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Owing to the coronavirus disease 2019 (COVID-19) pandemic, understanding how to hold future online academic conferences effectively is imperative. We assessed the impact of COVID-19 on academic conferences, including facilities and settings for attendance, participation status, cost burden, and preferences for future styles of holding conferences, through a web-based questionnaire survey of 2,739 Japanese medical professionals, from December 2020 to February 2021. Of the participants, 28% preferred web conferences, 60% preferred a mix of web and on-site conferences, and 12% preferred on-site conferences. Additionally, 27% of the presenters stopped presenting new findings at web conferences. The proportion of participants who audio-recorded or filmed the sessions, despite prohibition, was six times higher at web than face-to-face conferences. Since the COVID-19 outbreak, the percentage of participants attending general presentations decreased from 91 to 51%. While web conferencing offers advantages, these are offset by a decrease in presentations pertaining to novel findings and data.

To determine the intracellular behavior of p62, a marker of selective autophagy, in oral potentially malignant disorders (OPMDs). This retrospective study includes 70 patients who underwent biopsy or surgical resection and were definitively diagnosed with OPMDs. Immunohistochemical staining for p62, XPO1, p53, and ki67 was performed on all samples and positive cell occupancy was calculated. We statistically investigated the correlation between protein expression in OPMDs and the association between malignant transformation, clinicopathological characteristics, and occupancy. ki67 expression was negatively correlated with p62 expression in the nucleus (p < 0.01) and positively correlated with p62 expression in the cytoplasm (p < 0.01). For malignant transformation, the expression of p62 in the nucleus (p = 0.03) was significantly lower in malignant transformation cases, whereas the expression of p62 in the cytoplasm (p = 0.03) and the aggregation expression (p < 0.01) were significantly higher. Our results suggest that the function of p62 is altered by its subcellular localization. In addition, defects in selective autophagy occur in cases of malignant transformation, suggesting that p62 is a potential biomarker of the risk of malignant transformation of OPMDs.

Abstract In this study, our aim was to validate whether the automated measurement of salivary testosterone and cortisol concentrations and the testosterone-to-cortisol (T/C) ratio, considering their individual circadian rhythms can be used to assess the stress response of male athletes to different exercise intensities accurately and effectively. We measured the salivary testosterone and cortisol concentrations and their respective serum concentrations that were collected from 20 male long-distance runners via passive drooling in the morning and evening for two consecutive days involving different exercise intensities. An electrochemiluminescence immunoassay was performed to evaluate the salivary testosterone and cortisol concentrations. The results showed a positive correlation between the salivary testosterone and cortisol concentrations and their respective serum concentrations. The participants were divided into two groups: with and without interval training. The interval training group showed a significantly higher rate of change in the salivary cortisol concentration and a significantly lower rate of change in the T/C ratio in the evening interval training on day 1 than lower-intensity running on day 2. Our results indicated that the salivary cortisol concentrations and the T/C ratio could distinguish between exercises at different intensities, which may be beneficial for detecting differences in stress responses among athletes.

Mechanical thrombectomy (MT) is a highly effective treatment for acute ischemic stroke, and hemorrhagic complications caused by vessel injury are rare. However, there is no evidence regarding the efficacy of MT for multiple large vessel occlusion or its procedural strategy. Herein, we report a case of MT with a stent retriever for multiple large vessel occlusion in the internal carotid artery and middle cerebral artery M1 distal, which resulted in vessel perforation in a single pass. A 79-year-old woman underwent MT for internal carotid artery occlusion, and multiple large vessel occlusion was observed on digital subtraction angiography. A longer and larger stent retriever was selected for thrombus retrieval in a single pass. Immediately after retrieval, digital subtraction angiography revealed internal carotid artery recanalization. Then, extravasation was observed from the M1 distal occlusion. Treatment was interrupted after hemostasis was confirmed. Nevertheless, rebleeding occurred after 4 hours. Emergency trapping was performed, and vessel perforation of >1 mm was observed. When retrieving a thrombus in a single pass with a stent retriever for multiple large vessel occlusion, vessel perforation may occur if the device is selected according to the diameter of the proximal occluded vessel. Based on the type of device, even a single pass may result in vessel perforation. Although aggressive MT intervention should be performed for multiple large vessel occlusion, a device that is appropriate for the pathological condition must be selected.

Abstract Background High-sensitivity Troponin I (hs-cTnI) has largely replaced conventional troponin assays in an effort to improve detection of myocardial infarction. However, the mean displacement of hs-cTnI following coronary artery bypass graft (CABG) and the optimal threshold to detect perioperative myocardial infarction (MI) is unclear. Our objective is to describe mean hs-cTnI values at 6–12 h post-CABG and to determine the highest specificity while maintaining 100% sensitivity hs-cTnI cut-off values for diagnosis of perioperative or type-5 MI. Methods Between 2016 and 2018, 374 patients underwent non-emergent, isolated CABG. Pre-operative and 6 h post-operative hs-cTnI values were recorded as well as ECG, echocardiographic and angiographic data. Results Of 374 patients, 151 (40.3%) had normal and 224 (59.7%) had elevated preoperative hs-cTnI. Patients with normal preoperative hs-cTnI had a mean 6 h hs-cTnI of 9193 ng/l or 270X the upper normal value. Eleven patients (7.3%) presented with post-operative MI with a mean 6 h hs-cTnI of 50,218 ng/l or 1477X the upper normal value. Patients with elevated preoperative hs-cTnI had a mean 6 h hs-cTnI of 9449 ng/l or 292X the upper normal value. Eleven patients (4.9%) who presented with post-operative MI had a mean 6 h hs-cTnI of 26,823 ng/l or 789X the upper normal value. Conclusions We suggest hs-cTnI threshold of 80-fold in patients with normal pre-operative hs-cTnI and 2.7-fold in patients with elevated pre-operative hs-cTnI. These results have important implications for perioperative care and for surgical trial reporting.

Abstract Background Macrophages infiltrating the tumor microenvironment are defined as tumor‐associated macrophages (TAMs). TAMs can be polarized into different phenotypes, that is, proinflammatory M1 macrophages or anti‐inflammatory M2 macrophages. Particularly, M2 macrophages promote angiogenesis, wound healing, and tumor growth. This study aimed to evaluate whether M2 TAMs can serve as a useful marker to predict prognosis and benefit from adjuvant chemotherapy in patients with surgically resected lung squamous cell carcinomas (SCCs). Methods We examined 104 patients with SCC. Tissue microarrays were constructed, and the density of TAMs was analyzed by immunohistochemistry for expression of CD68 and CD163. The relationship between CD68 and CD163 expression and the CD163/CD68 expression rate and clinicopathological characteristics including patient outcomes were investigated. In addition, propensity score matching (PSM) analysis was conducted to test the hypothesis that these cells significantly influenced chemotherapy responses. Results Univariate analysis revealed that pathological stage, CD163 expression, and the CD163/CD68 expression ratio were significant prognostic factors. Multivariate analysis showed that these factors were all independent prognostic factors. Thirty‐four pairs were determined by using PSM analysis. Patients with a low CD163/CD68 expression ratio benefited more from adjuvant chemotherapy than those with a high ratio. Conclusion We suggest that M2 TAMs may be a useful marker to predict prognosis and differential benefit from adjuvant chemotherapy in patients with surgically resected lung SCCs.

Abstract We performed comprehensive analyses of somatic copy number alterations (SCNAs) and gene expression profiles of gastric intramucosal neoplasia (IMN) using array‐based methods in 97 intestinal‐type IMNs, including 39 low‐grade dysplasias (LGDs), 37 high‐grade dysplasias (HGDs), and 26 intramucosal carcinomas (IMCs) with stromal invasion of the lamina propria to identify the molecular mechanism of IMN. In addition, we examined gene mutations using gene panel analyses. We used cluster analyses for exclusion of arbitrariness to identify SCNA patterns and expression profiles. IMNs were classified into two distinct subgroups (subgroups 1 and 2) based on SCNA patterns. Subgroup 1 showed a genomic stable pattern due to the low frequency of SCNAs, whereas subgroup 2 exhibited a chromosomal instability pattern due to the high frequencies of SCNAs and TP53 mutations. Interestingly, although the frequencies of LGD and HGD were significantly higher in subgroup 1 than in subgroup 2, IMC was commonly found in both types. Although the expression profiles of specific mRNAs could be used to categorise subgroups 1 and 2, no clinicopathological findings correlated with either subgroup. We examined signalling pathways specific to subgroups 1 and 2 to identify the association of each subgroup with signalling pathways based on gene ontology tree visualisation: subgroups 1 and 2 were associated with haem metabolism and chromosomal instability, respectively. These findings reveal a comprehensive genomic landscape that highlights the molecular complexity of IMNs and provide a road map to facilitate our understanding of gastric IMNs.

ABSTRACTOvercoming hepatitis B virus (HBV) is a challenging problem because HBV deceives the host immune system. We have found that DENN domain-containing 2A (DENND2A) was essential for HBV maintenance, although its role remains unclear. In this study, we elucidate its function by screening a novel DENND2A-binding peptide, DENP4-3S. DENP4-3S exhibits homology to SAM and SH3 domain-containing protein 1 (SASH1), a scaffold protein involved in Toll-like receptor signaling that promotes proinflammatory cytokine production. We confirmed that DENND2A interacts with SASH1 specifically. Overexpression and knockdown experiments showed that overexpression of DENND2A suppressed the transcriptional activity of NF-κB, and the knockdown of DENND2A promoted it and the production of cytokines and interferons. Here, we constructed a fusion protein (10M-DEN3SN) consisting of an anti-asialoglycoprotein receptor antibody and DENP4-3S to deliver the peptide to hepatocytes specifically. 10M-DEN3SN inhibited the interaction between DENND2A and SASH1, and rescued SASH1 trapped by DENND2A, leading to the upregulation of NF-κB and its downstream signaling. In addition, 10M-DEN3SN suppressed HBV proliferation in PXB chimeric mice. These results with the DENND2A-binding peptide delivered into hepatocytes suggested the involvement of DENND2A, SASH, and NF-κB signaling pathway in the HBV infection and onset of hepatitis. In conclusion, this study indicates that HBV utilizes DENND2A and SASH1 to evade the immune system.IMPORTANCEHepatitis B virus (HBV) is a serious liver infection with no established cure, causing an abnormal host immune response. Here, we identified a novel peptide that interacts with DENN domain-containing 2A (DENND2A), a host factor essential for HBV maintenance. The resulting peptide showed sequence homology, revealing an interaction between DENND2A and the immune system regulator SASH1. This study suggests that DENND2A contributes to HBV infection by suppressing the cellular immune system by inhibiting SASH1. The DENND2A-binding peptide, incorporated into our hepatocyte-specific peptide delivery system, inhibited the DENND2A-SASH1 interaction and promoted the production of cytokines and interferons in cultured hepatocytes. As a consequence, the peptide suppressed HBV proliferation in humanized mice. We report new insights into the role of DENND2A and SASH1 in HBV maintenance and highlight the importance of the immune system.

Abstract We herein report a case of interstitial lung changes in a patient with prolonged coronavirus disease 2019 (COVID‐19) with follicular lymphoma receiving rituximab and bendamustine who recovered after treatment with a combination therapy consisting of corticosteroids and immunosuppressive agents. There is currently no treatment strategy for prolonged pneumonitis following COVID‐19, which can be life‐threatening for immunocompromised patients. Thus, further investigation is warranted.

Age-related neurodegenerative disorders like Alzheimer's disease (AD) and Parkinson's disease (PD) are characterized by deposits of protein aggregates, or amyloid, in various regions of the brain. Historically, aggregation of a single protein was observed to be correlated with these different pathologies: tau in AD and α-synuclein (αS) in PD. However, there is increasing evidence that the pathologies of these two diseases overlap, and the individual proteins may even promote each other's aggregation. Both tau and αS are intrinsically disordered proteins (IDPs), lacking stable secondary and tertiary structure under physiological conditions. In this study we used a combination of biochemical and biophysical techniques to interrogate the interaction of tau with both soluble and fibrillar αS. Fluorescence correlation spectroscopy (FCS) was used to assess the interactions of specific domains of fluorescently labeled tau with full length and C-terminally truncated αS in both monomer and fibrillar forms. We found that full-length tau as well as individual tau domains interact with monomer αS weakly, but this interaction is much more pronounced with αS aggregates. αS aggregates also mildly slow the rate of tau aggregation, although not the final degree of aggregation. Our findings suggest that co-occurrence of tau and αS in disease are more likely to occur through monomer-fiber binding interactions, rather than monomer-monomer or co-aggregation.

Although dietary potassium restriction is an acceptable approach to hyperkalemia prevention, it may be insufficient for outpatients with chronic kidney disease (CKD). Most outpatients with CKD use community pharmacies owing to the free access scheme in Japan. The MieYaku-CKD project included a community pharmacist-led nutritional intervention for dietary potassium restriction, with the goal of determining its efficacy for patients' awareness of potassium restriction and serum potassium levels in outpatients with CKD. This was a five-community pharmacy multicenter prospective cohort study with an open-label, before-and-after comparison design. Eligible patients (n = 25) with an estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 received nutritional guidance from community pharmacists. The primary outcome was a change in serum potassium levels at 12 weeks post-intervention. The eligible patients' knowledge, awareness, and implementation of potassium restriction were evaluated using a questionnaire. The median value of serum potassium was significantly reduced from 4.7 mEq/L before to 4.4 mEq/L after the intervention [p < 0.001, 95% confidence interval (CI): 0.156-0.500], with no changes in eGFR (p = 0.563, 95% CI: -2.427-2.555) and blood urine nitrogen/serum creatinine ratio (p = 0.904, 95% CI: -1.793-1.214). The value of serum potassium had a tendency of attenuation from 5.3 to 4.6 mEq/L (p = 0.046, 95% CI: 0.272-1.114) in the eGFR < 30 mL/min/1.73 m2 group. A questionnaire revealed that after the intervention, knowledge and attitudes regarding dietary potassium restriction were much greater than before, suggesting that the decrease in serum potassium levels may be related to this nutritional guidance. Our findings indicate that implementing a dietary potassium restriction guidance program in community pharmacies is feasible and may result in lower serum potassium levels in outpatients with CKD.

Orofacial granulomatosis (OFG) is a rare disease entity characterized by nonnecrotizing granulomatous inflammation in the oral and maxillofacial regions, typically characterized by recurrent or persistent edema, primarily in the lips and occasionally in the gingiva. OFG is often associated with Crohn’s disease and sarcoidosis, and an accurate diagnosis requires systemic examination of patients. Pediatric patients possess unique oral conditions where dental plaque rapidly forms, especially during tooth replacement due to tooth crowding. Moreover, controlling oral hygiene can be challenging, rendering it difficult to distinguish plaque-induced gingivitis from nonplaque-induced gingivitis. We elucidate the reports of pediatric patients who developed OFG in the lips and/or gingiva alone, which was well controlled through corticosteroid treatment. The patients demonstrated recurrent lips and/or gingival swelling with redness, which failed to improve despite oral health care and treatment with antibiotics and/or corticosteroid ointment. Incision biopsy was performed, which demonstrated granulomatous inflammation. Further systemic examination ruled out Crohn’s disease and sarcoidosis and confirmed OFG diagnosis. Corticosteroid treatment orally or through gargling was administered to the patients, which provided improvement of symptoms after 1 month. As OFG may be associated with intractable diseases, monitoring the patient regularly is crucial. Pediatric patients with OFG require a collaborative approach with pediatricians and pediatric dentists to manage their oral and overall health.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had an unprecedented impact on health care and cardiac surgery. We report cardiac surgeons concerns, perceptions, and responses during the COVID-19 pandemic. METHODS: A detailed survey was sent to recruit participating adult cardiac surgery centers in North America. Data regarding cardiac surgeons perceptions and changes in practice were analyzed. RESULTS: Our study comprises 67 institutions with diverse geographic distribution across North America. Nurses were most likely to be redeployed (88%), followed by advanced care practitioners (69%), trainees (28%), and surgeons (25%). Examining surgeon concerns in regard to COVID-19, they were most worried with exposing their family to COVID-19 (81%), followed by contracting COVID-19 (68%), running out of personal protective equipment (PPE) (28%), and hospital resources (28%). In terms of PPE conservation strategies among users of N95 respirators, nearly half were recycling via decontamination with ultraviolet light (49%), followed by sterilization with heat (13%) and at home or with other modalities (13%). Reuse of N95 respirators for 1 day (22%), 1 week (21%) or 1 month (6%) was reported. There were differences in adoption of methods to conserve N95 respirators based on institutional pandemic phase and COVID-19 burden, with higher COVID-19 burden institutions more likely to resort to PPE conservation strategies. CONCLUSIONS: The present study demonstrates the impact of COVID-19 on North American cardiac surgeons. Our study should stimulate further discussions to identify optimal solutions to improve workforce preparedness for subsequent surges, as well as facilitate the navigation of future healthcare crises.

Abstract Inflammatory myofibroblastic tumor (IMT) is a rare disease that is considered an intermediate neoplasm, with the risk of recurrence and metastasis. Surgical treatment is the standard therapy for IMT, although there are only a few reports of surgery for lung metastasis of pulmonary IMT. We opine that surgical treatment might be effective not only for localized tumors, but also for cases of lung metastasis of IMT.

In this study, we evaluated the effects of pre-maturational culture (pre-IVM) on the developmental competence of bovine oocytes derived from an 8-day in vitro growth (IVG) culture system. IVG oocytes were subjected to 5 h pre-IVM before in vitro maturation, followed by in vitro fertilization (IVF). The proportion of oocytes that progressed to the germinal vesicle breakdown stage was similar between groups with and without pre-IVM. Although metaphase II oocytes and cleavage rates after IVF were similar regardless of pre-IVM culture, the blastocyst rate was significantly higher in the group with pre-IVM (22.5%) than without pre-IVM (11.0%, P < 0.05). In conclusion, pre-IVM culture improved the developmental competence of bovine oocytes derived from an 8-day IVG system.

Abstract Background Cerebral amyloid angiopathy is a common cause of subcortical hemorrhage in older adults. Although open hematoma removal may be performed for severe subcortical hemorrhage, its safety in patients with cerebral amyloid angiopathy has not been established, and postoperative rebleeding may occur. Therefore, this study aimed to investigate factors associated with postoperative rebleeding. Methods Out of 145 consecutive patients who had undergone craniotomy for surgical removal of subcortical intracerebral hemorrhage between April 2010 and August 2019 at a single institution in Japan, we examined 109 patients with subcortical hemorrhage who met the inclusion criteria. After excluding 30 patients whose tissue samples were unsuitable for the study, the final study cohort comprised 79 patients. Results Of the 79 patients, 50 (63%) were diagnosed with cerebral amyloid angiopathy (cerebral amyloid angiopathy group) and 29 (37%) were not diagnosed with noncerebral amyloid angiopathy (noncerebral amyloid angiopathy group). Postoperative rebleeding occurred in 12 patients (24%) in the cerebral amyloid angiopathy group and in 2 patients (7%) in the noncerebral amyloid angiopathy group. Preoperative prothrombin time–international normalized ratio and intraoperative bleeding volume were significantly associated with postoperative rebleeding in the cerebral amyloid angiopathy group (odds ratio = 42.4, 95% confidence interval = 1.14–1578; p = 0.042 and odds ratio = 1.005, 95% confidence interval = 1.001–1.008; p = 0.007, respectively). Conclusions Patients with cerebral amyloid angiopathy-related cerebral hemorrhage who are receiving antithrombotic therapy, particularly warfarin therapy, are at a high risk of postoperative rebleeding. Trial registration Registry and Registration Number of the study: 19–220, 2019/12/23, retrospectively registered.

Abstract In lung cancer, immune checkpoint inhibitors (ICIs) are often inadequate for tumor growth inhibition. Angiogenic inhibitors (AIs) are required to normalize tumor vasculature for improved immune cell infiltration. However, in clinical practice, ICIs and cytotoxic antineoplastic agents are simultaneously administered with an AI when tumor vessels are abnormal. Therefore, we examined the effects of pre‐administering an AI for lung cancer immunotherapy in a mouse lung cancer model. Using DC101, an anti‐vascular endothelial growth factor receptor 2 (VEGFR2) monoclonal antibody, a murine subcutaneous Lewis lung cancer (LLC) model was used to determine the timing of vascular normalization. Microvessel density (MVD), pericyte coverage, tissue hypoxia, and CD8‐positive cell infiltration were analyzed. The effects of an ICI and paclitaxel after DC101 pre‐administration were investigated. On Day 3, increased pericyte coverage and alleviated tumor hypoxia represented the highest vascular normalization. CD8+ T‐cell infiltration was also highest on Day 3. When combined with an ICI, DC101 pre‐administration significantly reduced PD‐L1 expression. When combined with an ICI and paclitaxel, only DC101 pre‐administration significantly inhibited tumor growth, but simultaneous administration did not. AI pre‐administration, and not simultaneous administration, may increase the therapeutic effects of ICIs due to improved immune cell infiltration.

Background: Whether statins reliably reduce the risk of postoperative atrial fibrillation (POAF) in patients undergoing cardiac surgery remains controversial. We sought to determine the impact of statin use on new-onset postdischarge POAF in the Post-Surgical Enhanced Monitoring for Cardiac Arrhythmias and Atrial Fibrillation (SEARCH-AF) CardioLink-1 randomized controlled trial. Methods: We randomized 336 patients with risk factors for stroke (CHA2DS2-VASc score ≥ 2) and no history of preoperative atrial fibrillation (AF) to 30-day continuous cardiac rhythm monitoring after discharge from cardiac surgery with a wearable, patched-based device or to usual care. The primary endpoint was the occurrence of cumulative AF and/or atrial flutter lasting for ≥ 6 minutes detected by continuous monitoring, or AF and/or atrial flutter documented by a 12-lead electrocardiogram within 30 days of randomization. Results: The 260 patients (77.4%) discharged on statins were more likely to be male (P = 0.018) and to have lower CHA2DS2-VASc scores (P = 0.011). Patients treated with statins at discharge had a 2-fold lower rate of POAF than those who were not treated with statins in the entire cohort (18.4% vs 8.1%, log-rank P = 0.0076). On multivariable Cox regression including the CHA2DS2-VASc score adjustment, statin use was associated with a lower risk of POAF (hazard ratio 0.43, 95% confidence interval: 0.25-0.98, P = 0.043). Use of statins at a higher intensity was associated with lower risk of POAF, suggestive of a dose–response effect (log-rank Ptrend = 0.0082). Conclusions: The use of statins was associated with a reduction in postdischarge POAF risk among patients undergoing cardiac surgery. The routine use of high-intensity statin to prevent subacute POAF after discharge deserves further study. Résumé: Contexte: L’efficacité des statines dans la réduction du risque de fibrillation auriculaire postopératoire (FAPO) chez les patients ayant subi une chirurgie cardiaque ne fait pas l’unanimité. Nous avons tenté de déterminer l’effet de l’utilisation des statines sur la survenue d’une FAPO inaugurale consécutive au congé de l’hôpital dans l’essai SEARCH-AF CardioLink-1, un essai contrôlé à répartition aléatoire sur le suivi étroit en postopératoire des arythmies cardiaques et de la fibrillation auriculaire. Méthodologie: Nous avons réparti aléatoirement 336 patients présentant des facteurs de risque d’AVC (score CHA2DS2-VASc ≥ 2) sans antécédents de fibrillation auriculaire (FA) préopératoire dans deux groupes : les patients du premier groupe étaient équipés d’un dispositif portable sous forme de timbre pour la surveillance continue du rythme cardiaque pendant 30 jours après la sortie de l’hôpital suivant une chirurgie cardiaque; les patients du second groupe étaient suivis de façon conventionnelle. Le critère d’évaluation principal était la survenue cumulative de FA et/ou de flutter auriculaire durant ≥ 6 minutes détecté par la surveillance continue, ou la FA et/ou le flutter auriculaire confirmé par un électrocardiogramme à 12 dérivations dans les 30 jours suivant la répartition aléatoire. Résultats: Les 260 patients (77,4 %) prenant des statines à leur congé de l’hôpital étaient plus susceptibles d’être des hommes (p = 0,018) et d’avoir un score CHA2DS2-VASc plus faible (p = 0,011). Les patients traités par des statines à leur congé de l’hôpital avaient deux fois moins de risques de présenter une FAPO que les patients ne recevant pas de statines dans l’ensemble de la cohorte (18,4 % contre 8,1 %, valeur de p calculée selon le test de Mantel-Haenszel = 0,0076). Dans une régression de Cox multivariable incluant l’ajustement du score CHA2DS2-VASc, l’utilisation des statines a été associée à un risque moindre de FAPO (rapport des risques instantanés : 0,43, intervalle de confiance à 95 % de 0,25 à 0,98; p = 0,043). L’utilisation de statines à plus fortes doses a été associée à un risque moindre de FAPO, ce qui laisse croire à un effet dose-réponse (valeur de p de tendance selon le test de Mantel-Haenszel = 0,0082). Conclusions: L’utilisation de statines est associée à une réduction du risque de FAPO après le congé de l’hôpital chez les patients ayant subi une chirurgie cardiaque. L’utilisation systématique de statines à fortes doses pour prévenir la FAPO subaiguë après le congé d’hôpital mérite une étude plus approfondie.

The development of phenotypic assays with appropriate analyses is an important step in the drug discovery process. Assays using induced pluripotent stem cell (iPSC)-derived human neurons are emerging as powerful tools for drug discovery in neurological disease. We have previously shown that longitudinal single cell tracking enabled the quantification of survival and death of neurons after overexpression of α-synuclein with a familial Parkinson's disease mutation (A53T). The reliance of this method on manual counting, however, rendered the process labor intensive, time consuming and error prone. To overcome these hurdles, we have developed automated detection algorithms for neurons using the BioStation CT live imaging system and CL-Quant software. In the current study, we use these algorithms to successfully measure the risk of neuronal death caused by overexpression of α-synuclein (A53T) with similar accuracy and improved consistency as compared to manual counting. This novel method also provides additional key readouts of neuronal fitness including total neurite length and the number of neurite nodes projecting from the cell body. Finally, the algorithm reveals the neuroprotective effects of brain-derived neurotrophic factor (BDNF) treatment in neurons overexpressing α-synuclein (A53T). These data show that an automated algorithm improves the consistency and considerably shortens the analysis time of assessing neuronal health, making this method advantageous for small molecule screening for inhibitors of synucleinopathy and other neurodegenerative diseases.