Culture of menstrual endometrium with peritoneal explants and mesothelial monolayers confirms attachment to intact mesothelial cells

BACKGROUND: To evaluate adhesion of menstrual endometrium (ME) to intact peritoneal mesothelium. METHODS: Explants of peritoneum were cultured for 1 h with ME (n = 6). Specimens were serially sectioned for haematoxylin and eosin stain and immunohistochemistry using an anti-cytokeratin antibody to label mesothelium. Confocal laser scanning microscopy (CLSM) was performed to identify an intact layer of mesothelial cells (MC) underlying sites of ME attachment. Also, ME and MC were labelled with Cell-Tracker dyes. ME was cultured with mesothelial monolayers for 1 h (n = 10). Cultures were examined with differential interference contrast and CLSM. Optical sections were taken and a three-dimensional model was constructed. RESULTS: In the peritoneal explants, ME adhered to intact mesothelium. There was no evidence of transmesothelial invasion. CLSM of sections of the explants demonstrated an intact monolayer of cytokeratin positive cells below the sites of ME implantation. Cytokeratin negative and positive ME cells adhered to mesothelial cells. Likewise, the ME attached to cultured mesothelium. Orthogonal sections and three-dimensional reconstruction confirmed an intact monolayer of mesothelium underlying ME attachment sites. CONCLUSIONS: This study confirms that ME adheres rapidly to intact peritoneal mesothelium. Further studies are needed that characterize the mechanisms of ME adhesion to, and migration through, mesothelial cells.     

Fetal Electrocardiogram Extraction and Analysis Using Adaptive Noise Cancellation and Wavelet Transformation Techniques

Birth defect-related demise is mainly due to congenital heart defects. In the earlier stage of pregnancy, fetus problem can be identified by finding information about the fetus to avoid stillbirths. The gold standard used to monitor the health status of the fetus is by Cardiotachography(CTG), cannot be used for long durations and continuous monitoring. There is a need for continuous and long duration monitoring of fetal ECG signals to study the progressive health status of the fetus using portable devices. The non-invasive method of electrocardiogram recording is one of the best method used to diagnose fetal cardiac problem rather than the invasive methods.The monitoring of the fECG requires development of a miniaturized hardware and a efficient signal processing algorithms to extract the fECG embedded in the mother ECG. The paper discusses a prototype hardware developed to monitor and record the raw mother ECG signal containing the fECG and a signal processing algorithm to extract the fetal Electro Cardiogram signal. We have proposed two methods of signal processing, first is based on the Least Mean Square (LMS) Adaptive Noise Cancellation technique and the other method is based on the Wavelet Transformation technique. A prototype hardware was designed and developed to acquire the raw ECG signal containing the mother and fetal ECG and the signal processing techniques were used to eliminate the noises and extract the fetal ECG and the fetal Heart Rate Variability was studied. Both the methods were evaluated with the signal acquired from a fetal ECG simulator, from the Physionet database and that acquired from the subject. Both the methods are evaluated by finding heart rate and its variability, amplitude spectrum and mean value of extracted fetal ECG. Also the accuracy, sensitivity and positive predictive value are also determined for fetal QRS detection technique. In this paper adaptive filtering technique uses Sign-sign LMS algorithm and wavelet techniques with Daubechies wavelet, employed along with de noising techniques for the extraction of fetal Electrocardiogram.Both the methods are having good sensitivity and accuracy. In adaptive method the sensitivity is 96.83, accuracy 89.87, wavelet sensitivity is 95.97 and accuracy is 88.5. Additionally, time domain parameters from the plot of heart rate variability of mother and fetus are analyzed.     

Pharyngeal Electrical Stimulation for Dysphagia Associated with Multiple Sclerosis: A Pilot Study

ObjectiveTreatment options for dysphagia associated with multiple sclerosis (MS) are currently limited. In this study we investigated whether intraluminal electrical pharyngeal stimulation facilitates swallowing recovery in dysphagic MS patients.Patients and methodsTwenty dysphagic MS patients were randomized to receive 5 Hz “real” pharyngeal stimulation (10 patients) for 10 min or “sham” pharyngeal stimulation for 10 min (10 patients). Patients were evaluated by videofluoroscopic, and electromyographic examinations, and by the Penetration/Aspiration Scale (PAS) performed before (T₀) and immediately after the last session of 5 consecutive days of electrical pharyngeal stimulation (T₁), and then after two (T₂), and four (T₃) weeks of 5 consecutive days of pharyngeal electrical stimulation.ResultsPatients who received “real” stimulation showed a significant improvement in all the swallowing outcome measures as compared with those receiving “sham” stimulation.ConclusionsNo specific treatment for oro-pharyngeal dysphagia related to MS has been described to date. Our preliminary findings suggest a potential benefit of intraluminal electrical pharyngeal stimulation for the treatment of dysphagia caused by MS.     

Short interval intracortical facilitation correlates with the degree of disability in multiple sclerosis

BackgroundThe Expanded Disability Status Scale (EDSS) is the most widely used measure of disability in MS, however because of its limitations surrogate markers of clinical disability progression are of high interest. Transcranial magnetic stimulation (TMS) measures of demyelination and cortical excitability correlate with disability levels in MS.ObjectiveAim of this study was testing whether paired pulse (pp) TMS represents a reliable surrogate marker to measure clinical disability in MS.MethodsppTMS measures of intracortical synaptic transmission such as short interval intracortical inhibition (SICI), long interval intracortical inhibition (LICI), short interval intracortical facilitation (SICF) and intracortical facilitation (ICF) were collected from 74 patients affected by MS. Correlation of EDSS scores with ppTMS measures was analyzed.ResultsEDSS scores correlated with patient’s age, disease duration, Motor Evoked Potentials latency and thresholds and SICF measures but not with age of onset, SICI, ICF and LICI.ConclusionsThese findings support a possible use of SICF and MEP latency as surrogate markers of disability in MS. Further research is warranted to determine the role of SICF in the follow up of disease progression and to validate its use as an endpoint in multiple sclerosis clinical trials.     

Early use of high-efficacy disease‑modifying therapies makes the difference in people with multiple sclerosis: an expert opinion

Multiple sclerosis (MS) is a chronic and progressive neurological disease that is characterized by neuroinflammation, demyelination and neurodegeneration occurring from the earliest phases of the disease and that may be underestimated. MS patients accumulate disability through relapse-associated worsening or progression independent of relapse activity. Early intervention with high-efficacy disease-modifying therapies (HE-DMTs) may represent the best window of opportunity to delay irreversible central nervous system damage and MS-related disability progression by hindering underlying heterogeneous pathophysiological processes contributing to disability progression. In line with this, growing evidence suggests that early use of HE-DMTs is associated with a significant greater reduction not only of inflammatory activity (clinical relapses and new lesion formation at magnetic resonance imaging) but also of disease progression, in terms of accumulation of irreversible clinical disability and neurodegeneration compared to delayed HE-DMT use or escalation strategy. These beneficial effects seem to be associated with acceptable long-term safety risks, thus configuring this treatment approach as that with the most positive benefit/risk profile. Accordingly, it should be mandatory to treat people with MS early with HE-DMTs in case of prognostic factors suggestive of aggressive disease, and it may be advisable to offer an HE-DMT to MS patients early after diagnosis, taking into account drug safety profile, disease severity, clinical and/or radiological activity, and patient-related factors, including possible comorbidities, family planning, and patients’ preference in agreement with the EAN/ECTRIMS and AAN guidelines. Barriers for an early use of HE-DMTs include concerns for long-term safety, challenges in the management of treatment initiation and monitoring, negative MS patients’ preferences, restricted access to HE-DMTs according to guidelines and regulatory rules, and sustainability. However, these barriers do not apply to each HE-DMT and none of these appear insuperable.

     

Acute severe asthma

Acute exacerbations of asthma are very common reasons for a presentation to emergency departments. This paper focuses on defining the high‐risk group, consideration of the concept of phenotypes of acute asthma, the assessment of severe and life‐threatening exacerbations and an emphasis on the management of the more severe end of the exacerbation severity. A number of evidence‐based guidelines exist throughout the world and are all slightly different. This reflects the poor evidence base for some of those recommendations. Thus, a large variation of treatment drugs, doses and regimen are used and clearly not standardised. This paper aims to present a summary of the best evidence and discuss some of these controversies. The most important aspect of treating an exacerbation of acute asthma is to review regularly and assess response to treatment. Severe and life‐threatening episodes should be treated with early use of intravenous treatment in a stepwise manner following the local guidelines. Non‐invasive ventilation and high flow nasal cannulae delivery of oxygen in the emergency department are evolving modalities, but evidence for their use is currently limited.