Immunoinformatic approach for multi-epitope vaccine design against Staphylococcus aureus based on hemolysin proteins.

Staphylococcus aureus is a common bacterium that causes a variety of infections in humans. This microorganism produces several virulence factors, including hemolysins, which contribute to its disease-causing ability. The treatment of S. aureus infections typically involves the use of antibiotics. However, the emergence of antibiotic-resistant strains has become a major concern. Therefore, vaccination against S. aureus has gained attention as an alternative approach. Vaccination has the advantage of stimulating the immune system to produce specific antibodies that can neutralize bacteria and prevent infection. However, developing an effective vaccine against S. aureus has proven to be challenging. This study aimed to use in silico methods to design a multi-epitope vaccine against S. aureus infection based on hemolysin proteins. The designed vaccine contained four B-cell epitopes, four CTL epitopes, and four HTL epitopes, as well as the ribosomal protein L7/L12 and pan-HLA DR-binding epitope, included as adjuvants. Furthermore, the vaccine was non-allergenic and non-toxic with the potential to stimulate the TLR2-, TLR-4, and TLR-6 receptors. The predicted vaccine exhibited a high degree of antigenicity and stability, suggesting potential for further development as a viable vaccine candidate. The population coverage of the vaccine was 94.4 %, indicating potential widespread protection against S. aureus. Overall, these findings provide valuable insights into the design of an effective multi-epitope vaccine against S. aureus infection and pave the way for future experimental validations.

Computational Exploration of Berberis lycium Royle: A Hidden Treasure Trove for Antiviral Development.

Viral infections and associated illnesses account for approximately 3.5 million global fatalities and public health problems. Medicinal plants, with their wide therapeutic range and minimal side effects, have gained limelight particularly in response to growing concerns about drug resistance and sluggish development of antiviral drugs. This study computationally assessed 11 chemical compounds from Berberis lycium along with two antiviral drugs to inhibit SARS CoV 2 (coronavirus disease 2019 [COVID-19]) RNA-dependent RNA polymerase (RdRP), influenza virus RdRP, and two crucial dengue virus (DENV) enzymes (NS2B/NS3 protease and NS5 polymerase). Berberine and oxyberberine passed all pharmacokinetics analysis filters including Lipinski rule, blood-brain barrier permeant, and cytochrome suppression and demonstrated drug-likeness, bioavailability, and a non-toxic profile. Docking of phytochemicals from B lycium returned promising results with selected viral proteins, ie, DENV NS2BNS3 (punjabine -10.9 kcal/mol), DENV NS5 (punjabine -10.4 kcal/mol), COVID-19 RdRP (oxyacanthine -9.5 kcal/mol), and influenza RdRP (punjabine -10.4 kcal/mol). The optimal pharmacokinetics of berberine exhibited good binding energies with NS2BNS3 (-8.0 kcal/mol), NS5 (-8.3 kcal/mol), COVID RdRP (-7.7 kcal/mol), and influenza RdRP (-8.3 kcal/mol), while molecular dynamics simulation of a 50-ns time scale by GROMACS software package provided insights into the flexibility and stability of the complexes. A hidden treasure trove for antiviral research, berberine, berbamine, berbamunine, oxyberberine, oxyacanthine, baluchistanamine, and sindamine has showed encouraging findings as possible lead compounds. Pharmacological analyses provide credence for the proposed study; nevertheless, as the antiviral mechanisms of action of these phytochemicals are not well understood, additional research and clinical trials are required to demonstrate both their efficacy and toxicity through in vitro and in vivo studies.

Distinct inflammatory markers in primary and secondary dengue infection: can cytokines CXCL5, CXCL9, and CCL17 act as surrogate markers?

Dengue fever poses a significant global health threat, with symptoms including dengue hemorrhagic fever and dengue shock syndrome. Each year, India experiences fatal dengue outbreaks with severe manifestations. The primary cause of severe inflammatory responses in dengue is a cytokine storm. Individuals with a secondary dengue infection of a different serotype face an increased risk of complications due to antibody-dependent enhancement. Therefore, it is crucial to identify potential risk factors and biomarkers for effective disease management. In the current study, we assessed the prevalence of dengue infection in and around Aligarh, India, and explored the role of cytokines, including CXCL5, CXCL9, and CCL17, in primary and secondary dengue infections, correlating them with various clinical indices. Among 1,500 suspected cases, 367 tested positive for dengue using Real-Time PCR and ELISA. In secondary dengue infections, the serum levels of CXCL5, CXCL9, and CCL17 were significantly higher than in primary infections (P < 0.05). Dengue virus (DENV)-2 showed the highest concentrations of CXCL5 and CCL17, whereas DENV-1 showed the highest concentrations of CXCL9. Early detection of these cytokines could serve as potential biomarkers for diagnosing severe dengue, and downregulation of these cytokines may prove beneficial for the treatment of severe dengue infections.

Seroprevalence and risk factor analysis of brucellosis among dairy farmers in Aligarh region, North India: creating awareness of a neglected disease.

Introduction. Brucellosis, a globally distributed zoonotic disease, is caused by the Gram-negative bacteria known as Brucella. Humans acquire infection through direct contact with the blood, urine and placenta of animals, inhalation of dust or aerosols at infected animal farms, and raw milk and meat intake. This study aimed to assess the prevalence of brucellosis in dairy farmers in and around the Aligarh region of North India, to document various clinical signs and symptoms in Brucella-positive individuals, and to create awareness in dairy farmers concerning brucellosis and ways to prevent it. Methods. This was an observational study that included 125 dairy farmers in and around the Aligarh region. Serum samples were taken from this high-risk group after obtaining informed consent. Further, a pre-designed proforma was used to collect information about their knowledge, attitude and practices (KAP) concerning brucellosis and assess the risk factors for the disease. The Rose Bengal test (RBT), serum agglutination test (SAT) and enzyme-linked immunosorbent assay (ELISA) were performed to detect the seroprevalence of brucellosis. Result.Brucella infection was diagnosed in 64 (51.20 %) cases by indirect ELISA (IgM+IgG), 41 (32.8 %) by RBT and 4 (3.2 %) by SAT. Significant clustering of patients was seen in the 20-55 years age group. The most common symptoms in ELISA IgM-positive patients were joint pain (16.07 %), fatigue (14.28 %), anorexia (12.50 %), weight loss (8.92 %), malaise (5.35 %), undulant fever (3.57 %), night sweats (3.57 %) and headache (1.78 %). The findings of this study indicate that ELISA (IgM+IgG) exhibits great sensitivity as compared to SAT and RBT. KAP was very poor among dairy farmers. Conclusion. In India, Brucella is a frequent but severely underreported illness. ELISA is the most sensitive serological test for diagnosing brucellosis. No potential vaccine has yet been introduced for humans against brucellosis. Thus, it is necessary to impart awareness and sensitize high-risk groups concerning brucellosis.

Characterization of two novel fusariviruses co-infecting a single isolate of phytopathogenic fungus Botrytis cinerea.

A wide diversity of mycoviruses has been reported from Botrytis species, some with the potential to suppress the pathogenic abilities of this fungus. Considering their importance, this study was devised to find potential hypovirulence-associated mycoviruses found in Botrytis cinerea strains isolated from Pakistani strawberry fields. Here we report the complete genome characterization of two fusariviruses co-infecting a single isolate of phytopathogenic fungus B. cinerea (Kst14a). The viral genomes were sequenced by deep sequencing using total RNA fractions of the Kst14a isolate. The identified viruses were tentatively named Botrytis cinerea fusarivirus 9 (BcFV9) and Botrytis cinerea fusarivirus 3a (BcFV3a). Both viruses had a single-segmented (ssRNA) genome having a size of 6424 and 8370 nucleotides encoding two discontinuous open reading frames (ORFs). ORF-1 of both mycoviruses encodes for a polyprotein having a conserved domain of RNA-dependent RNA polymerase (RdRP) and a helicase domain (Hel) which function in RNA replication, while ORF2 encodes a hypothetical protein with an unknown function, respectively. Phylogenetic analysis indicated that BcFV9 made a clade with the genus Alphafusarivirus and BcFV3a fall in the genus Betafusarivirus in the family Fusariviridae. To our knowledge, this is the first report of two fusariviruses identified in isolates of B. cinerea from Pakistan. Both mycoviruses successfully transfected to a compatible strain of B. cinerea (Mst11). A comparison of virus-free (VF) and virus-infected (VI) isogenic lines showed the presence of these viruses was causing hypovirulence in infected strains. Virus-infected strains also had a small lesion size while testing the pathogenicity via apple assay.

The minimal important difference in orthodontic treatment duration: a survey across adult patients.

BACKGROUND: The minimal important difference (MID) is defined as the smallest difference that the patient perceives as important. Furthermore, the smallest worthwhile effect (SWE) is the important change measured with the benefit-harm trade-off method. The aim of this study was to evaluate the MID in orthodontic treatment duration to inform the decision regarding seeking procedures to accelerate orthodontic tooth movement and reduce treatment duration. METHODS: We constructed a survey eliciting views of the MID from adult participants from four countries undergoing orthodontic treatment. Ten questions addressed reduction in the treatment duration for both durations 12 and 24 months, and four questions were related to the reduction in treatment duration that the patients would require to undergo surgical or non-surgical adjunctive procedures. We applied a univariable random effects logistic regression model to examine the association between the participants' characteristics and the MID. Then, we fitted a multivariable logistic random effects regression including significant predictors. RESULTS: Four hundred and fifty adults, with a median age of 21 (interquartile range: 19-24), undergoing orthodontic treatment participated in the survey. Of the respondents, 60% considered 15 days as a trivial reduction from 12 months duration of therapy and 70% considered 15 days a trivial reduction from 24 months. Of the respondents, 48% considered the period of 2 months a moderate reduction from 12 months, and 60% considered 2 months a moderate reduction from 24 months. From these results, we inferred that patients considered reductions of approximately 1 month as the MID in the treatment duration for both 12 and 24 months. However, SWE was considerably more than the MID for most of the participants to decide undergoing surgical adjunctive procedures to reduce the time of therapy. The participants required smaller SWE to undergo non-surgical procedures compared to surgical procedures. CONCLUSION: The MID in the treatment duration is one month for both treatment durations 12 and 24 months. Patients require a greater SWE than the MID to undergo adjunctive procedures to shorten the duration, particularly for surgical procedures.

Application of fourier transform infrared photoacoustic spectroscopy for quantification of nutrient contents and their plant availability in manure and digestate.

In this study, we assess the feasibility of using Fourier Transform Infrared Photoacoustic Spectroscopy (FTIR-PAS) to predict macro- and micro-nutrients in a diverse set of manures and digestates. Furthermore, the prediction capabilities of FTIR-PAS were assessed using a novel error tolerance-based interval method in view of the accuracy required for application in agricultural practices. Partial Least-Squares Regression (PLSR) was used to correlate the FTIR-PAS spectra with nutrient contents. The prediction results were then assessed with conventional assessment methods (root mean square error (RMSE), coefficient of determination R2, and the ratio of prediction to deviation (RPD)). The results show the potential of FTIR-PAS to be used as a rapid analysis technique, with promising prediction results (R2 > 0.91 and RPD >2.5) for all elements except for bicarbonate-extractable P, K, and NH4+-N (0.8 < R2 < 0.9 and 2 < RPD <2.5). The results for nitrogen and phosphorus were further evaluated using the proposed error tolerance-based interval method. The probability of prediction for nitrogen within the allowed limit is calculated to be 94.6 % and for phosphorus 83.8 %. The proposed error tolerance-based interval method provides a better measure to decide if the FTIR-PAS in its current state could be used to meet the required accuracy in agriculture for the quantification of nutrient content in manure and digestate.

The Common Retention Practices Among Orthodontists from Different Countries.

Objective: To investigate the most common retention practices, factors influencing the retention protocol, and the differences among orthodontists regarding retention practices. Methods: An online validated questionnaire was anonymously sent to 3,000 orthodontic residents and clinicians. The survey consisted of 19 questions regarding the participants' demographics, prescribed retention appliances, factors affecting retention appliance choices, and adjunctive retention procedures. Descriptive statistics, Chi2 and Kendall's Tau-b tests were applied. Results: Five hundred fifty-five orthodontic residents and clinicians, 53.3% males and 46.7% females, completed the survey, indicating a response rate of 18.5%. Although participants' demographics, type of treatment and pre-treatment malocclusion influence the choice of retention protocols, thermoplastic retainers (TR) were the most popular retention regime for the maxillary arch for both adults (47.4%) and adolescents (42.3%). Bonded retainers (BR) were the favored option for the mandibular arch (44.9% of adults and 40.7% of adolescents). The degree of arch expansion (64.1%) and the degree of interdigitation (50.1%) after treatment were the most influential factors for the choice of the preferred type of retainers by the respondents. 68.6% of the participants thought professional retention guidelines would be useful. Conclusion: Thermoplastic retainers were the most common retention appliances for adults and adolescents in the maxilla. At the same time, BR was the most favored retainer in the mandibular arch, with clinical experience, practice setting, and malocclusion- and treatment-related factors influencing the type of the chosen appliance. The demographic differences and the uneven participation in the survey need to be considered while interpreting the findings of this study.

Do statistical heterogeneity methods impact the results of meta- analyses? A meta epidemiological study.

BACKGROUND: Orthodontic systematic reviews (SRs) use different methods to pool the individual studies in a meta-analysis when indicated. However, the number of studies included in orthodontic meta-analyses is relatively small. This study aimed to evaluate the direction of estimate changes of orthodontic meta-analyses (MAs) using different between-study variance methods considering the level of heterogeneity when few trials were pooled. METHODS: Search and study selection: Systematic reviews (SRs) published over the last three years, from the 1st of January 2020 to the 31st of December 2022, in six main orthodontic journals with at least one MA pooling five or lesser primary studies were identified. Data collection and analysis: Data were extracted from each eligible MA, which was replicated in a random effect model using DerSimonian and Laird (DL), Paule-Mandel (PM), Restricted maximum-likelihood (REML), Hartung Knapp and Sidik Jonkman (HKSJ) methods. The results were reported using median and interquartile range (IQR) for continuous data and frequencies for categorical data and analyzed using non-parametric tests. The Boruta algorithm was used to assess the significant predictors for the significant change in the confidence interval between the different methods compared to the DL method, which was only feasible using the HKSJ method. RESULTS: 146 MAs were included, most applying the random effect model (n = 111; 76%) and pooling continuous data using mean difference (n = 121; 83%). The median number of studies was three (range 2, 4), and the overall statistical heterogeneity (I2 ranged from 0 to 99% with a median of 68%). Close to 60% of the significant findings became non-significant when HKSJ was applied compared to the DL method and when the heterogeneity was present I2>0%. On the other hand, 30.43% of the non-significant meta-analyses using the DL method became significant when HKSJ was used when the heterogeneity was absent I2 = 0%. CONCLUSION: Orthodontic MAs with few studies can produce different results based on the between-study variance method and the statistical heterogeneity level. Compared to DL, HKSJ method is overconservative when I2 is greater than 0% and may result in false positive findings when the heterogeneity is absent.

ABA INSENSITIVE 2 promotes flowering by inhibiting OST1/ABI5-dependent FLOWERING LOCUS C transcription in Arabidopsis.

The plant hormone abscisic acid (ABA) is an important regulator of plant growth and development and plays a crucial role in both biotic and abiotic stress responses. ABA modulates flowering time, but the precise molecular mechanism remains poorly understood. Here we report that ABA INSENSITIVE 2 (ABI2) is the only phosphatase from the ABA-signaling core that positively regulates the transition to flowering in Arabidopsis. Loss-of-function abi2-2 mutant shows significantly delayed flowering both under long day and short day conditions. Expression of floral repressor genes such as FLOWERING LOCUS C (FLC) and CYCLING DOF FACTOR 1 (CDF1) was significantly up-regulated in abi2-2 plants while expression of the flowering promoting genes FLOWERING LOCUS T (FT) and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1) was down-regulated. Through genetic interactions we further found that ost1-3 and abi5-1 mutations are epistatic to abi2-2, as both of them individually rescued the late flowering phenotype of abi2-2. Interestingly, phosphorylation and protein stability of ABA INSENSITIVE 5 (ABI5) were enhanced in abi2-2 plants suggesting that ABI2 dephosphorylates ABI5, thereby reducing protein stability and the capacity to induce FLC expression. Our findings uncovered the unexpected role of ABI2 in promoting flowering by inhibiting ABI5-mediated FLC expression in Arabidopsis.

Aeroelastic tailoring for aerospace applications.

This study presents a brief account of the seminal works on aeroelastic tailoring for aerospace applications. Tailoring using advanced composites is a revolutionary process in the ever-evolving realm of aerospace design. The rapid growth in scientific knowledge and research necessitates the consolidation of the latest research and technological advancements every few years. The current work is part of this process. The major portion of the study covers the latest developments and state-of-the-art research in this century, with a special focus on the last ten years. However, a brief account of the historical background, the theoretical foundation, and a few seminal works from the later part of the previous century and the early part of this century have also been included to form a comprehensive starting point for new researchers entering the field of aeroelastic tailoring and to assist them in identifying the directions of their future endeavours. A critical evaluation of different research contributions, including their advantages, limitations, and prospects for future work, has been presented. Emphasis has been laid on flutter mitigation and aeroelastic optimization for passive aeroelastic control. New material and structural technologies (like curvilinear fibres, tow steering, functional grading, thickness distributions, selective reinforcing, additive manufacturing, and unconventional structural configurations), and novel tailoring optimization techniques (like lamination parameters, blending constraints, active aeroelastic wing design, shape functions, surrogate modelling, reduced order modelling, uncertainty quantification, matrix perturbation theory, modal-strain-energy analyses, and multiple indigenous optimization algorithms) have been identified as active research areas and prospective enabling tools for future work. The challenges faced in the full-scale employment of aeroelastic tailoring include quick, robust, and cost-effective optimization to cater for all design variables and constraints, experimental validation of new methodologies, certification of new material and structural configurations through relevant bodies and standards and gaining the confidence of industrialists for investment in technologies with a few highly focused areas of applications.

Attenuation of quorum sensing regulated virulence functions and biofilm of pathogenic bacteria by medicinal plant Artemisia annua and its phytoconstituent 1, 8-cineole.

The emergence of multidrug resistance (MDR) in bacterial pathogens is a serious public health concern. A significant therapeutic target for MDR infections is the quorum sensing-regulated bacterial pathogenicity. Determining the anti-quorum sensing abilities of certain medicinal plants against bacterial pathogens as well as the in-silico interactions of particular bioactive phytocompounds with QS and biofilm-associated proteins were the objectives of the present study. In this study, 6 medicinal plants were selected based on their ethnopharmacological usage, screened for Anti-QS activity and Artemisia annua leaf extract (AALE) demonstrated pigment inhibitory activity against Chromobacterium violaceum CV12472. Further, the methanol active fraction significantly inhibited the virulence factors (pyocyanin, pyoverdine, rhamnolipid and swarming motility) of Pseudomonas aeruginosa PAO1 and Serratia marcescens MTCC 97 at respective sub-MICs. The inhibition of biofilm was determined using a microtiter plate test and scanning electron microscopy. Biofilm formation was impaired by 70%, 72% and 74% in P. aeruginosa, C. violaceum and S. marcescens, respectively at 0.5xMIC of the extract. The phytochemical content of the extract was studied using GC-MS and 1, 8-cineole was identified as major bioactive compound. Furthermore, 1, 8-cineole was docked with quorum sensing (QS) proteins (LasI, LasR, CviR, and rhlR) and biofilm proteins (PilY1 and PilT). In silico docking and dynamics simulations studies suggested interactions with QS-receptors CviR', LasI, LasR, and biofilm proteins PilY1, PilT for anti-QS activity. Further, 1, 8-cineole demonstrated 66% and 51% reduction in violacein production and biofilm formation, respectively to validate the findings of computational analysis. Findings of the present investigation suggests that 1, 8-cineole plays a crucial role in the QS and biofilm inhibitory activity demonstrated by Artemisia annua extract. RESEARCH HIGHLIGHTS: Artemisia annua leaf extract (AALE) methanol fraction demonstrated broad-spectrum QS and biofilm inhibition Scanning electron microscopy (SEM) confirmed biofilm inhibition Molecular docking and simulation studies suggested positive interactions of 1,8-cineol with QS-receptors and biofilm proteins.

Clinico-epidemiological profile of non-survivors of COVID-19 during the last two waves in a tertiary care hospital of North India: A retrospective descriptive study.

Background: SARS-CoV-causing COVID-19 resulted in mortality, and the clinic-epidemiological profile at the time of admission of patients who died later could provide an insight into pathophysiological consequences due to infection. Method: Retrospective observational study of 64 RTPCR-confirmed COVID-19 non-survivors was conducted from April - June 2021 and January February 2022. Data were analyzed, and a P value<0.05 was taken as significant. Results: 60.94% and 39.06 % were males and females, and 26.57% & 73.43 % of patients had moderate and severe disease, respectively. Fever, cough, and dyspnea were the most common presenting symptoms. 78.12% and 21.88% had pre-existing (diabetes and hypertension were most common) and no co-morbidities, respectively. 65.62 & 17.19 % of patients had bilateral and unilateral ground glass opacities, respectively. Thrombocytopenia, lymphopenia, neutrophilia, elevated monocytes, and neutrophil-lymphocyte ratio (NLR) of 7.52 were hematological findings. D dimer was elevated. ABG showed low PaO2 and SPO2 %. ALT and AST were elevated. Tachycardia was also present. Compared to the first wave, no significant association of gender with severity was found. However, the percentage of male patients was higher. The association of the duration of stay and co-morbidity with disease severity was significant in both the first and subsequent waves of COVID-19. Conclusion: Co-morbidity, disease severity, and radiological lung opacities play a role in the outcome of COVID-19. The associated findings are hematological, renal, liver, cardiovascular, and arterial blood gas derangements.

Antibiofilm and anti-quorum sensing activity of Psidium guajava L. leaf extract: In vitro and in silico approach.

The quorum sensing mechanism relies on the detection and response to chemical signals, termed autoinducers, which regulate the synthesis of virulence factors including toxins, enzymes, and biofilms. Emerging therapeutic strategies for infection control encompass approaches that attenuate quorum-sensing systems. In this study, we evaluated the antibacterial, anti-quorum sensing, and anti-biofilm activities of Psidium guajava L. methanolic leaf extracts (PGME). Minimum Inhibitory Concentrations (MICs) of PGME were determined as 500 µg/ml for C. violaceum and 1000 µg/ml for P. aeruginosa PAO1. Significantly, even at sub-MIC concentrations, PGME exhibited noteworthy anti-quorum sensing properties, as evidenced by concentration-dependent inhibition of pigment production in C. violaceum 12742. Furthermore, PGME effectively suppressed quorum-sensing controlled virulence factors in P. aeruginosa PAO1, including biofilm formation, pyoverdin, pyocyanin, and rhamnolipid production, with concentration-dependent inhibitory effects. Phytochemical analysis utilizing GC-MS revealed the presence of compounds such as alpha-copaene, caryophyllene, and nerolidol. In-silico docking studies indicated a plausible mechanism for the observed anti-quorum sensing activity, involving favorable binding and interactions with QS-receptors, including RhlR, CviR', LasI, and LasR proteins. These interactions were found to potentially disrupt QS pathways through suppression of AHL production and receptor protein blockade. Collectively, our findings propose PGME as a promising candidate for the treatment of bacterial infections. Its attributes that mitigate biofilm development and impede quorum-sensing mechanisms highlight its potential therapeutic value.

Antibacterial and antibiofilm activity of Abroma augusta stabilized silver (Ag) nanoparticles against drug-resistant clinical pathogens.

Infectious diseases remain among the most pressing concerns for human health. This issue has grown even more complex with the emergence of multidrug-resistant (MDR) bacteria. To address bacterial infections, nanoparticles have emerged as a promising avenue, offering the potential to target bacteria at multiple levels and effectively eliminate them. In this study, silver nanoparticles (AA-AgNPs) were synthesized using the leaf extract of a medicinal plant, Abroma augusta. The synthesis method is straightforward, safe, cost-effective, and environment friendly, utilizing the leaf extract of this Ayurvedic herb. The UV-vis absorbance peak at 424 nm indicated the formation of AA-AgNPs, with the involvement of numerous functional groups in the synthesis and stabilization of the particles. AA-AgNPs exhibited robust antibacterial and antibiofilm activities against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE). The MIC values of AA-AgNPs ranged from 8 to 32 µg/mL. Electron microscopic examination of the interaction of AA-AgNPs with the test bacterial pathogens showed a deleterious impact on bacterial morphology, resulting from membrane rupture and leakage of intracellular components. AA-AgNPs also demonstrated a dose-dependent effect in curtailing biofilm formation below inhibitory doses. Overall, this study highlights the potential of AA-AgNPs in the successful inhibition of both the growth and biofilms of MRSA and VRE bacteria. Following studies on toxicity and dose optimization, such AgNPs could be developed into effective medical remedies against infections.

Successful Management of Recurrent Cholangitis Post Cholecystectomy in a Primary Care Hospital.

Cholangitis, a pathological disease characterized by inflammation of the biliary system, often occurs in conjunction with gallstone blockage and may lead to various problems, persisting for extended periods after cholecystectomy. The present report provides a comprehensive account of a clinical case involving a 35-year-old female patient who had undergone cholecystectomy three years before and is now experiencing symptoms consistent with cholangitis. The individual was originally given conservative therapy, which included the administration of intravenous ceftriaxone antibiotics, analgesics, fluids, and gastrointestinal treatment. Subsequently, they were sent to a tertiary care hospital for the performance of endoscopic retrograde cholangiopancreatography (ERCP) and the placement of a stent. Following a period of seven days, laboratory tests showed a return to normalcy, showing a positive outcome in response to the use of conservative management strategies. The patient made the decision to have an elective laparoscopic cholecystectomy, resulting in a favorable recuperation and a hospitalization period of 24 hours. The aforementioned results jointly demonstrate the efficacy of conservative therapy in treating cholangitis and the potential for eventual elective surgery in individuals experiencing prolonged gallbladder problems. In conclusion, this case underscores the need to maintain a state of alertness with respect to complications associated with cholecystectomy, such as cholangitis. It also emphasizes the effectiveness of conservative treatment approaches and the probable necessity for elective surgical intervention.

Green Synthesis of Copper Oxide Nanoparticles from the Leaves of Aegle marmelos and Their Antimicrobial Activity and Photocatalytic Activities.

The leaves of the Aegle marmelos plant were used for the green synthesis of copper oxide nanoparticles and further characterized by different techniques, including (Ultra Violet-Visible) UV-Vis, Scanning electron microscopy (SEM), Energy dispersive X-ray (EDX), Transmission electron microscopy (TEM) and X-ray diffraction (XRD). The UV-Vis showed a peak at 330 nm, which may be due to the Surface Plasmon Resonance phenomenon. XRD analysis showed the crystalline nature of copper oxide nanoparticles (CuO NPs). In contrast, SEM showed that nanoparticles were not aggregated or clumped, EDX showed the presence of elemental copper., and further, the TEM analysis revealed the average particle size of copper oxide nanoparticles to be 32 nm. The Minimum Inhibitory Concentration (MIC) for Escherichia coli (E. coli) and Staphylococcusaureus (S. aureus) was found to be 400 µg/mL, whereas for Candida albicans (C. albicans) and Candida dubliniensis (C. dubliniensis) it was 800 µg/mL. The zone of inhibition in the well diffusion assay showed the antimicrobial activity of copper oxide nanoparticles, and it also showed that as the concentration of copper oxide nanoparticles increased, the zone of inhibition also increased. Further, the electron microscopic view of the interaction between copper oxide nanoparticles and C. albicans cells showed that CuO NPs were internalized and attached to the cell membrane, which caused changes in the cellular structure and caused deformities which eventually led to cell death. The prepared CuO NPs showed significant photocatalytic degradation of organic dyes in the presence of sunlight.

Insufficient information size and potentially false results in orthodontic meta-analyses using trial sequential analysis.

BACKGROUND: Meta-analysis (MA) is a common mathematical method used in systematic reviews (SRs) to gather data from different studies. MA may result in overestimation or underestimation of the effect due to systematic and random errors. Trial sequential analysis (TSA) has been used to overcome the limitations of conventional MA. The objective of this study was to re-evaluate the findings of orthodontic MAs using TSA to investigate the conclusiveness of the effect and to estimate the required information size (IS). METHODS: Orthodontic SRs with MA published between 1 January 2013 and 31 December 2022 in the leading orthodontic journals were sourced. Data from arm-level MAs were extracted and re-entered in TSA software. RESULTS: A total of 180 papers were assessed against the inclusion criteria. Finally, 50 SRs with MAs were included. TSA found that almost half of the MAs with significant results demonstrated firm evidence of effect. While 38% of the significant MAs confirmed potentially spurious evidence of effect. In contrast, only one MA with insignificant findings showed a lack of effect. Furthermore, a larger number of patients were needed when the evidence of the effect was absent. CONCLUSIONS: TSA revealed that many orthodontic MAs have potentially false-positive results and have insufficient IS.

Are units of analysis properly considered in orthodontic meta-analyses?

BACKGROUND: Assessment of unit of analysis (UoA) in meta-analysis with cluster, split-mouth, repeated measures designs, and multiple intervention groups is a fundamental step in the analysis. The objective of this study was to evaluate the UoAs in orthodontic meta-analysis and determine the error of the analysis. METHODS: An electronic search was conducted in the Cochrane Library and PubMed to identify orthodontic systematic reviews (SRs) with meta-analyses published in Cochrane and in the highest impact orthodontic journals between 1 January 2013 and 31 December 2022. SRs with meta-analysis assessing at least one of the following UoAs; cluster trials, crossover trials, multiple observations, or multiple intervention groups were included. Screening and data extraction were undertaken by two investigators independently. Descriptive statistics for the study characteristics were provided. The associations between avoiding the unit analysis error (yes, no) and the study characteristics were examined using Fisher's exact test and chi-square test. Logistic regression was undertaken for the significant predictors. RESULTS: Eighty SRs were deemed eligible for inclusion. Only 30 per cent of the included SRs avoided UoA errors. Compared to the split-mouth design, repeated measures designs had higher odds of avoiding UoA error (odds ratio: 9.6, 95% confidence interval: 2.8-32.3, P < 0.001). In contrast, fewer odds of avoiding the UoA error were found in the cluster design (OR: 0.2, 95% CI: 0.4-1.3, P = 0.09). Though multiple intervention groups have higher odds of avoiding UoA error than split-mouth studies, this was not statistically significant (OR: 2.1, 95% CI: 0.5-8, P = 0.28). None of the SRs characteristics have influenced the appropriate handling of the unit analysis except the type of the journal; the odds of avoiding the UoA error were higher in Cochrane reviews than the non-Cochrane reviews (OR: 3.3, 95% CI: 1.2-8.7, P = 0.02), and the number of authors (P < 0.05). CONCLUSIONS: UoA errors are common in orthodontic meta-analyses and were only partially avoided in split-mouth design, repeated measures design, and multiple intervention groups.

The good, the bad and the cryptic: The multifaceted roles of mycoviruses and their potential applications for a sustainable agriculture.

Mycoviruses are natural inhabitants of fungi and have been identified in almost all fungal taxonomic groups. Mycoviruses that infect phytopathogenic fungi are now becoming a hot research area due to their potential for the biocontrol of important plant pathogens. But, before considering a mycovirus for biocontrol, we should be fully aware of the effects it induces in a fungal host and its interactions with other viruses, fungal strains and even the host plants. Mycoviral infections are generally associated with different effects, ranging from hypovirulence to hypervirulence, but they can often be cryptic (latent infections). The cryptic lifestyle has been associated to many mycoviruses, but thanks to growing knowledge we are now aware that it is often associated to axenic conditions while the real effects can be observed only in nature. Other mycoviruses either promote (hypervirulence) or (hypovirulence) fungal pathogenicity by a strong impact on the fungal physiology or by blocking the production of toxins or effectors. Finally, indirect effects of mycoviral infections can also be provided to the plant that hosts the fungal isolate, highlighting not only their potential as direct biocontrol agents but also as priming agents for plant resilience to biotic and abiotic stresses. This review provides a broad overview of mycoviral interactions both with their hosts and with other mycoviruses, highlighting the most interesting examples. In contrast to what has been observed to date, we believe that the collective availability of these data will not only improve our understanding of mycoviruses, but also increase our confidence in considering them as alternative measures against fungal diseases to improve the sustainable production of food and feed commodities.