Advances and potential new developments in imaging techniques for posterior uveitis Part 2: invasive imaging methods

The aim of this review was to identify the imaging methods at our disposal to optimally manage posterior uveitis at the present time. The focus was put on methods that have become available since the 1990s, some 30 years after fluorescein angiography had revolutionised imaging of posterior uveitis in particular imaging of the retinal vascular structures in the 1960s. We have focussed our review on precise imaging methods that have been standardised and validated and can be used universally thanks to commercially produced and available instruments for the diagnosis and follow-up of posterior uveitis. The second part of this imaging review will deal with invasive imaging methods and in particular ocular angiography.Subject terms: Uveal diseases, Medical imaging     

Transmitter-receptor mismatch in GABAergic synapses in the absence of activity

Competition among different axons to reach the somatodendritic region of the target neuron is an important event during development to achieve the final architecture typical of the mature brain. Trasmitter-receptor matching is a critical step for the signaling between neurons. In the cerebellar cortex, there is a persistent competition between the two glutamatergic inputs, the parallel fibers and the climbing fibers, for the innervation of the Purkinje cells. The activity of the latter input is necessary to maintain its own synaptic contacts on the proximal dendritic domain and to confine the parallel fibers in the distal one. Here, we show that climbing fiber activity also limits the distribution of the GABAergic input in the proximal domain. In addition, blocking the activity by tetrodotoxin infusion in Wistar rat cerebellum, a synapse made by GABAergic terminals onto the recently formed Purkinje cell spines appear in the proximal dendrites. The density of GABAergic terminals is increased, and unexpected double symmetric/asymmetric postsynaptic densities add to the typical symmetric phenotype of the GABAergic shaft synapses. Moreover, glutamate receptors appear in these ectopic synapses even in the absence of glutamate transmitter inside the presynaptic terminal and close to GABA receptors. These results suggest that the Purkinje cell has an intrinsic tendency to develop postsynaptic assemblies of excitatory types, including glutamate receptors, over the entire dendritic territory. GABA receptors are induced in these assemblies when contacted by GABAergic terminals, thus leading to the formation of hybrid synapses.     

Malignant lentigo-melanoma—A comparative histological and electron microscopy study

We examined, by light and electron microscopy, three cases of malignant lentigo, one of which was in the vertical growth phase. The purpose of our work was to compare the diverse patterns between superficial spreading melanoma and malignant lentigo. The observations suggest the following major findings: 1) the cells of malignant lentigo differ from normal melanocytes, and in the same specimen they differ from one another; 2) in malignant lentigo, melanosomes at stage II-IV are visible; and 3) in spreading melanoma, the melanosomes do not attain complete maturation. These morphological features explain the different behaviour of these two types of tumors.     

Value congruence and depressive symptoms among critical care clinicians: The mediating role of moral distress

Clinicians working in intensive care units are often exposed to several job stressors that can negatively affect their mental health. Literature has acknowledged the role of value congruence and job control in determining clinicians' psychological well‐being and depressive symptoms. However, potential mediators of this association have been scarcely examined. This study aimed to test the mediating role of moral distress in the relationship between value congruence and job control, on the one hand, and depression, on the other hand. A cross‐sectional study involving physicians, nurses, and residents working in 7 intensive care units in the north of Italy was conducted. Clinicians were administered in the Italian Moral Distress Scale—Revised, the value and control subscales of the Areas of Worklife Scale, and the Beck Depression Inventory II. Structural equation modeling was used to test the mediation model. Analysis on 170 questionnaires (response rate 72%) found no relations between job control and moral distress. A total indirect effect of value congruence on depression through moral distress (β = ?.12; p = .02) was found. Moral distress contributes to the development of depressive symptoms among critical care clinicians who perceive a value incongruence with their organization and therefore should be addressed.     

Paroxetine inhibits acute effects of 3,4-methylenedioxymethamphetamine on the immune system in humans

The effect of pretreatment with paroxetine on cell-mediated immune response and release of cytokines after the administration of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") was investigated in a double-blind, randomized, crossover, controlled clinical trial in which 12 healthy male recreational users of MDMA participated. Subjects received 20 mg/day paroxetine (or placebo) for the 3 days before MDMA challenge (100 mg). Acute MDMA administration produced a time-dependent decrease in CD4 T-helper cells, a decrease in the functional responsiveness of lymphocytes to mitogenic stimulation, a simultaneous increase in natural killer (NK) cells as well as cortisol and prolactin stimulation kinetics. A high increase in the release of anti-inflammatory cytokines (transforming growth factor-beta and interleukin-10) with a simultaneous decrease of anti-inflammatory response (interleukin-2) was also observed. Pretreatment with paroxetine partially reduced MDMA effects on CD4 T and NK cells, whereas totally inhibiting the suppression of the immune response to mitogens and alterations in cytokines release. MDMA-induced alterations in the immune system as well as antagonistic effects mediated by paroxetine show a trend toward baseline levels at 24 h. These findings suggest that acute effects of MDMA on immune system are mainly mediated by its interaction with the serotonin transporter and subsequent serotonin release with a possible participation of other neuroendocrine regulatory systems.     

Elevated lipid peroxidation biomarkers and low antioxidant status in atherosclerotic patients with increased carotid or iliofemoral intima media thickness.

OBJECTIVES: Lipid peroxidation plays an important role in the development of atherosclerosis, a chronic, age-related disease process of the arterial wall with onset decades prior to its clinical manifestations. The aim of the study was to assess the association between the intima media thickness (IMT) of the major arteries as a clinical marker of atherosclerosis and markers of lipid peroxidation along with the antioxidant status in humans. DESIGN: Case-control study. SETTING: A university-affiliated outpatient clinic. SUBJECTS: Thirty patients (22 males, 8 females; 70.4 +/- 7.3 years) with atherosclerosis of the carotid or iliofemoral arteries and 62 healthy controls (30 males, 32 females; 68.3 +/- 4.3 years). METHODS: Plasma levels of 8,12-isoprostane F2alpha-VI (8,12-IPF2alpha-VI) were measured by gas chromatography/mass spectrometry, whereas levels of malondialdehyde (MDA), vitamins A (retinol) and E (alpha- and gamma-tocopherol), and carotenoids were determined by high-performance liquid chromatography. The IMT was measured by B-mode ultrasonography. RESULTS: Patients showed, independent of fruit and vegetable intake, significantly lower plasma levels of retinol, alpha-tocopherol, and all carotenoids excluding beta-cryptoxanthin compared with controls. On the contrary, plasma 8,12-IPF2alpha-VI levels were almost doubled (p < .001) and MDA levels increased by one-third (p < .01) in atherosclerotic patients compared with controls. CONCLUSIONS: The analyses of isoprostanes and antioxidant nutrients in plasma as markers of oxidative stress and the parallel evaluation of IMT as a structural marker of atherosclerosis are suitable tools for investigating the role of antioxidants and oxidative stress in atherosclerosis.     

HBV-related liver disease in renal insufficiency: successful antiviral therapy with entecavir

Hepatitis B virus (HBV) infection persists among patients with renal insufficiency in the industrialized world. A variety of therapeutic options are now available for the treatment of chronic hepatitis B infection, including potent new nucleos(t)ide analogs, along with standard and pegylated interferon. We report on a patient with aggressive hepatitis B and renal insufficiency who was successfully treated with nucleoside analogs (mostly entecavir monotherapy) for two years. He received intense immunosuppression for severe myopathy of lower limbs, probably related to vasculitis. HBV DNA (at the beginning, > 1 x 10(8) IU/mL) was no longer detectable in serum after a few months of antiviral therapy, while HBeAg and HBsAg seroconversion occurred with ALT normalization. Clinical signs of vasculitis disappeared. Five months after discontinuation of entecavir therapy, he remained HBsAg negative with detectable anti-HBs antibody in serum. We conclude that nucleos(t)ide analogs can offer excellent response in selected patients with renal insufficiency and hepatitis B-related liver disease. Prospective, controlled clinical trials are needed to confirm these encouraging results.     

Ultrastructural evidence of ependymal differentiation in a genetically proven atypical teratoid/rhabdoid tumor

Introduction  

We describe a case of genetically proven atypical teratoid/rhabdoid tumor (ATRT), showing ultrastructural evidence of ependymal differentiation. Such differentiation has not been reported so far in ATRT.