Vertebrate-class-specific binding modes of the alphavirus receptor MXRA8.

MXRA8 is a receptor for chikungunya (CHIKV) and other arthritogenic alphaviruses with mammalian hosts. However, mammalian MXRA8 does not bind to alphaviruses that infect humans and have avian reservoirs. Here, we show that avian, but not mammalian, MXRA8 can act as a receptor for Sindbis, western equine encephalitis (WEEV), and related alphaviruses with avian reservoirs. Structural analysis of duck MXRA8 complexed with WEEV reveals an inverted binding mode compared with mammalian MXRA8 bound to CHIKV. Whereas both domains of mammalian MXRA8 bind CHIKV E1 and E2, only domain 1 of avian MXRA8 engages WEEV E1, and no appreciable contacts are made with WEEV E2. Using these results, we generated a chimeric avian-mammalian MXRA8 decoy-receptor that neutralizes infection of multiple alphaviruses from distinct antigenic groups in vitro and in vivo. Thus, different alphaviruses can bind MXRA8 encoded by different vertebrate classes with distinct engagement modes, which enables development of broad-spectrum inhibitors.

A SARS-CoV-2 Infection Model in Mice Demonstrates Protection by Neutralizing Antibodies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic with millions of human infections. One limitation to the evaluation of potential therapies and vaccines to inhibit SARS-CoV-2 infection and ameliorate disease is the lack of susceptible small animals in large numbers. Commercially available laboratory strains of mice are not readily infected by SARS-CoV-2 because of species-specific differences in their angiotensin-converting enzyme 2 (ACE2) receptors. Here, we transduced replication-defective adenoviruses encoding human ACE2 via intranasal administration into BALB/c mice and established receptor expression in lung tissues. hACE2-transduced mice were productively infected with SARS-CoV-2, and this resulted in high viral titers in the lung, lung pathology, and weight loss. Passive transfer of a neutralizing monoclonal antibody reduced viral burden in the lung and mitigated inflammation and weight loss. The development of an accessible mouse model of SARS-CoV-2 infection and pathogenesis will expedite the testing and deployment of therapeutics and vaccines.

A Single-Dose Intranasal ChAd Vaccine Protects Upper and Lower Respiratory Tracts against SARS-CoV-2.

The coronavirus disease 2019 pandemic has made deployment of an effective vaccine a global health priority. We evaluated the protective activity of a chimpanzee adenovirus-vectored vaccine encoding a prefusion stabilized spike protein (ChAd-SARS-CoV-2-S) in challenge studies with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mice expressing the human angiotensin-converting enzyme 2 receptor. Intramuscular dosing of ChAd-SARS-CoV-2-S induces robust systemic humoral and cell-mediated immune responses and protects against lung infection, inflammation, and pathology but does not confer sterilizing immunity, as evidenced by detection of viral RNA and induction of anti-nucleoprotein antibodies after SARS-CoV-2 challenge. In contrast, a single intranasal dose of ChAd-SARS-CoV-2-S induces high levels of neutralizing antibodies, promotes systemic and mucosal immunoglobulin A (IgA) and T cell responses, and almost entirely prevents SARS-CoV-2 infection in both the upper and lower respiratory tracts. Intranasal administration of ChAd-SARS-CoV-2-S is a candidate for preventing SARS-CoV-2 infection and transmission and curtailing pandemic spread.

Sequential early-life viral infections modulate the microbiota and adaptive immune responses to systemic and mucosal vaccination.

Increasing evidence points to the microbial exposome as a critical factor in maturing and shaping the host immune system, thereby influencing responses to immune challenges such as infections or vaccines. To investigate the effect of early-life viral exposures on immune development and vaccine responses, we inoculated mice with six distinct viral pathogens in sequence beginning in the neonatal period, and then evaluated their immune signatures before and after intramuscular or intranasal vaccination against SARS-CoV-2. Sequential viral infection drove profound changes in all aspects of the immune system, including increasing circulating leukocytes, altering innate and adaptive immune cell lineages in tissues, and markedly influencing serum cytokine and total antibody levels. Beyond changes in the immune responses, these exposures also modulated the composition of the endogenous intestinal microbiota. Although sequentially-infected mice exhibited increased systemic immune activation and T cell responses after intramuscular and intranasal SARS-CoV-2 immunization, we observed decreased vaccine-induced antibody responses in these animals. These results suggest that early-life viral exposures are sufficient to diminish antibody responses to vaccination in mice, and highlight the potential importance of considering prior microbial exposures when investigating vaccine responses.

Potently neutralizing and protective human antibodies against SARS-CoV-2.

The ongoing pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major threat to global health1 and the medical countermeasures available so far are limited2,3. Moreover, we currently lack a thorough understanding of the mechanisms of humoral immunity to SARS-CoV-24. Here we analyse a large panel of human monoclonal antibodies that target the spike (S) glycoprotein5, and identify several that exhibit potent neutralizing activity and fully block the receptor-binding domain of the S protein (SRBD) from interacting with human angiotensin-converting enzyme 2 (ACE2). Using competition-binding, structural and functional studies, we show that the monoclonal antibodies can be clustered into classes that recognize distinct epitopes on the SRBD, as well as distinct conformational states of the S trimer. Two potently neutralizing monoclonal antibodies, COV2-2196 and COV2-2130, which recognize non-overlapping sites, bound simultaneously to the S protein and neutralized wild-type SARS-CoV-2 virus in a synergistic manner. In two mouse models of SARS-CoV-2 infection, passive transfer of COV2-2196, COV2-2130 or a combination of both of these antibodies protected mice from weight loss and reduced the viral burden and levels of inflammation in the lungs. In addition, passive transfer of either of two of the most potent ACE2-blocking monoclonal antibodies (COV2-2196 or COV2-2381) as monotherapy protected rhesus macaques from SARS-CoV-2 infection. These results identify protective epitopes on the SRBD and provide a structure-based framework for rational vaccine design and the selection of robust immunotherapeutic agents.

Synergistic immunomodulatory effect of synbiotics pre- and postoperative resection of pancreatic ductal adenocarcinoma: a randomized controlled study.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a highly immunosuppressive microenvironment. This single-blind, randomized study aimed to evaluate the synergistic immunomodulatory effects of synbiotics (probiotics and inulin prebiotics), as well as their impact on postoperative complications and outcomes, compared to the use of probiotics alone. Ninety patients diagnosed with PDAC were enrolled and randomly assigned into three groups: the placebo group, the probiotics group (receiving a mixture of ten strains of Lactobacillus, Bifidobacterium, and Streptococcus bacteria at a dose of 25 billion CFUs), and the synbiotics group (the same probiotics along with inulin prebiotics). The interventions were administered for 14 days before the surgery and continued for one month postoperatively. Tumor tissue infiltration of CD8 + T cells and the expression of IFN γ were assessed by immunohistochemistry (IHC). Inflammatory cytokines concentrations, including Il 1 B, IL 6, and IL 10, were evaluated as well by ELISA at various time points pre- and postoperative. Furthermore, patients were followed up after the surgery to assess postoperative short-term outcomes. Our results showed a significant elevation of CD8 + T cell proportion and IFN γ expression in the synbiotics group compared to the probiotics group (p = 0.049, p = 0.013, respectively). Inflammatory cytokines showed a significant gradual decrease in the synbiotics group compared to placebo and probiotics-treated groups (p = 0.000 for both). Administration of synbiotics and probiotics significantly decreased the rate of postoperative complications including anastomotic leakage, diarrhea, and abdominal distension (p = 0.032, p = 0.044, p = 0.042, respectively), with a remarkable reduction in bacteremia in the synbiotics group. These results revealed that this synbiotics formulation potentially enhances the immune response and reduces complications associated with surgery.Clinical trial identification: NCT06199752 (27-12-2023).

Genome-wide analysis of MYB transcription factor family and AsMYB1R subfamily contribution to ROS homeostasis regulation in Avena sativa under PEG-induced drought stress.

BACKGROUND: The myeloblastosis (MYB) transcription factor (TF) family is one of the largest and most important TF families in plants, playing an important role in a life cycle and abiotic stress. RESULTS: In this study, 268 Avena sativa MYB (AsMYB) TFs from Avena sativa were identified and named according to their order of location on the chromosomes, respectively. Phylogenetic analysis of the AsMYB and Arabidopsis MYB proteins were performed to determine their homology, the AsMYB1R proteins were classified into 5 subgroups, and the AsMYB2R proteins were classified into 34 subgroups. The conserved domains and gene structure were highly conserved among the subgroups. Eight differentially expressed AsMYB genes were screened in the transcriptome of transcriptional data and validated through RT-qPCR. Three genes in AsMYB2R subgroup, which are related to the shortened growth period, stomatal closure, and nutrient and water transport by PEG-induced drought stress, were investigated in more details. The AsMYB1R subgroup genes LHY and REV 1, together with GST, regulate ROS homeostasis to ensure ROS signal transduction and scavenge excess ROS to avoid oxidative damage. CONCLUSION: The results of this study confirmed that the AsMYB TFs family is involved in the homeostatic regulation of ROS under drought stress. This lays the foundation for further investigating the involvement of the AsMYB TFs family in regulating A. sativa drought response mechanisms.

SARS-CoV-2-specific immunoglobulin Y antibodies are protective in infected mice.

Safe, passive immunization methods are required against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its variants. Immunization of chickens with antigen is known to induce specific IgY antibodies concentrated in the egg yolk and has a good safety profile, high yield of IgY per egg, can be topically applied, not requiring parenteral delivery. Our data provide the first evidence of the prophylactic efficacy of Immunoglobulin Y antibodies against SARS-CoV-2 in mice. Lohmann hens were injected with recombinant SARS-CoV-2 RBD protein; IgY-Abs were extracted from the eggs and characterized using SDS-PAGE. Antiviral activity was evaluated using plaque reduction neutralization tests. In additional experiments, IgY-RBD efficacy was examined in mice sensitized to SARS-CoV-2 infection by transduction with Ad5-hACE2 (mild disease) or by using mouse-adapted virus (severe disease). In both cases, prophylactic intranasal administration of IgY-Abs reduced SARS-CoV-2 replication, and reduced morbidity, inflammatory cell infiltration, hemorrhage, and edema in the lungs and increased survival compared to control groups that received non-specific IgY-Abs. These results indicate that further evaluation of IgY-RBD antibodies in humans is warranted.

Cuticle Development And The Underlying Transcriptome-Metabolome Associations During Early Seedling Establishment.

The plant cuticle is a complex extracellular lipid barrier that has multiple protective functions. We investigated cuticle deposition by integrating metabolomics and transcriptomics data gathered from six different maize seedling organs of four genotypes, the inbred lines B73 and Mo17, and their reciprocal hybrids. These datasets captured the developmental transition of the seedling from heterotrophic skotomorphogenic growth to autotrophic photomorphogenic growth, which is a transition that is highly vulnerable to environmental stresses. Statistical interrogation of these data reveals that the predominant determinant of cuticle composition is seedling organ type, whereas the seedling genotype has a smaller effect on this phenotype. Gene-to-metabolite associations assessed by integrated statistical analyses identified three gene networks connected with the deposition of different elements of the cuticle: a) cuticular waxes; b) monomers of lipidized cell wall biopolymers, including cutin and suberin; and c) both of these elements. These gene networks reveal three metabolic programs that appear to support cuticle deposition, including processes of chloroplast biogenesis, lipid metabolism, and molecular regulation (e.g., transcription factors, post-translational regulators and phytohormones). This study demonstrates the wider physiological metabolic context that can determine cuticle deposition and lays the groundwork for new targets for modulating properties of this protective barrier.

Atorvastatin for reduction of 28-day mortality in severe and critical COVID-19 patients: a randomized controlled trial.

BACKGROUND: COVID-19 is an abnormal host response to the SARS-CoV-2 infection, which is associated with endothelial dysfunction and multi-organ failure. Atorvastatin has been proposed to reduce COVID-19 severity and mortality in chronic and de-novo users. METHODS: This randomized double-blind trial included 220 COVID-19 patients admitted to Mansoura University's isolation hospital in Egypt. One hundred and ten cases were given 40 mg of atorvastatin once daily for 28 days (group A), while 110 received a placebo (group B). All patients received treatment as per hospital protocol. The primary outcome is all-cause mortality at 28 days. We also tracked 6-month mortality, time to clinical improvement, the risk of invasive mechanical ventilation, acute kidney injury, potential adverse events, and hospital and intensive care length of stay. RESULTS: The 28-day all-cause mortality was 52/104 (50%) in group A vs. 54/103 (52.4%) in group B, odds ratio (OR) = 0.907 (0.526, 1.565), P = 0.727; adjusted OR = 0.773 (0.407, 1.47), P = 0.433. Six-month mortality occurred in 53/102 (52%) and 59/79 (60.8%) in group A vs. B, respectively, P = 0.208. Among hospital survivors in group A vs. group B, the median time to clinical improvement was 10 days (7-14) vs. 10 (7-15), P = 0.715; the duration of hospital stay was 10 days (7-14) vs. 10 (8-17), P = 0.378. Discontinuation was higher in group B (four vs. one), but statistically insignificant, P = 0.369. CONCLUSIONS: In adults with severe or critical COVID-19, atorvastatin did not reduce the risk of 28-day or 6-month mortality and did not shorten the length of hospital stay or time to clinical improvement. Trial registration Clinical Trial Registry (NCT04952350) on July 1st, 2021. https://clinicaltrials.gov/ct2/show/NCT04952350.

The impact of immunosuppression on the mortality and hospitalization of Monkeypox: a systematic review and meta-analysis of the 2022 outbreak.

BACKGROUND: Limited data is available regarding the severity and mortality of Mpox in individuals with immunocompromised conditions. Therefore, we performed this meta-analysis to understand the impact of HIV- or non-HIV-associated immunosuppression on the severity of Mpox requiring hospitalization and mortality. METHODS: A thorough literature search was performed from 2022 up to January 2024. The results were presented as odds ratios (ORs). We only included patients who required hospitalization for severity rather than isolation. RESULTS: A total of 34 studies were included in this analysis. Our analysis did not find a significant difference in the hospitalization risk between HIV-positive individuals and those who were HIV-negative (OR = 1.03; P = 0.85; 7 studies; CD4 count of fewer than 200 cells/µL was less than 0.5% across all studies). Patients with a CD4 count lower than 200 cells/µL or an unsuppressed RNA viral load (> 200 copies/ml) had a significantly higher hospitalization risk (OR = 5.3, P < 0.001) and (OR = 3, P < 0.001), respectively. Most of the reported deaths were reported in patients with HIV with CD4 counts below 200 cells/µL, with some fatal cases occurring in non-HIV immunosuppressed patients, particularly organ transplant recipients. Based on the autopsy findings, Mpox was confirmed in multiple organs, particularly the digestive tract, lung, and testes. Furthermore, some studies documented cases of death that were suspected to be related to hemophagocytic lymphohistiocytosis (HLH) and immune reconstitution inflammatory syndrome (IRIS). Most of the death reports showed concomitant non-Mpox infections at the time of hospitalization and death CONCLUSIONS: Our finding shows that Mpox acts as an opportunistic pathogen in immunocompromised individuals. These individuals should be prioritized for early care and closely monitored for signs of deteriorating clinical conditions. Clinical manifestations and autopsy findings strongly suggest Mpox dissemination to multiple organs, particularly the digestive tract, and lungs. However, the presence of concomitant non-Mpox infections complicates the assessment of the attribution of Mpox to death. Caution should be exercised when interpreting data suggesting poorer outcomes in individuals with non-HIV immunosuppression, as current evidence is scarce and further research is needed.

2D MXenes Nanosheets for Advanced Energy Conversion and Storage Devices: Recent Advances and Future Prospects.

Since the initial MXenes were discovered in 2011, several MXene compositions constructed using combinations of various transition metals have been developed. MXenes are ideal candidates for different applications in energy conversion and storage, because of their unique and interesting characteristics, which included good electrical conductivity, hydrophilicity, and simplicity of large-scale synthesis. Herein, we study the current developments in two-dimensional (2D) MXene nanosheets for energy storage and conversion technologies. First, we discuss the introduction to energy storage and conversion devices. Later, we emphasized on 2D MXenes and some specific properties of MXenes. Subsequently, research advances in MXene-based electrode materials for energy storage such as supercapacitors and rechargeable batteries is summarized. We provide the relevant energy storage processes, common challenges, and potential approaches to an acceptable solution for 2D MXene-based energy storage. In addition, recent advances for MXenes used in energy conversion devices like solar cells, fuel cells and catalysis is also summarized. Finally, the future prospective of growing MXene-based energy conversion and storage are highlighted.

Diastolic dysfunction: assessment and implications on the single ventricle circulation.

PURPOSE OF REVIEW: Patients with a functionally single ventricle (SV) are palliated with a series of procedures leading to a Fontan circulation. Over the life span, a substantial proportion of SV patients develop heart failure that can arise from circulatory or ventricular failure. Diastolic dysfunction (DD) is an important determinant of adverse outcomes in SV patients. However, assessment and categorization of DD in the SV remains elusive. We review recent literature and developments in assessment of DD in the SV and its relation to clinical outcomes. RECENT FINDINGS: DD is prevalent in the SV and associated with worse outcomes. Occult DD can be exposed with provocative testing by exercise or preload challenge during catheterization. Likewise, sensitivity to detect DD may be increased via assessment of atrial function and strain imaging. Recent studies revisiting previous concepts such as incoordinate diastolic wall motion show that these are associated with SV end-diastolic pressures and post-Fontan recovery, yielding accessible DD assessment. Emerging technologies such as ultrafast ultrasound (UFUS) can provide noninvasive assessment of myocardial stiffness, inefficient diastolic flow patterns and intraventricular pressure gradients, thereby yielding new tools and insights into diastolic myocardial and hemodynamic properties. SUMMARY: Characterizing DD in the SV continues to have substantial limitations, necessitating synthesis of multiple parameters into an overall assessment, accounting for their change over time, and in the context of the patient's clinical status. New and emerging techniques may help advance DD assessment and the ability to track response to treatment of new targets.

Synthesis and biological evaluation of O4'-benzyl-hispidol derivatives and analogs as dual monoamine oxidase-B inhibitors and anti-neuroinflammatory agents.

Design, synthesis, and biological evaluation of two series of O4'-benzyl-hispidol derivatives and the analogous corresponding O3'-benzyl derivatives aiming to develop selective monoamine oxidase-B inhibitors endowed with anti-neuroinflammatory activity is reported herein. The first O4'-benzyl-hispidol derivatives series afforded several more potentially active and MAO-B inhibitors than the O3'-benzyl derivatives series. The most potential compound 2e of O4'-benzyl derivatives elicited sub-micromolar MAO-B IC50 of 0.38 µM with a selectivity index >264 whereas most potential compound 3b of O3'-benzyl derivatives showed only 0.95 MAO-B IC50 and a selectivity index >105. Advancement of the most active compounds showing sub-micromolar activities to further cellular evaluations of viability and induced production of pro-neuroinflammatory mediators confirmed compound 2e as a potential lead compound inhibiting the production of the neuroinflammatory mediator nitric oxide significantly by microglial BV2 cells at 3 µM concentration without significant cytotoxicity up to 30 µM. In silico molecular docking study predicted plausible binding modes with MAO enzymes and provided insights at the molecular level. Overall, this report presents compound 2e as a potential lead compound to develop potential multifunctional compounds.

Evaluating the effectiveness of combined T4 and T3 therapy or desiccated thyroid versus T4 monotherapy in hypothyroidism: a systematic review and meta-analysis.

BACKGROUND: Persistent symptoms in hypothyroid patients despite normalized TSH levels suggest the need for alternative treatments. This study aims to evaluate the effectiveness of combined T4 and T3 therapy or desiccated thyroid (DTE) compared to T4 monotherapy, with a focus on thyroid profile, lipid profile, and quality of life metrics. METHODS: We conducted a systematic review in Embase, Medline/PubMed, and Web of Science up to 11/23/2023. We used the following keywords: "Armour Thyroid," OR "Thyroid extract," OR "Natural desiccated thyroid," OR "Nature-Throid," "desiccated thyroid," OR "np thyroid," OR "Synthroid," OR "levothyroxine," OR "Liothyronine," "Cytomel," OR "Thyroid USP," OR "Unithroid." AND "hypothyroidism. " We only included RCTs and excluded non-RCT, case-control studies, and non-English articles. RESULTS: From 6,394 identified records, 16 studies qualified after screening and eligibility checks. We included two studies on desiccated thyroid and 15 studies on combined therapy. In this meta-analysis, combination therapy with T4 + T3 revealed significantly lower Free T4 levels (mean difference (MD): -0.34; 95% CI: -0.47, -0.20), Total T4 levels (mean difference: -2.20; 95% CI: -3.03, -1.37), and GHQ-28 scores (MD: -2.89; 95% CI: -3.16, -2.63), compared to T4 monotherapy. Total T3 levels were significantly higher in combined therapy (MD: 29.82; 95% CI: 22.40, 37.25). The analyses demonstrated moderate to high heterogeneity. There was no significant difference in Heart Rate, SHBG, TSH, Lipid profile, TSQ-36, and BDI Score. Subjects on DTE had significantly higher serum Total T3 levels (MD: 50.90; 95% CI: 42.39, 59.42) and significantly lower serum Total T4 (MD: -3.11; 95% CI: -3.64, -2.58) and Free T4 levels (MD: -0.50; 95% CI: -0.57, -0.43) compared to T4 monotherapy. Moreover, DTE treatment showed modestly higher TSH levels (MD: 0.49; 95% CI: 0.17, 0.80). The analyses indicated low heterogeneity. There was no significant difference in Heart Rate, SHBG, Lipid profile, TSQ-36, GHQ-28, and BDI Score. CONCLUSIONS: Our study revealed that combined therapy and DTE lead to higher T3 and lower T4 levels, compared to T4 monotherapy in hypothyroidism. However, no significant effects on heart rate, lipid profile, or quality of life were noted. Given the heterogeneity of results, personalized treatment approaches are recommended.

Discovery of a stilbenoid-flavanone hybrid as an antitumor Wnt/ß-catenin signaling pathway inhibitor.

A series of designed stilbenoid-flavanone hybrids featuring sp3-hybridized C2 and C3 atoms of C-ring was evaluated against colorectal cancers presented compounds 4, 17, and 20 as the most potential compounds among explored compounds. Evaluation of the anticancer activity spectrum of compounds 4, 17, and 20 against diverse solid tumors presented compounds 17 and 20 with interesting anticancer spectrum. The potencies of compounds 17 and 20 were assessed in comparison with FDA-approved anticancer drugs. Compound 17 was the, in general, the most potent showing low micromolar GI50 values that were more potent than the standard FDA-approved drugs against several solid tumors including colon, brain, skin, renal, prostate and breast tumors. Compound 17 was subjected for evaluation against normal cell lines and was subjected to a mechanism study in HCT116 colon cancer cells which presented it as an inhibitor of Wnt signaling pathway triggering G2/M cell cycle arrest though activation of p53-p21 pathway as well as intrinsic and extrinsic apoptotic death of colon cancer cells. Compound 17 might be a candidate for further development against diverse solid tumors including colon cancer.

An investigation of the acaricidal activity of benzyl alcohol on Rhipicephalus annulatus and Rhipicephalus sanguineus and its synergistic or antagonistic interaction with commonly used acaricides.

The most economically significant ectoparasites in the tropics and subtropics are ixodid ticks, especially Rhipicephalus annulatus and Rhipicephalus sanguineus. Years of extensive use of the readily available acaricides have resulted in widespread resistance development in these ticks, as well as negative environmental consequences. Benzyl alcohol (BA) has been frequently used to treat pediculosis and scabies, and it may be an effective alternative to commonly used acaricides. The main aim of the present study was to evaluate the acaricide activity of BA and its combination with the regularly used chemical acaricides against R. annulatus and R. sanguineus. Different concentrations of BA alone and in combination with deltamethrin, cypermethrin and chlorpyrifos were tested in vitro against adult and larvae of both tick species. The results showed that BA is toxic to R. annulatus and R. sanguineus larvae, with 100% larval mortality at concentrations of ≥50 mL/L, and LC50 and LC90 attained the concentrations of 19.8 and 33.8 mL/L for R. annulatus and 18.8 and 31.8 mL/L for R. sanguineus, respectively. Furthermore, BA in combination with deltamethrin, cypermethrin and chlorpyrifos exhibited synergistic factors of 2.48, 1.26 and 1.68 against R. annulatus larvae and 1.64, 11.1 and 1.14 against R. sanguineus larvae for deltamethrin + BA, cypermethrin + BA and chlorpyrifos + BA, respectively. BA induced 100% mortality in adult R. annulatus at concentrations of ≥250 mL/L with LC50 and LC90 reached the concentrations of 111 and 154 mL/L, respectively. Additionally, BA had ovicidal activity causing complete inhibition of larval hatching at 100 mL/L. The combination of BA with deltamethrin and cypermethrin increased acetylcholinesterase inhibition, whereas the combination of BA with chlorpyrifos decreased glutathione (GSH) activity and malondialdehyde levels. In the field application, the combination of BA 50 mL/L and deltamethrin (DBA) resulted in a significant reduction in the percentage of ticks by 30.9% 28 days post-treatment when compared with groups treated with deltamethrin alone. In conclusion, BA causes mortality in laboratory and field studies alone and in combination with cypermethrin or deltamethrin. BA can be used for control of ticks of different life stages, that is, eggs and larvae, through application to the ground.

Detection of Hepatitis E Virus (HEV) Among Ruminant Animals.

BACKGROUND: HEV is endemic in several Middle Eastern countries including Saudi Arabia, which hosts the annual pilgrimage for Muslims from around the world. One of the Hajj rituals is the sacrifice of animals, including camels, cows, goats, and sheep. HEV Zoonosis is established in swine and other suspected species, including deer, rabbits, dromedary, and Bactrian camels. HEV was identified in small, domesticized animals like goats, cows, sheep, and horses. We previously investigated HEV seroprevalence in Camels. This study aimed to evaluate HEV seroprevalence in other highly consumed ruminants in Saudi Arabia, namely cows, sheep, and goats. METHODS: Sera from cows (n = 47), goats (n = 56), and sheep (n = 67) were analyzed for the presence of HEV-IgG by using in-house developed ELISA assays. RESULTS: The highest seroprevalence was found in sheep (62.7%), followed by cows (38.3%), and then goats (14.3%), with a p-value of < 0.001. No other demographic characteristics of the animals were significantly correlated with the HEV seroprevalence. CONCLUSIONS: This study provides baseline data as the first study on the seroprevalence of HEV in ruminant animals in Saudi Arabia. The high seroprevalence found in sheep and cows must be further investigated for the potential zoonotic HEV transmission to humans. Further studies are needed to investigate the active viremia in these animal species through nucleic acid detection and sequencing to provide data on the circulating HEV genotypes among the targeted animal species. The detection of HEV in different animal products, such as milk, liver, and others, also remains an important study area to consider.

Trends of fully alcohol-attributable mortality rates before and during COVID-19 in the Baltic and other European countries.

AIMS: We tested the polarization hypothesis, which postulates that during times of crises, such as the COVID-19 pandemic, alcohol consumption increases among the heaviest drinkers but decreases among most other drinkers, resulting in an overall decrease in consumption among the population. We posited the increase in heavy drinking would lead to increases in 100% alcohol-attributable (AA) mortality. Furthermore, based on the high level of alcohol consumption in the Baltic countries compared to other European countries, we predicted that the increases in AA mortality would be more pronounced in these countries. METHODS: Data for 100% AA deaths were obtained from the World Health Organization for the period 2010 to 2022, and standardized to the regional age distribution for 2010. Parametric and non-parametric tests were used to test the study hypotheses. RESULTS: The mean age-standardized 100% AA mortality rate increased during the COVID-19 pandemic in the 19 European countries with data by 3.12 deaths per 100,000 population, constituting an 18% increase (tested against no change: t = 2.52; df = 18; p = 0.021). This increase was higher in the Baltic countries (mean difference = 13.41 deaths per 100,000 population; standard deviation (SD) = 7.44; 46% increase) than for other European countries (mean difference = 1.19; SD = 1.55; 8% increase). The increases in 100% AA mortality were associated with decreases in the level of alcohol consumption in the majority of countries. CONCLUSIONS: As predicted, 100% AA mortality increased in 19 European countries during the COVID-19 pandemic, with the Baltic countries seeing a higher increase. Renewed alcohol control policy efforts should be considered.

Surgeon handedness affects the acetabular cup positioning during primary total hip arthroplasty regardless of the surgical approach. a systematic review and metanalysis.

PURPOSE: The aim was to investigate the effect of surgeon handedness on acetabular cup positioning, functional outcomes, and dislocation incidence during primary THA. METHODS: A systematic review was conducted according to the PRISMA guidelines. Studies published in English were searched in three databases (PubMed, Embase, and Scopus). A dominant side is a right-handed (RHD) or left-handed (LHD) surgeon who operates on the right or left hip, respectively. The opposite is considered to be the non-dominant side. We used odds ratios for dichotomous data and mean differences for continuous data, with 95% confidence intervals for quantitative data synthesis. Heterogeneity was assessed using the I² test, with outcomes graphically represented in a forest plot and a p-value of < 0.05 considered statistically significant; analyses were performed using Review Manager 5.4 (RevMan 5.4.1). >. RESULT: Four observational studies were included out of 98 articles. Ten experienced surgeons participated (8 RHD and 2 LHD) and operated on 822 patients (1484 hips), divided equally between dominant and non-dominant sides, and the posterolateral approach was utilized in 80.9% of THAs. RHD surgeons operated on 1404 (94.6%) THAs. The pooled synthesis for inclination indicated no significant difference between either side [MD: 0.10 (95% CI -2.10 to 2.30, P = 0.93, I² = 91%)]. While the difference was significant for anteversion [MD: -2.37 (95% CI -3.82 to -0.93, P = 0.001, I² = 31%)]. The functional outcome was better on the dominant side [MD: 1.44 (95% CI 0.41 to 2.48, P = 0.006, I² = 0%)], and the dislocation incidence was significantly higher on the non-dominant side [OR: 0.45 (95% CI 0.25 to 0.81, P = 0.008, I² = 0%)]. CONCLUSION: Surgeon handedness and whether operating on the dominant or non-dominant side could affect the acetabular cup positioning and outcomes during primary THAs, even in the hands of high-volume surgeons.