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Vaccination is of paramount importance to global health. With the advent of the more recent pandemics, the urgency to expand the range has become even more evident. However, the potential limited availability and affordability of vaccines to resource low- and middle-income countries has created a need for solutions that will ensure cost-effective vaccine production methods for these countries. Pichia pastoris (P. pastoris) (also known as Komagataella phaffii) is one of the most promising candidates for expression of heterologous proteins in vaccines development. It combines the speed and ease of highly efficient prokaryotic platforms with some key capabilities of mammalian systems, potentially reducing manufacturing costs. This review will examine the latest developments in P. pastoris from cell engineering and design to industrial production systems with focus on vaccine development and with reference to specific key case studies.
Pichia pastoris (Komagataella phaffii) as a Cost-Effective Tool for Vaccine Production for Low- and Middle-Income Countries (LMICs)
Carfentanil is a powerful synthetic opioid that is approximately 100 times more potent than fentanyl and 10,000 times more potent than morphine. Carfentanil was originally intended to be used as a sedative for big game animals in a veterinary setting, but it is becoming increasingly recognized as a public health concern. We set out to investigate the effectiveness of naloxone against a potentially lethal dose of inhaled carfentanil in male ferrets. Ferrets were implanted with telemetry devices to study cardiac parameters and exposed to aerosolized carfentanil in a whole-body plethysmography chamber to record respiratory parameters. We observed profound respiratory depression in exposed animals, which led to apneic periods constituting 24-31% of the exposure period. Concomitant with these apneic periods, we also observed cardiac abnormalities in the form of premature junctional contractions (PJCs). At our acute exposure dose, lethal in 3% of our animals, na?ve ferrets were unresponsive and incapacitated for a total of 126.1 24.6 minutes. When administered intramuscularly at human equivalent doses (HEDs) of either 5 mg or 10 mg, naloxone significantly reduced the time that ferrets were incapacitated following exposure, although we observed no significant difference in the reduction of time that the animals were incapacitated between the treatment groups. Naloxone was able to quickly resolve the respiratory depression, significantly reducing the frequency of apneic periods in carfentanil-exposed ferrets. Our results suggest that naloxone, when administered via intramuscular injection following incapacitation, is a viable treatment against the effects of a potentially lethal dose of inhaled carfentanil.
Assessment of Naloxone as a Therapeutic for Inhaled Carfentanil in the Ferret
Objective: To evaluate the necessity of Covid-19 vaccination in children aged < 12 y by comparing the clinical characteristics in unvaccinated children aged < 12 y with vaccinated patients aged > 12y during the Delta surge (B.1.617.2) in Putian, Fujian, China. Methods: A total of 226 patients with SARS-Cov-2 Delta variant (B.1.167.2; confirmed by Realtime PCR positive and sequencing) were enrolled from Sep 10th to Oct 20th, 2021, including 77 unvaccinated children (aged < 12y) and 149 people aged > 12y, mostly vaccinated. The transmission route was explored and the clinical data of two groups were compared;the effect factors for the time of the nucleic acid negativization (NAN) were examined by R statistical analysis. Results: The Delta surge in Putian spread from children in schools to factories, mostly through family contact. Compared with those aged; 12y, patients aged < 12y accounted for 34.07% of the total and showed milder fever, less cough and fatigue; they reported higher peripheral blood lymphocyte counts [1.84(1.32,2.71)x 10^9/L vs. 1.31(0.94,1.85)x 10^9/L; p<0.05), higher normal CRP rate (92.21% vs. 57.72%), lower IL-6 levels [5.28(3.31,8.13) vs. 9.10(4.37,15.14); p<0.05]. Upon admission, their COVID19 antibodies (IgM and IgG) and IgG in convalescence were lower [0.13(0.00,0.09) vs. 0.12(0.03,0.41), p<0.05; 0.02(0.00,0.14) vs. 1.94(0.54,6.40), p <0.05; 5.46(2.41,9.26) vs. 73.63 (54.63,86.55), p<0.05, respectively], but longer NAN time (18 days vs. 16 days, p=0.13). Conclusion: Children aged < 12y may be critical hidden spreaders, which indicates an urgent need of vaccination for this particular population.
A need of COVID19 vaccination for children aged <12 years: Comparative evidence from the clinical characteristics in patients during a recent Delta surge (B.1.617.2)
BACKGROUND The main concern with the use of the pipeline embolization device (PED) in treating cerebral aneurysms is the risk of hemorrhagic and thromboembolic complications. OBJECTIVE To investigate if P2Y12 reaction unit (PRU) values are associated with hemorrhagic and thromboembolic complications after treatment with the PED and to find an optimal range of preprocedural PRU values. METHODS Two hundred thirty-one patients with 248 cerebral aneurysms treated with the PED were retrospectively identified. Patients were started on dual-antiplatelet treatment at least 10 days before the intervention. PRU values were checked. Univariate and multivariate logistic regression were performed. Youden Indices were calculated to determine cutoffs for optimal PRU values. RESULTS Mean patient age was 57 years. Mean last preprocedural PRU was 132 (range: 1-382). The combined rate of major hemorrhagic complications (4%) and major thromboembolic complications (5.6%) was 9.6%. Analysis using Youden indices suggested an optimal PRU range of 70 to 150 with higher odds of complications outside this range (P = .01, odds ratio [OR] = 3 [1.2-7.5]). PRU <60 was a significant predictor of hemorrhagic complications (P = .04, OR = 2.45 [1.01-5.9]) and PRU >240 was a significant predictor of any thromboembolic complication (P = .04, OR = 3.6 [1.04-12]) and cerebral thromboembolic complications (P = .02, OR = 4 [1.2-14]). CONCLUSION Target preoperative PRU values should be between 60 and 240 and ideally between 70 and 150. Values below this range and above it carry higher odds of hemorrhagic and thromboembolic complications, respectively.
P2Y12 Reaction Units: Effect on Hemorrhagic and Thromboembolic Complications in Patients With Cerebral Aneurysms Treated With the Pipeline Embolization Device.
In this report, we discovered a new entity named cataract, alopecia, oral mucosal disorder, and psoriasis\like (CAOP) syndrome in two unrelated and ethnically diverse patients. Furthermore, patient 1 failed to respond to regular treatment. We found that CAOP syndrome was caused by an autosomal recessive defect in the mitochondrial membrane\bound transcription factor peptidase/site\1 protease (MBTPS1, S1P). Mitochondrial abnormalities were observed in patient 1 with CAOP syndrome. Furthermore, we found that S1P is a novel mitochondrial protein that forms a trimeric complex with ETFA/ETFB. S1P enhances ETFA/ETFB flavination and maintains its stability. Patient S1P variants destabilize ETFA/ETFB, impair mitochondrial respiration, decrease fatty acid ©\oxidation activity, and shift mitochondrial oxidative phosphorylation (OXPHOS) to glycolysis. Mitochondrial dysfunction and inflammatory lesions in patient 1 were significantly ameliorated by riboflavin supplementation, which restored the stability of ETFA/ETFB. Our study discovered that mutations in MBTPS1 resulted in a new entity of CAOP syndrome and elucidated the mechanism of the mutations in the new disease.
S1P defects cause a new entity of cataract, alopecia, oral mucosal disorder, and psoriasis\like syndrome
The pandemic created by SARS-CoV-2 has caused a shortage in the supplies of N95 filtering facepiece respirators (FFRs), disposable respirators with at least 95% efficiency to remove non-oily airborne particles, due to increasing cases all over the world. The current article reviewed various possible decontamination methods for FFR reuse including ultraviolet germicidal irradiation (UVGI), hydrogen peroxide vapor (HPV), microwave-generated steam (MGS), hydrogen peroxide gas plasma (HPGP), and 70% or higher ethanol solution. HPV decontamination was effective against bacterial spores (6 log10 reduction of Geobacillus stearothermophilus spores) on FFRs and viruses (> 4 log10 reduction of various types of viruses) on inanimate surfaces, and no degradation of respirator materials and fit has been reported. 70% or higher ethanol decontamination showed high efficacy in inactivation of coronaviruses on inanimate surfaces (> 3.9 log10 reduction) but it was lower on FFRs which filtration efficiency was also decreased. UVGI method had good biocidal efficacy on FFRs (> 3 log10 reduction of H1N1 virus) combined with inexpensive, readily available equipment; however, it was more time-consuming to ensure sufficient reduction in SARS-CoV-2. MGS treatment also provided good viral decontamination on FFRs (> 4 log10 reduction of H1N1 virus) along with less time-intensive process and readily available equipment while inconsistent disinfection on the treated surfaces and deterioration of nose cushion of FFRs were observed. HPGP was a good virucidal system (> 6 log10 reduction of Vesicular stomatitis virus) but filtration efficiency after decontamination was inconsistent. Overall, HPV appeared to be one of the most promising methods based on the high biocidal efficacy on FFRs, preservation of respirator performance after multiple cycles, and no residual chemical toxicity. Nonetheless, equipment cost and time of the HPV process and a suitable operating room need to be considered.
Decontamination of respirators amid shortages due to SARS-CoV-2
Aim: To determine the COVID-19 fear level of family physicians during the pandemic working in Sivas and its relationship to their experienced problems. Methods: This descriptive study was delivered to 225 family physicians in Sivas between December-January 2021 via an online survey containing 24 questions of participants' sociodemographic data, the problems they experienced in family medicine, and the COVID-19 Fear Scale. Descriptive statistics and logistic regression analysis were used to analyze the data. Results: A total of 138 family physicians whose mean age was 37.67.3, with 52.2% males and 47.8% females, included. Participants 16.7% had the COVID-19 infection. COVID-19 Fear Scale mean score of 18.36.5, appearing significantly higher in females (19.65.8) than in males (17.26.9). 28.3% of subjects needed taking professional psychological support, on which increase of working period in family medicine and COVID-19 Fear Scale Score and being single had a positive effect. Also, 86.2% experienced primary health care services problems, most frequently ranked as cancer screening, mobile service, and chronic illness follow-up. Conclusion: Necessary psychosocial support should be provided to all healthcare workers, especially family physicians, during the pandemic. So, we recommend authorities take proper precautions to continue without interruption for primary preventive health services. ? 2021, Eurasian Society of Family Medicine. All rights reserved.
Problems experienced by family physicians in sivas during the pandemic period and its relationship with covid-19 fear
OBJECTIVE To determine relationship between the therapeutic effect of repetitive transcranial magnetic stimulation (rTMS) on cognitive impairment and brain derived neurotrophic factor (BDNF), glial cell derived neurotrophic factor (GDNF) levels in treatment resistant depression (TRD). STUDY DESIGN Descriptive study. PLACE AND DURATION OF STUDY Psychiatry Clinic of Konya Beyhekim Training and Research Hospital in Turkey, between June and November 2019. METHODOLOGY The study included 33 TRD patients and 33 healthy subjects. Patients received a total of 20 sessions of rTMS treatment. Serum BDNF and GDNF levels were measured before and after rTMS treatment. Additionally, the severity of depression as well as cognitive functions were assessed at the baseline and after the treatment. RESULTS The rTMS treatment significantly improved depressive and cognitive symptoms in patients with TRD. Although the level of serum BDNF and GDNF increased after rTMS treatment, it was associated with the improvement in symptoms, but not significantly. CONCLUSIONS rTMS treatment contributes to the antidepressant effect by normalising serum BDNF and GDNF levels in patients with TRD. Adding rTMS to antidepressants is, therefore, an appropriate treatment option for depressive patients with cognitive impairment. Key Words: rTMS, BDNF, GDNF, Cognitive function.
Neurotrophic Factor Levels and Cognitive Functions before and after the Repetitive Transcranial Magnetic Stimulation in Treatment Resistant Depression.
An outbreak of severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) infection started in December 2019 in China that resulted in a global health emergency The World Health Organization later named the disease as coronavirus disease 2019 (COVID-19) Currently, there is no effective treatment available and the data are evolving through continuous clinical trials and ongoing research Severe infections present with hypoxemic respiratory failure from acute respiratory distress syndrome as one of the major complications We report two cases of COVID-19 patients who initially presented with moderate to severe symptoms Later, their clinical course worsened despite ongoing treatment with multiple medications such as hydroxychloroquine and azithromycin until they were started on tocilizumab Within a short period after they were administered tocilizumab, their oxygen saturation improved and other inflammatory markers such as D-dimer levels, lactate dehydrogenase, and ferritin levels decreased There is an increase in the amount of research citing the role of various cytokines in the pathophysiology of COVID-19 Targeting the inflammatory mediators in the pathogenesis, especially interleukin-6 pathway inhibitors, would improve overall morbidity and mortality, thus decreasing the burden on healthcare systems
The Role of Interleukin-6 Inhibitors in the Treatment of COVID-19 Infections: A Case Series
The environment in which physicians practice and patients receive care continues to change. Increasing employment of physicians, changing practice models, new regulatory requirements, and market dynamics all affect medical practice; some changes may also place greater emphasis on the business of medicine. Fundamental ethical principles and professional values about the patient-physician relationship, the primacy of patient welfare over self-interest, and the role of medicine as a moral community and learned profession need to be applied to the changing environment, and physicians must consider the effect the practice environment has on their ethical and professional responsibilities. Recognizing that all health care delivery arrangements come with advantages, disadvantages, and salient questions for ethics and professionalism, this American College of Physicians policy paper examines the ethical implications of issues that are particularly relevant today, including incentives in the shift to value-based care, physician contract clauses that affect care, private equity ownership, clinical priority setting, and physician leadership. Physicians should take the lead in helping to ensure that relationships and practices are structured to explicitly recognize and support the commitments of the physician and the profession of medicine to patients and patient care.
Ethical and Professionalism Implications of Physician Employment and Health Care Business Practices: A Policy Paper From the American College of Physicians
Background: The COVID-19 pandemic caused by SARS-CoV-2 has led to disruption of health services globally. I assessed the effect of the ongoing pandemic on the Deliveries and Home Based New Born Care (HBNC) in India. The author is curious and suspects a rise in maternal and neonatal mortality due to possible negative effects of COVID-19 on maternal institutional delivery and HBNC. Hence author decided to find out answer to the research question mentioned as title above. Methods: : I conducted a retrospective cross-sectional comparative study among total numbers of women and newborn who have received delivery and HBNC care at different health facilities in 36 states and union territories across India during the pandemic years with pre-pandemic years (comparing 2020 and 2021(up to May) with previous two years of pre-pandemic era i.e. 2018-2019). The data for the research study is extracted from electronic records of HMIS (health management information system) of MoHFW (ministry of health and family welfare), Govt. of India and analysed with stata and Microsoft office. Results: : The mean number of home deliveries attended by SBA [(Skill Birth Attendant) (Doctor/Nurse/ANM/ Midwife)] during the pandemic year 2021 with total number of observation of 5 months across India was 15491, for years 2020, 2019,2018 it was 16429.25 ,19006.58 , 21317.83 respectively with total number of observation of 12 months across India for these three years. This research study revealed that pandemic years have negative impact on number of home deliveries attended by SBA [(Skill Birth Attendant) (Doctor/Nurse/ANM/ Midwife)]. This research study revealed that pandemic years have negative impact on number of home deliveries attended by SBA [(Skill Birth Attendant) (Doctor/Nurse/ANM/ Midwife)]. There is a decrease of 27.33 % in mean number of home deliveries attended by SBA in 2021 as compared to 2018. Conclusions: : The ongoing COVID-19 pandemic has had negative effects on Deliveries and Home Based New Born Care (HBNC) in India. More research is required to investigate the direct and indirect consequence of the pandemic on birth and provision of HBNC as well as the health facility type which are not performing well in providing respectful maternity care and newborn services during pandemic period. The facility based research analysis is under process by the author which will be available in next version of this article.
What is the impact of COVID-19 pandemic years on Deliveries and Home Based New Born Care in India? (preprint)/ en
Coronavirus Disease 2019 (COVID-19) predominantly involves the respiratory system and shows a wide range of severity. There is a growing body of evidence about the occurrence of thromboembolic events in COVID-19. Case Report: We report the case of a 48-year-old female patient who presented with sudden-onset abdominal pain. Physical examination revealed ascites and tender hepatomegaly. Subsequently, abdominal computed tomography was performed which revealed thrombosis in the hepatic vein and inferior vena cava in keeping with Budd-Chiari Syndrome. The patient was started on low-molecular-weight heparin and supportive care. Clinical improvement was observed over the course of the treatment and the patient was discharged after 10 days from the presentation. Thromboembolic events could be the first manifestation of COVID-19. Early recognition of these complications is crucial for prompt management.
Budd-Chiari Syndrome: A Case Report of a Rare Presentation of COVID-19
Background: Adoptive cell immunotherapies for opportunistic virus in immunocompromised patients using haploidentical memory T cells have shown to be safe and effective. Since severe cases of COVID-19 present a dysregulated immune system with T cell lymphopenia and a hyper-inflammatory state we have proposed that a similar strategy could be proven to be efficient for COVID-19 patients. This is a study protocol of an open-label, multicenter, double-arm, randomized, dose-finding phase I/II clinical trial to evaluate the feasibility, safety, tolerability, and efficacy of the administration of a single dose of allogenic SARS-CoV-2 specific memory CD45RA - T cells and Natural Killer (NK) cells in COVID-19 patients with lymphopenia and pneumonia. The aim of the study is to find efficient treatments for patients with moderate/severe COVID-19. Identification of Specific memory T cells and NK cells: i)Memory T Cells: we first determined the existence of SARS-CoV-2 specific T cells within the CD45RA - T memory cells of the blood of convalescent donors. Memory T cells can respond quickly to the infection and provide long-term immune protection to reduce the severity of the COVID-19 symptoms without inducing classically T cell alloreactivity. Also, CD45RA - memory T cells confer protection for other pathogens the donors encountered in their life. ii)NK cells: we determined the phenotype of NK cells after COVID-19 and the main characteristic of SARS-CoV-2 specific NK population in the blood of convalescent donors, as it has been shown for cytomegalovirus infections. Also, NK cells confer protection for other pathogens the donors encountered in their life. Pilot Phase I- Safety, feasibility, and dose escalation: Between September and November 2020 a phase 1, dose-escalation, single-center clinical trial was conducted to evaluate the safety and feasibility of the infusion of CD45RA - memory T cells containing SARS-CoV-2 specific T cells as adoptive cell therapy against moderate/severe cases of COVID-19. Nine participants with pneumonia and/or lymphopenia and with at least one human leukocyte antigen (HLA) match with the donor were infused. The first three subjects received the lowest dose (1x10 5 cells/kg), the next three received the intermediate dose (5x10 5 cells/kg) and the last three received the highest dose (1x10 6 cells/kg) of CD45RA - memory T cells. Clinicaltrials.gov registration: NCT04578210. Findings: All participants' clinical status measured by National Early Warning Score (NEWS) and 7-category point ordinal scales showed improvement six days after infusion. No serious adverse events were reported. Inflammatory parameters were stabilized post-infusion and the participants showed lymphocyte recovery two weeks after the procedure. Donor microchimerism was observed at least for three weeks after infusion in all patients. Interpretation: This study provides preliminary evidence supporting the idea that treatment of COVID-19 patients with moderate/severe symptoms using convalescent SARS-CoV-2 specific CD45RA - memory T cells is feasible and safe. We did not find dose-liming toxicity. The Recommended Phase 2 dose was 1x10 6 CD45RA - T cells. Phase II- Efficacy: Between January 2021 and July 2021 patients have been enrolled based on the matched with the HLA genotype of the convalescent donors and following the protocol inclusion/exclusion criteria. The primary outcome is the incidence of patient recovery at day 14, defined as normalization of fever and oxygen saturation or lymphopenia recovery. Secondary outcomes are the time to normal level of lymphocytes, the proportion of patients showing clinical improvement at day 7, time to first negative SARS-CoV-2 PCR, the incidence of treatment-related adverse events, duration of hospitalization, time to discharge, time to improvement by one category a 7-point ordinal scale or NEWS score, the proportion of patients requiring intensive care unit, and all-cause mortality. In addition, lymphocyte recovery by multiparametric flow cytometry and donor chimerism by real-time PCR in the experimental arm was monitored weekly during the first month. This study provides preliminary evidence supporting the idea that treatment of COVID-19 patients with moderate/severe symptoms using convalescent CD45RA - memory T cells is safe and feasible. The phase II clinical trial is ongoing to demonstrate efficacy. Figure 1 Disclosures Soria: Celgene: Other: Fees; Gilead: Other: Fees; AbbVie: Other: Fees.
A Phase I/II Dose-Escalation Multi-Center Study to Evaluate the Safety of Infusion of Natural Killer Cells or Memory T Cells As Adoptive Therapy in Coronavirus Pneumonia and/or Lymphopenia: (RELEASE NCT04578210)
SIMPLE SUMMARY: Mints are aromatic herbs with a millenary tradition of use for diverse medicinal purposes since ancient civilizations, and they are still presently used in different clinical practices. Mints have been used since ancient Babylon, but it was in Classical Antiquity that their medical uses flourished, with major contributions from Pliny the Elder. In the Middle Ages, the increased knowledge surrounding mints came from Byzantine physicians, while, in the Modern Age, technological developments allowed the production of mint-based products, such as extracts and essential oils, which have become part of elaborate galenic formulas employed by an increasing number of physicians, and have also stimulated both scientific and artistic interests alike. In present-day medicine, several mints and mint-based products are being researched as potential therapeutic alternatives for many diseases, while also being vastly employed in food and cosmetic industries. ABSTRACT: Mints have been among the most widely used herbs for medicinal purposes since ancient civilizations. They are still presently used for numerous purposes, including non-medicinal, which makes them economically relevant herbs. Information regarding the medical and scientific uses given to mints throughout history are vastly scattered and/or incomplete. The aim of this paper is to provide an extensive descriptive overview of the medical uses given to these herbs, highlighting both the authors in medical culture responsible for their dissemination, as well as their major galenic formulations. Databases on medical science, reference textbooks on medical history, botanics (aromatic herbs), and pharmacognosy were consulted. The use of mints remotes to Classical Antiquity, with major contributions from Pliny the Elder. In the Middle Ages, the increased knowledge surrounding mints came from Byzantine physicians, while, in the Modern Age, technological developments allowed the production of mint-based products which have become part of elaborate galenic formulas employed by an increasing number of physicians, as well as have also stimulated both scientific and artistic interests alike. In present-day medicine, several mints and mint-based products are being researched as potential therapeutic alternatives for many diseases, while also being vastly employed in food and cosmetic industries.
A Descriptive Overview of the Medical Uses Given to Mentha Aromatic Herbs throughout History
Maternal circadian rhythms provide highly important input into the entrainment and programming of fetal and newborn circadian rhythms. The light-dark cycle is an important regulator of the internal biological clock. Even though pregnant women spend a greater part of the day at home during the latter stages of pregnancy, natural light exposure is crucial for the fetus. The current recommended COVID-19 lockdown might dramatically alter normal environmental lighting conditions of pregnant women, resulting in exposure to extremely low levels of natural daylight and high-intensity artificial light sources during both day and night. This article summarizes the potential effects on pregnant woman and their fetuses due to prolonged exposure to altered photoperiod and as consequence altered circadian system, known as chronodisruption, that may result from the COVID-19 lockdown.
Effects of altered photoperiod due to COVID-19 lockdown on pregnant women and their fetuses
As some of the most stable and important structures in our society, colleges and universities are rarely described as nimble Yet, when the COVID-19 pandemic hit in March 2020, institutions across the globe not only shifted within days to online instruction, but many academic researchers also immediately launched efforts to understand the virus, identify treatments, produce medical supplies, and study its impacts While some investigators managed to make progress, other talented researchers lacked timely access to funding for key personnel, lab supplies, and incentives for study participants--the needed fuel for discoveries The urgency of developing more agile research funding mechanisms is considerable, given the size of the academic research enterprise In 2018 alone, U S colleges and universities conducted nearly $80 billion in academic research funded by the federal government, nonprofit organizations, industry, state and local governments, and colleges and universities themselves
A New Way to Distribute Research Seed Funding: Peer Review Without Formal Review
In vitro and in vivo studies suggest that palmitoyl-oleoyl-phosphatidylglycerol (POPG) could help prevent or treat RSV infection.
CD14; lymphocyte antigen 96 (LY96; MD2)
Phenoxazines have gained enormous interest because of their diverse applications in both material science and chemotherapy They exhibit numerous biological activities, ranging from anti-malarial, anticancer, antiviral, antidiabetic, anti-Alzheimer, antioxidant, anti-inflammatory, to antibiotic and many more Actinomycin D, for instance, which embodies a phenoxazine scaffold, displays both antibiotic and anticancer property Phenoxaxines have also found usefulness in organic light-emitting diodes, fluorescent probes and dye-sensitized solar cells Over the years, various research groups have strived for several structural modifications targeting new derivatives of phenoxazines with improved properties This present review highlights the progress, challenges and prospects in medicinal and material applications of phenoxazine moiety to provide greater insight into the development of future derivatives with improved properties
Recent Development in Applications of Synthetic Phenoxazines and Their Related Congeners: A Mini-Review
OBJECTIVES: The Pediatric Emergency Research Network (PERN) was launched in 2009 with the intent for existing national and regional research networks in pediatric emergency care to organize globally for the conduct of collaborative research across networks. METHODS: The Pediatric Emergency Research Network has grown from 5- to 8-member networks over the past decade. With an executive committee comprising representatives from all member networks, PERN plays a supportive and collaborative rather than governing role. The full impact of PERN's facilitation of international collaborative research, although somewhat difficult to quantify empirically, can be measured indirectly by the observed growth of the field, the nature of the increasingly challenging research questions now being addressed, and the collective capacity to generate and implement new knowledge in treating acutely ill and injured children. RESULTS: Beginning as a pandemic response with a high-quality retrospective case-controlled study of H1N1 influenza risk factors, PERN research has progressed to multiple observational studies and ongoing global randomized controlled trials. As a recent example, PERN has developed sufficient network infrastructure to enable the rapid initiation of a prospective observational study in response to the current coronavirus disease 2019 pandemic. In light of the ongoing need for translation of research knowledge into equitable clinical practice and to promote health equity, PERN is committed to a coordinated international effort to increase the uptake of evidence-based management of common and treatable acute conditions in all emergency department settings. CONCLUSIONS: The Pediatric Emergency Research Network's successes with global research, measured by prospective observational and interventional studies, mean that the network can now move to improve its ability to promote the implementation of scientific advances into everyday clinical practice. Achieving this goal will involve focus in 4 areas: (1) expanding the capacity for global randomized controlled trials; (2) deepening the focus on implementation science; (3) increasing attention to healthcare disparities and their origins, with growing momentum toward equity; and (4) expanding PERN's global reach through addition of sites and networks from resource-restricted regions. Through these actions, PERN will be able to build on successes to face the challenges ahead and meet the needs of acutely ill and injured children throughout the world.
The Pediatric Emergency Research Network: A Decade of Global Research Cooperation in Pediatric Emergency Care
OBJECTIVES: To report the postmortem findings of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive individual who died in Lagos (Nigeria) in June 2020 and to investigate the cause, pathogenesis as well as pathological changes noticed during the examination. METHODS: Complete postmortem examination was performed according to standard procedures in a regular autopsy suite using personal protective equipment including N95 masks, goggles and disposable gowns. The diagnosis of coronavirus disease 2019 (COVID-19) was confirmed by real-time reverse transcription polymerase chain reaction (RT-PCR) testing on postmortem nasopharyngeal swabs. RESULTS: A 47-year-old man with a medical history of well controlled hypertension and dyslipidaemia died after long hours of transportation for medical care in a hospital in Lagos. He tested positive for SARS-CoV-2 on ante- and postmortem nasopharyngeal swabs. Autopsy revealed pneumonia with diffuse alveolar damage, disseminated intravascular coagulopathy and hypovolaemic shock. CONCLUSIONS: Autopsy can be performed on decedents who died from or with SARS-CoV-2 infection in a low resource environment such as ours. A standard autopsy room was used while deploying recommended infection prevention control and regular decontamination. The clinical details, autopsy findings such as diffuse alveolar damage and airway inflammation were consistent with a COVID-19 related pathology. While the decedent had controlled co-morbidity, he succumbed to multi-organ failure occasioned by shock and disseminated intravascular coagulopathy.
Full autopsy in a confirmed COVID-19 patient in Lagos, Nigeria C A case report

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