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27, Number 1, November 2011
Chen Pac-Soo, Dafydd G Lloyd, Marcela P Vizcaychipi, Daqing Ma
Statins: The Role in the Treatment and Prevention of Alzheimer’s Neurodegeneration
Abstract: Alzheimer’s disease (AD) is a progressive neurodegenerative disease commonly seen in the elderly and is characterized by progressive cognitive and physical decline. Current understanding of AD pathogenesis revolves around amyloid-β peptide (Aβ), a product of the sequential proteolytic cleavage of the transmembrane amyloid-β protein precursor (AβPP) by β- and γ-secretase, enzymes found predominantly in the cholesterol rich micro domains of the cell membrane. Several risk factors for AD are associated with cholesterol metabolism, including dyslipidaemia, coronary artery and cerebrovascular disease. Statins are widely prescribed for their cholesterol lowering ability and show a favorable side effect profile overall. By competitive inhibition of hydroxymethyl co-enzyme A-reductase, statins reduce the production of cholesterol and isoprenoid intermediates including geranylgeranyl and farnesyl pyrophosphate. These isoprenoids modify recently translated proteins such as small GTPase molecules that are essential in numerous cell-signaling pathways, including vesicular trafficking and inflammation. In experimental models of AD, statins reduce the production of Aβ by disrupting secretase enzyme function and by reducing neuroinflammation. Furthermore, epidemiological studies suggest that statins may reduce the incidence of AD. Consequently, statins, secondary of their anti-hypercholesterolaemic, plieotropic and anti-inflammatory effects, are being investigated for a potential therapeutic role. This review will discuss evidence for the role of statins in the treatment and prevention of AD neurodegeneration.
Mira Didic, Emmanuel J. Barbeau, Olivier Felician, Eve Tramoni, Eric Guedj, Michel Poncet, Mathieu Ceccaldi (Handling Associate Editor: Flavio Nobili)
Which Memory System is Impaired First in Alzheimer’s disease?
Abstract: Diagnosis of Alzheimer’s disease (AD) in its earliest stages becomes increasingly important as disease modifying agents are being developed. In this area of research, many clinical and neuroimaging studies focus on markers of hippocampal dysfunction. However, during the “transentorhinal stage” of AD, neurofibrillary tangles (NFT), related to tau protein pathology, develop in the anterior subhippocampal (perirhinal/entorhinal) cortex before the hippocampus. NFT are tightly correlated with clinical symptoms. Therefore, an accurate understanding of the behavioral correlate of transentorhinal dysfunction could critically contribute to the early diagnosis of the disease. Recent findings from studies in animals and human brain-damaged patients suggest that the anterior subhippocampal region, functionally integrated into an anterior mesiotemporal network, is involved in object based context-free memory. In this article, we evaluate the hypothesis according to which tau deposition in the anterior subhippocampal region during the earliest stages of the most common form of AD, with predominant MTL dysfunction, will lead to dysfunction of neural networks implicated in context-free memory. We challenge the view that impaired episodic memory is the hallmark of early AD. Instead, a model that integrates the localization and temporal sequence of NFT within the mesial temporal lobe (MTL) is proposed. Paralleling the development of NFT in anterior subhippocampal areas, impaired context-free, object-based, memory could be the first detectable sign in AD. In a subsequent, “hippocampal” stage, context-rich, episodic and spatial memory, becomes altered as well. The question as to the “episodic” nature of “episodic memory tasks” is also addressed.
Jinghong Kou, HongDuck Kim, Abhinandan Pattanayak, Min Song, Jeong-Eun Lim, Hiroaki Taguchi, Sudhir Paul, John R. Cirrito, Selvarangan Ponnazhagan, Ken-ichiro Fukuchi (Handling Associate Editor: Robert Friedland)
Anti-Amyloid-β Single-Chain Antibody Brain Delivery Via AAV Reduces Amyloid Load But May Increase Cerebral Hemorrhages in an Alzheimer’s disease Mouse Model
Abstract: Accumulation of amyloid-β protein (Aβ) in the brain is thought to be a causal event in Alzheimer’s disease (AD). Immunotherapy targeting Aβ holds great promise for reducing Aβ in the brain. Here, we evaluated the efficacy and safety of anti-Aβ single-chain antibody (scFv59) delivery via recombinant adeno-associated virus (rAAV) on reducing Aβ deposits in an AD mouse model (TgAβPPswe/PS1dE9). First, delivery of scFv59 to the brain was optimized by injecting rAAV serotypes 1, 2, and 5 into the right lateral ventricle. Symmetrical high expression of scFv59 was found throughout the hippocampus and partly in the neocortex in both hemispheres via rAAV1 or rAAV5, while scFv59 expression via rAAV2 was mostly limited to one hemisphere. rAAV1, however, induced apoptosis and microglial activation but rAAV5 did not. Therefore, rAAV5 was selected for therapeutic scFv59 delivery in TgAβPPswe/PS1dE9 mice. rAAV5 was similarly injected into the ventricle of 10-month-old TgAβPPswe/PS1dE9 mice and 5 months later its efficacy and safety were evaluated. Immunoreactive Aβ deposits reduced in the hippocampus. Aβ42 levels in cerebrospinal fluid (CSF) tended to increase and the Aβ40:42 ratio decreased in CSF, suggesting that Aβ42 was relocated from the parenchyma to CSF. Hemorrhages associated with a focal increase in blood vessel amyloid were found in the brain. While immunotherapy has great potential for clearing cerebral Aβ, caution for cerebrovascular effects should be exercised when rAAV-mediated anti-Aβ immunotherapy is applied.
Supplementary Data for Kou et al. article (PDF)
Karine Pérès, Catherine Helmer, Hélène Amieva, Fanny Matharan, Laure Carcaillon, Hélène Jacqmin-Gadda, Sophie Auriacombe, Jean-Marc Orgogozo, Pascale Barberger-Gateau, Jean-François Dartigues
Gender Differences in the Prodromal Signs of Dementia: Memory Complaint and IADL-Restriction
Abstract: Subjective memory complaint (SMC) and restriction in cognitively-complex activities of daily living (such as instrumental ADL) are two early symptoms observed in the prodromal phase of dementia and may represent useful alarm signals for general practitioners for an increased risk of subsequent dementia. We here studied in a large population-based epidemiological cohort on aging, the risk of dementia associated with SMC and restriction in IADL, with a specific interest in a potential interaction by gender. The sample included 2,901 subjects, aged 65 years and over, initially free of dementia and followed over 15 years. After controlling for education, marital status, depressive symptomatology, and global cognition (MMSE), IADL-restriction was associated with an increased risk of dementia only in men (HR=2.04, 1.27 to 3.29), whereas SMC was not (p=0.95). The reverse was observed in females, in whom SMC almost doubled the risk of dementia (1.48 to 2.41), with no association with IADL-restriction (p=0.74). Finally, we distinguished the risk of dementia at short-term (in the first 5 years), mid-term (between 5 and 10 years), and long-term (between 10 and 15 years). In women, SMC was significantly associated with greater risk of dementia whatever the risk period considered, even at longer term (HR=1.61, p=0.0216), whereas in men the increased risk was also observed with IADL-restriction and only in the first 5 years. To conclude, women would report the first symptoms very early in the process by SMC, whereas men would tend to later report their difficulties and only in terms of IADL-restriction.
Sean S. Davies, Chris Bodine, Elena Matafonova, Brooke G. Pantazides, Nathalie Bernoud-Hubac, Fiona E. Harrison, Sandra J. Olson, Thomas J. Montine, Venkataraman Amarnath, L. Jackson Roberts II (Handling Associate Editor: Samar Basu)
Treatment with a γ-Ketoaldehyde Scavenger Prevents Working Memory Deficits in hApoE4 Mice
Abstract: Both inflammation and oxidative injury are features of Alzheimer’s disease (AD), but the contribution of these intertwined phenomena to the loss of working memory in this disease is unclear. We tested the hypothesis that highly reactive γ-ketoaldehydes that are formed both by non-enzymatic free radical catalyzed lipid peroxidation and by cyclooxygenases may be causally linked to the development of memory impairment in AD. We found that levels of γ-ketoaldehyde protein adducts were increased in the hippocampus of brains obtained postmortem from patients with AD compared to age-matched controls, but that levels of γ-ketoaldehyde protein adducts in the cerebellum were not different in the two groups. Moreover, immunohistochemistry revealed that adducts localized to hippocampal pyramidal neurons. We tested the effect of an orally available γ-ketoaldehyde scavenger, salicylamine, on the development of spatial working memory deficits in hApoE4 targeted replacement mice, a mouse model of dementia. Long-term salicylamine supplementation did not significantly alter body weight or survival, but protected against the development of age-related deficits in spatial working memory in 12-14 month old ApoE4 mice. These findings suggest that γ-ketoaldehyde adduct formation is associated with damage to hippocampal neurons in patients with AD and can contribute to the pathogenesis of spatial working memory deficits in hApoE4 mice. These data provide a rational basis for future studies exploring whether γ-ketoaldehyde scavengers may mitigate the development of cognitive dysfunction in patients with AD.
Supplementary Data for Davies et al. article (PDF)
Ricardo J. S. Viana, Clifford J. Steer, Cecília M. P. Rodrigues
Amyloid-β Peptide-Induced Secretion of Endoplasmic Reticulum Chaperone Glycoprotein GRP94
Abstract: Amyloid-β (Aβ) peptide-induced neurotoxicity is typically associated with cell death through mechanisms not entirely understood. Here, we investigated stress signaling events triggered by soluble Aβ in differentiated rat neuronal-like PC12 cells. Morphologic evaluation of apoptosis confirmed that Aβ induced nuclear fragmentation that was prevented by pre-treatment with the antiapoptotic bile acid tauroursodeoxycholic acid (TUDCA). In addition, Aβ exposure triggered an early signaling response by the endoplasmic reticulum (ER) and caspase-12-mediated apoptosis, which, however, was independent of the ER-stress pathway. Furthermore, ER stress markers, including GRP94, ATF-6α, CHOP, and eIF2α, were strongly downregulated by Aβ, independent of protein degradation, and partially restored by TUDCA. Calpain inhibition prevented caspase-12 activation and reduced levels of ATF-6α. Importantly, Aβ-induced GRP94 downregulation was related to protein secretion and partially rescued through inhibition of the secretory pathway by geldanamycin and brefeldin. In conclusion, we showed that the ER is a proximal stress sensor for soluble Aβ-induced toxicity, resulting in caspase-12 activation and cell death in PC12 neuronal cells. Moreover, ER chaperone GRP94 secretion was associated with Aβ-induced apoptotic signaling. These data provide new information linking apoptotic properties of Aβ peptide to distinct subcellular mechanisms of toxicity. Further characterization of this signaling pathway is likely to provide new perspectives for modulation of amyloid-induced apoptosis.
Supplementary Data for Viana et al. article (PDF)
Nyosha Alikhani*, Lan Guo*, Shiqiang Yan, Heng Du, Catarina Moreira Pinho, John Xi Chen, Elzbieta Glaser, Shirley ShiDu Yan *These authors contributed equally to this work.
Decreased Proteolytic Activity of the Mitochondrial Amyloid-β Degrading Enzyme, PreP Peptidasome, in Alzheimer’s Disease Brain Mitochondria
Abstract: Accumulation of amyloid-β peptide (Aβ), the neurotoxic peptide implicated in the pathogenesis of Alzheimer’s disease (AD), has been shown in brain mitochondria of AD patients and of AD transgenic mouse models. The presence of Aβ in mitochondria leads to free radical generation and neuronal stress. Recently, we identified the presequence protease, PreP, localized in the mitochondrial matrix in mammalian mitochondria as the novel mitochondrial Aβ-degrading enzyme. In the present study, we examined PreP activity in the mitochondrial matrix of the human brain’s temporal lobe, an area of the brain highly susceptible to Aβ accumulation and reactive oxygen species (ROS) production. We found significantly lower hPreP activity in AD brains compared with non-AD age-matched controls. By contrast, in the cerebellum, a brain region typically spared from Aβ accumulation, there was no significant difference in hPreP activity when comparing AD samples to non-AD controls. We also found significantly reduced PreP activity in the mitochondrial matrix of AD transgenic mouse brains (Tg mAβPP and Tg mAβPP/ABAD) when compared to non-transgenic aged-matched mice. Furthermore, mitochondrial fractions isolated from AD brains and Tg mAβPP mice had higher levels of 4-hydroxynonenal, an oxidative product, as compared with those from non-AD and nonTg mice. Accordingly, activity of cytochrome c oxidase was significantly reduced in the AD mitochondria. These findings suggest that decreased PreP proteolytic activity, possibly due to enhanced ROS production, contributes to Aβ accumulation in mitochondria leading to the mitochondrial toxicity and neuronal death that is exacerbated in AD. Clearance of mitochondrial Aβ by PreP may thus be of importance in the pathology of AD.
Jun-xiang Yin, Gregory H. Turner, Hao-jie Lin, Stephen W. Coons, Jiong Shi (Handling Associate Editor: Xiongwei Zhu)
Deficits in Spatial Learning and Memory is Associated with Hippocampal Volume Loss in Aged Apolipoprotein E4 Mice
Abstract: Apolipoprotein E ε4 (ApoE4) has been implicated as a potential genetic risk factor for dementia. In this study, we investigate the effect of ApoE4 on learning and memory, changes in brain volume and neuroinflammatory responses in brain of ApoE4 transgenic mice. Four groups of male mice with ApoE4 and age-matched wild type (WT) (6-, 12-, 18- and 24-month) were studied. Spatial learning and retaining of mice was examined in the Morris Water Maze (MWM). Changes in brain volume (including the whole brain, hippocampus, cortex, total ventricles, and caudate putamen) were assessed by using 7T small animal MRI. Neuroinflammatory responses were analyzed by measuring the levels of microglia (Iba-1), iNOS, TNFα, and IL-6 quantitatively. In the MWM, ApoE4 mice showed longer escape latency (p<0.05) and swim distance (p<0.05) at age 12 month and older, comparing with the WT mice. They also demonstrated poor memory retention in the probe test (p<0.05). Brain atrophy was significant in ApoE4 mice than age-matched WT mice (18 months: 0.079±0.004 versus 0.086±0.003, p=0.018; and 24 months: 0.074±0.005 versus 0.084±0.006, p=0.008). The expression of Iba-1, iNOS, and TNFα in hippocampus and cortex were significantly higher in ApoE4 mice than in WT mice at 12 months and older. These data suggest that ApoE4 plays an important role in learning and memory impairment. These deficits are associated with neuroinflammatory responses that may in turn lead to atrophy in hippocampus and cortex.
Yair Fisher, Anna Nemirovsky, Rona Baron, Alon Monsonego (Handling Associate Editor: Takeshi Tabira)
Dendritic Cells Regulate Amyloid-β-Specific T-Cell Entry Into the Brain: The Role of Perivascular Amyloid-β
Abstract: Amyloid-β (Aβ) accumulation in the brain is one of the hallmarks of Alzheimer's disease (AD). T-cell entry into vascular and parenchymal brain areas loaded with Aβ has been observed with both beneficial as well as detrimental effects. Using a new AD mouse model, we studied the molecular mechanisms allowing CD4 T cells to specifically target Aβ-loaded brain areas. We observed that following Aβ immunization, CD11c+ dendritic cells (DCs) and CD4 T cells occurred primarily in the perivascular and leptomeningial spaces of cerebral vessels deposited with Aβ. CD11c+ cells expressed high levels of the DC maturation markers DEC-205, MHC class II and CD86. Notably, the majority of cerebral blood vessels were found adjacent to Aβ plaques, expressing high levels of the ICAM-1 and VCAM-1 adhesion molecules. We propose that the drainage of Aβ to the leptomeningeal and perivascular spaces and its deposition there provide the antigenic source for DCs to stimulate Aβ-specific T cells on their way to target amyloid plaques within the brain tissue.
Supplementary Data for Fisher et al. article (PDF)
Hongqian Yang, Yaroslav Lyutvinskiy, Hilkka Soininen, Roman A. Zubarev
Alzheimer’s Disease and Mild Cognitive Impairment are Associated with Elevated Levels of Isoaspartyl Residues in Blood Plasma Proteins
Abstract: Increased levels of isoaspartyl residues (isoAsp) have previously been found in proteins of Alzheimer’s disease (AD) brains and in blood proteins of patients suffering from uremia, the disease sharing common pathological features with AD. One can hypothesize that higher levels of isoAsp should be present in blood proteins of AD patients. Also, because of higher AD prevalence in females, they can be expected to have higher level of isoAsp than males. Here we modified our recently developed proteome-wide isoAsp analysis approach for testing these hypotheses. Eight blood plasma samples pooled from 218 individuals suffering from either mild cognitive impairment (MCI) or AD were analyzed by tandem mass spectrometry using electron transfer dissociation. Based on specific fragmentation pattern of isoAsp, the healthy controls were found to contain lower level of isoAsp compared with age-matched MCI and AD patients (p=0.03). This result was further validated (p=0.05) by 96 individual sample analyses, giving the combined value of p≈0.01. Female pooled samples were found to contain higher level of isoAsp than male in both pooled and individual samples, with overall p≈0.01. These findings verify the above hypotheses, and provide protein candidates for further investigation of the link between isoAsp and AD.
Supplementary Data for Yang et al. article (PDF)
Walter Maetzler, Anne Schäfer, Claudia Schulte, Ann-Kathrin Hauser, Stefanie Lerche, Isabel Wurster, Erwin Schleicher, Arthur Melms, Daniela Berg (Handling Associate Editor: Irina Alafuzoff)
Serum and Cerebrospinal Fluid Uric Acid Levels in Lewy Body Disorders: Associations with Disease Occurrence and Amyloid-β Pathway
Abstract: Recent studies have provided evidence that uric acid (UA), a natural antioxidant, may play a role in the development and progression of Parkinson’s disease (PD) and of dementia. In this clinical study we were therefore interested in the role of UA in Lewy body disorders (LBD), which includes Parkinson’s disease (PD) and a common form of neurodegenerative dementias, dementia with Lewy bodies (DLB). Ninety-five LBD patients (55 non-demented PD patients, PDND; 20 PD patients with dementia, PDD; and 20 DLB patients) and 76 controls underwent clinical and biochemical analyses including, from a subcohort, cerebrospinal fluid (CSF) analyses, and analysis of three single nucleotide polymorphisms (SNPs) known to be associated with altered serum UA levels. We confirmed previous findings of lowered serum UA levels in LBD patients compared to controls. In CSF, UA levels were significantly higher in PDND patients (median 0.7 mg/dl) compared only to demented LBD patients (0.4 mg/dl; p=0.03), but not to controls (0.5 mg/dl; p=0.12). CSF UA levels correlated positively with CSF Aβ42 levels. This correlation was highest in controls (ρ=0.67), intermediate in PDND (ρ=0.49), but not observable in demented LBD patients (ρ=0.10). These findings suggest an involvement of serum UA in LBD occurrence, and an involvement of CSF UA in cognitive decline in LBD, possibly through the Aβ pathway. SNP rs1165205 (SLC17A3) was weakly associated with altered CSF UA levels. Taken together, our results provide first evidence for disease-relevant but potentially distinct roles of UA in the blood and CSF compartment, respectively, in LBD.
Im Seop Choi, Young-Jung Lee, Dong-Young Choi, Yong Kyung Lee, Yeun Hee Lee, Ki Ho Kim, Young Heui Kim, Young Ho Jeon, Eun Hee Kim, Sang Bae Han, Jae Kyung Jung, Yeo Pyo Yun, Ki-Wan Oh, Dae Youn Hwang, Jin Tae Hong
4-O-Methylhonokiol Attenuated Memory Impairment Through Modulation of Oxidative Damage of Enzymes Involving Amyloid-β Generation and Accumulation in a Mouse Model of Alzheimer’s Disease
Abstract: Accumulations of amyloid-β (Aβ) and oxidative damage are critical pathological mechanisms in the development of Alzheimer’s disease (AD). We previously found that 4-O-methylhonokiol, a compound extracted from Magnolia officinalis, improved memory dysfunction in Aβ-injected and presenilin 2 mutant mice through the reduction of accumulated Aβ. To investigate mechanisms of the reduced Aβ accumulation, we examined generation, degradation, efflux and aggregation of Aβ in Swedish AβPP AD model (AβPPsw) mice pre-treated with 4-O-methylhonokiol (1.0 mg/kg) for 3 months. 4-O-methylhonokiol treatment recovered memory impairment and prevented neuronal cell death. This memory improving activity was associated with 4-O-methylhonokiol-induced reduction of Aβ1-42 accumulation in the brains of AβPPsw mice. According to the reduction of Aβ1-42 accumulation, 4-O-methylhonkiol modulated oxidative damage sensitive enzymes. 4-O-methylhonkiol decreased expression and activity of brain beta-site AβPP cleaving enzyme (BACE1), but increased clearance of Aβ in the brain through an increase of expressions and activities of Aβ degradation enzymes; insulin degrading enzyme and neprilysin. 4-O-methylhonkiol also increased expression of Aβ transport molecule, low density lipoprotein receptor-related protein-1 in the brain and liver. 4-O-methylhonkiol decreased carbonyl protein and lipid peroxidation, but increased glutathione levels in the brains of AβPPsw mice suggesting that oxidative damage of protein and lipid is critical in the impairment of those enzyme activities. 4-O-methylhonokiol treatment also prevented neuronal cell death in the AβPPsw mousee brain through inactivation of caspase-3 and BAX. These results suggest that 4-O-methylhonokiol might prevent the development and progression of AD by reducing Aβ accumulation through an increase of clearance and decrease of Aβ generation via antioxidant mechanisms.
Supplementary Data for Choi et al. article (PDF)
Alberto Cornejo , José M. Jiménez, Leonardo Caballero, Francisco Melo, Ricardo B. Maccioni
Fulvic Acid Inhibits Aggregation and Promotes Disassembly of Tau Fibrils Associated with Alzheimer’s Disease
Abstract: Alzheimer’s disease is a neurodegenerative disorder involving extracellular plaques (amyloid-β) and intracellular tangles of tau protein. Recently, tangle formation has been identified as a major event involved in the neurodegenerative process, due to the conversion of either soluble peptides or oligomers into insoluble filaments. At present, the current therapeutic strategies are aimed at natural phytocomplexes and polyphenolics compounds able to either inhibit the formation of tau filaments or disaggregate them. However, only a few polyphenolic molecules have emerged to prevent tau aggregation, and natural drugs targeting tau have not been approved yet. Fulvic acid, a humic substance, has several nutraceutical properties with potential activity to protect cognitive impairment. In this work we provide evidence to show that the aggregation process of tau protein, forming paired helical filaments (PHFs) in vitro, is inhibited by fulvic acid affecting the length of fibrils and their morphology. In addition, we investigated whether fulvic acid is capable of disassembling preformed PHFs. We show that the fulvic acid is an active compound against preformed fibrils affecting the whole structure by diminishing length of PHFs and probably acting at the hydrophobic level, as we observed by atomic force techniques. Thus, fulvic acid is likely to provide new insights in the development of potential treatments for Alzheimer´s disease using natural products.
Renaud David, Leah Friedman, Emmanuel Mulin, Art Noda, Franck Le Duff, Quinn Kennedy, Rene Garcia, Philippe H. Robert, Jerome A. Yesavage, Jamie M. Zeitze, For the Alzheimer’s Disease Neuroimaging Initiative
Lack of Association Between COMT Polymorphisms and Apathy in Alzheimer’s Disease
Abstract: We tested the hypothesis that single nucleotide polymorphisms (SNPs) in catechol-O-methyltransferase (COMT) are associated with apathy in individuals with Alzheimer’s disease (AD). We analyzed a cohort of 105 Caucasian individuals with AD (age=79.3 ± 7.03 years; MMSE=20.2 ± 4.4) according to the presence of apathy, as defined either by the Neuropsychiatric Inventory or the Apathy Inventory. Polymorphisms in seventeen SNPs in COMT were examined. A replication cohort consisting of 176 Caucasian AD subjects in the ADNI database was also analyzed. None of the candidate gene SNPs were significantly associated with the presence of apathy in either cohort. We did not find any SNPs in COMT that were consistently associated with apathy in individuals with AD.
Jussi Mattila, Juha Koikkalainen, Arho Virkki, Anja Simonsen, Mark van Gils, Gunhild Waldemar, Hilkka Soininen, Jyrki Lötjönen; for The Alzheimer’s Disease Neuroimaging Initiative
A Disease State Fingerprint for Evaluation of Alzheimer’s Disease
Abstract: Diagnostic processes of Alzheimer’s disease (AD) are evolving. Knowledge about disease-specific biomarkers is constantly increasing and larger volumes of data are being measured from patients. To gain additional benefits from the collected data, a novel statistical modeling and data visualization system is proposed for supporting clinical diagnosis of AD. The proposed system computes an evidence-based estimate of a patient’s AD state by comparing his or her heterogeneous neuropsychological, clinical, and biomarker data to previously diagnosed cases. The AD state in this context denotes a patient’s degree of similarity to previously diagnosed disease population. A summary of patient data and results of the computation are displayed in a succinct Disease State Fingerprint (DSF) visualization. The visualization clearly discloses how patient data contributes to the AD state, facilitating rapid interpretation of the information. To model the AD state from complex and heterogeneous patient data, a statistical Disease State Index (DSI) method underlying the DSF has been developed. Using baseline data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), the ability of the DSI to model disease progression from elderly healthy controls to AD and its ability to predict conversion from mild cognitive impairment (MCI) to AD were assessed. It was found that the DSI provides well-behaving AD state estimates, corresponding well with the actual diagnoses. For predicting conversion from MCI to AD, the DSI attains performance similar to state-of-the-art reference classifiers. The results suggest that the DSF establishes an effective decision support and data visualization framework for improving AD diagnostics, allowing clinicians to rapidly analyze large quantities of diverse patient data.
Supplementary Data for Mattila et al. article (PDF)
Clarice Câmara Correia, Fábia Lima, Franco Junqueira, Marília Siqueira Campos, Othon Bastos, Kátia Petribú, Jerson Laks, James E Galvin
AD8-Brazil: Cross-Cultural Validation of the Ascertaining Dementia Interview in Portuguese
Abstract: Dementia is a global public health problem and detection in the primary care setting, particularly in developing countries, is challenging. The aim of this research was to produce the cross-cultural validation of the AD8 interview to the Brazilian Portuguese Language. The original version of the AD8 was submitted to translation, back-translation, and application of the questionnaire to 20 elderly informants for face validation. The AD8-Brazil was then evaluated in 109 community-dwelling elderly with a sociodemographic questionnaire, clinical examination, Mini Mental State Examination (MMSE), Katz Inventory of Activities of Daily Living (ADL), and Clinical Dementia Rating scale (CDR). The AD8-Brazil was compared with the other instruments and with the clinical diagnosis (DSM-IV) for criterion validation. There was significant agreement of AD8-Brazil with diagnosis of dementia (p<0.001), MMSE (p=0.047), and ADL (PFisher=0.004). Also, the AD8-Brazil was able to differentiate the stages of dementia by CDR scale. The reliability was high (alpha=0.818) and reproducibility analysis showed excellent inter-rater (kappa=0.889) and test-retest consistency (kappa=0.814). The AD8-Brazil showed excellent discrimination between CDR 0 and CDR>0 (area under the curve 86.1%) and between CDR 0 and CDR 0.5 (area under the curve 76.9%). The administration of the questionnaire took 2.3±0.1 minutes. The Brazilian version of the AD8 is a valid, reliable, quick, and easy screening instrument for dementia.
Ramon Luengo-Fernandez, Jose Leal, Alastair M. Gray (Handling Associate Editor: Julio López-Bastida)
Cost of Dementia in the Pre-Enlargement Countries of the European Union
Abstract: Dementia has a significant impact on the health and social care systems of the European Union (EU), on patients, on family and friends who provide unpaid care, and on the wider economy and society. Information about its economic burden will be helpful when deciding the allocation of future research funds. We included the 15 countries who were members of the EU (EU-15) before the Eastern enlargement in 2004. The economic burden of dementia was estimated using patient-level studies and aggregate data on morbidity, mortality, and health and social care use. The same methodological approach was used across all countries. Healthcare and social care costs were estimated from expenditure on nursing and residential home care; and primary, outpatient, emergency and inpatient care, as well as drug treatment. Costs of unpaid care and lost earnings due to morbidity and premature death were also included in the study. Dementia was estimated to cost the EU-15 €189 billion in 2007. 68% of total costs were due to informal care, 26% to social care, 5% to health care and 1% to productivity losses. In conclusion, dementia poses a significant economic burden to European health and social care systems, and society overall. Our results will be helpful for policy makers in evaluating policy impact and prioritising research expenditures. This study also highlights the need for more accurate and comparable dementia-related data across the European countries.
Supplementary Data for Luengo-Fernandez et al. article (PDF)
Aleksandra Maruszak, Krzysztof Safranow, Wojciech Branicki, Katarzyna Gawęda-Walerych, Ewelina Pośpiech, Tomasz Gabryelewicz, Jeffrey A. Canter, Maria Barcikowska, Cezary Żekanowski (Handling Associate Editor: Russell Swerdlow)
The Impact of Mitochondrial and Nuclear DNA Variants on Late-Onset Alzheimer’s Disease Risk
Abstract: We investigated the potential contribution of mitochondrial DNA (mtDNA) variants, haplogroups, and polymorphisms in nuclear genes essential for mitochondrial biogenesis and function (PGC-1α TFAM) to late-onset Alzheimer’s disease (LOAD) risk. Epistatic interaction analysis was conducted between the studied variables. Our results demonstrate that mtDNA haplogroups and subhaplogroups with putative role in partial uncoupling of oxidative phosphorylation are significantly associated with a decreased LOAD risk (OR<1). Conversely, mtDNA haplogroup H (p=0.049) and HV cluster (p=0.018) are significant LOAD risk factors, which was additionally confirmed by meta-analysis (OR=1.22, OR=1.25, respectively). Haplogroup K was demonstrated to exert a neutralizing effect on the high risk associated with APOE4+ status (p=0.014). Further, two synergistic interactions between subhaplogroup H5 and APOE4 status (p=0.009) and between TFAM rs1937 and APOE4 status (p<0.001) were detected, influencing LOAD risk. No interaction pointing to a dual mitochondrial-nuclear genome variation effect on LOAD occurrence was identified.
Supplementary Data for Maruszak et al. article (PDF)
Magali Dumont, Khatuna Kipiani, Fangmin Yu, Elizabeth Wille, Maya Katz, Noel Y. Calingasan, Gunnar K. Gouras, Michael T. Lin, M. Flint Beal
Coenzyme Q10 Decreases Amyloid Pathology and Improves Behavior in a Transgenic Mouse Model of Alzheimer’s Disease
Abstract: Increased oxidative stress is implicated in the pathogenesis of Alzheimer’s disease (AD). A large body of evidence suggests that mitochondrial dysfunction and increased reactive oxygen species occur prior to amyloid-β (Aβ) deposition. Coenzyme Q10 (CoQ10), a component of the mitochondrial electron transport chain, is well characterized as a neuroprotective antioxidant in animal models and human trials of Huntington’s disease and Parkinson’s disease, and reduces plaque burden in AβPP/PS1 mice. We now show that CoQ10 reduces oxidative stress and amyloid pathology and improves behavioral performance in the Tg19959 mouse model of AD. CoQ10 treatment decreased brain levels of protein carbonyls, a marker of oxidative stress. CoQ10 treatment resulted in decreased plaque area and number in hippocampus and in overlying cortex immunostained with an Aβ42-specific antibody. Brain Aβ42 levels were also decreased by CoQ10 supplementation. Levels of amyloid-β protein precursor (AβPP) β-carboxyterminal fragments were decreased. Importantly, CoQ10-treated mice showed improved cognitive performance during Morris water maze testing. Our results show decreased pathology and improved behavior in transgenic AD mice treated with the naturally occurring antioxidant compound CoQ10. CoQ10 is well tolerated in humans and may be promising for therapeutic trials in AD.
Linqing Ma, Yasumasa Ohyagi, Norimichi Nakamura, Kyoko M. Iinuma, Katsue Miyoshi, Eri Himeno, Naoko Soejima, Yuki T. Yanagihara, Nobutaka Sakae, Ryo Yamasaki, Jun-ichi Kira (Handling Associate Editor: Takeshi Tabira)
Activation of Glutathione Peroxidase and Inhibition of p53-Related Apoptosis by Apomorphine
Abstract: Apomorphine hydrochloride (APO) is known to be a dopamine receptor agonist, and has recently been found to be a novel drug for Alzheimer’s disease (AD). We found that APO treatment ameliorated oxidative stress in an AD mouse model and specifically attenuated the hydrogen peroxide-induced p53-related apoptosis in the SH-SY5Y neuroblastoma cell line. To further understand the mechanism behind this action, we investigated the actions of APO on intracellular redox systems, such as the glutathione cycle and catalase. We studied the effects of specific inhibitors for glutathione peroxidase (GPx), glutathione reductase (GR), and catalase (BCNU, MCS, and ATZ, respectively) on the effects of APO. Treatments with MCS or BCNU, but not ATZ, significantly attenuated the protective effects of APO. Interestingly, APO treatment elevated GPx activity, but did not increase the expression of the GPx1 protein. Although BCNU treatment attenuated APO effects, GR activity was not elevated by APO treatment. The same effects were observed in primary neuronal cultures. In addition, treatment with dopamine D1, D2, D3 and D4 receptor antagonists did not counteract the protective action of APO. Thus, APO may enhance GPx activity through dopamine receptor-independent pathways.

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Various pouch sizes, materials and types of closure capabilities
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The Redland City Bulletin has today wrongly stated in headline that the City Plan Due Out This Week and further stated that the City Plan 2015 ‘are (sic) expected to be released this week’. (Note the Draft City Plan 2015 was also submitted for State approval for public release in November 2014 not February 2015 as stated).
• Council has yet to formally meet and consider the release of the plan and the period for public consultation. A Special Meeting of Council on Thursday 3 September is expected to decide on both issues.
• The Public display of the Draft City Plan 2015 will depend on the date Council decides to begin public consultation.
• The full plan will be made publicly available on the date when formal consultation begins.
• Once the City Plan 2015 consultation period is agreed, there will be community wide advertising of public consultation opportunities including extensive City Plan website details and supporting information and advertised City Plan public consultation activities at venues across the city.
• Until then, those interested in the City Plan are encouraged to keep an eye out for public notices in the media and on council’s website and to visit the draft plan website www.redland.qld.gov.au/cityplan to view background details and register this interest in receiving future details on the plan consultation.

domain: news


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Yes, it is true, Nana Plaza – The World’s Largest Adult Playground – will be open this afternoon just not to the general public.
The bars will be closed, there will be no bright lights, dancing dollybirds, thumping music or copious amounts of booze being consumed because today isn’t a party, but a day to give back to the thousands of people who work in Nana Plaza and help out in a time of need.
Nana Partners, the owners of Nana Plaza, will be offering 1,000 care packages to staff still here in Bangkok who for one reason or another haven’t returned to their home province and no doubt finding things tough with entertainment and nightlife currently on pause due to the COVID-19 crisis.
5,000 kilograms of rice, 30,000 eggs, Mama noodles, canned foods, fish sauce plus a wide range of other groceries and supplies will be distributed throughout the afternoon.
Anyone who works in Nana Plaza, no matter their job or position, be it a dancer, DJ or doormen; cook, cleaner or cashier, everyone is invited along and welcome to come along.
Thailand Reopens Railway Service To Laos
The State Railway of Thailand announced that the railway service connecting Thailand’s Nong Khai province with Thanaleng station in Laos has resumed operation since Sept 16.
Columbia Pictures’ Aquaverse Theme Park Set To Open Next Month
Sony Pictures Entertainment will open a theme and water park based on popular characters from films produced by Columbia Pictures next month in Thailand as it seeks to cash in on a rebound in tourism.


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Frozen is great. It’s a fun movie with catchy songs and cute characters like Olaf the snowman and Sven the reindeer. But too much Frozen is not for everyone. Case in point: Disney is pulling Olaf’s Frozen Adventure from the beginning of Coco. Why? Too many people complained that the Olaf short, which has a running time of 21 minutes, was much too long. That’s definitely too long to be considered a “short,” if you ask us.
Other moviegoers are upset that the Olaf short was paired with Coco in the first place. As we know, Frozen is a story of all white characters (plus a snowman and a reindeer). Coco is a beautiful tale that celebrates people of color and Latnix culture. The jarring juxtaposition of goofy Olaf and the Frozen world was not sitting well with many audiences.
The majority of Disney and Pixar shorts tend to be about 10 minutes. The Olaf short is over twice as long. It is no secret that Disney tends to focus primarily on white stories. By removing the Olaf short, they are doing the right thing: Celebrating Coco as the inclusive film it is. It doesn’t seem fair to play a story focused on white characters before a movie that celebrates Latinx culture.
making us endure Olaf's Frozen Adventure to get to Coco is a metaphor for the Mexican American experience I just haven't figured out how yet
— JuanPa (@jpbrammer) November 27, 2017
Without the Olaf short, what will movie theaters do with all of their spare minutes? Mashable projects that the extra time will be used for more showings of Coco. Though Disney has yet to comment, we certainly hope that’s the case. Coco is excellent and deserves to be in the spotlight.
Naturally, people had ~opinions~ about the removal of the Olafshort.
So apparently starting Dec 8th the 21 minute long Frozen "short" that plays before Coco is gonna be removed...I can finally take people to see that movie without having to apologize in advance
— LeslieLu (@LeslieLuMarie) December 3, 2017
The general vibe is “sorry not sorry.”
I’m gonna be honest: I have no sympathy for those who are sad the frozen short is being removed before coco
— ChristmasPineapplePrincess (@hecallsmePP) December 3, 2017
But if you really want to see the Olaf short, you have until December 8th.
If you want to see Olaf's Frozen Adventure (which plays before Coco) you better go soon! It will be removed from Coco starting December 8th, thanks to the Scrooges who complained it's too long.
— Baylee Jae (@Baylee_Jae) December 3, 2017
Overall, people seem to be happy with the decision.
"the frozen short is removed from theaters"
— ollie @ CAMILLA CAME HOME!!! (@crushkeys) December 3, 2017
Either way, definitely go see Coco and celebrate one of the best movies of the year, Olaf short or not.
Watch the "Coco" trailer here:
Watch movie trailers and more on go90.

domain: artistic


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SURFACES WE REFINISH
Application of New Surface
Technology seems to be changing everything these days and coatings are no different. Typically either an acrylic or urethane based coating will be applied with special application equipment. These coatings, available in custom colors, will dry to the touch within minutes. Special-T® manufactures some of the most advanced, hi-tech coatings available on the market today. These coatings produce such a hard, glossy surface that most people cannot distinguish between a new and refinished surface. Through different techniques and procedures, a refinished surface can be ready to use within 24 hours.
One aspect of refinishing which tends to set Special-T® apart, is the attention given to finishing the job. Care is taken to polish the surface to remove dust particles or other imperfections in the finish and the work area is thoroughly cleaned up.

domain: chemistry


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Antoine Griezmann has told friends that he has decided to snub a big-money move to the Premier League in favour of staying at Atletico Madrid this summer.
According to the Daily Telegraph, Griezmann is more than happy to continue playing under Diego Simeone at the Vicente Calderon, believing it is the best place for him to reach the top of the game.
The 25-year-old has had two stellar seasons in an Atletico Madrid shirt, scoring 56 goals in total since his move from Real Sociedad. Unsurprisingly, he has attracted the interest of some of the Premier League's elite as a result.
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Chelsea, Manchester City and Manchester United have all been tracking Griezmann in recent months with reports suggesting an offer in excess of £60m could be heading towards the Spanish capital.
His release clause currently stands at £63m and it is the Old Trafford outfit who appear most willing to break the British transfer record to sign him. Whether Louis van Gaal is in charge next season or not, the Red Devils are in dire need of a new world-class striker and Griezmann certainly fits the bill.
However, the lure of Premier League football appears to be too weak to attract the rapid striker. In fact, Diego Simeone is so confident of keeping his star man, he has already told players that Griezmann won't be sold in the summer. He is also telling potential summer signings that, should they join, they will definitely be pairing up with the Frenchman.
It now seems much more likely that Griezmann will sign a new deal with Atletico Madrid rather than leave. His current deal does not expire until 2020 but the club are keen to reward him for his fine form and also increase his buy-out clause to £79m to guard against clubs like Manchester United meeting it.
Unsurprisingly, Simeone's commitment to the club has been key to Griezmann's decision. The Argentine has also been linked with a move to the Premier League but it seems he is committed to leading the club into their new stadium, scheduled to be ready in time for the 2017/18 season.
Best place for it
Having come so close to winning La Liga this season, Atletico proved they are capable of competing with Barcelona and Real Madrid for major honours. They could still finish the campaign with a historic Champions League title, but must first beat their city rivals in the final later this month.
In comparison, both Manchester United and Chelsea have proved themselves incapable of challenging for either the Premier League or Champions League. Indeed, it seems likely that neither of them will qualify for the latter competition next season.
For now, Griezmann appears to be in the very best place to win trophies, unless, of course, one of Spain's elite two clubs come calling. Then everything changes.


It’s time that we, as a collective, talk about monopolies in the world of the Internet. As a society, we have grown as dependent on the Internet as we have to utilities such as water, gas or electricity. It’s no wonder that for some, access to the Internet has become a basic human right. It's as fundamental as the freedom of expression and opinion. So what if the Internet suddenly becomes victim to “The Cycle,” a term coined by Harvard law professor Tim Wu, which describes what has happened to many different information technologies in the past including telegram, telephone, cinema, radio, and television? The fear is, the Internet is likely to be next! What is “The Cycle?” Is the Internet at risk? What are the dangers? What can we do to prevent them? These are questions that will be touched upon in this post and discussed at more length during the upcoming WCIT 2019.
What is The Cycle?
So what is The Cycle? According to Tim Wu, The Cycle is a process in “which information industries rise, consolidate, monopolize, capture governments, force out competitors, and, eventually, fragment into something less grandiose, less perfect, but more vibrant, open, and innovative.” History has shown that this Cycle is one that repeats itself. An inventor will discover the technology, then early-adopting pioneers and enthusiasts will start making use of it. The technology becomes commercialized, perfected, popularized and scaled. Then the corporations gain enough power that they get the government involved, allowing them to become the ruling monopolies. This is followed by a period of general inactivity until a new technology is discovered, and The Cycle starts over again. The question at hand is, will it be different this time?
We are currently fighting to maintain the Open Internet, a concept whereby “the information across the World Wide Web is equally free and available, without variables that depend on the financial motives of Internet Service Providers.” The whole process of the cycle involves taking an open system and turning it into something closed. Right now, the internet is considered to be in its 4th step in The Cycle. The Internet has already been commercialized. There have been monopolies and powerful stakeholders gathering around the Internet for decades, which have refined and scaled it (think YouTube, WordPress, Flickr, Wikipedia, Google, Netflix, etc.). These pose a serious threat to the freedom and openness of the Internet as we know it. Key players include governments, telecom monopolies, Internet giants, startups, NGOs, hackers and more. This war may very well define today’s society, as we determine who controls human communication, and how.
Why is this dangerous?
The biggest fear is that we will lose sight of capitalism and replace it with corporatism instead. While capitalism is a lot more chaotic, it is also more healthy for society than allowing a central body, like big corporations and/or governments, to make choices for us. By giving in to corporatism we would be stifling the opportunities not only for small business to grow and thrive but also for the process of innovation to take place. This, of course, leads to the issue of widening the gap of the rich getting richer while the poor get poorer. Those who currently have more power will become even more powerful, pushing out any competitors and keeping the playing field in their favor.
Once these monopolies collect this power, they will either buy out their competitors or prevent them from growing in the first place. There have been examples of attempts already. Like when telecommunication company Verizon blocked Google Wallet from their phones in favor of their own application, ISIS. Other means of placing restrictions on the internet come from Internet Service Providers (ISPs) who can potentially slow down internet speed for certain websites and applications. A hypothetical example would be if Comcast, the largest cable provider in the US, wanted to push consumers to watch NBC (owned by them) over Netflix. In this scenario, they might decide to slow down their major competitors’ content. Research has shown that people are so impatient that slowing down a website by even 250 milliseconds is enough for them to leave it.
Who are the Monopolies?
Let’s quickly get to know those who are currently in control. Half of the ten largest corporations in the world are internet companies, and one of them is an ISP. Internet companies are taking the lead because they control information, communication, and even politics! In the war for the open Internet, the main stakeholders of central focus are ISPs. For the purposes of this article, we are going to take a look at examples in the US. For broadband, there’s Cox (which recently acquired Time Warner), and Comcast (which controls 56% of US’ broadband). For wireless, there’s AT&T and Verizon (which control two-thirds of the wireless market). If given free rein, ISPs would hinder free market competition by any means necessary. This is where Net Neutrality comes in as a defense mechanism to help keep ISPs in check by preventing them from:
× Blocking content from websites
× Slowing down content from websites
× Accepting money from websites to speed up their content
Meanwhile, half of all of the internet traffic goes to only 30 websites. Considering how over-saturated and chaotic the Internet is, that's significant! This means that, while launching a website has become more affordable, it costs more to actually become visible to a wide audience. Here, Facebook and Google advertisements dominate the sphere by making up 85% of all online advertising. And while this is concerning now, it has the potential to become a big problem in the future. The benevolent monopolists who currently run these organizations may pass their power on to less benevolent successors in time. Again, Net Neutrality rules intend to help level the playing field so that rich and powerful corporations will not be able to buy priority access to the internet. This will give the small startups, businesses, blogs and content creators a chance to compete.
What is the future without Net Neutrality?
Let’s paint a clearer picture of what is in store for us if we continue down a path without Net Neutrality. In a future without Net Neutrality, websites may have to pay ISPs to become accessible for their customers. Otherwise, they may as well be invisible. Their other choice would be to allow a walled garden (such as Facebook or Apple) pay the ISPs on their behalf. This comes at a price, however. In exchange, they would have to lose some control. This includes allowing the walled gardens to place (competitor) ads into their website, use their data and sell it to their competitors, and even redirect their audience to competitors who are willing to pay. Let’s face it, it’s not a pretty picture.
This is why it is so important to discuss the options and what we can do today to protect the open internet of the future. Otherwise, we risk losing this very important war. The aim is to make sure that the Internet, the most powerful tool for communication, information, and creativity in the history of mankind, continues to benefit the public and not just a select few controlling corporations and governments. Society can save the open Internet, and the first step is to raise awareness and discuss these issues in forums, like those included within the frameworks of WCIT 2019. Together, it is possible to break The Cycle and foster free capitalism online.


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Tesla Motor’s advance into the Chinese market has been slow and fraught with obstacles, none bigger than a trademark infringement with a local Chinese businessman. Is this another case of legalese or blatant ransom money?
Tesla sued in China over name
It’s been a while since we’ve heard of Tesla being sued in China. Unfortunately, the news is now resurfacing with the infamous Chinese businessman, Zhang Baosheng taking the company back to court. Mr. Zhang has long been seen as Tesla’s biggest obstacle to its entry in the highly profitable Chinese car market. He registered the word “Tesla” in China before the company arrived there. For this, he estimates the plump sum of $3.85 million, or 23.9 million yuan will suffice for compensation. But Mr. Zhang won’t stop here insisting that the company stops all sales, marketing, shutting down showrooms, as well as its Superchargers, according to his lawyer Zhu Dongxing.
No one is commenting, Tesla China nor our businessman Mr. Zhang.
Ransom, or serious infringement?
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Konsequenzen nach dem Ergebnis des EU Referendums im Vereinigten Königreich16_12_01_einladung_dresden_de
180 years after Berlin fashion designers established one of the most successful clothing industry’s in Europe. Nazis destroyed in 1938, just 100 years after the foundation, Jewish fashion design in Germany.
The German federal ministry of justice, today based in the Hausvogteiplatz region of Berlin, took the initiative to remember what happened.
With his gift for provocation, you could only wish Kanye West’s fashion had more fangs. There was nothing here that he hadn’t done before.
Linking fashion performance with historical, political and social locations seems to be a privilege of US artists. Interesting to know: Berlin fashion designers, movie producers and painters (Macke) as well as DADA performance artists (R. Hausmann) were closely connected by there ideas in the 1920th and even into the 1930th.
This tradition and creative power was destroyed by the Nazis. Leading fashion designers and artists became “entartete Kunst” (degenerated art) after 1933. Terrible to see how the Nazi promoted fashison designers started to support Hitlers regime soon after it was installed.
Maybe it is time to remember this part of the fashion tradition in Berlin. The enclosed BoF article gives some clues on how to do it.
Having worked for this broadcast for quite a bit of time I have understood what it means to anchor a radio radio show. It’s still on air.
I am writing to you with reference to your current exhibition:
Stolen Heart: The Theft of Jewish Property in Berlin’s Historic Center, 1933–1945 that is promoted on your website: https://www.lbi.org/2016/03/stolen-heart-exhibition/
The Stolen Heart Video Map: http://www.cgpartnersllc.com/fresh/post/video-map-charts-injustice-leo-baeck-institute/ illustrates the expropriation of five Jewish family homes in Berlin during the Third Reich.
Although I have not seen the exhibition personally, I would like to point out some historical inaccuracies, which detract from its impact.
Even today, the massive scale of Nazi expropriation of Jewish property is not fully appreciated and is all too often played down by some politicians, historians or simply ignored by those industry leaders in Germany whose companies were involved in so many ways in those Nazi-era crimes.
In 1989, I published Berliner Konfektion und Mode 1836 – 1939 – Die Zerstörung einer Tradition, second edition1994. After German reunification in 1990, I had the opportunity to conduct research in former East German archives and at the Oberfinanzdirektion Berlin. I discovered that roughly 1,900 small and medium-sized Jewish enterprises (only) in the fashion and textile industry were either confiscated, went insolvent due to bank restrictions against Jews or “aryanized” by German businesses or the Nazi state. The total value of properties and businesses belonging to Jewish textile and fashion firms was the equivalent of what would be today about $1 billion.
The forces behind the confiscation was the Nazi interior ministry, the Victoria Insurance (still in existence and now a subsidiary of the global ERGO-Insurance company which has many branches in the US) and greedy German businessmen who leapt at the opportunity to get rid of Jewish competition. A document I recently found at the German state archives reveals the intention of Nazi officials to take over functioning Jewish cloth businesses, which had large export quotas, for their own and well-known purposes. One of the leading Nazi politicians involved in this enterprise was Joseph Neckermann (between 1950-1985 Neckermann was the biggest mail order company in Germany) as well as the owner of the internationally known men’s fashion company HUGO BOSS. Mr. Neckermann (CEO) built his company’s post-war fortune on the confiscated Jewish property and businesses. HUGO BOSS was deeply involved in exploiting and killing Russian prisoners of war at the concentration camp Lietzmannstadt/Lodz (where these poor souls were exploited as forced laborers producing German uniforms using the very same machinery confiscated earlier from Jewish firms in Berlin and all over the Reich).
Regrettably, I think your current exhibition is a wasted opportunity. It does not display, and fails to illustrate, the catastrophe of the confiscations and the resultant crimes even though all the relevant information is available, having already been thoroughly researched. Jacob Toury, a member of the LBI Jerusalem, wrote most of the history of the Nazi expropriation of Jewish firms and its scale in the LBI book, volume 42, published in Tuebingen 1984 (Jüdische Textilunternehmer in Baden Wurttemberg 1683 – 1938). In his essay and research, Toury pointed out the vital role the confiscation of ‘Jewish fashion and textile businesses’ and property played to the Nazi state.
Having explored the history of the Berlin Jewish fashion industry in two more books over 30 years, (Berliner Konfektion und Mode 1836 – 1939; Ehrenfried & Cohn, novel, Lichtig Verlag-Berlin, 2015) it is clear to me that ignoring the scale of “state organized theft of Jewish textile and fashion firms” (a term I coined in 1992) seriously under-states what actually happened.
Besides, the number of restitution cases filed by former owners of Jewish fashion and textile firms that were based in Berlin between 1945 -1990 was roughly 470. Most of these claimants received restitution, even though more should have done so but were unable to succeed due to missing documents relating to their former companies which languished in East German archives. After German unification an estimated 100,000 claims were lodged with the German government and those responsible at the Berlin Senate. In September 1990 a federal law (§4 and 5 of the Gesetz zur Regelung offener Vermögensfragen (Vermögensgesetz – VermG, ) opened the door for claims for Jewish restitution and Jewish property as well as other claims concerning property and real estate in the former eastern part of Berlin – and therefore Berlin Mitte – among other suburbs of Berlin. 1992 was the deadline for claims, but not for restitution, as the Jewish Claims Conference (JCC) stressed in its report 2014. The bulk of compensated, often unclaimed Jewish property went to the JCC, which reached a deal with the German government in the range of $ 90m. Furthermore, the JCC became the guardian of further compensation programs for individual survivors, pension funds and financial help for many Eastern European Jews.
In 2004 the BRDV (central German government office for such restitution claims – among other cases) was, and still is, in charge of negotiations for restitution either to individuals or with the help of the JCC.
Further information see the following links:
To say, as the LBI in the exhibition does, there were only about 15 successful restitution cases in Berlin-Mitte after 1990 is simply a distortion of the facts and it ultimately minimizes the scale of stolen Jewish property and belongings in Greater Berlin and the restitution paid as well. Furthermore, even though the number of 15 restituted Jewish properties seems to be rather low, the BRVD pointed out to me, the fact that properties and the ground on which those buildings stand in the old center of Berlin – Mitte – were sold according to § 5 VermG, because nobody claimed ownership. This seems to me an outrageous procedure, but in the ultimate balance of things, restitution cash went to the JCC. They, in turn, used that money to take care of Jews in Eastern Europe in particular (but also elsewhere) by establishing many extra funds for social issues. Can there be justice in the final instance and after so many crimes and so much suffering? Possibly not. But those responsible did, as far as I can see, try. An uncomfortable feeling remains.
As we all know, financial restitution did not compensate for the pain and loss of those whose property was expropriated. I personally have worked with US, UK and German lawyers on 73 successful restitution cases, i.e. Norbert Jutschenka, L. Lindemann and L. Seligmann (all of them belonged to first class fashion and clothing producers in the former East Berlin until 1935-39) after German unification. Not forgetting the fur producers around Krausenstrasse and Jerusalemerstrasse near Hausvogteiplatz in Berlin (most of them Jewish).
In short, I would like to see the prestigious LBI make a greater effort to be historically accurate and, much more importantly, to mount an exhibition illustrating the full effect of the grand scale theft that happened in the center and outskirts of Greater Berlin (as opposed to exhibiting a mere 5 cases).
I would be most willing to act as a consultant to such a project. Incidentally, I donated some my research papers from which I wrote my books to the LBI in NY. Feel free to consult the Westphal collection. I am currently updating my book on the destruction of the Jewish fashion industry and am looking for an English translator and publisher. If you were able to help me on this, I would welcome your advice.
“Verstörend und schockierend für meine Familie”
Erstmals äußert sich C&A-Eigentümer Maurice Brenninkmeijer öffentlich zur NS-Geschichte seiner Familie. In der ZEIT spricht er von Opportunismus und Herzlosigkeit.
Den Artikel auf Zeit Online lesen
“Die Arisierung, ein außerordentlicher Glücksfall…”
Die Recherchen in Sachen der NS Involvierung der C & A Familie Brenninkmeijer sind interessant, geben aber eben nur einen kleinen Einblick in das, was die modische Bekleidungsindustrie vor allem in Berlin seit 1933 antrieb: Gier, Betrug, die Aussicht ohne jüdische Bekleidungsfirmen konkurrenzlos besser wirken zu können, erschreckender Judenhass. Nach 1945 ging es rasch weiter: die Fähigkeit nach dem Krieg eine boomtown Berliner Mode zu schaffen, die fast ausschließlich auf geraubtem jüdischem Kapital beruhte.
Herr Brenninkmeijer, Sie haben weiterhin die Chance den Fokus etwas weiter zu ziehen.
Insgesamt wurden allein in Berlin zw. 1933 -1944 ca. 2 400 jüdische Textil und Bekleidungsfirmen “arisiert” oder deren Eigentum konfisziert. Ich hatte Gelegenheit mit gut 80 der ehemaligen (emigrierten) jüdischen Firmenbesitzer seit 1985 zu sprechen, in den USA, England und Israel. Die Geschichten ähnelten sich. Nicht selten wurden die jüdischen Besitzer von Modefirmen mit hohen Exportquoten mit vorgehaltener Pistole zur Vertragsunterzeichnung gezwungen. Restitution nach dem Krieg wurde kaum geleistet. So im Fall der seinerzeit prominenten Firma des Norbert Jutschenka, einer der großen Stars der Modeszene der 20/30er Jahre; die neuen arischen Besitzer verbrannten vor dem Jutschenka Geschäftshaus am Hausvogteiplatz die Firmenunterlagen.
Die Arisierung der jüdischen Modefirmen rund um den Hausvogteiplatz in Berlin „…war für uns junge, arische Moderschaffende ein außerordentlicher Glücksfall…“, kommentierte 1988 Detlev Albers, Top-Designer der 50er – 70 Jahre in Berlin/Deutschland, den organisierten Raubzug der Nazis auf die Modeindustrie.
Die Zwangsarbeitslager der Textilfirmen wurden logistisch von jenen Designern und Geschäftsleuten organisiert, die das know how aus der Vorkriegsmode gut kannten.
Und die Industrieverbände? Bis heute hat es keiner der Textil-und Bekleidungsverbände geschafft, die Tradition jüdischer Firmen vor allem in Berlin zu würdigen. In diesem Jahr hätte man Anlass gehabt die 180 jährige Tradition der Berliner Konfektions-und Modebranche zu begehen. Doch man ignoriert das lieber, im Schatten der Fashion Week, denn die Verwicklung der Branche in die Naziverbrechen soll offensichtlich nicht aufgearbeitet werden.
Es gehörten eben nicht nur Neckermann, Hugo Boss, Neckermann und – wie wir nun wissen – die Familie Brennikmeijer zu den Treibern des unter staatlichem Schutz vorangetriebenen Raubs auf die jüdischen Modefirmen, sie waren substantieller Bestandteil der Zwangsarbeit und der Konfiszierung jüdischem Eigentums.
Jüdische Firmeneigentümer die nach dem Krieg nach West-Berlin kamen, wurden vom Verband der deutschen Bekleidungsindustrie abgewiesen. Der Verein der Berliner Kaufleute und Industrieller (VBKI) stellte sich taub zu deren Forderungen.
Warum sich bis heute niemand der wenigen und talentierten Modedesigner und der Industrieverbände für diesen Teil ihrer Geschichte interessiert, bedarf der Erklärung.
Im Gegenteil dazu: im Mai feierte die New York Times – und die Designer – 100 Jahre jüdisches Modedesign in der Männermode.
Herr Brenninkmeijer, machen Sie doch nun den nächsten Schritt und ermuntern die Branche, so wie Sie es für Ihr Unternehmen taten, den Blick in die Vergangenheit nicht mehr zu scheuen. Richten Sie einen Fonds für die Nachfahren der Zwangsarbeiter-Familien ein. Sorgen Sie für die Verleihung eines Modedesign Awards im Namen der jüdischen Gründer der Berliner Mode.
+ Uwe Westphal, Berliner Mode und Konfektion 1836 – 1939 – Die Zerstörung einer Tradition; + Uwe Westphal, Ehrenfried & Cohn, Roman über den erzwungenen Untergang einer jüdischen Modefirma, Lichtig Verlag, Berlin.
“Nachdem David Cameron einen „fairen Deal für Großbritannien“ mit der EU ausgehandelt hat, kann die britische Bevölkerung am 23. Juni darüber entscheiden, ob das Land diesen akzeptieren oder die EU verlassen soll. Sowohl diesseits wie jenseits des Ärmelkanals wird heftig darüber diskutiert, was für wen die bessere Lösung wäre.”
REINHARD BÜTIKOFER: MdEP, Co-Vorsitzender der Europäischen Grünen Partei, Brüssel
STEFAN KADELBACH: Professor für Öffentliches Recht, Europarecht und Völkerrecht, Goethe-Universität Frankfurt/Main
RALF SOTSCHEK: Taz- Korrespondent für Irland und Großbritannien, Dublin
MELANIE SULLY: Politikwissenschaftlerin, Leiterin des Instituts für Go-Governance, Wien
UWE WESTPHAL: hr2 kultur, Frankfurt/Main
DISKUSSIONMONTAG, 04. JULI 2016, 19:00 UHR
SCHÜTZENSTRASSE 12, FRANKFURT/MAI
German fashion icon Hugo Boss – Nazi history.
Keep an eye on HUGO BOSS’ fashion collection at the Berlin Fashion Week until 01. July 2016
Hugo Boss clothing was founded in 1924 in a small South German town. Soon they advertised for National Socialist uniforms.
After bankruptcy in 1931 Mr. Boss became a member, sponsor of the National Socialist Party Nazi, and supported the SS in Germany. With the promotion and large contracts with various Nazi organizations, Hugo Boss supplied and sold uniforms for all purposes. Their profits increased.
Like most proto Nazi cloth producers, particularly those who confiscated Jewish fashion firms, they used prisoners of war and forced labor workers “…in the Baltic States, Belgium, France, Italy, Austria, Poland, Czechoslovakia, and the Soviet Union. According to German historian Henning Kober, the company managers were fervent Nazis who were all great admirers of Adolf Hitler. In 1945 Hugo Boss had a photograph in his apartment of him with Hitler, taken at Hitler’s Obersalzberg retreat.…” (source: Wikipedia)
You will find the same shocking facts many times throughout the Berlin fashion industry between 1933 and 1940. Nazis confiscated and forced Berlins Jewish fashion designers to give up their business and or expropriated them. From once 2 400 Jewish clothing firms and export strong fashion industry in 1943 just a few were left. The entire industry of creative fashion firms were destroyed. The effects are still present in the talent search more than 70 years after it happened.
I write from Germany as a journalist, broadcaster and author with experience of some 85 pending restitution cases involving Jewish property and businesses within the Berlin fashion industry. Dina Gold’s book hits exactly the right note. I wholeheartedly endorse Michael Pinto-Duschinsky’s excellent article “Holocaust Survivors Are Still Waiting For Justice” (March/April edition) and what he described as “everyday denial of their Nazi past and obstruction by some German corporations”. Actually it is, according to my experience, much worse than that. Although freedom of information exists and former East German archives are now open and available to the public, many new hurdles have been established for those seeking restitution and compensation. Data protection is a major stumbling block. Even Nazi confiscation documents of Jewish property issued between 1933 -1944 by German officials, insurers and banks are difficult to obtain. Another problem is that a new generation, those aged 30 – 45, who are only too well aware of the Holocaust are, nevertheless, more than happy to make use of the trade names of Nazi-era confiscated Jewish companies. Indeed, they now use these names for their own, newly established, businesses in the heart of the Berlin fashion industry. And thus, a fresh “cartel of silence” has been created by the next generation of Germans. At the same time, textile producer associations, the Victoria insurance company (which foreclosed on so many Jewish buildings during the Third Reich, including that of Dina Gold’s family), the Berlin Chamber of Commerce, university departments of history and fashion, even fashion companies themselves all deny, ignore and lie about the long lost tradition of Jewish entrepreneurship in the German fashion industry since 1836. Dina Gold’s book makes a decisive move toward bringing the issue of restitution and compensation into the 21st century.

domain: history


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“Sampol” is a popular dish in the Maldives that typically refers to a type of dried or smoked fish. The dish is made by salting and sun-drying or smoking the fish, which helps to preserve it for a longer period of time.
The types of fish used for sampol can vary, but common species include tuna, skipjack, and other local fish found in the waters around the Maldives. The dried fish is then often rehydrated and used in a variety of traditional dishes, such as curries and stews, as well as being eaten as a snack on its own.
Sampol is considered a staple food in the Maldives and has been a part of the local cuisine for centuries. The dish is highly prized for its unique flavor and versatility, and is enjoyed by both tourists and locals alike.

domain: travel


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Todayâ€™s pedal line is from Peter Trabucchi. If you have a pedal line (doesnâ€™t have to be in a board) for your rig, please email me a photo, bio, description of pedals and routing to firstname.lastname@example.org. Every Friday Iâ€™ll showcase a pedal line submission. Make sure you include any links to your band or music page.
I play with this pedal setup in my band Roadside Manor.Â I use a Vox AC30 an my main guitar is a Mexican made Fender Stratocaster with Lace Sensor Gold Pickups (easy adjustment to make a MIM Strat sound amazing).
This is my pedal line from the instrument-amplifier:
* Dunlop Crybaby Wah *: A true classic…
* Boss PH-3 Phase Shifter *: This is a pretty sweet phaser many different modes and sounds in such a small pedal (I have a Boss FS-5L attached to it as the expression pedal to change the rate)
* Digitech Whammy *: This is one of my newest pedals.Â You can get all kinds of sweet harmonizing sounds with this pedal and it’s really a blast to play with
* Keeley Katana Clean Boost *: This pedal is a great boost pedal.Â The volume knob pulls out to convert into an overdrive pedal as well.Â I use this when I need a nice, crisp solo sound
* Ibanez TS9DX Turbo Tube Screamer *: This pedal is much like the TS9 made by Ibanez, but it has different modes you can set it to.Â This one works well for getting a real dirty, crunchy solo tone
* Ibanez TS9 Tube Screamer *: Another classic, works great for a real crunchy tone
* Boomerang III Phrase Sampler *: A sweet loop pedal that can loop up to 17 minutes of recorded audio.Â It has many different functions, including a reverse function which will play back what you are playing in reverse (it records 8 second chunks and plays that 8 seconds while you continue playing and it is recording another 8 seconds and so on, I haven’t mastered it just yet but it seems like it could be interesting to use)
* Boss TU-3 Chromatic Tuner *: A nice, simple tuner pedal
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domain: hobby


text:
A comedic look at the life of Steve Jobs.
- Stars:Bob Burnquist, Miles Daisher, Mike Douglas, J.T. Holmes, Kent Kreitler, Justin Long, Art Evans, Juzo Yoshida, Brian Huskey, Jorge Garcia, Allan McLeod, Avin Das, Ben Parks, Madeline Wager, Paul Walter Hauser, Kevin Pedersen, Jason Sheridan, Michael R. Carlson, James Urbaniak, Michaela Watkins,
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iSteve torrent reviews
Jos R (br) wrote: Amazing movie and incredible actors Mamounov and Iankowski.I hope the Academy of Hollywood next year made a nominee for the best foreign movie .
Aryn A (gb) wrote: Driven by personal narrative, Dakota Skye will warm your heart from the start or its not for you. You might say its a chick flick. OK. The fact that its about truth and lies in relationships ought to push it across that arbitrary boundary. This is a charmer, no doubt. If you enjoyed "Away we go" for its pace and intimate moments but didn't like it for being over the top at times, you will love this movie as I did.
Peter M (de) wrote: Grass traces the roots of marijuana back in dramatic fashion, but feels too one sided.
Michael O (es) wrote: What a disappointment...Bette has lost her game when it comes to her last few movies over the years (Drowning Mona, Stepford Wives, etc.)...
Cheryl R (it) wrote: one of my moms fav movies i had to whatch over and over
Shelly l (de) wrote: Only William Holden will make this kind of character lovable .....the movie is basically about love, taboos, prejudices...and society's moral boundaries .
Eben B (es) wrote: I have never forgiven "MYSTERY SCIENCE THEATRE 3000" for mocking this movie. If you look at the (hilarious) monster alone, this may seem like another desperate 1950s 'alien invasion' sci-fi movies made in the phenomina of "THE WAR OF THE WORLDS". But what makes this movie unique is that the way the alien conquers us is actually terrifying. It can control what we are most reliant on - technology. Not only that, but it can slowly control our minds and make us fight among ourselves and cuase us to panic, until the world is in shambles. A real hidden gem. Not avaiable on DVD (yet) but you can easily buy the VHS on the Internet. If you like old sci-fi movies than this is one you HAVE to get!
Eduardo Y (gb) wrote: this is a very good movie, is touching


We would also be happy to send your invoices electronically. We’ve compiled some information for you on how e-invoicing works, the advantages it brings, and what’s needed to implement it.
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text:
An inquiry has begun into the death at Withington Hospital, Manchester, last Friday. Medical staff in the lift with Frank Cummings, 64, of Withington, who was on a trolley, fought to keep him alive while workmen battled to bring the lift down.
They eventually got the lift working again and Mr Cummings - who was suffering from internal bleeding after a routine hernia operation - was taken to theatre where he died about 30 minutes after surgery began.
Mr Cummings was recovering in a normal ward from his hernia repair when he suddenly developed bleeding in another part of his body.
'The patient, who required emergency surgery, was in the process of being taken to theatre in a lift which became trapped between two floors,' a hospital spokesman said last night.
'Every attempt was made to release him, but unfortunately it was some 40 minutes later that exit was achieved.'
The spokesman added: 'The hospital has conveyed its deepest sympathy to the relatives of the patient. The lift becoming stuck like this was one of our worst nightmares - a one in a million chance. This incident was also upsetting for the hospital staff involved. A full investigation is taking place. The Health and Safety Executive has been informed.'
Mr Cummings's family was too upset to talk about the incident. The Manchester city coroner has ruled out an inquest because death was due to natural causes.


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Kangna Ranaut recently shot mujra song ‘Kaleja Hai Hajir Khanjar Kahan Hai’ composed by Uttam Singh and choreographed by Ganesh Acharya.
Kangana says, “Rajjo is really close to my heart and I am glad it is being released this festive season. As for competition with other films, there would be one every week in any case. I am sure my producers are taking a good call and it comes from the trust and confidence they have in the product. I am particularly proud of the film and my work. The film is special and it will fetch an audience of it’s own. I strongly believe in director Vishwas Patil and music director Uttam Singh. Once you see the promos, which would be out very soon, you would know what I mean.”
Choreographer Ganesh Acharya, says, “Kangana has always been known as a powerhouse performer but now you will see her with new perspective. I was thrilled to see her dedication and the end result. It will be the best performance of Kangana’s life.”


text:
Not a long ago, I met a guy. He was a hard worker, an incredible father, funny, reliable, and stable. I thought he met all of my criteria. I was excited to be finally finding a potential romantic partner and possibly sharing a life together.
But one thing gnawed at me. My intuition was telling me there was something off. I didn’t know why or how. I liked this guy so much that I brushed this intuitive feeling off.
I found myself trying so hard and sharing intimate information about myself. We exchanged information. I thought it was great that this guy was emotionally open and very honest with everything.
I could not find anything wrong with him. As we build the relationship and getting to know each other, this stinky feeling won’t go away.
I realized I was not feeling safe to be vulnerable with him. This guy was aloof at times. I did not take it personally, but I found myself becoming nervous to open up emotionally.
It was a red flag for a reason. There was a reason my intuition went into overdrive alerting me that I was about to walk into a toxic relationship.
We were few months into our friendship. One day, we had a conversation that took a turn, and at the point from on, our friendship also took a nosedive.
This guy admitted he was seeing several women. There. That was the stinky feeling. It was the red flag trying to warn me. That was why I did not feel safe to be vulnerable with him.
It was an eye-opening, and I declined his date. Then, he became distant. It was hard at first but relieved that I do not become trapped in toxicity.
This lesson is critical because it is essential to be feeling SAFE with your potential partner. Vulnerability and trust go in hand in hand.
If you do not feel safe in sharing your life and cannot trust your potential life partner, don’t do it. Don’t waste your time. Walk away to protect your happiness, health, and mental.
Yes, it is hard to walk away and to feel defeated, but love is never scarce or limited. Being with a toxic partner confines your mind, body, and spiritual.
Being with an emotionally available, trustworthy, reliable, mature, and evolved partner expands each bit of you. It also frees you. Love extends you beautifully, lovely, and strongly.
You are much worth than toxicity, restrictions, rules, and fear. You deserve to feel protected with your partner.


text:
Cambridge Library Collection - Hakluyt First Series: Narrative of a Voyage to the West Indies and Mexico in the Years 1599-1602: Translated from the Original and Unpublished Manuscript (Paperback)Samuel Champlain (author), Alice Wilmere (editor and translator), Norton Shaw (editor)
Paperback 208 Pages / Published: 20/05/2010
- We can order this
The publications of the Hakluyt Society (founded in 1846) made available edited (and sometimes translated) early accounts of exploration. The first series, which ran from 1847 to 1899, consists of 100 books containing published or previously unpublished works by authors from Christopher Columbus to Sir Francis Drake, and covering voyages to the New World, to China and Japan, to Russia and to Africa and India. The author of this volume, Samuel Champlain, is better known for his writings on Canada and for founding Quebec City. This account of his 1599 journey with his uncle to the West Indies and Mexico, originally intended for Henri IV of France and translated for the series in 1859, had never previously appeared in print. Champlain provides a valuable illustrated report on natural history and social, economic and political conditions of the region in the early colonial period.
Publisher: Cambridge University Press
Number of pages: 208
Weight: 270 g
Dimensions: 216 x 140 x 12 mm
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domain: library


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domain: geography


text:
In the last 2 years, Covid-19 turned our world upside down and caused millions of deaths. In most of the reported cases, the common symptoms of Covid are cold, cough, fever and lung infection, but till now no exact treatment for Coronavirus has been discovered. And because the virus is being treated based on symptoms, people started taking medicines like Dolo-650 fiercely even without medical advice.
However, do you know that there are many potential side effects of this medication? While there are benefits, there are also side effects — some even life-threatening. Therefore, we must understand the side effects of this medicine.
Reason Why Dolo is Widely Used:
Dolo-650 is a medication that contains paracetamol, which helps against fever and other symptoms noticed among Covid-19 patients. Additionally, Dolo-650 also provides relief in headache, toothache, back pain, nerve pain, muscle pain, which is why this medicine has been used fiercely without any prescription.
After the use of this medicine, it reduces the pain signals sent to the brain, which gives relief to the patients. The use of this medicine also inhibits the chemical prostaglandins released in our bodies. Doctors have found that this chemical is responsible for increasing pain and body temperature.
Common Side-Effects Of Dolo:
Low blood pressure
Serious Side-Effects of Dolo:
Swelling of vocal cord
Shortness of breath
Nervous system affected
Read all the Latest News, Breaking News and Coronavirus News here.

domain: medical