Restless ‘rest’: intrinsic sensory hyperactivity and disinhibition in post-traumatic stress disorder

Abstract

Post-traumatic stress disorder is characterized by exaggerated threat response, and theoretical accounts to date have focused on impaired threat processing and dysregulated prefrontal-cortex-amygdala circuitry. Nevertheless, evidence is accruing for broad, threat-neutral sensory hyperactivity in post-traumatic stress disorder. As low-level, sensory processing impacts higher-order operations, such sensory anomalies can contribute to widespread dysfunctions, presenting an additional aetiological mechanism for post-traumatic stress disorder. To elucidate a sensory pathology of post-traumatic stress disorder, we examined intrinsic visual cortical activity (based on posterior alpha oscillations) and bottom-up sensory-driven causal connectivity (Granger causality in the alpha band) during a resting state (eyes open) and a passive, serial picture viewing state. Compared to patients with generalized anxiety disorder (n = 24) and healthy control subjects (n = 20), patients with post-traumatic stress disorder (n = 25) demonstrated intrinsic sensory hyperactivity (suppressed posterior alpha power, source-localized to the visual cortex—cuneus and precuneus) and bottom-up inhibition deficits (reduced posterior→frontal Granger causality). As sensory input increased from resting to passive picture viewing, patients with post-traumatic stress disorder failed to demonstrate alpha adaptation, highlighting a rigid, set mode of sensory hyperactivity. Interestingly, patients with post-traumatic stress disorder also showed heightened frontal processing (augmented frontal gamma power, source-localized to the superior frontal gyrus and dorsal cingulate cortex), accompanied by attenuated top–down inhibition (reduced frontal→posterior causality). Importantly, not only did suppressed alpha power and bottom-up causality correlate with heightened frontal gamma power, they also correlated with increased severity of sensory and executive dysfunctions (i.e. hypervigilance and impulse control deficits, respectively). Therefore, sensory aberrations help construct a vicious cycle in post-traumatic stress disorder that is in action even at rest, implicating dysregulated triangular sensory-prefrontal-cortex-amygdala circuitry: intrinsic sensory hyperactivity and disinhibition give rise to frontal overload and disrupt executive control, fuelling and perpetuating post-traumatic stress disorder symptoms. Absent in generalized anxiety disorder, these aberrations highlight a unique sensory pathology of post-traumatic stress disorder (ruling out effects merely reflecting anxious hyperarousal), motivating new interventions targeting sensory processing and the sensory brain in these patients.

http://ift.tt/2qM68SD

HSCT Based Approaches for Tolerance Induction in Renal Transplant.

Renal transplantation has become the preferred treatment for end stage kidney failure. Although short-term graft survival has significantly improved as advances in immunosuppression have occurred, long term patient and graft survival have not. Approximately only 50% of renal transplant recipients are alive at 10 years due to the toxicities of immunosuppression and alloimmunity. Emerging research on cell-based therapies is opening a new door for patients to receive the organs they need without sacrificing quality of life and longevity because of drug based immunosuppression. Research has focused upon inducing tolerance, a state in which the body accepts the transplant and graft function is stable. Cell-based therapies to facilitate chimerism and achieve tolerance in MHC-disparate recipients have been developed in mouse, swine, canine, and nonhuman primate models. These finding are now being translated into the clinic in several trials currently underway. Protocols that utilize a combination of traditional therapeutic agents paired with cell populations including hematopoietic stem cells (HSC), regulatory T cells (Treg), and facilitating cells (FCRx) are being conducted with the objective to harness the donor immune system to protect the transplanted tissue. The benefits and feasibility of the clinical application of cell-based therapy has been demonstrated and promising results have been achieved. Here we discuss the preclinical work that has led to the clinical application of the various approaches and a summary of the most current clinical data from groups throughout the world. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2qQPFYP

Advanced Donation Programs and Deceased Donor Initiated Chains - 2 Innovations in Kidney Paired Donation.

Kidney paired donation strategies have facilitated compatible living-donor kidney transplants for end stage renal disease patients with willing but incompatible living donors. Success has inspired further innovations that expand opportunities for kidney-paired donation. Two such innovations are the advanced donation strategy in which a donor provides a kidney before their recipient is matched, or even in need of, a kidney transplant, and deceased donor initiated chains in which chains are started with deceased donors rather than altruistic living donors. While these innovations may expand kidney paired donation, they raise several ethical issues. Specific concerns raised by advanced donation include the management of uncertainty, the extent of donor and recipient consent, the scope of the obligation that the organization has to the kidney exchange paired recipient, the naming of alternative recipients, and the potential to unfairly advantage the recipient. Use of deceased donors for chain initiating kidneys raises ethical issues concerning the consent process for each involved party, the prioritization of deceased donor kidneys, the allocation of chain ending kidneys, and the value of a living donor kidney versus a deceased donor kidney. We outline each ethical issue and discuss how it can be conceptualized and managed so that these kidney paired donation innovations programs are ultimately successful. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2rlRlwM

Supplementation of Syzygium cumini seed powder prevented obesity, glucose intolerance, hyperlipidemia and oxidative stress in high carbohydrate high fat diet induced obese rats

Obesity and related complications have now became epidemic both in developed and developing countries. Cafeteria type diet mainly composed of high fat high carbohydrate components which plays a significant rol...

http://ift.tt/2rCexaL

Changes in pancreatic histology, insulin secretion and oxidative status in diabetic rats following treatment with Ficus deltoidea and vitexin

The potential application of Ficus deltoidea and vitexin for the management of symptomatologies associated with diabetes mellitus (DM) has gained much attention. However, less firm evidence comes from data to aug...

http://ift.tt/2szUGWM

Smooth pursuits decrease balance control during locomotion in young and older healthy females

Abstract

Dynamic balance control—characterised as movement of the trunk and lower limbs—was assessed during fixation of a fixed target, smooth pursuits and saccadic eye movements in ten young (22.9 ± 1.5 years) and ten older (72.1 ± 8.2 years) healthy females walking overground. Participants were presented with visual stimuli to initiate eye movements, and posture and gaze were assessed with motion analysis and eye tracking equipment. The results showed an increase in medial/lateral (ML) trunk movement (C7: p = 0.012; sacrum: p = 0.009) and step-width variability (p = 0.052) during smooth pursuits compared to a fixed target, with no changes for saccades compared to a fixed target. The elders demonstrated greater ML trunk movement (sacrum: p = 0.037) and step-width variability (p = 0.037) than the younger adults throughout, although this did not interact with the eye movements. The findings showed that smooth pursuits decreased balance control in young and older adults similarly, which was likely a consequence of more complicated retinal flow. Since healthy elders are typically already at a postural disadvantage, further decreases in balance caused by smooth pursuits are undesirable.

http://ift.tt/2rmfFi3

Severe complicated neutropenia in two patients with metastatic non-small-cell lung cancer treated with nivolumab.

Checkpoint inhibitors effectively enhance the natural immune response against cancer, but they are also known to induce a unique spectrum of immune-related adverse events. Here, we report the first case of isolated neutropenia subsequent to nivolumab therapy. Prominent activated T-cells were found in the patient's serum and bone marrow alongside evidence of maturational defects in neutrophil precursors. Antineutrophil antibodies were not detected despite reliable testing techniques. A T-cell-mediated response is probable, consistent with the established mechanism for the development of other immune-related toxicities. Awareness of this rare and severe side effect reinforces the importance of early diagnosis and prompt initiation of proper treatment. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2soKelO