Environmental metabolomics uncovers oxidative stress, amino acid dysregulation, and energy impairment in Daphnia magna with exposure to industrial effluents.

Anthropogenic activities are regarded as point sources of pollution entering freshwater bodies worldwide. With over 350,000 chemicals used in manufacturing, wastewater treatment and industrial effluents are comprised of complex mixtures of organic and inorganic pollutants of known and unknown origins. Consequently, their combined toxicity and mode of action are not well understood in aquatic organisms such as Daphnia magna. In this study, effluent samples from wastewater treatment and industrial sectors were used to examine molecular-level perturbations to the polar metabolic profile of D. magna. To determine if the industrial sector and/or the effluent chemistries played a role in the observed biochemical responses, Daphnia were acutely (48 h) exposed to undiluted (100%) and diluted (10, 25, and 50%) effluent samples. Endogenous metabolites were extracted from single daphnids and analyzed using targeted mass spectrometry-based metabolomics. The metabolic profile of Daphnia exposed to effluent samples resulted in significant separation compared to the unexposed controls. Linear regression analysis determined that no single pollutant detected in the effluents was significantly correlated with the responses of metabolites. Significant perturbations were uncovered across many classes of metabolites (amino acids, nucleosides, nucleotides, polyamines, and their derivatives) which serve as intermediates in keystone biochemical processes. The combined metabolic responses are consistent with oxidative stress, disruptions to energy metabolism, and protein dysregulation which were identified through biochemical pathway analysis. These results provide insight into the molecular processes driving stress responses in D. magna. Overall, we determined that the metabolic profile of Daphnia could not be predicted by the chemical composition of environmentally relevant mixtures. The findings of this study demonstrate the advantage of metabolomics in conjunction with chemical analyses to assess the interactions of industrial effluents. This work further demonstrates the ability of environmental metabolomics to characterize molecular-level perturbations in aquatic organisms exposed to complex chemical mixtures directly.

Finely-tuned gamma oscillations: Spectral characteristics and links to dyskinesia.

Gamma oscillations comprise a loosely defined, heterogeneous group of functionally different activities between 30 and 100 Hz in the cortical and subcortical local field potential (LFP) of the motor network. Two distinct patterns seem to emerge which are easily conflated: Finely-tuned gamma (FTG) oscillations - a narrowband activity with peaks between 60 and 90 Hz - have been observed in multiple movement disorders and are induced by dopaminergic medication or deep brain stimulation (DBS). FTG has been linked with levodopa or DBS-induced dyskinesias, which makes it a putative biomarker for adaptive DBS. On the other hand, gamma activity can also present as a broad phenomenon (30-100 Hz) in the context of motor activation and dynamic processing. Here, we contrast FTG, either levodopa-induced or DBS-induced, from movement-related broadband gamma synchronisation and further elaborate on the functional role of FTG and its potential implications for adaptive DBS. Given the unclear distinction of FTG and broad gamma in literature, we appeal for more careful separation of the two. To better characterise cortical and subcortical FTG as biomarkers for dyskinesia, their sensitivity and specificity need to be investigated in a large clinical trial.

Thalamic deep brain stimulation for post-traumatic neuropathic limb pain: Efficacy at five years' follow-up and effective volume of activated brain tissue.

Chronic neuropathic pain affects 7%-10% of the population. Deep brain stimulation (DBS) has shown variable but promising results in its treatment. This study prospectively assessed the long-term effectiveness of DBS in a series of patients with chronic neuropathic pain, correlating clinical results with neuroimaging. Sixteen patients received 5 years' post-surgical follow-up in a single center. Six had phantom limb pain after amputation and 10 had deafferentation pain after traumatic brachial plexus injury. Patient-reported outcome measures were completed before and after surgery, using VAS, UWNPS, BPI and SF-36 scores. Neuroimaging evaluated electrode location and effective volumes of activated tissue (VAT). Two subgroups were created based on the percentage of VAT superimposed upon the ventroposterolateral thalamic nucleus (eVAT), and clinical outcomes were compared. Analgesic effect was assessed at 5 years and compared to preoperative pain, with an improvement on VAS of 76.4% (p=0.0001), on UW-NPS of 35.2% (p=0.3582), on BPI of 65.1% (p=0.0505) and on SF-36 of 5% (p=0.7406). Eight patients with higher eVAT showed improvement on VAS of 67.5% (p=0.0017) while the remaining patients, with lower eVAT, improved by 50.6% (p=0.03607). DBS remained effective in improving chronic neuropathic pain after 5 years. While VPL-targeting contributes to success, analgesia is also obtained by stimulating surrounding posterior ventrobasal thalamic structures and related spinothalamocortical tracts.

Fulminant intracranial hypertension secondary to oxytetracycline requiring urgent ventriculo-peritoneal shunt insertion.

Idiopathic intracranial hypertension is a syndrome that presents with headaches and visual loss. Its pathogenesis is unknown. Treatment options include acetazolamide, therapeutic lumbar punctures or permanent CSF diversion. We present the only reported case of acute drug-induced intracranial hypertension secondary to oxytetracycline requiring urgent cerebrospinal fluid diversion. The patient's rapid visual failure progressed daily despite discontinuation of the drug and required an urgent ventriculo-peritoneal (VP) shunt insertion. Patients should be counselled about the rare potential risk of developing intracranial hypertension when commencing oxytetracycline. Rapid visual failure in IIH is a neurosurgical emergency necessitating urgent ventriculoperitoneal shunt insertion.

Subthalamic deep brain stimulation induces finely-tuned gamma oscillations in the absence of levodopa.

Finely-tuned gamma (FTG) oscillations can be recorded from cortex or the subthalamic nucleus (STN) in patients with Parkinson's disease (PD) on dopaminergic medication, and have been associated with dyskinesias. When recorded during deep brain stimulation (DBS) on medication the FTG is entrained to half the stimulation frequency. We investigated whether these characteristics are shared off medication by recording local field potentials (LFP) from the STN from externalised DBS leads in 14 PD patients after overnight withdrawal of medication. FTG was induced de-novo by DBS in the absence of dyskinesias in a third of our cohort. The FTG could outlast stimulation or arise only after DBS ceased. FTG frequencies decreased during and across consecutive DBS blocks, but did not shift with changing stimulation frequency off medication. Together with the sustained after-effects this argues against simple entrainment by DBS in the off medication state. We also found significant coherence between STN-LFP and electroencephalogram (EEG) signals at FTG frequencies. We conclude that FTG is a network phenomenon that behaves differently in the off medication state, when it is neither associated with dyskinesias nor susceptible to entrainment.

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.

Hypomimia in Parkinson's disease: an axial sign responsive to levodopa.

BACKGROUND AND PURPOSE: Hypomimia is a prominent clinical feature in people with Parkinson's disease (PD), but it remains under-investigated. We aimed to examine the clinical correlates of hypomimia in PD and to determine whether this is a levodopa-responsive sign. METHODS: We included 89 people with PD. Hypomimia was assessed from digital video recordings by movement disorder specialists. Clinical evaluation included use of the Unified Parkinson's Disease Rating Scale part III (UPDRS-III), and assessment of motor and non-motor symptoms using standardized clinical scales. The relationships between hypomimia and other clinical data were analysed using Mann-Whitney U-tests and regression analysis. RESULTS: Hypomimia occurred in up to 70% of patients with PD. Patients with hypomimia had worse UPDRS-III 'off-medication' scores, mainly driven by bradykinesia and rigidity subscores. Patients with hypomimia also had worse apathy than patients without hypomimia. Finally, we found that hypomimia was levodopa-responsive and its improvement mirrored the change by levodopa in axial motor symptoms. CONCLUSION: Our study provides novel information regarding the clinical correlates of hypomimia in people with PD. A better understanding of hypomimia may be relevant for improving treatment and quality of life in PD.

Local field potential activity dynamics in response to deep brain stimulation of the subthalamic nucleus in Parkinson's disease.

Local field potentials (LFPs) may afford insight into the mechanisms of action of deep brain stimulation (DBS) and potential feedback signals for adaptive DBS. In Parkinson's disease (PD) DBS of the subthalamic nucleus (STN) suppresses spontaneous activity in the beta band and drives evoked resonant neural activity (ERNA). Here, we investigate how STN LFP activities change over time following the onset and offset of DBS. To this end we recorded LFPs from the STN in 14 PD patients during long (mean: 181.2 s) and short (14.2 s) blocks of continuous stimulation at 130 Hz. LFP activities were evaluated in the temporal and spectral domains. During long stimulation blocks, the frequency and amplitude of the ERNA decreased before reaching a steady state after ~70 s. Maximal ERNA amplitudes diminished over repeated stimulation blocks. Upon DBS cessation, the ERNA was revealed as an under-damped oscillation, and was more marked and lasted longer after short duration stimulation blocks. In contrast, activity in the beta band suppressed within 0.5 s of continuous DBS onset and drifted less over time. Spontaneous activity was also suppressed in the low gamma band, suggesting that the effects of high frequency stimulation on spontaneous oscillations may not be selective for pathological beta activity. High frequency oscillations were present in only six STN recordings before stimulation onset and their frequency was depressed by stimulation. The different dynamics of the ERNA and beta activity with stimulation imply different DBS mechanisms and may impact how these activities may be used in adaptive feedback.

Intraspinal anomalies in early-onset idiopathic scoliosis.

AIMS: In the United Kingdom, lower incidences of intraspinal abnormalities in patients with early onset idiopathic scoliosis have been observed than in studies in other countries. We aimed to determine the rates of these abnormalities in United Kingdom patients diagnosed with idiopathic scoliosis before the age of 11 years. PATIENTS AND METHODS: This retrospective study of patients attending an urban scoliosis clinic identified 71 patients satisfying a criteria of: clinical diagnosis of idiopathic scoliosis; age of onset ten years and 11 months or less; MRI screening for intraspinal abnormalities. United Kingdom census data combined with patient referral data was used to calculate incidence. RESULTS: Mean age at diagnosis was six years with 39 right-sided and 32 left-sided curves. Four patients (5.6%) were found to have intraspinal abnormalities on MRI. These consisted of: two combined Arnold-Chiari type 1 malformations with syrinx; one syrinx with a low lying conus; and one isolated syrinx. Overall annual incidence of early onset idiopathic scoliosis was one out of 182 000 (0.0006%). CONCLUSION: This study reports the lowest rates to date of intraspinal anomalies in patients with early onset idiopathic scoliosis, adding to knowledge regarding current incidences of these abnormalities as well as any geographical variation in the nature of the disease. Cite this article: Bone Joint J 2017;99-B:829-33.

Role of radiology in central nervous system stimulation.

Central nervous system (CNS) stimulation is becoming increasingly prevalent. Deep brain stimulation (DBS) has been proven to be an invaluable treatment for movement disorders and is also useful in many other neurological conditions refractory to medical treatment, such as chronic pain and epilepsy. Neuroimaging plays an important role in operative planning, target localization and post-operative follow-up. The use of imaging in determining the underlying mechanisms of DBS is increasing, and the dependence on imaging is likely to expand as deep brain targeting becomes more refined. This article will address the expanding role of radiology and highlight issues, including MRI safety concerns, that radiologists may encounter when confronted with a patient with CNS stimulation equipment in situ.

Efeito da fração não-oleosa doRicinus communisna biodistribuição comTecnécio-99m em camundongos / Effect of non-oily fraction ofRicinus communis on the bio distribution with Technetium-99m in mice

RESUMO Ricinus communisé uma planta pertence à família Euforbiaceae. A partir de seus frutos é extraído o óleo de rícino e outra fração altamente tóxica (fração não-oleosa). Neste estudo, foi avaliado o efeito da fração não oleosa de R. communis(FNORC) na biodistribuição do Tc-99m em camundongos sadios e em animais transplantados com Sarcoma-180 (S180). Para avaliação da biodistribuição do Tc-99m, o percentual de atividade radioativa total injetada (ATI%) foi mensurada utilizando um contador gama. Os resultados mostraram que, em animais sadios, houve aumento da captação do Tc-99m após o tratamento com FNORC pelos rins, cérebro e estômago. Apenas houve diminuição da absorção deste radioisótopo nos músculos. Em animais com tumor, houve redução significativa da captação do Tc-99m no coração, pulmões e tumor, e foi observado o aumento da captação apenas nos rins. Foi observada também a diminuição da concentração das proteínas plasmáticas totais em animais com tumor após tratamento com FNORC e atividade antitumoral significativa. Diante desses dados, conclui-se que fração não oleosa de R. communis possui atividade antitumoral significativa, porém altera a biodistribuição do Tc-99m, fato este que pode resultar em falhas nos processos de diagnóstico por imagem que utilizem este radioisótopo como marcador.

ABSTRACT Ricinus communis is a plant belonging to the Euforbiaceae family. From its fruits, it is extracted the castor oil and another highly toxic fraction (non-oily fraction). In this study, we evaluated the effect of the non-oily fraction of R. communis (NOFRC) on the bio distribution of Tc-99m in healthy mice and in animals transplanted with Sarcoma-180 (S180). To evaluate the bio distribution of theTc-99m, the percentage of the total injected radioactivity (% TIR) was measured through a gamma counter. There was an increase in the capitation of Tc-99m after the treatment with NOFRC in the kidneys, brain, and stomach of healthy animals. A decrease in the reception of this radionuclide was only found in the muscles. In animals with tumour, there was a significant reduction in the uptake of Tc-99m in the heart, lungs and tumour. An increase in the capitation was only observed in the kidneys. It was also observed a reduction in the total plasma protein concentration in animals with tumours after the treatment with NOFRC, besides significant antitumor activity. We concluded that there is antitumor activity in the NOFRC, but that it alters the biodistribution of Tc-99m, a fact which may result in failures in the diagnostic imaging process using this radioisotope as a marker.

Influence of acute exercise on the osmotic stability of the human erythrocyte membrane.

This study evaluated the effects of 2 different types of acute aerobic exercise on the osmotic stability of human erythrocyte membrane and on different hematological and biochemical variables that are associated with this membrane property. The study population consisted of 20 healthy and active men. Participants performed single sessions of 2 types of exercise. The first session consisted of 60 min of moderate-intensity continuous exercise (MICE). The second session, executed a week later, consisted of high-intensity interval exercise (HIIE) until exhaustion. The osmotic stability of the erythrocyte membrane was represented by the inverse of the salt concentration (1/H50) at the midpoint of the sigmoidal curve of dependence between the absorbance of hemoglobin and the NaCl concentration. The values of 1/H50 changed from 2.29±0.1 to 2.33±0.09 after MICE and from 2.30±0.08 to 2.23±0.12 after HIIE. During MICE mean corpuscular volume increased, probably due to in vivo lysis of older erythrocytes, with preservation of cells that were larger and more resistant to in vitro lysis. The study showed that a single bout of acute exercise affected erythrocyte stability, which increased after MICE and decreased after HIIE.

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.

La maladie de Grisel treated by combined C1-2 transarticular and C1 lateral mass screw fixation.

The authors describe a novel posterior approach to atlantoaxial stabilization combining C1-2 transarticular and C1 lateral mass screws with vertical connecting rods to create a strong construct with four-point fixation. They present here a case of atlanto-axial instability secondary to infection, Grisel's syndrome, necessitating instrumented stabilization after a period of close clinical and radiological observation following the initial cervical decompression and evacuation of retropharyngeal and epidural abscesses.

Neurosurgery as a first foundation year training post.

Neurosurgery has traditionally been regarded as a surgical speciality unsuitable for doctors in their first clinical year after graduation with limited prior experience of such patients. However, the advent of UK Modernising Medical Careers' Foundation Year training and the European Working Time Directive mean neurosurgery is now available as a clinical placement for newly qualified doctors. The authors describe the development of such a post, first implemented in August 2008, which both facilitated safe and effective care of neurosurgical patients and enabled the trainee to achieve many of the goals of UK Foundation training. Suggestions are made for the implementation of further similar posts.

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.

The contribution of genes required for anaerobic respiration to the virulence of Salmonella enterica serovar Gallinarum for chickens

Salmonella enterica serovar Gallinarum (SG) is an intracellular pathogen of chickens. To survive, to invade and to multiply in the intestinal tract and intracellularly it depends on its ability to produce energy in anaerobic conditions. The fumarate reductase (frdABCD), dimethyl sulfoxide (DMSO)-trimethylamine N-oxide (TMAO) reductase (dmsABC), and nitrate reductase (narGHIJ) operons in Salmonella Typhimurium (STM) encode enzymes involved in anaerobic respiration to the electron acceptors fumarate, DMSO, TMAO, and nitrate, respectively. They are regulated in response to nitrate and oxygen availability and changes in cell growth rate. In this study mortality rates of chickens challenged with mutants of Salmonella Gallinarum, which were defective in utilising anaerobic electron acceptors, were assessed in comparison to group of bird challenged with wild strain. The greatest degree of attenuation was observed with mutations affecting nitrate reductase (napA, narG) with additional attenuations induced by a mutation affecting fumarate reductase (frdA) and a double mutant (dmsA torC) affecting DMSO and TMAO reductase.

Neurosciences intensive care medicine in initial neurosurgical training.

The authors describe a novel 4-month clinical placement in neurosciences intensive care medicine (NICM) undertaken in the first specialty registrar (ST1) year of neurosurgical training as part of a clinical neurosciences themed training year. Neurosurgery is unique among British surgical specialties in having pioneered themed early years in run-through training to replace basic surgical training in general surgical specialties as part of Modernising Medical Careers. After describing events leading to the new neurosurgical training, the knowledge, skills and attitudes acquired in NICM are highlighted alongside discussion of logistic aspects and future directions from an inaugural experience.