CaRMeN: a tool for analysing and deriving kinetics in the real world.

This paper presents the concepts of an open software tool (CaRMeN) that can be used to rapidly analyse and derive models, in particular chemical kinetics. The software automates the workflow of comparing model vs. experiment, which must currently be done manually and is thus a time-consuming and error-prone task. The capabilities of the software are illustrated through a case study. Experimental data for the conversion of methane over rhodium catalysts in a wide range of conditions and experimental setups are numerically simulated using five different mechanisms from the literature. The applicability of the mechanisms as well as differences between flow and diffusion models are evaluated. The results show that no single mechanism reliably predicts the chemical conversions of all of the experiments. Although the software was initially developed for chemical kinetics applications, it can also be extended to run any simulation code, and can therefore be applied in other scenarios.

Indole-3-butyric acid promotes adventitious rooting in Arabidopsis thaliana thin cell layers by conversion into indole-3-acetic acid and stimulation of anthranilate synthase activity.

BACKGROUND: Indole-3-acetic acid (IAA), and its precursor indole-3-butyric acid (IBA), control adventitious root (AR) formation in planta. Adventitious roots are also crucial for propagation via cuttings. However, IBA role(s) is/are still far to be elucidated. In Arabidopsis thaliana stem cuttings, 10 µM IBA is more AR-inductive than 10 µM IAA, and, in thin cell layers (TCLs), IBA induces ARs when combined with 0.1 µM kinetin (Kin). It is unknown whether arabidopsis TCLs produce ARs under IBA alone (10 µM) or IAA alone (10 µM), and whether they contain endogenous IAA/IBA at culture onset, possibly interfering with the exogenous IBA/IAA input. Moreover, it is unknown whether an IBA-to-IAA conversion is active in TCLs, and positively affects AR formation, possibly through the activity of the nitric oxide (NO) deriving from the conversion process. RESULTS: Revealed undetectable levels of both auxins at culture onset, showing that arabidopsis TCLs were optimal for investigating AR-formation under the total control of exogenous auxins. The AR-response of TCLs from various ecotypes, transgenic lines and knockout mutants was analyzed under different treatments. It was shown that ARs are better induced by IBA than IAA and IBA + Kin. IBA induced IAA-efflux (PIN1) and IAA-influx (AUX1/LAX3) genes, IAA-influx carriers activities, and expression of ANTHRANILATE SYNTHASE -alpha1 (ASA1), a gene involved in IAA-biosynthesis. ASA1 and ANTHRANILATE SYNTHASE -beta1 (ASB1), the other subunit of the same enzyme, positively affected AR-formation in the presence of exogenous IBA, because the AR-response in the TCLs of their mutant wei2wei7 was highly reduced. The AR-response of IBA-treated TCLs from ech2ibr10 mutant, blocked into IBA-to-IAA-conversion, was also strongly reduced. Nitric oxide, an IAA downstream signal and a by-product of IBA-to-IAA conversion, was early detected in IAA- and IBA-treated TCLs, but at higher levels in the latter explants. CONCLUSIONS: Altogether, results showed that IBA induced AR-formation by conversion into IAA involving NO activity, and by a positive action on IAA-transport and ASA1/ASB1-mediated IAA-biosynthesis. Results are important for applications aimed to overcome rooting recalcitrance in species of economic value, but mainly for helping to understand IBA involvement in the natural process of adventitious rooting.

Ethylene and auxin interaction in the control of adventitious rooting in Arabidopsis thaliana.

Adventitious roots (ARs) are post-embryonic roots essential for plant survival and propagation. Indole-3-acetic acid (IAA) is the auxin that controls AR formation; however, its precursor indole-3-butyric acid (IBA) is known to enhance it. Ethylene affects many auxin-dependent processes by affecting IAA synthesis, transport and/or signaling, but its role in AR formation has not been elucidated. This research investigated the role of ethylene in AR formation in dark-grown Arabidopsis thaliana seedlings, and its interaction with IAA/IBA. A number of mutants/transgenic lines were exposed to various treatments, and mRNA in situ hybridizations were carried out and hormones were quantified In the wild-type, the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC) at 0.1 µM enhanced AR formation when combined with IBA (10 µM), but reduced it when applied alone; this effect did not occur in the ein3eil1 ethylene-insensitive mutant. ACC inhibited the expression of the IAA-biosynthetic genes WEI2, WEI7, and YUC6, but enhanced IBA-to-IAA conversion, as shown by the response of the ech2ibr10 mutant and an increase in the endogenous levels of IAA. The ethylene effect was independent of auxin-signaling by TIR1-AFB2 and IBA-efflux by ABCG carriers, but it was dependent on IAA-influx by AUX1/LAX3.Taken together, the results demonstrate that a crosstalk involving ethylene signaling, IAA-influx, and IBA-to-IAA conversion exists between ethylene and IAA in the control of AR formation.

Arabidopsis SHR and SCR transcription factors and AUX1 auxin influx carrier control the switch between adventitious rooting and xylogenesis in planta and in in vitro cultured thin cell layers.

BACKGROUND AND AIMS: Adventitious roots (ARs) are essential for vegetative propagation. The Arabidopsis thaliana transcription factors SHORT ROOT (SHR) and SCARECROW (SCR) affect primary/lateral root development, but their involvement in AR formation is uncertain. LAX3 and AUX1 auxin influx carriers contribute to primary/lateral root development. LAX3 expression is regulated by SHR, and LAX3 contributes to AR tip auxin maximum. In contrast, AUX1 involvement in AR development is unknown. Xylogenesis is induced by auxin plus cytokinin as is AR formation, but the genes involved are largely unknown. Stem thin cell layers (TCLs) form ARs and undergo xylogenesis under the same auxin plus cytokinin input. The aim of this research was to investigate SHR, SCR, AUX1 and LAX3 involvement in AR formation and xylogenesis in intact hypocotyls and stem TCLs in arabidopsis. METHODS: Hypocotyls of scr-1, shr-1, lax3, aux1-21 and lax3/aux1-21 Arabidopsis thaliana null mutant seedlings grown with or without auxin plus cytokinin were examined histologically, as were stem TCLs cultured with auxin plus cytokinin. SCR and AUX1 expression was monitored using pSCR::GFP and AUX1::GUS lines, and LAX3 expression and auxin localization during xylogenesis were monitored by using LAX3::GUS and DR5::GUS lines. KEY RESULTS: AR formation was inhibited in all mutants, except lax3. SCR was expressed in pericycle anticlinally derived AR-forming cells of intact hypocotyls, and in cell clumps forming AR meristemoids of TCLs. The apex was anomalous in shr and scr ARs. In all mutant hypocotyls, the pericycle divided periclinally to produce xylogenesis. Xylary element maturation was favoured by auxin plus cytokinin in shr and aux1-21. Xylogenesis was enhanced in TCLs, and in aux1-21 and shr in particular. AUX1 was expressed before LAX3, i.e. in the early derivatives leading to either ARs or xylogenesis. CONCLUSIONS: AR formation and xylogenesis are developmental programmes that are inversely related, but they involve fine-tuning by the same proteins, namely SHR, SCR and AUX1. Pericycle activity is central for the equilibrium between xylary development and AR formation in the hypocotyl, with a role for AUX1 in switching between, and balancing of, the two developmental programmes.

Cold perception and gene expression differ in Olea europaea seed coat and embryo during drupe cold acclimation.

FAD2 and FAD7 desaturases are involved in cold acclimation of olive (Olea europaea) mesocarp. There is no research information available on cold acclimation of seeds during mesocarp cold acclimation or on differences in the cold response of the seed coat and embryo. How FAD2 and FAD7 affect seed coat and embryo cold responses is unknown. Osmotin positively affects cold acclimation in olive tree vegetative organs, but its role in the seeds requires investigation. OeFAD2.1, OeFAD2.2, OeFAD7 and Oeosmotin were investigated before and after mesocarp acclimation by transcriptomic, lipidomic and immunolabelling analyses, and cytosolic calcium concentration ([Ca(2+)](cyt)) signalling, F-actin changes and seed development were investigated by epifluorescence/histological analyses. Transient [Ca(2+)](cyt) rises and F-actin disassembly were found in cold-shocked protoplasts from the seed coat, but not from the embryo. The thickness of the outer endosperm cuticle increased during drupe exposure to lowering of temperature, whereas the embryo protoderm always lacked cuticle. OeFAD2 transcription increased in both the embryo and seed coat in the cold-acclimated drupe, but linoleic acid (i.e. the product of FAD2 activity) increased solely in the seed coat. Osmotin was immunodetected in the seed coat and endosperm of the cold-acclimated drupe, and not in the embryo. The results show cold responsiveness in the seed coat and cold tolerance in the embryo. We propose a role for the seed coat in maintaining embryo cold tolerance by increasing endosperm cutinization through FAD2 and osmotin activities.

Auxin and cytokinin control formation of the quiescent centre in the adventitious root apex of Arabidopsis.

BACKGROUND AND AIMS: Adventitious roots (ARs) are part of the root system in numerous plants, and are required for successful micropropagation. In the Arabidopsis thaliana primary root (PR) and lateral roots (LRs), the quiescent centre (QC) in the stem cell niche of the meristem controls apical growth with the involvement of auxin and cytokinin. In arabidopsis, ARs emerge in planta from the hypocotyl pericycle, and from different tissues in in vitro cultured explants, e.g. from the stem endodermis in thin cell layer (TCL) explants. The aim of this study was to investigate the establishment and maintenance of the QC in arabidopsis ARs, in planta and in TCL explants, because information about this process is still lacking, and it has potential use for biotechnological applications. METHODS: Expression of PR/LR QC markers and auxin influx (LAX3)/efflux (PIN1) genes was investigated in the presence/absence of exogenous auxin and cytokinin. Auxin was monitored by the DR5::GUS system and cytokinin by immunolocalization. The expression of the auxin-biosynthetic YUCCA6 gene was also investigated by in situ hybridization in planta and in AR-forming TCLs from the indole acetic acid (IAA)-overproducing superroot2-1 mutant and its wild type. KEY RESULTS: The accumulation of auxin and the expression of the QC marker WOX5 characterized the early derivatives of the AR founder cells, in planta and in in vitro cultured TCLs. By determination of PIN1 auxin efflux carrier and LAX3 auxin influx carrier activities, an auxin maximum was determined to occur at the AR tip, to which WOX5 expression was restricted, establishing the positioning of the QC. Cytokinin caused a restriction of LAX3 and PIN1 expression domains, and concomitantly the auxin biosynthesis YUCCA6 gene was expressed in the apex. CONCLUSIONS: In ARs formed in planta and TCLs, the QC is established in a similar way, and auxin transport and biosynthesis are involved through cytokinin tuning.

A carcinoid tumor of the middle ear masquerading as a glomus tympanicum presenting with temporal lobe hemorrhage in a 70-year-old woman: Case report and review of the literature.

BACKGROUND: Paragangliomas in the central nervous system account for 0.6% of all head and neck neoplasms, with glomus tympanicum being the most common middle ear tumor. Carcinoid tumors are neuroendocrine tumors, representing less than 1% of neuroendocrine neoplasms in the middle ear. Misdiagnoses have been reported in the literature regarding glomus and carcinoid tumors, however, none have been in the central nervous system or middle ear. CASE DESCRIPTION: A 70-year-old female with a history of left temporal lobe tumor underwent unsuccessful resection due to intraoperative bleeding at an outside institution. However, biopsy prior to aborting the case led to the diagnosis of paraganglioma. Eight years postoperatively, the patient presented at our institution with acute confusion, aphasia, and altered mental status. Imaging revealed a 4cm left temporal intraparenchymal hematoma at the known tumor site with concern for intracranial tumor extension. Surgical resection was performed and previous symptoms resolved. Final pathology revealed a Grade II atypical carcinoid tumor with an unusually high Ki-67 of 50%. CONCLUSIONS: Carcinoid tumors of the middle ear constitute a differential diagnosis for patients presenting with temporal lobe hemorrhage. A combination of immunohistochemical staining with electron microscopy can assist in differentiating the tumor types. This atypical presentation for a carcinoid tumor in the middle ear suggests the need to consider carcinoid as the diagnosis in patients with a middle ear tumor invading into the temporal lobe and causing hemorrhage. These tumors may demonstrate an unusually high Ki-67 rate, in which case they should be treated aggressively.

Modified superior inverted internal limiting membrane flap technique with vitrectomy versus vitrectomy with internal limiting membrane peeling for retinal detachment with myopic macular hole.

PURPOSE: To evaluate the efficacy of the modified superior inverted internal limiting (ILM) membrane flap technique in retinal reattachment, macular hole closure and external retinal layers restoration in macular hole associated retinal detachment compared to ILM peeling. METHODS: Retrospective case series of 10 patients that required pars plana vitrectomy for retinal detachment with macular hole followed for more than 12 months. Data from medical records were retrospectively collected and patients were divided into the superior inverted flap (5 patients) and ILM peeling group (5 patients). We compared best corrected visual acuity (BCVA) before and after surgery, retinal attachment, macular hole closure rate and external retinal layer restoration between groups. RESULTS: There were significant improvements in BCVA in both groups before and after surgery, with no differences between the two groups at 12 months after surgery (p=0.9). The macular hole closed in 100% of cases in the inverted flap group and 80% of the ILM peeling group with no significant differences between groups. The retina was reattached in 100% of cases in both groups. Only 2 patients in the inverted flap group (40%) had external retinal layer restoration and none in ILM peeling group (p=0.62). CONCLUSIONS: ILM peeling and superior inverted flap techniques are useful for treating retinal detachment with macular hole in myopic eyes.

Cold affects the transcription of fatty acid desaturases and oil quality in the fruit of Olea europaea L. genotypes with different cold hardiness.

The olive tree lacks dormancy and is low temperature sensitive, with differences in cold tolerance and oil quality among genotypes. The oil is produced in the drupe, and the unsaturated fatty acids contribute to its quality. The aim of the present research was to investigate the relationship among development, cold response, expression of fatty acid desaturase (FAD) genes, and unsaturated fatty acid composition in drupes belonging to genotypes differing in leaf cold tolerance, but producing good oil (i.e. the non-hardy Moraiolo, the semi-hardy Frantoio, and the hardy Canino). In all genotypes, cold sensitivity, evaluated by cold-induced transient increases in cytosolic calcium, was high in the epi-mesocarp cells before oil body formation, and decreased during oil biogenesis. However, genotype-dependent differences in cold sensitivity appeared at the end of oil production. Genotype-dependent differences in FAD2.1, FAD2.2, FAD6, and FAD7 expression levels occurred in the epi-mesocarp cells during the oleogenic period. However, FAD2.1 and FAD7 were always the highest in the first part of this period. FAD2.2 and FAD7 increased after cold applications during oleogenesis, independently of the genotype. Unsaturated fatty acids increased in the drupes of the non-hardy genotype, but not in those of the hardy one, after cold exposure at the time of the highest FAD transcription. The results show a direct relationship between FAD expression and lipid desaturation in the drupes of the cold-sensitive genotype, and an inverse relationship in those of the cold-resistant genotype, suggesting that drupe cold acclimation requires a fine FAD post-transcriptional regulation. Hypotheses relating FAD desaturation to storage and membrane lipids, and genotype cold hardiness are discussed.

Neonicotinoids in the agroecosystem: In-field long-term assessment on honeybee colony strength and microbiome.

Bees can be severely affected by various plant protection products (PPP). Among these, neonicotinoid insecticides are of concern as they have been shown to be responsible for extensive honeybee colonies death when released into the environment. Also, sublethal neonicotinoid doses contaminating single honeybees and their colonies (e.g. through contaminated pollen) are responsible for honeybees physiological alterations with probable implication also on microbiome functionality. Honeybees show symbiotic interactions with specific gut bacteria that can enhance the adult host performances. Among the known mechanisms, the modulation of the immune system, the degradation of recalcitrant secondary plant metabolites, pollen digestion, and hormonal signaling, are the most important functional benefits for the host honeybee. To date, few research efforts have aimed at revealing the impact of PPP on the gut microbial community of managed and wild honeybees. The majority of the existing literature relays on cage or semifield tests of short duration for research investigating neonicotinoids-gut microbiome interactions. This research wanted to unravel the impact of two neonicotinoids (i.e. imidacloprid and thiacloprid) in natural field conditions up to 5 weeks of exposure. A long-term impact of neonicotinoids on gut microbial community of honeybees was observed. The alterations affected several microbial genera and species such as Frischella spp., lactobacilli and bifidobacteria, whose shifting is implicated in intestinal dysbiosis. Long-term impact leading to dysbiosis was detected in case of exposure to imidacloprid, whereas thiacloprid exposure stimulated temporary dysbiosis. Moreover, the microbial diversity was significantly reduced in neonicotinoid-treated groups. Overall, the reported results support a compromised functionality of the gut microbial community, that might reflect a lower efficiency in the ecosystemic functionality of honeybees.

Cadmium and arsenic-induced-stress differentially modulates Arabidopsis root architecture, peroxisome distribution, enzymatic activities and their nitric oxide content.

In plant cells, cadmium (Cd) and arsenic (As) exert toxicity mainly by inducing oxidative stress through an imbalance between the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), and their detoxification. Nitric oxide (NO) is a RNS acting as signalling molecule coordinating plant development and stress responses, but also as oxidative stress inducer, depending on its cellular concentration. Peroxisomes are versatile organelles involved in plant metabolism and signalling, with a role in cellular redox balance thanks to their antioxidant enzymes, and their RNS (mainly NO) and ROS. This study analysed Cd or As effects on peroxisomes, and NO production and distribution in the root system, including primary root (PR) and lateral roots (LRs). Arabidopsis thaliana wild-type and transgenic plants enabling peroxisomes to be visualized in vivo, through the expression of the 35S-cyan fluorescent protein fused to the peroxisomal targeting signal1 (PTS1) were used. Peroxisomal enzymatic activities including the antioxidant catalase, the H2O2-generating glycolate oxidase, and the hydroxypyruvate reductase, and root system morphology were also evaluated under Cd/As exposure. Results showed that Cd and As differently modulate these activities, however, catalase activity was inhibited by both. Moreover, Arabidopsis root system was altered, with the pollutants differently affecting PR growth, but similarly enhancing LR formation. Only in the PR apex, and not in LR one, Cd more than As caused significant changes in peroxisome distribution, size, and in peroxisomal NO content. By contrast, neither pollutant caused significant changes in peroxisomes size and peroxisomal NO content in the LR apex.

Preclinical ex vivo expansion of peripheral blood CD34+ selected cells from cancer patients mobilized with combination chemotherapy and granulocyte colony-stimulating factor.

BACKGROUND AND OBJECTIVES: Ex vivo peripheral blood progenitor cell (PBPC) expansion has been proposed as a strategy to increase the number of haematopoietic progenitors available for cell transplantation. We have expanded CD34+ cells from PBPCs obtained from four patients with haematological malignancies and one patient with an Ewing's sarcoma. MATERIALS AND METHODS: Cells were expanded in the Dideco 'Pluricell system'. After 12 days in culture, we evaluated cell phenotype, total nucleated cells, CD34+ fold increase, cell apoptosis and colony assay of expanded cells. Cell engraftment has been evaluated by transplanting two groups of irradiated non-obese diabetic/severe combined immunodeficient (NOD-SCID) mice with expanded and non-expanded cell populations. RESULTS: Total nucleated cells and CD34+ cells increased 59.5 and 4.0 times, respectively. The expanded cells were mainly constituted of myeloid and megakaryocytic cells. A significant increase in the number of colony-forming unit-granulocyte macrophage (CFU-GM) was observed in the CFU assay. Ten mice transplanted with expanded cells showed a best overall survival (80%) compared to 10 mice transplanted with non-expanded cells (20%). Human CD45+ cells were detected by flow cytometry and polymerase chain reaction in bone marrow and spleen of transplanted animals. The relative low engraftment level obtained with the expanded cells suggests a loss of SCID repopulating cells maybe due to cell differentiation during expansion. CONCLUSIONS: We have demonstrated the feasibility of the ex vivo expansion of mobilized PBPCs from cancer patients, evidencing a clonal expansion of CFUs and the ability of the expanded cells to engraft the bone marrow and spleen of immunosuppressed mice. The differentiation of the CD34+ stem cell compartment could be further minimized by ameliorating the expansion conditions.

Audiological and genetic features of the mtDNA mutations.

CONCLUSIONS: Significant difference in the incidence of mitochondrial DNA (mtDNA) mutations was found between the Chinese and USA populations. The identification of the mtDNA A1555G mutation in a large proportion of Chinese probands with nonsyndromic sensorineural hearing loss (NSHL) provides a molecular explanation for the high prevalence of aminoglycoside-induced deafness in China. OBJECTIVE: The aim was to characterize the audiological and genetic features of NSHL due to mutations in mtDNA. SUBJECTS AND METHODS: The mtDNA and audiogram analyses were performed in 498 NSHL patients (290 from China and 208 from the USA) with and without history of aminoglycoside exposure. A PCR and restriction enzyme digestion protocol was used for mutational screening and the European Workshop on Genetic Hearing Loss criteria were applied for audiological classification. RESULTS: All Chinese probands (15.5%) with mtDNA mutation were found to carry the homoplasmic mtDNA A1555G mutation, whereas four probands (1.9%) from the USA were found to carry the mtDNA A1555G and two (1%) had mtDNA G7444A. Approximately 63% of the probands with mtDNA mutations had post-lingual hearing loss and 56.8% of them had a medical history of exposure to aminoglycosides. Hearing losses are bilateral, sensorineural, and symmetric. The main audiogram shapes found were sloping.

The amyotrophic lateral sclerosis center: a model of multidisciplinary management.

Amyotrophic lateral sclerosis (ALS) is a devastating, progressive motor neuron disorder that poses a myriad of clinical problems. Patients who have ALS are best cared for in a multidisciplinary fashion, with involvement of clinicians from various specialties, including neurology, physical medicine and rehabilitation, pulmonary medicine, clinical nurse specialists or nurse practitioners, physical and occupational therapists, speech language pathologists, dietitians, psychologists, social workers, and case managers. This article provides a summary of the current research into the rehabilitation of ALS, including the role of exercise, spasticity management, mood disorders, pain, and palliative care.

Associations of the plasma interleukin 6 (IL-6) levels with disability and mortality in the elderly in the Treviso Longeva (Trelong) study.

IL-6 expression is regulated by the interplay of several transcriptional and hormonal factors, including sex steroids and glucocorticoids. In late life IL-6 expression increases as a result from loss of the normally inhibiting sex steroids. IL-6 is one of several proinflammatory cytokines. It has been proposed that many chronic inflammatory diseases are the result of a dysregulation of IL-6 expression. In this work we demonstrate that increased IL-6 levels in elderly are associated with higher disability and mortality, also independently of age and comorbidity.

The Treviso Longeva (Trelong) study: a biomedical, demographic, economic and social investigation on people 70 years and over in a typical town of North-East of Italy.

Longevity is a complex process resulting from genetic and environmental factors, as well as their interaction. These factors are poorly understood, and the comparison among health status, socio-economics, demographic and other characteristics of the elderly people can help in understanding these complex interactions. Such an interdisciplinary approach is necessary to allow an appropriate evaluation of longevity. Here we report the methodology and the first results of a representative study performed in 2003-2004 on people of 70 years and over, living in a typical town of North-East of Italy. In the research we collected biomedical, demographic, socio-economic and quality of life (QoL) data.

Balance sensory organization in children with profound hearing loss and cochlear implants.

OBJECTIVES: (1) To determine the feasibility of the use of a modified postural control test under altered sensory conditions in children over 8 years of age, and (2) to assess how deaf children use sensory information for postural control when they have normal or abnormal vestibular responses, and if hearing input from a unilateral cochlear implant, changes their postural behavior. PATIENTS: We selected 36 children, 8 to 11 years of age, with congenital or early-acquired profound sensorineural hearing loss, 13 of them with unilateral cochlear implantation and 22 normal-hearing children. METHODS: The Postural Control (PC) test consists of a force platform with 2 stimulation paradigm conditions: (1) standing on the platform with opened eyes; (2) standing on foam placed on the force platform with closed eyes. Implanted children were tested with the implant turn on and turn off in this condition, in order to evaluate eventual change in the postural control parameters when they have hearing habilitation. The body center of pressure distribution area (COP) and the body sway velocity (SV) were the parameter to evaluate the postural control. RESULTS: Deaf children were classified into two groups according with the vestibular responses: group A (n=28) Children with normal vestibular rotary responses; group B (n=8) children with hypoactive responses. Children in group A had diagnoses of syndromic and non-syndromic hereditary deafness, and children in group B had inner ear malformations, post-meningitis deafness, and one child had non-syndromic hereditary deafness with hypoactive vestibular response. In condition 1, when vestibular, somatosensory and visual information were enabled, the COP and SV values did not show any statistically significant differences between groups A, B and control. In condition 2, when visual information was removed and the somatosensory input strongly modified by standing on the foam, group B showed significant higher COP and SV values than groups A and control (p<0.05). In addition, the scalograms by wavelets of children in group B had higher amplitudes increasing the sway frequencies contents up to 3 Hz, not allowing them to maintain the up right stance in similar stimulation than in condition. Implanted children of the group A and B with the implant turn on, in the condition 2, did not show any significant difference in the SV, comparing when they had the implanted turn off. Group A p=0.395 and group B p=0.465 (Wilcoxon ranked test). CONCLUSION: These findings allow us to confirm that this postural test can be performed in children over 8 years old. Also our results suggest that deaf children with associated hypoactive vestibular responses included in our study, despite the etiology of the deafness, primarily use visual and somatosensory information to maintain their postural control. Hearing habilitation with a unilateral cochlear implant has no effect on the observed sensory organization strategy.

Effects of Dalfampridine Extended-release Tablets on 6-minute Walk Distance in Patients With Multiple Sclerosis: A Post Hoc Analysis of a Double-blind, Placebo-controlled Trial.

PURPOSE: Dalfampridine extended-release (ER) tablets 10 mg BID have been approved for use in improving walking in people with multiple sclerosis (MS). This subgroup analysis evaluated the effects of dalfampridine ER 5 and 10 mg BID on distance walked, as assessed using the 6-minute walk (6MW) test. METHODS: This analysis of data from a randomized, placebo-controlled, double-blind study (N = 430) included only the 153 patients with 6MW data available. Participants (aged 18-70 years) were randomly assigned in a 1:1:1 ratio to receive dalfampridine ER 5 or 10 mg or placebo, BID for 4 weeks. The 6MW was used for assessing walking distance at baseline and 2 weeks after the start of treatment at the 26 study sites that were able to perform this test. Participants were administered the 12-item MS Walking Scale (MSWS-12), a patient-reported measure of the impact of MS on walking. Post hoc outcomes included the percentages of patients who achieved an increase from baseline in 6MW distance of ≥20% and who achieved a minimal clinically important difference (MCID) from baseline in 6MW distance, defined as ≥+55 m. Changes from baseline in walking speed (MSWS-12) were compared, stratified by subgroup that achieved ≥20% versus <20% improvement on the 6MW. The correlation between change in walking speed over time and subgroup (by change in distance walked) was evaluated. The tolerability of dalfampridine was assessed based on the prevalence of treatment-emergent adverse events (TEAEs). FINDINGS: In the post hoc analysis, the percentage of patients with an improvement in 6MW distance that met or exceeded the MCID was significantly greater with dalfampridine ER 10 mg BID relative to placebo (37.3% vs 12.2%; nominal P = 0.004). Similarly, the percentage with an improvement in 6MW distance of ≥20% was significantly greater with dalfampridine 10 mg BID relative to placebo (45.1% vs 14.3%; nominal P < 0.001). Regardless of treatment allocation, improvement in MSWS-12 was significantly greater in the subgroup that achieved a ≥20% improvement on the 6MW compared with the subgroup with <20% improvement (mean changes, -15.5 vs -7.2; nominal P = 0.041). The prevalences and types of TEAEs were consistent with those reported in previous studies. IMPLICATIONS: Based on the MCID for 6MW, the use of dalfampridine ER 10 mg BID but not 5 mg BID was associated with statistically significant and clinically meaningful improvements in walking relative to placebo. The correlation between improvement on MSWS-12 and the 20% increase in 6MW distance suggests that an improvement on MSWS-12 is clinically relevant. These results, although highlighting a lack of efficacy of dalfampridine ER 5 mg BID, suggest that the 10-mg BID dose is effective for improving walking speed, as observed on short timed-walk tests, and for increasing distance walked over longer timed-walk periods. ClinicalTrials.gov identifier: NCT01328379.

Hippocampectomized monkeys can remember one place but not two.

In an earlier study by Parkinson et al. (J. Neurosci. 8, 4159-4167, 1988), hippocampectomized monkeys were found to be impaired on a task in which they were required to remember the spatial positions of trial-unique objects overlying two of the wells in a three-well test tray. There were two types of trial in the task. One type (object-place) required memory for the conjunction of object quality and object location, whereas the other (place only) required memory only for the location of the objects, i.e. independent of object quality. The hippocampectomized monkeys performed at near chance levels on both types of trials. The present study sought to determine whether the poor performance of the hippocampectomized monkeys on the place-only trials, which closely resembled spatial delayed response (an ability that is unaffected by hippocampectomy when similarly short delays are used), could have been due to interference from the simultaneous training they had received on the object-place trials. To this end, we examined the effect of hippocampal removals on performance of the "place-only" trial type when that was the only training given. The hippocampectomized monkeys in the present study were found to be just as severely impaired as those in the earlier study, thus ruling out the possible explanation outlined above. Since performance on this modified version of spatial delayed response, unlike performance on the classical version with the same delay, is critically dependent on the hippocampus, it appears that monkeys with hippocampectomy can remember one place after a short delay but not two.