Revival of light signalling in the postmortem mouse and human retina.

Death is defined as the irreversible cessation of circulatory, respiratory or brain activity. Many peripheral human organs can be transplanted from deceased donors using protocols to optimize viability. However, tissues from the central nervous system rapidly lose viability after circulation ceases1,2, impeding their potential for transplantation. The time course and mechanisms causing neuronal death and the potential for revival remain poorly defined. Here, using the retina as a model of the central nervous system, we systemically examine the kinetics of death and neuronal revival. We demonstrate the swift decline of neuronal signalling and identify conditions for reviving synchronous in vivo-like trans-synaptic transmission in postmortem mouse and human retina. We measure light-evoked responses in human macular photoreceptors in eyes removed up to 5 h after death and identify modifiable factors that drive reversible and irreversible loss of light signalling after death. Finally, we quantify the rate-limiting deactivation reaction of phototransduction, a model G protein signalling cascade, in peripheral and macular human and macaque retina. Our approach will have broad applications and impact by enabling transformative studies in the human central nervous system, raising questions about the irreversibility of neuronal cell death, and providing new avenues for visual rehabilitation.

Zone-specific computer-aided diagnosis system aimed at characterizing ISUP ≥ 2 prostate cancers on multiparametric magnetic resonance images: evaluation in a cohort of patients on active surveillance.

PURPOSE: To assess a region-of-interest-based computer-assisted diagnosis system (CAD) in characterizing aggressive prostate cancer on magnetic resonance imaging (MRI) from patients under active surveillance (AS). METHODS: A prospective biopsy database was retrospectively searched for patients under AS who underwent MRI and subsequent biopsy at our institution. MRI lesions targeted at baseline biopsy were retrospectively delineated to calculate the CAD score that was compared to the Prostate Imaging-Reporting and Data System (PI-RADS) version 2 score assigned at baseline biopsy. RESULTS: 186 patients were selected. At baseline biopsy, 51 and 15 patients had International Society of Urological Pathology (ISUP) grade ≥ 2 and ≥ 3 cancer respectively. The CAD score had significantly higher specificity for ISUP ≥ 2 cancers (60% [95% confidence interval (CI): 51-68]) than the PI-RADS score (≥ 3 dichotomization: 24% [CI: 17-33], p = 0.0003; ≥ 4 dichotomization: 32% [CI: 24-40], p = 0.0003). It had significantly lower sensitivity than the PI-RADS ≥ 3 dichotomization (85% [CI: 74-92] versus 98% [CI: 91-100], p = 0.015) but not than the PI-RADS ≥ 4 dichotomization (94% [CI:85-98], p = 0.104). Combining CAD findings and PSA density could have avoided 47/184 (26%) baseline biopsies, while missing 3/51 (6%) ISUP 2 and no ISUP ≥ 3 cancers. Patients with baseline negative CAD findings and PSAd < 0.15 ng/mL2 who stayed on AS after baseline biopsy had a 9% (4/44) risk of being diagnosed with ISUP ≥ 2 cancer during a median follow-up of 41 months, as opposed to 24% (18/74) for the others. CONCLUSION: The CAD could help define AS patients with low risk of aggressive cancer at baseline assessment and during subsequent follow-up.

An unusual occurrence of opsoclonus and liver enzymes elevation in a patient with acute motor and sensory axonal neuropathy subtype of Guillain-Barré syndrome.

BACKGROUND: Acute motor and sensory axonal neuropathy (AMSAN) is a subtype of Guillain-Barré syndrome (GBS) differentiated by nerve conduction studies (NCS) and characterized by symmetric ascending paralysis often involving respiratory muscles. While opsoclonus, which is involuntary chaotic rapid eye movements, is not a common manifestation of GBS. Moreover, little published data are available on the relation between liver enzymes elevation and GBS. CASE PRESENTATION: A 42-year-old man presented to Al Mouwassat University Hospital with weakness in all limbs and dyspnea. Examination showed an elevated respiratory rate, hyporeflexia, and decreased strength of upper and lower limbs. Analysis of cerebrospinal fluid revealed an albuminocyto-dissociation suggesting the diagnosis of GBS and subsequent plasmapheresis. NCS confirmed a diagnosis of AMSAN. Elevation in liver enzymes was noticed prompting further exploration with no positive findings. Despite treatment efforts, the patient developed severe dyspnea, deterioration in cognitive abilities, and opsoclonus with a normal brain MRI. Unfortunately, he developed respiratory failure which lead to his death. CONCLUSION: In this case, we highlight the occurrence of opsoclonus which is a rarely-encountered manifestation of GBS, in addition to an unexplained elevated liver enzyme, the thing that could contribute to larger research to further comprehend the pathophysiology of GBS.

Diverging levels of COVID-19 governmental response satisfaction across middle eastern Arab countries: a multinational study.

BACKGROUND: Public acceptance of governmental measures are key to controlling the spread of infectious diseases. The COVID-19 pandemic has placed a significant burden on healthcare systems for high-income countries as well as low- and middle-income countries (LMICs). The ability of LMICs to respond to the challenge of the COVID-19 pandemic has been limited and may have affected the impact of governmental strategies to control the spread of COVID-19. This study aimed to evaluate and compare public opinion on the governmental COVID-19 response of high and LMICs in the Middle East and benchmark it to international countries. METHODS: An online, self-administered questionnaire was distributed among different Middle Eastern Arab countries. Participants' demographics and level of satisfaction with governmental responses to COVID-19 were analyzed and reported. Scores were benchmarked against 19 international values. RESULTS: A total of 7395 responses were included. Bahrain scored highest for satisfaction with the governmental response with 38.29 ± 2.93 on a scale of 40, followed by the Kingdom of Saudi Arabia (37.13 ± 3.27), United Arab Emirates (36.56 ± 3.44), Kuwait (35.74 ± 4.85), Jordan (23.08 ± 6.41), and Lebanon (15.39 ± 5.28). Participants' country of residence was a significant predictor of the satisfaction score (P < 0.001), and participants who suffered income reduction due to the pandemic, had a history of SARS-CoV-2 infection, and held higher educational degrees had significantly lower satisfaction scores (P < 0.001). When benchmarked with other international publics, countries from the Gulf Cooperation Council had the highest satisfaction level, Jordan had an average score, and Lebanon had one of the lowest satisfaction scores. CONCLUSION: The political crisis in Lebanon merged with the existing corruption were associated with the lowest public satisfaction score whereas the economical instability of Jordan placed the country just before the lowest position. On the other hand, the solid economy plus good planning and public trust in the government placed the other countries of the Gulf Cooperation Council on top of the scale. Further investigation is necessary to find out how the governments of other low-income countries may have handled the situation wisely and gained the trust of their publics. This may help convey a clearer picture to Arab governments that have suffered during the pandemic.

Fast diagnostic test for familial Mediterranean fever based on a kinase inhibitor.

BACKGROUND AND OBJECTIVE: Familial Mediterranean fever (FMF) is the most frequent hereditary autoinflammatory disease. Its diagnosis relies on a set of clinical criteria and a genetic confirmation on identification of biallelic pathogenic MEFV variants. MEFV encodes pyrin, an inflammasome sensor. Using a kinase inhibitor, UCN-01, we recently identified that dephosphorylation of FMF-associated pyrin mutants leads to inflammasome activation. The aim of this study was to assess whether quantifying UCN-01-mediated inflammasome activation could discriminate FMF patients from healthy donors (HD) and from patients with other inflammatory disorders (OID). METHODS: Real-time pyroptosis and IL-1ß secretion were monitored in response to UCN-01 in monocytes from FMF patients (n=67), HD (n=71) and OID patients (n=40). Sensitivity and specificity of the resulting diagnostic tests were determined by receiver operating characteristic curve analyses. RESULTS: Inflammasome monitoring in response to UCN-01 discriminates FMF patients from other individuals. Pyroptosis assessment leads to a fast FMF diagnosis while combining pyroptosis and IL-1ß dosage renders UCN-01-based assays highly sensitive and specific. UCN-01-triggered monocytes responses were influenced by MEFV gene dosage and MEFV mutations in a similar way as clinical phenotypes are. CONCLUSIONS: UCN-01-based inflammasome assays could be used to rapidly diagnose FMF, with high sensitivity and specificity.

Gestational trophoblastic neoplasia with brain metastasis at initial presentation: a retrospective study.

OBJECTIVE: To evaluate the survival and functional outcome of patients with brain metastasis due to gestational trophoblastic neoplasia (GTN). METHODS: A 17-year retrospective study based on case review of women with brain metastasis from GTN identified by the electronic databases held in the French Reference Centre. PRIMARY OUTCOME MEASURE: 5-year overall survival calculated with the Kaplan-Meier method. SECONDARY OUTCOME MEASURES: causes of death, prognostic factors and functional outcomes. RESULTS: 21 patients had GTN brain metastasis and were treated with multidrug chemotherapy without concomitant whole-brain radiation therapy. Three patients died early (< 4 weeks) of cerebral hemorrhage, 3 died ≥ 1 months after treatment initiation and 15 were alive at the date of last contact. The overall survival rate at 5 years was 69.8% (95% CI 44.3-85.3). After excluding early deaths, the survival rate at 5 years was 81.5% (95% CI 52.3-93.7). No predictive factor of survival was identified. Although 11 of the 12 (92%) surviving patients contacted still reported sequelae, nine of them (75%) had resumed a normal life. CONCLUSIONS: After excluding early deaths, this study implies a high survival rate in patients with brain metastasis from GTN. These results were achieved in the total absence of whole-brain radiotherapy and almost completely without the need for intrathecal methotrexate.

Specialty preference and intentions to study abroad of Syrian medical students during the crisis.

BACKGROUND: Little research addresses how medical students develop their choice of specialty training in crisis and resource-poor settings. The newly graduated medical students determine the future of the healthcare system. This study aims to elucidate the factors influencing Syrian medical students' specialty selection and students' intentions to study abroad. METHODS: A cross-sectional study carried out at the universities of Damascus, Al-Kalamoon and the Syrian Private University in Syria using self-administered questionnaire to investigate medical students' specialty preferences and plans for career future. The questionnaire included questions about students' demographic and educational characteristics, intention to train abroad, the chosen country for training. RESULTS: Randomly selected 450 students completed the questionnaire. The two most common specialties selected were general surgery (27.6%) and internal medicine (23.5%). The most influencing factors on their decision were 'flexibility of specialty' (74.8%) and 'Better work opportunities after specializing' (69.1%). Most participants stated that they are interested in specializing abroad outside Syria (78.7%). The two most common countries of choice were Germany (35.5%) and the United States of America (24.6%). Acquiring a visa to the foreign country was the most common obstacle of specializing abroad (n = 186, 53.6%). Male gender, having a previous clinical training abroad, and having friends or relatives living abroad were significant factors in predicting students' interest in specializing abroad. CONCLUSION: Internal medicine and surgery are the most reported specialties of choice in this study and most of the participants reported intentions to study abroad. Their specialty preferences are influenced by both familiar epidemiological and war-driven factors. These data can be useful to design further cohort study to understand the war-related affecting factors on students' plans for their career in the effort of improving the balance of healthcare system in Syria.

Peers versus professional training of basic life support in Syria: a randomized controlled trial.

BACKGROUND: Peer training has been identified as a useful tool for delivering undergraduate training in basic life support (BLS) which is fundamental as an initial response in cases of emergency. This study aimed to (1) Evaluate the efficacy of peer-led model in basic life support training among medical students in their first three years of study, compared to professional-led training and (2) To assess the efficacy of the course program and students' satisfaction of peer-led training. METHODS: A randomized controlled trial with blinded assessors was conducted on 72 medical students from the pre-clinical years (1st to 3rd years in Syria) at Syrian Private University. Students were randomly assigned to peer-led or to professional-led training group for one-day-course of basic life support skills. Sixty-four students who underwent checklist based assessment using objective structured clinical examination design (OSCE) (practical assessment of BLS skills) and answered BLS knowledge checkpoint-questionnaire were included in the analysis. RESULTS: There was no statistically significant difference between the two groups in delivering BLS skills to medical students in practical (P = 0.850) and BLS knowledge questionnaire outcomes (P = 0.900). Both groups showed statistically significant improvement from pre- to post-course assessment with significant statistical difference in both practical skills and theoretical knowledge (P-Value < 0.001). Students were satisfied with the peer model of training. CONCLUSION: Peer-led training of basic life support for medical students was beneficial and it provided a quality of education which was as effective as training conducted by professionals. This method is applicable and desirable especially in poor-resource countries and in crisis situation.

PD-L1 Expression in Premalignant and Malignant Trophoblasts From Gestational Trophoblastic Diseases Is Ubiquitous and Independent of Clinical Outcomes.

OBJECTIVE: Recently reported expression of programmed cell death 1 ligand 1 (PD-L1) in gestational trophoblastic diseases (GTDs) suggests that the immune tolerance of pregnancy might be hijacked during neoplastic process. We assessed PD-L1 protein expression in premalignant and malignant GTD lesions and analyzed associations with disease severity and chemotherapy outcomes. METHODS: We included 83 GTD whole-tissue sections from 76 patients in different treatment settings. PD-L1 protein expression was assessed with immunohistochemistry in each trophoblast subtype with the Allred total score (ATS), which combines intensity and proportion expression on a 0- to 8-point scale. Peritumoral immune infiltrate was scored on hematoxylin-eosin-safran-stained slides. RESULTS: PD-L1 expression was ubiquitous and strong in all GTD trophoblast subtypes. For invasive moles, ATS scores were maximal at 8 in 100%, 100%, and 75% of syncytiotrophoblast, villous cytotrophoblast, and extravillous cytotrophoblast specimens, respectively. For choriocarcinomas, ATS was 8 in 80% of specimens. Immune infiltrates were moderate to severe in 61%, 100%, and 100% of peritumoral zones of choriocarcinoma, epithelioid trophoblastic tumor, and invasive moles, respectively. Because of the homogeneous pathological findings, no significant differences in PD-L1 expression profiles or peritumoral immune infiltrates were found regarding FIGO (International Federation of Gynecology Obstetrics) prognostic score, fatal outcome, or chemosensitivity. CONCLUSIONS: We confirm that PD-L1 is constitutively expressed in all GTD premalignant and malignant trophoblast subtypes, independently from FIGO score, chemoresistance, or fatal outcomes, thereby suggesting a crucial role for PD-L1 in the development and tolerance of GTD. Assessment of anti-PD-L1 drug in GTD patients has been activated.

Crocodiles and alligators: Antiamoebic and antitumor compounds of crocodiles.

Crocodiles exist in unsanitary environments, feed on rotten meat, are often exposed to heavy metals such as arsenic, cadmium, cobalt, chromium, mercury, nickel, lead, selenium, tolerate high levels of radiation, and are amid the very few species to survive the catastrophic Cretaceous-Tertiary extinction event, nonetheless they can live for up to a 100 years. Moreover, as they live in unhygienic conditions, they regularly come across pathogens. Logically, we postulate that crocodiles possess mechanisms to defend themselves from noxious agents as well as protecting themselves from pathogens. To test this hypothesis, various organ lysates and serum of Crocodylus palustris were prepared. Amoebicidal assays were performed using Acanthamoeba castellanii belonging to the T4 genotype. Cytotoxicity assays were performed using Prostate cancer cells culture by measuring lactate dehydrogenase release as a marker for cell death. Growth inhibition assays were performed to determine the growth inhibitory effects of various organ lysates. Serum and heart lysates of Crocodylus palustris exhibited powerful anti-tumor activity exhibiting more than 70% Prostate cancer cell death (P < 0.05). Additionally, lysates from gall bladder and bile also showed significant host cell cytotoxicity, however intestine, lungs and brain showed partial cytotoxicity. Both sera and heart lysates of Crocodylus palustris abolished Prostate cells growth. Moreover, serum completely abolished A. castellanii viability. For the first time, these findings showed that the organ lysates of Crocodylus palustris exhibit potent anti-amoebic and anti-tumor activity. The discovery of antimicrobial and antitumor activity in crocodile will stimulate research in finding therapeutic molecules from unusual sources, and has potential for the development of novel antitumor/antimicrobial compound(s) that may also overcome drug resistance. Nevertheless, rigorous research in the next few years will be necessary to realize these expectations.

Psychological distress among medical students in conflicts: a cross-sectional study from Syria.

BACKGROUND: Medical education can be a time of great psychological distress for students. The ongoing Syrian conflict represents an additional factor potentially contributing to poor mental health among medical students. Studies revealed high levels of psychological distress among Syrians. We aimed to investigate the prevalence and risk factors of depression, anxiety and stress among medical students at Damascus University during this period of war. METHODS: A cross-sectional study was conducted using the Depression, Anxiety and Stress Scale (DASS-21) in addition to questions about demographic and financial characteristics, and questions about the effects of the ongoing war on the participants' lives. RESULTS: 350 students were included. Prevalence of depression, anxiety and stress was 60.6%, 35.1%, and 52.6%, respectively. Depression was more likely in females and those with "intermediate" or "insufficient" personal income. Anxiety was more likely in females and those with "insufficient" personal income while less likely in fifth- and sixth-year compared to second-year students. Stress was lower in fifth-year compared to second-year students and higher in "insufficient" personal income compared to "sufficient" personal income. CONCLUSIONS: We concluded that Syrian medical students suffer from high rates of psychological distress. Females, second-year students, and those with "insufficient" personal income were the most affected. Students' perception of their own financial status, rather than the financial status per se was related to psychological distress. There was no evidence of a direct relationship between the ongoing conflict and psychological distress. Further investigations of causes and consequences of poor mental health in Syrian medical students are essential.

Multiple strategy peer-taught evidence-based medicine course in a poor resource setting.

BACKGROUND: Teaching Evidence Based Medicine (EBM) is becoming a priority in the healthcare process. For undergraduates, it has been proved that integrating multiple strategies in teaching EBM yields better results than a single, short-duration strategy. However, there is a lack of evidence on applying EBM educational interventions in developing countries. In this study, we aim to evaluate the effectiveness of a multiple strategy peer-taught online course in improving EBM awareness and skills among medical students in two developing countries, Syria and Egypt. METHODS: We conducted a prospective study with pre- and post- course assessment of 84 medical students in three universities, using the Berlin questionnaire and a set of self-reported questions which studied the students' EBM knowledge, attitude and competencies. The educational intervention was a peer-taught online course consisting of six sessions (90 min each) presented over six weeks, and integrated with assignments, group discussions, and two workshops. RESULTS: The mean score of pre- and post-course Berlin tests was 3.5 (95% CI: 2.94-4.06) and 5.5 (95% CI: 4.74-6.26) respectively, increasing by 2 marks (95% CI: 1.112-2.888; p-value <0.001), which indicates a statistically significant increase in students' EBM knowledge and skill, similar to a previous expert-taught face to face contact course. Self-reported confidences also increased significantly. However, our course did not have a major effect on students' attitudes toward EBM (1.9-10.8%; p-value: 0.12-0.99). CONCLUSION: In developing countries, multiple strategy peer-taught online courses may be an effective alternative to face to face expert-taught courses, especially in the short term.

Predictive factors of relapse in low-risk gestational trophoblastic neoplasia patients successfully treated with methotrexate alone.

BACKGROUND: Patients with 2000 FIGO low-risk gestational trophoblastic neoplasia are commonly treated with single-agent chemotherapy. Methotrexate is widely used in this indication in Europe. Analysis of relapse after treatment and identification of factors associated with relapse would help understand their potential impacts on 2000 FIGO score evolution and chemotherapy management of gestational trophoblastic neoplasia patients. OBJECTIVE: This retrospective study analyzes the predictive factors of relapse in low-risk gestational trophoblastic neoplasia patients whose hormone chorionic gonadotropin (hCG) normalized with methotrexate alone. STUDY DESIGN: Between 1999 and 2014, 993 patients with gestational trophoblastic neoplasia were identified in the French Trophoblastic Disease Reference Center database, of which 465 were low-risk patients whose hCG normalized with methotrexate alone. Using univariate and multivariate analysis we identified significant predictive factors for relapse after methotrexate. The Kaplan-Meier method was used to plot the outcome of patients. RESULTS: The 5-year recurrence rate of low-risk gestational trophoblastic neoplasia patients whose hCG normalized with methotrexate alone was 5.7% (confidence interval [IC], 3.86-8.46). Univariate analysis identified an antecedent pregnancy resulting in a delivery (HR = 5.96; 95% CI, 1.40-25.4, P = .016), a number of methotrexate courses superior to 5 courses (5-8 courses vs 1-4: HR = 6.19; 95% CI, 1.43-26.8, P = .015; 9 courses and more vs 1-4: HR = 6.80; 95% CI, 1.32-35.1, P = .022), and hCG normalization delay centered to the mean as predictive factors of recurrence (HR = 1.27; 95% CI, 1.09-1.49, P = .003). Multivariate analysis confirmed the type of antecedent pregnancy and the number of methotrexate courses as independent predictive factors of recurrence. A low-risk gestational trophoblastic neoplasia arising after a normal delivery had an 8.66 times higher relapse risk than that of a postmole gestational trophoblastic neoplasia (95% CI, 1.98-37.9], P = .0042). A patient who received 5-8 courses of methotrexate had a 6.7 times higher relapse risk than a patient who received 1-4 courses (95% CI, 1.54-29.2, P = .011). A patient who received 9 courses or more had an 8.1 times higher relapse risk than a patient who received 1-4 courses of methotrexate (95% CI, 1.54-42.6, P = .014). CONCLUSION: Low-risk gestational trophoblastic neoplasia following a delivery and patients who need more than 4 courses of methotrexate to normalization are at a higher risk of relapse than other low-risk patients. Allotting a higher score to the "antecedent pregnancy" FIGO item should be considered for postdelivery gestational trophoblastic neoplasia. Further analysis of the need for consolidation courses is warranted.

Impact of leukoaraiosis on parenchymal hemorrhage in elderly patients treated with thrombolysis.

INTRODUCTION: Severity of vascular damage of white matter may predict hemorrhagic transformation (HT). We assess the relationship between leukoaraiosis (LA) severity and the type of hemorrhagic transformation in elderly patients treated with thrombolysis. METHODS: We retrospectively analyzed the clinical data and pretreatment magnetic resonance imaging (MRI) of 180 consecutive ischemic stroke patients aged over 75 years. LA severity was graded according to the Fazekas scale, and acute diffusion-weighted-imaging (DWI) lesion volumes were semi-automatically outlined. Predictors of hemorrhagic infarction (HI) and parenchymal hemorrhage (PH) were identified using logistic regression analysis and exact multinomial logistic analysis. RESULTS: HT occurred in 31 patients (17 %). Baseline National Institute of Health Stroke Score (NIHSS; p = 0.008), severe LA (p = 0.02), and diffusion lesion volume (p = 0.02) were predictors of HT in univariable logistic regression. Adjusted to lesion volume and baseline NIHSS score, exact multinomial logistic analysis showed that severe LA was the only independent predictor of parenchymal hemorrhage (p = 0.03). CONCLUSION: In elderly patients, LA severity better predicts parenchymal hemorrhage than infarct size.

q-Rung orthopair fuzzy 2-tuple linguistic WASPAS algorithm for patients' prioritization based on prioritized Maclaurin symmetric mean aggregation operators.

Due to the fuzziness of the medical field, q-rung orthopair fuzzy 2-tuple linguistic (q-RF2L) set is the privileged way to aid medical professionals in conveying their assessments in the patient prioritization problem. The theme of the present study is to put forward a novel approach centered around the merging of prioritized averaging (PA) and the Maclaurin symmetric mean (MSM) operator within q-RF2L context. According to the prioritization of the professionals and the correlation among the defined criteria, we apply both PA and MSM to assess priority degrees and relationships, respectively. Keeping the pluses of the PA and MSM operators in mind, we introduce two aggregation operators (AOs), namely q-RF2L prioritized Maclaurin symmetric mean and q-RF2L prioritized dual Maclaurin symmetric mean operators. Meanwhile, some essential features and remarks of the proposed AOs are discussed at length. Based on the formulated AOs, we extend the weighted aggregated sum product assessment methodology to cope with q-RF2L decision-making problems. Ultimately, to illustrate the practicality and effectiveness of the stated methodology, a real-world example of patients' prioritization problem is addressed, and an in-depth analysis with prevailing methods is performed.

An integrated group decision-making method under q-rung orthopair fuzzy 2-tuple linguistic context with partial weight information.

Considering the advantages of q-rung orthopair fuzzy 2-tuple linguistic set (q-RFLS), which includes both linguistic and numeric data to describe evaluations, this article aims to design a new decision-making methodology by integrating Vlsekriterijumska Optimizacija I Kompromisno Resenje (VIKOR) and qualitative flexible (QUALIFLEX) methods based on the revised aggregation operators to solve multiple criteria group decision making (MCGDM). To accomplish this, we first revise the extant operational laws of q-RFLSs to make up for their shortcomings. Based on novel operational laws, we develop q-rung orthopair fuzzy 2-tuple linguistic (q-RFL) weighted averaging and geometric operators and provide the corresponding results. Next, we develop a maximization deviation model to determine the criterion weights in the decision-making procedure, which accounts for partial weight unknown information. Then, the VIKOR and QUALIFLEX methodologies are combined, which can assess the concordance index of each ranking combination using group utility and individual maximum regret value of alternative and acquire the ranking result based on each permutation's general concordance index values. Consequently, a case study is conducted to select the best bike-sharing recycling supplier utilizing the suggested VIKOR-QUALIFLEX MCGDM method, demonstrating the method's applicability and availability. Finally, through sensitivity and comparative analysis, the validity and superiority of the proposed method are demonstrated.

Clinical experiences and learning curves from robot-assisted neurosurgical biopsies with Stealth Autoguide™.

Background: Biopsies of intracranial lesions are a cornerstone in the diagnosis of unresectable tumors to guide neurooncological treatment; however, the procedure is also associated with risks. The results from the cranial robot guidance system Stealth Autoguide™ were studied after introduction at a neurosurgical department. Primary aims include the presentation of clinical and radiological data, accuracy of radiological diagnosis, learning curves of the new technology, diagnostic yield, and precision. The secondary aim was to study complications. Methods: Retrospective data inclusion was performed on patients ≥ 18 years undergoing biopsy with Stealth Autoguide™ due to suspected brain tumors in the first 3 years after the introduction of the technique. Data regarding clinical characteristics, intraoperative variables, pathological diagnosis, and complications were recorded. Analyses of learning curves were performed. Results: A total of 79 procedures were performed on 78 patients with a mean age of 62 years (SD 12.7, range 23-82), 30.8% were female. Tumors were often multifocal (63.3%) and supratentorial (89.9%). The diagnostic yield was 87.3%. The first-hand radiological diagnosis was correct in 62.0%. A slight decrease in operation time was observed, although not significant. The surgeon contributed to 12% of the variability. Conclusions: Robot-assisted biopsies with Stealth Autoguide™ seem to be comparable, with regards to complications, to frame-based and other frameless neurosurgical biopsies. Learning curves demonstrated no statistical differences in time of surgery and only 12% surgeon-related variation (ie, variation caused by the change of performing surgeon), suggesting a successful implementation of this technical adjunct.

Kinetics and functional consequences of BK channels activation by N-type Ca2+ channels in the dendrite of mouse neocortical layer-5 pyramidal neurons.

The back-propagation of an action potential (AP) from the axon/soma to the dendrites plays a central role in dendritic integration. This process involves an intricate orchestration of various ion channels, but a comprehensive understanding of the contribution of each channel type remains elusive. In this study, we leverage ultrafast membrane potential recordings (Vm) and Ca2+ imaging techniques to shed light on the involvement of N-type voltage-gated Ca2+ channels (VGCCs) in layer-5 neocortical pyramidal neurons' apical dendrites. We found a selective interaction between N-type VGCCs and large-conductance Ca2+-activated K+ channels (BK CAKCs). Remarkably, we observe that BK CAKCs are activated within a mere 500 µs after the AP peak, preceding the peak of the Ca2+ current triggered by the AP. Consequently, when N-type VGCCs are inhibited, the early broadening of the AP shape amplifies the activity of other VGCCs, leading to an augmented total Ca2+ influx. A NEURON model, constructed to replicate and support these experimental results, reveals the critical coupling between N-type and BK channels. This study not only redefines the conventional role of N-type VGCCs as primarily involved in presynaptic neurotransmitter release but also establishes their distinct and essential function as activators of BK CAKCs in neuronal dendrites. Furthermore, our results provide original functional validation of a physical interaction between Ca2+ and K+ channels, elucidated through ultrafast kinetic reconstruction. This insight enhances our understanding of the intricate mechanisms governing neuronal signaling and may have far-reaching implications in the field.

Analysis of the effect of the scorpion toxin AaH-II on action potential generation in the axon initial segment.

The toxin AaH-II, from the scorpion Androctonus australis Hector venom, is a 64 amino acid peptide that targets voltage-gated Na+ channels (VGNCs) and slows their inactivation. While at macroscopic cellular level AaH-II prolongs the action potential (AP), a functional analysis of the effect of the toxin in the axon initial segment (AIS), where VGNCs are highly expressed, was never performed so far. Here, we report an original analysis of the effect of AaH-II on the AP generation in the AIS of neocortical layer-5 pyramidal neurons from mouse brain slices. After determining that AaH-II does not discriminate between Nav1.2 and Nav1.6, i.e. between the two VGNC isoforms expressed in this neuron, we established that 7 nM was the smallest toxin concentration producing a minimal detectable deformation of the somatic AP after local delivery of the toxin. Using membrane potential imaging, we found that, at this minimal concentration, AaH-II substantially widened the AP in the AIS. Using ultrafast Na+ imaging, we found that local application of 7 nM AaH-II caused a large increase in the slower component of the Na+ influx in the AIS. Finally, using ultrafast Ca2+ imaging, we observed that 7 nM AaH-II produces a spurious slow Ca2+ influx via Ca2+-permeable VGNCs. Molecules targeting VGNCs, including peptides, are proposed as potential therapeutic tools. Thus, the present analysis in the AIS can be considered a general proof-of-principle on how high-resolution imaging techniques can disclose drug effects that cannot be observed when tested at the macroscopic level.