Teaching vocabulary and reading comprehension during social studies instruction is critical for reading development and the acquisition of content knowledge. This study systematically investigated ...how elementary teachers integrate vocabulary and reading comprehension instruction during social studies teaching, as well as the extent to which this instruction aligned with evidence-based practices. Thirty-three fourth grade teachers from 12 schools across three school districts recorded their social studies instruction for a total of 2429 min. Findings revealed that two-thirds of social studies instructional time integrated practices for developing vocabulary and reading comprehension. Yet, the approaches for teaching comprehension and methods for instructional delivery (e.g., explicit instruction, high-quality feedback) teachers used infrequently aligned with those identified as effective in previous research. We present opportunities for improving content-area instruction and future research.
To evaluate trends in the incidence of premenopausal unilateral and bilateral oophorectomy between 1950 and 2018.
The Rochester Epidemiology Project medical records-linkage system was used to ...identify all women aged 18-49 years who were residents of Olmsted County, Minnesota, and underwent unilateral or bilateral oophorectomy before spontaneous menopause between January 1, 1950, and December 31, 2018. Population denominators were derived from the U.S. Decennial Censuses for the years 1950-2010, and intercensal year population denominators were linearly interpolated. For 2011-2018, the annual population denominators were obtained from the U.S. Census projections. Where appropriate, overall incidence rates were age-adjusted to the total U.S. female population from the 2010 Census.
There were 5,154 oophorectomies in Olmsted County across the 69-year period between 1950 and 2018, and 2.9% showed malignant disease on pathology. A total of 2,092 (40.6%) women underwent unilateral oophorectomy, and 3,062 (59.4%) women underwent bilateral oophorectomy. More than half (n=1,750, 57.2%) of the bilateral oophorectomies occurred between 1990 and 2009. Until 1975-1979, the incidence of unilateral oophorectomy was mostly higher than bilateral oophorectomy. From 1980-1984 until 2000-2004, the incidence of bilateral oophorectomy more than doubled and the incidence of unilateral oophorectomy declined. After 2005, both procedures declined and converged to a similar incidence in 2015-2018. The decline in premenopausal bilateral oophorectomy over the past 14 years (2005-2018) was most pronounced for women who underwent oophorectomy concurrently with hysterectomy or did not have any ovarian indication.
The incidence rates of unilateral and bilateral oophorectomy have varied greatly across the 69-year period of this study. In the past 14 years, the incidence of premenopausal unilateral and bilateral oophorectomy has decreased. These trends reflect the effects of the initial 2005-2006 publications and the subsequent expanding body of evidence against the practice of oophorectomy for noncancer indications.
Abstract
Background
Several mechanisms underlying the depression-to-cardiovascular disease (CVD) relationship have been proposed; however, few studies have examined whether depression promotes CVD ...through potentiating traditional cardiovascular risk factors.
Purpose
To test the combined influence of three cardiovascular risk factors and lifetime depressive disorder on incident CVD in a large, diverse, and nationally representative sample of U.S. adults.
Methods
Respondents were 26,840 adults without baseline CVD who participated in Waves 1 (2001–2002) and 2 (2004–2005) of the National Epidemiologic Survey on Alcohol and Related Conditions. Lifetime depressive disorder, tobacco use, hypertension, and incident CVD were determined from structured interviews, and body mass index (BMI) was computed from self-reported height and weight.
Results
Logistic regression models predicting incident CVD (1,046 cases) revealed evidence of moderation, as the interactions between lifetime depressive disorder and current tobacco use (p = .002), hypertension (p < .001), and BMI (p = .031) were significant. The Former Tobacco Use × Lifetime Depressive Disorder interaction was not significant (p = .85). In models stratified by lifetime depressive disorder, current tobacco use (OR = 1.78, 95% CI = 1.36–2.32, p < .001 vs. OR = 1.41, 95% CI = 1.24–1.60, p < .001), hypertension (OR = 2.46, 95% CI = 1.98–3.07, p < .001 vs. OR = 1.39, 95% CI = 1.28–1.51, p < .001), and BMI (OR = 1.10, 95% CI = 1.01–1.20, p = .031 vs. OR = 1.03, 95% CI = 0.99–1.07, p = .16) were stronger predictors of incident CVD in adults with versus without a lifetime depressive disorder.
Conclusions
Our findings suggest that amplifying the atherogenic effects of traditional cardiovascular risk factors may be yet another candidate mechanism that helps to explain the excess CVD risk of people with depression.
Tobacco use, hypertension, and elevated body mass index are more strongly associated with future cardiovascular disease in adults with a lifetime history of depression than in those without such a history.
Glucocorticoid (GC) excess adversely affects skin integrity, inducing thinning and impaired wound healing. Aged skin, particularly that which has been photo-exposed, shares a similar phenotype. ...Previously, we demonstrated age-induced expression of the GC-activating enzyme 11 beta -hydroxysteroid dehydrogenase type 1 (11 beta -HSD1) in cultured human dermal fibroblasts (HDFs). Here, we determined 11 beta -HSD1 levels in human skin biopsies from young and older volunteers and examined the aged 11 beta -HSD1 KO mouse skin phenotype. 11 beta -HSD1 activity was elevated in aged human and mouse skin and in PE compared with donor-matched photo-protected human biopsies. Age-induced dermal atrophy with deranged collagen structural organization was prevented in 11 beta -HSD1 KO mice, which also exhibited increased collagen density. We found that treatment of HDFs with physiological concentrations of Cortisol inhibited rate-limiting steps in collagen biosynthesis and processing. Furthermore, topical 11 beta -HSD1 inhibitor treatment accelerated healing of full-thickness mouse dorsal wounds, with improved healing also observed in aged 11 beta -HSD1 KO mice. These findings suggest that elevated 11 beta -HSD1 activity in aging skin leads to increased local GC generation, which may account for adverse changes occurring in the elderly, and 11 beta -HSD1 inhibitors maybe useful in the treatment of age-associated impairments in dermal integrity and wound healing.
The ocean economy is experiencing rapid growth that will provide benefits but will also pose environmental and social risks. With limited space and degraded resources in coastal areas, offshore ...waters will be a particular focus of Blue Economy expansion over the next decade. When emerging and established economic sectors expand in offshore waters (within national Exclusive Economic Zones), different potential Blue Economy opportunities and challenges will arise. Following a series of interdisciplinary workshops, we imagine two technically possible futures for the offshore Blue Economy and we identify the actions required to achieve the more sustainable outcome. Under a business as usual scenario the focus will remain on economic growth, the commodification of nature, the dominance of private over public and cultural interests, and prioritisation of the interests of current over future generations. A more sustainable scenario would meet multiple UN Sustainable Development Goals and ensure inclusive economic developments, environmental sustainability, and fair and equitable access to resources and technologies across users, nations, and generations. Challenges to this more sustainable future are a lack of infrastructure and technology to support emerging offshore sectors, limited understanding of environmental impacts, inequitable outcomes, and a lack of planning and governmental oversight. Addressing these challenges will require a shift in societal values, a more balanced allocation of funding to offshore activities, transparency in information sharing between industries and across nations, and adjustment of international legal and institutional mechanisms. The sustainable and equitable offshore Blue Economy we envisage is achievable and provides a unique opportunity to build global capacity and partnership.
Graphic abstract
Group 3 tumors account for 28% of medulloblastomas and have the worst prognosis. FTY720, an immunosuppressant currently approved for treatment of multiple sclerosis, has shown antitumor effects in ...several human cancer cell lines. We hypothesized that treatment with FTY720 (fingolimod) would decrease tumorigenicity in medulloblastoma patient-derived xenografts (PDXs). Three Group 3 medulloblastoma PDXs (D341, D384 and D425) were utilized. Expression of PP2A and its endogenous inhibitors I2PP2A and CIP2A was detected by immunohistochemistry and immunoblotting. PP2A activation was measured via phosphatase activation kit. Cell viability, proliferation, migration and invasion assays were performed after treatment with FTY720. Cell cycle analysis was completed using flow cytometry. A flank model using D425 human medulloblastoma PDX cells was used to assess the in vivo effects of FTY720. FTY720 activated PP2A and led to decreased medulloblastoma PDX cell viability, proliferation, migration and invasion and G1 cell cycle arrest in all three PDXs. FTY720 treatment of mice bearing D425 medulloblastoma PDX tumors resulted in a significant decrease in tumor growth compared to vehicle treated animals. FTY720 decreased viability, proliferation, and motility in Group 3 medulloblastoma PDX cells and significantly decreased tumor growth in vivo. These results suggest that FTY720 should be investigated further as a potential therapeutic agent for medulloblastoma.
Protein phosphatase 2A (PP2A) functions as an inhibitor of cancer cell proliferation, and its tumor suppressor function is attenuated in many cancers. Previous studies utilized FTY720, an ...immunomodulating compound known to activate PP2A, and demonstrated a decrease in the malignant phenotype in neuroblastoma. We wished to investigate the effects of two novel PP2A activators, ATUX-792 (792) and DBK-1154 (1154).
Long-term passage neuroblastoma cell lines and human neuroblastoma patient-derived xenograft (PDX) cells were used. Cells were treated with 792 or 1154, and viability, proliferation, and motility were examined. The effect on tumor growth was investigated using a murine flank tumor model.
Treatment with 792 or 1154 resulted in PP2A activation, decreased cell survival, proliferation, and motility in neuroblastoma cells. Immunoblotting revealed a decrease in MYCN protein expression with increasing concentrations of 792 and 1154. Treatment with 792 led to tumor necrosis and decreased tumor growth in vivo.
PP2A activation with 792 or 1154 decreased survival, proliferation, and motility of neuroblastoma in vitro and tumor growth in vivo. Both compounds resulted in decreased expression of the oncogenic protein MYCN. These findings indicate a potential therapeutic role for these novel PP2A activators in neuroblastoma.
Chemoresistance contributes to relapse in high-risk neuroblastoma. Cancer cells acquire resistance through multiple mechanisms, including drug efflux pumps. In neuroblastoma, multidrug ...resistance-associated protein-1 (MRP1/ABCC1) efflux pump expression correlates with worse outcomes. These pumps are regulated by PIM kinases, a family of serine–threonine kinases, overexpressed in neuroblastoma. We hypothesized PIM kinase inhibition would sensitize neuroblastoma cells by modulating MRP1.
Kocak database query evaluated ABCC1, PIM1, PIM2, and PIM3 expression in neuroblastoma patients. SK-N-AS and SK-N-BE(2) cells were treated with doxorubicin or the pan-PIM kinase inhibitor, AZD1208. Flow cytometry assessed intracellular doxorubicin accumulation. AlamarBlue assay measured viability. The lethal dose 50% (LD50) of each drug and combination indices (CI) were calculated and isobolograms constructed to determine synergy.
Kocak database query demonstrated positive correlation between PIM genes and ABCC1. PIM kinase inhibition increased intracellular doxorubicin accumulation in both cell lines, suggesting PIM kinase regulation of MRP1. Isobolograms showed synergy between AZD1208 and doxorubicin.
The correlation between PIM and ABCC1 gene expression suggests PIM kinases may contribute to neuroblastoma chemotherapeutic resistance. PIM kinase inhibition increased intracellular doxorubicin accumulation. Combination treatment with AZD1208 and doxorubicin decreased neuroblastoma cell viability in a synergistic fashion. These findings support further investigations of PIM kinase inhibition in neuroblastoma.
Basic Science Research.
NA.
•PIM kinases are oncogenes implicated in drug resistance in numerous malignancies, though understanding of their role in neuroblastoma is lacking.•MRP1 is a drug efflux pump which removes doxorubicin, a commonly used neuroblastoma therapeutic, and is potentially targetable through PIM kinase inhibition.•Inhibition of PIM kinases results in increased intracellular doxorubicin accumulation and a more differentiated neuronal cell phenotype.
Smoldering multiple myeloma (SMM) is a precursor condition of multiple myeloma (MM) with a 10% annual risk of progression. Various prognostic models exist for risk stratification; however, those are ...based on solely clinical metrics. The discovery of genomic alterations that underlie disease progression to MM could improve current risk models.
We used next-generation sequencing to study 214 patients with SMM. We performed whole-exome sequencing on 166 tumors, including 5 with serial samples, and deep targeted sequencing on 48 tumors.
We observed that most of the genetic alterations necessary for progression have already been acquired by the diagnosis of SMM. Particularly, we found that alterations of the mitogen-activated protein kinase pathway (
and
single nucleotide variants SNVs), the DNA repair pathway (deletion 17p,
, and
SNVs), and
(translocations or copy number variations) were all independent risk factors of progression after accounting for clinical risk staging. We validated these findings in an external SMM cohort by showing that patients who have any of these three features have a higher risk of progressing to MM. Moreover, APOBEC associated mutations were enriched in patients who progressed and were associated with a shorter time to progression in our cohort.
SMM is a genetically mature entity whereby most driver genetic alterations have already occurred, which suggests the existence of a right-skewed model of genetic evolution from monoclonal gammopathy of undetermined significance to MM. We identified and externally validated genomic predictors of progression that could distinguish patients at high risk of progression to MM and, thus, improve on the precision of current clinical models.
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