Application of fluorescein sodium videoangiography in aneurysm surgery.

BACKGROUND: The use of fluorescent technologies in vascular neurosurgery emerged after indocyanine green video angiography (ICG-VA) was first described in 2003. As data supporting the efficiency of ICG in preventing postoperative complications has grown substantially, it has now established itself as the standard of care. However, the predominant literature centers on ICG techniques, leaving the evaluation of cost-effective fluorescein tools pending. We report the results of a prospective study in which we demonstrated the impact of intraoperative fluorescein videoangiography (FL-VA) in aneurysm surgery. METHODS: Between December 2021 and September 2022, a total of 57 patients underwent craniotomy for intracranial aneurysm surgery. After aneurysm clipping, we administered a 0.5 mg/Kg of sodium fluorescein, and the intracranial area of interest was inspected through the microscope integrated module. The following data were collected: patient age and sex; number of clipped aneurysms; aneurysm location, size, and rupture status; Hunt Hess grade; intraoperative rupture; aneurysm calcification and thrombosed aneurysm; visualization of blood flow in perforating arteries; need for a clip adjustment after FL-VA analysis by neurosurgeon. RESULTS: For the surgical clipping of 64 aneurysms in 57 patients, 80 FL-VA studies were performed. Clip adjustments were performed following FL-VA in 13 aneurysms. FL-VA had an impact on 20 % of the clipping. In seven aneurysms, clip adjustment was due to the "presence of residual aneurysm", in three cases due to the "presence of neck", and in three cases due to "adjacent vessel stenosis". Regarding the evaluation of flow in the perforating vessels, it was possible, with a good and detailed image in all cases. CONCLUSION: The use of FL-VA has a significant impact in aneurysm surgery, enhancing effectiveness and safety. The dosage of 0.5 mg/kg administered is sufficient for assessing both aneurysm occlusion and the presence of flow in adjacent vessels.

Strain dynamics of contaminating bacteria modulate the yield of ethanol biorefineries.

Bioethanol is a sustainable energy alternative and can contribute to global greenhouse-gas emission reductions by over 60%. Its industrial production faces various bottlenecks, including sub-optimal efficiency resulting from bacteria. Broad-spectrum removal of these contaminants results in negligible gains, suggesting that the process is shaped by ecological interactions within the microbial community. Here, we survey the microbiome across all process steps at two biorefineries, over three timepoints in a production season. Leveraging shotgun metagenomics and cultivation-based approaches, we identify beneficial bacteria and find improved outcome when yeast-to-bacteria ratios increase during fermentation. We provide a microbial gene catalogue which reveals bacteria-specific pathways associated with performance. We also show that Limosilactobacillus fermentum overgrowth lowers production, with one strain reducing yield by ~5% in laboratory fermentations, potentially due to its metabolite profile. Temperature is found to be a major driver for strain-level dynamics. Improved microbial management strategies could unlock environmental and economic gains in this US $ 60 billion industry enabling its wider adoption.

Antiviral activity of intracellular nanobodies targeting the influenza virus RNA-polymerase core.

Influenza viruses transcribe and replicate their genome in the nucleus of the infected cells, two functions that are supported by the viral RNA-dependent RNA-polymerase (FluPol). FluPol displays structural flexibility related to distinct functional states, from an inactive form to conformations competent for replication and transcription. FluPol machinery is constituted by a structurally-invariant core comprising the PB1 subunit stabilized with PA and PB2 domains, whereas the PA endonuclease and PB2 C-domains can pack in different configurations around the core. To get insights into the functioning of FluPol, we selected single-domain nanobodies (VHHs) specific of the influenza A FluPol core. When expressed intracellularly, some of them exhibited inhibitory activity on type A FluPol, but not on the type B one. The most potent VHH (VHH16) binds PA and the PA-PB1 dimer with an affinity below the nanomolar range. Ectopic intracellular expression of VHH16 in virus permissive cells blocks multiplication of different influenza A subtypes, even when induced at late times post-infection. VHH16 was found to interfere with the transport of the PA-PB1 dimer to the nucleus, without affecting its handling by the importin ß RanBP5 and subsequent steps in FluPol assembly. Using FluPol mutants selected after passaging in VHH16-expressing cells, we identified the VHH16 binding site at the interface formed by PA residues with the N-terminus of PB1, overlapping or close to binding sites of two host proteins, ANP32A and RNA-polymerase II RPB1 subunit which are critical for virus replication and transcription, respectively. These data suggest that the VHH16 neutralization is likely due to several activities, altering the import of the PA-PB1 dimer into the nucleus as well as inhibiting specifically virus transcription and replication. Thus, the VHH16 binding site represents a new Achilles' heel for FluPol and as such, a potential target for antiviral development.

Ribonuclease activity undermines immune sensing of naked extracellular RNA.

The plasma membrane and the membrane of endosomal vesicles are considered physical barriers preventing extracellular RNA uptake. While naked RNA can be spontaneously internalized by certain cells types, functional delivery of naked RNA into the cytosol has been rarely observed. Here we show that extracellular ribonucleases, mainly derived from cell culture supplements, have so far hindered the study of extracellular RNA functionality. In the presence of active ribonuclease inhibitors (RI), naked bacterial RNA is pro-inflammatory when spiked in the media of dendritic cells and macrophages. In murine cells, this response mainly depends on the action of endosomal Toll-like receptors. However, we also show that naked RNA can perform endosomal escape and engage with cytosolic RNA sensors and ribosomes. For example, naked mRNAs encoding reporter proteins can be spontaneously internalized and translated by a variety of cell types, in an RI-dependent manner. In vivo, RI co-injection enhances the activation induced by naked extracellular RNA on splenic lymphocytes and myeloid-derived leukocytes. Furthermore, naked extracellular RNA is inherently pro-inflammatory in ribonuclease-poor compartments such as the peritoneal cavity. Overall, these results demonstrate that naked RNA is bioactive and does not need encapsulation inside synthetic or biological lipid vesicles for functional uptake, making a case for nonvesicular extracellular RNA-mediated intercellular communication.

Sociodemographic factors and lifestyle behaviours associated with bullying victimization and perpetration in a sample of Brazilian adolescents.

This article aims to identify the association of sociodemographic factors and lifestyle behaviours with bullying perpetration and victimization among high school students. The adolescents (n=852) answered a questionnaire about bullying (victims and perpetrators), sociodemographic factors (sex, age, maternal education, and participant's work status), tobacco use, alcohol use, illicit drug experimentation, physical activity, screen time, and sleep duration. Multilevel logistic regression models were performed. Older adolescents were less likely to be victims of bullying. Females were less likely to be perpetrators or victims of bullying. Adolescents who were working were more likely to be involved in bullying in both forms. Participation in non-sport activities and alcohol consumption were associated with higher odds of bullying victimization. We have identified specific populational subgroups that are more susceptible to being victims and/or perpetrators of bullying, which could support tailor-specific interventions to prevent bullying.

Factors Associated With Loss to Follow-Up in Surgical Trials: A Systematic Review and Meta-Analysis.

INTRODUCTION: Loss to follow-up (LTFU) distorts results of randomized controlled trials (RCTs). Understanding trial characteristics that contribute to LTFU may enable investigators to anticipate the extent of LTFU and plan retention strategies. The objective of this systematic review and meta-analysis was to investigate the extent of LTFU in surgical RCTs and evaluate associations between trial characteristics and LTFU. METHODS: MEDLINE, Embase, and PubMed Central were searched for surgical RCTs published between January 2002 and December 2021 in the 30 highest impact factor surgical journals. Two-hundred eligible RCTs were randomly selected. The pooled LTFU rate was estimated using random intercept Poisson regression. Associations between trial characteristics and LTFU were assessed using metaregression. RESULTS: The 200 RCTs included 37,914 participants and 1307 LTFU events. The pooled LTFU rate was 3.10 participants per 100 patient-years (95% confidence interval [CI] 1.85-5.17). Trial characteristics associated with reduced LTFU were standard-of-care outcome assessments (rate ratio [RR] 0.17; 95% CI 0.06-0.48), surgery for transplantation (RR 0.08; 95% CI 0.01-0.43), and surgery for cancer (RR 0.10; 95% CI 0.02-0.53). Increased LTFU was associated with patient-reported outcomes (RR 14.21; 95% CI 4.82-41.91) and follow-up duration ≥ three months (odds ratio 10.09; 95% CI 4.79-21.28). CONCLUSIONS: LTFU in surgical RCTs is uncommon. Participants may be at increased risk of LTFU in trials with outcomes assessed beyond the standard of care, surgical indications other than cancer or transplant, patient-reported outcomes, and longer follow-up. Investigators should consider the impact of design on LTFU and plan retention strategies accordingly.

Prognostic impact of corticosteroid and tocilizumab use following chimeric antigen receptor T-cell therapy for multiple myeloma.

Despite being the mainstay of management for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), there is limited data regarding the impact of tocilizumab (TCZ) and corticosteroids (CCS) on chimeric antigen receptor (CAR) T-cell efficacy in multiple myeloma (MM). The present study aims to evaluate the prognostic impact of these immunosuppressants in recipients of BCMA- or GPRC5D-directed CAR T cells for relapsed/refractory MM. Our retrospective cohort involved patients treated with commercial or investigational autologous CAR T-cell products at a single institution from March 2017-March 2023. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response rate (ORR), complete response rate (CRR), and overall survival (OS). In total, 101 patients (91% treated with anti-BCMA CAR T cells and 9% treated with anti-GPRC5D CAR T cells) were analyzed. Within 30 days post-infusion, 34% received CCS and 49% received TCZ for CRS/ICANS management. At a median follow-up of 27.4 months, no significant difference in PFS was observed between CCS and non-CCS groups (log-rank p = 0.35) or between TCZ and non-TCZ groups (log-rank p = 0.69). ORR, CRR, and OS were also comparable between evaluated groups. In our multivariable model, administering CCS with/without TCZ for CRS/ICANS management did not independently influence PFS (HR, 0.74; 95% CI, 0.36-1.51). These findings suggest that, among patients with relapsed/refractory MM, the timely and appropriate use of CCS or TCZ for mitigating immune-mediated toxicities does not appear to impact the antitumor activity and long-term outcomes of CAR T-cell therapy.

Influence of Pathophysiological Patterns of Coronary Artery Disease on Immediate Percutaneous Coronary Intervention Outcomes.

BACKGROUND: Diffuse coronary artery disease (CAD) impacts the safety and efficacy of percutaneous coronary intervention (PCI). Pathophysiological CAD patterns can be quantified using fractional flow reserve (FFR) pullbacks incorporating the pullback pressure gradient (PPG) calculation. This study aimed to establish the capacity of PPG to predict optimal revascularisation and procedural outcomes. METHODS: This prospective, investigator-initiated, single-arm, multicentre study enrolled patients with at least one epicardial lesion with an FFR ≤ 0.80 scheduled for PCI. Manual FFR pullbacks were employed to calculate PPG. The primary outcome of optimal revascularisation was defined as a post-PCI FFR ≥ 0.88. RESULTS: 993 patients with 1044 vessels were included. The mean FFR was 0.68 ± 0.12, PPG 0.62 ± 0.17, and post-PCI FFR 0.87 ± 0.07. PPG was significantly correlated with the change in FFR after PCI (r=0.65, 95% CI 0.61-0.69, p<0.001) and demonstrated excellent predicted capacity for optimal revascularisation (AUC 0.82, 95% CI 0.79-0.84, p<0.001). Conversely, FFR alone did not predict revascularisation outcomes (AUC 0.54, 95% CI 0.50-0.57). PPG influenced treatment decisions in 14% of patients, redirecting them from PCI to alternative treatment modalities. Periprocedural myocardial infarction occurred more frequently in patients with low PPG (<0.62) compared to those with focal disease (OR 1.71, 95% CI: 1.00-2.97). CONCLUSIONS: Pathophysiological CAD patterns distinctly affect the safety and effectiveness of PCI. The PPG showed an excellent predictive capacity for optimal revascularisation and demonstrated added value compared to a FFR measurement.

The Potential of the Fibronectin Inhibitor Arg-Gly-Asp-Ser in the Development of Therapies for Glioblastoma.

Glioblastoma (GBM) is the most lethal and common malignant primary brain tumor in adults. An important feature that supports GBM aggressiveness is the unique composition of its extracellular matrix (ECM). Particularly, fibronectin plays an important role in cancer cell adhesion, differentiation, proliferation, and chemoresistance. Thus, herein, a hydrogel with mechanical properties compatible with the brain and the ability to disrupt the dynamic and reciprocal interaction between fibronectin and tumor cells was produced. High-molecular-weight hyaluronic acid (HMW-HA) functionalized with the inhibitory fibronectin peptide Arg-Gly-Asp-Ser (RGDS) was used to produce the polymeric matrix. Liposomes encapsulating doxorubicin (DOX) were also included in the hydrogel to kill GBM cells. The resulting hydrogel containing liposomes with therapeutic DOX concentrations presented rheological properties like a healthy brain. In vitro assays demonstrated that unmodified HMW-HA hydrogels only caused GBM cell killing after DOX incorporation. Conversely, RGDS-functionalized hydrogels displayed per se cytotoxicity. As GBM cells produce several proteolytic enzymes capable of disrupting the peptide-HA bond, we selected MMP-2 to illustrate this phenomenon. Therefore, RGDS internalization can induce GBM cell apoptosis. Importantly, RGDS-functionalized hydrogel incorporating DOX efficiently damaged GBM cells without affecting astrocyte viability, proving its safety. Overall, the results demonstrate the potential of the RGDS-functionalized hydrogel to develop safe and effective GBM treatments.

Comparison of infectious complications with BCMA-directed therapies in multiple myeloma.

B-cell-maturation-antigen (BCMA)-directed therapies are highly active for multiple myeloma, but infections are emerging as a major challenge. In this retrospective, single-center analysis we evaluated infectious complications after BCMA-targeted chimeric-antigen-receptor T-cell therapy (CAR-T), bispecific-antibodies (BsAb) and antibody-drug-conjugates (ADC). The primary endpoint was severe (grade ≥3) infection incidence. Amongst 256 patients, 92 received CAR-T, 55 BsAb and 109 ADC. The incidence of severe infections was higher with BsAb (40%) than CAR-T (26%) or ADC (8%), including grade 5 infections (7% vs 0% vs 0%, respectively). Comparing T-cell redirecting therapies, the incidence rate of severe infections was significantly lower with CAR-T compared to BsAb at 1-year (incidence-rate-ratio [IRR] = 0.43, 95%CI 0.25-0.76, P = 0.004). During periods of treatment-emergent hypogammaglobulinemia, BsAb recipients had higher infection rates (IRR:2.27, 1.31-3.98, P = 0.004) and time to severe infection (HR 2.04, 1.05-3.96, P = 0.036) than their CAR-T counterparts. During periods of non-neutropenia, CAR-T recipients had a lower risk (HR 0.44, 95%CI 0.21-0.93, P = 0.032) and incidence rate (IRR:0.32, 95% 0.17-0.59, P < 0.001) of severe infections than BsAb. In conclusion, we observed an overall higher and more persistent risk of severe infections with BsAb. Our results also suggest a higher infection risk during periods of hypogammaglobulinemia with BsAb, and with neutropenia in CAR-T recipients.

Mortalidade por homicídio de policiais civis do estado da Bahia, Brasil / Mortality by murder of civil police officials in the state of Bahia, Brazil / Mortalidad por asesinato de policías civiles en el estado de Bahía, Brasil

Os homicídios de policiais estão associados a fatores individuais, sociais e do trabalho. Dessa forma, o objetivo deste artigo é caracterizar a mortalidade por homicídio de policiais civis da Bahia entre 2012 e 2019. Trata-se de estudo descritivo de vigilância da mortalidade de homicídios de policiais civis da ativa. As variáveis estudadas foram sociodemográficas, da atividade policial e da ocorrência. Na análise foram realizados cálculos de taxas de mortalidade e da estatística descritiva, por meio da linguagem computacional R versão 4.2.2. Foram registrados 27 homicídios de policiais civis da ativa, o que equivale a uma taxa média de 0,58/1000. Na caracterização, todos eram homens, com idade média de 52,5 anos (42 a 63 anos) e 95% negros. Em relação à atividade policial, 76% eram investigadores, com média de 17,9 anos (3 a 33 anos) de serviço e 81% das mortes ocorreram em horário de folga. Em 90% dos homicídios a arma de fogo foi o instrumento causador da morte, e em 62% dos casos a autoria não foi identificada. Conclui-se que o perfil sociodemográfico, do trabalho e das ocorrências de homicídios de policiais civis é semelhante ao perfil encontrado entre policiais militares e sobretudo aos homicídios da população geral.

Police homicides are associated with individual, social, and work-related factors. To characterize mortality due to homicide cases of civil police officers in the State of Bahia from 2012 to 2019.This is a descriptive study of mortality surveillance regarding the homicides of active civil police officers. The variables studied included sociodemographic, police activity, and event occurrence rates. In the analysis, mortality rates and descriptive statistics were calculated using the computational language R, version 4.2.2. Overall, 27 cases of homicide of civil police officers were registered, with an average rate of 0.58/1000 civil police officers. In the characterization, all victims were men with an average age of 52.5 years (42 to 63 years) and a 95% percent Black ethnicity. Regarding police activity, 76% were investigators, with an average of 17.9 years (3 to 33 years) of service, and 81% of deaths occurred during off-duty hours. In 90% of homicide cases, firearms were the instrument that caused death, and in 62% of cases the perpetrator was unidentified. The sociodemographic, work, and homicide profile of civil police officers resembles the profile among military police officers and especially that of homicides in the general population.

Los homicidios de policías están asociados a factores individuales, sociales y laborales. El objetivo de este artículo fue caracterizar la mortalidad por homicidio de policías civiles en el estado de Bahía (Brasil), en el período entre 2012 y 2019. Se trata de un estudio descriptivo de la vigilancia de la mortalidad por homicidios de policías civiles en activo. Las variables estudiadas fueron sociodemográficas, actividad policial y ocurrencia. En el análisis se realizaron cálculos de tasas de mortalidad y estadísticas descriptivas utilizando el lenguaje computacional R, versión 4.2.2.Se registraron 27 homicidios de policías civiles en activo, con una media de 0,58/1000 policías civiles. En la caracterización, todos eran hombres, con media de edad de 52,5 años (42 a 63 años), y el 95%, negros. Con relación a la actividad policial, el 76% se desempeñaban como investigadores, con un promedio de 17,9 años (3 a 33 años) de servicio y el 81% de las muertes ocurrieron fuera de servicio. En el 90% de los homicidios, el arma de fuego fue el instrumento que provocó la muerte y en el 62% de los casos no se identificó al autor. Se concluye que el perfil sociodemográfico, laboral y de homicidios de los policías civiles es similar al perfil encontrado entre los policías militares y, especialmente, a los homicidios en la población general.

Comparative efficacy of carfilzomib, lenalidomide, and dexamethasone (KRd) versus bortezomib, lenalidomide, and dexamethasone (VRd) in newly-diagnosed multiple myeloma: A systematic review and meta-analysis.

In view of the increasing data evaluating carfilzomib-based induction for newly-diagnosed multiple myeloma (NDMM), we conducted a systematic review and meta-analysis comparing the efficacy of carfilzomib/lenalidomide/dexamethasone (KRd) versus bortezomib/lenalidomide/dexamethasone (VRd). Three studies totaling 1597 patients (50% KRd-treated, 50% VRd-treated) were included. Despite similar survival outcomes and overall response rate compared with the VRd arm, KRd-treated subjects showed higher odds of achieving complete responses and measurable residual disease negativity. Among patients with high-risk cytogenetics (n = 348), KRd was associated with significant improvement in progression-free survival (HR = 0.70; 95% CI = 0.50-0.97; p = .03; I2 = 0%), suggesting carfilzomib-based induction may be preferable in this NDMM subpopulation.

Perfil da mortalidade de policiais militares por causas violentas, segundo cor da pele, na Bahia, Brasil / Profile of military police officers' mortality from violent causes, according to skin color, in Bahia, Brazil / Perfil de mortalidad por causas violentas de policías militares según el color de piel en Bahía, Brasil

O Brasil é um país com altas taxas de violência, o que afeta, além da sociedade civil, os agentes das forças da segurança pública, cujas taxas de mortalidade por causas violentas são superiores às da população geral. Portanto, objetivou-se caracterizar o perfil da mortalidade de policiais militares por causas violentas, segundo a cor da pele, no estado da Bahia. Neste estudo, foram analisadas as mortes violentas de policiais militares da ativa ocorridas entre 2012 e 2019, considerando variáveis tanto sociodemográficas quanto relacionadas à corporação policial e às circunstâncias da ocorrência. A análise dos resultados foi realizada por meio da linguagem computacional R versão 4.2.2. Foram registradas 110 mortes de policiais militares, em sua maioria negros (83,64%). Em relação à faixa etária, os policiais militares negros morreram mais jovens, entre 30 e 39 anos (41,30%), enquanto os brancos, entre 40 e 49 anos (61,11%). Em 50% dos casos envolvendo policiais militares negros, a motivação do crime permaneceu desconhecida, enquanto 33,33% das mortes envolvendo policiais brancos foram por confronto com criminosos. Conclui-se que o perfil das mortes de policiais militares no estado da Bahia é semelhante ao da população em geral, com predomínio de homens, negros, jovens e solteiros.

Brazil is a country with high rates of violence, which affects, in addition to civil society, public security agents, whose mortality rates from violent causes are higher than those of the general population. Therefore, the objective was to characterize the profile of mortality of military police officers due to violent causes, according to skin color, in the state of Bahia. This study analyzed violent deaths of active military police officers that occurred between 2012 and 2019, considering both sociodemographic variables and those related to the police force and the circumstances of the occurrence. The analysis of the results was carried out using the computational language R version 4.2.2. A total of 110 military police deaths were recorded, most were black (83.64%). Regarding age group, black military police officers died younger, between 30 and 39 years old (41.30%), whereas white military police officers, between 40 and 49 years old (61.11%). In 50% of cases involving black military police officers, the motivation for the crime remained unknown, whereas 33.33% of deaths involving white police officers were due to confrontation with criminals. In conclusion, the profile of military police deaths in the state of Bahia is similar to that of the general population, with a predominance of male, black, young, and single people.

Brasil tiene altos índices de violencia que no solo afectan a la sociedad civil, sino también a los agentes de seguridad pública, cuyas tasas de mortalidad por causas violentas superan a las de la población general. Así, el objetivo de este estudio fue caracterizar el perfil de mortalidad por causas violentas de los policías militares según el color de la piel, en el estado de Bahía (Brasil). En este estudio se analizaron muertes violentas de policías militares en activo, ocurridas entre 2012 y 2019, considerando variables sociodemográficas relacionadas con el cuerpo policial y las circunstancias de la ocurrencia. El análisis de los resultados se realizó utilizando el lenguaje computacional R, versión 4.2.2. Se registraron 110 muertes de policías militares, la mayoría negros (83,64%). Con relación al grupo de edad, los policías militares negros murieron más jóvenes, de entre 30 y 39 años (41,30%), que los policías militares blancos, de entre 40 y 49 años (61,11%). En el 50% de los casos que involucraron a policías militares negros, la motivación del crimen seguía siendo desconocida, mientras que en el 33,33% de las muertes que involucraron a policías blancos se debieron a enfrentamientos con delincuentes. Se concluye que el perfil de las muertes de policías militares en Bahía es similar al de la población general, con predominio de hombres, negros, jóvenes y solteros.

Cervical dorsal rhizotomy for upper limbs spasticity. Case report.

Spasticity is a prevalent symptom of upper motor neuron syndrome, becoming debilitating when hindering voluntary movement and motor function and causing contractures and pain. Functional neurosurgery plays a crucial role in treating severe spasticity. Despite extensive literature on SDR for lower limb spasticity, there is a scarcity of papers regarding the procedure in the cervical region to alleviate upper limb spasticity. This case report details a cervical dorsal rhizotomy (CDR) performed for upper limb spasticity, resulting in significant improvement in spasticity with sustained outcomes and low complication rates. Neuroablative procedures like CDR become an option to treat spasticity.

Genomic characterization of equine influenza A subtype H3N8 viruses by long read sequencing and functional analyses of the PB1-F2 virulence factor of A/equine/Paris/1/2018.

Equine influenza virus (EIV) remains a threat to horses, despite the availability of vaccines. Strategies to monitor the virus and prevent potential vaccine failure revolve around serological assays, RT-qPCR amplification, and sequencing the viral hemagglutinin (HA) and neuraminidase (NA) genes. These approaches overlook the contribution of other viral proteins in driving virulence. This study assesses the potential of long-read nanopore sequencing for fast and precise sequencing of circulating equine influenza viruses. Therefore, two French Florida Clade 1 strains, including the one circulating in winter 2018-2019 exhibiting more pronounced pathogenicity than usual, as well as the two currently OIE-recommended vaccine strains, were sequenced. Our results demonstrated the reliability of this sequencing method in generating accurate sequences. Sequence analysis of HA revealed a subtle antigenic drift in the French EIV strains, with specific substitutions, such as T163I in A/equine/Paris/1/2018 and the N188T mutation in post-2015 strains; both substitutions were in antigenic site B. Antigenic site E exhibited modifications in post-2018 strains, with the N63D substitution. Segment 2 sequencing also revealed that the A/equine/Paris/1/2018 strain encodes a longer variant of the PB1-F2 protein when compared to other Florida clade 1 strains (90 amino acids long versus 81 amino acids long). Further biological and biochemistry assays demonstrated that this PB1-F2 variant has enhanced abilities to abolish the mitochondrial membrane potential ΔΨm and permeabilize synthetic membranes. Altogether, our results highlight the interest in rapidly characterizing the complete genome of circulating strains with next-generation sequencing technologies to adapt vaccines and identify specific virulence markers of EIV.

From inspection to analysis: A combined approach to identifying counterfeit whiskeys using HS-GC-FID and bottle integrity.

Counterfeiting of alcoholic beverages, particularly high-value spirits such as whiskey, presents significant challenges for regulators, manufacturers, and consumers. In this study, we introduce and validate a novel application of headspace extraction (HS) followed by gas chromatography with flame ionization detection (GC-FID) for the quantitative determination of ethanol content in 42 suspected counterfeit brazilian samples of whiskeys. This method, in conjunction with visual inspection of material inconsistencies, offers a combined approach to identify potential cases of fraud. The HS-GC-FID findings revealed that only 19% of the analyzed samples had ethanol content in the limits declared on the label, emphasizing the role of ethanol content as a chemical marker for suspected beverage fraud.

Uncovering the Counterfeit: A study of whiskey authenticity through volatile organic compound fingerprinting, aroma and color sensory analysis.

This study presents a method employing gas chromatography coupled with mass spectrometry and headspace solid-phase microextraction (HS-SPME-GC-MS), supplemented with chemometrics (Soft independent modelling of class analogies - SIMCA), to analyze volatile organic compound (VOCs) profiles in suspect whiskey samples. Furthermore, a sensory analysis of aroma and color was conducted with a panel of 52 non-trained volunteers to evaluate their ability to discriminate and preference for counterfeit whiskeys. The HS-SPME-GC-MS method successfully distinguished 41 seized samples from authentic beverages. Interestingly, sensory analysis revealed that panelists could differentiate between counterfeit and authentic samples with a reference standard but did not consistently show a preference for aroma. In some cases, there was even a preference for the color of counterfeit whiskeys. The findings suggest that sensorial tests alone may not effectively distinguish counterfeit from authentic whiskeys, especially for non-expert consumers, highlighting the need for analytical instrumentation methods in fraud detection.

Ticagrelor or Clopidogrel Monotherapy vs Dual Antiplatelet Therapy After Percutaneous Coronary Intervention: A Systematic Review and Patient-Level Meta-Analysis.

Importance: Among patients undergoing percutaneous coronary intervention (PCI), it remains unclear whether the treatment efficacy of P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy (DAPT) depends on the type of P2Y12 inhibitor. Objective: To assess the risks and benefits of ticagrelor monotherapy or clopidogrel monotherapy compared with standard DAPT after PCI. Data Sources: MEDLINE, Embase, TCTMD, and the European Society of Cardiology website were searched from inception to September 10, 2023, without language restriction. Study Selection: Included studies were randomized clinical trials comparing P2Y12 inhibitor monotherapy with DAPT on adjudicated end points in patients without indication to oral anticoagulation undergoing PCI. Data Extraction and Synthesis: Patient-level data provided by each trial were synthesized into a pooled dataset and analyzed using a 1-step mixed-effects model. The study is reported following the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data. Main Outcomes and Measures: The primary objective was to determine noninferiority of ticagrelor or clopidogrel monotherapy vs DAPT on the composite of death, myocardial infarction (MI), or stroke in the per-protocol analysis with a 1.15 margin for the hazard ratio (HR). Key secondary end points were major bleeding and net adverse clinical events (NACE), including the primary end point and major bleeding. Results: Analyses included 6 randomized trials including 25 960 patients undergoing PCI, of whom 24 394 patients (12 403 patients receiving DAPT; 8292 patients receiving ticagrelor monotherapy; 3654 patients receiving clopidogrel monotherapy; 45 patients receiving prasugrel monotherapy) were retained in the per-protocol analysis. Trials of ticagrelor monotherapy were conducted in Asia, Europe, and North America; trials of clopidogrel monotherapy were all conducted in Asia. Ticagrelor was noninferior to DAPT for the primary end point (HR, 0.89; 95% CI, 0.74-1.06; P for noninferiority = .004), but clopidogrel was not noninferior (HR, 1.37; 95% CI, 1.01-1.87; P for noninferiority > .99), with this finding driven by noncardiovascular death. The risk of major bleeding was lower with both ticagrelor (HR, 0.47; 95% CI, 0.36-0.62; P < .001) and clopidogrel monotherapy (HR, 0.49; 95% CI, 0.30-0.81; P = .006; P for interaction = 0.88). NACE were lower with ticagrelor (HR, 0.74; 95% CI, 0.64-0.86, P < .001) but not with clopidogrel monotherapy (HR, 1.00; 95% CI, 0.78-1.28; P = .99; P for interaction = .04). Conclusions and Relevance: This systematic review and meta-analysis found that ticagrelor monotherapy was noninferior to DAPT for all-cause death, MI, or stroke and superior for major bleeding and NACE. Clopidogrel monotherapy was similarly associated with reduced bleeding but was not noninferior to DAPT for all-cause death, MI, or stroke, largely because of risk observed in 1 trial that exclusively included East Asian patients and a hazard that was driven by an excess of noncardiovascular death.

Thromboembolic risk of carfilzomib or bortezomib in combination with lenalidomide and dexamethasone for newly diagnosed multiple myeloma: A comparative systematic review and meta-analysis.

Thrombosis represents a frequent and potentially severe complication in individuals diagnosed with multiple myeloma (MM). These events can be driven by both the disease as well as the therapies themselves. Overall, available evidence is inconclusive about the differential thrombogenicity of carfilzomib/lenalidomide/dexamethasone (KRd) and bortezomib/lenalidomide/dexamethasone (VRd). This meta-analysis compares the risk for venous thromboembolism (VTE; including deep venous thrombosis and pulmonary embolism) and arterial thromboembolism (ATE; including myocardial infarction and ischemic stroke) with KRd versus VRd as primary therapy for newly diagnosed MM (NDMM). Out of 510 studies identified after deduplication, one randomized controlled trial and five retrospective cohort studies were included. We analyzed 2304 patients (VRd: 1380; KRd: 924) for VTE events and 2179 patients (VRd: 1316; KRd: 863) for ATE events. Lower rates of VTE were observed in the VRd group when compared with the KRd group (6.16% vs. 8.87%; odds ratio [OR], 0.53; 95% confidence interval [CI], 0.32-0.88; p = .01). Both treatment groups exhibited minimal ATE incidence, with no significant difference between them (0.91% vs. 1.16%; OR, 1.01; 95% CI, 0.24-4.20; p = .99). In view of potential biases from retrospective studies, heterogeneity of baseline population characteristics, and limited access to patient-level data (e.g., VTE risk stratification and type of thromboprophylaxis regimen used) inherent to this meta-analysis, additional research is warranted to further validate our findings and refine strategies for thrombosis prevention in MM.