Evidence for a cognitive control network for goal-directed attention in simple sustained attention

The deterioration of performance over time is characteristic for sustained attention tasks. This so-called "performance decrement" is measured by the increase of reaction time (RT) over time. Some behavioural and neurobiological mechanisms of this phenomenon are not yet fully understood. Behaviourally, we examined the increase of RT over time and the inter-individual differences of this performance decrement. On the neurophysiological level, we investigated the task-relevant brain areas where neural activity was modulated by RT and searched for brain areas involved in good performance (i.e. participants with no or moderate performance decrement) as compared to poor performance (i.e. participants with a steep performance decrement). For this purpose, 20 healthy, young subjects performed a carefully designed task for simple sustained attention, namely a low-demanding version of the Rapid Visual Information Processing task. We employed a rapid event-related functional magnetic resonance imaging (fMRI) design. The behavioural results showed a significant increase of RT over time in the whole group, and also revealed that some participants were not as prone to the performance decrement as others. The latter was statistically significant comparing good versus poor performers. Moreover, high BOLD-responses were linked to longer RTs in a task-relevant bilateral fronto-cingulate-insular-parietal network. Among these regions, good performance was associated with significantly higher RT-BOLD correlations in the pre-supplementary motor area (pre-SMA). We concluded that the task-relevant bilateral fronto-cingulate-insular-parietal network was a cognitive control network responsible for goal-directed attention. The pre-SMA in particular might be associated with the performance decrement insofar that good performers could sustain activity in this brain region in order to monitor performance declines and adjust behavioural output.

In need of psychiatric help--leave a message after the beep

Every day, a substantial proportion of the general population experiences the distressing and frightening signs of an upcoming psychiatric illness. The consequences can be enormous because severe psychiatric disorders typically cause the loss of the ability to work and often mean a long-term burden for both the patients and their families. Even though most developed countries have an exceptionally high density of general practitioners and psychiatrists in private practice, getting a mental health appointment and seeing a doctor is often very difficult for patients with acute psychiatric symptoms. This study aimed at quantifying the time delay involved in seeking medical attendance when psychiatric disorders begin to develop.

Transmission dynamics of extended-spectrum β-lactamase-producing Enterobacteriaceae in the tertiary care hospital and the household setting

Studies about transmission rates of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae in hospitals and households are scarce.

Elevated glycodelin-A concentrations in serum and peritoneal fluid of women with ovarian endometriosis

The aim of this study was to evaluate serum and peritoneal fluid (PF) glycodelin-A concentrations in women with ovarian endometriosis. Ninety-nine matched pairs of serum and PF samples were included in our study. The case group comprised 57 women with ovarian endometriosis and the control group 42 healthy women undergoing sterilization or patients with benign ovarian cysts. Glycodelin-A concentrations were measured using ELISA. Endometriosis patients had significantly higher serum and PF glycodelin-A concentrations compared to controls, and this increase was observed in both proliferative and secretory cycle phases. Glycodelin-A concentrations were more than 10-fold higher in PF than in serum and correlated with each other. Intensity and frequency of menstrual pain positively correlated with glycodelin-A concentrations. Sensitivity and specificity of glycodelin-A as a biomarker for ovarian endometriosis were 82.1% and 78.4% in serum, and 79.7% and 77.5% in PF, respectively. These results indicate that Glycodelin-A has a potential role as a biomarker to be used in combination with other, independent marker molecules.

Evidence of viral adaptation to HLA class I-restricted immune pressure in chronic hepatitis C virus infection

Cellular immune responses are an important correlate of hepatitis C virus (HCV) infection outcome. These responses are governed by the host's human leukocyte antigen (HLA) type, and HLA-restricted viral escape mutants are a critical aspect of this host-virus interaction. We examined the driving forces of HCV evolution by characterizing the in vivo selective pressure(s) exerted on single amino acid residues within nonstructural protein 3 (NS3) by the HLA types present in two host populations. Associations between polymorphisms within NS3 and HLA class I alleles were assessed in 118 individuals from Western Australia and Switzerland with chronic hepatitis C infection, of whom 82 (69%) were coinfected with human immunodeficiency virus. The levels and locations of amino acid polymorphisms exhibited within NS3 were remarkably similar between the two cohorts and revealed regions under functional constraint and selective pressures. We identified specific HCV mutations within and flanking published epitopes with the correct HLA restriction and predicted escaped amino acid. Additional HLA-restricted mutations were identified that mark putative epitopes targeted by cell-mediated immune responses. This analysis of host-virus interaction reveals evidence of HCV adaptation to HLA class I-restricted immune pressure and identifies in vivo targets of cellular immune responses at the population level.

Effect of oral donepezil on intraocular pressure in normotensive Alzheimer patients

Donepezil, a selective acetylcholinesterase (AChE) inhibitor, has been shown to reduce intraocular pressure (IOP) in ocular normotensive rabbit eyes. The aim of this investigation was to evaluate the effect of oral donepezil on IOP and pupil diameter after mid-term oral treatment in normotensive persons. Thirty-two newly diagnosed Alzheimer patients with normal IOP and no further antiglaucomatous treatment were included in the study. IOP and pupil diameter were evaluated before and 4 weeks after daily intake of 5 mg donepezil. IOP and pupil diameter were significantly lower/smaller after 4 weeks of treatment. The mean IOP of all 63 eyes was 14.1 mmHg before and 12.8 mmHg after treatment (8.8% reduction). Mean pupil diameter constricted from 3.9 to 3.6 mm (-7.4%). These findings show that donepezil, and, possibly, other selective AChE inhibitors, can potentially be used to treat glaucoma. They are also known to have neuroprotective effects in Alzheimer's, and, therefore, might have an additional therapeutic benefit.

Educating...for what?: Creativity and Resilience

Higgins School of the Humanities/Difficult Dialogues: Video Recording from 12/1/2011 event featuring Katja Esson, Li- Young Lee and Alison Granucci titled "Creativity and Resilience" Event Description: To be creative is one of life’s most engaging and satisfying experiences. Can we insure that students trust those capacities and processes in themselves, and develop reliable paths toward them? Can we encourage the cultivation of the imagination in our students, as well as the resilience to weather discouragement, whether in their creative search or other aspects of life? Our guests for a conversation on creativity and resilience are filmmaker Katja Esson, poet Li-Young Lee, and co-producer Alison Granucci. They are collaborators on the new film Poetry of Resilience.

Excessive erythrocytosis in adult mice overexpressing erythropoietin leads to hepatic, renal, neuronal, and muscular degeneration

To investigate the consequences of inborn excessive erythrocytosis, we made use of our transgenic mouse line (tg6) that constitutively overexpresses erythropoietin (Epo) in a hypoxia-independent manner, thereby reaching hematocrit levels of up to 0.89. We detected expression of human Epo in the brain and, to a lesser extent, in the lung but not in the heart, kidney, or liver of tg6 mice. Although no acute cardiovascular complications are observed, tg6 animals have a reduced lifespan. Decreased swim performance was observed in 5-mo-old tg6 mice. At about 7 mo, several tg6 animals developed spastic contractions of the hindlimbs followed by paralysis. Morphological analysis by light and electron microscopy showed degenerative processes in liver and kidney characterized by increased vascular permeability, chronic progressive inflammation, hemosiderin deposition, and general vasodilatation. Moreover, most of the animals showed severe nerve fiber degeneration of the sciatic nerve, decreased number of neuromuscular junctions, and degeneration of skeletal muscle fibers. Most probably, the developing demyelinating neuropathy resulted in muscular degeneration demonstrated in the extensor digitorum longus muscle. Taken together, chronically increased Epo levels inducing excessive erythrocytosis leads to multiple organ degeneration and reduced life expectancy. This model allows investigation of the impact of excessive erythrocytosis in individuals suffering from polycythemia vera, chronic mountain sickness, or in subjects tempted to abuse Epo by means of gene doping.

Examining the gateway to the limbic system with diffusion tensor imaging: the perforant pathway in dementia

Current treatments for Alzheimer's disease (AD) are only able to slow the progression of mental deterioration, making early and reliable diagnosis an essential part of any promising therapeutic strategy. In the initial stages of AD, the first neuropathological alterations occur in the perforant pathway (PP), a large neuronal fiber tract located at the entrance to the limbic system. However, to date, there is no sensitive diagnostic tool for performing in vivo assessments of this structure. In the present bimodal magnetic resonance imaging (MRI) study, we examined 10 elderly controls, 10 subjects suffering from mild cognitive impairment (MCI), and 10 AD patients in order to evaluate the sensitivity of diffusion tensor imaging (DTI), a new MRI technique, for detecting changes in the PP. Furthermore, the diagnostic explanatory power of DTI data of the PP should be compared to high-resolution MRI volumetry and intervoxel coherences (COH) of the hippocampus and the entorhinal cortex, two limbic regions also involved in the pathophysiology of early AD. DTI revealed a marked decrease in COH values in the PP region of MCI (right side: 26%, left side: 29%, as compared to controls) and AD patients (right side: 37%, left side: 43%, as compared to controls). Reductions in COH values of the PP region were significantly correlated with cognitive impairment. DTI data of the PP zone were the only parameter differing significantly between control subjects and MCI patients, while the volumetric measures and the COH values of the hippocampus and the entorhinal cortex did not. DTI of medial temporal brain regions is a promising non-invasive tool for the in vivo diagnosis of the early/preclinical stages of AD.

Help-seeking pathways in early psychosis

INTRODUCTION: Understanding the help-seeking pathways of patients with a putative risk of developing psychosis helps improving development of specialised care services. This study aimed at obtaining information about: type of health professionals contacted by patients at putative risk for psychosis on their help-seeking pathways; number of contacts; type of symptoms leading to contacts with health professionals; interval between initial contact and referral to a specialised outpatient service. METHOD: The help-seeking pathways were assessed as part of a prospective study in 104 patients with suspected at-risk states for psychosis. RESULTS: The mean number of contacts prior to referral was 2.38. Patients with psychotic symptoms more often contacted mental health professionals, whereas patients with insidious and more unspecific features more frequently contacted general practitioners (GPs). CONCLUSIONS: GPs have been found to under-identify the insidious features of emerging psychosis (Simon et al. (2005) Br J Psychiatry 187:274-281). The fact that they were most often contacted by patients with exactly these features calls for focussed and specialised help for primary care physicians. Thus, delays along the help-seeking pathways may be shortened. This may be of particular relevance for patients with the deficit syndrome of schizophrenia.

Breast cancer and human papillomavirus (HPV) infection: No evidence of a viral etiology in a group of Swiss women

There are controversial data on the meaning of viral induction of breast cancer. The aim of this study was to investigate the presence of human papillomavirus (HPV) DNA in patients with breast carcinoma and the correlation of viral infection with disease outcome. Paraffin-embedded sections from 81 patients with breast cancer were analyzed for HPV DNA by polymerase chain reaction (PCR) using the SPF1/2 primers covering about 40 different low-, intermediate- and high-risk types. We found all samples were negative for HPV DNA. Our analysis could not support a role of HPV in breast carcinoma. Controversial published data indicate a need for further, larger epidemiologic studies.