Antimicrobial use and antimicrobial resistance monitoring in pig production in the United States of America.

Monitoring antimicrobial use (AMU) and antimicrobial resistance (AMR) on farms is recognised as an important component of antimicrobial stewardship, yet the process can be resource intensive. This paper describes a subset of findings from the first year of a collaboration across government, academia and a private sector veterinary practice focused on swine production in the Midwestern United States. The work is supported by participating farmers and the greater swine industry. Twice-annual collection of samples from pigs along with AMU monitoring occurred on 138 swine farms. Detection and resistance of Escherichia coli from pig tissues was assessed, and associations between AMU and AMR were evaluated. This paper describes the methods utilised and the first-year E. coli-related results from this project. Higher minimum inhibitory concentrations (MIC) for enrofloxacin and danofloxacin in E. coli from swine tissues were associated with the purchase of fluoroquinolones. There were no other significant associations between MIC and AMU combinations in E. coli isolated from pig tissues. This project represents one of the first attempts to monitor AMU as well as AMR in E. coli in a large-scale commercial swine system in the United States of America.

Alors même que la surveillance exercée sur l'utilisation des agents antimicrobiens (UAM) et sur la résistance aux agents antimicrobiens (RAM) dans les élevages est une composante majeure reconnue de la gestion des antimicrobiens, le processus en lui-même exige une mobilisation intensive de ressources. Les auteurs décrivent un sous-ensemble de résultats obtenus au cours de la première année d'une collaboration entre les pouvoirs publics, les universités et une clinique vétérinaire privée, axée sur la production porcine dans le Midwest des états-Unis d'Amérique. Ce travail est soutenu par les éleveurs participants et par le secteur porcin au sens large. Une collecte d'échantillons porcins a été effectuée deux fois par an, parallèlement à la surveillance de l'UAM dans 138 élevages. Il a été procédé à une recherche des Escherichia coli présents dans les tissus porcins prélevés puis à la détermination de la résistance aux antimicrobiens chez les microorganismes détectés ; les corrélations éventuelles entre l'UAM et la RAM ont ensuite été évaluées. Les auteurs décrivent les méthodes utilisées dans la cadre de ce projet ainsi que les résultats en lien avec les E. coli obtenus au cours de la première année. Une corrélation a été constatée entre l'augmentation des concentrations minimales inhibitrices (CMI) recueillies pour l'enrofloxacine et la danofloxacine vis-à-vis d'E. coli dans les tissus porcins analysés, d'une part, et l'achat de fluoroquinolones, d'autre part. Aucune autre corrélation significative n'a été décelée entre les CMI recueillies et les profils d'UAM concernant les E. coli isolés à partir des tissus porcins. Ce projet représente l'une des premières tentatives conduites aux états-Unis d'Amérique pour surveiller parallèlement l'UAM et la RAM chez les E. coli dans un système commercial de production porcine à grande échelle.

Aunque se tiene por sabido que la vigilancia en las explotaciones del uso de agentes antimicrobianos (UAM) y de la resistencia a los antimicrobianos (RAM) es un importante componente de la gestión de estos fármacos, no es menos cierto que el proceso puede consumir cuantiosos recursos. Los autores exponen un ubconjunto de observaciones realizadas durante el primer año de un proyecto de colaboración entre la administración pública, el mundo universitario y una clínica veterinaria privada que tenía por objeto de estudio la producción porcina en la zona del medio oeste de los Estados Unidos de América. Respaldaban el proyecto los productores que participaban en él y el sector de la industria porcina en general. Dos veces al año se obtuvieron muestras en 138 explotaciones porcinas, en las que también se seguía de cerca el UAM. Tras realizar pruebas de detección de Escherichia coli en tejidos porcinos y analizar la resistencia de esos microorganismos a antimicrobianos, se buscaron correlaciones entre el uso de estos fármacos y la presencia de eventuales resistencias. Los autores describen los métodos empleados y los resultados obtenidos el primer año del proyecto en relación con E. coli. Se observó una correlación entre la compra de fluoroquinolonas y el aumento de la concentración inhibitoria mínima (MIC) de enrofloxacina y de danofloxacina en los E. coli analizados. No se constató ninguna otra asociación significativa entre las MIC y el uso de diferentes antimicrobianos en los E. coli aislados a partir de tejido porcino. Este proyecto constituye una de las primeras tentativas de hacer seguimiento y balance del uso de agentes antimicrobianos y de la resistencia de E. coli a estos fármacos en el sistema de producción porcina industrial de los Estados Unidos de América.

Neuroablative surgical treatments for pain due to cancer.

Cancer pain is common and challenging to manage - it is estimated that approximately 30% of cancer patients have pain that is not adequately controlled by analgesia. This paper discusses safe and effective neuroablative treatment options for refractory cancer pain. Current management of cancer pain predominantly focuses on the use of medications, resulting in a relative loss of knowledge of these surgical techniques and the erosion of the skills required to perform them. Here, we review surgical methods of modulating various points of the neural axis with the aim to expand the knowledge base of those managing cancer pain. Integration of neuroablative approaches may lead to higher rates of pain relief, and the opportunity to dose reduce analgesic agents with potential deleterious side effects. With an ever-increasing population of cancer patients, it is essential that neurosurgeons maintain or train in these techniques in tandem with the oncological multi-disciplinary team.

Modulation of the Wnt pathway through inhibition of CLK2 and DYRK1A by lorecivivint as a novel, potentially disease-modifying approach for knee osteoarthritis treatment.

OBJECTIVES: Wnt pathway upregulation contributes to knee osteoarthritis (OA) through osteoblast differentiation, increased catabolic enzymes, and inflammation. The small-molecule Wnt pathway inhibitor, lorecivivint (SM04690), which previously demonstrated chondrogenesis and cartilage protection in an animal OA model, was evaluated to elucidate its mechanism of action. DESIGN: Biochemical assays measured kinase activity. Western blots measured protein phosphorylation in human mesenchymal stem cells (hMSCs), chondrocytes, and synovial fibroblasts. siRNA knockdown effects in hMSCs and BEAS-2B cells on Wnt pathway, chondrogenic genes, and LPS-induced inflammatory cytokines was measured by qPCR. In vivo anti-inflammation, pain, and function were evaluated following single intra-articular (IA) lorecivivint or vehicle injection in the monosodium iodoacetate (MIA)-induced rat OA model. RESULTS: Lorecivivint inhibited intranuclear kinases CDC-like kinase 2 (CLK2) and dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A). Lorecivivint inhibited CLK2-mediated phosphorylation of serine/arginine-rich (SR) splicing factors and DYRK1A-mediated phosphorylation of SIRT1 and FOXO1. siRNA knockdowns identified a role for CLK2 and DYRK1A in Wnt pathway modulation without affecting ß-catenin with CLK2 inhibition inducing early chondrogenesis and DYRK1A inhibition enhancing mature chondrocyte function. NF-κB and STAT3 inhibition by lorecivivint reduced inflammation. DYRK1A knockdown was sufficient for anti-inflammatory effects, while combined DYRK1A/CLK2 knockdown enhanced this effect. In the MIA model, lorecivivint inhibited production of inflammatory cytokines and cartilage degradative enzymes, resulting in increased joint cartilage, decreased pain, and improved weight-bearing function. CONCLUSIONS: Lorecivivint inhibition of CLK2 and DYRK1A suggested a novel mechanism for Wnt pathway inhibition, enhancing chondrogenesis, chondrocyte function, and anti-inflammation. Lorecivivint shows potential to modify structure and improve symptoms of knee OA.

Spectral and phase-amplitude coupling signatures in human deep brain oscillations during propofol-induced anaesthesia.

BACKGROUND: Both the cerebral cortex and subcortical structures play important roles in consciousness. Some evidence points to general anaesthesia-induced unconsciousness being associated with distinct patterns of superficial cortical electrophysiological oscillations, but how general anaesthetics influence deep brain neural oscillations and interactions between oscillations in humans is poorly understood. METHODS: Local field potentials were recorded in discrete deep brain regions, including anterior cingulate cortex, sensory thalamus, and periaqueductal grey, in humans with implanted deep brain electrodes during induction of unconsciousness with propofol. Power-frequency spectra, phase-amplitude coupling, coherence, and directed functional connectivity analysis were used to characterise local field potentials in the awake and unconscious states. RESULTS: An increase in alpha (7-13 Hz) power and decrease in gamma (30-90 Hz) power were observed in both deep cortical (ACC, anterior cingulate cortex) and subcortical (sensory thalamus, periaqueductal grey) areas during propofol-induced unconsciousness. Robust alpha-low gamma (30-60 Hz) phase-amplitude coupling induced by general anaesthesia was observed in the anterior cingulate cortex but not in other regions studied. Moreover, alpha oscillations during unconsciousness were highly coherent within the anterior cingulate cortex, and this rhythm exhibited a bidirectional information flow between left and right anterior cingulate cortex but stronger left-to-right flow. CONCLUSION: Propofol increases alpha oscillations and attenuates gamma oscillations in both cortical and subcortical areas. The alpha-gamma phase-amplitude coupling and the functional connectivity of alpha oscillations in the anterior cingulate cortex could be specific markers for loss of consciousness.

Thalamic Directional Deep Brain Stimulation for tremor: Spend less, get more.

BACKGROUND: Directional Deep Brain Stimulation (D-DBS) allows axially asymmetric electrical field shaping, away from structures causing side-effects. However, concerns regarding the impact on device lifespan and complexity of the monopolar survey have contributed to sparing use of these features. OBJECTIVE: To investigate whether chronically implanted D-DBS systems can improve the therapeutic window, without a negative impact on device lifespan, in thalamic deep brain stimulation (DBS). METHODS: We evaluated stable outcomes of initial programming sessions (4-6 weeks post-implantation) retrospectively in 8 patients with drug-resistant disabling tremor syndromes. We assessed the impact of directional stimulation on the Therapeutic Window (TW), Therapeutic Current Strength (TCS), tremor scores, disability scores and total electrical energy delivered. Finally, we performed Volume of Tissue Activation (VTA) modelling, based on a range of parameters. RESULTS: We report significant gains in TW (91%) and reductions in TCS (31%) with stimulation in the best direction compared to best omnidirectional stimulation alternative. Tremor and ADL scores improvements remained unchanged at six months. There was no increase in averaged IPG power consumption (there is a 6% reduction over the omnidirectional-only alternative). Illustrative VTA modelling shows that D-DBS achieves 85% of the total activation volume at just 69% of the stimulation amplitude of non-directional configuration. CONCLUSIONS: D-DBS can improve the therapeutic window over non-directional DBS, leading to significant reduction in disability that may be sustained without additional reprogramming visits. When averaged across the cohort, power output and predicted device lifespan was not impacted by the use of directional stimulation in this study.

The timing of deep brain stimulation for Parkinson disease in the UK from 1997 to 2012.

BACKGROUND AND PURPOSE: Deep brain stimulation (DBS) for Parkinson disease (PD) has traditionally been reserved for the late stages of the disease. There is evidence that DBS is also effective if applied earlier in the disease course. Changes in the frequency of DBS procedures in the UK over a 15-year period were investigated. METHODS: A retrospective review was performed of patient age and disease duration for DBS surgery for PD in UK neurosurgical units from 1997 to 2012 using departmental databases. RESULTS: The number of DBS procedures in the UK increased from three in 1997 to over 80 per year during this period. The mean age at the time of surgery (60 years) and the mean duration of PD at the time of DBS (11 years) remained unchanged over 15 years. CONCLUSIONS: The age and disease duration at which DBS is performed for PD in the UK has been static over a 15-year period and DBS appears to remain a therapy for PD applied late in its course. This may change in the light of clinical evidence suggesting a benefit for earlier DBS.

Managerial practices regarding workers working while ill.

Surveillance data indicate that handling of food by an ill worker is a cause of almost half of all restaurant-related outbreaks. The U.S. Food and Drug Administration (FDA) Food Code contains recommendations for food service establishments, including restaurants, aimed at reducing the frequency with which food workers work while ill. However, few data exist on the extent to which restaurants have implemented FDA recommendations. The Centers for Disease Control and Prevention's Environmental Health Specialists Network (EHS-Net) conducted a study on the topic of ill food workers in restaurants. We interviewed restaurant managers (n = 426) in nine EHS-Net sites. We found that many restaurant policies concerning ill food workers do not follow FDA recommendations. For example, one-third of the restaurants' policies did not specifically address the circumstances under which ill food workers should be excluded from work (i.e., not be allowed to work). We also found that, in many restaurants, managers are not actively involved in decisions about whether ill food workers should work. Additionally, almost 70% of managers said they had worked while ill; 10% said they had worked while having nausea or "stomach flu," possible symptoms of foodborne illness. When asked why they had worked when ill, a third of the managers said they felt obligated to work or their strong work ethic compelled them to work. Other reasons cited were that the restaurant was understaffed or no one was available to replace them (26%), they felt that their symptoms were mild or not contagious (19%), they had special managerial responsibilities that no one else could fulfill (11%), there was non-food handling work they could do (7%), and they would not get paid if they did not work or the restaurant had no sick leave policy (5%). Data from this study can inform future research and help policy makers target interventions designed to reduce the frequency with which food workers work while ill.

Long-term outcome of deep brain stimulation in generalised dystonia: a series of 60 cases.

BACKGROUND: There is solid evidence of the long term efficacy of deep brain stimulation of the globus pallidus pars interna in the treatment of generalised dystonia. However there are conflicting reports concerning whether certain subgroups gain more benefit from treatment than others. We analysed the results of a series of 60 cases to evaluate the effects of previously proposed prognostic factors including dystonia aetiology, dystonia phenotype, age at onset of dystonia, and duration of dystonia prior to treatment. METHODS: 60 patients with medically intractable primary or secondary generalised dystonia were treated with deep brain stimulation of the globus pallidus pars interna during the period 1999-2010 at the Department of Neurosurgery in Oxford, UK. Patients were assessed using the Burke-Fahn-Marsden (BFM) Dystonia Rating Scale prior to surgery, 6 months after implantation and thereafter at 1 year, 2 years and 5 years follow-up. RESULTS: The group showed mean improvements in the BFM severity and disability scores of 43% and 27%, respectively, by 6 months, and this was sustained. The results in 11 patients with DYT gene mutations were significantly better than in non-genetic primary cases. The results in 12 patients with secondary dystonia were not as good as those seen in non-genetic primary cases but there remained a significant beneficial effect. Age of onset of dystonia, duration of disease prior to surgery, and myoclonic versus torsional disease phenotype had no significant effect on outcome. CONCLUSIONS: The aetiology of dystonia was the sole factor predicting a better or poorer outcome from globus pallidus pars interna stimulation in this series of patients with generalised dystonia. However even the secondary cases that responded the least well had a substantial reduction in BFM scores compared with preoperative clinical assessments, and these patients should still be considered for deep brain stimulation.

Deep brain stimulation for tremor resulting from acquired brain injury.

OBJECTIVES: To evaluate the efficacy of deep brain stimulation (DBS) in the treatment of tremor resulting from acquired brain injury (ABI). METHODS: A series of eight consecutive patients with post-ABI tremor were treated with DBS of the ventro-oralis posterior (VOP)/zona incerta (ZI) region, and subsequently underwent blinded assessments using Bain's tremor severity scale. RESULTS: VOP/ZI DBS produced a mean reduction in tremor severity of 80.75% based on Bain's tremor severity scale, with significant reductions in all five component tremor subscores: rest, postural, kinetic, proximal and distal. No adverse neurological complications were reported, although one patient experienced exacerbation of pre-existing gait ataxia. CONCLUSION: VOP/ZI stimulation is demonstrated here to be an effective and safe approach for the treatment of post-ABI tremor in the largest series published at the time of writing.

Distribution of Culicoides sonorensis (Diptera: Ceratopogonidae) in Nebraska, South Dakota, and North Dakota: clarifying the epidemiology of bluetongue disease in the northern Great Plains region of the United States.

The presence or absence of the biting midge Culicoides sonorensis Wirth & Jones (Diptera: Ceratopogonidae), a primary vector of bluetongue viruses (genus Orbivirus, family Reoviridae, BTV) in North America, was assessed on ranches and farms across the Northern Great Plains region of the United States, specifically Nebraska, South Dakota, and North Dakota, as part of a 2-yr regional study of BTV exposure among cattle. Blacklight/suction trap samples totaling 280 2-night intervals were taken at 140 aquatic sites (potential larval habitat for C. sonorensis) on 82 livestock operations (ranches and farms) that span a south-to-north gradient of expected decreasing risk for exposure to BTV. In Nebraska, C. sonorensis populations were common and widespread, present at 15 of 18 operations. Of 32 operations sampled in South Dakota, seven of which were sampled in successive years, 18 were positive for C. sonorensis; 13 of 14 operations located west of the Missouri River were positive, whereas 13 of 18 operations east of the river were negative. Of 32 operations sampled in North Dakota, seven of which were sampled both years, 12 were positive for C. sonorensis. Six of eight operations located west and south of the Missouri River in North Dakota were positive, whereas 18 of 24 operations east and north of the river were negative for C. sonorensis. These data illustrate a well-defined pattern of C. sonorensis spatial distribution, with populations consistently present across Nebraska, western South Dakota, and western North Dakota; western South Dakota, and North Dakota encompass the Northwestern Plains Ecoregion where soils are nonglaciated and evaporation exceeds precipitation. In contrast, C. sonorensis populations were largely absent east of the Missouri River in South Dakota and North Dakota; this area comprises the Northwestern Glaciated Plains Ecoregion and Northern Glaciated Plains Ecoregion where surface soils reflect Wisconsinan glaciation and precipitation exceeds evaporation. In defining a well-demarcated pattern of population presence or absence on a regional scale, the data suggest that biogeographic factors regulate the distribution of C. sonorensis and in turn BTV exposure. These factors, ostensibly climate and soil type as they affect the suitability of larval habitat, may explain the absence of C. sonorensis, hence limited risk for exposure to BTV, across the eastern Northern Plains, upper Midwest, and possibly Northeast, regions of the United States.

Acute foramen magnum syndrome from acquired Chiari I malformation relieved by ventriculoperitoneal shunt revision.

An adult case of shunt malfunction presenting with acute quadriparesis as a manifestation of foramen magnum syndrome with acquired Chiari type I malformation is described in this study. The corticospinal function was restored after shunt revision. MRI showing considerable ascent of cerebellar tonsils after surgery is shown. Theories regarding the formation of acquired Chiari I malformations, alongside the possible synergistic roles of intracranial pathologies and cerebrospinal fluid drainage in the development of this entity are discussed.

Perioperative seizures following deep brain stimulation in patients with multiple sclerosis.

Following a total of 386 deep brain stimulation (DBS) procedures in Oxford, only two seizures have been recorded in the peri-operative period. Both patients had MS and underwent thalamic DBS for tremor and these 2 cases are presented here. The incidence of peri-operative seizures in MS patients undergoing DBS procedures is more than 8-fold greater than that expected for patients undergoing DBS procedures. Further experience with DBS procedures in MS patients is needed to determine whether there is a role for peri-operative anticonvulsants in these patients.

Implantation of an intercostal nerve stimulator for chronic abdominal pain.

Chronic abdominal pain is not uncommon and can be difficult to manage. We present the case of a 17-year-old man with a 4-year history of chronic abdominal pain. The patient had previously undergone abdominal surgery by way of laparoscopic appendicectomy and right nephrectomy for a mal-rotated kidney. The patient continued to suffer right-sided abdominal pain which was not controlled by analgesia. We report the successful implantation of a right D11 intercostal nerve stimulator to control the patient's pain. This is the first report of an implantable intercostal nerve stimulator to control intractable chronic abdominal pain.

Posterior occipitocervical instrumented fusion for dropped head syndrome after deep brain stimulation.

We describe dropped head syndrome in a patient with Parkinson's disease receiving subthalamic nucleus deep brain stimulation (DBS). Posterior occipitocervical instrumented fusion after transarticular screw fixation of an odontoid fracture is shown and its rationale explained. Pedunculopontine nucleus DBS as treatment for fall-predominant Parkinson's disease, and globus pallidus interna DBS for dystonia-predominant Parkinson's disease, are discussed.

Local field potentials reveal a distinctive neural signature of cluster headache in the hypothalamus.

Cluster headache (CH) is a debilitating neurovascular condition characterized by severe unilateral periorbital head pain. Deep brain stimulation of the posterior hypothalamus has shown potential in alleviating CH in its most severe, chronic form. During surgical implantation of stimulating macroelectrodes for cluster head pain, one of our patients suffered a CH attack. During the attack local field potentials displayed a significant increase in power of approximately 20 Hz. To the authors' knowledge, this is the first recorded account of neuronal activity observed during a cluster attack. Our results both support and extend the current literature, which has long implicated hypothalamic activation as key to CH generation, predominantly through indirect haemodynamic neuroimaging techniques. Our findings reveal a potential locus in CH neurogenesis and a potential rationale for efficacious stimulator titration.

Awake stereotactic brainstem biopsy via a contralateral, transfrontal, transventricular approach.

The authors describe a novel approach to stereotactic biopsy of lesions of the lateral pons and medial cerebellar peduncle, and its diagnostic success without morbidity. A contralateral approach laterally expands the accessible infratentorial area. It may also confer a theoretical reduction in neurological deficit with passage through non-dominant right hemisphere.

Factors associated with occurrence and recovery of nonambulatory dairy cows in the United States.

The primary objective of this study was to compare characteristics of US dairy operations that had one or more nonambulatory cows (unable to rise for any period of time) (cases) with operations that had no nonambulatory cows (controls) during 2004. A secondary objective was to describe factors associated with recovery of the last nonambulatory cow on the operation during 2004. Case dairy operations (n = 1,822) more often fed a total mixed ration [odds ratio (OR) = 2.0; confidence interval (CI): 1.1-3.4], produced more than 9,090 kg of milk (OR = 2.8; CI: 1.8-4.5), and were more likely to be of medium to large herd size (100 or more head of adult cows, OR = 3.7; CI: 2.2-6.2) compared with control dairies (n = 151). Compared with operations where the predominant flooring surface on which lactating cows stood or walked in winter was pasture, operations where pasture was not the predominant surface were at increased risk of having nonambulatory cows (OR = 4.7; CI: 2.2-10.2). Cows nonambulatory for less than 24 h were more likely to recover compared with cows nonambulatory for 24 h or more (OR = 3.0; CI: 2.0-4.4). Cows that received calcium, phosphorus, or potassium while non-ambulatory were more likely to recover (OR = 3.6; CI: 2.1-6.1) than cattle that did not receive these treatments. Cattle that were not repositioned periodically were more likely to recover (OR = 2.1; CI: 1.4-3.1), as were cattle that were not treated by a veterinarian before becoming nonambulatory (OR = 1.9; CI: 1.1-3.3). These findings are consistent with prolonged recumbency and prior history of health issues, respectively. Nonambulatory cattle with hypocalcemia were more likely to recover (OR = 6.0; CI: 3.4-10.7) compared with nonambulatory cows with all other causes of a nonambulatory condition (analyzed collectively as a single variable but including cancer, clinical mastitis, digestive conditions, metabolic imbalances, neurological problems, respiratory disease, other, unknown). The results of this study reveal that the majority of US dairy operations have at least one nonambulatory dairy cow over the course of a year. Additionally, individual animal factors associated with being nonambulatory may lead to improved identification and treatment of animals that are nonambulatory for a prolonged period. From the perspective of recovery, considering euthanasia is appropriate for cows that have been nonambulatory for more than 24 h.