Patrik Brundin, Avindra Nath, J. David Beckham. Is COVID-19 a Perfect Storm for Parkinson’s Disease? Trends in Neurosciences, 2020; DOI: 10.1016/j.tins.2020.10.009

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COVID-19 and Multiple Sclerosis: Predisposition and Precautions in Treatment: SN Comprehensive Clinical Medicine, by Shaghayegh Sadeghmousavi and Nima Rezaei.


Study Conclusion:
“Multiple Sclerosis is a chronic inflammatory disease of the CNS with an autoimmune etiology. The pathology of this disease starts with increased migration of autoreactive lym- phocytes across the BBB. Regulatory defects allow these cells to transit from physiological states to a pathological cascade. Both genetic and environmental factors in MS patients can cause this impairment of the regulatory lymphocytes functions to suppress effector cells. Microbial infections can act as triggers for inducing autoimmunity and clinical disease manifestations in genetically predisposed individuals. Studies have suggested a robust relationship between viral infections and exacerbations of MS. Based on the aforementioned studies, COVID-19 carries additional reasons for concern because of taking immunosuppressive therapies in MS patients and also the fact that viral infections may contribute to MS exacerbation and relapses as an environmental factor.  This study provides some insights regarding the impact of COVID-19 disease on actively treated patients with MS.
For clarification of the exact relationship between COVID- 19 and MS, further studies are needed. Meanwhile, clinicians should take care of patients with MS during the pandemic regarding the possible reciprocal association between the MS and COVID-19.”

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A case of (seemingly identical) twins with same environment and initial symptoms, but different disease progression and outcome.

Ann. Intern. Med. 2020 Dec 8;L20-1207.doi: 10.7326/L20-1207. Online ahead of print.

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1. schools/food allergies/index.htm

It ha been estimated that approximately 8%of children have food allergies (commonly: milk, eggs, fish, crustacean shellfish, wheat, soy, peanuts, tree nuts). Additionally, it has been reported that there is a 21 % increase in childhood peanut allergy since 2010. Ref: .

Additionally, it has been reported that 10-44% of individuals who work with laboratory animals will develop allergic symptoms. An estimated 10% of laboratory workers may also develop occupation-related asthma. Ref: .

2. Whether a test substance is safe, is  dose-dependent. Ki, Kd, IC50 values are important to know when evaluating drug target and side-effects. Additionally, test substances may interfere with drug metabolism of other medications (and genotype is important when evaluating drug-drug interactions as well).

3. Examples of adverse drug-drug interactions:

Tylenol (acetaminophen) metabolism creates harmful products (N-acetyl-p-benzoquinone imine) . Drinking alcohol while taking acetaminophen, creates more harmful products and may lead to liver damage. Ref: .

Pharmacological (high) doses of health food supplements do not always produce healthy outcomes. For example, high dose beta-carotene food supplements produced an increased incidence of lung cancer in smokers, but not in non-smoker test subjects. Ref: Goodman GE et al., The Beta-Carotene and Retinol Efficacy Trial: incidence of lung cancer and cardiovascular disease mortality during 6-year follow-up after stopping beta-carotene and retinol supplements. J. Natl. Cancer Inst. 96(23): 1743-1750 (2004). . Also see:
Herbal medicine for psychiatric disorders: Psychopharmacology and neuroscience-based nomenclature.  World J. Biol. Psychiatry 2019 Oct;20(8):586-604.  doi: 10.1080/15622975.2017.1346279. .

Cancer stem cells (CSCs) are tumor cells with stem cell-like qualities that promote tumor progression, adaption to stress, and resistance to chemotherapy. Bhattacharya et al. found that aspirin targets CSCs in a way that may enhance the efficacy of chemotherapy in patients with basal-like breast cancers. In cultured CSCs from invasive breast tumors or in a mouse model of breast cancer, aspirin suppressed the synthesis of the drug efflux pump ABCG2 by relieving the repression of the transcription cofactor SMAR1 by pluripotency factors. Aspirin prevented doxorubicin-induced repression of SMAR1 and proliferation of CSCs, consequently enhancing the cytotoxicity of doxorubicin. Thus, in addition to its current use as an anti-inflammatory for inflammation-driven premalignancies and cancers, aspirin might also be used to target CSCs in invasive breast cancer.”
SMAR1 repression by pluripotency factors and consequent chemoresistance in breast cancer stem-like cells is reversed by aspirin. Science Signaling 13(654): eaay6077 (Oct.20, 2020); DOI: 10.1126/scisignal.aay6077.

4. Some products for sale to the general public are not safe to use. Example: outbreak of lung injury associated with E-cigarette use/vaping. Ref: .





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This edition of Prudent Practices in the Laboratory builds on the work provided in previous editions. Among other changes, it has two new chapters, one on Emergency Planning and one on Laboratory Security, described above, and the discussion of EHS (environment, health, and safety) management systems has been extensively revised. Chapters 2, 3, and 10 cover administrative and organizational concerns that affect the laboratory environment; Chapters 4–8 discuss practical concerns when working in a laboratory; Chapter 9 discusses laboratory facilities; and Chapter 11 provides an overview of federal regulations that affect laboratory activities. Acknowledging the stronger regulatory environment that exists today, this edition provides more references to relevant codes, standards, and regulations than the prior versions. This is not intended to imply that safety has become a matter of regulation rather than of good practice; it is a reflection of laboratory practice today and is intended to provide a resource for personnel who must remain in compliance with these regulations or face legal consequences.

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We conducted postmortem high-resolution magnetic resonance imaging (magnetic resonance microscopy) of the brains of patients with coronavirus disease 2019 (Covid-19) (median age, 50 years) and histopathological examination that focused on microvascular changes in the olfactory bulb and brain stem. (See the Materials and Methods section in the Supplementary Appendix, available with the full text of this letter at Images were obtained from the brains of 13 patients with the use of an 11.7-Tesla scanner at a resolution of 25 μm for the olfactory bulb and at a resolution of 100 μm for the brain. Abnormalities were seen in the brains of 10 patients. We examined the brains of patients that showed abnormalities by means of multiplex fluorescence imaging (in 5 patients) and by means of chromogenic immunostaining (in 10 patients). We performed conventional histopathological examination of the brains of 18 patients. Fourteen patients had chronic illnesses, including diabetes and hypertension, and 11 had been found dead or had died suddenly and unexpectedly. Of the 16 patients with available medical histories, 1 had delirium, 5 had mild respiratory symptoms, 4 had acute respiratory distress syndrome, 2 had pulmonary embolism, and the symptoms were not known in 3 (Table S1 in the Supplementary Appendix).

Pathological Studies of Microvascular Injury in the Brains of Patients Who Died from Covid-19.

Magnetic resonance microscopy showed punctate hyperintensities in 9 patients, which represented areas of microvascular injury and fibrinogen leakage. These features were observed on corresponding histopathological examination performed with the use of fluorescence imaging (Figure 1A and 1B). These areas showed thinning of the basal lamina of the endothelial cells, as determined by collagen IV immunostaining in 5 patients (Fig. 1B1 and 1B2). Punctate hypointensities on imaging in 10 patients corresponded to congested blood vessels (Figure 1C) with surrounding areas of fibrinogen leakage (Figure 1D and Fig. S1) and relatively intact vasculature (Figure 1E). Areas of linear hypointensities were interpreted as microhemorrhages (Figure 1F and Fig. S2). There was minimal perivascular inflammation in the specimens examined, but there was no vascular occlusion, as previously described in the Journal.1 Perivascular-activated microglia, macrophage infiltrates, and hypertrophic astrocytes were seen in 13 patients (Figure 1G and 1H, Fig. S3, and Table S4).2 There were CD3+ and CD8+ T cells in the perivascular spaces and in lumens adjacent to endothelial cells in 8 patients, which may have contributed to vascular injury (Figure 1I and 1J), as suggested in a previous report.3 Activated microglia were found adjacent to neurons in 5 patients, which is suggestive of neuronophagia in the olfactory bulb, substantia nigra, dorsal motor nucleus of the vagal nerve, and the pre-Bötzinger complex in the medulla, which is involved in the generation of spontaneous rhythmic breathing (Figure 1K through 1N and Fig. S3). ….”

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