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Exploring COVID-19: Relating the spike protein to infectivity, pathogenicity and Immunogenicity

Published on: 27th January, 2021

OCLC Number/Unique Identifier: 8906007931

Introduction: SARS-CoV-2 life cycle: The disease which reportedly began in Chinese city Wuhan in November-December 2019 manifesting as severe respiratory illness, soon spread to various parts of the world, and was named COVID-19, and declared a pandemic by WHO. The life cycle of SARS-CoV-2 begins with membrane fusion mediated by Spike (S) protein binding to the ACE2 receptors. Following viral entry and release of genome into the host cell cytoplasm there occurs replication and transcription to generate viral structural and non-structural proteins. Finally, VLPs are produced and the mature virions are released from the host cell. Immunogenicity of the spike protein: The S protein is considered the main antigenic component among structural proteins of SARS-CoV-2 and responsible for inducing the host immune response. The neutralising antibodies (nAbs) targeting the S protein are produced and may confer a protective immunity against the viral infection. Further, the role of the S protein in infectivity also makes it an important tool for diagnostic antigen-based testing and vaccine development. The S-specific antibodies, memory B and circulating TFH cells are consistently elicited following SARS-CoV-2 infection, and COVID-19 vaccine shots in clinical trials. The emerging SARS-CoV-2 variants: The early genomic variations in SARS-CoV-2 have gone almost unnoticed having lacked an impact on disease transmission or its clinical course. Some of the recently discovered mutations, however, have impact on transmissibility, infectivity, or immune response. One such mutation is the D614G variant, which has increased in prevalence to currently become the dominant variant world-over. Another, relatively new variant, named VUI-202012/01 or B.1.1.7 has acquired 17 genomic alterations and carries the risk of enhanced infectivity. Further, its potential impact on vaccine efficacy is a worrisome issue. Conclusion: THE UNMET CHALLENGES: COVID-19 as a disease and SARS-CoV-2 as its causative organism, continue to remain an enigma. While we continue to explore the agent factors, disease transmission dynamics, pathogenesis and clinical spectrum of the disease, and therapeutic modalities, the grievous nature of the disease has led to emergency authorizations for COVID-19 vaccines in various countries. Further, the virus may continue to persist and afflict for years to come, as future course of the disease is linked to certain unknown factors like effects of seasonality on virus transmission and unpredictable nature of immune response to the disease.
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Living with ‘Long COVID-19’: The long-term complications and sequelae

Published on: 16th February, 2021

OCLC Number/Unique Identifier: 9031344522

Introduction - the perennial pandemic: It is being increasingly realised that the COVID-19 may have become the new reality associated with human existence world over and the mankind may have to live with it for years or even decades. Further, the grievous nature of the disease is evolving further with the genomic changes in the virus in form of mutations and evolution of variants, with enhanced infectivity and probably virulence. There are serious challenges posed by the SARS-CoV-2 virus and COVID-19 as the disease. COVID-19 as acute and chronic disease: On exposure to the SARS-CoV-2 virus, not all patients develop a disease. Further, for those who develop the disease, there is a large variation in disease severity. The known factors including the constituent factors and several still unknown factors influence the disease manifestations, its course, and later the convalescent phase as well. In fact, substantial continuing morbidity after resolution of the infection indicates persisting multisystem effects of COVID-19. The ‘long COVID-19’ or ‘long haulers’: The patients who continue to suffer with persisting symptoms have been described as long haulers and the clinical condition has been called post-COVID-19 or ‘long COVID-19’. The diagnosis should be entertained if various symptoms and signs linger well beyond the period of convalescence in COVID-19. With the chronicity, there occur inflammatory changes and damage in various organs, and the extent of organ damage determines the long-term effects. Management of ‘long COVID’ syndrome: The ‘long COVID’ syndrome has multi-system involvement, variable presentation, and unpredictable course. Following clinical and investigational assessment, the patients should be managed as per clinical manifestations, extent of organ damage and associated complications. The findings from various studies indicate that preventing further organ damage in ‘long COVID’ is crucial. The long COVID’s prognostic challenges: As apparent, the ‘long COVID’ afflictions are more common than realized earlier. The symptoms can escalate in patients with co-morbid conditions. The persistent symptoms among COVID-19 survivors pose new challenges to the healthcare providers and may be suitably managed with a combination of pharmacological and non-pharmacological treatments, and holistic healthcare. 
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COVID-19 New variant and air pollution relationship: how airborne mutagens agent can act on genoma viruses expression: Hypothesis of work

Published on: 16th February, 2021

OCLC Number/Unique Identifier: 9031333670

Before actual COVID-19 pandemia coronavirus was not so dangerous like now. In December 2019 - January 2020 in Wuhan first and then in other places this coronavirus was responsible of a first wave of severe pulmonitis responsible of many deaths. Wuhan and other region involved first was high level air polluted and industrial area. New COVID-19 variant in last part of 2020 and in first month of 2021 was responsible of great diffusion of this pandemic disease. UK, South Africa and brasilian new variant show higher diffusion then the first wave of COVID-19. Aim of this work is to analyze relationship with air pollution and the possibility that mutagen substantia inside of this microenvironment can produce new variant trough an genetic pressure process. RNA viruses are normally subjected by natural mutation but some phenomena can contribute to accelerate this process and their airborne – aeresols microenvironment is relevant. Some air pollutants are recognized as mutagen factors by literature.
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Impact of COVID-19 pandemic on anti-microbial resistance and secondary microbial infections

Published on: 25th February, 2021

OCLC Number/Unique Identifier: 9031335484

Corona Virus Disease-2019 (COVID-19) has become one of the most serious diseases in the history of mankind. It has captured the entire world and solutions are yet to be discovered to fight this global crisis. The outcomes of COVID-19 are influenced by a variety of pre-existing factors. The secondary microbial infections are one of the prominent ones that are major contributors for Antimicrobial Resistance (AMR) as they warrant the use of antimicrobial medications. The present review aimed at exploring the potential relationship between AMR under such circumstances and COVID-19 related outcomes. The published literature across the globe has delineated that the impact of COVID-19 may have worsened by a great degree due to the presence of secondary infections majorly bacterial ones. The consequences of COVID-19 have been fatal and a significant proportion can be a major attributor to AMR, either directly or indirectly. Although, there is a dearth of studies that can establish a very strong and direct relationship between AMR and negative COVID-19 outcomes so in-depth research on this topic is required to further explain this relationship in detail. 
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A systemic review on various pertinences and simulations of rotavirus

Published on: 28th April, 2021

OCLC Number/Unique Identifier: 9023206447

Rotavirus induced disease are a main source of dreadful, serious and drying out gastroenteritis in kids (less than five years old). Instead of the worldwide presentation of immunizations for rotavirus longer than 10 years back, rotavirus infections still result in more than 200,000 yearly passings, generally in developing countries. Rotavirus basically infects enterocytes and cause diarrheal through the demolition of absorptive enterocytes. Intestinal secretions are invigorated by rotavirus (non-auxiliary/structural protein) to enactment of the enteric sensory system. Rotavirus diseases can prompt viraemia and antigenaemia (term related with more serious indications of intense gastroenteritis). Rotavirus reinfections are regular throughout the life, even though the sickness seriousness is diminished with rehash contaminations. The resistant relates of assurance against rotavirus reinfection and recuperation from disease is inadequately perceived. This study takes a step forward to the administration of rotavirus disease centers, primarily on control and cure of dehydration, even though the utilization of antiviral and hostile to purgative medications can be demonstrated at some cases.
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Prevalence of ESBL urinary tract infection in children

Published on: 8th August, 2019

OCLC Number/Unique Identifier: 8207299945

Urinary tract infection (UTI) is one of the extremely popular causes of febrile illness in children, demanding antimicrobial therapy [1]. Overall, 8% of females and 2% of males, experience at least one incident of UTI by seven years of age, and recurrence takes place in up to 30% during a year [2].
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Aripiprazole-induced seizures in children with autism spectrum disorder and epilepsy

Published on: 31st January, 2020

OCLC Number/Unique Identifier: 8530277855

Purpose: Children with autism spectrum disorder are at an increased risk for developing seizures, which can be triggered by classical antipsychotics. Aripiprazole is an atypical antipsychotic that has a safer drug profile. The objective is to present the experience with seizure control in autistic children who are placed on Aripiprazole. Methods: Series of consecutive autistic children with comorbid epilepsy treated with Aripiprazole were identified prospectively over a 3-year period. Monthly follow up by one pediatric neurologist was performed to document seizure control. Results: 56 autistic children with comorbid epilepsy were placed on Aripiprazole. Most children (59%) were seizure free for at least 6 months. The initial Aripiprazole dose was 5 mg in all patients. Follow up ranged between 5-8 months (mean 6.9). A total of 5 (9%) children developed seizure provocation (3/5) or worsening seizure control (2/5). There were 3 males and 2 females with ages ranging between 6-11.5 years (mean 8.5). Three of these children had a previous history of seizure worsening with other antipsychotic drugs (respiridone in 2 and haloperidol in 1). One child with seizure provocation developed status epilepticus 5 days after introducing Aripiprazole that required intensive care admission. The drug was stopped in all 5 children with no long-term effects. Conclusion: Seizure provocation or worsening seizure control is not uncommon following the introduction of Aripiprazole in autistic children with controlled epilepsy. Although the risk is low, parents should be warned and advised on what to do, particularly in the first month of therapy.
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Case-based education to improve learning and faculty teaching of residents and students in a clinical setting

Published on: 5th February, 2020

OCLC Number/Unique Identifier: 8553243394

Introduction: Current pediatric residents spend less time in the neonatal intensive care unit (NICU) and as a result, resident exposure to neonatal pathophysiology has decreased. Engaging learners efficiently while balancing clinical demands is challenging. Practices to enhance adult education include integration of problem centered learning into the demands of daily life in an environment in which learners feel safe asking questions and expressing themselves. Methods: With this principal in mind, we developed a curriculum to enhance resident and medical student education during busy NICU rotations. The curriculum was case-based, available on-line and facilitated by neonatology faculty and fellows. A template designed to be concise and interactive was used to create and present the cases. After the case vignette, the template prompted medical students and residents to generate a differential diagnosis, order a diagnostic workup and narrow the diagnosis. Discussion of the diagnoses occurred at the conclusion of the cases; however, the template discouraged didactic lectures. Results: In two years, cases were viewed 2,362 times. Facilitators and learners rated the quality and utility of the cases favorably overall. Cases took approximately 20 minutes to complete. Approximately 57% of survey respondents reviewed 1-2 cases per week and 9.6% reviewed 3-5 cases per week. Discussion: A template with a concise and consistent format to construct and present cases allows for the creation of a curriculum that can be incorporated into a clinically demanding service and may enhance clinical teaching and learner engagement.
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Air pollution and respiratory health

Published on: 1st September, 2020

As per report of WHO [1] (World Health Organization), air pollution (ambient/outdoor and household/indoor air pollution) kills an estimated seven million people worldwide every year largely as a result of increased mortality from stroke, heart disease, chronic obstructive pulmonary disease, lung cancer and acute respiratory infections. Data of WHO shows that 9 out of 10 people breathe air containing high levels of pollutants. World Health Organization is working with countries to monitor air pollution and improve air quality. From smog hanging over cities to smoke inside the home, air pollution poses a major threat to health and climate. More than 80% of people living in urban areas and around 91% of the world’s population live in places where air quality levels exceed WHO limits, with developing and under-developed countries suffering from the highest exposures, both indoors and outdoors [1]. While outdoor air pollution comes from the motor vehicles, burning of fossil fuels and other industrialization activities, indoor air pollution is the result of tobacco smoke and burning fuel for cooking & heating. Furniture and construction materials also emit such pollutants. Both outdoor and indoor air pollution are harmful to the human health.
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Parents’ perception of the school nurse’s role

Published on: 21st December, 2020

Background: School nurses possess an essential role in treating and helping children maintain health. However, the full scope of their role has not been identified by parents. Therefore, the purpose of this study was to explore parents’ perceptions of the role of the school nurse. Methods: Descriptive statistics were used to analyze the data. One hundred eighty parents participated in the study. The perception of the roles of school nurses was assessed by a 16-item questionnaire, which was adapted from a study by Kirchofer, et al. 2007. Results: The four most important school nurses’ roles perceived by the parents were providing first aid and emergency care to children, communicating with parents and health care providers in the presence of a problem, providing medical treatment, and preventing and controlling diseases. Conclusion: School nurses have many important roles, and while parents identified some essential roles, they did not recognize other vital roles as being very important. Increasing awareness of school nurses’ multifaceted roles among parents is essential so that they can utilize nurses’ expertise in maintaining their student’s health as well as tap into a key resource in the coordination of care for their child.
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The association between hypoxia, chronic ischemia and alters prostate structure and progress of chronic prostatic disease

Published on: 20th September, 2019

OCLC Number/Unique Identifier: 8286560822

Chronic prostatitis today show high level of relapses and recurrent pathological events even if using the best pharmacological therapy. A better understanding of physiopathological effect of ischemic hypoxic condition (pelvic, prostate tissue) and the lymphatic congestion in same body region contribute in evolution of a complex condition. The same focusing the strategy in biofilm reduction or in leukocyte infiltration can be a right way to reduce relapses and progression of the prostatic disease. Hypoxia is also related to prostatic cancer progression and prostatic biofilm if responsible of making a new micro- environment often drug resistance. A deep knowledge in this kind of phenomena can improve the clinical effect of drug therapy.
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Co-extract mixture from Strophanthus hispidus (roots) and Aframomum meleguta (seeds) show phytochemical synergy in its anti-inflammatory activity

Published on: 11th December, 2019

OCLC Number/Unique Identifier: 8500735034

Background: Combination of extracts from multiple plants are typically used in ethnomedicine to putatively offer more potent chemotherapeutic and chemopreventive effects than that of individual extracts from single plants. Aqueous extracts from two multipurpose plants Strophanthus hispidus (roots) and Aframomum meleguta (seeds) are topically co-administered in the nasal cavities for the ethnomedicinal management of chronic sinusitis. Aim: This study assessed the potential phytochemical synergy between constituent extracts of Strophanthus hispidus (roots) and Aframomum meleguta (seeds) in its anti-inflammation, anti-microbial and anti-oxidant effects. Methods and Materials: Broth dilution assay assessed anti-microbial activities. DPPH radical scavenging assay examined the scope of anti-oxidant activities and inhibition of carrageenan-induced 7-day old chick feet oedema revealed anti-inflammatory activities. Results: Anti-microbial activities of individual plant extracts in broth dilution assay showed comparable potency to that of the co-extract mixture. Similarly, individual extracts showed levels of DPPH radical scavenging activities in anti-oxidant assay that was comparable to those found for the co-extract mixture. In contrast to these two effects, inhibition of carrageenan-induced 7-day old chick feet oedema revealed an anti-inflammatory activity evoked by co-extract mixtures that was greater than the sum of the individual potencies of the two extracts. Conclusion: The potential phytochemical synergy of the two plants extracts in its anti-inflammatory response largely validates ethnomedicinal practice and generally confirms growing literature reports that ascribe the net pharmacological activities of herbal extracts to the combined multi-activities of unique phytochemical entities at multiple target sites.
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An Audit on the implementation of administering Ondansetron in children with acute gastroenteritis and its effect on admission rate

Published on: 25th March, 2021

OCLC Number/Unique Identifier: 8984626581

Acute gastroenteritis (AGE) is a common presenting complaint in paediatrics. Most often, the reason for admission into hospital is to initiate intravenous rehydration in patients with severe dehydration and inability to tolerate oral intake. We found that Ondansetron acts as a potent antiemetic to support an increased number of children receiving oral hydration, and subsequently leading to decreased rates of admission. This study aims to audit the use of Ondansetron to Oral Rehydration Therapy (ORT) on children with acute gastroenteritis, and its effect on admission rates from the emergency department in University Hospital, Limerick (UHL). Data collected over a 3-month period from June to August 2017 in which Ondansetron was not used was compared to another 3-month period when Ondansetron was used. Several outcomes were measured including admission to hospital. The rate of admission decreased by 15% [26/74 (35%) in 2017 to 16/81 (20%) in 2019 p = 0.22]. 81 patients received Ondansetron, of which 79% were successfully rehydrated orally. The administration of Ondansetron reduced the need for intravenous fluids and hospital admission overall in these children with AGE. This reduction ultimately accounted for lower costs incurred by the Health Services Executive per patient, and also suggested the anti-emetic use as a cost effective measure for managing and treating patients with AGE.
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Factors associated with zinc prescription practice among children with diarrhea who visited public health facilities in Addis Ababa, Ethiopia: A cross sectional study

Published on: 25th March, 2021

OCLC Number/Unique Identifier: 8984625020

Background: Diarrhea and nutrient deficiency worsen each other, and zinc is recommended to be included in clinical management of diarrhea. Therefore, this investigation was done to assess zinc prescription practice to children with diarrhea, identify factors associated with zinc prescription, and assess caregivers’ zinc’s perceived cost and willingness to pay for. Methods: A health institution based cross-sectional study was done. Caretakers of 609 children with diarrhea attending health centers in Addis Ababa were included. Logistic regression was applied to identify variables associated with zinc prescription. Results: Zinc was prescribed to 62.1% of children. About 74.9% of the caregivers were willing to pay for zinc. Previous use of zinc (AOR = 2.3; 95% CI: 1.34-4.01), exposure to zinc related message (AOR = 2.6, 95% CI: 1.53-4.60) and willingness to pay for zinc (AOR = 6.9; 95% CI: 3.84-12.66) were associated with zinc prescription. Conclusion: Zinc was not administered to considerable proportion of children with diarrhea. Previous use of zinc, exposure to zinc related message and willingness to pay for positively contributed to zinc prescription. Health care workers shall be encouraged on zinc prescription. Intervention to increase willingness to pay for zinc and zinc benefit communication shall be strengthened in parallel with operational researches.
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Efficacy of intravenous immunoglobulins in the prophylaxis of neonatal sepsis

Published on: 14th April, 2021

OCLC Number/Unique Identifier: 9006870046

Despite critical care advances, robust antibiotic therapy and improved strategies in early detection and prevention of infection, the incidence of morbidity and mortality from neonatal sepsis worldwide in preterm and low birth weight neonates remains overwhelmingly high. Neonatal sepsis is characterised by a clinical syndrome of systemic signs of infection and bloodstream bacteraemia in newborns within the first months of life. The risk of sepsis in neonates is inversely proportional to gestational age and birth weight due to deficiency in humoral immunity and the need for more invasive supportive neonatal intensive care unit interventions. Adverse effects such as necrotising enterocolitis associated with antimicrobial therapy are serious enough to warrant exploration of alternative therapeutic strategies. Immunoglobulin replacement therapy offers hope of enhancing immune competence and reducing infection rates in vulnerable populations. It is evident from the relevant studies to date that the benefits offered by intravenous immunoglobulin prophylaxis may not be significant enough for routine hospital implementation. Further research to better understand the mechanisms underlying immunodeficiency will lead to the realisation of alternative therapeutic and prophylactic interventions.
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Medicinal plant extract associated with bacterial cellulose membrane: Antibacterial activity and physicochemical properties

Published on: 4th February, 2020

OCLC Number/Unique Identifier: 8531081943

Burns injuries induce a state of immunodepression that predisposes to a bacterial infectious complication that leads to several comorbid diseases and high mortality rate. Previous studies about anti-inflammatory, antimicrobial and antioxidant properties of Aloe vera (L.) Burm., Calendula officinalis L.and Matricaria recutita L. are acknowledge by antimicrobial effects. Previous studies about anti-inflammatory, antimicrobial and antioxidant properties of Aloe vera (L.) Burm., Calendula officinalis L. and Matricaria recutita L. are knowledge by antimicrobial effects. Bacterial cellulose membrane (nature BCM) is a potential carrier as a drug delivery system in the wound and burn treatment. The present study aimed to evaluate the antibacterial activity of extracts of A. vera, C. officinalis, and M. recutita incorporated in BCM against bacterial strains commonly present in wound and burns. The agar-dilution susceptibility testing was used to determine the minimum inhibitory concentration (MIC) for S. aureus, E. coli, and P. aeruginosa. The standardized extracts of A. vera, M. recutita, and C. officinalis were, respectively, used at 3.25% of total polysaccharides, 1% of apigenin 7-O-glucoside and 0.084% of total flavonoids expressed in quercetin. The BCM incorporated with A. vera extract was efficient to prevent the growth of P. aeruginosa and S. aureus. BCM loaded with C. officinalis inhibited the growth of S. aureus. The BCM loaded with A. vera and C. officinalis extract showed better antibacterial activities against P. aeruginosa and S. aureus and, consequently, properties to prevent infectious disease in the wound or burn caused by these bacteria.
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Anticancer activity of novel surface functionalized metal doped hydroxyapatite

Published on: 3rd June, 2020

OCLC Number/Unique Identifier: 8616336600

In this manuscript it has been described a novel synthesis of mercury doped hydroxyapatite (Hap) and its application on human liver carcinoma cell line (Hep G2) and human lung fibroblast carcinoma cell line (MRC 5). Nano-sized hydroxyapatite doped with Hg2+ was synthesized by a solution based chemical method along with mercury ion. The surface of nanoparticle of mercury doped hydroxyapatite (MHAp) was functionalized by using phosphonomethyl iminodiacetic acid (PMIDA) for making it stable as dispersed phase with negative zeta potential. Surface functionalization was confirmed by FTIR measurements. Crystalline nature, morphology and surface topology were studied by powder XRD, FESEM and AFM measurements. Particle size of the well dispersed sample was obtained by HRTEM image. The studies on cell viability of Hep G2 and MRC 5 cell in presence of mercury doped HAp nanoparticle (MHAp) were determined through WST assay. It was observed that nanocomposite exhibited a site specific action towards MRC 5 cell lines along with reduction of toxicity toward normal cells.
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Clinical picture of pulmonary plague observed in the paediatric wards of antananarivo

Published on: 13th May, 2021

OCLC Number/Unique Identifier: 9272358036

Introduction: In Madagascar, plague is a highly contagious acute endemic infectious disease. The diagnosis of the most severe form of pneumonic plague remains difficult in children, hence the objectives of the present study; which is to identify the clinical signs of this clinical form in children and to describe its epidemiological and evolutionary profile. Methods: A retrospective case-control study was conducted in four pediatric wards in Antananarivo during the urban pneumonic plague outbreak from September 2017 to January 2018. Those cases were defined as children aged 0-15 years old suspected of having plague with positive RDT and PCR, and they were defined as children aged 0-15 years old with negative RDT and PCR. Results: Fifty-two cases of pneumonic plague were identified, half of which (50%) were under 24 months of age. A male predominance was noted with a sex ratio of 1.23 and 86.54% of the patients were from urban areas. Several clinical signs were found but none was specific for pneumonic plague: cough (59.62% p: 0.5), dyspnea (3.85% p: 0.16), chest pain (3.85% p: 0.26%), hemoptysis (7.69% p: 0.17), vomiting (9.62% p: 0.14), diarrhea (11.54% p: 0.45), altered general condition (38.46% p: 0.24%). Two deaths were noted (3.8%). Conclusion: No specific clinical warning signs have been identified in childhood pneumonic plague. In the event of an epidemic of urban pneumonic plague, any bacterial pneumonia should at least initially include active treatment against Yersinia pestis.
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Rapidly involuting congenital hemangioma associated with Kasabach-Merritt Syndrome

Published on: 17th May, 2021

OCLC Number/Unique Identifier: 9272395700

Background: Rapidly involuting congenital hemangioma (RICH) is a rare vascular tumor that is present at birth and involutes during the first year of life. Kasabach-Merritt syndrome (KMS) is a complication of some vascular tumors such as kaposiform hemangioendothelioma and tufted angioma associated with thrombocytopenia and coagulopathy. Results: The case of a 2-month-old infant with a diagnosis of RICH with thrombocytopenia and coagulation disorder, successfully treated with surgical excision without complications or recurrence is presented. Conclusion: The association between RICH and KMS is rare. Histopathological study, immunohistochemistry and ultrasound findings are important for the diagnosis. Brief summary: This report covers the rare association between rapidly involuting congenital hemangioma and Kasabach-Merritt syndrome in a 2-months-old female infant.
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COVID-19 immunologic and toxicological implication: Innate immune sensor and immune escape

Published on: 25th March, 2021

OCLC Number/Unique Identifier: 8980360578

Related COVID-19 and new Variant and treatment like vaccine it is relevant to deeply verify the immunologic implication and in a special way regarding the innate immune sensor system and the evasion of the immune system. This can be crucial to search for new strategies to fight this severe disease under a Toxicology-antidotes point of view. The rapid emergence of a new variant is under study by researchers because some of these show different responses to antibodies as reported in literature (vaccine efficacy?). In this article after a review part it is submitted a collection of hypothesis of solution to contrast COVID-19. Spread and mortality and project hypothesis. A new toxicological approach also in a viral respiratory disease can be a novelty to adequately fight this severe condition and this focusing not only towards specific immunity but also a specific measures. A toxicological approach in drug- vaccine like products designing makes it possible to get the clinical outcomes needed.
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