To determine the overall effectiveness of interventions designed to increase physical activity (PA) behavior among community-dwelling older adults.
Comprehensive literature searching identified ...eligible PA intervention studies among community-dwelling adults aged 65 and older, or sample mean age of 70. Diverse study characteristics were extracted and outcome data were duplicate coded. Overall mean effect sizes (ESs) were synthesized using a random-effects model. Heterogeneity of effects was analyzed using Q and I(2) statistics. Moderator analyses were conducted using meta-analytic analogues of ANOVA and regression for dichotomous and continuous moderators, respectively.
ESs were calculated from 13,829 primary study subjects. The overall mean ES for two-group posttest comparisons was 0.18 (95% CI 0.10-0.26, p < .001). This represents a difference of 620 steps/day or 73 min of PA/week between treatment and control groups. Significant moderators included the use of theory, how interventions were delivered, and cognitive plus behavioral-type intervention components. Non-significant moderators include the type of interventionist, delivery setting, and various measures of intervention dose.
PA interventions significantly improved PA behavior among community-dwelling older adults. Effective PA interventions may be efficiently delivered using already available resources and personnel. Future PA intervention research should be theoretically based, incorporate more diverse subjects, and compare intervention delivery methods.
Polysaccharide-based nanoparticles have attracted interest as carriers for imaging and therapeutic agents because of their unique physicochemical properties, including biocompatibility and ...biodegradability. In addition, the functional groups of the polysaccharide backbone allow facile chemical modification to develop nanoparticles with diverse structures. Some polysaccharides have the intrinsic ability to recognize specific cell types, facilitating the design of targeted-drug delivery systems through receptor-mediated endocytosis. The main objective of this review is to provide an overview of various polysaccharide-based nanoparticles and to highlight the recent efforts that have been made to improve the characteristics of polysaccharide-based nanoparticles for drug delivery and biomedical imaging.
This systematic review applied meta-analytic procedures to synthesize medication adherence interventions that focus on adults with hypertension. Comprehensive searching located trials with medication ...adherence behavior outcomes. Study sample, design, intervention characteristics, and outcomes were coded. Random-effects models were used in calculating standardized mean difference effect sizes. Moderator analyses were conducted using meta-analytic analogues of ANOVA and regression to explore associations between effect sizes and sample, design, and intervention characteristics. Effect sizes were calculated for 112 eligible treatment-vs.-control group outcome comparisons of 34,272 subjects. The overall standardized mean difference effect size between treatment and control subjects was 0.300. Exploratory moderator analyses revealed interventions were most effective among female, older, and moderate- or high-income participants. The most promising intervention components were those linking adherence behavior with habits, giving adherence feedback to patients, self-monitoring of blood pressure, using pill boxes and other special packaging, and motivational interviewing. The most effective interventions employed multiple components and were delivered over many days. Future research should strive for minimizing risks of bias common in this literature, especially avoiding self-report adherence measures.
Exposure to environmental estrogens (xenoestrogens) may play a causal role in the increased breast cancer incidence which has been observed in Europe and the US over the last 50 years. The ...xenoestrogen bisphenol A (BPA) leaches from plastic food/beverage containers and dental materials. Fetal exposure to BPA induces preneoplastic and neoplastic lesions in the adult rat mammary gland. Previous results suggest that BPA acts through the estrogen receptors which are detected exclusively in the mesenchyme during the exposure period by directly altering gene expression, leading to alterations of the reciprocal interactions between mesenchyme and epithelium. This initiates a long sequence of altered morphogenetic events leading to neoplastic transformation. Additionally, BPA induces epigenetic changes in some tissues. To explore this mechanism in the mammary gland, Wistar-Furth rats were exposed subcutaneously via osmotic pumps to vehicle or 250 µg BPA/kg BW/day, a dose that induced ductal carcinomas in situ. Females exposed from gestational day 9 to postnatal day (PND) 1 were sacrificed at PND4, PND21 and at first estrus after PND50. Genomic DNA (gDNA) was isolated from the mammary tissue and immuno-precipitated using anti-5-methylcytosine antibodies. Detection and quantification of gDNA methylation status using the Nimblegen ChIP array revealed 7412 differentially methylated gDNA segments (out of 58207 segments), with the majority of changes occurring at PND21. Transcriptomal analysis revealed that the majority of gene expression differences between BPA- and vehicle-treated animals were observed later (PND50). BPA exposure resulted in higher levels of pro-activation histone H3K4 trimethylation at the transcriptional initiation site of the alpha-lactalbumin gene at PND4, concomitantly enhancing mRNA expression of this gene. These results show that fetal BPA exposure triggers changes in the postnatal and adult mammary gland epigenome and alters gene expression patterns. These events may contribute to the development of pre-neoplastic and neoplastic lesions that manifest during adulthood.
Recovery-oriented mental health service has become the focus of global change in mental health services. Most of North industrialized countries have adopted and implemented this paradigm in the last ...two decades. Only recently that some developing countries are trying to follow this step. In Indonesia's case, there has been little attention to developing a recovery orientation by mental health authorities. The aim of this article is to synthesize and analyze the recovery-oriented guidelines from five industrialized countries that we can use as a primary model for developing a protocol to be implemented in community health centre in Kulonprogo District, Yogyakarta, Indonesia.
We used a narrative literature review by searching for guidelines from many different sources. We found 57 guidelines, but only 13 from five countries met the criteria, including five guidelines from Australia, one from Ireland, three from Canada, two from the UK, and two from the US. To analyze the data, we used an inductive thematic analysis to explore the themes of each principle as described by the guideline.
The results of the thematic analysis revealed seven recovery principles, including (1) cultivating positive hope, (2) establishing partnerships and collaboration, (3) ensuring organizational commitment and evaluation, (4) recognizing the consumer's rights, (5) focusing on person-centeredness and empowerment, (6) recognizing an individual's uniqueness and social context, and (7) facilitating social support,. These seven principles are not independent, rather they are interrelated and overlap each other.
The principle of person-centeredness and empowerment is central to the recovery-oriented mental health system, while the principle of hope is also essential to embracing all the other principles. We will adjust and implement the result of the review in our project focusing on developing recovery-oriented mental health service in the community health center in Yogyakarta, Indonesia. We hope that this framework will be adopted by the central government in Indonesia and other developing countries.
Multi-protein complexes called inflammasomes have recently been identified and shown to contribute to cell death in tissue injury. Intravenous immunoglobulin (IVIg) is an FDA-approved therapeutic ...modality used for various inflammatory diseases. The objective of this study is to investigate dynamic responses of the NLRP1 and NLRP3 inflammasomes in stroke and to determine whether the NLRP1 and NLRP3 inflammasomes can be targeted with IVIg for therapeutic intervention. Primary cortical neurons were subjected to glucose deprivation (GD), oxygen-glucose deprivation (OGD) or simulated ischemia-reperfusion (I/R). Ischemic stroke was induced in C57BL/6J mice by middle cerebral artery occlusion, followed by reperfusion. Neurological assessment was performed, brain tissue damage was quantified, and NLRP1 and NLRP3 inflammasome protein levels were evaluated. NLRP1 and NLRP3 inflammasome components were also analyzed in postmortem brain tissue samples from stroke patients. Ischemia-like conditions increased the levels of NLRP1 and NLRP3 inflammasome proteins, and IL-1β and IL-18, in primary cortical neurons. Similarly, levels of NLRP1 and NLRP3 inflammasome proteins, IL-1β and IL-18 were elevated in ipsilateral brain tissues of cerebral I/R mice and stroke patients. Caspase-1 inhibitor treatment protected cultured cortical neurons and brain cells in vivo in experimental stroke models. IVIg treatment protected neurons in experimental stroke models by a mechanism involving suppression of NLRP1 and NLRP3 inflammasome activity. Our findings provide evidence that the NLRP1 and NLRP3 inflammasomes have a major role in neuronal cell death and behavioral deficits in stroke. We also identified NLRP1 and NLRP3 inflammasome inhibition as a novel mechanism by which IVIg can protect brain cells against ischemic damage, suggesting a potential clinical benefit of therapeutic interventions that target inflammasome assembly and activity.
The katanin microtubule-severing proteins are essential regulators of microtubule dynamics in a diverse range of species. Here we have defined critical roles for the poorly characterised katanin ...protein KATNAL2 in multiple aspects of spermatogenesis: the initiation of sperm tail growth from the basal body, sperm head shaping via the manchette, acrosome attachment, and ultimately sperm release. We present data suggesting that depending on context, KATNAL2 can partner with the regulatory protein KATNB1 or act autonomously. Moreover, our data indicate KATNAL2 may regulate δ- and ε-tubulin rather than classical α-β-tubulin microtubule polymers, suggesting the katanin family has a greater diversity of function than previously realised. Together with our previous research, showing the essential requirement of katanin proteins KATNAL1 and KATNB1 during spermatogenesis, our data supports the concept that in higher order species the presence of multiple katanins has allowed for subspecialisation of function within complex cellular settings such as the seminiferous epithelium.
The purpose of this article is to present a plausible framework to initiate discussion regarding the concept of emergence in grounded theory. Using ontological and epistemological positions to ...develop three research paradigms, and applying these paradigms to various uptakes of grounded theory demonstrates differences in the definition of emergence. Discovery emergence is presented as a unidirectional relationship between the constituent parts (data) and the emergent property (theory) observed by an external postpositivist grounded theorist. Mechanistic emergence is presented as having a bidirectional relationship between the constituent part (data) and the emergent property (theory) observed by an external constructionist grounded theorist. Finally, reflective emergence is presented as having a bidirectional relationship between the constituent parts (data) and the emergent property (theory) interpreted by an interpretivist grounded theorist.
ABSTRACT
Spermatogenesis is a dynamic process involving self‐renewal and differentiation of spermatogonial stem cells, meiosis, and ultimately, the differentiation of haploid spermatids into sperm. ...Centrosomal protein 55 kDa (CEP55) is necessary for somatic cell abscission during cytokinesis. It facilitates equal segregation of cytoplasmic contents between daughter cells by recruiting endosomal sorting complex required for transport machinery (ESCRT) at the midbody. In germ cells, CEP55, in partnership with testes expressed‐14 (TEX14) protein, has also been shown to be an integral component of intercellular bridge before meiosis. Various in vitro studies have demonstrated a role for CEP55 in multiple cancers and other diseases. However, its oncogenic potential in vivo remains elusive. To investigate, we generated ubiquitously overexpressing Cep55 transgenic (Cep55Tg/Tg)mice aiming to characterize its oncogenic role in cancer. Unexpectedly, we found that Cep55Tg/Tg male mice were sterile and had severe and progressive defects in spermatogenesis related to spermatogenic arrest and lack of spermatids in the testes. In this study, we characterized this male‐specific phenotype and showed that excessively high levels of Cep55 results in hyperactivation of PI3K/protein kinase B (Akt) signaling in testis. In line with this finding, we observed increased phosphorylation of forkhead box protein O1 (FoxO1), and suppression of its nuclear retention, along with the relative enrichment of promyelocytic leukemia zinc finger (PLZF)—positive cells. Independently, we observed that Cep55 amplification favored upregulation of ret (Ret) proto‐oncogene and glial‐derived neurotrophic factor family receptor a‐1 (Gfra1). Consistent with these data, we observed selective down‐regulation of genes associated with germ cell differentiation in Cep55‐overexpressing testes at postnatal day 10, including early growth response‐4 (Egr4) and spermatogenesis and oogenesis specific basic helix‐loop‐helix‐1 (Sohlh1). Thus, Cep55 amplification leads to a shift toward the initial maintenance of undifferentiated spermatogonia and ultimately results in progressive germ cell loss. Collectively, our findings demonstrate that Cep55 overexpression causes change in germ cell proportions and manifests as a Sertoli cell only tubule phenotype, similar to that seen in many azoospermic men.—Sinha, D., Kalimutho, M., Bowles, J., Chan, A.‐L., Merriner, D. J., Bain, A. L., Simmons, J. L., Freire, R., Lopez, J. A., Hobbs, R. M., O'Bryan, M. K., Khanna, K. K. Cep55 overexpression causes male‐specific sterility in mice by suppressing Foxo1 nuclear retention through sustained activation of PI3K/Akt signaling. FASEB J. 32, 4984–4999 (2018). www.fasebj.org
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