Radiological insights into rheumatoid meningitis - a rare central nervous system manifestation of rheumatoid arthritis: a retrospective review of six cases.

BACKGROUND: The objective is to analyze and review the clinical, laboratory, and neuroimaging characteristics of rheumatoid meningitis (RM) in six patients with known rheumatoid arthritis (RA). METHODS: We performed a retrospective review of patients diagnosed with RM from August 2012 to June 2023. To identify the cases, we used medical term search engines and the hospital´s radiology case database. Clinical information and laboratory findings were gathered from the medical records. A neuroradiologist with five years of experience reviewed and analyzed the RM to determine the characteristics findings of RM. RESULTS: Six patients with RM are included. Seizures along with headaches were among the clinical signs that were documented. All the patients had high levels of rheumatoid factor (RF) and anti-cyclic citrullinated peptides (ACPA) in the peripheral blood. Biopsy in two cases confirmed typical rheumatoid nodules. Leptomeningeal enhancement was found bilaterally in all cases and was predominantly found in the frontoparietal region. "Mismatch DWI/FLAIR" was found in five patients. Bilateral subdural collections could be found in two patients. Brain PET scan revealed increased metabolism in two cases. CONCLUSION: Rheumatoid meningitis is a rare complication of rheumatoid arthritis (RA) with challenging clinical diagnosis due to non-specific symptoms. This study highlights the importance of MR in detecting characteristic neuroimaging patterns, including "mismatch DWI/FLAIR", to aid in early diagnosis. Increased awareness of this condition may facilitate timely intervention and improve prognosis. These results still need to be verified by large studies.

Cellular Response of Adapted and Non-Adapted Tetrahymena thermophila Strains to Europium Eu(III) Compounds.

Europium is one of the most reactive lanthanides and humans use it in many different applications, but we still know little about its potential toxicity and cellular response to its exposure. Two strains of the eukaryotic microorganism model Tetrahymena thermophila were adapted to high concentrations of two Eu(III) compounds (EuCl3 or Eu2O3) and compared to a control strain and cultures treated with both compounds. In this ciliate, EuCl3 is more toxic than Eu2O3. LC50 values show that this microorganism is more resistant to these Eu(III) compounds than other microorganisms. Oxidative stress originated mainly by Eu2O3 is minimized by overexpression of genes encoding important antioxidant enzymes. The overexpression of metallothionein genes under treatment with Eu(III) compounds supports the possibility that this lanthanide may interact with the -SH groups of the cysteine residues from metallothioneins and/or displace essential cations of these proteins during their homeostatic function. Both lipid metabolism (lipid droplets fusing with europium-containing vacuoles) and autophagy are involved in the cellular response to europium stress. Bioaccumulation, together with a possible biomineralization to europium phosphate, seems to be the main mechanism of Eu(III) detoxification in these cells.

Preclinical characterization of a non-peptidomimetic HIV protease inhibitor with improved metabolic stability.

Protease inhibitors (PIs) remain an important component of antiretroviral therapy for the treatment of HIV-1 infection due to their high genetic barrier to resistance development. Nevertheless, the two most commonly prescribed HIV PIs, atazanavir and darunavir, still require co-administration with a pharmacokinetic boosting agent to maintain sufficient drug plasma levels which can lead to undesirable drug-drug interactions. Herein, we describe GS-9770, a novel investigational non-peptidomimetic HIV PI with unboosted once-daily oral dosing potential due to improvements in its metabolic stability and its pharmacokinetic properties in preclinical animal species. This compound demonstrates potent inhibitory activity and high on-target selectivity for recombinant HIV-1 protease versus other aspartic proteases tested. In cell culture, GS-9770 inhibits Gag polyprotein cleavage and shows nanomolar anti-HIV-1 potency in primary human cells permissive to HIV-1 infection and against a broad range of HIV subtypes. GS-9770 demonstrates an improved resistance profile against a panel of patient-derived HIV-1 isolates with resistance to atazanavir and darunavir. In resistance selection experiments, GS-9770 prevented the emergence of breakthrough HIV-1 variants at all fixed drug concentrations tested and required multiple protease substitutions to enable outgrowth of virus exposed to escalating concentrations of GS-9770. This compound also remained fully active against viruses resistant to drugs from other antiviral classes and showed no in vitro antagonism when combined pairwise with drugs from other antiretroviral classes. Collectively, these preclinical data identify GS-9770 as a potent, non-peptidomimetic once-daily oral HIV PI with potential to overcome the persistent requirement for pharmacological boosting with this class of antiretroviral agents.

18F-FDG-PET/CT response after first-line treatment as a prognostic factor for survival in peripheral T-cell lymphoma: a Spanish retrospective study.

BACKGROUND: An accurate assessment of tumor viability after first-line treatment is critical for predicting treatment failure in peripheral T-cell lymphomas (PTCLs). 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) has been adopted as the preferred assessment method in clinical trials, but its impact in clinical practice should be examined. This study aims to determine the prognostic significance of18F-FDG-PET/CT for survival following first-line treatment in PTCL patients. RESEARCH DESIGN AND METHODS: Retrospective observational study including 175 patients diagnosed with PTCL between 2008 and 2013 in 13 Spanish sites. RESULTS: Fifty patients were evaluated with18F-FDG-PET/CT following first-line therapy: 58% were18F-FDG-PET/CT-negative and 42% were18F-FDG-PET/CT-positive. Disease progression occurred in 37.9% of18F-FDG-PET/CT-negative patients and in 80.9% of18F-FDG-PET/CT-positive patients (p = 0.0037). Median progression-free survival and overall survival were 67 and 74 months for18F-FDG-PET/CT-negative patients, and 5 (p < 0.0001) and 10 months (p < 0.0001), respectively, in18F-FDG-PET/CT-positive patients. After multivariate analysis, only B symptoms emerged as a negative predictive factor of complete response (RR 7.08; 95% CI 1.60-31.31; p = 0.001). CONCLUSIONS: 18F-FDG-PET/CT identifies high-risk PTCL patients who will have poor prognosis and survival following first-line treatment. However, more research is needed to confirm the best treatment options for PTCL patients.

Prognostic factors of progressive fibrotic hypersensitivity pneumonitis: a large, retrospective, multicentre, observational cohort study.

Background: Fibrotic hypersensitivity pneumonitis (fHP) is an immune-mediated interstitial lung disease caused by sensitisation to chronic allergen inhalation. This study aimed to determine prognostic indicators of progression and mortality in fHP. Methods: This was a retrospective, multicentre, observational, cross-sectional cohort study of consecutive patients diagnosed with fHP from 1 January 2012 to 31 December 2021. Multivariate Cox regression analyses were used to calculate hazard ratios (HRs) with 95% confidence intervals for predictors of progression and survival. Results: A total of 403 patients were diagnosed with fHP: median (interquartile range) age 66.5 (14.0) years, 51.9% females and 55.1% never-smokers. The cause of fHP was mainly fungal (39.7%) or avian (41.4%). Lung biopsy was performed in 269 cases (66.7%). In the whole cohort the variables that were related to mortality or lung transplant were older age (HR 1.08; p<0.001), percentage predicted forced vital capacity (HR 0.96; p=0.001), lymphocytosis in bronchoalveolar lavage (BAL) (HR 0.93; p=0.001), presence of acute exacerbation during follow-up (HR 3.04; p=0.001) and GAP (gender, age and lung physiology) index (HR 1.96; p<0.01). In the group of biopsied patients, the presence of fibroblastic foci at biopsy (HR 8.39; p<0.001) stands out in multivariate Cox regression analyses as a highly significant predictor for increased mortality or lung transplant. GAP index (HR 1.26; p=0.009), lymphocytosis in BAL (HR 0.97; p=0.018) and age (HR 1.03; p=0.018) are also predictors of progression. Conclusions: The study identified several prognostic factors for progression and/or survival in fHP. The presence of fibroblastic foci at biopsy was a consistent predictor for increased mortality and the presence of lymphocytosis in BAL was inversely related to mortality.

Occurrence of Pseudomonas syringae pvs. actinidiae, actinidifoliorum and Other P. syringae Strains on Kiwifruit in Northern Spain.

Pseudomonas syringae pv. actinidiae (Psa), the agent causing bacterial canker of kiwifruit, has been present in the Principality of Asturias (PA), Northern Spain, since 2013, although with restricted distribution. In this study, 53 strains collected in kiwifruit orchards in PA during the period 2014-2020 were characterized by a polyphasic approach including biochemical and phylogenetic analysis. Thirty-three strains, previously identified by PCR as Psa, have been found to be a homogeneous group in phylogenetic analysis, which seems to indicate that there have been few introductions of the pathogen into the region. Two strains were confirmed as P. syringae pv. actinidifoliorum (Pfm), so this is the first report of Pfm in the PA. The remaining 18 strains were found to be close to P. avellanae and P. syringae pv. antirrhini or to strains described as Pfm look-alikes. Pathogenicity tests carried out on peppers with a selection of strains have shown that both Psa and Pfm caused clear damage, while the 18 atypical strains caused variable lesions. It would be necessary to carry out pathogenicity testing of atypical strains on kiwifruit plants to study the role of these strains in the kiwifruit pathosystem to evaluate their pathogenic potential in this crop.

Use of Transesophageal Echocardiography During Orthotopic Liver Transplantation: Simplifying the Procedure.

The intraoperative management of patients undergoing orthotopic liver transplantation (OLT) is influenced by the cardiovascular manifestations typically found in the context of end-stage liver disease, by the presence of concomitant cardiovascular disease, and by the significant hemodynamic changes that occur during surgery. Hypotension and intraoperative blood pressure fluctuations during OLT are associated with liver graft dysfunction, acute kidney failure, and increased risk of 30-d mortality. Patients also frequently present hemodynamic instability due to various causes, including cardiac arrest. Recent evidence has shown transesophageal echocardiography (TEE) to be a useful minimally invasive monitoring tool in patients undergoing OLT that gives valuable real-time information on biventricular function and volume status and can help to detect OLT-specific complications or situations. TEE also facilitates rapid diagnosis of life-threatening conditions in each stage of OLT, which is difficult to identify with other types of monitoring commonly used. Although there is no consensus on the best approach to intraoperative monitoring in these patients, intraoperative TEE is safe and useful and should be recommended during OLT, according to experts, for assessing hemodynamic changes, identifying possible complications, and guiding treatment with fluids and inotropes to achieve optimal patient care.

Asymmetric framework motion of TCRαß controls load-dependent peptide discrimination.

Mechanical force is critical for the interaction between an αß T cell receptor (TCR) and a peptide-bound major histocompatibility complex (pMHC) molecule to initiate productive T-cell activation. However, the underlying mechanism remains unclear. We use all-atom molecular dynamics simulations to examine the A6 TCR bound to HLA-A*02:01 presenting agonist or antagonist peptides under different extensions to simulate the effects of applied load on the complex, elucidating their divergent biological responses. We found that TCR α and ß chains move asymmetrically, which impacts the interface with pMHC, in particular the peptide-sensing CDR3 loops. For the wild-type agonist, the complex stabilizes in a load-dependent manner while antagonists destabilize it. Simulations of the Cß FG-loop deletion, which reduces the catch bond response, and simulations with in silico mutant peptides further support the observed behaviors. The present results highlight the combined role of interdomain motion, fluctuating forces, and interfacial contacts in determining the mechanical response and fine peptide discrimination by a TCR, thereby resolving the conundrum of nearly identical crystal structures of TCRαß-pMHC agonist and antagonist complexes.

Effectiveness of Mepolizumab in Patients with Severe Eosinophilic Asthma with/without Nasal Polyposis: A Real-Life Study.

INTRODUCTION: Asthma is one of the most common chronic diseases and affects around 334 million people worldwide. The estimated prevalence of severe asthma is 3-10% of the asthmatic population. Mepolizumab has demonstrated efficacy in reducing exacerbations, oral corticosteroid use, and improving quality of life, asthma control, and lung function in patients with severe eosinophilic asthma (SEA). Our study aimed to check the response to mepolizumab in a series of severe asthma patients regarding exacerbations, oral corticosteroid use, asthma control, quality of life, and lung function and to compare the response between patients with and without nasal polyps. METHOD: This is a retrospective, multicenter study of RE-ASGRAMUR (Register of Severe Asthma of the Region of Murcia) performed in eight hospitals of the Region of Murcia (Spain) under routine clinical practice conditions. We included patients diagnosed with SEA who completed at least 1 year of treatment with mepolizumab. We analyzed clinical characteristics, drug tolerance, and effectiveness: exacerbations, ACT, miniAQLQ, forced expiratory volume in 1 s (FEV1), and use of oral corticosteroids. We also compared the results between patients with and without nasal polyps. RESULTS: The median of exacerbations before treatment was 3 and decreased to 0 after treatment (mean decrease of 77.4%). The median diary oral prednisone intake was 15 mg before treatment and 5 mg after treatment (mean 56% reduction). We have obtained a significant improvement in other variables: ED visits and hospitalizations, asthma control (ACT), quality of life (miniAQLQ), and lung function (FEV1). Thirty-four out of 70 patients (48.57%) fulfilled the criteria of super-responder, and 17 out of 70 (24.29%) had a complete response. More patients in the group with nasal polyps fulfilled the criteria of super-responder and complete response to mepolizumab. CONCLUSIONS: Mepolizumab is a safe and effective treatment for SEA patients, improving exacerbations, oral corticosteroid intake, asthma control, quality of life, and lung function. In patients with associated nasal polyposis, there is a statistically significant higher proportion of super-responders and complete responders.

Use of a barrier membrane to repair congenital hard palate defects and to close oronasal fistulae remaining after cleft palate repair: seven dogs (2019-2022).

OBJECTIVE: To describe the use of a barrier membrane in dogs for repair of congenital hard palate defects and closure of oronasal fistulae (ONF) remaining after previous cleft palate (CFP) repair. ANIMALS: 7 client-owned dogs. METHODS: The hard palate defect was closed with medially positioned flaps (Von Langenbeck technique) or pedicle flaps (2-flap palatoplasty) and a membrane composed of autologous auricular cartilage from the pinna or allogenous fascia lata underlying the mucoperiosteal flaps. RESULTS: All palate defects were considered to have a high risk of dehiscence based on their type and size and the characteristics of the surrounding tissue. The barrier membrane was used in 5 dogs for repair of congenital hard palate defects and in 2 dogs for closure of ONF remaining after previous CFP repair. Resolution of clinical signs occurred in all cases. Complete success (ie, complete closure of the palate defect and absence of clinical signs) was achieved in 5 dogs (4 with congenital hard palate defects and 1 with an ONF remaining after previous CFP repair). The persistent ONF in 1 dog with functional success (incomplete closure, but no clinical signs) was smaller than prior to surgery. CLINICAL RELEVANCE: Barrier membranes underlying mucoperiosteal flaps may constitute an alternative technique in dogs for repair of congenital hard palate defects and closure of ONF remaining after previous CFP repair.

Oral Pyogenic Granuloma: A Narrative Review.

Pyogenic granuloma (PG) is a benign vascular lesion found predominantly in the oral cavity. Characterized by rapid growth and propensity to bleed, PG presents diagnostic challenges due to its similarity and alarming proliferation. This narrative review synthesizes current knowledge on the epidemiology, etiopathogenesis, clinical manifestations, and management of oral PG, with emphasis on recent advances in diagnostic and therapeutic approaches. The epidemiology of the injury is meticulously analyzed, revealing a higher incidence in women and a wide range of ages of onset. It delves into the etiopathogenesis, highlighting the uncertainty surrounding the exact causal factors, although historical attributions suggest an infectious origin. It exhaustively analyzes the clinical and histopathological aspects of oral PG, offering information on its various presentations and the importance of an accurate diagnosis to guide effective treatment. It details treatment strategies, emphasizing the personalized approach based on individual patient characteristics. This comprehensive review consolidates current knowledge on oral PG, highlighting the need for further research to clarify its pathogenesis and optimize treatment protocols.

Enhanced SREBP2-driven cholesterol biosynthesis by PKCλ/ι deficiency in intestinal epithelial cells promotes aggressive serrated tumorigenesis.

The metabolic and signaling pathways regulating aggressive mesenchymal colorectal cancer (CRC) initiation and progression through the serrated route are largely unknown. Although relatively well characterized as BRAF mutant cancers, their poor response to current targeted therapy, difficult preneoplastic detection, and challenging endoscopic resection make the identification of their metabolic requirements a priority. Here, we demonstrate that the phosphorylation of SCAP by the atypical PKC (aPKC), PKCλ/ι promotes its degradation and inhibits the processing and activation of SREBP2, the master regulator of cholesterol biosynthesis. We show that the upregulation of SREBP2 and cholesterol by reduced aPKC levels is essential for controlling metaplasia and generating the most aggressive cell subpopulation in serrated tumors in mice and humans. Since these alterations are also detected prior to neoplastic transformation, together with the sensitivity of these tumors to cholesterol metabolism inhibitors, our data indicate that targeting cholesterol biosynthesis is a potential mechanism for serrated chemoprevention.

Epidemiological characterization of ischemic heart disease at different altitudes: A nationwide population-based analysis from 2011 to 2021 in Ecuador.

BACKGROUND: Cardiovascular diseases, including ischemic heart disease, are the leading cause of premature death and disability worldwide. While traditional risk factors such as smoking, obesity, and diabetes have been thoroughly investigated, non-traditional risk factors like high-altitude exposure remain underexplored. This study aims to examine the incidence and mortality rates of ischemic heart disease over the past decade in Ecuador, a country with a diverse altitude profile spanning from 0 to 4,300 meters. METHODS: We conducted a geographic distribution analysis of ischemic heart disease in Ecuador, utilizing hospital discharge and mortality data from the National Institute of Census and Statistics for the years 2011-2021. Altitude exposure was categorized according to two distinct classifications: the traditional division into low (< 2,500 m) and high (> 2,500 m) altitudes, as well as the classification proposed by the International Society of Mountain Medicine, which delineates low (< 1,500 m), moderate (1,500-2,500 m), high (2,500-3,500 m), and very high (3,500-5,800 m) altitudes. FINDINGS: From 2011-2021, we analyzed 49,765 IHD-related hospital admissions and 62,620 deaths. Men had an age-adjusted incidence rate of 55.08/100,000 and a mortality rate of 47.2/100,000, compared to 20.77/100,000 and 34.8/100,000 in women. Incidence and mortality surged in 2020 by 83% in men and 75% in women. Altitudinal stratification revealed higher IHD rates at lower altitudes (<2500 m), averaging 61.65 and 121.8 per 100,000 for incidence and mortality, which declined to 25.9 and 38.5 at elevations >2500 m. Men had more pronounced rates across altitudes, exhibiting 138.7% and 150.0% higher incidence at low and high altitudes respectively, and mortality rates increased by 48.3% at low altitudes and 23.2% at high altitudes relative to women. CONCLUSION: Ecuador bears a significant burden of ischemic heart disease (IHD), with men being more affected than women in terms of incidence. However, women have a higher percentage of mortality post-hospital admission. Regarding elevation, our analysis, using two different altitude cutoff points, reveals higher mortality rates in low-altitude regions compared to high-altitude areas, suggesting a potential protective effect of high elevation on IHD risk. Nevertheless, a definitive dose-response relationship between high altitude and reduced IHD risk could not be conclusively established.

Seed removal by the squirrel Notocitellus adocetus (Rodentia: Sciuridae) in Western México

Introduction: Seed dispersal and seed predation have important impacts on plant diversity and community structure. Rodents participate in both of these types of interactions. Objectives: To evaluate the removal of the seeds of Crescentia alata, Randia capitata, and Zea mays by the squirrel Notocitellus adocetus to determine how it affects these plant species, by dispersing or preying on their seeds. Methods: We studied 14 individuals for C. alata, 24 for R. capitata, and for Z. mays 35 individuals. We observed foraging and used camera traps to determine the part of the fruit (seed and/or pulp) consumed by the squirrels and the amount of fruit or seed consumed. We also placed fine sand traps (FST) to measure the percentage of seed removal. We quantified the fruits produced by the plant species studied and the percentage of damage caused by N. adocetus throughout the plots. Results: Notocitellus adocetus feeds on the seeds and pulp of C. alata and Z. mays. The species with the highest removal rate and the highest percentage of damage was C. alata. Zea mays was the plant species that had the highest percentage of removal from FST, the largest number of fruits, and the lowest percentage of damage. On FST, R. capitata had the lowest seed remotion. Conclusions: Notocitellus adocetus is considered a seed predator; however, due to its behavior and the characteristics of the fruits of C. alata and R. capitata, this rodent could make the seeds available to secondary seed dispersers.

Introducción: La dispersión y depredación de semillas tienen efectos importantes en la diversidad de plantas y estructura de las comunidades. Los roedores participan en estos tipos de interacciones. Objetivos: Evaluar la remoción de semillas de Crescentia alata, Randia capitata y Zea mays por la ardilla Notocitellus adocetus, para determinar su efecto en estas especies de plantas, dispersando o depredando semillas. Métodos: Estudiamos 14 individuos de C. alata, 24 para R. capitata y 35 individuos para Z. mays. Observamos el forrajeo y usamos cámaras trampas para determinar la parte del fruto (semilla y/o pulpa) consumida y la intensidad de consumo por las ardillas. También colocamos trampas de arena fina (FST) para medir el porcentaje de remoción de semillas. Cuantificamos los frutos producidos por las especies estudiadas y el porcentaje de daño ocasionado por N. adocetus, mediante parcelas. Resultados: Notocitellus adocetus se alimenta de las semillas y pulpa de C. alata y Z. mays. La especie que tuvo mayor tasa de remoción y mayor porcentaje de daño fue C. alata. La especie con mayor porcentaje de remoción, mayor número de frutos y menor daño en las FST fue Z. mays. En las trampas de arena fina, R. capitata tuvo la menor remoción de semillas. Conclusiones: Notocitellus adocetus es considerada depredadora de semillas, no obstante, por su comportamiento y las características de los frutos de C. alata y R. capitata, este roedor podría dejar disponibles las semillas a dispersores secundarios de semillas.

Real world data on the demographic and clinicopathological profile and management of patients with early-stage HER2-positive breast cancer and residual disease treated with adjuvant trastuzumab emtansine (KARMA study).

INTRODUCTION: Trastuzumab emtansine (T-DM1) significantly improves invasive disease-free survival and reduces the risk of recurrence in patients with HER2-positive early breast cancer (EBC) with residual disease (RD). The KARMA study aimed to describe the characteristics and management of these patients in clinical practice in Spain. MATERIAL AND METHODS: We conducted a multicentre retrospective study in patients with HER2-positive EBC with RD following neoadjuvant treatment (NeoT) and who had received ≥1 dose of T-DM1 as adjuvant treatment. The primary endpoint was the evaluation of sociodemographic and clinicopathological characteristics of these patients. RESULTS: A total of 114 patients were included (March-July 2020). At diagnosis, most tumours were infiltrating ductal carcinoma (IDC) (93.9 %), grade 2 (56.1 %), and hormone receptor (HR)-positive (79.8 %). Over 75 % of patients had disease in operable clinical stages (T1-3 N0-1). In the neoadjuvant setting, 86.8 % of patients received trastuzumab plus pertuzumab, and 23.6 % achieved radiological complete response. Breast-conserving surgery was performed in 55.8 % of patients. Surgical specimens showed that 89.5 % of patients had IDC, 49.1 % grade 2, 84.1 % HR-positive, and 8.3 % HER2-negative disease. Most patients had RD classified as RCB-II and Miller/Payne grade 3/4. Grade 3 treatment-related adverse events (trAEs) occurred in 5.3 % of patients. No grade 4/5 AEs occurred. Over 95 % of patients were free of invasive-disease during T-DM1 adjuvant treatment. CONCLUSION: The KARMA study describes the characteristics of patients with HER2-positive EBC with RD after NeoT and the real-life management of a T-DM1 adjuvant regimen, which showed a manageable safety profile in line with the KATHERINE trial data.

Preparation and Characterization of Extruded PLA Films Coated with Polyaniline or Polypyrrole by In Situ Chemical Polymerization.

Conductive polymers, such as polypyrrole and polyaniline, have been extensively studied for their notable intrinsic electronic and ionic conductivities, rendering them suitable for a range of diverse applications. In this study, in situ chemical polymerization was employed to coat extruded PLA films with PPy and PANi. Morphological analysis reveals a uniform and compact deposition of both polyaniline and polypyrrole after polymerization periods of 3 and 1 h, respectively. Furthermore, the PLA-PANi-3h and PLA-PPy-1h composites exhibited the highest electrical conductivity, with values of 0.042 and 0.022 S cm-1, respectively. These findings were in agreement with the XPS results, as the polyaniline-coated film showed a higher proportion of charge carriers compared to the polypyrrole composite. The elastic modulus of the coated films showed an increase compared with that of pure PLA films. Additionally, the inflection temperatures for the PLA-PANi-3h and PLA-PPy-1h composites were 368.7 and 367.2 °C, respectively, while for pure PLA, it reached 341.47 °C. This improvement in mechanical and thermal properties revealed the effective interfacial adhesion between the PLA matrix and the conducting polymer. Therefore, this work demonstrates that coating biopolymeric matrices with PANi or PPy enables the production of functional and environmentally friendly conductive materials suitable for potential use in the removal of heavy metals in water treatment.

Molecular survey on vector-borne pathogens in clinically healthy stray cats in Zaragoza (Spain).

BACKGROUND: In Europe, feline vector-borne infections are gaining importance because of the changing climate, expanding habitats of potential vectors and expanding pathogen reservoirs. The main objective of this study was to assess the prevalence of vector-borne pathogens (VBPs) in stray cats in Zaragoza, Spain, and to investigate potential risk factors for infection, including feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV). METHODS: Blood samples from stray cats presented to the veterinary faculty in Zaragoza between February 2020 and 2022 were tested by polymerase chain reaction (PCR) for the presence of Anaplasma phagocytophilum, Anaplasma platys, Bartonella henselae, Ehrlichia canis, Rickettsia spp., haemotropic Mycoplasma spp., Hepatozoon spp., Leishmania infantum, piroplasms and microfilariae at the LABOKLIN laboratory. The cats were also tested for FeLV and FIV by PCR. RESULTS: Nearly half of the cats (158/332, 47.6%) were positive for at least one VBP. Hepatozoon spp. were detected in 25.6%, haemotropic Mycoplasma spp. in 22.9%, B. henselae in 9.3% and L. infantum in 2.1% of the cats. Male sex had a statistically significant association with test results for haemotropic Mycoplasma spp. (odds ratio 1.38 [1.21;1.57]); regionality with Hepatozoon spp., B. henseale and FIV; and seasonality with Hepatozoon spp., haemotropic Mycoplasma spp., L. infantum and FeLV (P ≤ 0.05 each). A strong positive correlation was reported for the amount of rainfall and the number of cats that tested positive for Hepatozoon spp. (ρ = 753, P = 0.05). None of the cats tested positive for A. phagocytophilum, A. platys, E. canis, Rickettsia spp., piroplasms, or microfilariae. Co-infections with multiple VBPs were detected in 56 out of 332 cats (16.9%). Thirty-one of the 332 cats included in the study (9.3%) tested positive for FeLV (6.9%) and for FIV (3.6%). In 20/31 cats (64.5%) that tested positive for FeLV/FIV, coinfections with VBP were detected (P = 0.048, OR 2.15 [0.99; 4.64]). CONCLUSIONS: VBPs were frequently detected in stray cats in Zaragoza. In particular, regionality and seasonality had a statistically significant association with PCR results for most VBPs included in the study.

Antioxidants Prevent Iron Accumulation and Lipid Peroxidation, but Do Not Correct Autophagy Dysfunction or Mitochondrial Bioenergetics in Cellular Models of BPAN.

Neurodegeneration with brain iron accumulation (NBIA) is a group of rare neurogenetic disorders frequently associated with iron accumulation in the basal nuclei of the brain. Among NBIA subtypes, ß-propeller protein-associated neurodegeneration (BPAN) is associated with mutations in the autophagy gene WDR45. The aim of this study was to demonstrate the autophagic defects and secondary pathological consequences in cellular models derived from two patients harboring WDR45 mutations. Both protein and mRNA expression levels of WDR45 were decreased in patient-derived fibroblasts. In addition, the increase of LC3B upon treatments with autophagy inducers or inhibitors was lower in mutant cells compared to control cells, suggesting decreased autophagosome formation and impaired autophagic flux. A transmission electron microscopy (TEM) analysis showed mitochondrial vacuolization associated with the accumulation of lipofuscin-like aggregates containing undegraded material. Autophagy dysregulation was also associated with iron accumulation and lipid peroxidation. In addition, mutant fibroblasts showed altered mitochondrial bioenergetics. Antioxidants such as pantothenate, vitamin E and α-lipoic prevented lipid peroxidation and iron accumulation. However, antioxidants were not able to correct the expression levels of WDR45, neither the autophagy defect nor cell bioenergetics. Our study demonstrated that WDR45 mutations in BPAN cellular models impaired autophagy, iron metabolism and cell bioenergetics. Antioxidants partially improved cell physiopathology; however, autophagy and cell bioenergetics remained affected.

Complex Surgical Intervention for Small Bowel Obstruction Secondary to Metastatic Colorectal Cancer.

Small bowel obstruction (SBO) refers to the inability of contents to pass through the lumen of the small intestine. This is a common surgical emergency in the United States. Although intra-abdominal adhesions are the predominant cause, SBO can occur secondarily to various etiologies, be it one cause or several. Management of SBO secondary to adhesions and metastasized rectal adenocarcinoma, complicated by pulmonary, hepatic, and ureteral disease, highlights the criticality of a multidisciplinary approach. We present a case of a 59-year-old male with SBO secondary to rectal adenocarcinoma. Treatment included surgical resection, acute stabilization, referral for outpatient surgical follow-up, and oncologic management.