Far-infrared Radiation Improves Motor Dysfunction and Neuropathology in Spinocerebellar Ataxia Type 3 Mice.

Spinocerebellar ataxia type 3 (SCA3) is a polyglutamine neurodegenerative disease resulting from the misfolding and accumulation of a pathogenic protein, causing cerebellar dysfunction, and this disease currently has no effective treatments. Far-infrared radiation (FIR) has been found to protect the viability of SCA3 cells by preventing mutant ataxin-3 protein aggregation and promoting autophagy. However, this possible treatment still lacks in vivo evidence. This study assessed the effect of FIR therapy on SCA3 in vivo by using a mouse model over 28 weeks. Control mice carried a healthy wild-type ATXN3 allele that had a polyglutamine tract with 15 CAG repeats (15Q), whereas SCA3 transgenic mice possessed an allele with a pathological polyglutamine tract with expanded 84 CAG (84Q) repeats. The results showed that the 84Q SCA3 mice displayed impaired motor coordination, balance abilities, and gait performance, along with the associated loss of Purkinje cells in the cerebellum, compared with the normal 15Q controls; nevertheless, FIR treatment was sufficient to prevent those defects. FIR significantly improved performance in terms of maximal contact area, stride length, and base support in the forepaws, hindpaws, or both. Moreover, FIR treatment supported the survival of Purkinje cells in the cerebellum and promoted the autophagy, as reflected by the induction of autophagic markers, LC3II and Beclin-1, concomitant with the reduction of p62 and ataxin-3 accumulation in cerebellar Purkinje cells, which might partially contribute to the rescue mechanism. In summary, our results reveal that FIR confers therapeutic effects in an SCA3 transgenic animal model and therefore has considerable potential for future clinical use.

Spontaneous spinal epidural hemorrhage from intense piano playing.

Spontaneous spinal epidural hematoma (SSEH) is a rare but real neurosurgical emergency. It is caused by atraumatic rupture of the vertebral epidural vein that results in nerve root or spinal cord compression. Most cases of SSEH have a multifactorial etiology, including congenital and acquired coagulopathies; platelet dysfunction; vascular malformation; tumors; uncontrolled hypertension; pregnancy; and, very rarely, activities requiring Valsalva. Herein we reported the case of a young pianist who was attacked by SSEH during piano practice. Playing the piano is a joyful, relaxing entertainment; however, this musical activity can be a highly demanding physical and mental exercise for pianists. Emotional and expressive performance, especially in professional performing, has been reported to result in significant increase of sympathetic and decrease of parasympathetic activities and thus influence the cardiorespiratory variables. The increased biomechanical stress from fluctuating hemodynamics was thought to trigger the rupture of her spinal arteriovenous malformation.

ClinOleic Impairs ROS Production and Phagocytosis in M1 Macrophages Without Affecting M1 Differentiation.

Lipid emulsions are the primary source of calories and fatty acids that are used to provide essential energy and nutrients to patients suffering from severe intestinal failure and critical illness. However, their use has been linked to adverse effects on patient outcomes, notably affecting immune defenses and inflammatory responses. ClinOleic is a lipid emulsion containing a mixture of olive oil and soybean oil (80:20). The effect of ClinOleic on the differentiation of M1 macrophages remains unclear. In this study, we isolated human monocytes and added ClinOleic to differentiation culture media to investigate whether it affects monocyte polarization into M1 macrophages and macrophage functions, such as reactive oxygen species (ROS) production and phagocytosis. ROS production was stimulated by live S. aureus and detected with L-012, a chemiluminescence emission agent. Phagocytic capacity was assayed using pHrodo™ Green S. aureus Bioparticles® Conjugate. We found that M1 cell morphology, surface markers (CD80 and CD86), and M1-associated cytokines (TNF-α and IL-6) did not significantly change upon incubation with ClinOleic during M1 polarization. However, S. aureus-triggered ROS production was significantly lower in M1 macrophages differentiated with ClinOleic than in those not treated with ClinOleic. The inhibitory effect of ClinOleic on macrophage function also appeared in the phagocytosis assay. Taken together, these findings reveal that ClinOleic has a limited impact on the M1 differentiation phenotype but obviously reduces ROS production and phagocytosis.

Formoterol Acting via ß2-Adrenoreceptor Restores Mitochondrial Dysfunction Caused by Parkinson's Disease-Related UQCRC1 Mutation and Improves Mitochondrial Homeostasis Including Dynamic and Transport.

Formoterol, a ß2-adrenergic receptor (ß2AR) agonist, shows promise in various diseases, but its effectiveness in Parkinson's disease (PD) is debated, with unclear regulation of mitochondrial homeostasis. This study employed a cell model featuring mitochondrial ubiquinol-cytochrome c reductase core protein 1 (UQCRC1) variants associated with familial parkinsonism, demonstrating mitochondrial dysfunction and dynamic imbalance, exploring the therapeutic effects and underlying mechanisms of formoterol. Results revealed that 24-h formoterol treatment enhanced cell proliferation, viability, and neuroprotection against oxidative stress. Mitochondrial function, encompassing DNA copy number, repatriation, and complex III-linked respiration, was comprehensively restored, along with the dynamic rebalance of fusion/fission events. Formoterol reduced extensive hypertubulation, in contrast to mitophagy, by significantly upregulating protein Drp-1, in contrast to fusion protein Mfn2, mitophagy-related protein Parkin. The upstream mechanism involved the restoration of ERK signaling and the inhibition of Akt overactivity, contingent on the activation of ß2-adrenergic receptors. Formoterol additionally aided in segregating healthy mitochondria for distribution and transport, therefore normalizing mitochondrial arrangement in mutant cells. This study provides preliminary evidence that formoterol offers neuroprotection, acting as a mitochondrial dynamic balance regulator, making it a promising therapeutic candidate for PD.

Anti-Inflammatory and Anti-Oxidative Effects of Polysaccharides Extracted from Unripe Carica papaya L. Fruit.

This study evaluated the antioxidative and anti-inflammatory activities of polysaccharides extracted from unripe Carica papaya L. (papaya) fruit. Three papaya polysaccharide (PP) fractions, namely PP-1, PP-2, and PP-3, with molecular weights of 2252, 2448, and 3741 kDa, containing abundant xylose, galacturonic acid, and mannose constituents, respectively, were obtained using diethylaminoethyl-Sepharose™ anion exchange chromatography. The antioxidant capacity of the PPs, hydroxyl radical scavenging assay, ferrous ion-chelating assay, and reducing power assay revealed that the PP-3 fraction had the highest antioxidant activity, with an EC50 (the concentration for 50% of the maximal effect) of 0.96 mg/mL, EC50 of 0.10 mg/mL, and Abs700 nm of 1.581 for the hydroxyl radical scavenging assay, ferrous ion-chelating assay, and reducing power assay, respectively. In addition, PP-3 significantly decreased reactive oxygen species production by 45.3%, NF-κB activation by 32.0%, and tumor necrosis factor-alpha and interleukin-6 generation by 33.5% and 34.4%, respectively, in H2O2-induced human epidermal keratinocytes. PP-3 exerts potent antioxidative and anti-inflammatory effects; thus, it is a potential biofunctional ingredient in the cosmetic industry.

Amount and focus of physical therapy and occupational therapy for young children with cerebral palsy.

The aims of this study were to describe physical therapy (PT) and occupational therapy (OT) services for a cohort of 399 children with cerebral palsy (CP), 2-6 years old, residing in the United States and Canada. Parents completed a services questionnaire by telephone interview. Therapists classified children's Gross Motor Function Classification System (GMFCS) level. Mean minutes per month of PT and OT were greater for children receiving services in both an educational and clinic setting. Mean minutes per month of PT and OT were greater for children in levels IV-V than children in level I and greater for children in the United States than children in Canada. Parents reported that interventions focused a moderate to great extent on primary impairments, secondary impairments, activity, and structured play activities, a moderate extent on environmental modifications and equipment; and a moderate to small extent on self-care routines. The results support the importance of coordination of PT and OT services.

High BRCA1 gene expression increases the risk of early distant metastasis in ER+ breast cancers.

Although the function of the BRCA1 gene has been extensively studied, the relationship between BRCA1 gene expression and tumor aggressiveness remains controversial in sporadic breast cancers. Because the BRCA1 protein is known to regulate estrogen signaling, we selected microarray data of ER+ breast cancers from the GEO public repository to resolve previous conflicting findings. The BRCA1 gene expression level in highly proliferative luminal B tumors was shown to be higher than that in luminal A tumors. Survival analysis using a cure model indicated that patients of early ER+ breast cancers with high BRCA1 expression developed rapid distant metastasis. In addition, the proliferation marker genes MKI67 and PCNA, which are characteristic of aggressive tumors, were also highly expressed in patients with high BRCA1 expression. The associations among high BRCA1 expression, high proliferation marker expression, and high risk of distant metastasis emerged in independent datasets, regardless of tamoxifen treatment. Tamoxifen therapy could improve the metastasis-free fraction of high BRCA1 expression patients. Our findings link BRCA1 expression with proliferation and possibly distant metastasis via the ER signaling pathway. We propose a testable hypothesis based on these consistent results and offer an interpretation for our reported associations.

A protein containing the DUF1471 domain regulates biofilm formation and capsule production in Klebsiella pneumoniae.

BACKGROUND/PURPOSE: Biofilms formed by Klebsiella pneumoniae on medical devices increase infection risk. Fimbriae and capsule polysaccharides (CPSs) are important factors involved in biofilm formation. KP1_4563 in K. pneumoniae NTUH-K2044, a small protein containing the DUF1471 domain, was reported to inhibit type 3 fimbriae function. In this study, we aimed to determine whether the KP1_4563 homolog is conserved in each K. pneumoniae isolate and what role it has in Klebsiella biofilms. METHODS: The genomes of K. pneumoniae NTUH-K2044, CG43, MGH78578, KPPR1 and STU1 were compared. The KP1_4563 homolog in K. pneumoniae STU1 was named orfX. Biofilms of wild-type and orfX mutant strains from K. pneumoniae STU1 and one clinical isolate, 83535, were quantified. Transcription levels of the type 3 fimbrial genes, mrkA and mrkH, were investigated by RT-qPCR. MrkA of the wild-type and orfX mutant were observed by Western blotting. The morphology of bacterial cells was observed by transmission electron microscopy (TEM). Bacterial CPSs were quantified. RESULTS: The gene and upstream region of orfX were conserved among the five K. pneumoniae isolates. Deletion of orfX enhanced Klebsiella biofilm formation. However, the amount of mRNA from mrkA and mrkH and the level of MrkA protein were not different between the wild type and orfX mutant. In contrast, the amount of CPS in orfX mutants was increased, compared to their parental strains, STU1 and 83535. CONCLUSION: The role of orfX is speculated to be conserved in most K. pneumoniae isolates. OrfX negatively controlled biofilm formation by reducing CPS, not type 3 fimbriae, production.

Regulation of mitochondrial fusion and mitophagy by intra-tumoral delivery of membrane-fused mitochondria or Midiv-1 enhances sensitivity to doxorubicin in triple-negative breast cancer.

Increasing mitochondrial fusion by intra-tumoral grafting of membrane-fused mitochondria created with Pep-1 conjugation (P-Mito) contributes to breast cancer treatment, but it needs to be validated. Using mitochondrial division inhibitor-1 (Mdivi-1, Mdi) to disturb mitochondrial dynamics, we showed that the antitumor action of P-Mito in a mouse model of triple-negative breast cancer depends upon mitochondrial fusion and that Mdi treatment alone is ineffective. P-Mito significantly enhanced Doxorubicin (Dox) sensitivity by inducing mitochondrial fusion and mitophagy, and the same efficiency was also achieved with Mdi by inhibiting mitophagy. Cell death was induced via the p53 pathway and AIF nuclear translocation in the case of P-Mito, versus the caspase-dependent pathway for Mdi. Notably, both mitochondrial treatments reduced oxidative stress and blood vessel density of xenograft tumors, especially P-Mito, which was accompanied by inhibition of nuclear factor kappa-B activation. Furthermore, through enrichment analysis, four microRNAs in serum microvesicles induced by P-Mito caused expression of predicted targets via the PI3K-Akt pathway, and significantly impacted regulation of nuclear processes and myeloid cell differentiation. Clustering of gene-sets implicated a major steroid catabolic network. This study showed diverse roles of mitochondria in breast cancer and revealed effective adjuvant therapy targeting mitochondrial fusion and mitophagy.

Post-coital vaginal douching is risky for non-regression of low-grade squamous intraepithelial lesion of the cervix.

BACKGROUND: Vaginal douching is a common practice worldwide. Its effect on the natural history of the early lesion of human papillomavirus (HPV) infection, low-grade squamous intraepithelial lesion (LSIL), is unknown. METHODS: In a prospective nation-wide cohort (n=1332), epidemiological variables including habit of vaginal douching after intercourse and outcomes of LSIL were studied. Colposcopy-confirmed LSIL women (n=295) were followed every 3 months. Parameters of HPV infection, sexual behavior, personal hygiene and environmental exposures were compared with the follow-up outcomes. RESULTS: There was a 15% chance of HSIL co-existing with the LSIL cytology result. Eight percent of colposcopy-confirmed LSIL were found with HSIL in 1 year. With a follow-up of up to 36 months, 83% LSIL regressed, 11% progressed and 6% persisted. The mean time (95% CIs) to regression and progression were 5.2 (4.7-5.8) and 8.0 (5.8-10.3) months, respectively. Risk factors of the non-regression of LSIL included HPV prevalence on enrollment, habit of vaginal douching after intercourse with a hygiene product and non-regular Pap screening, with odd ratio of 4.4 (1.9-10.3), 3.14 (1.04-9.49) and 2.12 (1.24-3.62), respectively. HPV prevalence and vaginal douching also conferred a slower regression of LSIL (8.0 vs. 4.1 months, P<.001 and 8.0 vs. 5.6 months, P=0.02, respectively). CONCLUSION: The study disclosed a transient but warning nature of cytological LSIL. Practicing of vaginal douching after intercourse, especially with hygiene products, is associated with non-regression of LSIL.

Synthesis of 2,3,5,6-tetrahydro-1-alkyl/aryl-1H-benzo[f]chromen-3-ol derivatives from ß-tetralones and α,ß-unsaturated aldehydes.

Organocatalytic domino Michael-hemiacetalization of ß-tetralones with α,ß-unsaturated aldehydes is presented. Treatment of ß-tetralones with α,ß-unsaturated aldehydes in the presence of diphenylprolinol silyl ether gave 2,3,5,6-tetrahydro-1-alkyl/aryl-1H-benzo[f]chromen-3-ol derivatives with high to excellent chemical yields (50-99%) and high levels of enantioselectivities (up to 96% ee).

Three Lipid Emulsions Reduce Staphylococcus aureus-Stimulated Phagocytosis in Mouse RAW264.7 Cells.

Soybean oil (SO)-, SO medium-chain triglyceride (MCT)-, olive oil (OO)-, and fish oil (FO)-based lipid emulsions are generally applied in clinical practice via intravenous injection for patients with nutritional requirements. The function of lipid emulsions on immune modulation remains inconsistent, and their effects on macrophages are limited. In the present study, we used a model of S. aureus-infected mouse RAW264.7 macrophages to determine the influence of three different compositions of lipid emulsions (Lipofundin, ClinOleic, and Omegaven) on reactive oxygen species (ROS) production, phagocytosis, and bacterial survival. The three individual lipid emulsions similarly enhanced bacterial survival but reduced S. aureus-stimulated ROS, phagocytosis of S. aureus bioparticles conjugate, polymerization of F-actin, and phosphorylation of AKT, JNK, and ERK. Compared with the JNK and ERK inhibitors, the PI3K inhibitor markedly suppressed the phagocytosis of S. aureus bioparticles conjugate and the polymerization of F-actin, whereas it significantly increased the bacterial survival. These results suggest that the three lipid emulsions diminished ROS production and phagocytosis, resulting in increased bacterial survival. PI3K predominantly mediated the inhibitory effects of the lipid emulsions on the phagocytosis of mouse RAW264.7 macrophages.

Intranasal delivery of mitochondria for treatment of Parkinson's Disease model rats lesioned with 6-hydroxydopamine.

The feasibility of delivering mitochondria intranasally so as to bypass the blood-brain barrier in treating Parkinson's disease (PD), was evaluated in unilaterally 6-OHDA-lesioned rats. Intranasal infusion of allogeneic mitochondria conjugated with Pep-1 (P-Mito) or unconjugated (Mito) was performed once a week on the ipsilateral sides of lesioned brains for three months. A significant improvement of rotational and locomotor behaviors in PD rats was observed in both mitochondrial groups, compared to sham or Pep-1-only groups. Dopaminergic (DA) neuron survival and recovery > 60% occurred in lesions of the substantia nigra (SN) and striatum in Mito and P-Mito rats. The treatment effect was stronger in the P-Mito group than the Mito group, but the difference was insignificant. This recovery was associated with restoration of mitochondrial function and attenuation of oxidative damage in lesioned SN. Notably, P-Mito suppressed plasma levels of inflammatory cytokines. Mitochondria penetrated the accessory olfactory bulb and doublecortin-positive neurons of the rostral migratory stream (RMS) on the ipsilateral sides of lesions and were expressed in striatal, but not SN DA neurons, of both cerebral hemispheres, evidently via commissural fibers. This study shows promise for intranasal delivery of mitochondria, confirming mitochondrial internalization and migration via RMS neurons in the olfactory bulb for PD therapy.

START-Play Physical Therapy Intervention Impacts Motor and Cognitive Outcomes in Infants With Neuromotor Disorders: A Multisite Randomized Clinical Trial.

OBJECTIVE: Our objective was to evaluate the efficacy of the Sitting Together and Reaching to Play (START-Play) intervention in young infants with neuromotor disorders. METHOD: This randomized controlled trial compared usual care early intervention (UC-EI) with START-Play plus UC-EI. Analyses included 112 infants with motor delay (55 UC-EI, 57 START-Play) recruited at 7 to 16 months of age across 5 sites. START-Play included twice-weekly home visits with the infant and caregiver for 12 weeks provided by physical therapists trained in the START-Play intervention; UC-EI was not disrupted. Outcome measures were the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley); the Gross Motor Function Measure; reaching frequency; and the Assessment of Problem Solving in Play (APSP). Comparisons for the full group as well as separate comparisons for infants with mild motor delay and infants with significant motor delay were conducted. Piecewise linear mixed modeling estimated short- and long-term effects. RESULTS: For infants with significant motor delay, positive effects of START-Play were observed at 3 months for Bayley cognition, Bayley fine motor, and APSP and at 12 months for Bayley fine motor and reaching frequency outcomes. For infants with mild motor delay, positive effects of START-Play for the Bayley receptive communication outcome were found. For the UC-EI group, the only difference between groups was a positive effect for the APSP outcome, observed at 3 months. CONCLUSION: START-Play may advance reaching, problem solving, cognitive, and fine motor skills for young infants with significant motor delay over UC-EI in the short term. START-Play in addition to UC-EI may not improve motor/cognitive outcomes for infants with milder motor delays over and above usual care. IMPACT: Concepts of embodied cognition, applied to early intervention in the START-Play intervention, may serve to advance cognition and motor skills in young infants with significant motor delays over usual care early intervention. LAY SUMMARY: If you have a young infant with significant delays in motor skills, your physical therapist can work with you to develop play opportunities to enhance your child's problem solving, such as that used in the START-Play intervention, in addition to usual care to help your child advance cognitive and motor skills.

Detection of novel 3' untranslated region extensions with 3' expression microarrays.

BACKGROUND: The 3' untranslated regions (UTRs) of transcripts are not well characterized for many genes and often extend beyond the annotated regions. Since Affymetrix 3' expression arrays were designed based on expressed sequence tags, many probesets map to intergenic regions downstream of genes. We used expression information from these probesets to predict transcript extension beyond currently known boundaries. RESULTS: Based on our dataset encompassing expression in 22 different murine tissues, we identified 845 genes with predicted 3'UTR extensions. These extensions have a similar conservation as known 3'UTRs, which is distinctly higher than intergenic regions. We verified 8 of the predictions by PCR and found all of the predicted regions to be expressed. The method can be extended to other 3' expression microarray platforms as we demonstrate with human data. Additional confirming evidence was obtained from public paired end read data. CONCLUSIONS: We show that many genes have 3'UTR regions extending beyond currently known gene regions and provide a method to identify such regions based on microarray expression data. Since 3' UTR contain microRNA binding sites and other stability determining regions, identification of the full length 3' UTR is important to elucidate posttranscriptional regulation.

Antitumor Actions of Intratumoral Delivery of Membrane-Fused Mitochondria in a Mouse Model of Triple-Negative Breast Cancers.

BACKGROUND: The transfer of whole mitochondria has been demonstrated to be beneficial for treating breast cancer because it induces apoptosis and drug sensitivity; however, in vivo evidence of this benefit remains scant. The present study compared the transplantation of mitochondria with instinctive (Mito) and membrane-fused morphologies induced by Pep-1 conjugation (P-Mito) using a mouse model of triple-negative breast cancers. MATERIALS AND METHODS: Mice with advanced severe immunodeficiency received orthotopic implantation of MDA-MB-231 human breast cancer cells followed by transplants of 5-bromo-2'-deoxyuridine (BrdU)-labeled Mito or P-Mito (200 µg [10 µg/µL]) through intratumoral injection at multiple points once a week for 4 weeks. RESULTS: After 1 month of consecutive treatment, 8.2% and 14.2% of the BrdU-labeled mitochondria were preserved in tumors of the Mito and P-Mito groups, respectively. Both Pep-1 and P-Mito treatments reduced tumor weight (21.7% ± 2.43% vs 40.6% ± 2.28%) and led to marked inhibition of Ki67 staining and angiogenesis. However, only the P-Mito group exhibited obvious necrosis and DNA fragmentation accompanied by an altered tumor microenvironment, which included reduced oxidative stress and size of cancer-associated fibroblast populations and enhanced immune cell infiltration. Transmission electron microscopy images further revealed an elongated network of perinuclear mitochondria fused with a few peripheral mitochondria in the nonnecrotic area in the P-Mito group as well as increases in mitochondrial fusion proteins and parkin compared with mitochondrial fission proteins. CONCLUSION: In this study, the results of mitochondrial transplantation emphasized that the facilitation of mitochondrial fusion is a critical regulator in breast cancer therapy.

Mitochondrial transplantation regulates antitumour activity, chemoresistance and mitochondrial dynamics in breast cancer.

BACKGROUND: The transfer of whole mitochondria that occurs during cell contact has been found to support cancer progression. However, the regulatory role of mitochondria alone is difficult to elucidate due to the complex microenvironment. Currently, mitochondrial transplantation is an available approach for restoring mitochondrial function in mitochondrial diseases but remains unclear in breast cancer. Herein, effects of mitochondrial transplantation via different approaches in breast cancer were investigated. METHODS: Whole mitochondria (approximately 10.5 µg/ml) were transported into MCF-7 breast cancer cells via passive uptake or Pep-1-mediated delivery. Fresh mitochondria isolated from homeoplasmic 143B osteosarcoma cybrids containing mitochondrial DNA (mtDNA) derived from health individuals (Mito) or mtDNA with the A8344G mutation (Mito8344) were conjugated with cell-penetrating peptide Pep-1 (P-Mito) or not conjugated prior to cell co-culture. Before isolation, mitochondria were stained with MitoTracker dye as the tracking label. After 3 days of treatment, cell viability, proliferation, oxidative stress, drug sensitivity to Doxorubicin/Paclitaxel and mitochondrial function were assessed. RESULTS: Compared with P-Mito, a small portion of Mito adhered to the cell membrane, and this was accompanied by a slightly lower fluorescent signal by foreign mitochondria in MCF-7 cells. Both transplantations induced cell apoptosis by increasing the nuclear translocation of apoptosis-inducing factor; inhibited cell growth and decreased oxidative stress in MCF-7 cells; and increased the cellular susceptibility of both the MCF-7 and MDA-MB-231 cell lines to Doxorubicin and Paclitaxel. Mitochondrial transplantation also consistently decreased Drp-1, which resulted in an enhancement of the tubular mitochondrial network, but a distinct machinery through the increase of parkin and mitochondrial fusion proteins was observed in the Mito and P-Mito groups, respectively. Furthermore, although there were no differences in energy metabolism after transplantation of normal mitochondria, metabolism was switched to the energetic and glycolytic phenotypes when the mitochondria were replaced with dysfunctional mitochondria, namely, Mito8344 and P-Mito8344, due to dramatically induced glycolysis and reduced mitochondrial respiration, respectively. Consequently, transplant-induced growth inhibition was abolished, and cell growth in the Mito8344 group was even higher than that in the control group. CONCLUSION: This study reveals the antitumour potential of mitochondrial transplantation in breast cancer via distinct regulation of mitochondrial function.

Sitting Together And Reaching To Play (START-Play): Protocol for a Multisite Randomized Controlled Efficacy Trial on Intervention for Infants With Neuromotor Disorders.

Background: There is limited research examining the efficacy of early physical therapy on infants with neuromotor dysfunction. In addition, most early motor interventions have not been directly linked to learning, despite the clear association between motor activity and cognition during infancy. Objective: The aim of this project is to evaluate the efficacy of Sitting Together And Reaching To Play (START-Play), an intervention designed to target sitting, reaching, and motor-based problem solving to advance global development in infants with motor delays or neuromotor dysfunction. Design: This study is a longitudinal multisite randomized controlled trial. Infants in the START-Play group are compared to infants receiving usual care in early intervention (EI). Setting: The research takes place in homes in Pennsylvania, Delaware, Washington, and Virginia. Participants: There will be 140 infants with neuromotor dysfunction participating, beginning between 7 to 16 months of age. Infants will have motor delays and emerging sitting skill. Intervention: START-Play provides individualized twice-weekly home intervention for 12 weeks with families to enhance cognition through sitting, reaching, and problem-solving activities for infants. Ten interventionists provide the intervention, with each child assigned 1 therapist. Measurements: The primary outcome measure is the Bayley III Scales of Infant Development. Secondary measures include change in the Early Problem Solving Indicator, change in the Gross Motor Function Measure, and change in the type and duration of toy contacts during reaching. Additional measures include sitting posture control and parent-child interaction. Limitations: Limitations include variability in usual EI care and the lack of blinding for interventionists and families. Conclusions: This study describes usual care in EI across 4 US regions and compares outcomes of the START-Play intervention to usual care.

Development of a Needs Scale for Nurses Receiving In-Service Palliative Care Education.

BACKGROUND: Nurses play pivotal roles on palliative care teams and are able to spend more time with patients and their families than are other healthcare professionals. As a consequence, assessing the needs for palliative care education in connection with in-service classes for nurses is clearly extremely important and can help in the planning of appropriate palliative care classes to enhance the quality of care. OBJECTIVES: The goals of this study were to investigate the content needs of nurses with regard to a palliative care in-service education program and to perform exploratory factor analysis on those needs. METHODS: This study used a cross-sectional questionnaire survey. A total of 614 questionnaires were distributed, and 600 valid questionnaires were returned (97.72%). Data analysis was performed by means of descriptive statistics, reliability analysis, factor analysis, and Pearson correlation. RESULTS: The 6 factors discovered by exploratory factor analysis were handling of pain and symptoms, ethical issues concerning terminal patients, hospice preparation and care, the concept of palliative care, communication and counseling, and cultural and spiritual factors, which together explained 77.22% of the variance. CONCLUSION: The results of this study shed light on the program needs for in-service education about palliative care and the 6 factors most associated with those needs. IMPLICATIONS FOR PRACTICE: In order to realize the whole-person concept of care, future efforts should target the planning of palliative care in-service education programs, strengthening of nurse training, coordination of administrative resources, and interteam cooperation.

Child Engagement in Daily Life: a measure of participation for young children with cerebral palsy.

PURPOSE: The objectives of this study were to determine the: (1) internal consistency and test-retest reliability of the Child Engagement in Daily Life measure; (2) construct validity of the measure (known groups methods), that is, the ability of the measure to discriminate participation in family and recreational activities and self-care among young children of varying age and motor ability and between children with and without cerebral palsy, and (3) stability and hierarchical ordering of the items for young children with CP to devise an interval-level scoring system. METHODS: 429 children with CP and their parents and 110 parents of children without CP participated in this methodological study. Parents completed the Child Engagement in Daily Life measure and therapists assessed the children's gross motor function. Rasch analysis was used to create an interval-level measure. RESULTS: Children's frequency in and enjoyment of participation in family and recreational activities and self-care varied by age and gross motor ability. Internal consistency of the domains of the measure was high, Cronbach alpha values ranging from 0.86 to 0.91; test-retest for participation in family and recreational activities was acceptable, ICC = 0.70, and in self-care was high, ICC = 0.96. The items in the measure had a good fit and a logical hierarchical ordering. CONCLUSION: Study results support the validity and reliability of the Child Engagement in Daily Life measure as an assessment of participation in family and recreational activities and self-care for young children with CP. IMPLICATIONS FOR REHABILITATION: Participation in family and recreational activities and self-care for young children with cerebral palsy can be reliably and validly assessed using the Child Engagement in Daily Life measure. Service providers are encouraged to support young children's participation in family and recreational activities and self-care.