HDAC and MAPK/ERK Inhibitors Cooperate To Reduce Viability and Stemness in Medulloblastoma

Journal of Molecular Neuroscience - Medulloblastoma (MB), which originates from embryonic neural stem cells (NSCs) or neural precursors in the developing cerebellum, is the most common malignant...     

Association of Race and Neighborhood Disadvantage with Patient Engagement in a Home-Based COVID-19 Remote Monitoring Program

BackgroundCOVID-positive outpatients may benefit from remote monitoring, but such a program often relies on smartphone apps. This may introduce racial and socio-economic barriers to participation. Offering multiple methods for participation may address these barriers.Objectives(1) To examine associations of race and neighborhood disadvantage with patient retention in a monitoring program offering two participation methods. (2) To measure the association of the program with emergency department visits and hospital admissions.DesignRetrospective propensity-matched cohort study.ParticipantsCOVID-positive outpatients at a single university-affiliated healthcare system and propensity-matched controls.InterventionsA home monitoring program providing daily symptom tracking via patient portal app or telephone calls.Main MeasuresAmong program enrollees, retention (until 14 days, symptom resolution, or hospital admission) by race and neighborhood disadvantage, with stratification by program arm. In enrollees versus matched controls, emergency department utilization and hospital admission within 30 days.Key ResultsThere were 7592 enrolled patients and 9710 matched controls. Black enrollees chose the telephone arm more frequently than White enrollees (68% versus 44%, p = 0.009), as did those from more versus less disadvantaged neighborhoods (59% versus 43%, p = 0.02). Retention was similar in Black enrollees and White enrollees (63% versus 62%, p = 0.76) and in more versus less disadvantaged neighborhoods (63% versus 62%, p = 0.44). When stratified by program arm, Black enrollees had lower retention than White enrollees in the app arm (49% versus 55%, p = 0.01), but not in the telephone arm (69% versus 71%, p = 0.12). Compared to controls, enrollees more frequently visited the emergency department (HR 1.71 [95% CI 1.56–1.87]) and were admitted to the hospital (HR 1.16 [95% CI 1.02–1.31]).ConclusionsIn a COVID-19 remote patient monitoring program, Black enrollees preferentially selected, and had higher retention in, telephone- over app-based monitoring. As a result, overall retention was similar between races. Remote monitoring programs with multiple modes may reduce barriers to participation.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-021-07207-4.KEY WORDS: ambulatory monitoring, COVID-19, race factors, facilities and services utilization     

Descending cervical mediastinitis: the multidisciplinary surgical approach

European Archives of Oto-Rhino-Laryngology - Descending cervical mediastinitis (DCM) is defined as spread of oropharyngeal or odontogenic infection into the mediastinum. It occurs uncommonly and...     

Decreased Complement Mediated Binding of Antibody/3H-dsDNA Immune Complexes to the Red Blood Cells of Patients with Systemic Lupus Erythematosus,Rheumatoid Arthritis,and Hematologic Malignancies

The complement mediated binding of prepared antibody/³H-dsDNA immune complexes to the red blood cells obtained from a number of patient populations has been investigated. Patients with solid tumors have binding activity similar to that seen in a normal group of individuals. However, a significant fraction of patients with systemic lupus erythematosus, rheumatoid arthritis, and hematologic malignancies have lowered binding activity compared with normal subjects. Quantitative studies indicate the lowered activity probably arises due to a decrease in complement receptors on the respective red blood cells. The potential importance and implications of these findings are briefly discussed.     

Evaluation of the Safety of a Plant-Based Infant Formula Containing Almonds and Buckwheat in a Neonatal Piglet Model

A randomized neonatal piglet trial was conducted to evaluate the safety and the effects of a plant-based formula containing almonds and buckwheat as the main ingredients on growth and plasma parameters. From postnatal day (PND) 2 to 21, the piglets were fed a dairy-based milk formula (Similac Advance) or a plant-based formula (Else Nutrition) and all piglets were euthanized at day 21. No diarrhea was observed after PND 8 and all the piglets completed the trial. Body growth, kcal intake, the complete plasma count parameters and hematological parameters were within the reference range in both groups. Organ growth and development was similar between the two groups. Plasma glucose was higher in the dairy-based-fed piglets relative to the plant-based at 2 weeks of age. Liver function biomarkers levels were greater in the plasma of the plant-based compared to the dairy-based fed group. In addition, calcium levels were higher in the plant-based fed piglets at 1 week of age. Thus, the plant-based formula tested in this study was well tolerated by the piglets and supported similar growth compared to dairy-based milk formula. Therefore, the results support the safety of the tested plant-based infant formula during the neonatal period in comparison to the dairy-based formula fed group.     

Microbubble drug conjugate and focused ultrasound blood brain barrier delivery of AAV-2 SIRT-3

BackgroundDelivery of viral vectors as gene therapies to treat neurodegenerative diseases has been hampered by the inability to penetrate the blood brain barrier (BBB) and invasive or non-targeted delivery options prone to inducing immune responses. MR guided focused ultrasound (MR-g-FUS) and microbubbles have demonstrated safe, temporary, targeted BBB permeabilization clinically.MethodsWe developed clinically scalable, microbubble drug conjugates (MDCs) for the viral gene therapy, AAV.SIRT3-myc [adeno-associated virus expressing myc-tagged SIRT3], which has previously been shown to have disease modifying effects in animal models of Parkinson’s disease (PD). The lipid shells of the perfluorocarbon gas MDCs were covalently conjugated to antibodies with binding specificity to AAVs. Following systemic (iv) delivery of AAV.SIRT3-myc MDCs, MR-g-FUS was used to deliver SIRT3-myc to brain regions affected in PD. SIRT3-myc expression was determined post mortem, using immunohistochemistry.ResultsAn in vitro, SH-SY5Y cell culture model was used to show that the localized destruction of MDCs using ultrasound exposures within biological safety limits dissociated AAV2-GFP (green fluorescent protein) from the MDCs in the targeted area while maintaining their transduction capacity. In rats, MR-g-FUS resulted in BBB permeabilization in the striatum and substantia nigra (SNc). SIRT3-myc was expressed in the striatum, but not the SNc.ConclusionThese studies demonstrate that MDCs combined with MR-g-FUS are an effective method for delivery of viral vector gene therapies, such as AAV.SIRT3, to brain regions affected in PD. This technology may prove useful as a disease-modifying strategy in PD and other neurodegenerative disorders.     

Antibodies to sm in patients with systemic lupus erythematosus. correlation of sm antibody titers with disease activity and other laboratory parameters

Thirty patients with systemic lupus erythematosus (SLE( were studied over a 2.5-year period. The group was divided into 14 patients with antibodies to Sm and a control group which failed to exhibit antibodies to Sm over the study period. The titer of antibodies to Sm fluctuated in all 14. A rising titer of antibodies to Sm 1) predicted a flare of disease in 50% and 2) correlated with an exacerbation of disease in 60%. Patients with antibodies to Sm had a comparable incidence of severe disease, renal disease, and central nervous system disease. They exhibited significantly more leukopenia and antibodies to non-Sm, non-RNP extractable nuclear antigen. In only 1 patient, a rise in titer of antibodies to Sm did not correlate with or predict a disease flare in contradistinction to other serologic markers of SLE, specifically antibodies to double-stranded DNA and cryoglobulins. Though infrequently detected, antibodies to Sm can help in the management of patients with SLE.     

Characterization of mGluR5R,a novel,metabotropic glutamate receptor 5-related gene

We report here the isolation of a novel gene termed mGluR5R (mGluR5-related). The N-terminus of mGluR5R is highly similar to the extracellular domain of metabotropic glutamate receptor 5 (mGluR5) whereas the C-terminus bears similarity to the testis-specific gene, RNF18. mGluR5R is expressed in the human CNS in a coordinate fashion with mGluR5. Although the sequence suggests that mGluR5R may be a secreted glutamate binding protein, we found that when expressed in HEK293 cells it was membrane associated and not secreted. Furthermore, mGluR5R was incapable of binding the metabotropic glutamate receptor class I selective agonist, quisqualate. Although mGluR5R could not form disulfide-mediated covalent homodimers, it was able to form a homomeric complex, presumably through noncovalent interactions. mGluR5R also formed noncovalent heteromeric associations with an engineered construct of the extracellular domain of mGluR5 as well as with full-length mGluR5 and mGluR1alpha. The ability of mGluR5R to associate with mGluR1alpha and mGluR5 suggests that it may be a modulator of class I metabotropic glutamate receptor function.