Knowledge and Practices of Disinfectants and Sanitizers Use during COVID-19 Pandemic in Jordan

Background: The use of antimicrobials has been expanded during the COVID-19 pandemic. This study aims to assess the knowledge and practices of disinfectants and sanitizers use among Jordanian people during the (COVID-19) pandemic. Methods: A web-based cross-sectional descriptive questionnaire was distributed across Jordan between August and September 2020. The questionnaire consisted of three sections inquiring about demographics and general characteristics of the surveyed sample, evaluating the respondents' knowledge about disinfectants, as well as respondents' practices. The questionnaire was completed by 403 literate adult respondents. Results: Our results indicate that Jordanian adults have used disinfectants increasingly during the COVID-19 outbreak. Knowledge of our study sample was considerably affected by gender (p=0.044), income (p=0.001), and profession (p<0.001). 80.8% of those participants reported skin-related side effects due to disinfectant use during the pandemic. The most used disinfectants were ethanol, followed by soap and water. Generally, study respondents showed positive practices toward the use of disinfectants during the time of the pandemic with few high-risk practices reported. Interestingly, the positive practices applied by Jordanian adults were minimally and not significantly affected by the knowledge about antimicrobials' safe and effective use. Conclusions: There is an urgent need for a structured effort to increase public awareness regarding the safe and effective use of disinfectants against SARS-CoV-2 transmission. © 2023 DSR Publishers/The University of Jordan.

Correlation between BOD/COD Ratio and Octanol/Water Partition Coefficient for Mixture Organic Compounds

Correlation between the BOD/COD ratio and Partition coefficient of octanol/ water (Pow) on a single organic substance shows that the Pow value is directly proportional to the toxicity level and inversely proportional to BOD/COD ratio. This research examined the correlation to a mixture of organic substances. The objective is to obtain a varied range of substances, as well as determining the quality of wastewater discharging to fresh waters. Need for analysis of organic substances used as antiseptics during the Covid-19 pandemic. In addition, organic substances from the organophosphate pesticide class, diazinon, were used. BOD5, COD, Pow, and LC50-96h toxicity tests using Daphnia magna were used. Six types of the mixture of organic substances included diazinon-formaldehyde-isopropyl alcohol, ethanol-oxalic acid-formaldehyde, isopropyl alcohol-glycerol-lactose, acetic acid-isopropyl alcohol-formaldehyde, sucrose-glycerol-acetic acid, and oxalic acid-formaldehyde-diazinon, with 3 different concentrations of 10, 100, and 1000 mg/L, three repetitions. The lowest BOD/COD ratio (<0.2) and the highest Pow value (>4) are found in diazinon-formaldehyde-IPA. Its toxicity in D. magna also showed the lowest LC-50 (11.82 mg/L). Whereas, sucrose-glycerol-acetic acid had the highest BOD/COD ratio (>0.7) and lowest Pow (<0.7) with the highest LC-50 (567.88 mg/L). Other organic substances mixtures have characteristics in the range of these mixtures. Pow variability and the BOD/COD ratio have a negative correlation. A mixture of organic matter is more biodegradable making it has a higher tendency to dissolve in water.Copyright © 2022 Informatics Publishing Limited and The Society of Toxicology. All rights reserved.

Recovery of Platinum and Palladium from Spent Automotive Catalysts: Study of a New Leaching System Using a Complete Factorial Design

The recovery of materials and energy from end-of-life products is increasingly a fundamental factor in the sustainable development of various countries. Recovering metals from different types of waste is not only a practice in support of the environment, but is also a profitable economic activity. For this reason, exhausted automotive catalysts can become renewable sources of critical raw materials such as Pt, Pd, and Rh. However, recovering Pt and Pd from spent catalysts through an efficient, economical, and green method remains a challenge. This article presents a new leaching process for the hydrometallurgical recovery of Pt and Pd from exhausted automotive catalysts. The leaching solution consists of an aqueous mixture of hydrochloric acid, two organic acids (citric acid and acetic acid) and hydrogen peroxide. A complete factorial plan on two levels (2k) was performed in order to evaluate the main effects of the analyzed factors and their interactions. The factors that were presumed to be the most influential on the leaching of Pt and Pd were the concentrations of the different reagents and the reaction time. The optimal circumstances for achieving the largest recovery (over 80% Pt and 100% Pd) were achieved using the following conditions: a concentration of HCl of 5 M, a concentration of H2O2 of 10% wt./vol., a concentration of C2H4O2 of 10%vol./vol., and a reaction time of 3 h.

Cycloferon as a Means for Prevention, Treatment, and Control of COVID-19: Multidisciplinary and Comparative Historical Aspects.

The study of coronaviruses, including those capable of causing life-threatening diseases, continued for many decades. So did the study of interferons, as well as acridine acetic acid, which is a powerful interferon inducer. For a long time, both directions of research developed in parallel to each other. However, the discovery of SARS-CoV and the creation of Cycloferon based on acridine acetic acid made both research directions converge. To date, the abundance of factual and theoretical tenets is enough to estimate the potential effectiveness of acridine acetic acid against COVID-19.Copyright © Team of Authors, 2022.

A Novel and Robust Analytical Technique for Determining Covid-19 Medications Used in Emergencies

To treat mild to moderate COVID-19, an investigational drug called nirmatrelvir in combination with ritonavir is being researched for which the potential hazards with this are still unknown. Nirmatrelvir has been approved for immediate use by the US Food and drug intake in conjunction with the drug ritonavir for the treatment of mild to medium COVID-19 in grown ups and individuals of more than 12 years who test positive for the virus and are at a high risk to develop severe COVID-19.To quantify the drugs simultaneously in tablet dosage forms, a novel, sensitive and reproducible reverse phase liquid chromatography method has been developed. Thechromatographic separation was performed using Phenomenex (250x4.6mm,5micro particle size) column. The separation and elution were carried out at an ambient temperature using a mobile phase consisting of 0.1% trifluoro acetic acid &acetonitrile in the ratio of 50:50%v/v. The maximum absorbance by UV spectrophotometer shown at wavelength 258.3nm& 271.4nm for nirmatrelvir and ritonavir. Also, 266nm was selected as detector wavelength by a photodiode array detector for the HPLC chromatrographic method.Beer lambert's law obeyed in the linear range of 37.5-225microg/mL(R2=0.9998) for nirmatrelvir and 25-150 microg/mL(R2=0.9994) for ritonavir. The method shows method and system precision with % RSD less than 1%.The percentage mean recovery was found to be 99.9-100.2%& 100.0-100.2%. The LOD 1.5 microg/mL &1 microg/mL values indicates the method sensitivity. The proposed stability indicating method was validated for precision,accuracy, specificity, selectivity, robustness and stability studies according to ICH guidelines.Copyright © 2022, Anka Publishers. All rights reserved.

Transcriptome and metabolome profiling unveils the mechanisms of naphthalene acetic acid in promoting cordycepin synthesis in Cordyceps militaris.

Cordycepin, an important active substance in Cordyceps militaris, possesses antiviral and other beneficial activities. In addition, it has been reported to effectively promote the comprehensive treatment of COVID-19 and thus has become a research hotspot. The addition of naphthalene acetic acid (NAA) is known to significantly improve the yield of cordycepin; however, its related molecular mechanism remains unclear. We conducted a preliminary study on C. militaris with different concentrations of NAA. We found that treatment with different concentrations of NAA inhibited the growth of C. militaris, and an increase in its concentration significantly improved the cordycepin content. In addition, we conducted a transcriptome and metabolomics association analysis on C. militaris treated with NAA to understand the relevant metabolic pathway of cordycepin synthesis under NAA treatment and elucidate the relevant regulatory network of cordycepin synthesis. Weighted gene co-expression network analysis (WGCNA), transcriptome, and metabolome association analysis revealed that genes and metabolites encoding cordycepin synthesis in the purine metabolic pathway varied significantly with the concentration of NAA. Finally, we proposed a metabolic pathway by analyzing the relationship between gene-gene and gene-metabolite regulatory networks, including the interaction of cordycepin synthesis key genes; key metabolites; purine metabolism; TCA cycle; pentose phosphate pathway; alanine, aspartate, and glutamate metabolism; and histidine metabolism. In addition, we found the ABC transporter pathway to be significantly enriched. The ABC transporters are known to transport numerous amino acids, such as L-glutamate, and participate in the amino acid metabolism that affects the synthesis of cordycepin. Altogether, multiple channels work together to double the cordycepin yield, thereby providing an important reference for the molecular network relationship between the transcription and metabolism of cordycepin synthesis.

Cycloferon as a Means for Prevention, Treatment, and Control of COVID-19: Multidisciplinary and Comparative Historical Aspects

The study of coronaviruses, including those capable of causing life-threatening diseases, continued for many decades. So did the study of interferons, as well as acridine acetic acid, which is a powerful interferon inducer. For a long time, both directions of research developed in parallel to each other. However, the discovery of SARS-CoV and the creation of Cycloferon based on acridine acetic acid made both research directions converge. To date, the abundance of factual and theoretical tenets is enough to estimate the potential effectiveness of acridine acetic acid against COVID-19.

Conservative Management of Acquired Tracheo-Esophageal Fistula after Lithium Button Battery Ingestion

Introduction:Acquired tracheo-esophageal fistula (TEF) is a dreaded complication of lithium button battery (LBB) ingestion in the pediatric population. Traditionally acquired TEFs are managed with surgical interventions. Very few case reports have described successful closure of a TEF secondary to LBB with conservative management. There is no reported literature on the use fibrin glue or laser therapy to enhance closure. Here we describe successful conversative management of TEF secondary to LBB and for the first time, attempted trial of fibrin glue and argon laser therapy. Case presentation: 13-month-old female presented to the emergency department with a 3-day history of croupy cough. Neck X ray demonstrated a radio-opaque foreign body suggestive of a button battery. Patient urgently underwent rigid esophagoscopy and found to have a 20 mm lithium battery in the proximal esophagus. The negative pole was facing anteriorly. Battery was retrieved and inspection revealed a Zagar 2 B grade mucosal injury. Site was washed with 0.25% acetic acid. Direct laryngoscopy and bronchoscopy noted significant posterior tracheal wall edema. Patient was kept NPO overnight and an esophagram obtained next day was reassuring. Therefore, diet was advanced as tolerated and patient discharged next day with plan to repeat esophagram in 2 weeks and endoscopy in 4 weeks. Patient presented 3 days later with drooling, coughing, nasal congestion. She tested positive for SARS Covid 19 PCR on admission. Esophagram at admission noted irregularity and distension of the proximal esophagus with persistent focal outpouching. Patient was kept strict NPO and a repeat esophagram 24 hours later showed large volume aspiration associated with excessive coughing. A nasogastric tube was placed, and tube feedings initiated. Esophogastroduodenoscopy (EGD) was delayed by 1 week due to COVID positive status and upper respiratory symptoms. Initial EGD demonstrated purulent exudates in proximal esophagus and a 6 mm fistulous opening surrounded by ulcerated margins. Bronchoscopy confirmed tracheal end of fistula in addition to posterior tracheal wall ulceration. A fiber-optic scope was used to advance the endotracheal tube so that its distal end was positioned beyond the inflamed mucosa. Patient was kept intubated and sedated, on IV antibiotics and PPI, and on NG tube feeds in the ICU. Repeat scope 7 days post TEF diagnosis showed a 4 mm fistula with healing of the ulcerated mucosa. Fibrin glue was injected into the fistula from the tracheal side in an attempt to close the TEF, but this was unsuccessful and lead to dislodgment of fibrin glue into airway creating a foreign body which necessitated endoscopic retrieval. EGD, 14 days after diagnosis of TEF demonstrated a fistula now ~ 3 mm wide. Argon plasma coagulation (APC) probe (Beamer unit flow of 0.5 L/min,15 W) was directed at the mucosa lining the esophageal end of the fistula with an aim to promote healing by secondary intention. At 21 days post TEF diagnosis complete closure of the fistula was demonstrated on EGD and bronchoscopy and the per-operative esophogram was reported as normal. Patient was discharged 5 days later tolerating an age-appropriate diet. A follow-up esophogram 2 weeks later was reassuring. Patient was asymptomatic on clinical follow up visit 4 weeks from discharge. Discussion(s): Acquired TEF secondary to LBB ingestion is traditionally managened through endoscopic or open surgical repair. However, these procedures can be complicated by high rates of recurrent laryngeal nerve injury, tracheal stenosis, recurrent fistula, and mortality. Thus, experts have started to advocate the use of esophageal rest as conservative management of acquired TEF to permit closure by secondary intention. Five pediatric cases to date have reported sustained closure of TEF secondary to LBB with conservative management including strict NPO status and tube feeds/parenteral nutrition. The duration of healing has varied from 4 -11 weeks. We documented successful healing of acquired TEF within 21 days of initial diagnosis making it the shortest recovery period to date. We report the use of argon plasma coagulation at low settings to produce controlled heat coagulation at the fistula site in order to expose the submucosa and enhance healing by secondary intention. Successful closure of congenital TEF have been reported with injection of fibrin glue into the fistulous tract but this technique may not work for acquired TEF because of surrounding inflammation and a patulous tract. We opted to keep our patient sedated and intubated for 2 weeks to minimize movement, and promote healing of the TEF, but risk vs benefit needs to be weighed on a case-to-case basis. In conclusion, conservative management of acquired TEF is a feasible first step and may be considered before opting for surgical repair. Use of APC at low setting may reduce duration of closure of acquired TEF but high-powered, multi-center studies are needed.

Comparison of abiraterone acetate and prednisolone (AAP) or combination enzalutamide (ENZ) + AAP for metastatic hormone sensitive prostate cancer (mHSPC) starting androgen deprivation therapy (ADT): Overall survival (OS) results of 2 randomised phase III trials from the STAMPEDE protocol

Background: AAP or ENZ added to ADT improves outcomes for mHSPC. Any benefit of combining ENZ & AAP in this disease setting is uncertain. Methods: STAMPEDE is a multi-arm, multi-stage (MAMS), platform protocol conducted at 117 sites in the UK & Switzerland. 2 trials with no overlapping controls randomised mHSPC patients (pts) 1:1 to ADT +/- AAP (1000mg od AA + 5mg od P) or AAP + ENZ (160mg od). Treatment was continued to progression. From Jan 2016 docetaxel 75mg/m2 3-weekly with P 10mg od was permitted + ADT. Using meta-analysis methods, we tested for evidence of a difference in OS and secondary outcomes (as described previously: failure-free, metastatic progression-free, progression-free & prostate cancer specific survival) across the 2 trials using data frozen 3 Jul 2022. All confidence intervals (CI) 95%. Restricted mean survival times (RMST) restricted to 84 months (m). Results: Between Nov 2011 & Jan 2014, 1003 pts were randomised ADT +/- AAP & between Jul 2014 & Mar 2016, 916 pts were randomised ADT +/- AAP + ENZ. Randomised groups were well balanced across both trials. Pt cohort: age, median 68 years (yr), IQR 63, 72;PSA prior to ADT, median 95.7 ng/ml, IQR 26.5, 346;de novo 94%, relapsed after radical treatment, 6%. In AAP + ENZ trial, 9% had docetaxel + ADT. OS benefit in AAP + ENZ trial, HR 0.65 (CI 0.55‒0.77) p = 1.4×10-6;in AAP trial, HR 0.62 (0.53, 0.73) p = 1.6×10-9. No evidence of a difference in treatment effect (interaction HR 1.05 CI 0.83‒1.32, p = 0.71) or between-trial heterogeneity (I2 p = 0.70). Same for secondary end-points. % (CI) of pts reporting grade 3-5 toxicity in 1st 5 yr: AAP trial, ADT: 38.5 (34.2-42.8), + AAP: 54.4 (50.0-58.8);AAP + ENZ trial, ADT: 45.2 (40.6 – 49.8), + AAP + ENZ: 67.9 (63.5 – 72.2);most frequently increased with AAP or AAP + ENZ = liver derangement, hypertension. At 7 yr in AAP trial (median follow-up: 95.8m), % (CI) pts alive with ADT: 30 (26, 34) versus with ADT + AAP: 48 (43, 52);RMST: ADT: 50.4m, ADT + AAP: 60.6m, p = 6.6 x 10-9. Conclusions: ENZ + AAP need not be combined for mHSPC. Clinically important improvements in OS when adding AAP to ADT are maintained at 7 yr. Clinical trial identification: NCT00268476. Legal entity responsible for the study: Medical Research Council Clinical Trials Unit at University College London. Funding: Cancer Research UK, Medical Research Council, Janssen, Astellas. Disclosure: G. Attard: Financial Interests, Personal, Invited Speaker: Janssen, Astellas, AstraZeneca;Financial Interests, Personal, Advisory Board: Janssen, Astellas, Novartis, Bayer, AstraZeneca, Pfizer, Sanofi, Sapience, Orion;Financial Interests, Personal, Royalties, Included in list of rewards to discoverers of abiraterone: Institute of Cancer Research;Financial Interests, Institutional, Research Grant: Janssen, Astellas;Non-Financial Interests, Principal Investigator: Janssen, Astellas;Non-Financial Interests, Advisory Role: Janssen, AstraZeneca. W.R. Cross: Financial Interests, Personal, Invited Speaker, Speaker fee: Myriad Genetics, Janssen, Astellas;Financial Interests, Personal, Advisory Board, Advisory Board fee: Bayer;Financial Interests, Institutional, Research Grant, Research grant: Myriad Genetics. S. Gillessen: Financial Interests, Personal, Advisory Board, 2018: Sanofi, Roche;Financial Interests, Personal, Advisory Board, 2018, 2019: Orion;Financial Interests, Personal, Invited Speaker, 2019 Speaker's Bureau: Janssen Cilag;Financial Interests, Personal, Advisory Board, 2020: Amgen;Financial Interests, Personal, Invited Speaker, 2020: ESMO;Financial Interests, Personal, Other, Travel Grant 2020: ProteoMEdiX;Financial Interests, Institutional, Advisory Board, 2018, 2019, 2022: Bayer;Financial Interests, Institutional, Advisory Board, 2020: Janssen Cilag, Roche, MSD Merck Sharp & Dohme, Pfizer;Financial Interests, Institutional, Advisory Board, 2018: AAA International, Menarini Silicon Biosystems;Financial Interests, Institutional, Advisory Board, 2019, 2020: Astellas Pharma;Financial Interests, Institutional, Advisory B ard, 2019: Tolero Pharmaceuticals;Financial Interests, Personal, Invited Speaker, 2021, 2022: SAKK, DESO;Financial Interests, Institutional, Advisory Board, 2021: Telixpharma, BMS, AAA International, Novartis, Modra Pharmaceuticas Holding B.V.;Financial Interests, Institutional, Other, Steering Committee 2021: Amgen;Financial Interests, Institutional, Advisory Board, 2021, 2022: Orion, Bayer;Financial Interests, Personal, Invited Speaker, 2021: SAKK, SAKK, SAMO - IBCSG (Swiss Academy of Multidisciplinary oncology);Financial Interests, Personal, Advisory Board, 2021: MSD Merck Sharp & Dhome;Financial Interests, Personal, 2021: RSI (Televisione Svizzera Italiana);Financial Interests, Institutional, Invited Speaker, 2021: Silvio Grasso Consulting;Financial Interests, Institutional, Other, Faculty activity 2022: WebMD-Medscape;Financial Interests, Institutional, Advisory Board, 2022: Myriad genetics, AstraZeneca;Financial Interests, Institutional, Invited Speaker, 2022: TOLREMO;Financial Interests, Personal, Other, Travel support 2022: AstraZeneca;Financial Interests, Institutional, Funding, 2021, Unrestricted grant for a Covid related study as co-investigator: Astellas;Non-Financial Interests, Advisory Role, 2019: Menarini Silicon Biosystems, Aranda;Non-Financial Interests, Advisory Role, Continuing: ProteoMediX. C. Pezaro: Financial Interests, Personal, Advisory Board, Ad board Dec 2020: Advanced Accelerator Applications;Financial Interests, Personal, Advisory Board, Aug 2021: Astellas;Financial Interests, Personal, Advisory Board, Oct 2021: Bayer;Financial Interests, Personal, Invited Speaker, Sept-Oct 2020: AstraZeneca;Financial Interests, Personal, Invited Speaker, Oct 2020: Janssen;Financial Interests, Personal, Advisory Board, July-Sept 2022: Pfizer. Z. Malik: Financial Interests, Personal, Advisory Board, advisry board for new hormonal therapy for breast cancer: sanofi;Financial Interests, Institutional, Invited Speaker, research grant for CHROME study: sanofi;Other, Other, support to attend meetings or advisory boards in the past: Astellas,Jaansen,Bayer;Other, Other, Sponsorship to attend ASCO meeting 2022: Bayer. M.R. Sydes: Financial Interests, Personal, Invited Speaker, Speaker fees at clinical trial statistics training sessions for clinicians (no discussion of particular drugs): Janssen;Financial Interests, Personal, Invited Speaker, Speaker fees at clinical trial statistics training session for clinicians (no discussion of particular drugs): Eli Lilly;Financial Interests, Institutional, Research Grant, Educational grant and drug for STAMPEDE trial: Astellas, Janssen, Novartis, Pfizer, Sanofi;Financial Interests, Institutional, Research Grant, Educational grant and biomarker costs for STAMPEDE trial: Clovis Oncology. L.C. brown: Financial Interests, Institutional, Research Grant, £170k educational grant for the FOCUS4-C Trial from June 2017 to Dec 2021: AstraZeneca;Financial Interests, Institutional, Funding, Various grants awarded to my institution for work undertaken as part of the STAMPEDE Trial: janssen pharmaceuticals;Non-Financial Interests, Other, I am a member of the CRUK CERP funding advisory panel and my Institution also receive grant funding from CRUK for the STAMPEDE and FOCUS4 trials: Cancer Research UK. M.K. Parmar: Financial Interests, Institutional, Full or part-time Employment, Director at MRC Clinical Trials Unit at UCL: Medical Research Council Clinical Trials Unit at UCL;Financial Interests, Institutional, Research Grant: AstraZeneca, Astellas, Janssen, Clovis;Non-Financial Interests, Advisory Role, Euro Ewing Consortium: University College London;Non-Financial Interests, Advisory Role, rEECur: University of Birmingham;Non-Financial Interests, Advisory Role, CompARE Trial: University of Birmingham. N.D. James: Financial Interests, Personal, Advisory Board, Advice around PARP inhibitors: AstraZeneca;Financial Interests, Personal, Advisory Board, Prostate cancer therapies: Janssen, Clovis, Novartis;Financial Interests, Institutional, Expert Testimony, Assisted with submissions regarding licencing for abiraterone: Janssen;Financial Interests, Personal, Advisory Board, Docetaxel: Sanofi;Financial Interests, Institutional, Expert Testimony, Providing STAMPEDE trial data to facilitate licence extensions internationally for docetaxel: Sanofi;Financial Interests, Personal, Advisory Board, Bladder cancer therapy: Merck;Financial Interests, Personal, Advisory Board, Advice around novel hormone therapies for prostate cancer: Bayer;Financial Interests, Personal, Invited Speaker, Lecture tour in Brazil August 2022 - speaking on therapy for advanced prostate cancer: Merck Sharp & Dohme (UK) Limited;Financial Interests, Institutional, Invited Speaker, Funding for STAMPEDE trial: Janssen, Astellas;Financial Interests, Institutional, Invited Speaker, Funding for RADIO trial bladder cancer: AstraZeneca. All other authors have declared no conflicts of interest.

Immunostimulating Study of Active Agent Fraction from Sungkai (Peronema canescens Jack.) Leaf from SARS-COV-2 Virus Antigen Exposure to NK and CD8+T Cells

Introduction: Sungkai (Peronema canescens Jack.) plant had been used as an immune system enhancer. Aim: In this study, the effect of Sungkai leaf extracts from 4 different fractions, namely n-hexane, ethyl acetate, butanol and residual water with 3 variations in doses of 1,10 and 100 mg/kg bw on the activity of NK and CD8+T cells in male white mice that have been exposed to SARS-Cov-2 virus antigen was investigated. Methods: The experimental animals used were 60 animals divided into 12 groups with 14 days of treatment which had previously been induced with SARS-Cov-2 virus antigen (Moderna) and given with Sungkai leaf extracts for 14 days and evaluated on day 15. The evaluation results of NK cells concentrations sequentially were 2.96;4.66;5.38;5.43;4.05;2.89;3.56;4.21;2.88;1.99;2.07;4.40;3.21;3.40;and 6.93 ng/ml. On the other hand, the evaluation results of CD8+T cells concentrations sequentially were 27.47;28.96;29.19;27.90;21.85;25.79;27.98;23.50;23.39;26.56;22.62;25.19;23,55;26,75;and 29,69 ng/ml. One-way ANOVA and Duncan test were used for the data analysis. Results: The results showed significant increase of concentration (p<0.05) towards concentration of NK cells in the butanol fraction at a dose of 1 mg/kg BW and CD8+T cells in the residual water fraction at a dose of 100 mg/kg BW. Conclusion: It can be concluded that fraction from sungkai (Peronema canescens Jack.) at doses of 1,10 and 100 mg/kg bw shows immunostimulatory activity.

The Effectiveness of Pap and Visual Inspection With Acetic Acid (VIAA) Tests in Cervical Dysplasia Screenings During the COVID-19 Pandemic.

Objective This study was aimed at analyzing the validity and reliability of the Papanicolaou (Pap) test and visual inspection with acetic acid (VIAA) tests for cervical dysplasia screenings during the COVID-19 pandemic. Material and methods This was a retrospective study of patients 21 years or older seen at the Luis Negreiros Primary Care Center in Lima, Peru between 2020 and 2021, who underwent cervical dysplasia screening (Pap or VIAA). Relevant information regarding patient age, date of service, and Pap and VIAA results were collected. Parallel form reliability was analyzed with chi-square tests, and phi, contingency and Cramer's V coefficients. The validity of these tests was analyzed through the calculation of the sensitivity, specificity, and positive and negative predictive values with confidence intervals. A p-value less than 0.05 indicated statistical significance. Results From 4,503 records, the sensitivity, specificity, and positive and negative predictive values for Pap were 0.87 (0.81-0.92), 1.0 (1.0-1.0), 1.0 (1.0-1.0) and 0.99 (0.98-0.99), respectively, and those for VIAA were 0.22 (0.14-0.31), 0.10 (0.10-0.10), 0.53 (0.38-0.69) and 0.10 (0.10-0.10), respectively. Test validity varied slightly according to patient age and the year of testing. The correlation, although significant, was inverse; chi-square = 39.18, p <0.001, phi = -0.60, contingency = 0.51 and Cramer's V = -0.59. Conclusion The validity and reliability of Pap testing and VIAA for cervical dysplasia screening significantly decreased during the COVID-19 pandemic. The correlation between these tests, although significant, was inverse. More larger-scale studies are needed to confirm these findings and understand the reasons underlying the decreased effectiveness of these tests.

Polymer Membranes for Enthalpy Exchangers

A membrane-based enthalpy exchanger is a device used for heat and humidity recovery in ventilated buildings. The energy-saving potential of such a device is dependent on the parameters responsible for heat and moisture recovery. The trend is toward composite membranes, which are custom produced, and their parameters can be adjusted for a given application;therefore, the diffusion and sorption characteristics of such membranes are unknown. In order to obtain the values of the water vapor diffusivity of three investigated handmade membranes, a serial resistance model using a Field and Laboratory Emission Cell (FLEC) is proposed. Experiments were conducted to identify the resistance in each step of the moisture transfer process to extract the moisture diffusivity in the membranes. The calculated moisture diffusivities in the membranes were 8.99 × 10−12 (m2/s) for the membranes from cellulose acetate, 1.9 × 10−10 (m2/s) for the microporous PE/PUR membranes, and 1.53 × 10−11 (m2/s) for the PET/PUR microfibrous membranes. The obtained membrane diffusivities were then used in the proposed effectiveness-NTU-based model of an exchanger with a cross-flow arrangement to predict performance under various operating conditions. The results show that the highest latent effectiveness was found for the exchanger core made from the PE/PUR membrane and the lowest was for the one with the PE/PUR membrane core.

Cervical cancer prevention program in Nepal: A comprehensive “train the trainer” approach

Background: Cervical cancer is the leading cause of cancer and cancer-related deaths among women in Nepal, due in part to a lack of access to screening and limited medical providers trained to diagnose and treat women with preinvasive cervical disease. Cancer Care Nepal has partnered with The University of Texas MD Anderson Cancer Center (MD Anderson) and the American Society of Clinical Oncology (ASCO) to implement a 'train the trainer' (TOT) program to teach visual inspection with acetic acid (VIA), colposcopy, cervical biopsy, cryotherapy, thermal ablation, and loop electrosurgical excision procedure (LEEP). Methods: An initial cervical cancer prevention course was held in Kathmandu, Nepal in November 2019, supported by ASCO and with faculty from Civil Service Hospital, Bhaktapur Cancer Hospital, and National Academy of Medical Sciences and MD Anderson. As a continuation of this program, a TOT course was implemented for local specialists from five participating institutions throughout Nepal to learn how to deliver these trainings. Each participating institution then holds their own local course for nurses and doctors in their region. The training is complemented with monthly Project ECHO (Extension for Community Healthcare Outcomes) telementoring videoconferences. Results: The program was launched in November 2021. To date, two TOT training courses (2-day duration) have been held for clinicians from the 5 participating regions. Due to COVID-19 pandemic travel restrictions, didactic lectures were held virtually with MD Anderson and ASCO staff and included epidemiology of cervical cancer, screening guidelines, colposcopy, and treatment of cervical dysplasia. This was followed by hands-on training using simulation models to teach VIA, colposcopy, ablation and LEEP, led by the Nepalese faculty who had participated in the 2019 course. There were 41 participants in total (23 in the first course and 18 in the second course), including 21 gynecologists, 4 gynecologic oncologists, 1 medical oncologist, 1 general practitioner, and 14 nurses. 39 participants (73%) completed both the pre-and post-survey results. 86% of respondents from the first course and 100% of respondents from the second course reported that they intended to change their practice as a result of knowledge gained from the course. In addition, Cancer Care Nepal became a new hub for Project ECHO and held its first session in January 2022, with 20 participants representing two regions. The specialists from each of the 5 participating sites will be holding local courses for doctors and nurses in their respective regions throughout 2022. Conclusions: Our work shows that the TOT strategy can widen the reach of training in cervical cancer prevention in Nepal. Despite travel restrictions during the COVID-19 pandemic, global health training and mentoring can continue, though they require adaptions and use of virtual platforms.

Volatile Chemical Profile of Ethanol-based Hand Sanitizer Marketed in Brazil by HS-SPME/GC-MS

Aims: This study aims to determine the volatile chemical profile of ethanol-based hand sanitizer marketed in Brazil by HS-SPME/GC-MS. Background: Ethanol-based hand sanitizer has been used to protect against coronavirus disease (COVID-19). In general, these formulations are prepared using a carbomer. In 2020 and 2021, the production of hand sanitizer has increased due to the COVID-19 epidemic. Therefore, it is important to know the composition of this formulation because certain molecules present in some alcoholic mixtures can cause health problems. Methods: Ethanol-based hand sanitizer, AL1, AL2, BL1, CL1, DL1, EL1, FL1, and GL1 (ethanol derivative of fuel station), was purchased from manufacturers commercialized in Araguaína-TO and analyzed by HS-SPME/GC-MS for determining volatile chemical profile. Results: The analyses showed different compositions for the ethanol-based hand sanitizers. Samples AL1 and AL2 contained isopropyl alcohol, ethyl acetate, benzene, ethane-1,1-diethoxy, limonene, and other compounds. Linear alkanes were also detected. Only ethyl acetate and ethane-1,1-diethoxy were detected in CL1, in addition to ethanol. Thus, it is the most suitable sample among those analyzed. The presence of benzene, alkanes, and other hydrocarbons may be associated with the use of fuel ethanol to prepare these sanitizers, as shown in the sample GL1. Benzene, xylene, and toluene were found in FL1. This sample is the most contaminated among those analyzed. Conclusion: The chemical profile of commercial ethanol-based hand sanitizer from eight different samples sold in Araguaína-Brazil was established by GC-MS. Compounds like benzene and other alkanes were found in some samples. These results suggested possible contamination by alcohols unqualified in producing pharmaceutical substances. These analyzes are particularly relevant due to the pandemic situation to avoid COVID-19 proliferation. Benzene and other alkanes are harmful to human health and should be avoided in hand sanitizer production.

Hematopoietic Stem/Progenitor Cells and Engineering: HALF-TRUTH: GRAFT CRYOPRESERVATION DOES NOT IMPACT ENGRAFTMENT AFTER ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANT (ALLO-HCT)-A SINGLE CENTER EXPERIENCE FROM INDIA

Background & Aim: Background: Traditionally, ‘fresh’ Hematopoietic progenitors cell (HPC) infusions have been preferred over cryopreserved HPC in Allo-HCT because cryopreservation and thawing leads to cell loss, besides DMSO-related adverse reactions in patients. Emergence of COVID-19 pandemic has severely affected fresh HPC infusions and most professional bodies recommend cryopreservation of HPC products before initiating conditioning chemotherapy. Although some western studies suggest no significant impact of graft manipulation on patient outcome, there is no available data from the developing world.Aim: We compare neutrophil and platelet engraftment in patients undergoing Allo-HCT with fresh and cryopreserved HPC products. Methods, Results & Conclusion: Material and Method: Allo-HCT data from October 2018 to October 2021 were analyzed. Cryopreservation was performed by controlled-rate freezing using 10% DMSO, plasmalyte- A and human albumin ( 1:2:1) as cryoprotectant. Cryopreserved products were stored in vapour-phase of Liquid nitrogen tank. CD34+ enumeration and viablity( by 7-AAD) was done on Flow-cytometry on fresh and post-thaw HPC samples. Neutrophil engraftment was defined as absolute neutrophil count >0.5 ×109/L for 3 days. Platelet engraftment was defined as independence from platelet transfusion for at least 7 days with a platelet count >20 × 109/L. Statistical analysis using Wilcoxon Rank Sum test. Results: Ninety-six patients underwent allo-HCT (46 received fresh and 50 received cryopreserved HPC products) (Table 1). There was no significant difference in neutrophil engraftment with fresh and cryopreserved grafts (p>0.05) in different types of transplants( Matched related/unrelated and haploidentical). 22% (11/50) of cryopreserved graft infusions were associated with Grade-1 DMSO-related adverse reactions, which were managed with symptomatic treatment. Cryopreservation increased the cost of related allogeneic transplants by USD1100. No cryopreserved HPC product was culture positive on microbiological assessment. Conclusion: In our experience, the engraftment kinetics were similar with fresh and cryopreserved HPC products as CD34+cell dose administered was almost the same. Cryopreserved grafts had a median 7% CD34+cell loss, associated with mild DMSO-related adverse reactions and cost increment. Even though, graft cryopreservation is a feasible alternative during the pandemic, it is crucial to ensure graft quality and promptly manage DMSO-related adverse reactions.(Table Presented) Table 1 Comparison of Fresh and cryopreserved HPC products in Allo-HCT

Hematopoietic Stem/Progenitor Cells and Engineering: 20-YEAR HEMATOPOIETIC PROGENITOR CELL STABILITY – THE MAYO CLINIC EXPERIENCE

Background & Aim: Hematopoietic progenitor cells (HPCs) are infused for hematopoietic reconstitution in the setting of malignancy and inherited or acquired hematological deficiencies. Given the global COVID-19 pandemic, the recommendation was made to cryopreserve all allogeneic HPCs to protect recipients by allowing for subclinical cases of infection to present prior to infusion. As such, consideration of HPC stability programs (SP) and their rigor has risen. The goal of a SP is to prove the rigor of a transplant program’s cryopreservation and storage standard operating procedures so that sufficient HPC viability and potency are maintained for engraftment. SPs are also required by accreditation agencies such as AABB and FACT. Many HPC SP have validated product expirations out to 10 years. Here we share our SP to 20 years with ongoing validation for 30-year expiration. Methods, Results & Conclusion: Program Design: Current testing frequency of our SP is within the first year, and then at three-year intervals (3, 6, 9, 12, 15, 19, 21). Our rolling SP includes 2 additional (Figure Presented) Fig. 1.Current vs proposed HPC product testing and cryopreseveration schema. samples tested at 0, 5, & 9 years, then at 3-year intervals (12, 15, 19, 21, 24, 27, 30). SP samples are collected from donors requiring additional days to reach their goal but are in excess at the conclusion of collection (e.g., Day 1 collection 4.5e6 CD34+ cells/Kg, goal 5e6 CD34+ cells/ Kg). Samples are collected on a quarterly basis with ten 1mL cryovials being drawn (Figure 1). CD3+ and CD34+ viabilities are tested after cryopreservation with an acceptable threshold set at ≥75% for both. Conclusion: We are validating our SP up to 20 years with intention to validate to 30 years. Thus far, our SP reveals product age has no to low correlation with engraftment, suggesting maintenance of potency over time in a cryopreservative of 10% DMSO, 10% plasma, and 30% PlasmaLyte-A with a final cell concentration of ≤3×108 NC/mL (Figure 2). Successful engraftment has been seen in all recipients. Transplant programs should modify testing frequency, acceptance criteria, and product expiration to meet individual need while working towards standardization in the field. Given the frequency of DLIs and 2nd/3rd transplants at the Mayo Clinic, a 30-year SP reflects the need of our transplant program.(Figure Presented)Fig. 2 . ANC and platelet engraftment dates for ≥10-year-old HPC products

LONGITUDINAL MULTI-OMICS REVEALS MECHANISMS UNDERLYING BENEFICIAL EFFECTS OF A NOVEL MICROBIOME IMMUNITY FORMULA (SIM01) IN COVID-19 PATIENTS

Introduction: Gut dysbiosis is associated with immune dysfunction and severity in COVID- 191-2. This study aimed to determine targeting dysbiosis as a therapy and its effect on antibody formation, gut dysbiosis and immune profile in patients with COVID-19. Material & Methods: In an open-label study, 25 consecutive hospitalized patients with COVID- 19 received a novel microbiome immunity formula (SIM01) for 28 days;30 patients who did not receive the intervention acted as controls. We collected fecal and blood samples at baseline and week 5 and followed subjects from admission up to five weeks. We performed multi-omics analysis using data from peripheral blood mononuclear cell (PBMC) transcriptome, fecal metagenomic sequencing and fecal metabolomic profiling (Figure 1A). Results: Significantly more COVID-19 patients on SIM01 developed anti-SARS-CoV-2 IgG than the control group at 2 weeks (Figure 1B). Patients on SIM01 (but not controls) showed a significant reduction of plasma levels of interleukin (IL)-6, macrophage colony-stimulating factor (M-CSF), tumour necrosis factor (TNF-a), IL-1RA (Figure 1C) and downregulated COVID-19 related signalling pathway in PBMC at Week 5. Fecal samples of subjects on SIM01 were enriched in commensal bacteria and reduced in opportunistic pathogens at week 4 and 5. Elevated plasma acetic acid in SIM01 group showed a negative correlation with SARS-CoV-2 viral load in nasopharyngeal samples (Figure 2A). Increased relative abundance of Bifidobacteria adolescentis and Coprococcus comes in fecal samples in SIM01 group positively correlated with plasma acetic acid levels (Figure 2B). Conclusion: We showed for the first time a novel microbiome formula SIM01 was effective in hastening antibody formation against SARS-CoV-2, reduced pro-inflammatory immune markers and restored gut dysbiosis in hospitalised COVID-19 patients. References: 1. Zuo T, Zhang F, Lui GCY, et al. Alterations in gut microbiota of patients with COVID-19 during time of hospitalization. Gastroenterology 2020;159:944-955 e8. 2. Yeoh YK, Zuo T, Lui GC, et al. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID- 19. Gut 2021;70:698-706. (Figure Presented) (Figure Presented)

EVALUATING HPV TESTING for CERVICAL CANCER SCREENING in FOUR COUNTRY'S HIV PROGRAMS

Background: Cervical cancer disproportionately affects women in resource-limited settings, as access to secondary prevention is currently limited. Women living with HIV (WLHIV) are at increased risk of human papillomavirus (HPV) infection and once infected are at greater risk of progression to cancer;therefore, timely screening and treatment is of utmost concern. The goal of the pilots was to introduce integrated HPV testing using existing NAT platforms in public health HIV programs in sub-Saharan Africa and describe the cascade of care. Methods: Observational, prospective pilot studies were conducted across 32 facilities in Malawi, Nigeria, Uganda, and Zimbabwe between September 2019 and April 2021. All countries except Zimbabwe utilized near-point-of-care (POC) devices for HPV testing. Zimbabwe conducted testing on platforms at a centralized laboratory;Uganda conducted HPV testing on both near-POC and centralized platforms. Self-collected sampling was offered as an alternative to clinician-sampling in Malawi, Nigeria, and Uganda. The target population was WLHIV;age-inclusion criteria followed country guidelines, ranging from 25-49 years. All women identified as HPV-positive were to receive visual inspection with acetic acid (VIA), and if pre-cancerous or cancerous lesions were evident, receive treatment or referral. Results: Across the four countries, 14155 tests were conducted, with 4% of tests invalid and 5% missing results, leaving 12962 valid results (Table). HPV prevalence was 35%. 66% of HPV-positive women received their result (median time to result: 34 days, interquartile range: 7-64). Among women who received VIA, 584 (22%) were VIA-positive and among those 86% received treatment (70% on same-day as VIA). 30 (1%) were suspected of cancer and of those 80% had a documented referral for tertiary care. In Uganda, 53% of HPV-positive women tested at centralized laboratory received VIA versus 73% of women tested on near-POC devices (p=0.07). Conclusion: HPV testing was found to be feasible across the four pilot countries in a public health setting. While many women did not receive their HPV results, these pilots were conducted during COVID-19, where lockdowns and other disruptions to health-seeking behavior were major barriers. Once women did receive VIA, most who required treatment received it, the majority on the same day. With proper systems in place, use of HPV testing for cervical cancer screening program as recommended by WHO is a promising model in low-and middle-income countries.

Antimicrobial Activity of Aspergillus sp. from the Amazon Biome: Isolation of Kojic Acid

The antimicrobial potential of Aspergillus sp., isolated from the Amazon biome, which is stored at the Amazon Fungi Collection-CFAM at ILMD/FIOCRUZ, was evaluated. The fungal culture was cultivated in yeast extract agar and sucrose (YES) for cold extraction of the biocompounds in ethyl acetate at 28 °C for 7 days in a BOD type incubator. The obtained extract was evaluated for its antimicrobial activity against Candida albicans and Gram-positive and negative bacteria by the “cup plate” method and the determination of the minimum inhibitory concentration (MIC) by the broth microdilution method. The extract was subjected to thin layer chromatography (TLC) and fractionated by open and semipreparative column chromatography. The fractions of interest had their chemical constituents elucidated by nuclear magnetic resonance and mass spectrometry. The elucidated molecule was evaluated for cytotoxicity against the human fibroblast strain (MRC5). The extract presented inhibitory activity against both Gram-positive and negative bacteria, with the range of inhibition halos from 5.3 to 14 mm in diameter and an MIC ranging from 500 to 15.6 μg/mL. Seventy-one fractions were collected and TLC analysis suggested the presence of substances with double bond groups: coumarins, flavonoids, phenolic, alkaloids, and terpenes. NMR and MS analyses demonstrated that the isolated molecule was kojic acid. The results of the cytotoxicity test showed that MRC5 cells presented viability at concentrations from 500 to 7.81 μg/mL. The kojic acid molecule of Aspergillus sp., with antibacterial activity and moderate toxicity at the concentrations tested, is a promising prototype of an alternative active principle of an antimicrobial drug.

In Silico and Experimental Investigation of the Biological Potential of Some Recently Developed Carprofen Derivatives

The efficient regioselective bromination and iodination of the nonsteroidal anti-inflammatory drug (NSAID) carprofen were achieved by using bromine and iodine monochloride in glacial acetic acid. The novel halogenated carprofen derivatives were functionalized at the carboxylic group by esterification. The regioselectivity of the halogenation reaction was evidenced by NMR spectroscopy and confirmed by X-ray analysis. The compounds were screened for their in vitro antibacterial activity against planktonic cells and also for their anti-biofilm effect, using Gram-positive bacteria (Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212) and Gram-negative bacteria (Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853). The cytotoxic activity of the novel compounds was tested against HeLa cells. The pharmacokinetic and pharmacodynamic profiles of carprofen derivatives, as well as their toxicity, were established by in silico analyses.