BACKGROUND:The objective of this study was to assess the relationship between exposure to methylprednisolone (MP) and improvements in motor function among patients with acute traumatic spinal cord ...injury (TSCI). MP therapy for patients with TSCI is controversial because of the current conflicting evidence documenting its benefits and risks.
METHODS:We conducted a retrospective cohort study from September 2007 to November 2014 of 311 patients with acute TSCI who were enrolled into a model systems database of a regional, level I trauma center. We linked outcomes and covariate data from the model systems database with MP exposure data from the electronic medical record. The primary outcomes were rehabilitation discharge in American Spinal Injury Association (ASIA) motor scores (sum of 10 key muscles bilaterally as per International Standards for Neurological Classification of Spinal Cord Injury, range, 0–100) and Functional Independence Measure (FIM) motor scores (range, 13–91). Secondary outcomes measured infection risk and gastrointestinal (GI) complications among MP recipients. For the primary outcomes, multivariable linear regression was used.
RESULTS:There were 160 MP recipients and 151 nonrecipients. Adjusting for age, sex, weight, race, respective baseline motor score, surgical intervention, injury level, ASIA Impairment Scale (AIS) grade, education, and insurance status, there was no association with improvement in discharge ASIA motor function or FIM motor score among MP recipients−0.34 (95% CI, −2.8, 2.1) and 0.75 (95% CI, −2.8, 4.3), respectively. Adjusting for age, sex, race, weight, injury level, and receipt of surgery, no association with increased risk of infection or GI complications was observed.
CONCLUSIONS:This retrospective cohort study involving patients with acute TSCI observed no short-term improvements in motor function among MP recipients compared with nonrecipients. Our findings support current recommendations that MP use in this population should be limited.
"Mycobacterium aviumsubsp.hominissuis" is an important cause of pulmonary disease. It is acquired from environmental sources, but there is no methodology for large population studies. We evaluated ...the potential of variable-number tandem-repeat (VNTR) analysis. Clinical and household biofilmM. aviumisolates underwent molecular identification. Testing for IS901was done to separateM. aviumsubsp.aviumfromM. aviumsubsp.hominissuis VNTR types were defined using VNTR loci, and subtyping was performed using 3'hsp65and internal transcribed spacer (ITS) sequencing. Forty-nine VNTR types and eight subtypes ofM. aviumsubsp.hominissuis(IS901negative) were identified among 416 isolates ofM. aviumfrom 121 patients and 80 biofilm sites. Of those types, 67% were found only among patient isolates, 11% only among household water isolates, and 23% among both. Of 13 VNTR types that included ≥4 patients, the majority (61.5%) represented geographic clustering (same city). Most VNTR types with multiple patients belonged to the same 3'hsp65sequence code (sequevar). A total of 44 isolates belonging to fourM. aviumsubsp.hominissuisVNTR types (8%), including three with the rare Mav-F ITS sequence and 0/8 subspecies, produced amplicons with IS901PCR primers. By sequencing, all 44 amplicons were not IS901but ISMav6, which was recently observed in Japan but had not been previously described among U.S. isolates. VNTR analysis ofM. aviumsubsp.hominissuisisolates is easier and faster than pulsed-field gel electrophoresis. Seven VNTR loci separated 417 isolates into 49 types. No isolates ofM. aviumsubsp.aviumwere identified. The distributions of the VNTR copy numbers, the allelic diversity, and the low prevalence of ISMav6 differed from the findings for respiratory isolates reported from Japan.
The RNA degradosome is a multiprotein macromolecular complex that is involved in the degradation of messenger RNA in bacteria. The composition of this complex has been found to display a high degree ...of evolutionary divergence, which may reflect the adaptation of species to different environments. Recently, a degradosome-like complex identified in Bacillus subtilis was found to be distinct from those found in proteobacteria, the degradosomes of which are assembled around the unstructured C-terminus of ribonuclease E, a protein not present in B. subtilis. In this report, we have investigated in vitro the binary interactions between degradosome components and have characterized interactions between glycolytic enzymes, RNA-degrading enzymes, and those that appear to link these two cellular processes. The crystal structures of the glycolytic enzymes phosphofructokinase and enolase are presented and discussed in relation to their roles in the mediation of complex protein assemblies. Taken together, these data provide valuable insights into the structure and dynamics of the RNA degradosome, a fascinating and complex macromolecular assembly that links RNA degradation with central carbon metabolism.
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► The degradosome is a molecular machine that links RNA processing and glycolysis. ► The interactions at the core of the degradosome have physiological relevance. ► The crystal structures of degradosome components suggest an assembly platform. ► The product of enolase inhibits another glycolytic enzyme, phosphofructokinase.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The specific mechanisms underlying general anesthesia are primarily unknown. The intravenous general anesthetic etomidate acts by potentiating GABA(A) receptors, with selectivity for beta2 and beta3 ...subunit-containing receptors determined by a single asparagine residue. We generated a genetically modified mouse containing an etomidate-insensitive beta2 subunit (beta2 N265S) to determine the role of beta2 and beta3 subunits in etomidate-induced anesthesia. Loss of pedal withdrawal reflex and burst suppression in the electroencephalogram were still observed in the mutant mouse, indicating that loss of consciousness can be mediated purely through beta3-containing receptors. The sedation produced by subanesthetic doses of etomidate and during recovery from anesthesia was present only in wild-type mice, indicating that the beta2 subunit mediates the sedative properties of anesthetics. These findings show that anesthesia and sedation are mediated by distinct GABA(A) receptor subtypes.
As pressure on coastal marine resources is increasing globally, the need to quantitatively assess vulnerable fish stocks is crucial in order to avoid the ecological consequences of stock depletions. ...Species of Sciaenidae (croakers, drums) are important components of tropical and temperate fisheries and are especially vulnerable to exploitation. The black‐spotted croaker, Protonibea diacanthus, is the only large sciaenid in coastal waters of northern Australia where it is targeted by commercial, recreational and indigenous fishers due to its food value and predictable aggregating behaviour. Localized declines in the abundance of this species have been observed, highlighting the urgent requirement by managers for information on fine‐ and broad‐scale population connectivity. This study examined the population structure of P. diacanthus across north‐western Australia using three complementary methods: genetic variation in microsatellite markers, otolith elemental composition and parasite assemblage composition. The genetic analyses demonstrated that there were at least five genetically distinct populations across the study region, with gene flow most likely restricted by inshore biogeographic barriers such as the Dampier Peninsula. The otolith chemistry and parasite analyses also revealed strong spatial variation among locations within broad‐scale regions, suggesting fine‐scale location fidelity within the lifetimes of individual fish. The complementarity of the three techniques elucidated patterns of connectivity over a range of spatial and temporal scales. We conclude that fisheries stock assessments and management are required at fine scales (100 s of km) to account for the restricted exchange among populations (stocks) and to prevent localized extirpations of this species. Realistic management arrangements may involve the successive closure and opening of fishing areas to reduce fishing pressure.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
BACKGROUND:Idiopathic intracranial hypertension (IIH) mostly affects overweight and obese women. Severe obesity is associated with poorer visual outcomes in IIH, and weight gain can precipitate IIH ...and increase the risk of recurrence. Conversely, weight loss can decrease intracranial pressure and is an effective IIH treatment. Therefore, accurate monitoring of weight and body mass index (BMI) is important to help guide the management of IIH patients. Our goal was to compare estimated and measured BMI among patients with presumed IIH and non-IIH controls to determine whether these vital signs should be systematically measured when evaluating patients for IIH.
METHODS:A retrospective chart review was performed of consecutive patients with reported and measured weight and height seen in one ophthalmology-based neuro-ophthalmology clinic for IIH between January 2, 2018 and September 10, 2018. Patients with IIH or presumed IIH were compared to non-IIH controls, matched according to age (±5 years), BMI (±5 kg/m unless ≥40 kg/m), sex, and race. Patients with confirmed IIH were asked to self-report their weight when seen in follow-up and they were weighed to compare their self-reported vs measured percent weight change.
RESULTS:We included 379 subjects (140 patients; 239 controls) among whom 75 of the IIH patients were matched to non-IIH controls. Patients with presumed or definite IIH accurately estimated their height and generally underestimated their weight by a median of 1.8 kg (4 lb), resulting in a median BMI underestimate of 0.9 kg/m. There was no difference in BMI underestimation when comparing presumed or definite IIH patients to matched non-IIH controls while controlling for insurance status, smoking, diabetes, and vascular disease (P = 0.66). As BMI increased, all subjects underestimated their BMI more (by 0.9% per 10 measured BMI unit increase), when controlling for age, sex, and race (P < 0.003). Sixteen confirmed IIH patients were seen in follow-up. At initial neuro-ophthalmology consultation, these subjects underestimated their weight by a mean of 3.2%. At last follow-up they underestimated their weight by only 1.2% (P = 0.03).
CONCLUSIONS:There was no evidence that IIH or presumed IIH patients had a different perception of their weight than non-IIH controls at initial neuro-ophthalmology consultation. Both patients and matched controls tended to underestimate their weight by the same amount, resulting in an overall BMI underestimation of approximately 1% per 10 measured BMI unit increase. Heavier subjects tended to underestimate their body weight and resultant BMI more, and IIH patients tended to estimate their weight more accurately at follow-up. Our results emphasize the need to systematically objectively measure the weight of presumed IIH patients seen in an ophthalmology clinic.
BACKGROUND: The American Red Cross (ARC) initiated a comprehensive donor hemovigilance program in 2003. We provide an overview of reported complications after whole blood (WB), apheresis platelet ...(PLT), or automated red cell (R2) donation and analyze factors contributing to the variability in reported complication rates in our national program.
STUDY DESIGN AND METHODS: Complications recorded at the collection site or reported after allogeneic WB, apheresis PLT, and R2 donation procedures in 36 regional blood centers in 2006 were analyzed by univariate and multivariate logistic regression.
RESULTS: Complications after 6,014,472 WB, 449,594 PLT, and 228,183 R2 procedures totaled 209,815, 25,966, and 12,282 (348.9, 577.5, and 538.3 per 10,000 donations), respectively, the vast majority of which were minor presyncopal reactions and small hematomas. Regional center, donor age, sex, and donation status were independently associated with complication rates after WB, PLT, and R2 donation. Seasonal variability in complications rates after WB and R2 donation correlated with the proportion of donors under 20 years old. Excluding large hematomas, the overall rate of major complications was 7.4, 5.2, and 3.3 per 10,000 collections for WB, PLT, and R2 procedures, respectively. Outside medical care was recorded at similar rates for both WB and automated collections (3.2 vs. 2.9 per 10,000 donations, respectively).
CONCLUSION: The ARC data describe the current risks of blood donation in a model multicenter hemovigilance system using standardized definitions and reporting protocols. Reported reaction rates varied by regional center independently of donor demographics, limiting direct comparison of different regional blood centers.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The gas‐phase extrusion–insertion reactions of the copper complex bathophenanthroline (Bphen)CuI(O2CC6H5)2−, generated via electrospray ionization, was studied in a linear ion trap mass spectrometer ...with the combination of collision‐induced dissociation (CID) and ion‐molecule reaction (IMR) events. Multistage mass spectrometry (MSn) experiments and density functional theory (DFT) demonstrated that extrusion of carbon dioxide from (Bphen)Cu(O2CC6H5)2− (CID) gives the organometallic intermediate (Bphen)Cu(C6H5)2−, which subsequently reacts with carbon disulfide (IMR) via insertion to yield (Bphen)Cu (SC(S)C6H5)2−. The fragmentation of the product ion resulted in the formation of Bphen2−, (Bphen)Cu− and C6H5CS2− under CID conditions. The formation of the latter two charge separation products thus provides evidence of C–C bond formation in the IMR step. Although analogous studies with isocyanate, which is isoelectronic with CS2, showed a poor reactivity in the gas phase, the mechanistic understanding obtained from these model studies encourages future development of a solution phase protocol for the synthesis of amides from carboxylic acids and isocyanates mediated by copper(I) complexes.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Schizophrenia is a chronic and debilitating disease which is thought to arise from a neuro-developmental disorder. Both the stable tubule-only polypeptide (STOP) protein and the
N-methyl-
d-aspartate ...(NMDA) NR1 subunit are involved in neuronal development and physiology. It has therefore been postulated that transgenic mice lacking either the STOP or the NMDAR1 gene would show a ‘schizophrenic-like’ phenotype. Here, STOP knockout and NMDA NR1 hypomorphic mice were assessed in a behavioural measure that can be used to detect schizophrenic-like phenotypes: a change in sensorimotor gating, measured through prepulse inhibition (PPI). STOP knockout mice were further assessed in another measure of ‘schizophrenic-like behaviour’: hyperlocomotion. The PPI deficit exhibited by both the STOP knockout and NMDA knockdown mice could not be reversed by acute treatment with the atyptical antipsychotic, clozapine (1
mg/kg, i.p.) but the hyperlocomotion shown by the STOP knockout mice was reversed with the same acute dose of clozapine.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Aicardi Syndrome (AIC) is a rare neurodevelopmental disorder recognized by the classical triad of agenesis of the corpus callosum, chorioretinal lacunae and infantile epileptic spasms syndrome. The ...diagnostic criteria of AIC were revised in 2005 to include additional phenotypes that are frequently observed in this patient group. AIC has been traditionally considered as X-linked and male lethal because it almost exclusively affects females. Despite numerous genetic and genomic investigations on AIC, a unifying X-linked cause has not been identified. Here, we performed exome and genome sequencing of 10 females with AIC or suspected AIC based on current criteria. We identified a unique de novo variant, each in different genes: KMT2B, SLF1, SMARCB1, SZT2 and WNT8B, in five of these females. Notably, genomic analyses of coding and non-coding single nucleotide variants, short tandem repeats and structural variation highlighted a distinct lack of X-linked candidate genes. We assessed the likely pathogenicity of our candidate autosomal variants using the TOPflash assay for WNT8B and morpholino knockdown in zebrafish (Danio rerio) embryos for other candidates. We show expression of Wnt8b and Slf1 are restricted to clinically relevant cortical tissues during mouse development. Our findings suggest that AIC is genetically heterogeneous with implicated genes converging on molecular pathways central to cortical development.
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