Size-dependent influence of NOx on the growth rates of organic aerosol particles.

Atmospheric new-particle formation (NPF) affects climate by contributing to a large fraction of the cloud condensation nuclei (CCN). Highly oxygenated organic molecules (HOMs) drive the early particle growth and therefore substantially influence the survival of newly formed particles to CCN. Nitrogen oxide (NOx) is known to suppress the NPF driven by HOMs, but the underlying mechanism remains largely unclear. Here, we examine the response of particle growth to the changes of HOM formation caused by NOx. We show that NOx suppresses particle growth in general, but the suppression is rather nonuniform and size dependent, which can be quantitatively explained by the shifted HOM volatility after adding NOx. By illustrating how NOx affects the early growth of new particles, a critical step of CCN formation, our results help provide a refined assessment of the potential climatic effects caused by the diverse changes of NOx level in forest regions around the globe.

Ion-induced sulfuric acid-ammonia nucleation drives particle formation in coastal Antarctica.

Formation of new aerosol particles from trace gases is a major source of cloud condensation nuclei (CCN) in the global atmosphere, with potentially large effects on cloud optical properties and Earth's radiative balance. Controlled laboratory experiments have resolved, in detail, the different nucleation pathways likely responsible for atmospheric new particle formation, yet very little is known from field studies about the molecular steps and compounds involved in different regions of the atmosphere. The scarcity of primary particle sources makes secondary aerosol formation particularly important in the Antarctic atmosphere. Here, we report on the observation of ion-induced nucleation of sulfuric acid and ammonia-a process experimentally investigated by the CERN CLOUD experiment-as a major source of secondary aerosol particles over coastal Antarctica. We further show that measured high sulfuric acid concentrations, exceeding 107 molecules cm-3, are sufficient to explain the observed new particle growth rates. Our findings show that ion-induced nucleation is the dominant particle formation mechanism, implying that galactic cosmic radiation plays a key role in new particle formation in the pristine Antarctic atmosphere.

Syringomyelia and Craniocervical Junction Abnormalities in Chihuahuas.

BACKGROUND: Chiari-like malformation (CM) and syringomyelia (SM) are widely reported in Cavalier King Charles Spaniels and Griffon Bruxellois dogs. Increasing evidence indicates that CM and SM also occur in other small and toy breed dogs, such as Chihuahuas. OBJECTIVES: To describe the presence of SM and craniocervical junction (CCJ) abnormalities in Chihuahuas and to evaluate the possible association of CCJ abnormalities with SM. To describe CM/SM-related clinical signs and neurologic deficits and to investigate the association of CM/SM-related clinical signs with signalment, SM, or CCJ abnormalities. ANIMALS: Fifty-three client-owned Chihuahuas. METHODS: Prospective study. Questionnaire analyses and physical and neurologic examinations were obtained before magnetic resonance and computed tomography imaging. Images were evaluated for the presence of SM, CM, and atlantooccipital overlapping. Additionally, medullary kinking, dorsal spinal cord compression, and their sum indices were calculated. RESULTS: Scratching was the most common CM/SM-related clinical sign and decreased postural reaction the most common neurologic deficit in 73 and 87% of dogs, respectively. Chiari-like malformation and SM were present in 100 and 38% of dogs, respectively. Syringomyelia was associated with the presence of CM/SM-related clinical signs (P = 0.034), and medullary kinking and sum indices were higher in dogs with clinical signs (P = 0.016 and P = 0.007, respectively). CONCLUSIONS AND CLINICAL IMPORTANCE: Syringomyelia and CCJ abnormalities are prevalent in Chihuahuas. Syringomyelia was an important factor for the presence of CM/SM-related clinical signs, but many dogs suffered from similar clinical signs without being affected by SM, highlighting the clinical importance of CCJ abnormalities in Chihuahuas.

Diagnostic Utility of Wireless Video-Electroencephalography in Unsedated Dogs.

BACKGROUND: Poor agreement between observers on whether an unusual event is a seizure drives the need for a specific diagnostic tool provided by video-electroencephalography (video-EEG) in human pediatric epileptology. OBJECTIVE: That successful classification of events would be positively associated with increasing EEG recording length and higher event frequency reported before video-EEG evaluation; that a novel wireless video-EEG technique would clarify whether unusual behavioral events were seizures in unsedated dogs. ANIMALS: Eighty-one client-owned dogs of various breeds undergoing investigation of unusual behavioral events at 4 institutions. METHODS: Retrospective case series: evaluation of wireless video-EEG recordings in unsedated dogs performed at 4 institutions. RESULTS: Electroencephalography achieved/excluded diagnosis of epilepsy in 58 dogs (72%); 25 dogs confirmed with epileptic seizures based on ictal/interictal epileptiform discharges, and 33 dogs with no EEG abnormalities associated with their target events. As reported frequency of the target events decreased (annually, monthly, weekly, daily, hourly, minutes, seconds), EEG was less likely to achieve diagnosis (P < 0.001). Every increase in event frequency increased the odds of achieving diagnosis by 2.315 (95% confidence interval: 1.36-4.34). EEG recording length (mean = 3.69 hours, range: 0.17-22.5) was not associated (P = 0.2) with the likelihood of achieving a diagnosis. CONCLUSIONS AND CLINICAL IMPORTANCE: Wireless video-EEG in unsedated dogs had a high success for diagnosis of unusual behavioral events. This technique offered a reliable clinical tool to investigate the epileptic origin of behavioral events in dogs.

Paroxysmal Dyskinesia in Border Terriers: Clinical, Epidemiological, and Genetic Investigations.

BACKGROUND: In the last decade, a disorder characterized by episodes of involuntary movements and dystonia has been recognized in Border Terriers. OBJECTIVES: To define clinical features of paroxysmal dyskinesia (PD) in a large number of Border Terriers and to study the genetics of the disease. ANIMALS: 110 affected and 128 unaffected client-owned Border Terriers. METHODS: A questionnaire regarding clinical characteristics of PD was designed at Utrecht University and the University of Helsinki. Thirty-five affected Border Terriers underwent physical examination and blood testing (hematology and clinical biochemistry). Diagnostic imaging of the brain was performed in 17 affected dogs and electroencephalograms (EEG) between episodes were obtained in 10 affected dogs. A genomewide association study (GWAS) was performed with DNA of 110 affected and 128 unaffected dogs. RESULTS: One hundred forty-seven questionnaires were included in the study. The most characteristic signs during episodes were dystonia, muscle fasciculations, and falling over. The majority of owners believed that their dogs remained conscious during the episodes. A beneficial effect of anti-epileptic therapy was observed in 29 of 43 dogs. Fifteen owners changed their dogs' diet to a hypoallergenic, gluten-free diet, and all reported reasonable to good improvement of signs. Clinical examinations and diagnostic test results were unremarkable. The GWAS did not identify significantly associated chromosome regions. CONCLUSIONS AND CLINICAL IMPORTANCE: The survey results and EEG studies provided further evidence that the observed syndrome is a PD rather than epilepsy. Failure to achieve conclusive results by GWAS indicates that inheritance of PD in Border Terriers probably is complex.

Effect of dimethylamine on the gas phase sulfuric acid concentration measured by Chemical Ionization Mass Spectrometry.

Sulfuric acid is widely recognized as a very important substance driving atmospheric aerosol nucleation. Based on quantum chemical calculations it has been suggested that the quantitative detection of gas phase sulfuric acid (H2SO4) by use of Chemical Ionization Mass Spectrometry (CIMS) could be biased in the presence of gas phase amines such as dimethylamine (DMA). An experiment (CLOUD7 campaign) was set up at the CLOUD (Cosmics Leaving OUtdoor Droplets) chamber to investigate the quantitative detection of H2SO4 in the presence of dimethylamine by CIMS at atmospherically relevant concentrations. For the first time in the CLOUD experiment, the monomer sulfuric acid concentration was measured by a CIMS and by two CI-APi-TOF (Chemical Ionization-Atmospheric Pressure interface-Time Of Flight) mass spectrometers. In addition, neutral sulfuric acid clusters were measured with the CI-APi-TOFs. The CLOUD7 measurements show that in the presence of dimethylamine (<5 to 70 pptv) the sulfuric acid monomer measured by the CIMS represents only a fraction of the total H2SO4, contained in the monomer and the clusters that is available for particle growth. Although it was found that the addition of dimethylamine dramatically changes the H2SO4 cluster distribution compared to binary (H2SO4-H2O) conditions, the CIMS detection efficiency does not seem to depend substantially on whether an individual H2SO4 monomer is clustered with a DMA molecule. The experimental observations are supported by numerical simulations based on A Self-contained Atmospheric chemistry coDe coupled with a molecular process model (Sulfuric Acid Water NUCleation) operated in the kinetic limit.

LGI Proteins and Epilepsy in Human and Animals.

Leucine-rich glioma-inactivated (LGI) protein was first thought to have a suppressor effect in the formation of some cancers. Developments in physiology and medicine made it possible to characterize the function of the LGI protein family and its crucial role in different conditions more precisely. These proteins play an important role in synaptic transmission, and dysfunction may cause hyperexcitability. Genetic mutation of LGI1 was confirmed to be the cause of autosomal dominant lateral temporal lobe epilepsy in humans. The LGI2 mutation was identified in benign familial juvenile epilepsy in Lagotto Romagnolo (LR) dogs. Cats with familial spontaneous temporal lobe epilepsy have been reported, and the etiology might be associated with LGI protein family dysfunction. In addition, an autoimmune reaction against LGI1 was detected in humans and cats with limbic encephalitis. These advances prompted a review of LGI protein function and its role in different seizure disorders.

Behavioral Abnormalities in Lagotto Romagnolo Dogs with a History of Benign Familial Juvenile Epilepsy: A Long-Term Follow-Up Study.

BACKGROUND: Lagotto Romagnolo (LR) dogs with benign juvenile epilepsy syndrome often experience spontaneous remission of seizures. The long-term outcome in these dogs currently is unknown. In humans, behavioral and psychiatric comorbidities have been reported in pediatric and adult-onset epilepsies. HYPOTHESIS/OBJECTIVES: The objectives of this study were to investigate possible neurobehavioral comorbidities in LR with a history of benign familial juvenile epilepsy (BFJE) and to assess the occurrence of seizures after the remission of seizures in puppyhood. ANIMALS: A total of 25 LR with a history of BFJE and 91 control dogs of the same breed. METHODS: Owners of the LR dogs in the BFJE and control groups completed an online questionnaire about each dog's activity, impulsivity, and inattention. Principal component analysis (PCA) served to extract behavioral factors from the data. We then compared the scores of these factors between the 2 groups in a retrospective case-control study. We also interviewed all dog owners in the BFJE group by telephone to inquire specifically about possible seizures or other neurological problems after remission of seizures as a puppy. RESULTS: Lagotto Romagnolo dogs with BFJE showed significantly higher scores on the factors Inattention and Excitability/Impulsivity than did the control group (P = .003; P = .021, respectively). Only 1 of the 25 BFJE LR exhibited seizures after remission of epilepsy in puppyhood. CONCLUSIONS AND CLINICAL IMPORTANCE: Although the long-term seizure outcome in BFJE LR seems to be good, the dogs exhibit behavioral abnormalities resembling attention deficit hyperactivity disorder (ADHD) in humans, thus suggesting neurobehavioral comorbidities with epilepsy.

Topiramate as an add-on antiepileptic drug in treating refractory canine idiopathic epilepsy.

OBJECTIVES: To evaluate the efficacy and safety of topiramate as an add-on therapy in dogs with refractory idiopathic epilepsy. METHOD: Prospective, open label, non-comparative clinical trial of topiramate in dogs with idiopathic epilepsy and poor seizure control despite therapeutic serum concentrations of phenobarbital and potassium bromide. The efficacy of topiramate was evaluated by comparing seizure and seizure day frequencies during a retrospective 2-month period with a prospective short-term follow-up of 6 months. An additional long-term follow-up period ranging from 3 to 9 months was conducted on dogs that responded to topiramate therapy during the short-term follow-up. RESULTS: Ten dogs were included. Five (50%) responded to topiramate therapy during the short-term follow-up showing a significant (P=0·04) decrease of 66% in seizure frequency. Three of the five dogs remained responders during the long-term follow-up. Weight loss, sedation and ataxia were the most common adverse effects of topiramate therapy, but in dogs with moderate sedation or ataxia, signs subsided in a few weeks to few months to mild sedation or ataxia. CLINICAL SIGNIFICANCE: Topiramate may be effective as an add-on medication in treating canine idiopathic epilepsy. Apart from sedation and ataxia reported in some of the dogs, topiramate was well-tolerated.

Dermoid sinus and spina bifida in three dogs and a cat.

This case series describes four cases of concomitant dermoid sinus and spina bifida in a Chinese crested dog, two Swedish vallhunds and a Burmese cat. The diagnosis was confirmed by computed tomography, computed tomography fistulography and pathology. Two dogs that showed abnormalities during neurological examination underwent magnetic resonance imaging. One of them had imaging findings interpreted as syringohydromyelia. All the dogs underwent surgery and the outcome was considered good in all the cases. Based on clinical and pathological examination as well as diagnostic imaging findings, two of the dermoid sinuses were classified as type IV, and two of them showed a previously unreported type of dermoid sinus. This new type is suggested here as type VI.

Polyneuropathy of Finnish horses characterised by inflammatory demyelination and intracisternal Schwann cell inclusions.

REASON FOR PERFORMING STUDY: A neurological disorder characterised by pelvic limb metatarsophalangeal joint extensor paresis has been observed in numerous horses in Scandinavia for the last decade. Very little has been formally reported and there have been no detailed assessments of the neurological signs or neuropathological lesions. OBJECTIVES: To describe the epidemiological and pathological features of an outbreak of 'Scandinavian knuckling syndrome' in a riding stable in southern Finland. METHODS: Clinical neurological examination of 4 cases and neuropathological assessment of tissues of one case were performed. RESULTS: Eleven out of 17 horses fed on ryegrass from a common source showed progressive clinical signs of metatarsophalangeal extensor paresis necessitating euthanasia of 7 horses. Nervous system lesions in one horse consisted of a novel demyelinating, mildly inflammatory peripheral neuropathy, with BiP/GRP positive rough endoplasmatic reticulum Schwann cell inclusions. CONCLUSIONS: The clinical signs and lesions documented differ from any previously described equine polyneuropathy and suggest a primary Schwann cell lesion. POTENTIAL RELEVANCE: The classification of this disease as a novel demyelinating polyneuropathy may assist focused epidemiological investigations.

Benign familial juvenile epilepsy in Lagotto Romagnolo dogs.

BACKGROUND: Idiopathic childhood epilepsies with benign outcomes are well recognized in human medicine, but are not reported in veterinary literature. We recognized such a neurologic syndrome in Lagotto Romagnolo dogs. ANIMALS: Twenty-five Lagotto Romagnolo puppies from 9 different litters examined because of simple or complex focal seizures and 3 adult Lagotto Romagnolo dogs exhibiting similar clinical signs were used. METHODS: Clinical and diagnostic evaluations of affected dogs were conducted, including electromyography, electroencephalography, and other testing. RESULTS: Seizures in puppies began at 5 to 9 weeks of age and usually resolved spontaneously by 8 to 13 weeks. Those with the most severe seizures also had signs of neurologic disease between these seizures, including generalized ataxia and hypermetria. There were no abnormalities in routine laboratory screenings of blood, urine, and cerebrospinal fluid. Electromyography, brainstem auditory-evoked potentials, and magnetic resonance imaging revealed no specific and consistent abnormalities. Fourteen of 16 (87.5%) affected puppies and 2 of 3 (67%) adult dogs revealed epileptiform activity in the electroencephalogram. Histopathologic examination in 1 puppy and 1 adult dog revealed lesions of Purkinje cell inclusions and vacuolation of their axons restricted to the cerebellum. Pedigree analysis suggests an autosomal recessive mode of inheritance. CONCLUSIONS AND CLINICAL IMPORTANCE: This disorder, with simple or complex focal seizures and cerebellar lesions, represents a newly recognized epileptic syndrome in dogs.

Cerebellar cortical abiotrophy in Lagotto Romagnolo dogs.

This case report documents two pathological variations of potentially inherited, cerebellar cortical abiotrophy in two unrelated Lagotto Romagnolo breed dogs. The first dog had an atypical lesion in the cerebellar cortex with depletion of cerebellar granular cell layer and sparing of the Purkinje cell layer. The second case had degenerative changes in both Purkinje and granular cell layers. The clinical picture was similar in both cases presented, although the severity of the signs of cerebellar dysfunction varied.

Magnetic resonance imaging findings in Finnish Spitz dogs with focal epilepsy.

Eleven Finnish Spitz dogs with focal seizures and 3 healthy controls were evaluated. General clinical and neurological examinations, blood examination, urinalysis, cerebrospinal fluid examination, electroencephalography (EEG), and magnetic resonance imaging (MRI) of the brain were performed on all dogs. On EEG examination, focal epileptic activity was found in 7 of 11 dogs (64%), and generalized epileptic activity was observed in 4 of 11 dogs (36%). MRI (performed with 1.5 T equipment) detected changes in 1 epileptic dog. Mild contrast enhancement after gadolinium injection was identified in this dog's right parietal cortex. However, no such changes were observed in repeated magnetic resonance images. Special emphasis was given to seizure history to determine any correlations between seizure intervals and MRI findings. Our results indicate that Finnish Spitz dogs with focal seizures suffer from focal idiopathic epilepsy and have nondetectable findings on MRI or pathology. MRI showed poor sensitivity in detecting epileptogenic areas in our patients with focal seizures. Reversible MRI changes in 1 dog could have been caused by seizures.

Effect of composition and different fractions of hay dust suspension on inflammation in lungs of heaves-affected horses: MMP-9 and MMP-2 as indicators of tissue destruction.

REASONS FOR PERFORMING STUDY: Airway matrix metalloproteinases (MMPs) increase following inhalation of organic dust. The relative contribution of dust components to this elevation is unknown. OBJECTIVE: To identify components of organic dust responsible for elevated MMP levels in equine airways. METHODS: Bronchoalveolar lavage (BALF) from 7 heaves-susceptible horses, collected 6 h following inhalation challenges with saline, 2 different hay dust suspensions (HDS-1 and -2) and soluble and particulate fractions of HDS-1, were analysed for MMP-2 and -9 using SDS-page gelatin zymography. RESULTS: HDS-1 challenge increased BALF proMMP-9 and total MMP-9. HDS-1 fractions, or the particulate fraction with added lipopolysaccharide, increased BALF proMMP-9 and total MMP-9 in combination, but not when inhaled separately. HDS-2 inhalation elevated BALF complex forms, proMMP-9, active MMP-9, total MMP-9 and total MMP-2. CONCLUSIONS: The results suggest synergistic action of soluble and particulate organic dust components. The fact that HDS-1 and HDS-2 had different glucan concentrations supports a role for moulds in the activation of MMP-9. POTENTIAL RELEVANCE: Activation and release of MMPs in response to inhaled moulds are involved in the aetiopathogenesis of heaves. Endotoxin contributes to the synergistic action of the dust components, but the overall MMP response to organic dust inhalation in heaves-susceptible horses largely reflects the mould content of the dust. In the future, inhibition of MMP production and release may offer therapeutic means for treatment and prevention of heaves and recommendations for acceptable dust levels can be given.

Dose responses to inhalation of endotoxin, hay dust suspension and Aspergillus fumigatus extract in horses as measured by levels and activation of matrix metalloproteinase-9.

REASONS FOR PERFORMING STUDY: Airway matrix metalloproteinases (MMPs) increase after endotoxin (LPS) exposure, but there are no reports describing dose-dependent increases or activation following exposure. OBJECTIVES: To study matrix metalloproteinase-9 (MMP-9) and -2 (MMP-2) responses in bronchoalveolar lavage fluid (BALF) from heaves-susceptible and control horses following inhalation of hay dust suspension (HDS), LPS and Aspergillus fumigatus extract (AFE). METHODS: Heaves-susceptible (n = 7) and control (n = 6) horses received inhalation challenges with 3 different doses of HDS and LPS. Heaves-susceptible horses (n = 6) also received 3 different doses of AFE and one dose of AFE depleted of endotoxin (AFE-LPS). BALF collected following inhalation challenges was analysed using gelatin zymography. Gelatinolytic bands were identified as complex, pro-MMP-9, active MMP-9, pro-MMP-2 and active MMP-2 based on molecular weights. RESULTS: Each challenge substance induced a dose-dependent elevation in gelatinolytic activity. The dose-dependency was most evident for pro-MMP-9 and total MMP-9 levels in heaves-susceptible horses following LPS challenges. CONCLUSIONS: There is a dose-dependent elevation in MMP-9 in BALF of heaves-susceptible and control horses following inhalation challenge with organic dust and some of its components, elevation being more marked in heaves-susceptible horses. Organic dust components vary in their pro-inflammatory potential. POTENTIAL RELEVANCE: This study supports the role of MMPs in the pathogenesis of heaves and highlights the potential value of protease inhibitors in attenuating the airway inflammatory response to inhaled organic dust.

A new visual performance test offers new variables for assessing daytime vigilance: short pauses in performance.

A new visual performance test, VigiMouse, was evaluated with the aid of 6 volunteering pediatry residents. The results were compared with a visual analogue scale in differentiating four different states: mild sleep deprivation, low blood alcohol level, a combination of both, and the normal state. A normal night shift at a busy pediatric ward was chosen to represent sleep deprivation. A new set of parameters based on short pauses in performance proved to be more sensitive in detecting small changes in performance than parameters based on reaction times.

Use of computerized visual performance test in assessing day-time vigilance in patients with sleep apneas and restless sleep.

We have studied day-time vigilance in 31 patients (median age 49 years) with suspected sleep disorders using a new visual reaction time and performance test. The findings in the day-time vigilance test were compared with the number of desaturation events and movement arousals measured with a sensitive movement detector in the night-time. In our statistical model the high number of desaturations correlated with a high dispersion in reaction-times. The squared multiple r was 0.465 in a model where the dispersion of reaction times was the dependent variable and the number of desaturations, duration of quiet sleep and the mode of oxygen saturation were independent variables. A high amount of body movements (movement arousals, duration less than 5 seconds) correlated with gradual deterioration in the performance test. The squared multiple r was 0.447 in a model where the regression coefficient of reaction times was the dependent variable and active sleep and number of body movements less than 5 seconds in duration were the independent variables. Frequent arousals in apnoeic patients are observed in hyper-excitable responders and are known to cause sleep deprivation and hypersomnia. Our findings in desaturating patients indicate that in those with a low chemoreceptor response to hypoxia the failure in day-time regulation of vigilance may differ from the failure associated with sleep-deprivation.

Topical anaesthesia of gingival mucosa by 5% eutectic mixture of lignocaine and prilocaine or by 10% lignocaine spray.

The analgesic effect of topical application of local anaesthetics on the gingival mucosa and the absorption of the local anaesthetics into the blood were investigated in healthy volunteers by using a 5% eutectic mixture of the local anaesthetics lignocaine (100 mg) and prilocaine (100 mg) plus emulsifier (EMLA) or 10% lignocaine (200 mg) spray (Xylocain). The pain threshold on labial gingiva was measured by using the stimulator of an EMG-apparatus and a pair of stimulating electrodes, specially constructed for this purpose. There were no differences between the two methods in producing analgesia which was at its maximum in 13 to 14 minutes, on average. Sensation of the gingiva (pain thresholds), had usually returned to normal within 30 minutes. In the dosages used, the absorption of the local anaesthetics was more rapid after the mixture application than after spray application. No toxic reactions occurred.

Lumbar sympathectomy in the treatment of severe lower limb ischaemia in old people.

One hundred and twenty lumbar sympathectomies were performed in 110 old people (over 65 years of age) as the treatment for severe lower limb ischaemia. Only one quarter of the patients benefited from the operation. In nearly half the cases the limb was ultimately amputated. The operative mortality was 7%, with pneumonia the most common cause of death. Age and mild diabetes mellitus had no effect on the result of treatment. Diabetics on insulin, however, derived no benefit from the operation. the degree of severity of the ischaemia, and the location of the arterial occlusion affected the result of treatment.