Positive regulation of Vav1 by Themis controls CD4 T cell pathogenicity in a mouse model of central nervous system inflammation.

The susceptibility to autoimmune diseases is conditioned by the association of modest genetic alterations which altogether weaken self-tolerance. The mechanism whereby these genetic interactions modulate T-cell pathogenicity remains largely uncovered. Here, we investigated the epistatic interaction of two interacting proteins involved in T Cell Receptor signaling and which were previously associated with the development of Multiple Sclerosis.

Eomes-dependent mitochondrial regulation promotes survival of pathogenic CD4+ T cells during inflammation.

The mechanisms whereby Eomes controls tissue accumulation of T cells and strengthens inflammation remain ill-defined. Here, we show that Eomes deletion in antigen-specific CD4+ T cells is sufficient to protect against central nervous system (CNS) inflammation. While Eomes is dispensable for the initial priming of CD4+ T cells, it is required for long-term maintenance of CNS-infiltrating CD4+ T cells.

THEMIS enhances the magnitude of normal and neuroinflammatory type 1 immune responses by promoting TCR-independent signals.

Signals that determine the differentiation of naïve CD4 T helper (T) cells into specific effector cell subsets are primarily stimulated by cytokines, but additional signals are required to adjust the magnitude of T cell responses and set the balance between effective immunity and immunological tolerance. By inducing the post-thymic deletion of the T cell lineage signaling protein THEMIS, we showed that THEMIS promoted the development of optimal type 1 immune responses to foreign antigens but stimulated signals that favored encephalitogenic responses to self-neuroantigens. THEMIS was required to stimulate the expression of the gene encoding the transcriptional regulator T-BET and the production of the cytokine interferon-γ (IFN-γ), and it enhanced the ability of encephalitogenic CD4 T cells to migrate into the central nervous system.

Developmental dysplasia of the hip: real world data from a retrospective analysis to evaluate the effectiveness of universal screening.

Aims: Developmental dysplasia of the hip is an important cause of disability in children and young adult and it also has a significant socio-economic impact in our society. The main objective of our study is to evaluate, in our hospital, the effectiveness of a universal ultrasound screening protocol and to assess the general knowledge about the theme of pediatricians and neonatologists.

Methods: Retrospective study of infants born from January 2016 to April 2019, evaluated with hip ultrasound (Graf method).

Resolution of femoral metaphyseal dysplasia in CINCA syndrome after long-term treatment with interleukin-1 blockade.

Chronic infantile neurological cutaneous articular (CINCA) syndrome is a rare autoinflammatory disorder driven by uncontrolled hypersecretion of interleukin (IL)-1, which can be clinically depicted by striking cutaneous, neurologic, and skeletal features. Little is known about the exact pathogenesis of CINCA bone disease, which mainly involves the knees. We report a 20-year-old CINCA patient, who was consecutively treated firstly with anakinra, started at 7 years, then with full dose canakinumab, started at 17 years, focusing on the typical bone abnormalities of the syndrome: the comparison of radiographs of knees performed at 7 and 20 years has shown the disappearance of a typical metaphyseal dysplasia occurring in the femurs of this CINCA patient, regularly treated with IL-1 blockade for a period of 13 years.

Paracetamol-codeine compared to ketorolac for pain control in the Emergency Department.

Objective: Paracetamol /codeine has shown a strong analgesic activity in several studies conducted among different kind of subjects, including those with trauma. Nevertheless, its efficacy in patients accessing the Emergency Department (ED) for different kind of pain has never been tested.

Patients And Methods: This is a cross-sectional, observational, prospective, cohort study.

Quantitative immunohistochemical assessment of IgA, IgM, IgG and antigen-specific immunoglobulin secreting plasma cells in pig small intestinal lamina propria.

Intestinal immune response plays an important defensive role for pathogens, particularly for those transmitted by the oro-faecal route or for foecal shedding modulation. This work examined three parts of intestine from twelve gilts experimentally infected with PCV2-spiked semen, six vaccinated (V group) and six unvaccinated (NV group) against PCV2, 29 and 53 days post infection (DPI). An immunohistochemical investigation for IgA-, IgG- and IgM-antibody bearing plasma cells (PCs) was run on intestinal samples coupled with a sandwich immunohistochemical method to reveal anti-PCV2 antibody-secreting PCs.

Long-term response after 6-year treatment with anakinra and onset of focal bone erosion in neonatal-onset multisystem inflammatory disease (NOMID/CINCA).

The exact elucidation of skeletal and cartilagineous involvement in neonatal-onset multisystem inflammatory disease (NOMID) is still poorly known, and there are few data providing the long-term response to treatment with the available interleukin-1 inhibitors. We present here a 13-year-old boy with NOMID treated with anakinra and low-dose methylprednisolone since he was 7 years old for an overall period of 6 years. Every clinical manifestation was highly responsive to interleukin-1 blockade, with the exception of his bone abnormalities.

Exercise-induced rhabdomyolysis and transient loss of deambulation as outset of partial carnitine palmityl transferase II deficiency.

We report the case of a 13-year-old boy with an abrupt onset of leg pain and muscle weakness, incapability of deambulation and a laboratory picture of exercise-induced acute rhabdomyolysis. Intravenous hyperhydration and forced diuresis were adopted to avoid renal complications. No evidence of articular or residual muscular damage was appreciated in the short-term.

Transcranial magnetic stimulation over MT/MST fails to impair judgments of implied motion.

The medial temporal and medial superior temporal cortex (MT/MST) is involved in the processing of visual motion, and fMRI experiments indicate that there is greater activation when subjects view static images that imply motion than when they view images that do not imply motion at all. We applied transcranial magnetic stimulation (TMS) to MT/MST in order to assess the functional necessity of this region for the processing of implied motion represented in static images. Area MT/MST was localized by the use of a TMS-induced misperception of visual motion, and its location was verified through the monitored completion of a motion discrimination task.

Normal attention orienting but abnormal stimulus alerting and conflict effect in combined subtype of ADHD.

Recent pharmacological studies in animals and neuroimaging studies in normal humans suggest that the spatial and nonspatial cues in tasks measuring reflexive attention may be modulated by different neurotransmitter systems. The efficiency with which attention is oriented to explicit spatial cues may be altered by manipulating levels of brain acetylcholine, whereas reactions to nonspatial cues may be influenced by altering brain noradrenaline levels but not acetylcholine levels. In humans, however, previous attention studies have implicated dopamine when either explicit or implicit cueing is used.

Attentional validity effect across the human menstrual cycle varies with basal temperature changes.

This study examined the correlation between covert attention and basal temperature change during menstrual cycle phase in 22 adult females. Previous work showing beneficial effects of estrogen on working memory led us to hypothesize that attentional function would be facilitated at the apparent time of ovulation. Menstrual phase was determined through questionnaires and objective measurements of basal body temperature (BBT) spikes over a 1 month period.

Norepinephrine and acetylcholine mediation of the components of reflexive attention: implications for attention deficit disorders.

Attention deficit hyperactivity disorders (ADHD) create major learning barriers for children and significant social and legal handicaps for adults worldwide. Important advances in the genetic basis of the disease have been made, but reliable, biological, diagnostic markers remain elusive. This review takes the position that future progress in treating the core symptom of attention deficits requires a clearer understanding of the neuroscience of attention in normal individuals.

Salivary cotinine levels in human tobacco smokers predict the attentional validity effect size during smoking abstinence.

Rationale: The link between attention and brain cholinergic neurotransmission is widely accepted. Human chronic tobacco smokers maintain high levels of nicotine in plasma and body tissues and show enhanced attentional orienting and other attentional tasks.

Objective: We wished to test whether abstinence from smoking caused levels of the nicotine metabolite cotinine to decline and attentional enhancement to be reduced in a correlated manner.

Electrical microstimulation of primate posterior parietal cortex initiates orienting and alerting components of covert attention.

The posterior parietal cortex (PPC) is implicated in the control of visuospatial orienting, including both overt saccadic eye movements and covert shifts of attention (i.e., attention to a location other than at visual fixation).

Cholinergic modulation of covert attention in the rat.

Rationale: Nicotine is known to facilitate attentional processing, but its role in processing spatial and non-spatial cues is not well established in rodents.

Objective: These experiments tested the hypothesis that nicotine facilitates the orienting of attention in space but has no effect on non-spatial cues and that the benefits are blocked by the nicotinic antagonist mecamylamine.

Methods: Eight male rats were trained to insert their noses in an opening, which triggered the presentation of cue and target lights in a modified covert orienting task.

Attention as a target of intoxication: insights and methods from studies of drug abuse.

A symposium was convened to discuss recent developments in the assessment of attention and the effects of drugs and toxic chemicals on attention at the 17th annual meeting of the Behavioral Toxicology Society on May 1, 1999, in Research Triangle Park, NC. Speakers addressed issues including the methodology of assessing cognitive function, the neurobiology of specific aspects of attention, the dual roles of attention as a target of intoxication and as a mediating variable in the development of addiction to psychoactive drugs, the changes in attention that accompany neuropsychological disorders of schizophrenia, senile dementia of the Alzheimer type and attention deficit hyperactivity disorder, and potential therapies for these disorders. This article provides an overview of the objectives of the symposium, followed by summaries of each of the talks given.

Head-related transfer functions of the Rhesus monkey.

Head-related transfer functions (HRTFs) are direction-specific acoustic filters formed by the head, the pinnae and the ear canals. They can be used to assess acoustical cues available for sound localization and to construct virtual auditory environments. We measured the HRTFs of three anesthetized Rhesus monkeys (Macaca mulatta) from 591 locations in the frontal hemisphere ranging from -90 degrees (left) to 90 degrees (right) in azimuth and -60 degrees (down) to 90 degrees (up) in elevation for frequencies between 0.

Local infusion of scopolamine into intraparietal cortex slows covert orienting in rhesus monkeys.

There is accumulating evidence to suggest that cholinergic neurotransmission may play an important role in visuospatial attention, but the brain sites at which acetylcholine modulates attention are not well understood. The present work tested the hypothesis that the cholinergic influences within the intraparietal cortex are necessary for normal attentional shifting (covert orienting) in nonhuman primates. Two rhesus monkeys were trained to perform a visual, cued target detection task for liquid reinforcement.

Scopolamine slows the orienting of attention in primates to cued visual targets.

The cholinergic agonist nicotine facilitates visuospatial attention shifting, but the role of muscarinic cholinergic drugs in this behavior is unclear. In order to establish the generality of cholinergic action in attention shifting, we administered the muscarinic antagonist scopolamine to two rhesus monkeys trained to perform a cued target detection (Posner) task. In this task, monkeys signaled the detection of a peripheral visual target by releasing a switch and their reaction times were measured.

Ribosomal RNA genes of Phaseolus coccineus. IV. Structure and comparative-analysis of the intergenic spacer: possible involvement of some nucleotides in the transcription control of coding sequences. Sequence of the intergenic spacer of ribosomal genes.

The sequence of the intergenic spacer (IGS) of Phaseolus coccineus is determined. The IGS contains three distinct regions: Region A, constant in length; Region B, heterogeneous in length among genes, including two very similar segments 162 and 177 bp long, repeated two and nine times respectively in the investigated clone; Region C, constant in length, comprising five islands. The putative promoters and the sites of termination, processing and methylation are detected by a comparison with other plant systems.

Effects of altering brain cholinergic activity on covert orienting of attention: comparison of monkey and human performance.

Experiments were conducted to elucidate the role of the cholinergic neurotransmitter system in arousal and the orienting of attention to peripheral targets. Rhesus monkeys and humans fixated a visual stimulus and responded to the onset of visual targets presented randomly in two visual field locations. The target was preceded by a valid cue (cue and target at the same location), an invalid cue (cue and target to opposite locations), a double cue (cues to both spatial locations, target to one), or, the cue was omitted (no-cue, target to either location).

Alteration of brain noradrenergic activity in rhesus monkeys affects the alerting component of covert orienting.

Experiments were conducted to elucidate the role of the noradrenergic neurotransmitter system in arousal and the orienting of attention. Rhesus monkeys were trained to perform a peripherally cued, covert orienting task for juice reward, and their manual reaction times (RTs) to visual stimuli were measured. The effects of parenteral injections of the alpha-2 adrenergic agonists clonidine and guanfacine, and normal saline were compared on the covert task.

Visual orienting and alerting in rhesus monkeys: comparison with humans.

The behavioral capacities of the rhesus monkey for several sensory and cognitive tasks appear quite similar to those of humans. To evaluate the monkey's attentional capacities, we have compared monkey and human performance on a visuospatial attentional task, the cued target detection (CTD) paradigm. Animals were trained to fixate a small spot of light while a cue and a subsequent target, are flashed in the visual periphery.