Sensory modulation of fasciculation discharge frequency.

INTRODUCTION: Fasciculations are a marker for the diagnosis of amyotrophic lateral sclerosis (ALS) and reflect increased lower motor neuron (LMN) excitability. METHODS: We investigated modulation of fasciculation frequency in the first dorsal interosseous (FDI) muscle of the right hand following peripheral sensory nerve electrical stimulation, and vibration over the muscle-tendon region (50 and 100 Hz), in patients with ALS, spinal muscular atrophy, and benign fasciculation syndrome. FDI muscles of ALS patients were classified by the presence or absence of neurogenic changes on needle electromyography. RESULTS: Both sensory nerve electrical stimulation and vibration significantly increased the frequency of fasciculations in neurogenic FDI muscles of ALS patients, but not in the remaining groups. DISCUSSION: Our results favour increased excitability of LMNs when affected by the disease process in ALS. We found that some fasciculations originating in these neurons in ALS are susceptible to modulation by sensory input. Muscle Nerve 59:688-693, 2019.

Religious Affiliation Modulates Weekly Cycles of Cropland Burning in Sub-Saharan Africa.

Vegetation burning is a common land management practice in Africa, where fire is used for hunting, livestock husbandry, pest control, food gathering, cropland fertilization, and wildfire prevention. Given such strong anthropogenic control of fire, we tested the hypotheses that fire activity displays weekly cycles, and that the week day with the fewest fires depends on regionally predominant religious affiliation. We also analyzed the effect of land use (anthrome) on weekly fire cycle significance. Fire density (fire counts.km-2) observed per week day in each region was modeled using a negative binomial regression model, with fire counts as response variable, region area as offset and a structured random effect to account for spatial dependence. Anthrome (settled, cropland, natural, rangeland), religion (Christian, Muslim, mixed) week day, and their 2-way and 3-way interactions were used as independent variables. Models were also built separately for each anthrome, relating regional fire density with week day and religious affiliation. Analysis revealed a significant interaction between religion and week day, i.e. regions with different religious affiliation (Christian, Muslim) display distinct weekly cycles of burning. However, the religion vs. week day interaction only is significant for croplands, i.e. fire activity in African croplands is significantly lower on Sunday in Christian regions and on Friday in Muslim regions. Magnitude of fire activity does not differ significantly among week days in rangelands and in natural areas, where fire use is under less strict control than in croplands. These findings can contribute towards improved specification of ignition patterns in regional/global vegetation fire models, and may lead to more accurate meteorological and chemical weather forecasting.

First Incidence and Progression Study for Diabetic Retinopathy in Portugal, the RETINODIAB Study: Evaluation of the Screening Program for Lisbon Region.

PURPOSE: To estimate the 5-year incidence and progression of diabetic retinopathy (DR) among persons with type 2 diabetes mellitus (DM). DESIGN: Population-based, prospective, cohort study. PARTICIPANTS: The RETINODIAB (Study Group for Diabetic Retinopathy Screening) program was implemented in the Lisbon and Tagus Valley area between July 2009 and December 2014. A total of 109 543 readable screening examinations were performed and corresponded to 56 903 patients who attended the screening program at entry. A total of 30 641 patients (53.85%) had at least 1 further screening event within the study period and were included in the analysis. METHODS: Participants underwent two 45° nonstereoscopic retinal digital photographs per eye according to RETINODIAB protocol. All images were graded according to the International Clinical Diabetic Retinopathy Scale. Referable diabetic retinopathy (RDR) was defined for all patients graded as moderate nonproliferative DR (NPDR), severe NPDR, or proliferative DR (PDR), with or without maculopathy or mild NPDR with maculopathy. Nonparametric estimates of the annual and cumulative incidences were obtained by Turnbull's estimator. Associations between the potential risk factors and the time to onset/progression of retinopathy were assessed through a parametric survival analysis for interval-censored data. MAIN OUTCOME MEASURES: The authors estimated the onset and progression incidence rates of DR. RESULTS: Yearly incidence of any DR in patients without retinopathy at baseline was 4.60% (95% confidence interval [CI], 3.96-4.76) in the first year, decreasing to 3.87% (95% CI, 2.57-5.78) in the fifth year. In participants with mild NPDR at baseline, the progression rate to RDR in year 1 was 1.18% (95% CI, 0.96-1.33). Incidence of any DR and RDR and DR progression rate were associated with known duration of diabetes, age at diagnosis, and use of insulin treatment. CONCLUSIONS: This longitudinal epidemiologic study provides the first Portuguese incidence DR data in a large-scale population-based cohort of type 2 diabetes after a 5-year follow-up. Duration of diabetes, age at diagnosis, and insulin treatment were associated with increasing risk of incidence and progression of DR. A personalized schedule distribution of screening intervals according to the individual patient's profile should be implemented, with resulting benefits in terms of health costs.

Stomach cancer incidence in Southern Portugal 1998-2006: a spatio-temporal analysis.

Stomach cancer belongs to the most common malignant tumors in Portugal. Main causal factors are age, dietary habits, smoking, and Helicobacter pylori infections. As these factors do not only operate on different time dimensions, such as age, period, or birth cohort, but may also vary along space, it is of utmost interest to model temporal and spatial trends jointly. In this paper, we analyze incidence of stomach cancer in Southern Portugal between 1998 and 2006 for females and males jointly using a spatial multivariate age-period-cohort model. Thus, we avoid age aggregation and allow the exploration of heterogeneous time trends between males and females across age, period, birth cohort, and space. Model estimation is performed within a Bayesian setting assuming (gender specific) smoothing priors. Our results show that the posterior expected rate of stomach cancer is decreasing for all counties in Southern Portugal and that males around 70 have a two times higher risk of getting stomach cancer compared with their female counterparts. We further found that, except for some few counties, the spatial influence is almost constant over time and negligible in the southern counties of Southern Portugal.

Sensitivity of MUP parameters in detecting change in early ALS.

OBJECTIVES: We aimed to identify the most appropriate MUP parameter to evaluate reinnervation in very early ALS. METHODS: We studied tibialis anterior (TA), initially of normal strength with normal MUP analysis parameters, in 15 patients with ALS of recent onset. They were studied at the initial diagnostic assessment, and then 3 and 6 months later. Spontaneous EMG activity was recorded. Conventional MUP analysis included mean amplitude, mean area, mean duration, mean number of phases, mean number of turns, % polyphasic potentials, mean jitter, % unstable pairs and % pairs with blocking. Non-parametric statistics were utilised in the analysis. RESULTS: Fasciculations were recorded in 72% in TA and increased jitter in 33% at study entry, but without EMG features of denervation. Mean amplitude, mean duration, mean area and the three measures of neuromuscular transmission increased significantly and linearly at each evaluation. Median duration showed the lowest variation and, together with jitter, the largest relative time effect. CONCLUSIONS: Mean duration and mean jitter are the most effective measures of early reinnervation in a very early affected muscle, in ALS. SIGNIFICANCE: Mean MUP duration is a simple and easy measure that should be useful in evaluating reinnervation, for example in a future clinical trial.

Motor unit firing in amyotrophic lateral sclerosis and other upper and lower motor neurone disorders.

OBJECTIVE: Motor unit recruitment order and firing rate was investigated in healthy subjects, and in small numbers of patients 50years ago. We aimed to investigate firing rate in different disorders, testing the same target muscle with normal strength, to evaluate possible application in diagnosing upper motor neuron (UMN) lesion. METHODS: We studied motor unit firing in the tibialis anterior muscle in six groups of subjects; normal subjects (n=45), patients with amyotrophic lateral sclerosis (ALS) (n=36), primary lateral sclerosis (PLS) (n=21), progressive muscular atrophy (PMA) (n=14), various upper motor neurone lesions (n=16) and polyneuropathy (n=42). In all these subjects the tibialis anterior muscle was of normal strength. Motor units were recruited during slight contraction in order to study 2-5 motor units at each recording site, using a standard concentric needle electrode, so that 20-22 motor units were recorded in each muscle. We analysed the coefficient of variation (CV) for amplitude, area, duration and firing rate in these motor units, and the correlation between motor unit potential size and recruitment order. RESULTS: The mean MU firing rate in this task was similar in each group. No recruitment order was disclosed within the limits of the study task. The CV of firing rate was decreased in UMN and PLS groups. ALS patients with marked spasticity showed a lower CV of motor unit firing rate. The CV of amplitude, area and duration was similar between groups. CONCLUSIONS: These results in tibialis anterior indicate that physiological modulation of lower motor neuron (LMN) firing rate is decreased in patients with lower limb spasticity. The variability of MU discharges tends to be greater in diseases affecting the LMN. SIGNIFICANCE: These results suggest that, notwithstanding the simplicity of the task we have used, the physiological variability of motor unit firing may be a useful variable in assessing UMN involvement in motor system disorders.

Nonparametric Bayesian estimation of the three-way receiver operating characteristic surface.

We describe a nonparametric Bayesian approach for estimating the three-way ROC surface based on mixtures of finite Polya trees (MFPT) priors. Mixtures of finite Polya trees are robust models that can handle nonstandard features in the data. We address the difficulties in modeling continuous diagnostic data with skewness, multimodality, or other nonstandard features, and how parametric approaches can lead to misleading results in such cases. Robust, data-driven inference for the ROC surface and for the volume under the ROC surface is obtained. A simulation study is performed to assess the performance of the proposed method. Methods are applied to data from a magnetic resonance spectroscopy study on human immunodeficiency virus patients.

Influence of soil fertility on dye flavonoids production in weld (Reseda luteola L.) accessions from Portugal.

A HPLC-diode array detector (DAD) methodology was developed to allow the simultaneous identification and quantification of Reseda luteola L. (weld) dye flavonoids, luteolin, apigenin, luteolin 7-O-glucoside, apigenin 7-O-glucoside, luteolin 3',7-O-diglucoside and luteolin 4'-O-glucoside. The method was validated with excellent results in linearity, sensibility, accuracy and precision. This method was applied to evaluate the influence of soil fertility on the production of weld dye flavonoids. The results showed that weld dye capacity is dependent on soil fertility and the origin of seeds. This method proved its reproducibility and can be used to evaluate the dyeing potential of R. luteola samples in a simple and accurate way.

Serial changes in oxidized low-density lipoprotein associated with culprit vessel in ST-elevation myocardial infarction--a promising marker?

The aim of the present study was to investigate variations in oxidized LDL (oxLDL) at the onset of acute myocardial infarction (AMI) and over the recovery period, exploring their relationship with coronary disease severity. A follow-up of 50 AMI patients was evaluated against 25 healthy volunteers (reference group). The AMI patients were evaluated at three time points: at admission before the administration of IIb/IIIa inhibitors and angioplasty, and two and 40 days after intervention. Plasma oxLDL concentrations were measured by ELISA. oxLDL was found to be significantly higher in AMI patients in the acute phase relative to reference levels, decreasing progressively over the recovery period. The results also demonstrated that oxLDL levels were decreased in patients with the left circumflex artery (LCX) as culprit vessel compared to the left anterior descending coronary (LAD) or right coronary artery (RCA). The results highlight a significant increase in oxLDL concentration related to coronary artery disease severity, as conditions such as LCX lesions are usually associated with a favorable prognosis, contrasting with LAD-associated conditions that can compromise large areas of myocardium. The results thus suggest that oxLDL may constitute a promising marker in assessment of AMI evolution.

Predicting respiratory insufficiency in amyotrophic lateral sclerosis: the role of phrenic nerve studies.

OBJECTIVE: Respiratory function tests are used to detect early signs of hypoventilation in amyotrophic lateral sclerosis (ALS). However, there are few studies of the predictive value of these tests in detecting hypoventilation. METHODS: We included 199 ALS patients. ALS was bulbar-onset in 68 and spinal-onset in 131. Twenty-four had hypercapnia (pCO(2)>45 mmHg), thus defining hypoventilation. The following measurements were recorded: forced vital capacity (FVC); maximal static inspiratory and expiratory pressures (PImax and PEmax); mouth inspiratory pressure at 100 ms (P0.1); amplitude of motor responses from phrenic nerve stimulation. RESULTS: Defining the "cut-off" point by the normative values, the positive predictive value was low and the negative predictive value was high for all measurements. Receiver operator characteristic (ROC) analysis and a logistic regression model confirmed that FVC and phrenic nerve stimulation were discriminative for the whole population of 199 patients and for the bulbar-onset group, and phrenic nerve stimulation was discriminative for the spinal-onset group. CONCLUSIONS: Phrenic nerve stimulation is discriminative in predicting hypoventilation as defined by hypercapnia breathing room air for both bulbar- and spinal-onset ALS patients, with high specificity, sensitivity and negative predictive value but with low positive predictive value. SIGNIFICANCE: Phrenic nerve studies are useful in ALS patients.

Motor responses evoked by transcranial magnetic stimulation and peripheral nerve stimulation in the ulnar innervation in amyotrophic lateral sclerosis: the effect of upper and lower motor neuron lesion.

We studied the upper (UMN) and lower motor neuron (LMN) innervations of 159 hands from 81 patients with amyotrophic lateral sclerosis (ALS). Eleven patients with various chronic LMN disorders causing weakness in the abductor digiti minimi (ADM) muscle served as LMN controls. Thirty healthy subjects served as normal controls. Cortical motor threshold, central conduction time (CMCT), and motor-evoked response amplitude (MEP) after transcranial magnetic stimulation (TMS) were studied, and the MEP/M wave ratio was calculated. The data was analyzed in the ALS subjects in groups defined by ADM muscle strength and by the presence or absence of clinical signs of UMN involvement. CMCT was not increased in the ALS or LMN disease groups. The threshold was higher in limbs with both weak ADM muscles and UMN signs. The MEP/M wave amplitude ratio was increased in weak muscles in the ALS patients, notably in limbs with no UMN signs, and also in weak muscles in patients with other chronic LMN disorders. It was frequently decreased in strong muscles. There was no difference between bulbar-onset and limb-onset ALS groups, and there was no correlation between threshold and disease duration. We suggest that expressing the data as an index and utilising the MEP/M wave amplitude ratio as a variable is a sensitive method for detecting UMN abnormality in ALS in particular in early affected muscles.