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Background: The recreational use of nitrous oxide (N2O) has increased in recent years with a noticeable surge in the incidence of nitrous oxide-related myeloneuropathy., Objectives: To raise awareness of increasing myeloneuropathy due to recreational nitrous oxide misuse in Israel., Methods: We conducted a case series documenting the clinical and investigative features of eight patients presenting with nitrous oxide-induced myeloneuropathy who were admitted to our departments., Results: Paresthesia was the chief complaint in all patients, with sensory gait ataxia being a common feature, which was often accompanied by Romberg's sign and mild lower limb weakness. Vitamin B12 levels were below the normal range in seven patients, accompanied by elevated homocysteine and methylmalonic acid levels. Magnetic resonance imaging scans revealed hyperintense signals in the dorsal columns of the cervical spine. All patients improved following vitamin B12 injections., Conclusions: Enhancing awareness, prompting the use of appropriate investigations, and advocating for timely treatment are needed to overcome the risks associated with nitrous oxide misuse.

A 67-year-old man presented with 5 months of worsening memory impairment and sensory gait ataxia on the background of symptomatic anaemia. He experienced falls, agitation and became socially withdrawn over 3 weeks, resulting in hospital admission. On examination, he had sensory gait ataxia consistent with a dorsal column syndrome. He scored 13/30 on the Montreal Cognitive Assessment. Serum analysis showed normocytic anaemia and leucopenia, severe hypocupraemia, reduced caeruloplasmin and normal zinc levels. Overuse of zinc-containing denture cream was the cause of excess zinc ingestion and resultant copper deficiency, leading to blood dyscrasia and myelopathy. The cream was withdrawn and intravenous and then oral copper supplementation was implemented. Direct questions with regard to excess zinc in the diet and serological testing of copper and zinc should be considered in any patient with a dorsal column syndrome, particularly with concurrent anaemia. Copper deficiency may also have a role in exacerbating pre-existing cognitive impairment., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Diagnosis of sacroiliac region pain is supported by a positive response to sacroiliac region analgesia (SIRA). Varying techniques have been described for SIRA; with clinician preference often dictating method. Potential complications following SIRA include ataxia and recumbency. No study has specifically evaluated the prevalence of complications., Objectives: To describe the complication prevalence following SIRA in a referral clinic., Study Design: Retrospective cohort study., Methods: Review of records from horses presented to two of the authors at Rossdales, Newmarket, between January 2014 and December 2018, that underwent SIRA. Injection was performed using a blind midline approach with 20 mL mepivacaine (Intra-Epicaine 20mg/ml; Dechra) infiltrated through a straight 18 gauge 8.9cm spinal needle subdivided into four sub-locations per block., Results: 118 horses were included, with 167 individual blocks. One horse showed a mild hindlimb gait abnormality following SIRA, which resolved uneventfully over 3 hours; complication rate 1/118 horses (0.85%; 95% CI: 0,2.5%), 1/167 joints (0.60%; 95% CI: 0,1.8%). SIRA subjectively improved lameness/performance in 132/167 (79%) joints. 49/118 (42%) received bilateral SIRA with 53/118 (45%) evaluated ridden following SIRA., Main Limitations: Small population numbers with low complication prevalence rate., Conclusions: SIRA, using the described technique, has a low (0.85%) prevalence of complications., Competing Interests: The authors have declared that no competing interests exist.

Background: Hyperammonemic encephalopathy is a rare and serious adverse reaction to valproate. Although there is documentation of this reaction in previous reports, very little is still known about the exact mechanism of action. In addition, there are no established guidelines of the next steps needed when a patient does develop this reaction. Therefore, this case report highlights what is known as well as the areas of research still needed., Case Presentation: Our patient was a 57-year-old Caucasian woman with a medical history of bipolar I disorder, opioid use disorder, benzodiazepine use disorder, and Crohn's disease who was admitted to our behavioral health unit for suicidal ideation. She had been experiencing multiple panic attacks for 2.5 weeks along with poor sleep, increased energy, excessive spending, and feelings of helplessness. The patient was diagnosed with bipolar I disorder, manic episode without psychotic features, and benzodiazepine use disorder. She was started on valproic acid, citalopram, propranolol, and quetiapine. By day 6 of her hospitalization, the patient had altered mental status, varying levels of consciousness, confusion, and ataxic gait. Her ammonia levels were found to be elevated. All of her medications were discontinued, and lactulose was initiated. She returned to her baseline mentation within 48 hours and was discharged with lithium and quetiapine. The treatment team concluded that this patient had valproate-induced hyperammonemic encephalopathy, a rare but reversible reaction to valproate., Conclusion: Fortunately, rapid identification of this rare condition led to a favorable outcome in our patient. This case report illustrates the course of treatment in a patient who experienced this reaction and reviews current knowledge as well as areas of needed research in regard to valproate-induced hyperammonemic encephalopathy.

Background: A decrease in fatty acid amide hydrolase (FAAH) activity increases the levels of endogenous analogues of cannabinoids, or endocannabinoids. FAAH inhibitors have shown analgesic and antiinflammatory activity in animal models, and some have been tested in phase 1 and 2 studies. In a phase 1 study, BIA 10-2474, an orally administered reversible FAAH inhibitor, was given to healthy volunteers to assess safety., Methods: Single doses (0.25 to 100 mg) and repeated oral doses (2.5 to 20 mg for 10 days) of BIA 10-2474 had been administered to 84 healthy volunteers in sequential cohorts; no severe adverse events had been reported. Another cohort of participants was then assigned to placebo (2 participants) or 50 mg of BIA 10-2474 per day (6 participants). This report focuses on neurologic adverse events in participants in this final cohort. A total of 4 of the 6 participants who received active treatment consented to have their clinical and radiologic data included in this report., Results: An acute and rapidly progressive neurologic syndrome developed in three of the four participants starting on the fifth day of drug administration. The main clinical features were headache, a cerebellar syndrome, memory impairment, and altered consciousness. Magnetic resonance imaging showed bilateral and symmetric cerebral lesions, including microhemorrhages and hyperintensities on fluid-attenuated inversion recovery and diffusion-weighted imaging sequences predominantly involving the pons and hippocampi. One patient became brain dead; the condition of two patients subsequently improved, but one patient had residual memory impairment, and the other patient had a residual cerebellar syndrome. One patient remained asymptomatic., Conclusions: An unanticipated severe neurologic disorder occurred after ingestion of BIA 10-2474 at the highest dose level used in a phase 1 trial. The underlying mechanism of this toxic cerebral syndrome remains unknown.

We present a case of adverse neurological effects of methylphenidate therapy for attention deficit and hyperactivity disorder (ADHD). A 7-year-old boy presented to the emergency department (ED) having developed ataxic gait, orofacial dyskinesias and choreoathetosis of the limbs. The results of all blood investigations, EEG and CT scan of the head were unremarkable. Subsequently, a detailed history revealed he was being treated for ADHD, being started on methylphenidate in the past 3 months. Discontinuation of methylphenidate led to significant and rapid amelioration of neurological adverse effects., (2015 BMJ Publishing Group Ltd.)

Venipuncture is common in children, and topical anesthetics are often used to alleviate the pain of the procedure. The J-Tip (National Medical Products, Inc, Irvine, Calif) device has become popular as a rapid and effective means of delivering lidocaine noninvasively. We report a case of a positive lidocaine blood toxicology screen after the use of the J-Tip device in a child pre-venipuncture. A repeat toxicology screen obtained 1 hour later by venipuncture without J-Tip use was negative. This report serves to remind clinicians that topical anesthetics may interfere with toxicology assays, leading to unreliable toxicology results.

Background: Exposure to cyanide from cassava foods is present in communities where ataxic polyneuropathy is endemic. Ataxic polyneuropathy is endemic in coastal parts of southwest and southeast Nigeria, and coastal Newala, south India, but it has been reported in epidemic or endemic forms from Africa, Asia, or Caribbean. This study was done to determine if cyanogenicity of cassava cultivars is higher in lowland than highland areas, and if areas of endemicity of ataxic polyneuropathy colocalize with areas of highest cyanogenicity of cassava., Methods: Roots of cassava cultivars were collected from 150 farmers in 32 of 37 administrative areas in Nigeria. Global positioning system was used to determine the location of the roots. Roots were assayed for concentrations of cyanogens. Thin Plate Spline regression was used to produce the contour map of cyanogenicity of the study area. Contour maps of altitude of the endemic areas were produced. Relationship of cyanogenicity of cassava cultivars and altitude, and of locations of areas of high cyanogenicity and areas of endemicity were determined., Results: Geometrical mean (95% CI) cyanogen concentration was 182 (142-233) mg HCN eq/kg dry wt for cassava cultivars in areas ≤ 25 m above sea level, but 54 (43-66) mg HCN eq/kg dry wt for areas > 375 m. Non-spatial linear regression of altitude on logarithm transformed concentrations of cyanogens showed highly significant association, (p < 0.0001). Contour map of concentrations of cyanogens in cassava cultivars in Nigeria showed four areas with average concentrations of cassava cyanogens > 250 mg HCN eq/kg dry wt, and one area of moderately high cyanogen concentration > 150 mg HCN eq/kg dry wt. The endemic areas colocalized with areas of highest cassava cyanogenicity in lowland areas close to the Atlantic Ocean., Conclusion: This study shows strong geospatial association of areas of endemicity of ataxic polyneuropathy and areas of highest cyanogenicity of cassava cultivars. Finding of higher cyanogenicity of cassava in lowland than highland areas indicate strong influence of altitude on expression of cyanogens in cassava cultivars.

Objective: To report a case of risperidone-induced Pisa syndrome in a patient with multiple sclerosis (MS) that resolved with lurasidone, recurred with chlorpromazine, and was complicated by possible drug-drug interactions., Case Summary: A 31-year-old white male with MS developed Pisa syndrome after years of treatment with risperidone at varying doses for behavioral symptoms associated with pervasive developmental disorder. The patient experienced improvement in symptoms after treatment was switched to lurasidone; however, due to psychiatric decompensation, a switch to chlorpromazine was made and Pisa syndrome recurred. To maintain control of the patient's behavioral symptoms, chlorpromazine was not discontinued., Discussion: Pisa syndrome is a rare adverse drug reaction induced most often by neuroleptic medications. The reaction is characterized by dystonia affecting cervical and lumbar musculature, resulting in flexion of the head and body to one side with axial rotation of the trunk. The etiology is believed to involve a dopaminergic-cholinergic imbalance. Most practitioners are not familiar with this syndrome, and it has not been reported previously in a patient with MS. Definitive diagnostic criteria and treatment have not been established. We identified 15 case reports involving risperidone, paliperidone, chlorpromazine, clomipramine, or valproic acid. The time to development of Pisa syndrome, patient demographics, dosing and titration of causative medications, approach to treatment, and resolution of Pisa syndrome varied widely in these reports. Dystonia in MS often presents differently than Pisa syndrome. The Naranjo probability scale indicated a probable relationship between either risperidone or chlorpromazine in each instance of Pisa syndrome in our patient., Conclusions: Pisa syndrome is a rare adverse drug reaction associated with neuroleptic medications. Our report highlights the importance of identifying this uncommon type of dystonia in order to consider modification of the medication regimen when appropriate.

Propensity to develop acute functional (or within session) tolerance to alcohol (ethanol) may influence the amount of alcohol consumed, with higher drinking associated with greater acute functional tolerance (AFT). The goal of this study was to assess this potential correlated response between alcohol preference and AFT in second and third replicate lines of mice selectively bred for high (HAP2 and HAP3) and low (LAP2 and LAP3) alcohol preference drinking. Male and female mice were tested for development of AFT on a static dowel task, which requires that animals maintain balance on a wooden dowel in order to prevent falling. On test day, each mouse received one (1.75 g/kg; Experiment 1) or two (1.75 and 2.0 g/kg; Experiment 2) injections of ethanol; an initial administration before being placed on the dowel and in Experiment 2, an additional administration after the first regain of balance on the dowel. Blood samples were taken immediately after loss of balance [when blood ethanol concentrations (BECs) were rising] and at recovery (during falling BECs) in Experiment 1, and after first and second recovery in Experiment 2. It was found that HAP mice fell from the dowel significantly earlier and at lower BECs than LAP mice following the initial injection of ethanol and were therefore more sensitive to its early effects. Furthermore, Experiment 1 detected significantly greater AFT development (BECfalling--BECrising) in HAP mice when compared with LAP mice, which occurred within ~30 min, supporting our hypothesis. However, AFT was not different between lines in Experiment 2, indicating that ~30-60 min following alcohol administration, AFT development was similar in both lines. These data show that high alcohol drinking genetically associates with both high initial sensitivity and very early tolerance to the ataxic effects of ethanol., (© 2012 The Authors. Genes, Brain and Behavior © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.)

Despite recent advances in the understanding of ethanol's biological action, many of the molecular targets of ethanol and mechanisms behind ethanol's effect on behavior remain poorly understood. In an effort to identify novel genes, the products of which regulate behavioral responses to ethanol, we recently identified a mutation in the dtao gene that confers resistance to the locomotor stimulating effect of ethanol in Drosophila. dtao encodes a member of the Ste20 family of serine/threonine kinases implicated in MAP kinase signaling pathways. In this study, we report that conditional ablation of the mouse dtao homolog, Taok2, constitutively and specifically in the nervous system, results in strain-specific and overlapping alterations in ethanol-dependent behaviors. These data suggest a functional conservation of dtao and Taok2 in mediating ethanol's biological action and identify Taok2 as a putative candidate gene for ethanol use disorders in humans., (© 2012 The Authors. Genes, Brain and Behavior © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.)

More sensitive assays of mouse motor ataxia may provide a better understanding of the pathological profile. Treadmill gait analysis using ventral imaging allows for unhindered access to the ambulating mouse. In contrast to genetic mutations or exogenous brain injury, ethanol (EtOH) allows for the detection of dose dependent changes in motor behavior, which can be used to assess an assay's detection sensitivity. EtOH induced ataxia was assessed in C57BL/6J (B6) and 129X1/SvJ (129) mice using the DigiGait imaging system. Gait was analyzed across EtOH dosage (1.75, 2.25 and 2.75 g/kg) in each strain using a linear mixed effects model. Overall, 129 mice displayed greater susceptibility to EtOH ataxia than their B6 counterparts. In both strains, hind paws exhibited greater sensitivity to EtOH dosage than fore paws. Across most variables analyzed, only a modest EtOH-induced change in motor behavior was observed in each strain with the 1.75 g/kg EtOH doses failing to elicit significant change. These data indicate the ability to detect motor differences between strains, yet only moderate ability to detect change across EtOH dosage using the automated treadmill. Rotarod assays, however, were able to detect motor impairment at lower doses of EtOH. The significant, but opposite changes in paw placement with increasing EtOH doses highlight strain-specific differences in biophysical adaptations in response to acute EtOH intoxication., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: We conducted a prospective randomized controlled study on the influence of multiple doses of activated charcoal (MDAC) in patients with supratherapeutic serum phenytoin levels;, Methods: Patients with serum phenytoin levels greater than 30 mg/L upon presentation to the ED were recruited from two urban teaching hospitals. Patients enrolled were older than 18, nonpregnant, able to tolerate activated charcoal by mouth and able to give written consent. They were randomized to receive 50 g activated charcoal by mouth every 4 hours or no activated charcoal. They continued in the study until the patient was discharged or the serum level was <25 mg/L. Serum levels were drawn every 6 hours initially, then every 24 hours after the 1st day. The presence of gait abnormalities and nystagmus was recorded and mini-mental status exam (MMSE) scores were collected from each patient enrolled. Time to reach subtoxic levels was recorded;, Results: Seventeen patients were enrolled in the study. Seven patients received MDAC, eight patients served as controls and two patients who were initially enrolled as controls inadvertently received one dose of activated charcoal and were excluded from the analysis. Both groups were comparable in age and all were male. The median time to reach a subtoxic level was 41.1 hours (range, 11.6-196) and 19.3 hours (range, 13-33) in the control and charcoal groups, respectively (p = 0.049). The median and range peak serum levels were 40.0 hours (range, 32.0-47.6) and 35.6 hours (range, 32.5-40.0) in the control and charcoal groups, respectively (p = 0.082). The median and range MMSE scores were 20 points (range, 12-30) and 19.5 points (range, 16-29) in the control and charcoal groups, respectively;, Conclusion: Further study is needed to determine if MDAC decreases the time to reach a subtoxic level of phenytoin in patients with supratherapeutic phenytoin levels.

Objective: This is to present reversible inferior colliculus lesions in metronidazole-induced encephalopathy, to focus on the diffusion-weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR) imaging., Materials and Methods: From November 2005 to September 2007, 8 patients (5 men and 3 women) were diagnosed as having metronidazole-induced encephalopathy (age range; 43-78 years). They had been taking metronidazole (total dosage, 45-120 g; duration, 30 days to 2 months) to treat the infection in various organs. Initial brain magnetic resonance imaging (MRI) were obtained after the hospitalization, including DWI (8/8), apparent diffusion coefficient (ADC) map (4/8), FLAIR (7/8), and T2-weighted image (8/8). Follow-up MRIs were performed on 5 patients from third to 14th days after discontinuation of metronidazole administration. Findings of initial and follow-up MRIs were retrospectively evaluated by 2 neuroradiologists by consensus, to analyze the presence of abnormal signal intensities, their locations, and signal changes on follow-up images., Results: Initial MRIs showed abnormal high signal intensities on DWI and FLAIR (or T2-weighted image) at the dentate nucleus (8/8), inferior colliculus (6/8), corpus callosum (2/8), pons (2/8), medulla (1/8), and bilateral cerebral white matter (1/8). High-signal intensity lesions on DWI tended to show low signal intensity on ADC map (3/4), but in one patient, high signal intensity was shown at bilateral dentate nuclei on not only DWI but also ADC map. All the lesions in dentate, inferior colliculus, pons, and medullas had been resolved completely on follow-up MRIs in 5 patients, but in 1 patient of them, corpus callosal lesion persisted., Conclusions: Reversible inferior colliculus lesions could be considered as the characteristic for metronidazole-induced encephalopathy, next to the dentate nucleus involvement.

Vitamin B12 deficiency causes haematological, gastrointestinal and neurological diseases. Subacute combined degeneration (SCD) of the spinal cord is characterised by degeneration of the posterior and lateral columns. We report a case of SCD associated with nitrous oxide anaesthesia.

Levetiracetam (LEV) monotherapy was investigated in 35 patients (pts) (16M/19F, 71.9+/-7.3 years of age) with late-onset post-stroke seizures (i.e. seizures occurring at least 2 weeks after an ischemic stroke) in a prospective open-label study. Overall, 27 pts (77.1%) achieved a condition of seizure freedom (defined as 1 year without seizures): 19 (54.3%) at a daily LEV dose of 1000mg, 7 (20.0%) at 1500mg, 1 (2.8%) at 2000mg. Four pts (11.4%) discontinued the drug because of intolerable side effects (drowsiness associated to gait disturbance in 1 pt, and aggressive behaviour in the remaining 3 pts); 3 pts were unresponsive at a dose of 3000mg, and 1 pt was lost at follow-up. These observations suggest that LEV exhibits safety and efficacy profiles which make it an optimal candidate as a first-choice drug against post-stroke seizures.

Paradichlorobenzene (PDB) is a common household deodorant and pesticide found in room deodorizers, toilet bowl fresheners, and some mothballs. Although human exposure to the compound is generally limited and harmless, PDB in larger doses can produce neurotoxic effects, including a chemical "high" similar to that seen with inhalants such as toluene. Although rare, frank addiction to PDB has been reported, and, in such cases, has been associated with gait ataxia, tremor, dysarthria, limb weakness, and bradyphrenia, in various combinations. In such cases, the adverse neurologic consequences have been presumed to result from a direct toxic effect of this small, organic molecule. We report a case of chronic mothball ingestion where profound encephalopathy with cognitive, pyramidal, extrapyramidal, and cerebellar features appears to have been largely the result of PDB withdrawal, rather than direct toxicity. This case raises important questions about the mechanism of PDB neurotoxicity and possible treatment options for PDB-addicted patients. We propose that in cases with clear clinical deterioration after abstinence, readministration and gradual taper of PDB might be considered a therapeutic option.

The autonomic nervous function, blood pressure, coordinate motor and blood alcohol Concentration (BAG) of twenty-one healthy Han volunteers were examined before and after alcohol intake. The purpose was to assess the acute effects of low and moderate doses of alcohol on their coordinate motor and autonomic nervous function. The results showed that after alcohol intake the subjects' heart rate increased and the total power value (TPV) decreased significantly. After the intake of alcohol at low dose, the parasympathetic nervous function of the subjects lying supoine was inhibited significantly. After the intake of alcohol at moderate dose, both the parasympathetic and the sympathetic nervous functions were inhibited. After the intake of alcohol at low dose, both the systolic pressure and the diastolic pressure of the subjects standing up-right were decreased and the diastolic pressure of those lying supine were also decreased. After the intake of alcohol at moderate dose, the systolic and diastolic pressures of the subjects, either lying supine or standing up-right, were decreased. Some subjects showed ataxia after the intake of alcohol at low dose ,and some showed aggravated ataxia after intake of alcohol at moderate dose of alcohol. There was no relationship of BAG with the degree of changes in autonomic nervous function, blood pressure and ataxia. The results indicated that ataxia was induced to come on and the autonomic nervous function was inhibited in some subjects who had taken low and moderate doses of alcohol ,and the cardiovascular regulation was affected too. These suggested that the increase of alcohol intake is adverse to human body's adaptation to the sharp change of circumstance.

Methyl bromide is toxic to the central and peripheral nervous systems. A patient with occupational exposure to this agent is described. MRI showed strikingly symmetric brainstem and cerebellar lesions. The patient's clinical course and the topography and resolution of his MRI abnormalities suggest that this condition is an energy deprivation syndrome.

Identification of genetic and physiological mechanisms underlying a drug's or mutation's effects on motor performance could be aided by the existence of a simple observation-based rating scale of ataxia for mice. Rating scales were developed to assess ataxia after ethanol (2.75, 3.0, and 3.25 g/kg) in nine inbred mouse strains. Each scale independently rates a single behavior. Raters, blinded to dose, scored four behaviors (splay of hind legs, wobbling, nose down, and belly drag) at each of four time points after injection. The severities of hind leg splaying and wobbling were quantifiable, whereas nose down and belly dragging were expressed in all-or-none fashion. Interrater reliabilities were substantial (0.75 0 at some time), but all doses were equally effective. Incidence of nose down and belly dragging behaviors increased strain dependently after ethanol, but strains did not differentially respond to dose. Ethanol-induced splaying was modestly, and negatively, genetically correlated with wobbling. Nose down and belly dragging tended to be associated with splaying and wobbling at later times. Four distinct ataxia-related behaviors were sensitive to ethanol. Strains differed in ethanol sensitivity for all measures. Modest strain mean correlations among behaviors indicate that these behaviors are probably under control of largely different genes and that ataxia rating scales should rate separate behaviors on discrete scales.

To examine whether delayed neuropathy is prevented or alleviated when Ca is administered to experimental animals before or after organophosphorus compounds (OPs) dosing, we observed the effects of Calcicol administration as a calcium tonic on delayed neurotoxicity by OPs in hens. The hens (n=28) were randomly divided into seven groups (four in each group). One group received glycerol formal as vehicle group, two groups received 30 mg/kg leptophos or 40 mg/kg triortho-cresyl phosphate (TOCP) (L group and T group), two groups received 2.4 mg/kg Ca(2+) (0.3 ml/kg Calcicol) 24 h before leptophos or TOCP administration, and the last two groups received 2.4 mg/kg Ca after leptophos or TOCP administration, respectively. Although delayed polyneuropathy induced by OPs could not be prevented completely by Calcicol, the clinical signs of organophosphorus-induced delayed neuropathy (OPIDN) in hens that received Calcicol soon before or after OPs administration were less severe than those in hens that received only OPs and there were significant differences in OPIDN score between groups (P<0.05). This shows that polyneuropathy and the recovery function of nerves and muscles suffering from polyneuropathy can be alleviated, as long as calcium tonic is administered before the clinical signs develop. This study offers hope of recovery to humans who are exposed to these OPs because of work, attempted suicide, accidental ingestion or other accidents, etc. Meanwhile, our results indicate further that there is a relationship between a decrease in Ca(2+) concentration in tissues and induction of delayed neuropathy.