Selective neuroprotective effects of the S18Y polymorphic variant of UCH-L1 in the dopaminergic system

Genetic studies have implicated the neuronal ubiquitin C-terminal hydrolase (UCH) protein UCH-L1 in Parkinson's disease (PD) pathogenesis. Moreover, the function of UCH-L1 may be lost in the brains of PD and Alzheimer's disease patients. We have previously reported that the UCH-L1 polymorphic variant S18Y, potentially protective against PD in population studies, demonstrates specific antioxidant functions in cell culture. Albeit genetic, biochemical and neuropathological data support an association between UCH-L1, PD, synaptic degeneration and oxidative stress, the relationship between the dopaminergic system and UCH-L1 status remains obscure. In the current study, we have examined the dopaminergic system of mice lacking endogenous UCH-L1 protein (gracile axonal dystrophy mice). Our findings show that the lack of wild-type (WT) UCH-L1 does not influence to any significant degree the dopaminergic system at baseline or following injections of the neurotoxin methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Furthermore, using a novel intrastriatal adenoviral injection protocol, we have found that mouse nigral neurons retrogradely transduced with S18Y UCH-L1, but not the WT protein, are significantly protected against MPTP toxicity. Overall, these data provide evidence for an antioxidant and neuroprotective effect of the S18Y variant of UCH-L1, but not of the WT protein, in the dopaminergic system, and may have implications for the pathogenesis of PD or related neurodegenerative conditions, in which oxidative stress might play a role.     

Posttraumatic stress disorder, depression, and suicide in veterans

Suicidal behavior is a critical problem in war veterans. Combat veterans are not only more likely to have suicidal ideation, often associated with posttraumatic stress disorder (PTSD) and depression, but they are more likely to act on a suicidal plan. Especially since veterans may be less likely to seek help from a mental health professional, non-mental-health physicians are in a key position to screen for PTSD, depression, and suicidal ideation in these patients. The authors discuss the association of PTSD, depression, and suicide in veterans, keys to assessment of suicide risk, and interventions.     

Tickling in juvenile but not adult female rats conditions sexual partner preference

Female rats display a conditioned partner preference for males that bear odors paired with different types of rewarding unconditioned stimuli (UCS). Here we examined whether tickling constitutes a rewarding UCS that supports the development of partner preferences. In Experiment 1, we tested the possibility that odors associated with a tickling UCS in prepubescent rats would induce a conditioned partner preference in adulthood. Two groups were formed with 31-day-old, single-housed females, tickled for 6 min daily for 10 days, by a hand that wore a scented glove (almond or lemon). At 47 days of age, females were ovariectomized (OVX), hormone-primed (EB+P), and tested for sexual partner preference with two scented stud males (one almond and one lemon). In each group, females displayed a sexual preference toward males bearing the odor paired with tickling, as observed with longer visits, more solicitations, hops & darts, and receiving more intromissions and ejaculations from the preferred male. In Experiment 2, we used 3-month old, OVX, hormone-primed rats conditioned every 4 days for 10 trials. In contrast to juvenile females, adult females failed to prefer males that bore the odor paired with tickling but instead preferred the novel male. These results suggest that tickling has opposite age-dependent effects in the conditioning of partner preference. Tickling in juvenile females appears to act as a rewarding UCS, whereas in adult females it may act as an aversive UCS. Further research is needed to understand brain mechanisms that might account for such differences.     

STrengthening the Reporting of OBservational studies in Epidemiology--Molecular Epidemiology (STROBE-ME): an extension of the STROBE statement

Advances in laboratory techniques have led to a rapidly increasing use of biomarkers in epidemiological studies. Biomarkers of internal dose, early biological change, susceptibility and clinical outcomes are used as proxies for investigating interactions between external and / or endogenous agents and body components or processes. The need for improved reporting of scientific research led to influential statements of recommendations such as the STrengthening Reporting of OBservational studies in Epidemiology (STROBE) statement. The STROBE initiative established in 2004 aimed to provide guidance on how to report observational research. Its guidelines provide a user-friendly checklist of 22 items to be reported in epidemiological studies, with items specific to the three main study designs: cohort studies, case-control studies and cross-sectional studies. The present STrengthening the Reporting of OBservational studies in Epidemiology - Molecular Epidemiology (STROBE-ME) initiative builds on the STROBE statement implementing nine existing items of STROBE and providing 17 additional items to the 22 items of STROBE checklist. The additions relate to the use of biomarkers in epidemiological studies, concerning collection, handling and storage of biological samples; laboratory methods, validity and reliability of biomarkers; specificities of study design; and ethical considerations. The STROBE-ME recommendations are intended to complement the STROBE recommendations.     

Clinical outcome of spontaneous non-aneurysmal subarachnoid hemorrhage in 108 patients

Background: The cause of spontaneous subarachnoid hemorrhage (SAH) is unknown in 15% of cases; idiopathic SAH has a better prognosis than aneurysmal SAH. When bleeding is confined to the perimesencephalic cisterns, SAH has an especially benign course. Methods: We retrospectively studied 108 patients admitted for spontaneous non‐aneurysmal SAH between 1991 and 2004. We divided patients into two groups according to the bleeding pattern at cranial CT: perimesencephalic pattern (n = 60) and aneurysmal pattern (n = 48). We included only patients in whom no source of bleeding was detected at angiography; patients with aneurysmal pattern underwent at least two angiographic examinations. Mean follow‐up was 5.5 years; follow‐up consisted of telephone interview in 84.7% of patients. Results: All but one patient with perimesencephalic pattern were classified as grade I or II on the Hunt and Hess scale; the exception was the only patient in this group with a complication (hydrocephalus), who was classified as grade IV. Three‐quarters of the patients with aneurysmal pattern were classified as grade I or II on the Hunt and Hess scale; 5 patients presented with hydrocephalus that required drainage and 2 with vasospasms without repercussions. No rebleeding or long‐term complications were observed in either group. Conclusions: Non‐aneurysmal SAH with a perimesencephalic pattern of bleeding has a benign course and excellent short‐term and long‐term prognosis. Patients with non‐aneurysmal SAH with an aneurysmal pattern of bleeding have more complications, and the initial clinical situation has a significant impact on their prognosis.     

Information-Theoretic Approach for Automated White Matter Fiber Tracts Reconstruction

Fiber tracking is the most popular technique for creating white matter connectivity maps from diffusion tensor imaging (DTI). This approach requires a seeding process which is challenging because it is not clear how and where the seeds have to be placed. On the other hand, to enhance the interpretation of fiber maps, segmentation and clustering techniques are applied to organize fibers into anatomical structures. In this paper, we propose a new approach to automatically obtain bundles of fibers grouped into anatomical regions. This method applies an information-theoretic split-and-merge algorithm that considers fractional anisotropy and fiber orientation information to automatically segment white matter into volumes of interest (VOIs) of similar FA and eigenvector orientation. For each VOI, a number of planes and seeds is automatically placed in order to create the fiber bundles. The proposed approach avoids the need for the user to define seeding or selection regions. The whole process requires less than a minute and minimal user interaction. The agreement between the automated and manual approaches has been measured for 10 tracts in a DTI brain atlas and found to be almost perfect (kappa >?0.8) and substantial (kappa >?0.6). This method has also been evaluated on real DTI data considering 5?tracts. Agreement was substantial (kappa >?0.6) in most of the cases.     

Unsuspected visceral leishmaniasis infiltrating a squamous cell carcinoma

Amastigotes of the genus Leishmania have been observed in biopsies of apparently unrelated lesions in patients with AIDS and visceral leishmaniasis. We describe the case of a 40-year-old man with human immunodeficiency virus infection and severe immunodepression in whom the presence of the parasite was detected as an incidental finding on histological study of a perianal squamous cell carcinoma. This finding led to the diagnosis and subsequent treatment of previously unsuspected visceral leishmaniasis. In a review of the literature we have found no previous examples of this association.     

Neurotoxic/neuroprotective activity of haloperidol, risperidone and paliperidone in neuroblastoma cells

The neurotoxicity of antipsychotic (AP) drugs seems to be linked with neurological side effects like extrapyramidal symptoms (EPS). On the other hand, neuroprotective effects can mitigate or slow the progressive degenerative structural changes in the brain leading to improved outcome of schizophrenia. First and second-generation antipsychotics may differ in their neurotoxic and neuroprotective properties. The aim of this study was to compare the neurotoxic/neuroprotective activity of haloperidol, a first-generation antipsychotic, and risperidone, a second-generation one, with paliperidone, a relatively new second-generation antipsychotic, in SK-N-SH cells. Haloperidol, risperidone and paliperidone (10, 50, 100 μM) were administered, either alone or in combination with dopamine (100 μM), to human neuroblastoma SK-N-SH. We examined the effects of the drugs on cell viability (measured by alamarBlue®), caspase-3 activity (measured by fluorimetric assay) and cell death (by measuring the externalization of phosphatidylserine). Haloperidol significantly decreased cell viability and increased caspase-3 activity and cell death. Risperidone and paliperidone did not affect cell viability or cell death. Both second-generation APs decreased caspase-3 activity, especially paliperidone. In cells treated with dopamine in combination with antipsychotics, only paliperidone (10 μM) induced a slight improvement in cell viability. While haloperidol potentiated the dopamine-induced increase in caspase-3 activity, risperidone and paliperidone reduced this effect. The results indicate that haloperidol induces apoptosis, whereas risperidone and paliperidone may afford protection against it. Of the APs tested, paliperidone always showed the strongest neuroprotective effect. The different antipsychotic effects on survival and cell death might be related to differences in their capacity to induce EPS.