Anti-Inflammatory Treatment Efficacy in Major Depressive Disorder: A Systematic Review of Meta-Analyses.

Purpose: Immune imbalances in major depressive disorder (MDD) have been targeted by anti-inflammatory treatment approaches in clinical trials to increase responsiveness to therapy. However, even after several meta-analyses, no translation of evidence into clinical practice has taken place. We performed a systematic review to evaluate meta-analytic evidence of randomized controlled trials on the use of anti-inflammatory agents for MDD to summarize efficacy estimates and elucidate shortcomings.

Integration of Heterogeneous Biological Data in Multiscale Mechanistic Model Calibration: Application to Lung Adenocarcinoma.

Mechanistic models are built using knowledge as the primary information source, with well-established biological and physical laws determining the causal relationships within the model. Once the causal structure of the model is determined, parameters must be defined in order to accurately reproduce relevant data. Determining parameters and their values is particularly challenging in the case of models of pathophysiology, for which data for calibration is sparse.

Symptom Recognition Is Impaired in Patients With Orthostatic Hypotension.

Failure to recognize symptoms of orthostatic hypotension (OH) may result in falls, syncope, and injuries. The relationship between orthostatic changes in blood pressure and symptom occurrence and severity is not known. The goal of the present study was to define the relationship between the occurrence and severity of the symptoms of orthostatic hypotension (OH) and (1) the upright systolic blood pressure (SBP) and (2) the fall in SBP after tilting in patients with OH.

Autonomic testing, methods and techniques.

The evaluation of autonomic function requires indirect assessment of neurophysiologic function using specialized equipment that is often available only at tertiary care centers, with few specialists available. However, the evaluation of autonomic function is rooted in basic physiology, and the results can be interpreted by careful consideration of the context of the problem. Many automated devices have become widely available to test autonomic function, but they tend to gather inadequate data leading to frequent misdiagnosis and clinical confusion.

Feature selection and prediction of treatment failure in tuberculosis.

Background: Tuberculosis is a major cause of morbidity and mortality in the developing world. Drug resistance, which is predicted to rise in many countries worldwide, threatens tuberculosis treatment and control.

Objective: To identify features associated with treatment failure and to predict which patients are at highest risk of treatment failure.

Vascular Endothelial Growth Factor Prevents Endothelial-to-Mesenchymal Transition in Hypertrophy.

Background: In hypertrophy, progressive loss of function caused by impaired diastolic compliance correlates with advancing cardiac fibrosis. Endothelial cells contribute to this process through endothelial-to-mesenchymal transition (EndMT) resulting from inductive signals such as transforming growth factor (TGF-β). Vascular endothelial growth factor (VEGF) has proven effective in preserving systolic function and delaying the onset of failure.

Subsequent Bilateral Hippocampal Diffusion Restriction and Atrophy in Repeated Status Epilepticus.

Background: Cortical lesions in status epilepticus have been reported but the underlying mechanisms are poorly elucidated.

Case Summary: We report on afemale patient (75 years) with a history of alcohol abuse who presented with complex partial status epilepticus and lateralized epileptiform discharges in the left frontal and temporal regions in EEG. While cranial magnetic resonance imaging (MRI) showed left hippocampal T2-hyperintensity and diffusion restriction, cerebrospinal fluid was normal and revealed no limbic encephalitis-related antibodies.

Distention of the Immature Left Ventricle Triggers Development of Endocardial Fibroelastosis: An Animal Model of Endocardial Fibroelastosis Introducing Morphopathological Features of Evolving Fetal Hypoplastic Left Heart Syndrome.

Background: Endocardial fibroelastosis (EFE), characterized by a diffuse endocardial thickening through collagen and elastin fibers, develops in the human fetal heart restricting growth of the left ventricle (LV). Recent advances in fetal imaging indicate that EFE development is directly associated with a distended, poorly contractile LV in evolving hypoplastic left heart syndrome (HLHS). In this study, we developed an animal model of EFE by introducing this human fetal LV morphopathology to an immature rat heart.

Bio-inspired cryo-ink preserves red blood cell phenotype and function during nanoliter vitrification.

Current red-blood-cell cryopreservation methods utilize bulk volumes, causing cryo-injury of cells, which results in irreversible disruption of cell morphology, mechanics, and function. An innovative approach to preserve human red-blood-cell morphology, mechanics, and function following vitrification in nanoliter volumes is developed using a novel cryo-ink integrated with a bioprinting approach.

Laser Doppler imaging in the detection of peripheral neuropathy.

Small fiber neuropathy is common in a number of systemic diseases and is often challenging to diagnose. Laser Doppler imaging (LDI) is a test of small fiber neurovascular function that can quantify the integrity of the vasomotor C-fiber mediated axon-reflex, but no standardized method of analysis exists. We developed a novel LDI analysis technique and tested it in a human model of small fiber neuropathy.

A human model of small fiber neuropathy to study wound healing.

The aim of this study was to develop a human model of acute wound healing that isolated the effects of small fiber neuropathy on the healing process. Twenty-five healthy subjects had the transient receptor vanilloid 1 agonist capsaicin and placebo creams topically applied to contralateral areas on the skin of the thigh for 48 hours. Subjects had shallow (1.

Quantification of sudomotor innervation: a comparison of three methods.

Peripheral sudomotor dysfunction is present in many peripheral neuropathies, but structural assessments of sudomotor fibers rarely occur. We evaluated 36 diabetic and 72 healthy control subjects who underwent detailed neurologic examinations and punch skin biopsies. Physical exam findings were quantified by neuropathy impairment score in the lower limb.

CXCR4 enhances engraftment of muscle progenitor cells.

Cell-based therapy is a possible avenue for the treatment of Duchenne muscular dystrophy (DMD), an X-linked skeletal muscle-wasting disease. We have demonstrated that cultured myogenic progenitors derived from the adult skeletal muscle side population can engraft into dystrophic fibers of non-irradiated, non-chemically injured mouse models of DMD (mdx(5cv)) after intravenous and intraarterial transplantation, with engraftment rates approaching 10%. In an effort to elucidate the cell-surface markers that promote progenitor cell extravasation and engraftment after systemic transplantation, we found that expression of the chemokine receptor CXCR4, whose ligand SDF-1 is overexpressed in dystrophic muscle, enhances the extravasation of these cultured progenitor cells into skeletal muscle after intraarterial transplantation.

Quantification of sweat gland innervation: a clinical-pathologic correlation.

Objective: To evaluate a novel method to quantify the density of nerve fibers innervating sweat glands in healthy control and diabetic subjects, to compare the results to an unbiased stereologic technique, and to identify the relationship to standardized physical examination and patient-reported symptom scores.

Methods: Thirty diabetic and 64 healthy subjects had skin biopsies performed at the distal leg and distal and proximal thigh. Nerve fibers innervating sweat glands, stained with PGP 9.

Sweat testing to evaluate autonomic function.

Sudomotor dysfunction is common in many subtypes of neuropathy but is one of the earliest detectable neurophysiologic abnormalities in distal small fiber neuropathy. Clinical assessments of sudomotor function include thermoregulatory sweat testing (TST), quantitative sudomotor axon reflex testing (QSART), silicone impressions, the sympathetic skin response (SSR), the acetylcholine sweat-spot test and quantitative direct and indirect axon reflex testing (QDIRT). These testing techniques, when used in combination, can detect and localize pre- and postganglionic lesions, can provide early diagnosis of sudomotor dysfunction and can monitor disease progression or disease recovery.

QDIRT: quantitative direct and indirect test of sudomotor function.

Objective: To develop a novel assessment of sudomotor function.

Background: Postganglionic sudomotor function is currently evaluated using the quantitative sudomotor axon reflex test (QSART) or silicone impressions. We hypothesize that high-resolution digital photography has advanced sufficiently to allow quantitative direct and indirect reflex testing of sudomotor function (QDIRT) with spatial and temporal resolution comparable to these techniques.

Prolongation of alloskin graft survival by catalytic scavengers of reactive oxygen species.

We tested the effects of salen manganese (Salen-Mn) complexes, which are scavengers of reactive oxygen species exhibiting superoxide dismutase and catalase activities on the rejection of and alloresponse to fully allogeneic skin grafts in mice. We showed that pre-transplant treatment of C57Bl/6 donor skin or of BALB/c recipients with Salen-Mn complexes significantly delayed allograft rejection. ELISPOT analysis of alloimmune response of treated mice revealed a significant reduction of the frequency of type 1 cytokine (pro-inflammatory) producing T-cells, while the number of activated T-cells producing type 2 cytokines was elevated.

Muscle engraftment of myogenic progenitor cells following intraarterial transplantation.

Cell-based therapy continues to be a promising avenue for the treatment of Duchenne muscular dystrophy (DMD), an X-linked skeletal muscle-wasting disease. Recently, we demonstrated that freshly isolated myogenic progenitors contained within the adult skeletal muscle side population (SP) can engraft into dystrophic fibers of nonirradiated mdx(5cv) mice after intravenous transplantation. Engraftment rates, however, have not been therapeutically significant, achieving at most 1% of skeletal muscle myofibers expressing protein from donor-derived nuclei.

Tolerance to noninherited maternal MHC antigens in mice.

The phenomenon of tolerance to noninherited maternal Ags (NIMA) is poorly understood. To analyze the NIMA effect C57BL/6 (H-2(b/b)) males were mated with B6D2F(1) (H-2(b/d)) females, whereby 50% of the offspring are H-2(b/b) mice that have been exposed to maternal H-2(d) alloantigens. Controls were H-2(b/b) offspring of C57BL/6 mothers, either inbred C57BL/6 mice or F(1) backcross mice from breedings with H-2(b/d) fathers.

Nonmyeloablative conditioning is sufficient to allow engraftment of EGFP-expressing bone marrow and subsequent acceptance of EGFP-transgenic skin grafts in mice.

Immunologic reactions against gene therapy products may prove to be a frequent problem in clinical gene therapy protocols. Enhanced green fluorescence protein (EGFP) is commonly used as a marker in gene transfer protocols, and immune responses against EGFP-expressing cells have been documented. The present study was designed to investigate the effect of a pharmacologic, nonmyeloablative, conditioning regimen on the development of EGFP+ donor/recipient mixed bone marrow chimerism and ensuing tolerance to EGFP-expressing transplants.

T-cell response to cardiac myosin persists in the absence of an alloimmune response in recipients with chronic cardiac allograft rejection.

Background: Immune-mediated injury to the graft has been implicated in the pathogenesis of chronic rejection. However, little is known regarding the nature of the antigen(s) involved in this immune process. We demonstrated that cardiac transplantation in mice induces an autoimmune T-cell response to a heart tissue-specific protein, cardiac myosin (CM).

Modulation of tissue-specific immune response to cardiac myosin can prolong survival of allogeneic heart transplants.

The role of immune response to tissue-specific Ags in transplant rejection is poorly defined. We have previously reported that transplantation of cardiac allografts triggers a CD4(+) Th1 cell response to cardiac myosin (CM), a major contractile protein of the heart, and that pretransplant activation of proinflammatory CM-specific T cells accelerates rejection. In this study, we show that administration of CM together with IFA (CM/IFA) can prevent acute rejection of an allogeneic heart transplant.