+) with three 20-min [18F]flutemetamol scans generated on an mCT. The subjects were classified as Aß- or Aß+ using a cutoff CL of 20. All scans were reconstructed using low-, medium-, and high-resolution configurations, and Aß CLs were calculated using CapAIBL. Since linear Aß accumulation was assumed over a 10-y interval, for each reconstruction configuration, Aß accumulation rate differences (ARDs) between the second and first periods were calculated for all subjects. Zero ARD was used as a consistency metric. The number of Aß accumulators was also used to compare the sensitivity of CL across reconstruction configurations. Results: In the cross-sectional study, CLs in both the Aß- and the Aß+ groups were impacted by the FWHM of the reconstruction method. Without postreconstruction smoothing, Aß- CLs increased for a FWHM of 4.5 mm or more, whereas Aß+ CLs decreased across the FWHM range. High-resolution reconstructions provided the best statistical separation between groups. In the longitudinal study, the median ARD of low-resolution reconstructed data for the Aß- group was greater than zero whereas the ARDs of higher-resolution reconstructions were not significantly different from zero, indicating more consistent rate estimates in the higher-resolution reconstructions. Higher-resolution reconstructions identified 10 additional Aß accumulators in the Aß- group, resulting in a 22% increased group size compared with the low-resolution reconstructions. Higher-resolution reconstructions reduced the average CLs of the negative group by 12 points. Conclusion: High-resolution PET reconstructions, inherently less impacted by partial-volume effect, may improve Aß PET quantitation in both cross-sectional and longitudinal data. In the cross-sectional analysis, separation of CLs between Aß- and Aß+ cohorts increased with spatial resolution. Higher-resolution reconstructions also exhibited both improved consistency and improved sensitivity in measures of Aß accumulation. These features suggest that higher-resolution reconstructions may be advantageous in early-stage AD therapies.

Utility and usability of a wearable system and progressive-challenge cued exercise program for encouraging use of the more involved arm at-home after stroke-a feasibility study with case reports.

BACKGROUND: Understanding the role of adherence to home exercise programs for survivors of stroke is critical to ensure patients perform prescribed exercises and maximize effectiveness of recovery. METHODS: Survivors of hemiparetic stroke with impaired motor function were recruited into a 7-day study designed to test the utility and usability of a low-cost wearable system and progressive-challenge cued exercise program for encouraging graded-challenge exercise at-home. The wearable system comprised two wrist-worn MetaMotionR+ activity monitors and a custom smartphone app. The progressive-challenge cued exercise program included high-intensity activities (one repetition every 30 s) dosed at 1.5 h per day, embedded within 8 h of passive activity monitoring per day. Utility was assessed using measures of system uptime and cue response rate. Usability and user experience were assessed using well-validated quantitative surveys of system usability and user experience. Self-efficacy was assessed at the end of each day on a visual analog scale that ranged from 0 to 100. RESULTS: The system and exercise program had objective utility: system uptime was 92 ± 6.9% of intended hours and the rate of successful cue delivery was 99 ± 2.7%. The system and program also were effective in motivating cued exercise: activity was detected within 5-s of the cue 98 ± 3.1% of the time. As shown via two case studies, accelerometry data can accurately reflect graded-challenge exercise instructions and reveal differentiable activity levels across exercise stages. User experience surveys indicated positive overall usability in the home settings, strong levels of personal motivation to use the system, and high degrees of satisfaction with the devices and provided training. Self-efficacy assessments indicated a strong perception of proficiency across participants (95 ± 5.0). CONCLUSIONS: This study demonstrates that a low-cost wearable system providing frequent haptic cues to encourage graded-challenge exercise after stroke can have utility and can provide an overall positive user experience in home settings. The study also demonstrates how combining a graded exercise program with all-day activity monitoring can provide insight into the potential for wearable systems to assess adherence to-and effectiveness of-home-based exercise programs on an individualized basis.