Assessing cognitive dysfunction in Parkinson’s: An online tool to detect visuo-perceptual deficits

BACKGROUND: People with Parkinson’s disease (PD) who develop visuo-perceptual deficits are at higher risk of dementia, but we lack tests that detect subtle visuoperceptual deficits and can be performed by untrained personnel. Hallucinations are associated with cognitive impairment and typically involve perception of complex objects. Changes in object perception may therefore be a sensitive marker of visuo-perceptual deficits in PD. Objective: We developed an online platform to test visuo-perceptual function. We hypothesised that (1) visuo-perceptual deficits in PD could be detected using online tests, (2) object perception would be preferentially affected, and (3) these deficits would be caused by changes in perception rather than response bias. METHODS: We assessed 91 people with PD and 275 controls. Performance was compared using classical frequentist statistics. We then fitted a hierarchical Bayesian signal detection theory model to a subset of tasks. RESULTS: People with PD were worse than controls at object recognition, showing no deficits in other visuoperceptual tests. Specifically, they were worse at identifying skewed images (P <.0001); at detecting hidden objects (P 5.0039); at identifying objects in peripheral vision (P <.0001); and at detecting biological motion (P 5.0065). In contrast, people with PD were not worse at mental rotation or subjective size perception. Using signal detection modelling, we found this effect was driven by change in perceptual sensitivity rather than response bias. CONCLUSIONS: Online tests can detect visuo-perceptual defi- cits in people with PD, with object recognition particularly affected. Ultimately, visuo-perceptual tests may be developed to identify at-risk patients for clinical trials to slow PD dementia

Progesterone Receptor Activates Msx2 Expression by Downregulating TNAP/Akp2 and Activating the Bmp Pathway in EpH4 Mouse Mammary Epithelial Cells

Previously we demonstrated that EpH4 mouse mammary epithelial cells induced the homeobox transcription factor Msx2 either when transfected with the progesterone receptor (PR) or when treated with Bmp2/4. Msx2 upregulation was unaffected by Wnt inhibitors s-FRP or Dkk1, but was inhibited by the Bmp antagonist Noggin. We therefore hypothesized that PR signaling to Msx2 acts through the Bmp receptor pathway. Herein, we confirm that transcripts for Alk2/ActR1A, a non-canonical BmpR Type I, are upregulated in mammary epithelial cells overexpressing PR (EpH4-PR). Increased phosphorylation of Smads 1,5, 8, known substrates for Alk2 and other BmpR Type I proteins, was observed as was their translocation to the nucleus in EpH4-PR cells. Analysis also showed that Tissue Non-Specific Alkaline Phosphatase (TNAP/Akp2) was also found to be downregulated in EpH4-PR cells. When an Akp2 promoter-reporter construct containing a ½PRE site was transfected into EpH4-PR cells, its expression was downregulated. Moreover, siRNA mediated knockdown of Akp2 increased both Alk2 and Msx2 expression. Collectively these data suggest that PR inhibition of Akp2 results in increased Alk2 activity, increased phosphorylation of Smads 1,5,8, and ultimately upregulation of Msx2. These studies imply that re-activation of the Akp2 gene could be helpful in downregulating aberrant Msx2 expression in PR+ breast cancers

Electronic learning can facilitate student performance in undergraduate surgical education: a prospective observational study

BACKGROUND: Our institution recently introduced a novel internet accessible computer aided learning (iCAL) programme to complement existing surgical undergraduate teaching methods. On graduation of the first full cycle of undergraduate students to whom this resource was available we assessed the utility of this new teaching facility. METHOD: The computer programme prospectively records usage of the system on an individual user basis. We evaluated the utilisation of the web-based programme and its impact on class ranking changes from an entry-test evaluation to an exit examination in surgery. RESULTS: 74.4% of students were able to access iCAL from off-campus internet access. The majority of iCAL usage (64.6%) took place during working hours (08:00–18:00) with little usage on the weekend (21.1%). Working hours usage was positively associated with improvement in class rank (P = 0.025, n = 148) but out-of hours usage was not (P = 0.306). Usage during weekdays was associated with improved rank (P = 0.04), whereas weekend usage was not (P = 0.504). There were no significant differences in usage between genders (P = 0.3). Usage of the iCAL system was positively correlated with improvement in class rank from the entry to the exit examination (P = 0.046). Students with lower ranks on entry examination, were found to use the computer system more frequently (P = 0.01). CONCLUSION: Electronic learning complements traditional teaching methods in undergraduate surgical teaching. Its is more frequently used by students achieving lower class ranking with traditional teaching methods, and this usage is associated with improvements in class ranking

Radio Emission from Ultra-Cool Dwarfs

The 2001 discovery of radio emission from ultra-cool dwarfs (UCDs), the very low-mass stars and brown dwarfs with spectral types of ~M7 and later, revealed that these objects can generate and dissipate powerful magnetic fields. Radio observations provide unparalleled insight into UCD magnetism: detections extend to brown dwarfs with temperatures <1000 K, where no other observational probes are effective. The data reveal that UCDs can generate strong (kG) fields, sometimes with a stable dipolar structure; that they can produce and retain nonthermal plasmas with electron acceleration extending to MeV energies; and that they can drive auroral current systems resulting in significant atmospheric energy deposition and powerful, coherent radio bursts. Still to be understood are the underlying dynamo processes, the precise means by which particles are accelerated around these objects, the observed diversity of magnetic phenomenologies, and how all of these factors change as the mass of the central object approaches that of Jupiter. The answers to these questions are doubly important because UCDs are both potential exoplanet hosts, as in the TRAPPIST-1 system, and analogues of extrasolar giant planets themselves.Comment: 19 pages; submitted chapter to the Handbook of Exoplanets, eds. Hans J. Deeg and Juan Antonio Belmonte (Springer-Verlag

Skp is a multivalent chaperone of outer membrane proteins

The trimeric chaperone Skp sequesters outer-membrane proteins (OMPs) within a hydrophobic cage, thereby preventing their aggregation during transport across the periplasm in Gram-negative bacteria. Here, we studied the interaction between Escherichia coli Skp and five OMPs of varying size. Investigations of the kinetics of OMP folding revealed that higher Skp/OMP ratios are required to prevent the folding of 16-stranded OMPs compared with their 8-stranded counterparts. Ion mobility spectrometry–mass spectrometry (IMS–MS) data, computer modeling and molecular dynamics simulations provided evidence that 10- to 16-stranded OMPs are encapsulated within an expanded Skp substrate cage. For OMPs that cannot be fully accommodated in the expanded cavity, sequestration is achieved by binding of an additional Skp trimer. The results suggest a new mechanism for Skp chaperone activity involving the coordination of multiple copies of Skp in protecting a single substrate from aggregation

Signal transduction in cells of the immune system in microgravity

Life on Earth developed in the presence and under the constant influence of gravity. Gravity has been present during the entire evolution, from the first organic molecule to mammals and humans. Modern research revealed clearly that gravity is important, probably indispensable for the function of living systems, from unicellular organisms to men. Thus, gravity research is no more or less a fundamental question about the conditions of life on Earth. Since the first space missions and supported thereafter by a multitude of space and ground-based experiments, it is well known that immune cell function is severely suppressed in microgravity, which renders the cells of the immune system an ideal model organism to investigate the influence of gravity on the cellular and molecular level. Here we review the current knowledge about the question, if and how cellular signal transduction depends on the existence of gravity, with special focus on cells of the immune system. Since immune cell function is fundamental to keep the organism under imnological surveillance during the defence against pathogens, to investigate the effects and possible molecular mechanisms of altered gravity is indispensable for long-term space flights to Earth Moon or Mars. Thus, understanding the impact of gravity on cellular functions on Earth will provide not only important informations about the development of life on Earth, but also for therapeutic and preventive strategies to cope successfully with medical problems during space exploration

Internal medicine residency training for unhealthy alcohol and other drug use: recommendations for curriculum design

<p>Abstract</p> <p>Background</p> <p>Unhealthy substance use is the spectrum from use that risks harm, to use associated with problems, to the diagnosable conditions of substance abuse and dependence, often referred to as substance abuse disorders. Despite the prevalence and impact of unhealthy substance use, medical education in this area remains lacking, not providing physicians with the necessary expertise to effectively address one of the most common and costly health conditions. Medical educators have begun to address the need for physician training in unhealthy substance use, and formal curricula have been developed and evaluated, though broad integration into busy residency curricula remains a challenge.</p> <p>Discussion</p> <p>We review the development of unhealthy substance use related competencies, and describe a curriculum in unhealthy substance use that integrates these competencies into internal medicine resident physician training. We outline strategies to facilitate adoption of such curricula by the residency programs. This paper provides an outline for the actual implementation of the curriculum within the structure of a training program, with examples using common teaching venues. We describe and link the content to the core competencies mandated by the Accreditation Council for Graduate Medical Education, the formal accrediting body for residency training programs in the United States. Specific topics are recommended, with suggestions on how to integrate such teaching into existing internal medicine residency training program curricula.</p> <p>Summary</p> <p>Given the burden of disease and effective interventions available that can be delivered by internal medicine physicians, teaching about unhealthy substance use must be incorporated into internal medicine residency training, and can be done within existing teaching venues.</p