Memory reorganization following anterior temporal lobe resection: a longitudinal functional MRI study

Anterior temporal lobe resection controls seizures in 50-60% of patients with intractable temporal lobe epilepsy but may impair memory function, typically verbal memory following left, and visual memory following right anterior temporal lobe resection. Functional reorganization can occur within the ipsilateral and contralateral hemispheres. We investigated the reorganization of memory function in patients with temporal lobe epilepsy before and after left or right anterior temporal lobe resection and the efficiency of postoperative memory networks. We studied 46 patients with unilateral medial temporal lobe epilepsy (25/26 left hippocampal sclerosis, 16/20 right hippocampal sclerosis) before and after anterior temporal lobe resection on a 3 T General Electric magnetic resonance imaging scanner. All subjects had neuropsychological testing and performed a functional magnetic resonance imaging memory encoding paradigm for words, pictures and faces, testing verbal and visual memory in a single scanning session, preoperatively and again 4 months after surgery. Event-related analysis revealed that patients with left temporal lobe epilepsy had greater activation in the left posterior medial temporal lobe when successfully encoding words postoperatively than preoperatively. Greater pre- than postoperative activation in the ipsilateral posterior medial temporal lobe for encoding words correlated with better verbal memory outcome after left anterior temporal lobe resection. In contrast, greater postoperative than preoperative activation in the ipsilateral posterior medial temporal lobe correlated with worse postoperative verbal memory performance. These postoperative effects were not observed for visual memory function after right anterior temporal lobe resection. Our findings provide evidence for effective preoperative reorganization of verbal memory function to the ipsilateral posterior medial temporal lobe due to the underlying disease, suggesting that it is the capacity of the posterior remnant of the ipsilateral hippocampus rather than the functional reserve of the contralateral hippocampus that is important for maintaining verbal memory function after anterior temporal lobe resection. Early postoperative reorganization to ipsilateral posterior or contralateral medial temporal lobe structures does not underpin better performance. Additionally our results suggest that visual memory function in right temporal lobe epilepsy is affected differently by right anterior temporal lobe resection than verbal memory in left temporal lobe epilepsy

Deletion of the gabra2 gene results in hypersensitivity to the acute effects of ethanol but does not alter ethanol self administration

Human genetic studies have suggested that polymorphisms of the GABRA2 gene encoding the GABA(A) α2-subunit are associated with ethanol dependence. Variations in this gene also convey sensitivity to the subjective effects of ethanol, indicating a role in mediating ethanol-related behaviours. We therefore investigated the consequences of deleting the α2-subunit on the ataxic and rewarding properties of ethanol in mice. Ataxic and sedative effects of ethanol were explored in GABA(A) α2-subunit wildtype (WT) and knockout (KO) mice using a Rotarod apparatus, wire hang and the duration of loss of righting reflex. Following training, KO mice showed shorter latencies to fall than WT littermates under ethanol (2 g/kg i.p.) in both Rotarod and wire hang tests. After administration of ethanol (3.5 g/kg i.p.), KO mice took longer to regain the righting reflex than WT mice. To ensure the acute effects are not due to the gabra2 deletion affecting pharmacokinetics, blood ethanol concentrations were measured at 20 minute intervals after acute administration (2 g/kg i.p.), and did not differ between genotypes. To investigate ethanol's rewarding properties, WT and KO mice were trained to lever press to receive increasing concentrations of ethanol on an FR4 schedule of reinforcement. Both WT and KO mice self-administered ethanol at similar rates, with no differences in the numbers of reinforcers earned. These data indicate a protective role for α2-subunits, against the acute sedative and ataxic effects of ethanol. However, no change was observed in ethanol self administration, suggesting the rewarding effects of ethanol remain unchange

An affordable, quality-assured community-based system for high-resolution entomological surveillance of vector mosquitoes that reflects human malaria infection risk patterns.

ABSTRACT: BACKGROUND: More sensitive and scalable entomological surveillance tools are required to monitor low levels of transmission that are increasingly common across the tropics, particularly where vector control has been successful. A large-scale larviciding programme in urban Dar es Salaam, Tanzania is supported by a community-based (CB) system for trapping adult mosquito densities to monitor programme performance. Methodology An intensive and extensive CB system for routine, longitudinal, programmatic surveillance of malaria vectors and other mosquitoes using the Ifakara Tent Trap (ITT-C) was developed in Urban Dar es Salaam, Tanzania, and validated by comparison with quality assurance (QA) surveys using either ITT-C or human landing catches (HLC), as well as a cross-sectional survey of malaria parasite prevalence in the same housing compounds. RESULTS: Community-based ITT-C had much lower sensitivity per person-night of sampling than HLC (Relative Rate (RR) [95% Confidence Interval (CI)] = 0.079 [0.051, 0.121], P < 0.001 for Anopheles gambiae s.l. and 0.153 [0.137, 0.171], P < 0.001 for Culicines) but only moderately differed from QA surveys with the same trap (0.536 [0.406,0.617], P = 0.001 and 0.747 [0.677,0.824], P < 0.001, for An. gambiae or Culex respectively). Despite the poor sensitivity of the ITT per night of sampling, when CB-ITT was compared with QA-HLC, it proved at least comparably sensitive in absolute terms (171 versus 169 primary vectors caught) and cost-effective (153US$versus 187US$ per An. gambiae caught) because it allowed more spatially extensive and temporally intensive sampling (4284 versus 335 trap nights distributed over 615 versus 240 locations with a mean number of samples per year of 143 versus 141). Despite the very low vectors densities (Annual estimate of about 170 An gambiae s.l bites per person per year), CB-ITT was the only entomological predictor of parasite infection risk (Odds Ratio [95% CI] = 4.43[3.027,7. 454] per An. gambiae or Anopheles funestus caught per night, P =0.0373). Discussion and conclusion CB trapping approaches could be improved with more sensitive traps, but already offer a practical, safe and affordable system for routine programmatic mosquito surveillance and clusters could be distributed across entire countries by adapting the sample submission and quality assurance procedures accordingly

The Novel μ-Opioid Receptor Antagonist GSK1521498 Decreases Both Alcohol Seeking and Drinking: Evidence from a New Preclinical Model of Alcohol Seeking.

Distinct environmental and conditioned stimuli influencing ethanol-associated appetitive and consummatory behaviors may jointly contribute to alcohol addiction. To develop an effective translational animal model that illuminates this interaction, daily seeking responses, maintained by alcohol-associated conditioned stimuli (CSs), need to be dissociated from alcohol drinking behavior. For this, we established a procedure whereby alcohol seeking maintained by alcohol-associated CSs is followed by a period during which rats have the opportunity to drink alcohol. This cue-controlled alcohol-seeking procedure was used to compare the effects of naltrexone and GSK1521498, a novel selective μ-opioid receptor antagonist, on both voluntary alcohol-intake and alcohol-seeking behaviors. Rederived alcohol-preferring, alcohol-nonpreferring, and high-alcohol-drinking replicate 1 line of rats (Indiana University) first received 18 sessions of 24 h home cage access to 10% alcohol and water under a 2-bottle choice procedure. They were trained subsequently to respond instrumentally for access to 15% alcohol under a second-order schedule of reinforcement, in which a prolonged period of alcohol-seeking behavior was maintained by contingent presentations of an alcohol-associated CS acting as a conditioned reinforcer. This seeking period was terminated by 20 min of free alcohol drinking access that achieved significant blood alcohol concentrations. The influence of pretreatment with either naltrexone (0.1-1-3 mg/kg) or GSK1521498 (0.1-1-3 mg/kg) before instrumental sessions was measured on both seeking and drinking behaviors, as well as on drinking in the 2-bottle choice procedure. Naltrexone and GSK1521498 dose-dependently reduced both cue-controlled alcohol seeking and alcohol intake in the instrumental context as well as alcohol intake in the choice procedure. However, GSK1521498 showed significantly greater effectiveness than naltrexone, supporting its potential use for promoting abstinence and preventing relapse in alcohol addiction.The present study was funded by Medical Research Council Programme Grant (no. G1002231) and by GlaxoSmithKline (GSK), which has a commercial interest in GSK1521498. Charles R. Goodlett was funded by a grant from the IUPUI International Development Fund, which supported his sabbatical leave at the University of Cambridge. Maria Pilar Garcia-Pardo was funded by Val+id para investigadores en formación (Conselleria de educacion, Generalitat Valenciana), which also supported her stay at the University of Cambridge (January-April 2014) as a Visiting Student.This is the accepted manuscript. The final version is available from NPG at http://dx.doi.org/10.1038/npp.2015.15

Description of a strain from an atypical population of Aspergillus parasiticus that produces aflatoxins B only, and the impact of temperature on fungal growth and mycotoxin production

In this study, an atypical strain of Aspergillus parasiticus is described. This strain, reported from Portuguese almonds, was named Aspergillus parasiticus B strain. The strain is herein characterised at the morphological and physiological levels, and compared with the typical A. parasiticus strain and other similar species in section Flavi. Previously published morphological and molecular data support that the B strain is very closely related to the A. parasiticus type strain. However, while A. parasiticus typically produces aflatoxins B and G, B strain produces aflatoxins B only. Furthermore, this atypical strain showed to differ from the typical strain in the fact that higher growth (colony diameter) and strain. This strain can become a major food safety concern in colder regions where the typical A. parasiticus strains are not well adapted.NORTE-07-0124-FEDER-000028PEst-OE/EQB/LA0023/2013PEst-OE/AGR/UI0690/201

Management and prognostic factors of recurrent pleomorphic adenoma of the parotid gland: personal experience and review of the literature

The aim of this study was to investigate the management and prognostic determinants of recurrent pleomorphic adenoma (RPA). A retrospective analysis was performed to examine the clinical features, the prevalence of surgical complications, and new recurrences of RPA. Tumor recurrence rate was estimated by the Kaplan–Meier method, and the prognostic value of some of the variables was tested by univariate analysis using the log rank test. The study focused on 33 patients, 18 female (54.5%) and 15 male (45.5%), aged 12–71 years (median 41). A total or extended total parotidectomy was performed in 16 cases (48.5%), a superficial parotidectomy in 10 cases (30.3%), and a local excision in 7 cases (21.2%). In ten patients (30.3%), a branch or the trunk of the facial nerve was deliberately sacrificed. Major complications included one unexpected definitive paralysis of the marginal mandibular branch of the facial nerve and 14 cases of Frey syndrome. Follow-up varied from 2 to 25 years (median 10.5 years), and there were 11 new recurrences (33.3%) within a period varying from 1 to 16 years (median 6 years). The estimated tumor recurrence rates were 14.1 ± 6.6% at 5 years, 31.4 ± 9.4% at 10 years, 43.0 ± 10.8% at 15 years, and 57.2 ± 14.8% at 20 years. Presence of a multinodular lesion and the type of intervention performed were significantly associated with a higher probability of recurrence. RPAs are prone to new recurrences, especially when multinodular and treated with a local excision. Surgical treatment should include facial nerve resection in selected cases. Follow-up for the patient’s lifetime is warranted

Dynamic 3D shape of the plantar surface of the foot using coded structured light:a technical report

The foot provides a crucial contribution to the balance and stability of the musculoskeletal system, and accurate foot measurements are important in applications such as designing custom insoles/footwear. With better understanding of the dynamic behavior of the foot, dynamic foot reconstruction techniques are surfacing as useful ways to properly measure the shape of the foot. This paper presents a novel design and implementation of a structured-light prototype system providing dense three dimensional (3D) measurements of the foot in motion. The input to the system is a video sequence of a foot during a single step; the output is a 3D reconstruction of the plantar surface of the foot for each frame of the input. Methods Engineering and clinical tests were carried out to test the accuracy and repeatability of the system. Accuracy experiments involved imaging a planar surface from different orientations and elevations and measuring the fitting errors of the data to a plane. Repeatability experiments were done using reconstructions from 27 different subjects, where for each one both right and left feet were reconstructed in static and dynamic conditions over two different days. Results The static accuracy of the system was found to be 0.3 mm with planar test objects. In tests with real feet, the system proved repeatable, with reconstruction differences between trials one week apart averaging 2.4 mm (static case) and 2.8 mm (dynamic case). Conclusion The results obtained in the experiments show positive accuracy and repeatability results when compared to current literature. The design also shows to be superior to the systems available in the literature in several factors. Further studies need to be done to quantify the reliability of the system in clinical environment

Crenarchaeal CdvA Forms Double-Helical Filaments Containing DNA and Interacts with ESCRT-III-Like CdvB

International audienceBACKGROUND: The phylum Crenarchaeota lacks the FtsZ cell division hallmark of bacteria and employs instead Cdv proteins. While CdvB and CdvC are homologues of the eukaryotic ESCRT-III and Vps4 proteins, implicated in membrane fission processes during multivesicular body biogenesis, cytokinesis and budding of some enveloped viruses, little is known about the structure and function of CdvA. Here, we report the biochemical and biophysical characterization of the three Cdv proteins from the hyperthermophilic archaeon Metallospherae sedula. METHODOLOGY/PRINCIPAL FINDINGS: Using sucrose density gradient ultracentrifugation and negative staining electron microscopy, we evidenced for the first time that CdvA forms polymers in association with DNA, similar to known bacterial DNA partitioning proteins. We also observed that, in contrast to full-lengh CdvB that was purified as a monodisperse protein, the C-terminally deleted CdvB construct forms filamentous polymers, a phenomenon previously observed with eukaryotic ESCRT-III proteins. Based on size exclusion chromatography data combined with detection by multi-angle laser light scattering analysis, we demonstrated that CdvC assembles, in a nucleotide-independent way, as homopolymers resembling dodecamers and endowed with ATPase activity in vitro. The interactions between these putative cell division partners were further explored. Thus, besides confirming the previous observations that CdvB interacts with both CdvA and CdvC, our data demonstrate that CdvA/CdvB and CdvC/CdvB interactions are not mutually exclusive. CONCLUSIONS/SIGNIFICANCE: Our data reinforce the concept that Cdv proteins are closely related to the eukaryotic ESCRT-III counterparts and suggest that the organization of the ESCRT-III machinery at the Crenarchaeal cell division septum is organized by CdvA an ancient cytoskeleton protein that might help to coordinate genome segregation