Monitoring kinetic and frequency-domain properties of eyelid responses in mice with magnetic distance measurement technique

Classical eye-blink conditioning in mutant mice can be used to study the molecular mechanisms underlying associative learning. To measure the kinetic and frequency domain properties of conditioned (tone - periorbital shock procedure) and unconditioned eyelid responses in freely moving mice, we developed a method that allows adequate, absolute, and continuous determination of their eyelid movements in time and space while using an electrical shock as the unconditioned stimulus. The basic principle is to generate a local magnetic field that moves with the animal and that is picked up by either a field-sensitive chip or coil. With the use of this magnetic distance measurement technique (MDMT), but not with the use of electromyographic recordings, we were able to measure mean latency, peak amplitude, velocity, and acceleration of unconditioned eyelid responses, which equaled 7.9 +/- 0.2 ms, 1.2 +/- 0.02 mm, 28.5 +/- 1 mm/s, and 637 +/- 22 mm/s(2), respectively (means +/- SD). During conditioning, the mice reached an average of 78% of conditioned responses over four training sessions, while animals that were subjected to randomly paired conditioned and unconditioned stimuli showed no significant increases. The mean latency of the conditioned responses decreased from 222 +/- 40 ms in session 2 to 127 +/- 6 ms in session 4, while their mean peak latency increased from 321 +/- 45 to 416 +/- 67 ms. The mean peak amplitudes, peak velocities, and peak acceleration of these responses increased from 0.62 +/- 0.02 to 0.77 +/- 0.02 mm, from 3.9 +/- 0.3 to 7.7 +/- 0.5 mm/s, and from 81 +/- 7 to 139 +/- 10 mm/s(2), respectively. Power spectra of acceleration records illustrated that both the unconditioned and conditioned responses of mice had oscillatory properties with a dominant peak frequency close to 25 Hz that was not dependent on training session, interstimulus interval, or response size. These data show that MDMT can be used to measure the kinetics and frequency domain properties of conditioned eyelid responses in mice and that these properties follow the dynamic characteristics of other mammals

High frequency and diversity of parechovirus A in a cohort of Malawian children

Parechoviruses (PeVs) are highly prevalent viruses worldwide. Over the last decades, several studies have been published on PeV epidemiology in Europe, Asia and North America, while information on other continents is lacking. The aim of this study was to describe PeV circulation in a cohort of children in Malawi, Africa. A total of 749 stool samples obtained from Malawian children aged 6 to 60 months were tested for the presence of PeV by real-time PCR. We performed typing by phylogenetic and Basic Local Alignment Search Tool (BLAST) analysis. PeV was found in 57% of stool samples. Age was signifcantly associated with PeV positivity (p = 0.01). Typing by phylogenetic analysis resulted in 15 diferent types, while BLAST typing resulted in 14 diferent types and several indeterminate strains. In total, six strains showed inconsistencies in typing between the two methods. One strain, P02-4058, remained untypable by all methods, but appeared to belong to the recently reclassifed PeV-A19 genotype. PeV-A1, -A2 and -A3 were the most prevalent types (26.8%, 13.8% and 9.8%, respectively). Both the prevalence and genetic diversity found in our study were remarkably high. Our data provide an important contribution to the scarce data available on PeV epidemiology in Africa

Spinal Autofluorescent Flavoprotein Imaging in a Rat Model of Nerve Injury-Induced Pain and the Effect of Spinal Cord Stimulation

Nerve injury may cause neuropathic pain, which involves hyperexcitability of spinal dorsal horn neurons. The mechanisms of action of spinal cord stimulation (SCS), an established treatment for intractable neuropathic pain, are only partially understood. We used Autofluorescent Flavoprotein Imaging (AFI) to study changes in spinal dorsal horn metabolic activity. In the Seltzer model of nerve-injury induced pain, hypersensitivity was confirmed using the von Frey and hotplate test. 14 Days after nerve-injury, rats were anesthetized, a bipolar electrode was placed around the affected sciatic nerve and the spinal cord was exposed by a laminectomy at T13. AFI recordings were obtained in neuropathic rats and a control group of naýve rats following 10 seconds of electrical stimulation of the sciatic nerve at C-fiber strength, or following non-noxious palpation. Neuropathic rats were then treated with 30 minutes of SCS or sham stimulation and AFI recordings were obtained for up to 60 minutes after cessation of SCS/sham. Although AFI responses to noxious electrical stimulation were similar in neuropathic and naýve rats, only neuropathic rats demonstrated an AFI-response to palpation. Secondly, an immediate, short-lasting, but strong reduction in AFI intensity and area of excitation occurred following SCS, but not following sham stimulation. Our data confirm that AFI can be used to directly visualize changes in spinal metabolic activity following nerve injury and they imply that SCS acts through rapid modulation of nociceptive processing at the spinal level

The benefits outweigh the risks for patients undergoing chiropractic care for neck pain: a prospective, multicenter, cohort study.

Objective: This study describes both positive clinical outcomes and adverse events in patients treated for neck pain by a chiropractor. Methods: This study was a prospective, multicenter, observational cohort study. Patients with neck pain of any duration who fulfilled the inclusion criteria were recruited in a practice-based study. Data were collected on the patients and from the chiropractors at baseline, the first 3 visits, and at 3 and 12 months. Clinical outcome measures included (1) neck pain in the 24 hours preceding the visit, (2) neck disability, (3) treatment satisfaction, (4) global assessment, and (5) adverse events. Recovery was defined as "completely improved" or "much better" using the global assessment scale. An adverse event was defined as either a new related complaint or a worsening of the presenting or existing complaint by >30% based upon an 11-point numerical rating scale. Results: In all, 79 chiropractors participated, recruiting 529 subjects, representing 4891 treatment consultations. Follow-up was possible for 90% and 92%, respectively, at 3 and 12 months. Most patients had chronic, recurrent complaints; mild to moderate disability of the neck; and a mild amount of pain at baseline; and two thirds had sought previous care for the presenting complaint in the preceding 6 months. Adverse events after any of the first 3 treatments were reported by 56%, and 13% of the study population reported these events to be severe in intensity. The most common adverse events affected the musculoskeletal system or were pain related, whereas symptoms such as tiredness, dizziness, nausea, or ringing in the ears were uncommon (<8%). Only 5 subjects (1%) reported to be much worse at 12 months. No serious adverse events were recorded during the study period. Of the patients who returned for a fourth visit, approximately half reported to be recovered, whereas approximately two thirds of the cohort were recovered at 3 and 12 months. Conclusion: Adverse events may be common, but are rarely severe in intensity. Most of the patients report recovery, particularly in the long term. Therefore, the benefits of chiropractic care for neck pain seem to outweigh the potential risks. © 2007 National University of Health Sciences

Predictors of adverse events following chiropractic care for patients with neck pain

Objective: This study examines which variables may predict adverse events in subjects undergoing chiropractic treatment for neck pain. Methods: This was a prospective, multi-center, cohort study. All new patients, 18 to 65 years of age with neck pain of any duration, who had not undergone chiropractic care or manual therapy in the prior 3 months, were eligible. Sources of data were questionnaires administered during the first 3 treatments. In all, 60 putative prognostic variables were examined, including descriptors of the patient, chiropractor, and type of treatment delivered. Adverse events were defined as either a new complaint, or the worsening of an existing complaint by more than 30% on an 11-point numerical rating scale. Multivariate random coefficients logistic regression analyses were conducted to determine predictors for the following outcome variables: (1) any adverse event after any of the first 3 visits, (2) any type of adverse event after the first visit only, and (3) specific types of adverse events after the first visit only (ie, headache, increased neck pain, pain and/or stiffness at the treated area). Results: In total, 579 patients were recruited, of whom 529 fulfilled the inclusion criteria. The reported use of a manipulative technique involving cervical rotation, and working status of the patient (sick leave or workers' compensation) were moderately associated with an adverse event after any of the first 3 visits. Patients who had visited their general practitioner in the 6 months before treatment, however, were less likely to have an adverse event. A longer duration with neck pain in the preceding year was moderately associated with specific types of events after the first visit, namely, headache or worsening of the presenting neck pain. Increased neck pain after the first visit was the easiest outcome variable to predict (area under the curve, 0.88; 95% confidence interval, 0.84-0.91). Conclusions: Of the 60 independent variables examined, only 4 were found to be predictive of adverse events after chiropractic treatment for neck pain, one of which was found to be protective. The chiropractic practitioner can identify 3 of these variables before initiating treatment. © 2008 National University of Health Sciences

Performance of VIDISCA-454 in feces-suspensions and serum

Virus discovery combining sequence unbiased amplification with next generation sequencing is now state-of-the-art. We have previously determined that the performance of the unbiased amplification technique which is operational at our institute, VIDISCA-454, is efficient when respiratory samples are used as input. The performance of the assay is, however, not known for other clinical materials like blood or stool samples. Here, we investigated the sensitivity of VIDISCA-454 with feces-suspensions and serum samples that are positive and that have been quantified for norovirus and human immunodeficiency virus type 1, respectively. The performance of VIDISCA-454 in serum samples was equal to its performance in respiratory material, with an estimated lower threshold of 1,000 viral genome copies. The estimated threshold in feces-suspension is around 200,000 viral genome copies. The decreased sensitivity in feces suspension is mainly due to sequences that share no recognizable identity with known sequences. Most likely these sequences originate from bacteria and phages which are not completely sequenced

Healthcare utilization and costs among intracranial meningioma patients during long-term follow-up

Purpose Few studies have reported on healthcare utilization and costs for intracranial meningioma patients, while the tumor and its treatment profoundly affect patients’ functioning and well-being. Here we evaluated healthcare utilization and costs, including their determinants. Methods A multicenter cross-sectional study of adult meningioma patients ≥ 5 years after intervention. Patients completed three validated patient-reported outcome measures (PROMs) assessing patients ‘functioning and wellbeing (SF-36, EORTC QLQ-BN20, and HADS) and a study-specific questionnaire assessing healthcare utilization over the previous twelve months. Healthcare costs of the twelve months prior were calculated using reported healthcare utilization ≥ 5 years after intervention by the Dutch Manual for Economic Evaluation in Healthcare. Determinants for healthcare utilization and costs were determined with regression analyses. Results We included 190 patients with WHO grade I or II meningioma after a mean follow-up since intervention of 9.2 years (SD 4.0). The general practitioner (80.5%), physiotherapist (37.9%), and neurologist (25.4%) were visited most often by patients. Median annual healthcare costs were €871 (IQR €262–€1933). Main contributors to these costs were medication (45.8% of total costs, of which anti-seizure medication was utilized most [21.6%]), specialist care (17.7%), and physiotherapy (15.5%). Lower HRQoL was a significant determinant for higher healthcare utilization and costs. Conclusion In patients with meningioma, medication costs constituted the largest expenditure of total healthcare costs, in particular anti-seizure medication. Particularly a lower HRQoL was a determinant for healthcare utilization and costs. A patient-specific approach aimed at improving patients’ HRQoL and needs could be beneficial in reducing disease burden and functional recovery