Biomechanical comparison of bone staple fixation methods with suture material for median sternotomy closure using 3D-printed bone models.

AIM: To compare the biomechanical properties of three different sternal closure techniques in a 3D-printed bone model of a sternum from a 30-kg dog. METHODS: Median sternotomy was performed on a total of 90 three-dimensional (3D) copies of a polycarbonate (PC) model of a sternum, generated from the CT images of the sternum of a 30-kg German Shepherd dog. Three different methods were used to repair the sternotomies: polydioxanone suture (group PDS, n = 30), stainless steel bone staples (group SS, n = 30), and nitinol bone staples (group NS, n = 30). Each repair method was tested by applying tensile force in one of three ways (longitudinally, laterally, or torsionally) resulting in a sample size of n = 10 for each repair method-loading combination. In all experiments, the loads at 1-mm and 2-mm gap formation, failure, and the displacement at the failure point were measured. RESULTS: In lateral distraction and longitudinal shear tests, NS and SS staple repairs required application of significantly greater force than PDS across all displacement criteria (1 and 2 mm). NS exhibited significantly greater failure load than PDS. In torsion tests, NS required significantly greater application of force compared to SS or PDS at all displacement criteria (1 and 2 mm) and exhibited a greater failure load than PDS. In terms of displacement at failure point, PDS suture showed more displacement than SS or NS across all experiments (laterally, longitudinally, torsionally). CONCLUSIONS: In this study, bone staples were mechanically superior to PDS suture in median sternotomy closure using 3D-printed bone model in terms of 1-mm, 2-mm displacement loads, and displacement at failure. NS had a higher failure load than PDS under lateral, longitudinal, and torsional distraction. CLINICAL RELEVANCE: These study results imply that bone staples can be considered as an alternative surgical method for median sternotomy closure in dogs.

Photobiomodulation of Gingival Cells Challenged with Viable Oral Microbes.

The oral cavity, a unique ecosystem harboring diverse microorganisms, maintains health through a balanced microflora. Disruption may lead to disease, emphasizing the protective role of gingival epithelial cells (GECs) in preventing harm from pathogenic oral microbes. Shifting GECs' response from proinflammatory to antimicrobial could be a novel strategy for periodontitis. Photobiomodulation therapy (PBMT), a nonpharmacologic host modulatory approach, is considered an alternative to drugs. While the host cell response induced by a single type of pathogen-associated molecular patterns (PAMPs) was widely studied, this model does not address the cellular response to intact microbes that exhibit multiple PAMPs that might modulate the response. Inspired by this, we developed an in vitro model that simulates direct interactions between host cells and intact pathogens and evaluated the effect of PBMT on the response of human gingival keratinocytes (HGKs) to challenge viable oral microbes at both the cellular and molecular levels. Our data demonstrated that LED pretreatment on microbially challenged HGKs with specific continuous wavelengths (red: 615 nm; near-infrared: 880 nm) induced the production of various antimicrobial peptides, enhanced cell viability and proliferation, promoted reactive oxygen species scavenging, and down-modulated proinflammatory activity. The data also suggest a potential explanation regarding the superior efficacy of near-infrared light treatment compared with red light in enhancing antimicrobial activity and reducing cellular inflammation of HGKs. Taken together, the findings suggest that PBMT enhances the overall barrier function of gingival epithelium while minimizing inflammation-mediated breakdown of the underlying structures.

The Lunar Environment Heliophysics X-ray Imager (LEXI) Mission.

The Lunar Environment heliospheric X-ray Imager (LEXI) is a wide field-of-view soft X-ray telescope developed to study solar wind-magnetosphere coupling. LEXI is part of the Blue Ghost 1 mission comprised of 10 payloads to be deployed on the lunar surface. LEXI monitors the dayside magnetopause position and shape as a function of time by observing soft X-rays (0.1-2 keV) emitted from solar wind charge-exchange between exospheric neutrals and high charge-state solar wind plasma in the dayside magnetosheath. Measurements of the shape and position of the magnetopause are used to test temporal models of meso- and macro-scale magnetic reconnection. To image the boundary, LEXI employs lobster-eye optics to focus X-rays to a microchannel plate detector with a 9.1×∘9.1∘ field of view.

Inhomogeneous Photosusceptibility of VO_{2} Films at the Nanoscale.

Pump-probe nano-optical experiments were used to study the light-induced insulator to metal transition (IMT) in thin films of vanadium dioxide (VO_{2}), a prototypical correlated electron system. We show that inhomogeneous optical contrast is prompted by spatially uniform photoexcitation, indicating an inhomogeneous photosusceptibility of VO_{2}. We locally characterize temperature and time dependent variations of the photoexcitation threshold necessary to induce the IMT on picosecond timescales with hundred nanometer spatial resolution. We separately measure the critical temperature T_{L}, where the IMT onsets and the local transient electronic nano-optical contrast at the nanoscale. Our data reveal variations in the photosusceptibility of VO_{2} within nanoscopic regions characterized by the same critical temperature T_{L} where metallic domains can first nucleate.

Internal Rotation Limitation is Prevalent Following Modern Reverse Shoulder Arthroplasty and Negatively Affects Patients' Subjective Rating of the Procedure.

BACKGROUND: While forward elevation, abduction, and external rotation are often successfully restored, internal rotation (IR) is frequently not satisfactorily recovered following reverse shoulder arthroplasty (RSA), affecting patients' ability to perform certain daily activities. This study examined the prevalence of limited IR in patients receiving modern RSA and its impact on clinical outcomes and patient satisfaction with their RSA. METHODS: A cross-sectional study was conducted on patients who had undergone primary RSA using a modern RSA prosthesis with a minimum one-year follow-up. Patients returned for a research visit where they were examined for range of motion and surveyed for patient-reported outcome measures (PROMs) and subjective rating of the success level of their RSA. Postoperative range of motion data were compared with the preoperative data. The relationship of postoperative IR with PROMs and patients' subjective rating of RSA was analyzed. Logistic regression was performed to identify factors affecting patients' subjective rating of RSA. RESULTS: A total of 78 patients met the criteria and completed the study. A significant portion (59%) reported subjective IR limitations, and 41% showed objective IR limitations. Comparison of preoperative and postoperative IR showed that 24% had worsened IR, while 33% improved. Limited IR was associated with lower patients' subjective rating of RSA and negatively impacted PROMs, especially when the dominant side was operated on. Regression analysis showed that limited IR was the only independent determining factor that was significantly associated with lower subjective rating of RSA. DISCUSSION: Despite advancements in RSA design, limited IR remains a prevalent issue, significantly affecting patients' satisfaction and clinical outcomes. This study underscores the need for setting appropriate expectations regarding IR through patient education and focused efforts to improve IR limitations in RSA patients, particularly on the dominant side.

Assisted reproductive techniques and subsequent risk of asthma and allergic rhinitis in offspring: a nationwide birth cohort study in South Korea.

OBJECTIVE: The relationship between assisted reproductive techniques (ART) and the risk of asthma and allergic rhinitis (AR) is controversial. Thus, we aimed to investigate the relationship between ART and the risk of asthma and AR in a nationwide, large-scale birth cohort. PATIENTS AND METHODS: This study utilized the National Health Insurance Service data in South Korea to conduct a nationwide, large-scale, population-based birth cohort. We included all infants born between 2017 and 2018. AR, asthma, food allergies, and atopic dermatitis were defined using the International Classification of Diseases tenth edition codes. Asthma was classified as allergic or non-allergic based on accompanying allergic diseases (AR, food allergy, or atopic dermatitis). Using 1:10 propensity score matching, we compared infants conceived through ART with those conceived naturally (non-ART). After matching, logistic regression was used to compare the hazard ratio for asthma and AR between the two groups. RESULTS: We included 543,178 infants [male infants, 280,194 (51.38%)]. After matching, 8,925 and 74,229 infants were selected for the ART and non-ART groups, respectively. The ART group showed a decreased risk of asthma in the offspring [adjusted hazard ratio (aHR), 0.45; 95% confidence interval (CI), 0.41-0.48]. Similarly, for AR, being conceived by ART was associated with a decreased risk of AR (aHR, 0.25; 95% CI, 0.12-0.37). ART offspring showed a decreased risk of asthma and AR in offspring compared to that observed in non-ART offspring. CONCLUSIONS: Our study offers important insights for clinicians, researchers, and parents regarding the health outcomes of ART-conceived infants and enhances our understanding of ART's impact on respiratory health.

Efficacy and safety of shunt surgery in patients with idiopathic normal-pressure hydrocephalus: can we predict shunt response by preoperative magnetic resonance imaging (MRI)?

AIM: The aim of this study was to identify preoperative magnetic resonance imaging (MRI) findings that can predict the shunt responsiveness in idiopathic normal-pressure hydrocephalus (iNPH) patients and to investigate postoperative outcome and complications. MATERIALS AND METHODS: A total of 192 patients with iNPH who underwent shunt at our hospital between 2000 and 2021 were included to investigate complications. Of these, after exclusion, 127 (1-month postoperative follow-up) and 77 (1-year postoperative follow-up) patients were evaluated. The preoperative MRI features (the presence of tightness of the high-convexity subarachnoid space, Sylvian fissure enlargement, Evans' index, and callosal angle) of the shunt-response and nonresponse groups were compared, and a systematic review was conducted to evaluate whether preoperative MRI findings could predict shunt response. RESULTS: Postoperative complications within one month after surgery were observed in 6.8% (13/192), and the most common complication was hemorrhage. Changes in corpus callosum were observed in 4.2% (8/192). The shunt-response rates were 83.5% (106/127) in the 1-month follow-up group and 70.1% (54/77) in 1-year follow-up group. In the logistic regression analysis, only Evans' index measuring >0.4 had a significant negative relationship with shunt response at 1-month follow-up; however, no significant relationship was observed at 1-year follow-up. According to our systematic review, it is still controversial whether preoperative MRI findings could predict shunt response. CONCLUSION: Evans' index measure of >0.4 had a significant relationship with the shunt response in the 1-month follow-up group. In systematic reviews, there is ongoing debate about whether preoperative MRI findings can accurately predict responses to shunt surgery. Postoperative corpus callosal change was observed in 4.2% of iNPH patients.

A Walk on the Wild Side: Genome Editing of Tuber-Bearing Solanum bulbocastanum.

Solanum bulbocastanum is a wild diploid tuber-bearing plant. We here demonstrate transgene-free genome editing of S. bulbocastanum protoplasts and regeneration of gene-edited plants. We use ribonucleoproteins, consisting of Cas9 and sgRNA, assembled in vitro, to target a gene belonging to the nitrate and peptide transporter family. Four different sgRNAs were designed and we observed efficiency in gene-editing in the protoplast pool between 8.5% and 12.4%. Twenty-one plants were re-generated from microcalli developed from individual protoplasts. In three of the plants we found that the target gene had been edited. Two of the edited plants had deletion mutations introduced into both alleles, whereas one only had a mutation in one of the alleles. Our work demonstrates that protocols for the transformation of Solanum tuberosum can be optimized to be applied to a wild Solanum species.

Cash outs during in-play sports betting: Who, why, and what it reveals.

Cashing out is a popular feature of modern 'in-play' sports betting that allows sports bettors to withdraw a bet before the sporting event on which the bet was placed is finalized. Previous studies have shown that use of the cash out feature is positively related to problem gambling symptomatology. However, little is known about demographic and psychological characteristics of in-play sports bettors who use the cash out feature, or their motivations for use. To fill this knowledge gap, we recruited 224 adults (18 + years) from Ontario who engaged in in-play sports betting in the past three months. Participants completed self-report measures of psychological and gambling-related variables. Participants also provided qualitative responses for their motivations for using the cash out feature. Approximately half (51.8 %) of the participants reported using the cash out feature. No statistically significant demographic differences were found between participants who used and did not use the cash out feature. Participants who used the feature (compared to those who did not) reported higher problematic alcohol and cannabis use, feelings of depression, anxiety, and stress, and were motivated to gamble to make money. The primary reasons for cashing out were to access money immediately, to cut losses, and because cashing out felt like a less risky option. The current findings shed light on underlying psychological vulnerabilities associated with individuals who use the cash out feature, which can inform initiatives to reduce the harms associated with this popular feature of sports betting.

EDITOR SPOTLIGHT: Interview with Cholinergic Mechanisms Special Issue Guest Editor Hermona Soreq.

Hermona Soreq holds a Hebrew University Slesinger Chair in Molecular Neuroscience and is among the founding members of the Edmond and Lily Safra Center of Brain Sciences (ELSC). Soreq's research (H-impact: 98) focuses on acetylcholine (ACh)-related pathways and combines RNA-sequencing technologies, transgenic engineering, and molecular biology tests with in-depth analysis approaches. Her work addresses microRNAs (miRs) and transfer RNA fragments (tRFs) which have rapidly acquired wide recognition as global controllers of regulatory processes in healthy and diseased brain and body, including anxiety, inflammation, and cognition. Altogether, Soreq's work leads to molecular neuroscience-driven prevention and/or intervention with diseases involving impaired ACh signaling, including schizophrenia, bipolar disorder, Alzheimer's disease, and stress. Hermona led this Special Issue based on the 17th Symposium on Cholinergic Mechanisms (ISCM2022). We interviewed her on the progress in the field, what she wants to achieve as Senior Editor for the Gene Regulation and Genetics category at the Journal of Neurochemistry, key moments, and future directions.

Impact of PTSD treatment on postconcussive symptoms in veterans: A comparison of sertraline, prolonged exposure, and their combination.

Many Veterans who served in Iraq and Afghanistan struggle with posttraumatic stress disorder (PTSD) and the effects of traumatic brain injuries (TBI). Some people with a history of TBI report a constellation of somatic, cognitive, and emotional complaints that are often referred to as postconcussive symptoms (PCS). Research suggests these symptoms may not be specific to TBI. This study examined the impact of PTSD treatment on PCS in combat Veterans seeking treatment for PTSD. As part of a larger randomized control trial, 198 Operation Iraqi Freedom, Operation Enduring Freedom, Operation New Dawn (OIF/OEF/OND) Veterans with PTSD received Prolonged Exposure Therapy, sertraline, or the combination. Potential deployment related TBI, PCS, PTSD and depression symptoms were assessed throughout treatment. Linear mixed models were used to predict PCS change over time across the full sample and treatment arms, and the association of change in PTSD and depression symptoms on PCS was also examined. Patterns of change for the full sample and the subsample of those who reported a head injury were examined. Results showed that PCS decreased with treatment. There were no significant differences across treatments. No significant differences were found in the pattern of symptom change based on TBI screening status. Shifts in PCS were predicted by change PTSD and depression. Results suggest that PCS reduced with PTSD treatment in this population and are related to shift in depression and PTSD severity, further supporting that reported PCS symptoms may be better understood as non-specific symptoms.

Comparison of diagnostic spectrum between inflammation of unknown origin and fever of unknown origin: A systematic review and meta-analysis.

BACKGROUND: Patients with inflammation of unknown origin (IUO) and fever of unknown origin (FUO) are commonly considered a single population. Differences in underlying causes between both groups may steer the diagnostic work-up. METHODS: PubMed, Embase, Web of Science, and ClinicalTrials.gov were searched from July 2009 through December 2023. Studies including both FUO and IUO patients with a sample size of ≥20 were considered. The primary outcome was the difference in the rate of patients affected by predefined diagnostic categories according to meeting FUO or IUO criteria. Data were pooled using random-effects models. RESULTS: A total of 8 studies met criteria for inclusion, with a total of 1452 patients (466 with IUO and 986 with FUO). The median rate of IUO patients among the included studies was 32 % (range 25-39 %). Patients with IUO had a lower likelihood of infection (OR 0.59 [95 % CI; 0.36-0.95]; I2 0 %). There were no significant differences in the rate of noninfectious inflammatory disorders, malignancies, miscellaneous disorders, or remaining undiagnosed. Comparison of diagnostic subgroups revealed that IUO patients were less likely to have systemic autoinflammatory disorders (OR 0.17 [95 % CI, 0.05-0.58]; I2 42 %) and more likely to have vasculitis (OR 2.04 [95 % CI, 1.23-3.38]; I2 21 %) and rheumatoid arthritis or spondylarthritis (OR 3.52 [95 % CI, 1.16-10.69]; I2 0 %). CONCLUSION: Based on our findings, there is little reason to assume that FUO and IUO patients would benefit from a different initial diagnostic approach.

Cluster of Nontoxigenic Corynebacterium diphtheriae Infective Endocarditis and Rising Background C. diphtheriae Cases-Seattle, Washington, 2020-2023.

BACKGROUND: Nontoxigenic Corynebacterium diphtheriae, often associated with wounds, can rarely cause infective endocarditis (IE). Five patients with C. diphtheriae IE were identified within 12 months at a Seattle-based hospital system. We reviewed prior C. diphtheriae-positive cultures to determine if detections had increased over time and evaluated epidemiologic trends. METHODS: We conducted a formal electronic health record search to identify all patients aged ≥18 years with C. diphtheriae detected in a clinical specimen (ie, wound, blood, sputum) between 1 September 2020 and 1 April 2023. We collected patient demographics, housing status, comorbidities, substance-use history, and level of medical care required at detection. We extracted laboratory data on susceptibilities of C. diphtheriae isolates and on other pathogens detected at the time of C. diphtheriae identification. RESULTS: Between 1 September 2020 and 1 April 2023, 44 patients (median age, 44 years) had a C. diphtheriae-positive clinical culture, with most detections occurring after March 2022. Patients were predominantly male (75%), White (66%), unstably housed (77%), and had a lifetime history of injecting drugs (75%). Most C. diphtheriae-positive cultures were polymicrobial, including wound cultures from 36 (82%) patients and blood cultures from 6 (14%) patients, not mutually exclusive. Thirty-four patients (77%), including all 5 patients with C. diphtheriae IE, required hospital admission for C. diphtheriae or a related condition. Of the 5 patients with IE, 3 died of IE and 1 from COVID-19. CONCLUSIONS: Findings suggest a high-morbidity outbreak disproportionately affecting patients who use substances and are unstably housed.

Dynamic changes in the mouse hepatic lipidome following warm ischemia reperfusion injury.

Liver failure secondary to metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most common cause for liver transplantation in many parts of the world. Moreover, the prevalence of MASLD not only increases the demand for liver transplantation, but also limits the supply of suitable donor organs because steatosis predisposes grafts to ischemia-reperfusion injury (IRI). There are currently no pharmacological interventions to limit hepatic IRI because the mechanisms by which steatosis leads to increased injury are unclear. To identify potential novel mediators of IRI, we used liquid chromatography and mass spectrometry to assess temporal changes in the hepatic lipidome in steatotic and non-steatotic livers after warm IRI in mice. Our untargeted analyses revealed distinct differences between the steatotic and non-steatotic response to IRI and highlighted dynamic changes in lipid composition with marked changes in glycerophospholipids. These findings enhance our knowledge of the lipidomic changes that occur following IRI and provide a foundation for future mechanistic studies. A better understanding of the mechanisms underlying such changes will lead to novel therapeutic strategies to combat IRI.

Comparison of clinical outcomes of patients with serial negative surveillance cultures according to a subsequent polymerase chain reaction test for carbapenemase-producing Enterobacterales.

BACKGROUND: Carbapenemase-producing Enterobacterales (CPE) are of serious concern worldwide due to high morbidity and mortality. AIM: To evaluate the impact of the result of a subsequent polymerase chain reaction (PCR) test for carbapenemase after serial negative surveillance cultures on positive culture conversion in patients with three consecutive negative surveillance cultures for CPE, and to identify risk factors for conversion. METHODS: A retrospective study of patients with positive CPE cultures on CHROMagar KPC medium was performed in a Korean tertiary hospital from October 2018 to December 2022. PCR for blaKPC, blaNDM, blaIMP, blaVIM, blaGES, and blaOXA-48 was performed after three consecutive negative rectal swab cultures. Clinical characteristics and outcomes of patients were compared according to whether follow-up PCR was positive (CNPP) or negative (CNPN). FINDINGS: Of 1075 patients with positive CPE cultures, 150 (14.0%) yielded three consecutive negative rectal swab cultures. Of these, 50 (33.3%) were CNPP, and 100 (66.7%) were CNPN. Risk factors associated with a positive PCR result on multivariate analysis were: age, central venous catheter, and Escherichia coli infection. CNPP patients were more likely to have positive culture conversion for CPE than CNPN patients (39/44 (88.6%) vs 21/50 (42.0%), P<0.001). In multivariate analysis, independent risk factors for culture conversion were: a positive PCR result after surveillance cultures, diabetes mellitus, central venous catheter, and Klebsiella pneumoniae. CONCLUSION: CNPP patients have higher rates of culture conversion than CNPN patients, and a follow-up PCR test after serial negative surveillance cultures is useful in deciding whether or not to discontinue contact precautions.

CRISPR-Cas9 and beyond: identifying target genes for developing disease-resistant plants.

Throughout the history of crop domestication, desirable traits have been selected in agricultural products. However, such selection often leads to crops and vegetables with weaker vitality and viability than their wild ancestors when exposed to adverse environmental conditions. Considering the increasing human population and climate change challenges, it is crucial to enhance crop quality and quantity. Accordingly, the identification and utilization of diverse genetic resources are imperative for developing disease-resistant plants that can withstand unexpected epidemics of plant diseases. In this review, we provide a brief overview of recent progress in genome-editing technologies, including zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) technologies. In particular, we classify disease-resistant mutants of Arabidopsis thaliana and several crop plants based on the roles or functions of the mutated genes in plant immunity and suggest potential target genes for molecular breeding of genome-edited disease-resistant plants. Genome-editing technologies are resilient tools for sustainable development and promising solutions for coping with climate change and population increases.

Impact of continuity of care on older adults diagnosed with mental and behavioural disorders at risk of death due to intentional self-harm: a retrospective Korean cohort study.

OBJECTIVES: The aim of this study was to evaluate the impact of continuity of care on older adults diagnosed with mental and behavioural disorders who are at risk of death due to intentional self-harm. STUDY DESIGN: This was a retrospective cohort study. METHODS: Data from the Korean National Health Insurance Service-Elderly Cohort Database (2002-2013) were used. A total of 53,980 patients who had visited the outpatient clinic three or more times within the year following the initial diagnosis of mental and behavioural disorders were included. A generalised estimating equation model was generated to examine the impact of continuity of care (CoC) on the risk of death due to intentional self-harm among older adults with mental illnesses. RESULTS: The risk of death due to intentional self-harm was significantly higher in those with poor CoC for mental and behavioural disorders than in those with good CoC. The risk ratio, adjusting for all covariates, was larger for the Usual Provider of Care index (adjusted risk ratio [aRR]: 1.63, 95% confidence interval [CI]: 1.25-2.12) than for the CoC index (aRR: 1.50, 95% CI: 1.18-1.90), indicating a stronger association with the concentration of contact with the most frequently visited provider. CONCLUSIONS: Poor CoC among Korean older adults diagnosed with mental and behavioural disorders was identified as a significant risk factor for death due to intentional self-harm. The results of this study highlight the need for interventions that can prevent suicidal behaviour in older adults, such as institutionalising the usual providers of mental health care for older adults.

Pulmonary artery wave intensity analysis in pulmonary hypertension associated with heart failure and reduced left ventricular ejection fraction.

Wave intensity analysis (WIA) uses simultaneous changes in pressure and flow velocity to determine wave energy, type, and timing of traveling waves in the circulation. In this study, we characterized wave propagation in the pulmonary artery in patients with pulmonary hypertension associated with left-sided heart disease (PHLHD) and the effects of dobutamine. During right heart catheterization, pressure and velocity data were acquired using a dual-tipped pressure and Doppler flow sensor wire (Combowire; Phillips Volcano), and processed offline using customized Matlab software (MathWorks). Patients with low cardiac output underwent dobutamine challenge. Twenty patients with PHLHD (all heart failure with reduced left ventricular ejection fraction) were studied. Right ventricular systole produced a forward compression wave (FCW), followed by a forward decompression wave (FDW) during diastole. Wave reflection manifesting as backward compression wave (BCW) following the FCW was observed in 14 patients. Compared to patients without BCW, patients with BCW had higher mean pulmonary artery pressure (28.7 ± 6.12 vs. 38.6 ± 6.5 mmHg, p = 0.005), and lower pulmonary arterial capacitance (PAC: 2.88 ± 1.75 vs. 1.73 ± 1.16, p = 0.002). Pulmonary vascular resistance was comparable. Mean pulmonary artery pressure of 34.5 mmHg (area under the curve [AUC]: 0.881) and PAC of 2.29 mL/mmHg (AUC: 0.833) predicted BCW. The magnitude of the FCW increased with dobutamine (n = 11) and correlated with pulmonary artery wedge pressure. Wave reflection in PHLHD is more likely at higher pulmonary artery pressures and lower PAC and the magnitude of reflected waves correlated with pulmonary artery wedge pressure. Dobutamine increased FCW but did not affect wave reflection.

CSF1R-mediated myeloid cell depletion shifts the ratio of motor cortical excitatory to inhibitory neurons in a multiple system atrophy model.

Motor cortical circuit functions depend on the coordinated fine-tuning of two functionally diverse neuronal populations: glutamatergic pyramidal neurons providing synaptic excitation and GABAergic interneurons adjusting the response of pyramidal neurons through synaptic inhibition. Microglia are brain resident macrophages which dynamically refine cortical circuits by monitoring perineuronal extracellular matrix and remodelling synapses. Previously, we showed that colony-stimulating factor 1 receptor (CSF1R)-mediated myeloid cell depletion extended the lifespan, but impaired motor functions of MBP29 mice, a mouse model for multiple system atrophy. In order to better understand the mechanisms underlying these motor deficits we characterized the microglial involvement in the cortical balance of GABAergic interneurons and glutamatergic pyramidal neurons in 4-months-old MBP29 mice following CSF1R inhibition for 12 weeks. Lack of myeloid cells resulted in a decreased number of COUP TF1 interacting protein 2-positive (CTIP2+) layer V pyramidal neurons, however in a proportional increase of calretinin-positive GABAergic interneurons in MBP29 mice. While myeloid cell depletion did not alter the expression of important presynaptic and postsynaptic proteins, the loss of cortical perineuronal net area was attenuated by CSF1R inhibition in MBP29 mice. These cortical changes may restrict synaptic plasticity and potentially modify parvalbumin-positive perisomatic input. Collectively, this study suggests, that the lack of myeloid cells shifts the neuronal balance toward an increased inhibitory connectivity in the motor cortex of MBP29 mice thereby potentially deteriorating motor functions.