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Two important pathological features found in the brains of patients with Alzheimer's disease are senile plaques containing amyloid, and neurofibrillary tangles, which are irregular masses of neurofilaments. While neuropathological features have historically been the prime focus of research on Alzheimer's disease, evidence is accumulating that abnormalities also exist outside the brain. One of the most convenient tissues for direct laboratory study is skin, as a small sample of living skin may be obtained with only a minimum of discomfort and risk to the patient. Cells from these skin biopsies called fibroblasts may then be grown in culture dishes in the laboratory for detailed study that is not possible with brain tissue. The evaluation of 19 different fibroblast cultures grown from skin biopsies of patients with Alzheimer's disease has shown that under some conditions, these cells develop pathological changes that resemble those occurring in the brain. Cells in culture dishes are not identical to cells in the body, and it is possible to alter the characteristics of cultured cells by changing the conditions of their feeding and incubation. When these conditions were altered in a way that tends to favor the expression of some brain cell characteristics, it was possible to demonstrate the appearance of some antigens similar to those seen in the brains of patients with Alzheimer's disease. Using antibodies to the paired helical filaments, which are a part of the tangles in brains of Alzheimer's patients, as well as additional antibodies, the cultured cells shown by immunocytochemical staining techniques to contain the abnormal antigens. Control cells from normal elderly individuals showed this antigen expression only rarely. However, examination with the electron microscope failed to reveal any tangled structures corresponding to the neurofibrillary tangles. These results indicate that under specific culture conditions, skin fibroblasts from patients with Alzheimer's disease bear immunological similarities to abnormal brain cells, thus adding to the evidence that the pathological effects of Alzheimer's disease are not limited to the brain. (Consumer Summary produced by Reliance Medical Information, Inc.)

Arrhythmias, or deviations from the normal rhythmic heartbeat, are an important risk factor for cardiac death. In several studies of patients recovering from heart attacks, it was found that, despite the high risk associated with arrhythmias, treatment with antiarrhythmic drugs provided no benefit. A major study was designed to reliably establish the role, if any, that antiarrhythmic drugs might have in the treatment of heart attack victims. A total of 1,498 patients were enrolled in the study; all had suffered a heart attack within the previous two years and all had premature ventricular contractions at least six times per hour as determined by electrocardiographic monitoring. These patients received encainide, flecainide, or placebo. The study was terminated before its planned date as it became clear that the antiarrhythmic drugs were causing significant harm. Of the 755 patients taking active drugs, 43 died of factors relating to arrhythmia, while only 16 of 743 patients taking placebo died of similar causes. Furthermore, 17 patients taking active drugs died of cardiac causes unrelated to arrhythmias, compared with only 5 patients receiving placebo. With such an excess of deaths in the drug-treatment groups, it would be expected that these groups would also have an excess of nonfatal cardiac events as well. However, this was not observed. Nonfatal events, which included tachycardia (rapid heart rate), fainting, requiring a pacemaker, heart attack, heart failure, and angina, were equally distributed among the experimental and control groups. The mechanisms by which encainide and flecainide treatment contribute to increased mortality without contributing to increased nonfatal illness are not known. (Consumer Summary produced by Reliance Medical Information, Inc.)

A wide variety of pathological changes have been identified in the brains of patients with Alzheimer's disease. Among these are neurofibrillary tangles, microscopically visible abnormalities of the cellular skeleton of the neurons. Neurofibrillary tangles are found in some, but not all, neurons of virtually all patients with Alzheimer's disease, and are found in some other unrelated brain diseases, as well. However, pathologic examination is not always sufficient to determine cause from effect. Are the deficits of Alzheimer's disease a result of neurofibrillary tangles? Or are the deficits, neuronal death, and tangles all due to another cause? Perhaps some fundamental underlying cause promotes the formation of tangles, which are then responsible for other aspects of neuronal dysfunction. One candidate for the possible underlying deficit in Alzheimer's disease is alterations in oxidative phosphorylation. This process, which accounts for the utilization of glucose to provide energy in the brain, has been shown to be abnormal in the brain of Alzheimer's patients and also in skin cells of Alzheimer's patients grown in the laboratory. New research has shown that the disruption of oxidative phosphorylation can produce changes in skin cells which in some ways resembles neurofibrillary tangles. Using skin fibroblasts (connective tissue-precursor cells) grown from small biopsies from apparently normal people, investigators disrupted oxidative phosphorylation using the chemical carbonyl cyanide m-chlorophenylhydrazone, or CCCP. This compound works by letting protons leak out of the energy-generating mitochondria within the cell. The cells were then stained with antibodies that recognize the neurofibrillary tangles from the brains of Alzheimer's patients. The antibodies recognized the appearance of Alzheimer's-like antigen within some of the cells, but the staining pattern was not that of the classic tangled appearance. It is tempting to speculate that a disorder of oxidative phosphorylation may result in some of the pathological changes in Alzheimer's disease. (Consumer Summary produced by Reliance Medical Information, Inc.)

SHE SANG 'I Dived Into the Shallow End of the Gene Pool' from her short film, The Banker (2004) to film producer Trudie Styler (wife of English pop singer Sting), [...]

Objectives: Garcinia mangostana Linn. ("mangosteen") pericarp contains bioactive compounds that may target biological pathways implicated in schizophrenia. We conducted a double-blind randomized placebo-controlled trial evaluating the efficacy of adjunctive mangosteen pericarp, compared to placebo, in the treatment of schizophrenia. Methods: People diagnosed with schizophrenia or schizoaffective disorder (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition), recruited across 2 sites (Brisbane and Victoria, Australia), were randomized to receive 24 weeks of adjunctive mangosteen pericarp (1,000 mg/day) or matched placebo. The primary outcome measure was the Positive and Negative Symptom Scale total score. Secondary outcomes included positive and negative symptoms, general psychopathology, clinical global severity and improvement, participant reported overall improvement, depressive symptoms, functioning, quality of life, and safety data at 24 and 28 weeks (4 weeks postdiscontinuation). Data were collected from July 2016 to February 2019. Results: Baseline assessments were conducted on 148 people (mangosteen = 74, placebo = 74); data analyses were conducted on 136 (92%) participants with postbaseline data. The treatment group had significantly higher symptom severity compared to placebo, and both groups significantly improved on all symptom, functioning, and quality of life measures over time. No between-group differences were found for the rate of change between baseline and 24 or 28 weeks. Conclusion: Despite promising preclinical and clinical work, our results do not support mangosteen pericarp extract as an adjunctive treatment for schizophrenia or schizoaffective disorder. [ABSTRACT FROM AUTHOR]

Abstract Background Single-stranded RNA viruses, infectious to the European honeybee, Apis mellifera L. are known to reside at low levels in colonies, with typically no apparent signs of infection observed in the honeybees. Reverse transcription-PCR (RT-PCR) of regions of the RNA-dependent RNA polymerase (RdRp) is often used to diagnose their presence in apiaries and also to classify the type of virus detected. Results Analysis of RdRp conserved domains was undertaken on members of the newly defined order, the Picornavirales; focusing in particular on the amino acid residues and motifs known to be conserved. Consensus sequences were compiled using partial and complete honeybee virus sequences published to date. Certain members within the iflaviruses, deformed wing virus (DWV), Kakugo virus (KV) and Varroa destructor virus (VDV); and the dicistroviruses, acute bee paralysis virus (ABPV), Israeli paralysis virus (IAPV) and Kashmir bee virus (KBV), shared greater than 98% and 92% homology across the RdRp conserved domains, respectively. Conclusion RdRp was validated as a suitable taxonomic marker for the assignment of members of the order Picornavirales, with the potential for use independent of other genetic or phenotypic markers. Despite the current use of the RdRp as a genetic marker for the detection of specific honeybee viruses, we provide overwhelming evidence that care should be taken with the primer set design. We demonstrated that DWV, VDV and KV, or ABPV, IAPV and KBV, respectively are all recent descendents or variants of each other, meaning caution should be applied when assigning presence or absence to any of these viruses when using current RdRp primer sets. Moreover, it is more likely that some primer sets (regardless of what gene is used) are too specific and thus are underestimating the diversity of honeybee viruses.

In October 2017, #metoo 2.0 reinforces the gendered sexual violence in the creative sector [Marghitu, 2018. "It's Just art: Auteur Apologism in the Post-Weinstein era", Feminist Media Studies, 18(93): 491–494] Building on this movement, on 11 November that year, 2912 women "testified about the situation in the Swedish music industry", signing an open letter condemning sexual violence [Nyheter, 2017. "2192 Women in the Swedish Music Industry Behind Appeal Against Sexism." Dagens Nyheter, November 17. ]. After the Swedish initiative, on 12 December 2017, the #meNOmore hashtag was established by 1000 women who signed an open letter to the Australian music industry speaking out against similar behaviour [Whyte, 2017a. "Artists Speak Out Against Sexual Harassment in the Music Industry." AM – ABC Radio, December 13. https://www.abc.net.au/radio/programs/am/sexual-harassment-in-the-music-industry/9253956]. Using a content analysis framework, this study examines the media framing of 26 stories about #meNOmore by the Western press from 22 November 2017 (height of the Swedish campaign) to 21 December 2017 (a week after the hashtag surfaced in Australia). Research from journalism studies and musicology highlights that sexual violence is historically engrained in the media and music industries. However, findings from our study of the first month's coverage of the #meNOmore content analysis in 2017 reveal that media reports about women and sexual violence were framed around addressing gender inequality and systemic structural issues in the music industry. This raises the question, has the media has turned a corner when covering sexual violence in the post #metoo era? [ABSTRACT FROM AUTHOR]