TRPM channels are required for rhythmicity in the ultradian defecation rhythm of C. elegans.

BACKGROUND: Ultradian rhythms, rhythms with a period of less than 24 hours, are a widespread and fundamental aspect of life. The mechanisms underlying the control of such rhythms remain only partially understood. Defecation in C. elegans is a very tightly controlled rhythmic process. Underlying the defecation motor programme is an oscillator which functions in the intestinal cells of the animal. This mechanism includes periodic calcium release and subsequent intercellular calcium waves which in turn regulate the muscle contractions that make up the defecation motor programme. Here we investigate the role of TRPM cation channels in this process. RESULTS: We use RNA interference (RNAi) to perturb TRPM channel gene expression. We show that combined knock down of two of the TRPM encoding genes, gon-2 and gtl-1, results in an increase in the variability of the cycle but no change in the mean, in normal culture conditions. By altering the mean using environmental (temperature) and genetic approaches we show that this increase in variability is separable from changes in the mean. We show that gon-2 and gtl-1 interact with components of the calcium signalling machinery (itr-1 the C. elegans inositol 1,4,5-trisphosphate receptor) and with plasma membrane ion channels (flr-1 and kqt-3) which are known to regulate the defecation oscillator. Interactions with these genes result in changes to the mean period and variability. We also show that knocking down a putative transcription factor can suppress the increased variability caused by reduction of gon-2 and gtl-1 function. We also identify a previously unrecognised tendency of the defecation cycle to compensate for cycles with aberrant length by adjusting the length of the following cycle. CONCLUSION: Thus TRPM channels regulate the variability of the defecation oscillator in C. elegans. We conclude that the mean and the variability of the defecation oscillator are separable. Our results support the notion that there is a strong underlying pacemaker which is able to function independently of the observable defecation rhythm and is not perturbed by increases in the variability of the cycle. The interaction of gon-2 and gtl-1 with other components of the oscillator shows that TRPM channels play an important role in the oscillator machinery. Such a role may be through either regulation of cation levels or membrane properties or both. Specifically our results support previous proposals that gon-2 and gtl-1 regulate IP3 signalling and that kqt-3 may act by altering calcium influx. Our results provide novel insights into the properties of the defecation oscillator and thus to our understanding of ultradian rhythms.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Maternal psychological distress in primary care and association with child behavioural outcomes at age three

Observational studies indicate children whose mothers have poor mental health are at increased risk of socio-emotional behavioural difficulties, but it is unknown whether these outcomes vary by the mothers’ mental health recognition and treatment status. To examine this question, we analysed linked longitudinal primary care and research data from 1078 women enrolled in the Born in Bradford cohort. A latent class analysis of treatment status and self-reported distress broadly categorised women as (a) not having a common mental disorder (CMD) that persisted through pregnancy and the first 2 years after delivery (N = 756, 70.1 %), (b) treated for CMD (N = 67, 6.2 %), or (c) untreated (N = 255, 23.7 %). Compared to children of mothers without CMD, 3-year-old children with mothers classified as having untreated CMD had higher standardised factor scores on the Strengths and Difficulties Questionnaire (d = 0.32), as did children with mothers classified as having treated CMD (d = 0.27). Results were only slightly attenuated in adjusted analyses. Children of mothers with CMD may be at risk for socio-emotional and behavioural difficulties. The development of effective treatments for CMD needs to be balanced by greater attempts to identify and treat women. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00787-015-0777-2) contains supplementary material, which is available to authorized users

Effect of magnesium sulphate added to lidocaine on inferior alveolar nerve block success in patients with symptoms of irreversible pulpitis: a prospective, randomized clinical trial

AIM: To investigate the effect of magnesium sulphate used as an adjuvant to lidocaine with epinephrine local anaesthetic on the success of inferior alveolar nerve blocks (IANB) in patients with irreversible pulpitis undergoing root canal treatment. METHODOLOGY: In a double-blind clinical trial, following power calculation, 124 patients with symptoms of irreversible pulpitis in mandibular molar teeth were selected and initial pain data was collected using a Heft-Parker (Heft & Parker 1984) visual analogue scale. The first group (control) received IANB with 1.8 mL of a local anaesthetic solution containing 1.8% lidocaine with 1:88,000 epinephrine whist the second group (test) received IANB with 1.8 mL of an anaesthetic solution containing 1% magnesium sulphate, and 1.8% lidocaine with 1:88,000 epinephrine. Pain data was collected after access cavity and penetration of files in the canals using a Heft-Parker visual analog scale. Two patients were not included in the study as they did not consent and a further 54 patients were excluded as they did not report lip numbness within 15 minutes after IANB administration, thus the data presented in this study is related to 68 patients. The data were analyzed using chi-square and t- test (α=0.05). RESULTS: The success of pulpal anaesthesia with IANB was 82% for the magnesium sulphate group and 53% for the control group. There was a significant difference in the effectiveness of the IANB between the 2 groups (P < 0.001). There was no significant difference between the magnesium sulphate and control groups regarding gender (P =0.598) or age (P = 0.208) or initial pain scores (P = 0.431). CONCLUSIONS: The addition of 1% magnesium sulphate to 1.8% lidocaine with 1:88,000 epinephrine resulted in a positive impact for the success of IANB in patients with a diagnosis of irreversible pulpitis related to mandibular molar teeth undergoing root canal treatment. Thus magnesium sulphate may be used as adjuvant for achieving profound pulpal anaesthesia in challenging cases. However, more studies with larger sample size and different concentration doses must be carried out to establish an appropriate conclusion before its routine clinical use

Implementation of immunohistochemistry on frozen ear notch tissue samples in diagnosis of bovine viral diarrhea virus in persistently infected cattle

<p>Abstract</p> <p>Background</p> <p>Bovine viral diarrhea is a contagious disease of domestic and wild ruminants and one of the most economically important diseases in cattle. Bovine viral diarrhea virus belongs to the genus <it>Pestivirus</it>, within the family <it>Flaviviridae</it>. The identification and elimination of the persistently infected animals from herds is the initial step in the control and eradication programs. It is therefore necessary to have reliable methods for diagnosis of bovine viral diarrhea virus. One of those methods is immunohistochemistry. Immunohistochemistry on formalin fixed, paraffin embedded tissue is a routine technique in diagnosis of persistently infected cattle from ear notch tissue samples. However, such technique is inappropriate due to complicated tissue fixation process and it requires more days for preparation. On the contrary, immunohistochemistry on frozen tissue was usually applied on organs from dead animals. In this paper, for the first time, the imunohistochemistry on frozen ear notch tissue samples was described.</p> <p>Findings</p> <p>Seventeen ear notch tissue samples were obtained during the period 2008-2009 from persistently infected cattle. Samples were fixed in liquid nitrogen and stored on -20°C until testing. Ear notch tissue samples from all persistently infected cattle showed positive results with good section quality and possibility to determinate type of infected cells.</p> <p>Conclusions</p> <p>Although the number of samples was limited, this study indicated that immunohistochemistry on formalin fixed paraffin embedded tissue can be successfully replaced with immunohistochemistry on frozen ear notch tissue samples in diagnosis of persistently infected cattle.</p

Vivid visual mental imagery in the absence of the primary visual cortex

The role of the primary visual cortex in visual mental imagery has provided significant debate in the imagery literature. Functional neuroimaging studies show considerable variation depending on task and technique. Patient studies can be difficult to interpret due to the diverse nature of cortical damage. The type of cortical damage in patient SBR is exceedingly rare as it is restricted to the gray matter of the calcarine sulcus. In this study, we show that in spite of his near-complete cortical blindness, SBR exhibits vivid visual mental imagery both behaviorally and when measured with functional magnetic resonance imaging. The pattern of cortical activation to visual mental imagery in SBR is indistinguishable from individual sighted subjects, in contrast to the visual perceptual responses, which are greatly attenuated

Lemierre's syndrome, reemergence of a forgotten disease: a case report

Lemierre's syndrome is a rare disorder of young adults caused by the anaerobic bacterium, Fusobacterium necrophorum and occasionally by other Fusobacterium species (F. nucleatum, F. mortiferum and F. varium etc). The condition is characterized by a primary oropharyngeal infection with evidence of septic thrombophlebitis, exhibited by positive blood cultures, clinical or radiographic evidence of internal jugular vein thrombosis, and at least one metastatic focus. The incidence of Lemierre's syndrome is reported to be nearly one in a million. In the pre-antibiotic era, Lemierre's syndrome followed a fulminant, often fatal course. During the 1960s and 1970s, the syndrome was rarely reported when penicillin was commonly prescribed to treat oropharyngeal infections. Today, antibiotic-resistant organisms are a major concern, thus causing more prudent prescribing of antibiotics. We present a case report of a 27-year-old man with worsening pharyngitis, which illustrates that subsequent reemergence of this often forgotten disease may become more common in clinical setting

Review of mobile applications for optimizing the follow-up care of patients with diabetes

© 2018, The Author(s). Background: Several smartphone applications aim at facilitating communication between patients and healthcare providers. In this review, we evaluate and compare the most promising applications in the field of diabetes mellitus (DM) and obesity. Most applications monitor body weight, fasting or postprandial blood glucose, glycosylated hemoglobin (Hgb) A1c (HgbA1c), and units and types of insulin used. Methods: Nine clinically tested applications and two Web platforms were grouped into three categories that were evaluated and compared. Group 1 included seven applications focusing mainly on monitoring DM, fitness and weight, blood glucose levels, and HbA1c. Group 2 included two applications that focus on insulin dosage calculators and glucose self-monitoring tests. Group 3 included two web-platforms that interact with patients via SMS (short message service) messaging. Results: A common feature of the applications examined was the limited number of clinical parameters tested, the small number of subjects taking part in the evaluation, and the fact that the controls were not randomized. Furthermore, the interfaces of the applications varied and were not standardized. Finally, another common characteristic across applications was the lack of standardization of the interface and the overall structure due to language barriers, the devices usually having been designed around a specific language. Lastly, most applications lacked a critical mass of evaluators and were thus not worthy of being considered of serious clinical relevance. Conclusions: The current smartphone applications for DM are characterized by a limited number of participants, a small number of parameters, and a lack of standardization.Published versio

Predicting Clinical Outcome of Stroke Patients with Tractographic Feature

The volume of stroke lesion is the gold standard for predicting the clinical outcome of stroke patients. However, the presence of stroke lesion may cause neural disruptions to other brain regions, and these potentially damaged regions may affect the clinical outcome of stroke patients. In this paper, we introduce the tractographic feature to capture these potentially damaged regions and predict the modified Rankin Scale (mRS), which is a widely used outcome measure in stroke clinical trials. The tractographic feature is built from the stroke lesion and average connectome information from a group of normal subjects. The tractographic feature takes into account different functional regions that may be affected by the stroke, thus complementing the commonly used stroke volume features. The proposed tractographic feature is tested on a public stroke benchmark Ischemic Stroke Lesion Segmentation 2017 and achieves higher accuracy than the stroke volume and the state-of-the-art feature on predicting the mRS grades of stroke patients. In addition, the tractographic feature also yields a lower average absolute error than the commonly used stroke volume feature.Comment: 12 pages, 4 figures, 3 tables. Accepted by MICCAI-BrainLesion 2019 as an oral presentatio