Natural antimicrobials: An introduction

From historical point of view, nature has always been a rich source of materials, and medicines also came from this vast and immeasurable resource. Ethnologically-based information still has great potential for future explanations of bioactivities of such medicines. Although epidemiological measures (vaccinations) and antimicrobial treatments curb infectious diseases, there is still an urgent need for well-defined molecules from nature. With the decline of de novo synthesis of new chemical entities, the main focus of nature-derived molecule research among the group of antimicrobials is clear definition of antimicrobial spectrum of activities, mechanism of action, stability, mutagenicity and genotoxicity. The possible road is also in silico studies of antimicrobial activities of natural molecules from natural products databases. Cleary displayed preclinical studies may lead to the in vivo studies which can prove the indication of such natural molecules. The main obstacles such as low bioavailability, short half-life and low PK/PD values will be a great challenge for future research. Considering the emerging new diseases, such as SARS-CoV-2 nowadays, and rising scientific awareness about testing known natural molecules, the area of natural antimicrobials is fast, prominent and still encouraging. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2022. All rights reserved.

Nanotechnology and stem cell therapy for combating COVID-19

After the initial occurrence in Wuhan, Hubei Province, China, at the end of the year 2019, Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2, has wreaked havoc on livelihoods and health worldwide. By the end of June 2021, more than 3 million deaths and a total of more than 179 million positive cases have been registered, and the numbers are steadily climbing (https://covid19.who.int/). The principal life-threatening manifestations of COVID-19 illness are caused by the dysregulated immune system and inflammatory response triggered by a surge of cytokines known as cytokine storm. This makes the lower respiratory tract more susceptible to infection resulting in acute lung injury/acute respiratory distress syndrome intermittently resulting in the death of the patient. The range of medicinal therapy available to treat COVID-19 is continuously expanding and includes both the Food and Drug Administration (FDA)-approved drugs as well as medications approved for emergency use by the FDA. The world has greeted extremely encouraging and long-awaited COVID-19 vaccination. A total of 2,624,733,776 vaccine doses have been globally administered (https://covid19.who.int/) by June 23, 2021. Even though prevention therapy in form of vaccinations is currently accessible to some, logistics and limited supplies will make it months before the entire world gets vaccinated. Even after more than one and a half years of this global threat, there are no specific therapeutics to treat this viral infection with only a few repurposed drugs authorized to treat COVID-19. Hence, multiple treatment strategies to reduce the severity of COVID-19 impact on patients must be explored. © 2023 Elsevier Inc. All rights reserved.

The influence of the first coronavirus wave on the two-week-wait head and neck cancer referrals to a London hospital

The coronavirus Covid-19 has sent reverberations in all aspects of healthcare, where its spread in 2019 has impacted multiple National Health Services, including the head and neck cancer clinics. Early diagnosis combined with the appropriate treatment plays an unquestionable significant role in the survival rates and prognosis for head and neck cancer patients. King's College Hospital sits in the heart of south-east London, serving a population of 700,000;however also acts as a tertiary care centre receiving referrals for a multitude of specialties from across the South of England. A retrospective review was conducted of 365 cases referred for suspected head and neck cancer to the Oral and Maxillofacial Surgery and Oral Medicine two-week-wait clinic at King's College Hospital during the first coronavirus wave (1st of March 2020 to 31st of September 2020) and the same time period in 2019. A total of 233 suspected head and neck cancer referrals were made via the Pan London referral pathway during the first wave in 2020, compared to 132 referrals made in 2019. A total of 3.4% (n = 8) of the patients referred during the first wave were diagnosed with a subtype of head and neck cancer, compared with 9.8%(n = 13) in 2019. Of these referrals, the proportion of patients not seen within the required 14-day period only slightly increased from 3.03% (n = 4) in 2019 to 3.86% (n = 9) in 2020. There was a significant impact from the government-enforced lockdown where reduced face-to-face examinations impacted the quantity of referrals and their diagnosis via the two-week-wait pathway. This study allows reflection of the impact of the first coronavirus wave on the two-week-wait head and neck cancer referrals and gives valuable insight for service implementation and staff reallocation in the event of future periods of waves to prevent overburdening of services.Copyright © 2021

Telenephrology: Managing Chronic Kidney Disease during Covid-19 Pandemic

Introduction: The management of kidney diseases is challenging in areas where discrepancy exist between number of nephrologist and patient with kidney disease. COVID-19 pandemic added to these challenges. We initiated a tele-nephrology service in 2020 with primary aim of education, targeted screening and treatment of kidney diseases focusing where there was no nephrologist. Method(s): In this study locally available paramedics were mobilized for information dissemination and follow up of index patient population. The consultation was performed by internists and nephrologist. After initial registration in telemedicine service, social media apps were used for communication. The mode of communication used was audio, text, photography, and video call when needed. Follow-up consultation was done as required and in 3 months which involved review of reports and medical advised as needed including medication. We analyzed the data from the records of tele-nephrology service provided from April 2020 to April 2021 and who has completed at least 6 months of follow up. Result(s): A total of 266 participants who were known to have chronic kidney disease and hypertension were enrolled and followed up. The mean age of the participant was 54.21 + 17 years. Females constitute 53% (n=141). The most common mode of communication was WhatsApp (86.5%), followed by Viber (5.6%). Patients were advised to undergoes investigations in nearby health care facilities as needed. Most of the participants (88.0%, n=232) were managed without need for physical hospital visit. Physical visit to hospital was needed in 84 patients (17%) and 4.1% (n=11) needed hospital admission. During follow up, half of the participants (n=134) had performed tests as advised and 44.4% (n=118) followed the treatment advised, in initial consultation and needed further advice to do so. Five persons died during follow-up (1.9%). Few participants 1.1%(n=3) said that they don't want to use the telemedicine service again. Conclusion(s): Tele-nephrology services can bridge the gap in care in nephrology where access to nephrologists is limited. No conflict of interestCopyright © 2023

Post-COVID-19 Lung disease (PCLD) patients show a strong correlation between IL-6 and SUVmax on FDG PET/ CT

Aim/Introduction: COVID-19 can cause lung dysfunction postinfection. Respiratory complications are critical sequelae of severe COVID-19 infection and several patients suffer from PCLD after testing RT-PCR negative. Interleukin-6 (IL-6) acts as a key cytokine playing a role in inflammation in lung and other tissues in COVID-19. IL-6 level is increased in patients with non-specific interstitial pneumonia/fibrosis. Injured lungs are major source of IL- 6. Studies have shown association between IL-6 and development of lung injury evaluated by CT scan. Persistent 18F-FDG uptake in lung parenchyma is seen in PCLD patients indicating residual inflammation. Thus the study aimed to evaluate the metabolic activity of lung disease on FDG PET/CT and correlate it with IL-6 in PCLD patients. Material(s) and Method(s): The study was approved by Institutional Review Board and Ethics committee. 32 patients having persistent (>4 weeks) respiratory symptoms post-acute COVID-19 infection after testing RTPCR negative (PCLD) underwent 18F-FDG PET/CT. Simultaneously blood sample was collected on the day of the FDG PET/CT scan in EDTA vial before FDG injection. Serum level of IL-6 was measured by ELISA. FDG PET/CT images were analyzed and SUVmax of metabolic active lung lesions were calculated. The FDG PET/CT findings were correlated with IL-6 using PSM correlation test. Result(s): The mean age of patients (n = 32) was 55.7 years (range 36-71 years) of which 25 were males. 13 (41%) patients had dyspnoea at rest while the remaining had dyspnoea on exertion (59%). Similar age and gender-matched healthy controls were included in our study. All patients had bilateral ground-glass opacities (GGO) in the lung parenchyma. Out of 32 patients, 30 (94%) had a metabolically active lesion in the bilateral lung parenchyma. The mean SUVmax was 3.6 (range 2 - 12.7) and the median was 2.7. Corresponding CT had extensive lung disease including bilateral GGO seen in all patients, consolidation (n=14), and interstitial thickening (n = 20), with more than one feature in some. The Median IL-6 level was significantly higher in patients suffering from PCLD compared to healthy control (326.96 vs 281.5, p=0.0023). Serum IL-6 strongly correlated with SUVmax score of PCLD (r=0.675). The patients were treated with steroids and antifibrotic as per institute's protocol. Conclusion(s): PCLD with ongoing active inflammation as detected by 18F-FDG PET/CT is noted in patients with persistent pulmonary symptoms and it correlates strongly with elevated IL-6 levels. This may play a role in future to monitor the patient with prolonged disease.

Brain phaeohyphomycosis secondary to immunosuppressant therapy due to Rhinocladiella mackenziei

Two cases of Rhinocladiella mackenziei have been noted in our institute, the first case in 2015 (post-renal transplant) and the second case in 2021 (post-COVID infection). Both the patients had received immunosuppressants for varying dura-tion. Both the cases presented to the hospital with neurological deficit secondary to brain abscess. On initial assessment, the melanized fungus was noted which was later identified as Rhinocladiella on culture and further confirmed with molecular meth-ods. Both the cases were treated with injection of L AmB, voriconazole and 5FC for a prolonged duration and later discharged when the condition improved. The renal transplant patient was advised lifelong voriconazole since he would continue to be on immunosuppressants. To our knowledge, the second patient diagnosed post-COVID could be the first case report of invasive dematiaceous fungal infection in an apparently immunocompetent individual. Both cases also highlight the challenges in man-agement such as designing an appropriate regimen, deciding the optimum duration of antifungal therapy, and managing the toxicities associated with long-term antifungal use. R. mackenziei is a frequently fatal melanized neurotropic fungus known to carry almost 100% mortality despite the combination of antifungal agents and surgery. Central nervous system infections due to R. mackenziei have been exclusively reported from the Middle East, except for cases recently reported from India.

Effect of Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Booster on Human Immunodeficiency Virus Reservoirs and Immune Markers.

We investigated effects of the severe acute respiratory syndrome coronavirus 2 (SARV-CoV-2) booster vaccination on human immunodeficiency virus (HIV) reservoir size, immune markers, and host immune responses in people with HIV receiving antiretroviral therapy. Our data suggest that the SARS-CoV-2 booster vaccine is not likely to replenish the persistent HIV reservoir nor provide an immunologic environment to facilitate active HIV expression/replication.

Interval between prior SARS-CoV-2 infection and booster vaccination impacts magnitude and quality of antibody and B cell responses.

SARS-CoV-2 mRNA booster vaccines provide protection from severe disease, eliciting strong immunity that is further boosted by previous infection. However, it is unclear whether these immune responses are affected by the interval between infection and vaccination. Over a 2-month period, we evaluated antibody and B cell responses to a third-dose mRNA vaccine in 66 individuals with different infection histories. Uninfected and post-boost but not previously infected individuals mounted robust ancestral and variant spike-binding and neutralizing antibodies and memory B cells. Spike-specific B cell responses from recent infection (<180 days) were elevated at pre-boost but comparatively less so at 60 days post-boost compared with uninfected individuals, and these differences were linked to baseline frequencies of CD27lo B cells. Day 60 to baseline ratio of BCR signaling measured by phosphorylation of Syk was inversely correlated to days between infection and vaccination. Thus, B cell responses to booster vaccines are impeded by recent infection.

Nanotechnological applications in virology

Nanotechnological Applications in Virology explores the use of nanoparticles-based technologies to fight against viruses, also discussing the use of nanoparticles in the preparation of nano masks and as sanitizing agents. The role of nanotechnology against HIV, Hepatitis, Influenza, Herpes, Ebola and Zika using rapid detection and diagnostic techniques is included, as is a brief description of SARS, MERS, the novel Coronavirus, and recent advancements in its treatment process. Other sections cover the formulation of novel nano-vaccines for the treatment and control of viral infections like HIV, Hepatitis and COVID-19. Included toxicological studies of nanoparticles provide readers with a brief overview on global scenarios regarding viral infections. Nanotechnology is the present age technology, with wide usage in different areas of medical science, including drug delivery, gene therapy, antimicrobials, biosensors and bio-labelling. Nanoparticles play a competent role as an anti-infection agent and thus act as efficient antiviral agents. © 2022 Elsevier Inc. All rights reserved.

Unique advantages of nanomaterials in drug delivery and therapy against viruses

Viruses have caused some of most deadly epidemics and pandemics of humanity. They can cause major health problems, the collapse of the health and economic systems, as well as have negative social and psychological implications. Although science has aided in the management of some viruses, it still requires additional research on new and emerging viruses. The virus SARS-CoV-2 has caused the COVID-19 pandemic leading to the death of many people globally. Several vaccinations have been developed to try to eradicate the virus;however, due to the high mutation rate of the virus, vaccines are still rigorously tested in research and trials. Nanotechnology is a pretty modern technology that offers the potential to treat viruses. For the introduction of advanced antiviral medicines and vaccines, research in this field is becoming increasingly crucial. Furthermore, in a pandemic situation, employing nanomaterials to regulate drug distribution can be a fantastic method to make them successful across a broad range of activity. This book chapter is aimed to highlight recent studies and new technologies on the use of nanomaterials as antiviral therapy, focusing on the drug delivery system, its principles, potential, and economic viability. Because we are in the midst of a COVID-19 epidemic, this research is critical in determining the potential of nanotechnology in medicine, as well as future prospects for drug delivery and nanotherapies generated from NPs of promising nanomaterials. © 2022 Elsevier Inc. All rights reserved.

Nanotechnological applications in old and emerging viral infections: Opportunities and challenges

Nanotechnology is the recent emerging technology in the field of therapeutics and diagnostics. Nanomaterials play a crucial role in diagnosis, drug delivery, drug formulations, and therapy to overcome several life-threatening diseases like diabetes, cancer, bacterial and fungal infections, neurodegenerative diseases, and AIDS. Viruses and viral infections are problematic due to their wide-spreading nature and also the ability to sustain the development through genetic mutation. In the last few decades, the cases of viral infections have severely increased including SARS severe acute respiratory syndrome (SARS), middle east respiratory syndrome (MERS), Nipah virus, Zika virus, dengue fever, and the recent global pandemic COVID-19. These episodes of viral epidemics have emerged unexpectedly and caused substantial damage to the social and economic structure of society. Due to the high mortality rate and global transmission capacity viral infections need immediate attention for the development of detection, treatment, and vaccination techniques. Nanoparticles due to their unique properties and smaller size offer a plethora of opportunities in the field of medical innovations. Nanotechnology-based therapeutic approaches and their drug delivery potential can essentially help in the diagnosis and therapy of virus-related infections. In the present chapter, we provide an overview of virus-related infections and nanotechnology-based solutions for the detection, drug delivery, and treatment of virus infections have been discussed. © 2022 Elsevier Inc. All rights reserved.

Strategies on functionalization of organic and inorganic nanocarriers to inactivate SARS-CoV-2

The COVID-19 disease is taking the lives of more patients with underlying diseases. There is a necessity for preparing vaccines owing to the existence of few antiviral drugs such as dexamethasone as antiinflammatory corticosteroid with sufficient efficacy against COVID-19. Several novel strategies for reducing or removing coronavirus from body before clinical presentation as severe acute respiratory syndrome are presented. In this way, nanobiotechnology has exploited efficient nanomaterials to inactivate microorganisms specifically viruses owing to their smaller size (1–100nm), which can bestow unique physicochemical properties such as large surface-area-to-volume ratio. Among the nanomaterials, nanoparticles, nanoplates, nanorods, nanowires, and nanotubes in particular composed of metal or metal oxide materials can hinder viruses by releasing metal ions in the medium of viruses, wherein biological macromolecules and structure of viruses can be damaged under stress of reactive oxygen species. Antiviral activity of these nanomaterials can be influenced by their physicochemical properties including size, morphology, and charge. Other inorganic or organic nanomaterials such as liposomes, solid lipid nanoparticles, and polymeric nanoparticles may be functionalized by antiviral agents or antibodies to synergize antiviral activity as well as active targeting of SARS-CoV-2. In this regard, one promising strategy for passive immunization is the therapy based on convalescent plasma. Short-lived immunity and serious side effects are recognized as major drawbacks for the application of this therapy, which could be improved using functionalized nanocarriers containing specific antibodies. Therefore, in this book chapter, efficiency of nanomaterials for the inactivation of SARS-CoV-2 is discussed to obtain a comprehensive view point of future antiviral agents. © 2022 Elsevier Inc. All rights reserved.

Multidisciplinary Approach to Brain Fog and Related Persisting Symptoms Post COVID-19.

A third of patients who developed COVID-19 experience a persisting, diverse array of symptoms including respiratory, neurological, and psychiatric complaints referred to as post-acute sequelae of COVID-19 (PASC). Symptoms can last for months after the original infection and appear unrelated to the severity of the initial illness, which suggests that even patients who did not require extensive interventions at the acute stage may experience new and/or long-term symptoms. Brain fog is a colloquial term for a common complaint among patients with PASC and generally implies cognitive impairment in domains of attention and processing speed. There are multiple hypotheses for etiologies and explanations of mechanisms contributing to brain fog in PASC. In this paper, we describe some of the mechanisms associated with brain fog post COVID-19 and provide readers with treatment recommendations that encompass cognition, mood disorders, sleep disorders, and neuroinflammation.

COVID-19 Related Extensive Thrombosis

Introduction: While the COVID-19 syndrome triggered by SARSCoV-2 was initially seen predominantly as a pulmonary disease, thenumber of vascular complications has recently increased. Theseinclude venous and arterial thromboembolic events as well as localthromboses, which can form directly on the endothelium at the site ofcytokine release. With a rate of approximately 20%, deep veinthrombosis (DVT) of the leg is one of the most common thromboembolic events in COVID-19 patients requiring intensive care unit.Aims &Objectives: To know that COVID-19 infection can causeextensive thrombosis.Materials &Methods: Blood samples for Covid RTPCR.Result: All the tests for evaluation of common causes of extensivethrombosis were ruled out. Even covidrtpcr was negative, but SARSCoV IgG was elevated more than 30 times the upper normal range.Conclusions: Extensive thrombosis in the body can be due to covid19 infection.

An Unusual Case of Pancytopenia

Introduction: HLH should be considered in patients with underlyingautoimmune disorder, immunodeficiency or infection presenting withfever, pancytopenia, organomegaly.Aims &Objectives: Treatable cause of pancytopenia in post-covidpatient must be evaluated.Materials &Methods: A 58 yr female, known case of Type IIDiabetes Mellitus, Hypertension and Rheumatoid Arthritis on treatment for 10 years;and Severe COVID-19 pneumonia 2 months back,presented with generalized weakness and easy fatiguability for1.5 months and fever for 1 month.Patient had no history of cough,breathlessness, recent increase in joint pain, rash, bleeding or anyother localizing sign of infection.On examinations patient was febrile (101.7 F) with PR-108/min andBP-150/88 mm.Pallor was present, Rest all general and systemicexamination finding was unremarkable. On Investigating patient wasfound to have pancytopenia without Neutrophylic/lymphocyticreversal, with correct retic count of 3.3%, Ferritin-628 ng/ml,LDH-370 U/L, Fasting Triglyceride-310 mg/dl, Procalcitonin-0.5 ng/dl, Other causes of pancytopenia were ruled out.Result: Bone marrow aspiration was done which showed hypercellular particulate marrow with many macrophage exhibitingerythrophagocytosis. HLH 2004 Diagnostic Criteria score was 5/8suggestive of HLH. H-Score of the patient 183. Patient was treatedwith oral prednisolone rest of the complains was managed symptomatically. Fever and pancytopenia improved and patient wasdischarged with stable vitals.Conclusions: HLH is a rare syndrome in adult. Delay in diagnosisdue to lack of suspicion and non-specific clinical and lab findings. AllHLH patient dont need aggressive chemotherapy. Clinicallystable patients should undergo treatment for the trigger.

Impact of covid-19 pandemic on suicidal and homicidal deaths in Jabalpur, Madhya Pradesh, India

Introduction: The novel coronavirus-2019 (COVID-19) pandemic has impacted significantly on many sectors globally, and has also impacted mental health of many individuals. actually infected with the disease. The World Health Organization declared the virus outbreak as a pandemic in March 2020. Current lockdown scenarios have led to different behavioural consequences which lead to increase in homicidal cases and suicidal behaviours. Aim: To study the effect of COVID-19 pandemic on suicidal and homicidal deaths in Jabalpur district between months' March to July 2020, to cause awareness among health care professionals about impact of COVID-19 on mental health. Materials and Methods: Present study was conducted in the department of forensic medicine and toxicology, Netaji Subhash Chandra Bose Medical College, Jabalpur. Only confirmed cases of suicide and homicide were included in the study based on post mortem reports and police inquest. Result: COVID-19 pandemic caused an expected rise in the number of suicide and homicidal cases in the year 2020 in Jabalpur, when compared with the year 2019. Conclusion: A need for adequate mental health programs to combat the increase in mental health problems by initiatives along with tele-mental health care, where mental health providers are expected to play a vital role in promoting psychological and emotional well-being, strengthening problem-solving and health-promoting habits in service recipients. © 2021, Punjab Academy of Forensic Medicine and Toxicology. All rights reserved.

Impact of Meteorological factors and population size on the transmission of Micro-size respiratory droplets based Coronavirus: A brief study of highly infected cities in Pakistan (preprint)

Ongoing Coronavirus epidemic (COVID-19) identified first in Wuhan, China posed huge impact on public health and economy around the globe. Both cough and sneeze based droplets or aerosols encapsulated COVID-19 particles are responsible for air borne transmission of this virus and caused unexpected escalation and high mortality worldwide. Current study intends to investigate correlation of COVID-19 epidemic with meteorological parameters particularly, temperature, rainfall, humidity, and wind speed along with population size. Data set of COVID-19 for highly infected cities of Pakistan was collected from the official website of National Institute of health (NIH). Spearman rank (rs) correlation coefficient test employed for data analysis revealed significant correlation between temperature minimum (TM), temperature average (TA), wind speed (WS) and population size (PS) with COVID-19 pandemic. Furthermore, receiver operating characteristics (ROC) curve was used to analyze the sensitivity of TA, WS, and PS on transmission rate of COVID-19 in selected cities of Pakistan. The results obtained for sensitivity and specificity analysis for all selected parameters signifies sensitivity and direct correlation of COVID-19 transmission with temperature variation, WS and PS. Positive correlation and strong association of PS parameter with COVID-19 pandemic suggested need of more strict actions and control measures for highly populated cities. These findings will be helpful for health regulatory authorities and policymakers to take specific measures to combat COVID-19 epidemic in Pakistan.