Partial decellularization eliminates immunogenicity in tracheal allografts.

There is currently no suitable autologous tissue to bridge large tracheal defects. As a result, no standard of care exists for long-segment tracheal reconstruction. Tissue engineering has the potential to create a scaffold from allografts or xenografts that can support neotissue regeneration identical to the native trachea. Recent advances in tissue engineering have led to the idea of partial decellularization that allows for the creation of tracheal scaffolds that supports tracheal epithelial formation while preserving mechanical properties. However, the ability of partial decellularization to eliminate graft immunogenicity remains unknown, and understanding the immunogenic properties of partially decellularized tracheal grafts (PDTG) is a critical step toward clinical translation. Here, we determined that tracheal allograft immunogenicity results in epithelial cell sloughing and replacement with dysplastic columnar epithelium and that partial decellularization creates grafts that are able to support an epithelium without histologic signs of rejection. Moreover, allograft implantation elicits CD8+ T-cell infiltration, a mediator of rejection, while PDTG did not. Hence, we establish that partial decellularization eliminates allograft immunogenicity while creating a scaffold for implantation that can support spatially appropriate airway regeneration.

Role of Resilience in the Psychological Recovery of Women With Acute Myocardial Infarction.

Background Psychological well-being is important among individuals with myocardial infarction (MI) given the clear links between stress, depression, and adverse cardiovascular outcomes. Stress and depressive disorders are more prevalent in women than men after MI. Resilience may protect against stress and depressive disorders after a traumatic event. Longitudinal data are lacking in populations post MI. We examined the role of resilience in the psychological recovery of women post MI, over time. Methods and Results We analyzed a sample from a longitudinal observational multicenter study (United States, Canada) of women post MI, between 2016 and 2020. Perceived stress (Perceived Stress Scale-4 [PSS-4]) and depressive symptoms (Patient Health Questionnaire-2 [PHQ-2]) were assessed at baseline (time of MI) and 2 months post MI. Demographics, clinical characteristics, and resilience (Brief Resilience Scale [BRS]) were collected at baseline. Low and normal/high resilience groups were established as per published cutoffs (BRS scores <3 or ≥3). Mixed-effects modeling was used to examine associations between resilience and psychological recovery over 2 months. The sample included 449 women, mean (SD) age, 62.2 (13.2) years, of whom 61.1% identified as non-Hispanic White, 18.5% as non-Hispanic Black, and 15.4% as Hispanic/Latina. Twenty-three percent had low resilience. The low resilience group had significantly higher PSS-4 and PHQ-2 scores than the normal/high resilience group at all time points. In adjusted models, both groups showed a decrease in PSS-4 scores over time. Conclusions In a diverse cohort of women post MI, higher resilience is associated with better psychological recovery over time. Future work should focus on developing strategies to strengthen resilience and improve psychological well-being for women with MI. Registration URL: https://clinicaltrials.gov/ct2/show/NCT02905357; Unique identifier: NCT02905357.

Tissue-engineered composite tracheal grafts create mechanically stable and biocompatible airway replacements.

We tested composite tracheal grafts (CTG) composed of a partially decellularized tracheal graft (PDTG) combined with a 3-dimensional (3D)-printed airway splint for use in long-segment airway reconstruction. CTG is designed to recapitulate the 3D extracellular matrix of the trachea with stable mechanical properties imparted from the extraluminal airway splint. We performed segmental orthotopic tracheal replacement in a mouse microsurgical model. MicroCT was used to measure graft patency. Tracheal neotissue formation was quantified histologically. Airflow dynamic properties were analyzed using computational fluid dynamics. We found that CTG are easily implanted and did not result in vascular erosion, tracheal injury, or inflammation. Graft epithelialization and endothelialization were comparable with CTG to control. Tracheal collapse was absent with CTG. Composite tracheal scaffolds combine biocompatible synthetic support with PDTG, supporting the regeneration of host epithelium while maintaining graft structure.

An Open Trial of Telephone-Delivered Mindfulness-Based Cognitive Therapy: Feasibility, Acceptability, and Preliminary Efficacy for Reducing Depressive Symptoms.

Mindfulness-based cognitive therapy (MBCT) is a promising intervention for reducing depressive symptoms in individuals with comorbid chronic disease, but the program's attendance demands make it inaccessible to many who might benefit. We tested the feasibility, acceptability, safety, and preliminary efficacy of an abbreviated, telephone-delivered adaptation of the in-person mindfulness-based cognitive therapy (MBCT-T) program in a sample of patients with depressive symptoms and hypertension. Participants (n = 14; 78.6% female, mean age = 60.6) with mild to moderate depressive symptoms and hypertension participated in the 8-week MBCT-T program. Feasibility was indexed via session attendance and home-based practice completion. Acceptability was indexed via self-reported satisfaction scores. Safety was assessed via reports of symptomatic decline or need for additional mental health treatment. Depressive symptoms (Quick Inventory of Depressive Symptomatology-Self-Report [QIDS-SR]) and anxiety (Hospital Anxiety and Depression Scale-Anxiety subscale; HADS-A) were assessed at baseline and immediately following the intervention. Sixty-four percent of participants (n = 9) attended ≥4 intervention sessions. Seventy-one percent (n = 6) of participants reported completing all assigned formal home practice and 89.2% (n = 8) reported completing all assigned informal practice. Participants were either very satisfied (75%; n = 6) or mostly satisfied (25%; n = 2) with the intervention. There were no adverse events or additional need for mental health treatment. Depressive symptom scores were 4.09 points lower postintervention (p = .004). Anxiety scores were 3.18 points lower postintervention (p = .039). Results support the feasibility, acceptability, safety, and preliminary efficacy of an abbreviated, telephone-delivered version of MBCT for reducing depressive and anxiety symptoms in individuals with co-occurring chronic disease.

Waking up to the problem of sleep: can mindfulness help? A review of theory and evidence for the effects of mindfulness for sleep.

The high incidence of poor sleep and associated negative health consequences substantiates the need for effective behavioral sleep interventions. We offer an integrative model of sleep disturbance whereby key risk factors for compromised sleep quality and quantity are targeted through mindfulness practice-namely, experiential awareness, attentional control, and acceptance. Theoretical considerations and burgeoning evidence suggest that mindfulness-based interventions (MBIs) may be promising treatments for improving sleep outcomes. However, evidence is mixed due to heterogeneity in design and methods across studies. More rigorous RCTs are needed to determine the efficacy and underlying mechanisms of MBI's for sleep. MBIs that are affordable, accessible, and scalable are needed to improve sleep outcomes at the population level.

New mutations in MAPT gene causing frontotemporal lobar degeneration: biochemical and structural characterization.

Frontotemporal lobar degeneration (FTLD) can be sporadic or familial. The genes encoding the microtubule-associated protein tau (MAPT) and progranulin (GRN) are the most relevant genes so far known causing the hereditary forms. Following genetic screening of patients affected by FTLD, we identified 2 new MAPT mutations, P364S and G366R, the former in a sporadic case. In the study we report the clinical and genetic features of the patients carrying these mutations, and the functional effects of the mutations, analyzed in vitro in order to investigate their pathogenic character. Both mutations resulted in reduced ability of tau to promote microtubule polymerization; the P364S protein variant also showed a high propensity to aggregate into filaments. These results suggest a high probability that these mutations are pathogenic. Our findings highlight the importance of genetic analysis also in sporadic forms of FTLD, and the role of in vitro studies to evaluate the pathologic features of new mutations.

Covert person recognition: its fadeout in a case of temporal lobe degeneration.

Covert person recognition was investigated longitudinally over a three-year period in a patient suffering from "Crossmodal Familiar Person Agnosia", possibly due to a fronto-temporal dementia in its right temporal variant (Gentileschi et al., 2001). The progressive neuronal degeneration in the cortical regions critical for face recognition (viz., right infero-temporal areas) presented us with the opportunity to check Burton et al.'s (1991) and Farah et al.'s (1993) hypothesis on the dissociation between overt and covert face recognition in a neuropsychological condition which, however, is neurologically and cognitively different from that of focal "associative prosopagnosia". Covert person recognition starting from overtly unrecognised faces was assessed by means of learning tasks of face/name association involving celebrities. It was assumed that some unconsciously spared information would selectively enhance the relearning rates when famous faces were paired with their true names. In fact, the true-name advantage (i.e., selective saving for experimental relearning of true name pairings) reached significance at first assessment, carried out five years from clinical onset. Effect faded away two and three years later on, thus abolishing the overt/covert dissociation in face recognition. These findings support Burton et al.'s (1991) and Farah et al.'s (1993) hypothesis of covert face recognition as the consequence of partial and incomplete activation of person semantics, due, in the present case, to the impoverishment of Gentileschi et al.'s (2001) "exemplar semantics" storehouse. Moreover, it turned out that covert recognition does not imply a different learning slope, but an overall different level of the learning profile.