Evaluation of Candida Scoring Systems to Predict Early Candidemia: A Prospective and Observational Study at a Tertiary Care Hospital, Uttarakhand.

BACKGROUND: Candidemia in critically ill patients is usually a severe and life-threatening condition. Furthermore, due to its nonspecific presentation, it is difficult to diagnose leading to delayed treatment, prolonged hospitalization, and increased health-care costs with increase in morbidity and mortality. OBJECTIVES: In view of lack of data on "Candida scoring systems," this study was designed to evaluate the effectiveness of these scoring systems in predicting the development of candidemia among the Intensive Care Unit patients. MATERIALS AND METHODS: The "Candida score" was calculated at the onset of systemic inflammatory response syndrome, sepsis, or shock. Various scoring systems were compared using the area under the receiver operating characteristic curve. RESULTS: Among all three bedside risk scoring systems to predict candidemia both Leon score and Wenzel score offered significant discrimination between candidemic and noncandidemic patients with P = 0.000 and 0.001, respectively. The area under the curve for the scoring systems was 0.946 (95% confidence interval [CI] = 0.89-1) and 0.818 (95% CI = 0.687-0.949). CONCLUSION: Leon scoring system was found to have highest specificity, diagnostic accuracy, and positive likelihood ratio among all. Thus, we might conclude that a Leon score of ≥2.5 was most suitable for diagnosis of candidemia with significant accuracy and shortening of turnaround time when compared to the gold standard of blood culture. To the best of our knowledge, this is the first report on the subject.

Outbreak of an emerging zoonotic Nipah virus: An emerging concern.

The Nipah virus (NiV) infection is one of the newly emerging deadly zoonotic diseases which carries a significant weightage of mortality among its victims. Due to the relatively recent history of its emergence and only a few known outbreaks, we cannot predict but foresee its potential to create havoc, which can be far more dreadful than the current ongoing COVID-19 pandemic. Here we have tried to depict the fatal potential of the virus and the increased propensity with which it can spread to rest of the world.

Omicron (B.1.1.529) variant and its subvariants and lineages may lead to another COVID-19 wave in the world? -An overview of current evidence and counteracting strategies.

The highly contagious Omicron variant of SARS-CoV-2 is a recent cause of concern during the COVID-19 pandemic. The World Health Organization (WHO) has classified SARS-CoV-2 variants into variants of concern (VOCs), variants of interest (VOIs), and variants under monitoring (VUMs). VOCs were categorized as Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2). Omicron (B.1.1.529) was a further modified strain that has a short incubation period; it was called VOC by the WHO, and it became fifth on the list of variants. Omicron has spread faster than any other variant since its emergence in late 2021. Omicron is currently the only circulating VOC. The various subvariants of Omicron are BA.1 (B.1.1.529.1), BA.2 (B.1.1.529.2), BA.3 (B.1.1.529.3), BA.4, BA.5, and descendent lineages. More recently, identified Omicron subvariants and sublineages BQ.1, BQ.1.1, BA.4.6, BF.7, BA.2.75.2, XBB.1, and BF.7 have also attracted global attention. The BA.5 strain of Omicron is the most contagious and dominant subvariant globally. Recent spikes in cases in China are due to the BF.7 subvariant. With the large increase in the number of cases, there has been an increase in hospitalisations in countries worldwide. In many countries, the lifting of infection prevention protocols, such as the use of masks and physical distancing, contributes to the spread of the virus. This article highlights the potential impacts of SARS-CoV-2 variants and subvariants, which have made the pandemic far from over. Effective vaccination remains the safest option to kerb transmission of these variants. Therefore, people must be vaccinated, wear masks, perform regular hand hygiene, and observe social distancing. Additionally, genome sequencing of positive samples can help detect various virus variants; thus, mapping cases in a particular area can be performed.

Interpretation of Antimicrobial Susceptibility Testing Using European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Clinical and Laboratory Standards Institute (CLSI) Breakpoints: Analysis of Agreement.

OBJECTIVES: Breakpoints provided by European Committee on Antimicrobial Susceptibility Testing (EUCAST) are now being used in many countries. This study was planned to ascertain the agreement in antimicrobial susceptibility using the Clinical and Laboratory Standards Institute (CLSI) and EUCAST breakpoints during the Kirby-Bauer disk diffusion method. METHODS:  This was a prospective observational study. Clinical isolates belonging to the family Enterobacteriaceae recovered between January and December, 2022, were included in the analysis. The diameter of the zone of inhibition of the 14 antimicrobials (viz. amoxicillin/clavulanic acid, cefazolin, ceftriaxone, cefuroxime, cefixime, aztreonam, meropenem, gentamicin, amikacin, ciprofloxacin, levofloxacin, norfloxacin, trimethoprim/sulfamethoxazole and fosfomycin) was analysed. Antimicrobial susceptibility was interpreted using CLSI 2022 and EUCAST 2022 guidelines.  Results: Susceptibility data from a total of 356 isolates showed a slight increase in the percentage of resistant isolates with most of the drugs using EUCAST guidelines. The level of agreement varied from almost perfect to slight. For two drugs, i.e., fosfomycin and cefazolin, the agreement was least among the drug analysed (kappa (κ) value < 0.5, p < 0.001). For Ceftriaxone and Aztreonam, with EUCAST, susceptible (S) isolates would have been categorised in the newly redefined "I" category. It would have indicated the use of higher dosages of drugs.  Conclusion: Change in the breakpoints impacts the interpretation of the susceptibility. It can also lead to a change in the dosage of the drug used for treatment. Therefore, there is an urgent need to see the impact of recent modifications "I" category of EUCAST on the clinical outcome and usage of antimicrobials.

Clinical Profile of Adult Bronchial Asthma Patients Presenting at a Tertiary Care Teaching Institute in Northern India.

BACKGROUND: In the previous four decades there have been remarkable changes and development in the approach toward the diagnosis and management of asthma. There are wide variations in the clinical profile of asthma patients in different parts of a vast country like India due to significant variations in the geography, culture, ethnicity, and socioeconomic profile of the Indian population. In the present study, we have aimed to study the clinical profile of adult asthmatic patients in a tertiary care teaching institute in Northern India. METHODS: In this observational cross-sectional study, a total of 966 asthma patients were included from August 2020 to July 2021 after following strict inclusion and exclusion criteria. After a thorough history and clinical examination, patients were subjected to relevant investigations including spirometry. RESULTS: Our study showed slight female preponderance (51.7%) over males among asthma patients. A maximum number of patients were of comparatively younger age groups and urban. The most common symptom at the time of presentation was breathlessness (94.5%) followed by cough in about 59.8%. Family history was present in about 9.3% of patients. A maximum number of patients presented in the months of November and December and rhinitis was the most commonly associated atopic condition. The majority (65.28%) of previously diagnosed patients had uncontrolled asthma at the time of their first presentation in our department. CONCLUSION: Results of our study endorse the poor awareness in society towards education and management of asthma. Females and comparatively younger patients are more commonly affected. Significant differences in our study from previous studies in different parts of India confirm that the pattern and clinical profile of asthma patients in one region cannot be extrapolated to other regions and the need for future studies in other regions of our country is also required.

Epidemiologic Situation of HIV and Monkeypox Coinfection: A Systematic Review.

The most recent monkeypox (Mpox) outbreak is mostly affecting men who have sex with men (MSM) who participate in high-risk sexual behaviors, which is typically the case among human immunodeficiency virus (HIV) carriers, according to clinical and epidemiological statistics. The objective of this research is to determine the epidemiological situation of HIV and smallpox co-infection. Until 1 October 2022, a thorough evaluation of the literature was conducted utilizing the databases PubMed, Embase, Scopus, and Web of Science. Studies were evaluated based on the criteria for selection. Fifty-three studies met the selection criteria. A total of 6345 confirmed cases of monkeypox were recorded, and 40.32% (n = 2558) of these cases also had HIV co-infection. In addition, 51.36% (n = 3259) of the men (91.44%; n = 5802), whose ages ranged from 18 to 71 years, exhibited MSM-specific sexual behaviors. Co-infection with these two viruses can be especially dangerous because it can exacerbate the symptoms of both diseases and make them more difficult to treat. People with HIV are more vulnerable to certain infections, including monkeypox, because their immune systems are weakened. Therefore, it is important that they take measures to prevent infection, such as avoiding contact with infected animals, risky behaviors, and maintaining good hygiene.

Ebola Virus Disease Vaccines: Development, Current Perspectives & Challenges.

The global outgoing outbreaks of Ebola virus disease (EVD) in different regions of Sudan, Uganda, and Western Africa have brought into focus the inadequacies and restrictions of pre-designed vaccines for use in the battle against EVD, which has affirmed the urgent need for the development of a systematic protocol to produce Ebola vaccines prior to an outbreak. There are several vaccines available being developed by preclinical trials and human-based clinical trials. The group of vaccines includes virus-like particle-based vaccines, DNA-based vaccines, whole virus recombinant vaccines, incompetent replication originated vaccines, and competent replication vaccines. The limitations and challenges faced in the development of Ebola vaccines are the selection of immunogenic, rapid-responsive, cross-protective immunity-based vaccinations with assurances of prolonged protection. Another issue for the manufacturing and distribution of vaccines involves post authorization, licensing, and surveillance to ensure a vaccine's efficacy towards combating the Ebola outbreak. The current review focuses on the development process, the current perspective on the development of an Ebola vaccine, and future challenges for combatting future emerging Ebola infectious disease.

Unravelling COVID-19 vaccination attributes worldwide: an extensive review regarding uptake, hesitancy, and future implication.

Since the declaration of the coronavirus disease 2019 pandemic, all efforts were directed towards limiting the transfer of the disease and preventing severe disease forms from occurring. In this regard, numerous vaccines were quickly developed to limit the associated morbidity and mortality of the disease and to reduce the burden on healthcare systems worldwide. However, to date, vaccine hesitancy remains a major limitation to vaccine distribution, with varying degrees in different countries. Therefore, the authors conducted this literature review to highlight the magnitude of this issue throughout the globe and summarize some of its major causes (i.e. governmental, healthcare system-related, population-related, and vaccine-related) and contributing factors (i.e. knowledge/awareness, social media, etc.). In addition, the authors highlighted some of the main motivating factors that can minimize the burden of vaccine hesitancy at the population, governmental, and worldwide levels. These include structural (i.e. government, country), extrinsic (i.e. family, friends), intrinsic (i.e. self-perception), and other factors (financial and nonfinancial). Finally, the authors proposed some implications for future research to ease the vaccination process and hopefully, put an end to this problem.

The Global Monkeypox (Mpox) Outbreak: A Comprehensive Review.

Monkeypox (Mpox) is a contagious illness that is caused by the monkeypox virus, which is part of the same family of viruses as variola, vaccinia, and cowpox. It was first detected in the Democratic Republic of the Congo in 1970 and has since caused sporadic cases and outbreaks in a few countries in West and Central Africa. In July 2022, the World Health Organization (WHO) declared a public-health emergency of international concern due to the unprecedented global spread of the disease. Despite breakthroughs in medical treatments, vaccines, and diagnostics, diseases like monkeypox still cause death and suffering around the world and have a heavy economic impact. The 85,189 reported cases of Mpox as of 29 January 2023 have raised alarm bells. Vaccines for the vaccinia virus can protect against monkeypox, but these immunizations were stopped after smallpox was eradicated. There are, however, treatments available once the illness has taken hold. During the 2022 outbreak, most cases occurred among men who had sex with men, and there was a range of 7-10 days between exposure and the onset of symptoms. Three vaccines are currently used against the Monkeypox virus. Two of these vaccines were initially developed for smallpox, and the third is specifically designed for biological-terrorism protection. The first vaccine is an attenuated, nonreplicating smallpox vaccine that can also be used for immunocompromised individuals, marketed under different names in different regions. The second vaccine, ACAM2000, is a recombinant second-generation vaccine initially developed for smallpox. It is recommended for use in preventing monkeypox infection but is not recommended for individuals with certain health conditions or during pregnancy. The third vaccine, LC16m8, is a licensed attenuated smallpox vaccine designed to lack the B5R envelope-protein gene to reduce neurotoxicity. It generates neutralizing antibodies to multiple poxviruses and broad T-cell responses. The immune response takes 14 days after the second dose of the first two vaccines and 4 weeks after the ACAM2000 dose for maximal immunity development. The efficacy of these vaccines in the current outbreak of monkeypox is uncertain. Adverse events have been reported, and a next generation of safer and specific vaccines is needed. Although some experts claim that developing vaccines with a large spectrum of specificity can be advantageous, epitope-focused immunogens are often more effective in enhancing neutralization.

A proposed management classification for spinal brucellosis from India.

INTRODUCTION: The myriad presentation of osteoarticular brucellosis make the patient seek the help of general practitioners, orthopaedic and rheumatology specialists. Moreover, the lack of disease-specific symptomatology is the leading cause of the delay in diagnosing osteoarticular brucellosis. Given the increasing number of spinal brucellosis cases across the country, no literature is presented on the systematic management of spinal brucellosis. However, with our experience, we formulated a classification for managing spinal brucellosis. METHODS: A single-centred prospective observational study was conducted with 25 confirmed cases of spinal brucellosis. Patients were analysed and graded clinically, serologically, and radiologically and were managed with antibiotics for 10-12 weeks, and if necessary, stabilisation and fusion were done based on the treatment classification devised. All patients were followed up to ensure disease clearance at serial follow-up with relevant investigations. RESULTS: The mean age of the study participants was 52.16 ± 12.53 years. According to spondylodiscitis severity code (SSC) grading, four patients belong to grades 1, 12 to grade 2 and 9 to grade 3 at presentation. Erythrocyte sedimentation rate (p = 0.02), c-reactive protein (p < 0.001), Brucella agglutination titers (p < 0.001), and radiological outcomes improved statistically by six months. The treatment duration was individualised according to the patient's response to the treatment, with a mean time of 11.42 ± 2.66 weeks. The mean follow-up period was 14.42 ± 8 months. CONCLUSION: High index of suspicion of patients from endemic regions, proper clinical assessment, serological evaluation, radiological assessment, appropriate decision-making (medical/surgical) in treatment, and regular follow-up were the key to successful comprehensive management of spinal brucellosis.

COVID-19 vaccines and their underbelly: Are we going the right way?

Background: Historically, a critical aetiological agent of health concern stays till eternity after its discovery, so shall it be with the COVID-19 outbreak. It has transformed human life to a 'new normal' with huge tolls on the social, psychological, intellectual and financial spheres. Aim: This perspective aimed to collate numerous reported COVID-19 vaccine-associated adverse events and the predisposing factors. It focussed on the efficacy of mix-n-match (cocktail) vaccines to effectively counter COVID-19 infection to facilitate future research and possible interventions. Material and Methods: Databases like Scopus, Pubmed and the Web-of-science were searched for published literature on 'adverse events associated with COVID-19 vaccine'. The reports and updates from health agencies like the WHO and CDC were also considered for the purpose. The details with respect to the adverse events associated with COVID-19 vaccination and the predisposing factors were compiled to obtain insights and suggest possible future directions in vaccine research. Results: India stood strong to manage its health resources in time and turned into a dominant global vaccine supplier at a time when healthcare infrastructure of many countries was still significantly challenged. Developing indigenous vaccines and the vaccination drive in India were its major achievements during the second and the subsequent COVID-19 waves. The fully indigenous Covaxin vaccine, primarily as an emergency intervention, was successfully rapidly launched. Similar such vaccines for emergency use were developed elsewhere as well. However, all of these reached the marketplace with a 'emergency use only' tag, without formal clinical trials and other associated formalities to validate and verify them as these would require much longer incubation time before they are available for human use. Discussion: Many adverse events associated with either the first or the second/booster vaccination doses were reported. Evidently, these associated adverse events were considered as 'usually rare' or were often underreported. Without the additional financial or ethical burden on the vaccine companies, fortunately, the Phase IV (human) clinical trials of their manufactured vaccines are occurring by default as the human population receives these under the tag 'emergency use'. Thus, focused and collaborative strategies to unveil the molecular mechanisms in vaccine-related adverse events in a time-bound manner are suggested. Conclusion: Reliable data particularly on the safety of children is lacking as majority of the current over-the-counter COVID-19 vaccines were for emergency use. Many of these were still in their Phase III and Phase IV trials. The need for a mutant-proof, next-gen COVID-19 vaccine in the face of vaccine-associated adverse events is opined.

Emergence of Marburg virus: a global perspective on fatal outbreaks and clinical challenges.

The Marburg virus (MV), identified in 1967, has caused deadly outbreaks worldwide, the mortality rate of Marburg virus disease (MVD) varies depending on the outbreak and virus strain, but the average case fatality rate is around 50%. However, case fatality rates have varied from 24 to 88% in past outbreaks depending on virus strain and case management. Designated a priority pathogen by the National Institute of Allergy and Infectious Diseases (NIAID), MV induces hemorrhagic fever, organ failure, and coagulation issues in both humans and non-human primates. This review presents an extensive exploration of MVD outbreak evolution, virus structure, and genome, as well as the sources and transmission routes of MV, including human-to-human spread and involvement of natural hosts such as the Egyptian fruit bat (Rousettus aegyptiacus) and other Chiroptera species. The disease progression involves early viral replication impacting immune cells like monocytes, macrophages, and dendritic cells, followed by damage to the spleen, liver, and secondary lymphoid organs. Subsequent spread occurs to hepatocytes, endothelial cells, fibroblasts, and epithelial cells. MV can evade host immune response by inhibiting interferon type I (IFN-1) synthesis. This comprehensive investigation aims to enhance understanding of pathophysiology, cellular tropism, and injury sites in the host, aiding insights into MVD causes. Clinical data and treatments are discussed, albeit current methods to halt MVD outbreaks remain elusive. By elucidating MV infection's history and mechanisms, this review seeks to advance MV disease treatment, drug development, and vaccine creation. The World Health Organization (WHO) considers MV a high-concern filovirus causing severe and fatal hemorrhagic fever, with a death rate ranging from 24 to 88%. The virus often spreads through contact with infected individuals, originating from animals. Visitors to bat habitats like caves or mines face higher risk. We tailored this search strategy for four databases: Scopus, Web of Science, Google Scholar, and PubMed. we primarily utilized search terms such as "Marburg virus," "Epidemiology," "Vaccine," "Outbreak," and "Transmission." To enhance comprehension of the virus and associated disease, this summary offers a comprehensive overview of MV outbreaks, pathophysiology, and management strategies. Continued research and learning hold promise for preventing and controlling future MVD outbreaks. GRAPHICAL ABSTRACT.

Socio-demographic determinants of Monkeypox virus preventive behavior: A cross-sectional study in Pakistan.

BACKGROUND: Monkeypox (mpox), re-emerging zoonotic infectious disease, is striking the world with serious public health concerns, especially in non-endemic countries. The public's knowledge and attitude towards the monkeypox virus (MPXV) influence their adherence to preventive strategies. Therefore, we aimed to assess the public's knowledge, attitudes, and perceptions (KAP) of MPXV in Pakistan. METHODS: We collected data for this cross-sectional study from 1040 participants via online self-reported questionnaire from July 5th, 2022, to August 1st, 2022. The questionnaire consisted of a total of 29 items in four sections, assessing socio-demographics, knowledge, attitudes, and practices regarding MPXV. The data were analyzed using IBM SPSS V.25, and factors associated with MPXV knowledge, attitude, and practices were identified by using logistic regression analyses. RESULTS: A total of 1040 participants were included. 61.4% were male, and 57.2% had graduation level education. Only 34.4% had good knowledge about MPXV, and 30% knew the effectiveness of the smallpox vaccine against MPXV. 41.7% had a positive attitude, 48.6% agreed that it is a fatal disease, and 44.6% were in favour of banning travel from endemic to non-endemic regions. 57.7% had good practices, and 69.9% would use protective measures if MPXV became an epidemic. Binary logistic regression analysis revealed that gender and education significantly impacted knowledge (p<0.05). While monthly income status had a significant impact on attitudes (p<0.05). The practices were positively correlated with gender and education (p<0.05). CONCLUSION: The majority of study participants had inadequate levels of knowledge, and attitudes regarding MPXV. To prevent the emergence and spread of MPXV in Pakistan, a comprehensive strategic framework for public health education must be established and implemented.

Vaccine Derived Poliovirus (VDPV).

Poliomyelitis is caused by Poliovirus, a member of a large group of enteroviruses. Vaccine-derived polioviruses (VDPVs) stem from mutated live poliovirus, which is contained in the Oral Polio Virus vaccine (OPV). In addition, the emergence of VDPV is one of the global challenges for the eradication of poliomyelitis. VDPVs continue to affect different parts of the world; 1081 cases occurred in 2020 and 682 cases in 2021. There are several reasons that may have caused the increase in circulating vaccine-derived poliovirus (cVDPV) after the "switch" from the trivalent to the bivalent oral polio vaccine. One reason is the low vaccination rate among the targeted population, which has been further aggravated by the COVID-19 pandemic. Several strategies could control the spread of VDPV including the use of the monovalent OPV (mOPV-2). The risk of VDPV can be minimized through increased immunization rates and the use of safer vaccine alternatives. The global effort to eradicate polio has made significant progress over the years, but continued vigilance and investment in immunization programs are needed to achieve the ultimate goal of a polio-free world.

Monkeypox-Associated Manifestations and Complications Involving the Eye: A Systematic Review and Meta-Analysis of Previous and Current Outbreaks.

PURPOSE: The purpose of this study was to pool the prevalence rate of monkeypox-associated eye manifestations and/or complications during the current and previous outbreaks. DESIGN: A systematic review and meta-analysis. MATERIALS AND METHODS: On August 7, 2022, PubMed, Scopus, Web of Science, EMBASE, and Google Scholar were searched for relevant articles. We included all studies that reported the involvement of the eye (either as a manifestation or a complication) among patients with monkeypox. The primary outcome included pooling the effect size (ES) of reported manifestations and complications, and the secondary outcome included the conduct of a subgroup analysis based on the timing of the monkeypox outbreak (before vs. during 2022). RESULTS: Eleven studies reporting 3179 monkeypox-confirmed cases were included. Eye manifestations included conjunctivitis, corneal, conjunctival, and eyelid lesions, photophobia, and eye pain. Compared with previous monkeypox outbreaks, the current outbreak revealed much lower rates of ocular involvement in terms of conjunctivitis (ES=1%; 95% CI: 0%-1% vs. ES=17%; 95% CI: 11%-22%), corneal and conjunctival lesions (ES=1%; 95% CI: 0%-2% vs. ES=13%; 95% CI: 4%-22%), and eyelid lesions (ES=1%; 95% CI: 0%-4% vs. ES=13%; 95% CI: 5%-28%). Monkeypox-associated eye complications were reported only in the previous outbreaks which included keratitis (ES=4%; 95% CI: 3%-6%), corneal ulceration (ES=4%; 95% CI: 2%-5%), unilateral (ES=3%; 95% CI: 1%-4%) and bilateral blindness (ES=0%; 95% CI: 0%-2%), and impaired vision (ES=4%; 95% CI: 1%-8%). CONCLUSIONS: Ophthalmic manifestations and complications are common among monkeypox-confirmed cases. Although these data are mainly related to previous outbreaks, health care workers should familiarize themselves with these signs to provide better care for monkeypox patients.

Environmental detection and spreading of mpox in healthcare settings: a narrative review.

Monkeypox virus (MPXV), which causes Monkeypox (Mpox), has recently been found outside its usual geographic distribution and has spread to 117 different nations. The World Health Organization (WHO) designated the epidemic a Public Health Emergency of International Concern (PHEIC). Humans are at risk from MPXV's spread, which has raised concerns, particularly in the wake of the SARS-CoV-2 epidemic. The risk of virus transmission may rise due to the persistence of MPXV on surfaces or in wastewater. The risk of infection may also increase due to insufficient wastewater treatment allowing the virus to survive in the environment. To manage the infection cycle, it is essential to investigate the viral shedding from various lesions, the persistence of MPXV on multiple surfaces, and the length of surface contamination. Environmental contamination may contribute to virus persistence and future infection transmission. The best possible infection control and disinfection techniques depend on this knowledge. It is thought to spread mainly through intimate contact. However, the idea of virus transmission by environmental contamination creates great concern and discussion. There are more cases of environmental surfaces and wastewater contamination. We will talk about wastewater contamination, methods of disinfection, and the present wastewater treatment in this review as well as the persistence of MPXV on various environmental surfaces.

Exploring the theranostic potentials of miRNA and epigenetic networks in autoimmune diseases: A comprehensive review.

BACKGROUND: Autoimmune diseases (AD) are severe pathophysiological ailments that are stimulated by an exaggerated immunogenic response towards self-antigens, which can cause systemic or site-specific organ damage. An array of complex genetic and epigenetic facets majorly contributes to the progression of AD, thus providing significant insight into the regulatory mechanism of microRNA (miRNA). miRNAs are short, non-coding RNAs that have been identified as essential contributors to the post-transcriptional regulation of host genome expression and as crucial regulators of a myriad of biological processes such as immune homeostasis, T helper cell differentiation, central and peripheral tolerance, and immune cell development. AIMS: This article tends to deliberate and conceptualize the brief pathogenesis and pertinent epigenetic regulatory mechanism as well as miRNA networks majorly affecting five different ADs namely rheumatoid arthritis (RA), type 1 diabetes, multiple sclerosis (MS), systemic lupus erythematosus (SLE) and inflammatory bowel disorder (IBD) thereby providing novel miRNA-based theranostic interventions. RESULTS & DISCUSSION: Pertaining to the differential expression of miRNA attributed in target tissues and cellular bodies of innate and adaptive immunity, a paradigm of scientific expeditions suggests an optimistic correlation between immunogenic dysfunction and miRNA alterations. CONCLUSION: Therefore, it is not astonishing that dysregulations in miRNA expression patterns are now recognized in a wide spectrum of disorders, establishing themselves as potential biomarkers and therapeutic targets. Owing to its theranostic potencies, miRNA targets have been widely utilized in the development of biosensors and other therapeutic molecules originating from the same.

The use of antivirals in the treatment of human monkeypox outbreaks: a systematic review.

OBJECTIVES: Human monkeypox virus (MPXV) infection is a recently declared public health emergency of international concern by the World Health Organization. Besides, there is scant literature available on the use of antivirals in MPXV infection. This systematic review compiles all evidence of various antivirals used on their efficacy and safety and summarizes their mechanisms of action. METHODS: A review was done of all original studies mentioning individual patient data on the use of antivirals in patients with MPXV infection. RESULTS: Of the total 487 non-duplicate studies, 18 studies with 71 individuals were included. Tecovirimat was used in 61 individuals, followed by cidofovir in seven and brincidofovir (BCV) in three individuals. Topical trifluridine was used in four ophthalmic cases in addition to tecovirimat. Of the total, 59 (83.1%) were reported to have complete resolution of symptoms; one was experiencing waxing and waning of symptoms, only one (1.8%) had died, and the others were having a resolution of symptoms. The death was thought unrelated to tecovirimat. Elevated hepatic panels were reported among all individuals treated with BCV (leading to treatment discontinuation) and five treated with tecovirimat. CONCLUSION: Tecovirimat is the most used and has proven beneficial in several aggravating cases. No major safety concerns were detected upon its use. Topical trifluridine was used as an adjuvant treatment option along with tecovirimat. BCV and cidofovir were seldom used, with the latter often being used due to the unavailability of tecovirimat. BCV was associated with treatment discontinuation due to adverse events.

Virulence traits and novel drug delivery strategies for mucormycosis post-COVID-19: a comprehensive review.

The outbreak of a fatal black fungus infection after the resurgence of the cadaverous COVID-19 has exhorted scientists worldwide to develop a nutshell by repurposing or designing new formulations to address the crisis. Patients expressing COVID-19 are more susceptible to Mucormycosis (MCR) and thus fall easy prey to decease accounting for this global threat. Their mortality rates range around 32-70% depending on the organs affected and grow even higher despite the treatment. The many contemporary recommendations strongly advise using liposomal amphotericin B and surgery as first-line therapy whenever practicable. MCR is a dangerous infection that requires an antifungal drug administration on appropriate prescription, typically one of the following: Amphotericin B, Posaconazole, or Isavuconazole since the fungi that cause MCR are resistant to other medications like fluconazole, voriconazole, and echinocandins. Amphotericin B and Posaconazole are administered through veins (intravenously), and isavuconazole by mouth (orally). From last several years so many compounds are developed against invasive fungal disease but only few of them are able to induce effective treatment against the micorals. Adjuvant medicines, more particularly, are difficult to assess without prospective randomized controlled investigations, which are challenging to conduct given the lower incidence and higher mortality from Mucormycosis. The present analysis provides insight into pathogenesis, epidemiology, clinical manifestations, underlying fungal virulence, and growth mechanisms. In addition, current therapy for MCR in Post Covid-19 individuals includes conventional and novel nano-based advanced management systems for procuring against deadly fungal infection. The study urges involving nanomedicine to prevent fungal growth at the commencement of infection, delay the progression, and mitigate fatality risk.