Non-Invasive Transcutaneous Afferent Patterned Stimulation Therapy Offers Action Tremor Relief in Parkinson's Disease.

Background: Many patients with Parkinson's disease (PD) experience action tremor (including postural and kinetic tremors) that impair activities of daily living. Transcutaneous afferent patterned stimulation (TAPS) is a non-invasive neuromodulation therapy that modulates tremorgenic activity at the ventral intermediate nucleus (VIM). Most TAPS evidence evaluated relief of action tremor associated with essential tremor (ET). This study evaluated whether TAPS results in similar relief of action tremor associated with PD. Methods: Forty PD patients with action tremors were enrolled in a prospective, single-arm, open-label study with four weeks of unsupervised at-home TAPS sessions in the dominant hand twice daily in between supervised TAPS sessions at two telemedicine appointments. The primary endpoint was change in tremor power as measured by the on-board accelerometer before and immediately after a stimulation session. Additional study endpoints included change in Movement Disorder Society-Sponsored Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS), change in Bain and Findley Activities of Daily Living (BF-ADL) scale, and clinician and patient global impressions of improvement (CGI-I and PGI-I). Results: TAPS reduced tremor power by 64% (54%-79%) (median (interquartile range), p < 0.001), with 79% of patients experiencing at least 50% reduction. When comparing pre-stimulation scores at visit 1 to post-stimulation scores at visit 2, TAPS improved per-task MDS-UPDRS III ratings of postural and kinetic tremors (0.6 ± 0.5, t(34) = 7.05, p < 0.001) and per-task patient-ratings of BF-ADL ADL upper limb motion ratings (0.5 ± 0.5, t(34) = 5.69, p < 0.001). Clinicians reported improvement in 78-83% of patients and 75-80% of patients reported improvement. Adverse events, most commonly skin reaction at the stimulation site, occurred in 18% of patients. Conclusion: Objective, clinician-rated, and patient-rated assessments demonstrated that TAPS provided clinically meaningful relief of action tremor in patients with PD.

High-fidelity transmission of high-frequency burst stimuli from peripheral nerve to thalamic nuclei in children with dystonia.

High-frequency peripheral nerve stimulation has emerged as a noninvasive alternative to thalamic deep brain stimulation for some patients with essential tremor. It is not known whether such techniques might be effective for movement disorders in children, nor is the mechanism and transmission of the peripheral stimuli to central brain structures understood. This study was designed to investigate the fidelity of transmission from peripheral nerves to thalamic nuclei in children with dystonia undergoing deep brain stimulation surgery. The ventralis intermediate (VIM) thalamus nuclei showed a robust evoked response to peripheral high-frequency burst stimulation, with a greatest response magnitude to intra-burst frequencies between 50 and 100 Hz, and reliable but smaller responses up to 170 Hz. The earliest response occurred at 12-15 ms following stimulation onset, suggesting rapid high-fidelity transmission between peripheral nerve and thalamic nuclei. A high-bandwidth, low-latency transmission path from peripheral nerve to VIM thalamus is consistent with the importance of rapid and accurate sensory information for the control of coordination and movement via the cerebello-thalamo-cortical pathway. Our results suggest the possibility of non-invasive modulation of thalamic activity in children with dystonia, and therefore the possibility that a subset of children could have beneficial clinical response without the need for invasive deep brain stimulation.

Highlighting the promise of qPCR-based environmental monitoring: response of the ribosomal RNA:DNA ratio of calanoid copepods to toxic cyanobacteria.

Calanoid copepods are integral to aquatic food webs and may drive the bioaccumulation of toxins and heavy metals, spread of infectious diseases, and occurrence of toxic cyanobacterial harmful algal blooms (HABs) in freshwater aquatic systems. However, interrelationships between copepod and cyanobacterial population dynamics and ecophysiology remain unclear. Insights into these relationships are important to aquatic resource management, as they may help guide mitigation efforts. We developed a calanoid copepod qPCR assay to investigate how copepod abundance and physiological status relate to the abundance of cyanobacteria and the concentration of total microcystin in a HAB-prone freshwater multi-use eutrophic lake. Through in silico and in vitro validation of primers and analyses of time series, we demonstrate that our assay can be used as a reliable tool for environmental monitoring. Importantly, copepod RNA:DNA ratios on and shortly after the day when microcystin concentration was at its highest within the lake were not significantly lower (or higher) than before or after this period, suggesting that copepods may have been tolerant of microcystin levels observed and capable of perpetuating bloom events by consuming competitors of toxic cyanobacteria.

Evoked Potentials During Peripheral Stimulation Confirm Electrode Location in Thalamic Subnuclei in Children With Secondary Dystonia.

Deep brain stimulation is an elective surgical intervention that improves the function and quality of life in children with dystonia and other movement disorders. Both basal ganglia and thalamic nuclei have been found to be relevant targets for treatment of dystonia in children, including the ventral intermediate nucleus of the thalamus, in which stimulation can control dystonic spasms. Electrophysiological confirmation of correct electrode location within the ventralis intermediate nucleus is thus important for the success of the surgical outcome. The present work shows the evoked potentials response during contralateral median-nerve stimulation at the wrist at low frequency (9 Hz) provides physiological evidence of the electrode's localization within the thalamus. We show the correlation between evoked potentials and magnetic resonance imaging (MRI) and computed tomography (CT) in 14 children undergoing implantation of deep brain stimulation electrodes for secondary dystonia. High fidelity and reproducibility of our results provides a new approach to ensure the electrode localization in the thalamic subnuclei.

Pediatric Deep Brain Stimulation Using Awake Recording and Stimulation for Target Selection in an Inpatient Neuromodulation Monitoring Unit.

Deep brain stimulation (DBS) for secondary (acquired, combined) dystonia does not reach the high degree of efficacy achieved in primary (genetic, isolated) dystonia. We hypothesize that this may be due to variability in the underlying injury, so that different children may require placement of electrodes in different regions of basal ganglia and thalamus. We describe a new targeting procedure in which temporary depth electrodes are placed at multiple possible targets in basal ganglia and thalamus, and probing for efficacy is performed using test stimulation and recording while children remain for one week in an inpatient Neuromodulation Monitoring Unit (NMU). Nine Children with severe secondary dystonia underwent the NMU targeting procedure. In all cases, 4 electrodes were implanted. We compared the results to 6 children who had previously had 4 electrodes implanted using standard intraoperative microelectrode targeting techniques. Results showed a significant benefit, with 80% of children with NMU targeting achieving greater than 5-point improvement on the Burke⁻Fahn⁻Marsden Dystonia Rating Scale (BFMDRS), compared with 50% of children using intraoperative targeting. NMU targeting improved BFMDRS by an average of 17.1 whereas intraoperative targeting improved by an average of 10.3. These preliminary results support the use of test stimulation and recording in a Neuromodulation Monitoring Unit (NMU) as a new technique with the potential to improve outcomes following DBS in children with secondary (acquired) dystonia. A larger sample size will be needed to confirm these results.

Microbial degradation of Cold Lake Blend and Western Canadian select dilbits by freshwater enrichments.

Treatability experiments were conducted to determine the biodegradation of diluted bitumen (dilbit) at 5 and 25 °C for 72 and 60 days, respectively. Microbial consortia obtained from the Kalamazoo River Enbridge Energy spill site were enriched on dilbit at both 5 (cryo) and 25 (meso) ºC. On every sampling day, triplicates were sacrificed and residual hydrocarbon concentrations (alkanes and polycyclic aromatic hydrocarbons) were determined by GCMS/MS. The composition and relative abundance of different bacterial groups were identified by 16S rRNA gene sequencing analysis. While some physicochemical differences were observed between the two dilbits, their biodegradation profiles were similar. The rates and extent of degradation were greater at 25 °C. Both consortia metabolized 99.9% of alkanes; however, the meso consortium was more effective at removing aromatics than the cryo consortium (97.5 vs 70%). Known hydrocarbon-degrading bacteria were present in both consortia (Pseudomonas, Rhodococcus, Hydrogenophaga, Parvibaculum, Arthrobacter, Acidovorax), although their relative abundances depended on the temperatures at which they were enriched. Regardless of the dilbit type, the microbial community structure significantly changed as a response to the diminishing hydrocarbon load. Our results demonstrate that dilbit can be effectively degraded by autochthonous microbial consortia from sites with recent exposure to dilbit contamination.

Maternal smoking during pregnancy and fetal organ growth: a magnetic resonance imaging study.

OBJECTIVE: To study whether maternal cigarette smoking during pregnancy is associated with alterations in the growth of fetal lungs, kidneys, liver, brain, and placenta. DESIGN: A case-control study, with operators performing the image analysis blinded. SETTING: Study performed on a research-dedicated magnetic resonance imaging (MRI) scanner (1.5 T) with participants recruited from a large teaching hospital in the United Kingdom. PARTICIPANTS: A total of 26 pregnant women (13 current smokers, 13 non smokers) were recruited; 18 women (10 current smokers, 8 nonsmokers) returned for the second scan later in their pregnancy. METHODS: Each fetus was scanned with MRI at 22-27 weeks and 33-38 weeks gestational age (GA). MAIN OUTCOME MEASURES: Images obtained with MRI were used to measure volumes of the fetal brain, kidneys, lungs, liver and overall fetal size, as well as placental volumes. RESULTS: Exposed fetuses showed lower brain volumes, kidney volumes, and total fetal volumes, with this effect being greater at visit 2 than at visit 1 for brain and kidney volumes, and greater at visit 1 than at visit 2 for total fetal volume. Exposed fetuses also demonstrated lower lung volume and placental volume, and this effect was similar at both visits. No difference was found between the exposed and nonexposed fetuses with regards to liver volume. CONCLUSION: Magnetic resonance imaging has been used to show that maternal smoking is associated with reduced growth of fetal brain, lung and kidney; this effect persists even when the volumes are corrected for maternal education, gestational age, and fetal sex. As expected, the fetuses exposed to maternal smoking are smaller in size. Similarly, placental volumes are smaller in smoking versus nonsmoking pregnant women.

Doppler imaging in the diagnosis of ovarian disease.

INTRODUCTION: Pelvic ultrasonography remains the non-invasive imaging modality of choice for detecting and characterising adnexal masses. The use of Doppler ultrasound has improved the differential diagnosis of ovarian disease and helped to widen the understanding of the aetiology and possible pathophysiology of the various underlying conditions with an aim of improved diagnosis and management. AREAS COVERED: This review describes the basis of different Doppler techniques and their application in ovarian disease. The present evidence is critically analysed in an attempt to define the current role of Doppler ultrasound of the ovaries. The technique holds promise in certain ovarian diseases but remains controversial in others. EXPERT OPINION: Doppler ultrasound has a role in both the clinical and research settings. Clinically, it can be used to differentiate benign and malignant disease and help confirm diagnoses suggested on grey-scale imaging giving the user more confidence. Its use here, however, is generally restricted to a subjective impression of colour flow rather than a quantitative analysis of vascularity or blood flow velocity. These measures are more relevant in the research setting where quantitative Doppler is being used to clarify the possible underlying aetiology of various ovarian diseases such as polycystic ovarian syndrome and benign cysts. Doppler ultrasound has also been used in various models to evaluate the response to ovarian stimulation and the effect of surgery on the ovary.

An analysis of 46 static telecytology cases over a period of two years.

We analysed 46 telecytology cases sent from two rural hospitals about 500 km from a tertiary cancer centre. The cases were submitted for second opinion over a period of two years and evaluated using a static store and forward telecytology approach. A total of 715 digital images were studied (average 15 per case). Forty-one of the 46 cases (89%) were reported within 3 days and 54% of cases were reported within one working day. The aspiration smears and images were found to be of diagnosable quality in 89 and 93% of the cases, respectively. The diagnostic concordance was assessed by comparing the telecytology diagnosis, glass slide diagnosis and final histopathology diagnosis (when available). A clinically useful diagnosis was rendered in 91% cases with 74% complete concordance. Five out of 46 cases (11%) were deferred for glass slide review. Store and forward telecytology using the Internet is a rapid and effective method of providing expert diagnosis in cytology.