PD-L1 engagement on T cells promotes self-tolerance and suppression of neighboring macrophages and effector T cells in cancer.

Programmed cell death protein 1 (PD-1) ligation delimits immunogenic responses in T cells. However, the consequences of programmed cell death 1 ligand 1 (PD-L1) ligation in T cells are uncertain. We found that T cell expression of PD-L1 in cancer was regulated by tumor antigen and sterile inflammatory cues. PD-L1+ T cells exerted tumor-promoting tolerance via three distinct mechanisms: (1) binding of PD-L1 induced STAT3-dependent 'back-signaling' in CD4+ T cells, which prevented activation, reduced TH1-polarization and directed TH17-differentiation. PD-L1 signaling also induced an anergic T-bet-IFN-γ- phenotype in CD8+ T cells and was equally suppressive compared to PD-1 signaling; (2) PD-L1+ T cells restrained effector T cells via the canonical PD-L1-PD-1 axis and were sufficient to accelerate tumorigenesis, even in the absence of endogenous PD-L1; (3) PD-L1+ T cells engaged PD-1+ macrophages, inducing an alternative M2-like program, which had crippling effects on adaptive antitumor immunity. Collectively, we demonstrate that PD-L1+ T cells have diverse tolerogenic effects on tumor immunity.

Evolutionary history influences the microbiomes of a female symbiotic reproductive organ in cephalopods.

Many female squids and cuttlefishes have a symbiotic reproductive organ called the accessory nidamental gland (ANG) that hosts a bacterial consortium involved with egg defense against pathogens and fouling organisms. While the ANG is found in multiple cephalopod families, little is known about the global microbial diversity of these ANG bacterial symbionts. We used 16S rRNA gene community analysis to characterize the ANG microbiome from different cephalopod species and assess the relationship between host and symbiont phylogenies. The ANG microbiome of 11 species of cephalopods from four families (superorder: Decapodiformes) that span seven geographic locations was characterized. Bacteria of class Alphaproteobacteria, Gammaproteobacteria, and Flavobacteriia were found in all species, yet analysis of amplicon sequence variants by multiple distance metrics revealed a significant difference between ANG microbiomes of cephalopod families (weighted/unweighted UniFrac, Bray-Curtis, P = 0.001). Despite being collected from widely disparate geographic locations, members of the family Sepiolidae (bobtail squid) shared many bacterial taxa including (~50%) Opitutae (Verrucomicrobia) and Ruegeria (Alphaproteobacteria) species. Furthermore, we tested for phylosymbiosis and found a positive correlation between host phylogenetic distance and bacterial community dissimilarity (Mantel test r = 0.7). These data suggest that closely related sepiolids select for distinct symbionts from similar bacterial taxa. Overall, the ANGs of different cephalopod species harbor distinct microbiomes and thus offer a diverse symbiont community to explore antimicrobial activity and other functional roles in host fitness.IMPORTANCEMany aquatic organisms recruit microbial symbionts from the environment that provide a variety of functions, including defense from pathogens. Some female cephalopods (squids, bobtail squids, and cuttlefish) have a reproductive organ called the accessory nidamental gland (ANG) that contains a bacterial consortium that protects eggs from pathogens. Despite the wide distribution of these cephalopods, whether they share similar microbiomes is unknown. Here, we studied the microbial diversity of the ANG in 11 species of cephalopods distributed over a broad geographic range and representing 15-120 million years of host divergence. The ANG microbiomes shared some bacterial taxa, but each cephalopod species had unique symbiotic members. Additionally, analysis of host-symbiont phylogenies suggests that the evolutionary histories of the partners have been important in shaping the ANG microbiome. This study advances our knowledge of cephalopod-bacteria relationships and provides a foundation to explore defensive symbionts in other systems.

Subconjunctival liposomal sirolimus vs. cyclosporine or tacrolimus as treatment of keratoconjunctivitis sicca in dogs: A double-blind, randomized study.

PURPOSE: To compare the safety and efficacy of a 100 microgram subconjunctival injection of liposome-encapsulated sirolimus (SCJS) to cyclosporine (CsA) or tacrolimus (CsA/T) for the treatment of keratoconjunctivitis sicca (KCS) in dogs. METHODS: Dogs with signs and symptoms of KCS were block-randomized to one of two treatment groups: Biweekly SCJS or conventional treatment (CsA/T). Schirmer tear test 1 (STT-1) scores, conjunctival hyperemia (CH) scores, corneal opacity (CO) scores, and clinical evaluation of potential side effects were recorded every 2 weeks for 14 weeks for both groups. Differences between groups were analyzed using the mixed results ANOVA and U-Mann Whitney tests (p < .05 was considered significant). RESULTS: A total of 30 eyes were included in the study, of which 20 eyes completed follow-up. There was no statistically significant interaction between the treatment group and time on STT-1 score (p = .165), and median CH and CO scores showed no statistically significant differences between groups (p = .353 and p = .393, respectively). There were no clinically significant side effects present in any subject at any time. CONCLUSION: In this trial, a 1 mg/mL (100 micrograms) SCJS every 2 weeks showed similar safety and efficacy profiles as daily CsA/T in dogs with KS after 14 weeks of treatment. Larger studies should be performed to further assess SCJS as an alternative treatment for KCS.

Machine Learning Applications in Optical Fiber Sensing: A Research Agenda.

The constant monitoring and control of various health, infrastructure, and natural factors have led to the design and development of technological devices in a wide range of fields. This has resulted in the creation of different types of sensors that can be used to monitor and control different environments, such as fire, water, temperature, and movement, among others. These sensors detect anomalies in the input data to the system, allowing alerts to be generated for early risk detection. The advancement of artificial intelligence has led to improved sensor systems and networks, resulting in devices with better performance and more precise results by incorporating various features. The aim of this work is to conduct a bibliometric analysis using the PRISMA 2020 set to identify research trends in the development of machine learning applications in fiber optic sensors. This methodology facilitates the analysis of a dataset comprised of documents obtained from Scopus and Web of Science databases. It enables the evaluation of both the quantity and quality of publications in the study area based on specific criteria, such as trends, key concepts, and advances in concepts over time. The study found that deep learning techniques and fiber Bragg gratings have been extensively researched in infrastructure, with a focus on using fiber optic sensors for structural health monitoring in future research. One of the main limitations is the lack of research on the use of novel materials, such as graphite, for designing fiber optic sensors. One of the main limitations is the lack of research on the use of novel materials, such as graphite, for designing fiber optic sensors. This presents an opportunity for future studies.

Dental patients as partners in promoting quality and safety: a qualitative exploratory study.

OBJECTIVE: Active patient involvement in promoting quality and safety is a priority for healthcare. We investigated how dental patients perceive their role as partners in promoting quality and safety across various dental care settings. METHODS: Focus group sessions were conducted at three dental practice settings: an academic dental center, a community dental clinic, and a large group private practice, from October 2018-July 2019. Patients were recruited through flyers or word-of-mouth invitations. Each session lasted 2.5 h and patients completed a demographic and informational survey at the beginning. Audio recordings were transcribed, and a hybrid thematic analysis was performed by two independent reviewers using Dedoose. RESULTS: Forty-seven participants took part in eight focus group sessions; 70.2% were females and 38.3% were aged 45-64 years. Results were organized into three major themes: patients' overall perception of dental quality and safety; patients' reaction to an adverse dental event; and patients' role in promoting quality and safety. Dental patients were willing to participate in promoting quality and safety by careful provider selection, shared decision-making, self-advocacy, and providing post-treatment provider evaluations. Their reactions towards adverse dental events varied based on the type of dental practice setting. Some factors that influenced a patient's overall perception of dental quality and safety included provider credentials, communication skills, cleanliness, and durability of dental treatment. CONCLUSION: The type of dental practice setting affected patients' desire to work as partners in promoting dental quality and safety. Although patients acknowledged having an important role to play in their care, their willingness to participate depended on their relationship with their provider and their perception of provider receptivity to patient feedback.

Insights of tricuspid regurgitation mechanisms in patients with right ventricular apical pacing by three-dimensional echocardiography.

OBJECTIVE: Device lead-induced tricuspid regurgitation (LITR) mechanisms are well-defined by 3D transthoracic echocardiography (3D-TTE). There is a lack of data on the Latin-American population. The objective of this study was to describe the prevalence of several mechanisms and insights in patients with permanent right ventricular (RV) implanted devices by 3D-TTE examination. METHODS: We performed a cross-sectional analysis of 101 patients with permanent cardiac devices such as pacemakers or defibrillators. 3D-TTE was obtained on all patients in RV-focused apical views to perform a complete tricuspid valve (TV) evaluation: leaflets, subvalvular apparatus, precise lead location, and functional assessment to evaluate possible mechanisms of tricuspid regurgitation (TR). RESULTS: In a total of 101 patients, the leads did not interfere with TV function in 53 p. (59%), while LITR was observed in 38 (41%) patients. Adherent, impinging, entangled, and mixed lead-induced mechanisms were observed. Time in years since device implantation was significantly higher in patients with LITR. CONCLUSIONS: LITR was present in a high proportion of our population. LITR is the result of damage to the TV as well as its subvalvular apparatus due to the fibrotic and inflammatory response over time when leads are situated in unfavorable locations.

Disseminated idiopathic lipid keratopathy in a normolipemic cat.

OBJECTIVE: To report a case of idiopathic lipid keratopathy in a normolipemic cat. ANIMAL STUDIED: A 10-year-old neutered female European domestic cat. RESULTS: A cat was evaluated for bilateral white corneal deposits. Slit-lamp examination revealed multiple, well-defined, round, stromal, cream-colored deposits of different sizes associated with generalized superficial corneal vascularization. Blood lipids were normal, and no history of travel to tropical locations or ocular trauma was present. Topical betamethasone/gentamicin 0.1% suspension q 12 hours did not result in any improvement of clinical appearance after one week. Tomography following the initial therapy revealed dense, hyperreflective deposits with posterior shadowing in the anterior and mid stroma of both corneas. A four-week course of itraconazole 0.01% ophthalmic cream was prescribed q 12 hours with no improvement. Four months after the initial examination, a diagnostic superficial keratectomy and amniotic membrane implantation were performed. Histopathological analysis showed membrane bound vacuoles with infiltration of foamy macrophages suggesting a diagnosis of primary lipidosis. The post-surgical period was unremarkable, and ten days later, the patient was re-examined. Opacification from a corneal leukoma was observed in the excision site with mild fibrotic tissue. Two months post-keratectomy, no further changes were detected in the cornea, and the patient was managed only with topical lubricant. CONCLUSIONS: To our knowledge, this is the first report of idiopathic corneal lipidosis in a cat and may be considered as a differential diagnosis of corneal disease in felines.

γδ T Cells Promote Steatohepatitis by Orchestrating Innate and Adaptive Immune Programming.

BACKGROUND AND AIMS: The recruitment and activation of inflammatory cells in the liver delineates the transition from hepatic steatosis to steatohepatitis (SH). APPROACH AND RESULTS: We found that in SH, γδT cells are recruited to the liver by C-C chemokine receptor (CCR) 2, CCR5, and nucleotide-binding oligomerization domain-containing protein 2 signaling and are skewed toward an interleukin (IL)-17A+ phenotype in an inducible costimulator (ICOS)/ICOS ligand-dependent manner. γδT cells exhibit a distinct Vγ4+ , PD1+ , Ly6C+ CD44+ phenotype in SH. Moreover, γδT cells up-regulate both CD1d, which is necessary for lipid-based antigens presentation, and the free fatty acid receptor, CD36. γδT cells are stimulated to express IL-17A by palmitic acid and CD1d ligation. Deletion, depletion, and targeted interruption of γδT cell recruitment protects against diet-induced SH and accelerates disease resolution. CONCLUSIONS: We demonstrate that hepatic γδT cells exacerbate SH, independent of IL-17 expression, by mitigating conventional CD4+ T-cell expansion and modulating their inflammatory program by CD1d-dependent vascular endothelial growth factor expression.

Intravitreal bromfenac liposomal suspension (100 µg / 0.1 ml). A safety study in rabbit eyes.

INTRODUCTION: There is a need to find alternative treatments for MEe. Bromfenac has shown promise in inhibiting the COX-2 enzymatic pathway that partially causes the inflammatory cascade which contributes to the precipitation of ME. However, like other NSAID's, its intraocular half-life is limited. We hypothesize that a delayed-release liposome formulation containing bromfenac might provide a similar anti-inflammatory effect as long-lasting steroid release systems without the well-known steroidal side-effects. We introduced a novel formulation with these characteristics into the vitreous cavity of rabbit eyes in order to evaluate its safety profile. MATERIAL AND METHODS: 10 left eyes of rabbits were injected with the liposome-encapsulated bromfenac suspension (100 µg/0.1 ml). Basal ERG's were recorded. Total follow-up time was 3 months, at which point ERG's were repeated and eyes were enucleated for histopathological study. Total amplitude and implicit times were recorded. A difference of 25% in either recording was considered significant. Significance was assessed using the paired-t test and Wilcoxon matched-pairs signed-rank test. A p-value of <0.05 was considered significant. RESULTS: No significant changes were recorded in ERG measurements after 3 months when compared to basal measurements. Histopathological analysis of retinal specimens found no traces of liposome-induced toxicity. CONCLUSION: The liposome-encapsulated bromfenac suspension (100 µg/0.1 ml) is not toxic and has been proven safe to use in an animal model. Therefore, this formulation shows promise as a possible future alternative treatment for ME and should be further studied to show its biological effect and efficacy.

Infestation of the Parasitic Isopod Mothocya parvostis on Juveniles of the Black Sea Bream Acanthopagrus schlegelii as an Optional Intermediate Host in Hiroshima Bay.

In Hiroshima Bay, parasitic isopods of the genus Mothocya infest the black sea bream Acanthopagrus schlegelii (Bleeker, 1854) and the Japanese halfbeak Hyporhamphus sajori (Temminck and Schlegel, 1846), two fish species that are abundant and commercially important in the Seto Inland Sea of Japan. Immature and mature Mothocya individuals can infect both juveniles and adults of H. sajori, while immature Mothocya are known to parasitize juveniles of A. schlegelii; i.e., no Mothocya parasites are found in adult A. schlegelii. The identification of the immature Mothocya parasitizing juveniles of A. schlegelii remains uncertain, because Mothocya species are morphologically identifiable only based on adult females. Also, the biological/ecological relationship between the hosts and parasites has not been studied. Here, we identified the parasites on A. schlegelii as Mothocya parvostis Bruce, 1986 by molecular sequence analyses along with other parasites obtained from H. sajori, the latter being morphologically confirmed by comparison with paratype materials of M. parvostis as well as the similar congener Mothocya sajori Bruce, 1986. The growth rates of the infected A. schlegelii juveniles from June to September in the years 2013-2015 and 2018 were significantly lower than those of the uninfected ones, suggesting a negative effect of the infection on the hosts. Our data on the prevalence and duration of the infection, as well as the body size gain of the hosts and parasites, corroborate a hypothesis that M. parvostis would utilize A. schlegelii as an optional intermediate host before it reaches the final host, H. sajori.

Alternative Calibration of Cup Anemometers: A Way to Reduce the Uncertainty of Wind Power Density Estimation.

This study presents a procedure to reduce the uncertainty of wind power density estimations, which is useful to improve the energy production predictions of wind farms. Power density is usually determined from the wind speed measured by a cup anemometer and the air density value (conventional procedure). An alternative procedure based on wind speed and dynamic pressure estimations provided by a cup anemometer is proposed. The dynamic pressure is obtained by means of a calibration curve that relates the anemometer rotation frequency and the dynamic pressure measured by a Pitot tube. The quadratic regression, used to define the calibration curve, and its uncertainty are both detailed. A comparison between the alternative procedure and the conventional one points out the advantage of the proposed alternative since results show a high reduction of the indirect measurement uncertainty of wind power density.

Use of a stainless steel locking calcaneal plate for quadrilateral plate buttress in the treatment of acetabular fractures.

Operative fixation of acetabular fractures involving the quadrilateral surface presents a challenging clinical scenario. Classically, quadrilateral plate buttress was achieved via the use of a "seven" plate. More recently, the use of an anatomic, pre-contoured design has been gaining popularity due to its pre-contoured shape and larger footprint, allowing for a wider quadrilateral plate buttress. The current study presents using a stainless steel locking calcaneal plate to obtain similar surface area coverage as the modern pre-contoured quadrilateral plate, but at a lower cost.Level of evidence IV.

Comparison of 10% vs. 30% Velocity Loss during Squat Training with Low Loads on Strength and Sport-Specific Performance in Young Soccer Players.

The aim of this study was to compare the effects of two velocity-based resistance training (RT) programs using moderate loads (45-60% 1RM) but different magnitudes of velocity loss (VL) limits (10% vs. 30%) on the changes in physical performance in young soccer players. Twenty young soccer players were randomly allocated into two groups: VL10% (n = 10) and VL30% (n = 10). All participants were assessed before and after the 8-week RT program (twice a week) involving the following tests: 20 m running sprint (T20), countermovement jump (CMJ), kicking a ball (KB), and progressive loading test in the full squat (SQ) exercise. The RT program was conducted using only the SQ exercise and movement velocity was monitored in all repetitions. Significant 'time × group' interaction (p < 0.05) was observed for sprint performance, KB and 1RM in the SQ exercise in favor of VL10%. No significant changes between groups at post-test were observed. The VL10% resulted in significant (p < 0.05-0.001) intra-group changes in all variables analyzed, except for KB, whereas VL30% only showed significant (p < 0.05) performance increments in a sprint test and 1RM in the SQ exercise. The percentage of change and the intra-group's effect size were of greater magnitude for VL10% in all variables analyzed compared to VL30%. In conclusion, our results suggest that, for non-trained young soccer players, squat training with low to moderate relative loads and 10%VL is sufficient to elicit significant increases in muscle strength and sport-specific actions compared to 30%VL in the set.

LEADERSHIP DEVELOPMENT TRAINING FOR BRAZILIAN ORTHOPEDIC SURGEONS.

Objective: To report on the experience and impressions of the Brazilian orthopedic trauma surgeons attending the Leadership Development Program (LDP) hosted by the Sociedade Brasileira do Trauma Ortopédico (SBTO) in Sao Paulo, Brazil on November 4, 2022. Methods: Forty-eight orthopedic trauma surgeons from five different regions throughout Brazil were provided a link to complete The Big Five Test, a validated online personality assessment. The questionnaire was available in Portuguese and was intended to provide a background on individual personality traits and their influence on interpersonal interactions. The LDP integrated content from literature reviews specific to Latin America, established leadership programs from leading business schools, and various subject matter experts. Prior to the start of the LDP, participants received a pre-course survey evaluating demographic information, a needs assessment, and the prioritization of leadership topics utilizing a 5-point Likert-scale. Attendees participated in the one-day, interactive LDP focusing on the fundamental principles of leadership development, communication, personal development, emotional intelligence and negotiation. Following the LDP, a post-course evaluation was administered to determine the participants' overall experience, and suggestions for LDP improvement. Results: Forty-one of the forty-eight course participants completed the pre-course evaluation, whereas forty-six of the forty-eight participants completed the post-course evaluations. Overwhelmingly, the lack of opportunity was most prevalently reported as the main obstacle to attending a leadership course, as cited by 56% of respondents. Conclusion: Expanding the accessibility, diversity, and customizability of leadership programs can facilitate the development of personal tools needed to move healthcare forward. Critical topics include emotional intelligence and other differentiating leadership qualities that distinguish true transformational and servant leaders. Advancing leadership skills can stimulate networking, expose learners to experiential learning styles, inspire others to create positive change, and engender creative solutions for systematic improvements and health outcomes. Level of Evidence III; Individual Case-Control Studies.

Objetivo: Relatar a experiência e as impressões de cirurgiões de trauma ortopédico brasileiros participantes do Programa de Desenvolvimento de Liderança (PDL), organizado pela Sociedade Brasileira do Trauma Ortopédico (SBTO), em São Paulo, Brasil, em 4 de novembro de 2022. Métodos: Quarenta e oito cirurgiões de trauma ortopédico de cinco regiões diferentes do Brasil receberam um link para preencher o The Big Five Test, uma avaliação de personalidade on-line validada. O questionário estava disponível em português e pretendia fornecer informações básicas sobre traços de personalidade individuais e sua influência nas interações interpessoais. O PDL integrou conteúdo de análises de literatura específicas da América Latina, e programas de liderança estabelecidos pelas principais escolas de negócios e por vários especialistas no assunto. Antes do início do PDL, os participantes receberam uma pesquisa pré-curso solicitando informações demográficas, uma avaliação de necessidades e a priorização de tópicos de liderança utilizando uma escala Likert de 5 pontos. Os participantes participaram do PDL interativo de um dia com foco nos princípios fundamentais de desenvolvimento de liderança, comunicação, desenvolvimento pessoal, inteligência emocional e negociação. Após o PDL, foi realizada uma avaliação pós-curso para determinar a experiência geral dos participantes e sugestões para melhoria do PDL. Resultados: Quarenta e um dos quarenta e oito participantes do curso concluíram a avaliação pré-curso, enquanto quarenta e seis dos quarenta e oito participantes concluíram a avaliação pós-curso. A falta de oportunidade foi relatada com maior prevalência como o principal obstáculo para frequentar um curso de liderança, conforme citado por 56% dos entrevistados. Conclusão: Expandir a acessibilidade, a diversidade e a personalização dos programas de liderança podem facilitar o desenvolvimento de ferramentas pessoais necessárias para fazer avançar os cuidados de saúde. Os tópicos críticos incluem inteligência emocional e outras qualidades de liderança diferenciadas, que distinguem verdadeiros líderes transformacionais e servidores O avanço das competências de liderança pode estimular o networking, expor os alunos a estilos de aprendizagem experiencial, inspirar outros a criar mudanças positivas e gerar soluções criativas para melhorias sistemáticas dos resultados na saúde. Nível de Evidência III; Estudos de caso-controle individuais.

Newcastle disease virus vector-based SARS-CoV-2 vaccine candidate AVX/COVID-12 activates T cells and is recognized by antibodies from COVID-19 patients and vaccinated individuals.

Introduction: Several effective vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and implemented in the population. However, the current production capacity falls short of meeting global demand. Therefore, it is crucial to further develop novel vaccine platforms that can bridge the distribution gap. AVX/COVID-12 is a vector-based vaccine that utilizes the Newcastle Disease virus (NDV) to present the SARS-CoV-2 spike protein to the immune system. Methods: This study aims to analyze the antigenicity of the vaccine candidate by examining antibody binding and T-cell activation in individuals infected with SARS-CoV-2 or variants of concern (VOCs), as well as in healthy volunteers who received coronavirus disease 2019 (COVID-19) vaccinations. Results: Our findings indicate that the vaccine effectively binds antibodies and activates T-cells in individuals who received 2 or 3 doses of BNT162b2 or AZ/ChAdOx-1-S vaccines. Furthermore, the stimulation of T-cells from patients and vaccine recipients with AVX/COVID-12 resulted in their proliferation and secretion of interferon-gamma (IFN-γ) in both CD4+ and CD8+ T-cells. Discussion: The AVX/COVID-12 vectored vaccine candidate demonstrates the ability to stimulate robust cellular responses and is recognized by antibodies primed by the spike protein present in SARS-CoV-2 viruses that infected patients, as well as in the mRNA BNT162b2 and AZ/ChAdOx-1-S vaccines. These results support the inclusion of the AVX/COVID-12 vaccine as a booster in vaccination programs aimed at addressing COVID-19 caused by SARS-CoV-2 and its VOCs.

Reduced exposure to calcineurin inhibitors early after liver transplantation prevents recurrence of hepatocellular carcinoma.

BACKGROUND & AIMS: Recurrence of hepatocellular carcinoma (HCC) is a major complication after liver transplantation (LT). The initial immunosuppression protocol may influence HCC recurrence, but the optimal regimen is still unknown. METHODS: 219 HCC consecutive patients under Milan criteria, who received an LT at 2 European centres between 2000 and 2010, were included. Median follow-up was 51 months (IQR 26-93). Demographic characteristics, HCC features, and immunosuppression protocol within the first month after LT were evaluated against HCC recurrence by using Cox regression. RESULTS: In the explanted liver, 110 patients (50%) had multinodular HCC, and largest nodule diameter was 3±2.1cm. Macrovascular invasion was incidentally detected in 11 patients (5%), and microvascular invasion was present in 41 patients (18.7%). HCC recurrence rates were 13.3% at 3 years and 17.6% at 5 years. HCC recurrence was not influenced by the use/non-use of steroids and antimetabolites (p=0.69 and p=0.70 respectively), and was similar with tacrolimus or cyclosporine (p=0.25). Higher exposure to calcineurin inhibitors within the first month after LT (mean tacrolimus trough concentrations >10ng/ml or cyclosporine trough concentrations >300ng/ml), but not thereafter, was associated with increased risk of HCC recurrence (27.7% vs. 14.7% at 5 years; p=0.007). The independent predictors of HCC recurrence by multivariate analysis were: high exposure to calcineurin inhibitors defined as above (RR=2.82; p=0.005), diameter of the largest nodule (RR=1.31; p<0.001), microvascular invasion (RR=2.98; p=0.003) and macrovascular invasion (RR=4.57; p=0.003). CONCLUSIONS: Immunosuppression protocols with early CNI minimization should be preferred in LT patients with HCC in order to minimize tumour recurrence.

Antegrade posterior column screw fixation for acetabular fractures: It's time to standardize the surgical technique.

Antegrade fixation of posterior column fractures of the acetabulum is challenging due to the narrow corridor and risk of screw misplacement. Although both antegrade and retrograde lag screws have been previously described for posterior column fracture fixation, the literature lacks a standardized technique for correct and safe screw placement, especially in an antegrade fashion. This technical note aims to optimize intraoperative images during posterior screw insertion using the antegrade technique, according to predetermined landmarks to save surgical time, decrease radiation exposition, and prevent surgical complications.

Atlantic Oceanic Squids in the "Grey Speciation Zone".

Cryptic species complexes represent an important challenge for the adequate characterization of Earth's biodiversity. Oceanic organisms tend to have greater unrecognized cryptic biodiversity since the marine realm was often considered to lack hard barriers to genetic exchange. Here, we tested the effect of several Atlantic and Mediterranean oceanic barriers on 16 morphospecies of oceanic squids of the orders Oegopsida and Bathyteuthida using three mitochondrial and one nuclear molecular marker and five species delimitation methods. Number of species recognized within each morphospecies differed among different markers and analyses, but we found strong evidence of cryptic biodiversity in at least four of the studied species (Chtenopteryx sicula, Chtenopteryx canariensis, Ancistrocheirus lesueurii, and Galiteuthis armata). There were highly geographically structured units within Helicocranchia navossae that could either represent recently diverged species or population structure. Although the species studied here can be considered relatively passive with respect to oceanic currents, cryptic speciation patterns showed few signs of being related to oceanic currents. We hypothesize that the bathymetry of the egg masses and duration of the paralarval stage might influence the geographic distribution of oceanic squids. Because the results of different markers and different species delimitation methods are inconsistent and because molecular data encompassing broad geographic sampling areas for oceanic squids are scarce and finding morphological diagnostic characters for early life stages is difficult, it is challenging to assess the species boundaries for many of these species. Thus, we consider many to be in the "grey speciation zone." As many oceanic squids have cosmopolitan distributions, new studies combining genomic and morphological information from specimens collected worldwide are needed to correctly assess the actual oceanic squid biodiversity.

Emergence of novel genomic regulatory regions associated with light-organ development in the bobtail squid.

Light organs (LO) with symbiotic bioluminescent bacteria are hallmarks of many bobtail squid species. These organs possess structural and functional features to modulate light, analogous to those found in coleoid eyes. Previous studies identified four transcription factors and modulators (SIX, EYA, PAX6, DAC) associated with both eyes and light organ development, suggesting co-option of a highly conserved gene regulatory network. Using available topological, open chromatin, and transcriptomic data, we explore the regulatory landscape around the four transcription factors as well as genes associated with LO and shared LO/eye expression. This analysis revealed several closely associated and putatively co-regulated genes. Comparative genomic analyses identified distinct evolutionary origins of these putative regulatory associations, with the DAC locus showing a unique topological and evolutionarily recent organization. We discuss different scenarios of modifications to genome topology and how these changes may have contributed to the evolutionary emergence of the light organ.

Magnetic resonance imaging findings of spontaneous pyomyoma in a premenopausal woman managed with myomectomy: A case report.

BACKGROUND: Acute fibroid complications are rare. However, failure to recognize and treat acute complications expeditiously when they occur can lead to catastrophic, even deadly, complications. Pyomyoma is a rare but potentially fatal condition resulting from infarction and infection of a fibroid through bacterial seeding and direct, hematogenous, or lymphatic dissemination. Even though the diagnosis is established through clinical and laboratory findings, imaging is an important complementary method to support the suspected diagnosis. CASE SUMMARY: Herein, we report a case of a pyomyoma in a nulliparous woman previously diagnosed with uterine leiomyomatosis according to ultrasound findings. The patient had previously attended the emergency room due to hypogastric pain unresponsive to analgesics. After a week of persistent pain, she developed sepsis without any identifiable foci. Magnetic resonance imaging revealed findings compatible with uterine myomatosis with red degeneration, and a possible diagnosis of a pyomyoma was made according to the imaging findings along with the patient's clinical features. We decided to perform myomectomy (which is an infrequently performed surgical treatment due to the procedure's intrinsic implications) due to the patient's desire to preserve fertility. Histopathologic results revealed a uterine leiomyoma with coagulative and liquefactive necrosis, while the tissue culture showed gram-negative cocci bacteria, which were successfully treated using antibiotic therapy. The patient's health status improved after several days. CONCLUSION: The main diagnostic tools to evaluate pyomyomas are the clinical and laboratory findings as well as tissue cultures. Nonetheless, magnetic resonance imaging can help to corroborate these findings as well as to better characterize myomas with its different complications.