Repositioning of anti-infective compounds against monkeypox virus core cysteine proteinase: a molecular dynamics study.

Monkeypox virus (MPXV) core cysteine proteinase (CCP) is one of the major drug targets used to examine the inhibitory action of chemical moieties. In this study, an in silico technique was applied to screen 1395 anti-infective compounds to find out the potential molecules against the MPXV-CCP. The top five hits were selected after screening and processed for exhaustive docking based on the docked score of ≤ -9.5 kcal/mol. Later, the top three hits based on the exhaustive-docking score and interaction profile were selected to perform MD simulations. The overall RMSD suggested that two compounds, SC75741 and ammonium glycyrrhizinate, showed a highly stable complex with a standard deviation of 0.18 and 0.23 nm, respectively. Later, the MM/GBSA binding free energies of complexes showed significant binding strength with ΔGTOTAL from -21.59 to -15 kcal/mol. This report reported the potential inhibitory activity of SC75741 and ammonium glycyrrhizinate against MPXV-CCP by competitively inhibiting the binding of the native substrate.

The Quality of AI-Generated Dental Caries Multiple Choice Questions: A Comparative Analysis of ChatGPT and Google Bard Language Models.

Statement of problem: AI technology presents a variety of benefits and challenges for educators. Purpose: To investigate whether ChatGPT and Google Bard (now is named Gemini) are valuable resources for generating multiple-choice questions for educators of dental caries. Material and methods: A book on dental caries was used. Sixteen paragraphs were extracted by an expert consultant based on applicability and potential for developing multiple-choice questions. ChatGPT and Bard language models were used to produce multiple-choice questions based on this input, and 64 questions were generated. Three dental specialists assessed the relevance, accuracy, and complexity of the generated questions. The questions were qualitatively evaluated using cognitive learning objectives and item writing flaws. Paired sample t-tests and two-way analysis of variance (ANOVA) were used to compare the generated multiple-choice questions and answers between ChatGPT and Bard. Results: There were no significant differences between the questions generated by ChatGPT and Bard. Moreover, the analysis of variance found no significant differences in question quality. Bard-generated questions tended to have higher cognitive levels than those of ChatGPT. Format error was predominant in ChatGPT-generated questions. Finally, Bard exhibited more absolute terms than ChatGPT. Conclusions: ChatGPT and Bard could generate questions related to dental caries, mainly at the cognitive level of knowledge and comprehension. Clinical significance: Language models are crucial for generating subject-specific questions used in quizzes, tests, and education. By using these models, educators can save time and focus on lesson preparation and student engagement instead of solely focusing on assessment creation. Additionally, language models are adept at generating numerous questions, making them particularly valuable for large-scale exams. However, educators must carefully review and adapt the questions to ensure they align with their learning goals.

Exploring the impact of the extent of the partially edentulous area on the accuracy of two intraoral scanners.

STATEMENT OF PROBLEM: The accuracy of intraoral scans, particularly in edentulous areas, remains a concern despite the increasing use of digital technology, especially intraoral scanners. PURPOSE: The purpose of this in vitro study was to assess the impact of the extent of an edentulous area on the accuracy (trueness and precision) of intraoral scans from 2 intraoral scanners. MATERIAL AND METHODS: A KaVo dentoform with epoxy resin teeth was used to generate 9 groups with different numbers of teeth removed. A laboratory scanner served as the reference dataset, and 2 intraoral scanners (TRIOS 3 and Primescan AC) were evaluated. A single operator performed all scans following standardized protocols and calibration. Trueness and precision were assessed by using root mean square (RMS) values. Analysis of variance was used to compare trueness and precision values obtained from the 2 scanners and different partially edentulous conditions (α=.05). RESULTS: A significant difference was found in the trueness of intraoral scans of the 2 scanners and under different partially edentulous extensions. Primescan AC exhibited significantly lower trueness than TRIOS 3 (P<.001). For the individual edentulous conditions, Primescan had a significantly higher RMS mean than TRIOS 3 for G0, G3, G4, G6, G7, and G8 (P<.001) and a significantly lower RMS mean than TRIOS 3 for G1 and G4 (P<.001), while no significant difference in RMS mean was found between the 2 scanners for G2 (P=.999). For precision, no significant difference was found between the 2 scanners or different edentulous conditions [(F 8, 90)=1.82, P=.085]. CONCLUSIONS: The accuracy of intraoral scans was influenced by the length of edentulous areas and the scanner used. Primescan AC demonstrated lower trueness than TRIOS 3 for most partially edentulous conditions, while the scanners were similar in precision. These findings highlight the need for careful scanner selection in specific clinical situations, as scanning accuracy may vary depending on the scanner and edentulous condition.

Color reproduction trueness of 3D-printed full-color dental casts with scans derived from an intraoral scanner.

PURPOSE: To investigate the effects of shade tab color variations (tooth-colored vs. gingiva-colored) and surface treatment (application of mineral oil) on the trueness of color reproduction from dental shade tabs to 3D-printed full-color dental casts, using digital scans obtained from an intraoral scanner. MATERIALS AND METHODS: Pristine tooth-colored (with 16 shade tabs) and gingiva-colored (with five shade tabs) shade guides were digitally scanned using an intraoral scanner, and subsequently, 3D-printed replicas were created using a full-color material jetting 3D printer. Three color measurements using a contact type digital spectrophotometer were recorded, including actual shade tabs (R0), dried 3D-printed study samples (RP1 ), and study samples with mineral oil application (RP2 ), in this study to calculate color differences between the actual shade tabs and 3D-printed ones. The CIEDE2000 formula was used to calculate the color differences (color reproduction trueness) between reference shade tabs and 3D-printed full-color study samples-without and with mineral oil, ∆E00 (RP1 ), and ∆E00 (RP2 ). ∆E00 (RP1 ) and ∆E00 (RP2 ) were compared with a 50:50% accessibility threshold (AT) and a 50:50% perceptibility threshold (PT). A grading system, based on the relative ranges of AT and PT, was employed. The percentage of samples falling into each color-matching category was then recorded. The data collected were subjected to statistical analysis, utilizing a mixed model ANOVA to evaluate the effects of shade tab color and mineral oil application on color differences, α = 0.05. RESULTS: The application of mineral oil significantly affected the ∆E00 [F(1, 378) = 19.1, p = < 0.0001]. However, this effect was only significant for the gingiva-colored study samples; the mineral oil application significantly decreased color difference, showing ∆E00 (RP1 ) of 8.71 ± 3.78 and ∆E00 (RP2 ) of 6.55 ± 2.14 (p < 0.0001). For the tooth-colored groups, the mineral oil application did not yield any color difference, showing ∆E00 (RP1 ) of 7.05 ± 2.35 and ∆E00 (RP2 ) of 6.94 ± 2.35 (p = 0.497). In the absence of mineral oil, gingiva-colored samples revealed a significantly larger ∆E00 (RP1 ) of 8.71 ± 3.78 compared to tooth-colored samples at 7.05 ± 2.35 (p = 0.017). Conversely, mineral oil application rendered comparable ∆E00 (RP2 ) values between gingiva-colored (6.55 ± 2.14) and tooth-colored (6.94 ± 2.35) samples (p = 0.558). All 3D-printed full-color samples showed Grade 1 (extremely unacceptable mismatch) and Grade 2 (clearly unacceptable mismatch), regardless of the shades or the presence of mineral oil. CONCLUSIONS: Utilizing an intraoral scanner to gather digital color data, along with an MJ 3D printer, offers the potential for producing 3D-printed full-color dental casts for prosthesis characterization in the dental laboratory. While mineral oil improves the color reproduction trueness of gingiva-colored objects, all 3D-printed full-color samples exhibited unacceptable mismatches when compared to their target objects. This underscores the need for future improvement in the digital color data acquisition process and color optimization protocols in 3D printing processes.

Pooled rates and demographics of POTS following SARS-CoV-2 infection versus COVID-19 vaccination: Systematic review and meta-analysis.

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.

A Review of the Resistance Mechanisms for ß-Lactams, Macrolides and Fluoroquinolones among Streptococcus pneumoniae.

Streptococcus pneumoniae (S. pneumoniae) is a bacterial species often associated with the occurrence of community-acquired pneumonia (CAP). CAP refers to a specific kind of pneumonia that occurs in individuals who acquire the infection outside of a healthcare setting. It represents the leading cause of both death and morbidity on a global scale. Moreover, the declaration of S. pneumoniae as one of the 12 leading pathogens was made by the World Health Organization (WHO) in 2017. Antibiotics like ß-lactams, macrolides, and fluoroquinolones are the primary classes of antimicrobial medicines used for the treatment of S. pneumoniae infections. Nevertheless, the efficacy of these antibiotics is diminishing as a result of the establishment of resistance in S. pneumoniae against these antimicrobial agents. In 2019, the WHO declared that antibiotic resistance was among the top 10 hazards to worldwide health. It is believed that penicillin-binding protein genetic alteration causes ß-lactam antibiotic resistance. Ribosomal target site alterations and active efflux pumps cause macrolide resistance. Numerous factors, including the accumulation of mutations, enhanced efflux mechanisms, and plasmid gene acquisition, cause fluoroquinolone resistance. Furthermore, despite the advancements in pneumococcal vaccinations and artificial intelligence (AI), it is not feasible for individuals to rely on them indefinitely. The ongoing development of AI for combating antimicrobial resistance necessitates more research and development efforts. A few strategies can be performed to curb this resistance issue, including providing educational initiatives and guidelines, conducting surveillance, and establishing new antibiotics targeting another part of the bacteria. Hence, understanding the resistance mechanism of S. pneumoniae may aid researchers in developing a more efficacious antibiotic in future endeavors.

Prevalence of Hepatocellular Carcinoma in Hepatitis B Population within Southeast Asia: A Systematic Review and Meta-Analysis of 39,050 Participants.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is a significant complication of hepatitis B and still poses a global public health concern. This systematic review and meta-analysis provide adequate details on the prevalence of HCC in the HBV population within Southeast Asian countries. METHOD: Following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) criteria, a thorough search for literature discussing the prevalence of HCC in the HBV population within southeast Asia was performed. Eligible studies were subjected to a meta-analysis utilising a DerSimonian and Laird approach and a random effect model. A protocol was registered with PROSPERO (CRD42023423953). RESULT: Our study meticulously recovered 41 articles from seven countries in Southeast Asia, namely Cambodia, Indonesia, Malaysia, the Philippines, Singapore, Thailand, and Vietnam. A total of 39,050 HBV patients and 7479 HCC cases in southeast Asia were analysed. The pooled prevalence of HCC in HBV cases within southeast Asia was 45.8% (95% CI, 34.3-57.8%, I2 = 99.51%, p < 0.001). Singapore (62.5%, CI: 42.4-79.1) had the highest pooled prevalence of HCC in the HBV population compared to Vietnam, with the lowest estimate (22.4%, CI: 9.9-44.9). There was a drop in the pooled prevalence of HCC in HBV from 2016 until now (37.6%, CI: 19.2-60.5). CONCLUSION: The findings of this review reveal a high pooled prevalence of HCC in the HBV population and therefore stir the need for routine screening, management, and surveillance.

Performance of the caries diagnosis feature of intraoral scanners and near-infrared imaging technology-A narrative review.

PURPOSE: To describe and discuss the benefits and drawbacks of various dental caries diagnostic techniques, including the use of intraoral scanners for caries diagnosis based on near-infrared imaging (NIR) technology. MATERIAL AND METHODS: A MEDLINE search from 1980-2023 focused on dental caries diagnostic techniques, emphasizing intraoral scanners using NIR technology. Alternative caries detection methods were also evaluated for their advantages and limitations, enabling a comparison with NIR. The review included traditional caries tools, the latest detection methods, and NIR's role in intraoral scanners, drawing from case reports and both in vivo and in vitro studies. Keywords like "caries detection," "intraoral scanners," and "Near Infrared Imaging (NIRI)" guided the search. After screening titles and abstracts for relevance, full texts with valuable insights were thoroughly analyzed. The data was grouped into three: traditional diagnostics, advanced digital methods, and intraoral scanner-based detection. RESULTS: This comprehensive narrative review described and discussed the current state of dental caries diagnostic methods, given the insufficient number of clinical investigations suitable for a systematic review. Traditional caries diagnosis techniques have shown variable accuracy dependent on a dentist's experience and the potential over-removal of healthy tooth structures. Intraoral scanners have emerged as a novel caries detection method, because of their integration of NIR technology. Various studies have confirmed the efficacy of NIR in detecting interproximal caries and in the early diagnosis of non-cavitated caries. Specifically, intraoral scanners have demonstrated promising results, proving comparable to established diagnostic methods like bitewing radiography. Nevertheless, while the integration of NIR into intraoral scanners seems promising, the technology still faces challenges, notably its accuracy in detecting secondary and subgingival cavities. However, with anticipated integrations of AI, NIR in intraoral scanners could revolutionize early caries detection. CONCLUSIONS: Intraoral scanners with NIR technology offer non-destructive imaging, real-time lesion visuals, and enhanced patient communication. Although comparable to bitewing radiography in some studies, a universally accepted diagnostic tool is lacking. Future research should compare them with existing methods, focusing on clinical outcomes, cost-effectiveness, and patient acceptance.

Seroprevalence, Risk Factors and Maternal-Fetal Outcomes of Toxoplasma gondii in Pregnant Women from WHO Eastern Mediterranean Region: Systematic Review and Meta-Analysis.

BACKGROUND: The protozoan parasite Toxoplasma gondii may cause serious illness in the immunocompromised. The Toxoplasma gondii seropositive prevalence in pregnant women in WHO Eastern Mediterranean Region countries is inconsistent in the literature and it is associated with outcomes that have not be fully elucidated, hence the need for a better understanding of the pooled seroprevalence and associated maternal and fetal outcomes. OBJECTIVE: The objective was to conduct a systematic literature review and determine the pooled prevalence of WHO Eastern Mediterranean Regional countries' pregnant women's seroprevalence of Toxoplasma gondii and the maternal-fetal outcomes. METHODS: This quantitative study examined WHO Eastern Mediterranean countries' maternal-fetal outcomes and Toxoplasma gondii prevalence in pregnant women. The targeted population was pregnant women, while the primary outcome was seropositivity of Toxoplasma gondii, while other outcomes such as maternal and fetal associations and risk factors were determined PubMed, SCOPUS, MEDLINE, and Index Medicus for the Eastern Mediterranean Region (IMEMR) databases were searched up until 30 January 2023. The search terms used were "Toxoplasma gondii" OR "Toxoplasma infection" AND "Pregnant woman" or pregnan* OR Antenatal OR Prenatal OR Gravidity OR Parturition OR Maternal AND WHO Eastern Mediterranean Region). OpenMeta-Analyst and Jamovi were used to analyze the generated data. RESULTS: In total, 95 of 2947 articles meeting the inclusion criteria examined Toxoplasma gondii prevalence in pregnant women from WHO Eastern Mediterranean countries. The pooled prevalence of Toxoplasma gondii in pregnant women was 36.5% (95%CI: 32.6-40.4) with a median value of 35.64%, range values of 1.38-75.30%, with 99.61% heterogeneity. The pooled seroprevalence of IgG of Toxoplasma gondii was 33.5% (95%CI: 29.8-37.2) with a median value of 33.51%, and a range values of 1.38-69.92%; the pooled seroprevalence of IgM was 3.6% (95%CI: 3.1-4.1)) with a median value of 3.62 and range values of 0.20-17.47%, while cases of pooled seroprevalence of both IgG and IgM positivity was 3.0% (95%CI: 1.9-4.4) with a median value of 2.05 and a range values of 0.05-16.62%. Of the Toxoplasma gondii seropositive women, 1281/3389 (34.8%) 174/1765 (32.9%), 1311/3101 (43.7%), and 715/1683 (40.8%) of them had contact with cats, drank unprocessed milk, ate raw or undercooked meat and ate unwashed raw vegetables, respectively. The maternal-fetal outcomes associated with Toxoplasma gondii seropositivity were a history of abortions, miscarriage, stillbirth, intrauterine fetal death, and premature birth, which were found in 868/2990 (32.5%), 112/300 (36.1%), 111/375 (25.7%), 3/157 (1.9%) and 96/362 (20.1%) of women who tested positive for Toxoplasma gondii antibodies. CONCLUSION: The study found a high proportion of Toxoplasma gondii seroprevalence in pregnant women in the WHO Eastern Mediterranean Region, which may be linked to poor outcomes for mothers and their babies. Thus, pregnant women require monitoring and comprehensive prevention strategies for Toxoplasma gondii infection.

Experimental drugs in randomized controlled trials for long-COVID: what's in the pipeline? A systematic and critical review.

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.

Highlights on the Development, Related Patents, and Prospects of Lenacapavir: The First-in-Class HIV-1 Capsid Inhibitor for the Treatment of Multi-Drug-Resistant HIV-1 Infection.

The multidrug-resistant (MDR) human immunodeficiency virus 1 (HIV-1) infection is an unmet medical need. HIV-1 capsid plays an important role at different stages of the HIV-1 replication cycle and is an attractive drug target for developing therapies against MDR HIV-1 infection. Lenacapavir (LEN) is the first-in-class HIV-1 capsid inhibitor approved by the USFDA, EMA, and Health Canada for treating MDR HIV-1 infection. This article highlights the development, pharmaceutical aspects, clinical studies, patent literature, and future directions on LEN-based therapies. The literature for this review was collected from PubMed, authentic websites (USFDA, EMA, Health Canada, Gilead, and NIH), and the free patent database (Espacenet, USPTO, and Patent scope). LEN has been developed by Gilead and is marketed as Sunlenca (tablet and subcutaneous injection). The long-acting and patient-compliant LEN demonstrated a low level of drug-related mutations, is active against MDR HIV-1 infection, and does not reveal cross-resistance to other anti-HIV drugs. LEN is also an excellent drug for patients having difficult or limited access to healthcare facilities. The literature has established additive/synergistic effects of combining LEN with rilpivirine, cabotegravir, islatravir, bictegravir, and tenofovir. HIV-1 infection may be accompanied by opportunistic infections such as tuberculosis (TB). The associated diseases make HIV treatment complex and warrant drug interaction studies (drug-drug, drug-food, and drug-disease interaction). Many inventions on different aspects of LEN have been claimed in patent literature. However, there is a great scope for developing more inventions related to the drug combination of LEN with anti-HIV/anti-TB drugs in a single dosage form, new formulations, and methods of treating HIV and TB co-infection. Additional research may provide more LEN-based treatments with favorable pharmacokinetic parameters for MDR HIV-1 infections and associated opportunistic infections such as TB.

Antibodies to Combat Fungal Infections: Development Strategies and Progress.

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.

Marginal Fit, Mechanical Properties, and Esthetic Outcomes of CAD/CAM Interim Fixed Dental Prostheses (FDPs): A Systematic Review.

This systematic review aimed to study the outcomes of CAD-CAM (milled and 3D-printed) interim dental prostheses when compared to conventional ones. The focused question of "In natural teeth, what are the outcomes of CAD-CAM interim FDPs compared to the conventionally-manufactured ones regarding marginal fit, mechanical properties, esthetics, and color stability" was formulated. The systematic search was conducted electronically in the PubMed/MEDLINE, CENTRAL, EMBASE, Web of Science, New York Academy of Medicine Grey Literature Report, and Google Scholar databases by using the MeSH keywords and keywords associated with the focused question and limiting articles to those published between 2000 and 2022. A manual search was conducted in selected dental journals. The results were analyzed qualitatively and are presented in table format. Of the included studies, 18 studies were in vitro and 1 was a randomized clinical trial. Of the eight studies analyzing the mechanical properties, five studies favored the milled interim restorations, one study favored both 3D-printed and milled interim restorations, and two studies reported better mechanical properties in conventional interim restorations. Among four studies evaluating the marginal discrepancies, two studies favored the marginal fit in milled interim restorations, one study reported a better marginal fit in both milled and 3D-printed interim restorations, and one study found conventional interim restorations have a better marginal fit and smaller marginal discrepancy when compared to both milled and 3D-printed restorations. Among five studies that evaluated both the mechanical properties and marginal fit, 1 study favored 3D-printed interim restorations and four studies favored milled interim restorations over the conventional ones. Two studies analyzing the esthetics outcomes demonstrated better results with milled interim restorations compared to conventional and 3D-printed interim restorations in terms of their color stabilities. The risk of bias was low for all the studies reviewed. The high level of heterogeneity within the studies excluded meta-analysis. Most of the studies favored the milled interim restorations over the 3D-printed and conventional restorations. The results suggested that milled interim restorations offer a better marginal fit, higher mechanical properties, and better esthetic outcomes in terms of color stabilities.

Growth in chikungunya virus-related research in ASEAN and South Asian countries from 1967 to 2022 following disease emergence: a bibliometric and graphical analysis.

BACKGROUND: ASEAN (Association of Southeast Asian Nations) is composed of ten Southeast Asian countries bound by socio-cultural ties that promote regional peace and stability. South Asia, located in the southern subregion of Asia, includes nine countries sharing similarities in geographical and ethno-cultural factors. Chikungunya is one of the most significant problems in Southeast and South Asian countries. Much of the current chikungunya epidemic in Southeast Asia is caused by the emergence of a virus strain that originated in Africa and spread to Southeast Asia. Meanwhile, in South Asia, three confirmed lineages are in circulation. Given the positive correlation between research activity and the improvement of the clinical framework of biomedical research, this article aimed to examine the growth of chikungunya virus-related research in ASEAN and South Asian countries. METHODS: The Scopus database was used for this bibliometric analysis. The retrieved publications were subjected to a number of analyses, including those for the most prolific countries, journals, authors, institutions, and articles. Co-occurrence mapping of terms and keywords was used to determine the current state, emerging topics, and future prospects of chikungunya virus-related research. Bibliometrix and VOSviewer were used to analyze the data and visualize the collaboration network mapping. RESULTS: The Scopus search engine identified 1280 chikungunya-related documents published by ASEAN and South Asian countries between 1967 and 2022. According to our findings, India was the most productive country in South Asia, and Thailand was the most productive country in Southeast Asia. In the early stages of the study, researchers investigated the vectors and outbreaks of the chikungunya virus. In recent years, the development of antivirus agents has emerged as a prominent topic. CONCLUSIONS: Our study is the first to present the growth of chikungunya virus-related research in ASEAN and South Asian countries from 1967 to 2022. In this study, the evaluation of the comprehensive profile of research on chikungunya can serve as a guide for future studies. In addition, a bibliometric analysis may serve as a resource for healthcare policymakers.

Updated Insights into the T Cell-Mediated Immune Response against SARS-CoV-2: A Step towards Efficient and Reliable Vaccines.

The emergence of novel variants of SARS-CoV-2 and their abilities to evade the immune response elicited through presently available vaccination makes it essential to recognize the mechanisms through which SARS-CoV-2 interacts with the human immune response. It is essential not only to comprehend the infection mechanism of SARS-CoV-2 but also for the generation of effective and reliable vaccines against COVID-19. The effectiveness of the vaccine is supported by the adaptive immune response, which mainly consists of B and T cells, which play a critical role in deciding the prognosis of the COVID-19 disease. T cells are essential for reducing the viral load and containing the infection. A plethora of viral proteins can be recognized by T cells and provide a broad range of protection, especially amid the emergence of novel variants of SARS-CoV-2. However, the hyperactivation of the effector T cells and reduced number of lymphocytes have been found to be the key characteristics of the severe disease. Notably, excessive T cell activation may cause acute respiratory distress syndrome (ARDS) by producing unwarranted and excessive amounts of cytokines and chemokines. Nevertheless, it is still unknown how T-cell-mediated immune responses function in determining the prognosis of SARS-CoV-2 infection. Additionally, it is unknown how the functional perturbations in the T cells lead to the severe form of the disease and to reduced protection not only against SARS-CoV-2 but many other viral infections. Hence, an updated review has been developed to understand the involvement of T cells in the infection mechanism, which in turn determines the prognosis of the disease. Importantly, we have also focused on the T cells' exhaustion under certain conditions and how these functional perturbations can be modulated for an effective immune response against SARS-CoV-2. Additionally, a range of therapeutic strategies has been discussed that can elevate the T cell-mediated immune response either directly or indirectly.

Psychogenetic, genetic and epigenetic mechanisms in Candida auris: Role in drug resistance.

In recent years, we are facing the challenge of drug resistance emergence in fungi. The availability of limited antifungals and development of multi-drug resistance in fungal pathogens has become a serious concern in the past years in the health sector. Although several cellular, molecular, and genetic mechanisms have been proposed to explain the drug resistance mechanism in fungi, but a complete understanding of the molecular and genetic mechanisms is still lacking. Besides the genetic mechanism, epigenetic mechanisms are pivotal in the fungal lifecycle and disease biology. However, very little is understood about the role of epigenetic mechanisms in the emergence of multi-drug resistance in fungi, especially in Candida auris (C. auris). The current narrative review summaries the clinical characteristics, genomic organization, and molecular/genetic/epigenetic mechanisms underlying the emergence of drug resistance in C. auris. A very few studies have attempted to evaluate the role of epigenetic mechanisms in C. auris. Furthermore, advanced genetic tools such as the CRISP-Cas9 system can be utilized to elucidate the epigenetic mechanisms and their role in the emergence of multi-drug resistance in C. auris.

Tensile bond strength of auto-polymerizing and heat-polymerizing denture reliners on the conventional and CAD-CAM denture base materials.

PURPOSE: The study aimed to compare the tensile bond strength (TBS) of auto-polymerizing and heat-polymerizing denture reliners on the conventional (compression-molding and injection-molding) and computer-aided design and computer-aided manufacturing (milled and 3D-printed) denture base materials. MATERIALS AND METHODS: Eighty standard dogbone-shaped specimens were fabricated from four materials: compression-molding, injection-molding, milled, and 3D-printed denture base materials. A 3-mm cutoff was removed from each specimen at the midsection, and all specimens were reattached with either auto-polymerizing (n = 10) or heat-polymerizing (n = 10) reliner. The TBS was measured on the universal testing machine. A scanning electron microscope (SEM) was used to examine the fractured surfaces at cross sections to determine the dominant failure mode in each group. Two-way ANOVA was used to examine the effects of denture base material and reliner on the TBS (α = 0.05). Weibull survival analysis was also used to determine the survival probability curves. RESULTS: Heat-polymerizing reliner led to a higher TBS than the auto-polymerizing reliner, except in the compression-molding (p = 0.573) groups. Compression-molding denture base material connected with a heat-polymerizing reliner showed the highest TBS (29.8 ± 6.9 MPa), whereas 3D-printed denture base material connected with an auto-polymerizing reliner showed the lowest TBS (7.2 ± 0.9 MPa). The survival probability based on the Weibull model demonstrated that the compression-molding denture base material connected with either auto-polymerizing or heat-polymerizing reliners had the longest survival time to failure, whereas 3D-printed denture base material relined with auto-polymerizing reline material showed the shortest survival time to failure. Under the SEM, the compression-molding groups demonstrated that the failure modes were mixed but predominantly cohesive. The injection-molding and milled groups showed predominantly adhesive failures at the denture base-reline material interfaces. The dominant mode of failure in the 3D-printed groups was cohesive failures within the bonding adhesive. CONCLUSIONS: Although the heat-polymerizing reliner led to a higher TBS than the auto-polymerizing reliner in most denture base materials, the compression-molding denture base material can achieve high TBS with both reliners. When the auto-polymerizing reliner is used with 3D-printed denture base material, clinicians should be aware of lower TBS value and possible cohesive failures, and the detachment of the reliner from the denture base.

Inflammatory and vascular biomarkers in post-COVID-19 syndrome: A systematic review and meta-analysis of over 20 biomarkers.

Severe acute respiratory syndrome coronavirus 2 may inflict a post-viral condition known as post-COVID-19 syndrome (PCS) or long-COVID. Studies measuring levels of inflammatory and vascular biomarkers in blood, serum, or plasma of COVID-19 survivors with PCS versus non-PCS controls have produced mixed findings. Our review sought to meta-analyse those studies. A systematic literature search was performed across five databases until 25 June 2022, with an updated search on 1 November 2022. Data analyses were performed with Review Manager and R Studio statistical software. Twenty-four biomarkers from 23 studies were meta-analysed. Higher levels of C-reactive protein (Standardized mean difference (SMD) = 0.20; 95% CI: 0.02-0.39), D-dimer (SMD = 0.27; 95% CI: 0.09-0.46), lactate dehydrogenase (SMD = 0.30; 95% CI: 0.05-0.54), and leukocytes (SMD = 0.34; 95% CI: 0.02-0.66) were found in COVID-19 survivors with PCS than in those without PCS. After sensitivity analyses, lymphocytes (SMD = 0.30; 95% CI: 0.12-0.48) and interleukin-6 (SMD = 0.30; 95% CI: 0.12-0.49) were also significantly higher in PCS than non-PCS cases. No significant differences were noted in the remaining biomarkers investigated (e.g., ferritin, platelets, troponin, and fibrinogen). Subgroup analyses suggested the biomarker changes were mainly driven by PCS cases diagnosed via manifestation of organ abnormalities rather than symptomatic persistence, as well as PCS cases with duration of <6 than ≥6 months. In conclusion, our review pinpointed certain inflammatory and vascular biomarkers associated with PCS, which may shed light on potential new approaches to understanding, diagnosing, and treating PCS.

SARS-CoV-2 infection and multi-organ system damage: A review.

The SARS-CoV-2 infection causes COVID-19, which has affected approximately six hundred million people globally as of August 2022. Organs and cells harboring angiotensin-converting enzyme 2 (ACE2) surface receptors are the primary targets of the virus. However, once it enters the body through the respiratory system, the virus can spread hematogenously to infect other body organs. Therefore, COVID-19 affects many organs, causing severe and long-term complications, even after the disease has ended, thus worsening the quality of life. Although it is known that the respiratory system is most affected by the SARS-CoV-2 infection, many organs/systems are affected in the short and long term. Since the COVID-19 disease simultaneously affects many organs, redesigning diagnostic and therapy policies to fit the damaged organs is strongly recommended. Even though the pathophysiology of many problems the infection causes is unknown, the frequency of COVID-19 cases rises with age and the existence of preexisting symptoms. This study aims to update our knowledge of SARS-CoV-2 infection and multi-organ dysfunction interaction based on clinical and theoretical evidence. For this purpose, the study comprehensively elucidates the most recent studies on the effects of SARS-CoV-2 infection on multiple organs and systems, including respiratory, cardiovascular, gastrointestinal, renal, nervous, endocrine, reproductive, immune, and parts of the integumentary system. Understanding the range of atypical COVID-19 symptoms could improve disease surveillance, limit transmission, and avoid additional multi-organ-system problems.

The trueness of scans using one intraoral scanner in different partially edentulous conditions.

PURPOSE: To investigate the trueness of intraoral scanning in 8 commonly seen partially edentulous conditions. MATERIALS AND METHODS: A maxillary dentoform was modified into the 8 commonly seen partially edentulous conditions. Each modification was scanned with a laboratory desktop scanner. Each modification was then scanned 10 times (n = 10) with an intraoral scanner. All scans were exported as STL files and then imported into a surface matching software using the best-fit alignment method. The dimensional differences between the study STL files from the intraoral scanner were compared to the corresponding reference STL files. The measurements were calculated as the root mean square (RMS) and defined as the trueness of the intraoral scans. In addition to the RMS values, qualitative assessments were completed on the color maps. The color maps produced by the surface matching software were used to visualize the areas of deviation between scans from the intraoral scanner and their corresponding reference files. One-way analysis of variance (ANOVA), followed by pair-wise comparisons using Fisher's Protected Least Significant Difference were utilized to compare the differences between the groups in RMS values (α = 0.05). RESULTS: Partially edentulous condition significantly affected the trueness of the intraoral scans. Group 8 (Class IV) had significantly lower RMS (0.1878 ± 0.0455 mm) than all other groups (p < 0.001). Group 2 (Class II) and Group 7 (Class III modification I) are not significantly different from each other (Group 2: 0.5758 ± 0.0300 mm; Group 7: 0.5602 ± 0.0231 mm, p = 0.571), while they both had significantly higher RMS than all other groups (p < 0.001). The remaining groups showed the RMS values were within the range of 0.3001 ± 0.0891 mm (Group 6 - Class III with Long Edentulous Span) and 0.4541 ± 0.1039 mm (Group 1 - Class I). CONCLUSION: Different partially edentulous conditions affected the trueness of the scans generated from the selected intraoral scanner. Class IV edentulous condition had the highest intraoral scan trueness. It is unknown if RMS values are clinically significant, and the validity of using intraoral scans directly for PRDP fabrication will need further studies.