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The budget of reactive nitrogen species, which play a central role in atmospheric chemistry (e.g. in photochemical O3 production), is poorly understood in forested regions. In this study, through observations of NO, NO2, NOy, and O3 in the Rambouillet Forest near Paris, France, we have examined nighttime processes controlling NOx in an anthropogenically impacted forest environment. The O3 mixing ratios displayed a strong diel profile at the site that was driven by a variable but generally rapid deposition to soil and foliar surfaces. The O3 diel profile was strongly influenced by relative humidity and temperature inversion. Only when the O3 mixing ratio was sufficiently low (and thus the NO lifetime sufficiently long) were sustained NO peaks observed above the instrumental detection limit, enabling the derivation of average NO emission rates of ∼1.4 ppbv h−1 from the soil. Observations of the lack of increase in NO2 at night, despite a significant production rate from the reaction of NO with O3, enabled an effective lifetime of NO2 of ∼0.5–3 h to be derived. As the loss of NO2 was not compensated for by the formation of gas- or particle-phase reactive nitrogen species, it was presumably either driven by deposition to soil and foliar surfaces or any products formed were themselves short-lived with respect to deposition. By comparison, the daytime lifetime of NO2 with respect to loss by reaction with OH is about 1 d. Our results indicate that the nighttime deposition of NO2 is a major sink of boundary layer NOx in this temperate forest environment.

We present direct measurements of biogenic volatile organic compound (BVOC)-induced nitrate radical (NO3) reactivity (kVOC) through the diel cycle in the suburban, temperate forest of Rambouillet near Paris (France). The data were obtained in a 6-week summer period in 2022 as part of the Atmospheric ChemistRy Of the Suburban foreSt (ACROSS) campaign. kVOC was measured in a small (700 m2) clearing mainly at a height of 5.5 m above ground level but also at 40 m (for 5 d and nights). At nighttime, mean values (and 25th–75th percentile ranges) of knightVOC(5.5m) = (0.24-0.06+0.32) s−1 and knightVOC(40m) = (0.016-0.007+0.018) s−1 indicate a significant vertical gradient and low NO3 reactivity above the canopy, whereas knightVOC(5.5 m) showed peak values of up to 2 s−1 close to the ground. The strong vertical gradient in NO3 reactivity could be confirmed by measurements between 0 and 24 m on one particular night characterized by a strong temperature inversion and is a result of the decoupling of air masses aloft from the ground- and canopy-level sources of BVOCs (and nitric oxide, NO). No strong vertical gradient was observed in the mean daytime NO3 reactivity, with kdayVOC(5.5m) = (0.12 ± 0.04) s−1 for the entire campaign and kdayVOC(40m) = (0.07 ± 0.02) s−1 during the 5 d period. Within the clearing, the fractional contribution of VOCs to the total NO3 loss rate coefficient (ktot, determined by photolysis, reaction with NO and VOCs) was 80 %–90 % during the night and ∼ 50 % during the day. In terms of chemical losses of α-pinene below canopy height in the clearing, we find that at nighttime hydroxyl radicals (OH) and ozone (O3) dominate, with NO3 contributing “only” 17 %, which decreases further to 8.5 % during the day. Based on measured OH, measured O3, and calculated NO3 concentrations, the chemical lifetime of BVOCs at noon is about 1 h and is likely to be longer than timescales of transport out of the canopy (typically of the order of minutes), thus significantly reducing the importance of daytime in-canopy processing. Clearly, in forested regions where sufficient nitric oxide and nitrogen dioxide (NOx) is available, the role of NO3 and OH as initiators of BVOC oxidation is not strictly limited to nighttime and daytime, respectively, as often implied in e.g. atmospheric chemistry textbooks.

Cellular senescence is a condition characterized by stable, irreversible cell cycle arrest linked to the aging process. The accumulation of senescent cells in the cardiac muscle can contribute to various cardiovascular diseases (CVD). Telomere shortening, epigenetic modifications, DNA damage, mitochondrial dysfunction, and oxidative stress are known contributors to the onset of cellular senescence in the heart. The link between mitochondrial processes and cellular senescence contributed to the age-related decline in cardiac function. These include changes in mitochondrial functions and behaviours that arise from various factors, including impaired dynamics, dysregulated biogenesis, mitophagy, mitochondrial DNA (mtDNA), reduced respiratory capacity, and mitochondrial structural changes. Thus, regulation of mitochondrial biology has a role in cellular senescence and cardiac function in aging hearts. Targeting senescent cells may provide a novel therapeutic approach for treating and preventing CVD associated with aging. CYP epoxygenases metabolize N-3 and N-6 polyunsaturated fatty acids (PUFA) into epoxylipids that are readily hydrolyzed to diol products by soluble epoxide hydrolase (sEH). Increasing epoxylipids levels or inhibition of sEH has demonstrated protective effects in the aging heart. Evidence suggests they may play a role in cellular senescence by regulating mitochondria, thus reducing adverse effects of aging in the heart. In this review, we discuss how mitochondria induce cellular senescence and how epoxylipids affect the senescence process in the aged heart.

Background Health and social care professionals must develop health literacy responsiveness to best identify and address health literacy challenges in individuals. Education in health literacy responsiveness has been recommended for inclusion in professional degree programs at university.Aim The HeLPER (Health Literacy Program to Enhance Responsiveness) initiative aims to enhance health literacy responsiveness in university students, ensuring they are well-prepared to meet the health literacy needs of the community.Methods The HeLPER initiative will be an education initiative developed by two Western Australian universities and co-designed with local community members, health and social care professions students, working health and social care professionals and academic staff. The co-design process will be directed using the Ophelia (Optimising Health Literacy and Access) process in four phases. Phase 1 will engage community representatives to identify health literacy strengths, needs and action ideas. Phase 2 will involve community representatives co-designing actionable statements from the action ideas, which will be reviewed by health literacy experts. Students, professionals and academic staff will discuss strategies to co-design lesson plans from the actionable statements. In phase 3, all HeLPER education material and assessment components will be developed by the research team, and pilot tested with a small cohort of students. Community representatives, students, professionals and academic staff will review the results of the pilot test and recommend modifications. Phase 4 will involve embedding HeLPER into existing health and social care curricula across two universities with regular quality improvement cycles to ensure material remains contemporary, relevant and meaningful.Discussion This will result in the first co-designed health literacy responsiveness education for university-level health and social care professions students. Short-, medium- and long-term outcomes will benefit emerging health and social care professionals, individuals, carers and the community to provide targeted health literacy support, leading to overall improved health outcomes.

Immune exhaustion is a hallmark of ovarian cancer. Using multiparametric flow cytometry, the study aimed to analyze protein expression of novel immunological targets on CD3+ T cells isolated from the peripheral blood (n = 20), malignant ascites (n = 16), and tumor tissue (n = 6) of patients with ovarian cancer (OVCA). The study revealed an increased proportion of effector memory CD8+ T cells in OVCA tissue and malignant ascites. An OVCA-characteristic PD-1high CD8+ T cell population was detected, which differed from PD-1lowCD8+ T cells by increased co-expression of TIGIT, CD39, and HLA-DR. In addition, these OVCA-characteristic CD8+ T cells showed reduced expression of the transcription factor TCF-1, which may also indicate reduced effector function and memory formation. On the contrary, the transcription factor TOX, which significantly regulates terminal T cell-exhaustion, was found more frequently in these cells. Further protein and gene analysis showed that CD39 and CD73 were also expressed on OVCA tumor cells isolated from solid tumors (n = 14) and malignant ascites (n = 9). In the latter compartment, CD39 and CD73 were also associated with the expression of the “don’t eat me” molecule CD24 on tumor cells. Additionally, ascites-derived CD24+EpCAM+ tumor cells showed a higher frequency of CD39+ or CD73+ cells. Furthermore, CD39 expression was associated with unfavorable clinical parameters. Expression of CD39 on T cells was upregulated through CD3/CD28 stimulation and its blockade by a newly developed nanobody construct resulted in increased proliferation (eFluor), activation (CD25 and CD134), and production of cytotoxic cytokines (IFN-γ, TNF-α, and granzyme-B) of CD8+ T cells.

Decarbonization of energy production is key in today’s societies and nuclear energy holds an essential place in this prospect. Besides heavy-duty electricity production, other industrial and communal needs could be served by integrating novel nuclear energy production systems, among which are low-power nuclear devices, like small modular reactors (SMRs). The ELSMOR (towards European Licensing of Small Modular Reactors) European project addresses this topic as an answer to the Horizon 2020 Euratom NFRP-2018-3 call. The consortium includes 15 partners from eight European countries, involving research institutes, major European nuclear companies and technical support organizations. The 3.5-year project, launched in September 2019, investigates selected safety features of light-water (LW) SMRs with focus on licensing aspects. Providing a comprehensive compliance framework that regulators can adopt and operate, the licensing process of such SMRs could be optimized, helping their deployment. In this prospect, as a result of ELSMOR’s work, this article gives an overview of the specific issues that LW-SMRs may bring about in the different domains of nuclear safety, in terms of: • Methodological standpoints: safety goals, safety requirements, safety principles (defence-in-depth implementation); • Main safety functions of reactivity control, decay heat removal and confinement management; • Severe accident management; • Other safety issues particular to SMRs: use of shared systems; performing of multi-unit probabilistic safety assessment (PSA); spent fuel management, transport and disposal management. In this article, adequate methodologies are developed to deal with these issues and to help assess the safety of LW-SMRs. This work gives a precious synthesis of the safety assessment issues of LW-SMRs and of the associated methodologies developed in the context of the ELSMOR European project.

Abstract Background Body contouring surgery after massive weight loss is associated with different risk factors. Wound healing disorders and seromas commonly occur postoperatively. Bariatric interventions lead to massive weight loss with excess skin and soft tissue. In this study, perioperatively collected laboratory markers of this special patient population were analyzed. Methods Fifty-nine patients were analyzed retrospectively regarding bariatric surgery, weight loss, body contouring surgery, laboratory markers, and complication rates. Results Body contouring surgery (n = 117) was performed in 59 patients. Weight loss was achieved after gastric bypass (40.1%), gastric banding (33.9%), or sleeve gastrectomy (26.0%), with an average of 69.2 kg. The most common body contouring procedure included abdominoplasty (n = 50), followed by thigh lift (n = 29), mammaplasty (n = 19), brachioplasty (n = 14), and upper body lift (n = 5). Analysis of laboratory markers revealed no exceptional and clinically relevant variations. Correlation analysis revealed associations between resection weight, amount of drain fluid, and particular laboratory markers. Conclusion Analysis of perioperative laboratory markers in this special patient population after massive weight loss did not indicate clinically relevant risk factors regardless of the type of bariatric or body contouring surgery. Body contouring surgeries after bariatric interventions prove to be safe and low risk concerning perioperative laboratory markers and postoperative hospitalization.

Abstract Although increased aerobic glycolysis is common in various cancers, pancreatic ductal adenocarcinoma (PDAC) cells can survive a state of glycolysis suppression. We aimed to identify potential therapeutic targets in glycolysis-suppressed PDAC cells. By screening anticancer metabolic compounds, we identified SP-2509, an inhibitor of lysine-specific histone demethylase 1A (LSD1), which dramatically decreased the growth of PDAC PANC-1 cells and showed an anti-tumoral effect in tumor-bearing mice. The growth of glycolysis-suppressed PANC-1 cells was also inhibited by another LSD1 inhibitor, OG-L002. Similarly, the other two PDAC cells (PK-1 and KLM-1) with suppressed glycolysis exhibited anticancer effects against SP-2509. However, the anticancer effects on PDAC cells were unrelated to LSD1. To investigate how PDAC cells survive in a glycolysis-suppressed condition, we conducted proteomic analyses. These results combined with our previous findings suggested that glucose-starvation causes PDAC cells to enhance mitochondrial oxidative phosphorylation. In particular, mitochondrial fatty acid metabolism was identified as a key factor contributing to the survival of PDAC cells under glycolysis suppression. We further demonstrated that SP-2509 and OG-L002 disturbed fatty acid metabolism and induced lipid droplet accumulation through the impairment of lipophagy, but not bulk autophagy. These findings indicate a significant potential association of lipophagy and anticancer effects in glycolysis-suppressed PDAC cells, offering ideas for new therapeutic strategies for PDAC by dual inhibition of glycolysis and fatty acids metabolism.

Abstract Objectives This study aimed to explore the dental staff knowledge of simulated patient methodology and support for its use to investigate dental staffs' triaging ability. Material and Methods Staff at dental practices in Western Australia were invited to participate in a cross‐sectional online questionnaire, consisting of demographic questions, questions on triaging, and knowledge of simulated patient methodology. Descriptive and parametric tests were undertaken for quantitative data; qualitative responses were thematically analyzed. Results Of the 100 participants, most were female (71%), aged 25−39 years (57%), dentists (46%), and worked in private practices (60%). While 82% of participants triaged dental appointment enquiries, only 26% had heard of simulated patient studies. The majority (66%) of participants spent 1−5 min when triaging appointments and less than half (29%) asked about medical history, aggravating or alleviating factors. Although there was a general positive attitude toward use of simulated patient methodology to investigate practice, some concerns were identified. Conclusions The findings of our exploratory study suggests that there may be a potential for utilizing simulated patient studies to improve the care of patients by dental receptionists in general dental practices.

Hand disorders can reduce wrist range of motion (ROM). The SARS-CoV-2 pandemic highlighted challenges in routine follow-up exams, making telemedicine a viable solution. This study evaluates the feasibility and accuracy of patient self-measured wrist ROM using a self-designed goniometer template. The template was designed to measure flexion/extension and radial/ulnar abduction movements. A cohort of 50 adults (25 males/25 females) participated in this prospective study. The exclusion criteria included wrist immobilization and ages outside of 18–65 years. Participants self-assessed their wrist ROM with the goniometer template. Measurements were independently performed by a student and a specialist using standard goniometry, as well as a resident using the self-designed goniometer. The results were blinded for unbiased analysis. Mean differences in ROM varied across movement directions, with minimal differences for ulnar abduction and more substantial deviations for radial abduction, extension and flexion. The patient–specialist comparison showed deviations below 5 degrees for flexion and ulnar abduction in 50% of cases. Telemedicine, expanded by the COVID-19 pandemic, offers significant potential for hand rehabilitation. Current methods of ROM assessment lack cost-effectiveness and simplicity. Our method, demonstrating comparable accuracy for most movements, provides a cost-effective, reliable alternative for remote ROM assessment, enhancing telemedicine practices in hand rehabilitation.

Myocardial infarction (MI) accounts for a significant proportion of death and morbidity in aged individuals. The risk for MI in females increases as they enter the peri-menopausal period, generally occurring in middle-age. Cytochrome (CYP) 450 metabolizes N-3 and N-6 polyunsaturated fatty acids (PUFA) into numerous lipid mediators, oxylipids, which are further metabolised by soluble epoxide hydrolase (sEH), reducing their activity. The objective of this study was to characterize oxylipid metabolism in the left ventricle (LV) following ischemic injury in females. Human LV specimens were procured from female patients with ischemic cardiomyopathy (ICM) or non-failing controls (NFC). Female C57BL6 (WT) and sEH null mice averaging 13-16 months old underwent permanent occlusion of the left anterior descending coronary artery (LAD) to induce myocardial infarction. WT (wild type) mice received vehicle or sEH inhibitor, trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (tAUCB), in their drinking water ad libitum for 28 days. Cardiac function was assessed using echocardiography and electrocardiogram. Protein expression was determined using immunoblotting, mitochondrial activity by spectrophotometry, and cardiac fibre respiration was measured using a Clark-type electrode. A full metabolite profile was determined by LC-MS/MS. sEH was significantly elevated in ischemic LV specimens from patients, associated with fundamental changes in oxylipid metabolite formation and significant decreases in mitochondrial enzymatic function. In mice, pre-treatment with tAUCB or genetic deletion of sEH significantly improved survival, preserved cardiac function, and maintained mitochondrial quality following MI in female mice. These data indicate that sEH may be a relevant pharmacologic target for women with MI. Although future studies are needed to determine the mechanisms, in this pilot study we suggest targeting sEH may be an effective strategy for reducing ischemic injury and mortality in middle-aged females.

This article re-contextualises applied drama practice in the wake of COVID-19, with a particular focus on cognitive diversity. From an inclusive perspective, it asks how encouraging self-expression helps to diversify the still often one-dimensional perception of people with learning disabilities in media reports. It thereby continues an on-going argument around empowered representation within disability drama and culture. The article traces arts practice that engaged a group of women with learning disabilities in reflections about the lockdown 2020. The practice section of the article documents three concrete examples from a workshop series with the members of Powerhouse, a group of women with learning disabilities from the East of London.

Objectives Clearly understanding and describing professional behaviours of pharmacists allows the profession, researchers and policy-makers to observe and monitor the professionalism of pharmacists, and design interventions to improve it where needed. The primary objective of this review was to identify which behaviours are discussed to contribute to professionalism in registered pharmacists in peer-reviewed literature. The secondary objective was to review the identified behaviours using a behavioural specification framework to understand how they are expressed.Design A scoping literature review was conducted.Data sources An electronic database search of Scopus, Embase, PsycINFO, PsychArticles, Emcare and Medline limited to articles published in English from 1 January 2000 to 21 October 2022 was conducted.Eligibility criteria Eligible articles contributed behaviourally relevant content with reference to registered pharmacists’ professionalism.Data extraction and synthesis Extracted behaviourally relevant content was subject to researcher’s familiarisation, then deductive coding to one of two overarching definitions of technical or non-technical behaviour. Data were then inductively coded through assignment of a descriptive code to identify categories of professional behaviour within these two overarching types of behaviour.Results Seven articles were identified and included in the final analysis. From the extracted behaviourally relevant content, 18 categories of behaviours were identified. All articles identified behaviours in categories titled ‘establishes effective relationships’ and ‘complies with regulations codes and operating procedures’. Identified behaviours were often broadly described and merged with descriptions of influences on them and broader outcomes that they contribute to.Conclusions Behaviours described to contribute to pharmacists’ professionalism in the literature are broad and non-specific.

Background Identifying new therapeutic targets for preventing the myocardial ischemia–reperfusion injury would have profound implications in cardiovascular medicine. Myocardial ischemia–reperfusion injury remains a major clinical burden in patients with coronary artery disease. Methods and Results We studied several key mechanistic pathways known to mediate cardioprotection in myocardial ischemia–reperfusion in 2 independent genetic models with reduced cardiac phosphoinositide 3‐kinase‐α (PI3Kα) activity. P3Kα‐deficient genetic models (PI3KαDN and PI3Kα‐Mer‐Cre‐Mer) showed profound resistance to myocardial ischemia–reperfusion injury. In an ex vivo reperfusion protocol, PI3Kα‐deficient hearts had an 80% recovery of function compared with ≈10% recovery in the wild‐type. Using an in vivo reperfusion protocol, PI3Kα‐deficient hearts showed a 40% reduction in infarct size compared with wild‐type hearts. Lack of PI3Kα increased late Na+ current, generating an influx of Na+, facilitating the lowering of mitochondrial Ca2+, thereby maintaining mitochondrial membrane potential and oxidative phosphorylation. Consistent with these functional differences, mitochondrial structure in PI3Kα‐deficient hearts was preserved following ischemia–reperfusion injury. Computer modeling predicted that PIP3, the product of PI3Kα action, can interact with the murine and human NaV1.5 channels binding to the hydrophobic pocket below the selectivity filter and occluding the channel. Conclusions Loss of PI3Kα protects from global ischemic–reperfusion injury linked to improved mitochondrial structure and function associated with increased late Na+ current. Our results strongly support enhancement of mitochondrial function as a therapeutic strategy to minimize ischemia–reperfusion injury.

Objective: To investigate the optimal combination of somatosensory- and transcranial motor-evoked potential (SSEP/tcMEP) modalities and monitored extremities during clip reconstruction of aneurysms of the anterior cerebral artery (ACA) and its branches. Methods: A retrospective review of 104 cases of surgical clipping of ruptured and unruptured aneurysms was performed. SSEP/tcMEP changes and postoperative motor deficits (PMDs) were assessed from upper and lower extremities (UE/LE) to determine the diagnostic accuracy of each modality separately and in combination. Results: PMDs were reported in 9 of 104 patients; 7 LE and 8 UE (3.6% of 415 extremities). Evoked potential (EP) monitoring failed to predict a PMD in 8 extremities (1.9%). Seven of 8 false negatives had subarachnoid hemorrhage. Sensitivity and specificity in LE were 50% and 97% for tcMEP, 71% and 98% for SSEP, and 83% and 98% for dual-monitoring of both tcMEP/SSEP. Sensitivity and specificity in UE were 38% and 99% for tcMEP, and 50% and 97% for tcMEP/SSEP, respectively. Conclusions: Combined tcMEP/SSEP is more accurate than single-modality monitoring for LE but is relatively insensitive for UE PMDs. Significance: During ACA aneurysm clipping, multiple factors may confound the ability of EP monitoring to predict PMDs, especially brachiofacial hemiparesis caused by perforator insufficiency.

Abstract Background Guidelines and practice standards exist to communicate the conduct and behaviour expected of health care professionals and ensure consistent quality practice. It is important that they describe behaviours explicitly so they can be interpreted, enacted and measured with ease. The AACTT framework specifies behaviour in terms of the: Action to be performed, Actor who performs the action, Context where the action occurs, Target who the action is performed with/for and Time when the action is performed (AACTT). It provides the most up to date framework for specifying behaviours and is particularly relevant to complex behavioural problems that involve sequences of behaviours performed by different people. Behavioural specificity within pharmacy practice standards has not been explored. Aim To determine if behaviours described in the Professional Practice Standards for Australian Pharmacists specify Action, Actor, Context, Target and Time. Methods Two researchers independently reviewed the scope and structure of the practice standards and one extracted action statements (behaviours) verbatim. Through an iterative process, the researchers modified and developed the existing AACTT definitions to operationalise them for application to review of the action statements in the practice standards. The operational definitions, decision criteria and curated examples were combined in a codebook. The definitions were consistently applied through a directed content analysis approach to evaluate all extracted action statements by one researcher. For consistency 20% was independently checked for agreement by a second researcher. Results A novel codebook to apply AACTT criteria to evaluate practice standards was developed. Application of this codebook identified 768 independent behaviours. Of these, 300 (39%) described at least one discrete observable action, none specified an actor, 25 (3%) specified context, 131 (17%) specified target and 88 (11%) specified time. Conclusion(s) The behaviours detailed in practice standards for Australian pharmacists do not consistently specify behaviours in terms of Action, Actor, Context, Target and Time. Developers in the pharmacy profession, and beyond, should consider the behavioural specificity of their documents to improve interpretability, usability and adherence to the behaviours detailed. This also has implications for the development and evaluation of interventions to change such behaviours and improve quality of care.

Background Leukemia-associated macrophages (LAMs) represent an important cell population within the tumor microenvironment, but little is known about the phenotype, function, and plasticity of these cells. The present study provides an extensive characterization of macrophages in patients with acute myeloid leukemia (AML).Methods The phenotype and expression of coregulatory markers were assessed on bone marrow (BM)-derived LAM populations, using multiparametric flow cytometry. BM and blood aspirates were obtained from patients with newly diagnosed acute myeloid leukemia (pAML, n=59), patients in long-term remission (lrAML, n=8), patients with relapsed acute myeloid leukemia (rAML, n=7) and monocyte-derived macrophages of the blood from healthy donors (HD, n=17). LAM subpopulations were correlated with clinical parameters. Using a blocking anti-T-cell immunoreceptor with Ig and ITIM domains (TIGIT) antibody or mouse IgG2α isotype control, we investigated polarization, secretion of cytokines, and phagocytosis on LAMs and healthy monocyte-derived macrophages in vitro.Results In pAML and rAML, M1 LAMs were reduced and the predominant macrophage population consisted of immunosuppressive M2 LAMs defined by expression of CD163, CD204, CD206, and CD86. M2 LAMs in active AML highly expressed inhibitory receptors such as TIGIT, T-cell immunoglobulin and mucin-domain containing-3 protein (TIM-3), and lymphocyte-activation gene 3 (LAG-3). High expression of CD163 was associated with a poor overall survival (OS). In addition, increased frequencies of TIGIT+ M2 LAMs were associated with an intermediate or adverse risk according to the European Leukemia Network criteria and the FLT3 ITD mutation. In vitro blockade of TIGIT shifted the polarization of primary LAMs or peripheral blood-derived M2 macrophages toward the M1 phenotype and increased secretion of M1-associated cytokines and chemokines. Moreover, the blockade of TIGIT augmented the anti-CD47-mediated phagocytosis of AML cell lines and primary AML cells.Conclusion Our findings suggest that immunosuppressive TIGIT+ M2 LAMs can be redirected into an efficient effector population that may be of direct clinical relevance in the near future.

Abstract This study aimed at quantifying the annual transverse growth of the maxilla using skeletal landmarks in three different regions on cone-beam computed tomography (CBCT) scans. CBCT scans taken before and after orthodontic treatment of 100 child and adolescent patients (50 male, 50 female) without maxillary transverse deficiencies were used to determine the transverse linear distances between the greater palatine foramina (GPFd), the lateral walls of the nasal cavity (NCd), and the infraorbital foramina (IOFd). We found that all distances increased significantly with growth in both genders (p 0.05) correlations between patient age and the annual changes in GPFd, NCd, and IOFd. These results suggest that the positions of the greater palatine foramina, the lateral walls of the nasal cavity, and the infraorbital foramina change consistently with maxillary transverse growth. Clinicians can use the growth rates as population averages to more confidently estimate the amount of skeletal transverse deficiency or evaluate the long-term effects of maxillary expansion treatment.

Neurodegenerative disorders such as Parkinson's Disease (PD), PD dementia (PDD) and Dementia with Lewy bodies (DLB) are characterized by progressive accumulation of α-synuclein (α-syn) in neurons. Recent studies have proposed that neuron-to-neuron propagation of α-syn plays a role in the pathogenesis of these disorders. We have previously shown that antibodies against the C-terminus of α-syn reduce the intra-neuronal accumulation of α-syn and related deficits in transgenic models of synucleinopathy, probably by abrogating the axonal transport and accumulation of α-syn in in vivo models. Here, we assessed the effect of passive immunization against α-syn in a new mouse model of axonal transport and accumulation of α-syn. For these purpose, non-transgenic, α-syn knock-out and mThy1-α-syn tg (line 61) mice received unilateral intra-cerebral injections with a lentiviral (LV)-α-syn vector construct followed by systemic administration of the monoclonal antibody 1H7 (recognizes amino acids 91-99) or control IgG for 3 months. Cerebral α-syn accumulation and axonopathy was assessed by immunohistochemistry and effects on behavior were assessed by Morris water maze. Unilateral LV-α-syn injection resulted in axonal propagation of α-syn in the contra-lateral site with subsequent behavioral deficits and axonal degeneration. Passive immunization with 1H7 antibody reduced the axonal accumulation of α-syn in the contra-lateral side and ameliorated the behavioral deficits. Together this study supports the notion that immunotherapy might improve the deficits in models of synucleinopathy by reducing the axonal propagation and accumulation of α-syn. This represents a potential new mode of action through which α-syn immunization might work.

BackgroundFree vascularized medial femoral condyle (MFC) bone grafts can lead to increased vascularity of the proximal pole and restore scaphoid architecture in scaphoid nonunions. The intraoperative perfusion assessment of the bone graft is challenging because the conventional clinical examination is difficult. Indocyanine green (ICG) angiography has previously been shown to provide a real-time intraoperative evaluation of soft tissue perfusion in reconstructive surgery. The present study investigated the utility of ICG angiography in patients treated with a free medial femoral condyle graft for scaphoid nonunions.MethodsWe performed a retrospective analysis of patients with scaphoid nonunions, in which ICG angiography was used intraoperatively for perfusion assessment. The medical records, radiographs, intraoperative imaging, and operative reports of all patients were reviewed. Intraoperative ICG dye was administered intravenously, and laser angiography was performed to assess bone perfusion. The scaphoid union was examined using postoperative CT scans.ResultsTwo patients had documented osteonecrosis of the proximal pole at the time of surgery. Four patients received a nonvascularized prior bone graft procedure, and a prior spongiosa graft procedure was performed in one patient. The mean time from injury to the MFC bone graft surgery was 52.7 months, and the mean time from prior failed surgery was 10.4 months. Perfusion of the vascular pedicle of the MFC and the periosteum could be detected in all patients. In two patients, even perfusion of the cancellous bone could be demonstrated by ICG angiography. Following transplantation of the bone graft, patency of the vascular anastomosis and perfusion of the periost were confirmed by ICG angiography in the assessed cases. No additional surgery regarding a salvage procedure for a scaphoid nonunion advanced collapse was necessary for the further course.ConclusionICG-angiography has shown to be a promising tool in the treatment of scaphoid nonunion with medial femoral condyle bone grafts. It enables intraoperative decision making by assessment of the microvascular blood supply of the periosteum and the vascular pedicle of the MFC bone graft. Further studies need to evaluate the impact on union rates in a long-term follow-up.

Accelerated neurocognitive decline after general anesthesia/surgery, also known as perioperative neurocognitive disorder (PND), is a widely recognized public health problem that may affect millions of patients each year. Advanced age, with its increasing prevalence of heightened stress, inflammation, and neurodegenerative alterations, is a consistent contributing factor to the development of PND. Although a strong homeostatic reserve in young adults makes them more resilient to PND, animal data suggest that young adults with pathophysiological conditions characterized by excessive stress and inflammation may be vulnerable to PND, and this altered phenotype may be passed to future offspring (intergenerational PND). The purpose of this narrative review of data in the literature and the authors’ own experimental findings in rodents is to draw attention to the possibility of intergenerational PND, a new phenomenon which, if confirmed in humans, may unravel a big new population that may be affected by parental PND. In particular, we discuss the roles of stress, inflammation, and epigenetic alterations in the development of PND. We also discuss experimental findings that demonstrate the effects of surgery, traumatic brain injury, and the general anesthetic sevoflurane that interact to induce persistent dysregulation of the stress response system, inflammation markers, and behavior in young adult male rats and in their future offspring who have neither trauma nor anesthetic exposure (i.e., an animal model of intergenerational PND).

Abstract Human activities in coastal areas are accelerating ecosystem changes at an unprecedented pace, resulting in habitat loss, hydrological modifications, and predatory species declines. Understanding how these changes potentially cascade across marine and freshwater ecosystems requires knowing how mobile euryhaline species link these seemingly disparate systems. As upper trophic level predators, bull sharks (Carcharhinus leucas) play a crucial role in marine and freshwater ecosystem health. Telemetry studies in Mobile Bay, Alabama, suggest that bull sharks extensively use the northern portions of the bay, an estuarine–freshwater interface known as the Mobile‐Tensaw Delta. To assess whether bull sharks use freshwater habitats in this region, environmental DNA surveys were conducted during the dry summer and wet winter seasons in 2018. In each season, 5 × 1 L water samples were collected at each of 21 sites: five sites in Mobile Bay, six sites in the Mobile‐Tensaw Delta, and ten sites throughout the Mobile‐Tombigbee and Tensaw‐Alabama Rivers. Water samples were vacuum‐filtered, DNA extractions were performed on the particulate, and DNA extracts were analyzed with Droplet Digital™ Polymerase Chain Reaction using species‐specific primers and an internal probe to amplify a 237‐base pair fragment of the mitochondrial NADH dehydrogenase subunit 2 gene in bull sharks. One water sample collected during the summer in the Alabama River met the criteria for a positive detection, thereby confirming the presence of bull shark DNA. While preliminary, this finding suggests that bull sharks use less‐urbanized, riverine habitats up to 120 km upriver during Alabama's dry summer season.

BackgroundHidradenitis suppurativa is manifested by painful abscesses and scarring of sweat glands. Axillary, inguinal and genital regions are mostly affected. Multiple options exist in the treatment of hidradenitis suppurativa. The aim of this retrospective, mono-center cohort study was to analyze the outcome of different treatment methods after radical excision of hidradenitis suppurativa.MethodsWe retrospectively evaluated the treatment strategy and recurrence rate of hidradenitis suppurativa. We included all eligible patients of legal age between February 2003 and October 2021, with the diagnosis of Hidradenitis suppurativa and the necessity for surgical treatment. All patients with surgical treatment and direct wound closure by suture were excluded. Bacterial load and flora were analyzed for primary and secondary reconstruction in combination with negative-pressure wound therapy. Patient data were analyzed for recurrence rate and remission time according to different reconstructive techniques.ResultsIn 44 affected anatomical sites (n = 23 patients) we treated 15 patients with negative-pressure wound therapy. Bacterial load and flora were lower in the last wound swab of patients with multi-surgical procedures (22 localizations) compared to the first wound swab independent of the use of negative-pressure wound therapy.Wound closure, independent of a direct and multi-stage procedure was achieved by local fasciocutaneous flaps (n = 12), secondary intention healing (n = 7), secondary intention healing with buried chip skin grafts (n = 10), or split-thickness skin grafts (n = 15). Radical excision combined with split-thickness skin grafts showed the lowest recurrence rate in the follow-up (16%; n = 4).ConclusionRadical excision of hidradenitis suppurativa as gold standard for surgical treatment combined with negative-pressure wound therapy as multi-stage procedures ultimately reduced bacterial load and flora in our study. The use of split-thickness skin grafts showed the lowest recurrence rate.

Background Myocardial iron deficiency (MID) in heart failure (HF) remains largely unexplored. We aim to establish defining criterion for MID, evaluate its pathophysiological role, and evaluate the applicability of monitoring it non‐invasively in human explanted hearts. Methods and Results Biventricular tissue iron levels were measured in both failing (n=138) and non‐failing control (NFC, n=46) explanted human hearts. Clinical phenotyping was complemented with comprehensive assessment of myocardial remodeling and mitochondrial functional profiles, including metabolic and oxidative stress. Myocardial iron status was further investigated by cardiac magnetic resonance imaging. Myocardial iron content in the left ventricle was lower in HF versus NFC (121.4 [88.1–150.3] versus 137.4 [109.2–165.9] μg/g dry weight), which was absent in the right ventricle. With a priori cutoff of 86.1 μg/g d.w. in left ventricle, we identified 23% of HF patients with MID (HF‐MID) associated with higher NYHA class and worsened left ventricle function. Respiratory chain and Krebs cycle enzymatic activities were suppressed and strongly correlated with depleted iron stores in HF‐MID hearts. Defenses against oxidative stress were severely impaired in association with worsened adverse remodeling in iron‐deficient hearts. Mechanistically, iron uptake pathways were impeded in HF‐MID including decreased translocation to the sarcolemma, while transmembrane fraction of ferroportin positively correlated with MID. Cardiac magnetic resonance with T2* effectively captured myocardial iron levels in failing hearts. Conclusions MID is highly prevalent in advanced human HF and exacerbates pathological remodeling in HF driven primarily by dysfunctional mitochondria and increased oxidative stress in the left ventricle. Cardiac magnetic resonance demonstrates clinical potential to non‐invasively monitor MID.

ObjectiveMetabolites derived from N−3 and N−6 polyunsaturated fatty acids (PUFAs) have both beneficial and detrimental effects on the heart. However, contribution of these lipid mediators to dilated cardiomyopathy (DCM)-associated mitochondrial dysfunction remains unknown. This study aimed to characterize DCM-specific alterations in the PUFA metabolome in conjunction with cardiac mitochondrial quality in human explanted heart tissues.MethodsLeft ventricular tissues obtained from non-failing control (NFC) or DCM explanted hearts, were assessed for N−3 and N−6 PUFA metabolite levels using LC-MS/MS. mRNA and protein expression of CYP2J2, CYP2C8 and epoxide hydrolase enzymes involved in N−3 and N−6 PUFA metabolism were quantified. Cardiac mitochondrial quality was assessed by transmission electron microscopy, measurement of respiratory chain complex activities and oxygen consumption (respiratory control ratio, RCR) during ADP-stimulated ATP production.ResultsFormation of cardioprotective CYP-derived lipid mediators, epoxy fatty acids (EpFAs), and their corresponding diols were enhanced in DCM hearts. These findings were corroborated by increased expression of CYP2J2 and CYP2C8 enzymes, as well as microsomal and soluble epoxide hydrolase enzymes, suggesting enhanced metabolic flux and EpFA substrate turnover. DCM hearts demonstrated marked damage to mitochondrial ultrastructure and attenuated mitochondrial function. Incubation of fresh DCM cardiac fibers with the protective EpFA, 19,20-EDP, significantly improved mitochondrial function.ConclusionsThe current study demonstrates that increased expressions of CYP-epoxygenase enzymes and epoxide hydrolases in the DCM heart correspond with enhanced PUFA-derived EpFA turnover. This is accompanied by severe mitochondrial functional impairment which can be rescued by the administration of exogenous EpFAs.

AimsMyocardial ischemia can result in marked mitochondrial damage leading to cardiac dysfunction, as such identifying novel mechanisms to limit mitochondrial injury is important. This study investigated the hypothesis that inhibiting soluble epoxide hydrolase (sEH), responsible for converting epoxyeicosatrienoic acids to dihydroxyeicosatrienoic acids protects mitochondrial from injury caused by myocardial infarction.MethodssEH null and WT littermate mice were subjected to surgical occlusion of the left anterior descending (LAD) artery or sham operation. A parallel group of WT mice received an sEH inhibitor, trans-4-[4-(3-adamantan-1-y1-ureido)-cyclohexyloxy]-benzoic acid (tAUCB; 10 mg/L) or vehicle in the drinking water 4 days prior and 7 days post-MI. Cardiac function was assessed by echocardiography prior- and 7-days post-surgery. Heart tissues were dissected into infarct, peri-, and non-infarct regions to assess ultrastructure by electron microscopy. Complexes I, II, IV, citrate synthase, PI3K activities, and mitochondrial respiration were assessed in non-infarct regions. Isolated working hearts were used to measure the rates of glucose and palmitate oxidation.ResultsEchocardiography revealed that tAUCB treatment or sEH deficiency significantly improved systolic and diastolic function post-MI compared to controls. Reduced infarct expansion and less adverse cardiac remodeling were observed in tAUCB-treated and sEH null groups. EM data demonstrated mitochondrial ultrastructure damage occurred in infarct and peri-infarct regions but not in non-infarct regions. Inhibition of sEH resulted in significant improvements in mitochondrial respiration, ATP content, mitochondrial enzymatic activities and restored insulin sensitivity and PI3K activity.ConclusionInhibition or genetic deletion of sEH protects against long-term ischemia by preserving cardiac function and maintaining mitochondrial efficiency.