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The purpose of this secondary qualitative analysis was to explore the play interactions of children with autism ( n = 10) and their pets in the home environment. Researchers coded 115 minutes of video of children playing with their pets at home and transcripts from eight caregiver interviews. Thematic analysis revealed six codes which represented three themes, including children with ASD play with pets in a variety of ways, playing with pets supports child development , and playing with pets yields benefits for children with ASD . Findings suggest playing with pets may be beneficial for developing responsibility and social skills of children with ASD, particularly in how they interact with animals. Future research should examine perspectives of families who do not own or who have relinquished pets and perspectives of adults with ASD to better understand positive and negative aspects of pet play., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Rocky Mountain spotted fever (RMSF) is a disease that now causes significant morbidity and mortality on several American Indian reservations in Arizona. Although the disease is treatable, reported RMSF case fatality rates from this region are high (7%) compared to the rest of the nation (<1%), suggesting a need to identify clinical points for intervention., Methods: The first 205 cases from this region were reviewed and fatal RMSF cases were compared to nonfatal cases to determine clinical risk factors for fatal outcome., Results: Doxycycline was initiated significantly later in fatal cases (median, day 7) than nonfatal cases (median, day 3), although both groups of case patients presented for care early (median, day 2). Multiple factors increased the risk of doxycycline delay and fatal outcome, such as early symptoms of nausea and diarrhea, history of alcoholism or chronic lung disease, and abnormal laboratory results such as elevated liver aminotransferases. Rash, history of tick bite, thrombocytopenia, and hyponatremia were often absent at initial presentation., Conclusions: Earlier treatment with doxycycline can decrease morbidity and mortality from RMSF in this region. Recognition of risk factors associated with doxycycline delay and fatal outcome, such as early gastrointestinal symptoms and a history of alcoholism or chronic lung disease, may be useful in guiding early treatment decisions. Healthcare providers should have a low threshold for initiating doxycycline whenever treating febrile or potentially septic patients from tribal lands in Arizona, even if an alternative diagnosis seems more likely and classic findings of RMSF are absent., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Rocky Mountain spotted fever (RMSF) has emerged as a significant cause of morbidity and mortality since 2002 on tribal lands in Arizona. The explosive nature of this outbreak and the recognition of an unexpected tick vector, Rhipicephalus sanguineus, prompted an investigation to characterize RMSF in this unique setting and compare RMSF cases to similar illnesses., Methods: We compared medical records of 205 patients with RMSF and 175 with non-RMSF illnesses that prompted RMSF testing during 2002-2011 from 2 Indian reservations in Arizona., Results: RMSF cases in Arizona occurred year-round and peaked later (July-September) than RMSF cases reported from other US regions. Cases were younger (median age, 11 years) and reported fever and rash less frequently, compared to cases from other US regions. Fever was present in 81% of cases but not significantly different from that in patients with non-RMSF illnesses. Classic laboratory abnormalities such as low sodium and platelet counts had small and subtle differences between cases and patients with non-RMSF illnesses. Imaging studies reflected the variability and complexity of the illness but proved unhelpful in clarifying the early diagnosis., Conclusions: RMSF epidemiology in this region appears different than RMSF elsewhere in the United States. No specific pattern of signs, symptoms, or laboratory findings occurred with enough frequency to consistently differentiate RMSF from other illnesses. Due to the nonspecific and variable nature of RMSF presentations, clinicians in this region should aggressively treat febrile illnesses and sepsis with doxycycline for suspected RMSF., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

To assess the extent of abnormal gene expression in clones, we assessed global gene expression by microarray analysis on RNA from the placentas and livers of neonatal cloned mice derived by nuclear transfer (NT) from both cultured embryonic stem cells and freshly isolated cumulus cells. Direct comparison of gene expression profiles of more than 10,000 genes showed that for both donor cell types approximately 4% of the expressed genes in the NT placentas differed dramatically in expression levels from those in controls and that the majority of abnormally expressed genes were common to both types of clones. Importantly, however, the expression of a smaller set of genes differed between the embryonic stem cell- and cumulus cell-derived clones. The livers of the cloned mice also showed abnormal gene expression, although to a lesser extent, and with a different set of affected genes, than seen in the placentas. Our results demonstrate frequent abnormal gene expression in clones, in which most expression abnormalities appear common to the NT procedure whereas others appear to reflect the particular donor nucleus.

Biallelic expression of Igf2 is frequently seen in cancers because Igf2 functions as a survival factor. In many tumors the activation of Igf2 expression has been correlated with de novo methylation of the imprinted region. We have compared the intrinsic susceptibilities of the imprinted region of Igf2 and H19, other imprinted genes, bulk genomic DNA, and repetitive retroviral sequences to Dnmt1 overexpression. At low Dnmt1 methyltransferase levels repetitive retroviral elements were methylated and silenced. The nonmethylated imprinted region of Igf2 and H19 was resistant to methylation at low Dnmt1 levels but became fully methylated when Dnmt1 was overexpressed from a bacterial artificial chromosome transgene. Methylation caused the activation of the silent Igf2 allele in wild-type and Dnmt1 knockout cells, leading to biallelic Igf2 expression. In contrast, the imprinted genes Igf2r, Peg3, Snrpn, and Grf1 were completely resistant to de novo methylation, even when Dnmt1 was overexpressed. Therefore, the intrinsic difference between the imprinted region of Igf2 and H19 and of other imprinted genes to postzygotic de novo methylation may be the molecular basis for the frequently observed de novo methylation and upregulation of Igf2 in neoplastic cells and tumors. Injection of Dnmt1-overexpressing embryonic stem cells in diploid or tetraploid blastocysts resulted in lethality of the embryo, which resembled embryonic lethality caused by Dnmt1 deficiency.

The generation of adult animals by nuclear cloning from adult donor cells is extremely inefficient, with most clones dying soon after implantation. In contrast, cloning from embryonic stem cell donor nuclei is significanty more efficient than from adult donor cells. However, regardless of donor cell type, all clones that survive to birth and beyond suffer serious phenotypic and gene expression abnormalities. All available evidence is consistent with the notion that the anomalous phenotypes of cloned animals are caused by faulty epigenetic reprogramming of the donor nucleus. Faulty reprogramming appears to be caused by the cloning process itself as well as by the epigenetic state of the donor nucleus. In contrast to reproductive cloning, faulty reprogramming of the donor nucleus does not tend to interfere with the application of nuclear transfer technology for therapeutic purposes (therapeutic cloning).

Cloning by nuclear transfer (NT) is an inefficient process in which most clones die before birth and survivors often display growth abnormalities. In an effort to correlate gene expression with survival and fetal overgrowth, we have examined imprinted gene expression in both mice cloned by nuclear transfer and in the embryonic stem (ES) cell donor populations from which they were derived. The epigenetic state of the ES cell genome was found to be extremely unstable. Similarly, variation in imprinted gene expression was observed in most cloned mice, even in those derived from ES cells of the same subclone. Many of the animals survived to adulthood despite widespread gene dysregulation, indicating that mammalian development may be rather tolerant to epigenetic aberrations of the genome. These data imply that even apparently normal cloned animals may have subtle abnormalities in gene expression.