The acute influence of amateur boxing on cerebral autoregulation and cerebrovascular reactivity to carbon dioxide

This is the author accepted manuscriptPurpose: The purpose of this study was to investigate the acute effect of head impacts, sustained over the course of three rounds of amateur boxing, on indices of cerebrovascular function. Methods: 18 university amateur boxers (six female) completed three experimental trials in a randomised order; 1) three rounds of boxing (BOX), 2) an equivalent bout of pad boxing (where no blows to the head were sustained; PAD), and 3) a time-matched seated control trial (CON). Indices of cerebrovascular function were determined immediately before and 45 minutes after each trial. Specifically, dynamic cerebral autoregulation (dCA) was determined by considering the relationship between changes in cerebral blood velocity and mean arterial pressure during five minutes of squat-stand manoeuvres at 0.05 and 0.10 Hz. Cerebrovascular reactivity was determined using serial breath holding and hyperventilation attempts. Results: Participants received an average of 40 ± 16 punches to the head during the BOX trial. Diastolic, mean and systolic dCA phase during squat stand manoeuvres at 0.05 Hz was lower after BOX compared to pre BOX (P≤0.02, effect size (d)≥0.74). No other alterations in dCA outcomes were observed at 0.05 or 0.10 Hz. The number of head impacts received during the BOX trial was associated with the change in systolic phase (r=0.50, P=0.03). No differences in cerebrovascular reactivity to breath holding or hyperventilation were observed. Conclusion: A typical bout of amateur boxing (i.e. three rounds) can subtly alter cerebral pressure-flow dynamics, and the magnitude of this change may be related to head impact exposure

Deficiency of mannan-binding lectin associated serine protease-2 due to missense polymorphisms

Mannan-binding lectin (MBL) and ficolins distinguish between self, non-self and altered-self by recognizing patterns of ligands on the surface of microorganisms or aberrant cells. When this happens MBL-associated serine protease-2 (MASP-2) is activated and cleaves complement factors to start inflammatory actions. We examined human populations for MASP-2 levels, MASP-2 function and for the presence of mutations in coding exons of MASP2. The MASP-2 levels were lowest in Africans from Zambia (median, 196ng/ml) followed by Hong Kong Chinese (262ng/ml), Brazilian Amerindians (290ng/ml) and Danish Caucasians (416ng/ml). In the Chinese population, we uncovered a novel four amino-acid tandem duplication (p.156_159dupCHNH) associated with low levels of MASP-2. The frequency of this mutation as well as the SNPs p.R99C, p.R118C, p.D120G, p.P126L and p.V377A were analyzed. The p.156_159dupCHNH was only found in Chinese (gene frequency 0.26%) and p.D120G was found only in Caucasians and Inuits from West-Greenland. The p.P126L and p.R99Q were present in Africans and Amerindians only, except for p.R99Q in one Caucasian. The MASP-2 levels were reduced in individuals with p.V377A present. The MASP-2 present in individuals homozygous for p.377A or p.99Q had a normal enzyme activity whereas MASP-2 in individuals homozygous for p.126L was non-functional.link_to_subscribed_fulltex

Plugging the leak in Dengue shock

Recent structural and functional advances provide fresh insight into the biology of the dengue virus non-structural protein, NS1 and suggest new avenues of research. The work of our lab and others have shown that the secreted, hexameric form of NS1 has a systemic toxic effect, inducing inflammatory cytokines and acting directly on endothelial cells to produce the hallmark of dengue disease, vascular leak. We also demonstrated that NS1 exerts its toxic activity through recognition by the innate immune receptor TLR4, mimicking the bacterial endotoxin LPS. This monograph covers the background underpinning these new findings and discusses new avenues for antiviral and vaccine intervention