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Abstract The authors present a short review of the personality, clinical and scientific contributions of a distinguished member of our Academy, the Artery Society and so many others, where he contributed landmark advances in many fields of arterial function and cardiovascular risk. The Editorial Board of the Artery Research Journal and the Executive Committee of the Artery Society present their due respects to Prof. Michel Safar.

Background Dendritic spines are tiny protrusions found along the dendrites of neurons, and their number is a measure of the density of synaptic connections. Altered density and morphology is observed in several pathologies, and spine formation as well as morphological changes correlate with learning and memory. The detection of spines in microscopy images and the analysis of their morphology is therefore a prerequisite for many studies. We have developed a new open-source, freely available, plugin for ImageJ/FIJI, called Spot Spine, that allows detection and morphological measurements of spines in three dimensional images. Method Local maxima are detected in spine heads, and the intensity distribution around the local maximum is computed to perform the segmentation of each spine head. Spine necks are then traced from the spine head to the dendrite. Several parameters can be set to optimize detection and segmentation, and manual correction gives further control over the result of the process. Results The plugin allows the analysis of images of dendrites obtained with various labeling and imaging methods. Quantitative measurements are retrieved including spine head volume and surface, and neck length. Conclusion The plugin and instructions for use are available at https://imagej.net/plugins/spot-spine.

Thrust manipulation is one of the most commonly used techniques for managing musculoskeletal pain in clinical practice. This involves the application of a high-velocity, low-amplitude force directed to the joints with the intent of achieving joint cavitation. This current case report describes a female in her mid-20s who presented with excessive bilateral and involuntary hand muscle contractions after bilateral thrust manipulation. Dystonia appeared both at rest and during voluntary movements but was aggravated by actions such as finger flexion or spreading and disappeared during sleep. A diagnosis of complex regional pain syndrome (CRPS) type I combined with dystonia was made. Prednisolone administered between 2 and 5 weeks after symptom onset significantly reduced CRPS symptoms, but intramuscular botulinum toxin injection 5 weeks after symptom onset was ineffective at controlling her symptoms. Seven weeks after symptom onset, the patient was administered 2 mg trihexyphenidyl oral twice a day, 2.5 mg diazepam oral twice a day and 5 mg baclofen oral three times a day for 1 month and this significantly reduced dystonia, but complete resolution was not achieved. Clinicians should be aware that dystonia is a rare complication of thrust manipulation.

Background Dendritic spines are tiny protrusions found along the dendrites of neurons, and their number is a measure of the density of synaptic connections. Altered density and morphology is observed in several pathologies, and spine formation as well as morphological changes correlate with learning and memory. The detection of spines in microscopy images and the analysis of their morphology is therefore a prerequisite for many studies. We have developed a new open-source, freely available, plugin for ImageJ/FIJI, called Spot Spine, that allows detection and morphological measurements of spines in three dimensional images. Method Local maxima are detected in spine heads, and the intensity distribution around the local maximum is computed to perform the segmentation of each spine head. Spine necks are then traced from the spine head to the dendrite. Several parameters can be set to optimize detection and segmentation, and manual correction gives further control over the result of the process. Results The plugin allows the analysis of images of dendrites obtained with various labeling and imaging methods. Quantitative measurements are retrieved including spine head volume and surface, and neck length. Conclusion The plugin and instructions for use are available at https://imagej.net/plugins/spot-spine.

Abstract Background Intra-breath oscillometry has been proposed as a sensitive means of detecting airway obstruction in young children. We aimed to assess the impact of early life wheezing and lower respiratory tract illness on lung function, using both standard and intra-breath oscillometry in 3 year old children. Methods History of doctor-diagnosed asthma, wheezing, bronchiolitis and bronchitis and hospitalisation for respiratory problems were assessed by questionnaires in 384 population-based children. Association of respiratory history with standard and intra-breath oscillometry parameters, including resistance at 7 Hz (R7), frequency-dependence of resistance (R7 − 19), reactance at 7 Hz (X7), area of the reactance curve (AX), end-inspiratory and end-expiratory R (ReI, ReE) and X (XeI, XeE), and volume-dependence of resistance (ΔR = ReE-ReI) was estimated by linear regression adjusted on confounders. Results Among the 320 children who accepted the oscillometry test, 281 (88%) performed 3 technically acceptable and reproducible standard oscillometry measurements and 251 children also performed one intra-breath oscillometry measurement. Asthma was associated with higher ReI, ReE, ΔR and R7 and wheezing was associated with higher ΔR. Bronchiolitis was associated with higher R7 and AX and lower XeI and bronchitis with higher ReI. No statistically significant association was observed for hospitalisation. Conclusions Our findings confirm the good success rate of oscillometry in 3-year-old children and indicate an association between a history of early-life wheezing and lower respiratory tract illness and lower lung function as assessed by both standard and intra-breath oscillometry. Our study supports the relevance of using intra-breath oscillometry parameters as sensitive outcome measures in preschool children in epidemiological cohorts.

Gyu-Sik Choi,1 Mathieu Boudier-Revéret,2 Min Cheol Chang3 1Cheokbareun Rehabilitation Clinic, Pohang-si, Gyeonsangbuk-do, South Korea; 2Department of Physical Medicine and Rehabilitation, Centre Hospitalier de l’Université de Montréal, Montréal, QC, Canada; 3Department of Rehabilitation Medicine, College of Medicine, Yeungnam University, Daegu, Republic of KoreaCorrespondence: Min Cheol Chang, Department of Physical Medicine and Rehabilitation, College of Medicine, Yeungnam University, 317-1, Daemyungdong, Namku, Daegu, 705-717, Republic of Korea, Tel +82-53-620-4862, Email wheel633@gmail.comPurpose: In this study, we evaluated the therapeutic outcomes of transforaminal epidural steroid injection (TFESI) in managing chronic radicular pain due to foraminal stenosis. Furthermore, we evaluated its effectiveness according to isthmic spondylolisthesis (IS) severity.Patients and Methods: We included 40 patients with radicular pain due to IS-derived foraminal stenosis in our study and treated them with TFESI. Two patients were lost during follow-up. Based on the lateral lumbar radiograph findings, we allocated the recruited patients with < 25% slippage by IS to Group 1 (n = 23) and those having 25– 50% slippage to Group 2 (n = 15). The degree of pain was measured using a numeric rating scale (NRS) at pre-treatment and 1 and 2 months after TFESI.Results: In 38 patients who completed the study, the NRS at pre-treatment was significantly reduced at the 1- and 2-month follow-ups. In the Group analysis, the NRS scores were significantly reduced after TFESI in both Groups 1 and 2, regardless of IS severity. However, the reduction in NRS scores 1 month after TFESI was significantly greater in Group 1 than in Group 2. Moreover, the rate of successful treatment outcomes was significantly higher (65.2%) in Group 1 than in Group 2 (26.7%).Conclusion: After TFESI, chronic radicular pain was significantly reduced regardless of IS severity, and its effect persisted for at least 2 months. However, its effect was superior when the vertebra slippage by IS was less than 25% compared to patients with 25%– 50%.Keywords: isthmic spondylolisthesis, foraminal spinal stenosis, lumbar spinal transforaminal epidural steroid injection, magnetic resonance imaging, corticosteroids

Background Dendritic spines are tiny protrusions found along the dendrites of neurons, and their number is a measure of the density of synaptic connections. Altered density and morphology is observed in several pathologies, and spine formation as well as morphological changes correlate with learning and memory. The detection of spines in microscopy images and the analysis of their morphology is therefore a prerequisite for many studies. We have developed a new open-source, freely available, plugin for ImageJ/FIJI, called Spot Spine, that allows detection and morphological measurements of spines in three dimensional images. Method Local maxima are detected in spine heads, and the intensity distribution around the local maximum is computed to perform the segmentation of each spine head. Spine necks are then traced from the spine head to the dendrite. Several parameters can be set to optimize detection and segmentation, and manual correction gives further control over the result of the process. Results The plugin allows the analysis of images of dendrites obtained with various labeling and imaging methods. Quantitative measurements are retrieved including spine head volume and surface, and neck length. Conclusion The plugin and instructions for use are available at https://imagej.net/plugins/spot-spine.

IntroductionExposure to respiratory viruses is a significant cause of morbidity and affects virus-specific antibody levels. Little is known about determinants associated with immune response to these viruses. We aimed to investigate the determinants of respiratory syncytial virus (RSV)- and rhinovirus (RV)- specific IgG responses in both children and adults.MethodsThe study is based on the EGEA cohort, composed of 530 samples of children in EGEA1 (1991-95) and 1241 samples of adults in EGEA2 (2003-07). Cumulative RV-specific IgG levels (species A, B and C) and IgG levels to RSV-G protein were measured by using micro-array technoloy. Multiple linear mixed models (random effect to account for familial dependence) were performed to assess associations between age, sex, body mass index (BMI), tobacco smoke exposure and season of blood sampling with RSV-and RV-specific IgG levels.ResultsIn children (11.1 ± 2.8 years old, 57% boys), higher RV-specific IgG levels were associated with older age (only for RV-B), female sex and lower BMI, while only older age was associated with higher RSV-specific IgG levels. In adults (43.5 ± 16.7 years old, 48% men), younger age, female sex, lower BMI, active smoking and all seasons except summer were associated with higher RV-specific IgG levels. Older age, active smoking and all seasons except summer were associated with higher RSV-specific IgG levels.ConclusionPersonal and seasonal determinants of RSV- and RV-specific IgG levels seem to vary according to the respiratory virus type and between children and adults, suggesting different patterns of responses along the life course.

Abstract Background Triple negative breast cancers (TNBC) account for approximately 15% of all breast cancers and are associated with a shorter median survival mainly due to locally advanced tumor and high risk of metastasis. The current neoadjuvant treatment for TNBC consists of a regimen of immune checkpoint blocker and chemotherapy (chemo-ICB). Despite the frequent use of this combination for TNBC treatment, moderate results are observed and its clinical benefit in TNBC remains difficult to predict. Patient-derived tumor organoids (PDTO) are 3D in vitro cellular structures obtained from patient’s tumor samples. More and more evidence suggest that these models could predict the response of the tumor from which they are derived. PDTO may thus be used as a tool to predict chemo-ICB efficacy in TNBC patients. Method The TRIPLEX study is a single-center observational study conducted to investigate the feasibility of generating PDTO from TNBC and to evaluate their ability to predict clinical response. PDTO will be obtained after the dissociation of biopsies and embedding into extra cellular matrix. PDTO will be cultured in a medium supplemented with growth factors and signal pathway inhibitors. Molecular and histological analyses will be performed on established PDTO lines to validate their phenotypic proximity with the original tumor. Response of PDTO to chemo-ICB will be assessed using co-cultures with autologous immune cells collected from patient blood samples. PDTO response will finally be compared with the response of the patient to evaluate the predictive potential of the model. Discussion This study will allow to assess the feasibility of using PDTO as predictive tools for the evaluation of the response of TNBC patients to treatments. In the event that PDTO could faithfully predict patient response in clinically relevant time frames, a prospective clinical trial could be designed to use PDTO to guide clinical decision. This study will also permit the establishment of a living biobank of TNBC PDTO usable for future innovative strategies evaluation. Trial registration The clinical trial (version 1.2) has been validated by local research ethic committee on December 30th 2021 and registered at ClinicalTrials.gov with the identifier NCT05404321 on June 3rd 2022, version 1.2.

BackgroundNon-invasive neurostimulation like muscle tendon vibration (VIB) and transcranial magnetic stimulation (TMS) can provide valuable insights on mechanisms underlying sensorimotor dysfunctions. However, their feasibility in the context of painful musculoskeletal disorders like shoulder impingement syndrome (SIS) remain uncertain.MethodsThe present work used a case series design including 15 participants with SIS, as well as a secondary group-based analysis comparing participants with SIS to 15 healthy counterparts. Proprioceptive processing was tested by VIB-induced kinesthetic illusions of shoulder abduction, and TMS tested corticospinal excitability of the upper trapezius. Detailed individual data were collected, including any technical challenges and feasibility issues encountered.ResultsVIB was in general well-tolerated and elicited a perceptible kinesthetic illusion in 13 participants with SIS and 14 controls. TMS presented with several challenges related to discomfort, fear-related behaviors, technical problems and high motor thresholds, especially in participants with SIS. It was only possible to collect all TMS measures in 5 participants with SIS (for both the painful and non/less-painful sides), in 7 controls on their dominant side and 10 controls on the non-dominant side. The only significant group-based analysis was a lower illusion speed/amplitude on the painful versus non-painful side in persons with SIS (p = 0.035).ConclusionOur study provides preliminary data on challenges encountered with TMS and VIB of trunk/proximal muscle in persons with SIS and healthy counterparts. It might help future studies to better address those challenges beforehand and improve the overall feasibility and impact of neurostimulation tools in musculoskeletal disorders.

BackgroundChronic pain is common, disruptive, and often treatment-resistant. Hence, researchers and clinicians seek alternative therapies for chronic pain. Transcranial alternating current stimulation (tACS) is an emerging neuromodulation technique that non-invasively modulates neural oscillations in the human brain. tACS induces pain relief by allowing the neural network to restore adequate synchronization. We reviewed studies on the effectiveness of tACS in controlling chronic pain.MethodsThe PubMed, SCOPUS, Embase, and Cochrane Library databases were systematically searched for relevant studies published until December 6, 2023. The key search phrase for identifying potentially relevant articles was [(Transcranial Alternating Current Stimulation OR tACS) AND pain]. The following inclusion criteria were applied for article selection: (1) studies involving patients with chronic pain; (2) tACS was applied for controlling pain; and (3) follow-up evaluations were performed to assess the degree of pain reduction after the application of tACS.ResultsWe identified 2,330 potentially relevant articles. After reading the titles and abstracts and assessing eligibility based on the full-text articles, we included four articles in our review. Among the included studies, tACS was used for fibromyalgia in one study, low back pain (LBP) in two studies, and migraine in one study. In the study on fibromyalgia, it did not show a better pain-reducing effect of tACS compared with sham stimulation. Two studies on LBP showed conflicting results. In migraine, tACS showed a positive pain-reducing effect 24–48 h after its application.ConclusionThere is insufficient research to draw a conclusive judgment on the effectiveness of tACS in controlling chronic pain. More studies across various chronic pain-related diseases are required for a definitive conclusion.

Summary: Background: While the adverse effects of short-term ambient ozone exposure on lung function are well-documented, the impact of long-term exposure remains poorly understood, especially in adults. Methods: We aimed to investigate the association between long-term ozone exposure and lung function decline. The 3014 participants were drawn from 17 centers across eight countries, all of which were from the European Community Respiratory Health Survey (ECRHS). Spirometry was conducted to measure pre-bronchodilation forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) at approximately 35, 44, and 55 years of age. We assigned annual mean values of daily maximum running 8-h average ozone concentrations to individual residential addresses. Adjustments were made for PM2.5, NO2, and greenness. To capture the ozone-related change in spirometric parameters, our linear mixed effects regression models included an interaction term between long-term ozone exposure and age. Findings: Mean ambient ozone concentrations were approximately 65 μg/m³. A one interquartile range increase of 7 μg/m³ in ozone was associated with a faster decline in FEV1 of −2.08 mL/year (95% confidence interval: −2.79, −1.36) and in FVC of −2.86 mL/year (−3.73, −1.99) mL/year over the study period. Associations were robust after adjusting for PM2.5, NO2, and greenness. The associations were more pronounced in residents of northern Europe and individuals who were older at baseline. No consistent associations were detected with the FEV1/FVC ratio. Interpretation: Long-term exposure to elevated ambient ozone concentrations was associated with a faster decline of spirometric lung function among middle-aged European adults over a 20-year period. Funding: German Research Foundation.

Abstract Background We report an enhancement of the dorsal roots on gadolinium-enhanced cervical magnetic resonance imaging (MRI) in a patient with acute autonomic and sensory neuropathy (AASN). Case presentation A 38-year-old woman visited our university hospital for dizziness and fainting while rising from sitting or lying down and a tingling sensation in the whole body, including her limbs, torso, and abdomen, which was sustained for 15 days. The patient had hyperalgesia in nearly her entire body and slight motor weakness in her bilateral upper and lower limbs. Autonomic dysfunction was confirmed using autonomic testing. Furthermore, the nerve conduction study showed an absence of sensory nerve action potentials in all evaluated peripheral nerves. Cervical MRI was performed 18 days after dysautonomia onset. In the axial T1-gadolinum-enhanced MRIs, enhancement in cervical ventral and dorsal nerve roots and the posterior column of the spinal cord were observed, and the axial T2-weighted MRI showed high signal intensity in the posterior column of the cervical spinal cord. Considering the clinical, electrophysiological and imaging findings, the patient was diagnosed with AASN. A total dose of 90 g (2 g/kg) of intravenous immunoglobulin was administered over 5 days. At the follow-up at 4 years after AASN symptom onset, the hyperalgesia and orthostatic hypotension symptoms improved. However, her systolic blood pressure intermittently decreased to

Background: The few studies that have examined associations between greenspace and lung function in adulthood have yielded conflicting results and none have examined whether the rate of lung function decline is affected. Objective: We explored the association between residential greenspace and change in lung function over 20 years in 5559 adults from 22 centers in 11 countries participating in the population-based, international European Community Respiratory Health Survey. Methods: Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were measured by spirometry when participants were approximately 35 (1990–1994), 44 (1999–2003), and 55 (2010–2014) years old. Greenness was assessed as the mean Normalized Difference Vegetation Index (NDVI) in 500 m, 300 m, and 100 m circular buffers around the residential addresses at the time of lung function measurement. Green spaces were defined as the presence of agricultural, natural, or urban green spaces in a circular 300 m buffer. Associations of these greenspace parameters with the rate of lung function change were assessed using adjusted linear mixed effects regression models with random intercepts for subjects nested within centers. Sensitivity analyses considered air pollution exposures. Results: A 0.2-increase (average interquartile range) in NDVI in the 500 m buffer was consistently associated with a faster decline in FVC (−1.25 mL/year [95% confidence interval: −2.18 to −0.33]). These associations were especially pronounced in females and those living in areas with low PM10 levels. We found no consistent associations with FEV1 and the FEV1/FVC ratio. Residing near forests or urban green spaces was associated with a faster decline in FEV1, while agricultural land and forests were related to a greater decline in FVC. Conclusions: More residential greenspace was not associated with better lung function in middle-aged European adults. Instead, we observed slight but consistent declines in lung function parameters. The potentially detrimental association requires verification in future studies.

Thienoguanosine (thG) is an isomorphic guanosine (G) surrogate that almost perfectly mimics G in nucleic acids. To exploit its full potential and lay the foundation for future applications, 20 DNA duplexes, where the bases facing and neighboring thG were systematically varied, were thoroughly studied using fluorescence spectroscopy, molecular dynamics simulations, and mixed quantum mechanical/molecular mechanics calculations, yielding a comprehensive understanding of its photophysics in DNA. In matched duplexes, thG's hypochromism was larger for flanking G/C residues but its fluorescence quantum yield (QY) and lifetime values were almost independent of the flanking bases. This was attributed to high duplex stability, which maintains a steady orientation and distance between nucleobases, so that a similar charge transfer (CT) mechanism governs the photophysics of thG independently of its flanking nucleobases. thG can therefore replace any G residue in matched duplexes, while always maintaining similar photophysical features. In contrast, the local destabilization induced by a mismatch or an abasic site restores a strong dependence of thG's QY and lifetime values on its environmental context, depending on the CT route efficiency and solvent exposure of thG. Due to this exquisite sensitivity, thG appears ideal for monitoring local structural changes and single nucleotide polymorphism. Moreover, thG's dominant fluorescence lifetime in DNA is unusually long (9-29 ns), facilitating its selective measurement in complex media using a lifetime-based or a time-gated detection scheme. Taken together, our data highlight thG as an outstanding emissive substitute for G with good QY, long fluorescence lifetimes, and exquisite sensitivity to local structural changes.