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Stokholm Thorsen opublikował 5 miesięcy, 1 tydzień temu
The brown booby (Sula leucogaster Boddaert, 1783) has a wide geographic distribution, being found throughout the intertropical range except for the west coast of South America. Chewing lice (Phthiraptera Amblycera and Ischnocera) are ectoparasites commonly found in association with a wide variety of bird species, and extensive infestations can lead to severe itching and irritation that causes skin lesions, damage to the plumage, and abandonment of nests. Sula leucogaster lice have an atypical distribution, not fully following the distribution of their host. In the years 2018 and 2019, 4 marine animal rehabilitation centers located in Rio de Janeiro and São Paulo, Brazil received live birds and carcasses of Sula leucogaster. The animals were deloused and lice of 2 different species were collected. Identification was performed by optical microscopy, and the species found were Eidmanniella albescens Piaget, 1880 and Pectinopygus garbeiPessoa and Guimarães, 1935. This is the first record of both species in Rio de Janeiro.Human γ-globin is predominantly expressed in fetal liver erythroid cells during gestation from 2 nearly identical genes, HBG1 and HBG2, that are both perinatally silenced. Reactivation of these fetal genes in adult red blood cells can ameliorate many symptoms associated with the inherited β-globinopathies, sickle cell disease, and Cooley anemia. Although promising genetic strategies to reactivate the γ-globin genes to treat these diseases have been explored, there are significant barriers to their effective implementation worldwide; alternatively, pharmacological induction of γ-globin synthesis could readily reach the majority of affected individuals. In this study, we generated a CRISPR knockout library that targeted all erythroid genes for which prospective or actual therapeutic compounds already exist. By probing this library for genes that repress fetal hemoglobin (HbF), we identified several novel, potentially druggable, γ-globin repressors, including VHL and PTEN. We demonstrate that deletion of VHL induces HbF through activation of the HIF1α pathway and that deletion of PTEN induces HbF through AKT pathway stimulation. Finally, we show that small-molecule inhibitors of PTEN and EZH induce HbF in both healthy and β-thalassemic human primary erythroid cells.Fibrillins (FBNs) are a family of genes in cyanobacteria, algae, and plants. The proteins they encode possess a lipid binding motif, exist in various types of plastids, and are associated with lipid bodies called plastoglobules (PGs), implicating them in lipid metabolism. FBNs present in the thylakoid and stroma are involved in the storage, transport, and synthesis of lipid molecules for photoprotective functions against high-light stress. In this review, the diversity of subplastid locations in the evolution of FBNs, regulation of expression of FBNs by various stresses, and the role of FBNs in plastid lipid metabolism are comprehensively summarized and directions for future research are discussed.
Youth with obesity and abnormal glucose tolerance have an increased risk for atherosclerosis but the relative contributions of insulin resistance and hyperglycemia to dyslipidemia and the development of subclinical atherosclerosis are unknown.
This work aims to determine the association between insulin resistance, dyslipidemia, and carotid intimal thickness (cIMT) in adolescents with normal and abnormal glucose tolerance.
An observational cohort study in 155 youth 44 obese insulin sensitive (OIS; fasting insulin ≤ 20 µM/mL, body mass index [BMI] ≥ 95th percentile), 35 obese insulin resistant (OIR; fasting insulin > 20 µM/mL, BMI ≥ 95th percentile), 34 obese abnormal glucose tolerant (AGT; BMI ≥ 95th percentile), and 42 Lean (BMI 5th-85th percentile). Lipids, lipoprotein particle size and concentration (-P), insulin sensitivity (SI an intravenous glucose test), and CMIT were compared using linear models adjusted for age, race/ethnicity, biological sex, and Tanner stage. Lipid/lipoprotein profile and Ccemia in youth with obesity.
Among youth with obesity, insulin resistance was associated with an atherogenic lipoprotein/lipid profile and cIMT, regardless of glucose tolerance status. Insulin resistance in AGT youth was associated with a shift to smaller HDL-P compared to normoglycemic youth with obesity. Alterations in HDL-P metabolism may be early adverse manifestations of hyperglycemia in youth with obesity.
To examine how intergenerational support varies by parents’ living arrangements and whether there are gender differences in received support in Puerto Rico.
Data come from the 2006-2007 Puerto Rican Elderly and Health Conditions Project, a representative longitudinal study of adults aged 60 and older in Puerto Rico (n=2,288). We examined the association between parents’ living arrangements (alone, with spouse/partner only, with children) and their receipt of functional (help with errands/housework/transport) and health (help when sick) support from children, and whether parents’ gender moderates the association.
Intergenerational coresidence was associated with higher odds of receiving functional and health support than living alone. Women were more likely than men to receive both forms of support. Parents’ gender significantly moderated the association between living arrangements and receiving health support – men living with their partners were less likely to receive health support from children than women in similar living arrangements. These associations persisted when analyses were restricted to those with disability.
Our findings suggest that parents’ receipt of support from children is conditioned upon their living arrangement and gender, even when their functional health is jeopardized. We discuss these results in relation to the heterogeneous influence of living arrangements for older adults’ support needs and provide suggestions for policy and directions for future research in rapidly aging Puerto Rico.
Our findings suggest that parents’ receipt of support from children is conditioned upon their living arrangement and gender, even when their functional health is jeopardized. We discuss these results in relation to the heterogeneous influence of living arrangements for older adults’ support needs and provide suggestions for policy and directions for future research in rapidly aging Puerto Rico.Polatuzumab vedotin (PV) is an antibody-drug conjugate targeting CD79b that is approved for patients with relapsed/refractory large B-cell lymphoma (LBCL). Patients who relapse after chimeric antigen receptor (CAR) T-cell therapy were not included in the registration study, and reports of PV use after CAR T cells are limited. This multicenter retrospective analysis included patients with LBCL who relapsed or progressed after CAR T-cell therapy and subsequently received PV with or without rituximab and bendamustine between July 2019 and May 2021. Response to treatment and progression were assessed based on the 2014 Lugano criteria. Fifty-seven patients were included in the study 18 (32%) patients were primary refractory to CAR T-cell therapy, and 34 (60%) patients received PV-based therapy immediately after CAR T-cell therapy. PV was combined with rituximab in 54 (95%) patients and administered with bendamustine in 35 (61%) patients. A response was achieved in 25 (44%) patients, including complete remission in 8 (14%). No significant association between baseline characteristics and response was observed. After a median follow-up of 47 weeks (95% confidence interval [CI], 40-54), 46 (81%) patients had disease progression or died, and the median progression-free survival was 10 weeks (95% CI, 5-15). On a multivariate analysis, bone marrow involvement (hazard ratio, 5.2; 95% CI, 1.8-15; P = .003) and elevated lactate dehydrogenase levels (hazard ratio, 5.0; 95% CI, 1.4-16; P = .01) were associated with shorter progression-free survival. Studies aimed at better characterizing the intrinsic mechanism of resistance and identifying optimal consolidation strategies for these patients are warranted.Patients with blood disorders who are immune suppressed are at increased risk for infection with severe acute respiratory syndrome coronavirus 2. Sequelae of infection can include severe respiratory disease and/or prolonged duration of viral shedding. Cellular therapies may protect these vulnerable patients by providing antiviral cellular immunity and/or immune modulation. In this recent review of the field, phase 1/2 trials evaluating adoptive cellular therapies with virus-specific T cells or natural killer cells are described along with trials evaluating the safety, feasibility, and preliminary efficacy of immune modulating cellular therapies including regulatory T cells and mesenchymal stromal cells. In addition, the immunologic basis for these therapies is discussed.
Automated office blood pressure (AOBP) using 3-5 measurements taken with an oscillometric device with or without an attendant in the room may decrease „white coat” effect. We evaluated the impact of the presence or absence of the attendant and rest on BP and diagnosis of hypertension.
We randomly assigned 133 adults aged 18-85 with high BP at baseline (≥140/90 mm Hg), no hypertensive diagnosis and no antihypertensive medications to either attended AOBP first, unattended second, or unattended AOBP first, attended second. Outcomes included within-person BP difference for attended vs. unattended measurements; 5 vs. 15 minutes of rest; and the diagnostic performance of AOBP compared with daytime automated blood pressure measurement (ABPM).
We found no significant differences between attended and unattended AOBP (mean difference attended – unattended [95% confidence interval, CI], systolic 0.14 mm Hg [-0.78, 1.06]; diastolic 0.16 mm Hg [-0.45, 0.78]) or by rest time (mean difference 15 – 5 minutes [95% CI], systolic -0.45 mm Hg [-1.36, 0.47]; diastolic 0.61 mm Hg [-1.23, 0.003]). AOBP was lower than mean daytime ABPM, regardless of attendance or rest (after 5 minutes rest systolic -3.6 and diastolic -2.55 mm Hg, P = 0.001 for both comparisons). Using daytime ABPM of ≥135/85 mm Hg as the diagnostic threshold, AOBP sensitivity and specificity after 5 minutes of rest were 71.0% and 54.1%, respectively.
The presence or absence of a clinic attendant during AOBP measurement and the amount of rest time before AOBP measurements had no effects on BP. AOBP measurements have low sensitivity and specificity for making a new diagnosis of hypertension.
The presence or absence of a clinic attendant during AOBP measurement and the amount of rest time before AOBP measurements had no effects on BP. AOBP measurements have low sensitivity and specificity for making a new diagnosis of hypertension.The standard of care treatment strategy for patients with relapsed or refractory large B-cell lymphoma (LBCL) has been high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) if chemotherapy sensitive in suitable patients. Because of treatment intensity, this approach has only been feasible in half of patients and because of chemotherapy resistance has only been successful in a quarter of transplant-eligible patients. Chimeric antigen receptor (CAR) T-cell therapy, using genetically modified autologous T cells targeting CD19, has been approved for third-line therapy of LBCL and has been associated with durable remissions in a proportion of patients. In this review, we interpret the design and results of 3 randomized phase 3 trials comparing CAR T-cell therapy and ASCT and their implications for CAR T-cell therapy as a potential new standard of care for second-line treatment in appropriate patients with refractory or early relapsing LBCL.