The misdiagnosis of epilepsy in people with intellectual disabilities: A systematic review

AbstractPurposeEpilepsy is common in people with intellectual disabilities. Epilepsy can be difficult to diagnose and may be misdiagnosed in around 25% of cases. A systematic review was conducted to explore:(i)How common the misdiagnosis of epilepsy is amongst people with intellectual disabilities.(ii)Reasons for misdiagnosis of epilepsy.(iii)Implications of misdiagnosis.(iv)Improving diagnosis.MethodsPrimary studies and systematic reviews published in the English language between 1998 and 2008 were identified from electronic databases, experts, the Internet, grey literature, and citation tracking. Included studies were critically appraised by team members using the appraisal tools produced by the Critical Appraisal Skills Programme (CASP) at the Public Health Resource Unit, Oxford.ResultsEight studies were included in the review and critically appraised: six cohort studies and two case studies. Where data was provided in the cohort studies between 32% and 38% of people with intellectual disabilities were diagnosed as not having epilepsy or as having nonepileptic events. The main reason for misdiagnosis was the misinterpretation of behavioural, physiological, syndrome related, medication related or psychological events by parents, paid carers and health professionals.ConclusionsThose working in epilepsy and intellectual disability services and families must be made more aware of the possibility of misdiagnosis. Future research is needed about the misdiagnosis of epilepsy amongst people with intellectual disabilities and carer knowledge

Water warming garment versus forced air warming system in prevention of intraoperative hypothermia during liver transplantation: a randomized controlled trial [ISRCTN32154832]

BACKGROUND: The authors compared two strategies for the maintenance of intraoperative normothermia during orthotopic liver transplantation (OLT): the routine forced-air warming system and the newly developed, whole body water garment. METHODS: In this prospective, randomized and open-labelled study, 24 adult patients were enrolled in one of two intraoperative temperature management groups during OLT. The water-garment group (N = 12) received warming with a body temperature (esophageal) set point of 36.8°C. The forced air-warmer group (N = 12) received routine warming therapy using upper- and lower-body forced-air warming system. Body core temperature (primary outcome) was recorded intraoperatively and during the two hours after surgery in both groups. RESULTS: The mean core temperatures during incision, one hour after incision and during the skin closing were significantly higher (p < 0.05, t test with Bonferroni corrections for the individual tests) in the water warmer group compared to the control group (36.7 ± 0.1, 36.7 ± 0.2, 36.8 ± 0.1 vs 36.1 ± 0.4, 36.1 ± 0.4, 36.07 ± 0.4°C, respectively). Moreover, significantly higher core temperatures were observed in the water warmer group than in the control group during the placement of cold liver allograft (36.75 ± 0.17 vs 36.09 ± 0.38°C, respectively) and during the allograft reperfusion period (36.3 ± 0.26 vs 35.52 ± 0.42°C, respectively). In addition, the core temperatures immediately after admission to the SICU (36.75 ± 0.13 vs 36.22 ± 0.3°C, respectively) and at one hr (36.95 ± 0.13 vs 36.46 ± 0.2°C, respectively) were significantly higher in the water warmer group, compared to the control group, whereas the core temperature did not differ significantly afte two hours in ICU in both groups. CONCLUSIONS: The investigated water warming system results in better maintenance of intraoperative normothermia than routine air forced warming applied to upper- and lower body

An alternative approach to combination vaccines: intradermal administration of isolated components for control of anthrax, botulism, plague and staphylococcal toxic shock

BACKGROUND: Combination vaccines reduce the total number of injections required for each component administered separately and generally provide the same level of disease protection. Yet, physical, chemical, and biological interactions between vaccine components are often detrimental to vaccine safety or efficacy. METHODS: As a possible alternative to combination vaccines, we used specially designed microneedles to inject rhesus macaques with four separate recombinant protein vaccines for anthrax, botulism, plague and staphylococcal toxic shock next to each other just below the surface of the skin, thus avoiding potentially incompatible vaccine mixtures. RESULTS: The intradermally-administered vaccines retained potent antibody responses and were well- tolerated by rhesus macaques. Based on tracking of the adjuvant, the vaccines were transported from the dermis to draining lymph nodes by antigen-presenting cells. Vaccinated primates were completely protected from an otherwise lethal aerosol challenge by Bacillus anthracis spores, botulinum neurotoxin A, or staphylococcal enterotoxin B. CONCLUSION: Our results demonstrated that the physical separation of vaccines both in the syringe and at the site of administration did not adversely affect the biological activity of each component. The vaccination method we describe may be scalable to include a greater number of antigens, while avoiding the physical and chemical incompatibilities encountered by combining multiple vaccines together in one product

Science Operations for the 2008 NASA Lunar Analog Field Test at Black Point Lava Flow, Arizona

Surface science operations on the Moon will require merging lessons from Apollo with new operation concepts that exploit the Constellation Lunar Architecture. Prototypes of lunar vehicles and robots are already under development and will change the way we conduct science operations compared to Apollo. To prepare for future surface operations on the Moon, NASA, along with several supporting agencies and institutions, conducted a high-fidelity lunar mission simulation with prototypes of the small pressurized rover (SPR) and unpressurized rover (UPR) (Fig. 1) at Black Point lava flow (Fig. 2), 40 km north of Flagstaff, Arizona from Oct. 19-31, 2008. This field test was primarily intended to evaluate and compare the surface mobility afforded by unpressurized and pressurized rovers, the latter critically depending on the innovative suit-port concept for efficient egress and ingress. The UPR vehicle transports two astronauts who remain in their EVA suits at all times, whereas the SPR concept enables astronauts to remain in a pressurized shirt-sleeve environment during long translations and while making contextual observations and enables rapid (less than or equal to 10 minutes) transfer to and from the surface via suit-ports. A team of field geologists provided realistic science scenarios for the simulations and served as crew members, field observers, and operators of a science backroom. Here, we present a description of the science team s operations and lessons learned

Escherichia coli O157 Exposure in Wyoming and Seattle: Serologic Evidence of Rural Risk

We tested the hypothesis that rural populations have increased exposure to Escherichia coli O157:H7. We measured circulating antibodies against the O157 lipopolysaccharide in rural Wyoming residents and in blood donors from Casper, Wyoming, and Seattle, Washington, by enzyme immunoassay (EIA). EIA readings were compared by analysis of variance and the least squares difference multiple comparison procedure. Rural Wyoming residents had higher antibody levels to O157 LPS than did Casper donors, who, in turn, had higher levels than did Seattle donors (respective least squares means: 0.356, 0.328, and 0.310; p<0.05, Seattle vs. Casper, p<0.001, rural Wyoming vs. either city). Lower age was significantly correlated with EIA scores; gender; and, in rural Wyoming, history of bloody diarrhea, town, duration of residence, and use of nontreated water at home were not significantly correlated. These data suggest that rural populations are more exposed to E. coli O157:H7 than urban populations

Perturbation of lipids and glucose metabolism associated with previous 2,4-D exposure: a cross-sectional study of NHANES III data, 1988-1994

<p>Abstract</p> <p>Background</p> <p>Results from previous population studies showed that mortality rates from acute myocardial infarction and type-2 diabetes during the 1980s and 1990s in rural, agricultural counties of Minnesota, Montana, North and South Dakota, were higher in counties with a higher level of spring wheat farming than in counties with lower levels of this crop. Spring wheat, one of the major field crops in these four states, was treated for 85% or more of its acreage with chlorophenoxy herbicides. In the current study NHANES III data were reviewed for associations of 2,4-dichlorophenoxy acetic acid (2,4-D) exposure, one of the most frequently used chlorophenoxy herbicides, with risk factors that are linked to the pathogenesis of acute myocardial infarction and type-2 diabetes, such as dyslipidemia and impaired glucose metabolism.</p> <p>Methods</p> <p>To investigate the toxicity pattern of chlorophenoxy herbicides, effects of a previous 2,4-D exposure were assessed by comparing levels of lipids, glucose metabolism, and thyroid stimulating hormone in healthy adult NHANES III subjects with urinary 2,4-D above and below the level of detection, using linear regression analysis. The analyses were conducted for all available subjects and for two susceptible subpopulations characterized by high glycosylated hemoglobin (upper 50^thpercentile) and low thyroxine (lower 50^thpercentile).</p> <p>Results</p> <p>Presence of urinary 2,4-D was associated with a decrease of HDL levels: 8.6% in the unadjusted data (p-value = 0.006), 4.8% in the adjusted data (p-value = 0.08), and 9% in the adjusted data for the susceptible subpopulation with low thyroxine (p-value = 0.02). An effect modification of the inverse triglycerides-HDL relation was observed in association with 2,4-D. Among subjects with low HDL, urinary 2,4-D was associated with increased levels of triglycerides, insulin, C-peptide, and thyroid stimulating hormone, especially in the susceptible subpopulations. In contrast, subjects with high HDL did not experience adverse 2,4-D associated effects.</p> <p>Conclusions</p> <p>The results indicate that exposure to 2,4-D was associated with changes in biomarkers that, based on the published literature, have been linked to risk factors for acute myocardial infarction and type-2 diabetes.</p

Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak

In its largest outbreak, Ebola virus disease is spreading through Guinea, Liberia, Sierra Leone, and Nigeria. We sequenced 99 Ebola virus genomes from 78 patients in Sierra Leone to ~2000× coverage. We observed a rapid accumulation of interhost and intrahost genetic variation, allowing us to characterize patterns of viral transmission over the initial weeks of the epidemic. This West African variant likely diverged from central African lineages around 2004, crossed from Guinea to Sierra Leone in May 2014, and has exhibited sustained human-to-human transmission subsequently, with no evidence of additional zoonotic sources. Because many of the mutations alter protein sequences and other biologically meaningful targets, they should be monitored for impact on diagnostics, vaccines, and therapies critical to outbreak response.Organismic and Evolutionary Biolog

Ebola virus epidemiology, transmission, and evolution during seven months in Sierra Leone

The 2013-2015 Ebola virus disease (EVD) epidemic is caused by the Makona variant of Ebola virus (EBOV). Early in the epidemic, genome sequencing provided insights into virus evolution and transmission and offered important information for outbreak response. Here, we analyze sequences from 232 patients sampled over 7 months in Sierra Leone, along with 86 previously released genomes from earlier in the epidemic. We confirm sustained human-to-human transmission within Sierra Leone and find no evidence for import or export of EBOV across national borders after its initial introduction. Using high-depth replicate sequencing, we observe both host-to-host transmission and recurrent emergence of intrahost genetic variants. We trace the increasing impact of purifying selection in suppressing the accumulation of nonsynonymous mutations over time. Finally, we note changes in the mucin-like domain of EBOV glycoprotein that merit further investigation. These findings clarify the movement of EBOV within the region and describe viral evolution during prolonged human-to-human transmission

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field