Intravascular Lithotripsy in an Adult With Fontan Pathway Obstruction.

Fontan pathway obstruction is a potentially serious complication characterized by an anatomical or functional narrowing anywhere in the cavo-pulmonary pathways. Here, we report the first case in the literature where an innovative Fontan conduit rehabilitation procedure with intravascular lithotripsy was used achieving a dramatic increase in the pathway size.

GLP-1 Analogs Are Superior in Mediating Weight Loss But Not Glycemic Control in Diabetic Patients on Antidepressant Medications: A Retrospective Cohort Study.

Objective: Both antipsychotic and antidepressant medications have been associated with weight gain and hyperglycemia. Our previously published retrospective cohort study suggests that GLP-1 (glucagon-like peptide-1) analogs may be superior to alternative regimens for both glycemic and weight control in patients on antipsychotic plus/minus antidepressant medications. In the current study, we asked whether GLP-1 analogs or SGLT-2 (sodium-glucose-transporter-2) inhibitors would be similarly beneficial in patients on antidepressant medications alone.Methods: In this retrospective cohort study, we included all patients with type 2 diabetes on antidepressant medications referred to our endocrine clinics between January 1, 2016, and January 1, 2017. Overall, 61 patients were started on a GLP-1 analog, 9 patients were started on an SGLT-2 inhibitor, and 134 were on alternative regimens (controls).Results: The groups did not differ in age, sex, ethnicity, and glycosylated hemoglobin (HbA1c) levels, although body mass index levels were higher in patients started on a GLP-1 analog (P < .0001). After 12 months, patients on GLP-1 analogs lost 4 kg, patients on SGLT-2 inhibitors lost 2.4 kg, and controls gained 0.8 kg (P < .001 for controls versus GLP-1 analog group). Subanalyses revealed that GLP-1 analog-related weight loss was most notable in women and patients on selective serotonin reuptake inhibitors. On the other hand, all serotonin-norepinephrine reuptake inhibitor users lost weight over time, independent of the antidiabetic regimen applied. In contrast to the above noted differences in weight control, HbA1c reductions were comparable and somewhat diminished in all patients on antidepressant medications (-0.3% to 0.6%).Conclusions: In this retrospective cohort study, we confirm superiority of GLP-1 analogs in mediating weight loss in patients on psychotropic and, more specifically, antidepressant medications. We also note overall blunted glycemic improvements in patients on antidepressant medications, a finding that was independent of the treatment strategy used. It could be a result of mental distress or suboptimal self-care and clearly requires further attention by future, prospective studies.

Espectro clínico de la Encefalitis Autoinmune no NMDAR en pediatría

En este trabajo se realizó una revisión narrativa de los principales hallazgos en la literatura médica sobre las manifestaciones clínicas de la encefalitis autoinmune pediátrica (EAP) no mediada por anticuerpos anti receptor del ácido N-metil-D-aspartato (NMDAR). Las EAP que se destacaron se asocian con anticuerpos específicos como el complejo de canales de potasio dependiente de voltaje, la decarboxilasa del ácido glutámico, el receptor del ácido alfa-amino-3-hidroxi-5-metil-4-isoxazolpropiónico y el receptor ácido-gamma-aminobutírico. El diagnóstico de esta patología es un desafío en pediatría debido a la complejidad de las manifestaciones psiquiátricas y neurológicas generadas por la afectación de la corteza, el sistema límbico, el tallo cerebral, los ganglios basales y el cerebelo. A su vez, la comprensión de sus síntomas permite identificar la superposición en las presentaciones clínicas entre los diferentes tipos de EAP y el diagnóstico diferencial con otras enfermedades inflamatorias del cerebro, infecciones, enfermedades metabólicas y trastornos psiquiátricos. El conocimiento biomédico y la sospecha clínica de las EAP no NMDAR establece un campo de investigación que crece en neuropsiquiatría y favorece el diagnóstico y tratamiento de las encefalitis subdiagnosticadas.

This work presents a narrative review of the main findings in the medical literature on the clinical manifestations of pediatric autoimmune encephalitis (PAE) not mediated by anti-N-methyl-Daspartate acid receptor (NMDAR) antibodies. Prominent PAEs are associated with specific antibodies, such as the voltage-gated potassium channel complex, glutamic acid decarboxylase, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, and alpha-amino -3-hydroxy-5. -methyl-4-isoxazolepropionic acid receptor. -gamma-aminobutyric. Diagnosis of this pathology is a challenge in pediatrics due to the complexity of psychiatric and neurological manifestations generated by involvement of cortex, limbic system, brainstem, basal ganglia and cerebellum. In turn, understanding its symptoms allows identifying the overlap in clinical presentations between the different types of PAE and the differential diagnosis with other inflammatory diseases of the brain, infections, metabolic diseases and psychiatric disorders. Biomedical knowledge and clinical suspicion of non-NMDAR PAE establishes a growing field of research in neuropsychiatry and favors the diagnosis and treatment of underdiagnosed encephalitides.

Large scale real-time PCR validation on gene expression measurements from two commercial long-oligonucleotide microarrays.

BACKGROUND: DNA microarrays are rapidly becoming a fundamental tool in discovery-based genomic and biomedical research. However, the reliability of the microarray results is being challenged due to the existence of different technologies and non-standard methods of data analysis and interpretation. In the absence of a "gold standard"/"reference method" for the gene expression measurements, studies evaluating and comparing the performance of various microarray platforms have often yielded subjective and conflicting conclusions. To address this issue we have conducted a large scale TaqMan Gene Expression Assay based real-time PCR experiment and used this data set as the reference to evaluate the performance of two representative commercial microarray platforms. RESULTS: In this study, we analyzed the gene expression profiles of three human tissues: brain, lung, liver and one universal human reference sample (UHR) using two representative commercial long-oligonucleotide microarray platforms: (1) Applied Biosystems Human Genome Survey Microarrays (based on single-color detection); (2) Agilent Whole Human Genome Oligo Microarrays (based on two-color detection). 1,375 genes represented by both microarray platforms and spanning a wide dynamic range in gene expression levels, were selected for TaqMan Gene Expression Assay based real-time PCR validation. For each platform, four technical replicates were performed on the same total RNA samples according to each manufacturer's standard protocols. For Agilent arrays, comparative hybridization was performed using incorporation of Cy5 for brain/lung/liver RNA and Cy3 for UHR RNA (common reference). Using the TaqMan Gene Expression Assay based real-time PCR data set as the reference set, the performance of the two microarray platforms was evaluated focusing on the following criteria: (1) Sensitivity and accuracy in detection of expression; (2) Fold change correlation with real-time PCR data in pair-wise tissues as well as in gene expression profiles determined across all tissues; (3) Sensitivity and accuracy in detection of differential expression. CONCLUSION: Our study provides one of the largest "reference" data set of gene expression measurements using TaqMan Gene Expression Assay based real-time PCR technology. This data set allowed us to use an alternative gene expression technology to evaluate the performance of different microarray platforms. We conclude that microarrays are indeed invaluable discovery tools with acceptable reliability for genome-wide gene expression screening, though validation of putative changes in gene expression remains advisable. Our study also characterizes the limitations of microarrays; understanding these limitations will enable researchers to more effectively evaluate microarray results in a more cautious and appropriate manner.

A novel assay to determine the sequence preference and affinity of DNA minor groove binding compounds.

Sequence-specific binding in the minor groove of DNA by small molecules is a growing area of research with possible therapeutic relevance. By selectively binding to DNA sequences required by critical transcription factors, these small molecules could potentially modulate the expression levels of disease-causing genes. Precise targeting of a critical transcription factor of a selected gene requires an understanding of the preferred sequence of the DNA binding compound. As new compounds are being synthesized, there is a need to evaluate their DNA recognition profile. We sought to establish a procedure to determine sequence preference of compounds with previously unknown binding properties. A novel procedure for determining the optimal DNA binding sequence of minor groove binding compounds is described here. The assay also allows for determination of the binding affinity to a particular sequence.