SummaryInnate immune molecules such as lung collectins and serum pentraxins have evolved as important host defence proteins against Aspergillus fumigatus, a medically important opportunistic fungal pathogen. Mannan-binding lectin (MBL), an opsonin and lectin complement pathway activator, constitutes another vital player of innate immunity against several pathogenic organisms in the serum. Studies have reported significant binding of MBL to A. fumigatus; however, the protective role of MBL against A. fumigatus-mediated invasive disease remains elusive. Henceforth, we investigated the contribution of externally administered recombinant human (rh) MBL towards anti-fungal defence in invasive pulmonary aspergillosis (IPA) by in vivo and in vitro studies. In murine models of IPA with corticosteroid-induced immunosuppression, rhMBL-treatedmiceshowed80%survivalcomparedtountreatedIPAmicewith no survivors. Treated IPA mice also showed a marked increase in tumour necrosis factor (TNF)-a and interleukin (IL)-1a and a significant decrease in pulmonary fungal hyphae and IL-10. In vitro, rhMBL-bound A. fumigatus conidia showed a dose-dependent increase in the deposition of C4b, the first product of the lectin pathway.There was an enhanced uptake of A. fumigatus conidia by the polymorphonuclear cells (PMNs) in the presence of rhMBL that increased further in the presence of MBL supplemented with MBL-deficient serum. However, an increase in the oxidative burst of PMNs and A. fumigatus killing were observed only when MBL was supplemented with MBL-deficient serum. The study suggests a therapeutic role of ex vivo-administered MBL in host defence against aspergillosis, possibly through MBL-mediated complement activation and other protective mechanisms aimed both directly at the pathogen, and indirectly through modulation of the host inflammatory responses.

IntroductionIt was estimated that 3.2 million Indians with diabetes injected insulin in 2010, but little is known about the techniques used.MethodsIn 2015 we conducted an injection technique questionnaire (ITQ) survey throughout India involving 1011 patients. Indian values were compared with those from 41 other countries participating in the ITQ, known here as rest of world (ROW).ResultsMean HbA1c was 8.6. BMI values in India were 1.5–3 units lower than in ROW depending on patient group, meaning the risk of intramuscular (IM) injections is high in India. The mean total daily dose (TDD) of insulin was lower in every category of Indian patient than in ROW, perhaps reflecting the lower BMI. Needle reuse, whether with pens or syringes, is much higher in India than ROW and so is the number of times the needle is used. The majority (56.8%) of Indian insulin users performed only 2 injections/day as opposed to ROW where 45% of patients performed at least 4 injections/day. Indian patients inject insulin in the thighs more often than patients in ROW, a site where IM injections are more risky. Many patients do not have proper access to sharps containers or have other risk factors that could lead to blood-borne pathogen spread. More than 60% of used sharps in India go into the rubbish, with nearly 12% not even having the minimum protection of a cap.DiscussionThe shortest needles are very common in India; however, the level of needle reuse is high. Multiple daily injections therapy is not as common in India as ROW. More focus needs to be given to dwell times under the skin, reconstitution of cloudy insulins, skinfolds, and safe sharps disposal.

IntroductionUsing the Indian and rest of world (ROW) injection technique questionnaire (ITQ) data, we address key insulin injection complications.MethodsIn 2015 we conducted an ITQ survey throughout India involving 1011 patients. Indian values were compared with those from 41 other countries participating in the ITQ, known here as ROW.ResultsMore than a quarter of Indian insulin users described lesions consistent with lipohypertrophy (LH) at their injection sites and approximately 1 in 5 were found to have LH by the examining nurse (using visual inspection and palpation). Just over half of Indian injectors report having pain on injection. Of these, 4 out of 5 report having painful injections only several times a month or year (i.e., not with every injection). Doctors and diabetes educators in India (as opposed to nurses) have a larger role in teaching patients how to inject than they do in ROW. Despite this specialized approach, a very high percentage of patients report that they have not been trained (at least cannot remember being trained) in a wide range of essential injection topics. Only about 30% of Indian injectors get their sites checked at least annually, with nearly a third only having sites checked when they specifically complained and nearly 4 out of 10 never having had their sites checked.ConclusionIndian HCPs can clearly do a better job covering all the vital topics essential to proper injection habits.

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Cortical spreading depression (CSD) has been at the center stage of migraine pathophysiology for approximately six decades. Reanalysis of CSD reveals several major unbridgeable gaps in this experimental neurophysiologic concept for migraine. Key phenotypic and pharmacological features of migraine challenge the assumed pathophysiologic role of CSD. Detection of subclinical infarct-like white matter lesions (WMLs) in the brain of some migraine patients stimulated the concept of CSD-related BBB disruption. Raised plasma levels of matrix metalloproteinases (MMPs) in migraine patients in the headache phase, specifically MMP-9, suggested a pathogenetic role for MMP elevation in the development of both migraine attacks and WMLs. Migraine attacks with or without aura present a unique, profound and protracted vasodilatory challenge to the homeostatic systems of the brain. To accommodate the rather sudden increase in cerebral blood flow, the brain circulatory network must dilate and the BBB must expand considerably. MMPs can influence expansion of the extracellular matrix of the BBB and loosening of the intercellular tight junctions between endothelial cells through proteolytic degradation during migrainous cerebrovascular dilatation. WMLs most probably reflect transient and discrete breakdown of the BBB consequent to sustained cerebral hyperperfusion rather than hypoperfusion. Systemic elevations of MMPs are not specific to migraine but are found in a variety of neurological and extra-neurological disorders. This perspective presents a conceptual dissociation between the effects of CSD on the brain of experimental animals and the clinical phenomena in migraine patients.