TLR3 controls constitutive IFN-β antiviral immunity in human fibroblasts and cortical neurons

Human herpes simplex virus 1 (HSV-1) encephalitis can be caused by inborn errors of the TLR3 pathway, resulting in impairment of CNS cell-intrinsic antiviral immunity. Deficiencies of the TLR3 pathway impair cell-intrinsic immunity to vesicular stomatitis virus (VSV) and HSV-1 in fibroblasts, and to HSV-1 in cortical but not trigeminal neurons. The underlying molecular mechanism is thought to involve impaired IFN-α/β induction by the TLR3 recognition of dsRNA viral intermediates or by-products. However, we show here that human TLR3 controls constitutive levels of IFNB mRNA and secreted bioactive IFN-β protein, and thereby also controls constitutive mRNA levels for IFN-stimulated genes (ISGs) in fibroblasts. Tlr3^–/– mouse embryonic fibroblasts also have lower basal ISG levels. Moreover, human TLR3 controls basal levels of IFN-β secretion and ISG mRNA in induced pluripotent stem cell–derived cortical neurons. Consistently, TLR3-deficient human fibroblasts and cortical neurons are vulnerable not only to both VSV and HSV-1, but also to several other families of viruses. The mechanism by which TLR3 restricts viral growth in human fibroblasts and cortical neurons in vitro and, by inference, by which the human CNS prevents infection by HSV-1 in vivo, is therefore based on the control of early viral infection by basal IFN-β immunity.     

Cortical thickness as predictor of response to exercise in people with Parkinson's disease

We previously showed that dual‐task cost (DTC) on gait speed in people with Parkinson''s disease (PD) improved after 6 weeks of the Agility Boot Camp with Cognitive Challenge (ABC‐C) exercise program. Since deficits in dual‐task gait speed are associated with freezing of gait and gray matter atrophy, here we performed preplanned secondary analyses to answer two questions: (a) Do people with PD who are freezers present similar improvements compared to nonfreezers in DTC on gait speed with ABC‐C? (b) Can cortical thickness at baseline predict responsiveness to the ABC‐C? The DTC from 39 freezers and 43 nonfreezers who completed 6 weeks of ABC‐C were analyzed. A subset of 51 participants (21 freezers and 30 nonfreezers) with high quality imaging data were used to characterize relationships between baseline cortical thickness and delta (Δ) DTC on gait speed following ABC‐C. Freezers showed larger ΔDTC on gait speed than nonfreezers with ABC‐C program (p < .05). Cortical thickness in visual and fronto‐parietal areas predicted ΔDTC on gait speed in freezers, whereas sensorimotor‐lateral thickness predicted ΔDTC on gait speed in nonfreezers (p < .05). When matched for motor severity, visual cortical thickness was a common predictor of response to exercise in all individuals, presenting the largest effect size. In conclusion, freezers improved gait automaticity even more than nonfreezers from cognitively challenging exercise. DTC on gait speed improvement was associated with larger baseline cortical thickness from different brain areas, depending on freezing status, but visual cortex thickness showed the most robust relationship with exercise‐induced improvements in DTC.     

The match-play running performance of elite Camogie players across halves of play

Sport Sciences for Health - Camogie is one of the most popular female sports in Ireland, yet the demands of match-play are unknown. The current study aimed to examine the match-play running...     

CT quantification of hemoperitoneum volume in abdominal haemorrhage: a new method

Introduction

In emergency departments, focused assessment for sonographic examination of trauma patients (FAST) accurately detects hemoperitoneum in unstable patients. Currently, only an approximation of the volume of free intraperitoneal fluid (FIPF) can be done using ultrasound (US) and CT scans. We previously reported a new method developed on an experimental cadaveric model using US examination of the abdomen and applying a mathematic formula to effusion measurements to evaluate the exact volume of FIPF. The aim of this prospective study is to extrapolate this method in a clinical practice and apply it to CT measurements of the same area.

Patients and methods

We included prospectively eleven patients admitted with acute intraperitoneal haemorrhage: 10 patients with post-traumatic hemoperitoneum and 1 patient with a ruptured extra-uterine pregnancy. The mean age was 43.2 years (extremes: 21–82). There were six males and five females. All of these patients had to undergo emergency surgery by laparotomy or laparoscopy. The amount of FIPF was assessed preoperatively on axial sections of CT scan, by measuring fluid thickness in millimetres in the hepatorenal pouch (Morrison’s pouch), between the inferior aspect of the liver and the anterior aspect of the right kidney. During the emergency surgical procedure, we collected and quantified FIPF volume by direct measure in all cases.

Results

The correlation between fluid thickness x (mm) on the CT scan and the estimated amount of FIPF was established by the following linear function: volume (mL) = 81.068x + 263.2. The Spearman’s R obtained is 0.779 and the significance level is 0.005. We found a constant correlation between FIPF measured by radiologic procedure and direct per-operative measurement of FIPF.

Conclusion

This new linear function can be used to measure the exact volume of FIPF. This evaluation can help surgical decisions, especially when abdominal trauma is associated with other haemorrhagic lesions.     

Prenatal diagnosis of anomalous connection of the inferior caval vein to the left atrium associated with common arterial trunk

Anomalous connection of the inferior caval vein to the left atrium is exceedingly rare, and has even been considered by some authors an anatomic and embryologic impossibility. This study demonstrates for the first time the existence of this rare malformation, diagnosed on prenatal echo, and confirmed on post-mortem examination in a 24 WG fetus, in association with a common arterial trunk.