Academic Functioning and Mental Health in Adolescence

The current study examines patterns of academic functioning and mental health in 184 middle school children and the relation of such patterns to their prior and subsequent functioning. Data were collected from children during their second, third, fourth, eighth, and ninth grade school years. Cluster analyses were used to delineate patterns of academic functioning and mental health during eighth grade. The authors examined the relation of these patterns to academic functioning and mental health 1 year later the transition to high school, and then examined the long-term developmental roots of the eighth grade patterns using data collected during elementary school years. Results indicated variegated patterns of academic and emotional functioning at eighth grade and stability in these patterns across the high school transition. Some long-term continuity was found among children showing uniformly positive or negative functioning at eighth grade. Studying child functioning across multiple domains and time periods is discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68127/2/10.1177_0743558499142002.pd

Mortality Among Adults With Cancer Undergoing Chemotherapy or Immunotherapy and Infected With COVID-19

Importance: Large cohorts of patients with active cancers and COVID-19 infection are needed to provide evidence of the association of recent cancer treatment and cancer type with COVID-19 mortality. // Objective: To evaluate whether systemic anticancer treatments (SACTs), tumor subtypes, patient demographic characteristics (age and sex), and comorbidities are associated with COVID-19 mortality. // Design, Setting, and Participants: The UK Coronavirus Cancer Monitoring Project (UKCCMP) is a prospective cohort study conducted at 69 UK cancer hospitals among adult patients (≥18 years) with an active cancer and a clinical diagnosis of COVID-19. Patients registered from March 18 to August 1, 2020, were included in this analysis. // Exposures: SACT, tumor subtype, patient demographic characteristics (eg, age, sex, body mass index, race and ethnicity, smoking history), and comorbidities were investigated. // Main Outcomes and Measures: The primary end point was all-cause mortality within the primary hospitalization. // Results: Overall, 2515 of 2786 patients registered during the study period were included; 1464 (58%) were men; and the median (IQR) age was 72 (62-80) years. The mortality rate was 38% (966 patients). The data suggest an association between higher mortality in patients with hematological malignant neoplasms irrespective of recent SACT, particularly in those with acute leukemias or myelodysplastic syndrome (OR, 2.16; 95% CI, 1.30-3.60) and myeloma or plasmacytoma (OR, 1.53; 95% CI, 1.04-2.26). Lung cancer was also significantly associated with higher COVID-19–related mortality (OR, 1.58; 95% CI, 1.11-2.25). No association between higher mortality and receiving chemotherapy in the 4 weeks before COVID-19 diagnosis was observed after correcting for the crucial confounders of age, sex, and comorbidities. An association between lower mortality and receiving immunotherapy in the 4 weeks before COVID-19 diagnosis was observed (immunotherapy vs no cancer therapy: OR, 0.52; 95% CI, 0.31-0.86). // Conclusions and Relevance: The findings of this study of patients with active cancer suggest that recent SACT is not associated with inferior outcomes from COVID-19 infection. This has relevance for the care of patients with cancer requiring treatment, particularly in countries experiencing an increase in COVID-19 case numbers. Important differences in outcomes among patients with hematological and lung cancers were observed

The clinical course of COVID-19 in pregnant versus non-pregnant women requiring hospitalisation: results from the multicentre UK CA-COVID-19 study.

The impact of COVID-19 infection on pregnant women remains relatively unknown but the physiological changes of pregnancy and hypercoagulability of COVID-19 may further increase thrombotic risk. In this retrospective multicentre observational study, we report clinical characteristics and outcomes in 36 pregnant women requiring hospitalisation for COVID-19 compared to a propensity matched cohort of non-pregnant women. Pregnant women had lower haemoglobin and higher lymphocyte counts but no differences in other haematological or biochemical parameters on admission compared to non-pregnant women. There was no significant difference in the duration of hospitalisation; median 2days (1-77) for pregnant women vs 8days (1-49) for non-pregnant. A higher proportion of non-pregnant women required mechanical ventilation [11/36 (31%) vs 3/36 (8%), p=0.03] and received thromboprophylaxis with low molecular weight heparin within 24hrs of admission [25/36 (69%) vs 15 /36(42%), p=0.03] compared to pregnant women. One pregnant woman required extracorporeal membrane oxygenation. Rate of thrombosis was similar in both groups (1 in each group). No women developed major bleeding or died. Data suggests that although non-pregnant women had severe clinical course, overall outcomes were not different between women with or without pregnancy. Use of thromboprophylaxis was inconsistent, demonstrating a need for establishing evidence-based guidance for COVID-19 during pregnancy

Targeting Bcl-2-IP3 receptor interaction to reverse Bcl-2's inhibition of apoptotic calcium signals

The antiapoptotic protein Bcl-2 inhibits Ca2+ release from the endoplasmic reticulum (ER). One proposed mechanism involves an interaction of Bcl-2 with the inositol 1,4,5-trisphosphate receptor (IP3R) Ca2+ channel localized with Bcl-2 on the ER. Here we document Bcl-2-IP3R interaction within cells by FRET and identify a Bcl-2 interacting region in the regulatory and coupling domain of the IP3R. A peptide based on this IP3R sequence displaced Bcl-2 from the IP3R and reversed Bcl-2-mediated inhibition of IP3R channel activity in vitro, IP3-induced ER Ca2+ release in permeabilized cells, and cell-permeable IP3 ester-induced Ca2+ elevation in intact cells. This peptide also reversed Bcl-2's inhibition of T cell receptor-induced Ca2+ elevation and apoptosis. Thus, the interaction of Bcl-2 with IP3Rs contributes to the regulation of proapoptotic Ca2+ signals by Bcl-2, suggesting the Bcl-2-IP3R interaction as a potential therapeutic target in diseases associated with Bcl-2's inhibition of cell death