The Emotion Regulation Checklist with Young Autistic Children: Data Set for Comparative Use in Intervention Studies.

PURPOSE: Comparative data of autism-sensitive standardized measures of emotion regulation and lability, describing percentage change over time for populations of young autistic children, are currently publicly unavailable. We propose publication of such data as a support for future therapeutic intervention studies. METHODS: We generate and present data of the Emotion Regulation Checklist (and subscales) for a comparative array of percentage change over time (10 months) for autistic children not receiving psychological or behavioral therapies (N = 98, ages 4-8). RESULTS: Comparative data summaries are presented here, and the full data set is presented as Online Resource 1. CONCLUSION: We propose that this autism-sensitive measure, now with autism-specific comparative data to provide a comparison group in studies of therapeutic intervention, is well placed to assess co-occurring affective, regulatory, and behavioral factors of personal development for autistic children.

Rhythmic Relating: Bidirectional Support for Social Timing in Autism Therapies.

We propose Rhythmic Relating for autism: a system of supports for friends, therapists, parents, and educators; a system which aims to augment bidirectional communication and complement existing therapeutic approaches. We begin by summarizing the developmental significance of social timing and the social-motor-synchrony challenges observed in early autism. Meta-analyses conclude the early primacy of such challenges, yet cite the lack of focused therapies. We identify core relational parameters in support of social-motor-synchrony and systematize these using the communicative musicality constructs: pulse; quality; and narrative. Rhythmic Relating aims to augment the clarity, contiguity, and pulse-beat of spontaneous behavior by recruiting rhythmic supports (cues, accents, turbulence) and relatable vitality; facilitating the predictive flow and just-ahead-in-time planning needed for good-enough social timing. From here, we describe possibilities for playful therapeutic interaction, small-step co-regulation, and layered sensorimotor integration. Lastly, we include several clinical case examples demonstrating the use of Rhythmic Relating within four different therapeutic approaches (Dance Movement Therapy, Improvisational Music Therapy, Play Therapy, and Musical Interaction Therapy). These clinical case examples are introduced here and several more are included in the Supplementary Material (Examples of Rhythmic Relating in Practice). A suite of pilot intervention studies is proposed to assess the efficacy of combining Rhythmic Relating with different therapeutic approaches in playful work with individuals with autism. Further experimental hypotheses are outlined, designed to clarify the significance of certain key features of the Rhythmic Relating approach.

Trends in the Utilization of Palliative Care in Patients With Gynecologic Cancer Who Subsequently Died During Hospitalization.

OBJECTIVE: To determine factors associated with the utilization of palliative care (PC) in patients with metastatic gynecologic cancer who died while hospitalized. METHODS: Data were abstracted from the National Inpatient Sample database for patients with cervical, uterine, and ovarian cancers from 2005 to 2011. Chi-squared and logistic regression models were used for statistical analyses. RESULTS: Of 4559 women (median age: 65 years; range: 19-102), 1066 (23.4%) utilized PC. Patients were 24.9% low socioeconomic status (SES), 23.9% low-middle, 23.7% middle-high, and 25.1% high SES. Medicare, Medicaid, and private insurance coverage were listed at 46.2%, 37.5%, 11.3% of patients; 36.2%, 21.1%, 18.1%, 24.6% were treated in the South, West, Midwest, and Northeast. Over the 7 year study period, the use of PC increased from 12% to 45%. Older age (odds ratio [OR]: 1.36; 95% CI: 1.11-1.68; P = .003), high SES (OR: 1.41; 95% CI: 1.12-1.78; P = .003), more recent treatment (OR: 9.22; 95% CI: 6.8-12.51; P < .0001), private insurance (OR: 1.81; 95% CI: 1.46-2.25; P < .001), and treatment at large-volume hospitals (OR: 1.36; 95% CI: 1.04-1.77; P = .02), Western (OR: 2.00; 95% CI: 1.61-2.49; P < .001) and Midwestern hospitals (OR: 1.35; 95% CI: 1.08-1.68; P = .001) were associated with higher utilization of PC. CONCLUSIONS: The use of inpatient PC for patients with gynecologic cancer increased over time. The lower utilization of PC for terminal illness was associated with younger age, lower SES, government-issued insurance coverage, and treatment in Southern and smaller volume hospitals, and warrants further attention.

TGL-mediated lipolysis in Manduca sexta fat body: possible roles for lipoamide-dehydrogenase (LipDH) and high-density lipophorin (HDLp).

Triglyceride-lipase (TGL) is a major fat body lipase in Manduca sexta. The knowledge of how TGL activity is regulated is very limited. A WWE domain, presumably involved in protein-protein interactions, has been previously identified in the N-terminal region of TGL. In this study, we searched for proteins partners that interact with the N-terminal region of TGL. Thirteen proteins were identified by mass spectrometry, and the interaction with four of these proteins was confirmed by immunoblot. The oxidoreductase lipoamide-dehydrogenase (LipDH) and the apolipoprotein components of the lipid transporter, HDLp, were among these proteins. LipDH is the common component of the mitochondrial α-keto acid dehydrogenase complexes whereas HDLp occurs in the hemolymph. However, subcellular fractionation demonstrated that these two proteins are relatively abundant in the soluble fraction of fat body adipocytes. The cofactor lipoate found in typical LipDH substrates was not detected in TGL. However, TGL proved to have critical thiol groups. Additional studies with inhibitors are consistent with the notion that LipDH acting as a diaphorase could preserve the activity of TGL by controlling the redox state of thiol groups. On the other hand, when TG hydrolase activity of TGL was assayed in the presence of HDLp, the production of diacylglycerol (DG) increased. TGL-HDLp interaction could drive the intracellular transport of DG. TGL may be directly involved in the lipoprotein assembly and loading with DG, a process that occurs in the fat body and is essential for insects to mobilize fatty acids. Overall the study suggests that TGL occurs as a multi-protein complex supported by interactions through the WWE domain.

Oxygen therapy in critical illness: precise control of arterial oxygenation and permissive hypoxemia.

OBJECTIVE: The management of hypoxemia in critically ill patients is challenging. Whilst the harms of tissue hypoxia are well recognized, the possibility of harm from excess oxygen administration, or other interventions targeted at mitigating hypoxemia, may be inadequately appreciated. The benefits of attempting to fully reverse arterial hypoxemia may be outweighed by the harms associated with high concentrations of supplemental oxygen and invasive mechanical ventilation strategies. We propose two novel related strategies for the management of hypoxemia in critically ill patients. First, we describe precise control of arterial oxygenation involving the specific targeting of arterial partial pressure of oxygen or arterial hemoglobin oxygen saturation to individualized target values, with the avoidance of significant variation from these levels. The aim of precise control of arterial oxygenation is to avoid the harms associated with inadvertent hyperoxia or hypoxia through careful and precise control of arterial oxygen levels. Secondly, we describe permissive hypoxemia: the acceptance of levels of arterial oxygenation lower than is conventionally tolerated in patients. The aim of permissive hypoxemia is to minimize the possible harms caused by restoration of normoxemia while avoiding tissue hypoxia. This review sets out to discuss the strengths and limitations of precise control of arterial oxygenation and permissive hypoxemia as candidate management strategies in hypoxemic critically ill patients. DESIGN: We searched PubMed for references to "permissive hypoxemia/hypoxaemia" and "precise control of arterial oxygenation" as well as reference to "profound hypoxemia/hypoxaemia/hypoxia," "severe hypoxemia/hypoxaemia/hypoxia." We searched personal reference libraries in the areas of critical illness and high altitude physiology and medicine. We also identified large clinical studies in patients with critical illness characterized by hypoxemia such as acute respiratory distress syndrome. SUBJECTS: Studies were selected that explored the physiology of hypoxemia in healthy volunteers or critically ill patients. SETTING: The data were subjectively assessed and combined to generate the narrative. RESULTS: Inadequate tissue oxygenation and excessive oxygen administration can be detrimental to outcome but safety thresholds lack definition in critically ill patients. Precise control of arterial oxygenation provides a rational approach to the management of arterial oxygenation that reflects recent clinical developments in other settings. Permissive hypoxemia is a concept that is untested clinically and requires robust investigation prior to consideration of implementation. Both strategies will require accurate monitoring of oxygen administration and arterial oxygenation. Effective, reliable measurement of tissue oxygenation along with the use of selected biomarkers to identify suitable candidates and monitor harm will aid the development of permissive hypoxemia as viable clinical strategy. CONCLUSIONS: Implementation of precise control of arterial oxygenation may avoid the harms associated with excessive and inadequate oxygenation. However, at present there is no direct evidence to support the immediate implementation of permissive hypoxemia and a comprehensive evaluation of its value in critically ill patients should be a high research priority.

Differential cytokine expression and regulation of human anti-pig xenogeneic responses by modified porcine dendritic cells.

BACKGROUND: Porcine dendritic cells (DC) are likely to be pivotal cells in the initiation of stimulatory and potential tolerogenic responses to xenoantigens, however, there are limited studies characterizing these antigen presenting cells. METHODS: Porcine PBMC (CD172a(+)) were cultured with GM-CSF and IL-4 and phenotype and functional capabilities assessed. Lipopolysaccharide (LPS), IL-10, and IL-3 were added to the GM-CSF/IL-4 DC cultures to determine phenotypic and functional changes. Quantitative real-time polymerase chain reaction (PCR) for key cytokines was performed and the modified porcine DC were further assessed by primary mixed lymphocyte reaction to determine the effect of LPS, IL-10, and IL-3 on stimulatory capability. RESULTS: Porcine PBMC (CD172(+)) cultured with GM-CSF and IL-4 produced cells with DC morphology, which were major histocompatability complex (MHC) class II(+), CD14(-/lo), and CD1a(lo). Addition of IL-10 or IL-3 to GM-CSF/IL-4 DC cultures produced cells with lower levels of MHC class II and higher levels of antigen uptake consistent with less mature DC. Quantitative real-time PCR of DC showed the addition of IL-10 induced an increase in IL-10 mRNA, no detectable IL-12, and reduced IL-6 mRNA. The addition of IL-3 to DC cultures decreased IL-12, IL-6 and tumor necrosis factor (TNF), with no change in IL-10 mRNA. GM-CSF/IL-4 DC induced strong human lymphocyte proliferation, compared with significantly reduced stimulatory capacity induced by IL-10 and IL-3 treated DC cultures. CONCLUSIONS: The profound effect on differential DC cytokine profile and reduced human anti-pig responses has important therapeutic implications in xenotransplantation. The mechanism of altered regulation warrants further investigation.

Disorganized rhythm and synchrony: early signs of autism and Rett syndrome.

We interpret early age-related developments in intentions and socially responsive behaviour with data from home videos of infants who later develop autism or Rett syndrome. Detailed evidence is given from a micro-analytic study of videos of monozygotic twin girls at 11 months, one of whom became autistic in the second year. Changes in this twin's attention, motor tonus, initiative and emotion reduce her prospective control of movements and her anticipations in awareness compared to her sister. These changes were reflected in the child's asynchronous social behaviour, which frustrated the father's attempts to support her attempts to walk, share toys, or play a game, confusing his anticipations, and this further reduced mutual attention and joint activity. Observations of the development of girls with Rett syndrome in the first year reveal changes in motor coordination, attention and communicative initiative, indicative of a failure of intrinsic core brain regulations of neural development and conscious activity. Notwithstanding that the two conditions show clear differences in both brain growth and early development of skills and sociability, the first signs of autism and Rett syndrome have important similarities. We conclude with recommendations for an approach to early diagnosis and treatment, applicable for the whole range of developmental brain disorders, including Rett syndrome and autism, that attempts to identify residual capacities for sympathetic motivation and collaborative learning-an approach that deliberately tries to support weakened rhythmic impulses for motor, perceptual and communicative functions in the growing infant brain.