Sleepwalking in Parkinson's disease: a questionnaire-based survey

Sleepwalking (SW) corresponds to a complex sleep-associated behavior that includes locomotion, mental confusion, and amnesia. SW is present in about 10% of children and 2-3% of adults. In a retrospective series of 165 patients with Parkinson's disease (PD), we found adult-onset ("de novo”) SW "de novo” in six (4%) of them. The aim of this study was to assess prospectively and systematically the frequency and characteristics of SW in PD patients. A questionnaire including items on sleep quality, sleep disorders, and specifically also SW and REM sleep behavior disorder (RBD), PD characteristics and severity, was sent to the members of the national PD patients organization in Switzerland. In the study, 36/417 patients (9%) reported SW, of which 22 (5%) had adult-onset SW. Patients with SW had significantly longer disease duration (p=0.035), they reported more often hallucinations (p=0.004) and nightmares (p=0.003), and they had higher scores, suggestive for RBD in a validated questionnaire (p=0.001). Patients with SW were also sleepier (trend to a higher Epworth Sleepiness Scale score, p=0.055). Our data suggest that SW in PD patients is (1) more common than in the general population, and (2) is associated with RBD, nightmares, and hallucinations. Further studies including polysomnographic recordings are needed to confirm the results of this questionnaire-based analysis, to understand the relationship between SW and other nighttime wandering behaviors in PD, and to clarify the underlying mechanism

Diagnostic telepathology: long-term experience of a single institution

Objectives: The paper reviews the development of the application of telepathology in a department of surgical pathology between 1991 and 2003. The goal of the efforts during this time was to give up the concept of programming a single application, available only between two fixed workstations with sophisticated devices and special software, and to find the virtual "largest common denominator” for implementing as many different applications as possible with the same basic system. Methods: A new telepathology system was designed as a client-server system with a relational database at its centre. The clients interact together by transferring the questions (texts and images) to a record (case) in the database on the server and by transferring the answers to the same record on the database. Results: The new "open” telepathology system iPath ( http://telepath.patho.unibas.ch ) has been very well accepted by many groups around the world. The main application fields are: consultations between pathologists and medical institutions without a pathologist (e.g. for frozen section diagnoses or for surgical diagnoses in hospitals in South Asia or Africa), tumour boards, field studies and distance education ( http://teleteach.patho.unibas.ch ). Conclusions: Having observed that with iPath we have succeeded in satisfying all our telepathology needs, we are inclined to put the emphasis on the nature of the tasks being performed, as opposed to the methods or technical means for performing a given task. The three organisation models proposed by Weinstein et al. (2001) [24] can be reduced to only two models: the model of discussion groups and the model of expert groups (virtual institutes

The L&E of Intellectual Property – Do we get maximum innovation with the current regime?

Innovation is crucial to economic growth – the essential path for lifting much of the world population out of dire poverty and for maintaining the living standard of those who already have. To stimulate innovation, the legal system has to support the means through which innovators seek to get rewarded for their efforts. Amongst these means, some, such as the first mover advantage or 'lead time,' are not directly legal; but secrets and intellectual property rights are legal institutions supported for the specific purpose of stimulating innovation. Whilst the protection of secrets has not changed very much over recent years, intellectual property (or IP) has. IP borrows some features from ordinary property rights, but is also distinct, in that, unlike physical goods, information, the object of IP, is not inherently scarce; indeed as information and communication technologies expand, the creation and distribution of information is becoming ever cheaper and in many circumstances abundant, so that selection is of the essence ('on the internet, point of view is everything'). Where rights on information extend too far, their monopolising effect may hamper innovation. The paper investigates the underlying structure of IP rights and surveys what we know empirically about the incentive effects of IP as about industries that flourish without formal IP

Cerebrospinal fluid HIV-1 escape in patients with neurocognitive symptoms: pooled data from a neuro-HIV platform and the NAMACO study.

BACKGROUND Despite modern antiretroviral therapy, HIV-1 RNA escape into the cerebrospinal fluid (CSF) may occur. We examined the prevalence of and factors associated with CSF HIV-1 escape among people living with HIV (PLWH) in Switzerland. SETTING The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study is an ongoing, prospective, longitudinal, multicenter study within the Swiss HIV Cohort Study. The neuro-HIV platform is a multi-disciplinary, single-day outpatient consultation at Lausanne University Hospital. METHODS We pooled data from the NAMACO study and the neuro-HIV platform participants who underwent lumbar puncture (LP) between 2011 and 2019. Both patient groups had neurocognitive symptoms. CSF HIV-1 escape was defined as the presence of quantifiable CSF HIV-1 RNA when plasma HIV-1 RNA was suppressed or CSF HIV-1 RNA greater than plasma HIV-1 RNA when the latter was detectable. RESULTS Of 1166 PLWH assessed, 288 underwent LP. CSF HIV-1 escape was observed in 25 PLWH (8.7%) of whom 19 (76%) had supressed plasma HIV-1 RNA. Characteristics of PLWH were comparable whether they had CSF HIV-1 escape or not, including comorbidities, time since HIV diagnosis (15 vs 16 years, p=0.9), median CD4 nadir (158.5/mm3 vs 171/mm3, p=0.6), antiretroviral CSF-Penetration-Effectiveness score (7 vs 7 points, p=0.8), neurocognitive diagnosis based on Frascati criteria and radiological findings. CONCLUSIONS In this large pooled sample of PLWH with neurocognitive symptoms, CSF HIV-1 escape occurred in 8.7% of PLWH. PLWH with CSF HIV-1 escape presented no distinctive clinical or paraclinical characteristics. We conclude that LP is unavoidable in confirming CSF HIV-1 escape

Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. 1. Sildenafil analogs

Author Posting. © The Author(s), 2012. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Bioorganic & Medicinal Chemistry Letters 22 (2012): 2579-2581, doi:10.1016/j.bmcl.2012.01.119.Parasitic diseases, such as African sleeping sickness, have a significant impact on the health and well-being in the poorest regions of the world. Pragmatic drug discovery efforts are needed to find new therapeutic agents. In this report we describe target repurposing efforts focused on trypanosomal phosphodiesterases. We outline the synthesis and biological evaluation of analogs of sildenafil (1), a human PDE5 inhibitor, for activities against trypanosomal PDEB1 (TbrPDEB1). We find that, while low potency analogs can be prepared, this chemical class is a sub-optimal starting point for further development of TbrPDE inhibitors.This work was supported by the National Institutes of Health (R01AI082577), Boston University and Northeastern University

Target repurposing for neglected diseases

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Future Science for personal use, not for redistribution. The definitive version was published in Future Medicinal Chemistry 3 (2011): 1307-1315, doi:10.4155/fmc.11.92.Infectious diseases are an enormous burden to global health, and since drug discovery is costly, those infectious diseases that affect the developing world are often not pursued by commercial drug discovery efforts. Therefore, pragmatic means by which new therapeutics can be discovered are needed. One such approach is target repurposing, where pathogen targets are matched with homologous human targets that have been pursued for drug discovery for other indications. In many cases, the medicinal chemistry, structural biology, and biochemistry knowledge around these human targets can be directly repurposed to launch and accelerate new drug discovery efforts against the pathogen targets. This article describes the overarching strategy of target repurposing as a tool for initiating and prosecuting neglected disease drug discovery programs, highlighting this approach with three case studies.Support from the National Institutes of Health (R01 AI082577) is gratefully acknowledged.2012-08-0

Frequency and evolution of sleep-wake disturbances after ischemic stroke: A 2-year prospective study of 437 patients.

OBJECTIVE In the absence of systematic and longitudinal data, this study prospectively assessed both frequency and evolution of sleep-wake disturbances (SWD) after stroke. METHODS In 437 consecutively recruited patients with ischemic stroke or transient ischemic attack (TIA), stroke characteristics and outcome were assessed within the 1st week and 3.2 ± 0.3 years (M±SD) after the acute event. SWD were assessed by interview and questionnaires at 1 and 3 months as well as 1 and 2 years after the acute event. Sleep disordered breathing (SDB) was assessed by respirography in the acute phase and repeated in one fifth of the participants 3 months and 1 year later. RESULTS Patients (63.8% male, 87% ischemic stroke and mean age 65.1 ± 13.0 years) presented with mean NIHSS-score of 3.5 ± 4.5 at admission. In the acute phase, respiratory event index was >15/h in 34% and >30/h in 15% of patients. Over the entire observation period, the frequencies of excessive daytime sleepiness (EDS), fatigue and insomnia varied between 10-14%, 22-28% and 20-28%, respectively. Mean insomnia and EDS scores decreased from acute to chronic stroke, whereas restless legs syndrome (RLS) percentages (6-9%) and mean fatigue scores remained similar. Mean self-reported sleep duration was enhanced at acute stroke (month 1: 07:54 ± 01:27h) and decreased at chronic stage (year 2: 07:43 ± 01:20h). CONCLUSIONS This study documents a high frequency of SDB, insomnia, fatigue and a prolonged sleep duration after stroke/TIA, which can persist for years. Considering the negative effects of SWD on physical, brain and mental health these data suggest the need for a systematic assessment and management of post-stroke SWD

Clinical Utility of Advanced Microbiology Testing Tools

Advanced microbiology technologies are rapidly changing our ability to diagnose infections, improve patient care, and enhance clinical workflow. These tools are increasing the breadth, depth, and speed of diagnostic data generated per patient, and testing is being moved closer to the patient through rapid diagnostic technologies, including point-of-care (POC) technologies. While select stakeholders have an appreciation of the value/importance of improvements in the microbial diagnostic field, there remains a disconnect between clinicians and some payers and hospital administrators in terms of understanding the potential clinical utility of these novel technologies. Therefore, a key challenge for the clinical microbiology community is to clearly articulate the value proposition of these technologies to encourage payers to cover and hospitals to adopt advanced microbiology tests. Specific guidance on how to define and demonstrate clinical utility would be valuable. Addressing this challenge will require alignment on this topic, not just by microbiologists but also by primary care and emergency room (ER) physicians, infectious disease specialists, pharmacists, hospital administrators, and government entities with an interest in public health. In this article, we discuss how to best conduct clinical studies to demonstrate and communicate clinical utility to payers and to set reasonable expectations for what diagnostic manufacturers should be required to demonstrate to support reimbursement from commercial payers and utilization by hospital systems

Proteomic analysis of the Plasmodium male gamete reveals the key role for glycolysis in flagellar motility.

BACKGROUND: Gametogenesis and fertilization play crucial roles in malaria transmission. While male gametes are thought to be amongst the simplest eukaryotic cells and are proven targets of transmission blocking immunity, little is known about their molecular organization. For example, the pathway of energy metabolism that power motility, a feature that facilitates gamete encounter and fertilization, is unknown. METHODS: Plasmodium berghei microgametes were purified and analysed by whole-cell proteomic analysis for the first time. Data are available via ProteomeXchange with identifier PXD001163. RESULTS: 615 proteins were recovered, they included all male gamete proteins described thus far. Amongst them were the 11 enzymes of the glycolytic pathway. The hexose transporter was localized to the gamete plasma membrane and it was shown that microgamete motility can be suppressed effectively by inhibitors of this transporter and of the glycolytic pathway. CONCLUSIONS: This study describes the first whole-cell proteomic analysis of the malaria male gamete. It identifies glycolysis as the likely exclusive source of energy for flagellar beat, and provides new insights in original features of Plasmodium flagellar organization

Missing effects of zinc in a porcine model of recurrent endotoxemia

BACKGROUND: Chronic human sepsis often is characterised by the compensatory anti-inflammatory response syndrome (CARS). During CARS, anti-inflammatory cytokines depress the inflammatory response leading to secondary and opportunistic infections. Proved in vitro as well as in vivo, zinc's pro-inflammatory effect might overcome this depression. METHODS: We used the model of porcine LPS-induced endotoxemia established by Klosterhalfen et al. 10 pigs were divided into two groups (n = 5). Endotoxemia was induced by recurrent intravenous LPS-application (1.0 μg/kg E. coli WO 111:B4) at hours 0, 5, and 12. At hour 10, each group received an intravenous treatment (group I = saline, group II = 5.0 mg/kg elementary zinc). Monitoring included hemodynamics, blood gas analysis, and the thermal dilution technique for the measurement of extravascular lung water and intrapulmonary shunt. Plasma concentrations of IL-6 and TNF-alpha were measured by ELISA. Morphology included weight of the lungs, width of the alveolar septae, and rate of paracentral liver necrosis. RESULTS: Zinc's application only trended to partly improve the pulmonary function. Compared to saline, significant differences were very rare. IL-6 and TNF-alpha were predominately measured higher in the zinc group. Again, significance was only reached sporadically. Hemodynamics and morphology revealed no significant differences at all. CONCLUSION: The application of zinc in this model of recurrent endotoxemia is feasible and without harmful effects. However, a protection or restoration of clinical relevance is not evident in our setting. The pulmonary function just trends to improve, cytokine liberation is only partly activated, hemodynamics and morphology were not influenced. Further pre-clinical studies have to define zinc's role as a therapeutic tool during CARS