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Howell Bock posted an update 3 months, 2 weeks ago
ABO-incompatible hematopoietic stem cell transplantations (HSCTs) are widely practiced; however, the delay in erythrocyte engraftment can be problematic. While erythrocyte engraftment is usually indicated by an increase in reticulocyte levels without the need for erythrocyte transfusions, the disappearance of recipient-derived anti-A/B isoagglutinin and detection of donor-derived A/B antigens can also be used as other parameters. We conducted a retrospective analysis of 68 ABO-incompatible HSCTs, focusing on major and bidirectional mismatch. We analyzed known clinical risk factors associated with delayed erythrocyte engraftment using the three parameters (disappearance of anti-A/B isoagglutinin in recipient, detection of donor-derived A/B antigen, and reticulocyte levels >1%). Although the three parameters were well correlated, the results showed heterogeneity when analyzing the associated risk factors for delayed erythrocyte engraftment. In the analysis of all cases, the requirement for an HLA-matched platelet transfusion was a common risk factor. Furthermore, erythrocyte engraftment was slower in adults than in children. In adults, cytomegalovirus antigenemia was a risk factor for two parameters; however, in children, underlying disease was a common risk factor for all parameters. There is a complex relationship between erythrocyte engraftment and various factors related to HSCTs. Our results suggest that greater accuracy is possible by using analysis methods other than the measurement of reticulocyte levels.Cell signaling relies on second messengers to transduce signals from the sensory apparatus to downstream signaling pathway components. In bacteria, one of the most important and ubiquitous second messenger is the small molecule cyclic diguanosine monophosphate (c-di-GMP). While the biosynthesis, degradation, and regulatory pathways controlled by c-di-GMP are well characterized, the mechanisms through which c-di-GMP controls these processes are not entirely understood. Herein we present the report of a c-di-GMP sensing sensor histidine kinase PdtaS (Rv3220c), which binds to c-di-GMP at submicromolar concentrations, subsequently perturbing signaling of the PdtaS-PdtaR (Rv1626) two-component system. Aided by biochemical analysis, genetics, molecular docking, FRET microscopy, and structural modelling, we have characterized the binding of c-di-GMP in the GAF domain of PdtaS. We show that a pdtaS knockout in Mycobacterium smegmatis is severely compromised in growth on amino acid deficient media and exhibits global transcriptional dysregulation. The perturbation of the c-di-GMP-PdtaS-PdtaR axis results in a cascade of cellular changes recorded by a multiparametric systems’ approach of transcriptomics, unbiased metabolomics, and lipid analyses.
We present a novel perfusion phantom for validation of arterial spin labeled (ASL) perfusion MRI methods and protocols.
Impinging jets, driven by a peristaltic pump, were used to achieve perfusion-like mixing of magnetically labeled inflowing fluid within a perfusion compartment. The phantom was validated by varying pump rates and obtaining ASL-MRI data at multiple postlabeling delays using a pseudo-continuous ASL sequence with a 3D stack-of-spirals readout. An additional data set was acquired using a pseudo-continuous ASL sequence with a 2D EPI readout. Phantom sensitivity to pseudo-continuous ASL labeling efficiency was also tested.
Fluid dynamics simulations predicted that maximum mixing would occur near the central axis of the perfusion compartment. Experimentally observed signal changes within this region were reproducible and well fit by the standard Buxton general kinetic model. Simulations and experimental data showed no label outflow from the perfusion chamber and calculated perfusion rates, averaged over the entire phantom volume, agreed with the expected volumetric flow rates provided by the flow pump. Phantom sensitivity to pseudo-continuous ASL labeling parameters was also demonstrated.
Perfusion-like signal can be simulated using impinging jets to create a well-mixed compartment. Observed perfusion and transit time values were reproducible and within the physiological range for brain perfusion. This phantom design has a broad range of potential applications in both basic and clinical research involving ASL MRI.
Perfusion-like signal can be simulated using impinging jets to create a well-mixed compartment. Observed perfusion and transit time values were reproducible and within the physiological range for brain perfusion. This phantom design has a broad range of potential applications in both basic and clinical research involving ASL MRI.
Diabetes is two to three times more prevalent in people with severe mental illness, yet little is known about the challenges of managing both conditions from the perspectives of people living with the co-morbidity, their family members or healthcare staff. Our aim was to understand these challenges and to explore the circumstances that influence access to and receipt of diabetes care for people with severe mental illness.
Framework analysis of qualitative semi-structured interviews with people with severe mental illness and diabetes, family members, and staff from UK primary care, mental health and diabetes services, selected using a maximum variation sampling strategy between April and December 2018.
In all, 39 adults with severe mental illness and diabetes (3 with type 1 diabetes and 36 with type 2 diabetes), nine family members and 30 healthcare staff participated. Five themes were identified (a) Severe mental illness governs everyday life including diabetes management; (b) mood influences capacity al illness are also needed.
To operationalize the National Institute on Aging – Alzheimer’s Association (NIA-AA) Research Framework for Alzheimer’s Disease 6-stage continuum of clinical progression for persons with abnormal amyloid.
The Mayo Clinic Study of Aging is a population-based longitudinal study of aging and cognitive impairment in Olmsted County, Minnesota. NF-κB inhibitor We evaluated persons without dementia having 3 consecutive clinical visits. Measures for cross-sectional categories included objective cognitive impairment (OBJ) and function (FXN). Measures for change included subjective cognitive impairment (SCD), objective cognitive change (ΔOBJ), and new onset of neurobehavioral symptoms (ΔNBS). We calculated frequencies of the stages using different cutoff points and assessed stability of the stages over 15 months.
Among 243 abnormal amyloid participants, the frequencies of the stages varied with age 66 to 90% were classified as stage 1 at age 50 but at age 80, 24 to 36% were stage 1, 32 to 47% were stage 2, 18 to 27% were stage 3, 1 to 3% were stage 4 to 6, and 3 to 9% were indeterminate.