Bilateral Spontaneous Pneumothorax in a Child with Multisystem Inflammatory Syndrome Associated with COVID-19

Introduction: Spontaneous pneumothorax is a rare complication of coronavirus disease 2019 (COVID-19), primarily reported in adults. Pediatric cases with bilateral pneumothorax are much less reported. Case Presentation: We presented the case of a five-year-old previously healthy boy who developed persistent fever, abdominal pain, generalized maculopapular rash, and dyspnea before admission. His chest computed tomography (CT) showed a viral involvement pattern of pneumonia suggestive of COVID-19. Subsequently, he was confirmed with multisystem inflammatory syndrome in children (MIS-C). While he responded well to the therapies, on the fifth day of admission, he developed respiratory distress again. A chest roentgenogram showed bilateral spontaneous pneumothorax. Bilateral chest tubes were inserted, and his condition improved sig-nificantly after five days of admission to the intensive care unit. Two weeks later, he was discharged in good condition. Conclusion(s): Children with MIS-C associated with COVID-19 may develop primary spontaneous pneumothorax. Owing to the clinical picture overlapping with MIS-C associated with COVID-19, the timely diagnosis of pneumothorax may be challenging in such patients.Copyright © 2022, Author(s).

A Review on the Effect of COVID-19 in Pregnant Women

Coronavirus Disease 2019 (COVID-19) is an emerging disease with a rapid increase in cases and deaths since its first discovery in December 2019, in Wuhan, China. Limited data are available on COVID-19 effects during pregnancy;however, information on diseases associated with other highly pathogenic coronaviruses (i.e. Severe Acute Respiratory Syndrome [SARS] and the Middle East respiratory syndrome [MERS]) may provide insight into the effects of COVID-19 during pregnancy. Coronaviruses cause illnesses ranging from the common cold to severe respiratory disease and death. The data indicate an average of 5 days incubation period (range: 2-14 days). The average age range of the hospitalized patients was 49-56 years, and a third to half of them have an underlying illness. Children were rarely mentioned. Within hospitalized cases, men were more frequent (54%-73%). Fever, cough, myalgia, vomiting, and diarrhea are common symptoms. This review aims at giving an in-depth understanding of COVID-19 by comparing its effects with SARS and MERS to evaluate its severity in pregnant women1. The results of varied studies show that COVID-19 affects pregnant women seriously and there is an alarming need to look into this aspect to prevent its harmful effects on the fetus.Copyright © 2020

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.

Prevention of vitamin D deficiency in children. The state of the problem in the world and in Ukraine.

The article presents current data on the prevalence of vitamin D deficiency and criteria for its deficiency in children in different countries. Vitamin D is recognized as one of the most important vitamins involved in many biochemical processes in the body. Its active metabolites play a key role in calcium absorption, bone mineralization and promote phosphate and magnesium metabolism. At the same time, in addition to affecting mineral metabolism, there is a wide range of conditions in which vitamin D also plays a preventive role. Vitamin D has been shown to play a vital role in innate immunity maintenance and is important in prevention of several diseases, including infections, autoimmune diseases, certain forms of cancer, type 1 and 2 diabetes, and cardiovascular diseases. Vitamin D is of particular importance for newborns and young children. This vitamin is involved in important physiological regulatory processes such as bone metabolism, lung development, maturation of the immune system and differentiation of the nervous system. Vitamin D deficiency increases risks of neonatal sepsis, necrotizing enterocolitis, respiratory distress syndrome, and bronchopulmonary dysplasia. Adequate intake of vitamin D and calcium during childhood can reduce the risk of osteoporosis and other diseases associated with vitamin D deficiency in adults. Recently, vitamin D deficiency has shown to be a potential risk factor for COVID-19 propensity. It has been established that to date most scientific pediatric societies have recognized the need to prevent vitamin D deficiency in healthy children of all ages, but data on the dosage of vitamin D in its prophylactic use differ. Most scientific societies recommend an average of 400-600 IU per day of vitamin D for prophylactic purposes. The analysis of published data shows the need to follow a strategy based on an individual approach, taking into account physiological characteristics, individual requirements and lifestyle.Copyright © 2021 University of Tartu Press. All rights reserved.

Managing Severe Acute Asthma Exacerbation in Pregnancy during the COVID-19 Pandemic: A Case Report from a Resource-limited Setting

BACKGROUND: One-third of pregnant women will experience worsening asthma requiring emergency hospitalization. However, no report comprehensively discussed the management of asthma attacks in pregnant women in impoverished settings. We attempt to illuminate what general practitioners can do to stabilize and improve the outcome of severe acute asthma exacerbations in primary care with resource limitations. CASE REPORT: A nulliparous 29-year-old woman in her 21st week of pregnancy presented severe acute asthma exacerbation in moderate persistent asthma with uncontrolled asthma status along with gestational hypertension, uncompensated metabolic acidosis with a high anion gap, anemia, respiratory infection, and asymptomatic bacteriuria, all of which influenced her exacerbations. This patient was admitted to our resource-limited subdistrict hospital in Indonesia during the COVID-19 pandemic for optimal stabilization. Crystalloid infusions, oxygen supplementation, nebulized beta-agonist with anticholinergic agents, inhaled corticosteroids, intravenous methylprednisolone, broad-spectrum antibiotics, subcutaneous terbutaline, mucolytics, magnesium sulphate, oral antihypertensives, and continuous positive airway pressure were used to treat her life-threatening asthma. After she was stabilized, we referred the patient to a higher-level hospital with more advanced pulmonary management under the supervision of a multidisciplinary team to anticipate the worst scenario of pregnancy termination. CONCLUSION(S): Limitations in primary care, including the lack of sophisticated intensive care units and laboratory panels, may complicate challenges in managing severe acute asthma exacerbation during pregnancy. To enhance maternal-fetal outcomes, all multidisciplinary team members should be well-informed about key asthma management strategies during pregnancy using evidence-based guidelines regarding the drug, rationale, and safety profile.Copyright © 2023 Muhammad Habiburrahman, Triya Damayanti, Mohammad Adya Firmansha Dilmy, Hariyono Winarto.

Modeling DNA Oligonucleotide Binding to DNA-mimetic Stem-Loop 1 of the SARS-CoV-2 RNA

SARS-CoV-2 is a positive-sense RNA virus that contains open reading frame 1ab (ORF1ab) to produce 16 nonstructural proteins (nsps). Five stem-loops (SL) are found in the 5' UTR of the RNA that are involved in myriad viral functions and are labeled SL1 through SL5. SL1 is crucial to viral replication. Upon viral infection, nsp1 binds the ribosomal 40S subunit to inhibit all host mRNA translation. Upon SL1 binding to nsp1, viral mRNA can be processed by the ribosome, allowing viral proteins to be produced. In this study, we are examining small DNA oligonucleotides that bind to SL1-mimetic DNA in order to block SL1-nsp1 interactions. We designed a DNA analog of the SL1 hairpin and two small DNA oligonucleotides that are complementary to either the helical stem or the loop region of SL1. The binding of these oligonucleotides to the SL1 hairpin should allow the formation of either an alternate duplex or a triplex structure. Isothermal titration calorimetry (ITC) and circular dichroism (CD) techniques were performed in 1 MKCl and 10 mM MgCl2 at two different pH (5.5 and 7.0) to examine structural and thermodynamics of binding. ITC of the two oligonucleotides showed modest binding. Results from DNA binding experiments, thermal denaturation, and CD show the hairpin structure is thermodynamically more favored and mostly remains intact under the conditions examined.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Spectrum of Biochemical Alterations in Patients with Covid-19

Background and objective: Millions of people worldwide have died from COVID-19, which has caused the failure of the lungs and other organs. The research assessed biochemical anomalies in COVID-19 patients to comprehend the illness and its effect better. Study Design: Retrospective longitudinal cohort analysis Place of study: ABWA Medical College Faisalabad Methods: A total of 150 adult patients (n=150) who tested positive for COVID-19 via RT-PCR were included in the study. A Roche Diagnostics Cobas C501 used spectrophotometry to measure calcium, magnesium, phosphate, lactate dehydrogenase (LDH), urea, creatinine, ferritin, and chloride in the blood. A NOVA electrolytic analyzer used Ion-selective electrodes to measure sodium, chloride, potassium, and bicarbonate. Result(s): In the study, 33.6% of patients had elevated urea levels, and 22.4% had elevated creatinine levels. Furthermore, 88.8% of patients had elevated ferritin levels, and 93.5% had elevated LDH levels. After 44 weeks, there was a drop in sodium-containing electrolytes, with 9% of patients experiencing a decrease in sodium, 22.4% in potassium, 53.3% in bicarbonate, 48.6% in calcium, and 23.4% in phosphorus. These changes in electrolyte levels suggest a long-term trend in electrolyte depletion among the patient population. There was no significant difference in biochemical anomalies between age groups (p > 0.05). Conclusion(s): These results suggest that COVID-19 patients have lung illness and multi-organ involvement, which should be considered when managing these patients. These biochemical alterations warrant careful monitoring for organ failure by healthcare practitioners. More study is required to comprehend the processes causing these biochemical anomalies in COVID-19 patients.Copyright © 2023 Lahore Medical And Dental College. All rights reserved.

Analyses of kidney biomarkers in patients with sars-cov-2 (Covid-19)

The new coronavirus was first reported in China and caused a widespread global outbreak of pneumonia that spread rapidly across this country and many other countries. Acute kidney injury is one of the important complications of COVID-19, which has been shown in some cases. Exploring the diagnostic features of biomarkers of kidney function in COVID-19 patients may lead to better patient management. We collected laboratory data from 206 people with confirmed COVID-19 disease and evaluated their renal biomarkers, Blood Urea Nitrogen (BUN), and creatinine. The age range of the patients was almost 62 years old. The mean age in the dead patients and recovered patients was 71 and 54 years old, respectively. The average LDH value was 755 U/L, and creatine phosphokinase (CPK) was 267 U/L in the patients. The average BUN was 59.1 U/L, and creatinine was 1.5 U/L in COVID-2019 patients. Among all 193 patients, laboratory results revealed that 163 (85.4%) patients had an elevated BUN level. Based on creatinine levels for total patients, laboratory results revealed that 49 (25.4%) patients had an elevated value. The average BUN value in dead patients was 85 mg/dL, while in recovered patients was 40.5 mg/dL (P<0.0001). Also, the average creatinine level in dead patients was 1.86 mg/dL, while in recovered patients was 1.24 mg/dL (P=0.0004). Inflammation following COVID-19 disease causes kidney damage and elevated urea and creatinine levels, which may increase the risk of death in these patients.Copyright © 2023 Tehran University of Medical Sciences.

Electrolyte abnormalities in hospitalized COVID-19 patients at tertiary referral centers in Tehran: Hypermagnesemia as a marker of fatality: A retrospective cross-sectional study.

Background and Aims: To evaluate biochemical abnormalities and their association with the outcome of hospitalized coronavirus disease 2019 (COVID-19) patients at a tertiary referral center in Iran. Methods: This retrospective study was conducted on COVID-19 patients who were admitted at tertiary referral centers in Tehran, Iran, from March 2021 to 2022. Demographic and biochemical laboratory data of the patients including blood sodium, potassium, calcium, and magnesium were collected from patient treatment sheets of severe COVID-19 patients admitted to a different ward of the hospital. A logistic regression model was fitted to identify the associated parameters with mortality. Results: Four hundred and ninety-nine patients with COVID-19, including 287 males (57.5%), who had a mean age of 58.95 ± 16.60 years, were enrolled. Thirty-eight patients (7.62%) died during hospitalization. The factors we found to be independently associated with an increased risk of in-hospital death were having comorbidity (mortality of 94.7%, vs. 61% among those without comorbidity; odds ratio, 17.71; 95% confidence interval [CI], 3.81-82.37), hypermagnesemia (34.2%, vs. 26.2% among those with normal magnesium; odds ratio, 9.71; 95% CI, 2.958-31.91), and having a male gender (34.2%, vs. 26.2% among those were female; odds ratio, 9.71; 95% CI, 2.958-31.91). Conclusions: Hypermagnesemia, having a male gender, and the existence of comorbidity in patients with COVID-19 is associated with an increase in mortality. Further studies on the pathogenic mechanisms and therapeutic implications need to be done.

Importance of Magnesium Status in COVID-19.

A large amount of published research points to the interesting concept (hypothesis) that magnesium (Mg) status may have relevance for the outcome of COVID-19 and that Mg could be protective during the COVID disease course. As an essential element, Mg plays basic biochemical, cellular, and physiological roles required for cardiovascular, immunological, respiratory, and neurological functions. Both low serum and dietary Mg have been associated with the severity of COVID-19 outcomes, including mortality; both are also associated with COVID-19 risk factors such as older age, obesity, type 2 diabetes, kidney disease, cardiovascular disease, hypertension, and asthma. In addition, populations with high rates of COVID-19 mortality and hospitalization tend to consume diets high in modern processed foods, which are generally low in Mg. In this review, we review the research to describe and consider the possible impact of Mg and Mg status on COVID-19 showing that (1) serum Mg between 2.19 and 2.26 mg/dL and dietary Mg intakes > 329 mg/day could be protective during the disease course and (2) inhaled Mg may improve oxygenation of hypoxic COVID-19 patients. In spite of such promise, oral Mg for COVID-19 has thus far been studied only in combination with other nutrients. Mg deficiency is involved in the occurrence and aggravation of neuropsychiatric complications of COVID-19, including memory loss, cognition, loss of taste and smell, ataxia, confusion, dizziness, and headache. Potential of zinc and/or Mg as useful for increasing drug therapy effectiveness or reducing adverse effect of anti-COVID-19 drugs is reviewed. Oral Mg trials of patients with COVID-19 are warranted.

A comparative study of serum Zn, Cu, Mg, Mn, Cr, and Fe levels and their association with the vulnerability of Iraqi COVID-19 patients.

BACKGROUND: For the immune system to protect the body from infectious diseases such as COVID-19, it needs the ideal amount of vital trace elements. Trace element levels, especially, zinc (Zn), copper (Cu), magnesium (Mg), manganese (Mn), chromium (Cr), and iron (Fe) levels, may affect how sensitive an individual is to COVID-19 and other viruses. The current study evaluated the level of those trace elements during stays in the isolation center and investigated their association with vulnerability to COVID-19. METHODS: A total of 120 individuals, 49 males and 71 females aged between 20 and 60 years, were included in this study. Forty individuals infected with COVID-19, 40 individuals who had recovered from it, and 40 healthy individuals, were all evaluated and studied. By using a flame atomic absorption spectrophotometer, levels of Zn, Cu, and Mg were assessed for all samples, whereas levels of Mn, and Cr were determined by a flameless atomic absorption spectrophotometer. RESULTS: The infected individuals had significantly lower levels of Zn, Mg, Mn, Cr, and Fe than recovered individuals and healthy control individuals (P < 0.0001). On the other hand, the total number of infected patients was found to have much higher levels of Cu than those in the recovered group and the control group. For the recovered and healthy control groups, no significant differences were observed in the levels of trace elements (P > 0.05), except for Zn (P < 0.01). Also, the findings indicated no association of trace elements with age and BMI (P > 0.05). CONCLUSION: These results show that an imbalance in the levels of essential trace elements could be associated with increasing the risk of COVID-19 infection. However, additional thorough research of greater scope is required considering the severity of the infection.

War, stress, pregnancy: how to reconcile problematic issues?

The article provides data on current stress loads in the population of Ukraine, which have significantly increased as a result of emotional overstrain (stress) and the reduction of periods of positive emotional states. The presence of active military operations in the country and, as a result, the appearance of the population with the status of "displaced persons”;the part of the population that is/was in the zone of temporary occupation;the appearance of the wounded and disabled persons among the civilian population led the completely new tasks for the organism adaptive systems, which it is not always ready to overcome them. Over the last two year, the life of a person in Ukraine has been affected by a combination of two "dark forces”, namely, the war and the COVID-19 pandemic, and this influence is still continuing. The war for almost a year led to the layering of acute stress on already existing problems, deterioration of the social situation;forced change of place/country of residence (often repeated changes);interruptions in the supply of quality food products, medicines, dietary supplements, etc.;violation of "doctor-patient” contacts and, as a result, the impossibility of receiving timely and high-quality consultations and treatment. On the background of these problems there are significant risks of wartime for pregnant women, which can hinder the favorable course and termination of pregnancy. Among the most significant difficulties is a severe psychological trauma. The problem of the impact of the war on the pregnant women and the results of childbirth in our country began to be considered since 2014, when as a result of Russia's aggression in the east of the country and in the Crimea a completely new part of the population appeared – internally displaced persons (IDPs) from these regions. To date, the significantly increased contingent of IDPs has also been joined by those persons who displaced to other countries because of the war from February 24, 2022. The stay of a pregnant woman in conditions of acute or long-term chronic stress negatively affects the course of pregnancy, increasing the number of complications and negatively affecting the condition of the fetus and newborn. Pregnancy can also be considered a significant adaptive load, which requires the woman's body to mobilize mechanisms for syn-chronization between indicators of the basic systems and a favorable course of the gestation and childbirth process. Even during its physiological course it has a certain influence on the psychological condition of a woman, and some authors consider it even as a crisis situation, or as a "period of psychological uncertainty”. Individual features of response to stress cannot be dismissed either. Yes, the degree of reaction of a pregnant woman can be completely different depending on the specifics of the situation. One of the effective and available ways to prevent the effects of long-term stress during pregnancy is magnesium (Mg) supple-mentation in its oral form, taking into account bioavailability and the daily dose for pregnant women. Magnesium is indis-pensable in maintaining the conduction of nerve impulses, serves as a natural muscle relaxant that relaxes smooth and skeletal muscles, has a positive effect on the functioning of the placenta and endothelium, ensures the full development of the fetus in synergy with other useful substances, in particular B vitamins. The preparations based on magnesium salts with organic acids (orotic acid, vitamin B6), in which the anion of the acid serves as a "magnesium carrier” (ligand) into the cell, are characterized by a high bioavailability. It is important in the context of the impact on the central nervous system during the war that magnesium, vitamin B6 and orotic acid potentiate each other's anti-stress effect. Our experience allows us to recommend a magnesium preparation for long-term use, starting with pre-gravid preparation, throughout pregnancy and lactation, which includes the chelated form of marine magnesium «Simag 55» (p ri fied natural marine mineral extract) with two conductors (vitamin B6 and orotic acid) to ensure the highest bioavailability. © The Author(s) 2023.

Initiating Home Parenteral Nutrition Therapy in a Patient at High Risk of Refeeding Syndrome After COVID-19 Infection

Background: An emerging finding about COVID-19 is its effect on nutrition and weight loss. The COVID-19 symptoms of fatigue, altered taste or smell, and lack of appetite are well known. But COVID-19 may have a more profound effect on clinical nutrition status. Two recent studies have identified that approximately one-third of ambulatory COVID-19 patients are at risk of experiencing weight loss >= 5% (Anker, et al;di Filippo, et al). The case study presented here discusses home start total parenteral nutrition (TPN) in a patient recently diagnosed with COVID-19 at high risk for refeeding syndrome. Method(s): N/A Results: Case Study: A 92-year-old patient was diagnosed with COVID-19 on June 8, 2022. Over the next week, she was hospitalized twice to manage symptoms of acute mental status changes, lethargy, aphasia, hypotension, and loss of appetite. The patient received nirmatrelvir/ritonavir, remdesivir, and bebtelovimab to treat COVID-19 at different times between June 9, 2022, and June 18, 2022. She remained COVID positive and continued to deteriorate clinically. On June 20, 2022, the patient began receiving 24/7 homecare, including intravenous (IV) fluids of dextrose 5% in normal saline (D5NS) 1000 mL daily for three days. She continued to experience loss of appetite and had no bowel movement for 3 days. On June 23, 2022, she was referred to this specialty infusion provider to initiate TPN therapy in the home setting. The patient's BMI was 18.2 kg/m2. Lab results revealed potassium 3.0 mmol/L, phosphate 1.6 mg/dL, and magnesium 1.6 mg/dL. High risk of refeeding syndrome was identified by the level of hypophosphatemia and hypokalemia. The specialty infusion provider's registered dietitian recommended to discontinue D5NS and begin NS with added potassium, phosphate, and magnesium. Thiamine 200mg daily was added to prevent Wernicke's encephalopathy. The patient's clinical status and lab values were monitored closely each day until her electrolyte levels stabilized (Table 1). Home TPN therapy was initiated on June 28, 2022, with <10% dextrose and 50% calorie requirement with 85% protein and 1.0 g/kg lipids. Three-day calorie count and nutrition education were performed four days post TPN initiation. Oral intake met only 25% of estimated needs. Over several days, theTPN formula was gradually increased to goal calories and the infusion cycle was slowly decreased. The following week, the patient's oral intake improved to 60%-75% of estimated needs. Her constipation resolved, and she showed improvement in functional status and mobility. Her appetite drastically improved when the TPN was cycled. Another three-day calorie count was performed when TPN calories reached goals. Oral intake demonstrated 100% estimated calorie and protein needs. TPN therapy was ultimately discontinued on July 14, 2022. As of September 30, 2022, the patient has stabilized at her pre-COVID weight of 45 kg with full recovery of appetite, function, and cognition. Discussion(s): The ASPEN Consensus Recommendations for Refeeding Syndrome (da Silva, et al) describe the repletion of electrolyte levels before introducing calories to prevent end-organ damage associated with refeeding syndrome (respiratory muscle dysfunction, decreased cardiac contractility, cardiac arrhythmias, and encephalopathy). Conclusion(s): This case study highlights the successful initiation of home TPN therapy in a patient at high risk of refeeding syndrome post COVID-19 infection. Although home start TPN and the risk of refeeding syndrome are not new concepts, they must be considered in the setting of COVID-19. Given the effects COVID-19 has on taste, smell, and appetite and the recent finding that one-third of patients with COVID infection may experience weight loss of >= 5%, nutrition support and patient education are vital components of overall patient care. (Figure Presented).

A Rare Etiology for Ulcerative Colitis Flare

Introduction: Prior to colonoscopy, it is well understood that patients must undergo bowel cleansing. Based on the type of laxative, colonoscopy preparations fall into two categories - polymer-based formulas (PEG) and saline-based formulas (NaP). Both types of bowel preparations are deemed to be relatively safe and part of routine practice. However, we describe the rare case of an ulcerative colitis (UC) flare due to the bowel preparation formula. Case Description/Methods: A 29-year-old female with diagnosis of UC, presently in clinical and biochemical remission on oral mesalamine, contracted COVID-19 and had reactivation of UC symptoms. After being on budesonide tablets and rectal foam for two months, patient achieved clinical remission, and a surveillance colonoscopy was performed which revealed normal colon and terminal ileum except mild congestion in the cecum (Figure A). Pathology revealed unremarkable mucosa in the entire colon except for chronic active colitis in the cecum. Immediately following this colonoscopy, the patient started to experience another severe UC flare requiring hospitalization. The patient's laboratory work-up was normal except for an elevated fecal calprotectin (1710). Stool infectious work-up was negative and the patient denied any NSAID or antibiotic use. The patient underwent a repeat colonoscopy which revealed severe Mayo 3 pancolitis (Figure B) in comparison to a stable colonoscopy a few weeks prior. It was revealed that for her initial colonoscopy, she had used SUPREP bowel prep kit. On prior colonoscopies she had used MiraLAX bowel prep with no adverse effects. During hospitalization, the patient was started on biologic therapy with good effect. Discussion(s): There are no clear guidelines on appropriate bowel preparation formula for the inflammatory bowel disease (IBD) population. Sufficient literature exists to confirm that NaP can irritate the intestinal mucosal wall. Moreover, numerous animal experiments have employed dextran sodium sulfate for chemical induction of intestinal inflammation to mimic UC flares in humans [1]. Thus, it can be surmised that because SUPREP ingredients contain sodium sulfate, the potential for UC flare is higher. It is pertinent for practitioners to be aware of the possible rare adverse effects of saline-based formulas, especially when treating the IBD population.

Post-Covid-syndrome and transient microvascular pathology in pulse-waveanalysis - association with Mg/Ca ratio and magnesium therapy-options

Post-COVID-syndromes have a high impact on incapacity for work: a mean of over 100 days has been reported in Germany [1]. Magnesium deficiency is documented as a riskincreasing factor for fatal outcome of acute covid disease [2, 3]. A first case report of post-COVID treatment with hybrid magnesium parenteral/ oral was presented in February 2021 during the Global Magnesium COVID 19 online conference. As of yet, there is no established explanation for post-COVID or long-COVID syndrome as well as there being no established treatment. In recourse to the hypothesis that magnesiumdepletion might favour microvascular early-aging and so favour neuro- degenerative prozesses [4] now preliminary observations of these parameters in post-covid patients in our primary care office result. This is done in connection with long years documentation of pulsewave-analysis (pwv), magnesium and Mg/Caprofiles in patients who suffered covid- disease. Figure 1 shows an over 6-year series of pulse-wave-analyses in a 59-year-old female patient who suffered from post-COVID syndrome. Her augmentation index (AIX) as an indicator of the actual microvascular condition increased from favorable 8% (2020) to highly pathological 39% in the post-COVID disease period - corresponding with the mean value of an 80-year-old person [5]. Another 67-year-old female post-COVID patient recovered clinically very well and quickly with high-dosed magnesium therapy and showed coincident positive decrease of AIX to 4%. Further case reports in the context of magnesium pretests and AIX are presented. Late controlled studies concerning magnesium supplementation and PWV focus on the other parameter - the (macrovascular determined) pulse-wave-velocity (PWV) and found no association of PWV with several months of magnesium supplementation [6]. Therefore, it must be emphasized that all our observations of the last years where not based on PWV but rather focused on AIX as a volatile but more magnesium-dependent parameter. Furthermore, our patients where mostly supplemented over years and not only 24 weeks. Evident is the overall small number of clinically manifesting post-COVID cases among our COVID patients (n= 10 when writing the ) among actually 470 Corona-context treatment cases. We have two working hypotheses for this. I: Persistently high magnesium levels may contrib- ute to reducing the number of post- COVID cases - and II: In the case of post-COVID syndrome, high-dose possibly hybrid magnesium therapy might favorably influence the course of the disease. The Corona pandemic and its microvascular consequences are possibly and unfortunately a non-intended turbo-experiment for microvascular early aging in a great number of undetected magnesium- depletion patients. Facing the burden of disease for individuals - and society as a whole - this justifies not only controlled studies but also the increased attention of medical doctors to the optimal magnesium status of these patients.

Pathogenesis of encephalopathy and delirium: neocortical neuronal membrane potential and action potential firing are changed by coronavirus-associated cytokines

Introduction: Encephalopathy and delirium are common following coronavirus infection [1], and the associated neuroinflammation often results in long-term behavioral and cognitive impairment. Neurovirulent cytokines (NVC) are strongly implicated in the pathogenesis of coronavirus encephalopathy [2]. We hypothesized that characterizing the abnormal signaling in NVC exposed neurons will enable us to identify targets to treat encephalopathy and prevent its downstream effects. Method(s): We incubated primary mouse neocortical cultures in NVC known to be increased in coronavirus encephalopathy (TNF-alpha, IL-1beta, IL-6, IL-12 and IL-15). Using whole-cell patch clamp methods, we tested how neuronal function was impacted by 22-28-h exposure to NVC. Result(s): We found that NVC depolarized the resting membrane potential (RMP), reduced the firing threshold of neocortical neurons, and increased baseline spontaneous action potential (AP) firing. NVC altered the sensitivity (or input-output properties) of single neurons to changes in their microenvironment. Specifically, decreasing external Ca2+ and Mg2+ from physiological to low (1.1-0.2 mM) levels increased evoked AP firing in control, but not following exposure to NVC. AP firing threshold and spontaneous firing rates returned to control levels 1 h after NVC wash-out. However, the RMP and attenuated sensitivity of evoked APs to changes in the microenvironment remained persistently abnormal suggesting two distinct mechanisms were at play. Interestingly, hyperpolarizing the RMP reversed this altered response. Conclusion(s): Sustained exposure to NVC reversibly depolarizes neocortical neuronal RMP, altering excitability and the ability of neurons to respond to microenvironment changes. By characterizing the pathogenesis of the underlying changes in neuronal function in our model of coronavirus encephalopathy we will identify intervenable drug targets.

A comprehensive review on the diagnosis and testing strategies for coronavirus disease

The COVID-19 outbreak has fashioned to severe threat to each and every individual in social and economic aspects in the country. This required improved wisdom to know how it is different and dominant, to diagnose and determine effective vaccines to avoid the transmission of these deadly causative agents. From this review, the probable property of these deadly transmissible viruses is related to that of SARS-CoV-2 as a fright zone of viruses. It also provides some sparks about effective and accurate diagnosis and treatment strategies. The effective management and control of panic zone of virus (PZV) and SARS-CoV-2 are more important to reduce the pandemic situation.Copyright © 2023 Inderscience Enterprises Ltd.

Follow-up 24-Urine Studies during and Post-Covid-19 Pandemic

INTRODUCTION AND OBJECTIVE: In New York State, March 16, 2020 marked the end of any in-restaurant dining due to the COVID- 19 pandemic. The general population was forced to do more cooking at home and less dining out. Dietary modifications like this are considered first line therapy for calcium stone formers due to an effort to reduce dietary sodium intake which is known to affect lithogenic risk factors including hypernatriuria and hypercalciuria. This study aims to see if dietary changes made during the pandemic changed the risk of stone disease as evidenced in 24-hour urine studies and if these changes ceased after the end of widespread shutdowns. METHOD(S): All patients with nephrolithiasis seen for an outpatient visit from April 1, 2020-December 31, 2020 were queried and included if they had a 24-hour urine study pre-COVID (before March 16, 2020) and during-COVID (March 16, 2020-December 31, 2020);a post- COVID study was included if available (January 1, 2021- October 31, 2022). Values were compared using paired, 2-tailed t-tests. RESULT(S): 93 patients (54 males, 39 females, mean age 60.1) were studied pre-COVID, during-COVID, and post-COVID time periods with 24-hour urine studies. Stone analysis revealed calcium oxalate (61%), calcium phosphate (15%), uric acid (15%), other (9%). The 24-hour urine revealed a significant reduction in urinary sodium (uNa) and urinary calcium (uCa) in these patients. uNa levels decreased from 166.15+/-7.5 mEq/L pre-COVID to 149.09+/-7.6 mEq/L during- COVID (p=0.015) and maintained improved at 138.55+/-6.83 mEq/L post-COVID era (p=0.0035). uCa levels decreased from 214.18+/-13.05 mEq/L pre-COVID to 191.48+/-13.03 mEq/L during- COVID levels (p=0.010) and remained improved at 185.33+/-12.61 mEq/L post-COVID (p=0.012). There were no significant differences in 24-hour urine total volume, magnesium, or citrate levels. CONCLUSION(S): During the COVID-19 lockdown, dietary choices limited to home cooked meals allowed patients to better identify their food choices. This study demonstrates that known urinary risk factors for lithogenesis, such as urinary sodium and calcium, improved during the lockdown and these improvements were maintained even after restrictions in restaurants were lifted. Moving forward, it will be imperative to monitor patient's 24-hour urine to ensure these dietary modifications are continued in the postpandemic era and to see if these improved urinary parameters will impact stone formation in these patients.

SARS-CoV-2 Nsp13 Catalytic Efficiency is Regulated by ATP: Mg2+ Stoichiometry and Functional Cooperativity Among Nsp13 Molecules

Coronavirus disease 19 (COVID-19) is a highly contagious and lethal disease caused by the SARS-CoV-2 positive-strand RNA virus. Nonstructural protein 13 (Nsp13) is the highly conserved ATPase/helicase required for replication of the SARS-CoV-2 genome which allows for the infection and transmission of COVID-19. We biochemically characterized the purified recombinant SARS-CoV-2 Nsp13 helicase protein expressed using a eukaryotic cell-based system and characterized its catalytic functions, focusing on optimization of its reaction conditions and assessment of functional cooperativity among Nsp13 molecules during unwinding of duplex RNA substrates. These studies allowed us to carefully determine the optimal reaction conditions for binding and unwinding various nucleic acid substrates. Previously, ATP concentration was suggested to be an important factor for optimal helicase activity by recombinant SARS-CoV-1 Nsp13. Apart from a single study conducted using fixed concentrations of ATP, the importance of the essential divalent cation for Nsp13 helicase activity had not been examined. Given the importance of the divalent metal ion cofactor for ATP hydrolysis and helicase activity, we assessed if the molar ratio of ATP to Mg2+ was important for optimal SARS-CoV-2 Nsp13 RNA helicase activity. We determined that Nsp13 RNA helicase activity was dependent on ATP and Mg2+ concentrations with an optimum of 1 mM Mg2+ and 2 mM ATP. Next, we examined Nsp13 helicase activity as a function of equimolar ATP:Mg2+ ratio and determined that helicase activity decreased as the equimolar concentration increased, especially above 5 mM. We determined that Nsp13 catalytic functions are sensitive to Mg2+ concentration suggesting a regulatory mechanism for ATP hydrolysis, duplex unwinding, and protein remodeling, processes that are implicated in SARS-CoV-2 replication and proofreading to ensure RNA synthesis fidelity. Evidence is presented that excess Mg2+ impairs Nsp13 helicase activity by dual mechanisms involving both allostery and ionic strength. In addition, using single-turnover reaction conditions, Nsp13 unwound partial duplex RNA substrates of increasing doublestranded regions (16-30 base pairs) with similar kinetic efficiency, suggesting the enzyme unwinds processively in this range under optimal reaction conditions. Furthermore, we determined that Nsp13 displayed sigmoidal behavior for helicase activity as a function of enzyme concentration, suggesting that functional cooperativity and oligomerization are important for optimal activity. The observed functional cooperativity of Nsp13 protomers suggests the essential coronavirus RNA helicase has roles in RNA processing events beyond its currently understood involvement in the SARS-CoV-2 replication-transcription complex (RTC), in which it was suggested that only one of the two Nsp13 subunits has a catalytic function, whereas the other has only a structural role in complex stability. Altogether, the intimate regulation of Nsp13 RNA helicase by divalent cation and protein oligomerization suggests drug targets for modulation of enzymatic activity that may prove useful for the development of novel anti-coronavirus therapeutic strategies. This work was supported by the Intramural Training Program, National Institute on Aging (NIA), NIH, and a Special COVID-19 Grant from the Office of the Scientific Director, NIA, NIH.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Thermodynamic Analysis of 1 x 2 Internal Loop Regions of SL1 of SARS-CoV-2 and SL of U6 snRNA

The genomic material of SARS-CoV-2 is a positive-sense single-stranded RNA. SARS-CoV-2 produces non-structural protein 1 (NSP1), which inhibits host cell translation by binding its' N-terminal to the host's 40S ribosomal subunit. Once NSP1 is bound its C-terminal domain folds and binds to the mRNA entry channel. Stem loop 1 (SL1) in the 5'-UTR of the viral mRNA binds to NSP1 to abrogate translation inhibition leading to the expression of viral proteins. SL1 contains a 1 x 2 internal loop that is not seen in other coronaviruses and may be involved in conformational changes that influence SL1-NSP1 interactions. The 1 x 2 internal loop of SL1 contains a putative A*C non-canonical base pair. The U6 snRNA also contains a 1 x 2 internal loop known to undergo conformation changes in response to pH and magnesium ion binding. Here we examine the thermodynamic properties and magnesium binding of the 1 x 2 internal loop of SL1 in varying helical contexts. Thermal denaturation experiments were performed on various DNA and RNA constructs in the presence of 1 M KCl or 10 mM magnesium chloride at a pH of 5.5 and 7. We show that formation of the A+*C base pair and the construct stability in the presence of magnesium ions is dependent on the helical context.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.