A Quality Improvement Project to Minimize COVID-19 Infections in Patients Receiving Haemodialysis and the Role of Routine Surveillance Using Nose and Throat Swabs for SARS-CoV-2 rRT-PCR and Serum Antibody Testing

<b><i>Background:</i></b> Patients receiving in-centre haemodialysis (ICHD) are highly vulnerable to COVID-19. <b><i>Objective:</i></b> We created a quality improvement (QI) project aimed to eliminate outbreaks of COVID-19 in haemodialysis units and evaluated the utility of surveillance rRT-PCR test and SARS-CoV-2 serum antibodies for prompt identification of patients infected with COVID-19. <b><i>Methods:</i></b> A multifaceted QI programme including a bundle of infection prevention control (IPC) measures was implemented across 5 ICHD units following the first wave of the pandemic in June 2020. Primary outcomes evaluated before and after QI implementation were incidence of outbreaks and severe COVID-19 illness defined as COVID-19-related death or hospitalization. Secondary outcomes included the proportion of patients identified in the pre-symptomatic/asymptomatic phase on surveillance rRT-PCR screening and the incidence and longevity of SARS-CoV-2 antibody response. <b><i>Results:</i></b> Following the implementation of the QI project, there were no further outbreaks. Pre- and post-implementation comparison showed a significant reduction in COVID-19-related mortality and hospitalization (26 vs. 13 events, respectively, <i>p</i> &#x3c; 0.001). Surveillance rRT-PCR screening identified 39 asymptomatic or pre-symptomatic cases out of a total of 59 rRT-PCR-positive patients (39/59, 66%). SARS-CoV-2 antibody levels were detected in 72/74 (97%) rRT-PCR-positive patients. Amongst rRT-PCR-positive patients diagnosed before August 2020, 96% had detectable antibodies until January 2021 (days from the rRT-PCR test to last antibody testing, 245–280). <b><i>Conclusions:</i></b> Systematic implementation of a bundle of IPC measures using QI methodology and surveillance rRT-PCR eliminated outbreaks in HD facilities. Most HD patients mount and sustain antibody response to COVID-19 for over 8 months.

Pregnancy in a patient with dilated cardiomyopathy (DCM)

Pregnancy in dilated cardiomyopathy (DCM) has an extremely high risk. However, DCM is usually asymptomatic at a young age. In pregnancy with DCM, it appears progressive and becomes symptomatic. and mimicking with peripartum cardiomyopathy (PPCM). We reported a case of a 23-year-old woman who was 20 weeks pregnant with her first child complained of chest palpitations and severe faintness. These progressive symptoms have happened and started during pregnancy. This case report suggests that physiological and emotional burdens are greater during pregnancy, especially for dilated cardiomyopathy (DCM) patients. This condition often leads to the progression of the DCM. The DCM often headways from the asymptomatic phase upturn to the symptomatic stage.

Detection of Chronic Wasting Disease Prions in Fetal Tissues of Free-Ranging White-Tailed Deer

The transmission of chronic wasting disease (CWD) has largely been attributed to contact with infectious prions shed in excretions (saliva, urine, feces, blood) by direct animal-to-animal exposure or indirect contact with the environment. Less-well studied has been the role that mother-to-offspring transmission may play in the facile transmission of CWD, and whether mother-to-offspring transmission before birth may contribute to the extensive spread of CWD. We thereby focused on a population of free-ranging white-tailed deer from West Virginia, USA, in which CWD has been detected. Fetal tissues, ranging from 113 to 158 days of gestation, were harvested from the uteri of CWD+ dams in the asymptomatic phase of infection. Using serial protein misfolding amplification (sPMCA), we detected evidence of prion seeds in 7 of 14 fetuses (50%) from 7 of 9 pregnancies (78%), with the earliest detection at 113 gestational days. This is the first report of CWD detection in free ranging white-tailed deer fetal tissues. Further investigation within cervid populations across North America will help define the role and impact of mother-to-offspring vertical transmission of CWD.

Understanding plant-pathogen interactions in Septoria tritici blotch infection of cereals

Zymoseptoria is a major fungal pathogen of wheat, responsible for the Septoria Tritici Blotch (STB) disease. Recently, STB has been the subject of intensive molecular studies. Notably, massive transcriptomic analyses have helped to explore this particular bi-phasic (asymptomatic/necrotrophic) infection process. Cytological analyses have also improved our understanding of the asymptomatic phase. These advances suggest that Zymoseptoria behaves as a hemi-biotrophic fungus, acting like an endophyte during its asymptomatic phase. STB is still difficult to control. The emergence of fungicide-resistant isolates has reduced the efficacy of many fungicides requiring the development of novel fungicides and methods to counteract/reduce fungicide resistance. Likewise, because Stb-resistant wheat cultivars have all been successively defeated by virulent isolates, there is a need to identify new resistance genes in wheat, and to develop better disease resistance management methods (pyramiding, mixture/alternation) to sustainably control this pathogen.

Re-Print Cell Impact: Pathophysiological Mechanism of Sars-Cov-2 in the Olfactory and Gustatory System

Smell and taste alterations are very common in patients with COVID 19, even when we are in an asymptomatic phase of the disease, it is reported that up to 80 to 90% of patients present anosmia and ageusia as a cardinal symptom of the disease. In this manuscript we will mention the alterations and the mode of action of the Sars-cov-2 virus at the level of the nasal and buccal fossae, taking into account the alterations at the cellular level as a result of this, based on current evidence, remembering that it is still unknown. A lot about this disease and the way this virus works.

Novel Trends in Electrochemical Biosensors for Early Diagnosis of Alzheimer’s Disease

Background. Alzheimer’s disease (AD) is a multifactorial progressive and irreversible neurodegenerative disorder affecting mainly the population over 65 years of age. It is becoming a global health and socioeconomic problem, and the current number of patients reaching 30–50 million people will be three times higher over the next thirty years. Objective. Late diagnosis caused by decades of the asymptomatic phase and invasive and cost-demanding diagnosis are problems that make the whole situation worse. Electrochemical biosensors could be the right tool for less invasive and inexpensive early diagnosis helping to reduce spend sources— both money and time. Method. This review is a survey of the latest advances in the design of electrochemical biosensors for the early diagnosis of Alzheimer’s disease. Biosensors are divided according to target biomarkers. Conclusion. Standard laboratory methodology could be improved by analyzing a combination of currently estimated markers along with neurotransmitters and genetic markers from blood samples, which make the test for AD diagnosis available to the wide public.

MicroRNAs as a Potential New Preventive Approach in the Transition from Asymptomatic to Symptomatic Multiple Myeloma Disease

Multiple myeloma (MM) is a hematological malignancy characterised by proliferation of clonal plasma cells (PCs) within the bone marrow (BM). Myelomagenesis is a multi-step process which goes from an asymptomatic phase, defined as monoclonal gammopathy of undetermined significance (MGUS), to a smouldering myeloma (SMM) stage, to a final active MM disease, characterised by hypercalcemia, renal failure, bone lesions anemia, and higher risk of infections. Overall, microRNAs (miRNAs) have shown to significantly impact on MM tumorigenesis, as a result of miRNA-dependent modulation of genes involved in pathways known to be crucial for MM pathogenesis and disease progression. We aim to revise the literature related to the role of miRNAs as potential diagnostic and prognostic biomarkers, thus highlighting their key role as novel players within the field of MM and related premalignant conditions.

SGLT2 Inhibitors: The “Metabolic Molecule” Or “Disease Modifying Anti Metabolic Drugs- DMAMDs”?

The major health hazard of the modern world, “Metabolic Syndrome” or “Syndrome X”, defined by WHO, as pathologic condition characterised by abdominal obesity, insulin resistance, hypertension and dyslipidemia [1]. The criteria for diagnosis are listed in Figure 1 [2]. It is being accepted almost a decade ago that we are in the phase of epidemic for this Non Communicable Condition. Though it was started in western world, spread of western lifestyle across the globe, truly it has now become the major global issue. Until recently the condition was far more prevalent in urban population than rural but in today’s time, especially in Country like India, the incidence showed trends towards becoming almost equal [3]. Though recognised all over the world, the condition is rather dealt as managing different component(s) of the syndrome rather than taking the syndrome per say as diagnosis. We rather tend to care much of those patients who actually show prominently one or more components of metabolic syndrome, and this approach is leading us to neglect rather major bulk of patients who, in spite qualifying for criteria of diagnosis of metabolic syndrome, where not only patients are in early asymptomatic phase, but also the physicians caring for them do not reinforce the importance of the needed care at this very moment to prevent or delay the progression of the condition. Healthcare all over world, particularly in India has shown enormous growth, in terms of not only infrastructure but also skill development [4]. Today we do have much better level of expertise in all the subspecialty with regards to high end care of all such conditions arise from one or more components of metabolic syndrome like Heart Failure, Chronic liver disease, chronic kidney disease and Diabetes (related complication). In developing country like India, somewhere 3 to 4 decades ago to subject a patient for liver or kidney transplant used to be mere dream of treating consultants but today we are not only doing the transplants smoothly but also survival rate is getting better and better [5]. But its quiet unfortunate that in spite of all these progresses, the actual numbers of such patients needing high end care is steadily on rise, thanks to increase in life expectancy in general and relatively better exposure to needed healthcare [5]. But author do strongly believe that still whatever we are seeing is more at treatment cum cure level but nothing much at prevention level is going on. In decades to come, we have large population at risk, at this very moment, for all such advanced staged chronic metabolic conditions. We are in genuine need of a molecule which can be offered to all such early or intermediate metabolic syndrome patient, expecting the improvement in almost all the aspect on the syndrome. Author do believe, the group of drugs known as “SGLT2 Inhibitors”, an originally used for Hyperglycemia management, has now expanded its preventive effects on various metabolic conditions, showing promising results in all the trials and early real world evidences, is the real nomination for the “Metabolic Molecule” or “Disease modifying anti metabolic drugs- DMAMDs” of today.

Atypical COVID-19 dynamics in a patient with mantle cell lymphoma exposed to rituximab

Patients with non-hodgkin lymphomas (NHL) represent a population of special interest during the current Coronavirus disease-19 (COVID-19) pandemics. NHLs are associated with disease- and treatment-related immunodeficiencies which may generate unusual COVID-19 dynamics and pose unique management challenges. We report the unusual clinical course of COVID-19 in a patient with mantle cell lymphoma (MCL) exposed to nine doses of Rituximab shortly before infection with severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). He had a prolonged asymptomatic phase, with negative molecular and antibody testing for SARS-CoV-2, followed by a rapidly progressive evolution to severe COVID-19. Despite detection of viral RNA overlapped with first symptoms occurrence, anti-SARS-CoV-2 antibodies displayed an asynchronous pattern, with IgG first appearing 2 days after RNA positivity and IgM never being detected throughout the entire clinical course. While disease-associated immune derangements and/or previous treatments involving anti-CD20 antibodies might have contributed to COVID-19 dynamics in our patient, data suggests that antibody testings, without concurrent molecular assessment for SARS-CoV-2, may turn inadequate for monitoring of MCL patients, and in general NHL patients heavily exposed to anti-CD20 antibodies, during the current pandemics. We suggest that repeated molecular testing of nasopharyngeal swab should be implemented in these subjects despite a negative serology and absence of symptoms of SARS-CoV-2 infection. For the same reasons, a customized strategy needs to be developed for patients exposed to anti-CD20 antibodies, based on different features and mechanism of action of available SARS-CoV-2 vaccines and novel vaccinomics developments.

Targeting novel LSD1-dependent ACE2 demethylation domains inhibits SARS-CoV-2 replication

Treatment options for COVID-19 remain limited, especially during the early or asymptomatic phase. Here, we report a novel SARS-CoV-2 viral replication mechanism mediated by interactions between ACE2 and the epigenetic eraser enzyme LSD1, and its interplay with the nuclear shuttling importin pathway. Recent studies have shown a critical role for the importin pathway in SARS-CoV-2 infection, and many RNA viruses hijack this axis to re-direct host cell transcription. LSD1 colocalized with ACE2 at the cell surface to maintain demethylated SARS-CoV-2 spike receptor-binding domain lysine 31 to promote virus–ACE2 interactions. Two newly developed peptide inhibitors competitively inhibited virus–ACE2 interactions, and demethylase access to significantly inhibit viral replication. Similar to some other predominantly plasma membrane proteins, ACE2 had a novel nuclear function: its cytoplasmic domain harbors a nuclear shuttling domain, which when demethylated by LSD1 promoted importin-α-dependent nuclear ACE2 entry following infection to regulate active transcription. A novel, cell permeable ACE2 peptide inhibitor prevented ACE2 nuclear entry, significantly inhibiting viral replication in SARS-CoV-2-infected cell lines, outperforming other LSD1 inhibitors. These data raise the prospect of post-exposure prophylaxis for SARS-CoV-2, either through repurposed LSD1 inhibitors or new, nuclear-specific ACE2 inhibitors.