This study uses longitudinal data to follow a cohort (N = 4,465) of all early childhood education teachers working in publicly funded, center-based settings in Louisiana over a 3-year period. We ...present the proportion of teachers still at their sites across six time points between 2016 and 2019, providing the first statewide, longitudinal estimates of within-year and multiyear retention. We find that less than 40% teachers in the fall of 2016 are still at their site by the fall of 2019. Turnover is particularly high among childcare teachers (compared to teachers at Head Start or school-based pre-kindergarten), teachers of toddlers, and teachers new to their sites. Policy implications are discussed.
Portal vein tumor thrombus (PVTT) is strongly correlated to a poor prognosis for patients with hepatocellular carcinoma (HCC). In this study, we uncovered a causative link between hepatitis B virus ...(HBV) infection and development of PVTT. Mechanistically, elevated TGF-β activity, associated with the persistent presence of HBV in the liver tissue, suppresses the expression of microRNA-34a, leading to enhanced production of chemokine CCL22, which recruits regulatory T (Treg) cells to facilitate immune escape. These findings strongly suggest that HBV infection and activity of the TGF-β-miR-34a-CCL22 axis serve as potent etiological factors to predispose HCC patients for the development of PVTT, possibly through the creation of an immune-subversive microenvironment to favor colonization of disseminated HCC cells in the portal venous system.
► HBV positive status predisposes HCC patients to develop PVTT ► MiR-34a expression inversely correlates with TGF-β activity and PVTT ► HBV-induced TGF-β recruits Treg cells via suppression of miR-34a and induction of CCL22 ► TGF-β-miR-34a-CCL22 promotes tumor growth and metastasis via changing microenvironment
Immune checkpoint blockade targeting the programmed death-1 (PD-1) pathway has shown efficacy in several types of cancers including mismatch-repair-deficient colorectal carcinoma. In some tumor ...types, programmed death-ligand 1 (PD-L1) expression detected by immunohistochemistry has shown utility as a predictive marker for response to anti-PD-1 therapies. This utility, however, remains to be determined in colorectal carcinoma. In addition, although tumor-infiltrating lymphocytes have been associated with better prognosis in colorectal carcinoma, the prognostic value of PD-1 expression in these lymphocytes and its interaction with PD-L1 expression still await investigation. To address these questions, we performed a pilot study to evaluate the patterns of PD-L1 and PD-1 immunohistochemical expression on colorectal carcinoma cells and their tumor-infiltrating lymphocytes, respectively. Using tissue microarray, we found that 5% (19/394) of colorectal carcinomas exhibited high tumor PD-L1 expression, and 19% (76/392) had elevated numbers of PD-1-positive tumor-infiltrating lymphocytes. PD-L1 levels correlated with PD-1 levels (P<0.001), and mismatch-repair-deficient tumors had significantly higher rates of high PD-L1 and PD-1 expression when compared with mismatch-repair-proficient tumors (18% vs 2% and 50% vs 13%, respectively; P<0.001 for both). Staining intensity was also stronger for both markers in mismatch-repair-deficient tumors. Furthermore, we observed that among patients with mismatch-repair-deficient colorectal carcinoma, PD-1/PD-L1 expression stratified recurrence-free survival in an inter-dependent manner: an association between high PD-1-positive tumor-infiltrating lymphocytes and improved recurrence-free survival (P=0.041) was maintained only when the tumors had low-level PD-L1 expression (P=0.006); patients whose tumors had both high PD-1-positive tumor-infiltrating lymphocytes and high PD-L1 expression had a significantly worse recurrence-free survival (P<0.001). Thus, our results not only provide a foundation for further assessment of PD-L1 immunohistochemistry as a predictive marker for anti-PD-1 therapy in colorectal carcinoma, they also shed light on the prognostic impact of tumor-infiltrating lymphocytes in different subsets of mismatch-repair-deficient colorectal carcinomas.
This study investigated conditions under which family structure matters most for child well-being. Using data from the Children of the National Longitudinal Survey of Youth (n = 3,936), a national ...sample of U.S. families, it was estimated how changes in family structure related to changes in children's behavior between age 3 and 12 separately by household income level to determine whether associations depended on families' resources. Early changes in family structure, particularly from a two-biological-parent to single-parent family, predicted increases in behavior problems more than later changes, and movements into single and stepparent families mattered more for children of higher versus lower income parents. Results suggest that for children of higher income parents, moving into a stepfamily may improve, not undermine, behavior.
Policy Points
Social indicators of young peoples’ conditions and circumstances, such as high school graduation, food insecurity, and smoking, are improving even as subjective indicators of mental ...health and well‐being have been worsening. This divergence suggests policies targeting the social indicators may not have improved overall mental health and well‐being.
There are several plausible reasons for this seeming contradiction. Available data suggest the culpability of one or several common exposures poorly captured by existing social indicators.
Resolving this disconnect requires significant investments in population‐level data systems to support a more holistic, child‐centric, and up‐to‐date understanding of young people's lives.
In a pediatric patients, the burden of diabetes lies within the family. In the current era of intensive insulin therapy, perceived parental burden may affect the family's efforts at effective ...diabetes management. The aims of this study were to re-examine and revise a measure of perceived parental burden associated with caring for a child with diabetes in the current era.
A geographically diverse population of young people (N = 376) with Type 1 diabetes and their parents included participants in the Juvenile Diabetes Research Foundation continuous glucose monitoring study and patients from the Joslin Diabetes Center. Participants provided data on demographics, diabetes management, diabetes-specific family conflict, and quality of life at baseline and after 6 months of follow-up.
Young people were 12.9 ± 2.7 years old with diabetes duration of 6.3 ± 3.5 years. Mean HbA(1C) was 8.0 ± 1.2%(64 mmol/mol), 58% received insulin pump therapy, and young people monitored blood glucose 5.2 ± 2.3 times/day. Factor analysis yielded two factors, 'Immediate Burden' and 'Theoretical Burden'. The Problem Areas in Diabetes Survey - Parent Revised version (PAID-PR) demonstrated excellent internal consistency (Cronbach's α = 0.87; factor 1 α = 0.78; factor 2 α = 0.83). Greater parental burden was associated with more frequent blood glucose monitoring, higher HbA(1C) levels, greater diabetes-specific family conflict, and lower quality of life. Test-retest analysis was acceptable (r = 0.62).
The PAID-PR demonstrated excellent internal consistency, good test-retest reliability, and associations with diabetes-specific family conflict and quality of life. This brief measure may have both clinical and research utility in the management of young people with Type 1 diabetes.
IRE1α-XBP1 signaling is emerging as a central orchestrator of malignant progression and immunosuppression in various cancer types. Employing a computational XBP1s detection method applied to TCGA ...datasets, we demonstrate that expression of the XBP1s mRNA isoform predicts poor survival in non-small cell lung cancer (NSCLC) patients. Ablation of IRE1α in malignant cells delays tumor progression and extends survival in mouse models of NSCLC. This protective effect is accompanied by alterations in intratumoral immune cell subsets eliciting durable adaptive anti-cancer immunity. Mechanistically, cancer cell-intrinsic IRE1α activation sustains mPGES-1 expression, enabling production of the immunosuppressive lipid mediator prostaglandin E
. Accordingly, restoring mPGES-1 expression in IRE1α
cancer cells rescues normal tumor progression. We have developed an IRE1α gene signature that predicts immune cell infiltration and overall survival in human NSCLC. Our study unveils an immunoregulatory role for cancer cell-intrinsic IRE1α activation and suggests that targeting this pathway may help enhance anti-tumor immunity in NSCLC.
Several conceptual models have been considered for the assessment of personality pathology in DSM-5. This study sought to extend our previous findings to compare the long-term predictive validity of ...three such models: the five-factor model (FFM), the schedule for nonadaptive and adaptive personality (SNAP), and DSM-IV personality disorders (PDs).
An inception cohort from the Collaborative Longitudinal Personality Disorder Study (CLPS) was followed for 10 years. Baseline data were used to predict long-term outcomes, including functioning, Axis I psychopathology, and medication use.
Each model was significantly valid, predicting a host of important clinical outcomes. Lower-order elements of the FFM system were not more valid than higher-order factors, and DSM-IV diagnostic categories were less valid than dimensional symptom counts. Approaches that integrate normative traits and personality pathology proved to be most predictive, as the SNAP, a system that integrates normal and pathological traits, generally showed the largest validity coefficients overall, and the DSM-IV PD syndromes and FFM traits tended to provide substantial incremental information relative to one another.
DSM-5 PD assessment should involve an integration of personality traits with characteristic features of PDs.
The prevalence and clinical characteristics of small bowel adenocarcinomas (SBA) in the setting of Lynch syndrome have not been well studied. We characterized SBA according to DNA mismatch repair ...and/or microsatellite instability (MMR/MSI) and germline mutation status and compared clinical outcomes.
A single-institution review identified 100 SBAs. Tumors were evaluated for MSI via MSIsensor and/or corresponding MMR protein expression via IHC staining. Germline DNA was analyzed for mutations in known cancer predisposition genes, including MMR (
, and
). Clinical variables were correlated with MMR/MSI status.
Twenty-six percent (26/100; 95% confidence interval, 18.4-35.4) of SBAs exhibited MMR deficiency (MMR-D). Lynch syndrome prevalence was 10% overall and 38.5% among MMR-D SBAs. Median age at SBA diagnosis was similar in non-Lynch syndrome MMR-D versus MMR-proficient (MMR-P) SBAs (65 vs. 61;
= 0.75), but significantly younger in Lynch syndrome (47.5 vs. 61;
= 0.03). The prevalence of synchronous/metachronous cancers was 9% (6/67) in MMR-P versus 34.6% (9/26) in MMR-D SBA, with 66.7% (6/9) of these in Lynch syndrome (
= 0.0002). In the MMR-P group, 52.2% (35/67) of patients presented with metastatic disease, compared with 23.1% (6/26) in the MMR-D group (
= 0.008). In MMR-P stage I/II patients, 88.2% (15/17) recurred, compared with 18.2% (2/11) in the MMR-D group (
= 0.0002).
When compared with MMR-P SBA, MMR-D SBA was associated with earlier stage disease and lower recurrence rates, similar to observations in colorectal cancer. With a 38.5% prevalence in MMR-D SBA, germline Lynch syndrome testing in MMR-D SBA is warranted.
PDF
