p70 S6 kinase and actin dynamics: A perspective

p70 S6 kinase (p70S6K), a member of the AGC serine/threonine kinase family, was initially identified as a key player, together with its downstream effector S6, in the regulation of cellular growth and survival. The p70S6K protein has emerged in recent years as a multifunctional protein which also regulates the actin cytoskeleton and thus plays a role in cell migration. This new function is through two important activities of p70S6K, namely actin cross-linking and Rac1 and Cdc42 activation. The testis is critically dependent on an intricate balance of fundamental cellular processes such as adhesion, migration, and differentiation. It is increasingly evident that Rho GTPases and actin binding proteins play fundamental roles in regulating spermatogenesis within the testis. In this review, we will discuss current findings of p70S6K in the control of actin cytoskeleton dynamics. In addition, the potential role of p70S6K in spermatogenesis and testicular function will be highlighted

Spin polarization versus lifetime effects at point contacts between superconducting niobium and normal metals

Point-contact Andreev reflection spectroscopy is used to measure the spin polarization of metals but analysis of the spectra has encountered a number of serious challenges, one of which is the difficulty to distinguish the effects of spin polarization from those of the finite lifetime of Cooper pairs. We have recently confirmed the polarization-lifetime ambiguity for Nb-Co and Nb-Cu contacts and suggested to use Fermi surface mismatch, the normal reflection due to the difference of Fermi wave vectors of the two electrodes, to solve this dilemma. Here we present further experiments on contacts between superconducting Nb and the ferromagnets Fe and Ni as well as the noble metals Ag and Pt that support our previous results. Our data indicate that the Nb - normal metal interfaces have a transparency of up to about 80 per cent and a small, if not negligible, spin polarization.Comment: 7 pages, 2 figures, submitted to Proceedings of the 26th Conference on Low Temperature Physic

Atlantoaxial subluxation as an early manifestation in an adolescent with undifferentiated spondyloarthritis: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Atlantoaxial instability has been described as a manifestation of ankylosing spondylitis (juvenile and adult onset), reactive arthritis, juvenile idiopathic arthritis, and rheumatoid arthritis; however, it has rarely been reported as an early manifestation of these disorders. We present this case report to increase awareness of the condition in the hope that earlier recognition of this disease may prevent further serious injury.</p> <p>Case presentation</p> <p>We report the case of a 17-year-old Hispanic adolescent woman who was initially diagnosed with undifferentiated spondyloarthritis due to peripheral arthritis, enthesitis, a positive human leukocyte antigen B27 result, and inflammatory spinal pain lasting two months. Our patient experienced persistent and worsening occipitocervical pain and signs of myelopathy three months after diagnosis; consequently, we found atlantoaxial instability along with cervical spine bone erosion and pannus formation. She was treated surgically with a C1-2 posterior instrumented fusion and at six weeks post-operatively was started on tumor necrosis factor α blockade. Her occipitocervical symptoms subsided following surgery and initiation of immunomodulation.</p> <p>Conclusions</p> <p>Our report serves to emphasize to pediatric and adult general practitioners, pediatricians, internists, family physicians, pediatric and adult rheumatologists and spine surgeons that atlantoaxial subluxation may be an early manifestation of spondyloarthritis, and that the condition is treatable by surgical intervention and immunomodulation.</p

Sins of Omission

Little is known about the relative incidence of serious errors of omission versus errors of commission. Objective : To identify the most common substantive medical errors identified by medical record review. Design : Retrospective cohort study. Setting : Twelve Veterans Affairs health care systems in 2 regions. Participants : Stratified random sample of 621 patients receiving care over a 2-year period. Main Outcome Measure : Classification of reported quality problems. Methods : Trained physicians reviewed the full inpatient and outpatient record and described quality problems, which were then classified as errors of omission versus commission. Results : Eighty-two percent of patients had at least 1 error reported over a 13-month period. The average number of errors reported per case was 4.7 (95% confidence intervals [CI]: 4.4, 5.0). Overall, 95.7% (95% CI: 94.9%, 96.4%) of errors were identified as being problems with underuse. Inadequate care for people with chronic illnesses was particularly common. Among errors of omission, obtaining insufficient information from histories and physicals (25.3%), inadequacies in diagnostic testing (33.9%), and patients not receiving needed medications (20.7%) were all common. Out of the 2,917 errors identified, only 27 were rated as being highly serious, and 26 (96%) of these were errors of omission. Conclusions : While preventing iatrogenic injury resulting from medical errors is a critically important part of quality improvement, we found that the overwhelming majority of substantive medical errors identifiable from the medical record were related to people getting too little medical care, especially for those with chronic medical conditions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74567/1/j.1525-1497.2005.0152.x.pd

Night Myopia Studied with an Adaptive Optics Visual Analyzer

PURPOSE: Eyes with distant objects in focus in daylight are thought to become myopic in dim light. This phenomenon, often called "night myopia" has been studied extensively for several decades. However, despite its general acceptance, its magnitude and causes are still controversial. A series of experiments were performed to understand night myopia in greater detail. METHODS: We used an adaptive optics instrument operating in invisible infrared light to elucidate the actual magnitude of night myopia and its main causes. The experimental setup allowed the manipulation of the eye's aberrations (and particularly spherical aberration) as well as the use of monochromatic and polychromatic stimuli. Eight subjects with normal vision monocularly determined their best focus position subjectively for a Maltese cross stimulus at different levels of luminance, from the baseline condition of 20 cd/m(2) to the lowest luminance of 22 × 10(-6) cd/m(2). While subjects performed the focusing tasks, their eye's defocus and aberrations were continuously measured with the 1050-nm Hartmann-Shack sensor incorporated in the adaptive optics instrument. The experiment was repeated for a variety of controlled conditions incorporating specific aberrations of the eye and chromatic content of the stimuli. RESULTS: We found large inter-subject variability and an average of -0.8 D myopic shift for low light conditions. The main cause responsible for night myopia was the accommodation shift occurring at low light levels. Other factors, traditionally suggested to explain night myopia, such as chromatic and spherical aberrations, have a much smaller effect in this mechanism. CONCLUSIONS: An adaptive optics visual analyzer was applied to study the phenomenon of night myopia. We found that the defocus shift occurring in dim light is mainly due to accommodation errors

Effectiveness of second-generation antipsychotics: a naturalistic, randomized comparison of olanzapine, quetiapine, risperidone, and ziprasidone

<p>Abstract</p> <p>Background</p> <p>No clear recommendations exist regarding which antipsychotic drug should be prescribed first for a patient suffering from psychosis. The primary aims of this naturalistic study were to assess the head-to-head effectiveness of first-line second-generation antipsychotics with regards to time until drug discontinuation, duration of index admission, time until readmission, change of psychopathology scores and tolerability outcomes.</p> <p>Methods</p> <p>Patients ≥ 18 years of age admitted to the emergency ward for symptoms of psychosis were consecutively randomized to risperidone (n = 53), olanzapine (n = 52), quetiapine (n = 50), or ziprasidone (n = 58), and followed for up to 2 years.</p> <p>Results</p> <p>A total of 213 patients were included, of which 68% were males. The sample represented a diverse population suffering from psychosis. At admittance the mean Positive and Negative Syndrome Scale (PANSS) total score was 74 points and 44% were antipsychotic drug naïve. The primary intention-to-treat analyses revealed no substantial differences between the drugs regarding the times until discontinuation of initial drug, until discharge from index admission, or until readmission. Quetiapine was superior to risperidone and olanzapine in reducing the PANSS total score and the positive subscore. Quetiapine was superior to the other drugs in decreasing the PANSS general psychopathology subscore; in decreasing the Clinical Global Impression - Severity of Illness scale score (CGI-S); and in increasing the Global Assessment of Functioning - Split version, Functions scale score (GAF-F). Ziprasidone was superior to risperidone in decreasing the PANSS positive symptoms subscore and the CGI-S score, and in increasing the GAF-F score. The drugs performed equally with regards to most tolerability outcomes except a higher increase of hip-circumference per day for olanzapine compared to risperidone, and more galactorrhoea for risperidone compared to the other groups.</p> <p>Conclusions</p> <p>Quetiapine appears to be a good starting drug candidate in this sample of patients admitted to hospital for symptoms of psychosis.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov ID; URL: <url>http://www.clinicaltrials.gov/</url>: NCT00932529</p

Evolutionary biology: a basic science for psychiatry?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65529/1/j.1600-0447.1992.tb03234.x.pd

Effectiveness of second generation antipsychotics: A systematic review of randomized trials

<p>Abstract</p> <p>Background</p> <p>Systematic reviews based on efficacy trials are inconclusive about which second generation antipsychotic drug (SGA) should be preferred in normal clinical practice, and studies with longer duration and more pragmatic designs are called for. Effectiveness studies, also known as naturalistic, pragmatic, practical or real life studies, adhere to these principles as they aim to mimic daily clinical practice and have longer follow-up.</p> <p>Objective</p> <p>To review the head-to-head effectiveness of SGAs in the domains of global outcomes, symptoms of disease, and tolerability.</p> <p>Methods</p> <p>Searches were made in Embase, PubMED, and the Cochrane central register of controlled trials for effectiveness studies published from 1980 to 2008, week 1. Different combinations of the keywords <it>antipsychotic*, neuroleptic* AND open, pragmatic, practical, naturalistic, real life, effectiveness, side effect*, unwanted effect*, tolera* AND compar* AND random* </it>were used.</p> <p>Results</p> <p>Sixteen different reports of randomized head-to-head comparisons of SGA effectiveness were located. There were differences regarding sample sizes, inclusion criteria and follow-up periods, as well as sources of financial sponsorship. In acute-phase and first-episode patients no differences between the SGAs were disclosed regarding alleviating symptoms of disease. Olanzapine was associated with more weight gain and adverse effects on serum lipids. In the chronic phase patients olanzapine groups had longer time to discontinuation of treatment and better treatment adherence compared to other SGAs. The majority of studies found no differences between the SGAs in alleviating symptoms of psychosis in chronically ill patients. Olanzapine was associated with more metabolic adverse effects compared to the others SGAs. There were surprisingly few between-drug differences regarding side effects. First generation antipsychotics were associated with lower total mental health care costs in 2 of 3 studies on chronically ill patients, but were also associated with more extrapyramidal side effects compared to the SGAs in several studies.</p> <p>Conclusion</p> <p>In chronically ill patients olanzapine may have an advantage over other SGAs regarding longer time to treatment discontinuation and better drug adherence, but the drug is also associated with more metabolic side effects. More effectiveness studies on first-episode psychosis are needed.</p

Anti-depressive effectiveness of olanzapine, quetiapine, risperidone and ziprasidone: a pragmatic, randomized trial

<p>Abstract</p> <p>Background</p> <p>Efficacy studies indicate anti-depressive effects of at least some second generation antipsychotics (SGAs). The Bergen Psychosis Project (BPP) is a 24-month, pragmatic, industry-independent, randomized, head-to-head comparison of olanzapine, quetiapine, risperidone and ziprasidone in patients acutely admitted with psychosis. The aim of the study is to investigate whether differential anti-depressive effectiveness exists among SGAs in a clinically relevant sample of patients acutely admitted with psychosis.</p> <p>Methods</p> <p>Adult patients acutely admitted to an emergency ward for psychosis were randomized to olanzapine, quetiapine, risperidone or ziprasidone and followed for up to 2 years. Participants were assessed repeatedly using the Positive and Negative Syndrome Scale - Depression factor (PANSS-D) and the Calgary Depression Scale for Schizophrenia (CDSS).</p> <p>Results</p> <p>A total of 226 patients were included. A significant time-effect showing a steady decline in depressive symptoms in all medication groups was demonstrated. There were no substantial differences among the SGAs in reducing the PANSS-D score or the CDSS sum score. Separate analyses of groups with CDSS sum scores > 6 or ≤6, respectively, reflecting degree of depressive morbidity, revealed essentially identical results to the primary analyses. There was a high correlation between the PANSS-D and the CDSS sum score (r = 0.77; p < 0.01).</p> <p>Conclusions</p> <p>There was no substantial difference in anti-depressive effectiveness among olanzapine, quetiapine, risperidone or ziprasidone in this clinically relevant sample of patients acutely admitted to hospital for symptoms of psychosis. Based on our findings we can make no recommendations concerning choice of any particular SGA for targeting symptoms of depression in a patient acutely admitted with psychosis.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov ID; URL: <url>http://www.clinicaltrials.gov/</url>: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00932529">NCT00932529</a></p