Measured and perceived environmental characteristics are related to accelerometer defined physical activity in older adults

<p>Abstract</p> <p>Background</p> <p>Few studies have investigated both the self-perceived and measured environment with objectively determined physical activity in older adults. Accordingly, the aim of this study was to examine measured and perceived environmental associations with physical activity of older adults residing across different neighborhood types.</p> <p>Methods</p> <p>One-hundred and forty-eight older individuals, mean age 64.3 ± 8.4, were randomly recruited from one of four neighborhoods that were pre-determined as either having high- or low walkable characteristics. Individual residences were geocoded and 200 m network buffers established. Both objective environment audit, and self-perceived environmental measures were collected, in conjunction with accelerometer derived physical activity behavior. Using both perceived and objective environment data, analysis consisted of a macro-level comparison of physical activity levels across neighborhood, and a micro-level analysis of individual environmental predictors of physical activity levels.</p> <p>Results</p> <p>Individuals residing in high-walkable neighborhoods on average engaged in 11 min of moderate to vigorous physical activity per day more than individuals residing in low-walkable neighborhoods. Both measured access to non-residential destinations (b = .11, <it>p </it>< .001) and self-perceived access to non-residential uses (b = 2.89, <it>p </it>= .031) were significant predictors of time spent in moderate to vigorous physical activity. Other environmental variables significantly predicting components of physical activity behavior included presence of measured neighborhood crime signage (b = .4785, <it>p </it>= .031), measured street safety (b = 26.8, <it>p </it>= .006), and perceived neighborhood satisfaction (b = .5.8, <it>p </it>= .003).</p> <p>Conclusions</p> <p>Older adult residents who live in high-walkable neighborhoods, who have easy and close access to nonresidential destinations, have lower social dysfunction pertinent to crime, and generally perceive the neighborhood to a higher overall satisfaction are likely to engage in higher levels of physical activity behavior. Efforts aimed at promoting more walkable neighborhoods could influence activity levels in older adults.</p

Human‐specific polymorphic pseudogenization of SIGLEC12 protects against advanced cancer progression

Compared with our closest living evolutionary cousins, humans appear unusually prone to develop carcinomas (cancers arising from epithelia). The SIGLEC12 gene, which encodes the Siglec-XII protein expressed on epithelial cells, has several uniquely human features: a fixed homozygous missense mutation inactivating its natural ligand recognition property; a polymorphic frameshift mutation eliminating full-length protein expression in ~60%-70% of worldwide human populations; and, genomic features suggesting a negative selective sweep favoring the pseudogene state. Despite the loss of canonical sialic acid binding, Siglec-XII still recruits Shp2 and accelerates tumor growth in a mouse model. We hypothesized that dysfunctional Siglec-XII facilitates human carcinoma progression, correlating with known tumorigenic signatures of Shp2-dependent cancers. Immunohistochemistry was used to detect Siglec-XII expression on tissue microarrays. PC-3 prostate cancer cells were transfected with Siglec-XII and transcription of genes enriched with Siglec-XII was determined. Genomic SIGLEC12 status was determined for four different cancer cohorts. Finally, a dot blot analysis of human urinary epithelial cells was established to determine the Siglec-XII expressors versus non-expressors. Forced expression in a SIGLEC12 null carcinoma cell line enriched transcription of genes associated with cancer progression. While Siglec-XII was detected as expected in ~30%-40% of normal epithelia, ~80% of advanced carcinomas showed strong expression. Notably, &gt;80% of late-stage colorectal cancers had a functional SIGLEC12 allele, correlating with overall increased mortality. Thus, advanced carcinomas are much more likely to occur in individuals whose genomes have an intact SIGLEC12 gene, likely because the encoded Siglec-XII protein recruits Shp2-related oncogenic pathways. The finding has prognostic, diagnostic, and therapeutic implications

Epidemiological Surveillance of Birth Defects Compatible with Thalidomide Embryopathy in Brazil

The thalidomide tragedy of the 1960s resulted in thousands of children being born with severe limb reduction defects (LRD), among other malformations. In Brazil, there are still babies born with thalidomide embryopathy (TE) because of leprosy prevalence, availability of thalidomide, and deficiencies in the control of drug dispensation. Our objective was to implement a system of proactive surveillance to identify birth defects compatible with TE. Along one year, newborns with LRD were assessed in the Brazilian hospitals participating in the Latin-American Collaborative Study of Congenital Malformations (ECLAMC). A phenotype of LRD called thalidomide embryopathy phenotype (TEP) was established for surveillance. Children with TEP born between the years 2000–2008 were monitored, and during the 2007–2008 period we clinically investigated in greater detail all cases with TEP (proactive period). The period from 1982 to 1999 was defined as the baseline period for the cumulative sum statistics. The frequency of TEP during the surveillance period, at 3.10/10,000 births (CI 95%: 2.50–3.70), was significantly higher than that observed in the baseline period (1.92/10,000 births; CI 95%: 1.60–2.20), and not uniformly distributed across different Brazilian regions. During the proactive surveillance (2007–2008), two cases of suspected TE were identified, although the two mothers had denied the use of the drug during pregnancy. Our results suggest that TEP has probably increased in recent years, which coincides with the period of greater thalidomide availability. Our proactive surveillance identified two newborns with suspected TE, proving to be a sensitive tool to detect TE. The high frequency of leprosy and the large use of thalidomide reinforce the need for a continuous monitoring of TEP across Brazil

Characterizing the tumor microenvironment in rare renal cancer histological types

The tumor microenvironment (TME), including immune cells, cancer-associated fibroblasts, endothelial cells, adjacent normal cells, and others, plays a crucial role in influencing tumor behavior and progression. Here, we characterized the TME in 83 primary renal tumors and matched metastatic or recurrence tissue samples (n&nbsp;= 15) from papillary renal cell carcinoma (pRCC) types 1 (n&nbsp;= 20) and 2 (n&nbsp;= 49), collecting duct carcinomas (CDC; n&nbsp;= 14), and high-grade urothelial carcinomas (HGUC; n&nbsp;= 5). We investigated 10 different markers of immune infiltration, vasculature, cell proliferation, and epithelial-to-mesenchymal transition by using machine learning image analysis in conjunction with immunohistochemistry. Marker expression was compared by Mann-Whitney and Kruskal-Wallis tests and correlations across markers using Spearman's rank correlation coefficient. Multivariable Poisson regression analysis was used to compare marker expression between histological types, while accounting for variation in tissue size. Several immune markers showed different rates of expression across histological types of renal carcinoma. Using pRCC1 as reference, the incidence rate ratio (IRR) of CD3+ T cells (IRR [95% confidence interval, CI]&nbsp;=&nbsp;2.48 [1.53-4.01]) and CD20+ B cells (IRR [95% CI]&nbsp;=&nbsp;4.38 [1.22-5.58]) was statistically significantly higher in CDC. In contrast, CD68+ macrophages predominated in pRCC1 (IRR [95% CI]&nbsp;=&nbsp;2.35 [1.42-3.9]). Spatial analysis revealed CD3+ T-cell and CD20+ B-cell expressions in CDC to be higher at the proximal (p&nbsp;&lt; 0.0001) and distal (p&nbsp;&lt; 0.0001) tumor periphery than within the central tumor core. In contrast, expression of CD68+ macrophages in pRCC2 was higher in the tumor center compared to the proximal (p&nbsp;= 0.0451) tumor periphery and pRCC1 showed a distance-dependent reduction, from the central tumor, in CD68+ macrophages with the lowest expression of CD68 marker at the distal tumor periphery (p&nbsp;= 0.004). This study provides novel insights into the TME of rare kidney cancer types, which are often understudied. Our findings of differences in marker expression and localization by histological subtype could have implications for tumor progression and response to immunotherapies or other targeted therapies

Molecular and functional profiling identifies therapeutically targetable vulnerabilities in plasmablastic lymphoma

Plasmablastic lymphoma (PBL) represents a rare and aggressive lymphoma subtype frequently associated with immunosuppression. Clinically, patients with PBL are characterized by poor outcome. The current understanding of the molecular pathogenesis is limited. A hallmark of PBL represents its plasmacytic differentiation with loss of B-cell markers and, in 60% of cases, its association with Epstein-Barr virus (EBV). Roughly 50% of PBLs harbor a MYC translocation. Here, we provide a comprehensive integrated genomic analysis using whole exome sequencing (WES) and genome-wide copy number determination in a large cohort of 96 primary PBL samples. We identify alterations activating the RAS-RAF, JAK-STAT, and NOTCH pathways as well as frequent high-level amplifications in MCL1 and IRF4. The functional impact of these alterations is assessed using an unbiased shRNA screen in a PBL model. These analyses identify the IRF4 and JAK-STAT pathways as promising molecular targets to improve outcome of PBL patients

Guided portfolio writing as a scaffold for reflective learning in in-service contexts: A case study

Language is widely recognized as an inescapable mediating tool for professional learning, and with this text we want to contribute to a better understanding of the particular role that guided writing can play in in-service professional reflective learning. We analysed one pre-school teacher’s written portfolio, the construction of which was guided to scaffold deep thinking about (and the transference of theory into) practice during participation in an in-service program about language education. Our case study shows that the writing process sustained robust learning about professional knowing, doing and learning itself: The teacher elaborated an integrative ethical understanding of the discussed theory, fully experienced newly informed practices and assessed her own learning by using theory to confront her previous knowledge and practices. Throughout the portfolio, the learning stance revealed by her voice varied accordingly. The study illustrates the potential of guided writing to scaffold reflective learning in in-service contexts.Fundação para a Ciência e a Tecnologia (FCT), Portugal. PEst-OE/CED/UI1661/2011] through CIEd (Centro de Estudos em Educação). PEst-OE/CED/UI0317/2014] through CIEC.info:eu-repo/semantics/publishedVersio

BC1-FMRP interaction is modulated by 2′-O-methylation: RNA-binding activity of the tudor domain and translational regulation at synapses

The brain cytoplasmic RNA, BC1, is a small non-coding RNA that is found in different RNP particles, some of which are involved in translational control. One component of BC1-containing RNP complexes is the fragile X mental retardation protein (FMRP) that is implicated in translational repression. Peptide mapping and computational simulations show that the tudor domain of FMRP makes specific contacts to BC1 RNA. Endogenous BC1 RNA is 2′-O-methylated in nucleotides that contact the FMRP interface, and methylation can affect this interaction. In the cell body BC1 2′-O-methylations are present in both the nucleus and the cytoplasm, but they are virtually absent at synapses where the FMRP–BC1–mRNA complex exerts its function. These results strongly suggest that subcellular region-specific modifications of BC1 affect the binding to FMRP and the interaction with its mRNA targets. We finally show that BC1 RNA has an important role in translation of certain mRNAs associated to FMRP. All together these findings provide further insights into the translational regulation by the FMRP–BC1 complex at synapses

W mass and Leptonic Z-decays in the NMSSM

We study a subset of electroweak-precision observables consisting of $M_W$, $\sin^2\theta_{{\tiny eff}}^{\tau}$, $BR(Z\to\tau^+\tau^-)$ and $\Gamma(Z\to\tau^+\tau^-)/\Gamma(Z\to e^+e^-)-1$ (characterizing leptonic $Z$-decays) in the context of the NMSSM. After a brief review of common MSSM-NMSSM effects, e.g. for $\Gamma(Z\to\tau^+\tau^-)/\Gamma(Z\to e^+e^-)-1$, which has been little discussed, even in the MSSM), specific NMSSM scenarios are studied, with the result that the NMSSM, considering existing constraints on its spectrum, is essentially consistent with available measurements, given the current accuracy.Comment: 25 pages, 12 figure