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Importance: Early identification of young children at risk of developmental coordination disorder (DCD) can support early intervention and prevent secondary sequelae., Objective: To examine the psychometric properties of a translated and cross-culturally adapted version of the Little Developmental Coordination Disorder Questionnaire-Taiwan (LDCDQ-TW)., Design: Prospective study., Setting: Kindergartens and preschools in north, central, and south Taiwan., Participants: In Phase 1 the participants were 1,124 parents of typically developing children ages 36-71 mo. Children with confirmed developmental diagnoses were excluded. Participants in Phase 3 were 162 children who had been recruited in Phase 2. Outcomes and Measures: The LDCDQ-TW, a 15-item parent questionnaire for identifying children at risk for DCD, and the Movement Assessment Battery for Children (2nd ed.; MABC-2), were administered., Results: The findings revealed excellent test-retest reliability (intraclass correlation coefficient [ICC] = .97) and poor interrater reliability (ICC = .47). On the basis of MABC-2 scores, the non-DCD group (≥15th percentile) scored significantly higher than the DCD and suspect-DCD groups on the LDCDQ-TW, but the latter two groups did not differ from one another. Using the 15th percentile as a cutoff for both the MABC-2 and the LDCDQ-TW, sensitivity was .96 and specificity was .68., Conclusions and Relevance: Although standardized performance-based assessments are required to confirm a diagnosis of DCD (typically after age 5 yr), the LDCDQ-TW demonstrated sound reliability and validity and can support the early identification of young children at risk of DCD in Taiwan. What This Article Adds: The LDCDQ-TW can facilitate early intervention for DCD and prevent secondary sequelae, improving outcomes for children with DCD., (Copyright © 2022 by the American Occupational Therapy Association, Inc.)

A deficit in pre-cognitively mirroring other people's actions and experiences may be related to the social impairments observed in autism spectrum disorder (ASD). However, it is unclear whether such embodied simulation deficits are unique to ASD or instead are related to motor impairment, which is commonly comorbid with ASD. Here we aim to disentangle how, neurologically, motor impairments contribute to simulation deficits and identify unique neural signatures of ASD. We compare children with ASD (N = 30) to children with Developmental Coordination Disorder (DCD; N = 23) as well as a typically developing group (N = 33) during fMRI tasks in which children observe, imitate, and mentalize about other people's actions. Results indicate a unique neural signature in ASD: during action observation, only the ASD group shows hypoactivity in a region important for simulation (inferior frontal gyrus, pars opercularis, IFGop). However, during a motor production task (imitation), the IFGop is hypoactive for both ASD and DCD groups. For all tasks, we find correlations across groups with motor ability, even after controlling for age, IQ, and social impairment. Conversely, across groups, mentalizing ability is correlated with activity in the dorsomedial prefrontal cortex when controlling for motor ability. These findings help identify the unique neurobiological basis of ASD for aspects of social processing. Furthermore, as no previous fMRI studies correlated brain activity with motor impairment in ASD, these findings help explain prior conflicting reports in these simulation networks., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

The present research aimed to evaluate the larvicidal activity of several recently discovered natural repellents formulated in lotions against larvae of Aedes aegypti. We used a modified larval bioassay method by the World Health Organization standards in evaluating larval mortality at 24-, 48-, and 72-h exposure. Among the test repellents, 2-undecanone showed 100% mortality of Ae. aegypti larvae, followed by catnip oil, capric acid, coconut oil fatty acids, methyl caprate, methyl laurate, and coconut oil methyl esters. The repellent, 2-undecanone showed median lethal concentration (LC50) values of 73.07, 26.45, and 15.68 ppm at 24-, 48-, and 72-h exposure, respectively. Larvicidal activity varied among the other repellents tested., (Copyright © 2020 by The American Mosquito Control Association, Inc.)

Abnormal sensory-based behaviors are a defining feature of autism spectrum disorders (ASD). Dr. A. Jean Ayres was the first occupational therapist to conceptualize Sensory Integration (SI) theories and therapies to address these deficits. Her work was based on neurological knowledge of the 1970's. Since then, advancements in neuroimaging techniques make it possible to better understand the brain areas that may underlie sensory processing deficits in ASD. In this article, we explore the postulates proposed by Ayres (i.e., registration, modulation, motivation) through current neuroimaging literature. To this end, we review the neural underpinnings of sensory processing and integration in ASD by examining the literature on neurophysiological responses to sensory stimuli in individuals with ASD as well as structural and network organization using a variety of neuroimaging techniques. Many aspects of Ayres' hypotheses about the nature of the disorder were found to be highly consistent with current literature on sensory processing in children with ASD but there are some discrepancies across various methodological techniques and ASD development. With additional characterization, neurophysiological profiles of sensory processing in ASD may serve as valuable biomarkers for diagnosis and monitoring of therapeutic interventions, such as SI therapy.

It is intriguing that a rare, inherited lysosomal storage disorder Niemann-Pick type C (NPC) shares similarities with Alzheimer's disease (AD). We have previously reported an enhanced processing of β-amyloid precursor protein (APP) by β-secretase (BACE1), a key enzyme in the pathogenesis of AD, in NPC1-null cells. In this work, we characterized regional and temporal expression and processing of the recently identified BACE1 substrates seizure protein 6 (Sez6) and seizure 6-like protein (Sez6L), and APP, in NPC1-/- (NPC1) and NPC1+/+ (wt) mouse brains. We analysed 4-weeks old brains to detect the earliest changes associated with NPC, and 10-weeks of age to identify changes at terminal disease stage. Sez6 and Sez6L were selected due to their predominant cleavage by BACE1, and their potential role in synaptic function that may contribute to presentation of seizures and/or motor impairments in NPC patients. While an enhanced BACE1-cleavage of all three substrates was detected in NPC1 vs. wt-mouse brains at 4-weeks of age, at 10-weeks increased proteolysis by BACE1 was observed for Sez6L in the cortex, hippocampus and cerebellum of NPC1-mice. Interestingly, both APP and Sez6L were found to be expressed in Purkinje neurons and their immunostaining was lost upon Purkinje cell neurodegeneration in 10-weeks old NPC1 mice. Furthermore, in NPC1- vs. wt-mouse primary cortical neurons, both Sez6 and Sez6L showed increased punctuate staining within the endolysosomal pathway as well as increased Sez6L and BACE1-positive puncta. This indicates that a trafficking defect within the endolysosomal pathway may play a key role in enhanced BACE1-proteolysis in NPC disease. Overall, our findings suggest that enhanced proteolysis by BACE1 could be a part of NPC disease pathogenesis. Understanding the basic biology of BACE1 and the functional impact of cleavage of its substrates is important to better evaluate the therapeutic potential of BACE1 against AD and, possibly, NPC disease., Competing Interests: The authors have declared that no competing interests exist.

Proper function of lysosomes is particularly important in neurons, as they cannot dilute accumulated toxic molecules and aggregates by cell division. Thus, impairment of lysosomal function plays an important role in neuronal degeneration and in the pathogenesis of numerous neurodegenerative diseases. In this work we analyzed how inhibition and/or loss of the major lysosomal proteases, the cysteine cathepsins B and L (CtsB/L), affects lysosomal function, cholesterol metabolism and degradation of the key Alzheimer's disease (AD) proteins. Here, we show that cysteine CtsB/L, and not the aspartyl cathepsin D (CtsD), represent a major lysosomal protease(s) that control lysosomal function, intracellular cholesterol trafficking and AD-like amyloidogenic features. Intriguingly, accumulation of free cholesterol in late endosomes/lysosomes upon CtsB/L inhibition resembled a phenotype characteristic for the rare neurodegenerative disorder Niemann-Pick type C (NPC). CtsB/L inhibition and not the inhibition of CtsD led to lysosomal impairment assessed by decreased degradation of EGF receptor, enhanced LysoTracker staining and accumulation of several lysosomal proteins LC3II, NPC1 and NPC2. By measuring the levels of NPC1 and ABCA1, the two major cholesterol efflux proteins, we showed that CtsB/L inhibition or genetic depletion caused accumulation of the NPC1 in lysosomes and downregulation of ABCA1 protein levels and its expression. Furthermore, we revealed that CtsB/L are involved in degradation of the key Alzheimer's proteins: amyloid-β peptides (Aβ) and C-terminal fragments of the amyloid precursor protein (APP) and in degradation of β-secretase (BACE1). Our results imply CtsB/L as major regulators of lysosomal function and demonstrate that CtsB/L may play an important role in intracellular cholesterol trafficking and in degradation of the key AD proteins. Our findings implicate that enhancing the activity or levels of CtsB/L could provide a promising and a common strategy for maintaining lysosomal function and for preventing and/or treating neurodegenerative diseases., Competing Interests: The authors have declared that no competing interests exist.

Objective: We sought to characterize sensory integration (SI) and praxis patterns of children with autism spectrum disorder (ASD) and discern whether these patterns relate to social participation., Method: We extracted Sensory Integration and Praxis Tests (SIPT) and Sensory Processing Measure (SPM) scores from clinical records of children with ASD ages 4-11 yr (N=89) and used SIPT and SPM standard scores to describe SI and praxis patterns. Correlation coefficients were generated to discern relationships among SI and praxis scores and these scores' associations with SPM Social Participation scores., Results: Children with ASD showed relative strengths in visual praxis. Marked difficulties were evident in imitation praxis, vestibular bilateral integration, somatosensory perception, and sensory reactivity. SPM Social Participation scores were inversely associated with areas of deficit on SIPT measures., Conclusion: Children with ASD characteristically display strengths in visuopraxis and difficulties with somatopraxis and vestibular functions, which appear to greatly affect participation., (Copyright © 2015 by the American Occupational Therapy Association, Inc.)

Cannabinoid receptor subtype 2 (CB2) has been shown to be up-regulated in activated microglia and therefore plays an important role in neuroinflammatory and neurodegenerative diseases such as multiple sclerosis, amyotrophic lateral sclerosis and Alzheimer's disease. The CB2 receptor is therefore considered as a very promising target for therapeutic approaches as well as for imaging. A promising 2-oxoquinoline derivative designated KP23 was synthesized and radiolabeled and its potential as a ligand for PET imaging the CB2 receptor was evaluated. [11C]KP23 was obtained in 10%-25% radiochemical yield (decay corrected) and 99% radiochemical purity. It showed high stability in phosphate buffer, rat and mouse plasma. In vitro autoradiography of rat and mouse spleen slices, as spleen expresses a high physiological expression of CB2 receptors, demonstrated that [11C]KP23 exhibits specific binding towards CB2. High spleen uptake of [11C]KP23 was observed in dynamic in vivo PET studies with Wistar rats. In conclusion, [11C]KP23 showed promising in vitro and in vivo characteristics. Further evaluation with diseased animal model which has higher CB2 expression levels in the brain is warranted.

With the idea of finding a more selective radiotracer for imaging herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene expression by means of positron emission tomography (PET), a novel [¹⁸F]fluorine radiolabeled pyrimidine with 4-hydroxy-3-(hydroxymethyl)butyl side chain at N-1 (HHB-5-[¹⁸F]FEP) was prepared and evaluated as a potential PET probe. Unlabeled reference compound, HHB-5-FEP, was synthesized via a five-step reaction sequence starting from 5-(2-acetoxyethyl)-4-methoxypyrimidin-2-one. The radiosynthesis of HHB-[¹⁸F]-FEP was accomplished by nucleophilic radiofluorination of a tosylate precursor using [¹⁸F]fluoride-cryptate complex in 45% ± 4 (n = 4) radiochemical yields and high purity (>99%). The biological evaluation indicated the feasibility of using HHB-5-[¹⁸F]FEP as a PET radiotracer for monitoring HSV1-tk expression in vivo.

Building on established relationships between the constructs of sensory integration in typical and special needs populations, in this retrospective study we examined patterns of sensory integrative dysfunction in 273 children ages 4-9 who had received occupational therapy evaluations in two private practice settings. Test results on the Sensory Integration and Praxis Tests, portions of the Sensory Processing Measure representing tactile overresponsiveness, and parent report of attention and activity level were included in the analyses. Exploratory factor analysis identified patterns similar to those found in early studies by Ayres (1965, 1966a, 1966b, 1969, 1972b, 1977, & 1989), namely Visuodyspraxia and Somatodyspraxia, Vestibular and Proprioceptive Bilateral Integration and Sequencing, Tactile and Visual Discrimination, and Tactile Defensiveness and Attention. Findings reinforce associations between constructs of sensory integration and assist with understanding sensory integration disorders that may affect childhood occupation. Limitations include the potential for subjective interpretation in factor analysis and inability to adjust measures available in charts in a retrospective research.

Objective: To examine the relation between length of institutionalization and sensory integration in children adopted from Eastern Europe., Method: The Sensory Integration and Praxis Tests (SIPT) and the Developmental and Sensory Processing Questionnaire were administered to 60 adopted children, 4 years to 8 years, 11 months of age. Thirty had longer institutionalization histories (mean: 34 months; LIH group) and the other 30 had shorter institutionalization histories (mean: 3 months; SIH group)., Results: The LIH group demonstrated significantly lower scores than the SIH group on the SIPT in vestibular-proprioceptive, visual, and praxis areas, and effect sizes ranged from .09 to 1.13. The LIH group also had significantly more frequent behaviors suggestive of sensory modulation dysfunction compared to the SIH group, particularly in touch and movement seeking, vision, and audition. Effect sizes ranged from 0 to 1.39., Conclusion: Longer lengths of institutionalization are associated with more atypical sensory discrimination, praxis, and sensory modulation scores in children adopted from Eastern European orphanages. The areas of sensory integration that appear to be more vulnerable to deprived conditions in early childhood are vestibular-proprioceptive, tactile, visual, auditory, and praxis. Adopted children with lengthy periods of institutionalization may benefit from occupational therapy for early sensory integrative and developmental screenings.

The authors present a case report of bleeding from the small dissection of descending aorta. Patient, 71 year old woman, with severe comorbidities (nephrotic syndrome based on membraneous glomerulonephritis, diabetes mellitus, lung emphysema, hepatopathy, polyneuropathy and others). One month after last stay in hospital chemotherapy et corticotherapy. In while on heparin during hospitalization at nephrologic department, patient developed right side haemothorax and haemomediastinum. An urgent transfer to surgical department with cardiopulmonary resuscitation was performed. The suspection of aneurysm on CT angioscan was non confirmed. The damage of oesophagus due to previous endoscopy (for chest pain) was non confirmed, too. During surgery masive sanquine effusion of mediastinum and right side haemothorax was found. The drainage and redrainage of the chest was performed. The cause of bleeding was not found. Critically ill patient had died and on autopsy a small dissection of thoracic aorta was found as a cause of bleeding. The problems of diagnosis and therapy are discussed. (Fig. 2, Ref. 7.)