Health Benefits, Therapeutic Applications, and Recent Advances of Cirsilineol in the Medicine: Potential Bioactive Natural Flavonoids of Genus Artemisia.

BACKGROUND: Herbal medicine and its derived products have been used in the medicine and nutraceutical sectors for the treatment of human disorders and associated secondary complications. Plant-derived products play an important role in our daily life due to their medicinal properties and pharmacological activities. The attention of scientists to natural products has increased due to their significant biological activities. Flavonoids represent one of the most important phytocompounds present in the higher plants, common fruits, vegetables, herbs, wine, juices, and dried fruits. Flavonoids exert potent antioxidant activity by blocking and scavenging free radicals. Cirsilineol, also called 4',5-dihydroxy-3',6,7-trimethoxyflavone, is an active phytochemical of Artemisia vestita, Artemisia monosperma, Artemisia asiatica, and Agrostis gigantea. METHODS: Medicinal importance and pharmacological activities of cirsilineol have been investigated in the present work with their analytical aspects in order to know the biological importance of cirsilineol in medicine. Literature data on cirsilineol were collected and analyzed in the present work to study its therapeutic potential against various human disorders and associated secondary complications. Scientific data were collected from Google, Google Scholar, PubMed, Science Direct, and Scopus and analyzed in the present work using the term herbal medicine, flavonoid and cirsilineol. RESULTS: Medicinal plants containing a significant amount of cirsilineol have biological applications in medicine due to their pharmacological activities. This present work signifies the biological importance of cirsilineol in medicine as it has anti-proliferative, gastroprotective, anti-Helicobacter pylori, anti-diabetic and anti-oxidant activities. Further therapeutic effectiveness of cirsilineol against different types of cancers, including breast carcinoma and lung carcinoma, has been discussed in the present work. The biological importance of cirsilineol against allergic rhinitis, inflammation, coronavirus, immune system, renal cellular membrane and protein glycation has also been discussed in the present work. However, the importance of analytical methods for the isolation and identification of cirsilineol in medicine has also been analyzed. CONCLUSION: This work aimed to summarize the health-beneficial aspects of cirsilineol in medicine which will be beneficial to explore the further therapeutic effectiveness of cirsilineol for the treatment of various forms of human disorders.

Memory SARS-CoV-2 T-cell response in convalescent COVID-19 patients with undetectable specific IgG antibodies: a comparative study.

Background: During the COVID-19 pandemic, a variable percentage of patients with SARS-CoV-2 infection failed to elicit humoral response. This study investigates whether patients with undetectable SARS-CoV-2 IgG are able to generate SARS-CoV-2 memory T cells with proliferative capacity upon stimulation. Methods: This cross-sectional study was conducted with convalescent COVID-19 patients, diagnosed with a positive real-time PCR (RT-PCR) from nasal and pharyngeal swab specimens. COVID-19 patients were enrolled ≥3 months after the last PCR positive. Proliferative T-cell response after whole blood stimulation was assessed using the FASCIA assay. Results: A total of 119 participants (86 PCR-confirmed COVID-19 patients and 33 healthy controls) were randomly filtered from an initial cohort. Of these 86 patients, 59 had detectable (seropositive) and 27 had undetectable (seronegative) SARS-CoV-2 IgG. Seropositive patients were subclassified as asymptomatic/mild or severe according to the oxygen supplementation requirement. SARS-CoV-2 CD3+ and CD4+ T cells showed significantly lower proliferative response in seronegative than in seropositive patients. The ROC curve analysis indicated that ≥ 5 CD4+ blasts/µL of blood defined a "positive SARS-CoV-2 T cell response". According to this cut-off, 93.2% of seropositive patients had a positive T-cell response compared to 50% of seronegative patients and 20% of negative controls (chi-square; p < 0.001). Conclusions: This proliferative assay is useful not only to discriminate convalescent patients from negative controls, but also to distinguish seropositive patients from those with undetectable SARS-CoV-2 IgG antibodies. Memory T cells in seronegative patients are able to respond to SARSCoV-2 peptides, although at a lower magnitude than seropositive patients.

Relapsing and Remitting Proliferative Glomerulonephritis With Monoclonal Immunoglobulin Deposits in Association With Infection and Vaccination: A Case Report.

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is the second most common monoclonal gammopathy of renal significance. Rates of progression to kidney failure as well as rates of recurrence after kidney transplantation are high, especially in the absence of treatment. Treatment is usually targeted toward the abnormal clone, but even in the absence of an identifiable clone, empiric treatment is still recommended to avoid worsening prognosis. In this report, we present an unusual course of a PGNMID case with a relapsing and remitting pattern of illness, likely triggered by infection and vaccination. The patient in this case showed subsequent improvement after each episode, with stable kidney function over the years. This case report highlights the importance of investigating possible recent infectious exposures or vaccinations as potential triggers for this disease. This association should be considered for future patients with PGNMID, especially when there is no identifiable clone to help guide therapy.

Effect of the COVID-19 Pandemic on Surgical Outcomes for Rhegmatogenous Retinal Detachments.

We reviewed the medical records of 438 eyes in 431 patients who had undergone surgeries for rhegmatogenous retinal detachments (RRD) or proliferative vitreoretinopathy (PVR ≥ Grade C) to determine whether the COVID-19 pandemic had affected outcomes. The patients were divided into 203 eyes in Group A that had undergone surgery from April to September 2020, during the pandemic, and 235 eyes in Group B that had undergone surgery from April to September 2019, before the pandemic. The pre- and postoperative visual acuity, macular detachment, type of retinal breaks, size of the RRD, and surgical outcomes were compared. The number of eyes in Group A was fewer by 14%. The incidence of men (p = 0.005) and PVR (p = 0.004) was significantly higher in Group A. Additionally, the patients in Group A were significantly younger than in Group B (p = 0.04). The differences in the preoperative and final visual acuity, incidence of macular detachment, posterior vitreous detachment, types of retinal breaks, and size of the RRD between the two groups were not significant. The initial reattachment rate was significantly lower at 92.6% in Group A than 98.3% in Group B (p = 0.004). The COVID-19 pandemic affected the surgical outcomes for RRD with higher incidences of men and PVR, younger aged patients and lower initial reattachment rates even though the final surgical outcomes were comparable.

Histophilus somni disease conditions with simultaneous infections by ovine gammaherpesvirus 2 in cattle herds from Southern Brazil.

This report investigated the cause of cattle mortality in two farms in Southern Brazil. The tissues of one animal from each farm (animals #1 and #2) respectively were used in pathological and molecular investigations to determine the possible cause of death. The principal pathological findings observed in animal #1 were pulmonary, myocardial, and encephalitic hemorrhages with vasculitis, and lymphoplasmacytic interstitial pneumonia with proliferative vascular lesions (PVL). The main pathological findings observed in animal #2 were purulent bronchopneumonia, hemorrhagic myocarditis, and lymphoplasmacytic interstitial pneumonia with PVL. An immunohistochemical assay detected intralesional antigens of a malignant catarrhal fever virus (MCFV) from multiple tissues of animal #2 while PCR confirmed that the MCFV amplified was ovine gammaherpesvirus 2 (OvGHV2), genus Macavirus, subfamily Gammaherpesvirinae; OvGHV2 was also amplified from multiple tissues of animal #1. Furthermore, PCR assays amplified Histophilus somni DNA from multiple fragments of both animals. However, the nucleic acids of Mannheimia haemolytica, Pasteurella multocida, Mycoplasma bovis, bovine respiratory syncytial virus, bovine alphaherpesvirus virus 1 and 5, bovine coronavirus, and bovine parainfluenza virus 3 were not amplified from any of the tissues analyzed, suggesting that these pathogens did not participate in the development of the lesions herein described. These findings demonstrated that both animals were concomitantly infected by H. somni and OvGHV2 and developed the septicemic and encephalitic manifestations of H. somni. Furthermore, the interstitial pneumonia observed in cow #2 was more likely associated with infection by OvGHV2.

Growth Arrest of Alveolar Cells in Response to Cytokines from Spike S1-Activated Macrophages: Role of IFN-γ.

Acute respiratory distress syndrome (ARDS) is characterized by severe hypoxemia and high-permeability pulmonary edema. A hallmark of the disease is the presence of lung inflammation with features of diffuse alveolar damage. The molecular pathogenetic mechanisms of COVID-19-associated ARDS (CARDS), secondary to SARS-CoV-2 infection, are still not fully understood. Here, we investigate the effects of a cytokine-enriched conditioned medium from Spike S1-activated macrophage on alveolar epithelial A549 cells in terms of cell proliferation, induction of autophagy, and expression of genes related to protein degradation. The protective effect of baricitinib, employed as an inhibitor of JAK-STAT, has been also tested. The results obtained indicate that A549 exhibits profound changes in cell morphology associated to a proliferative arrest in the G0/G1 phase. Other alterations occur, such as a blockade of protein synthesis and the activation of autophagy, along with an increase of the intracellular amino acids content, which is likely ascribable to the activation of protein degradation. These changes correlate to the induction of IFN-regulatory factor 1 (IRF-1) due to an increased secretion of IFN-γ in the conditioned medium from S1-activated macrophages. The addition of baricitinib prevents the observed effects. In conclusion, our findings suggest that the IFN-γ-IRF-1 signaling pathway may play a role in the alveolar epithelial damage observed in COVID-19-related ARDS.

COVID-19 impact on delayed clinical visits in diabetic retinopathy patients

Purpose : The COVID-19 pandemic created an unprecedented setback for diabetic retinopathy (DR) patients receiving routine anti-vascular endothelial growth factor (VEGF) injections. In this retrospective clinical study, we assessed visual and anatomical outcomes of “late follow-up” appointments cancelled or rescheduled during an 11-week quarantine period from March 15th- June 1st, 2020, due to the urgency to limit non-emergent clinical visits. This study tested the hypothesis that strict frequency of treatment is a requisite for successful therapy. Methods : To meet “late follow-up” requirements, all study patients had appointments scheduled within the quarantine period that were delayed past their previous physician recommended interval, beyond June 1st, 2020. Of the 7042 delayed patients, 5137 returned for examination. 2764 were injection patients, of which 616 were delayed beyond the quarantine period. These 616 patients were subsequently categorized by diagnosis. We then analyzed the electronic medical record (EMR) for 300 eyes with treatment-requiring diabetic retinopathy to establish baseline anatomical and visual status prior to the delayed clinical visit. The EMR of the follow-up appointment was subsequently viewed for comparison. Best-corrected visual acuity (BCVA) and retinal examination findings were recorded from both visits. All eyes received at least 1 anti-VEGF injection prior to March 15th, 2020. Results : 300 eyes were delayed beyond their previously scheduled interval an average of 14.04 weeks. Upon return, 37 eyes (12.3%) had improved BCVA, 169 (56.3%) remained stable, and 94 (31.4%) had worsened. Of the 300 eyes, there was an average of 2.2 lines lost (p=0.03). 29 delayed eyes (9.7%) returned with improved macular edema, 121 (40.3%) remained stable, and 143 (47.7%) had worsened upon examination. Due to vitreous hemorrhage, edema progression in 7 eyes (2.3%) was unknown. 290 eyes (96.7%) remained with non-proliferative DR, while 10 (3.3%) progressed to proliferative DR. 23 (7.6%) returned with new or worsened vitreous hemorrhages. No patients developed a retinal tear or detachment during this period. Conclusions : COVID-19 had a severe impact on routine clinical visits. Prolonged frequency of anti-VEGF treatment for DR is associated with increased risk for BCVA decline and negative anatomical outcomes. Effective therapy requires strict compliance with intravitreal injections and routine clinical appointments.

Expansion of a teleophthalmology program for diabetic retinopathy screening during the COVID19 pandemic

Purpose : The COVID-19 pandemic prompted efforts to encourage social distancing and minimize non-urgent in-person eye care. Here, we report the outcomes of a teleophthalmology program for diabetic retinopathy screening at an integrated health system in California that was expanded during the pandemic. Methods : We performed a retrospective review of patients who underwent remote retinal imaging as part of a teleophthalmology program for diabetic retinopathy (DR) screening using Current Procedural Terminology (CPT) codes 92227 and 92228 at the University of California, Davis Health system between May 31st , 2019 and June 8th , 2021. Retinal images were captured at primary care locations using a Topcon NW400, Nikon RetinaStation, or Optos Primary fundus cameras, and image grading were performed by trained ophthalmologists or optometrists using a store-and-forward method. Patient records were reviewed to collect demographic, follow-up, and clinical outcomes information. Results : During COVID19 pandemic, the teleophthalmology program screened 570 individuals (mean age 63.2 ± 13.7). There was a significant increase in the number of patients screened per month prior to and following the COVID-19 lock-down in March 2020 (5.0 ± 3.1 patients screened per month prior to and 39.1 ± 34.8 patients per month following, P = 0.0004). Among these, 204 patients received a recommendation for in-person eye care referral, of which 127 received a referral to the UC Davis Eye Center, 85 appointments were scheduled, and 82 patients were followed in person, with a median time of 108 days between screening and in-person follow-up. Follow-up rates were generally lower during the initial months after the pandemic and increased over time. Among the patients who followed in person (mean age 63.9 ± 13.8), 10% of eyes had mild non-proliferative DR (NPDR), 5% had moderate NPDR, 3% had severe NPDR, 2% had PDR, and 4% had diabetic macular edema (DME), with similar proportions before and after the COVID-19 lockdown. Conclusions : Expansion of a teleophthalmology program during the COVID19 pandemic demonstrated improved DR screening rates, increased referrals, and improved follow-up for diabetic eye care at an integrated health system in Northern California.

Agreeability of Tele-ophthalmology and Artificial Intelligence-Based Diagnosis of Diabetic Retinopathy

Purpose : The COVID-19 pandemic exposed the need for increased mobilization of teleophthalmology resources. Artificial intelligence (AI) may serve as a tool to assist physicians in triaging highest need patients if the AI's assessment of disease is comparable to the physician's assessment. This study assesses the ability of AI software to diagnose diabetic retinopathy (DR) as compared to Tele-ophthalmology and in-person examination by a retina specialist. Methods : Records of forty patients (average age 55.1±10.9 years) presenting to an urban retina clinic were reviewed retrospectively for factors including demographics, retinal photos taken by Canon CR-2 Plus AF Retinal Imaging camera (Tokyo, Japan), and diagnosis of DR based on the International Clinical Diabetic Retinopathy (ICDR) classification scale during an in-person clinic visit in which a fundus exam was performed. Retinal photos were graded by AI software, EyeArt (EyeNuk, CA), as Normal, Mild DR, or More than Mild DR. Retinal images were also graded remotely by a retina specialist using the ICDR classification scale via TeamViewer software (Tele). Agreement between Tele, AI, and inperson DR diagnosis was assessed using Cohen's Kappa (κ) coefficient using IBM® SPSS® Statistics software. Results : Among 80 eyes, 33 were diagnosed in-person with no DR, 5 with mild nonproliferative DR (NPDR), 9 with moderate NPDR, 3 with severe NPDR, 7 with proliferative diabetic retinopathy (PDR), and 23 with regressed PDR. Eleven and 26 eyes could not be graded by Tele or AI, respectively. κ±SE for in-Person diagnosis vs Tele was 0.859±0.058 (p<.001), in-person vs AI was 0.751±0.082 (p<.001), and Tele vs AI was 0.883±0.063 (p<.001). Conclusions : AI is a reliable tool for screening patients for DR and referring them for physician evaluation since AI had a substantial rate of agreement with the in-person diagnosis and near perfect agreement with Tele. Tele grading was in near perfect agreement with the in-person diagnosis, showing that Tele is a reliable option for a physician to remotely screen patients that may be ungradable by AI. However, improvements are needed due to the high number of images that are ungradable via Tele and AI. Further studies should assess ways to reduce the number of ungradable images via Tele and AI and create a trend analysis for multiple visits for a given patient.

COVID VACCINE ASSOCIATED GLOMERULAR DISEASES- A CASE SERIES

Introduction: Vaccination is a known trigger for the development of de-novo or flare of glomerular diseases. Here we present a case series of fourteen patients with COVID vaccine- associated glomerular diseases (CVAGD). Methods: Patients with new onset proteinuria, hematuria or renal failure after SARS- CoV2 vaccine were included in the study. Demographic and clinical details were collected and laboratory investigations including serum creatinine, albumin, urine microscopy and urine spot protein creatinine ratio were done. Renal biopsy specimens were subjected to light microscopy and immunofluorescence examination. Results: We cared for 14 patients with CVAGD. Of them, eight patients were males. The mean age was 25.7 years. Three patients had relapse of their previous disease while eleven patients had no previously detected renal diseases. Eleven patients had received COVISHIELD and three had received COVAXIN. All patients presented after the first vaccine dose. At presentation, seven patients had nephrotic syndrome, two patients had rapidly progressive renal failure and five patients had nephritic syndrome. The mean duration of symptom onset after vaccination was 18 days. Renal biopsy revealed IgA nephropathy in 3 patients, endocapillary proliferative glomerulonephritis in 2 patients, minimal change disease in 5 patients, pauci- immune glomerulonephritis (ANCA associated vasculitis) in one patient, lupus nephritis ISN/RPS class 3 in one and focal segmental glomerulosclerosis in two patients. There was no history of COVID infection in any of our patients. Three patients had renal failure at presentation but none required renal replacement therapy. The patients with MCD and FSGS were treated with steroids, patients with ANCA vasculitis and lupus nephritis were managed with the appropriate Cyclophosphamide and steroid regimens while the others were managed conservatively with anti-proteinuric medications. On follow up, five patients (One IgAN, three MCD, one endocapillary proliferative GN) achieved complete remission of proteinuria and resolution of renal failure, while the remaining eight patients achieved partial remission. One patient with MCD had a relapse of proteinuria 3 weeks after achieving partial remission, he responded well to steroid therapy. All 14 patients remain on close follow up. Conclusions: Although causality cannot be definitively established, there is a definite temporal association between the presentation of glomerular diseases and COVID vaccination, in the absence of other inciting factors. Hence, new-onset or relapse of glomerular diseases presenting post vaccination, although rare, should be observed as a possible adverse event. Intriguing questions such as how to proceed with the vaccination schedule in patients with CVAGD and would changing the vaccine type reduce the risk of relapse remain unanswered. No conflict of interest

Effect of the COVID-19 Pandemic Lockdown on the Management of Diabetic Retinopathy: A Cross-Sectional Study.

Introduction Worldwide, diabetic retinopathy (DR) is one of the leading causes of vision loss. Early treatment and screening for DR have a major role in reducing the rate of the disease and the coronavirus disease 2019 (COVID-19) pandemic-related restrictions have altered real-world practice patterns in managing DR. Aims and objectives To evaluate the impact of the COVID-19 pandemic on the management of DR amongst patients presenting to a tertiary eye care center in Gujarat, India. Methods This is a cross-sectional study comparison of ophthalmic findings of 72 patients who presented to a tertiary care hospital with the manifestation of DR before and after the COVID-19 outbreak and subsequent lockdown. All the patients underwent detailed ophthalmic examinations, including optical coherence tomography (OCT) and fundus fluorescein angiography (FFA). Results The mean age of participants was 54.5 years, with the mean duration of diabetes being five years since first detected. Diabetes was present in 26 patients out of 72. The number of follow-up visits to an ophthalmologist before COVID-19 was at least every one to three months, which significantly decreased after the lockdown of COVID-19. We found a significant progression of DR and clinically significant macular edema (CSME) in patients with diabetes. Before COVID-19, there were two mild non-proliferative diabetic retinopathy (NPDR), seven moderate NPDR, 15 severe NPDR, and 15 very severe NPDR, which were increased post lockdown to three, nine, 27, and 21, respectively. The proliferative diabetic retinopathy (PDR) vitreous hemorrhage (VH) and tractional retinal detachment (TRD) were also increased to 12 after lockdown as compared to only six before the COVID-19 lockdown. The causes for progression are inability to attend regular check-ups, inability to take proper treatment of diabetes and DR, poor control of diabetes, episode of COVID-19, history of high dose of steroid use, poor kidney function, and not knowing that there is a progression of the disease. A common reason for not visiting an ophthalmologist was fear of the unknown due to COVID-19. Conclusions COVID-19 has severely impacted the routine follow-up of DR and, in the subsequent years, there might be an increased incidence of severe outcomes due to DR. The second wave of COVID-19 and its lockdown have had very significant effects on the visual outcome of untreated DR patients.

Synthesis and Biological Evaluation of Imadazo[1,2-a]pyrazines as Anticancer and Antiviral Agents through Inhibition of CDK9 and Human Coronavirus.

In this work, novel imadazo[1,2-a]pyrazine derivatives were synthesized and evaluated as CDK9 inhibitors. The results of CDK9 assay showed that the derivatives with pyridin-4-yl in position 2 and benzyl in position 3 of imadazo[1,2-a]pyrazine 3c displayed the most potent CDK9 inhibitory activity with IC50 of 0.16 µM. The anti-proliferative effect of the new compounds was examined against breast cancer (MCF7), colorectal cancer (HCT116), and chronic myelogenous leukaemia (K652) cell lines. The data of MTT assay showed that the cytotoxic effect of the inhibitors is correlated to their inhibitory activity against CDK9. Compound 3c exhibited the most potent cytotoxicity effect with average IC50s of three cell lines of 6.66 µM. The drug likeness properties of 3c were predicated in silico and demonstrated that 3c have reasonable physiochemical and pharmacokinetic properties. Selected derivatives were assessed in antiviral assay against human coronavirus 229E. The results of this assay showed that the derivative with pyridin-4-yl in position 2 and cyclohexyl in position 3 of imadazo[1,2-a]pyrazine 3b exhibited the most potent anti-coronaviral activity with IC50 of 56.96 µM and selectivity index of 7.14. The target predication result revealed that 3b showed high affinity to protease enzyme. Docking studies of 3b with COVID-19 main protease was conducted and showed good binding affinity, which confirmed the in vitro assay data.

Potential Multifunctional Bioactive Compounds from Dysosma versipellis Explored by Bioaffinity Ultrafiltration-HPLC/MS with Topo I, Topo II, COX-2 and ACE2.

Background: Dysosma versipellis (D. versipellis) has been traditionally used as a folk medicine for ages. However, the specific phytochemicals responsible for their correlated anti-inflammatory, anti-proliferative and antiviral activities remain unknown. Purpose: This study aimed to explore the specific active components in D. versipellis responsible for its potential anti-inflammatory, anti-proliferative, and antiviral effects, and further elucidate the corresponding mechanisms of action. Methods: Bioaffinity ultrafiltration coupled to liquid chromatography-mass spectrometry (UF-LC/MS) was firstly hired to fast screen for the anti-inflammatory, anti-proliferative and antiviral compounds from rhizomes of D. versipellis, and then further validation was conducted using in vitro inhibition assays and molecular docking. Results: A total of 12, 12, 9 and 12 phytochemicals with considerable affinities to Topo I, Topo II, COX-2 and ACE2 were fished out, respectively. The anti-proliferative assay in vitro indicated that podophyllotoxin and quercetin exhibited comparably strong inhibitory rates on A549 and HT-29 cells compared with 5-FU and etoposide. Meanwhile, kaempferol displayed prominent dose-dependent inhibition against COX-2 with IC50 value at 0.36 ± 0.02 µM lower than indomethacin at 0.73 ± 0.07 µM. Furthermore, quercetin exerted stronger inhibitory effect against ACE2 with IC50 value at 104.79 ± 8.26 µM comparable to quercetin 3-O-glucoside at 135.25 ± 6.54 µM. Conclusion: We firstly showcased an experimental investigation on the correlations between bioactive phytochemicals of D. versipellis and their multiple drug targets reflecting its potential pharmacological activities, and further constructed a multi-target and multi-component network to decipher its empirical traditional applications. It could not only offer a reliable and valuable experimental basis to better comprehend the curative effects of D. versipellis but also provide more new insights and strategies for other traditional medicinal plants.

THE CLINICAL CASE: COVID-19 IN A CHILD WITH CHRONIC KIDNEY DISEASE

Since the spread of the novel coronavirus infection, most researchers have noted a low proportion of sick children in general pediatric cohort compared to adults, who had a mild disease course and rare complications. The most frequent clinical manifestations of the disease are respiratory and, some less frequently diarrheal syndromes. The disease has predominantly mild or asymptomatic course. The risk of adverse outcomes in children, similar to adults, clearly correlate with the presence of background chronic pathology. The need for respiratory support prevails in children with a severe premorbid burden. Here, a clinical case of ongoing novel coronavirus infection in adolescent patient comorbid with chronic kidney pathology is described. In adolescence, the patient was diagnosed with mesangioproliferative glomerulonephritis (IgA-nephropathy), and further registered at the dispensary receiving a combination therapy with angiotensin converting enzyme inhibitors and disaggregation drugs. The epidemiological history contained no established contacts with infectious patients. The clinical manifestations of COVID-19 in the patient are represented by catarrhal and diarrheal syndromes, transient renal dysfunction in the acute period of the disease. The onset of coronavirus infection was clinically characterized by symptoms of damaged gastrointestinal tract and was considered as acute gastroenteritis of infectious etiology. Empirically prescribed antibacterial therapy in combination with antiplatelet agents and symptomatic drugs had no effect. The diagnosis of the novel coronavirus infection was verified only on day 4 of hospitalization, clinical and laboratory signs of lung damage emerged. The inflammatory process developed in the patient lungs was secondary to the main pathology. The severity of the patient’s condition was determined by the presence of respiratory and renal insufficiency. Lung damage with minimal severity complaints and clinical data had a bimodal pattern and required respiratory support. A comprehensive approach to treatment, including respiratory, antiviral, enterosorption, anticoagulation, anti-inflammatory, antihypertensive, hepatoprotective, symptomatic therapy with change in antibacterial drugs allowed to achieve positive dynamics. On day 12 of the illness, the patient required no respiratory support. The presence of symptoms of gastrointestinal tract damage in COVID-19 necessitates the mandatory inclusion of PCR assay for SARS-CoV-2 into diagnostic protocol in patients with diarrheal syndrome to perform etiological disease interpretation.

Biological Importance of a Biflavonoid 'Bilobetin' in the Medicine: Medicinal Importance, Pharmacological Activities and Analytical Aspects.

BACKGROUND: Flavonoid class phytochemicals are natural compounds present in different medicinal plants, vegetables and fruits. Ginkgo biloba contains significant amounts of bioflavonoid 'bilobetin'. Bilobetin is an active phytochemical used for the treatment of human health complications due to its medicinal properties and therapeutic benefit. The purpose of this work is to collect and reviewed scientific data on bilobetin from different literature sources; highlight their biological properties, pharmacological activities and analytical aspects. METHODS: Health beneficial aspects of bilobetin have been investigated in the present work through scientific data analysis. PubMed, Google Scholar, Google, Scopus, etc. have been searched in the present work in order to collect scientific information on bilobetin. Medicinal importance and therapeutic benefit of bilobetin has been searched in the present work through these databases of bilobetin. Detailed pharmacological activities of bilobetin have been reviewed in the present work through literature data analysis of various scientific research works. However, analytical data of bilobetin were also collected and reviewed in the present reaserch. RESULTS: Literature data analysis of bilobetin in the present work revealed the medicinal properties and therapeutic potential of bilobetin mainly due to its anti-fungal, anti-inflammatory, anti-oxidant, antihyperlipidemic, and anti-proliferative activities. Literature data analysis revealed the effectiveness of bilobetin on osteoporosis, glucose metabolism, adipocytes, SARS CoV-2, Influenza A virus and human thrombin. Scientific data also revealed the importance of different analytical techniques for the isolation, separation, identification, and quantification of bilobetin. CONCLUSION: Scientific data analysis revealed biological importance and pharmacological activities of bilobetin in the health sector.

Targeting Metabolic Reprograming for the Prevention and Treatment of Proliferative Vitreoretinopathy

This is our first year on the project and we report that we have identified key metabolic reprogramming traits associated with proliferative vitreoretinopathy using our in-vitro model of epithelial-mesenchymal transition (EMT) of human retinal pigment epithelial cells (RPE). We have obtained IACUC and ACURO approval for our in-vivo rabbit model and completed training on rabbit handling and rabbit ocular surgery. We have also obtained IRB and HRPO approval for metabolomics analysis of human vitreous and sample collection is currently underway with samples scheduled for collection in the coming weeks. We have completed metabolomics analysis for our TGF-treated ARPE-19, revealing novel insights into metabolic pathway rewiring during EMT of RPE. We have begun testing the efficacy of metabolic drugs in blocking the TGF activity in ARPE-19. While we had a productive start toour grant in 2019, our progress has been hindered in 2020 due to a period of lab shut-down and restrictions on collection of human samples due to the COVID-19 pandemic.

Impact of Coronavirus Disease 2019 Restrictions on Retinal Detachment: A Multicenter Experience.

In this retrospective, multicenter study of 261 eyes (259 patients), patients who underwent rhegmatogenous retinal detachment repair during the coronavirus disease 2019 (COVID-19) post-lockdown period experienced an additional 22-day delay, leading to significantly more epiretinal membrane and proliferative vitreoretinopathy and lower single-surgery anatomic success rates. During lockdown, perfluoropropane gas was used more commonly, and pneumatic retinopexy was used more commonly in COVID-19-positive patients.

Management of acute proliferative diabetic retinopathy related complications during the first COVID-19 wave.

BACKGROUND: Routine hospital eye services (HES) across the National health service (NHS), and diabetic eye screening (DES) in Scotland were paused during the COVID-19 lockdown in March 2020. Alternate pathways for managing acute ophthalmic pathology were devised in NHS Grampian covering the North-East of Scotland. Emergency eye treatment centres (EETC) manned by community optometrists were set up to treat and triage referrals to HES. METHODS: Retrospective study analysing consecutive patients referred to a tertiary eye centre (Aberdeen Royal Infirmary) with proliferative diabetic retinopathy (PDR) related complications between March and August 2020. General demographical data, diabetic history, visual acuity, ocular complication, type of management, time to follow-up, and any appointment cancellations were extracted for analysis. RESULTS: Fifty two eyes of 46 patients with PDR related complications were identified. HES appointment had been delayed or cancelled in 22 patients (48%) due to COVID-19. Mean age was 54.5 years (±15.1), 21 (46%) were female, 21 (46%) had type 1 diabetes; mean HbA1c was 78 mmol/l (±18.7). Vision ranged from 6/6 to perception of light. 36 (78%) patients had unilateral vitreous haemorrhage (VH), 6 (13%) bilateral, 2 (4%) tractional retinal detachments and 3 (6.5%) had neovascular glaucoma. Of 48 acute PDR presentations, 18 (38%) were given anti-VEGF within 72 h and two (4%) had PRP the same day. 16 (33%) were rebooked into the laser clinic, 13 (27%) referred for urgent surgical review, and 17 (35%) advised observation and review in clinic. After a median follow-up of 6 months, 12 eyes (23%) of 11 patients progressed to have vitrectomy. CONCLUSION: Despite lockdown, hospital appointment cancellations and recommended footfall reduction limiting capacity due to COVID-19, patients reaching out with PDR complications were promptly referred to HES and appropriate treatments carried out with COVID-19 precautions as recommended.

POS-115 MINIMAL CHANGE DISEASE IN A HEALTHY WOMAN WITH TOXICODENDRON TOXICITY

Introduction: Minimal change disease (MCD) is a major cause of idiopathic nephrotic syndrome (NS) which is composed of heavy proteinuria, hypoalbuminemia, and edema. It represents 15% of idiopathic NS in adults and the proportion of cases decreases with age as other entities such as membranous nephropathy become more common. Kidney damage associated with Toxicodendron species toxicity is quite rare but there are three lesions already described: proliferative glomerulonephritis, arteritis and membranous nephropathy. Here we report a case of MCD associated to Toxicodendron toxicity. Methods: A 47 year old mexican woman with no history of chronic diseases was referred to the nephrology office. She has a positive familiar history for diabetes and hypertension and she was recently vaccinated for COVID-19. She was referred for proteinuria incidentally found during routine tests three months ago which has been persistent on urinary testing afterwards, she recalls a Toxicodendron spp (poison ivy) exposure which led to an self-limited dermatitis 5 days before the first urinary test was taken. Initial workup showed 3.54 gr/24h proteinuria, hypoalbuminemia (3.2 gr/L) and hypercholesterolemia (256 mg/dl) and a nephrotic syndrome diagnosis was made. Further testing included negative HIV, HCV and HBV serology, normal C3 and C4 levels and negative anti-PLA2R, P-ANCA, C-ANCA, antinuclear antibodies. Normal kidneys were visualized on ultrasound. A kidney biopsy was performed and reported a minimal change disease. Steroid glucocorticoids was administered with methylprednisolone for three days and she was discharged with oral glucocorticoid for maintenance. On ambulatory follow up the patient had a dramatic improvement of the proteinuria. Results: A 47 year old woman developed proteinuria a few days after ivy poison exposure with a subsequent nephrotic syndrome. Renal biopsy shows a minimal change disease and good glucocorticoid response was met. Conclusions: Our hypothesis is that ivy poison exposure is directly involved in MCD onset in this patient. No conflict of interest

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits triggered by COVID-19: a case report.

Acute kidney injury (AKI) frequently complicates corona virus disease 2019 (COVID-19) and is associated with significant mortality. Kidney disease in COVID-19 is usually due to acute tubular injury, but a variety of glomerular processes, especially collapsing glomerulopathy, have been increasingly described. Until recently, proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) had not been reported in the setting of COVID-19. We present a case of dialysis-dependent AKI developing soon after symptomatic COVID-19 which, on kidney biopsy, was found to be due to PGNMID with IgG3 kappa deposits. As is typical of PGNMID, a search for evidence of extra-renal monoclonal immunoglobulin or clonal lymphocyte population was negative. However, the patient had a favorable response to anti-plasma cell therapy and was ultimately able to stop hemodialysis. Though monoclonal gammopathy of renal significance (MGRS) is usually not associated with infection, other cases of post-viral MGRS, including PGNMID, have been previously reported. PGNMID has recently been linked specifically to COVID-19, with this representing one of only four cases reported thus far. Though causality between the preceding viral infection and the subsequent glomerulonephritis cannot be proven in these reports, nephrologists should be aware that not all kidney disease occurring in the aftermath of COVID-19 is due to tubular injury or collapsing glomerulopathy. As such, kidney biopsy should be routinely considered in the setting of COVID-19-associated glomerular disease as findings may change management. In the case of COVID-19-associated PGNMID data to guide treatment are limited, but our report suggests that anti-plasma cell therapy may be effective.