An underappreciated cause of ocean-related fatalities: A systematic review on the epidemiology, risk factors, and treatment of snorkelling-related drowning.

AIM: Snorkelling is a popular aquatic activity which may result in fatal and non-fatal drowning. However, little is known about the scale of injury, factors impacting risk and strategies for prevention. This review assesses the current literature on snorkelling-related drowning with the aim of assessing available data, improving safety recommendations and reducing the global mortality burden. METHODS: A systematic review of peer-reviewed literature in English, Spanish and Portuguese language published between 1 January 1980 and 31 October 2020 was conducted using the PRISMA guidelines. CINAHL Complete, Embase, Medline (Ovid), PubMed, SafetyLit, SportDiscus and grey literature were searched to identify studies reporting the incidence of fatal and non-fatal snorkelling-related drowning, or associated risk factors, prevention strategies, treatments or casualty characteristics. Quality was assessed using the NIH Quality Assessment Tool. RESULTS: Forty-three studies were included (26 reporting population data, 17 case series), of which 27 (62.8%) studies reported data from Australia. Incidence was reported as about 8% of total ocean-related drownings. Case series documented 144 fatalities over 17 years. Frequent casualty characteristics include male (82.6%), pre-existing heart disease (59.4%), tourists (73%) who were inexperienced (71.0%), and lack of a buddy system (89.6%). Two at-risk profiles identified were older adult tourists with pre-existing medical conditions and local, experienced spearfishers. Twenty-two expert recommendations were developed to improve the safety of snorkellers related to individuals, tourism companies, government agencies and diving organisations. CONCLUSION: Snorkelling-related drownings are not infrequent, and there are many opportunities to improve the safety of this activity based on available data.

A systematic review on the effectiveness of anti-choking suction devices and identification of research gaps.

AIM: Despite an obstructed airway (choking) being a relatively preventable injury, it has a considerable mortality burden globally, with increasing incidence. Given new technologies in choking management, this systematic review aimed to assess current literature on the effectiveness of anti-choking suction devices at relieving obstructions. METHODS: Ovid MEDLINE, Embase, PubMed, The Cochrane Library, SCOPUS, Web of Science, CINAHL Plus and the English websites of the devices were searched on September 23, 2019. Studies were included if they reported the anti-choking devices' dislodgment success rate (primary outcome) or associated adverse events (secondary outcome). Articles, conference abstracts or technical reports were included if peer reviewed. Certainty of evidence was assessed in accordance with GRADE. RESULTS: Five studies satisfied the inclusion criteria for this review. Two studies (40%) reported findings of a single centre mannequin trial, one (20%) of a single centre cadaveric trial, and two (40%) were case series. Cohen's Kappa for the first and second round of screening was 0.904 and 0.674 respectively. Although several devices have been manufactured worldwide, the LifeVac© has been most extensively studied, with a combined dislodgement success rate of 94.3% on first attempt. However, certainty of evidence for the primary outcome was evaluated as very low. CONCLUSIONS: There are many weaknesses in the available data and few unbiased trials that test the effectiveness of anti-choking suction devices resulting in insufficient evidence to support or discourage their use. Practitioners should continue to adhere to guidelines authored by local resuscitation authorities which align with ILCOR recommendations.

Comparison of sensory recovery at the subfascial and suprafascial donor sites of the free radial flap.

The radial flap may be raised using a subfascial or suprafascial approach. The latter donor site is associated with fewer healing complications. We retrospectively evaluated the quality of sensory recovery within two comparable groups of 30 patients with subfascial and suprafascial donor sites. When considering the two groups, two-point discrimination was the modality most commonly reduced, with 97% of patients in both groups having reduced sensation in at least one anatomical zone. Sensation of sharp touch was most often lost; 90% in the subfascial and 83% in the suprafascial groups lost sensation in at least one anatomical zone. Roughly half the patients had reduced perception of light touch (43% and 50%), whilst perception of heat (27% and 17%) and cold (33% and 27%) were lost least often. At least one modality in at least one anatomical zone was lost or reduced in all patients, and roughly two-thirds (73% and 63%) had a reduction in 3 or more. The only significant difference between the donor and non-donor arms was reduced perception of sharp touch in the anterior forearm in both groups (p<0.001). Perception at the two sites (including the anatomical snuff box) was similar except for superior thenar palmar light touch (p=0.015) in the suprafascial group, which may indicate injury to the thenar cutaneous sensory branches during subfascial dissection.

Biomechanical study of a unilocking T-plate system for prophylactic internal fixation of the radial osteocutaneous donor site using the sheep tibia model.

Prophylactic internal fixation (PIF), with a bone plate in either the anterior (over the section defect) or posterior (on intact cortex) position, has substantially reduced the incidence of fracture at the donor site of the radial osteocutaneous free flap. This study uses the sheep tibia model to compare the effectiveness of new T-shaped titanium plates utilising a unilocking screw system with a 3.5 mm steel plate and bicortical screw fixation system commonly applied for PIF. Forty matched pairs of adult sheep tibias were tested in torsion and 4-point bending. An osteotomised bone was significantly weaker (p<0.001) than an intact bone in both bending and torsion with a mean loss of 77% and 64% of strength respectively. The tibia withstood much greater bending loads. All of the constructs significantly strengthened an osteotomised bone by a factor of 1.73-2.43 times in bending and 1.54-2.63 in torsion. The 2.4 mm T-plate in an anterior position (section) was the baseline against which other plates in differing positions were compared. The 3.5 mm T-plate section, DCP section and DCP cortex constructs had 41%, 30% and 2% greater mean bending strengths respectively but only the 3.5 mm T-plate section result approached statistical significance (p=0.06). In torsion the DCP section, 3.5 mm T-plate section and DCP cortex constructs had 56% (p=0.01), 27% (p=0.06) and 25% greater mean strengths respectively. When compared to an intact bone the mean bending strength restored by the DCP section (84%) and 3.5 mm T-plate section (87%) constructs was greatest and effectively restored the strength to that of an intact bone (100%). In torsion the mean strength restored by the DCP section (62%), DCP cortex (44%), 3.5 mm T-plate section (40%) and 2.4 mm T-plate (36%) remained significantly less than an intact bone. All of the plate constructs significantly strengthened an osteotomised bone but overall the 3.5 mm T-plate section and DCP section were the strongest constructs and most suitable for PIF. The lighter 2.4 mm T-shaped titanium plate was least effective. The strongest reinforcement in bending and torsion was the 3.5 mm T-plate section and DCP section respectively. The 3.5 mm DCP section plate was significantly stronger (p=0.01) than the 3.5 mm T-plate in torsion and remains the most effective construct for resisting torsional stresses, which are probably the commonest cause of fracture in clinical practice.

Variant CJD infection in the spleen of a neurologically asymptomatic UK adult patient with haemophilia.

SUMMARY: All UK patients with bleeding disorders treated with any UK-sourced pooled factor concentrates between 1980 and 2001 have been informed that they may be at an increased risk of infection with variant Creutzfeldt-Jakob disease (vCJD). We describe a study to detect disease-associated, protease-resistant prion protein (PrP(res)) in 17 neurologically aymptomatic patients with haemophilia considered to be at increased risk of vCJD. Materials from 11 autopsy and seven biopsy cases were analysed for PrP(res). The tissues available from each case were variable, ranging from a single biopsy sample to a wide range of autopsy tissues. A single specimen from the spleen of one autopsy case gave a strong positive result on repeated testing for PrP(res) by Western blot analysis. This tissue came from a 73-year-old male patient with no history of neurological disease, who was heterozygous (methionine/valine) at codon 129 in the prion protein gene. He had received over 9000 units of factor VIII concentrate prepared from plasma pools known to include donations from a vCJD-infected donor, and some 400,000 units not known to include donations from vCJD-infected donors. He had also received 14 units of red blood cells and had undergone several surgical and invasive endoscopic procedures. Estimates of the relative risks of exposure through diet, surgery, endoscopy, blood transfusion and receipt of UK-sourced plasma products suggest that by far the most likely route of infection in this patient was receipt of UK plasma products.

Disease-associated prion protein is not detectable in human systemic amyloid deposits.

Cerebral and cardiac amyloid deposits have been reported after scrapie infection in transgenic mice expressing variant prion protein (PrP(C)) lacking the glycophosphatidylinositol anchor. The amyloid fibril protein in the systemic amyloid deposits was not characterized, and there is no clinical or pathological association between prion diseases and systemic amyloidosis in humans. Nevertheless, in view of the potential clinical significance of these murine observations, we tested both human amyloidotic tissues and isolated amyloid fibrils for the presence of PrP(Sc), the prion protein conformation associated with transmissible spongiform encephalopathy (TSE). We also sequenced the complete prion protein gene, PRNP, in amyloidosis patients. No specific immunohistochemical staining for PrP(Sc) was obtained in the amyloidotic cardiac and other visceral tissues of patients with different types of systemic amyloidosis. No protease-resistant prion protein, PrP(res), was detectable by Western blotting of amyloid fibrils isolated from cardiac and other systemic amyloid deposits. Only the complete normal wild-type PRNP gene sequence was identified, including the usual distribution of codon 129 polymorphisms. These reassuringly negative results do not support the idea that there is any relationship of prions or TSE with human systemic amyloidosis, including cardiac amyloid deposition.

In vitro amplification and detection of variant Creutzfeldt-Jakob disease PrPSc.

Variant Creutzfeldt-Jakob disease (vCJD) poses a serious risk of secondary transmission and the need to detect infectivity in asymptomatic individuals is therefore of major importance. Following infection, it is assumed that minute amounts of disease-associated prion protein (PrP(Sc)) replicate by conversion of the host cellular prion protein (PrP(C)). Therefore, methods of rapidly reproducing this conversion process in vitro would be valuable tools in the development of such tests. We show that one such technique, protein misfolding cyclic amplification (PMCA), can amplify vCJD PrP(Sc) from human brain tissue, and that the degree of amplification is dependent upon the substrate PRNP codon 129 polymorphism. Both human platelets and transgenic mouse brain are shown to be suitable alternative substrate sources, and amplified PrP(Sc) can be detected using a conformation-dependent immunoassay (CDI), allowing the detection of putative proteinase K sensitive forms of PrP(Sc).

BLOC-1 complex deficiency alters the targeting of adaptor protein complex-3 cargoes.

Mutational analyses have revealed many genes that are required for proper biogenesis of lysosomes and lysosome-related organelles. The proteins encoded by these genes assemble into five distinct complexes (AP-3, BLOC-1-3, and HOPS) that either sort membrane proteins or interact with SNAREs. Several of these seemingly distinct complexes cause similar phenotypic defects when they are rendered defective by mutation, but the underlying cellular mechanism is not understood. Here, we show that the BLOC-1 complex resides on microvesicles that also contain AP-3 subunits and membrane proteins that are known AP-3 cargoes. Mouse mutants that cause BLOC-1 or AP-3 deficiencies affected the targeting of LAMP1, phosphatidylinositol-4-kinase type II alpha, and VAMP7-TI. VAMP7-TI is an R-SNARE involved in vesicle fusion with late endosomes/lysosomes, and its cellular levels were selectively decreased in cells that were either AP-3- or BLOC-1-deficient. Furthermore, BLOC-1 deficiency selectively altered the subcellular distribution of VAMP7-TI cognate SNAREs. These results indicate that the BLOC-1 and AP-3 protein complexes affect the targeting of SNARE and non-SNARE AP-3 cargoes and suggest a function of the BLOC-1 complex in membrane protein sorting.

Abnormal prion protein in the retina of the most commonly occurring subtype of sporadic Creutzfeldt-Jakob disease.

BACKGROUND: Involvement of the eye has been reported in patients with variant Creutzfeldt-Jakob disease (vCJD), but there is disagreement on whether retinal involvement occurs in sporadic Creutzfeldt-Jakob disease (sCJD). METHODS: Western blotting, paraffin embedded tissue blotting, and immunohistochemistry were used to test whether the abnormal form of the prion protein (PrPSc) accumulates to detectable levels in the eye in a case of the most common subtype of sCJD (MM1). RESULTS: Low levels of PrPSc were detectable in the retina, localised to the plexiform layers of the central retina. PrPSc was not detectable in other ocular tissues. CONCLUSIONS: The abnormal form of the prion protein is present in the retina in the most common sCJD subtype (MM1), albeit at levels lower than those found previously in vCJD and in sCJD of the VV2 subtype.

Specificity of 14-3-3 isoform dimer interactions and phosphorylation.

Proteins that interact with 14-3-3 isoforms are involved in regulation of the cell cycle, intracellular trafficking/targeting, signal transduction, cytoskeletal structure and transcription. Recent novel roles for 14-3-3 isoforms include nuclear trafficking the direct interaction with cruciform DNA and with a number of receptors, small G-proteins and their regulators. Recent findings also show that the mechanism of interaction is also more complex than the initial finding of the novel phosphoserine/threonine motif. Non-phosphorylated binding motifs that can also be of high affinity may show a more isoform-dependent interaction and binding of a protein through two distinct binding motifs to a dimeric 14-3-3 may also be essential for full interaction. Phosphorylation of specific 14-3-3 isoforms can also regulate interactions. In many cases, they show a distinct preference for a particular isoform(s) of 14-3-3. A specific repertoire of dimer formation may influence which of the 14-3-3-interacting proteins could be brought together. Mammalian and yeast 14-3-3 isoforms show a preference for dimerization with specific partners in vivo.