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Dengue fever, caused by the dengue virus and transmitted through Aedes mosquitoes, is a growing public health concern, particularly in tropical and subtropical regions. Traditionally associated with febrile and hemorrhagic symptoms, recent research suggests a potential link between dengue and cognitive impairments. This systematic review assessed existing research to understand the association between dengue virus infection and cognitive impairments, including dementia, Alzheimer disease, memory loss, and confusion. This systematic review followed preferred reporting items for systematic reviews and meta-analyses guidelines. A comprehensive literature search was conducted in PubMed, EMBASE, and Web of Science up to January 18, 2024. Studies examining the prevalence and association of cognitive impairments in dengue patients were included. Data extraction and quality assessment were performed using Nested Knowledge software and the Newcastle-Ottawa Scale. Of the 1129 articles identified, 5 were included in the review, covering a total of 200 873 participants from Taiwan, Brazil, and France. Evidence from population-based cohort studies indicated short-term cognitive impairments, including confusion and memory loss, in some dengue patients. Additionally, long-term risks of dementia, including Alzheimer disease and vascular dementia, were observed, particularly among older adults. Although the findings suggest there might be an association between dengue infection and cognitive decline, the mechanisms underlying this link remain unclear. This systematic review suggests that dengue virus infection may affect cognitive function in both acute and long-term contexts. However, the current evidence is not strong enough to establish a conclusive link. Further research with larger sample sizes and longitudinal studies is essential to confirm the impact of dengue virus on cognitive health., (© The Author(s) 2024. Published by Oxford University Press on behalf of CINP.)

Non-coding RNAs (ncRNAs) contain circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and micro-ribonucleic acids (miRNAs). These RNAs receive good functionality in modulation of gene expressions & cellular roles. Recent research is shedding light on their pivotal roles in the pathophysiology of inflammatory meningitis, such as viral, fungal, or bacterial infections. This review addresses the intricate roles of non-coding RNAs (ncRNAs) that transcribe code-independent mRNA and other biological elements that control inflammation and immunological events extant during meningitis. ncRNAs, acting on a myriad of immune cell development, cytokine production, pathogen recognition, and so forth, finely orchestrate the host's immune response. Although lncRNAs and circRNAs are associated with gene networks regulating immune responses, miRNAs can precisely modulate the expression of pro- and anti-inflammatory cytokines. Moreover, ncRNAs have unique expression patterns in disease states and are stable in bio-fluids; therefore, they can serve as specific molecular biomarkers for meningitis concerning the diagnosis and prognosis. It might also be helpful to target ncRNAs as a therapeutic strategy to impact immune regulation and inflammation. Here, we review the current knowledge of how ncRNAs function in meningitis and discuss adopted approaches and perspectives and their implications for therapeutic strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier GmbH.)

The emergence of the human monkeypox virus (MPXV) and the lack of effective medications have necessitated the exploration of various strategies to combat its infection. This study employs a network-based approach to drug discovery, utilizing the BLASTn and phylogenetic analysis to compare the MPXV genome with those of 18 related orthopoxviruses, revealing over 75 % genomic similarity. Through a literature review, 160 human-host proteins linked to MPXV and its relatives were identified, leading to the construction of a human-host protein interactome. Analysis of this interactome highlighted 39 central hub proteins, which were then examined for potential drug targets. The process successfully revealed 15 targets already approved for use with medications. Additionally, the functional enrichment analysis provided insights into potential pathways and disorders connected with these targets. Four medications, namely Baricitinib, Infliximab, Adalimumab, and Etanercept, have been identified as potential candidates for repurposing to combat MPXV. In addition, the pharmacophore-based screening identified a molecule that is comparable to Baricitinib and has the potential to be effective against MPXV. The findings of the study suggest that ZINC22060520 is a promising medication for treating MPXV infection and proposes these medications as potential options for additional experimental and clinical assessment in the battle against MPXV., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Background: Malaria in pregnancy is a critical public health issue that can lead to severe adverse outcomes for both mother and fetus. This systematic review and meta-analysis evaluated the prevalence of adverse birth outcomes in malaria-infected pregnancies and examines their association with the condition., Method: We searched databases up to January 30, 2024, for observational studies on pregnant women with malaria. Data were analyzed using a random-effects model to calculate pooled prevalence rates and risk ratios (RRs) for adverse outcomes, with statistical support from R software version 4.3., Results: Thirty-one studies were included, showing high prevalence of low birth weight (LBW; 17.4 %), preterm birth (17.9 %), and small for gestational age (SGA; 16.1 %) in malaria-affected pregnancies. Infected mothers were significantly more likely to have LBW infants (RR = 1.755), preterm births (RR = 1.484), and SGA infants (RR = 1.554). The risk of stillbirth was not significantly increased (RR = 1.238)., Conclusion: Malaria in pregnancy significantly elevates the risk of LBW, preterm birth, and SGA, underscoring the need for effective malaria prevention and treatment strategies in endemic regions. Future research should aim to refine and implement these strategies to enhance maternal and neonatal health outcomes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Background: Multisystem Inflammatory Syndrome in Children (MIS-C) associated with SARS-CoV-2 can lead to severe cardiovascular complications. Anakinra, an interleukin-1 receptor antagonist, is proposed to benefit the hyperinflammatory state of MIS-C, potentially improving cardiac function. This systematic review evaluated the effectiveness of early Anakinra administration on cardiac outcomes in children with MIS-C., Methods: A comprehensive search across PubMed, Embase, and Web of Science until March 2024 identified studies using Anakinra to treat MIS-C with reported cardiac outcomes. Observational cohorts and clinical trials were included, with data extraction focusing on cardiac function metrics and inflammatory markers. Study quality was assessed using the Newcastle-Ottawa Scale., Results: Six studies met the inclusion criteria, ranging from retrospective cohorts to prospective clinical studies, predominantly from the USA. Anakinra dosages ranged from 2.3 to 10 mg/kg based on disease severity. Several studies showed significant improvements in left ventricular ejection fraction and reductions in inflammatory markers like C-reactive protein, suggesting Anakinra's role in enhancing cardiac function and mitigating inflammation. However, findings on vasoactive support needs were mixed, and some studies did not report significant changes in acute cardiac support requirements., Conclusion: Early Anakinra administration shows potential for improving cardiac function and reducing inflammation in children with MIS-C, particularly those with severe manifestations. However, the existing evidence is limited by the observational nature of most studies and lacks randomized controlled trials (RCTs). Further high-quality RCTs are necessary to conclusively determine Anakinra's effectiveness and optimize its use in MIS-C management for better long-term cardiac outcomes and standardized treatment protocols., (© 2024. The Author(s).)

Wild birds could be a reservoir of medically relevant microorganisms, particularly multidrug-resistant Enterococcus spp. Resistant bacteria's epidemiology and transmission between animals and humans has grown, and their zoonotic potential cannot be ignored. This is the first study to evaluate the status of vancomycin resistant enterococci (VRE) in various wild bird species using meta-analysis and a systematic review. In this study, the pooled prevalence was obtained by analyzing data from published articles on the occurrence of VRE in wild bird species. It's unclear how the antibiotic resistance gene transfer cycle affects wild birds. Google Scholar and PubMed were used to conduct the research. The data and study methodology was assessed and extracted by two reviewers independently, with a third reviewing the results. Heterogeneity between study and publication bias were analyzed using the random effect model. Thirty-eight studies were included in the meta-analysis. 382 out of the 4144 isolates tested, were VRE. The pooled prevalence of VRE among wild birds was estimated at 11.0% (95% CI; 6.9 -17.2%; I 2 = 93.204%; P < 0.001). There was high variability between study (t 2 = 2.156; heterogeneity I 2 = 93.204% with chi-square (Q) = 544.413, degrees of freedom (df) = 37, and P < 0.001). Egger's test verified the funnel plot's bias, while result from the leave-one-out forest plot had no effect on the pooled prevalence., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Zika virus (ZIKV) spread is considered a major public health threat by the World Health Organization (WHO). There are no vaccines or drugs available to control the infection of the Zika virus, therefore a highly effective medicinal molecule is urgently required. In this study, a computationally intensive investigation was performed to identify a potent natural compound that could inhibit the ZIKV NS5 methyltransferase. This research approach is based on target-based drug identification principles where the native inhibitor SAH (S-adenosylhomocysteine) of ZIKV NS5 methyltransferase was selected as a reference. High-throughput virtual screening and tanimoto similarity coefficient were applied to the natural compound library for ranking the potential candidates. The top five compounds were selected for interaction analysis, MD simulation, total binding free energy through MM/GBSA, and steered MD simulation. Among these compounds, Adenosine 5'-monophosphate monohydrate, Tubercidin, and 5-Iodotubercidin showed stable binding to the protein compared to the native compound, SAH. These three compounds also showed less fluctuations in RMSF in contrast to native compound. Additionally, the same interacting residues observed in SAH also made strong interactions with these three compounds. Adenosine 5'-monophosphate monohydrate and 5-Iodotubercidin had greater total binding free energies than the reference ligand. Moreover, the dissociation resistance of all three compounds was equivalent to that of the reference ligand. This study suggested binding properties of three-hit compounds that could be used to develop drugs against Zika virus infections.Communicated by Ramaswamy H. Sarma.

Purpose: To address recent concerns of postural orthostatic tachycardia syndrome (POTS) occurring after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination., Methods: We searched PubMed, Web of Science, and Scopus as of 1st June 2023. We performed a systematic review and meta-analysis of pooled POTS rate in SARS-CoV-2-infected and COVID-19-vaccinated groups from epidemiological studies, followed by subgroup analyses by characteristic. Meta-analysis of risk ratio was conducted to compare POTS rate in infected versus uninfected groups. Meta-analysis of demographics was also performed to compare cases of post-infection and post-vaccination POTS from case reports and series., Results: We estimated the pooled POTS rate of 107.75 (95 % CI: 9.73 to 273.52) and 3.94 (95 % CI: 0 to 16.39) cases per 10,000 (i.e., 1.08 % and 0.039 %) in infected and vaccinated individuals based on 5 and 2 studies, respectively. Meta-regression revealed age as a significant variable influencing 86.2 % variance of the pooled POTS rate in infected population (P < 0.05). Moreover, POTS was 2.12-fold more likely to occur in infected than uninfected individuals (RR = 2.12, 95 % CI: 1.71 to 2.62, P < 0.001). Meta-analyzed demographics for cases of post-infection (n = 43) and post-vaccination (n = 17) POTS found no significant differences in several variables between groups, except that the time from exposure to symptom onset was shorter for cases of post-vaccination POTS (P < 0.05)., Conclusion: Although evidence is limited for post-vaccination POTS, our study showed that POTS occur more frequently following SARS-CoV-2 infection than COVID-19 vaccination., Competing Interests: Declaration of competing interest The authors state that there is no conflict of interest to disclose., (Copyright © 2023. Published by Elsevier B.V.)

SARS-CoV-2, responsible for COVID-19, shares 79% and 50% of its identity with SARS-CoV-1 and MERS-CoV, respectively. It uses the same main cell attachment and entry receptor as SARS-CoV-1, which is the ACE-2 receptor. However, key residues in the receptor-binding domain of its S-protein seem to give it a stronger affinity for the receptor and a better ability to hide from the host immune system. Like SARS-CoV-1 and MERS-CoV, cytokine storms in critically ill COVID-19 patients cause ARDS, neurological pathology, multiorgan failure, and increased death. Though many issues remain, the global research effort and lessons from SARS-CoV-1 and MERS-CoV are hopeful. The emergence of novel SARS-CoV-2 variants and subvariants raised serious concerns among the scientific community amid the emergence of other viral diseases like monkeypox and Marburg virus, which are major concerns for healthcare settings worldwide. Hence, an updated review on the comparative analysis of various coronaviruses (CoVs) has been developed, which highlights the evolution of CoVs and their repercussions., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Multidrug resistance in bacterial strains known as superbugs is estimated to cause fatal infections worldwide. Migration and urbanization have resulted in overcrowding and inadequate sanitation, contributing to a high risk of superbug infections within and between different communities. The CRISPR-Cas system, mainly type II, has been projected as a robust tool to precisely edit drug-resistant bacterial genomes to combat antibiotic-resistant bacterial strains effectively. To entirely opt for its potential, advanced development in the CRISPR-Cas system is needed to reduce toxicity and promote efficacy in gene-editing applications. This might involve base-editing techniques used to produce point mutations. These methods employ designed Cas9 variations, such as the adenine base editor (ABE) and the cytidine base editor (CBE), to directly edit single base pairs without causing DSBs. The CBE and ABE could change a target base pair into a different one (for example, G-C to A-T or C-G to A-T). In this review, we addressed the limitations of the CRISPR/Cas system and explored strategies for circumventing these limitations by applying diverse base-editing techniques. Furthermore, we also discussed recent research showcasing the ability of base editors to eliminate drug-resistant microbes.

Introduction: Over three years have passed since the emergence of coronavirus disease 2019 (COVID-19), and yet the treatment for long-COVID, a post-COVID-19 syndrome, remains long overdue. Currently, there is no standardized treatment available for long-COVID, primarily due to the lack of funding for post-acute infection syndromes (PAIS). Nevertheless, the past few years have seen a renewed interest in long-COVID research, with billions of dollars allocated for this purpose. As a result, multiple randomized controlled trials (RCTs) have been funded in the quest to find an effective treatment for long-COVID., Areas Covered: This systematic review identified and evaluated the potential of current drug treatments for long-COVID, examining both completed and ongoing RCTs., Expert Opinion: We identified four completed and 22 ongoing RCTs, investigating 22 unique drugs. However, most drugs were deemed to not have high potential for treating long-COVID, according to three pre-specified domains, a testament to the ordeal of treating long-COVID. Given that long-COVID is highly multifaceted with several proposed subtypes, treatments likely need to be tailored accordingly. Currently, rintatolimod appears to have modest to high potential for treating the myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) subtype, LTY-100 and Treamid for pulmonary fibrosis subtype, and metformin for general long-COVID prevention.

Fungal infections are becoming one of the main causes of morbidity and mortality in people with weakened immune systems. Mycoses are becoming more common, despite greater knowledge and better treatment methods, due to the regular emergence of resistance to the antifungal medications used in clinical settings. Antifungal therapy is the mainstay of patient management for acute and chronic mycoses. However, the limited availability of antifungal drug classes limits the range of available treatments. Additionally, several drawbacks to treating mycoses include unfavourable side effects, a limited activity spectrum, a paucity of targets, and fungal resistance, all of which continue to be significant issues in developing antifungal drugs. The emergence of antifungal drug resistance has eliminated accessible drug classes as treatment choices, which significantly compromises the clinical management of fungal illnesses. In some situations, the emergence of strains resistant to many antifungal medications is a major concern. Although new medications have been developed to address this issue, antifungal drug resistance has grown more pronounced, particularly in patients who need long-term care or are undergoing antifungal prophylaxis. Moreover, the mechanisms that cause resistance must be well understood, including modifications in drug target affinities and abundances, along with biofilms and efflux pumps that diminish intracellular drug levels, to find novel antifungal drugs and drug targets. In this review, different classes of antifungal agents, and their resistance mechanisms, have been discussed. The latter part of the review focuses on the strategies by which we can overcome this serious issue of antifungal resistance in humans.

The finding that some mAbs are antifungal suggests that antibody immunity may play a key role in the defense of the host against mycotic infections. The discovery of antibodies that guard against fungi is a significant advancement because it gives rise to the possibility of developing vaccinations that trigger protective antibody immunity. These vaccines might work by inducing antibody opsonins that improve the function of non-specific (such as neutrophils, macrophages, and NK cells) and specific (such as lymphocyte) cell-mediated immunity and stop or aid in eradicating fungus infections. The ability of antibodies to defend against fungi has been demonstrated by using monoclonal antibody technology to reconsider the function of antibody immunity. The next step is to develop vaccines that induce protective antibody immunity and to comprehend the mechanisms through which antibodies mediate protective effects against fungus.

Mycobacterium tuberculosis ( Mtb ), an acid-fast bacillus that causes Tuberculosis (TB), is a pathogen that caused 1.5 million deaths in 2020. As per WHO estimates, another 4.1 million people are suffering from latent TB, either asymptomatic or not diagnosed, and the frequency of drug resistance is increasing due to intrinsically linked factors from both host and bacterium. For instance, poor access to TB diagnosis and reduced treatment in the era of the COVID-19 pandemic has resulted in more TB deaths and an 18% reduction in newly diagnosed cases of TB. Additionally, the detection of Mtb isolates exhibiting resistance to multiple drugs (MDR, XDR, and TDR) has complicated the scenario in the pathogen's favour. Moreover, the conventional methods to detect drug resistance may miss mutations, making it challenging to decide on the treatment regimen. However, owing to collaborative initiatives, the last two decades have witnessed several advancements in both the detection methods and drug discovery against drug-resistant isolates. The majority of them belong to nucleic acid detection techniques. In this review, we highlight and summarize the molecular mechanism underlying drug resistance in Mtb , the recent advancements in resistance detection methods, and the newer drugs used against drug-resistant TB.

Tuberculosis (TB) caused by the bacterial pathogen Mycobacterium tuberculosis ( Mtb ) remains a threat to mankind, with over a billion of deaths in the last two centuries. Recent advancements in science have contributed to an understanding of Mtb pathogenesis and developed effective control tools, including effective drugs to control the global pandemic. However, the emergence of drug resistant Mtb strains has seriously affected the TB eradication program around the world. There is, therefore, an urgent need to develop new drugs for TB treatment, which has grown researchers' interest in small molecule-based drug designing and development. The small molecules-based treatments hold significant potential to overcome drug resistance and even provide opportunities for multimodal therapy. In this context, various natural and synthetic flavonoids were reported for the effective treatment of TB. In this review, we have summarized the recent advancement in the understanding of Mtb pathogenesis and the importance of both natural and synthetic flavonoids against Mtb infection studied using in vitro and in silico methods. We have also included flavonoids that are able to inhibit the growth of non-tubercular mycobacterial organisms. Hence, understanding the therapeutic properties of flavonoids can be useful for the future treatment of TB.

Donors not meeting standard criteria, such as those with bacteremia, are now being used in response to the increasing need for organs for transplantation. Recommended strategies to prevent the occurrence of donor-derived bacteremia include the use of directed antibiotic prophylaxis. However, this approach does not eliminate the risk of infection transmission. Similarly, the management of organ recipients from donors with infective endocarditis (IE) remains uncharacterized. We report 2 cases of donor-derived bacterial infections in liver transplant recipients despite pathogen-specific antibiotic prophylaxis. In both instances, the donors had documented IE treated with appropriate antimicrobial therapy and clearance of bacteremia. Recipients had very distinctive clinical outcomes likely related to pathogen virulence and the extent of donor infection. Persistent infection in the transplanted liver should be suspected in organ recipients of a liver from donors with IE, despite the absence of bacteremia at the time of death and organ procurement. For eradication, recipients may require prolonged pathogen-directed antimicrobial therapy, such as is used for endovascular infections. Prompt recognition of donors with IE, appropriate notification, and prolonged antibiotic prophylaxis are key to reducing the risk of such donor-derived infections., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)