Relationship between EMG-detected and ultrasound-detected fasciculations in amyotrophic lateral sclerosis: A prospective cohort study

ObjectivesFasciculation potentials (FP) are an important consideration in the electrophysiological diagnosis of ALS. Muscle ultrasonography (MUS) has a higher sensitivity in detecting fasciculations than electromyography (EMG), while in some cases, it is unable to detect EMG-detected fasciculations. We aimed to investigate the differences of FP between the muscles with and without MUS-detected fasciculations (MUS-fas).MethodsThirty-one consecutive patients with sporadic ALS were prospectively recruited and in those, both needle EMG and MUS were performed. Analyses of the amplitude, duration, and number of phases of EMG-detected FPs were performed for seven muscles per patient, and results were compared between the muscles with and without MUS-fas in the total cohort.ResultsThe mean amplitude and phase number of FP were significantly lower in patients with EMG-detected FP alone (0.39 ± 0.25 mV and 3.21 ± 0.88, respectively) than in those with both FP and MUS-fas (1.22 ± 0.92 mV and 3.74 ± 1.39, respectively; p < 0.0001 and p = 0.017, Welch’s t-test).ConclusionSmall FP may be undetectable with MUS. MUS cannot replace EMG in the diagnostic approach for ALS.SignificanceClinicians should use a combination of EMG and MUS for the detection and quantitative analysis of fasciculation in ALS.     

Actin binding proteins,actin cytoskeleton and spermatogenesis – Lesson from toxicant models

Actin cytoskeleton is crucial to support spermatogenesis in the mammalian testis. However, the molecular mechanism(s) underlying changes of actin cytoskeletal organization in response to cellular events that take place across the seminiferous epithelium (e.g., self-renewal of spermatogonial stem cells, germ cell differentiation, meosis, spermiogenesis, spermiation) at specific stages of the epithelial cycle of spermatogenesis remain largely unexplored. This, at least in part, is due to the lack of suitable study models to identify the crucial regulatory proteins and to investigate how these proteins work in concert to support actin dynamics. Much of the information on the role of actin binding proteins in the literature, namely the actin bundling proteins, actin nucleation proteins and motor proteins, are either findings based on genetic models or morphological analyses. While this information is helpful to delineate the function of these proteins to support spermatogenesis, they are not helpful to identify the regulatory signaling proteins, the signaling pathways and the cascade of events to modulate actin cytoskeleton dynamics. Recent studies based on the use of toxicant models, both in vitro and in vivo, however, have bridged this gap by identifying putative regulatory and signaling proteins of actin cytoskeleton. Herein, we summarize and critically evaluate these findings. We also provide a hypothetical model by which actin cytoskeletal dynamics in Sertoli cells are regulated, which in turn supports spermatid transport across the seminiferous epithelium, and at the blood-testis barrier (BTB) during the epithelial cycle of spermatogenesis.     

A modality-specific somatosensory evoked potential test protocol for clinical evaluation: A feasibility study

ObjectiveWe aimed to establish an objective neurophysiological test protocol that can be used to assess the somatosensory nervous system.MethodsIn order to assess most fiber subtypes of the somatosensory nervous system, repetitive stimuli of seven different modalities (touch, vibration, pinprick, cold, contact heat, laser, and warmth) were synchronized with the electroencephalogram (EEG) and applied on the cheek and dorsum of the hand and dorsum of the foot in 21 healthy subjects and three polyneuropathy (PNP) patients. Latencies and amplitudes of the modalities were assessed and compared. Patients received quantitative sensory testing (QST) as reference.ResultsWe found reproducible evoked potentials recordings for touch, vibration, pinprick, contact-heat, and laser stimuli. The recording of warm-evoked potentials was challenging in young healthy subjects and not applicable in patients. Latencies were shortest within Aβ-fiber-mediated signals and longest within C-fibers. The test protocol detected function loss within the Aβ-fiber and Aδ-fiber-range in PNP patients. This function loss corresponded with QST findings.ConclusionIn this pilot study, we developed a neurophysiological test protocol that can specifically assess most of the somatosensory modalities. Despite technical challenges, initial patient data appear promising regarding a possible future clinical application.SignificanceEstablished and custom-made stimulators were combined to assess different fiber subtypes of the somatosensory nervous system using modality-specific evoked potentials.     

Derivation of internal dose-based thresholds of toxicological concern for occupational inhalation exposure to systemically acting organic chemicals

This study aimed at deriving occupational thresholds of toxicological concern for inhalation exposure to systemically-acting organic chemicals using predicted internal doses. The latter were also used to evaluate the quantitative relationship between occupational exposure limit and internal dose. Three internal dose measures were identified for investigation: (i) the daily area under the venous blood concentration vs. time curve, (ii) the daily rate of the amount of parent chemical metabolized, and (iii) the maximum venous blood concentration at the end of an 8-hr work shift. A dataset of 276 organic chemicals with 8-hr threshold limit values-time-weighted average was compiled along with their molecular structure and Cramer classes (Class I: low toxicity, Class II: intermediate toxicity, Class III: suggestive of significant toxicity). Using a human physiologically-based pharmacokinetic model, the three identified dose metrics were predicted for an 8-hr occupational inhalation exposure to the threshold limit value for each chemical. Distributional analyses of the predicted dose metrics were performed to identify the percentile values corresponding to the occupational thresholds of toxicological concern. Also, simple linear regression analyses were performed to evaluate the relationship between the 8-hr threshold limit value and each of the predicted dose metrics, respectively. No threshold of toxicological concern could be derived for class II due to few chemicals. Based on the daily rate of the amount of parent chemical metabolized, the proposed internal dose-based occupational thresholds of toxicological concern were 5.61?×?10^?2 and 9?×?10^?4 mmol/d at the 10th percentile level for classes I and III, respectively, while they were 4.55?×?10^?1 and 8.5?×?10^?3 mmol/d at the 25th percentile level. Even though high and significant correlations were observed between the 8-hr threshold limit values and the predicted dose metrics, the one with the rate of the amount of chemical metabolized was remarkable regardless of the Cramer class (r² = 0.81; n = 276). The proposed internal dose-based occupational thresholds of toxicological concern are potentially useful for screening-level assessments as well as prioritization within an integrated occupational risk assessment framework.     

ONRAB® oral rabies vaccine is shed from,but does not persist in,captive mammals

ONRAB® is a human adenovirus rabies glycoprotein recombinant vaccine developed to control rabies in wildlife. To support licensing and widespread use of the vaccine, safety studies are needed to assess its potential residual impact on wildlife populations. We examined the persistence of the ONRAB® vaccine virus in captive rabies vector and non-target mammals. This research complements work on important rabies vector species (raccoon, striped skunk, and red fox) but also adds to previous findings with the addition of some non-target species (Virginia opossum, Norway rats, and cotton rats) and a prolonged period of post vaccination monitoring (41 days). Animals were directly inoculated orally with the vaccine and vaccine shedding was monitored using quantitative real-time PCR applied to oral and rectal swabs. ONRAB® DNA was detected in both oral and rectal swabs from 6 h to 3 days post-inoculation in most animals, followed by a resurgence of shedding between days 17 and 34 in some species. Overall, the duration over which ONRAB® DNA was detectable was shorter for non-target mammals, and by day 41, no animal had detectable DNA in either oral or rectal swabs. All target species, as well as cotton rats and laboratory-bred Norway rats, developed robust humoral immune responses as measured by competitive ELISA, with all individuals being seropositive at day 31. Similarly, opossums showed good response (89% seropositive; 8/9), whereas only one of nine wild caught Norway rats was seropositive at day 31. These results support findings of other safety studies suggesting that ONRAB® does not persist in vector and non-target mammals exposed to the vaccine. As such, we interpret these data to reflect a low risk of adverse effects to wild populations following distribution of ONRAB® to control sylvatic rabies.     

The best strategy for red blood cell transfusion in severe burn patients,restrictive or liberal: A randomized controlled trial

IntroductionAlthough blood transfusion is common in burns, data are lacking in appropriate transfusion thresholds. It has been reported that a restrictive blood transfusion policy decreases blood utilization and improves outcomes in critically ill adults, but the impact of a restrictive blood transfusion policy in burn patients is unclear. We decided to investigate the outcome of decreasing the blood transfusion threshold.Material and methodsEighty patients with TBSA > 20% who met our inclusion criteria were included. They were randomly divided into control and intervention groups. The intervention group received packed cells only when Hemoglobin declined to less than 8 g/dL at routine laboratory evaluations. While the control group received packed-cell when hemoglobin was declined to less than 10 g/dl. The total number of the received packed cell before, during and after any surgical procedure was recorded. The outcome was measured by the evaluation of the infection rate and other complications.ResultThe mean hemoglobin level before transfusion was 7.7 ± 0.4 g/dL in the restrictive group and 8.8 ± 0.7 g/dL in the liberal group. The mean number of RBC unit transfusion per patient in the restrictive group was significantly lower than the traditional group (3.28 ± 2.2 units vs. 5.9 ± 3.7 units) (p-value = 0.006). The total number of RBC transfused units varied significantly between the two groups (p-value = 0.014). The number of transfused RBC units outside the operation room showed a significant difference between groups (restrictive: 2.8 ± 1.4 units vs. liberal: 4.4 ± 2.6 units) (p = 0.004). We did not find any significant difference in mortality rate or other outcome measures between groups.ConclusionApplying the restrictive transfusion strategy in thermal burn patients who are highly prone to all kinds of infection, does not adversely impact the patient outcome, and results in significant cost savings to the institution and lower rate of infection. We conclude that the restrictive transfusion practice during burn excision and grafting is well tolerated and effective in reducing the number of transfusions without increasing complications.Clinical Trial Registration ReferenceIRCT20190209042660N1.     

International Hand Function Study Following Distal Radial Access: The RATATOUILLE Study

BackgroundDistal radial access (DRA) has been proposed to improve procedure ergonomics and favor radial artery patency. Although promising data, nothing is known on evolving hand function after DRA.ObjectivesThis study sought to comprehensively evaluate hand function in patients undergoing DRA.MethodsReal-world patients undergoing DRA undertook a thorough multimodality assessment of hand function implementing multidomain questionnaires (Disabilities of the Arm, Shoulder and Hand and Levine-Katz), and motor (pinch grip test) and sensory (Semmes-Weinstein monofilaments test) examinations of both hands. All assessments were performed at preprocedural baseline and planned at 1-, 6-, and 12-month follow-up (FU). Adverse clinical and procedural events were documented too.ResultsData of 313 patients (220 men, age 66 ± 10 years) from 9 international centers were analyzed. The Disabilities of the Arm, Shoulder and Hand and the Levine-Katz scores slightly improved from baseline to FU (P = 0.008 and P = 0.029, respectively). Pinch strength mildly improved from baseline to FU (P < 0.001 for both the left and right hands). Similarly, touch pressure threshold appeared to faintly improve in both the left and right hands (P < 0.012 for all the sites). For both motor and sensory function tests, comparable findings were found for the DRA hand and the contralateral one, with no significant differences between them. Repeated assessment of all tests over all FU time points similarly showed lack of worsening hand function. Access-related adverse events included 19 harmless bleedings and 3 forearm radial artery and 3 distal radial artery occlusions. None affected hand function at FU.ConclusionsIn a systematic multidimensional assessment, DRA was not associated with hand function impairment. Moreover, DRA emerges as a safe alternative vascular access.     

Relationship between physical growth and motor development in the WHO Child Growth Standards

Aim: To examine relationships among physical growth indicators and ages of achievement of six gross motor milestones in the WHO Child Growth Standards population. Methods: Gross motor development assessments were performed longitudinally on the 816 children included in the WHO Child Growth Standards. Six milestones (sitting without support, hands-and-knees crawling, standing with assistance, walking with assistance, standing alone, walking alone) were assessed monthly from 4 until 12 mo of age and bimonthly thereafter until children could walk alone or reached 24 mo. Failure time models were used 1) to examine associations between specified ages of motor milestone achievement and attained growth z scores and 2) to quantify these relationships as delays or accelerations in ages of milestone achievement. Results: Statistically significant associations were noted between ages of achievement of sitting without support and attained weight-for-age, weight-for-length and BMI-for-age z scores. An increase of one unit z score in these indicators was associated with 3 to 6 d acceleration in the respective achievement age. Statistically significant associations also were noted between various milestone achievement ages and growth when 3- or 6-mo and birth length-for-age z scores were entered jointly in the failure time models. In these analyses, one unit z-score increase in length-for-age was associated with 1 to 3 d delay in the respective achievement age.
Conclusion: Sporadic, significant associations were observed between gross motor development and some physical growth indicators, but these were quantitatively of limited practical significance. These results suggest that, in healthy populations, the attainment of these six gross motor milestones is largely independent of variations in physical growth.