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Abstract Glucagon-like peptide 1 (GLP-1) stimulates insulin secretion and holds significant pharmacological potential. Nevertheless, the regulation of energy homeostasis by centrally-produced GLP-1 remains partially understood. Preproglucagon cells, known to release GLP-1, are found in the olfactory bulb (OB). We show that activating GLP-1 receptors (GLP-1R) in the OB stimulates insulin secretion in response to oral glucose in lean and diet-induced obese male mice. This is associated with reduced noradrenaline content in the pancreas and blocked by an α2-adrenergic receptor agonist, implicating functional involvement of the sympathetic nervous system (SNS). Inhibiting GABAA receptors in the paraventricular nucleus of the hypothalamus (PVN), the control centre of the SNS, abolishes the enhancing effect on insulin secretion induced by OB GLP-1R. Therefore, OB GLP-1-dependent regulation of insulin secretion relies on a relay within the PVN. This study provides evidence that OB GLP-1 signalling engages a top-down neural mechanism to control insulin secretion via the SNS.

Abstract Background The management of inappropriate medication use in older patients suffering from multimorbidity and polymedication is a major healthcare challenge. In a primary care setting, a medication review is an effective tool through which a pharmacist can collaborate with a practitioner to detect inappropriate drug use. Aim This project described the implementation of a systematic process for the management of potentially inappropriate medication use among Lebanese older adults. Its aim was to involve pharmacists in geriatric care and to suggest treatment optimization through the analysis of prescriptions using explicit and implicit criteria. Method This study evaluated the medications of patients over 65 years taking a minimum of five chronic medications a day in different regions of Lebanon. Descriptive statistics for all the included variables using mean and standard deviation (Mean (SD)) for continuous variables and frequency and percentage (n, (%)) for multinomial variables were then performed. Results A total of 850 patients (50.7% women, 28.6% frail, 75.7 (8.01) mean age (SD)) were included in this study. The mean number of drugs per prescription was 7.10 (2.45). Roughly 88% of patients (n = 748) had at least one potentially inappropriate drug prescription: 66.4% and 64.4% of the patients had at least 1 drug with an unfavorable benefit-to-risk ratio according to Beers and EU(7)-PIM respectively. Nearly 50.4% of patients took at least one medication with no indication. The pharmacists recommended discontinuing medication for 76.5% of the cases of drug related problems. 26.6% of the overall proposed interventions were implemented. Discussion The rate of potentially inappropriate drug prescribing (PIDP) (88%) was higher than the rates previously reported in Europe, US, and Canada. It was also higher than studies conducted in Lebanon where it varied from 22.4 to 80% depending on the explicit criteria used, the settings, and the medical conditions of the patients. We used both implicit and explicit criteria with five different lists to improve the detection of all types of inappropriate medication use since Lebanon obtains drugs from many different sources. Another potential source for variation is the lack of a standardized process for the assessment of outpatient medication use in the elderly. Conclusion The prevalence PIDP detected in the sample was higher than the percentages reported in previous literature. Systematic review of prescriptions has the capacity to identify and resolve pharmaceutical care issues thus improving geriatric care.

BackgroundThe association between omega-3 (ω-3) PUFAs and cognition, brain imaging and biomarkers is still not fully established.ObjectivesThe aim was to analyze the cross-sectional and retrospective longitudinal associations between erythrocyte ω-3 index and cognition, brain imaging, and biomarkers among older adults.MethodsA total of 832 Alzheimer's Disease Neuroimaging Initiative 3 (ADNI-3) participants, with a mean (SD) age of 74.0 (7.9) y, 50.8% female, 55.9% cognitively normal, 32.7% with mild cognitive impairment, and 11.4% with Alzheimer disease (AD) were included. A low ω-3 index (%EPA + %DHA) was defined as the lowest quartile (≤3.70%). Cognitive tests [composite score, AD Assessment Scale Cognitive (ADAS-Cog), Wechsler Memory Scale (WMS), Trail Making Test, Category Fluency, Mini-Mental State Examination, Montreal Cognitive Assessment] and brain variables [hippocampal volume, white matter hyperintensities (WMHs), positron emission tomography (PET) amyloid-β (Aβ) and tau] were considered as outcomes in regression models.ResultsLow ω-3 index was not associated with cognition, hippocampal, and WMH volume or brain Aβ and tau after adjustment for demographics, ApoEε4, cardiovascular disease, BMI, and total intracranial volume in the cross-sectional analysis. In the retrospective analysis, low ω-3 index was associated with greater Aβ accumulation (adjusted β = 0.02; 95% CI: 0.01, 0.03; P = 0.003). The composite cognitive score did not differ between groups; however, low ω-3 index was significantly associated with greater WMS-delayed recall cognitive decline (adjusted β = -1.18; 95% CI: -2.16, -0.19; P = 0.019), but unexpectedly lower total ADAS-Cog cognitive decline. Low ω-3 index was cross-sectionally associated with lower WMS performance (adjusted β = -1.81, SE = 0.73, P = 0.014) and higher tau accumulation among ApoE ε4 carriers.ConclusionsLongitudinally, low ω-3 index was associated with greater Aβ accumulation and WMS cognitive decline but unexpectedly with lower total ADAS-Cog cognitive decline. Although no associations were cross-sectionally found in the whole population, low ω-3 index was associated with lower WMS cognition and higher tau accumulation among ApoE ε4 carriers. The Alzheimer's Disease Neuroimaging Initiative (ADNI) is registered at clinicaltrials.gov as NCT00106899.

Abstract Earthworms are known to stimulate soil greenhouse gas (GHG) emissions, but the majority of previous studies have used simplified model systems or lacked continuous high-frequency measurements. To address this, we conducted a 2-year study using large lysimeters (5 m2 area and 1.5 m soil depth) in an ecotron facility, continuously measuring ecosystem-level CO2, N2O, and H2O fluxes. We investigated the impact of endogeic and anecic earthworms on GHG emissions and ecosystem water use efficiency (WUE) in a simulated agricultural setting. Although we observed transient stimulations of carbon fluxes in the presence of earthworms, cumulative fluxes over the study indicated no significant increase in CO2 emissions. Endogeic earthworms reduced N2O emissions during the wheat culture (− 44.6%), but this effect was not sustained throughout the experiment. No consistent effects on ecosystem evapotranspiration or WUE were found. Our study suggests that earthworms do not significantly contribute to GHG emissions over a two-year period in experimental conditions that mimic an agricultural setting. These findings highlight the need for realistic experiments and continuous GHG measurements.

Background and objectiveThe goal of this work was to determine whether midlife cardiac structure and function and their 25-year change from early to middle adulthood are associated with lower midlife cognition.MethodsWe studied 2,653 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study (57% women, 46% Black). Echocardiograms were obtained at year 5, 25, and 30 visits (participant mean age 30, 50, and 55 years) to assess left ventricular (LV) mass (LVM), LV systolic function with LV ejection fraction (LVEF), and LV diastolic function with left atrial volume (LAV) and early peak mitral velocity (E)/early peak mitral annular velocity (e') ratio. LVM and LAV were indexed to body surface area (LVMi and LAVi). At year 30, 5 cognitive domains were measured: global cognition, processing speed, executive function, delayed verbal memory, and verbal fluency. We investigated the association between midlife (year 30) and 25-year change in cardiac structure and function on midlife cognition using linear regressions.ResultsOver 25 years, LVMi and LAVi increased with mean change (SD) per year of 0.27 (0.28) g/m2 and 0.42 (0.15) mL/m2, while LVEF decreased by 0.11% (0.02%). After adjustment for demographics and education, 25-year increase (≥1 SD) in LVMi was associated with lower cognition on most tests (p ≤ 0.02); 25-year increase in LAVi was associated with lower global cognition (p = 0.04), but 25-year decrease in LVEF was not associated with cognition. Further adjustment for cardiovascular risk factors led to similar results. In addition, unlike year 30 E/e' ratio and LVEF, higher year 30 LVMi and LAVi were significantly associated with worse cognition on most cognitive tests.DiscussionMidlife cardiac structure and its change from early to middle adulthood are associated with lower midlife cognition even after accounting for confounders. Unlike systolic function, midlife LV diastolic function and its 25-year change were also linked to cognition. Our results provide information linking early to midlife cardiac structure and function to cognition.

Abstract Introduction Humanity is facing two great challenges: producing enough food for a growing population and mitigating greenhouse gas emissions. In this study, we investigated the choice of specific wheat varieties to improve carbon storage in soil while producing enough grain to assure food security. We hypothesize that ancient wheat varieties could store more carbon than modern ones, due to a likely bigger and deeper root system or to more recalcitrant root organic matter. Materials and Methods We conducted a field experiment with four modern and four ancient wheat varieties, on four different sites with contrasted soil properties. Root morphology was assessed by image analysis and potential CO2 emissions by incubation for 60 days. Since in situ carbon storage differences between ancient and modern varieties were expected to be weak and not cumulated due to rotation, we estimated expected CO2 emissions from root biomass and potential CO2 emissions. The grain yield was also measured. Results The breeding type (ancient vs. modern varieties) affected root length in two of our four sites, with longer roots for ancient varieties, but it did not affect other root traits such as biomass. The breeding type also affected CO2 emissions, with higher measured CO2 emissions for modern than ancient varieties in Arenic Cambisol conditions (Morvan), and higher estimated (considering root biomass variations) CO2 emissions for modern varieties in Rendzic Leptosol conditions (Saint Romain). Root traits and estimated CO2 emissions were also dependent on the soil properties of the different sites. We did not find any significant differences in grain yield between ancient and modern varieties. Conclusion A possible trade‐off between carbon storage and grain production was expected, but our results suggest that some types of soil can support both high grain yield and C storage, especially those with an important depth, a neutral pH and a fine texture.

ObjectivesTo examine the association of atrial fibrillation (AF) with incident dementia in older veterans and the effect of anticoagulation on that association.MethodsAround 407,871 veterans aged ≥55 years receiving care from US Veterans Health Administration between August 2003 and September 2015 were included in our retrospective study. AF and incident dementia were determined according to ICD-9-CM codes. Logistic regressions with veterans grouped into high-dimensional propensity scores deciles were used, and a mediation analysis was employed to examine the extent of cardio/cerebrovascular diseases that may also account for that association.ResultsAF was associated with greater dementia risk (odds ratio = 1.14; 95% confidence interval 1.07-1.22), partially mediated by cardio/cerebrovascular disease. Among veterans with AF taking anticoagulants, the risk of dementia was 44% higher (odds ratio =1.44; 95% CI 1.27-1.63) compared to those without anticoagulants, likely related to AF severity.ConclusionOur findings underscore the importance of considering cognitive function in the management of AF patients.

Abstract Introduction Adverse childhood events (ACEs) have been linked to widespread chronic pain (CP) in various cross-sectional studies, mainly in clinical populations. However, the independent role of different ACEs on the development of different types of CP remains elusive. Accordingly, we aimed to prospectively assess the associations between specific types of ACEs with the development of multisite CP in a large population-based cohort. Methods Data stemmed from the three first follow-up evaluations of CoLaus|PsyCoLaus, a prospective population-based cohort study of initially 6734 participants (age range: 35–75 years). The present sample included 1537 participants with 2161 analyzable intervals (49.7% men, mean age 57.3 years). Diagnostic criteria for ACEs were elicited using semi-structured interviews and CP was assessed by self-rating questionnaires. Multinomial logistic regressions with generalized estimating equations method analyzed the relationship between the different ACEs measured in the beginning of the interval and the risk of developing multisite CP during the follow-up. Sensitivity analyses were performed to assess the predictive value of ACEs on multisite CP with neuropathic features. Results Participants with a history of parental divorce or separation had an increased risk of developing multisite CP at during follow-up in comparison to those without (RR1.98; 95% CI 1.13–3.47). A strong association was highlighted between parental divorce or separation and the risk of subsequent CP with neuropathic characteristics (RR 4.21, 95% CI 1.45–12.18). Conclusion These results highlight the importance of psychotherapeutic management of people experiencing parental separation to prevent CP in the future.

ObjectiveTo determine whether orthostatic hypotension (OHYPO) and visit-to-visit blood pressure (BP) postural changes variability are associated with incident dementia.MethodsWe studied 2,131 older adults from the Health, Aging, and Body Composition cohort study. Orthostatic BP was repeatedly assessed over a 5-year baseline period. OHYPO was defined as a fall ≥15 mm Hg in systolic or ≥7 mm Hg in diastolic BP after standing from a sitting position for one-third or more of the visits. Systolic OHYPO and diastolic OHYPO were also examined separately. BP postural changes variability over time was evaluated with several indicators, including SD and coefficient of variation (CV). Incident dementia was determined over 12 years after the baseline period by dementia medication use, ≥1.5 SD decline in Modified Mini-Mental State Examination score, or hospitalization records.ResultsOf 2,131 participants (mean age 73 years, 53% female, 39% Black), 309 (14.5%) had OHYPO, 192 (9.0%) had systolic OHYPO, 132 (6.2%) had diastolic OHYPO, and 462 (21.7%) developed dementia. After adjustment for demographics, seated systolic BP (SBP), antihypertensive drugs, cerebrovascular disease, diabetes mellitus, depressive symptoms, smoking, alcohol, body mass index, and presence of 1 or 2 APOE ε4 alleles, systolic OHYPO was associated with greater dementia risk (adjusted hazard ratio [HR] 1.37, 95% confidence interval [CI] 1.01-1.88), unlike diastolic OHYPO and OHYPO. SBP postural changes variability was also associated with higher dementia risk (highest tertile of variability [CV]: adjusted HR 1.35, 95% CI 1.06-1.71).ConclusionSystolic OHYPO and visit-to-visit SBP postural changes variability were associated with greater dementia risk. Our findings raise the question of potential preventive interventions to control orthostatic SBP and its fluctuations.

PurposeBolus injection of fluid into subcutaneous tissue results in accumulation of fluid at the injection site. The fluid does not form a pool. Rather, the injection pressure forces the interstitial matrix to expand to accommodate the excess fluid in its volume, and the fluid becomes bound similar to that in a hydrogel. We seek to understand the properties and dynamics of externally tumesced (swollen) subcutaneous tissue as a first step in assessing whether tumescent antibiotic injections into wounds may provide a novel method of treatment.MethodsSubcutaneous injections of saline are performed in live and dead pigs and the physical properties (volume, expansion ratio, residence time, apparent diffusion constant) of the resulting fluid deposits are observed with diffusion-weighted magnetic resonance imaging, computed tomography, and 3D scanning.ResultsSubcutaneous tissue can expand to a few times its initial volume to accommodate the injected fluid, which is dispersed thoroughly throughout the tumescent volume. The fluid spreads to peripheral unexpanded regions over the course of a few minutes, after which it remains in place for several hours. Eventually the circulation absorbs the excess fluid and the tissue returns to its original state.ConclusionsGiven the evidence for dense fluid dispersal and several-hour residence time, a procedure is proposed whereby tumescent antibiotic injections are used to treat drug-resistant skin infections and chronic wounds that extend into the subcutaneous tissue. The procedure has the potential to effectively treat otherwise untreatable wounds by keeping drug concentrations above minimum inhibitory levels for extended lengths of time.

Human small intestinal crypts are the source of intestinal stem cells (ISCs) that are capable of undergoing self-renewal and differentiation to an epithelial layer. The development of methods to expand the ISCs has provided opportunities to model human intestinal epithelial disorders. Human crypt samples are usually obtained from either endoscopic or discarded surgical samples, and are thereby exposed to warm ischemia, which may impair their in vitro growth as three-dimensional culture as spheroids or enteroids. In this study we compared duodenal samples obtained from discarded surgical samples to those isolated from whole-body preserved cadaveric donors to generate in vitro cultures. We also examined the effect of storage solution (phosphate-buffered saline or University of Wisconsin [UW] solution) as well as multiple storage times on crypt isolation and growth in culture. We found that intestinal crypts were successfully isolated from cadaveric tissue stored for up to 144 h post-procurement and also were able to generate enteroids and spheroids in certain media conditions. Surgical samples stored in UW after procurement were sufficiently viable up to 24 h and also allowed the generation of enteroids and spheroids. We conclude that surgical samples stored for up to 24 h post-procurement in UW solution allowed for delayed crypt isolation and viable in vitro cultures. Furthermore, in situ, hypothermic preservation in cadaveric duodenal samples permitted crypt/ISC isolation, and successful culture of spheroids and enteroids from tissues held for up to 6 days post-procurement.

Adult intestinal epithelial stem cells are a promising resource for treatment of intestinal epithelial disorders that cause intestinal failure and for intestinal tissue engineering. We developed two different animal models to study the implantation of cultured murine and human intestinal epithelial cells in the less differentiated "spheroid" state and the more differentiated "enteroid" state into the denuded small intestine of mice. Engraftment of donor cells could not be achieved while the recipient intestine remained in continuity. However, we were able to demonstrate successful implantation of murine and human epithelial cells when the graft segment was in a bypassed loop of jejunum. Implantation of donor cells occurred in a random fashion in villus and crypt areas. Engraftment was observed in 75% of recipients for murine and 36% of recipients for human cells. Engrafted spheroid cells differentiated into the full complement of intestinal epithelial cells. These findings demonstrate for the first time successful engraftment into the small bowel which is optimized in a bypassed loop surgical model.

IntroductionLower cognitive functioning in old age has been associated with personality traits or systemic inflammatory markers. Associations have also been found between personality traits and inflammatory markers. However, no study has explored the inter-relationships between these three components simultaneously. The present study aims to better understand the inter-relationships among personality traits, inflammatory markers, and cognitive performance in elderly individuals without dementia.MethodsThis study utilizes a network analysis approach, a statistical method that allows visualization of the data’s unique pairwise associations. We performed a cross-sectional analysis on 720 elderly individuals without dementia, using data from Colaus|PsyColaus, a population-based study conducted in Lausanne, Switzerland. The Revised NEO Five-Factor Inventory (NEO-FFI-R) was used to assess personality traits, and interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were used as peripheral inflammatory markers. Cognitive domains were investigated using the Mini-Mental State Examination (MMSE), the Verbal Fluency Test, the Stroop Test, the DO40, and the Free and Cued Selective Reminding (FCSR) test.ResultsOpenness was associated with verbal fluency and Agreeableness with immediate free recall. In contrast, no association between inflammatory markers and personality traits or cognition was identified.DiscussionIn elderly individuals without dementia, a high level of Openness or Agreeableness was associated with executive functioning/semantic memory and episodic memory, respectively.

Abstract Background This work aimed to investigate the potential pathways involved in the association between social and lifestyle factors, biomarkers of Alzheimer’s disease and related dementia (ADRD), and cognition. Methods The authors studied 2323 participants from the Memento study, a French nationwide clinical cohort. Social and lifestyle factors were education level, current household incomes, physical activity, leisure activities, and social network from which two continuous latent variables were computed: an early to midlife (EML) and a latelife (LL) indicator. Brain magnetic resonance imaging (MRI), lumbar puncture, and amyloid-positron emission tomography (PET) were used to define three latent variables: neurodegeneration, small vessel disease (SVD), and AD pathology. Cognitive function was defined as the underlying factor of a latent variable with four cognitive tests. Structural equation models were used to evaluate cross-sectional pathways between social and lifestyle factors and cognition. Results Participants’ mean age was 70.9 years old, 62% were women, 28% were apolipoprotein-ε4 carriers, and 59% had a Clinical Dementia Rating (CDR) score of 0.5. Higher early to midlife social indicator was only directly associated with better cognitive function (direct β = 0.364 (0.322; 0.405), with no indirect pathway through ADRD biomarkers (total β = 0.392 (0.351; 0.429)). In addition to a direct effect on cognition (direct β = 0.076 (0.033; 0.118)), the association between latelife lifestyle indicator and cognition was also mostly mediated by an indirect effect through lower neurodegeneration (indirect β = 0.066 (0.042; 0.090) and direct β = − 0.116 (− 0.153; − 0.079)), but not through AD pathology nor SVD. Conclusions Early to midlife social factors are directly associated with higher cognitive functions. Latelife lifestyle factors may help preserve cognitive functions through lower neurodegeneration.

Managing pet obesity relies heavily on the active involvement of owners; however, a key challenge arises from misperceptions about their own pet’s body condition. Given evolving societal dynamics like the body positivity movement, understanding owners’ perceptions is increasingly pivotal. To evaluate the differences in owners’ perception, this study compared the use of verbal and visual body condition score scales versus the established nine-point body condition score system. The factors linked to underestimation were further specifically investigated. Owners of healthy adult dogs and cats attending vaccination consultations in Veterinary Hospitals in France between 2020 and 2022 were recruited. They were required to assess their pets’ body condition initially using an oral description and then with the nine-point BCS visual scale. Their assessments were then compared with the BCS determined by veterinary health care personnel, considered the primary investigator. A total of 304 dogs and 270 cats were included in the study. It was observed that 27% of dog owners and 24% of cat owners underestimated their pets’ body condition. Among dog and cat owners, factors associated with the underestimation of body condition were the pets’ overweight status and having children. This discovery emphasizes the need for a holistic One Health approach that prioritizes the health and well-being of both humans and their pets. When it comes to pet owners evaluating their pets’ body condition, underestimation proved to be the predominant misperception. Addressing this issue requires comprehensive education to empower owners to recognize and comprehend their pets’ overweight status, a critical step for the overall well-being of companion animals.

ObjectiveDuring the COVID-19 pandemic, older people and patients with psychiatric disorders had an increased risk of being isolated. The French National Authority for Health has recommended a reinforced follow-up of these patients. Cross-sectional studies reported an increased risk of developing anxiety and depression during pandemic. The aim of our study was to identify factors associated with higher anxiety during the pandemic in older patients with psychiatric disorders.MethodsSTERACOVID is a multicenter cohort study with 117 patients followed-up by phone in two French geriatric psychiatry units. In this work, we used cross-sectional data from a prospective follow-up conducted between January and May 2021.ResultsWe found that coping strategies, personality, and living conditions were associated with general anxiety (GA) level during the pandemic period. Higher GA was associated with less positive thinking coping strategy, more avoidance strategies, a lower level of extraversion, a higher level of neuroticism, more time spent watching the news, a higher feeling of loneliness, and a lack of physical contact.FindingsOur study identified factors associated with a poorer experience of pandemic crisis. Special attention should be paid to patients with a high level of neuroticism and a high feeling of loneliness. Support could aim to help patients use more functional strategies: reducing avoidance strategies and increasing positive thinking. Finally, reducing time watching news could also be an interesting prevention perspective.Clinical trial registrationclinicaltrials.gov, identifier NCT04760795.

The vertical rectus abdominis myocutaneous (VRAM) flap is a versatile and well-established reconstructive technique for many defects created as a result of colorectal and gynecologic extirpation. However, major re-operation in the pelvis following a VRAM flap reconstruction several months later is uncommon, and the safety and integrity of the VRAM flap in this setting has not been described. This case examines VRAM flap preservation during repeat exploratory laparotomy, and a unique view of the VRAM flap during interval exploration. We demonstrate an intact flap after lysis of adhesions with an audible Doppler signal, and maintenance of flap integrity in the postoperative period. This further substantiates its use as a durable rotational flap for perineal tissue defects.

Spring-mediated distraction enterogenesis has been studied as a novel treatment for short bowel syndrome (SBS). Previous approaches are limited by multiple surgeries to restore intestinal continuity. Purely endoluminal devices require a period of intestinal attachment for enterogenesis. The purpose of this study is to modify the device to prevent premature spring migration in a porcine model. Two models were created in juvenile mini-Yucatan pigs for the placement of three-dimensionally printed springs. (1) Two Roux-en-y jejunojenostomies with two Roux limbs were made. A spring with bidirectional hooked surface features was placed in one Roux limb and a spring with smooth surface was placed in the other Roux limb. (2) The in-continuity model had both hooked and smooth surface springs placed directly in intestinal continuity. Spring location was evaluated by weekly radiographs, and the intestine was retrieved after 2 to 4 weeks. Springs with smooth surfaces migrated between 1 to 3 weeks after placement in both porcine models. Springs with bidirectional hooked surface features were anchored to the intestine for up to 4 weeks without migration. Histologically, the jejunal architecture showed significantly increased crypt depth and muscularis thickness compared to normal jejunum. Bidirectional features printed on springs prevented the premature migration of endoluminal springs. These novel spring anchors allowed for their endoluminal placement without any sutures. This approach may lead to the endoscopic placement of the device for patients with SBS.

Abstract Some of the behavioral disorders observed in Parkinson’s disease (PD) may be related to an altered processing of social messages, including emotional expressions. Emotions conveyed by whole body movements may be difficult to generate and be detected by PD patients. The aim of the present study was to compare valence judgments of emotional whole body expressions in individuals with PD and in healthy controls matched for age, gender and education. Twenty-eight participants (13 PD patients and 15 healthy matched control participants) were asked to rate the emotional valence of short movies depicting emotional interactions between two human characters presented with the “Point Light Displays” technique. To ensure understanding of the perceived scene, participants were asked to briefly describe each of the evaluated movies. Patients’ emotional valence evaluations were less intense than those of controls for both positive (p

BackgroundDue to the lockdown linked to the COVID-19 pandemic, the French National Authority for Health has recommended reinforced follow-up of psychiatric patients, with particular attention to people over 65 years. Cross-sectional studies reported an increased risk of anxiety, depression, and suicide during this period. Older people with psychiatric disorders are at higher risk of developing severe COVID-19 and worsening their psychiatric symptoms.ObjectiveThe main objective is to evaluate the link between coping strategies and the onset of post-traumatic stress disorder (PTSD) after lockdown. The secondary objective is to assess the psychological factors influencing lockdown experiences such as personality, attachment type, or coping strategies.Method/Designthis is a multicenter cohort study including 117 patients followed up by phone in two French geriatric psychiatry units. Sociodemographic variables, psychiatric diagnoses, lockdown conditions, coping strategies, anxiety, and depressive symptoms reported during the first lockdown will be collected retrospectively from the medical file. A first prospective assessment including personality traits, attachment type, and traumatic life events will be conducted at 12 months (T1). Follow-up visits assessing anxious-depressive symptoms and PTSD will be made 18 (T2) and 24 months (T3) after the first lockdown. The primary outcome measure is PTSD symptoms. Secondary outcomes measures are coping strategies, generalized anxiety, anxiety about the COVID-19 pandemic, and quality of life.DiscussionThis study aims to determine if the type of coping strategies usually employed have an impact on the onset of PTSD after a lockdown period. It will also determine if these coping strategies are influenced by other factors such as sociodemographic variables, lockdown conditions, particular personality traits, attachment type, and traumatic life events. This study could help identify factors associated with a poorer experience of lockdowns and pandemic crisis in elderly patients followed in a psychiatric center, and guide support in future similar situations.Trial RegistrationClinicalTrials.gov: http://clinicaltrials.gov/show/NCT04760795, Registered 18 February 2021.

Background: Brain-derived neurotrophic factor (BDNF) -tropomyosin-related kinase receptor B (TrkB) signaling is a vital regulator of myocardial performance. Here, we tested the impact of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on heart function, metabolic parameters, and serum/cardiac BDNF (with its TrkB receptor) in animals fed a Western (WD) or regular diet (ND). Further, myocardial expression of pro-inflammatory cytokine interleukin-18 (IL-18) and cardioprotective molecule heme oxygens-1 (HO-1) were monitored. Methods: Wistar rats were divided into HIIT, MICT, and sedentary (SED), all fed a WD or ND, for 12 weeks. Heart function, protein expression, and serum factors were assessed via echocardiography, western blotting, and ELISA, respectively. Results: WD plus SED caused insulin resistance, dyslipidemia, visceral fat deposition, serum BDNF depletion as well as cardiac upregulation of IL-18 and downregulation of HO-1, without affecting, heart function and BDNF-TrkB expression. The cardiometabolic risk factors, serum BDNF losses, and IL-18 overexpression were similarly obviated by HIIT and MICT, although HO-1 expression was boosted by HIIT exclusively (even in ND). HIIT enhanced heart function, regardless of the diet. HIIT augmented cardiac BDNF expression, with a significant difference between ND and WD. Likewise, HIIT instigated TrkB expression only in ND. Conclusions: HIIT and MICT can cope with myocardial inflammation and cardiometabolic risk factors in WD consumers and, exclusively, HIIT may grant further protection by increasing heart function, BDNF-TrkB expression, and HO-1 expression. Thus, the HIIT paradigm should be considered as a preference for subjects who require heart function to be preserved or enhanced.

Intervention research is replete with examples of finely crafted innovations showing initial efficacy in tightly controlled experimental contexts only to fail when they are implemented in typical use settings. While the reasons for such failures are broad, implementation science shows a targeted and judicious use of appropriate competency drivers, such as coaching to innovation providers, increases the likelihood that promising interventions can be used with effectiveness. This article discusses how an implementation coaching framework is used to implement a novel career and university readiness (CCR) program. The SELF CARE program utilizes university residential life community directors to implement a manualized social-emotional learning (SEL) and community and cultural wealth (CCW) curriculum with the purpose of enhancing the protective and thriving skills of growth mind-set, sense of belonging, self-management, self-advocacy, and community and cultural wealth (see Appendix A). SELF CARE targets underserved university students with the goal of supporting their thriving at a predominantly White institution (PWI).

The purpose of this study was to determine the stiffness of mandibular soft tissues during mandibular distraction, from the perspective of improving distraction devices such as automated continuous distractors. Uncompleted osteotomy was performed on 11 fresh human hemimandibles via a greenstick fracture, to preserve the uplift of the internal periosteum of the mandibular corpus. In order to replicate continuous distraction, direct measurements were performed through a uniaxial quasi-static tensile test. For all specimens, linear regression was applied to the force-displacement curve for a force region of 10–20 N, and the slope extracted. The mean stiffness was estimated to be 9.12 ± 3.56 N/mm. This study is the first to measure directly the stiffness of the surrounding tissues of the human mandibular corpus, and paves the way to the design of a new generation of distractor devices. [ABSTRACT FROM AUTHOR]

Overnutrition is associated with the activation of inflammatory pathways in metabolically linked organs and an early hypothalamic inflammation is now known to disrupt the central control of metabolic function. Because we demonstrated that fatty acids (FA) target the pituitary and affect gonadotropin synthesis, we asked whether overnutrition induces pituitary inflammation that may contribute to obesity-associated disorders in the control of reproduction. We analyzed pituitary inflammation and hypothalamic-pituitary-testicular axis in male rats fed a short- (4 weeks) or long-term (20 weeks) high-fat diet. The effect of diet enrichment with the ω3 polyunsaturated FA, DHA, was also analyzed. After only 4 weeks and before weight gain of rats, high-fat diet caused a significant decrease in pituitary gonadotropin and hypothalamic GnRH transcript levels despite unchanged testosterone and inhibin B levels. Contrasting with the hypothalamus, there was no concomitant increases in gene expression of pituitary inflammatory mediators and even a reduction of prototypical cytokines such as interleukin-1β and TNF-α. No inflammation was still detected in the pituitary after 20 weeks although gonadotropin transcripts and circulating levels were still altered. Gonadotropins were the only pituitary hormones remaining affected at this stage of the regimen, underlying a differential susceptibility of pituitary lineages to metabolic disorders. DHA enrichment of the diet did not prevent alterations of gonadotrope activity due to either a long- or a short-term high-fat diet although it blocked early hypothalamic inflammation and attenuated several metabolic effects. Taken together, our findings suggest that high-fat diet-induced defects in gonadotrope activity in male rats occurred despite a lack of pituitary inflammation.

PurposeCurrent culture schema for human intestinal stem cells (hISCs) frequently rely on a 3D culture system using Matrigel™, a laminin-rich matrix derived from murine sarcoma that is not suitable for clinical use. We have developed a novel 2D culture system for the in vitro expansion of hISCs as an intestinal epithelial monolayer without the use of Matrigel.MethodsCadaveric duodenal samples were processed to isolate intestinal crypts from the mucosa. Crypts were cultured on a thin coat of type I collagen or laminin. Intestinal epithelial monolayers were supported with growth factors to promote self-renewal or differentiation of the hISCs. Proliferating monolayers were sub-cultured every 4-5days.ResultsIntestinal epithelial monolayers were capable of long-term cell renewal. Less differentiated monolayers expressed high levels of gene marker LGR5, while more differentiated monolayers had higher expressions of CDX2, MUC2, LYZ, DEF5, and CHGA. Furthermore, monolayers were capable of passaging into a 3D culture system to generate spheroids and enteroids.ConclusionThis 2D system is an important step to expand hISCs for further experimental studies and for clinical cell transplantation.Level of evidence1 Experimental.

Background & aimsIntestinal microfold (M) cells are specialized epithelial cells that act as gatekeepers of luminal antigens in the intestinal tract. They play a critical role in the intestinal mucosal immune response through transport of viruses, bacteria and other particles and antigens across the epithelium to immune cells within Peyer's patch regions and other mucosal sites. Recent studies in mice have demonstrated that M cells are generated from Lgr5+ intestinal stem cells (ISCs), and that infection with Salmonella enterica serovar Typhimurium increases M cell formation. However, it is not known whether and how these findings apply to primary human small intestinal epithelium propagated in an in vitro setting.MethodsHuman intestinal crypts were grown as monolayers with growth factors and treated with recombinant RANKL, and assessed for mRNA transcripts, immunofluorescence and uptake of microparticles and S. Typhimurium.ResultsFunctional M cells were generated by short-term culture of freshly isolated human intestinal crypts in a dose- and time-dependent fashion. RANKL stimulation of the monolayer cultures caused dramatic induction of the M cell-specific markers, SPIB, and Glycoprotein-2 (GP2) in a process primed by canonical WNT signaling. Confocal microscopy demonstrated a pseudopod phenotype of GP2-positive M cells that preferentially take up microparticles. Furthermore, infection of the M cell-enriched cultures with the M cell-tropic enteric pathogen, S. Typhimurium, led to preferential association of the bacteria with M cells, particularly at lower inoculum sizes. Larger inocula caused rapid induction of M cells.ConclusionsHuman intestinal crypts containing ISCs can be cultured and differentiate into an epithelial layer with functional M cells with characteristic morphological and functional properties. This study is the first to demonstrate that M cells can be induced to form from primary human intestinal epithelium, and that S. Typhimurium preferentially infect these cells in an in vitro setting. We anticipate that this model can be used to generate large numbers of M cells for further functional studies of these key cells of intestinal immune induction and their impact on controlling enteric pathogens and the intestinal microbiome.

Feeding behavior is exquisitely regulated by homeostatic and hedonic neural substrates that integrate energy demand as well as the reinforcing and rewarding aspects of food. Understanding the net contribution of homeostatic and reward-driven feeding has become critical because of the ubiquitous source of energy-dense foods and the consequent obesity epidemic. Hypothalamic agouti-related peptide-secreting neurons (AgRP neurons) provide the primary orexigenic drive of homeostatic feeding. Using models of neuronal inhibition or ablation, we demonstrate that the feeding response to a fast ghrelin or serotonin receptor agonist relies on AgRP neurons. However, when palatable food is provided, AgRP neurons are dispensable for an appropriate feeding response. In addition, AgRP-ablated mice present exacerbated stress-induced anorexia and palatable food intake--a hallmark of comfort feeding. These results suggest that, when AgRP neuron activity is impaired, neural circuits sensitive to emotion and stress are engaged and modulated by food palatability and dopamine signaling.