Dominant A1: angiographic and clinical correlations with anterior communicating artery aneurysms.

It has been observed but never proven that anomalies of the anterior communicating artery complex are associated with anterior communicating artery aneurysms (ACAA). Therefore, in an effort to understand the significance of haemodynamic factors in the genesis, as well as the clinical course of ACAA, we evaluated the correlation between certain angiographic patterns of flow in the anterior circulation and the clinical findings of 51 patients with ACAA compared with 50 matched controls. Four significant associations which have never been validated were identified: 1) a dominant A1 (filling both A2's) was found in 57% of ACAA patients versus 14% of controls (p less than 0.001). 2) Unilateral hypoplasia of the opposite A1 was present in 24% of ACAA patients versus 6% of controls (p = 0.01). 3) Exclusive filling of the ACAA from one A1 occurred in 78%. 4) No statistically significant relationship was found between the anatomic flow patterns studied and the patients clinical presentation including age, sex, or grade. We conclude that anterior communicating artery aneurysms are significantly related in a majority of patients with the presence of a dominant A1, probably as the result of enhanced haemodynamic stress caused by this anatomic abnormality in the circulation. However, this association is not constant, and a dominant pattern of flow did not correlate with the clinical course. This is probably a reflection of the differences between factors initiating aneurysm formation and those influencing its growth, as well as of the relative limitations of angiography when pathophysiological extrapolations are attempted.     

Brain tissue oxygenation in patients with cerebral occlusive disease and arteriovenous malformations

It is not clear if ventilation with oxygen increases brain tissue oxygen pressure (PO2) during ischaemia. We have measured brain tissue PO2, carbon dioxide pressure (PCO2) and pH during baseline anaesthesia and oxygen ventilation in non-ischaemic control patients (n = 9), patients with cerebral occlusive disease (n = 11) and patients with arteriovenous malformations (AVM, n = 12). The same anaesthetic treatment was given to all groups and anaesthesia was constant during the study. Arterial pressure, brain temperature and arterial blood-gas tensions were similar between groups. Under baseline conditions, brain tissue PO2 was mean 4.2 (SD 1.4) kPa in the controls and was 70% lower in patients with ischaemia and AVM. Patients with occlusive disease also had elevated tissue PCO2 and acidosis. During oxygen ventilation, PO2 increased to 7.5 (2.9) kPa in controls and this was 50% greater than the increase in the ischaemia and AVM patients. The results showed that baseline tissue oxygenation and increases in PO2 during hyperoxia were attenuated in patients with ischaemia or AVM.      

The impact of non-pharmaceutical interventions on COVID-19 epidemic growth in the 37 OECD member states

We estimated the impact of a comprehensive set of non-pharmeceutical interventions on the COVID-19 epidemic growth rate across the 37 member states of the Organisation for Economic Co-operation and Development during the early phase of the COVID-19 pandemic and between October and December 2020. For this task, we conducted a data-driven, longitudinal analysis using a multilevel modelling approach with both maximum likelihood and Bayesian estimation. We found that during the early phase of the epidemic: implementing restrictions on gatherings of more than 100 people, between 11 and 100 people, and 10 people or less was associated with a respective average reduction of 2.58%, 2.78% and 2.81% in the daily growth rate in weekly confirmed cases; requiring closing for some sectors or for all but essential workplaces with an average reduction of 1.51% and 1.78%; requiring closing of some school levels or all school levels with an average reduction of 1.12% or 1.65%; recommending mask wearing with an average reduction of 0.45%, requiring mask wearing country-wide in specific public spaces or in specific geographical areas within the country with an average reduction of 0.44%, requiring mask-wearing country-wide in all public places or all public places where social distancing is not possible with an average reduction of 0.96%; and number of tests per thousand population with an average reduction of 0.02% per unit increase. Between October and December 2020 work closing requirements and testing policy were significant predictors of the epidemic growth rate. These findings provide evidence to support policy decision-making regarding which NPIs to implement to control the spread of the COVID-19 pandemic.

     

Spatiotemporal analysis of tumour-infiltrating immune cells in biliary carcinogenesis

Background Intraductal papillary neoplasms (IPN) and biliary epithelial neoplasia (BilIN) are well‐defined precursor lesions of biliary tract carcinoma (BTC). The aim of this study was to provide a comprehensive characterisation of the inflammatory microenvironment in BTC precursor lesions.Methods Immunohistochemistry was employed to assess tumour-infiltrating immune cells in tissue samples from patients, for whom precursor lesions were identified alongside invasive BTC. The spatiotemporal evolution of the immune microenvironment during IPN-associated carcinogenesis was comprehensively analysed using triplet sample sets of non-neoplastic epithelium, precursor lesion and invasive BTC. Immune-cell dynamics during IPN- and BilIN-associated carcinogenesis were subsequently compared.Results Stromal CD3⁺ (P = 0.002), CD4⁺ (P = 0.007) and CD8⁺ (P < 0.001) T cells, CD20⁺ B cells (P = 0.008), MUM1⁺ plasma cells (P = 0.012) and CD163⁺ M2-like macrophages (P = 0.008) significantly decreased in IPN compared to non-tumorous biliary epithelium. Upon transition from IPN to invasive BTC, stromal CD68⁺ (P = 0.001) and CD163⁺ (P < 0.001) macrophages significantly increased. In contrast, BilIN-driven carcinogenesis was characterised by significant reduction of intraepithelial CD8⁺ T-lymphocytic infiltration from non-tumorous epithelium via BilIN (P = 0.008) to BTC (P = 0.004).Conclusion IPN and BilIN are immunologically distinct entities that undergo different immune-cell variations during biliary carcinogenesis. Intraepithelial CD8⁺ T-lymphocytic infiltration of biliary tissue decreased already at the IPN-precursor stage, whereas BilIN-associated carcinogenesis showed a slowly progressing reduction towards invasive carcinoma.Subject terms: Cancer microenvironment, Immunoediting, Biliary tract cancer     

Multiphoton microscopy for pre-clinical evaluation of flow-diverter stents for treating aneurysms

BackgroundConventional histological analyses are the gold standard for the study of aneurysms and vascular pathologies in pre-clinical research. Over the past decade, in vivo and ex vivo imaging using multiphoton microscopy have emerged as powerful pre-clinical tools for detailed tissue analyses that can assess morphology, the extracellular matrix (ECM), cell density and vascularisation. Multiphoton microscopy allows for deeper tissue penetration with minor phototoxicity.ObjectiveThe present study aimed to demonstrate the current status of multimodality imaging, including multiphoton microscopy, for detailed analyses of neo-endothelialisation and ECM evolution after flow-diverter stent (FDS) treatment in an experimental rabbit model of aneurysms.MethodsMultiphoton microscopy tools for assessing autofluorescence and second harmonic generation (SHG) signals from biological tissues were used to evaluate the endovascular treatment of intracranial aneurysms in an animal model of aneurysms (pig, rabbit). Results from multiphoton microscopy were compared to those from standard histology, electronic and bright field microscopy.ConclusionsThe present study describes novel evaluation modes based on multiphoton microscopy for visualising tissue morphology (e.g., collagen, elastin, and cells) to qualify and quantify the extent of neo-intimal formation of covered arteries and device integration into the arterial wall using a rabbit model of intracranial aneurysms treated with FDS.     

Retrograde leptomeningeal venous approach for dural arteriovenous fistulas at foramen magnum

A 72-year-old man presented with sudden right homonymous hemianopsia. Work-up imaging revealed a left occipital haematoma and an arteriovenous fistula supplied by the meningeal branches to the clivus from the left vertebral artery (VA) with a rostral venous reflux into cortical veins. A microcatheter was advanced through brainstem veins into the venous collector. A compliant balloon was placed in the left VA facing the origin of feeders. The balloon was inflated to protect the vertebrobasilar circulation from embolic migration. Onyx was injected by the transvenous catheter. Control angiogram revealed exclusion of the lesion.Informed consent was obtained from the patient.     

Self-Rated Health Among Saudi Adults: Findings from a National Survey, 2013

Self-rated health reflects a person’s integrated perception of health, including its biological, psychological, and social dimensions. It is a predictor of morbidity and mortality. To assess the current status of self-rated health and associated factors in the Kingdom of Saudi Arabia, we analyzed data from the Saudi Health Interview Survey. We conducted a large national survey of adults aged 15 years or older. A total of 10,735 participants completed a standardized health questionnaire. Respondents rated their health with a five-point scale. Data on socio-demographic characteristics, chronic diseases, health-related habits and behaviors, and anthropometric measurements were collected. Associated factors of self-rated health were analyzed using a backward elimination multivariate logistic regression model. More than 77 % of respondents rated their health as excellent/very good. Female sex [odds ratio (OR) 1.52, 95 % confidence interval (CI) 1.24–1.88], decades of age (OR 1.35, 95 % CI 1.25–1.46), diagnosed diabetes mellitus (OR 1.54, 95 % CI 1.22–1.93), diagnosed hypercholesterolemia (OR 1.37, 95 % CI 1.06–1.79), diagnosed hypertension (OR 1.55, 95 % CI 1.22–1.96), number of other diagnosed chronic diseases (OR 1.69, 95 % CI 1.41–2.03), limited vigorous activity (OR 3.59, 95 % CI 2.84–4.53), need for special equipment (OR 2.62, 95 % CI 1.96–3.51), and more than 3 h of daily television/computer screen time (OR 1.59, 95 % CI1.11–2.29) were positively associated with poor/fair health. Smoking, obesity, and physical inactivity were not associated with self-reported health. We found that preventable risk factors are not associated with Saudis’ self-rated health. This optimistic perception of health poses a challenge for preventive interventions in the Kingdom and calls for campaigns to educate the public about the harm of unhealthy behaviors.     

Capacitative calcium entry and transient receptor potential canonical 6 expression control human hepatoma cell proliferation

Store-operated calcium entry (SOCE) is the main Ca(2+) influx pathway involved in controlling proliferation of the human hepatoma cell lines Huh-7 and HepG2. However, the molecular nature of the calcium channels involved in this process remains unknown. Huh-7 and HepG2 cells express transient receptor potential canonical 1 (TRPC1) and TRPC6, as well as STIM1 and Orai1, and these 4 channels are the most likely candidates to account for the SOCE in these cells. We generated stable TRPC6-overexpressing or TRPC6-knockdown Huh-7 clones, in which we investigated correlations between the presence of the protein, the rate of cell proliferation, and SOCE amplitude. TRPC6-overexpressing Huh-7 cells proliferated 80% faster than did untransfected cells and their SOCE amplitude was 160% higher. By contrast, proliferation rate was 50% lower and SOCE amplitude 85% lower in TRPC6-knockdown clones than in untransfected cells. OAG (olyl acetyl glycerol)-induced calcium entry was similar in all cells, and small interfering RNA (siRNA) against TRPC1 had no effect on SOCE amplitude, highlighting the relationship among SOCE, TRPC6 and cell proliferation in Huh-7 cells. SOCE amplitude was reduced by STIM1 and Orai1 knockdowns, suggesting possible cooperation between these proteins and TRPC6 in these cells. Endothelial growth factor and hepatocyte growth factor increased TRPC6 expression and SOCE amplitude in Huh-7 cells, and cyclin D1 expression was decreased by STIM1, Orai1, and TRPC6 knockdowns. CONCLUSION: TRPC6 was very weakly expressed in isolated hepatocytes from healthy patients and expressed more strongly in tumoral samples from the liver of a cancer patient, strongly supporting a role for these calcium channels in liver oncogenesis.