RETROSPECTIVE STUDY OF VITAMIN D DEFICIENCY IN RHEUMATOLOGIC PATIENTS DURING THE COVID-19 PANDEMIC IN POLAND

BackgroundBefore the COVID-19 pandemic it was estimated that nearly 70% of the population is deficient in vitamin D - 25(OH)D <20ng/ml in Poland [1]. The percentage was expected to increase due to indoor isolation during the COVID-19 pandemic. Vitamin D has a positive effect on the condition of the bones, affects the course of autoimmune diseases, the course of neurological diseases, in type 2 diabetes, vitamin D supplementation improves glucose tolerance and reduces insulin resistance [2,3,4].ObjectivesThe aim of the retrospective study was to determine what percentage of rheumatology clinic patients suffer from vitamin D deficiency and whether this condition is effectively treated.MethodsIn January 2023, a retrospective analysis of the documentation of 172 patients treated at the Rheumatology Outpatient Clinic in Bełżyce (Poland) in 2022 was conducted.ResultsResults: The mean age of the 172 patients whose documentation was analyzed was 60.43 years (min 19, max 88). There were 132 women (76.8%) and 40 men (23.2%) in this group. The mean concentration of vitamin D was 25.57ng/ml±SD11.9 (min 5.7, max 75, Me 22.8). Vitamin D deficiency was found in 44% (serum concentration <20mg/ml), suboptimal concentration (20-30ng/ml) in 31%, optimal concentration (30-50ng/ml) in 21%, and high concentration (>50ng/ml) ml) in 4%. All those with a deficit or deficiency (75 people) were prescribed cholecalciferol in a dose of 20,000 units orally, 1 capsule twice a week after breakfast for 2 months [5]. Patients with optimal vitamin D levels were advised to take a dose of 2,000 units per day. Among the patients with deficit or deficiency, 48 people came for a follow-up visit to check the level of vitamin D (64% of the group with too low vitamin D concentration;28% of the entire group whose documentation was analyzed). In the follow-up examination, the mean concentration of vitamin D was 37.14±9.8ng/ml (min 28, max 84, Me 35.3). Therefore, a statistically significant increase in the concentration of vitamin D in the blood was noted (p<0.05). In the group of people who came for the follow-up examination, there were 35 women, whose mean age was 60.7 years and 13 men (mean age 68.2 years).Conclusion:1. During the COVID-19 pandemic in the group of outpatient rheumatology patients, 75% had a deficiency or suboptimal level of vitamin D.2. Treatment with cholecalciferol in a dose of 20,000 IU twice a week orally for 2 months is effective treatment of vitamin D deficiency.3. Too low percentage of patients diagnosed with vitamin D deficiency come for visits and check-ups.References[1]Hilger J., Friedel A., Herr R.. A systematic review of vitamin D status in populations worldwide. Br J Nutr. 2013;9: 1023.[2]Karczmarewicz E., Czekuć-Kryskiewicz E., Płudowski P. Effect of vitamin D status on pharmacological treatment efficiency-impact on cost- effective management in medicine. Dermatoendocrinology, 2013;5: 299-304.[3]Zhu J., Bing C., Wilding J.P.H. Vitamin d receptor ligands attenuate the inflammatory profile of IL-1β-stimulated human white preadipocytes via modulating the NF-κB and unfolded protein response pathways Biochemical and Biophysical Research Communications 2-18, 503: 1049-1056.[4]Luan W., Hammond L.A. Vuillermot S. Maternal vitamin d prevents abnormal dopaminergic development and function in a mouse model of prenatal immune activation. Scientific Reports 2018;8 (1) article numer 9741.[5]Płudowski P., Karczmarewicz E. i wsp. Witamina D: Rekomendacje dawkowania w populacji osób zdrowych oraz w grupach ryzyka deficytów.Wytyczne dla Europy Środkowej 2013 r. Standardy Medyczne/Pediatria 2013, 10, 573-578 (in Polish).Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Report of the Association Between Multisystem Inflammatory Syndrome and Severe Myocarditis

Introduction: The people worldwide have been affected by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection since its appearance in December, 2019. Kawasaki disease-like hyperinflammatory shock associated with SARS-CoV-2 infection in previously healthy children has been reported in the literature, which is now referred to as a multisystem inflammatory syndrome in children (MIS-C). Some aspects of MIS-C are similar to those of Kawasaki disease, toxic shock syndrome, secondary hemophagocytic syndrome, and macrophage activation syndrome. Case Presentation: This study reported an 11-year-old boy with MIS-C presented with periorbital and peripheral edema, abdominal pain, elevated liver enzymes, severe right pleural effusion, moderate ascites, and severe failure of right and left ventricles. Conclusion(s): Due to the increasing number of reported cases of critically ill patients afflicted with MIS-C and its life-threatening complications, it was recommended that further studies should be carried out in order to provide screening tests for myocardial dysfunction. Adopting a multidisciplinary approach was found inevitable.Copyright © 2023, Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.

Scientific rationale of Indian AYUSH Ministry advisory for COVID-19 prevention, prophylaxis, and immunomodulation

The current outbreak of COVID-19 is caused by the SARS-CoV-2 virus that has affected > 210 countries. Various steps are taken by different countries to tackle the current war-like health situation. In India, the Ministry of AYUSH released a self-care advisory for immunomodulation measures during the COVID-19 and this review article discusses the detailed scientific rationale associated with this advisory. Authors have spotted and presented in-depth insight of advisory in terms of immunomodulatory, antiviral, antibacterial, co-morbidity associated actions, and their probable mechanism of action. Immunomodulatory actions of advised herbs with no significant adverse drug reaction/toxicity strongly support the extension of advisory for COVID-19 prevention, prophylaxis, mitigations, and rehabilitation capacities. This advisory also emphasized Dhyana (meditation) and Yogasanas as a holistic approach in enhancing immunity, mental health, and quality of life. The present review may open-up new meadows for research and can provide better conceptual leads for future researches in immunomodulation, antiviral-development, psychoneuroimmunology, especially for COVID-19.Copyright © 2021, Institute of Korean Medicine, Kyung Hee University.

Patient Centricity: Design and Conduct of Clinical Trials in Orphan Diseases: Third of Three Sets of Expanded Proceedings from the 2020 ISCTM Autumn Conference on Pediatric Drug Development

This article expands on a session, titled "Patient Centricity: Design and Conduct of Clinical Trials in Orphan Diseases," that was presented as part of a two-day meeting on Pediatric Drug Development at the International Society for Central Nervous System (CNS) Clinical Trials and Methodology (ISCTM) Autumn Conference in Boston, Massachusetts, in October 2020. Speakers from various areas of pediatric drug development addressed a variety of implications of including children in drug development programs, including implications for rare/orphan diseases. The speakers have written summaries of their talks. The session's lead Chair was Dr. Joan Busner, who wrote introductory and closing comments. Dr. Simon Day, regulatory consultant, outlined some of the past mistakes that have plagued trials that did not consult with patient groups in the early design phase. Dr. Atul Mahableshwarkar provided an industry perspective of a recent trial that benefited from the inclusion of patient input. Drs. Lucas Kempf and Maria Sheean provided regulatory input from the perspectives of the United States (US) Food and Drug Administration (FDA) and European Medicines Agency (EMA), respectively. Dr. Judith Dunn outlined a novel approach for assessing and rank ordering patient and clinician clinical meaningfulness and the disconnect that may occur. Dr. Busner provided closing comments, tied together the presented issues, and provided a synopsis of the lively discussion that followed the session. In addition to the speakers above, the discussion included two representatives from patient advocacy groups, as well as an additional speaker who described the challenges of conducting a pediatric trial in the US and European Union (EU), given the often competing regulatory requirements. This article should serve as an expert-informed reference to those interested and involved in CNS drug development programs that are aimed at children and rare diseases and seek to ensure a patient-centric approach.Copyright © 2023, Matrix Medical Communications. All rights reserved.

Clinical characteristics of children with multisystemic inflammatory syndrome associated with COVID-19 Clinical characteristics of MIS-C associated with COVID-19

Aim: Coronavirus disease 2019 (COVID-19) has become a public health threat to people all over the world in 2020 and 2021. The Centers for Disease Control and Prevention (CDC) and WHO (World Health Organization) have named a novel disease multisystem inflammatory syndrome in children (MIS-C). Herein we aimed to present a group of pediatric patients with MIS-C, who were followed up in our clinic. Material(s) and Method(s): We retrospectively reviewed the medical records of patients who were followed up at our University Hospital with the diagnosis of MIS-C between January 2021 and May 2021. Result(s): The mean age of 9 patients was 87.4 +/-17.8 years (range 6-161 months);six of the patients were male. All patients had fever at admission. The duration of the fever was between 3 and 7 days. Four patients (44.4%) had terminal ileitis on ultrasonic examination. The laboratory tests of the patients revealed leukocytosis in 4 (44.4%) patients, anemia in 5 (55.5%) patients, thrombocytopenia in 1 (11.1%) patient, and a high CRP level in 8 (88.8%) patients. All patients had high sedimentation rates and procalcitonin levels. One (11.1%) patient was operated on for terminal ileitis. All patients were treated with steroids (1-2 mg/kg prednisolone) and IVIG (2gr/kg). Patients who needed ICU admission were also treated with vasoactive drug infusion (intravenous dopamine). Discussion(s): There is a need for increased awareness among pediatricians that MIS-C should come to mind, especially in patients with long-lasting fever and signs and symptoms that resemble Kawasaki disease.Copyright © 2022, Derman Medical Publishing. All rights reserved.

Adipose tissue, systematic inflammation, and neurodegenerative diseases

Obesity is associated with several diseases, including mental health. Adipose tissue is distributed around the internal organs, acting in the regulation of metabolism by storing and releasing fatty acids and adipokine in the tissues. Excessive nutritional intake results in hypertrophy and proliferation of adipocytes, leading to local hypoxia in adipose tissue and changes in these adipokine releases. This leads to the recruitment of immune cells to adipose tissue and the release of pro-inflammatory cytokines. The presence of high levels of free fatty acids and inflammatory molecules interfere with intracellular insulin signaling, which can generate a neuroinflammatory process. In this review, we provide an up-to-date discussion of how excessive obesity can lead to possible cognitive dysfunction. We also address the idea that obesity-associated systemic inflammation leads to neuroinflammation in the brain, particularly the hypothalamus and hippocampus, and that this is partially responsible for these negative cognitive outcomes. In addition, we discuss some clinical models and animal studies for obesity and clarify the mechanism of action of anti-obesity drugs in the central nervous system.Copyright © 2023 Wolters Kluwer Medknow Publications. All rights reserved.

Current Perspectives on Selective Dopamine D3 Receptor Antagonists/Partial Agonists as Pharmacotherapeutics for Opioid and Psychostimulant Use Disorders.

Over three decades of evidence indicate that dopamine (DA) D3 receptors (D3R) are involved in the control of drug-seeking behavior and may play an important role in the pathophysiology of substance use disorders (SUD). The expectation that a selective D3R antagonist/partial agonist would be efficacious for the treatment of SUD is based on the following key observations. First, D3R are distributed in strategic areas belonging to the mesolimbic DA system such as the ventral striatum, midbrain, and ventral pallidum, which have been associated with behaviors controlled by the presentation of drug-associated cues. Second, repeated exposure to drugs of abuse produces neuroadaptations in the D3R system. Third, the synthesis and characterization of highly potent and selective D3R antagonists/partial agonists have further strengthened the role of the D3R in SUD. Based on extensive preclinical and preliminary clinical evidence, the D3R shows promise as a target for the development of pharmacotherapies for SUD as reflected by their potential to (1) regulate the motivation to self-administer drugs and (2) disrupt the responsiveness to drug-associated stimuli that play a key role in reinstatement of drug-seeking behavior triggered by re-exposure to the drug itself, drug-associated environmental cues, or stress. The availability of PET ligands to assess clinically relevant receptor occupancy by selective D3R antagonists/partial agonists, the definition of reliable dosing, and the prospect of using human laboratory models may further guide the design of clinical proof of concept studies. Pivotal clinical trials for more rapid progression of this target toward regulatory approval are urgently required. Finally, the discovery that highly selective D3R antagonists, such as R-VK4-116 and R-VK4-40, do not adversely affect peripheral biometrics or cardiovascular effects alone or in the presence of oxycodone or cocaine suggests that this class of drugs has great potential in safely treating psychostimulant and/or opioid use disorders.

Idiopathic anomalous congenital band causing small intestinal obstruction in a 5-month-old dog

A 5-month-old, intact male, yellow Labrador retriever was presented with a 24-hour history of anorexia and vomiting. Abdominal imaging revealed the presence of a mechanical obstruction in the jejunum and peritoneal effusion. Cytologic evaluation and culture of the effusion prior to surgery identified a suppurative exudate with bacteria consistent with septic peritonitis and suspected to be related to the intestinal lesion. An exploratory laparotomy was performed, and a segment of jejunum was circumferentially severely constricted by an off-white, fibrous band of tissue. Resection and anastomosis of the strangulated segment of jejunum and excision of the constricting band provided resolution of the clinical signs. The dog made a complete recovery. Histologic evaluation revealed the band to be composed of fibrovascular and smooth muscle tissue, consistent with an idiopathic anomalous congenital band. No other gastrointestinal lesions were observed, either grossly at surgery or histologically in the resected segment of intestine. To our knowledge, a similar structure has not been reported in the veterinary literature.Copyright © 2022 Canadian Veterinary Medical Association. All rights reserved.

Study of the Antiviral Activity of Adamantane-Containing Chemical Compounds.

Influenza and coronavirus infections are especially dangerous due to being capable of causing pandemics and clinical complications in the nervous and cardiovascular systems, as well as exacerbation of chronic diseases (diabetes mellitus, heart failure, chronic obstructive bronchopneumonia, etc.), which can cause delayed death, especially in children under two years of age, the elderly, and individuals with poor health. The aim of the study was to search for compounds effective against these two topical viruses which possess constant epidemic activity - influenza virus and betacoronavirus - among new adamantane derivatives containing a NO-donor fragment or a dopamine residue. Another purpose of the study was determination of cytotoxicity and antiviral activity of compounds on cell lines permissive for influenza virus and betacoronavirus. The antiviral activity of 6 adamantane derivatives against strains of the influenza virus (H1N1) and betacoronavirus was studied. It was established that the NO-donor derivative of aminoadamantane succinate and the dopamine derivative of adamantanebenzoic acid had the greatest ability to suppress the development of the influenza virus with a chemotherapeutic index above 60. No promising compounds against betacoronavirus were identified.Copyright © Team of Authors, 2022.

Case report of congenital disorder of glycosylation type Ia combined with dilated cardiomyopathy.

Clinical data and follow-up of a case of congenital disorder of glycosylation type Ia (CDG-Ia) combined with dilated cardiomyopathy admitted to the Department of Cardiology, Children's Hospital of Nanjing Medical University were analyzed retrospectively.The 5-year-old female patient was admitted in December 2016 due to recu-rrent shortness of breath for 2 months.Clinical symptoms and signs included repeated attacks of shortness of breath, physical retardation, malnutrition, binocular esotropia, multiple episodes of hypoglycemia, hepatosplenomegaly, hypotonia and other multi-system damages.Cardiac echocardiography suggested the feature of dilated cardiomyopathy, including the significant enlargement of the left ventricle, and decreased systolic function.Genetic testing revealed a compound heterozygous mutation in the PMM2 gene, and as a result, the patient was diagnosed as CDG-Ia.The patient's condition improved after symptomatic treatments such as Cedilanid, Dopamine, Dobutamine, Furosemide, as well as support treatments like myocardium nutrition, blood sugar maintenance, liver protection, etc.After discharge, the patient was given oral Digoxin, Betaloc, Captopril and diuretics, and hypoglycemia-controlling agents.The patient was followed up every 3-6 months.After more than 2 years of follow-up, the heart function and heart enlargement gradually returned to normal.During the Corona Virus Disease 2019 outbreak, self-withdrawal continued for 2 months.Re-examinations showed decreased cardiac function and enlarged left ventricle again.Medications were resumed again, and the patient was followed up closely.This case report suggested that CDG-Ia may be associated with dilated cardiomyopathy, and the cardiac phenotype may be improved by symptomatic supportive treatment.Copyright © 2021 by the Chinese Medical Association.

Effectiveness of Probiotics

Background: To evaluate the potential of probiotics in stress management caused by the Covid-19 pandemic. Material(s) and Method(s): PubMed, Elsevier, New England journal of Medicine and Google Scholar were searched for the keywords "Probiotics and stress management during the Covid pandemic" up to 30th April 2022. Result(s): Probiotics have a great potential of managing mild stress. The pandemic has brought about physical as well psychological distress and has had a negative impact on the mental health of individuals. Stress increases the risk of cardiovascular diseases, hypertension and neuropsychiatric disorders. Probiotics can be used to alleviate mental stress. Probiotics maintain ecological balance of gut and provide immunity. They also affect mood and health of host by regulating gut-brain axis of host and may be used as Psychobiotics by altering various neurotransmitters like dopamine, serotonin, adrenocorticotrophic hormone, epinephrine, norepinephrine and GABA. The use of probiotics in mild stress will help reduce the risk of adverse effects and dependence associated with the psychotropic drugs. Conclusion(s): The ongoing studies on probiotics seems to be a good solution towards stress and related problems which is rapidly increasing due to COVID-19 pandemic. Probiotics seem to be beneficial in handling stress as they alter the release of neurotransmitters reducing stress level of an individual and have a positive effect on mood. The current pandemic is likely to continue and there is a need for greater preparedness of stress management, therefore, it is essential to explore the full potential of probiotics application in stress management.Copyright © 2022 Authors.

Advanced Nanomaterials-Based Electrochemical Biosensors for Catecholamines Detection: Challenges and Trends.

Catecholamines, including dopamine, epinephrine, and norepinephrine, are considered one of the most crucial subgroups of neurotransmitters in the central nervous system (CNS), in which they act at the brain's highest levels of mental function and play key roles in neurological disorders. Accordingly, the analysis of such catecholamines in biological samples has shown a great interest in clinical and pharmaceutical importance toward the early diagnosis of neurological diseases such as Epilepsy, Parkinson, and Alzheimer diseases. As promising routes for the real-time monitoring of catecholamine neurotransmitters, optical and electrochemical biosensors have been widely adopted and perceived as a dramatically accelerating development in the last decade. Therefore, this review aims to provide a comprehensive overview on the recent advances and main challenges in catecholamines biosensors. Particular emphasis is given to electrochemical biosensors, reviewing their sensing mechanism and the unique characteristics brought by the emergence of nanotechnology. Based on specific biosensors' performance metrics, multiple perspectives on the therapeutic use of nanomaterial for catecholamines analysis and future development trends are also summarized.

Dopamine Transmission Imbalance in Neuroinflammation: Perspectives on Long-Term COVID-19.

Dopamine (DA) is a key neurotransmitter in the basal ganglia, implicated in the control of movement and motivation. Alteration of DA levels is central in Parkinson's disease (PD), a common neurodegenerative disorder characterized by motor and non-motor manifestations and deposition of alpha-synuclein (α-syn) aggregates. Previous studies have hypothesized a link between PD and viral infections. Indeed, different cases of parkinsonism have been reported following COVID-19. However, whether SARS-CoV-2 may trigger a neurodegenerative process is still a matter of debate. Interestingly, evidence of brain inflammation has been described in postmortem samples of patients infected by SARS-CoV-2, which suggests immune-mediated mechanisms triggering the neurological sequelae. In this review, we discuss the role of proinflammatory molecules such as cytokines, chemokines, and oxygen reactive species in modulating DA homeostasis. Moreover, we review the existing literature on the possible mechanistic interplay between SARS-CoV-2-mediated neuroinflammation and nigrostriatal DAergic impairment, and the cross-talk with aberrant α-syn metabolism.

Dopamine Dysregulation and Altered Responses to Drugs Affecting Dopaminergic Transmission in a New Dopamine Transporter Knockout (DAT-KO) Rat Model.

Under normal conditions, dopamine (DA) clearance after release largely depends on uptake by the DA transporter (DAT). DAT expression/activity is reduced in some neuropsychiatric and neurological disorders. Our aim was to characterize the behavioral, neurochemical and electrophysiological effects of eliminating DAT in a novel knockout rat model we generated using CRISPR/Cas9. Consistent with existing DAT-KO models, our DAT-KO rats displayed increased locomotion, paradoxical calming by amphetamine, and reduced kinetics of DA clearance after stimulated release. Reduced DA kinetics were demonstrated using fast-scan cyclic voltammetry in brain slices containing the striatum or substantia nigra pars compacta (SNc) and in the dorsal striatum in vivo. Cocaine enhanced DA release in wild-type (WT) but not DAT-KO rats. Basal extracellular DA concentration measured with fast-scan controlled-adsorption voltammetry was higher in DAT-KO rats both in the striatum and SNc and was enhanced by L-DOPA (particularly after pharmacological block of monoamine oxidase), confirming that DA release after L-DOPA is not due to DAT reversal. The baseline firing frequency of SNc neurons was similar in both genotypes. However, D2 receptor-mediated inhibition of firing (by quinpirole or L-DOPA) was blunted in DAT-KO rats, while GABAB-mediated inhibition was preserved. We have also provided new data for the DAT-KO rat regarding the effects of slowing DA diffusion with dextran and blocking organic cation transporter 3 with corticosterone. Together, our results validate our DAT-KO rat and provide new insights into the mechanisms of chronic dysregulation of the DA system by addressing several unresolved issues in previous studies with other DAT-KO models.

Study of the Antiviral Activity of Adamantane-Containing Chemical Compounds

Influenza and coronavirus infections are especially dangerous due to being capable of causing pandemics and clinical complications in the nervous and cardiovascular systems, as well as exacerbation of chronic diseases (diabetes mellitus, heart failure, chronic obstructive bronchopneumonia, etc.), which can cause delayed death, especially in children under two years of age, the elderly, and individuals with poor health. The aim of the study was to search for compounds effective against these two topical viruses which possess constant epidemic activity - influenza virus and betacoronavirus - among new adamantane derivatives containing a NO-donor fragment or a dopamine residue. Another purpose of the study was determination of cytotoxicity and antiviral activity of compounds on cell lines permissive for influenza virus and betacoronavirus. The antiviral activity of 6 adamantane derivatives against strains of the influenza virus (H1N1) and betacoronavirus was studied. It was established that the NO-donor derivative of aminoadamantane succinate and the dopamine derivative of adamantanebenzoic acid had the greatest ability to suppress the development of the influenza virus with a chemotherapeutic index above 60. No promising compounds against betacoronavirus were identified.

Significance of Catecholamine Biosynthetic/Metabolic Pathway in SARS-CoV-2 Infection and COVID-19 Severity.

The SARS-CoV-2 infection was previously associated with the expression of the dopamine biosynthetic enzyme L-Dopa decarboxylase (DDC). Specifically, a negative correlation was detected between DDC mRNA and SARS-CoV-2 RNA levels in in vitro infected epithelial cells and the nasopharyngeal tissue of COVID-19 patients with mild/no symptoms. However, DDC, among other genes related to both DDC expression and SARS-CoV-2-infection (ACE2, dACE2, EPO), was upregulated in these patients, possibly attributed to an orchestrated host antiviral response. Herein, by comparing DDC expression in the nasopharyngeal swab samples of severe/critical to mild COVID-19 cases, we showed a 20 mean-fold reduction, highlighting the importance of the expression of this gene as a potential marker of COVID-19 severity. Moreover, we identified an association of SARS-CoV-2 infection with the expression of key catecholamine biosynthesis/metabolism-related genes, in whole blood samples from hospitalized patients and in cultured cells. Specifically, viral infection downregulated the biosynthetic part of the dopamine pathway (reduction in DDC expression up to 7.5 mean-fold), while enhanced the catabolizing part (increase in monoamine oxidases A and B expression up to 15 and 10 mean-fold, respectively) in vivo, irrespectively of the presence of comorbidities. In accordance, dopamine levels in the sera of severe cases were reduced (up to 3.8 mean-fold). Additionally, a moderate positive correlation between DDC and MAOA mRNA levels (r = 0.527, p < 00001) in the blood was identified upon SARS-CoV-2-infection. These observations were consistent to the gene expression data from SARS-CoV-2-infected Vero E6 and A549 epithelial cells. Furthermore, L-Dopa or dopamine treatment of infected cells attenuated the virus-derived cytopathic effect by 55% and 59%, respectively. The SARS-CoV-2 mediated suppression of dopamine biosynthesis in cell culture was, at least in part, attributed to hypoxia-like conditions triggered by viral infection. These findings suggest that L-Dopa/dopamine intake may have a preventive or therapeutic value for COVID-19 patients.

Virus removal from aqueous environments with polyelectrolyte coatings on a polypropylene fleece

The adsorption of viruses from aqueous solution is frequently performed to detect viruses. Charged filtration materials capture viruses via electrostatic interactions, but lack the specificity of biological virus‐binding substances like heparin. Herein, we present three methods to immobilize heparin‐mimicking, virus‐binding polymers to a filter material. Two mussel‐inspired approaches are used, based on dopamine or mussel‐inspired dendritic polyglycerol, and post‐functionalized with a block‐copolymer consisting of linear polyglycerol sulfate and amino groups as anchor (lPGS‐b‐NH2). As third method, a polymer coating based on lPGS with benzophenone anchor groups is tested (lPGS‐b‐BPh). All three methods yield dense and stable coatings. A positively charged dye serves as a tool to quantitatively analyze the sulfate content on coated fleece. Especially lPGS‐b‐BPh is shown to be a dense polymer brush coating with about 0.1 polymer chains per nm2. Proteins adsorb to the lPGS coated materials depending on their charge, as shown for lysozyme and human serum albumin. Finally, herpes simplex virus type 1 (HSV‐1) and severe acute respiratory syndrome coronavirus type 2 (SARS‐CoV‐2) can be removed from solution upon incubation with coated fleece materials by about 90% and 45%, respectively. In summary, the presented techniques may be a useful tool to collect viruses from aqueous environments.

The Aversive Lens: Stress effects on the prefrontal-cingulate cortical pathways that regulate emotion.

ARNSTEN, A.F.T., M.K.P. Joyce and A.C. Roberts. The Aversive Lens: Stress effects on the prefrontal-cingulate cortical pathways that regulate emotion. NEUROSCI BIOBEHAV REV XXX-XXX, 2022. The symptoms of major-depressive-disorder include psychic pain and anhedonia, i.e. seeing the world through an "aversive lens". The neurobiology underlying this shift in worldview is emerging. Here these data are reviewed, focusing on how activation of subgenual cingulate (BA25) induces an "aversive lens", and how higher prefrontal cortical (PFC) areas (BA46/10/32) provide top-down regulation of BA25 but are weakened by excessive dopamine and norepinephrine release during stress exposure, and dendritic spine loss with chronic stress exposure. These changes may generate an attractor state, which maintains the brain under the control of BA25, requiring medication or neuromodulatory treatments to return connectivity to a more flexible state. In line with this hypothesis, effective anti-depressant treatments reduce the activity of BA25 and restore top-down regulation by higher circuits, e.g. as seen with SSRI medications, ketamine, deep brain stimulation of BA25, or rTMS to strengthen dorsolateral PFC. This research has special relevance in an era of chronic stress caused by the COVID19 pandemic, political unrest and threat of climate change.