OpenWMB: An open-source and automated working memory task battery for OpenSesame.

Working memory capacity (WMC) has been measured with a plethora of cognitive tasks. Several preeminent automated batteries of working memory (WM) tasks have been developed recently. However, despite all their advantages, most batteries were programmed in paid platforms and/or only included a single WM paradigm. To address these issues, we developed the OpenWMB, an automated battery comprising seven tasks from three distinct paradigms (complex spans, updating tasks, and binding tasks) that tap into several functional aspects of WM (simultaneous storage and processing, updating, and binding). The battery runs on open-source software (OpenSesame) and is freely available online in a ready-to-download format. The OpenWMB possesses flexible features and includes a data processing script (that converts data into a format ready for statistical analysis). The instrument is available in Portuguese and English. However, we only assessed the psychometric properties of the former version. The Portuguese version presented good internal consistency and considerable internal and predictive validity: all tasks loaded into a single factor. Additionally, the WMC estimate was strongly correlated with a fluid intelligence factor. This study also tried to contribute to the ongoing debate regarding the best method to assess WMC. We computed a permutation analysis to compare the amount of variance shared between a fluid intelligence factor and (1) each WM task, (2) homogenous WMC factors (based on multiple tasks from the same paradigm), and (3) heterogeneous WMC factors (derived from triplets of tasks from different paradigms). Our results suggested that heterogeneous factors provided the best estimates of WMC.

Epidemiological profile of luxations injuries with or without dental fractures in permanent teeth: A 10-years retrospective study.

BACKGROUND/AIM: This study assessed the epidemiology of luxation injuries with or without dental fractures in patients attending the outpatient clinic of a Brazilian dental school over the past decade. MATERIAL AND METHODS: We reviewed clinical records from a specialized center for dental trauma care in Brazil, focusing on patients who experienced at least one traumatic dental injury (TDI) in a permanent tooth between 2012 and 2022. The extracted data included sex, age, etiology, time between trauma occurrence and the search for initial care, TDI classification, and the need for endodontic treatment. The statistical analysis involved Pearson's chi-squared and Fisher's exact tests at a 5% significance level. RESULTS: The 366 analyzed clinical records included 166 patients (350 teeth) with luxation injuries. Men (n = 102) showed a higher prevalence of luxation injuries than women (n = 64). Extrusive luxation prevailed (n = 99 patients and 208 teeth). Patients with luxation injuries sought care promptly after dental trauma incidents (p = .02) and demonstrated a higher incidence of endodontic treatment (p < .0001) than those without luxation injuries. Lateral luxation was notably associated with traffic accidents (p < .0001). The combination of luxation injuries and tooth fractures did not correlate with a higher need for endodontic treatment (p > .05). CONCLUSIONS: Age and trauma etiology seemed to have influenced the epidemiological profile of luxation injuries. Additionally, these injuries affected the time to seek initial care and the need for endodontic treatment.

Small-bodied males invest in larger testes when highly ornamented.

Sperm competition and male mating rate are two non-mutually exclusive key evolutionary pressures selecting for larger testes within and across animal taxa. A few studies have tried to test the role of mating rate in the absence of sperm competition. Under the mating rate hypothesis, particular phenotypes of a given population which are expected to gain more mates (e.g. more ornamented males) are expected to make higher investment in testes size (a proxy for sperm production). We test this prediction in Polistes simillimus, a neotropical paper wasp in which females are single-mated (no sperm competition) and males can mate with multiple partners. Testes size was predicted by body size (positive association), sexual ornamentation (negative association), and their interaction (among small males, testes size was positively related to ornamentation but the opposite pattern was observed among large males). We propose that small-bodied well-ornamented males may face the highest risk of sperm depletion. Small-bodied males make relatively higher investment in testes size when highly ornamented. This strategy might be less profitable to large males, as they have overall larger testes. Our results provide strong evidence for the mating rate hypothesis.

Does the potential strength of sexual selection differ between mating systems with and without defensive behaviours? A meta-analysis.

The Darwin-Bateman paradigm predicts that females enhance their fitness by being choosy and mating with high-quality males, while males should compete to mate with as many females as possible. In many species, males enhance their fitness by defending females and/or resources used by females. That is, males directly defend access to mating opportunities. However, paternity analyses have repeatedly shown that females in most species mate polyandrously, which contradicts traditional expectations that male defensive behaviours lead to monandry. Here, in an extensive meta-analysis, encompassing 109 species and 1026 effect sizes from across the animal kingdom, we tested if the occurrence of defensive behaviours modulates sexual selection on females and males. If so, we can illuminate the extent to which males really succeed in defending access to mating and fertilisation opportunities. We used four different indices of the opportunity for sexual selection that comprise pre-mating and/or post-mating episodes of selection. We found, for both sexes, that the occurrence of defensive behaviours does not modulate the potential strength of sexual selection. This implies that male defensive behaviours do not predict the true intensity of sexual selection. While the most extreme levels of sexual selection on males are in species with male defensive behaviours, which indicates that males do sometimes succeed in restricting females' re-mating ability (e.g. elephant seals, Mirounga leonina), estimates of the opportunity for sexual selection vary greatly across species, regardless of whether or not defensive behaviours occur. Indeed, widespread polyandry shows that females are usually not restricted by male defensive behaviours. In addition, our results indicate that post-mating episodes of selection, such as cryptic female choice and sperm competition, might be important factors modulating the opportunity for sexual selection. We discuss: (i) why male defensive behaviours fail to lower the opportunity for sexual selection among females or fail to elevate it for males; (ii) how post-mating events might influence sexual selection; and (iii) the role of females as active participants in sexual selection. We also highlight that inadequate data reporting in the literature prevented us from extracting effect sizes from many studies that had presumably collected the relevant data.

Bacillus velezensis iturins inhibit the hemolytic activity of Staphylococcus aureus.

Bovine mastitis caused by S. aureus has a major economic impact on the dairy sector. With the crucial need for new therapies, anti-virulence strategies have gained attention as alternatives to antibiotics. Here we aimed to identify novel compounds that inhibit the production/activity of hemolysins, a virulence factor of S. aureus associated with mastitis severity. We screened Bacillus strains obtained from diverse sources for compounds showing anti-hemolytic activity. Our results demonstrate that lipopeptides produced by Bacillus spp. completely prevented the hemolytic activity of S. aureus at certain concentrations. Following purification, both iturins, fengycins, and surfactins were able to reduce hemolysis caused by S. aureus, with iturins showing the highest anti-hemolytic activity (up to 76% reduction). The lipopeptides showed an effect at the post-translational level. Molecular docking simulations demonstrated that these compounds can bind to hemolysin, possibly interfering with enzyme action. Lastly, molecular dynamics analysis indicated general stability of important residues for hemolysin activity as well as the presence of hydrogen bonds between iturins and these residues, with longevous interactions. Our data reveals, for the first time, an anti-hemolytic activity of lipopeptides and highlights the potential application of iturins as an anti-virulence therapy to control bovine mastitis caused by S. aureus.

Comparing the effect of imputation reference panel composition in four distinct Latin American cohorts.

Genome-wide association studies have been useful in identifying genetic risk factors for various phenotypes. These studies rely on imputation and many existing panels are largely composed of individuals of European ancestry, resulting in lower levels of imputation quality in underrepresented populations. We aim to analyze how the composition of imputation reference panels affects imputation quality in four target Latin American cohorts. We compared imputation quality for chromosomes 7 and X when altering the imputation reference panel by: 1) increasing the number of Latin American individuals; 2) excluding either Latin American, African, or European individuals, or 3) increasing the Indigenous American (IA) admixture proportions of included Latin Americans. We found that increasing the number of Latin Americans in the reference panel improved imputation quality in the four populations; however, there were differences between chromosomes 7 and X in some cohorts. Excluding Latin Americans from analysis resulted in worse imputation quality in every cohort, while differential effects were seen when excluding Europeans and Africans between and within cohorts and between chromosomes 7 and X. Finally, increasing IA-like admixture proportions in the reference panel increased imputation quality at different levels in different populations. The difference in results between populations and chromosomes suggests that existing and future reference panels containing Latin American individuals are likely to perform differently in different Latin American populations.

Immune response in paper wasp workers: Task matters more than age.

Workers of social hymenopterans (ants, bees and wasps) display specific tasks depending on whether they are younger or older. The relative importance of behavior and age in modulating immune function has seldom been addressed. We compared the strength of encapsulation-melanization immune response (hereafter melanotic encapsulation) in paper wasps displaying age polyethism or experimentally prevented from behavioral specialization. Foragers of Polybia paulista had higher melanotic encapsulation than guards, regardless of their age. Nevertheless, melanotic encapsulation decreased with age when wasps were prevented from behavioral specialization. Thus, in this species, worker melanotic encapsulation seems more sensitive to task than age. Foraging is considered one of the riskier behaviors in terms of pathogen exposure, so upregulating melanotic encapsulation in foragers can possibly improve both individual and colony-level resistance against infections.

Reconstruction of large scalp defect in a brown howler monkey (Alouatta guariba clamitans): A case report.

This case report describes different repair techniques used to reconstruct a large scalp defect in a brown howler monkey (Alouatta guariba clamitans) hit by a vehicle. Three reconstructive procedures were performed in two surgical stages. The repair techniques had successful outcomes on the patient's rehabilitation.

Sodium dodecylbenzene sulphonate (SDBS) present in detergents: action on the gills, skin, and blood of D. rerio fish.

1. Sodium dodecylbenzene sulphonate (SDBS) is one of the surfactants used worldwide in detergents which, due to high residual discharges, has great potential to cause ecotoxicological impacts. Therefore, the sublethal effects of SDBS on the gills and skin of male Danio rerio fish were investigated.2. The fish were distributed into three groups: GC (control), GT1 (0.25 mg/L of SDBS), and GT2 (0.5 mg/L of SDBS) and exposed for 21 days. After the experiment, histopathological analyses of the gills, histochemical analyses (counting of mucous cells), and biochemical analyses (antioxidant defense enzyme analysis, SOD, and CAT) were conducted.3. A significant increase (p < 0.05) in the incidence of circulatory disorders, progressive, and regressive alterations occurred in the GT1 and GT2 groups. Due to these changes, the total histopathological index of the gills was higher in these groups. Mucous cells in the gills and skin increased. There was an increase in SOD activity and a reduction in CAT activity in these groups. Haematology revealed neutrophilia and lymphocytosis in the blood of GT1 and GT2.4. The results clearly demonstrate that a 21-day exposure to SDBS causes severe morphophysiological damage to the gills, skin, and blood of D. rerio fish.

Effects of sodium dodecylbenzene sulfonate (SDBS) on zebrafish (Danio rerio) gills and blood.

Sodium dodecylbenzene sulfonate (SDBS) is an important surfactant used as a cleaning agent and industrial additive to remove unwanted chemicals which have been detected in the aquatic environment. The aim of this study was to examine the toxicological potential of SDBS on the gills of adult male zebrafish (Danio rerio) exposed to this chemical. For the 96 hr acute exposure, fish were divided into three groups: control, 0.25 mg/L, and 0.5 mg/L of SDBS. After the experiment, morphophysiological analyses (gill histopathology and histochemistry), oxidative stress (determination of gill activities of superoxide dismutase (SOD) and catalase (CAT)), and hematological analyses (leukocyte differentiation) were conducted. Data demonstrated that SDBS at both tested concentrations altered the histopathological index and initiated circulatory disturbances, as well as adverse, progressive, and immunological changes in the gills. In the 0.5 mg/L group, SOD activity decreased significantly, but CAT activity was not altered. Prominent blood changes observed in this group were neutrophilia and lymphocytosis. The number of mucous and chloride cells increased significantly in both groups. Taken together, our findings demonstrated that exposure of D. rerio to SDBS, even for 96 hr, produced adverse morphological and hematological effects associated with a reduction in SOD activity. Our findings indicate that exposure of aquatic species to the anionic surfactant SDBS may lead to adverse consequences associated with oxidative stress. Therefore, this study highlights the risks that this substance may pose to aquatic ecosystems and emphasizes the need for further investigations and strict regulations on its disposal.

Severe COVID-19 and long COVID are associated with high expression of STING, cGAS and IFN-α.

The cGAS-STING pathway appears to contribute to dysregulated inflammation during coronavirus disease 2019 (COVID-19); however, inflammatory factors related to long COVID are still being investigated. In the present study, we evaluated the association of cGAS and STING gene expression levels and plasma IFN-α, TNF-α and IL-6 levels with COVID-19 severity in acute infection and long COVID, based on analysis of blood samples from 148 individuals, 87 with acute COVID-19 and 61 in the post-COVID-19 period. Quantification of gene expression was performed by real-time PCR, and cytokine levels were quantified by ELISA and flow cytometry. In acute COVID-19, cGAS, STING, IFN-α, TNF-α, and IL-6 levels were higher in patients with severe disease than in those with nonsevere manifestations (p < 0.05). Long COVID was associated with elevated cGAS, STING and IFN-α levels (p < 0.05). Activation of the cGAS-STING pathway may contribute to an intense systemic inflammatory state in severe COVID-19 and, after infection resolution, induce an autoinflammatory disease in some tissues, resulting in long COVID.

Three-dimensional simulation for interventional cardiology procedures: Face and content validity.

INTRODUCTION AND OBJECTIVES: Three-dimensional (3D) model simulation provides the opportunity to manipulate real devices and learn intervention skills in a realistic, controlled, and safe environment. To ensure that simulators provide a realistic surrogate to real procedures they must undergo scientific validation. We aimed to evaluate the 3D-printed simulator SimulHeart® for face and content validity to demonstrate its value as a training tool in interventional cardiology (IC). METHODS: Health professionals were recruited from sixteen Portuguese IC units. All participants received a 30-minute theoretical introduction, 10-minute demonstration of each task and then performed the intervention on a 3D-printed simulator (SimulHeart®). Finally, a post-training questionnaire focusing on the appearance of the simulation, simulation content, and satisfaction/self-efficacy was administered. RESULTS: We included 56 participants: 16 "experts" (general and interventional cardiologists), 26 "novices" (cardiology residents), and 14 nurses and allied professionals. On a five-point Likert scale, the overall mean score of face validity was 4.38±0.35 and the overall mean score of content validity was 4.69±0.32. There was no statistically significant difference in the scores provided by "experts" and "novices". Participants reported a high level of satisfaction/self-efficacy with 60.7% considering it strongly improved their skills. The majority (82.1%) "agreed" or "strongly agreed" that after the simulation they felt confident to perform the procedure on a patient. CONCLUSION: The 3D-printed simulator (SimulHeart®) showed excellent face and content validity. 3D simulation may play an important role in future IC training programs. Further research is required to correlate simulator performance with clinical performance in real patients.

The role of IL10 and IL17 gene polymorphisms in treatment response in children and adolescents with severe asthma.

OBJECTIVE: To determine whether polymorphisms of the IL10 and IL17 genes are associated with severe asthma control and bronchodilator reversibility in children and adolescents with severe asthma. METHODS: This was a cross-sectional study, nested within a prospective cohort study of patients with severe asthma. Two outcomes were evaluated: asthma control and bronchodilator reversibility. We extracted DNA from peripheral blood and genotyped three single nucleotide polymorphisms: rs3819024 and rs2275913 in the IL17A gene; and rs3024498 in the IL10 gene. For the association analyses, we performed logistic regression in three genetic models (allelic, additive, and dominant). RESULTS: The rs3024498 C allele in the IL10 gene was associated with failure to achieve asthma control despite regular treatment (p = 0.02). However, the G allele of the IL17A rs3819024 polymorphism was associated with failure to respond to stimulation with a b2 agonist. The rs2275913 polymorphism of the IL17A gene showed no relationship with asthma control or bronchodilator reversibility. CONCLUSIONS: In pediatric patients with severe asthma, the IL10 polymorphism appears to be associated with failure to achieve clinical control, whereas the IL17A polymorphism appears to be associated with a worse bronchodilator response. Knowledge of the involvement of these polymorphisms opens future directions for pharmacogenetic studies and for the implementation of individualized therapeutic management of severe asthma in pediatric patients.

Genome-wide study investigating effector genes and polygenic prediction for kidney function in persons with ancestry from Africa and the Americas.

Chronic kidney disease is a leading cause of death and disability globally and impacts individuals of African ancestry (AFR) or with ancestry in the Americas (AMS) who are under-represented in genome-wide association studies (GWASs) of kidney function. To address this bias, we conducted a large meta-analysis of GWASs of estimated glomerular filtration rate (eGFR) in 145,732 AFR and AMS individuals. We identified 41 loci at genome-wide significance (p < 5 × 10-8), of which two have not been previously reported in any ancestry group. We integrated fine-mapped loci with epigenomic and transcriptomic resources to highlight potential effector genes relevant to kidney physiology and disease, and reveal key regulatory elements and pathways involved in renal function and development. We demonstrate the varying but increased predictive power offered by a multi-ancestry polygenic score for eGFR and highlight the importance of population diversity in GWASs and multi-omics resources to enhance opportunities for clinical translation for all.

The impact of nursing practice environments on patient safety culture in primary health care: a scoping review.

BACKGROUND: Patient safety has in recent decades become a global concern. It is a key priority area of healthcare organisations, and has a direct impact on patient health and wellbeing. Work environments can strongly impact nurses' wellbeing and may ultimately produce different outcomes for both professionals and patients. The adverse events occurrence is an example of how work environments influence outcomes, and there is evidence of this correlation in several studies conducted in recent years. AIM: To map the knowledge regarding the impact that nursing practice environments have on safety culture in primary healthcare settings, as primary health care concentrates a significant portion of the population's care. DESIGN & SETTING: This review was conducted following the methodology proposed by the Joanna Briggs Institute (JBI) for scoping reviews. METHOD: Study selection, data extraction, and synthesis were performed by two independent reviewers. Based on Population (or participants), Concept, and Context (PCC) framework, studies were considered that addressed nurses' practice environment and patient safety culture in primary health care. All studies published or unpublished from 2002 to the present were considered. RESULTS: Seven studies were included in this review; however, the existing evidence on the relation between nurses' practice environments and patient safety is still limited in primary healthcare settings. Although clear evidence was not found, several characteristics of nursing practice environments that may impact healthcare safety were found, such as leadership, communication, and organisational culture and policies. CONCLUSION: More research directed at primary healthcare nursing practice settings is needed and could be valuable in defining and implementing strategies that promote the safety of care.

Simultaneous Optical and Mechanical Sensing Based on Optomechanical Resonators.

Optical and mechanical resonators have each been abundantly employed in sensing applications, albeit following separate development. Here we show that bringing together optical and mechanical resonances in a unique sensing device significantly improves the sensor performance. To that purpose, we employ nanoscale optomechanical disk resonators that simultaneously support high quality optical and mechanical modes localized in tiny volumes, which provide extraordinary sensitivities. We perform environmental sensing, but the conclusions of our work extend to other sensing applications. First, we determine optical and mechanical responsivities to temperature and relative humidity changes. Second, by characterizing mechanical and optical frequency stabilities, we determine the corresponding limits of detection. Mechanical modes appear more sensitive to relative humidity changes, while optical modes appear more sensitive to temperature ones, reaching, respectively, 0.05% and 0.6 mK of independent resolution. We then prove that simultaneous optical and mechanical monitoring enables disentangling both effects and demonstrates 0.1% and 1 mK resolution, even considering that both parameters may change at the same time. Finally, we highlight the importance of actively tracking the optical mode when optomechanical sensor devices. Not doing so enforces tedious independent calibration, influences the device sensitivity during the experiment, and shortens the sensing range. The present work hence clarifies the requirements for the optimal operation of optomechanical sensors, which will be of importance for chemical and biological sensing.

Efficacy of pharmacological interventions: a systematic review informing the 2023 EULAR recommendations for the management of fatigue in people with inflammatory rheumatic and musculoskeletal diseases.

OBJECTIVE: To identify the best evidence on the efficacy of pharmacological interventions in reducing fatigue in people with inflammatory rheumatic and musculoskeletal diseases (I-RMDs) and to summarise their safety in the identified studies to inform European Alliance of Associations for Rheumatology recommendations for the management of fatigue in people with I-RMDs. METHODS: Systematic review of adults with I-RMDs conducted according to the Cochrane Handbook. Search strategy ran in Medline, Embase, Cochrane Library, CINAHL Complete, PEDro, OTseeker and PsycINFO. Only randomised controlled trials (RCTs) or controlled clinical trials were eligible. Assessment of risk of bias, data extraction and synthesis performed by two reviewers independently and in duplicate. Data pooled in statistical meta-analyses. RESULTS: From 4151 records, 455 were selected for full-text review, 99 fulfilled the inclusion criteria and 19 RCTs were included in meta-analyses. Adalimumab was superior to placebo in reducing fatigue at 12 and 52 weeks in rheumatoid arthritis (RA) (n=3 and 2 RCTs; mean difference (MD)= -3.03, p<0.001; MD=-2.25, p=0.03, respectively). Golimumab (n=2 RCTs; 24 weeks: MD=-5.27, p<0.001), baricitinib (n=2 RCTs; 24 weeks: MD=-4.06, p<0.001), sarilumab (n=2 RCTs; 24 weeks: MD=-3.15, p<0.001), tocilizumab (n=3 RCTs; 24 weeks: MD=-3.69, p<0.001) and tofacitinib (n=3 RCTs; 12 weeks: MD=-4.44, p<0.001) were also superior to placebo in reducing fatigue in RA. A dose/effect relationship was observed for sarilumab, tocilizumab and tofacitinib. In spondyloarthritis (excluding psoriatic arthritis), secukinumab was superior to placebo in reducing fatigue at 16 weeks (n=2 RCTs; MD=-4.15, p<0.001), with a dose/effect relationship also observed. The narrative results of the RCTs not included in the meta-analysis indicated that several other pharmacological interventions were efficacious in reducing fatigue, with reassuring safety results. CONCLUSIONS: Several pharmacological interventions are efficacious and generally safe for managing fatigue in people with I-RMDs.

2023 EULAR recommendations for the management of fatigue in people with inflammatory rheumatic and musculoskeletal diseases.

OBJECTIVES: Fatigue is prevalent in people with inflammatory rheumatic and musculoskeletal diseases (I-RMDs) and recognised as one of the most challenging symptoms to manage. The existence of multiple factors associated with driving and maintaining fatigue, and the evidence about what improves fatigue has led to a multifaceted approach to its management. However, there are no recommendations for fatigue management in people with I-RMDs. This lack of guidance is challenging for those living with fatigue and health professionals delivering clinical care. Therefore, our aim was to develop EULAR recommendations for the management of fatigue in people with I-RMDs. METHODS: A multidisciplinary taskforce comprising 26 members from 14 European countries was convened, and two systematic reviews were conducted. The taskforce developed the recommendations based on the systematic review of evidence supplemented with taskforce members' experience of fatigue in I-RMDs. RESULTS: Four overarching principles (OAPs) and four recommendations were developed. OAPs include health professionals' awareness that fatigue encompasses multiple biological, psychological and social factors which should inform clinical care. Fatigue should be monitored and assessed, and people with I-RMDs should be offered management options. Recommendations include offering tailored physical activity and/or tailored psychoeducational interventions and/or, if clinically indicated, immunomodulatory treatment initiation or change. Patient-centred fatigue management should consider the individual's needs and preferences, their clinical disease activity, comorbidities and other psychosocial and contextual factors through shared decision-making. CONCLUSIONS: These 2023 EULAR recommendations provide consensus and up-to-date guidance on fatigue management in people with I-RMDs.

Is it possible to automate the discovery of process maps for the time-driven activity-based costing method? A systematic review.

OBJECTIVES: The main objective of this manuscript was to identify the methods used to create process maps for care pathways that utilized the time-driven activity-based costing method. METHODS: This is a systematic mapping review. Searches were performed in the Embase, PubMed, CINAHL, Scopus, and Web of Science electronic literature databases from 2004 to September 25, 2022. The included studies reported practical cases from healthcare institutions in all medical fields as long as the time-driven activity-based costing method was employed. We used the time-driven activity-based costing method and analyzed the created process maps and a qualitative approach to identify the main fields. RESULTS: A total of 412 studies were retrieved, and 70 articles were included. Most of the articles are related to the fields of orthopedics and childbirth-related to hospital surgical procedures. We also identified various studies in the field of oncology and telemedicine services. The main methods for creating the process maps were direct observational practices, complemented by the involvement of multidisciplinary teams through surveys and interviews. Only 33% of the studies used hospital documents or healthcare data records to integrate with the process maps, and in 67% of the studies, the created maps were not validated by specialists. CONCLUSIONS: The application of process mining techniques effectively automates models generated through clinical pathways. They are applied to the time-driven activity-based costing method, making the process more agile and contributing to the visualization of high degrees of variations encountered in processes, thereby making it possible to enhance and achieve continual improvements in processes.

Design of a multi-epitope vaccine (vme-VAC/MST-1) against cholera and vibriosis based on reverse vaccinology and immunoinformatics approaches.

Vibriosis and cholera are serious diseases distributed worldwide and caused by six marine bacteria of the Vibrio genus. Thousands of deaths occur each year due to these illnesses, necessitating the development of new preventive measures. Presently, the existing cholera vaccine demonstrates an effectiveness of approximately 60%. Here we describe a new multi-epitope vaccine, 'vme-VAC/MST-1' based on vaccine targets identified by reverse vaccinology and epitopes predicted by immunoinformatics, two currently effective tools for predicting new vaccines for bacterial pathogens. The vaccine was designed to combat vibriosis and cholera by incorporating epitopes predicted for CTL, HTL, and B cells. These epitopes were identified from six vaccine targets revealed through subtractive genomics, combined with reverse vaccinology, and were further filtered using immunoinformatics approaches based on their predicted immunogenicity. To construct the vaccine, 28 epitopes (24 CTL/B and 4 HTL/B) were linked to the sequence of the cholera toxin B subunit adjuvant. In silico analyses indicate that the resulting immunogen is stable, soluble, non-toxic, and non-allergenic. Furthermore, it exhibits no homology to the host and demonstrates a strong capacity to elicit innate, B-cell, and T-cell immune responses. Our analysis suggests that it is likely to elicit immune reactions mediated through the TLR5 pathway, as evidenced by the molecular docking of the vaccine with the receptor, which revealed high affinity and a favorable reaction. Thus, vme-VAC/MST-1 is predicted to be a safe and effective solution against pathogenic Vibrio spp. However, further experimental analyses are required to measure the vaccine's effects In vivo.Communicated by Ramaswamy H. Sarma.