Early transpyloric vs gastric feeding in preterm infants: a retrospective cohort study.

BACKGROUND: Neonatal transpyloric feeding (TPF) has not been rigorously studied since the 1980s. Our objective was to evaluate early TPF, defined as TPF initiated within the first week after birth, among preterm infants in the setting of modern neonatal practice. STUDY DESIGN: A retrospective cohort study was conducted between 2013 and 2017 for all extremely low birth weight (ELBW) infants born in a tertiary neonatal intensive care unit where early TPF is a common practice. Infants were excluded if they did not receive enteral feeding within the first week after birth or if they died prior to initiation of enteral feeding. The primary outcome was death or bronchopulmonary dysplasia (BPD). The association between early TPF and the primary outcome was assessed using multivariable logistic regression, with adjustment for gestational age, birth weight, and intubation status. RESULT: The study sample included 368 ELBW infants. Twenty-seven percent received early TPF. Death or BPD occurred in 58% of infants who received early TPF compared with 67% of infants who received gastric feeding, adjusted odds ratio 0.6, 95% confidence interval 0.3-0.9. Growth and adverse gastrointestinal outcomes did not differ between the two groups. CONCLUSION: Early TPF is associated with reduced risk of death or BPD among ELBW infants. Further investigation in the form of a randomized controlled trial is required to confirm a causal association between early TPF and improved clinical outcomes.

Neural Correlates of Abnormal Temporal Discrimination in Unaffected Relatives of Cervical Dystonia Patients.

Background: An abnormal temporal discrimination threshold in cervical dystonia (CD) is considered to be a mediational endophenotype; in unaffected relatives it is hypothesized to indicate non-manifesting gene carriage. The pathogenesis underlying this condition remains unknown. Investigation of the neural networks involved in disordered temporal discrimination may highlight its pathomechanisms. Objective: To examine resting state brain function in unaffected relatives of CD patients with normal and abnormal temporal discrimination. We hypothesized that the endophenotype, an abnormal temporal discrimination, would manifest as altered connectivity in relatives in regions associated with CD, thereby illuminating the neural substrates of the link between temporal discrimination and CD. Methods: Rs-fMRI data was analyzed from two sex- and age-matched cohorts: 16 unaffected relatives of CD patients with normal temporal discrimination and 16 with abnormal temporal discrimination. Regional and whole brain functional connectivity measures were extracted via Independent Component Analysis (ICA), Regional Homogeneity (ReHo), and Amplitude of Low Frequency (ALFF) analyses. Results: Our ICA analysis revealed increased connectivity within both the executive control and cerebellar networks and decreased connectivity within the sensorimotor network in relatives with abnormal temporal discrimination when compared to relatives with normal temporal discrimination. The ReHo and ALFF analyses complimented these results and demonstrated connectivity differences in areas corresponding to motor planning, movement coordination, visual information processing, and eye movements in unaffected relatives with abnormal temporal discrimination. Conclusion: Disordered connectivity in unaffected relatives with abnormal temporal discrimination illuminates neural substrates underlying endophenotype expression and supports the hypothesis that genetically determined aberrant connectivity, when later coupled with unknown environmental triggers, may lead to disease penetrance.

Reduced Frequency of Ipsilateral Express Saccades in Cervical Dystonia: Probing the Nigro-Tectal Pathway.

Background: Cervical dystonia is a hyperkinetic movement disorder of unknown cause. Symptoms of cervical dystonia have been induced in animals in which the integrity of the nigro-tectal pathway is disrupted, resulting in reduced inhibition of the deep layers of the superior colliculus. This same pathway is believed to play a critical role in saccade generation, particularly visually guided, express saccades. It was hypothesized that individuals with cervical dystonia would present with a higher frequency of express saccades and more directional errors. Methods: Eight individuals with cervical dystonia and 11 age- and sex-matched control participants performed three saccadic paradigms: pro-saccade, gap, and anti-saccade (120 trials per task). Eye movements were recorded using electro-oculography. Results: Mean saccadic reaction times were slower in the cervical dystonia group (only statistically significant in the anti-saccade task, F(1, 35)  =  4.76, p  =  0.036); participants with cervical dystonia produced fewer directional errors (mean 14% vs. 22%) in the anti-saccade task; and had similar frequencies of express saccades in the gap task relative to our control population (chi-square  =  1.13, p  =  0.287). All cervical dystonia participants had lower frequencies of express saccades ipsilateral to their dystonic side (the side to which their head turns), (chi-square  =  3.57, p  =  0.059). Discussion: The finding of slower saccadic reaction times in cervical dystonia does not support the concept of reduced inhibition in the nigro-tectal pathway. Further research is required to confirm the observed relationship between the lateralization of lower frequencies of express saccades and direction of head rotation in cervical dystonia.

Measurement & Analysis of the Temporal Discrimination Threshold Applied to Cervical Dystonia.

The temporal discrimination threshold (TDT) is the shortest time interval at which an observer can discriminate two sequential stimuli as being asynchronous (typically 30-50 ms). It has been shown to be abnormal (prolonged) in neurological disorders, including cervical dystonia, a phenotype of adult onset idiopathic isolated focal dystonia. The TDT is a quantitative measure of the ability to perceive rapid changes in the environment and is considered indicative of the behavior of the visual neurons in the superior colliculus, a key node in covert attentional orienting. This article sets out methods for measuring the TDT (including two hardware options and two modes of stimuli presentation). We also explore two approaches of data analysis and TDT calculation. The application of the assessment of temporal discrimination to the understanding of the pathogenesis of cervical dystonia and adult onset idiopathic isolated focal dystonia is also discussed.

Temporal Discrimination: Mechanisms and Relevance to Adult-Onset Dystonia.

Temporal discrimination is the ability to determine that two sequential sensory stimuli are separated in time. For any individual, the temporal discrimination threshold (TDT) is the minimum interval at which paired sequential stimuli are perceived as being asynchronous; this can be assessed, with high test-retest and inter-rater reliability, using a simple psychophysical test. Temporal discrimination is disordered in a number of basal ganglia diseases including adult-onset dystonia, of which the two most common phenotypes are cervical dystonia and blepharospasm. The causes of adult-onset focal dystonia are unknown; genetic, epigenetic, and environmental factors are relevant. Abnormal TDTs in adult-onset dystonia are associated with structural and neurophysiological changes considered to reflect defective inhibitory interneuronal processing within a network which includes the superior colliculus, basal ganglia, and primary somatosensory cortex. It is hypothesized that abnormal temporal discrimination is a mediational endophenotype and, when present in unaffected relatives of patients with adult-onset dystonia, indicates non-manifesting gene carriage. Using the mediational endophenotype concept, etiological factors in adult-onset dystonia may be examined including (i) the role of environmental exposures in disease penetrance and expression; (ii) sexual dimorphism in sex ratios at age of onset; (iii) the pathogenesis of non-motor symptoms of adult-onset dystonia; and (iv) subcortical mechanisms in disease pathogenesis.

Disrupted superior collicular activity may reveal cervical dystonia disease pathomechanisms.

Cervical dystonia is a common neurological movement disorder characterised by muscle contractions causing abnormal movements and postures affecting the head and neck. The neural networks underpinning this condition are incompletely understood. While animal models suggest a role for the superior colliculus in its pathophysiology, this link has yet to be established in humans. The present experiment was designed to test the hypothesis that disrupted superior collicular processing is evident in affected patients and in relatives harbouring a disease-specific endophenotype (abnormal temporal discrimination). The study participants were 16 cervical dystonia patients, 16 unaffected first-degree relatives with abnormal temporal discrimination, 16 unaffected first-degree relatives with normal temporal discrimination and 16 healthy controls. The response of participant's superior colliculi to looming stimuli was assessed by functional magnetic resonance imaging. Cervical dystonia patients and relatives with abnormal temporal discrimination demonstrated (i) significantly reduced superior collicular activation for whole brain and region of interest analysis; (ii) a statistically significant negative correlation between temporal discrimination threshold and superior collicular peak values. Our results support the hypothesis that disrupted superior collicular processing is involved in the pathogenesis of cervical dystonia. These findings, which align with animal models of cervical dystonia, shed new light on pathomechanisms in humans.

Menstrual cycle and the temporal discrimination threshold.

The temporal discrimination threshold (TDT) is a proposed pre-clinical biomarker (endophenotype) for adult onset isolated focal dystonia (AOIFD). Age- and sex-related effects on temporal discrimination demonstrate that women, before the age of 40 years, have faster temporal discrimination than men but their TDTs worsen with age at almost three times the rate of men. Thus after 40 years the TDT in women is progressively worse than in men. AOIFD is an increasingly female-predominant disorder after the age of 40; it is not clear whether this age-related sexually-dimorphic difference observed for both the TDT and sex ratio at disease onset in AOIFD is a hormonal or chromosomal effect. The aim of this study was to examine temporal discrimination at weekly intervals during two consecutive menstrual cycles in 14 healthy female volunteers to determine whether physiological hormonal changes affected temporal discrimination. We observed no significant differences in weekly temporal discrimination threshold values during the menstrual cycles and no significant correlation with the menstrual cycle stage. This observed stability of temporal discrimination during cyclical hormonal change raises interesting questions concerning the age-related sexually-dimorphic decline observed in temporal discrimination. Our findings pave the way for future studies exploring potential pathomechanisms for this age-related deterioration.

A comparison of stimulus presentation methods in temporal discrimination testing.

The temporal discrimination threshold (TDT) is the shortest time interval at which an individual detects two stimuli to be asynchronous (normal = 30-50 ms). It has been shown to be abnormal in patients with disorders affecting the basal ganglia including adult onset idiopathic focal dystonia (AOIFD). Up to 97% of patients have an abnormal TDT with age- and sex-related penetrance in unaffected relatives, demonstrating an autosomal dominant inheritance pattern. These findings support the use of the TDT as a pre-clinical biomarker for AOIFD. The usual stimulus presentation method involves the presentation of progressively asynchronous stimuli; when three sequential stimuli are reported asynchronous is taken as a participant's TDT. To investigate the robustness of the 'staircase' method of presentation, we introduced a method of randomised presentation order to explore any potential 'learning effect' that may be associated with this existing method. The aim of this study was to investigate differences in temporal discrimination using two methods of stimulus presentation. Thirty healthy volunteers were recruited to the study (mean age 33.73 ± 3.4 years). Visual and tactile TDT testing using a staircase and randomised method of presentation order was carried out in a single session. There was a strong relationship between the staircase and random method for TDT values. This observed consistency between testing methods suggests that the existing experimental approach is a robust method of recording an individual's TDT. In addition, our newly devised randomised paradigm is a reproducible and more efficient method for data acquisition in the clinic setting. However, the two presentation methods yield different absolute TDT results and either of the two methods should be used uniformly in all participants in any one particular study.

Índice de resistividade renal como preditor da revascularização renal para hipertensão renovascular / Renal resistance index predicting outcome of renal revascularization for renovascular hypertension

FUNDAMENTO: A estenose arterial renal (EAR) é uma causa potencialmente reversível de hipertensão arterial sistêmica (HAS) e nefropatia isquêmica. Apesar da revascularização bem sucedida, nem todos os pacientes (pt) apresentam melhora clínica e alguns podem piorar. OBJETIVO: O presente estudo se destina a avaliar o valor do índice de resistividade renal (IR) como preditor dos efeitos da revascularização renal. MÉTODOS: Entre janeiro de 1998 e fevereiro de 2001, 2.933 pacientes foram submetidos ao duplex ultrassom renal. 106 desses pacientes apresentaram EAR significativa e foram submetidos a angiografia e revascularização renal. A pressão arterial (PA) foi medida antes e depois da intervenção, em intervalos de até 2 anos e as medicações prescritas foram registradas. Antes da revascularização, o IR foi medido em 3 locais do rim, sendo obtida uma média dessas medições. RESULTADOS: Dos 106 pacientes, 81 tiveram IR<80 e 25 RI>80. A EAR foi corrigida somente por angioplastia (PTA) em 25 pts, PTA + stent em 56 pts e cirurgicamente em 25 pts. Dos pacientes que se beneficiaram da revascularização renal; 57 dos 81 pacientes com IR <80 apresentaram melhora em comparação a 5 de 25 com IR > 80. Usando um modelo de regressão logística múltipla, o IR esteve significativamente associado à evolução da PA (p = 0,001), ajustado de acordo com os efeitos da idade, sexo, PAS, PAD, duração da hipertensão, o tipo de revascularização, número de fármacos em uso, nível de creatinina, presença de diabete melito, hipercolesterolemia, volume sistólico, doença arterial periférica e coronariana e tamanho renal (OR 99,6-95 por centoCI para OR 6,1-1.621,2). CONCLUSÃO: A resistividade intrarrenal arterial, medida por duplex ultrassom, desempenha um papel importante na predição dos efeitos pós revascularização renal para EAR.

BACKGROUND: Renal artery stenosis (RAS) is a potentially correctable cause of hypertension and ischemic nephropathy. Despite successful renal revascularization, not all patients (pt) overcome it and some get worse. OBJECTIVE: This study was designed to assess the value of renal resistance index (RI) in predicting the outcome of renal revascularization. METHODS: Between Jan 1998 and Feb 2001, 2,933 pts were referred to renal duplex ultrasound. 106 out of these had significant RAS and underwent angiography and renal revascularization. Arterial blood pressure (BP) was measured before and after the intervention, at intervals of up to 2 years and medications recorded. Prior to revascularization, RI was measured at 3 sites of each kidney and averaged. RESULTS: Out of the 106 patients, 81 had RI<80 and 25 RI>80. RAS was corrected with angioplasty (PTA) alone in 25 pts, PTA + stent in 56 pts and corrected by surgery in 25 pts. Of patients who benefited from renal revascularization; 57 of the 81 patients with RI <80 improved as compared to 5 of 25 with RI>80. Using a multiple logistic regression model, RI was significantly associated with BP outcome (p=0.001), adjusted for the effects of age, sex, SBP, DBP, duration of hypertension, type of revascularization, number of medication in use, creatinine level, presence of diabetes mellitus, hypercholesterolemia, stroke, peripheral and coronary artery disease and kidney size (OR 99.6 - 95 percentCI for OR 6.1 to 1,621.2). CONCLUSION: Intrarenal arterial resistance measured by duplex ultrasound plays an important role in predicting BP outcome after renal revascularization for RAS.

[Renal resistance index predicting outcome of renal revascularization for renovascular hypertension]. / Indice de resistividade renal como preditor da revascularização renal para hipertensão renovascular.

BACKGROUND: Renal artery stenosis (RAS) is a potentially correctable cause of hypertension and ischemic nephropathy. Despite successful renal revascularization, not all patients (pt) overcome it and some get worse. OBJECTIVE: This study was designed to assess the value of renal resistance index (RI) in predicting the outcome of renal revascularization. METHODS: Between Jan 1998 and Feb 2001, 2,933 pts were referred to renal duplex ultrasound. 106 out of these had significant RAS and underwent angiography and renal revascularization. Arterial blood pressure (BP) was measured before and after the intervention, at intervals of up to 2 years and medications recorded. Prior to revascularization, RI was measured at 3 sites of each kidney and averaged. RESULTS: Out of the 106 patients, 81 had RI<80 and 25 RI>80. RAS was corrected with angioplasty (PTA) alone in 25 pts, PTA + stent in 56 pts and corrected by surgery in 25 pts. Of patients who benefited from renal revascularization; 57 of the 81 patients with RI <80 improved as compared to 5 of 25 with RI>80. Using a multiple logistic regression model, RI was significantly associated with BP outcome (p=0.001), adjusted for the effects of age, sex, SBP, DBP, duration of hypertension, type of revascularization, number of medication in use, creatinine level, presence of diabetes mellitus, hypercholesterolemia, stroke, peripheral and coronary artery disease and kidney size (OR 99.6 - 95%CI for OR 6.1 to 1,621.2). CONCLUSION: Intrarenal arterial resistance measured by duplex ultrasound plays an important role in predicting BP outcome after renal revascularization for RAS.

Tracking motor unit action potentials in the tibialis anterior during fatigue.

New surface electromyogram (SEMG) techniques offer the potential to advance knowledge of healthy and diseased motor units. Conduction velocity (CV) estimates, obtained from indwelling electrodes, may provide diagnostic information, but the standard method of CV estimation from SEMG may be of only limited value. We developed a motor unit (MU) tracking algorithm to extract motor unit conduction velocity (MUCV) and motor unit action potential (MUAP) amplitude estimates from SEMG. The technique is designed to provide a noninvasive means of accessing fatigue and recruitment behavior of individual MUs. We have applied this MU tracking algorithm to SEMG data recorded during isometric fatiguing contractions of the tibialis anterior (TA) muscle in nine healthy subjects, at 30%-40% maximum voluntary contraction (MVC). The results reveal that MUCVs and MUAP amplitudes of individual MUs can be estimated and tracked across time. Time-related changes in the MU population may also be monitored. Thus, the SEMG technique employed provides insight into the behavior of the underlying muscle at the MU level by noninvasive means.

A technique to track individual motor unit action potentials in surface EMG by monitoring their conduction velocities and amplitudes.

The speed of propagation of an action potential along a muscle fiber, its conduction velocity (CV), can be used as an indication of the physiological or pathological state of the muscle fiber membrane. The motor unit action potential (MUAP), the waveform resulting from the spatial and temporal summation of the individual muscle fiber action potentials of that motor unit (MU), propagates with a speed referred to as the motor unit conduction velocity (MUCV). This paper introduces a new algorithm, the MU tracking algorithm, which estimates MUCVs and MUAP amplitudes for individual MUs in a localized MU population using SEMG signals. By tracking these values across time, the electrical activity of the localized MU pool can be monitored. An assessment of the performance of the algorithm has been achieved using simulated SEMG signals. It is concluded that this analysis technique enhances the suitability of SEMG for clinical applications and points toward a future of noninvasive diagnosis and assessment of neuromuscular disorders.