Sources, analysis, and health implications of atmospheric microplastics

Microplastics (MPs) are emerging environmental contaminants pervasive in the environment. Studies have revealed that the majority of airborne MPs are in the form of fiber. Inhaled atmospheric MPs adversely impact human health, causing inflammation and oxidative stress. Atmospheric MPs may also carry hazardous chemical pollutants in addition to heavy metals. Many research studies have been conducted about MPs' presence in the environmental components, however questions about the presence and identification of atmospheric MPs remained unanswered. Based on the mentioned research gaps, this study examined the sources and abundance of MPs in the atmosphere and their generation, accumulation, and fate. The paper further studies and evaluates current methods for identifying and assessing airborne MPs and their impact on human health and the environment. According to the study findings, there are flaws and complexity in MPs assessment and technical procedures, which further challenges data comparability and dependability. In order to ensure data comparability and reliability, the abundance of atmospheric MPs needs to be expressed using a unified and standard methodology. Innovative and well-established identification methods, strategies to minimize the impacts of MPs, and appropriate steps to reduce this global pollution are required for the current state of MPs. It also provides an overview of atmospheric MPs' characteristics, sources, and airborne transmission and deposition mechanisms. Advances in bacterial degradation, sunlight-driven photocatalysts, fuels, and biodegradable plastics could revolutionize future studies on reducing plastic pollution. Future studies should include more research on the various aspects of atmospheric MPs. Despite several research studies conducted on the presence and identification of MPs in various environmental components, many questions regarding MPs in the atmosphere and from the perspectives of COVID-19 and One Health still need to be answered. This study will help the key stakeholders and policymakers in safeguarding public health and environment from the threats posed by airborne MPs.

Clinicopathological Spectrum of COVID-19

Objective: To analyse the clinicopathological spectrum of COVID-19 among 2000 patients. Study Design: Cross-sectional study. Place and Duration of Study: Combined Military Hospital, Abbottabad Pakistan, from Apr to Jun 2020. Methodology: The study included 2000 patients who came to CMH Abbottabad to seek medical attention during the first wave of the COVID-19 pandemic. Age, gender, contact history, history of foreign travel, clinical features, comorbid conditions and results of SARS-CoV-2 PCR were observed. Results: From 2000 cases, 1442(72%) were males, and 558(28%) were females. The mean age was 35.02±13.00 years, and 1275(63.8%) cases were from the 3rd to fourth decade of life. 900(45%) of the cases had a contact history with a COVID-19 patient, whereas only 4(0.2%) had a history of foreign travel. 1854(93.0%) of the cases were asymptomatic, whereas only 48(2.4%) presented with fever and cough, the most common symptoms. Only 26(1.3%) cases had associated comorbid conditions, and 263(13.0%) cases showed positive PCR results. The statistical association was found to be significant among age groups, gender, contact history and results of SARS-CoV-2 PCR,(p-value< 0.001). Conclusion: This study provides an overall view of the COVID-19 pandemic, which has grasped the globe within no time. Efficient preventive and control measures are mandatory, in addition to early identification and diagnosis, to overcome the infection.

Structural insights into the effect of mutations in the spike protein of SARS-CoV-2 on the binding with human furin protein.

The SARS COV-2 and its variants are spreading around the world at an alarming speed, due to its higher transmissibility and the conformational changes caused by mutations. The resulting COVID-19 pandemic has imposed severe health consequences on human health. Several countries of the world including Pakistan have studied its genome extensively and provided productive findings. In the current study, the mCSM, DynaMut2, and I-Mutant servers were used to analyze the effect of identified mutations on the structural stability of spike protein however, the molecular docking and simulations approaches were used to evaluate the dynamics of the bonding network between the wild-type and mutant spike proteins with furin. We addressed the mutational modifications that have occurred in the spike protein of SARS-COV-2 that were found in 215 Pakistani's isolates of COVID-19 patients to study the influence of mutations on the stability of the protein and its interaction with the host cell. We found 7 single amino acid substitute mutations in various domains that reside in spike protein. The H49Y, N74K, G181V, and G446V were found in the S1 domain while the D614A, V622F, and Q677H mutations were found in the central helices of the spike protein. Based on the observation, G181V, G446V, D614A, and V622F mutants were found highly destabilizing and responsible for structural perturbation. Protein-protein docking and molecular simulation analysis with that of furin have predicted that all the mutants enhanced the binding efficiency however, the V622F mutant has greatly altered the binding capacity which is further verified by the KD value (7.1 E-14) and therefore may enhance the spike protein cleavage by Furin and increase the rate of infectivity by SARS-CoV-2. On the other hand, the total binding energy for each complex was calculated which revealed -50.57 kcal/mol for the wild type, for G181V -52.69 kcal/mol, for G446V -56.44 kcal/mol, for D614A -59.78 kcal/mol while for V622F the TBE was calculated to be -85.84 kcal/mol. Overall, the current finding shows that these mutations have increased the binding of Furin for spike protein and shows that D614A and V622F have significant effects on the binding and infectivity.

Strategic drivers to overcome the impacts of the COVID-19 pandemic: implications for ensuring resilience in supply chains

The recent coronavirus (COVID-19) pandemic has affected the manufacturing industry's entire supply chain system. It is important to investigate the strategic drivers to deal with the impacts of COVID-19 in the manufacturing industry. Accordingly, this study aims to identify the strategic drivers to overcome the impacts of the COVID-19 pandemic and improve the resiliency of the Bangladeshi footwear industry, an emerging economy. The strategic drivers are identified after reviewing research papers, reports, blogs, and discussions on social media platforms. The main drivers and their respective sub-drivers are finalized by discussing with domain experts. To offer strategic plans for building resiliency, it is crucial to know the importance of the main drivers and sub-drivers;therefore, the best–worst method is applied to determine the priority importance of the strategic drivers. The findings indicate that the top five drivers to defeat the impacts of COVID-19 are "high capability of reconfigurability,” "enhance the relationship with suppliers,” "develop health protocols to continue manufacturing,” "government support through incentives, subsidy, tax rebate, etc.,” and "set a policy to stable material supply”. Based on the findings, this study also provides practical implications with proposed research themes for policymakers and operations managers towards mitigating the impacts of the COVID-19 pandemic. The study's contribution is unique and important for the footwear supply chain as the research on COVID-19 in the context of resiliency focusing on the footwear supply chain is non-existent.

Structural insights into the effect of mutations in the spike protein of SARS-CoV-2 on the binding with human furin protein

The SARS COV-2 and its variants are spreading around the world at an alarming speed, due to its higher transmissibility and the conformational changes caused by mutations. The resulting COVID-19 pandemic has imposed severe health consequences on human health. Several countries of the world including Pakistan have studied its genome extensively and provided productive findings. In the current study, the mCSM, DynaMut2, and I-Mutant servers were used to analyze the effect of identified mutations on the structural stability of spike protein however, the molecular docking and simulations approaches were used to evaluate the dynamics of the bonding network between the wild-type and mutant spike proteins with furin. We addressed the mutational modifications that have occurred in the spike protein of SARS-COV-2 that were found in 215 Pakistani's isolates of COVID-19 patients to study the influence of mutations on the stability of the protein and its interaction with the host cell. We found 7 single amino acid substitute mutations in various domains that reside in spike protein. The H49Y, N74K, G181V, and G446V were found in the S1 domain while the D614A, V622F, and Q677H mutations were found in the central helices of the spike protein. Based on the observation, G181V, G446V, D614A, and V622F mutants were found highly destabilizing and responsible for structural perturbation. Protein-protein docking and molecular simulation analysis with that of furin have predicted that all the mutants enhanced the binding efficiency however, the V622F mutant has greatly altered the binding capacity which is further verified by the KD value (7.1 E−14) and therefore may enhance the spike protein cleavage by Furin and increase the rate of infectivity by SARS-CoV-2. On the other hand, the total binding energy for each complex was calculated which revealed −50.57 kcal/mol for the wild type, for G181V −52.69 kcal/mol, for G446V −56.44 kcal/mol, for D614A −59.78 kcal/mol while for V622F the TBE was calculated to be −85.84 kcal/mol. Overall, the current finding shows that these mutations have increased the binding of Furin for spike protein and shows that D614A and V622F have significant effects on the binding and infectivity.

COVID-19: A UK Children's Hospital Experience.

OBJECTIVES: Reports from China relating to coronavirus disease (COVID-19) in children indicate a milder disease course compared with adults. Although a few pediatric COVID-19 reports from other parts of the world exist, there are none from the United Kingdom. We describe the clinical characteristics of children with COVID-19 admitted to a specialist children's hospital in United Kingdom. METHODS: Retrospective case-series of inpatients with a positive polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2, during a 6-week period from March 14 to April 24, 2020. RESULTS: Forty-five children tested positive for severe acute respiratory syndrome coronavirus 2 during the study period. Median (interquartile range) age was 3.5 (0.7-12) years, and 31 (69%) were male. Children with comorbidities constituted 64% (29 of 45) of the study population, including 44% (20 of 45) who were considered "extremely vulnerable." Fever (67%) and cough (55%) were the most common symptoms. High C-reactive protein (>10 mg/L) was observed in 68% (19 of 28). Lymphopenia (<1.2 × 109/L) was observed in 23% (9 of 40) of children, but it was related to coexisting medical conditions in 6 children. Nine children required supplemental oxygen, two of whom received high-flow nasal cannula oxygen; one needed noninvasive ventilation and one child required invasive mechanical ventilation. Median length of stay of children with an admission outcome (n = 42, 93%) was 3 (2-7) days. There were no COVID-19-related deaths. CONCLUSIONS: COVID-19 had a relatively mild course of illness in majority of the hospitalized children that included a subgroup of vulnerable children with significant comorbidities. Confirmation of this in larger nationwide studies of children is required.

A 3-year analysis of the impact of COVID-19 pandemic on NSTEMI incidence, clinical characteristics, management, and outcomes.

OBJECTIVE: The COVID-19 pandemic has been associated with decreased incidence of acute coronary syndrome with worsened outcomes. Few studies have addressed the effects beyond the initial phases of the pandemic. This study elucidated the incidence, clinical characteristics, management, and outcomes of NSTEMI at a tertiary referral center from sample time periods of 2019-2022. METHODS: This study included consecutive NSTEMI patients from March 14-May 9, 2019-2022. Variables included baseline characteristics, clinical features on arrival, management strategy, time parameters, and adverse outcomes. The primary outcome was defined as death, heart failure requiring diuretics, and/or sustained ventricular arrhythmia. RESULTS: This study comprised 250 patients of whom 181 who were admitted during the COVID-19 outbreak. Baseline characteristics were similar among groups. There was a reduction in door-to-angiography time from 29 h in 2019 to 19 h in 2020 [p = 0.01] and 20 h in 2021 [p = 0.02]. PCI intervention increased from 31.8% in 2019% to 50.0% in 2020 [p = 0.05] and 54.7% in 2021 [p < 0.01]. Median length-of-stay (LOS) was reduced from 3 days in 2019 to 2 days in 2020 [p = 0.03]. There was no significant change in outcomes in COVID-19 cohorts compared to control year. CONCLUSIONS: NSTEMI patients during the first 2 years of the COVID-19 pandemic were associated with reduced door-to-angiography times and increased percutaneous coronary intervention (PCI), and patients in year one were associated with reduced LOS. This study suggests that NSTEMI may be managed more efficiently thus reducing hospital bed utilization and potential costs.

Psychological Impact on the Orthodontic Postgraduate Residents and Their Anxiety Level during the COVID-19 Pandemic.

Background: COVID-19, a viral infection, has negatively impacted the physical and psychological health of the people worldwide. This was a descriptive, cross-sectional study, which aimed to investigate orthodontic postgraduate residents' knowledge regarding COVID-19, its association with anxiety around quality of their training, and performance of routine orthodontic procedures during the pandemic. A questionnaire was circulated online through WhatsApp to the orthodontic residents enrolled in the four-year postgraduate training program across the country which comprised the following sections: demographic data, questions to test knowledge of COVID-19, self-grading of anxiety around performing routine orthodontic procedures, academic aspects of the training program, and residents' thoughts on the current status of their training program in general during the pandemic. The residents were grouped based on their awareness on COVID-19, with >70% score taken as having adequate knowledge and ≤70% as inadequately updated. The association between COVID-19-related knowledge and the anxiety level of the residents experienced during training was assessed. Results were analyzed using SPSS (Statistical Package for Social Sciences) version 23.0. Counts and percentages were reported on baseline characteristics of studied samples. Descriptive methods were used to report the outcomes of this survey on knowledge of COVID-19, anxiety around performing orthodontic procedures, and different academic aspects of training. Statistical significance was set at p < 0.05 using the Pearson chi square test. Results: Most of the residents (51.5%) were adequately updated about the COVID-19 virus. Increased awareness was associated with more anxiety about the following: contracting the virus (p < 0.01), performing different orthodontic procedures (p < 0.05), disturbed patients' appointments (p < 0.01), timely completion of their cases (p < 0.01), and exam's preparation (p=0.04). The group with <70% COVID-19 related knowledge opted for extension of their training period (51.8%). Conclusion: COVID-19 related knowledge was clearly associated with anxiety experienced by the orthodontic residents during training in the pandemic. Awareness regarding the infection led to more anxiety around working during the pandemic, preparing for postgraduate exams, and concerns about its negative influence on the overall quality of the training program.

Mutational analysis of the spike protein of SARS-COV-2 isolates revealed atomistic features responsible for higher binding and infectivity.

Introduction: The perpetual appearance of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2), and its new variants devastated the public health and social fabric around the world. Understanding the genomic patterns and connecting them to phenotypic attributes is of great interest to devise a treatment strategy to control this pandemic. Materials and Methods: In this regard, computational methods to understand the evolution, dynamics and mutational spectrum of SARS-CoV-2 and its new variants are significantly important. Thus, herein, we used computational methods to screen the genomes of SARS-CoV-2 isolated from Pakistan and connect them to the phenotypic attributes of spike protein; we used stability-function correlation methods, protein-protein docking, and molecular dynamics simulation. Results: Using the Global initiative on sharing all influenza data (GISAID) a total of 21 unique mutations were identified, among which five were reported as stabilizing while 16 were destabilizing revealed through mCSM, DynaMut 2.0, and I-Mutant servers. Protein-protein docking with Angiotensin-converting enzyme 2 (ACE2) and monoclonal antibody (4A8) revealed that mutation G446V in the receptor-binding domain; R102S and G181V in the N-terminal domain (NTD) significantly affected the binding and thus increased the infectivity. The interaction pattern also revealed significant variations in the hydrogen bonding, salt bridges and non-bonded contact networks. The structural-dynamic features of these mutations revealed the global dynamic trend and the finding energy calculation further established that the G446V mutation increases the binding affinity towards ACE2 while R102S and G181V help in evading the host immune response. The other mutations reported supplement these processes indirectly. The binding free energy results revealed that wild type-RBD has a TBE of -60.55 kcal/mol while G446V-RBD reported a TBE of -73.49 kcal/mol. On the other hand, wild type-NTD reported -67.77 kcal/mol of TBE, R102S-NTD reported -51.25 kcal/mol of TBE while G181V-NTD reported a TBE of -63.68 kcal/mol. Conclusions: In conclusion, the current findings revealed basis for higher infectivity and immune evasion associated with the aforementioned mutations and structure-based drug discovery against such variants.

Industry 5.0 challenges for post-pandemic supply chain sustainability in an emerging economy

To ensure business continuity in the post-COVID-19 era, decision-makers should reconfigure their traditional supply chain (SC) networks, assisted by the development and implementation of cutting-edge technologies. Recently, Industry 5.0 (I5.0) has gained increasing attention as a paradigm offering salient features for the creation of resilient and inclusive operations by ensuring long-standing SC sustainability. However, there has been insufficient analysis of the challenges of implementing I5.0 in SCs. Therefore, this study aims to understand the challenges of implementing I5.0 when managing the impact of SC disruptions due to the COVID-19 pandemic in an emerging economy. Both qualitative and quantitative methods were used for this research. First, the challenges to I5.0 implementation were identified through a literature review and experts' feedback. Those challenges were examined and prioritised using the Best-Worst Method (BWM). Second, the contextual relationships amongst these challenges were analysed using interpretive structural modelling (ISM) with cross-impact matrix multiplication applied to classification (MICMAC) analysis. Findings showed that to adopt I5.0 initiatives successfully in order to manage the post-COVID-19 impact on SC sustainability, the active involvement of senior managers is required in the execution process. Findings also showed that financial support and funding (e.g., tax reduction, short loans, etc.) from investors and the government play a pivotal role in enabling sustainability in SCs. Finally, the challenges were classified using MICMAC analysis to provide valuable insights for managing future disruptions. This study is expected to help managers and decision-makers successfully overcome the challenges of implementing I5.0 in SCs and thus improve SC sustainability.

Mutational analysis of the spike protein of SARS-COV-2 isolates revealed atomistic features responsible for higher binding and infectivity

Introduction: The perpetual appearance of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2), and its new variants devastated the public health and social fabric around the world. Understanding the genomic patterns and connecting them to phenotypic attributes is of great interest to devise a treatment strategy to control this pandemic. Materials and Methods: In this regard, computational methods to understand the evolution, dynamics and mutational spectrum of SARS-CoV-2 and its new variants are significantly important. Thus, herein, we used computational methods to screen the genomes of SARS-CoV-2 isolated from Pakistan and connect them to the phenotypic attributes of spike protein;we used stability-function correlation methods, protein-protein docking, and molecular dynamics simulation. Results: Using the Global initiative on sharing all influenza data (GISAID) a total of 21 unique mutations were identified, among which five were reported as stabilizing while 16 were destabilizing revealed through mCSM, DynaMut 2.0, and I-Mutant servers. Protein-protein docking with Angiotensin-converting enzyme 2 (ACE2) and monoclonal antibody (4A8) revealed that mutation G446V in the receptor-binding domain;R102S and G181V in the N-terminal domain (NTD) significantly affected the binding and thus increased the infectivity. The interaction pattern also revealed significant variations in the hydrogen bonding, salt bridges and non-bonded contact networks. The structural-dynamic features of these mutations revealed the global dynamic trend and the finding energy calculation further established that the G446V mutation increases the binding affinity towards ACE2 while R102S and G181V help in evading the host immune response. The other mutations reported supplement these processes indirectly. The binding free energy results revealed that wild type-RBD has a TBE of −60.55 kcal/mol while G446V-RBD reported a TBE of −73.49 kcal/mol. On the other hand, wild type-NTD reported −67.77 kcal/mol of TBE, R102S-NTD reported −51.25 kcal/mol of TBE while G181V-NTD reported a TBE of −63.68 kcal/mol. Conclusions: In conclusion, the current findings revealed basis for higher infectivity and immune evasion associated with the aforementioned mutations and structure-based drug discovery against such variants.

Structural plasticity of omicron BA.5 and BA.2.75 for enhanced ACE-dependent entry into cells.

The current study investigated the binding variations among the wilt type, Omicron sub-variants BA.2.75 and BA.5, using protein-protein docking, protein structural graphs (P SG), and molecular simulation methods. HADDOCK predicted docking scores and dissociation constant (KD) revealed tighter binding of these sub-variants in contrast to the WT. Further investigation revealed variations in the hub residues, protein sub-networks, and GlobalMetapath in these variants as compared to the WT. A very unusual dynamic for BA.2.75 and BA.5 was observed, and secondary structure transition can also be witnessed in the loops (44-505). The results show that the flexibility of these three loops is increased by the mutations as an allosteric effect and thus enhances the chances of bonding with the nearby residues to connect and form a stable connection. Furthermore, the additional hydrogen bonding contacts steer the robust binding of these variants in contrast to the wild type. The total binding free energy for the wild type was calculated to be -61.38 kcal/mol, while for BA.2.75 and BA.5 variants the T BE was calculated to be -70.42 kcal/mol and 69.78 kcal/mol, respectively. We observed that the binding of BA.2.75 is steered by the electrostatic interactions while the BA.5 additional contacts are due to the vdW (Van der Waal) energy. From these findings, it can be observed the Spike (S) protein is undergoing structural adjustments to bind efficiently to the hACE2 (human angiotensin-converting enzyme 2) receptor and, in turn, increase entry to the host cells. The current study will aid the development of structure-based drugs against these variants.Communicated by Ramaswamy H. Sarma.

Psychological Impact on the Orthodontic Postgraduate Residents and Their Anxiety Level during the COVID-19 Pandemic

Background COVID-19, a viral infection, has negatively impacted the physical and psychological health of the people worldwide. This was a descriptive, cross-sectional study, which aimed to investigate orthodontic postgraduate residents' knowledge regarding COVID-19, its association with anxiety around quality of their training, and performance of routine orthodontic procedures during the pandemic. A questionnaire was circulated online through WhatsApp to the orthodontic residents enrolled in the four-year postgraduate training program across the country which comprised the following sections: demographic data, questions to test knowledge of COVID-19, self-grading of anxiety around performing routine orthodontic procedures, academic aspects of the training program, and residents' thoughts on the current status of their training program in general during the pandemic. The residents were grouped based on their awareness on COVID-19, with >70% score taken as having adequate knowledge and ≤70% as inadequately updated. The association between COVID-19-related knowledge and the anxiety level of the residents experienced during training was assessed. Results were analyzed using SPSS (Statistical Package for Social Sciences) version 23.0. Counts and percentages were reported on baseline characteristics of studied samples. Descriptive methods were used to report the outcomes of this survey on knowledge of COVID-19, anxiety around performing orthodontic procedures, and different academic aspects of training. Statistical significance was set at p < 0.05 using the Pearson chi square test. Results Most of the residents (51.5%) were adequately updated about the COVID-19 virus. Increased awareness was associated with more anxiety about the following: contracting the virus (p < 0.01), performing different orthodontic procedures (p < 0.05), disturbed patients' appointments (p < 0.01), timely completion of their cases (p < 0.01), and exam's preparation (p=0.04). The group with <70% COVID-19 related knowledge opted for extension of their training period (51.8%). Conclusion COVID-19 related knowledge was clearly associated with anxiety experienced by the orthodontic residents during training in the pandemic. Awareness regarding the infection led to more anxiety around working during the pandemic, preparing for postgraduate exams, and concerns about its negative influence on the overall quality of the training program.

The Efficacy of Conservative Management in Uncomplicated Acute Appendicitis - A Single-Center Retrospective Study.

Background Acute appendicitis remains the most common cause of lower abdominal pain leading to emergency visits. Even though the standard treatment of acute appendicitis remains appendectomy, in recent times, multiple randomized control trials and meta-analyses have deduced conservative treatment as a successful alternative treatment. During the coronavirus disease (COVID) pandemic, with a shortage of staff and resources, treatment with conservative management of uncomplicated acute appendicitis became very beneficial under certain circumstances and conditions. This study aimed to assess whether it is effective to manage patients with uncomplicated acute appendicitis with antibiotic therapy. Methodology This was a single hospital based retrospective, cross-sectional study from Jan 2015 to May 2020. Patients with clinical and radiological features of uncomplicated acute appendicitis with Alvarado's score >6 were included in the study. Patients were kept on antibiotics, intravenous fluids, and analgesia as part of a conservative regime. Those who failed to respond to conservative therapy were managed surgically. The follow-up period was six months. Results One hundred eighty-two cases of uncomplicated acute appendicitis were included and managed conservatively, of which 52.2% were males while 47.8% were females. The median age of the patients was 26 years. Conservative treatment was successful in 26.2% of the patients, with a recurrence of 5.5% in the six-month follow-up period. The mean number of days of hospital stay was three days in patients treated with conservative or surgical treatment. Conclusion Conservative management is gaining popularity, and many centers are inclined towards non-operative management; however, appendectomy remains the gold standard treatment for appendicitis.

Homoeopathy as an Adjuvant to Standard Care in Moderate and Severe Cases of COVID-19: A Single-Blind, Randomized, Placebo-Controlled Study.

OBJECTIVES: This study aimed to evaluate whether individualized homeopathic medicines have a greater adjunctive effect than adjunctive placebos in the treatment of moderate and severe cases of coronavirus disease 2019 (COVID-19). METHODS: The study was a randomized, single-blind, prospective, placebo-controlled clinical trial set in the clinical context of standard care. INTERVENTION: Patients of either sex, admitted in a tertiary care hospital, suffering from moderate or severe COVID-19 and above 18 years of age were included. In total, 150 patients were recruited and then randomly divided into two groups to receive either individualized homeopathic medicines or placebos, in addition to the standard treatment of COVID-19. OUTCOME MEASURES: The primary outcome was time taken to achieve RT-PCR-confirmed virus clearance for COVID-19. Secondary outcomes were changes in the Clinical Ordinal Outcomes Scale (COOS) of the World Health Organization, the patient-reported MYMOP2 scale, and several biochemical parameters. Parametric data were analyzed using unpaired t-test. Non-parametric data were analyzed using the Wilcoxon signed rank test. Categorical data were analyzed using Chi-square test. RESULTS: In total, 72 participants of the add-on homeopathy (AoH) group showed conversion of RT-PCR status to negative, in an average time of 7.53 ± 4.76 days (mean ± SD), as compared with 11.65 ± 9.54 days in the add-on placebo (AoP) group (p = 0.001). The mean COOS score decreased from 4.26 ± 0.44 to 3.64 ± 1.50 and from 4.3 ± 0.46 to 4.07 ± 1.8 in the AoH and AoP groups respectively (p = 0.130). The mortality rate for the AoH group was 9.7% compared with 17.3% in the AoP group. The MYMOP2 scores between the two groups differed significantly (p = 0.001), in favor of AoH. Inter-group differences in the pre- and post- mean values of C-reactive protein, fibrinogen, total leukocyte count, platelet count and alkaline phosphatase were each found to be statistically significant (p <0.05), favoring AoH; six other biochemical parameters showed no statistically significant differences. CONCLUSION: The study suggests homeopathy may be an effective adjunct to standard care for treating moderate and severe COVID-19 patients. More rigorous, including double-blinded, studies should be performed to confirm or refute these initial findings.

Invasive pulmonary aspergillosis in critically ill patients with pneumonia due to COVID-19, influenza, and community-acquired pneumonia: A prospective observational study.

Background and Purpose: Influenza A and SARS-CoV-2 are risk factors for invasive pulmonary aspergillosis. Both influenza-associated pulmonary aspergillosis and COVID-19-associated pulmonary aspergillosis result in high mortality and poor clinical outcomes. No prospective study has so far compared the features, treatment, and outcomes of influenza-associated pulmonary aspergillosis and COVID-19-associated pulmonary aspergillosis within a similar time frame. Therefore, this study aimed to determine the frequency, risk factors, and outcomes of invasive pulmonary aspergillosis in critically ill patients with influenza, COVID-19, and community-acquired pneumonia. Materials and Methods: This prospective study included adult patients with pneumonia and was conducted at The Aga Khan University Hospital in Karachi, Pakistan. Patients were divided into three groups, including community-acquired pneumonia, influenza pneumonia, and COVID-19 pneumonia. The data collected included information on demographic characteristics, comorbidities, clinical features, laboratory results, treatment, and outcomes. Results: A total of 140 patients were included in this study. These included 35 (25%), 70 (50%), and 35 (25%) patients with community-acquired pneumonia, influenza pneumonia, and COVID-19 pneumonia, respectively. In addition, 20 (14.2%) patients were found to have invasive aspergillosis, of whom 10/35 (28.5%), 9/70 (12.8%), and 1/35 (2.8%) patients were in the COVID-19, influenza, and community-acquired pneumonia groups, respectively. Moreover, nine (90%) COVID-19-associated pulmonary aspergillosis patients required vasopressors, compared to three (33%) patients with influenza-associated pulmonary aspergillosis (P=0.020). In total, seven (70%) COVID-19-associated pulmonary aspergillosis patients required invasive mechanical ventilation compared to four (44%) influenza-associated pulmonary aspergillosis patients (P=0.37). The mean±SD length of hospital stay was highest in the COVID-19-associated pulmonary aspergillosis patients (18.3±7.28 days) compared to influenza-associated pulmonary aspergillosis patients (11.7±5.34 days) (P=0.036). The number of deaths in influenza-associated pulmonary aspergillosis and COVID-19-associated pulmonary aspergillosis patients was three (33.3%) and five (50%), respectively (P=0.526). Conclusion: A higher proportion of patients with COVID-19 developed invasive aspergillosis compared to those with influenza. Although the mortality rate in COVID-19-associated pulmonary aspergillosis was comparable to that in influenza-associated pulmonary aspergillosis patients, COVID-19-associated pulmonary aspergillosis patients had a significantly longer stay in the hospital.

Modeling Impacts of COVID-19 in Supply Chain Activities: A Grey-DEMATEL Approach

The purpose of this study was to identify and exhibit the interrelationships among COVID-19's impacts on supply chain activities. Based on a literature review and the manager's input, twenty COVID-19 impacts were collected. An integrated approach of exploratory factor analysis (EFA) and grey-decision-making trial and evaluation laboratory (G-DEMATEL) was used to reveal the causal interrelationships among the COVID-19 impacts. Initially, a questionnaire survey was administered among 220 respondents for EFA. Based on the outcome of EFA, the twenty COVID-19 impacts were categorized into seven critical areas. Then, based on the experts' inputs, G-DEMATEL was utilized to reveal the causal interrelationships among various COVID-19 impacts. The results indicate that disruption management, relationship management, and production management are the top three critical areas that need to be addressed in the COVID-19 crisis. Disruption in supply, ripple effect on supply chain operations, and obsolescence of machines were found to be the most influential impacts while disproportionateness between supply and demand, difficulty in demand forecasting, and reduced cash inflow were found to be the most influenced impacts. This study's outcomes will help policymakers and supply chain managers develop strategies to restructure supply chain networks. This study is an original contribution to the analysis of COVID-19 impacts in the supply chain activities in India due to the use of EFA and G-DEMATEL. This study considers India only, and hence, the outcomes lack generalizability. A study considering multiple developing countries could generalize these findings.

Ultra-Large-Scale Screening of Natural Compounds and Free Energy Calculations Revealed Potential Inhibitors for the Receptor-Binding Domain (RBD) of SARS-CoV-2.

The emergence of immune-evading variants of SARS-CoV-2 further aggravated the ongoing pandemic. Despite the deployments of various vaccines, the acquired mutations are capable of escaping both natural and vaccine-induced immune responses. Therefore, further investigation is needed to design a decisive pharmacological treatment that could efficiently block the entry of this virus into cells. Hence, the current study used structure-based methods to target the RBD of the recombinant variant (Deltacron) of SARS-CoV-2, which was used as a model variant. From the virtual drug screenings of various databases, a total of four hits were identified as potential lead molecules. Key residues were blocked by these molecules with favorable structural dynamic features. The binding free energies further validated the potentials of these molecules. The TBE for MNP was calculated to be -32.86 ± 0.10 kcal/mol, for SANC00222 the TBE was -23.41 ± 0.15 kcal/mol, for Liriodenine the TBE was -34.29 ± 0.07 kcal/mol, while for Carviolin the TBE was calculated to be -27.67 ± 0.12 kcal/mol. Moreover, each complex demonstrated distinct internal motion and a free energy profile, indicating a different strategy for the interaction with and inhibition of the RBD. In conclusion, the current study demands further in vivo and in vitro validation for the possible usage of these compounds as potential drugs against SARS-CoV-2 and its variants.

Synthesis and performance evaluation of copper and magnesium-based metal organic framework supported ionic liquid membrane for CO2/N2 separation

The CO2 emission is enhancing drastically because of the continuous emission from industries and transport sector. Although the CO2 emission had decreased in the first half of 2020 by 8.8% due to COVID-19 restrictions however, it is again on the rise and it might exceed the estimated level in 2030. The current methods used for CO2 separation have serious operational and environmental constraints. To overcome these problems we have devised a supported ionic liquid membrane (SILM) incorporated with the blend of bimetallic metal-organic framework (MOF) of copper and magnesium ions (CuxMgx) and Trihexyltetradecylphosphonium chloride [P66614] [Cl] ionic liquid (IL). CuxMgx MOF were synthesized and characterized using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction analysis (XRD), and energy dispersive X-ray analysis (EDX). CuxMgx MOF with [P66614] [Cl] IL were immobilized on a flat sheet of polytetrafluoroethylene (PTFE) membrane. Single gas permeation tests of membranes loaded with 0.2/0.8 wt/wt% MOF/IL solution showed the highest CO2 permeability of 2937 Barrer and CO2/N2 selectivity of 33.26. The performance of SILM was also investigated with different water loadings of (30 wt % and 50 wt %) in addition to MOF/IL solution and at different feed pressure varying from 0.5 to 2 bars. Membranes showed enhancement in CO2 permeability to 3738 and 4628 Barrer whereas CO2/N2 selectivity decreased to 23.53 and 21.8 with membranes loaded with 30 and 50 wt % water, respectively, at a feed pressure of 2 bar. The gas permeation results show that the incorporation of CuxMgx MOF with IL in polymeric membrane enhances the CO2/N2 separation under humid conditions but slightly decreases CO2/N2 selectivity with an increase in feed pressure. The supported ionic liquids membrane synthesized in this research is highly viable for industrial flue gases because of the incorporation of phosphorous-based ILs that have high thermal stability.

NSP4 and ORF9b of SARS-CoV-2 Induce Pro-Inflammatory Mitochondrial DNA Release in Inner Membrane-Derived Vesicles.

Circulating cell-free mitochondrial DNA (cf-mtDNA) has been found in the plasma of severely ill COVID-19 patients and is now known as a strong predictor of mortality. However, the underlying mechanism of mtDNA release is unexplored. Here, we show a novel mechanism of SARS-CoV-2-mediated pro-inflammatory/pro-apoptotic mtDNA release and a rational therapeutic stem cell-based approach to mitigate these effects. We systematically screened the effects of 29 SARS-CoV-2 proteins on mitochondrial damage and cell death and found that NSP4 and ORF9b caused extensive mitochondrial structural changes, outer membrane macropore formation, and the release of inner membrane vesicles loaded with mtDNA. The macropore-forming ability of NSP4 was mediated through its interaction with BCL2 antagonist/killer (BAK), whereas ORF9b was found to inhibit the anti-apoptotic member of the BCL2 family protein myeloid cell leukemia-1 (MCL1) and induce inner membrane vesicle formation containing mtDNA. Knockdown of BAK and/or overexpression of MCL1 significantly reversed SARS-CoV-2-mediated mitochondrial damage. Therapeutically, we engineered human mesenchymal stem cells (MSCs) with a simultaneous knockdown of BAK and overexpression of MCL1 (MSCshBAK+MCL1) and named these cells IMAT-MSCs (intercellular mitochondrial transfer-assisted therapeutic MSCs). Upon co-culture with SARS-CoV-2-infected or NSP4/ORF9b-transduced airway epithelial cells, IMAT-MSCs displayed functional intercellular mitochondrial transfer (IMT) via tunneling nanotubes (TNTs). The mitochondrial donation by IMAT-MSCs attenuated the pro-inflammatory and pro-apoptotic mtDNA release from co-cultured epithelial cells. Our findings thus provide a new mechanistic basis for SARS-CoV-2-induced cell death and a novel therapeutic approach to engineering MSCs for the treatment of COVID-19.