Auditory-Perceptual Features of Speech in Children and Adults With Down Syndrome: A Speech Profile Analysis.

Purpose The aim of this study was to determine how the speech disorder profiles in Down syndrome (DS) relate to reduced intelligibility, atypical overall quality, and impairments in the subsystems of speech production (phonation, articulation, resonance, and prosody). Method Auditory-perceptual ratings of intelligibility, overall quality, and features associated with the subsystems of speech production were obtained from recordings of 79 children and adults with DS. Ratings were made for sustained vowels (62 of 79 speakers) and short sentences (79 speakers). The data were analyzed to determine the severity of the affected features in each speaking task and to detect patterns in the group data by means of principal components analysis. Results Reduced intelligibility was noted in 90% of the speakers, and atypical overall speech quality was noted in 100%. Affected speech features were distributed across the speech production subsystems. Principal components analysis revealed four components each for the vowel and sentence tasks, showing that individuals with DS are not homogeneous in the features of their speech disorder. Discussion The speech disorder in DS is complex in its perceptual features and reflects impairments across the subsystems of speech production, but the pattern is not uniform across individuals, indicating that attention must be given to individual variation in designing treatments.

Estimates of the prevalence of speech and motor speech disorders in adolescents with Down syndrome.

Although there is substantial rationale for a motor component in the speech of persons with Down syndrome (DS), there presently are no published estimates of the prevalence of subtypes of motor speech disorders in DS. The goal of this research is to provide initial estimates of the prevalence of types of speech disorders and motor speech disorders in adolescents with DS. Conversational speech samples from a convenience sample of 45 adolescents with DS, ages 10 to 20 years old, were analysed using perceptual and acoustic methods and measures in the Speech Disorders Classification System (SDCS). The SDCS cross-classified participants into five mutually exclusive speech classifications and five mutually exclusive motor speech classifications. For participants meeting criteria for Childhood Dysarthria or for Childhood Dysarthria concurrent with Childhood Apraxia of Speech, the SDCS provided information on participants' percentile status on five subtypes of dysarthria. A total of 97.8% of participants met SDCS criteria for Speech Disorders and 97.8% met criteria for Motor Speech Disorders, including Childhood Dysarthria (37.8%), Speech Motor Delay (26.7%), Childhood Dysarthria and Childhood Apraxia of Speech (22.2%), and Childhood Apraxia of Speech (11.1%). Ataxia was the most prevalent dysarthria subtype. Nearly all participants with DS in the present sample had some type of speech and motor speech disorder, with implications for theory, assessment, prediction, and treatment. Specific to treatment, the present findings are interpreted as support for motor speech disorders as a primary explanatory construct to guide the selection and sequencing of treatment targets for persons with DS. Abbreviations: CAS: Childhood Apraxia of Speech; CD: Childhood Dysarthria; DS: Down syndrome; NSA: Normal(ized) Speech Acquisition; PSD: Persistent Speech Delay; PSE: Persistent Speech Errors; SD: Speech Delay; SDCS: Speech Disorders Classification System; SE: Speech Errors; SMD: Speech Motor Delay.

Speech and motor speech disorders and intelligibility in adolescents with Down syndrome.

The goal of this research was to assess the support for motor speech disorders as explanatory constructs to guide research and treatment of reduced intelligibility in persons with Down syndrome (DS). Participants were the 45 adolescents with DS in the prior paper who were classified into five mutually-exclusive motor speech classifications using the Speech Disorders Classification System. An ordinal index classified participants' percentage of intelligible words in conversation as High (≥ 85%), Moderate (80% - 84.9%), or Low (< 80%). Statistical analyses tested for significant differences in intelligibility status associated with demographic, intelligence, and language variables, and intelligibility status associated with motor speech classifications and speech, prosody, and voice variables. For the 10 participants who met criteria for concurrent Childhood Dysarthria and Childhood Apraxia of Speech at assessment, 80% had reduced (Moderate or Low) intelligibility and 20% had High intelligibility (significant effect size: 0.644). Proportionally more of the 32 participants who met criteria for either dysarthria or apraxia had reduced intelligibility (significant effect size: 0.318). Low intelligibility was significantly associated with across-the-board reductions in phonemic and phonetic accuracy and with inappropriate prosody and voice. Findings are interpreted as support for motor speech disorders in adolescents with DS as explanatory constructs for their reduced intelligibility. Pending cross-validation of findings in diverse samples of persons with DS, studies are needed to assess the efficacy of motor speech classification status to guide selection of treatment methods and intelligibility targets. Abbreviations: CAS: Childhood Apraxia of Speech; CD: Childhood Dysarthria; DS: Down syndrome; II: Intelligibility Index; No MSD: No Motor Speech Disorder; OII: Ordinal Intelligibility Index; PSD: Persistent Speech Delay; SDCS: Speech Disorders Classification System; SMD: Speech Motor Delay.

Detecting Bulbar Motor Involvement in ALS: Comparing speech and chewing tasks.

Purpose: To compare two different tasks and kinematic measures in terms of their ability to detect Amyotrophic lateral sclerosis (ALS) and differences in ALS severity in order to establish potential candidate markers of bulbar decline.Method: We tracked jaw kinematics during speech and chewing to determine which is more affected by bulbar motor deterioration, based on measures of maximum speed and articulatory working space. Data were collected from 31 individuals diagnosed with ALS and 17 neurologically intact controls.Result: (1) Both sentence and chewing tasks were effective in distinguishing between the groups of individuals with ALS and controls, (2) jaw maximum speed for both chewing and speech was a more sensitive marker for bulbar dysfunction than articulatory working space, (3) the sentence task distinguished between ALS subgroups stratified by severity and (4) distinct jaw kinematic differences existed between chewing and sentence tasks. More specifically, movement speed for speech decreased with severity while movement speed for chewing increased with disease severity.Conclusion: The findings from the current investigation suggest that measures of jaw movement speed during chewing and sentence tasks are affected by bulbar deterioration, and jaw speed during a sentence task may serve as a candidate marker of bulbar disease onset and severity.

Formulation of High-Performance Dry Powder Aerosols for Pulmonary Protein Delivery.

PURPOSE: Pulmonary delivery of biologics is of great interest, as it can be used for the local treatment of respiratory diseases or as a route to systemic drug delivery. To reach the full potential of inhaled biologics, a formulation platform capable of producing high performance aerosols without altering protein native structure is required. METHODS: A formulation strategy using Particle Replication in Non-wetting Templates (PRINT) was developed to produce protein dry powders with precisely engineered particle morphology. Stability of the incorporated proteins was characterized and the aerosol properties of the protein dry powders was evaluated in vitro with an Andersen Cascade Impactor (ACI). RESULTS: Model proteins bovine serum albumin (BSA) and lysozyme were micromolded into 1 µm cylinders composed of more than 80% protein, by mass. Extensive characterization of the incorporated proteins found no evidence of alteration of native structures. The BSA formulation produced a mass median aerodynamic diameter (MMAD) of 1.77 µm ± 0.06 and a geometric standard deviation (GSD) of 1.51 ± 0.06 while the lysozyme formulation had an MMAD of 1.83 µm ± 0.12 and a GSD of 1.44 ± 0.03. CONCLUSION: Protein dry powders manufactured with PRINT could enable high-performance delivery of protein therapeutics to the lungs.

Spatial Characteristics of Jaw Movements During Chewing in Children with Cerebral Palsy: A Pilot Study.

This study compared jaw motion between children with cerebral palsy (CP) and their typically-developing (TD) peers during chewing. The jaw movements of 11 children with spastic CP (GMFCS levels II-V) all of whom were exclusively oral feeders with no reported clinical issues with feeding [mean age = 7.49 (2.30) years; 7 males, 4 females] and 11 age- and sex-matched TD peers [mean age = 7.54 (2.35) years] were recorded using optical motion capture. Participants chewed five trials of three different consistencies, including puree, mechanical soft, and solid. For each chewing sequence, the path distance (total amount of distance traveled by the jaw), average jaw speed, and working space (total 3-dimensional size of the jaw movements during chewing) were calculated. The CP group had greater path distances for mechanical soft and solids (p < 0.001) and larger working spaces (p < 0.001) than the TD group. Consistency differences were also found with path distances increasing for both groups with increased bolus consistency (p < 0.001). Puree was chewed most slowly for both groups (p = 0.05) and was associated with smaller working space than the other consistencies for both groups (p < 0.001). The TD group demonstrated slower speeds for mechanical soft as compared to solids (p = 0.05), a finding which was not observed in the CP group. The results suggest children with CP showed jaw movement differences during chewing despite being exclusive oral eaters with no reports of clinical feeding or deglutition disorders. Food consistency also influenced jaw movements in both children with CP and their TD peers.

Advancement in Texture in Early Complementary Feeding and the Relevance to Developmental Outcomes.

A child's transition to independent eating is a protracted process that progresses over the course of many years. Although major health agencies, such as the World Health Organization, now offer clear guidance when to begin introducing solids, advice about how to safely transition to progressively challenging foods is varied and comes from a staggering number of sources. The resulting conflicting views have promoted parental confusion and anxiety about what foods are appropriate and when to advance to new textures. Efforts to develop science-based recommendations for complementary feeding include research on the development of chewing motor skills. Chewing development is an essential aspect of feeding readiness that is often overlooked by agencies developing recommendations for complementary feeding, and little is known about the development of chewing motor skills and how children learn to accommodate foods with varying textures. Such information is essential for designing developmentally appropriate foods, minimizing food aversions, providing caregivers science-based guidance regarding the safety and appropriateness of new foods, and identifying children at risk for choking or feeding impairments.

Zwitterionic chitosan for the systemic treatment of sepsis.

Severe sepsis and septic shock are life-threatening conditions, with Gram-negative organisms responsible for most sepsis mortality. Systemic administration of compounds that block the action of lipopolysaccharide (LPS), a constituent of the Gram-negative outer cell membrane, is hampered by their hydrophobicity and cationic charge, the very properties responsible for their interactions with LPS. We hypothesize that a chitosan derivative zwitterionic chitosan (ZWC), previously shown to suppress the production of pro-inflammatory cellular mediators in LPS-challenged macrophages, will have protective effects in an animal model of sepsis induced by systemic injection of LPS. In this study, we evaluate whether ZWC attenuates the fatal effect of LPS in C57BL/6 mice and investigate the mechanism by which ZWC counteracts the LPS effect using a PMJ2-PC peritoneal macrophage cell line. Unlike its parent compound with low water solubility, intraperitoneally administered ZWC is readily absorbed with no local residue or adverse tissue reaction at the injection site. Whether administered at or prior to the LPS challenge, ZWC more than doubles the animals' median survival time. ZWC appears to protect the LPS-challenged organisms by forming a complex with LPS and thus attenuating pro-inflammatory signaling pathways. These findings suggest that ZWC have utility as a systemic anti-LPS agent.

Pulmonary Delivery of Butyrylcholinesterase as a Model Protein to the Lung.

Pulmonary delivery has great potential for delivering biologics to the lung if the challenges of maintaining activity, stability, and ideal aerosol characteristics can be overcome. To study the interactions of a biologic in the lung, we chose butyrylcholinesterase (BuChE) as our model enzyme, which has application for use as a bioscavenger protecting against organophosphate exposure or for use with pseudocholinesterase deficient patients. In mice, orotracheal administration of free BuChE resulted in 72 h detection in the lungs and 48 h in the broncheoalveolar lavage fluid (BALF). Free BuChE administered to the lung of all mouse backgrounds (Nude, C57BL/6, and BALB/c) showed evidence of an acute cytokine (IL-6, TNF-α, MIP2, and KC) and cellular immune response that subsided within 48 h, indicating relatively safe administration of this non-native biologic. We then developed a formulation of BuChE using Particle Replication in Non-Wetting Templates (PRINT). Aerosol characterization demonstrated biologically active BuChE 1 µm cylindrical particles with a mass median aerodynamic diameter of 2.77 µm, indicative of promising airway deposition via dry powder inhalers (DPI). Furthermore, particulate BuChE delivered via dry powder insufflation showed residence time of 48 h in the lungs and BALF. The in vivo residence time, immune response, and safety of particulate BuChE delivered via a pulmonary route, along with the cascade impaction distribution of dry powder PRINT BuChE, showed promise in the ability to deliver active enzymes with ideal deposition characteristics. These findings provide evidence for the feasibility of optimizing the use of BuChE in the clinic; PRINT BuChE particles can be readily formulated for use in DPIs, providing a convenient and effective treatment option.

Validation of Clinical Observations of Mastication in Persons with ALS.

Amyotrophic lateral sclerosis (ALS) is a progressive neurological disease that can result in difficulties with mastication leading to malnutrition, choking or aspiration, and reduced quality of life. When evaluating mastication, clinicians primarily observe spatial and temporal aspects of jaw motion. The reliability and validity of clinical observations for detecting jaw movement abnormalities is unknown. The purpose of this study is to determine the reliability and validity of clinician-based ratings of chewing performance in neuro-typical controls and persons with varying degrees of chewing impairments due to ALS. Adults chewed a solid food consistency while full-face video were recorded along with jaw kinematic data using a 3D optical motion capture system. Five experienced speech-language pathologists watched the videos and rated the spatial and temporal aspects of chewing performance. The jaw kinematic data served as the gold-standard for validating the clinicians' ratings. Results showed that the clinician-based rating of temporal aspects of chewing performance had strong inter-rater reliability and correlated well with comparable kinematic measures. In contrast, the reliability of rating the spatial and spatiotemporal aspects of chewing (i.e., range of motion of the jaw, consistency of the chewing pattern) was mixed. Specifically, ratings of range of motion were at best only moderately reliable. Ratings of chewing movement consistency were reliable but only weakly correlated with comparable measures of jaw kinematics. These findings suggest that clinician ratings of temporal aspects of chewing are appropriate for clinical use, whereas ratings of the spatial and spatiotemporal aspects of chewing may not be reliable or valid.

Intraperitoneal delivery of platinum with in-situ crosslinkable hyaluronic acid gel for local therapy of ovarian cancer.

Intraperitoneal (IP) chemotherapy is a promising post-surgical therapy of solid carcinomas confined within the peritoneal cavity, with potential benefits in locoregional and systemic management of residual tumors. In this study, we intended to increase local retention of platinum in the peritoneal cavity over a prolonged period of time using a nanoparticle form of platinum and an in-situ crosslinkable hyaluronic acid gel. Hyaluronic acid was chosen as a carrier due to the biocompatibility and biodegradability. We confirmed a sustained release of platinum from the nanoparticles (PtNPs) and nanoparticle/gel hybrid (PtNP/gel), receptor-mediated endocytosis of PtNPs, and retention of the gel in the peritoneal cavity over 4 weeks: conditions desirable for a prolonged local delivery of platinum. However, PtNPs and PtNP/gel did not show a greater anti-tumor efficacy than CDDP solution administered at the same dose but rather caused a slight increase in tumor burdens at later time points, which suggests a potential involvement of empty carriers and degradation products in the growth of residual tumors. This study alerts that although several materials considered biocompatible and safe are used as drug carriers, they may have unwanted biological effects on the residual targets once the drug is exhausted; therefore, more attention should be paid to the selection of drug carriers.

Dual-layer surface coating of PLGA-based nanoparticles provides slow-release drug delivery to achieve metronomic therapy in a paclitaxel-resistant murine ovarian cancer model.

Development of drug resistance is a central challenge to the treatment of ovarian cancer. Metronomic chemotherapy decreases the extent of drug-free periods, thereby hindering development of drug resistance. Intraperitoneal chemotherapy allows for treatment of tumors confined within the peritoneum, but achieving sustained tumor-localized chemotherapy remains difficult. We hypothesized that modulating the surface properties of poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles could enhance their drug retention ability and extend their release profile, thereby enabling metronomic, localized chemotherapy in vivo. Paclitaxel was encapsulated in particles coated with a layer of polydopamine and a subsequent layer of poly(ethylene glycol) (PEG). These particles achieved a 3.8-fold higher loading content compared to that of nanoparticles formulated from linear PLGA-PEG copolymers. In vitro release kinetic studies and in vivo drug distribution profiles demonstrate sustained release of paclitaxel. Although free drug conferred no survival advantage, low-dose intraperitoneal administration of paclitaxel-laden surface-coated nanoparticles to drug-resistant ovarian tumor-bearing mice resulted in significant survival benefits in the absence of any apparent systemic toxicity.

Stabilization of a hyaluronate-associated gene delivery system using calcium ions.

A "DPH" ternary complex consisting of plasmid DNA (pDNA), intracellularly degradable polyethyleneimine, and hyaluronic acid (HA) is a promising non-viral gene carrier with low toxicity and good gene transfection efficiency. HA plays a key role in providing an optimal balance between DNA protection and release, but it causes aggregation due to the entanglement of HA chains of neighbouring DPH particles. Here we report that the addition of an optimal level of Ca2+ successfully prevents particle aggregation and maintains a relatively small size. The Ca-stabilized DPH is comparable to DPH in cytotoxicity and gene transfection efficiency. MW monitoring and conductometric titration suggest that such size stabilization effect is partly mediated by the complexation between HA and Ca2+, which enables intra- and intermolecular interactions of HAs.

A kinematic description of the temporal characteristics of jaw motion for early chewing: preliminary findings.

PURPOSE: The purpose of this investigation was to describe age- and consistency-related changes in the temporal characteristics of chewing in typically developing children between the ages of 4 and 35 months and adults using high-resolution optically based motion capture technology. METHOD: Data were collected from 60 participants (48 children, 12 adults) across 5 age ranges (beginners, 7 months, 12 months, 35 months, and adults); each age group included 12 participants. Three different food consistencies were trialed as appropriate. The data were analyzed to assess changes in chewing rate, chewing sequence duration, and estimated number of chewing cycles. RESULTS: The results revealed both age- and consistency-related changes in chewing rate, sequence duration, and estimated number of chewing cycles, with consistency differences affecting masticatory timing in children as young as 7 months of age. Chewing rate varied as a function of age and consistency, and chewing sequence duration was shorter for adults than for children regardless of consistency type. In addition, the results from the estimated number of chewing cycles measure suggest that chewing effectiveness increased with age; this measure was also dependent on consistency type. CONCLUSIONS: The findings suggest that the different temporal chewing variables follow distinct developmental trajectories and are consistency dependent in children as young as 7 months of age. Clinical implications are detailed.

Lip movement exaggerations during infant-directed speech.

PURPOSE: Although a growing body of literature has identified the positive effects of visual speech on speech and language learning, oral movements of infant-directed speech (IDS) have rarely been studied. This investigation used 3-dimensional motion capture technology to describe how mothers modify their lip movements when talking to their infants. METHOD: Lip movements were recorded from 25 mothers as they spoke to their infants and other adults. Lip shapes were analyzed for differences across speaking conditions. The maximum fundamental frequency, duration, acoustic intensity, and first and second formant frequency of each vowel also were measured. RESULTS: Lip movements were significantly larger during IDS than during adult-directed speech, although the exaggerations were vowel specific. All of the vowels produced during IDS were characterized by an elevated vocal pitch and a slowed speaking rate when compared with vowels produced during adult-directed speech. CONCLUSION: The pattern of lip-shape exaggerations did not provide support for the hypothesis that mothers produce exemplar visual models of vowels during IDS. Future work is required to determine whether the observed increases in vertical lip aperture engender visual and acoustic enhancements that facilitate the early learning of speech.

Evaluation and management of vocal cord dysfunction in the athlete.

Vocal cord dysfunction (VCD) is defined by paradoxical vocal fold closure during inhalation, and rarely upon exhalation. The precise etiology of VCD is unknown; however, a variety of potential causes may include laryngeal hyperresponsiveness, laryngeal irritants, psychogenic causes, and rarely neurologic diseases. VCD can occur in athletes, particularly females, and the sports medicine professional likely is to care for patients with acute respiratory difficulties caused by this condition. Given its complex nature, a multidisciplinary approach to VCD evaluation and management is necessary and results in optimal outcomes.

The development of jaw motion for mastication.

The developmental course of early chewing has rarely been studied, although such knowledge is essential for understanding childhood feeding and swallowing disorders. The goal of this investigation was to quantitatively describe age- and consistency-related changes in jaw kinematics during early chewing development. An optical-motion tracking system was used to record jaw movements during chewing in 3-dimensions in 11 typically-developing participants longitudinally from 9-30 months of age. Age related changes in jaw movement were described for both puree and regular consistencies. The findings demonstrated that the development of rotary jaw motion, jaw motion speed, and management of consistency upgrades are protracted across the first two years of life. Young children did not differentiate their jaw closing speeds for puree and regular consistencies until 18-24 months of age, at which age the speed of movement was significantly slower for the puree than for the regular consistency. Horizontal jaw closing speed decreased significantly with age for the puree consistency, but not for the regular consistency. The emergence of a rotary chew pattern was not observed at the ages studied.

Early Feeding Abilities in Children with Cerebral Palsy: A Parental Report Study.

PURPOSE: The goals of this study were to 1) describe the feeding skills of young children with cerebral palsy (CP); and 2) elucidate the type and severity of feeding problems for children with and without oral-motor involvement. METHOD: Parents of 37 children (16 females, 21 males) with CP, who ranged in age from 11-58 months (mean age = 41 months), completed questionnaires regarding their child's past and current feeding abilities. Children were also clinically evaluated to determine whether each had evidence of oral-motor involvement. RESULTS: Children with CP and oral-motor involvement had significantly more difficulty with self-feeding, increased frequency of coughing and choking, increased prevalence of swallowing evaluation and feeding therapy, and were introduced to solid food at a later age relative to children with CP who did not have oral-motor involvement. Both groups of children were similar in their history of tube feeding, bottle feeding, difficulty with solid foods, use of adaptive equipment, duration of mealtimes, and presence of choking, coughing, and gagging. CONCLUSIONS: Children with and without oral-motor involvement initially presented with similar feeding difficulties. However, feeding problems appeared to resolve to a greater extent in children without oral-motor involvement. The difficulties identified early in life, for children with oral-motor involvement, appeared to persist with development.

Task specificity in early oral motor development.

This article addresses a long-standing clinical and theoretical debate regarding the potential relationship between speech and nonspeech behaviors in the developing system. The review is motivated by the high popularity of nonspeech oral motor exercises (NSOMEs), including alimentary behaviors such as chewing, in the treatment of speech disorders in young children. The similarities and differences in the behavioral characteristics, sensory requirements, and task goals for speech and nonspeech oromotor behaviors are compared. Integrated theoretical paradigms and empirical data on the development of early oromotor behaviors are discussed. Although the efficacy of NSOMEs remains empirically untested at this time, studies of typical developmental speech physiology fail to support a theoretical framework promoting the use of NSOMEs. Well-designed empirical studies are necessary, however, to establish the efficacy of NSOMEs for specific clinical population and treatment targets.

Estimating mandibular motion based on chin surface targets during speech.

PURPOSE: The movement of the jaw during speech and chewing has frequently been studied by tracking surface landmarks on the chin. However, the extent to which chin motions accurately represent those of the underlying mandible remains in question. In this investigation, the movements of a pellet attached to the incisor of the mandible were compared with those of pellets attached to different regions of the chin. METHOD: Ten healthy talkers served as participants. Three speaking contexts were recorded from each participant: word, sentence, and paragraph. Chin position errors were estimated by computing the standard distance between the mandibular incisor pellet and the chin pellets. RESULTS: Relative to the underlying mandible, chin pellets moved with an average absolute and relative error of 0.81 mm and 7.30%, respectively. The movements of chin and mandibular pellets were tightly coupled in time. CONCLUSION: The chin tracking errors observed in this investigation are considered acceptable for descriptive studies of oromotor behavior, particularly in situations where mandibular placements are not practical (e.g., young children or edentulous adults). The observed amount of error, however, may not be tolerable for fine-grained analyses of mandibular biomechanics. Several guidelines are provided for minimizing error associated with tracking surface landmarks on the chin.