Oral-diadochokinesis between Parkinson's disease and neurotypical elderly among Malaysian-Malay speakers.

BACKGROUND: Parkinson's disease (PD) has an impact on speech production, manifesting in various ways including alterations in voice quality, challenges in articulating sounds and a decrease in speech rate. Numerous investigations have been conducted to ascertain the oral-diadochokinesis (O-DDK) rate in individuals with PD. However, the existing literature lacks exploration of such O-DDK rates in Malaysia and does not provide consistent evidence regarding the advantage of real-word repetition. AIMS: To explore the effect of gender, stimuli type and PD status and their interactions on the O-DDK rates among Malaysian-Malay speakers. METHODS & PROCEDURES: O-DDK performance of 62 participants (29 individuals with PD and 33 healthy elderly) using a non-word ('pataka'), a Malay real-word ('patahkan') and an English real-word ('buttercake') was audio recorded. The number of syllables produced in 8 s was counted. A hierarchical linear modelling was performed to investigate the effects of stimuli type (non-word, Malay real-word, English real-word), PD status (yes, no), gender (male, female) and their interactions on the O-DDK rate. The model accounted for participants' age as well as the nesting of repeated measurements within participants, thereby providing unbiased estimates of the effects. OUTCOMES & RESULTS: The stimuli effect was significant (p < 0.0001). Malay real-word showed the lowest O-DDK rate (5.03 ± 0.11 syllables/s), followed by English real-word (5.25 ± 0.11 syllables/s) and non-word (5.42 ± 0.11 syllables/s). Individuals with PD showed a significantly lower O-DDK rate compared to healthy elderly (4.73 ± 0.15 syllables/s vs. 5.74 ± 0.14 syllables/s, adjusted p < 0.001). A subsequent analysis indicated that the O-DDK rate declined in a quadratic pattern. However, neither gender nor age effects were observed. Additionally, no significant two-way interactions were found between stimuli type, PD status and gender (all p > 0.05). Therefore, the choice of stimuli type has no or only limited effect considering the use of O-DDK tests in clinical practice for diagnostic purposes. CONCLUSIONS & IMPLICATIONS: The observed slowness in O-DDK among individuals with PD can be attributed to the impact of the movement disorder, specifically bradykinesia, on the physiological aspects of speech production. Speech-language pathologists can gain insights into the impact of PD on speech production and tailor appropriate intervention strategies to address the specific needs of individuals with PD according to disease stages. WHAT THIS PAPER ADDS: What is already known on this subject The observed slowness in O-DDK rates among individuals with PD may stem from the movement disorder's effects on the physiological aspects of speech production, particularly bradykinesia. However, there is a lack of consistent evidence regarding the influence of real-word repetition and how O-DDK rates vary across different PD stages. What this study adds to existing knowledge The O-DDK rates decline in a quadratic pattern as the PD progresses. The research provides insights into the advantage of real-word repetition in assessing O-DDK rates, with Malay real-word showing the lowest O-DDK rate, followed by English real-word and non-word. What are the potential or actual clinical implications of this work? Speech-language pathologists can better understand the evolving nature of speech motor impairments as PD progresses. This insight enables them to design targeted intervention strategies that are sensitive to the specific needs and challenges associated with each PD stage. This finding can guide clinicians in selecting appropriate assessment tools for evaluating speech motor function in PD patients.

Speech Performance among Healthy Malay Female Speakers during Dual Tasks and Sentence Complexity.

OBJECTIVES: This study aimed to identify how different dual tasks influence speech performance among young Malay speakers by manipulating the complexity of sentences. Fifteen female speakers (20-30 years old) were audio recorded while executing a series of simple and complex sentence repetition tasks. METHODS: Hierarchical linear modeling was conducted to examine the effects of task (speech task only, speech + cognitive tasks, speech + linguistic tasks, and speech + manual tasks) and sentence complexity (simple vs. complex), as well as their interaction on 3 outcome measures (word accuracy rate [WAR], response reaction time [RRT], and duration of sentence [DoS]). RESULTS: Significantly higher WAR were found when participants read the sentences only compared to when they completed another task simultaneously. The pairwise comparison further revealed that the conditions of speech + manual tasks produced the lowest WAR. For RRT, participants responded significantly faster when they only read the sentences (mean = 1.36, SE = 0.17) than when they read the sentences and conducted another task at the same time (mean = 1.66, SE = 0.14; p < 0.0001). A pairwise comparison showed that the conditions of speech + manual tasks produced the longest DoS. Neither the effect of sentence complexity nor the interaction between task and sentence complexity was statistically significant across WAR, RRT, and DoS. CONCLUSIONS: The results augment what is known about interference between speech and other concurrent tasks and provides evidence that divided attention affects manual task performance more than other tasks. In addition, sentence complexity did not affect speech performance in healthy adults. This paradigm could be used in future studies to serve as a clinical marker that can potentially distinguish mild cognitive impairment from normal aging.

Oral diadochokinetic rates across languages: Multilingual speakers comparison.

BACKGROUND: It is unclear whether oral diadochokinetic rate (oral-DDK) performance is affected by different languages within a multilingual country. AIMS: This study investigated the effects of age, sex, and stimulus type (real word in L1, L2 vs. non-word) on oral-DDK rates among healthy Malaysian-Malay speakers in order to establish language- and age-sensitive norms. The second aim was to compared the nonword 'pataka' oral-DDK rates produced by Malaysian-Malay speakers on currently available normative data for Hebrew speakers and Malaysian-Mandarin speakers. METHODS & PROCEDURES: Oral-DDK performance of 90 participants (aged 20-77 years) using nonword ('pataka'), Malay real word ('patahkan'), and English real word ('buttercake') was audio recorded. The number of syllables produced in 8 seconds was calculated. Mixed analysis of variance (ANOVA) was conducted to examine the effects of stimulus type (nonword, Malay, and English real word), sex (male, female), age (younger, 20-40 years; middle, 41-60 years; older, ≥61 years), and their interactions on the oral-DDK rate. Data obtained were also compared with the raw data of Malaysian-Mandarin and Hebrew speakers from the previous studies. OUTCOMES & RESULTS: A normative oral-DDK rate has been established for healthy Malaysian-Malay speakers. The oral-DDK rate was significantly affected by stimuli (p < 0.001). Malay real word showed the slowest rate, whereas there was no significant difference between English real word and nonword. The oral-DDK rate for Malay speakers was significantly higher than Mandarin and Hebrew speakers across stimuli (all p < 0.01). Interestingly, oral-DDK rates were not affected by age group for Malay speakers. CONCLUSIONS & IMPLICATIONS: Stimuli type and language affect the oral-DDK rate, indicating that speech-language therapists should consider using language-specific norms when assessing multilingual speakers. WHAT THIS PAPER ADDS: What is already known on the subject Age, sex, and language are factors that need to be considered when developing oral-DDK normative protocol. It is unclear whether oral-DDK performance is affected by different languages within a multilingual country. What this paper adds to existing knowledge No ageing effect across real word versus nonword on oral-DDK performance was observed among Malaysian-Malay speakers, contrasting with current available literature that speech movements slow down as we age. Additionally, Malaysian-Malay speakers have faster oral-DDK rates than Malaysian-Mandarin and Hebrew speakers across all stimuli. What are the potential or actual clinical implications of this work? Establishing normative data of different languages will enable speech-language therapists to select the appropriate reference dataset based on the language mastery of these multilingual speakers.

Wireless Sensing of Lower Lip and Thumb-Index Finger 'Ramp-and-Hold' Isometric Force Dynamics in a Small Cohort of Unilateral MCA Stroke: Discussion of Preliminary Findings.

Automated wireless sensing of force dynamics during a visuomotor control task was used to rapidly assess residual motor function during finger pinch (right and left hand) and lower lip compression in a cohort of seven adult males with chronic, unilateral middle cerebral artery (MCA) stroke with infarct confirmed by anatomic magnetic resonance imaging (MRI). A matched cohort of 25 neurotypical adult males served as controls. Dependent variables were extracted from digitized records of 'ramp-and-hold' isometric contractions to target levels (0.25, 0.5, 1, and 2 Newtons) presented in a randomized block design; and included force reaction time, peak force, and dF/dtmax associated with force recruitment, and end-point accuracy and variability metrics during the contraction hold-phase (mean, SD, criterion percentage 'on-target'). Maximum voluntary contraction force (MVCF) was also assessed to establish the force operating range. Results based on linear mixed modeling (LMM, adjusted for age and handedness) revealed significant patterns of dissolution in fine force regulation among MCA stroke participants, especially for the contralesional thumb-index finger followed by the ipsilesional digits, and the lower lip. For example, the contralesional thumb-index finger manifest increased reaction time, and greater overshoot in peak force during recruitment compared to controls. Impaired force regulation among MCA stroke participants during the contraction hold-phase was associated with significant increases in force SD, and dramatic reduction in the ability to regulate force output within prescribed target force window (±5% of target). Impaired force regulation during contraction hold-phase was greatest in the contralesional hand muscle group, followed by significant dissolution in ipsilateral digits, with smaller effects found for lower lip. These changes in fine force dynamics were accompanied by large reductions in the MVCF with the LMM marginal means for contralesional and ipsilesional pinch forces at just 34.77% (15.93 N vs. 45.82 N) and 66.45% (27.23 N vs. 40.98 N) of control performance, respectively. Biomechanical measures of fine force and MVCF performance in adult stroke survivors provide valuable information on the profile of residual motor function which can help inform clinical treatment strategies and quantitatively monitor the efficacy of rehabilitation or neuroprotection strategies.

Effect of Pacifier Design on Nonnutritive Suck Maturation and Weight Gain in Preterm Infants: A Pilot Study.

BACKGROUND: Pacifiers are effective in promoting oral feeding by increasing the maturation of nonnutritive sucking to nutritive suck in preterm neonates. It is unclear whether pacifier design can influence suck dynamics and weight loss during the first week of life. OBJECTIVES: This pilot study examined the feasibility of studying the effect of pacifier design on suck maturation and weight loss in preterm neonates. METHODS: Twenty-five preterm neonates (mean [SD] birth weight 1791 [344.9] grams, mean [SD] gestational age 33.1 [1.2] weeks) were studied in a single newborn intensive care unit. Neonates were assigned to either an orthodontic pacifier (n = 13) or a bulb-shaped pacifier (n = 12) immediately after birth. Suck dynamics (cycles per minute, total compressions per minute, cycle bursts, and amplitude) were assessed with an NTrainer (Innara Health, Olathe, Kansas). Weight was recorded during the first week of life on day 1.2 (±2.5 days) and day 6.0 (±2.1 days). Descriptive statistics were applied to analyze data. RESULTS: No significant differences were seen between groups with respect to birth weight and gestational age. Reproducible nonnutritive sucking measurements could be obtained with the NTrainer, with both types of pacifiers. No differences were detected in nonnutritive sucking dynamics or weight loss over time within each group or between groups. CONCLUSIONS: Data indicate that it is feasible to measure nonnutritive sucking dynamics and associated weight loss in relation to pacifier design in preterm neonates. Larger trials over longer time periods are needed to determine whether pacifier design influences suck dynamics and maturation, oromotor function, feeding/weight loss, and dental formation in preterm neonates. (Curr Ther Res Clin Exp. 2020; 81:XXX-XXX).

Genome Sequence and Transcriptome Analyses of Chrysochromulina tobin: Metabolic Tools for Enhanced Algal Fitness in the Prominent Order Prymnesiales (Haptophyceae).

Haptophytes are recognized as seminal players in aquatic ecosystem function. These algae are important in global carbon sequestration, form destructive harmful blooms, and given their rich fatty acid content, serve as a highly nutritive food source to a broad range of eco-cohorts. Haptophyte dominance in both fresh and marine waters is supported by the mixotrophic nature of many taxa. Despite their importance the nuclear genome sequence of only one haptophyte, Emiliania huxleyi (Isochrysidales), is available. Here we report the draft genome sequence of Chrysochromulina tobin (Prymnesiales), and transcriptome data collected at seven time points over a 24-hour light/dark cycle. The nuclear genome of C. tobin is small (59 Mb), compact (∼ 40% of the genome is protein coding) and encodes approximately 16,777 genes. Genes important to fatty acid synthesis, modification, and catabolism show distinct patterns of expression when monitored over the circadian photoperiod. The C. tobin genome harbors the first hybrid polyketide synthase/non-ribosomal peptide synthase gene complex reported for an algal species, and encodes potential anti-microbial peptides and proteins involved in multidrug and toxic compound extrusion. A new haptophyte xanthorhodopsin was also identified, together with two "red" RuBisCO activases that are shared across many algal lineages. The Chrysochromulina tobin genome sequence provides new information on the evolutionary history, ecology and economic importance of haptophytes.

Preterm Neurodevelopmental Outcomes Following Orosensory Entrainment Intervention.

Previous research indicates that the NTrainer, a pressurized pacifier programmed to produce pulsed pneumotactile stimulation during gavage feeds, has been found to facilitate non-nutritive suck development and shorten the length of hospital stay when used in the Neonatal Intensive Care Unit (NICU). Four groups of children, including infants of diabetic mothers (IDM), healthy controls (HI), and those with respiratory distress syndrome (RDS), or chronic lung disease (CLD), were randomly assigned to an NTrainer therapy or sham 'control' condition when in the NICU. At 30 months of age, 113/223 study participants were assessed using standardized language, motor, and cognitive assessments. No significant group differences were evident between the NTrainer and sham groups in language, motor, or cognitive functioning. The NTrainer did not improve nor adversely impact language, cognition, or motor outcomes.

Hemodynamic changes in cortical sensorimotor systems following hand and orofacial motor tasks and pulsed pneumotactile stimulation.

We performed a functional near-infrared spectroscopy (fNIRS) study of the evoked hemodynamic responses seen in hand and face sensorimotor cortical representations during (1) active motor tasks and (2) pulsed pneumotactile stimulation. Contralateral fNIRS measurements were performed on 22 healthy adult participants using a block paradigm that consisted of repetitive right hand and right oral angle somatosensory stimulation using a pulsed pneumotactile array stimulator, and repetitive right-hand grip compression and bilabial compressions on strain gages. Results revealed significant oxyhemoglobin (HbO) modulation across stimulus conditions in corresponding somatotopic cortical regions. Of the 22 participants, 86% exhibited a decreased HbO response during at least one of the stimulus conditions, which may be indicative of cortical steal, or hypo-oxygenation occurring in channels adjacent to the primary areas of activation. Across all conditions, 56% of participants' HbO responses were positive and 44% were negative. Hemodynamic responses most likely differed across hand and face motor and somatosensory cortical regions due to differences in regional arterial/venous anatomy, cortical vascular beds, extent and orientation of somatotopy, task dynamics, and mechanoreceptor typing in hand and face. The combination of optical imaging and task conditions allowed for non-invasive examination of hemodynamic changes in somatosensory and motor cortices using natural, pneumatic stimulation of glabrous hand and hairy skin of the lower face and functionally relevant and measurable motor tasks involving the same structures.

Age- and sex-related changes in vibrotactile sensitivity of hand and face in neurotypical adults.

Sensory perception decreases with age, and is altered as a function of sex. Very little is known about the age- and sex-related changes in vibrotactile detection thresholds (VDTs) of the face relative to the glabrous hand. This study utilized a single-interval up/down (SIUD) adaptive procedure to estimate the VDT for mechanical stimuli presented at 5, 10, 50, 150, 250, and 300 Hz at two sites on the face, including the right non-glabrous surface of the oral angle and the right lower lip vermilion; and on the hand on the glabrous surface of the distal phalanx of the right dominant index finger. Eighteen right-handed healthy younger adults and 18 right-handed healthy older adults participated in this study. VDTs were significantly different between the three stimulus sites (p < 0.0001), and dependent on stimulus frequency (p < 0.0001) and the sex of the participants (p < 0.005). VDTs were significantly higher for older adults when compared to younger adults for the finger stimulation condition (p < 0.05). There were significant differences (p < 0.05) in cheek and lower lip VDTs between male and female subjects. Difference in the VDTs between the three stimulation sites is presumed to reflect the unique typing and distribution of mechanoreceptors in the face and hand. Age-related differences in finger skin sensitivity are likely due to changes in the physical structure of skin, changes in the number and morphology of the mechanoreceptors, differences in the functional use of the hand, and its central representation. Sex-related differences in the VDTs may be due to the differences in tissue conformation and thickness, mechanoreceptor densities, skin hydration, or temperature characteristics.

Modulation of EEG spectral edge frequency during patterned pneumatic oral stimulation in preterm infants.

BACKGROUND: Stimulation of the nervous system plays a central role in brain development and neurodevelopmental outcomes. Thalamocortical and corticocortical development is diminished in premature infants and correlated to electroencephalography (EEG) progression. The purpose of this study was to determine the effects of orocutaneous stimulation on the modulation of spectral edge frequency fc = 90% (SEF-90), which is derived from EEG recordings in preterm infants. METHODS: A total of 22 preterm infants were randomized to experimental and control conditions. Pulsed orocutaneous stimulation was presented during gavage feedings begun at ~32 wk postmenstrual age. The SEF-90 was derived from two-channel EEG recordings. RESULTS: Compared with the control condition, the pulsed orocutaneous stimulation produced a significant reorganization of SEF-90 in the left (P = 0.005) and right (P < 0.0001) hemispheres. Notably, the left and right hemispheres showed a reversal in the polarity of frequency shift, demonstrating hemispheric asymmetry in the frequency domain. Pulsed orocutaneous stimulation also produced a significant pattern of short-term cortical adaptation and a long-term neural adaptation manifested as a 0.5 Hz elevation in SEF-90 after repeated stimulation sessions. CONCLUSION: This is the first study to demonstrate the modulating effects of a servo-controlled oral somatosensory input on the spectral features of EEG activity in preterm infants.

Integrated approach for studying adaptation mechanisms in the human somatosensory cortical network.

Magnetoencephalography and independent component analysis (ICA) was utilized to study and characterize neural adaptation in the somatosensory cortical network. Repetitive punctate tactile stimuli were applied unilaterally to the dominant hand and face using a custom-built pneumatic stimulator called the TAC-Cell. ICA-based source estimation from the evoked neuromagnetic responses indicated cortical activity in the contralateral primary somatosensory cortex (SI) for face stimulation, while hand stimulation resulted in robust contralateral SI and posterior parietal cortex (PPC) activation. Activity was also observed in the secondary somatosensory cortical area (SII) with reduced amplitude and higher variability across subjects. There was a significant difference in adaptation rate between SI and higher-order somatosensory cortices for hand stimulation. Adaptation was significantly dependent on stimulus frequency and pulse index within the stimulus train for both hand and face stimulation. The peak latency of the activity was significantly dependent on stimulation site (hand vs. face) and cortical area (SI vs. PPC). The difference in the peak latency of activity in SI and PPC is presumed to reflect a hierarchical serial-processing mechanism in the somatosensory cortex.

Instrumental Assessment of Aero-Resistive Expiratory Muscle Strength Rehabilitation Devices.

PURPOSE: Expiratory muscle strength training (EMST) is increasingly being used to treat voice, cough, and swallowing deficits in a wide range of conditions. However, a multitude of aero-resistive EMST models are commercially available, and the absence of side-by-side comparative data interferes with clinicians' ability to assess which model is best suited to a particular client's needs. The primary aim of this research was to test and compare the pressure and flow parameters of six currently available EMST models to help inform clinical decision making. METHOD: We identified and tested five devices of each of six different EMST models to generate benchmark data for minimum trigger pressures across settings. The reliability was tested within each device and between five devices of the same model across settings using coefficient of variation. RESULTS: All six models required higher pressures to initiate flow at the highest setting compared to the lowest setting, as expected. Detailed descriptive statistics for each model/setting combination include average flow-triggering pressure for each model/setting and the variability across trials within a device and across devices of the same model. From these, ranked order of the least to most stable EMST model was derived. CONCLUSIONS: Systematic testing of several commercially available expiratory resistance training devices yielded clinical benchmarks and reliability data to aid clinicians in selecting an appropriate therapy device and regimen for a client based on their available airflow and air pressure as well as reliability of the device. These findings allow clinicians to directly compare key parameters across EMST devices.

Adaptive changes in the neuromagnetic response of the primary and association somatosensory areas following repetitive tactile hand stimulation in humans.

Cortical adaptation in the primary somatosensory cortex (SI) has been probed using different stimulation modalities and recording techniques, in both human and animal studies. In contrast, considerably less knowledge has been gained about the adaptation profiles in other areas of the cortical somatosensory network. Using magnetoencephalography (MEG), we examined the patterns of short-term adaptation for evoked responses in SI and somatosensory association areas during tactile stimulation applied to the glabrous skin of the hand. Cutaneous stimuli were delivered as trains of serial pulses with a constant frequency of 2 Hz and 4 Hz in separate runs, and a constant inter-train interval of 5 s. The unilateral stimuli elicited transient responses to the serial pulses in the train, with several response components that were separated by independent component analysis. Subsequent source reconstruction techniques identified regional generators in the contralateral SI and somatosensory association areas in the posterior parietal cortex (PPC). Activity in the bilateral secondary somatosensory cortex (i.e., SII/PV) was also identified, although less consistently across subjects. The dynamics of the evoked activity in each area and the frequency-dependent adaptation effects were assessed from the changes in the relative amplitude of serial responses in each train. We show that the adaptation profiles in SI and PPC areas can be quantitatively characterized from neuromagnetic recordings using tactile stimulation, with the sensitivity to repetitive stimulation increasing from SI to PPC. A similar approach for SII/PV has proven less straightforward, potentially due to the tendency of these areas to respond selectively to certain stimuli.

Spectral features of non-nutritive suck dynamics in extremely preterm infants.

Background: Non-nutritive suck (NNS) is used to promote ororhythmic patterning and assess oral feeding readiness in preterm infants in the neonatal intensive care unit (NICU). While time domain measures of NNS are available in real time at cribside, our understanding of suck pattern generation in the frequency domain is limited. The aim of this study is to model the development of NNS in the frequency domain using Fourier and machine learning (ML) techniques in extremely preterm infants (EPIs). Methods: A total of 117 EPIs were randomized to a pulsed or sham orocutaneous intervention during tube feedings 3 times/day for 4 weeks, beginning at 30 weeks post-menstrual age (PMA). Infants were assessed 3 times/week for NNS dynamics until they attained 100% oral feeding or NICU discharge. Digitized NNS signals were processed in the frequency domain using two transforms, including the Welch power spectral density (PSD) method, and the Yule-Walker PSD method. Data analysis proceeded in two stages. Stage 1: ML longitudinal cluster analysis was conducted to identify groups (classes) of infants, each showing a unique pattern of change in Welch and Yule-Walker calculations during the interventions. Stage 2: linear mixed modeling (LMM) was performed for the Welch and Yule-Walker dependent variables to examine the effects of gestationally-aged (GA), PMA, sex (male, female), patient type [respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD)], treatment (NTrainer, Sham), intervention phase [1, 2, 3], cluster class, and phase-by-class interaction. Results: ML of Welch PSD method and Yule-Walker PSD method measures revealed three membership classes of NNS growth patterns. The dependent measures peak_Hz, PSD amplitude, and area under the curve (AUC) are highly dependent on PMA, but show little relation to respiratory status (RDS, BPD) or somatosensory intervention. Thus, neural regulation of NNS in the frequency domain is significantly different for each identified cluster (classes A, B, C) during this developmental period. Conclusions: Efforts to increase our knowledge of the evolution of the suck central pattern generator (sCPG) in preterm infants, including NNS rhythmogenesis will help us better understand the observed phenotypes of NNS production in both the frequency and time domains. Knowledge of those features of the NNS which are relatively invariant vs. other features which are modifiable by experience will likewise inform more effective treatment strategies in this fragile population.

Pim-1 kinase protects mitochondrial integrity in cardiomyocytes.

RATIONALE: Cardioprotective signaling mediates antiapoptotic actions through multiple mechanisms including maintenance of mitochondrial integrity. Pim-1 kinase is an essential downstream effector of AKT-mediated cardioprotection but the mechanistic basis for maintenance of mitochondrial integrity by Pim-1 remains unexplored. This study details antiapoptotic actions responsible for enhanced cell survival in cardiomyocytes with elevated Pim-1 activity. OBJECTIVE: The purpose of this study is to demonstrate that the cardioprotective kinase Pim-1 acts to inhibit cell death by preserving mitochondrial integrity in cardiomyocytes. METHODS AND RESULTS: A combination of biochemical, molecular, and microscopic analyses demonstrate beneficial effects of Pim-1 on mitochondrial integrity. Pim-1 protein level increases in the mitochondrial fraction with a corresponding decrease in the cytosolic fraction of myocardial lysates from hearts subjected to 30 minutes of ischemia followed by 30 minutes of reperfusion. Cardiac-specific overexpression of Pim-1 results in higher levels of antiapoptotic Bcl-X(L) and Bcl-2 compared to samples from normal hearts. In response to oxidative stress challenge, Pim-1 preserves the inner mitochondrial membrane potential. Ultrastructure of the mitochondria is maintained by Pim-1 activity, which prevents swelling induced by calcium overload. Finally, mitochondria isolated from hearts created with cardiac-specific overexpression of Pim-1 show inhibition of cytochrome c release triggered by a truncated form of proapoptotic Bid. CONCLUSION: Cardioprotective action of Pim-1 kinase includes preservation of mitochondrial integrity during cardiomyopathic challenge conditions, thereby raising the potential for Pim-1 kinase activation as a therapeutic interventional approach to inhibit cell death by antagonizing proapoptotic Bcl-2 family members that regulate the intrinsic apoptotic pathway.

Modification of perioral stiffness in patients with repaired cleft lip and palate.

OBJECTIVE: To measure and compare the perioral stiffness among three groups of pediatric subjects: a group of patients with a repaired cleft lip (and palate) who had a secondary lip revision surgery (revision), another group of patients with repaired cleft lip (and palate) who did not have secondary surgery (nonrevision), and a group of noncleft "normal" patients (noncleft). DESIGN: A parallel, three-group, nonrandomized clinical trial. PARTICIPANTS: A total of 16 patients with repaired cleft lip/palate who did not have lip revision, 13 patients with repaired cleft lip/palate who had lip revision surgery and were tested at 18 to 24 months postsurgery, and 27 noncleft patients. ANALYSIS: Nonparticipatory perioral stiffness was sampled using a recently developed face-referenced measurement technology known as OroSTIFF. Perioral stiffness, derived as a quotient from resultant force and interangle lip span, was modeled with multilevel regression techniques. Real-time calculation of the perioral stiffness function demonstrated a significant quadratic relation between imposed interangle stretch and resultant force for each of the three groups. RESULTS: This nonlinear stiffness growth function was significantly elevated in the nonrevision patients compared with the noncleft controls and is likely due to the presence of scar tissue in the upper lip; it was significantly lower among patients with cleft lip/palate who completed lip revision surgery. CONCLUSION: This study demonstrates the efficacy of applying an objective measurement to map differences in perioral tissue biomechanics among patients born with orofacial clefts.

Dynamic causal modeling of sensorimotor networks elicited by saltatory pneumotactile velocity in the glabrous hand.

BACKGROUND AND PURPOSE: The effective connectivity of neuronal networks during passive saltatory pneumotactile velocity stimulation to the glabrous hand with different velocities is still unknown. The present study investigated the effectivity connectivity elicited by saltatory pneumotactile velocity arrays placed on the glabrous hand at three velocities (5, 25, and 65 cm/second). METHODS: Dynamic causal modeling (DCM) was used on functional MRI data sampled from 20 neurotypical adults. Five brain regions, including the left primary somatosensory (SI) and motor (M1) cortices, bilateral secondary somatosensory (SII) cortices, and right cerebellar lobule VI, were used to build model space. RESULTS: Three velocities (5, 25, and 65 cm/second) of saltatory pneumotactile stimuli were processed in both serial and parallel modes within the sensorimotor networks. The medium velocity of 25 cm/second modulated forward interhemispheric connection from the contralateral SII to the ipsilateral SII. Pneumotactile stimulation at the medium velocity of 25 cm/second also influenced contralateral M1 through contralateral SI. Finally, the right cerebellar lobule VI was involved in the sensorimotor networks. CONCLUSIONS: Our DCM results suggest the coexistence of both serial and parallel processing for saltatory pneumotactile velocity stimulation. Significant contralateral M1 modulation promotes the prospect that the passive saltatory pneumotactile velocity arrays can be used to design sensorimotor rehabilitation protocols to activate M1. The effective connectivity from the right cerebellar lobule VI to other cortical regions demonstrates the cerebellum's role in the sensorimotor networks through feedforward and feedback neuronal pathways.

'Relieved to be seen'-patient and carer experiences of psychosocial assessment in the emergency department following self-harm: qualitative analysis of 102 free-text survey responses.

OBJECTIVES: We sought to explore patient and carer experiences of psychosocial assessments following presentations to hospital after self-harm. DESIGN: Thematic analysis of free-text responses to an open-ended online survey. SETTING: Between March and November 2019, we recruited 88 patients (82% women) and 14 carers aged ≥18 years from 16 English mental health trusts, community organisations, and via social media. RESULTS: Psychosocial assessments were experienced as helpful on some occasions but harmful on others. Participants felt better, less suicidal and less likely to repeat self-harm after good-quality compassionate and supportive assessments. However, negative experiences during the assessment pathway were common and, in some cases, contributed to greater distress, less engagement and further self-harm. Participants reported receiving negative and stigmatising comments about their injuries. Others reported that they were refused medical care or an anaesthetic. Stigmatising attitudes among some mental health staff centred on preconceived ideas over self-harm as a 'behavioural issue', inappropriate use of services and psychiatric diagnosis. CONCLUSION: Our findings highlight important patient experiences that can inform service provision and they demonstrate the value of involving patients/carers throughout the research process. Psychosocial assessments can be beneficial when empathetic and collaborative but less helpful when overly standardised, lacking in compassion and waiting times are unduly long. Patient views are essential to inform practice, particularly given the rapidly changing service context during and after the COVID-19 emergency.

Oral-diadochokinetic rates among healthy Malaysian-Mandarin speakers: A cross linguistic comparison.

PURPOSE: This study examined the effects of non-word versus real word, age, and gender on oral-DDK rates among healthy Malaysian-Mandarin speakers. Comparison between non-word of Malaysian-Mandarin and Hebrew speakers was examined. METHOD: One-hundred and seventeen speakers (18-83 years old, 46% men) were audio-recorded while performing non-word (repetition of "pataka") and real-word oral-DDK tasks ("butter cake" and " ([pha4tha1khan4])"). The number of syllables produced in 8 seconds was counted from the audio recording to derive the oral-DDK rates. A MANOVA was conducted to compare the rates between age groups (young = 18-40 years, n = 56; middle = 41-60 years, n = 39; older = 61-83 years, n = 22) and gender. In a second analysis, "pataka" results were compared between this study and previous findings with Hebrew speakers. RESULT: No gender effects were found. However, rates significantly decreased with age (p < 0.001). Repetition of real words was faster than that of non-words - English words (5.55 ± 1.19 syllables/s) > non-words (5.29 ± 1.23) > Mandarin words (4.91 ± 1.13). Malaysian-Mandarin speakers performed slower than Hebrew speakers on "pataka" task. CONCLUSION: Aging has a large impact on oromotor functions, indicating that speech-language pathologists should consider using age-adjusted norms.

Cutaneous stimulation of the digits and lips evokes responses with different adaptation patterns in primary somatosensory cortex.

Neuromagnetic evoked fields were recorded to compare the adaptation of the primary somatosensory cortex (SI) response to tactile stimuli delivered to the glabrous skin at the fingertips of the first three digits (condition 1) and between midline upper and lower lips (condition 2). The stimulation paradigm allowed to characterize the response adaptation in the presence of functional integration of tactile stimuli from adjacent skin areas in each condition. At each stimulation site, cutaneous stimuli (50 ms duration) were delivered in three runs, using trains of 6 pulses with regular stimulus onset asynchrony (SOA). The pulses were separated by SOAs of 500 ms, 250 ms or 125 ms in each run, respectively, while the inter-train interval was fixed (5s) across runs. The evoked activity in SI (contralateral to the stimulated hand, and bilaterally for lips stimulation) was characterized from the best-fit dipoles of the response component peaking around 70 ms for the hand stimulation, and 8 ms earlier (on average) for the lips stimulation. The SOA-dependent long-term adaptation effects were assessed from the change in the amplitude of the responses to the first stimulus in each train. The short-term adaptation was characterized by the lifetime of an exponentially saturating model function fitted to the set of suppression ratios of the second relative to the first SI response in each train. Our results indicate: 1) the presence of a rate-dependent long-term adaptation effect induced only by the tactile stimulation of the digits; and 2) shorter recovery lifetimes for the digits compared with the lips stimulation.