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Background Cardiac arrest (CA) survivors experience continuous exposures to potential traumas though chronic cognitive, physical and emotional sequelae and enduring somatic threats (ESTs) (i.e., recurring somatic traumatic reminders of the event). Sources of ESTs can include the daily sensation of an implantable cardioverter defibrillator (ICD), ICD-delivered shocks, pain from rescue compressions, fatigue, weakness, and changes in physical function. Mindfulness, defined as non-judgmental present-moment awareness, is a teachable skill that might help CA survivors cope with ESTs. Here we describe the severity of ESTs in a sample of long-term CA survivors and explore the cross-sectional relationship between mindfulness and severity of ESTs. Methods We analyzed survey data of long-term CA survivors who were members of the Sudden Cardiac Arrest Foundation (collected 10-11/2020). We assessed ESTs using 4 cardiac threat items from the Anxiety Sensitivity Index-revised (items range from 0 'very little' to 4 'very much') which we summed to create a score reflecting total EST burden (range 0-16). We assessed mindfulness using the Cognitive and Affective Mindfulness Scale-Revised. First, we summarized the distribution of EST scores. Second, we used linear regression to describe the relationship between mindfulness and EST severity adjusting for age, gender, time since arrest, COVID-19-related stress, and loss of income due to COVID. Results We included 145 CA survivors (mean age: 51 years, 52% male, 93.8% white, mean time since arrest: 6 years, 24.1% scored in the upper quarter of EST severity). Greater mindfulness ([beta]: -30, p = 0.002), older age ([beta]: -0.30, p = 0.01) and longer time since CA ([beta]: -0.23, p = 0.005) were associated with lower EST severity. Male sex was also associated with greater EST severity ([beta]: 0.21, p = 0.009). Conclusion ESTs are common among CA survivors. Mindfulness may be a protective skill that CA survivors use to cope with ESTs. Future psychosocial interventions for the CA population should consider using mindfulness as a core skill to reduce ESTs., Author(s): Alexander M. Presciutti [sup.1] [sup.2] , Sarah M. Bannon [sup.1] [sup.2] , Jolin B. Yamin [sup.3] , Mary M. Newman [sup.4] , Robert A. Parker [sup.5] [sup.6] , Jonathan [...]

BackgroundThe rabbit lumbar spine is a commonly utilized model for studying intervertebral disc degeneration and for the pre-clinical evaluation of regenerative therapies. Histopathology is the foundation for which alterations to disc morphology and cellularity with degeneration, or following repair or treatment are assessed. Despite this, no standardized histology grading scale has yet been established for the spine field for any of the frequently utilized animal models.AimsThe purpose of this study was to establish a new standardized scoring system to assess disc degeneration and regeneration in the rabbit model.Materials and methodsThe scoring system was formulated following a review of the literature and a survey of spine researchers. Validation of the scoring system was carried out using images provided by 4 independent laboratories, which were graded by 12 independent graders of varying experience levels. Reliability testing was performed via the computation of intra-class correlation coefficients (ICC) for each category and the total score. The scoring system was then further refined based on the results of the ICC analysis and discussions amongst the authors.ResultsThe final general scoring system involves scoring 7 features (nucleus pulposus shape, area, cellularity and matrix condensation, annulus fibrosus/nucleus pulposus border appearance, annulus fibrosus morphology, and endplate sclerosis/thickening) on a 0 (healthy) to 2 (severe degeneration) scale. ICCs demonstrated overall moderate to good agreement across graders. An addendum to the main scoring system is also included for use in studies evaluating regenerative therapeutics, which involves scoring cell cloning and morphology within the nucleus pulposus and inner annulus fibrosus.DiscussionOverall, this new scoring system provides an avenue to improve standardization, allow a more accurate comparison between labs and more robust evaluation of pathophysiology and regenerative treatments across the field.ConclusionThis study developed a histopathology scoring system for degeneration and regeneration in the rabbit model based on reported practice in the literature, a survey of spine researchers, and validation testing.

BackgroundCaregivers of patients with severe acute brain injuries (SABI) that lead to coma and require intensive care unit (ICU) treatment often experience chronic emotional distress. To address this need, we developed the Coma Family (COMA-F) program, a mindfulness-based resiliency intervention for these caregivers. ObjectiveWe will conduct an open pilot trial of COMA-F (National Institutes of Health Stage IA). Here we describe our study protocol and proposed intervention content. MethodsWe will enroll 15 caregivers of patients with SABIs during their loved one’s hospital course from 3 enrollment centers. A clinical psychologist will deliver the COMA-F intervention (6 sessions) over Zoom (Zoom Video Communications, Inc) or in person. We will iterate COMA-F after each caregiver completes the intervention and an exit interview. English-speaking adults who have emotional distress confirmed by the clinical team and are the primary caregivers of a patient with SABI are eligible. The adult patient must have been admitted to the neuro-ICU for SABI and (1) have had a Glasgow Coma Scale score below 9 while not intubated or an inability to follow meaningful commands while intubated at any point during their hospitalization for >24 hours due to SABI; (2) will be undergoing either tracheostomy or percutaneous endoscopic or surgical gastrostomy tube placement or have already received one or both; and (3) have a prognosis of survival >3 months. We will identify eligible caregivers through screening patients’ medical records and through direct referrals from clinicians in the neuro-ICU. During the intervention we will teach caregivers mind-body and resilience skills, including deep breathing, mindfulness, meditation, dialectical thinking, acceptance, cognitive restructuring, effective communication, behavioral activation, and meaning-making. Caregivers will complete self-report assessments (measures of emotional distress and resilience) before and after the intervention. Primary outcomes are feasibility (recruitment, quantitative measures, adherence, and therapist fidelity) and acceptability (treatment satisfaction, credibility, and expectancy). We will conduct brief qualitative exit interviews to gather feedback on refining the program and study procedures. We will examine frequencies and proportions to determine feasibility and acceptability and will analyze qualitative exit interview data using thematic analysis. We will also conduct 2-tailed t tests to explore signals of improvement in emotional distress and treatment targets. We will then conduct an explanatory-sequential mixed methods analysis to integrate quantitative and qualitative data to refine the COMA-F manual and study procedures. ResultsThis study has been approved by the institutional review board at 1 of the 3 enrollment centers (2023P000536), with approvals at the other 2 centers pending. We anticipate that the study will be completed by late 2024. ConclusionsWe will use our findings to refine the COMA-F intervention and prepare for a feasibility randomized controlled trial. Trial RegistrationClinicalTrials.gov NCT05761925; https://clinicaltrials.gov/study/NCT05761925 International Registered Report Identifier (IRRID)PRR1-10.2196/50860

Background: The clinical healing environment after a posterior spinal arthrodesis surgery is one of the most clinically challenging bone-healing environments across all orthopedic interventions due to the absence of a contained space and the need to form de novo bone. Our group has previously reported that sclerostin in expressed locally at high levels throughout a developing spinal fusion. However, the role of sclerostin in controlling bone fusion remains to be established. Methods: We computationally identified two FDA-approved drugs, as well as a single novel small-molecule drug, for their ability to disrupt the interaction between sclerostin and its receptor, LRP5/6. The drugs were tested in several in vitro biochemical assays using murine MC3T3 and MSCs, assessing their ability to (1) enhance canonical Wnt signaling, (2) promote the accumulation of the active (non-phosphorylated) form of β-catenin, and (3) enhance the intensity and signaling duration of BMP signaling. These drugs were then tested subcutaneously in rats as standalone osteoinductive agents on plain collagen sponges. Finally, the top drug candidates (called VA1 and C07) were tested in a rabbit posterolateral spine fusion model for their ability to achieve a successful fusion at 6 wk. Results: We show that by controlling GSK3b phosphorylation our three small-molecule inhibitors (SMIs) simultaneously enhance canonical Wnt signaling and potentiate canonical BMP signaling intensity and duration. We also demonstrate that the SMIs produce dose-dependent ectopic mineralization in vivo in rats as well as significantly increase posterolateral spine fusion rates in rabbits in vivo, both as standalone osteogenic drugs and in combination with autologous iliac crest bone graft. Conclusions: Few if any osteogenic small molecules possess the osteoinductive potency of BMP itself – that is, the ability to form de novo ectopic bone as a standalone agent. Herein, we describe two such SMIs that have this unique ability and were shown to induce de novo bone in a stringent in vivo environment. These SMIs may have the potential to be used in novel, cost-effective bone graft substitutes for either achieving spinal fusion or in the healing of critical-sized fracture defects. Funding: This work was supported by a Veteran Affairs Career Development Award (IK2-BX003845).

The paper presents an original methodology for the identification of intervention priorities through a tailored priority index IP in areas that are highly-exposed to port noise. The methodology is applied to a case study developed in the framework of the European project ANCHOR, acronym of Advanced Noise Control strategies in HarbOuR, funded as part of the announcement Life 2017.

This work is part of a research project aimed at developing a bio-based binder, composed mainly of polylactic acid (PLA), to produce Ti6Al4V feedstock suitable for use in MAM (Metal Additive Manufacturing) via mFFF (metal Fused Filament Fabrication), in order to manufacture a titanium alloy specimen. While in Bragaglia et al. the mechanical characteristics of this sample were analyzed, the aim used of this study is to compare the mentioned mFFF process with one of the most used MAM processes in aerospace applications, known as Selective Laser Sintering (SLS), based on the Life Cycle Assessment (LCA) method. Despite the excellent properties of the products manufactured via SLS, this 3D printing technology involves high upfront capital costs while mFFF is a cheaper process. Moreover, the mFFF process has the advantage of potentially being exported for production in microgravity or weightless environments for in-space use. Nevertheless, most scientific literature shows comparisons of the Fused Filament Fabrication (FFF) printing stage with other AM technologies, and there are no comparative LCA “Candle to Gate” studies with mFFF processes to manufacture the same metal sample. Therefore, both MAM processes are analyzed with the LCA “Candle to Gate” method, from the extraction of raw materials to the production of the finished titanium alloy sample. The main results demonstrate a higher impact (+50%) process for mFFF and higher electrical energy consumption (7.31 kWh) compared to SLS (0.32 kWh). After power consumption, the use of titanium becomes the main contributor of Global Warming Potential (GWP) and Abiotic Depletion Potential (ADP) for both processes. Finally, an alternative scenario is evaluated in which the electrical energy is exclusively generated through photovoltaics. In this case, the results show how the mFFF process develops a more sustainable outcome than SLS.

Intervertebral disc degeneration is the main contributor to low back pain, now the leading cause of disability worldwide. Gene transfer, either in a therapeutic attempt or in basic research to understand the mechanisms of disc degeneration, is a fascinating and promising tool to manipulate the complex physiology of the disc. Viral vectors based on the adeno-associated virus (AAV) have emerged as powerful transgene delivery vehicles yet a systematic investigation into their respective tropism, transduction efficiency, and relative toxicity have not yet been performed in the disc in vivo. Herein, we used in vivo bioluminescence imaging to systematically compare multiple AAV serotypes, injection volumes, titers, promoters, and luciferase reporters to determine which result in high transduction efficiency of murine nucleus pulposus (NP) cells in vivo. We find that AAV6 using a CAG promoter to drive transgene expression, delivered into the NP of murine caudal discs at a titer of 1011 GC/mL, provides excellent transduction efficiency/kinetics and low toxicity in vivo. We also show, for the first time, that the transduction of NP cells can be significantly boosted in vivo by the use of small cell permeabilization peptides. Finally, to our knowledge, we are the first to demonstrate the use of optical tissue clearing and three-dimensional lightsheet microscopy in the disc, which was used to visualize fine details of tissue and cell architecture in whole intact discs following AAV6 delivery. Taken together, these data will contribute to the success of using AAV-mediated gene delivery for basic and translational studies of the IVD.

Abstract Background In vitro studies using nucleus pulposus (NP) cells are commonly used to investigate disc cell biology and pathogenesis, or to aid in the development of new therapies. However, lab‐to‐lab variability jeopardizes the much‐needed progress in the field. Here, an international group of spine scientists collaborated to standardize extraction and expansion techniques for NP cells to reduce variability, improve comparability between labs and improve utilization of funding and resources. Methods The most commonly applied methods for NP cell extraction, expansion, and re‐differentiation were identified using a questionnaire to research groups worldwide. NP cell extraction methods from rat, rabbit, pig, dog, cow, and human NP tissue were experimentally assessed. Expansion and re‐differentiation media and techniques were also investigated. Results Recommended protocols are provided for extraction, expansion, and re‐differentiation of NP cells from common species utilized for NP cell culture. Conclusions This international, multilab and multispecies study identified cell extraction methods for greater cell yield and fewer gene expression changes by applying species‐specific pronase usage, 60–100 U/ml collagenase for shorter durations. Recommendations for NP cell expansion, passage number, and many factors driving successful cell culture in different species are also addressed to support harmonization, rigor, and cross‐lab comparisons on NP cells worldwide.

The aim of this work is to study possible models for the development of renewable energy communities (RECs) in public private partnership (PPP), aimed at supporting the transition of energy consumption of Italian public administrations towards renewable sources and the sharing of any energy-economic benefits with the community of reference. In particular, the research work analyses the correct balance of interests of the main protagonists of the operation: public concessionary authorities, private Concessionaire and the energy community as the subject that aggregates the interests of the reference community. Moreover, the work aims to highlight the main advantages and risks for each of the actors involved and examine in depth the system of rules and incentives that enhance the actors' interest in these operations. The economic–financial balance of PPP operations has been investigated in order to quantify the residual economic benefits, after the amortization of the investments and the absorption of management costs. The results highlight that the sustainability of the investments for REC establishment is achieved only under certain conditions with rather modest returns and, in some cases, with the necessity of public capital contributions. [ABSTRACT FROM AUTHOR]

This study describes medical interpreters' experiences with behavioral health (BH) services in a primary care clinic. Focus group data with medical interpreters representing multiple languages was analyzed using hybrid inductive-deductive thematic analysis. Themes related to interpreter roles were: (1) case management, (2) patient-interpreter relationship, and (3) patient-provider liaison. Themes related to barriers and facilitators to interpreter-mediated BH care were: (1) cultural factors, (2) patient-provider interactions, (3) BH-specific considerations, and (4) clinic factors. Results illustrate ways that interpreters directly (e.g. interpreter-mediated services) and indirectly (e.g. relationship building) support care. The interpreter-patient relationship reportedly helped improve patient attitudes and buy-in for BH. [ABSTRACT FROM AUTHOR]

Background Cardiac arrest survivorship refers to the lived experience of long‐term survivors of cardiac arrest and the many postdischarge challenges they experience. We aimed to gather a nuanced understanding of these challenges and of survivors' perceptions of ways to improve the recovery process. Methods and Results We conducted 15 semistructured, one‐on‐one interviews with cardiac arrest survivor members of the Sudden Cardiac Arrest Foundation; the interviews were conducted by telephone and recorded and transcribed verbatim. We used thematic analysis, informed by the Framework Method, to identify underlying themes regarding cardiac arrest survivorship challenges and recommendations to improve cardiac arrest survivorship. Regarding challenges, the overarching theme was a feeling of unpreparedness to confront postarrest challenges because of lack of resources, education, and appropriate expectations for recovery. Regarding recommendations, we uncovered 3 overarching themes including systemic recommendations (eg, providing appropriate resources and expectations, educating providers about survivorship, following up with survivors, including caregivers in treatment planning), social recommendations (eg, attending peer support groups, spending time with loved ones, providing support resources for family members), and individual coping recommendations (eg, acceptance, resilience, regaining control, seeking treatment, focusing on meaning and purpose). Conclusions We described common challenges that survivors of cardiac arrest face, such as lacking resources, education, and appropriate expectations for recovery. Additionally, we identified promising pathways that may improve cardiac arrest survivorship at systemic, social, and individual coping levels. Future studies could use our findings as targets for interventions to support and improve survivorship.

Background: While sudden cardiac arrest (CA) survivors are at risk for developing psychiatric disorders, little is known about the impact of preexisting mental health conditions on long-term survival or postacute healthcare utilization. We examined the prevalence of preexisting psychiatric conditions in CA patients who survived hospital discharge, characterized incidence and reason for inpatient psychiatry consultation during these patients' acute hospitalizations, and determined the association of pre-CA depression and anxiety with hospital readmission rates and long-term survival. We hypothesized that prior depression or anxiety would be associated with higher hospital readmission rates and lower long-term survival. Methods: We conducted a retrospective cohort study including patients resuscitated from in- and out-of-hospital CA who survived both admission and discharge from a single hospital between January 1, 2010, and December 31, 2017. We identified patients from our prospective registry, then performed a structured chart review to abstract past psychiatric history, prescription medications for psychiatric conditions, and identify inpatient psychiatric consultations. We used administrative data to identify readmissions within 1 year and vital status through December 31, 2020. We used multivariable Cox regressions controlling for patient demographics, medical comorbidities, discharge Cerebral Performance Category and disposition, depression, and anxiety history to predict long-term survival and hospital readmission. Results: We included 684 subjects. Past depression or anxiety was noted in 24% (n = 162) and 19% (n = 129) of subjects. A minority of subjects (n = 139, 20%) received a psychiatry consultation during the index hospitalization. Overall, 262 (39%) subjects had at least 1 readmission within 1 year. Past depression was associated with an increased hazard of hospital readmission (hazard ratio 1.50, 95% CI 1.11–2.04), while past anxiety was not associated with readmission. Neither depression nor anxiety were independently associated with long-term survival. Conclusions: Depression is an independent risk factor for hospital readmission in CA survivors. [ABSTRACT FROM AUTHOR]

Objective To determine the risk factors associated with radiographic changes and clinical outcomes following 3-level anterior cervical discectomy and fusion (ACDF) using rigidplate constructs and cortico-cancellous allograft. ACDF has demonstrated efficacy for treatment of multilevel degenerative cervical conditions, but current data exists in small heterogeneous forms. Methods A retrospective review included 98 patients with primary 3-level ACDF surgery at one institution from 2008 to 2013 with minimum 1-year follow-up. Cervical sagittal vertical axis (SVA), segmental height, fusion, and lordosis radiographs were measured preoperatively and at 2 postoperative periods. Results Rates of asymptomatic pseudarthroses and total reoperations were 18% and 4%, respectively. Results demonstrated immediate improvements in cervical lordosis (5.5°, p < 0.01) and segmental height (5.0-mm increase, p < 0.01) with little changes in the cervical SVA (3.2-mm increase, p < 0.01). The segmental height decreased from immediate postoperative period to final follow-up (1.7-mm decrease, p < 0.01). Older age was protective against radiolucent lines (p < 0.05). Patient-reported outcomes significantly improved following surgery (p < 0.01). Current smoking status and diagnosis of diabetes mellitus had no impact on radiographic or clinical outcomes. Risk factors were not identified for the 5 reoperations (4%). Conclusion Three-level ACDF with rigid-plating and cortico-cancellous allograft is an effective procedure for degenerative diseases of the cervical spine without the application of additional adjuncts or combined anteriorposterior cervical surgeries. Significant improvements in cervical lordosis, segmental height, and segmental alignment can be achieved with little change in cervical SVA and a low rate of reoperations over short-term follow-up. Similarly, patient-reported outcomes show significant improvements.

Abstract Background The rabbit lumbar spine is a commonly utilized model for studying intervertebral disc degeneration and for the pre‐clinical evaluation of regenerative therapies. Histopathology is the foundation for which alterations to disc morphology and cellularity with degeneration, or following repair or treatment are assessed. Despite this, no standardized histology grading scale has yet been established for the spine field for any of the frequently utilized animal models. Aims The purpose of this study was to establish a new standardized scoring system to assess disc degeneration and regeneration in the rabbit model. Materials and Methods The scoring system was formulated following a review of the literature and a survey of spine researchers. Validation of the scoring system was carried out using images provided by 4 independent laboratories, which were graded by 12 independent graders of varying experience levels. Reliability testing was performed via the computation of intra‐class correlation coefficients (ICC) for each category and the total score. The scoring system was then further refined based on the results of the ICC analysis and discussions amongst the authors. Results The final general scoring system involves scoring 7 features (nucleus pulposus shape, area, cellularity and matrix condensation, annulus fibrosus/nucleus pulposus border appearance, annulus fibrosus morphology, and endplate sclerosis/thickening) on a 0 (healthy) to 2 (severe degeneration) scale. ICCs demonstrated overall moderate to good agreement across graders. An addendum to the main scoring system is also included for use in studies evaluating regenerative therapeutics, which involves scoring cell cloning and morphology within the nucleus pulposus and inner annulus fibrosus. Discussion Overall, this new scoring system provides an avenue to improve standardization, allow a more accurate comparison between labs and more robust evaluation of pathophysiology and regenerative treatments across the field. Conclusion This study developed a histopathology scoring system for degeneration and regeneration in the rabbit model based on reported practice in the literature, a survey of spine researchers, and validation testing.

Abstract Background Rats are a widely accepted preclinical model for evaluating intervertebral disc (IVD) degeneration and regeneration. IVD morphology is commonly assessed using histology, which forms the foundation for quantifying the state of IVD degeneration. IVD degeneration severity is evaluated using different grading systems that focus on distinct degenerative features. A standard grading system would facilitate more accurate comparison across laboratories and more robust comparisons of different models and interventions. Aims This study aimed to develop a histology grading system to quantify IVD degeneration for different rat models. Materials & Methods This study involved a literature review, a survey of experts in the field, and a validation study using 25 slides that were scored by 15 graders from different international institutes to determine inter‐ and intra‐rater reliability. Results A new IVD degeneration grading system was established and it consists of eight significant degenerative features, including nucleus pulposus (NP) shape, NP area, NP cell number, NP cell morphology, annulus fibrosus (AF) lamellar organization, AF tears/fissures/disruptions, NP‐AF border appearance, as well as endplate disruptions/microfractures and osteophyte/ossification. The validation study indicated this system was easily adopted, and able to discern different severities of degenerative changes from different rat IVD degeneration models with high reproducibility for both experienced and inexperienced graders. In addition, a widely‐accepted protocol for histological preparation of rat IVD samples based on the survey findings include paraffin embedding, sagittal orientation, section thickness < 10 μm, and staining using H&E and/or SO/FG to facilitate comparison across laboratories. Conclusion The proposed histological preparation protocol and grading system provide a platform for more precise comparisons and more robust evaluation of rat IVD degeneration models and interventions across laboratories.