Fasciculation electromechanical latency is prolonged in amyotrophic lateral sclerosis.

OBJECTIVE: In amyotrophic lateral sclerosis (ALS), motor neurons become hyperexcitable and spontaneously discharge electrical impulses causing fasciculations. These can be detected by two noninvasive methods: high-density surface electromyography (HDSEMG) and muscle ultrasonography (MUS). We combined these methods simultaneously to explore the electromechanical properties of fasciculations, seeking a novel biomarker of disease. METHODS: Twelve ALS patients and thirteen healthy participants each provided up to 24 minutes of recordings from the right biceps brachii (BB) and gastrocnemius medialis (GM). Two automated algorithms (Surface Potential Quantification Engine and a Gaussian mixture model) were applied to HDSEMG and MUS data to identify correlated electromechanical fasciculation events. RESULTS: We identified 4,197 correlated electromechanical fasciculation events. HDSEMG reliably detected electromechanical events up to 30 mm below the skin surface with an inverse correlation between amplitude and depth in ALS muscles. Compared to Healthy-GM muscles (mean = 79.8 ms), electromechanical latency was prolonged in ALS-GM (mean = 108.8 ms; p = 0.0458) and ALS-BB (mean = 112.0 ms; p = 0.0128) muscles. Electromechanical latency did not correlate with disease duration, symptom burden, sum muscle power score or fasciculation frequency. CONCLUSIONS: Prolonged fasciculation electromechanical latency indicates impairment of the excitation-contraction coupling mechanism, warranting further exploration as a potential novel biomarker of disease in ALS. SIGNIFICANCE: This study points to an electromechanical defect within the muscles of ALS patients.

Diet and irritable bowel syndrome: an update from a UK consensus meeting.

There has been a renewed interest in the role of dietary therapies to manage irritable bowel syndrome (IBS), with diet high on the agenda for patients. Currently, interest has focussed on the use of traditional dietary advice (TDA), a gluten-free diet (GFD) and the low FODMAP diet (LFD). A consensus meeting was held to assess the role of these dietary therapies in IBS, in Sheffield, United Kingdom.Evidence for TDA is from case control studies and clinical experience. Randomised controlled trials (RCT) have demonstrated the benefit of soluble fibre in IBS. No studies have assessed TDA in comparison to a habitual or sham diet. There have been a number of RCTs demonstrating the efficacy of a GFD at short-term follow-up, with a lack of long-term outcomes. Whilst gluten may lead to symptom generation in IBS, other components of wheat may also play an important role, with recent interest in the role of fructans, wheat germ agglutinins, as well as alpha amylase trypsin inhibitors. There is good evidence for the use of a LFD at short-term follow-up, with emerging evidence demonstrating its efficacy at long-term follow-up. There is overlap between the LFD and GFD with IBS patients self-initiating gluten or wheat reduction as part of their LFD. Currently, there is a lack of evidence to suggest superiority of one diet over another, although TDA is more acceptable to patients.In view of this evidence, our consensus group recommends that dietary therapies for IBS should be offered by dietitians who first assess dietary triggers and then tailor the intervention according to patient choice. Given the lack of dietetic services, novel approaches such as employing group clinics and online webinars may maximise capacity and accessibility for patients. Further research is also required to assess the comparative efficacy of dietary therapies to other management strategies available to manage IBS.

Cumplimiento de las medidas de restricción del uso residencial de leña en la ciudad de Valdivia / Compliance with the measures of restrict the residential use of firewood in Valdivia, Chile

BACKGROUND: Atmospheric pollution is a problem that causes great concern and health risks for the population and the earth, as it affects developed countries and third world countries. Locally, there are no studies that prove the fulfillment level of the restriction about the usage of residential firewood, considering that since 2014 there is a procedure called "The Environmental Decontamination Plan" in Valdivia (PDAV). Aim: To determine the fulfillment level of the restriction about residential firewood and its related factors. MATERIAL AND METHODS: The population study were 594 homes that were assigned randomly and proportionally according to 2 territorial areas (A and B) established in the PDAV. The sample's characteristics were described, comparison techniques were applied by subgroups (sociodemographic, home's structures and humidity's perception and percentage of the firewood) to identify factors related mainly with the fulfillment of measurements about firewood usage. RESULTS: 52% of households do not comply with the residential firewood use restriction measure, having sociodemographic factors related with this failure, such as schooling, health insurance and home structure. Besides, it is noted that the knowledge level of PDAV is associated with the accomplish level of restriction measures. When people know more about PDAV, there is a higher proportion of accomplishment. Conclusion: In more than half of the households, the restriction on the use of woodstove is not complied. The lack of knowledge of the population about the PDAV directly influences its compliance, which requires strategies to promote adherence to this program.

Expert opinion: Stepwise ultrasound assessment of suspected placenta accreta spectrum using 2D, Doppler and 3D imaging.

Placenta Accreta Spectrum (PAS) describes a spectrum of conditions ranging from 'sticky' placenta to placenta accreta, increta and percreta-each describing progressively deeper invasion into the uterus. It is a major contributor to maternal and perinatal morbidity particularly where clinical facilities are not immediately available. Hence accurate diagnosis is important in determining timing and place of delivery, and logistical arrangements of the clinical team and specialties. Although many different ultrasound features have been described, their relationship to the final operative diagnosis remains variably described. Ultrasound manufactures have developed new imaging techniques particularly in relation to Doppler and 3D processing techniques. We describe a standardized imaging approach employing new ultrasound modalities matched to the attributes unique to invasive placenta. The '3V' system describes the stages of placental invasion: namely low-flow Doppler techniques to delineate the vascular anatomy of the placenta and delineating its interface with the myometrium, and 3D 'context preserving' post processing technologies defining the placental interface with maternal structures (vesicular invasion and visceral extension). Used together with well characterized 2D imaging signs, we describe pictorially by reference to clinical cases how this standardized methodology allows new insights into the ultrasound diagnosis of PAS.

Peritoneal mesothelioma presenting with 'kissing' liver metastases.

A 61-year-old woman was diagnosed with an incidental liver lesion with a satellite lesion that had features of a secondary liver metastasis. Investigations for primary sites did not reveal a primary tumour. The lesion was not amenable to biopsy due to location. Intraoperatively, the two lesions were adjacent, but the first was on the diaphragm and the lesion was in segment 7 of the liver. The liver lesion underwent non-anatomical resection and the diaphragmatic lesion was resected separately. The histopathology diagnosed peritoneal mesothelioma in the lesion removed from diaphragm and the liver lesion to be local metastatic spread to an area of liver that was in close contact (a 'kissing' lesion). This report portrays a rare occurrence of liver metastases from peritoneal mesothelioma and discusses the current evidence for diagnosis and treatment.

[Compliance with the measures of restrict the residential use of firewood in Valdivia, Chile]. / Cumplimiento de las medidas de restricción del uso residencial de leña en la ciudad de Valdivia.

BACKGROUND: Atmospheric pollution is a problem that causes great concern and health risks for the population and the earth, as it affects developed countries and third world countries. Locally, there are no studies that prove the fulfillment level of the restriction about the usage of residential firewood, considering that since 2014 there is a procedure called "The Environmental Decontamination Plan" in Valdivia (PDAV). AIM: To determine the fulfillment level of the restriction about residential firewood and its related factors. MATERIAL AND METHODS: The population study were 594 homes that were assigned randomly and proportionally according to 2 territorial areas (A and B) established in the PDAV. The sample's characteristics were described, comparison techniques were applied by subgroups (sociodemographic, home's structures and humidity's perception and percentage of the firewood) to identify factors related mainly with the fulfillment of measurements about firewood usage. RESULTS: 52% of households do not comply with the residential firewood use restriction measure, having sociodemographic factors related with this failure, such as schooling, health insurance and home structure. Besides, it is noted that the knowledge level of PDAV is associated with the accomplish level of restriction measures. When people know more about PDAV, there is a higher proportion of accomplishment. CONCLUSION: In more than half of the households, the restriction on the use of woodstove is not complied. The lack of knowledge of the population about the PDAV directly influences its compliance, which requires strategies to promote adherence to this program.

Additive Manufacturing In-situ and Ex-Situ Geometric Data Registration.

Recently, The number and types of measurement devices that collect data that is used to monitor Laser-Based Powder Bed Fusion of Metals processes and inspect Additive Manufacturing (AM) metal parts have increased rapidly. Each measurement device generates data in a unique coordinate system and in a unique format. Data alignment is the process of spatially aligning different datasets to a single coordinate system. It is part of a broader process called "Data Registration". This paper provides a data-registration procedure and includes an example of aligning data to a single, reference, coordinate system. Such a reference coordinate system is needed for downstream applications, including data analytic, artificial intelligence, and part qualification.

Cytokines profile in neonatal and adult wild-type mice post-injection of U. S. pediatric vaccination schedule.

INTRODUCTION: A recent study from our laboratory demonstrated a number of neurobehavioral abnormalities in mice colony injected with a mouse-weight equivalent dose of all vaccines that are administered to infants in their first 18 months of life according to the U. S. pediatric vaccination schedule.Cytokines have been studied extensively as blood immune and inflammatory biomarkers, and their association with neurodevelopmental disorders. Given the importance of cytokines in early neurodevelopment, we aimed to investigate the potential post-administration effects of the U. S. pediatric vaccines on circulatory cytokines in a mouse model.In the current study, cytokines have been assayed at early and late time points in mice vaccinated early in postnatal life and compared with placebo controls. MATERIALS AND METHODS: Newborn mouse pups were divided into three groups: i) vaccine (V1), ii) vaccine â€‹× â€‹3 (V3) and iii) placebo control. V1 group was injected with mouse weight-equivalent of the current U. S. pediatric vaccine schedule. V3 group was injected with same vaccines but at triple the dose and the placebo control was injected with saline. Pups were also divided according to the sampling age into two main groups: acute- and chronic-phase group. Blood samples were collected at postnatal day (PND) 23, two days following vaccine schedule for the acute-phase group or at 67 weeks post-vaccination for the chronic-phase groups. Fifteen cytokines were analyzed: GM-CSF, IFN-γ, IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-13, IL-17A, MCP-1, TNF-α, and VEGF-A. Wilcoxon Rank Sum test or unpaired Student's t-test was performed where applicable. RESULTS: IL-5 levels in plasma were significantly elevated in the V1 and V3 group compared with the control only in the acute-phase group. The elevation of IL-5 levels in the two vaccine groups were significant irrespective of whether the sexes were combined or analyzed separately. Other cytokines (VEGF-A, TNF-α, IL-10, MCP-1, GM-CSF, IL-6, and IL-13) were also impacted, although to a lesser extent and in a sex-dependent manner. In the acute-phase group, females showed a significant increase in IL-10 and MCP-1 levels and a decrease in VEGF-A levels in both V1 and V3 group compared to controls. In the acute-phase, a significant increase in MCP-1 levels in V3 group and CM-CSF levels in V1 and V3 group and decrease in TNF-α levels in V1 group were observed in treated males as compared with controls. In chronic-phase females, levels of VEGF-A in V1 and V3 group, TNF-α in V3 group, and IL-13 in V1 group were significantly decreased in contrast with controls. In chronic-phase males, TNF-α levels were significantly increased in V1 group and IL-6 levels decreased in V3 group in comparison to controls. The changes in levels of most tested cytokines were altered between the early and the late postnatal assays. CONCLUSIONS: IL-5 levels significantly increased in the acute-phase of the treatment in the plasma of both sexes that were subjected to V1 and V3 injections. These increases had diminished by the second test assayed at week 67. These results suggest that a profound, albeit transient, effect on cytokine levels may be induced by the whole vaccine administration supporting our recently published observations regarding the behavioral abnormalities in the same mice. These observations support the view that the administration of whole pediatric vaccines in a neonatal period may impact at least short-term CNS functions in mice.

Expectant management versus multifetal pregnancy reduction in dichorionic triamniotic (DCTA) triplets: Single centre experience.

OBJECTIVES: In trichorionic triplet pregnancies, multifetal pregnancy reduction (MFPR) reduces the risk of preterm birth, neonatal morbidity and mortality without increasing miscarriage. A similar benefit has been suggested in dichorionic triamniotic (DCTA) pregnancy, but multiple methods are currently used. This study investigates if the method of reduction used in DCTA triplet pregnancy influences the evidence of benefit from MFPR. METHODS: This is a retrospective cohort study of DCTA pregnancies between 2010 and 2019 who attended a single UK fetal medicine tertiary referral center. Cohorts were defined based on MFPR decision and method. The primary outcome was offspring survival until neonatal discharge. The secondary outcomes included miscarriage, preterm birth, livebirth, rates of small for gestational age (SGA) neonates, ans maternal morbidity. To evaluate the differences in neonatal survival until discharge we used Cox proportional regression to calculate hazard rates (HR) and 95% confidence intervals (CI). Differences in secondary outcomes were compared using univariate analysis. RESULTS: The study reports the outcomes for 83 DCTA pregnancies. MFPR to DCDA twins was chosen in 19 pregnancies (14 radiofrequency ablation, RFA; 5 intrafetal laser, IFL); in 9 pregnancies selective reduction to a singleton was performed by KCl injection. The rate of pregnancies in with ≥ 1 fetus born alive was not different between groups (p = 0.90). However, the number of expected neonates alive at discharge from hospital was highest in the RFA group (89%, HR 0.28, 95% CI 0.21-0.87, p = 0.02). Rates of premature delivery before 32 weeks (p = 0.02), low birth weight (p < 0.001) and birthweight < 10th percentile (p = 0.01) were all elevated in the expectant management group, compared to women who opted for reduction. There was no difference in miscarriage between groups. CONCLUSIONS: Our study suggests that MFPR by RFA, an established and widely available procedure, is of benefit in promoting neonatal survival until discharge in DCTA triplets.

Demystifying the spontaneous phenomena of motor hyperexcitability.

Possessing a discrete functional repertoire, the anterior horn cell can be in one of two electrophysiological states: on or off. Usually under tight regulatory control by the central nervous system, a hierarchical network of these specialist neurons ensures muscular strength is coordinated, gradated and adaptable. However, spontaneous activation of these cells and their axons can result in abnormal muscular twitching. The muscular twitch is the common building block of several distinct clinical patterns, namely fasciculation, myokymia and neuromyotonia. When attempting to distinguish these entities electromyographically, their unique temporal and morphological profiles must be appreciated. Detection and quantification of burst duration, firing frequency, multiplet patterns and amplitude are informative. A common feature is their persistence during sleep. In this review, we explain the accepted terminology used to describe the spontaneous phenomena of motor hyperexcitability, highlighting potential pitfalls amidst a bemusing and complex collection of overlapping terms. We outline the relevance of these findings within the context of disease, principally amyotrophic lateral sclerosis, Isaacs syndrome and Morvan syndrome. In addition, we highlight the use of high-density surface electromyography, suggesting that more widespread use of this non-invasive technique is likely to provide an enhanced understanding of these motor hyperexcitability syndromes.

Oxygen supply capacity breathes new life into critical oxygen partial pressure (Pcrit).

The critical oxygen partial pressure (Pcrit), typically defined as the PO2 below which an animal's metabolic rate (MR) is unsustainable, is widely interpreted as a measure of hypoxia tolerance. Here, Pcrit is defined as the PO2 at which physiological oxygen supply (α0) reaches its maximum capacity (α; µmol O2 g-1 h-1 kPa-1). α is a species- and temperature-specific constant describing the oxygen dependency of the maximum metabolic rate (MMR=PO2×α) or, equivalently, the MR dependence of Pcrit (Pcrit=MR/α). We describe the α-method, in which the MR is monitored as oxygen declines and, for each measurement period, is divided by the corresponding PO2 to provide the concurrent oxygen supply (α0=MR/PO2). The highest α0 value (or, more conservatively, the mean of the three highest values) is designated as α. The same value of α is reached at Pcrit for any MR regardless of previous or subsequent metabolic activity. The MR need not be constant (regulated), standardized or exhibit a clear breakpoint at Pcrit for accurate determination of α. The α-method has several advantages over Pcrit determination and non-linear analyses, including: (1) less ambiguity and greater accuracy, (2) fewer constraints in respirometry methodology and analysis, and (3) greater predictive power and ecological and physiological insight. Across the species evaluated here, α values are correlated with MR, but not Pcrit. Rather than an index of hypoxia tolerance, Pcrit is a reflection of α, which evolves to support maximum energy demands and aerobic scope at the prevailing temperature and oxygen level.

Cumulative effects of natural and anthropogenic disturbances on the forest carbon balance in the oil sands region of Alberta, Canada; a pilot study (1985-2012).

BACKGROUND: Assessing cumulative effects of anthropogenic and natural disturbances on forest carbon (C) stocks and fluxes, because of their relevance to climate change, is a requirement of environmental impact assessments (EIAs) in Canada. However, tools have not been developed specifically for these purposes, and in particular for the boreal forest of Canada, so current forest C assessments in EIAs take relatively simple approaches. Here, we demonstrate how an existing tool, the Generic Carbon Budget Model (GCBM), developed for national and international forest C reporting, was used for an assessment of the cumulative effects of anthropogenic and natural disturbances to support EIA requirements. We applied the GCBM to approximately 1.3 million ha of upland forest in a pilot study area of the oil sands region of Alberta that has experienced a large number of anthropogenic (forestry, energy sector) and natural (wildfire, insect) disturbances. RESULTS: Over the 28 years, 25% of the pilot study area was disturbed. Increasing disturbance emissions, combined with declining net primary productivity and reductions in forest area, changed the study area from a net C sink to a net C source. Forest C stocks changed from 332.2 Mt to 327.5 Mt, declining by 4.7 Mt at an average rate of 0.128 tC ha-1 yr-1. The largest cumulative areas of disturbance were caused by wildfire (139,000 ha), followed by the energy sector (110,000 ha), insects (33,000 ha) and harvesting (31,000 ha) but the largest cumulative disturbance emissions were caused by the energy sector (9.5 Mt C), followed by wildfire (5.5 Mt C), and then harvesting (1.3 Mt C). CONCLUSION: An existing forest C model was used successfully to provide a rigorous regional cumulative assessment of anthropogenic and natural disturbances on forest C, which meets requirements of EIAs in Canada. The assessment showed the relative importance of disturbances on C emissions in the pilot study area, but their relative importance is expected to change in other parts of the oil sands region because of its diversity in disturbance types, patterns and intensity. Future assessments should include peatland C stocks and fluxes, which could be addressed by using the Canadian Model for Peatlands.

COVID-19 in Kidney Transplant Patients From a Large UK Transplant Center: Exploring Risk Factors for Disease Severity.

BACKGROUND: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has raised concern for the health of immunocompromised individuals, who are potentially at higher risk of more severe infection and poorer outcomes. As a large London transplant center serving a diverse patient population, we report the outcomes of SARS-CoV-2 infection in our cohort of 2848 kidney and/or pancreas transplant patients. METHODS: Data were obtained retrospectively for all transplant patients who attended hospital during the peak of the pandemic and had a positive nasopharyngeal SARS-CoV-2 test. RESULTS: Sixty-six patients were found to be positive for SARS-CoV-2. Twenty percent were treated as outpatients, 59% were admitted to the general ward, and 21% required intensive care. Treatment consisted of reduced immunosuppression, antibiotics for pneumonia or sepsis, and other supportive treatments. Within our cohort, 12 patients died (18%), with an overall mortality of 0.4%. Predictive risk factors for COVID-19 severity were explored. CONCLUSIONS: Severe disease was associated with lower hemoglobin prior to COVID-19 diagnosis and lower lymphocyte count at the time of diagnosis but not age, sex, ethnicity, or preexisting comorbidities. Lower glomerular filtration rate and higher C-reactive protein were associated with more severe disease. Despite no use of hydroxychloroquine, azithromycin, antiviral, or immunomodulatory medications, our mortality rate (kidney and pancreas transplant patients) is similar to current international rates.

Retrospective analysis of the association between tooth loss and dementia: a population-based matched case-control study.

OBJECTIVE: To clarify the association between multiple tooth loss and dementia. BASIC RESEARCH DESIGN: Case-control study based on the claims data from National Health Insurance Research Database (NHIRD). Patients were divided into two groups: the dementia groups and non-dementia group. For each case patient, one control patient was randomly selected and frequency matched by age (per 5 years) and sex. The case group comprised patients newly diagnosed with dementia, and the index date was the the date of dementia diagnosis, which became the baseline for comorbidity and age calculations. RESULTS: Among the 43,026 individuals, patients with dementia had a significantly higher extraction density at ages 60-69 (p ⟨ 0.0001) and 70-79 (p = 0.04) years compared with control patients. CONCLUSIONS: This population-based retrospective study demonstrated an association between tooth loss and dementia. Patients in Taiwan with more tooth extraction experience are likely to have an increased risk of dementia.

The evolving role of surface electromyography in amyotrophic lateral sclerosis: A systematic review.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease that leads to inexorable motor decline and a median survival of three years from symptom onset. Surface EMG represents a major technological advance that has been harnessed in the development of novel neurophysiological biomarkers. We have systematically reviewed the current application of surface EMG techniques in ALS. METHODS: We searched PubMed to identify 42 studies focusing on surface EMG and its associated analytical methods in the diagnosis, prognosis and monitoring of ALS patients. RESULTS: A wide variety of analytical techniques were identified, involving motor unit decomposition from high-density grids, motor unit number estimation and measurements of neuronal hyperexcitability or neuromuscular architecture. Some studies have proposed specific diagnostic and prognostic criteria however clinical calibration in large ALS cohorts is currently lacking. The most validated method to monitor disease is the motor unit number index (MUNIX), which has been implemented as an outcome measure in two ALS clinical trials. CONCLUSION: Surface EMG offers significant practical and analytical flexibility compared to invasive techniques. To capitalise on this fully, emphasis must be placed upon the multi-disciplinary collaboration of clinicians, bioengineers, mathematicians and biostatisticians. SIGNIFICANCE: Surface EMG techniques can enrich effective biomarker development in ALS.

Impact of exercise training status on the fiber type-specific abundance of proteins regulating intramuscular lipid metabolism.

Endurance training enhances the capacity for fat oxidation during exercise due to increased utilization of intramuscular lipid (IMCL). This study quantitatively investigated the impact of exercise training status on muscle fiber type-specific abundance of regulatory proteins involved in IMCL utilization. Endurance-trained [n = 7 subjects, peak oxygen consumption (V̇o2peak) 62.6 ± 4.1 (SD) mL·min-1·kg-1] and non-endurance-trained (n = 8 subjects, V̇o2peak 44.9 ± 5.3 mL·min-1·kg-1) young men completed an incremental exercise test to determine maximal fat oxidation (MFO) and maximal oxygen uptake. Fiber type-specific IMCL content and protein abundance were assessed with immunofluorescence microscopy and immunoblot analysis of pooled single muscle fibers and whole muscle. Endurance-trained individuals displayed a higher MFO rate (0.45 ± 0.15 vs. 0.19 ± 0.07 g/min, P < 0.05), a greater proportion of type I muscle fibers, and higher IMCL content compared with untrained individuals (P < 0.05). Adipose triglyceride lipase, hormone-sensitive lipase, perilipin 2, perilipin 5, and hydroxyacyl-coenzyme A dehydrogenase abundances were ~2-3-fold higher in type I muscle fibers compared with type IIa fibers (P < 0.05). Correspondingly, these lipid proteins and oxidative enzymes were higher in endurance-trained individuals when assessed in whole muscle. MFO rate was strongly related to the proportion of type I fibers (R = 0.81, P < 0.01). The abundance of proteins involved in the regulation of IMCL storage and oxidation is highly muscle fiber type specific. The increased capacity for fat oxidation in endurance-trained individuals corresponded with increased IMCL content and elevated abundance of lipolytic and oxidative enzymes in combination with a greater proportion of type I muscle fibers.NEW & NOTEWORTHY We have utilized contemporary techniques to compare the fiber type-specific characteristics of skeletal muscle from endurance-trained athletes and untrained individuals. We show that type I muscle fibers have a coordinated upregulation of proteins controlling intramuscular lipid storage, mobilization, and oxidation. Furthermore, the enhanced capacity for intramuscular lipid storage and utilization in endurance-trained individuals is related to the increased expression of lipid regulatory proteins combined with a greater proportion of type I muscle fibers.