16 research outputs found

    Recommendations for Child Care Centers

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    Design guide for planning, programming and designing different types of child care facilities. Includes 115 patterns for the policy, planning and design of large centers, neighborhood centers and family day-care homes. Based on current research information. Highly illustrated with photographs and sketches. Received an Award for Applied Research from Progressive Architecture, 1980, and received the 1980 UWM Foundation Research Award. Reprinted 1981, with new photographs in 1984, 1988 and in 1991. Revised edition 1994.https://dc.uwm.edu/caupr_mono/1032/thumbnail.jp

    Contribution of Genetic Background, Traditional Risk Factors, and HIV-Related Factors to Coronary Artery Disease Events in HIV-Positive Persons

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    We show in human immunodeficiency virus-positive persons that the coronary artery disease effect of an unfavorable genetic background is comparable to previous studies in the general population, and comparable in size to traditional risk factors and antiretroviral regimens known to increase cardiovascular ris

    Recessive Mutation in FAM83G Associated with Palmoplantar Keratoderma and Exuberant Scalp Hair

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    To the Editor Palmoplantar keratodermas are a heterogeneous group of disorders characterized by abnormal thickening of the volar epidermis (Blaydon and Kelsell, 2014, Maruthappu et al., 2014). A subset of palmoplantar keratodermas are associated with syndromes linked to other cutaneous features (Betz et al., 2012) and also noncutaneous conditions such as hearing loss, cardiomyopathy, and esophageal cancer (Blaydon Diana et al., 2012, Kelsell et al., 2001). Palmoplantar keratodermas specifically associated with defects in hair development include the desmosomal disorders linked to phenotypes such as woolly hair and alopecia (Brooke et al., 2012). Two adult siblings from a consanguineous family of Pakistani origin, whose parents were first cousins, presented with an autosomal recessively inherited palmoplantar keratoderma, leukonychia, and exuberant curly scalp hair (Figure 1a). Both affected individuals described the progressive development of yellowish thickened scaly skin affecting the palms and soles since 2 years of age, and toenail dystrophy in their teenage years. Examination revealed marked diffuse, verrucous hyperkeratosis with deep fissuring affecting the soles (Figure 1a) and to a lesser extent, the palms. There was no evidence of transgradiens. The toenails were dystrophic with onycholysis and leukonychia was also present, most evident in the finger nails. Onychomycosis was excluded by negative fungal culture. No abnormalities of teeth or sweating were identified. The siblings also described having extremely thick, rapidly growing curly scalp hair since childhood, but without excessive hair growth elsewhere. Neither parent had a similar hair or skin phenotype, and they had no other offspring. Clinical photographs were obtained, and written consent was provided by patients for their publication. Blood samples were collected after written informed consent in adherence with the Declaration of Helsinki principles and approval of the East London and City Health Authority. Whole-exome capture from both siblings was performed using SeqCap EZ Human Exome Library v2.0 (Roche NimbleGen, Madison, WI) and sequenced with 100-bp paired-end reads on the HiSeq 2000 platform (Illumina, San Diego, CA). Resulting reads were mapped to the hg18 human reference genome using the Novoalign alignment tool (Novocraft Technologies Sdn Bhd, Selangor, Malaysia). Sequence variants were called with SAMtools and annotated with ANNOVAR (Wang et al., 2010)

    Investigating iRHOM2-Associated Transcriptional Changes in Tylosis With Esophageal Cancer

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    Background and Aims: Survival rates for esophageal squamous cell carcinoma (ESCC) are extremely low due to the late diagnosis of most cases. An understanding of the early molecular processes that lead to ESCC may facilitate opportunities for early diagnosis; however, these remain poorly defined. Tylosis with esophageal cancer (TOC) is a rare syndrome associated with a high lifetime risk of ESCC and germline mutations in RHBDF2, encoding iRhom2. Using TOC as a model of ESCC predisposition, this study aimed to identify early-stage transcriptional changes in ESCC development. Methods: Esophageal biopsies were obtained from control and TOC individuals, the latter undergoing surveillance endoscopy, and adjacent diagnostic biopsies were graded as having no dysplasia or malignancy. Bulk RNA-Seq was performed, and findings were compared with sporadic ESCC vs normal RNA-Seq datasets. Results: Multiple transcriptional changes were identified in TOC samples, relative to controls, and many were detected in ESCC. Accordingly, pathway analyses predicted an enrichment of cancer-associated processes linked to cellular proliferation and metastasis, and several transcription factors were predicted to be associated with TOC and ESCC, including negative enrichment of GRHL2. Subsequently, a filtering strategy revealed 22 genes that were significantly dysregulated in both TOC and ESCC. Moreover, Keratin 17, which was upregulated in TOC and ESCC, was also found to be overexpressed at the protein level in ‘normal’ TOC esophagus tissue. Conclusion: Transcriptional changes occur in TOC esophagus prior to the onset of dysplasia, many of which are associated with ESCC. These findings support the utility of TOC to help reveal the early molecular processes that lead to sporadic ESCC

    A mechanistic evaluation of the Syrian hamster embryo cell transformation assay (pH 6.7) and molecular events leading to senescence bypass in SHE cells

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    The implementation of the Syrian hamster embryo cell transformation assay (SHE CTA) into test batteries and its relevance in predicting carcinogenicity has been long debated. Despite prevalidation studies to ensure reproducibility and minimise the subjective nature of the assay’s endpoint, an underlying mechanistic and molecular basis supporting morphological transformation (MT) as an indicator of carcinogenesis is still missing. We found that only 20 % of benzo(a)pyrene-induced MT clones immortalised suggesting that, alone, the MT phenotype is insufficient for senescence bypass. From a total of 12 B(a)P- immortalised MT lines, inactivating p53 mutations were identified in 30 % of clones, and the majority of these were consistent with the potent carcinogen’s mode of action. Expression of p16 was commonly silenced or markedly reduced with extensive promoter methylation observed in 45 % of MT clones, while Bmi1 was strongly upregulated in 25 % of clones. In instances where secondary events to MT appeared necessary for senescence bypass, as evidenced by a transient cellular crisis, clonal growth correlated with monoallelic deletion of the CDKN2A/B locus. The findings further implicate the importance of p16 and p53 pathways in regulating senescence while providing a molecular evaluation of SHE CTA -derived variant MT clones induced by benzo(a)pyrene

    Cognitive and neurobehavioral symptoms in patients with non-metastatic prostate cancer treated with androgen deprivation therapy or observation: A mixed methods study

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    BACKGROUND: Few studies have investigated prostate cancer patients’ experiences of cognitive functioning or neurobehavioral symptoms (i.e., behavioral changes associated with neurological dysfunction) following androgen deprivation therapy (ADT). METHODS: Semi-structured interviews conducted from the US by phone and in-person were used to explore and characterize the: 1) experience of cognitive and neurobehavioral functioning in non-metastatic prostate cancer patients undergoing ADT (n=19) compared with patients who had not undergone ADT (n=20); 2) perceived causes of cognitive and neurobehavioral symptoms; 3) impact of these symptoms on quality of life; and 4) strategies used to cope with or compensate for these symptoms. Neuropsychological performance was assessed to characterize the sample. RESULTS: Overall, ADT patients experienced marginally more cognitive problems than non-ADT (nADT) patients even though there were no significant differences between groups in neuropsychological performance. ADT patients also experienced more declines in prospective memory and multi-tasking than nADT patients. Significant proportions of participants in both groups also experienced retrospective memory, attention and concentration, and information processing difficulties. With respect to neurobehavioral symptoms, more ADT patients experienced emotional lability and impulsivity (both aspects of disinhibition) than nADT patients. Among the causes to which participants attributed declines, both groups attributed them primarily to aging. A majority of ADT patients also attributed declines to ADT. For both groups, increased cognitive and neurobehavioral symptoms negatively impacted quality of life, and most participants developed strategies to ameliorate these problems. CONCLUSION: ADT patients are more vulnerable to experiencing specific cognitive and neurobehavioral symptoms than nADT patients. This study highlights the importance of capturing: a) cognitive symptoms not easily detected using neuropsychological tests; b) neurobehavioral symptoms that can be confused with psychological symptoms, and c) causal beliefs that may affect how people cope with these symptoms. Effective interventions are needed to assist prostate cancer patients in managing these symptoms
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