A perspective on SIDS pathogenesis. The hypotheses: plausibility and evidence

Several theories of the underlying mechanisms of Sudden Infant Death Syndrome (SIDS) have been proposed. These theories have born relatively narrow beach-head research programs attracting generous research funding sustained for many years at expense to the public purse. This perspective endeavors to critically examine the evidence and bases of these theories and determine their plausibility; and questions whether or not a safe and reasoned hypothesis lies at their foundation. The Opinion sets specific criteria by asking the following questions: 1. Does the hypothesis take into account the key pathological findings in SIDS? 2. Is the hypothesis congruent with the key epidemiological risk factors? 3. Does it link 1 and 2? Falling short of any one of these answers, by inference, would imply insufficient grounds for a sustainable hypothesis. Some of the hypotheses overlap, for instance, notional respiratory failure may encompass apnea, prone sleep position, and asphyxia which may be seen to be linked to co-sleeping. For the purposes of this paper, each element will be assessed on the above criteria

Effects of cagA+ and cagA- strains of Helicobacter pylori on the human gastric mucus layer thickness

Background:  Infection with cytotoxin-associated gene A (cagA) Helicobacter pylori is associated with severe gastric diseases, with contradictory views being expressed concerning the effect of H. pylori on the gastric mucus thickness. The aim of the present study was to differentiate between the effect of cagA+ and cagA– strains on gastric mucus thickness.\ud \ud Methods:  Ninety-nine patients without peptic ulcers who were not on medication were randomly recruited from consecutive endoscopy clinics: six biopsies (five antral, one body) were obtained from each patient. Cryostat sections (18 µm) were cut and stained using the modified periodic acid–Schiff/Alcian blue technique. Mucus thickness was measured using computer-assisted light microscopy. The H. pylori status was assessed by histology, Campylobacter-like organism (CLO)test and culture, and cagA+ status determined by polymerase chain reaction (PCR).\ud \ud Results:  There was no significant difference (P = 0.784) in mean mucus thickness between cagA+ (52.7 ± 1.2 µm, n = 10), cagA– (46.6 ± 1.1 µm, n = 18) or H. pylori-negative patients (51.3 ± 1.1 µm, n = 30). In cagA– patients, mucus thickness was significantly reduced with increased H. pylori colonization density, Spearman (rs) = −0.805, P < 0.0001. In contrast, in cagA+ patients there was a weak positive, but not significant, association between mucus thickness and H. pylori colonization density, rs = 0.333, P = 0.381.\ud \ud Conclusions:  The human gastric mucus thickness is not affected by infection with cagA+ or cagA– strains of H. pylori compared with uninfected. Although a trend of increased mucus thickness with cagA+ infection was observed

Colonizing while migrating: How do individual enteric neural crest cells behave?

Background Directed cell migration is essential for normal development. In most of the migratory cell populations that have been analysed in detail to date, all of the cells migrate as a collective from one location to another. However, there are also migratory cell populations that must populate the areas through which they migrate, and thus some cells get left behind while others advance. Very little is known about how individual cells behave to achieve concomitant directional migration and population of the migratory route. We examined the behavior of enteric neural crest-derived cells (ENCCs), which must both advance caudally to reach the anal end and populate each gut region. Results The behaviour of individual ENCCs was examined using live imaging and mice in which ENCCs express a photoconvertible protein. We show that individual ENCCs exhibit very variable directionalities and speed; as the migratory wavefront of ENCCs advances caudally, each gut region is populated primarily by some ENCCs migrating non-directionally. After populating each region, ENCCs remain migratory for at least 24 hours. Endothelin receptor type B (EDNRB) signaling is known to be essential for the normal advance of the ENCC population. We now show that perturbation of EDNRB principally affects individual ENCC speed rather than directionality. The trajectories of solitary ENCCs, which occur transiently at the wavefront, were consistent with an unbiased random walk and so cell-cell contact is essential for directional migration. ENCCs migrate in close association with neurites. We showed that although ENCCs often use neurites as substrates, ENCCs lead the way, neurites are not required for chain formation and neurite growth is more directional than the migration of ENCCs as a whole. Conclusions Each gut region is initially populated by sub-populations of ENCCs migrating non-directionally, rather than stopping. This might provide a mechanism for ensuring a uniform density of ENCCs along the growing gut