Peptide RL-QN15 promotes regeneration of epidermal nerve fibers and recovery of sensory function in diabetic skin wounds.

Epidermal nerve fiber regeneration and sensory function are severely impaired in skin wounds of diabetic patients. To date, however, research on post-traumatic nerve regeneration and sensory reconstruction remains scarce, and effective clinical therapeutics are lacking. In the current study, localized treatment with RL-QN15, considered as a drug candidate for intervention in skin wounds in our previous research, accelerated the healing of full-thickness dorsal skin wounds in diabetic mice and footpad skin wounds in diabetic rats. Interestingly, nerve density and axonal plasticity in the skin wounds of diabetic rats and mice, as well as plantar sensitivity in diabetic rats, were markedly enhanced by RL-QN15 treatment. Furthermore, RL-QN15 promoted the proliferation, migration, and axonal length of neuron-like PC12 cells, which was likely associated with activation of the phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt) signaling pathway. The therapeutic effects of RL-QN15 were partially reduced by blocking the PI3K/Akt signaling pathway with the inhibitor LY294002. Thus, RL-QN15 showed positive therapeutic effects on the distribution of epidermal nerve fibers and stimulated the recovery of sensory function after cutaneous injury. This study lays a solid foundation for the development of RL-QN15 peptide-based therapeutics against diabetic skin wounds.

Exploring symptom clusters in mild cognitive impairment and dementia with the NIH Toolbox.

OBJECTIVE: Symptom clustering research provides a unique opportunity for understanding complex medical conditions. The objective of this study was to apply a variable-centered analytic approach to understand how symptoms may cluster together, within and across domains of functioning in mild cognitive impairment (MCI) and dementia, to better understand these conditions and potential etiological, prevention, and intervention considerations. METHOD: Cognitive, motor, sensory, emotional, and social measures from the NIH Toolbox were analyzed using exploratory factor analysis (EFA) from a dataset of 165 individuals with a research diagnosis of either amnestic MCI or dementia of the Alzheimer's type. RESULTS: The six-factor EFA solution described here primarily replicated the intended structure of the NIH Toolbox with a few deviations, notably sensory and motor scores loading onto factors with measures of cognition, emotional, and social health. These findings suggest the presence of cross-domain symptom clusters in these populations. In particular, negative affect, stress, loneliness, and pain formed one unique symptom cluster that bridged the NIH Toolbox domains of physical, social, and emotional health. Olfaction and dexterity formed a second unique cluster with measures of executive functioning, working memory, episodic memory, and processing speed. A third novel cluster was detected for mobility, strength, and vision, which was considered to reflect a physical functioning factor. Somewhat unexpectedly, the hearing test included did not load strongly onto any factor. CONCLUSION: This research presents a preliminary effort to detect symptom clusters in amnestic MCI and dementia using an existing dataset of outcome measures from the NIH Toolbox.

Sensory Changes Related to Swallowing in Motor Neurone Disease.

Dysphagia is common in motor neurone disease (MND) and associated with negative health and psychosocial outcomes. Although largely considered a motor disease, a growing body of evidence suggests that MND can also affect the sensory system. As intact sensation is vital for safe swallowing, and sensory changes can influence the clinical management of dysphagia in people living with MND, this review evaluated and summarised the current evidence for sensory changes related to swallowing in MND. Of 3,481 articles originally identified, 29 met the inclusion criteria. Of these, 20 studies reported sensory changes, which included laryngeal sensation, taste, gag reflex, cough reflex, tongue sensation, smell, palatal and pharyngeal sensation, silent aspiration, and undefined sensation of the swallowing mechanism. Sensory changes were either described as decreased (n = 16) or heightened (n = 4). In the remaining nine studies, sensory function was reported as unaffected. The presence of changes to sensory function related to swallowing in MND remains inconclusive, although an increasing number of studies report sensory changes in some sensory domains. Future research is needed to evaluate the prevalence of sensory changes in MND and how such changes may influence dysphagia and its management.

Neurotropin® accelerates peripheral nerve regeneration in a rat sciatic nerve crush injury model.

BACKGROUND: Peripheral nerve injuries are common and serious conditions. The effect of Neurotropin® (NTP), a nonprotein extract derived from the inflamed skin of rabbits inoculated with vaccinia virus, on peripheral nerve regeneration has not been fully elucidated. However, it has analgesic properties via the activation of descending pain inhibitory systems. Therefore, the current study aimed to determine the effects of NTP on peripheral nerve regeneration. METHODS: We examined axonal outgrowth of dorsal root ganglion (DRG) neurons using immunocytochemistry in vitro. In addition, nerve regeneration was evaluated functionally, electrophysiologically, and histologically in a rat sciatic nerve crush injury model in vivo. Furthermore, gene expression of neurotrophic factors in the injured sciatic nerves and DRGs was evaluated. RESULTS: In the dorsal root ganglion neurons in vitro, NTP promoted axonal outgrowth at a concentration of 10 mNU/mL. Moreover, the systemic administration of NTP contributed to the recovery of motor and sensory function at 2 weeks, and of sensory function, nerve conduction velocity, terminal latency, and axon-remyelination 4 weeks after sciatic nerve injury. In the gene expression assessment, insulin-like growth factor 1 and vascular endothelial growth factor expressions were increased in the injured sciatic nerve 2 days postoperatively. CONCLUSIONS: Therefore, NTP might be effective in not only treating chronic pain but also promoting peripheral nerve regeneration after injury.

Role of Oxygen and Its Radicals in Peripheral Nerve Regeneration: From Hypoxia to Physoxia to Hyperoxia.

Oxygen is compulsory for mitochondrial function and energy supply, but it has numerous more nuanced roles. The different roles of oxygen in peripheral nerve regeneration range from energy supply, inflammation, phagocytosis, and oxidative cell destruction in the context of reperfusion injury to crucial redox signaling cascades that are necessary for effective axonal outgrowth. A fine balance between reactive oxygen species production and antioxidant activity draws the line between physiological and pathological nerve regeneration. There is compelling evidence that redox signaling mediated by the Nox family of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases plays an important role in peripheral nerve regeneration. Further research is needed to better characterize the role of Nox in physiological and pathological circumstances, but the available data suggest that the modulation of Nox activity fosters great therapeutic potential. One of the promising approaches to enhance nerve regeneration by modulating the redox environment is hyperbaric oxygen therapy. In this review, we highlight the influence of various oxygenation states, i.e., hypoxia, physoxia, and hyperoxia, on peripheral nerve repair and regeneration. We summarize the currently available data and knowledge on the effectiveness of using hyperbaric oxygen therapy to treat nerve injuries and discuss future directions.

Peripheral sensory function in non-freezing cold injury patients and matched controls.

NEW FINDINGS: What is the central question of this study? Is peripheral sensory function impaired in the chronic phase of non-freezing cold injury (NFCI)? What is the main finding and its importance? Warm and mechanical detection thresholds are elevated and intraepidermal nerve fibre density is reduced in individuals with NFCI in their feet when compared to matched controls. This indicates impaired sensory function in individuals with NFCI. Interindividual variation was observed in all groups, and therefore a diagnostic cut-off for NFCI has yet to be established. Longitudinal studies are required to follow NFCI progression from formation to resolution ABSTRACT: The aim of this study was to compare peripheral sensory neural function of individuals with non-freezing cold injury (NFCI) with matched controls (without NFCI) with either similar (COLD) or minimal previous cold exposure (CON). Thirteen individuals with chronic NFCI in their feet were matched with the control groups for sex, age, race, fitness, body mass index and foot volume. All undertook quantitative sensory testing (QST) on the foot. Intraepidermal nerve fibre density (IENFD) was assessed 10 cm above the lateral malleolus in nine NFCI and 12 COLD participants. Warm detection threshold was higher at the great toe in NFCI than COLD (NFCI 45.93 (4.71)°C vs. COLD 43.44 (2.72)°C, P = 0.046), but was non-significantly different from CON (CON 43.92 (5.01)°C, P = 0.295). Mechanical detection threshold on the dorsum of the foot was higher in NFCI (23.61 (33.59) mN) than in CON (3.83 (3.69) mN, P = 0.003), but was non-significantly different from COLD (10.49 (5.76) mN, P > 0.999). Remaining QST measures did not differ significantly between groups. IENFD was lower in NFCI than COLD (NFCI 8.47 (2.36) fibre/mm2 vs. COLD 11.93 (4.04) fibre/mm2 , P = 0.020). Elevated warm and mechanical detection thresholds may indicate hyposensitivity to sensory stimuli in the injured foot for individuals with NFCI and may be due to reduced innervation given the reduction in IENFD. Longitudinal studies are required to identify the progression of sensory neuropathy from the formation of injury to its resolution, with appropriate control groups employed.

Breast sensorisexual function: a novel patient-reported outcome measure of sexual sensory functions of the breast.

BACKGROUND: A validated measure assessing sexual sensory functions of the breast is needed to optimize sexual and other health outcomes after breast procedures. AIM: To describe the development of a patient-reported outcome measure (PROM) to assess breast sensorisexual function (BSF). METHODS: We applied the PROMIS standards (Patient Reported Outcomes Measurement Information System) for measure development and evaluation of validity. An initial conceptual model of BSF was developed with patients and experts. A literature review yielded a pool of 117 candidate items that underwent cognitive testing and iteration. Forty-eight items were administered to an ethnically diverse, national panel-based sample of sexually active women with breast cancer (n = 350) or without (n = 300). Psychometric analyses were performed. OUTCOMES: The main outcome was BSF, a measure that assesses affective (satisfaction, pleasure, importance, pain, discomfort) and functional (touch, pressure, thermoreception, nipple erection) sensorisexual domains. RESULTS: A bifactor model fit to 6 domains-excluding 2 domains with only 2 items each and 2 pain-related domains-revealed a single general factor representing BSF that may be adequately measured by the average of the items. This factor, with higher values denoting better function and with the standard deviation set to 1, was highest among women without breast cancer (mean, 0.24), intermediate among women with breast cancer but not bilateral mastectomy and reconstruction (-0.01), and lowest among those with bilateral mastectomy and reconstruction (-0.56). Between women with and without breast cancer, the BSF general factor accounted for 40%, 49%, and 100% of the difference in arousal, ability to orgasm, and sexual satisfaction, respectively. Items in each of 8 domains demonstrated unidimensionality (ie, they measured 1 underlying BSF trait) and high Cronbach's alphas for the entire sample (0.77-0.93) and the cancer group (0.71-0.95). Correlations with sexual function, health, and quality of life were positive for the BSF general factor and mostly negative for the pain domains. CLINICAL IMPLICATIONS: The BSF PROM can be used to assess the impact of breast surgery or other procedures on the sexual sensory functions of the breast in women with and without breast cancer. STRENGTHS AND LIMITATIONS: The BSF PROM was developed by using evidence-based standards, and it applies to sexually active women with and without breast cancer. Generalizability to sexually inactive women and other women warrants further study. CONCLUSION: The BSF PROM is a measure of women's breast sensorisexual function with evidence of validity among women affected and unaffected by breast cancer.

Impact of fractional amplitude of low-frequency fluctuations in motor- and sensory-related brain networks on spinal cord injury severity.

Spinal cord injury (SCI) can cause motor, sensory, and autonomic dysfunctions and may affect the cerebral functions. However, the mechanisms of plastic changes in the brain according to SCI severity remain poorly understood. Therefore, in the current study, we compared the brain activity of the entire neural network according to severity of SCI using fractional amplitude of low-frequency fluctuations (fALFF) analysis in resting-state functional magnetic resonance imaging (rs-fMRI). A total of 59 participants were included, consisting of 19 patients with complete SCI, 20 patients with incomplete SCI, and 20 healthy individuals. Their motor and sensory functions were evaluated. The rs-fMRI data of low-frequency fluctuations were analyzed based on fALFF. Differences in fALFF values among complete-SCI patients, incomplete-SCI patients, and healthy controls were assessed using ANOVA. Then post hoc analysis and two-sample t-tests were conducted to assess the differences between the three groups. Pearson correlation analyses were used to determine correlations between clinical measures and the z-score of the fALFF in the SCI groups. Patients with SCI (complete and incomplete) showed lower fALFF values in the superior medial frontal gyrus than the healthy controls, and were associated with poor motor and sensory function (p < .05). Higher fALFF values were observed in the putamen and thalamus, and were negatively associated with motor and sensory function (p < .05). In conclusion, alterations in the neural activity of the motor- and sensory-related networks of the brain were observed in complete-SCI and incomplete-SCI patients. Moreover, plastic changes in these brain regions were associated with motor and sensory function.

Cardiac autonomic neuropathy predicts diabetic retinopathy progression in Asian population with type 2 diabetes mellitus.

PURPOSE: To investigate the role of cardiac autonomic neuropathy (CAN), vascular condition, and sensory function in diabetic retinopathy (DR) progression. METHODS: This 3-year cohort study conducted in a community hospital included 4850 patients over 20 with type 2 diabetes mellitus. Participants were assessed in 2017 at baseline and were followed up in 2020. Patients were divided into two groups based on whether they had DR progression or not and were compared using the chi-square test or two-sample t-test. Beta coefficient and odds ratio (OR) with 95% confidence intervals were calculated using binary logistic regression. The receiver operating characteristic (ROC) curve of various independent variables for DR progression was provided with C-statistics. RESULTS: Abnormal hemoglobin A1c (HbA1c) level/variation, estimated glomerular filtration rate, urine albumin-to-creatinine ratio, R-R interval variation, standard deviation of the average NN intervals, autonomic nervous system function, power of high-frequency (HF) bands, balance, cardio-ankle vascular index (CAVI), and warm stimulation (WS) were associated with DR progression. Average HbA1c, HF, and proliferative diabetic retinopathy were independent factors for patients developing DR progression. The top three areas under the curve of ROCs were HF + baseline DR grading, WS + baseline DR grading, and CAVI + baseline DR grading. These variable combinations were the most reliable predictors of DR progression. CONCLUSION: CAN, abnormal vascular condition, and sensory function are associated with DR progression. The combination of HF, WS, and CAVI with baseline DR grading provides the most accurate predictive model for DR progression. Early detection of these factors is important to prevent DR progression.

Sensory and motor correlates of frailty: dissociation between frailty phenotype and frailty index.

BACKGROUND: Frailty has been associated with a decline in sensory and motor function. However, given that different frailty measures were shown to overlap but also differ in their diagnostic properties, sensory and motor correlates of frailty might be different depending on the operationalization of frailty. Our objective was to identify sensory and motor determinants of frailty and compare the results between frailty phenotype (FP) and frailty index (FI). METHODS: Data from 44 pre-frail and frail subjects aged 65 and above were used. Frailty was measured using the FP and the FI. Sensory function in the visual, auditory, and tactile domain was assessed using visual acuity, absolute hearing threshold and mechanical detection threshold. Upper extremity motor performance was evaluated by the Purdue Pegboard Test and the Short Physical Performance Battery was used to assess lower extremity motor function. Multiple logistic regression models were employed to determine associations of sensory and motor function with frailty vs. pre-frailty for both frailty measures. RESULTS: The frailty measures were moderately correlated (0.497, p ≤ 0.01) and had a Kappa agreement of 0.467 (p = 0.002). Using the FP, frailty was significantly associated with reduced upper extremity motor function only (OR = 0.50, 95% CI 0.29-0.87, p = 0.014). Frailty as assessed by the FI was significantly related to higher hearing thresholds (OR = 1.21, 95% CI 1.02-1.43, p = 0.027) and reduced lower extremity performance (OR = 0.32, 95% CI 0.13-0.77, p = 0.012). CONCLUSION: Frailty is related to reduced performance in measures of sensory and motor function. However, traditional measures of frailty might be differentially sensitive to capture sensory and motor decline, possibly contributing to the much-observed discordance between the diagnostic instruments. This should be taken into account by researchers and clinicians when planning and evaluating therapeutic interventions for frailty. TRIAL REGISTRATION: ClinicalTrials.gov NCT03666039 . Registered 11 September 2018 - Retrospectively registered.

Exploring the Use of the Current Perception Threshold in Pharyngeal Paresthesia Patients.

To explore pharyngeal sensory function by current perception threshold (CPT) measurement in paresthetic pharynx. In total, 58 healthy participants and 66 patients with pharyngeal paresthetic symptoms underwent CPT evaluation. Pharyngeal paresthesia (n = 66) was classified into three categories based on aetiologies: six cases with pain in pharynx; 34 neuropathic patients with glossopharyngeal nerve and/or vagus nerve or recurrent laryngeal nerve injury; and 26 patients with globus pharyngeus. CPT measurements were obtained from bilateral palatoglossal arch and tongue base at 2000, 250 and 5 Hz stimulation frequencies. Ranked from high to low, the CPT values for the bilateral palatoglossal arches and tongue bases were: lower cranial neuropathic patients, globus pharyngeus, healthy participants and patients with pain. The CPT values for neuropathic patients on the injured side were significantly higher than those on the healthy side (P < 0.05). The CPT values for patients with pain in pharynx were significantly lower than those of healthy participants (P < 0.05) when the bilateral tongue bases were stimulated. The CPT measurement is a reliable method for quantitatively assessing pharyngeal sensory function and able to differentiate pharyngeal paresthesia between lower cranial neuropathic and subjective discomfort. Pharyngeal sensory function is more sensitive in patients with pain in pharynx. Pharyngeal sensory function is significantly reduced in lower cranial neuropathic patients, especially on the injured side. Patients with globus pharyngeus have pharyngeal hyposensitivity.

Caenorhabditis elegans exhibits positive gravitaxis.

BACKGROUND: Gravity plays an important role in most life forms on Earth. Yet, a complete molecular understanding of sensing and responding to gravity is lacking. While there are anatomical differences among animals, there is a remarkable conservation across phylogeny at the molecular level. Caenorhabditis elegans is suitable for gene discovery approaches that may help identify molecular mechanisms of gravity sensing. It is unknown whether C. elegans can sense the direction of gravity. RESULTS: In aqueous solutions, motile C. elegans nematodes align their swimming direction with the gravity vector direction while immobile worms do not. The worms orient downward regardless of whether they are suspended in a solution less dense (downward sedimentation) or denser (upward sedimentation) than themselves. Gravitaxis is minimally affected by the animals' gait but requires sensory cilia and dopamine neurotransmission, as well as motility; it does not require genes that function in the body touch response. CONCLUSIONS: Gravitaxis is not mediated by passive forces such as non-uniform mass distribution or hydrodynamic effects. Rather, it is mediated by active neural processes that involve sensory cilia and dopamine. C. elegans provides a genetically tractable system to study molecular and neural mechanisms of gravity sensing.

Exploring Shared Effects of Multisensory Impairment, Physical Dysfunction, and Cognitive Impairment on Physical Activity: An Observational Study in a National Sample.

Multisensory, physical, and cognitive dysfunction share age-related physiologic disturbances and may have common health effects. We determined whether the effect of multisensory impairment on physical activity (PA) is explained by physical (timed up and go) or cognitive (Short Portable Mental Status Questionnaire) dysfunction. A National Social Life, Health, and Aging Project participant subset (n = 507) underwent objective sensory testing in 2005-2006 and wrist accelerometry in 2010-2011. We related multisensory impairment to PA using multivariate mixed-effects linear regression and compared the effect magnitude after adjusting for physical then cognitive dysfunction. Worse multisensory impairment predicted lower PA across three scales (Global Sensory Impairment: ß = -0.04, 95% confidence interval [-0.07, -0.02]; Total Sensory Burden: ß = -0.01, 95% confidence interval [-0.03, -0.003]; and Number of Impaired Senses: ß = -0.02, 95% confidence interval [-0.04, -0.004]). Effects were similar after accounting for physical and cognitive dysfunction. Findings suggest that sensory, physical, and cognitive dysfunction have unique mechanisms underlying their PA effects.

An observation of the clinical efficacy of combining Riluzole with mannitol and hyperbaric oxygen in treating acute spinal cord injury.

OBJECTIVE: To examine the clinical efficacy of combining Riluzole with mannitol and hyperbaric oxygen therapy in treating thoracolumbar vertebral fracture-induced acute spinal cord injury (ASCI). METHODS: From June 2015 to May 2018, 80 patients with thoracolumbar fractures and ASCI who were treated at Baoding First Central Hospital were selected. All patients underwent posterior laminectomy and screw fixation, and they were randomly divided into two groups using a random number table method. The control group received conventional postoperative treatment, while the experimental group was treated with riluzole combined with mannitol and hyperbaric oxygen on the basis of conventional treatment. The recovery of nerve function which included motor function and sensory function, and the changes of serum IL-6, CRP, BDNF, BFGF and other factors before treatment and four weeks after treatment of the two groups of patients were observed and evaluated. RESULTS: After treatment, the motor function scores and sensory function scores of the two groups of patients were improved compared with those before treatment (p<0.05). Compared with the control group, the experimental group improved significantly, and the difference was statistically significant (p<0.05). The levels of IL-6, BDNF and NFGF in the experimental group were significantly lower than those in the control group (p<0.05). CONCLUSIONS: For patients with thoracolumbar fractures and ASCI undergoing laminar decompression and fixation, the comprehensive treatment plan of riluzole combined with mannitol and hyperbaric oxygen has certain advantages. Compared with the conventional therapy, it may significantly improve the movement and sensory functions of patients, relieve the inflammatory response of spinal cord, and promote recovery from the injury.

Assessing the spatial distribution of cervical spinal cord activity during tactile stimulation of the upper extremity in humans with functional magnetic resonance imaging.

Dermatomal maps are a mainstay of clinical practice and provide information on the spatial distribution of the cutaneous innervation of spinal nerves. Dermatomal deficits can help isolate the level of spinal nerve root involvement in spinal conditions and guide clinicians in diagnosis and treatment. Dermatomal maps, however, have limitations, and the spatial distribution of spinal cord sensory activity in humans remains to be quantitatively assessed. Here we used spinal cord functional MRI to map and quantitatively compare the spatial distribution of sensory spinal cord activity during tactile stimulation of the left and right lateral shoulders (i.e. C5 dermatome) and dorsal third digits of the hands (i.e., C7 dermatome) in healthy humans (n â€‹= â€‹24, age â€‹= â€‹36.8 â€‹± â€‹11.8 years). Based on the central sites for processing of innocuous tactile sensory information, we hypothesized that the activity would be localized more to the ipsilateral dorsal spinal cord with the lateral shoulder stimulation activity being localized more superiorly than the dorsal third digit. The findings demonstrate lateralization of the activity with the left- and right-sided stimuli having more activation in the ipsilateral hemicord. Contradictory to our hypotheses, the activity for both stimulation sites was spread across the dorsal and ventral hemicords and did not demonstrate a clear superior-inferior localization. Instead, the activity for both stimuli had a broader than expected distribution, extending across the C5, C6, and C7 spinal cord segments. We highlight the complexity of the human spinal cord neuroanatomy and several sources of variability that may explain the observed patterns of activity. While the findings were not completely consistent with our a priori hypotheses, this study provides a foundation for continued work and is an important step towards developing normative quantitative spinal cord measures of sensory function, which may become useful objective MRI-based biomarkers of neurological injury and improve the management of spinal disorders.

Association of disease duration and sensorimotor function in type 2 diabetes mellitus: beyond diabetic peripheral neuropathy.

PURPOSE: The aim of the study is to assess association of the duration of diabetes and vibration, proprioception, muscle strength, reaction time and balance measures in people with type 2 diabetes mellitus (DM) without peripheral neuropathy. METHODS: Forty-seven type 2 diabetics without peripheral neuropathy and 23 healthy controls were recruited for the study. Patients with type 2 DM were further classified into 23 patients who suffered from diabetes for less than 5 years (<5yrDM) and 24 patients who had diabetes for 5 years and above (≥5yrDM). All participants were assessed for Michigan neuropathy screening instrument (MNSI), vibration perception threshold (VPT), proprioception, muscles strength, centre of pressure (COP) range, COP sway and reaction time. RESULTS: ≥5yrDM patients were found to significantly differ from healthy control in MNSI score (p ≤ 0.013), VPT score (p ≤ 0.002), reaction time (p ≤ 0.018), COP range (p ≤ 0.005) and COP sway (p ≤ 0.027). A significant difference was found only in reaction time (p < 0.002) except in the back direction (p = 0.089), and COP range (p ≤ 0.016) except in the front (p = 0.101) and right direction (p = 0.085) between <5yrDM patients and healthy controls. CONCLUSIONS: ≥5yrDM patients exhibit a subtle deterioration in VPT, reaction time, and balance measure while <5yr DM patients were impaired only in COP range and reaction time when compared with healthy control.

Randomized controlled trial protocol to improve multisensory neural processing, language and motor outcomes in preterm infants.

BACKGROUND: Premature infants are at risk for abnormal sensory development due to brain immaturity at birth and atypical early sensory experiences in the Neonatal Intensive Care Unit. This altered sensory development can have downstream effects on other more complex developmental processes. There are currently no interventions that address rehabilitation of sensory function in the neonatal period. METHODS: This study is a randomized controlled trial of preterm infants enrolled at 32-36 weeks postmenstrual age to either standard care or standard care plus multisensory intervention in order to study the effect of multisensory intervention as compared to standard care alone. The study population will consist of 100 preterm infants in each group (total n = 200). Both groups will receive standard care, consisting of non-contingent recorded parent's voice and skin-to-skin by parent. The multisensory group will also receive contemporaneous holding and light pressure containment for tactile stimulation, playing of the mother's voice contingent on the infant's pacifier sucking for auditory stimulation, exposure to a parent-scented cloth for olfactory stimulation, and exposure to carefully regulated therapist breathing that is mindful and responsive to the child's condition for vestibular stimulation. The primary outcome is a brain-based measure of multisensory processing, measured using time locked-EEG. Secondary outcomes include sensory adaptation, tactile processing, speech sound differentiation, motor and language function, measured at one and two years corrected gestational age. DISCUSSION: This is the first randomized controlled trial of a multisensory intervention using brain-based measurements in order to explain the causal effects of the multisensory intervention on neural processing changes to mediate neurodevelopmental outcomes in former preterm infants. In addition to contributing a critical link in our understanding of these processes, the protocolized multisensory intervention in this study is therapist administered, parent supported and leverages simple technology. Thus, this multisensory intervention has the potential to be widely implemented in various NICU settings, with the opportunity to potentially improve neurodevelopment of premature infants. TRIAL REGISTRATION: NIH Clinical Trials ( clinicaltrials.gov ): NCT03232931 . Registered July 2017.

An Integrated Brain-Machine Interface Platform With Thousands of Channels.

Brain-machine interfaces hold promise for the restoration of sensory and motor function and the treatment of neurological disorders, but clinical brain-machine interfaces have not yet been widely adopted, in part, because modest channel counts have limited their potential. In this white paper, we describe Neuralink's first steps toward a scalable high-bandwidth brain-machine interface system. We have built arrays of small and flexible electrode "threads," with as many as 3072 electrodes per array distributed across 96 threads. We have also built a neurosurgical robot capable of inserting six threads (192 electrodes) per minute. Each thread can be individually inserted into the brain with micron precision for avoidance of surface vasculature and targeting specific brain regions. The electrode array is packaged into a small implantable device that contains custom chips for low-power on-board amplification and digitization: The package for 3072 channels occupies less than 23×18.5×2 mm3. A single USB-C cable provides full-bandwidth data streaming from the device, recording from all channels simultaneously. This system has achieved a spiking yield of up to 70% in chronically implanted electrodes. Neuralink's approach to brain-machine interface has unprecedented packaging density and scalability in a clinically relevant package.

Influence of lower complete denture use on masseter muscles and masticatory function: A longitudinal study.

BACKGROUND: Edentulism can reduce mastication, leading to changes in food pattern, with possible consequences to masticatory muscle thickness. OBJECTIVES: This study verified masticatory function and oral perception in subjects who did not use lower CDs, and whether the insertion of new upper and lower CDs would improve such variables. METHODS: Fifteen edentulous elderly who wore only the upper CD were selected and received new upper and lower CD. Volunteers were evaluated at baseline and after 1, 3 and 6 months of new prosthesis use. Masticatory performance (MP) was assessed by the sieving method (X50 values). Masseter thickness (MT) was evaluated by ultrasonography. Oral sensorial ability (OSA) was assessed by oral stereognosis test and maximum tongue pressure (MTP) was verified by pressure sensors. Data were submitted to repeated measures ANOVA and Tukey-Kramer posthoc tests (α = 0.05). Correlation between OSA and MTP was verified by Person's correlation. RESULTS: X50 and MTP decreased (P < 0.05) after 1 month and remained stable (P > 0.05) for next assessments. After 3 months, MT in rest position was increased (P < 0.05), while during maximum voluntary contraction 1 month was enough to increase MT (P < 0.05). There were no differences for OSA (P > 0.05) and no correlation between OSA and MTP. CONCLUSION: Masticatory performance and masseter thickness of elderly who did not use the lower dentures were improved after 2 months using new upper and lower CDs. However, new CDs in both dental arch decreased MTP. Brazilian Registry of Clinical Trials (ReBEC #RBR-37gdst).

Shape-texture-identification-STI-A test for tactile gnosis: Concurrent validity of STI2.

STUDY DESIGN: Cross-sectional study. INTRODUCTION: The shape-texture-identification (STI) test (Össur Nordic AB, Sweden) is used to evaluate one aspect of tactile gnosis in nerve disorders, and it has proven good methodological properties. PURPOSE OF THE STUDY: A new version of the STI test was recently introduced-STI2 (www.sensory-test.com). The purpose of this study was to test the concurrent validity in STI2. METHODS: Using a cross-sectional design, this methodological study compared STI2 to the original version based on 2 cohorts; 1 including 20 persons (1 affected finger and corresponding finger on in opposite hand) with affected sensibility after hand injuries and 1 healthy group including 20 persons (digits II and V in both hands). The agreement between the 2 versions of the instrument was calculated statistically by a percentage comparison of the test results and weighted kappa. RESULTS: The 112 tested fingers showed a complete agreement, or 1-point accepted deviation, between the 2 tests in 92% with weighted kappa of 0.74 and 95% confidence interval of 0.63-0.89. The result showed that there is no significant deviation between the 2 versions of the test. DISCUSSION: The use of standardizes and evidence based assessment tools in clinical practice is paramount for a patient centered healthcare. Previous research has shown good psychometric proprties in the STI-test. This study contributes to the scientific evidence of the instrument. CONCLUSION: As the new STI2 proved good agreement within the accepted deviation, we conclude that there is evidence to use the new STI2 test in assessment of tactile gnosis.