Randomized clinical trial of low dose suramin intravenous infusions for treatment of autism spectrum disorder.

Background: There is a critical need for effective treatment of the core symptoms of autism spectrum disorder (ASD). The purinergic antagonist suramin may improve core symptoms through restoration of normal mitochondrial function and reduction of neuro-inflammation via its known antagonism of P2X and P2Y receptors. Nonclinical studies in fragile X knockout mice and the maternal immune activation model support these hypotheses.

Preoperative Breast MRI for Newly Diagnosed Ductal Carcinoma in Situ: Imaging Features and Performance in a Multicenter Setting (ECOG-ACRIN E4112 Trial).

Background There are limited data from clinical trials describing preoperative MRI features and performance in the evaluation of mammographically detected ductal carcinoma in situ (DCIS). Purpose To report qualitative MRI features of DCIS, MRI performance in the identification of additional disease, and associations of imaging features with pathologic, genomic, and surgical outcomes from the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) E4112 trial. Materials and Methods Secondary analyses of a multicenter prospective clinical trial from the ECOG-ACRIN Cancer Research Group included women with DCIS diagnosed with conventional imaging techniques (mammography and US), confirmed via core-needle biopsy (CNB), and enrolled between March 2015 and April 2016 who were candidates for wide local excision (WLE) based on conventional imaging and clinical examination results.

3D Printer Generated Tissue iMolds for Cleared Tissue Using Single- and Multi-Photon Microscopy for Deep Tissue Evaluation.

Background: Pathological analyses and methodology has recently undergone a dramatic revolution. With the creation of tissue clearing methods such as CLARITY and CUBIC, groups can now achieve complete transparency in tissue samples in nano-porous hydrogels. Cleared tissue is then imagined in a semi-aqueous medium that matches the refractive index of the objective being used.

Association of HIV diversity and virologic outcomes in early antiretroviral treatment: HPTN 052.

Higher HIV diversity has been associated with virologic outcomes in children on antiretroviral treatment (ART). We examined the association of HIV diversity with virologic outcomes in adults from the HPTN 052 trial who initiated ART at CD4 cell counts of 350-550 cells/mm3. A high resolution melting (HRM) assay was used to analyze baseline (pre-treatment) HIV diversity in six regions in the HIV genome (two in gag, one in pol, and three in env) from 95 participants who failed ART.

Diverse macrophage populations mediate acute lung inflammation and resolution.

Acute respiratory distress syndrome (ARDS) is a devastating disease with distinct pathological stages. Fundamental to ARDS is the acute onset of lung inflammation as a part of the body's immune response to a variety of local and systemic stimuli. In patients surviving the inflammatory and subsequent fibroproliferative stages, transition from injury to resolution and recovery is an active process dependent on a series of highly coordinated events regulated by the immune system.

Renal and cardiovascular sensory receptors and blood pressure regulation.

Studies over the past decade have highlighted important roles played by sensory receptors outside of traditionally sensory tissues; for example, taste receptors participate in pH sensing in the cerebrospinal fluid, bitter taste receptors mediate bronchodilation and ciliary beating in the lung (Deshpande DA, Wang WC, McIlmoyle EL, Robinett KS, Schillinger RM, An SS, Sham JS, Liggett SB. Nat Med 16: 1299-1304, 2010; Shah AS, Ben-Shahar Y, Moninger TO, Kline JN, Welsh MJ. Science 325: 1131-1134, 2009), and olfactory receptors play roles in both sperm chemotaxis and muscle cell migration (Griffin CA, Kafadar KA, Pavlath GK.

Antibody maturation and viral diversification in HIV-infected women.

Introduction: The Post-exposure Prophylaxis in Infants (PEPI)-Malawi trial evaluated infant antiretroviral regimens for prevention of post-natal HIV transmission. A multi-assay algorithm (MAA) that includes the BED capture immunoassay, an avidity assay, CD4 cell count, and viral load was used to identify women who were vs. were not recently infected at the time of enrollment (MAA recent, N = 73; MAA non-recent, N = 2,488); a subset of the women in the MAA non-recent group known to have been HIV infected for at least 2 years before enrollment (known non-recent, N = 54).

Lessons learned from community-based minority health care serving system participation in an NIH clinical trial.

To address the historically low rate of minority participation in clinical trials, the NIH and others have provided incentives to increase the diversity of patients and study sites involved in NIH-funded research. An example of the efforts to achieve this aim was the creation of the Partnerships Program to Reduce Cardiovascular Health Disparities," whereby a health care system that serves a predominantly minority patient population partners with a research-intensive medical center that has a track record of NIH-supported research. In the city of Baltimore, Maryland, the Bon Secours Baltimore Health System partnered with the University of Maryland and was awarded 1 of 7 U01 partnerships within cardiovascular health.

Acute renal venous obstruction is more detrimental to the kidney than arterial occlusion: implication for murine models of acute kidney injury.

In this study, we compared the traditional murine model with renal pedicle clamp with models that clamped the renal artery or vein alone as well as to a whole body ischemia-reperfusion injury (WBIRI) model. Male C57BL/6J mice underwent either clamping of the renal artery, vein, or both (whole pedicle) for 30 or 45 min followed by reperfusion, or 10 min of cardiac arrest followed by resuscitation up to 24 h. After 30 min of ischemia, the mice with renal vein clamping showed the mostly increased serum creatinine and the most severe renal tubule injury.

A late phase of LTD in cultured cerebellar Purkinje cells requires persistent dynamin-mediated endocytosis.

Long-term synaptic depression (LTD) of cerebellar parallel fiber-Purkinje cell synapses is a form of use-dependent synaptic plasticity that may be studied in cell culture. One form of LTD is induced postsynaptically through an mGlu1/Ca influx/protein kinase Cα (PKCα) cascade, and its initial expression requires phosphorylation of ser-880 in the COOH-terminal PDZ-ligand region of GluA2 and consequent binding of PICK1. This triggers postsynaptic clathrin/dynamin-mediated endocytosis of GluA2-containing surface AMPA receptors.

Recovery of baroreflex control of renal sympathetic nerve activity after spinal lesions in the rat.

Spinal cord injury (SCI) has serious long-term consequences on sympathetic cardiovascular regulation. Orthostatic intolerance results from insufficient baroreflex regulation (BR) of sympathetic outflow to maintain proper blood pressure upon postural changes. Autonomic dysreflexia occurs due to insufficient inhibition of spinal sources of sympathetic activity.

Spinal regions involved in baroreflex control of renal sympathetic nerve activity in the rat.

Spinal cord injury causes debilitating cardiovascular disturbances. The etiology of these disturbances remains obscure, partly because the locations of spinal cord pathways important for sympathetic control of cardiovascular function have not been thoroughly studied. To elucidate these pathways, we examined regions of the thoracic spinal cord important for reflex sympathetic control of arterial pressure (AP).

NHERF1 and NHERF2 are necessary for multiple but usually separate aspects of basal and acute regulation of NHE3 activity.

Na(+)/H(+) exchanger 3 (NHE3) is expressed in the brush border (BB) of intestinal epithelial cells and accounts for the majority of neutral NaCl absorption. It has been shown that the Na(+)/H(+) exchanger regulatory factor (NHERF) family members of multi-PDZ domain-containing scaffold proteins bind to the NHE3 COOH terminus and play necessary roles in NHE3 regulation in intestinal epithelial cells. Most studies of NHE3 regulation have been in cell models in which NHERF1 and/or NHERF2 were overexpressed.

Adenosine-induced activation of esophageal nociceptors.

Clinical studies implicate adenosine acting on esophageal nociceptive pathways in the pathogenesis of noncardiac chest pain originating from the esophagus. However, the effect of adenosine on esophageal afferent nerve subtypes is incompletely understood. We addressed the hypothesis that adenosine selectively activates esophageal nociceptors.

Clinical impact of integrated physiologic brain tumor imaging.

The development of new MRI techniques in the last two decades has provided neuroradiologists and neurosurgeons with additional noninvasive imaging tools for management and treatment of brain tumors. When coupled with standard structural MR sequences in imaging brain tumors, Blood Oxygenation Level Dependent (BOLD) functional MRI (fMRI), Perfusion Weighted Imaging (PWI) and Diffusion Tensor Imaging (DTI) provide additional physiologic information that is very useful for differential diagnosis, presurgical planning and prognosis. In this review after a brief technical description of BOLD fMRI, PWI and DTI, studies are described from the literature that have extensively validated these imaging techniques in comparison with invasive "gold standard" techniques such as intraoperative electrical cortical and subcortical stimulation mapping or biopsy.

Dose combinations of exendin-4 and salmon calcitonin produce additive and synergistic reductions in food intake in nonhuman primates.

Glucagon-like peptide-1 (GLP-1) and amylin mediate the feedback control of eating by seemingly separate, but overlapping mechanisms. This study examined the effects of combined doses of the GLP-1 agonist, exendin-4 (Ex-4), and the amylin analog, salmon calcitonin (sCT), on food intake and meal patterns in adult male rhesus monkeys. Monkeys received intramuscular injections of Ex-4 (0, 0.

VEGF and soluble VEGF receptor-1 (sFlt-1) distributions in peripheral arterial disease: an in silico model.

Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis, the growth of new capillaries from existing microvasculature. In peripheral arterial disease (PAD), lower extremity muscle ischemia develops downstream of atherosclerotic obstruction. A working hypothesis proposed that the maladaptive overexpression of soluble VEGF receptor 1 (sVEGFR1) in ischemic muscle tissues, and its subsequent antagonism of VEGF bioactivity, may contribute to the deficient angiogenic response in PAD, as well as the limited success of therapeutic angiogenesis strategies where exogenous VEGF genes/proteins are delivered.

Repeated binge access to a palatable food alters feeding behavior, hormone profile, and hindbrain c-Fos responses to a test meal in adult male rats.

Repetitive cycles of palatable food access and chronic calorie restriction alter feeding behaviors and forebrain neural systems. The purpose of this study was to determine the behavioral, endocrine, and meal-related hindbrain neural activation in adult male Sprague-Dawley rats exposed to a binge-access feeding schedule. The binge-access schedule consisted of repeated twice-per-week episodes of acute calorie restriction (to one-third of the previous day's intake) followed by 2 h of concurrent access to high-calorie palatable food (sweetened fat: 90% vegetable shortening-10% sucrose) and chow.

Xanthine oxidoreductase in respiratory and cardiovascular disorders.

In addition to its critical role in purine metabolism, xanthine oxidoreductase (XOR) has been implicated in the development of tissue oxidative damage in a wide variety of respiratory and cardiovascular disorders such as acute lung injury, ischemia-reperfusion injury, atherosclerosis, heart failure, and arterial hypertension. Although much remains to be clarified about the regulation and signaling pathways of this enzyme, it is quite evident from abundant investigation in animal models and some human trials that XOR inhibition can favorably alter critical disease processes and impact outcomes. From promising bench-to-bedside data, a better understanding of this enigmatic enzyme is emerging.

Apathy syndrome after traumatic brain injury compared with deficits in schizophrenia.

The authors compared the severity and clinical profiles of patients with two etiologically different apathy syndromes: apathy after traumatic brain injury (TBI) and deficit schizophrenia (DSS). Patients from both groups were equally apathetic, but those with DSS had more severe anhedonia, blunted affect, and alogia, as measured by the Scale for Assessment of Negative Symptoms. These findings suggest that patients with DSS have a more complex presentation of apathy.

Gabor atom density as a measure of seizure complexity.

The Gabor atom density (GAD) is a measure of complexity of a signal. It is based on the time-frequency decomposition obtained by the matching pursuit (MP) algorithm. The GAD/MP method was applied to EEG data recorded from intracranial electrodes in patients with intractable complex partial seizures.

VEGF gradients, receptor activation, and sprout guidance in resting and exercising skeletal muscle.

Extensive experimental studies have identified vascular endothelial growth factor (VEGF) concentrations and concentration gradients as major factors in angiogenesis; however, localized in vivo measurements of these parameters have not been possible. We developed a three-dimensional computational model of skeletal muscle fibers, blood vessels, and interstitial space. Here it is applied to rat extensor digitorum longus.

Interactions of VEGF isoforms with VEGFR-1, VEGFR-2, and neuropilin in vivo: a computational model of human skeletal muscle.

The vascular endothelial growth factor (VEGF) family of cytokines is involved in the maintenance of existing adult blood vessels as well as in angiogenesis, the sprouting of new vessels. To study the proangiogenic activation of VEGF receptors (VEGFRs) by VEGF family members in skeletal muscle, we develop a computational model of VEGF isoforms (VEGF(121), VEGF(165)), their cell surface receptors, and the extracellular matrix in in vivo tissue. We build upon our validated model of the biochemical interactions between VEGF isoforms and receptor tyrosine kinases (VEGFR-1 and VEGFR-2) and nonsignaling neuropilin-1 coreceptors in vitro.

Heart failure-associated alterations in troponin I phosphorylation impair ventricular relaxation-afterload and force-frequency responses and systolic function.

Recent studies have found that selective stimulation of troponin (Tn)I protein kinase A (PKA) phosphorylation enhances heart rate-dependent inotropy and blunts relaxation delay coupled to increased afterload. However, in failing hearts, TnI phosphorylation by PKA declines while protein kinase C (PKC) activity is enhanced, potentially augmenting TnI PKC phosphorylation. Accordingly, we hypothesized that these site-specific changes deleteriously affect both rate-responsive cardiac function and afterload dependence of relaxation, both prominent phenotypic features of the failing heart.

Transfer of lymphocytes from mice with renal ischemia can induce albuminuria in naive mice: a possible mechanism linking early injury and progressive renal disease?

Severe ischemia-reperfusion injury (IRI) predisposes to long-term impairment in kidney function both in patients and experimentally through unknown mechanisms. Given emerging evidence implicating lymphocytes in the pathogenesis of early injury to kidney, liver, and lung after IRI, we hypothesized that kidney IRI would potentially release or expose normally sequestered antigens that would lead to proliferation of antigen-recognizing lymphocytes. This, in turn, would directly participate in progressive kidney injury.