Right pulmonary artery torsion following surgical reimplantation

We report the case of a 3-month-old boy with an anomalous origin of right pulmonary artery (AORPA) from the ascending aorta who presented postoperatively with torsion of the right pulmonary artery demonstrated on 3-D volume-rendered CT angiogram. To our knowledge, CT images of this entity have not been reported. This case illustrates a rare surgical complication that can be easily imaged by CT.     

Mixed inhibitory synaptic balance correlates with glutamatergic synaptic phenotype in cerebellar unipolar brush cells

Inhibitory synapses display a great diversity through varying combinations of presynaptic GABA and glycine release and postsynaptic expression of GABA and glycine receptor subtypes. We hypothesized that increased flexibility offered by this dual transmitter system might serve to tune the inhibitory phenotype to the properties of afferent excitatory synaptic inputs in individual cells. Vestibulocerebellar unipolar brush cells (UBC) receive a single glutamatergic synapse from a mossy fiber (MF), which makes them an ideal model to study excitatory-inhibitory interactions. We examined the functional phenotypes of mixed inhibitory synapses formed by Golgi interneurons onto UBCs in rat slices. We show that glycinergic IPSCs are present in all cells. An additional GABAergic component of large amplitude is only detected in a subpopulation of UBCs. This GABAergic phenotype is strictly anti-correlated with the expression of type II, but not type I, metabotropic glutamate receptors (mGluRs) at the MF synapse. Immunohistochemical stainings and agonist applications show that global UBC expression of glycine and GABA(A) receptors matches the pharmacological profile of IPSCs. Paired recordings of Golgi cells and UBCs confirm the postsynaptic origin of the inhibitory phenotype, including the slow kinetics of glycinergic components. These results strongly suggest the presence of a functional coregulation of excitatory and inhibitory phenotypes at the single-cell level. We propose that slow glycinergic IPSCs may provide an inhibitory tone, setting the gain of the MF to UBC relay, whereas large and fast GABAergic IPSCs may in addition control spike timing in mGluRII-negative UBCs.     

Single versus double embryo transfer: cost-effectiveness analysis alongside a randomized clinical trial

BACKGROUND: Twin pregnancies after IVF are still frequent and are considered high-risk pregnancies leading to high costs. Transferring one embryo can reduce the twin pregnancy rate. We compared cost-effectiveness of one fresh cycle elective single embryo transfer (eSET) versus one fresh cycle double embryo transfer (DET) in an unselected patient population. METHODS: Patients starting their first IVF cycle were randomized between eSET and DET. Societal costs per couple were determined empirically, from hormonal stimulation up to 42 weeks after embryo transfer. An incremental cost-effectiveness ratio (ICER) was calculated, representing additional costs per successful pregnancy. RESULTS: Successful pregnancy rates were 20.8% for eSET and 39.6% for DET. Societal costs per couple were significantly lower after eSET (7334 euro) compared with DET (10,924 euro). The ICER of DET compared with eSET was 19,096 euro, meaning that each additional successful pregnancy in the DET group will cost 19,096 euro extra. CONCLUSIONS: One cycle eSET was less expensive, but also less effective compared to one cycle DET. It depends on the society's willingness to pay for one extra successful pregnancy, whether one cycle DET is preferred from a cost-effectiveness point of view.     

Reevaluating and optimizing polyomavirus BK and JC real-time PCR assays to detect rare sequence polymorphisms

PCR-based molecular assays have a central role in polyomavirus diagnostics. To assure optimal performance, target sequences should be regularly updated according to newly available sequences. The aim of this study was to review our in-house polyomavirus BK (BKV) and JC (JCV) real-time PCR assays. Database analysis revealed variations in the BKV target region which might affect the assay performance, while no significant changes were found in the JCV target region. We compared two degenerate versions of our BKV primers which accommodated at least 95% of all published genetic variants. Dilutions of cloned viral genomic DNA and probit analysis indicated an analytical sensitivity of the updated BKV assay of 4.15 copies/reaction and that of the JCV assay was 3.37 copies/reaction. The specificity was assessed by testing JCV- and BKV-positive samples that showed no cross-reactivity. The performance of the original and updated BKV assay was compared in 101 urine and 200 plasma samples submitted to our routine diagnostic laboratory revealed similar quantitative results. We conclude that our JCV and updated BKV real-time PCR assays are robust and detect rare variants possibly encountered in the clinical routine.     

Metabolic syndrome potentiates the cardiac action potential-prolonging action of drugs: a possible 'anti-proarrhythmic' role for amlodipine

Type II diabetes was shown to prolong the QT interval on the ECG and to promote cardiac arrhythmias. This is not so clear for metabolic syndrome, a precursor state of type II diabetes. The objectives of the present study were to generate a guinea pig model of metabolic syndrome by long-term exposure to diabetogenic diets, and to evaluate the monophasic action potential duration (MAPD)-modulating effects of drugs in these animals. Male Hartley guinea pigs were fed with either the control, the High Fat High Sucrose (HFHS) or the High Fat High Fructose (HFHF) diet for 150 days. Evolution of weight, blood cholesterol, triglycerides, urea and glucose tolerance were regularly monitored. Histopathological evolution was also evaluated in target organs such as pancreas, heart, liver and kidneys. Ex vivo experiments using the Langendorff retroperfusion technique, isolated hearts from guinea pigs either fed with the control, the HFHS or the HFHF diet were exposed to dofetilide 20 nM (D), chromanol 293B 10 μM (C) and amlodipine 100 nM (A) in different drug combinations and monophasic action potential duration was measured at 90% repolarization (MAPD₉₀). Our data show that it is possible to generate a guinea pig model of metabolic syndrome by chronic exposure to diabetogenic diets. Minor histopathological abnormalities were observed, mainly in the pancreas and the liver. Metabolic syndrome potentiates the MAPD-prolonging actions of I_Kr-blocking (dofetilide) and I_Ks-blocking (chromanol 293B) drugs, an effect that is reversible upon administration of the calcium channel blocker amlodipine.     

Follow-Up Chest X-Ray in Patients with Kawasaki Disease: The Significance and Clinical Application of Coronary Artery Macro-Calcification

Kawasaki disease (KD) related coronary artery (CA) aneurysms may lead to significant and potentially insidious progressive stenosis. It is also well recognized that CA scarring leads to heavy calcification in KD. We intended to correlate the angiographic anomalies associated with coronary calcifications in KD and to evaluate the chronology and the detection rate of KD-related CA calcification on plain chest X-ray. Between 1992 and 2006, 65 CA angiograms were performed in 50 KD patients. Chest fluoroscopies and angiograms were retrospectively reviewed. When angiograms were abnormal, chest X-rays were reviewed by two radiologists blinded to the results of angiograms. CA lesions were identified in 18/50 (36%) patients, including isolated CA aneurysms in 10. All 8 patients who had CA aneurysms associated with stenosis and/or occlusion had CA calcification identifiable on chest X-ray. All significant stenotic lesions were concomitant with calcification. Plain chest X-ray, a simple inexpensive low dose mean, easily identifies KD patients at risk for serious CA stenosis when specific search for CA calcification is pursued. When detected, a closer tracking of coronary artery patency is warranted via other imaging techniques, usually expensive, invasive, requiring sedation in children or exposing to high radiation.     

Mechanisms of speed encoding in the human middle temporal cortex measured by 7T fMRI

Perception of dynamic scenes in our environment results from the evaluation of visual features such as the fundamental spatial and temporal frequency components of a moving object. The ratio between these two components represents the object''s speed of motion. The human middle temporal cortex hMT+ has a crucial biological role in the direct encoding of object speed. However, the link between hMT+ speed encoding and the spatiotemporal frequency components of a moving object is still under explored. Here, we recorded high resolution 7T blood oxygen level‐dependent BOLD responses to different visual motion stimuli as a function of their fundamental spatial and temporal frequency components. We fitted each hMT+ BOLD response with a 2D Gaussian model allowing for two different speed encoding mechanisms: (1) distinct and independent selectivity for the spatial and temporal frequencies of the visual motion stimuli; (2) pure tuning for the speed of motion. We show that both mechanisms occur but in different neuronal groups within hMT+, with the largest subregion of the complex showing separable tuning for the spatial and temporal frequency of the visual stimuli. Both mechanisms were highly reproducible within participants, reconciling single cell recordings from MT in animals that have showed both encoding mechanisms. Our findings confirm that a more complex process is involved in the perception of speed than initially thought and suggest that hMT+ plays a primary role in the evaluation of the spatial features of the moving visual input.     

SARS-CoV-2 Seroprevalence among Canadian Blood Donors: The Advance of Omicron

With the emergence of the SARS-CoV-2 Omicron variant in late 2021, Canadian public health case/contact testing was scaled back due to high infection rates with milder symptoms in a highly vaccinated population. We monitored the seroprevalence of SARS-CoV-2 nucleocapsid (anti-N) and spike protein (anti-S) antibodies in blood donors across Canada from September 2021 to June 2022 in 202,123 randomly selected samples. Multivariable logistic regression of anti-N positivity with month, age, sex, racialization, region, material and social deprivation (based on postal code) identified as independent predictors. Piece-wise logistic regression analysed the association between anti-S concentration and month, and anti-N/anti-S positivity. Infection-related seroprevalence (anti-N positive) was 4.38% (95% CI: 3.96, 4.81) in September reaching 50.70% (50.15, 52.16) in June; nearly 100% were anti-S positive throughout. Anti-N positivity was associated with younger age, male sex, the Alberta and Prairies regions, greater material deprivation and less social deprivation (p < 0.001). Anti-S concentration was high initially (3306 U/mL, IQR 4280 U/mL), increased to (13,659 U/mL, IQR 28,224 U/mL) by June (p < 0.001), following the pattern of deployment of the third and fourth vaccine doses and was higher in those that were anti-N positive (p < 0.001). Despite already high vaccination-related seroprevalence, infection-related seroprevalence increased dramatically with the emergence of the Omicron SARS-CoV-2 variant.