A quantitative risk assessment for chronic traumatic encephalopathy (CTE) in football: How public health science evaluates evidence

How should science and policy interpret the recent finding that 110 of 111 former National Football League (NFL) players had brain pathology known as chronic traumatic encephalopathy (CTE) at autopsy? Some physicians view this (and related epidemiologic and mechanistic evidence) skeptically, emphasizing that the association between repeated head trauma (RHT) and CTE may be artifactual, that this “incidence” is biased by self-selection of players with cognitive or emotional symptoms, and that even if RHT causes CTE, the lesions themselves may be inconsequential. Public health scientists look at this emerging evidence quite differently; in particular, they tend not to fall prey to certain illogical arguments justifying inaction. We present a quantitative risk assessment showing that even accounting for the non-representativeness of the 110 cases, the risk of CTE in the NFL workforce amply meets both parts of the test for “a significant risk of material impairment of health” that would permit the U.S. Occupational Safety and Health Administration to intervene to reduce RHT exposure. We further conclude that according to available evidence, CTE is a public health problem, and that lawyers and physicians need to understand that this conclusion is based on standards of evidence at least as long-standing and robust as their own.     

Stretch-activated ion channel TMEM63B associates with developmental and epileptic encephalopathies and progressive neurodegeneration

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不同亚低温治疗时间对缺氧缺血性脑病新生患儿疗效的影响

目的:比较不同亚低温治疗时间对缺氧缺血性脑病患儿疗效及预后的影响,探讨亚低温治疗的最优时间,并且观察此治疗对新生儿有无不良影响。方法:选取我院收治的80例缺氧缺血性脑病(HIE)新生儿作为研究对象,将患儿随机分亚低温治疗48 h组、72 h组、96 h组和常规治疗组,每组20例患儿。所有患儿均给予常规治疗,亚低温组患儿在上述治疗基础上,在出生后6 h内加用选择性头部亚低温治疗。四组患儿生后28 d时进行神经测定(NBNA)评分,出生18月时进行Bayley评分。患儿接受治疗7天后统计血小板减少、电解质紊乱以及血糖紊乱的发生例数。结果:72 h组和96 h组患儿生后NBNA评分、Bayley评分比48 h组和常规治疗组高(P0.05),有统计学差异;72 h组和96 h组的NBNA评分、Bayley评分均没有统计学差异(P0.05),48 h组和常规组的评分也没有统计学差异(P0.05)。亚低温治疗96 h组患儿中,发生血小板减少、电解质紊乱及血糖紊乱等不良反应的比例较48 h组和72 h组明显增多(P0.05),有统计学差异;对比48 h组和72 h组不良反应的患儿比例,没有显著统计学差异(P0.05)。结论:亚低温治疗72 h对HIE患儿的治疗效果优于48 h,产生的副作用小于治疗96 h,建议临床亚低温治疗时间采用72 h以取得最佳治疗效果,产生最小不良反应。     

When amyloids become prions

The conformational diseases, linked to protein aggregation into amyloid conformations, range from non-infectious neurodegenerative disorders, such as Alzheimer''s disease (AD), to highly infectious ones, such as human transmissible spongiform encephalopathies (TSEs). They are commonly known as prion diseases. However, since all amyloids could be considered prions (from those involved in cell-to-cell transmission to those responsible for real neuronal invasion), it is necessary to find an underlying cause of the different capacity to infect that each of the proteins prone to form amyloids has. As proposed here, both the intrinsic cytotoxicity and the number of nuclei of aggregation per cell could be key factors in this transmission capacity of each amyloid.     

Human Risks from the Combustion of SRM-Derived Tallow in Ireland

The identification of meat and bone meal (MBM) as a significant factor in the spread of bovine spongiform encephalopathy (BSE) has resulted in the introduction of restrictions on the use and movement of MBM and tallow. This has led to a requirement for alternative uses for these products. This paper reports on a risk assessment performed on the use of tallow as a fuel oil extender in diesel engines. With up to 4000 tonnes of tallow being produced each year in Ireland, combustion with energy recovery represents a viable, cost-efficient utilization route. A stochastic (Latin Hypercube sampling) simulation model was developed to assess the infectiv-ity risk to humans associated with potential airborne exposure to the combustion products when using tallow as a combustion fuel in diesel engines. The model simulates the potential infectivity pathways that tallow follows, including its production from animals with potentially subclinical BSE and processing the tallow with segregation and heat treatments. The model uses probability distributions for the most important input parameters. The assessment takes into account a number of epidemiological parameters that include tissue infectivity, species barrier, disease incidence, and heat inactivation. Two scenarios, reflecting the infectivity risk in different animal tissues defined by the European Commissions Scientific Steering Committee (SSC), were performed. It is seen from the model results that the risk of a human contracting variant Creutzfeldt-Jakob Disease (vCJD) from potential airborne exposure to BSE, resulting from the combustion of tallow, is extremely small even when model uncertainty is taken into account (mean individual risk values ranging from 10^-11.43 to 10^-7.23 per year/person). The risks are a number of orders of magnitude less than the sporadic annual incidence level of Creutzfeldt-Jakob Disease 9CJD) in Europe (approximately 10^-6)     

Feasibility of allogeneic mesenchymal stem cells in pediatric hypoxic-ischemic encephalopathy: Phase I study

BACKGROUNDHypoxic-ischemic encephalopathy (HIE) is one of the leading causes of death and long-term neurological impairment in the pediatric population. Despite a limited number of treatments to cure HIE, stem cell therapies appear to be a potential treatment option for brain injury resulting from HIE.AIMTo investigate the efficacy and safety of stem cell-based therapies in pediatric patients with HIE.METHODSThe study inclusion criteria were determined as the presence of substantial deficit and disability caused by HIE. Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) were intrathecally (IT), intramuscularly (IM), and intravenously administered to participants at a dose of 1 × 10⁶/kg for each administration route twice monthly for 2 mo. In different follow-up durations, the effect of WJ-MSCs administration on HIE, the quality of life, prognosis of patients, and side effects were investigated, and patients were evaluated for neurological, cognitive functions, and spasticity using the Wee Functional Independence Measure (Wee FIM) Scale and Modified Ashworth (MA) Scale. RESULTSFor all participants (n = 6), the mean duration of exposure to hypoxia was 39.17 + 18.82 min, the mean time interval after HIE was 21.83 ± 26.60 mo, the mean baseline Wee FIM scale score was 13.5 ± 0.55, and the mean baseline MA scale score was 35 ± 9.08. Three patients developed only early complications such as low-grade fever, mild headache associated with IT injection, and muscle pain associated with IM injection, all of which were transient and disappeared within 24 h. The treatment was evaluated to be safe and effective as demonstrated by magnetic resonance imaging examinations, electroencephalographies, laboratory tests, and neurological and functional scores of patients. Patients exhibited significant improvements in all neurological functions through a 12-mo follow-up. The mean Wee FIM scale score of participants increased from 13.5 ± 0.55 to 15.17 ± 1.6 points (mean ± SD) at 1 mo (z = - 1.826, P = 0.068) and to 23.5 ± 3.39 points at 12 mo (z = -2.207, P = 0.027) post-treatment. The percentage of patients who achieved an excellent functional improvement (Wee FIM scale total score = 126) increased from 10.71% (at baseline) to 12.03% at 1 mo and to 18.65% at 12 mo post-treatment. CONCLUSIONBoth the triple-route and multiple WJ-MSC implantations were safe and effective in pediatric patients with HIE with significant neurological and functional improvements. The results of this study support conducting further randomized, placebo-controlled studies on this treatment in the pediatric population.