Function Behavior Research Articles

Selective enhancement of fear extinction by inhibiting neuronal adenylyl cyclase 1 (AC1) in aged mice

Adenylyl cyclase 1 (AC1) is a selective subtype of ACs, which is selectively expressed in neurons. The activation of AC1 is activity-dependent, and AC1 plays an important role in cortical excitation that contributes to chronic pain and related emotional disorders. Previous studies have reported that human-used NB001 (hNB001, a selective AC1 inhibitor) produced analgesic effects in different animal models of chronic pain. However, the potential effects of hNB001 on learning and memory have been less investigated. In the present study, we found that hNB001 affected neither the induction nor the expression of trace fear, but selectively enhanced the relearning ability during the extinction in aged mice. By contrast, the same application of hNB001 did not affect recent, remote auditory fear memory, or remote fear extinction in either adult or aged mice. Furthermore, a single or consecutive 30-day oral administration of hNB001 did not affect acute nociceptive response, motor function, or anxiety-like behavior in either adult or aged mice. Our results are consistent with previous findings that inhibition of AC1 did not affect general sensory, emotional, and motor functions in adult mice, and provide strong evidence that inhibiting the activity of AC1 may be beneficial for certain forms of learning and memory in aged mice.

PGC-1α integrates insulin signaling with mitochondrial physiology and behavior in a Drosophila model of Fragile X Syndrome

Fragile X Syndrome (FXS) is the most prevalent monogenetic form of intellectual disability and autism. Recently, dysregulation of insulin signaling (IS) and aberrations in mitochondrial function have emerged as robust, evolutionarily conserved components of FXS pathophysiology. However, the mechanisms by which altered IS and mitochondrial dysfunction impact behavior in the context of FXS remain elusive. Here, we show that normalization of IS improves mitochondrial volume and function in flies that lack expression of dfmr1, the Drosophila homolog of the causal gene of FXS in humans. Further, we demonstrate that dysregulation of IS underlies diminished expression of the mitochondrial master regulator PGC-1α/Spargel in dfmr1 mutant flies. These results are behaviorally relevant, as we show that pan-neuronal augmentation of PGC-1α/Spargel improves circadian behavior in dfmr1 mutants. Notably, we also show that modulation of PGC-1α/Spargel expression in wild-type flies phenocopies the dfmr1 mutant circadian defect. Taken together, the results presented herein provide a mechanistic link between mitochondrial function and circadian behavior both in FXS pathogenesis as well as more broadly at the interface between metabolism and behavioral output.

IFT88 maintains sensory function by localising signalling proteins along Drosophila cilia.

Ciliary defects cause several ciliopathies, some of which have late onset, suggesting cilia are actively maintained. Still, we have a poor understanding of the mechanisms underlying their maintenance. Here, we show Drosophila melanogaster IFT88 (DmIFT88/nompB) continues to move along fully formed sensory cilia. We further identify Inactive, a TRPV channel subunit involved in Drosophila hearing and negative-gravitaxis behaviour, and a yet uncharacterised Drosophila Guanylyl Cyclase 2d (DmGucy2d/CG34357) as DmIFT88 cargoes. We also show DmIFT88 binding to the cyclase´s intracellular part, which is evolutionarily conserved and mutated in several degenerative retinal diseases, is important for the ciliary localisation of DmGucy2d. Finally, acute knockdown of both DmIFT88 and DmGucy2d in ciliated neurons of adult flies caused defects in the maintenance of cilium function, impairing hearing and negative-gravitaxis behaviour, but did not significantly affect ciliary ultrastructure. We conclude that the sensory ciliary function underlying hearing in the adult fly requires an active maintenance program which involves DmIFT88 and at least two of its signalling transmembrane cargoes, DmGucy2d and Inactive.

Artificial light at night alters progression of cold neuropathy in a sex-dependent manner in a mouse model of type II diabetes mellitus

Artificial light at night (ALAN) is a pervasive circadian rhythm disruptor. Exposure to ALAN is associated with detrimental effects on physiology and behavior, including disrupted metabolism, immune function, endocrine function, and pain behavior. Given the detrimental effects of ALAN and other circadian rhythm disruptors on pain, we sought to understand how ALAN may alter the progression and severity of diabetic neuropathy. To do this, we used a previously reported high-fat diet and streptozotocin injection protocol to induce a type II diabetic phenotype in ∼8 week old female and male mice and then exposed the mice to either control or ALAN lighting conditions in 14:10 h light-dark cycles for 4 weeks. Male mice housed in control conditions exhibited reduced responsiveness to cold pain; in contrast, ALAN blunted this effect in male mice. ALAN exposure also elevated blood glucose and altered body mass loss in male mice. These effects were not present in female mice. The results of this study highlight the need to consider and study ALAN exposure and sex as a biological variable as risk factors in the treatment and mitigation of pain.

Modifiable Physical Factors That Influence Physical Function for People Receiving Peritoneal Dialysis

People receiving peritoneal dialysis experience physical function decline, impairing their ability to complete everyday activities, leading to poorer quality of life. Physical factors, including cardiorespiratory fitness, muscle strength, physical activity, and sedentary behavior are associated with physical function. However, little is known about this relationship, or temporal changes of these factors in this cohort. This study aimed to explore modifiable physical factors that are associated with physical function, identify which factor has the strongest influence, and explore temporal changes. Adults receiving peritoneal dialysis underwent objective and self-reported physical function, cardiorespiratory fitness, muscle strength, physical activity and sedentary behavior assessments 3 times over a 12-month observation period (at baseline, 6 months, and 12 months). Eighty-two participants underwent assessments. All modifiable physical factors were predominantly moderate to strongly associated with physical function at baseline. Cardiorespiratory fitness had the strongest and most consistent influence with every meter conferring a 0.08-unit (P< 0.01) and 0.01-unit (P< 0.05) increase in self-report and objective physical function score, respectively. Temporal changes were observed for modifiable physical factors with significant mean changes in cardiorespiratory fitness (-9.8%), quadricep strength (-5%), moderate-to-vigorous (-25.9%) and total (-16.2%) physical activity, and sedentary behavior (+7.1%). The results of this study indicate that cardiorespiratory fitness could be routinely monitored to detect risk of physical function decline and targeted through intervention to enhance physical function for people receiving peritoneal dialysis. Nevertheless, all factors should be considered when designing interventions to mitigate temporal changes and induce the numerous health benefits offered by being physically active.

Potential therapeutic effects of baicalin and baicalein.

Baicalin and baicalein are natural flavonoids reported for the first time from Scutellaria baicalensis Georgi. Recently, attention has been paid to these valuable flavonoids due to their promising effects. This paper aims to have a comprehensive review of their pharmacological effects. An extensive search through scientific databases including Scopus, PubMed, and ISI Web of Science was established. According to literature, these compounds have been mainly effective in the treatment of neurological and neurodegenerative diseases, hepatic and cardiovascular disorders, metabolic syndrome, and cancers through anti-inflammatory and antioxidant pathways. Induction of apoptosis and autophagy, and inhibition of migration and metastasis are the main mechanisms for their cytotoxic and antitumor activities. Decreasing inflammation, reducing oxidative stress, regulating the metabolism of lipids, and decreasing fibrosis, apoptosis, and steatosis are their main hepatoprotective mechanisms. Inhibiting the development of cardiac fibrosis and reducing inflammation, oxidative stress, and apoptosis are also the mechanisms suggested for cardioprotective activities. Decreasing the accumulation of inflammatory mediators and improving cognitive function and depressive-like behaviours are the main mechanisms for neurological and neurodegenerative activities. The findings suggest the therapeutic potential of baicalin and baicalein. However, complementary research in different in vitro and in vivo models to investigate their mechanisms of action as well as clinical trials to evaluate their efficacy and safety are suggested.

The influence of EU renewable energy directive policy to Indonesian palm oil exports to some EU countries

The objectives of this study are 1) to describe Indonesian palm oil export to some European Union (EU) countries and some export determinant variables, 2) to analyze the implementation of the EU renewable energy Directive (RED) as an instrument to guarantee that the traded products are environmentally friendly and sustainable, and 3) to analyze the effect of the RED on Indonesian palm oil exports. The effect of RED was estimated through the export function behavior of Indonesian palm oil to each selected EU country. The secondary data was used for period of 2000–2021. A simultaneous equation model using the 2SLS method was applied for the analysis. The research result implies that the 2003 Directive, and the rupiah real exchange rate have significant effect on Indonesian export to Spain, Italy and Germany. While the price of palm oil in the EU is significantly affected the Indonesian palm oil export to Italy and Germany, but not to Spain. The strengthening of the rupiah exchange rate caused a decrease in Indonesian palm oil exports to Spain but increased the exports of Indonesian palm oil to Italy and Germany, and also increased the palm oil prices in the EU market.

Effect of the combination of respiratory care with bronchodilators on pulmonary function, psychological well being, and health behaviors in COPD patients

Purpose: To investigate the effect of combining respiratory care with bronchodilators on pulmonary function, psychological well-being, and health behavior in patients with Chronic Obstructive Pulmonary Disease (COPD).&#x0D; Method: A retrospective analysis was conducted with 90 COPD patients treated in the First People's Hospital of Fuyang, Hangzhou, China between January 2021 and January 2023. Patients were divided into budegopher group (26 patients), symbicor group (28 patients), and combination group (36 patients treated with budegopher plus respiratory care). Lung function, psychological state (Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS), Health Behavior Scale (HPL), and any observed adverse reactions among these groups were recorded.&#x0D; Results: Significant differences were observed in lung function such as forced expiratory volume in 1 sec (FEV1) and forced vital capacity (FVC) among the three groups after treatment. Symbicor group showed superior results compared to budegopher group while combination group showed better improvement than budegopher group, and symbicor group (p &lt; 0.001). Pairwise comparisons of psychological state (SAS and SDS) and health behavior (HPL) revealed variations among groups. Lung function parameters (FEV1, FVC) had negative correlations with negative psychological attitudes (SAS, SDS) and moderate positive correlations with health-promoting behaviors (HPL). Negative psychological attitudes (SAS, SDS) were moderately and negatively correlated with health-promoting behaviors (HPL).&#x0D; Conclusion: Combining respiratory care with bronchodilators demonstrates notable potential to enhance pulmonary function, alleviate negative psychological states, promote healthful behaviors, and expedite the recovery process for COPD patients. However, subtle variations in the therapeutic effects of different drugs may exist, warranting further investigation.

Positive Correlation Between Motor Function and Neuropathic Pain-Like Behaviors After Spinal Cord Injury: A Longitudinal Study of Mice.

Abstract With the recovery of motor function, some spinal cord injury (SCI) patients still suffer from severe pain-like behaviors symptoms. Whether motor function correlates with neuropathic pain-like behaviors remain unclear. In this study, a longitudinal cohort study of mice with moderate thoracic 10 contusion was performed to explore the characteristics of neuropathic pain-like behaviors and its correlation with motor function in different sexes. Pain-like behaviors data up to 42 days post-injury (dpi) were collected and compared. Mice of both sexes were divided into three groups based on their Basso Mouse Scale at 42 dpi. There was no significant difference in motor function recovery between the sexes. Female mice showed more significant mechanical allodynia than males at 14 dpi, which was sustained until 42 dpi without significant dynamic changes. However, males showed a gradually worsening state and more severe mechanical allodynia than females at 28 dpi, and then the differences disappeared. Interestingly, male mice obtained more severe cold hyperalgesia symptoms than females. Additionally, we found that there was a correlation between the occurrence of mechanical allodynia and cold and thermal hyperalgesia. Importantly, motor function recovery was positively associated with the outcomes of neuropathic pain-like behaviors after SCI, which was more obvious in female mice. Our data not only revealed the characteristics of neuropathic pain-like behaviors but also clarified the correlations between motor function recovery and neuropathic pain-like behaviors after SCI. These findings may provide new opinions and suggestions for promoting the clinical diagnosis and treatment of neuropathic pain-like behaviors after SCI.

Effect of orthodontic appliances on masticatory muscle activity

There is limited and conflicting evidence regarding the impact of orthodontic appliances on masticatory muscle activity (MMA), jaw function, and oral parafunctional behaviours. Investigations in this field frequently utilise surface electromyography (sEMG) to analyse changes in muscle contractile activity. Fixed orthodontics appliances have been associated with significant reductions in MMA post archwire activation. Conversely, elevations in masseter and digastric muscle activity have been reported in response to removable functional appliances. Research into the effect of clear aligner therapy (CAT) on MMA is still in its infancy with few studies published. There is a lack of agreement on whether MMA increases or diminishes in response to CAT though there is evidence this relationship may change over time due to muscle adaptation. The impact of CAT on temporomandibular disorder (TMD) symptoms is unclear, particularly how pre-existing risk factors for TMD may alter and individual's response.

Diagnostic value and role of serum miR-15a-5p in patients with schizophrenia

BackgroundMore and more studies have confirmed that the heredity plays an important role in mental disorders, especially microRNA. The objective of this research was to explore the level of miR-15a-5p in patients with schizophrenia (SZ), and to evaluate the feasibility of this miRNA as a diagnostic marker of SZ.MethodsThe serum level of miR-15a-5p in patients with SZ and healthy people was detected by RT-qPCR. ROC curve was established to evaluate the clinical diagnostic significance of miR-15a-5p in SZ. Pearson correlation coefficient was used to evaluate the correlation between miR-15a-5p level and PANSS score. Logistic regression was used to assess the risk factors of SZ. A rat model of SZ was established, and the effects of miR-15a-5p on the behavior of SZ rats were observed through water maze test and open field test.ResultsThe serum level of miR-15a-5p in patients with SZ was significantly increased, and ROC analysis revealed that miR-15a-5p had clinical diagnostic value in SZ. High level of miR-15a-5p was positively correlated with the positive symptom, negative symptom and general psychopathology subscore of patients. Logistic regression results showed that miR-15a-5p was a risk factor affecting the occurrence of SZ. Animal studies showed that the serum level of miR-15a-5p was elevated in the SZ rats, and inhibiting the expression of miR-15a-5p has a positive effect on improving the cognitive function and anxiety behavior of SZ rats.ConclusionsSerum miR-15a-5p is a risk factor for SZ, which is of great significance for the diagnosis of SZ.

Comparative analyses of the Smith-Magenis syndrome protein RAI1 in mice and common marmoset monkeys.

Retinoic acid-induced 1 (RAI1) encodes a transcriptional regulator critical for brain development and function. RAI1 haploinsufficiency in humans causes a syndromic autism spectrum disorder known as Smith-Magenis syndrome (SMS). The neuroanatomical distribution of RAI1 has not been quantitatively analyzed during the development of the prefrontal cortex, a brain region critical for cognitive function and social behaviors and commonly implicated in autism spectrum disorders, including SMS. Here, we performed comparative analyses to uncover the evolutionarily convergent and divergent expression profiles of RAI1 in major cell types during prefrontal cortex maturation in common marmoset monkeys (Callithrix jacchus) and mice (Mus musculus). We found that while RAI1 in both species is enriched in neurons, the percentage of excitatory neurons that express RAI1 is higher in newborn mice than in newborn marmosets. By contrast, RAI1 shows similar neural distribution in adult marmosets and adult mice. In marmosets, RAI1 is expressed in several primate-specific cell types, including intralaminar astrocytes and MEIS2-expressing prefrontal GABAergic neurons. At the molecular level, we discovered that RAI1 forms a protein complex with transcription factor 20 (TCF20), PHD finger protein 14 (PHF14), and high mobility group 20A (HMG20A) in the marmoset brain. In vitro assays in human cells revealed that TCF20 regulates RAI1 protein abundance. This work demonstrates that RAI1 expression and protein interactions are largely conserved but with some unique expression in primate-specific cells. The results also suggest that altered RAI1 abundance could contribute to disease features in disorders caused by TCF20 dosage imbalance.

Exercise and brain health in patients with coronary artery disease: study protocol for the HEART-BRAIN randomized controlled trial.

Patients with coronary artery disease (CAD) have a higher risk of developing cognitive impairment and mental health disorders compared to the general population. Physical exercise might improve their brain health. The overall goal of the HEART-BRAIN randomized controlled trial (RCT) is to investigate the effects of different types of exercise on brain health outcomes in patients with CAD, and the underlying mechanisms. This three-arm, single-blinded RCT will include 90 patients with CAD (50-75 years). Participants will be randomized into: (1) control group-usual care (n = 30), (2) aerobic high-intensity interval training (HIIT) (n = 30), or (3) HIIT combined with resistance exercise training (n = 30). The 12-week intervention includes 3 supervised sessions (45-min each) per week for the exercise groups. Outcomes will be assessed at baseline and post-intervention. The primary outcome is to determine changes in cerebral blood flow assessed by magnetic resonance imaging. Secondary outcomes include changes in brain vascularization, cognitive measures (i.e., general cognition, executive function and episodic memory), and cardiorespiratory fitness. Additional health-related outcomes, and several potential mediators and moderators will be investigated (i.e., brain structure and function, cardiovascular and brain-based biomarkers, hemodynamics, physical function, body composition, mental health, and lifestyle behavior). The HEART-BRAIN RCT will provide novel insights on how exercise can impact brain health in patients with CAD and the potential mechanisms explaining the heart-brain connection, such as changes in cerebral blood flow. The results may have important clinical implications by increasing the evidence on the effectiveness of exercise-based strategies to delay cognitive decline in this high-risk population. ClinicalTrials.gov, identifier [NCT06214624].

Glucocorticoids rescue cell surface trafficking of R451C Neuroligin3 and enhance synapse formation.

Neuroligins are synaptic cell adhesion proteins with a role in synaptic function, implicated in neurodevelopmental disorders. The autism spectrum disorder-associated substitution Arg451Cys (R451C) in NLGN3 promotes a partial misfolding of the extracellular domain of the protein leading to retention in the endoplasmic reticulum (ER) and the induction of the unfolded protein response (UPR). The reduced trafficking of R451C NLGN3 to the cell surface leads to altered synaptic function and social behavior. A screening in HEK-293 cells overexpressing NLGN3 of 2662 compounds (FDA-approved small molecule drug library), led to the identification of several glucocorticoids such as alclometasone dipropionate, desonide, prednisolone sodium phosphate, and dexamethasone (DEX), with the ability to favor the exit of full-length R451C NLGN3 from the ER. DEX improved the stability of R451C NLGN3 and trafficking to the cell surface, reduced the activation of the UPR, and increased the formation of artificial synapses between HEK-293 and hippocampal primary neurons. The effect of DEX was validated on a novel model system represented by neural stem progenitor cells and differentiated neurons derived from the R451C NLGN3 knock-in mouse, expressing the endogenous protein. This work shows a potential rescue strategy for an autism-linked mutation affecting cell surface trafficking of a synaptic protein.

Emerging ferroelectric materials ScAlN: applications and prospects in memristors.

The research found that after doping with rare earth elements, a large number of electrons and holes will be produced on the surface of AlN, which makes the material have the characteristics of spontaneous polarization. A new type of ferroelectric material has made a new breakthrough in the application of nitride-materials in the field of integrated devices. In this paper, the application prospects and development trends of ferroelectric material ScAlN in memristors are reviewed. Firstly, various fabrication processes and structures of the current ScAlN thin films are described in detail to explore the implementation of their applications in synaptic devices. Secondly, a series of electrical properties of ScAlN films, such as the current switching ratio and long-term cycle durability, were tested to explore whether their electrical properties could meet the basic needs of memristor device materials. Finally, a series of summaries on the current research studies of ScAlN thin films in the synaptic simulation are made, and the working state of ScAlN thin films as a synaptic device is observed. The results show that the ScAlN ferroelectric material has high residual polarization, no wake-up function, excellent stability and obvious STDP behavior, which indicates that the modified material has wide application prospects in the research and development of memristors.

Value-based Identification of Eco-effective Mitigation Options for Manufacturing Processes

To avoid net greenhouse gases and decouple economic growth from resource use, manufacturers strive for solutions minimizing their emissions in operation whilst maximizing the perceived value to their customers offered by a product. One approach is the deployment of new manufacturing processes. The potential of these innovations is often limited to more eco-efficient solutions. However, current developments, e.g. global climate change and legal constraints, require engineering to broaden its focus on eco-effective solutions, covering function and system innovations and behavior change. Therefore, a methodology to identify eco-effective mitigation options for manufacturing processes is presented. By using the extended IPAT identity, the solution space for manufacturing processes to increase eco-effectiveness is highlighted. To consider behavior change, the concept of perceived value is embedded. The methodology is demonstrated on the example of additive manufacturing. The objective is to support engineers in identifying and evaluating market-relevant mitigation options for manufacturing processes addressing eco-effectiveness.

Diet enriched with high-phenolic cocoa potentiates hippocampal brain-derived neurotrophic factor expression and neurogenesis in healthy adult micewith subtle effects on memory.

Cocoa is widely known for its health benefits, but its neurocognitive impact remains underexplored. This preclinical study aimed to investigate the effects of cocoa and cocoa polyphenols on hippocampal neuroplasticity, cognitive function and emotional behavior. Seventy young-adult C57BL/6JRj male and female mice were fed either a standard diet (CTR) or a diet enriched with 10% high-phenolic content cocoa (HPC) or low-phenolic content cocoa (LPC) for at least four weeks. In a first experiment, behavioral tests assessing exploratory behavior, emotional responses and hippocampal-dependent memory were conducted four weeks into the diet, followed by animal sacrifice a week later. Adult hippocampal neurogenesis and brain-derived neurotrophic factor (BDNF) expression in the hippocampus and prefrontal cortex were evaluated using immunohistochemistry and western blot. In a different experiment, hippocampal synaptic response, long-term potentiation and presynaptic-dependent short-term plasticity were studied by electrophysiology. Cocoa-enriched diets had minimal effects on exploratory activity and anxiety-like behavior, except for reduced locomotion in the LPC group. Only the HPC diet enhanced object recognition memory, while place recognition memory and spatial navigation remained unaffected. The HPC diet also increased adult hippocampal neurogenesis, boosting the proliferation, survival and number of young adult-born neurons. However, both cocoa-enriched diets increased immobility in the forced swimming test and hippocampal BDNF expression. Hippocampal electrophysiology revealed no alterations in neuroplasticity among diets. The results were mostly unaffected by sex. Overall, the HPC diet demonstrated greater potential regarding cognitive and neuroplastic benefits, suggesting a key role of cocoa flavanols in dietary interventions aimed at enhancing brain health.

Ultra-low work function of caesiated surfaces and impact of selected gas species

Modern high-power negative hydrogen ion sources rely predominantly on the surface production of negative hydrogen ions. Hence, low work function converter surfaces are mandatory, for which the alkali metal Cs is commonly evaporated into the ion source to lower the work function of refractory metals by surface adsorption. To study the work function behaviour upon caesiation under the typically given non-ultra-high vacuum conditions, investigations are performed at a dedicated laboratory experiment. In a vacuum environment dominated by water vapour, the work function evolution is found to be dependent on the flux ratio of Cs to H2O onto the surface. For sufficiently high flux ratios, ultra-low work functions in the range of 1.25±0.10 eV are generated with excellent reproducibility. In the absence of Cs evaporation, the work function gradually increases under the influence of the residual gases, and re-caesiation processes lead to lower quantum efficiencies and higher work functions of typically 1.9–2.1 eV. While the addition of hydrogen and deuterium gas at several Pa as well as the leakage of inert gases (argon and nitrogen) into the vacuum system have a negligible influence on the caesiation process, small amounts of oxygen with partial pressures of ∼10-2–10-1 Pa lead to an instant reduction of the Cs density in the gas phase by several orders of magnitude and to an increase in the work function of the order of 1 eV. After the oxygen exposure is terminated, however, the Cs density and work function fully recover within several minutes.

Dietary fibre confers therapeutic effects in a preclinical model of Huntington’s disease

Huntington’s disease (HD) is a neurodegenerative disorder involving psychiatric, cognitive and motor deficits, as well as peripheral symptoms, including gastrointestinal dysfunction. The R6/1 HD mouse model expresses a mutant human huntingtin transgene and has been shown to provide an accurate disease model. Recent evidence of gut microbiome disruption was shown in preclinical and clinical HD. Therefore, we aimed to assess the potential role of gut microbial modulation in the treatment of HD. The R6/1 HD mice and wild-type littermate controls were randomised to receive diets containing different amounts of fibre: high-fibre (10 % fibre), control (5 % fibre), or zero-fibre (0 % fibre), from 6 to 20 weeks of age. We characterized the onset and progression of motor, cognitive and affective deficits, as well as gastrointestinal function and gut morphological changes. Faeces were collected for gut microbiome profiling using 16S rRNA sequencing, at 14 and 20 weeks of age. When compared to the control diet, high-fibre diet improved the performance of HD mice in behavioral tests of cognitive and affective function, as well as the gastrointestinal function of both HD and wild-type mice. While the diets changed the beta diversity of wild-type mice, no statistical significance was observed at 14 or 20 weeks of age within the HD mice. Analysis of Composition of Microbiomes with Bias Correction (ANCOM-BC) models were performed to evaluate microbiota composition, which identified differences, including a decreased relative abundance of the phyla Actinobacteriota, Campylobacterota and Proteobacteria and an increased relative abundance of the families Bacteroidaceae, Oscillospiraceae and Ruminococcaceae in HD mice when compared to wild-type mice after receiving high-fibre diet. PICRUSt2 revealed that high-fibre diet also decreased potentially pathogenic functional pathways in HD. In conclusion, high-fibre intake was effective in enhancing gastrointestinal function, cognition and affective behaviors in HD mice. These findings indicate that dietary fibre interventions may have therapeutic potential in Huntington’s disease to delay clinical onset, and have implications for related disorders exhibiting dysfunction of the gut-brain axis.

Feasibility of a Health Coach Intervention to Reduce Sitting Time and Improve Physical Functioning Among Breast Cancer Survivors: Pilot Intervention Study.

Sedentary behavior among breast cancer survivors is associated with increased risk of poor physical function and worse quality of life. While moderate to vigorous physical activity can improve outcomes for cancer survivors, many are unable to engage in that intensity of physical activity. Decreasing sitting time may be a more feasible behavioral target to potentially mitigate the impact of cancer and its treatments. The purpose of this study was to investigate the feasibility and preliminary impact of an intervention to reduce sitting time on changes to physical function and quality of life in breast cancer survivors, from baseline to a 3-month follow-up. Female breast cancer survivors with self-reported difficulties with physical function received one-on-one, in-person personalized health coaching sessions aimed at reducing sitting time. At baseline and follow-up, participants wore the activPAL (thigh-worn accelerometer; PAL Technologies) for 3 months and completed physical function tests (4-Meter Walk Test, Timed Up and Go, and 30-Second Chair Stand) and Patient-Reported Outcomes Measurement Information System (PROMIS) self-reported outcomes. Changes in physical function and sedentary behavior outcomes were assessed by linear mixed models. On average, participants (n=20) were aged 64.5 (SD 9.4) years; had a BMI of 30.4 (SD 4.5) kg/m2; and identified as Black or African American (n=3, 15%), Hispanic or Latina (n=4, 20%), and non-Hispanic White (n=14, 55%). Average time since diagnosis was 5.8 (SD 2.2) years with participants receiving chemotherapy (n=8, 40%), radiotherapy (n=18, 90%), or endocrine therapy (n=17, 85%). The intervention led to significant reductions in sitting time: activPAL average daily sitting time decreased from 645.7 (SD 72.4) to 532.7 (SD 142.1; β=-112.9; P=.001) minutes and average daily long sitting bouts (bout length ≥20 min) decreased from 468.3 (SD 94.9) to 366.9 (SD 150.4; β=-101.4; P=.002) minutes. All physical function tests had significant improvements: on average, 4-Meter Walk Test performance decreased from 4.23 (SD 0.95) to 3.61 (SD 2.53; β=-.63; P=.002) seconds, Timed Up and Go performance decreased from 10.30 (SD 3.32) to 8.84 (SD 1.58; β=-1.46; P=.003) seconds, and 30-Second Chair Stand performance increased from 9.75 (SD 2.81) to 13.20 completions (SD 2.53; β=3.45; P<.001). PROMIS self-reported physical function score improved from 44.59 (SD 4.40) to 47.12 (SD 5.68; β=2.53; P=.05) and average fatigue decreased from 52.51 (SD 10.38) to 47.73 (SD 8.43; β=-4.78; P=.02). This 3-month pilot study suggests that decreasing time spent sitting may be helpful for breast cancer survivors experiencing difficulties with physical function and fatigue. Reducing sitting time is a novel and potentially more feasible approach to improving health and quality of life in cancer survivors.