Notes

Depression Avoidance in Child Principal Proper care: Setup and Link between Interpersonal Psychotherapy-Adolescent Expertise Instruction.
with an increased risk for the development of distant metastases.
Older adults are exhibiting greater diversity in their aging trajectories. This has led to movements by the World Health Organization and AARP to reframe aging. We compare role-based framing and age-based framing of older adults over 210 years-a time span beyond the reach of traditional methods-and elucidate their respective sentiments and narratives.

We combined the Corpus of Historical American English with the Corpus of Contemporary American English to create a 600-million-word-dataset-the largest historical corpus of American English with over 150,000 texts collected from newspapers, magazines, fiction and non-fiction. We compiled the top descriptors of age-based terms (e.g., senior citizen) and role-based terms (e.g., grandparent) and rated them for stereotypic valence (negative to positive) over 21 decades.

Age-based framing evidenced a significantly higher increase in negativity (15%) compared to role-based framing (4%). We found a significant interaction effect between framing (age-based vs. role-based) and stereotypic content across two centuries (1800s and 1900s). The percentage of positive topics associated with role-based framing increased from 71% in the 1800s to 89% in the 1900s, with narratives of affection and wisdom becoming more prevalent. Conversely, the percentage of positive topics for age-based framing decreased from 82% to 38% over time, with narratives of burden, illness and death growing more prevalent.

We argue for a more role-centric approach when framing aging such that age ceases to be the chief determinant in how older adults are viewed in society.
We argue for a more role-centric approach when framing aging such that age ceases to be the chief determinant in how older adults are viewed in society.Long-term survivability is well-known for microorganisms in nutrient-depleted environments, but the damage accrued by proteins and the associated repair processes during the starvation and recovery phase of microbial life still remain enigmatic. We focused on aspartic acid (Asp) racemization and repair in the survival of Pyrococcus furiosus and Thermococcus litoralis under starvation conditions at high temperature. Despite the dramatic decrease of viability over time, 0.002% of P. furiosus cells (2.1×103 cells/mL) and 0.23% of T. litoralis cells (2.3×105 cells/mL) remained viable after 25 and 50 days, respectively. The D/L Asp ratio in the starved cells was approximately half of those from the autoclaved cells, suggesting that the starving cells were capable of partially repairing racemized Asp. Transcriptomic analyses of the recovered cells of T. litoralis indicated that the gene encoding Protein-L-isoaspartate (D-aspartate) O-methyltransferase (PIMT) might be involved in the repair of damaged proteins by converting D-Asp back to L-Asp during the resuscitation of starved cells. Collectively, our results provided evidence that Asp underwent racemization in the surviving hyperthermophilic cells under starved conditions and PIMT played a critical role in the repair of abnormal aspartyl residues during the initial recovery of starved, yet still viable, cells.Robustness and resilience are widely used in the biological sciences and related disciplines to describe how systems respond to change. Robustness is the ability to tolerate change without adapting or moving to another state. Resilience refers to the ability for a system to sustain a perturbation and maintain critical functions. Robustness and resilience transcend levels of biological organization, though they do not scale directly across levels. We live in an era of novel stressors and unprecedented change, including climate change, emerging environmental contaminants, and changes to earth's biogeochemical and hydrological cycles. We envision a common framework for developing models to predict the robustness and resilience of biological functions associated with complex systems that can transcend disciplinary boundaries. Conceptual and quantitative models of robustness and resilience must consider cross-scale interactions of potentially infinite complexity, but it is impossible to capture everything within a single model. Here, we discuss the need to balance accuracy and complexity when designing models, data collection, and downstream analyses to study robustness and resilience. We also consider the difficulties in defining the spatiotemporal domain when studying robustness and resilience as an emergent property of a complex system. We suggest a framework for implementing transdisciplinary research on robustness and resilience of biological systems that draws on participatory stakeholder engagement methods from the fields of conservation and natural resources management. Further, we suggest that a common, simplified model development framework for describing complex biological systems will provide new, broadly relevant educational tools. Efficient interdisciplinary collaboration to accurately develop a model of robustness and resilience would enable rapid, context-specific assessment of complex biological systems with benefits for a broad range of societally relevant problems.In an effort to expedite the publication of articles , AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.
Older age is a risk factor for TB in low incidence settings. Using data from the U.S. National TB Surveillance System and American Community Survey, we estimated trends and racial/ethnic differences in TB incidence among US-born cohorts aged ≥50 years.

42,000 TB cases among US-born persons ≥50 years were reported during 2001-2019. We used generalized additive regression models to decompose the effects of birth cohort and age on TB incidence rates, stratified by sex and race/ethnicity. Using genotype-based estimates of recent transmission (available 2011-2019), we implemented additional models to decompose incidence trends by estimated recent versus remote infection.

Estimated incidence rates declined with age, for the overall cohort and most sex and race/ethnicity strata. Average annual percentage declines flattened for older individuals, from 8.80% (95% confidence interval 8.34-9.23) in 51-year-olds to 4.51% (3.87-5.14) in 90-year-olds. Controlling for age, incidence rates were lower for more recent birth cohorts, dropping 8.79% (6.13-11.26) on average between successive cohort years. Incidence rates were substantially higher for racial/ethnic minorities, and these inequalities persisted across all birth cohorts. Rates from recent infection declined at approximately 10% per year as individuals aged. Rates from remote infection declined more slowly with age, and this annual percentage decline approached zero for the oldest individuals.

TB rates were highest for racial/ethnic minorities and for the earliest birth cohorts and declined with age. For the oldest individuals, annual percentage declines were low, and most cases were attributed to remote infection.
TB rates were highest for racial/ethnic minorities and for the earliest birth cohorts and declined with age. For the oldest individuals, annual percentage declines were low, and most cases were attributed to remote infection.Fc γ receptor IIB (FcγRIIB) is an inhibitory molecule capable of reducing antibody immunotherapy efficacy. We hypothesized its expression could confer resistance in patients with diffuse large B-cell lymphoma (DLBCL) treated with anti-CD20 monoclonal antibody (mAb) chemoimmunotherapy, with outcomes varying depending on mAb (rituximab [R]/obinutuzumab [G]) because of different mechanisms of action. We evaluated correlates between FCGR2B messenger RNA and/or FcγRIIB protein expression and outcomes in 3 de novo DLBCL discovery cohorts treated with R plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) reported by Arthur, Schmitz, and Reddy, and R-CHOP/G-CHOP-treated patients in the GOYA trial (NCT01287741). In the discovery cohorts, higher FCGR2B expression was associated with significantly shorter progression-free survival (PFS; Arthur hazard ratio [HR], 1.09; 95% confidence interval [CI], 1.01-1.19; P = .0360; Schmitz HR, 1.13; 95% CI, 1.02-1.26; P = .0243). Similar results were observed in GOYA with R-CHOP (HR, 1.26; 95% CI, 1.00-1.58; P = .0455), but not G-CHOP (HR, 0.91; 95% CI, 0.69-1.20; P = .50). A nonsignificant trend that high FCGR2B expression favored G-CHOP over R-CHOP was observed (HR, 0.67; 95% CI, 0.44-1.02; P = .0622); however, low FCGR2B expression favored R-CHOP (HR, 1.58; 95% CI, 1.00-2.50; P = .0503). In Arthur and GOYA, FCGR2B expression was associated with tumor FcγRIIB expression; correlating with shorter PFS for R-CHOP (HR, 2.17; 95% CI, 1.04-4.50; P = .0378), but not G-CHOP (HR, 1.37; 95% CI, 0.66-2.87; P = .3997). This effect was independent of established prognostic biomarkers. High FcγRIIB/FCGR2B expression has prognostic value in R-treated patients with DLBCL and may confer differential responsiveness to R-CHOP/G-CHOP.Single-nucleotide polymorphisms (SNPs) have been shown to influence Fcγ receptor (FcγR) affinity and activity, but their effect on treatment response is unclear. We assessed their importance in the efficacy of obinutuzumab or rituximab combined with chemotherapy in untreated advanced follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) in the GALLIUM (www.clinicaltrials.gov #NCT01332968) and GOYA (#NCT01287741) trials, respectively. Genomic DNA was extracted from patients enrolled in GALLIUM (n = 1202) and GOYA (n = 1418). Key germline SNPs, FCGR2A R131H (rs1801274), FCGR3A F158V (rs396991), and FCGR2B I232T (rs1050501), were genotyped and assessed for their impact on investigator-assessed progression-free survival (PFS). In both cohorts there was no prognostic effect of FCGR2A or FCGR3A. In FL, FCGR2B was associated with favorable PFS in univariate and multivariate analyses comparing I232T with I232I, with a more modest association for rituximab-treated (univariate hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.54-1.14; P = .21) vs obinutuzumab-treated patients (HR, 0.56; 95% CI, 0.34-0.91; P = .02). selleck products Comparing T232T with I232I, an association was found for obinutuzumab (univariate HR, 2.76; 95% CI, 1.02-7.5; P = .0459). Neither observation retained significance after multiple-test adjustment. FCGR2B was associated with poorer PFS in multivariate analyses comparing T232T with I232I in rituximab- but not obinutuzumab-treated patients with DLBCL (HR, 4.40; 95% CI, 1.71-11.32; P = .002; multiple-test-adjusted P = .03); however, this genotype was rare (n = 13). This study shows that FcγR genotype is not associated with response to rituximab/obinutuzumab plus chemotherapy in treatment-naive patients with advanced FL or DLBCL.Patients with ovarian clear cell carcinoma (OCCC) experience frequent recurrence, which is most likely due to chemoresistance. We used shotgun proteomics analysis and identified upregulation of ezrin-binding phosphoprotein 50 (EBP50) in recurrent OCCC samples. Cytoplasmic and/or nuclear (Cyt/N), but not membranous, EBP50 immunoreactivity was significantly higher in recurrent OCCC as compared to that of primary tumors. OCCC cells expressing cytoplasmic EBP50 were significantly less susceptible to cisplatin (CDDP)-induced apoptosis compared to cells expressing membranous EBP50. Abrogation of resistance following knockdown of cytoplasmic EBP50 was accompanied by decreased XIAP and BCL2, increased BAX and increased caspase-3 cleavage. We found that poly (ADP-ribose) polymerase1 (PARP1), which is involved in DNA damage detection and repair, binds to EBP50 through its PDZ1 domain. CDDP treatment of cells expressing cytoplasmic (but not membranous) EBP50 increased nuclear PARP1 expression, whereas knockdown of EBP50 cells decreased PARP1 expression and activity following CDDP treatment.
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