Biochemical fractionation of induced pluripotent stem cell derived motor neurons from an ALS patient with the Glycine-298-Serine TDP-43 mutation

Thesis (M.A.)--Boston UniversityTransactive response DNA-binding protein (TDP-43), and fused in sarcoma/translocated in liposarcoma (FUS/TLS) form protein aggregates in amyotrophic lateral sclerosis (ALS) and fronto-temporal lobar degeneration (FTLD). The sequencing of the TDP-43 gene TARDBP in a large patient population has shown more than 40 missense mutations that are now known to cause disease. The effect of genetic mutation on protein aggregation, and the pathogenesis of ALS is the focus of this study. In order to determine the effect of the TARDBP Glycine-298- Serine (G298S) missense mutation on protein aggregation in disease, induced pluripotent stem cells (iPSCs) were reprogrammed from control and G298S mutant fibroblasts, and differentiated into motor neurons using defined factors, and fractio- nated to determine the soluble and insoluble TDP-43 burden. There was an increase in insoluble TDP-43 in the ALS-patient-derived motor neuron lysates over a normal control, but the significance could not be assessed because of the small sample size. A toxicity assay using fluorescence activated cell sorting showed an unexpected trend towards healthier control neurons. Future studies should include quantified immunohistochemical analysis of motor neurons and use novel pharmaceuticals to attempt to correct aberrant TDP-43-mediated RNA processing

Incidence of postoperative acute kidney injury in patients with chronic kidney disease undergoing minimally invasive valve surgery

BackgroundWe hypothesize that minimally invasive valve surgery in patients with chronic kidney disease (CKD) is superior to a conventional median sternotomy.MethodsWe retrospectively analyzed 1945 consecutive patients who underwent isolated valve surgery. Included were patients with CKD stages 2 to 5. In-hospital mortality, composite complication rates, and intensive care unit and total hospital lengths of stay of those who underwent a minimally invasive approach were compared with those who underwent a standard median sternotomy. Resource use was approximated based on intensive care unit and total hospital lengths of stay.ResultsThere were 688 patients identified; 510 (74%) underwent minimally invasive surgery, and 178 (26%) underwent a median sternotomy. There was no significant difference in mortality. Minimally invasive surgery was associated with fewer composite complications (33.1% vs 49.4%; odds ratio, 0.5; P ≤ .001), shorter intensive care unit (48 [interquartile range {IQR}, 33-74] hours vs 71 [IQR, 42-96] hours; P < .01), and hospital (8 [IQR, 6-9] days vs 10 [IQR, 8-15] days; P < .001) lengths of stay, and a lower incidence of acute kidney injury (8% vs 14.7%; odds ratio, 0.5; P = .01), compared with median sternotomy. In a multivariable analysis, minimally invasive surgery was associated with a 60% reduction in the risk of development of postoperative acute kidney injury.ConclusionsIn patients with CKD undergoing isolated valve surgery, minimally invasive valve surgery is associated with reduced postoperative complications and lower resource use

PAK1 Protein Expression in the Auditory Cortex of Schizophrenia Subjects

Deficits in auditory processing are among the best documented endophenotypes in schizophrenia, possibly due to loss of excitatory synaptic connections. Dendritic spines, the principal post-synaptic target of excitatory projections, are reduced in schizophrenia. p21-activated kinase 1 (PAK1) regulates both the actin cytoskeleton and dendritic spine density, and is a downstream effector of both kalirin and CDC42, both of which have altered expression in schizophrenia. This study sought to determine if there is decreased auditory cortex PAK1 protein expression in schizophrenia through the use of quantitative western blots of 25 schizophrenia subjects and matched controls. There was no significant change in PAK1 level detected in the schizophrenia subjects in our cohort. PAK1 protein levels within subject pairs correlated positively with prior measures of total kalirin protein in the same pairs. PAK1 level also correlated with levels of a marker of dendritic spines, spinophilin. These latter two findings suggest that the lack of change in PAK1 level in schizophrenia is not due to limited sensitivity of our assay to detect meaningful differences in PAK1 protein expression. Future studies are needed to evaluate whether alterations in PAK1 phosphorylation states, or alterations in protein expression of other members of the PAK family, are present in schizophrenia

Liver failure due to relapsed myeloma and hepatic iron overload

Multiple myeloma is a hematologic malignancy that classically manifests with hypercalcaemia, renal insufficiency, anaemia and lytic bone lesions. Liver dysfunction in multiple myeloma is a lesser known complication that occurs through biliary obstruction, liver infiltration by plasma cells, amyloid/light chain deposition or due to liver injury from medications. Although transfusion-related hepatic iron overload-leading to significant liver disease-is a recognised complication in certain hematologic malignancies, little is known about transfusional iron overload in patients with multiple myeloma. We present a case of a 49-year-old female with relapsed/refractory multiple myeloma who presented with rapid onset liver failure, due to both iron deposition and malignant plasma cell infiltration of the liver as a terminal event. A review of the literature on hepatic complications in multiple myeloma patients is presented

Enhancement of the capabilities of liquid chromatography-mass spectrometry with derivatization: General principles and applications

10.1002/mas.20316Mass Spectrometry Reviews3061143-1172MSRV

Does a Standardized Discharge Communication Tool Improve Resident Performance and Overall Patient Satisfaction?

Introduction: The discharge conversation is a critical component of the emergency department encounter. Studies suggest that emergency medicine (EM) residency education is deficient in formally training residents on the patient discharge conversation. Our goal was to assess the proficiency of EM residents in addressing essential elements of a comprehensive discharge conversation; identify which components of the discharge conversation are omitted; introduce “DC HOME,” a standardized discharge mnemonic; and determine whether its implementation improved resident performance and patient satisfaction.Methods: This was a prospective observational pre- and post-intervention study done by convenience sampling of 400 resident discharge encounters. Resident physicians were observed by attending physicians who completed an evaluation, answering “yes” or “no” as to whether residents addressed six components of a comprehensive discharge. The six components include the following: diagnosis; care rendered; health and lifestyle modifications; obstacles after discharge; medications; and expectations – or “DC HOME.” Didactics introducing the mnemonic “DC HOME” was provided to resident physicians. Patient feedback and satisfaction were collected after each encounter, and we recorded differences between pre-intervention and post-intervention encounters.Results: Resident physicians improved significantly in all six components of “DC HOME” from pre-and-post intervention: discharge diagnosis (P = 0.0036) and the remaining five components (P&lt;0.0001). There was a statistically significant improvement in patients’ perception for health and lifestyle modifications, obstacles after discharge, medications, expectations after discharge (P&lt;0.0001), and discharge diagnosis (P = 0.0029). Patient satisfaction scores improved significantly (P = 0.005). Time spent with patients during discharge increased from 2 minutes and 42 seconds to 4 minutes and 4 seconds (P&lt;0.0001).Conclusion: EM residents frequently omit key components of the discharge conversation. The implementation of the “DC HOME” discharge mnemonic improves resident discharge performance, patient perception, and overall patient satisfaction

Does a Standardized Discharge Communication Tool Improve Resident Performance and Overall Patient Satisfaction?

Introduction: The discharge conversation is a critical component of the emergency department encounter. Studies suggest that emergency medicine (EM) residency education is deficient in formally training residents on the patient discharge conversation. Our goal was to assess the proficiency of EM residents in addressing essential elements of a comprehensive discharge conversation; identify which components of the discharge conversation are omitted; introduce “DC HOME,” a standardized discharge mnemonic; and determine whether its implementation improved resident performance and patient satisfaction.Methods: This was a prospective observational pre- and post-intervention study done by convenience sampling of 400 resident discharge encounters. Resident physicians were observed by attending physicians who completed an evaluation, answering “yes” or “no” as to whether residents addressed six components of a comprehensive discharge. The six components include the following: diagnosis; care rendered; health and lifestyle modifications; obstacles after discharge; medications; and expectations – or “DC HOME.” Didactics introducing the mnemonic “DC HOME” was provided to resident physicians. Patient feedback and satisfaction were collected after each encounter, and we recorded differences between pre-intervention and post-intervention encounters.Results: Resident physicians improved significantly in all six components of “DC HOME” from pre-and-post intervention: discharge diagnosis (P = 0.0036) and the remaining five components (P&lt;0.0001). There was a statistically significant improvement in patients’ perception for health and lifestyle modifications, obstacles after discharge, medications, expectations after discharge (P&lt;0.0001), and discharge diagnosis (P = 0.0029). Patient satisfaction scores improved significantly (P = 0.005). Time spent with patients during discharge increased from 2 minutes and 42 seconds to 4 minutes and 4 seconds (P&lt;0.0001).Conclusion: EM residents frequently omit key components of the discharge conversation. The implementation of the “DC HOME” discharge mnemonic improves resident discharge performance, patient perception, and overall patient satisfaction