Prevalence,Risk Factors,and Transmission Dynamics of Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae: a National Survey of Cattle Farms in Israel in 2013

Our objectives were to study the prevalence, risk factors for carriage, and transmission dynamics of extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae (ESBLPE) in a national survey of cattle. This was a point prevalence study conducted from July to October 2013 in Israel. Stool samples were collected from 1,226 cows in 123 sections on 40 farms of all production types. ESBLPE were identified in 291 samples (23.7%): 287 contained Escherichia coli and 4 contained Klebsiella pneumoniae. The number of ESBLPE-positive cows was the highest in quarantine stations and on fattening farms and was the lowest on pasture farms (P = 0.03). The number of ESBLPE-positive cows was the lowest in sections containing adult cows (age, >25 months) and highest in sections containing calves (age, <4 months) (P < 0.001). Infrastructure variables that were significant risk factors for ESBLPE carriage included crowding, a lack of manure cleaning, and a lack of a cooling (P < 0.001 for each), all of which were more common in sections containing calves. Antimicrobial prophylaxis was given almost exclusively to calves and was associated with a high number of ESBLPE carriers (P < 0.001). The 287 E. coli isolates were typed into 106 repetitive extragenic palindromic (REP)-PCR types and mostly harbored bla_CTX-M-1 or bla_CTX-M-9 group genes. The isolates on the six farms with ≥15 isolates of ESBLPE were of 4 to 7 different REP-PCR types, with one dominant type being harbored by about half of the isolates. Fourteen types were identified on more than one farm, with only six of the farms being adjacent to each other. The prevalence of ESBLPE carriage is high in calves in cowsheds where the use of antimicrobial prophylaxis is common. ESBLPE disseminate within cowsheds mainly by clonal spread, with limited intercowshed transmission occurring.     

Degrees of severity and recovery in agrammatism: Climbing up the syntactic tree

Background : Agrammatic aphasia impairs syntactic abilities in production and comprehension. The Tree Pruning Hypothesis (TPH) suggests that the syntactic deficit in production can be described in terms of inability to access the high nodes of the syntactic tree. Aims : The current study explored patterns of individual differences between individuals with agrammatic aphasia, and suggested a characterisation for different degrees of agrammatic severity using the syntactic tree. A second aim was to test the path of spontaneous recovery in agrammatic aphasia. Methods & Procedures : The first experiment tested 18 individuals with agrammatism: 16 were Hebrew speakers, and 2 were speakers of Palestinian Arabic. The syntactic ability of the participants was assessed with respect to three levels of the syntactic tree. To test the ability at the Agreement Phrase (AgrP) level, a task of agreement completion was used. To test the ability at the Tense Phrase (TP) level, a task of tense inflection completion was used. The ability at the highest level of the tree, the Complementiser Phrase (CP), was tested using elicitation tasks for two structures: Wh-questions and relative clauses. The second experiment tested the recovery of these four abilities over time in SB, an individual with agrammatism, starting 4.5 months post her brain injury until 18 months post-onset. Outcomes & Results : The main findings were that the variation between the performance of different individuals with agrammatism and degrees of agrammatic severity could be accounted for by different sites of pruning on the syntactic tree. Severe agrammatism results from inability to access TP and the nodes above it, which impairs both tense inflection and CP-related abilities like the production of embedded sentences and Wh-questions. Milder agrammatism results from the inaccessibility of a higher node, CP, which causes a deficit to embedded sentences and Wh-questions, but leaves tense unimpaired. For both degrees of severity, agreement inflection was unimpaired. The second experiment showed that the spontaneous recovery of SB proceeded on the syntactic tree: the starting point was impairment in AgrP, TP, and CP, at the next stage AgrP recovered, and at the following stage TP recovered too. Conclusions : The results show that the syntactic tree is not only a useful tool for the characterisation of agrammatic aphasia at one point in time; it can also account for individual differences as well as for degrees of agrammatic severity, and can describe stages of spontaneous recovery. A milder impairment, or improvement in agrammatism, manifests itself in the ability to access higher nodes of the syntactic tree.     

Hyperinsulinism of infancy: novel ABCC8 and KCNJ11 mutations and evidence for additional locus heterogeneity

Hyperinsulinism of infancy is a genetically heterogeneous disease characterized by dysregulation of insulin secretion resulting in severe hypoglycemia. To date, mutations in five different genes, the sulfonylurea receptor (SUR1, ABCC8), the inward rectifying potassium channel (K(IR)6.2, KCNJ11), glucokinase (GCK), glutamate dehydrogenase (GLUD1), and short-chain 3-hydroxyacyl-coenzyme A dehydrogenase (SCHAD), have been implicated. Previous reports suggest that, in 40% of patients, no mutation can be identified in any of these genes, suggesting additional locus heterogeneity. However, previous studies did not screen all five genes using direct sequencing, the most sensitive technique available for mutation detection. We selected 15 hyperinsulinism of infancy patients and systematically sequenced the promoter and all coding exons and intron/exon boundaries of ABCC8 and KCNJ11. If no mutation was identified, the coding sequence and intron/exon boundaries of GCK, GLUD1, and SCHAD were sequenced. Seven novel mutations were found in the ABCC8 coding region, one mutation was found in the KCNJ11 coding region, and one novel mutation was found in each of the two promoter regions screened. Functional studies on beta-cells from six patients showed abnormal ATP-sensitive K+ channel function in five of the patients; the sixth had normal channel activity, and no mutations were found. Photolabeling studies using a reconstituted system showed that all missense mutations altered intracellular trafficking. Each of the promoter mutations decreased expression of a reporter gene by about 60% in a heterologous expression system. In four patients (27%), no mutations were identified. Thus, further genetic heterogeneity is suggested in this disorder. These patients represent a cohort that can be used for searching for mutations in other candidate genes.     

Heat acclimation provides sustained improvement in functional recovery and attenuates apoptosis after traumatic brain injury

Heat acclimation (HA) offers functional neuroprotection in mice after traumatic brain injury (TBI). This study further characterizes endogenous neuroprotection acquired by HA (34±1°C, 30 d) after TBI. We establish here the ability of HA to induce sustained functional benefits and to reduce activation of apoptotic pathways. Neurobehavioral recovery, assessed by the Neurological Severity Score, was greater in HA mice up to 8 days after injury as compared with normothermic controls (P<0.05) and lesion volume was also smaller in the HA group (P<0.05). Reduced apoptotic cell death in HA mice was confirmed using caspase-3 activity measurements and immunohistochemistry. To investigate the underlying molecular pathways, expression levels of intrinsic apoptotic pathway-related proteins were examined. HA mice displayed higher mitochondrial levels of antiapoptotic Bcl-xL, accompanied by lower proapoptotic Bad levels and decreased cytochrome c release, suggesting a higher apoptotic threshold. Taken together with our previous reports, indicating increased Akt phosphorylation and antioxidative capacity, alongside with reduced tumor necrosis α levels after TBI in HA animals, the current results support the involvement of an antiapoptotic effect in HA-induced neuroprotection. Current results warrant further study as TBI-induced apoptosis may persist over weeks after injury, possibly providing a target for belated therapeutic intervention.