ANTI-INFLAMMATORY EFFECT OF Anadenanthera colubrina var. cebil (Griseb.) Altschul IN EXPERIMENTAL ELASTASE-INDUCED PULMONARY EMPHYSEMA IN RATS.

ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plants have shown promise in the search for new treatments of pulmonary emphysema. Anadenanthera colubrina, a species native to the Caatinga biome in northeastern Brazil, is widely recognized and traditionally employed in the treatment of pulmonary diseases. Many studies corroborate popular knowledge about the medicinal applications of A. colubrina, which has demonstrated a remarkable variety of pharmacological properties, however, its anti-inflammatory and antioxidant properties are highlighted. AIM OF THE STUDY: The objective of this study was to investigate the anti-inflammatory potential of the crude hydroethanolic extract of A. colubrina var. cebil (Griseb.) Altschul on pulmonary emphysema in rats as well as to determine its potential genotoxic and cytotoxic effects using the micronucleus assay. MATERIALS AND METHODS: The stem bark of the plant was collected in Pimenteiras-PI and sample was extracted by maceration using 70% ethanol. A portion of the extract underwent phytochemical analyses using TLC and HPLC. In this study, 8-week-old, male Wistar rats weighing approximately ± 200 g was utilized following approval by local ethics committee for animal experimentation (No. 718/2022). Pulmonary emphysema was induced through orotracheal instillation of elastase, and treatment with A. colubrina extract or dexamethasone (positive control) concomitantly during induction. Twenty-eight days after the initiation of the protocol, plasma was used for cytokine measurement. Bronchoalveolar lavage (BAL) was used for leukocyte count. After euthanasia, lung samples were processed for histological analysis and quantification of oxidative stress markers. The micronucleus test was performed by evaluating the number of polychromatic erythrocytes (PCE) with micronuclei (MNPCE) to verify potential genotoxic effects of A. colubrina. A differential count of PCE and normochromatic erythrocytes (NCE) was performed to verify the potential cytotoxicity of the extract. Parametric data were subjected to normality analysis and subsequently to analysis of variance and Tukey or Dunnett post-test, non-parametric data were treated using the Kruskal-Wallis test with Dunn's post-test for unpaired samples. P value <0.05 were considered significant. RESULTS: The A. colubrina extract did not show a significant increase in the number of MNPCE (p>0.05), demonstrating low genotoxicity. No changes were observed in the PCE/NCE ratio of treated animals, compared with the vehicle, suggesting low cytotoxic potential of the extract. A significant reduction (p<0.05) in neutrophilic inflammation was observed in the lungs of rats treated with the extract, evidenced by presence of these cells in both the tissue and BAL. The extract also demonstrated pulmonary antioxidant activity, with a significant decrease (p<0.05) in myeloperoxidase, malondialdehyde, and nitrite levels. TNFα, IL-1ß, and IL-6 levels, as well as alveolar damage, were significantly reduced in animals treated with A. colubrina extract. Phytochemical analyses identified the presence of phenolic compounds and hydrolysable tannins in the A. colubrina extract. CONCLUSIONS: The findings of this study highlights the safety of the hydroethanolic extract of Anadenanthera colubrina, and demonstrates its potential as a therapeutic approach in the treatment of emphysema. The observed properties of this medicinal plant provide an optimistic outlook in the development of therapies for the treatment of pulmonary emphysema.

Differential tissue immune stimulation through immersion in bacterial and viral agonists in the Antarctic Notothenia rossii.

The genome evolution of Antarctic notothenioids has been modulated by their extreme environment over millennia and more recently by human-caused constraints such as overfishing and climate change. Here we investigated the characteristics of the immune system in Notothenia rossii and how it responds to 8 h immersion in viral (Poly I:C, polyinosinic: polycytidylic acid) and bacterial (LPS, lipopolysaccharide) proxies. Blood plasma antiprotease activity and haematocrit were reduced in Poly I:C-treated fish only, while plasma protein, lysozyme activity and cortisol were unchanged with both treatments. The skin and duodenum transcriptomes responded strongly to the treatments, unlike the liver and spleen which had a mild response. Furthermore, the skin transcriptome responded most to the bacterial proxy (cell adhesion, metabolism and immune response processes) and the duodenum (metabolism, response to stress, regulation of intracellular signal transduction, and immune system responses) to the viral proxy. The differential tissue response to the two proxy challenges is indicative of immune specialisation of the duodenum and the skin towards pathogens. NOD-like and C-type lectin receptors may be central in recognising LPS and Poly I:C. Other antimicrobial compounds such as iron and selenium-related genes are essential defence mechanisms to protect the host from sepsis. In conclusion, our study revealed a specific response of two immune barrier tissue, the skin and duodenum, in Notothenia rossii when exposed to pathogen proxies by immersion, and this may represent an adaptation to pathogen infective strategies.

Revisiting the evolution of Family B1 GPCRs and ligands: Insights from mollusca.

Family B1 G protein-coupled receptors (GPCRs) are one of the most well studied neuropeptide receptor families since they play a central role in many biological processes including endocrine, gastrointestinal, cardiovascular and reproduction in animals. The genes for these receptors emerged from a common ancestral gene in bilaterian genomes and evolved via gene/genome duplications and deletions in vertebrate and invertebrate genomes. Their existence and function have mostly been characterized in vertebrates and few studies exist in invertebrate species. Recently, an increased interest in molluscs, means a series of genomes have become available, and since they are less modified than insect and nematode genomes, they are ideal to explore the origin and evolution of neuropeptide gene families. This review provides an overview of Family B1 GPCRs and their peptide ligands and incorporates new data obtained from Mollusca genomes and taking a comparative approach challenges existing models on their origin and evolution.

Prevalence of chronic cough, its risk factors and population attributable risk in the Burden of Obstructive Lung Disease (BOLD) study: a multinational cross-sectional study.

Background: Chronic cough is a common respiratory symptom with an impact on daily activities and quality of life. Global prevalence data are scarce and derive mainly from European and Asian countries and studies with outcomes other than chronic cough. In this study, we aimed to estimate the prevalence of chronic cough across a large number of study sites as well as to identify its main risk factors using a standardised protocol and definition. Methods: We analysed cross-sectional data from 33,983 adults (≥40 years), recruited between Jan 2, 2003 and Dec 26, 2016, in 41 sites (34 countries) from the Burden of Obstructive Lung Disease (BOLD) study. We estimated the prevalence of chronic cough for each site accounting for sampling design. To identify risk factors, we conducted multivariable logistic regression analysis within each site and then pooled estimates using random-effects meta-analysis. We also calculated the population attributable risk (PAR) associated with each of the identifed risk factors. Findings: The prevalence of chronic cough varied from 3% in India (rural Pune) to 24% in the United States of America (Lexington,KY). Chronic cough was more common among females, both current and passive smokers, those working in a dusty job, those with a history of tuberculosis, those who were obese, those with a low level of education and those with hypertension or airflow limitation. The most influential risk factors were current smoking and working in a dusty job. Interpretation: Our findings suggested that the prevalence of chronic cough varies widely across sites in different world regions. Cigarette smoking and exposure to dust in the workplace are its major risk factors. Funding: Wellcome Trust.

Core genes of biomineralization and cis-regulatory long non-coding RNA regulate shell growth in bivalves.

INTRODUCTION: Bivalve molluscs are abundant in marine and freshwater systems and contribute essential ecosystem services. They are characterized by an exuberant diversity of biomineralized shells and typically have two symmetric valves (a.k.a shells), but oysters (Ostreidae), some clams (Anomiidae and Chamidae) and scallops (Pectinida) have two asymmetrical valves. Predicting and modelling the likely consequences of ocean acidification on bivalve survival, biodiversity and aquaculture makes understanding shell biomineralization and its regulation a priority. OBJECTIVES: This study aimed to a) exploit the atypical asymmetric shell growth of some bivalves and through comparative analysis of the genome and transcriptome pinpoint candidate biomineralization-related genes and regulatory long non-coding RNAs (LncRNAs) and b) demonstrate their roles in regulating shell biomineralization/growth. METHODS: Meta-analysis of genomes, de novo generated mantle transcriptomes or transcriptomes and proteomes from public databases for six asymmetric to symmetric bivalve species was used to identify biomineralization-related genes. Bioinformatics filtering uncovered genes and regulatory modules characteristic of bivalves with asymmetric shells and identified candidate biomineralization-related genes and lncRNAs with a biased expression in asymmetric valves. A shell regrowth model in oyster and gene silencing experiments, were used to characterize candidate gene function. RESULTS: Shell matrix genes with asymmetric expression in the mantle of the two valves were identified and unique cis-regulatory lncRNA modules characterized in Ostreidae. LncRNAs that regulate the expression of the tissue inhibitor of metalloproteinases gene family (TIMPDR) and of the shell matrix protein domain family (SMPDR) were identified. In vitro and in vivo silencing experiments revealed the candidate genes and lncRNA were associated with divergent shell growth rates and modified the microstructure of calcium carbonate (CaCO3) crystals. CONCLUSION: LncRNAs are putative regulatory factors of the bivalve biomineralization toolbox. In the Ostreidae family of bivalves biomineralization-related genes are cis-regulated by lncRNA and modify the planar growth rate and spatial orientation of crystals in the shell.

Bidimensional ensemble entropy: Concepts and application to emphysema lung computerized tomography scans.

BACKGROUND AND OBJECTIVE: Bidimensional entropy algorithms provide meaningful quantitative information on image textures. These algorithms have the advantage of relying on well-known one-dimensional entropy measures dedicated to the analysis of time series. However, uni- and bidimensional algorithms require the adjustment of some parameters that influence the obtained results or even findings. To address this, ensemble entropy techniques have recently emerged as a solution for signal analysis, offering greater stability and reduced bias in data patterns during entropy estimation. However, such algorithms have not yet been extended to their two-dimensional forms. METHODS: We therefore propose six bidimensional algorithms, namely ensemble sample entropy, ensemble permutation entropy, ensemble dispersion entropy, ensemble distribution entropy, and two versions of ensemble fuzzy entropy based on different models or parameters initialization of an entropy algorithm. These new measures are first tested on synthetic images and further applied to a biomedical dataset. RESULTS: The results suggest that ensemble techniques are able to detect different levels of image dynamics and their degrees of randomness. These methods lead to more stable entropy values (lower coefficients of variations) for the synthetic data. The results also show that these new measures can obtain up to 92.7% accuracy and 88.4% sensitivity when classifying patients with pulmonary emphysema through a k-nearest neighbors algorithm. CONCLUSIONS: This is a further step towards the potential clinical deployment of bidimensional ensemble approaches to detect different levels of image dynamics and their successful performance on emphysema lung computerized tomography scans. These bidimensional ensemble entropy algorithms have potential to be used in various imaging applications thanks to their ability to distinguish more stable and less biased image patterns compared to their original counterparts.

Retiform purpura secondary to Rickettsia conorii / Púrpura retiforme secundaria a Rickettsia conorii

Retiform purpura consists of branching purpuric lesions caused by a complete blockage of blood flow in the dermal/subcutaneous vasculature. It is an acute life-threatening disorder characterized by intravascular thrombosis and hemorrhagic infarction of the skin complicated with disseminated intravascular coagulation. It is commonly seen in acute infections following meningococcal and streptococcal infections. Few cases have been described of retiform purpura following rickettsial infections in the literature and rarely with this magnitude. The purpose of this report is to highlight the possibility of this situation in critically ill patients. We report a case of a 62-year-old woman admitted in the intensive care unit with septic shock from Rickettsia conorii. She developed quickly an intense retiform purpura requiring several surgical interventions to control the necrosis. The dermatologic situation was only completely controlled with treatment of underlying situation. This is a severe complication of a critical infectious disease. (AU)

La púrpura retiforme consiste en lesiones purpúricas ramificadas causadas por un bloqueo completo del flujo sanguíneo en la vasculatura dérmica/subcutánea. Es un trastorno agudo potencialmente mortal caracterizado por trombosis intravascular e infarto hemorrágico de la piel complicado con coagulación intravascular diseminada. Se ve comúnmente en infecciones agudas después de infecciones meningocócicas y estreptocócicas. Se han descrito pocos casos de púrpura retiforme tras infecciones por rickettsiosis en la literatura y rara vez de esta magnitud. El propósito de este informe es resaltar la posibilidad de esta situación en pacientes críticamente enfermos. Presentamos el caso de una mujer de 62 años ingresada en la unidad de cuidados intensivos con shock séptico por Rickettsia conorii. Rápidamente desarrolló una intensa púrpura retiforme que requirió varias intervenciones quirúrgicas para controlar la necrosis. La situación dermatológica solo se controló por completo con el tratamiento de la situación subyacente. Esta es una complicación grave de una enfermedad infecciosa crítica. (AU)

Significant differences in black and brown carbon concentrations at urban and suburban sites.

Light-absorbing carbonaceous particles (LAC) may cause and/or exacerbate non-communicable diseases, interfere with the Earth's radiative balance, darken urban buildings and impair vistas. In this study, we explored the temporal behaviour of LAC concentrations measured at wavelengths of 370 nm (brown carbon, BrC) and 880 nm (black carbon, BC) at two sites of a mid-sized city in Brazil. We observed sharp changes in LAC concentrations at the city centre site in response to variations in traffic volume. The highest concentrations were observed when winds originated from both the city core and from the direction of the bus terminal. The suburban site exhibited a notably uniform diurnal pattern and consistently lower LAC concentrations throughout the day. Nevertheless, substantial increases during the evening led to mean BrC and BC concentrations (2.6 and 2.2 µg m-3, respectively) comparable to daytime peaks observed in the city centre (3 µg m-3 and 2.5 µg m-3). This phenomenon was attributed to the burning of residential waste and overgrown vegetation in nearby vacant lots. Moreover, the highest concentrations coincided with periods of low wind speeds, usually linked to non-buoyant plumes from point sources. BrC concentrations surpassed BC concentrations, even at the city centre site. Not only was the Ångström absorption exponent (Å370/880) larger at the suburban site compared to the city centre (95th percentiles of 1.73 and 1.38, respectively), but it also exhibited a wider span. Overall, the combined LAC and Å370/880 data indicated that i) biomass burning is a major source of LAC at the suburban site; ii) at the city centre, bare BC particles may become internally mixed with BrC from biomass or fossil fuel emissions and enhance absorption at lower wavelengths. The occurrence of LAC peaks outside the evening rush hours suggests that other sources but on-road vehicular emissions may contribute to the deterioration of the air quality in the urban core. Tackling air quality across the urban perimeter requires targeting other potential sources but traffic emissions.

Minimally Invasive Concomitant Aortic And Mitral Valve Surgery - Initial Experience Of A Single Centre.

INTRODUCTION: Valve surgery through a median sternotomy has been the standard approach, but in the past decade various minimally invasive procedures have gained increasing traction among physicians and patients. MATERIALS AND METHODS: We present a series of three patients submitted to minimally invasive combined aortic and mitral valve surgery, performed through right lateral thoracotomy. RESULTS: We report no postoperative complication or mortality. Mean length of stay was 5 days, with a self-reported pain score 2/5 (mild/annoying pain). CONCLUSIONS: We report our initial experience, describing surgical technique and postoperative results, showing this technique to be safe, reproductible and comparable to conventional surgery.

Retinal OCT speckle as a biomarker for glaucoma diagnosis and staging.

This paper presents a novel image analysis strategy that increases the potential of macular Optical Coherence Tomography (OCT) by using speckle features as biomarkers in different stages of glaucoma. A large pool of features (480) were computed for a subset of macular OCT volumes of the Leuven eye study cohort. The dataset contained 258 subjects that were divided into four groups based on their glaucoma severity: Healthy (56), Mild (94), Moderate (48), and Severe (60). The OCT speckle features were categorized as statistical properties, statistical distributions, contrast, spatial gray-level dependence matrices, and frequency domain features. The averaged thicknesses of ten retinal layers were also collected. Kruskal-Wallis H test and multivariable regression models were used to infer the most significant features related to glaucoma severity classification and to the correlation with visual field mean deviation. Four features were selected as being the most relevant: the ganglion cell layer (GCL) and the inner plexiform layer (IPL) thicknesses, and two OCT speckle features, the data skewness computed on the retinal nerve fiber layer (RNFL) and the scale parameter (a) of the generalized gamma distribution fitted to the GCL data. Based on a significance level of 0.05, the regression models revealed that RNFL skewness exhibited the highest significance among the features considered for glaucoma severity staging (p-values of 8.6×10-6 for the logistic model and 2.8×10-7 for the linear model). Furthermore, it demonstrated a strong negative correlation with the visual field mean deviation (ρ=-0.64). The post hoc analysis revealed that, when distinguishing healthy controls from glaucoma subjects, GCL thickness is the most relevant feature (p-value of 8.7×10-5). Conversely, when comparing the Mild versus Moderate stages of glaucoma, RNFL skewness emerged as the only feature exhibiting statistical significance (p-value = 0.001). This work shows that macular OCT speckle contains information that is currently not used in clinical practice, and not only complements structural measurements (thickness) but also has a potential for glaucoma staging.

The turtles from the middle Paleolithic site of Gruta Nova da Columbeira (Bombarral, Portugal): Update through an archaeozoological perspective.

Twenty-five years after the preliminary systematic study of the turtle remains (Agrionemys [=Testudo] hermanni and Emys or Mauremys) recovered from Gruta Nova da Columbeira site (Bombarral, Portugal), the results of its review from systematic and archaeozoological perspectives are presented here. Tortoise remains studies from pre-Upper Paleolithic sites worldwide have provided relevant data confirming its role as a dietary supply for hominid populations and informing about their ability to adapt to local environmental resources. The Iberian Peninsula record in general, and specifically, that from Portugal, have yielded substantial evidence to this highly debated topic. In this sense, turtle remains recovered in Gruta Nova da Columbeira site, discovered in the 1960s and the main ensemble chronologically ascribed to the MIS-5 (87.1 ± 6.3 ka BP), offer new information to this debate. Its detailed restudy, has allowed us the identification, justification, and figuration of remains attributed to two Iberian turtle taxa, Chersine hermanni and Emys orbicularis. Therefore, this update on the data concerning the turtle record from Gruta Nova da Columbeira provides new justified taxonomic evidence regarding the Iberian turtle taxa distribution during the Upper Pleistocene. The previously suggested hypothesis about the tortoise human consumption on the site is here evaluated through the development of an archaeozoological and taphonomical analysis, as well as considering the potential documentation of anthropic alterations (e.g., burning, cutmarks, percussion marks). In this sense, this hypothesis is confirmed. In addition, the presence of carnivore activity evidence indicates the engagement of other agents in the deposit formation.

Phase-Resolved Optical Coherence Elastography: An Insight into Tissue Displacement Estimation.

Robust methods to compute tissue displacements in optical coherence elastography (OCE) data are paramount, as they play a significant role in the accuracy of tissue elastic properties estimation. In this study, the accuracy of different phase estimators was evaluated on simulated OCE data, where the displacements can be accurately set, and on real data. Displacement (∆d) estimates were computed from (i) the original interferogram data (Δφori) and two phase-invariant mathematical manipulations of the interferogram: (ii) its first-order derivative (Δφd) and (iii) its integral (Δφint). We observed a dependence of the phase difference estimation accuracy on the initial depth location of the scatterer and the magnitude of the tissue displacement. However, by combining the three phase-difference estimates (Δdav), the error in phase difference estimation could be minimized. By using Δdav, the median root-mean-square error associated with displacement prediction in simulated OCE data was reduced by 85% and 70% in data with and without noise, respectively, in relation to the traditional estimate. Furthermore, a modest improvement in the minimum detectable displacement in real OCE data was also observed, particularly in data with low signal-to-noise ratios. The feasibility of using Δdav to estimate agarose phantoms' Young's modulus is illustrated.

Marchiafava-Bignami Disease: Report of a Subacute Case.

Marchiafava-Bignami disease (MBD) is rare and often associated with chronic alcohol consumption; however, cases have been described in non-alcoholic patients with nutritional deficits. This disease manifests itself through an array of neurological signs and symptoms, from mild dysarthria or mild confusion to coma and death, and can present acutely, subacutely, or chronically, depending on their severity. The evolution of imaging technology makes magnetic resonance imaging (MRI) the gold standard for the diagnosis of this disease, although computed tomography (CT) scan is usually in the first line owing to its greater availability. The main feature for the diagnosis of MBD by brain MRI is the identification of areas of demyelination and necrosis of the corpus callosum. We report a 55-year-old male with subacute neurological deterioration whose MRI demonstrated atrophy and demyelination of the corpus callosum.

Effect of inducing accessory corpus luteum formation with gonadotropin-releasing hormone or human chorionic gonadotropin on the day of embryo transfer on fertility of recipient dairy heifers and lactating cows.

The objective was to determine the effect of inducing an accessory corpus luteum (CL) using GnRH or human chorionic gonadotropin (hCG) on the day of in vitro-produced (IVP) embryo transfer (ET) on pregnancy per ET (P/ET) and calving/ET in dairy heifers and lactating cows. Dairy heifers (11-15 mo of age; n = 1,547) and lactating cows (n = 1,480) detected in estrus by tail chalk (d 0) were used as recipients. Before ET, the presence of a CL was evaluated by transrectal palpation from d 6 to 9 of the estrous cycle. Animals with a CL were randomly assigned to receive 1 of 3 treatments immediately before ET: control (no treatment; n = 1,009), GnRH (86 µg of GnRH; n = 1,085) and hCG (2,500 IU; n = 1,069). Embryos were implanted in the uterine horn ipsilateral to the ovary with a CL (fresh IVP embryos, n = 2,544; vitrified IVP embryos n = 545; slow-freezing IVP embryos, n = 74). Pregnancy diagnosis was performed on d 37 ± 3 of gestation by transrectal palpation. Pregnancy loss data and calving records were collected from the dairy farm management software. Treatment did not affect P/ET, calving/ET, or pregnancy loss either overall or within parity. When treatments inducing CL formation were combined (GnRH + hCG), heifers tended to have greater P/ET than controls (67.7 vs. 63.5%, respectively). Yet, calving/ET were similar. Response variables were also analyzed within embryo type and parity. For heifers receiving stage 6 (blastocyst) fresh IVP embryos, hCG had greater P/ET than controls (74.5 vs. 51.1%, respectively). In addition, GnRH tended to have greater P/ET than controls (67.8 vs. 51.2%, respectively). However, calving/ET in heifers receiving blastocyst fresh IVP embryos was similar among treatments. When only stage 7 (expanded blastocyst) fresh IVP embryos were considered, primiparous GnRH cows had greater P/ET (59.3 vs. 47.1%) and calving/ET (48.6 vs. 38.1%) than hCG. Moreover, hCG showed decreased calving/ET compared with controls in primiparous cows transferred with expanded blastocyst fresh IVP embryos. In summary, the effects of hCG or GnRH at ET on P/ET and calving/ET were inconsistent according to different embryo characteristics (e.g., embryo stage) and parity of recipients. Furthermore, treatment did not improve the overall fertility outcomes for recipient animals receiving IVP embryos.

Tricuspid repair in mitral regurgitation surgery: a systematic review and meta-analysis.

BACKGROUND: Concomitant tricuspid repair in MR surgery is indicated in patients with severa tricuspid regurgitation, however, concomitant repair in less-than-severe TR patients is still a matter of debate. METHODS: In December 2021, we systematically searched PubMed, Embase and Cochrane databases for randomised control trials (RCTs) comparing isolated MR surgery versus MR surgery with concomitant TR annuloplasty. Four studies were included, resulting in 651 patients (323 in the prophylactic tricuspid intervention group and 328 in the no tricuspid intervention group). RESULTS: Our meta-analysis showed a similar all-cause mortality and perioperative mortality for concomitant prophylactic tricuspid repair when compared with no tricuspid intervention (pooled odds ratio (OR), 0.54; 95% confidence interval (CI): 0.25-1.15, P = 0.11; I2 = 0% and pooled OR, 0.54; 95% CI: 0.25-1.15, P = 0.11; I2 = 0%, respectively) in patients undergoing MV surgery. despite a significantly lower TR progression (pooled OR, 0.06; 95% CI: 0.02-0.24, P < 0.01; I2 = 0%). Additionally, similar New York Heart Association (NYHA) classes III and IV were identified in both concomitant prophylactic tricuspid repair and no tricuspid intervention, despite a lower trend in the tricuspid intervention group (pooled OR, 0.63; 95% CI: 0.38-1.06, P = 0.08; I2 = 0%). CONCLUSIONS: Our pooled analyses suggested that TV repair at the time of MV surgery in patients with moderate or less-than-moderate TR did not impact on perioperative or postoperative all-cause mortality, despite reducing TR severity and TR progression following the intervention.

Bronchobiliary fistula after stenting of biliary duct as the management of iatrogenic bile duct injury during elective cholecystectomy.

BACKGROUND: Bronchobiliary fistula is a rare and complex entity defined by an abnormal communication between the biliary and bronchial systems. The etiopathogenesis is not completely understood, but the most common factors implicated are hepatobiliary tumors, biliary obstruction, iatrogenic damage or trauma. METHODS: Here we present a case of a 69-year-old man that developed a bronchobiliary fistula and a pulmonary abscess after migration of a bile duct stent placed as part of the treatment of an iatrogenic bile duct injury that occurred during elective cholecystectomy. RESULTS: A conservative approach, that included broad-spectrum antibiotic, removal of the stent, and sphincterotomy, was enough for the closure of the fistula and resolution of the symptoms. CONCLUSION: We emphasize the importance of prompt recognition of this entity and a concerted therapeutic strategy to optimize the probability of success, avoiding the destructive consequences of the bile in the pulmonary parenchyma and septic complications.

Tobacco effects on ocular surface, meibomian glands, and corneal epithelium and the benefits of treatment with a lipid-based lubricant.

PURPOSE: Our aim was to evaluate the ocular surface in chronic smokers and to assess the benefit of sodium hyaluronate (SH) versus semi-fluorinated alkane (SFA) eyedrops on tear film, meibomian glands, and corneal epithelial thickness (CET). METHODS: This prospective randomized single-blinded study included smokers, who applied one eyedrop of Hyabak® on one eye (SH group) and one eyedrop of EvoTears® on the fellow eye (SFA group) 4 times daily for 2 months, and age-matched non-smokers. Ocular surface parameters, including tear film break-up time (TBUT) test and corneal fluorescein staining (CFS) score, lipid layer thickness (LLT), meibography (LipiView®), and CET measurements (Zeiss Cirrus HD-5000®), were assessed at baseline and after treatment. RESULTS: Seventy-eight eyes were included in the smokers group (39 in the SH subgroup and 39 in the SFA subgroup) and 42 eyes in the control group. At baseline, the smokers group had a higher prevalence of dry eye (100% vs 0%, p < 0.001) and of meibomian gland dysfunction (MGD) and lower CET measurements than controls (p < 0.05). TBUT, CFS, and LLT (controls vs SFA group: 64.02 ± 1.87 nm vs 49.56 ± 4.33 nm, p = 0.05) improved in the SFA subgroup after treatment, but not in the SH subgroup, and became equivalent to those of controls. Prevalence of dry eye decreased in the smokers group after treatment (controls vs SH group vs SFA group: 0% vs 12.82% vs 16.26%, p > 0.05). Meibomian gland morphological parameters and CET did not improve after treatment (p < 0.05). CONCLUSIONS: Smoking is associated with dry eye, MGD, and corneal epithelial thinning that seem to be only partially reversible with topical lubricants, preferably SFA.

Early surgical intervention versus conservative management of asymptomatic severe aortic stenosis: a systematic review and meta-analysis.

OBJECTIVE: Timing of intervention for patients with asymptomatic severe aortic stenosis (AS) remains controversial. To compare the outcomes of early aortic valve replacement (AVR) versus watchful waiting (WW) in patients with asymptomatic severe AS. METHODS: We systematically searched PubMed, Embase and Cochrane databases, in December 2021, for studies comparing early AVR with WW in the treatment of asymptomatic severe AS. Random-effects meta-analysis was performed. RESULTS: Twelve studies were included in which two were randomised clinical trials. A total of 4130 patients were included, providing a 1092 pooled death events. Our meta-analysis showed a significantly lower all-cause mortality for the early AVR compared with WW group, although with a high amount of heterogeneity between studies in the magnitude of the effect (pooled OR 0.40; 95% CI 0.35 to 0.45, p<0.01; I²=61%). An early surgery strategy displayed a significantly lower cardiovascular mortality (pooled OR 0.33; 95% CI 0.19 to 0.56, p<0.01; I²=64%) and heart failure hospitalisation (pooled OR 0.19; 95% CI 0.10 to 0.39, p<0.01, I²=7%). However, both groups had similar rates of stroke (pooled OR 1.30; 95% CI 0.73 to 2.29, p=0.36, I²=0%) and myocardial infarction (pooled OR 0.49; 95% CI 0.19 to 1.27, p=0.14, I²= 0%). CONCLUSIONS: This study suggests that for patients with asymptomatic severe AS an early surgical intervention compared with a conservative WW strategy was associated with a lower heart failure hospitalisation and a similar rate of stroke or myocardial infarction, although with significant risk of bias. PROSPERO REGISTRATION NUMBER: CRD42021291144.

The lady's 'slippery' orchid: functions of the floral trap and aphid mimicry in a hoverfly-pollinated Phragmipedium species in Brazil.

BACKGROUND AND AIMS: Trap flowers are fascinating cases of adaptation, often linked to oviposition-site mimicry systems. Some trap flowers do not imprison pollinators for a pre-determined period, but rather force them to move through a specific path, manipulating their movements in a way that culminates in pollen transfer, often as they leave through a secondary opening. METHODS: We investigated the previously unknown pollination system of the lady's slipper orchid Phragmipedium vittatum and assessed the function of micro-morphological traits of its trap flowers. KEY RESULTS: Our observations revealed that P. vittatum is pollinated by females of two hoverfly species (Syrphidae). Eggs laid by flies on or near raised black spots on the flowers indicate that the orchid mimics aphids which serve as food for their aphidophagous larvae. Dark, elevated aphid-like spots appear to attract the attention of hoverflies to a slipping zone. This region has downward projecting papillate cells and mucilage secretion that promote slipperiness, causing potential pollinators to fall into the labellum. They then follow a specific upward route towards inner aphid-like spots by holding onto upward oriented hairs that aid their grip. As hoverflies are funnelled by the lateral constriction of the labellum, they pass the stigma, depositing pollen they may be carrying. Later, they squeeze under one of the articulated anthers which places pollen smears onto their upper thorax. Then, they depart through one of the narrow lateral holes by holding onto hairs projecting from the petals. CONCLUSIONS: This study confirms the system of aphid mimicry in Phragmipedium and highlights the sophisticated micro-morphological traits used by trap flowers in pollinator attraction, trapping, guidance and release, thus promoting precise pollen transfer.