Cm-p5, a molluscan-derived antifungal peptide exerts its activity by a membrane surface covering in a non-penetrating mode.

Amidst the health crisis caused by the rise of multi-resistant pathogenic microorganisms, Antimicrobial Peptides (AMPs) have emerged as a potential alternative to traditional antibiotics. In this sense, Cm-p5 is an AMP with fungistatic activity against the yeast Candida albicans. Its antimicrobial activity and selectivity have been well characterized; however, the mechanism of action is still unknown. This study used biophysical approaches to gain insight into how this peptide exerts its activity. Stability and fluidity of lipid membrane were explored by liposome leakage and Laurdan generalized polarization (GP) respectively, suggesting that Cm-p5 does not perturb lipid membranes even at very high concentrations (≥100µm.L-1). Likewise, no depolarizing action was observed using 3,3'-propil-2,2'-thyodicarbocianine, a potential membrane fluorescent reporter, with C. albicans cells or the corresponding liposome models. Changes in liposome size were analyzed by Dynamic Light Scattering (DLS) data, indicating that Cm-p5 covers the vesicular surface slightly increasing liposome hydrodynamic size, without liposome rupture. These results were further corroborated with Langmuir monolayer isotherms, where no significant changes in lateral pressure or area per lipid were detected, indicating little or no insertion. Finally, data obtained from molecular dynamics simulations aligned with in vitro observations, whereby Cm-p5 slightly interacted with the fungal membrane model surface without causing significant perturbation. These results suggest Cm-p5 is not a pore-forming anti-fungal peptide and that other mechanisms of action on the membrane as some limitation of fungal nutrition or receptor-dependent transduction for depressing growth development should be explored.

Efficacy and safety of Optilume® Paclitaxel-coated urethral dilatation balloon in real-life: Experience in a Spanish Multicenter Study.

INTRODUCTION: The Optilume® Paclitaxel-coated urethral dilatation balloon is an alternative to conventional endoscopic treatments that combines mechanical dilatation with local delivery of paclitaxel. OBJECTIVE: To describe the success rate and analyze the safety of the device in real clinical practice. To evaluate possible predictors of treatment failure. MATERIALS AND METHODS: Retrospective multicenter study in patients diagnosed with urethral stricture and treated with an Optilume® balloon in routine clinical practice. Data were collected from flowmetry, questionnaires (PROM and IPSS) and cystoscopy before surgery, and 3, 6 and 12 months after the procedure, according to standard practice. Surgical success was defined as the absence of subsequent urethral manipulation and a Qmax > 10 ml/s. RESULTS: 238 patients treated with Optilume® in 12 Spanish hospitals between May 2021 and April 2024 were included in the study. Of these, 156 who had a minimum follow-up of 3 months, were analyzed. Median stricture length: 1.5 cm (0.5 - 5.3), mainly in bulbar urethra (87.7%). Of the total, 12.8% of patients had a history of pelvic radiotherapy, and 81.4% had undergone prior urethral manipulation. Postoperative complications were reported in 14.2% of the total. The treatment success rate was 73.8%, with a median follow-up of 8 months (5-12). No predictors of stricture recurrence were identified. Recurrence rates were higher in strictures located in the posterior versus anterior urethra (42.9% vs. 24.6%, p = 0.126). No significant differences were observed between patients with and without prior urethral manipulation. CONCLUSION: Treatment with Optilume® has been shown to be safe and effective in short-term routine clinical practice.

Operando Spectroelectrochemical Imaging of Concentration Fields and Tafel Kinetics in Microfluidic Electrochemical Devices.

With the development of microtechnologies for energy conversion and storage, mass transfer and micromolar concentration variations need to be measured at the microscale. These advances need to be accompanied by novel imaging techniques with the capability of achieving high spatial resolution while detecting very small signal variations (less than 0.1%). Thus, in this study, a new microscopy technique is proposed based on a combination of electrochemical impedance spectroscopy (EIS) and visible imaging spectroscopy to measure the concentration fields at the micromolar scale in operando microfluidic fuel cells (MFCs). This technique exploits EIS modulation and Fourier analysis to reduce the noise during concentration field imaging. A mass transfer model in the periodic regime is derived to validate the measurements and to estimate the Tafel kinetics and mass diffusivities during potassium permanganate reduction from only one potential measurement. The proposed imaging method and mathematical framework presented in this study can be used to study binary electrochemical reactions without gas production.

Integrative taxonomy reveals two new species of Maritrema Nicoll, 1907 (Digenea: Microphallidae Ward, 1901), parasitizing birds in the Gulf of Mexico.

Members of the genus Maritrema Nicoll, 1907 include endoparasites of aquatic birds and mammals, distributed worldwide. Adult specimens were collected from the intestines of three bird species (the great black hawks, Buteogallus urubitinga Gmelin; laughing gull, Leucophaeus atricilla Linnaeus; and the willet, Tringa semipalmata Gmelin) in three localities along the Gulf of Mexico. Photogenophores were sequenced for the large subunit (LSU) from nuclear rDNA, and the new sequences were aligned with other microphalloid sequences available in GenBank. The maximum likelihood and Bayesian inference analyses revealed three independent lineages, one corresponding to a previously described species, Maritrema corai Hernández-Orts, Pinacho-Pinacho, García-Varela & Kostadinova, 2016, and two representing two undescribed species. These two new species are described in the current study. Maritrema itzamnai n. sp. can be morphologically differentiated from its four congeneric species occurring in coastal areas of Mexico by having smaller oral (20-29 × 20-38 µm) and ventral (20-39 × 19-33 µm) suckers. In addition, Maritrema itzamnai n. sp. possess annular vitellarium instead of a horseshoe-shaped vitellarium. Maritrema kukulkanni n. sp. can be distinguished from its congeneric species reported from Mexico by possessing a larger oesophagus (44-117µm) and by having a vitellarium distributed in both the hindbody and forebody. Maritrema corai is the third species recorded in this study parasitizing the great black hawk (Buteogallus urubitinga); this represents a new host and locality record, expanding its distribution range from the Mexican Pacific Ocean to the Gulf of Mexico.

[Beyond the plaque: immunological implications of risk factors in atherosclerosis]. / Mas allá de la placa: implicaciones inmunológicas de los factores de riesgo en la aterosclerosis.

The formation of atherosclerotic plaque results from the complex interaction between modifiable and non-modifiable risk factors, through immune mechanisms that orchestrate both inflammatory and anti-inflammatory processes. Atherosclerosis often culminates in ischemic heart disease or cerebrovascular events, which are the leading causes of mortality worldwide. Currently, primary prevention focuses on controlling modifiable risk factors. Therefore, understanding the molecular mechanisms underlying the damage induced by these risk factors is essential to develop more effective treatments. This article provides a detailed review of the immunological processes underlying the initiation and progression of atheroma plaque, exploring their relationship with traditional risk factor such as smoking, diabetes mellitus, dyslipidemia, and hypertension, as well as a new potential risk factor: microbiota dysbiosis. Furthermore, the attributable risk of each factor is independently assessed, and the effectiveness of risk factor control measures is demonstrated as the best strategy to date for the regression of atherosclerosis and the prevention of its complications.

La formación de la placa aterosclerótica resulta de la compleja interacción de factores de riesgo modificables y no modificables, a través de mecanismos inmunitarios que orquestan procesos tanto inflamatorios como antiinflamatorios. La aterosclerosis a menudo culmina en enfermedades isquémicas del corazón o eventos vasculares cerebrales, que son las principales causas de mortalidad en todo el mundo. Actualmente, la prevención primaria se centra en el control de los factores de riesgo modificables. Por lo tanto, es indispensable comprender los mecanismos moleculares que subyacen al daño inducido por estos factores de riesgo, para así poder desarrollar tratamientos más eficaces. Este artículo ofrece una revisión detallada del proceso inmunitario que subyace al inicio y la progresión de la placa de ateroma, explorando su relación con factores de riesgo tradicionales como el tabaquismo, la diabetes mellitus, la dislipidemia y la hipertensión arterial, así como con un nuevo factor de riesgo potencial: la disbiosis de la microbiota. Además, se evalúa de manera independiente el riesgo atribuible a cada factor de riesgo y se demuestra la eficacia de las medidas de control de estos factores como la estrategia más efectiva hasta la fecha para la regresión de la aterosclerosis y la prevención de sus complicaciones.

Types, behaviour and therapeutic requirements of inflammatory pouch disorders: Results from the RESERVO study of GETECCU.

BACKGROUND AND AIMS: Inflammatory pouch disorders exhibit a heterogeneous clinical spectrum and therapeutic requirements have not been properly studied. METHODS: This retrospective, multicentre study included ulcerative colitis patients with ileal pouch construction and were later diagnosed with an inflammatory pouch disorder between 1995 and 2020. Classifications, behaviour and therapies applied were recorded and compared in the long-term. RESULTS: Overall, 338 patients were recruited. The most common disorders were pouchitis (n = 258, 76%), Crohn's disease of the pouch (n = 55, 16%) and cuffitis (n = 25, 7%). Pouchitis presented mainly as chronic (65.2%) and recurrent (87%) forms. Crohn's disease manifested as stricturing/penetrating in 53% of cases and perianal disease in 42%. Patients received multiple therapies: 86% antibiotics, 42% steroids, 27% immunosuppressants, 43% biologics and 27% surgery. Compared with pouchitis, Crohn's disease of the pouch was characterised by a later diagnosis (99 vs. 55 months, p < 0.001) and greater needs for immunosuppressants (OR 3.53, 1.79-6.94, p < 0.0001), biologics (OR 5.45, 2.78-10.6, p < 0.0001) and surgeries (OR 2.65, 1.43-4.89, p < 0.001). CONCLUSIONS: Chronic pouchitis is the most common pouch disorder presentation. These entities have diverse therapeutics requirements, particularly for Crohn's disease of the pouch.

The P2Y6 receptor as a potential keystone in essential hypertension.

Essential hypertension (HT) is a highly prevalent cardiovascular disease of unclear physiopathology. Pharmacological studies suggest that purinergic P2Y6 receptors (P2ry6) play important roles in cardiovascular function and may contribute to angiotensin II (AgtII) pathophysiological effects. Here, we tested the hypothesis that functional coupling between P2ry6 and AgtII receptors mediates altered vascular reactivity in HT. For this, a multipronged approach was implemented using mesenteric vascular smooth muscle cells (VSMCs) and arteries from BPN (Blood Pressure Normal) and BPH (Blood Pressure High) mice. Differential transcriptome profiling of mesenteric artery VSMCs identified P2ry6 purinergic receptor mRNA as one of the top upregulated transcripts in BPH. P2Y receptor activation elicited distinct vascular responses in mesenteric arteries from BPN and BPH mice. Accordingly, 10 µM UTP produced a contraction close to half-maximal activation in BPH arteries but no response in BPN vessels. AgtII-induced contraction was also higher in BPH mice despite having lower AgtII receptor type-1 (Agtr1) expression and was sensitive to P2ry6 modulators. Proximity Ligation Assay (PLA) and super-resolution microscopy (SRM) showed closer localization of Agtr1 and P2ry6 at/near the membrane of BPH mice. This proximal association was reduced in BPN mice, suggesting a functional role for Agtr1-P2ry6 complexes in the hypertensive phenotype. Intriguingly, BPN mice were resistant to AgtII-induced HT and showed reduced P2ry6 expression in VSMCs. Altogether, results suggest that increased functional coupling between P2ry6 and Agtr1 may contribute to enhanced vascular reactivity during HT. In this regard, blocking P2ry6 could be a potential pharmacological strategy to treat HT.

[Cross-cultural adaptation of the scale balance evaluation systems (Mini-BESTest) assessment in patients with stroke]. / Adaptación transcultural de la escala «sistema de evaluación del equilibrio¼ (Mini-BESTest) en pacientes con accidente cerebrovascular.

OBJECTIVE: The purpose of this study is to adapt cross-culturally to Chilean Spanish the assessment scale "Balance Assessment Systems (Mini-BESTest)" so that it can be applied to patients with stroke. Since stroke is a syndrome that compromises the patient's balance, an essential ability to perform activities of daily living safely, the study of different alternatives to improve the living conditions of patients is considered essential. MATERIALS AND METHODS: Observational, descriptive, cross-sectional study. The process consisted of six stages: direct translation, translation synthesis, back translation, author approval, pre-test, and final consensus. In the pretest, the adapted scale was applied to a sample of stroke patients receiving rehabilitation therapy, who were able to stand up on their own, walk, and follow simple instructions. RESULTS: The process of cross-cultural adaptation to Chilean Spanish of the Mini-BESTest evaluation scale was satisfactorily completed. Interrater reliability obtained percentages of agreement greater than 92% and all were statistically significant, which suggests an excellent level of agreement. There was a trend for subacute patients to require a greater repetition of the command. CONCLUSIONS: Mini-BESTest shows an excellent level of agreement among physiotherapists. These findings offer the possibility of continuing with the validation process of the scale. It is suggested to repeat the instructions to patients with subacute stroke.

Validity of estimated aortic pulse wave velocity measured during the 6-min walk test to predict anaerobic fitness before major non-cardiac surgery.

BACKGROUND: This study aimed to assess the efficacy of estimated preoperative aortic pulse wave velocity (AoPWV) to discriminate between low and high 6 min walk test (6MWT) distance in patients awaiting major non-cardiac surgery. METHODS: Prospective observational study in 133 patients undergoing non cardiac surgery. AoPWV and the distance walked during a 6MWT were assessed. Receiver operating characteristic (ROC) curve analysis was used to determine two different AoPWV cut-points for predicting a distance of 427 m in the 6MWT. We also calculated lower and upper AoPWV cut-points (probability ≥ 0.75) for predicting a distance of < 427 m, ≥427 m, and also 563 m in the 6MWT. RESULTS: The ROC curve analysis for the < 427 m distance revealed an area under the curve (AUC) of 0.68 (95% confidence interval 0.56-0.79) and an AUC of 0.72 (95% confidence interval 0.61-0.83) for >563 m. Patients with AoPWV > 10.97 m/s should be considered high risk, while those with <9.42 m/s can be considered low risk. CONCLUSIONS: AoPWV is a simple, non-invasive, useful clinical tool for identifying and stratifying patients awaiting major non-cardiac surgery. In situations of clinical uncertainty, additional measures should be taken to assess the risk.

Development of a new reference material for accurate measurements of lithium in Li-clays.

Currently, there are no national and international certified reference materials (CRM) in lithium clays that can make reliable and traceable lithium measurements for the International System of Units (SI). Hence, it is necessary to have references to meet the needs in terms of mining and activities that involve the use of lithium to favor the economy derived from its multiple uses and associated benefits in the exploration, exploitation, and handling of lithium ore. In this study, a candidate for reference material (RM) of Li in clays was developed and certified based on the provisions of ISO 17034:2016 and ISO Guide 35:2017. Different mass sizes of the RM (0.05, 0.1, and 0.25 g) were used to evaluate homogeneity. An isochronous study (short-term stability) was carried out in the assessment of stability, influenced by the effects of transport at different temperatures (20, 40, and 50 °C) for a determined time of 6 weeks, in addition to a classic (long-term) study for 19 weeks. The sample was treated using microwave-assisted acid digestion and Li measurements were performed using the analytical technique of Flame Atomic Absorption Spectrometry (FAAS). The CRM is homogeneous for the sample mass sizes of 0.05 and 0.1 g, and the mass fraction of w(Li) was stable in the RM for temperatures of 20, 40, and 50 °C. The determined period of validity was 3 years.

Comparative study of emotional facial expression recognition among Prader-Willi syndrome subtypes.

BACKGROUND: Prader-Willi syndrome (PWS) is a congenital disease caused by a rare and generally non-inherited genetic disorder. The inability to recognise facial expressions of emotion is an apparent social cognition deficit in people diagnosed with PWS. The main objective of the present study is to compare the ability to recognise emotional facial expression, in both non-contextualised and contextualised scenarios, among the main subtypes of PWS and a control group. METHODS: The sample consisted of 46 children divided into three groups: deletion (n = 10), maternal uniparental disomy (mUPD) (n = 13) and control (n = 23). The protocol included the Facially Expressed Emotion Labeling and the Deusto-e-Motion 1.0. RESULTS: The control group recognised facial emotions more accurately and quickly in both non-contextualised and contextualised scenarios than children with PWS, regardless of genetic subtype. Despite no differences being detected between PWS subtypes when non-contextualised scenarios were analysed, in contextualised situations, a longer reaction time was observed in children with the mUPD subtype. CONCLUSIONS: This is the first study to assess the ability to recognise emotional facial expressions in contextualised situations among PWS subtypes and a control group. The findings suggest that some of the social cognitive deficits evidenced in children with mUPD PWS may be similar to those in autism spectrum disorder.

Effects on growth, weight and body composition after CFTR modulators in children with cystic fibrosis.

BACKGROUND: Cystic Fibrosis (CF) is associated with compromised nutrition status, which is responsible for morbidity and mortality along with lung function decline. This study was designed to examine changes in anthropometric markers and body composition parameters by bioelectrical impedance analysis after CFTR modulator (CFTRm) treatment. METHODS: We compared anthropometric parameters and body composition before and after 6 and 12 months of CFTRm treatment. Results are stratified into subgroups according to the modulator used with dual therapy with lumacaftor + ivacaftor or tezacaftor + ivacaftor (LUMA/TEZ + IVA) or triple therapy with elexacaftor + tezacaftor + ivacaftor (ELE + TEZ + IVA). Body composition data are available in patients treated with ELE + TEZ + IVA. RESULTS: Two hundred and thirty-four children (55.1% male) were recruited. The median age was 13.6 years (inter-quartile range [IQR] 10.7-16.1). We can observe a statistically significant increase in the weight Z score and BMI Z score after CFTRm. In terms of changes in body composition, we observe a significant increase in fat mass (FM) expressed both in kilograms and as a percentage at 6 months (p < .05; Wilcoxon-test), with no such differences found at 12 months. We also observe a statistically significant increase in fat-free-mass (FFM), expressed in kilograms at 6 and 12 months (p < .05; Wilcoxon-test). CONCLUSION: Weight status improved and changes in body composition occurred in children after CFTRm therapy, including an increase of fat mass. Further studies are needed to confirm these changes in body composition and their impact on disease progression.

Intraoperative goal-directed hemodynamic therapy through fluid administration to optimize the stroke volume: A meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the clinical impact of optimizing stroke volume (SV) through fluid administration as part of goal-directed hemodynamic therapy (GDHT) in adult patients undergoing elective major abdominal surgery. METHODS: This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and was registered in the PROSPERO database in January 2024. The intervention was defined as intraoperative GDHT based on the optimization or maximization of SV through fluid challenges, or by using dynamic indices of fluid responsiveness, including stroke volume variation, pulse pressure variation, and plethysmography variation index compared to usual fluid management. The primary outcome was postoperative complications. Secondary outcome variables included postoperative acute kidney injury (AKI), length of stay (LOS), intraoperative fluid administration, and 30-day mortality. RESULTS: A total of 29 randomized controlled trials (RCTs) met the inclusion criteria. There were no significant differences in the incidence of postoperative complications (RR 0.89; 95% CI, 0.78-1.00), postoperative AKI (OR 0.97; (95% IC, 0.55-1.70), and mortality (OR 0.80; 95% CI, 0.50-1.29). GDHT was associated with a reduced LOS compared to usual care (SMD: -0.17 [-0.32; -0.03]). The subgroup in which hydroxyethyl starch was used for hemodynamic optimization was associated with fewer complications (RR 0.79; 95% CI, 0.65-0.94), whereas the subgroup of patients in whom crystalloids were used was associated with an increased risk of postoperative complications (RR 1.08; 95% CI, 1.04-1.12). CONCLUSIONS: In adults undergoing major surgery, goal-directed hemodynamic therapy focused on fluid-based stroke volume optimization did not reduce postoperative morbidity and mortality.

Assessment of changes in sexual function in patients undergoing endoscopic surgery for upper urinary tract lithiasis.

OBJECTIVE: To evaluate the effect of endoscopic surgery on sexual function in patients with upper urinary tract (UUT) lithiasis. MATERIAL AND METHODS: We conducted an observational, prospective, longitudinal study with a single cohort of cases undergoing ureteroscopy (URS), retrograde intrarenal surgery (RIRS), or endoscopic combined intrarenal surgery (ECIRS). Patients' sexual response was assessed with questionnaires in the 30 days prior to surgery, and at one and three months after surgery. The International Index of Erectile Function (IIEF-t) was used in male patients, and the Female Sexual Function Index (FSFI) was used in female patients. RESULTS: Seventy patients - 34 men and 36 women - completed the study. Among men, the IIEF-t did not show significant difference between baseline scores (64.1 ±â€¯7.50) and those obtained at 3 months (63.8 ±â€¯9.51), with a non-significant decrease (p = 0.054) at the first month (61.4 ±â€¯10.4). Subdomains did not worsen at 3 months, and desire (IIEF-SD) improved from 7.3 ±â€¯1.9 to 8.0 ±â€¯1.8. Among women, the FSFI-t did not change significantly after surgery: baseline score (27.3 ±â€¯4.1), 1-month score (26.8 ±â€¯3.7) and 3-month score (27.5 ±â€¯4.2). No subdomain worsened at the third month. CONCLUSION: Endoscopic surgery for UUT is a safe technique in both sexes with no negative effect on sexual function. There are no differences between the baseline IIEF-t and FSFI-t scores and those obtained at 3 months.

Soluble biomarkers for immune checkpoint inhibitor-related encephalitis: A mini-review.

Immune checkpoint inhibitors lead to effective antitumour responses but also to immune-related adverse events (irAEs), which affect the nervous system in 1-5% of patients. Encephalitis is the most frequent central nervous system irAE and is clinically relevant due to its high severity and mortality. Early diagnosis is crucial but is hampered by the broad list of alternative diagnoses, the lack of established diagnostic criteria, and the need of extensive diagnostic procedures (e.g., spinal tap, brain MRI) alongside expert neurological evaluation. Additionally, the response to corticosteroids is inconsistent, and the management of corticosteroid-refractory patients remains poorly defined. This mini-review discusses the role of various soluble biomarkers in the diagnosis, prognostication, and management of ICI-encephalitis. Neural antibodies, which are well-established biomarkers of autoimmune and paraneoplastic encephalitis, are found in only a subset of ICI-encephalitis, in which they can aid to establish the diagnosis. The most prevalent are paraneoplastic neurological syndromes (PNS)-associated antibodies, which are found almost exclusively in focal ICI-encephalitis syndromes and are associated with poor outcomes, possibly due to predominantly cytotoxic T cell involvement leading to irreversible neuronal loss. Beside antibodies, serum brain injury biomarkers such as NfL and S100B are elevated in ICI-encephalitis and, even if non-specific, may be useful as a routine test to quickly identify patients in whom neurological evaluation and second-level diagnostic procedures should be prioritized. Additionally, higher serum and CSF NfL levels have been associated with lack of treatment response in ICI-encephalitis, suggesting they may have a prognostic role. Among cytokines, elevated interleukin 6 (IL6) levels have been observed in serum and/or CSF samples of some patients with ICI-encephalitis, but the role of IL6 as a biomarker for response to IL6-directed therapies requires further investigation. Likewise, the value of other biomarkers, including T cells markers and HLA haplotypes, still needs to be evaluated in large cohorts. Overall, neural antibodies are important diagnostic and prognostic biomarkers in ICI-encephalitis, and other soluble biomarkers, especially NfL, deserve further investigation since they have a promising application in clinical practice.

Developing an accurate and efficient tool for the internalizing spectrum: A simulation study of the adaptive algorithm to the Inventory of Depression and Anxiety Symptoms II (IDAS-II).

OBJECTIVES: This research simulates an adaptive version of the IDAS-II (IDAS-CAT). METHODS: 2021 participants from both community (n = 1692) and patients (n = 329) samples completed the IDAS-II. Item response theory metric properties of the IDAS-II full test and the 20-items of the general depression (GD) scale were obtained. The efficiency and accuracy of different computerized adaptive algorithms were simulated. Different subsamples completed additional external measures in order to gather evidence of validity of the scores estimated with the simulated adaptive algorithms selected. RESULTS: Both unidimensional computerized adaptive testing algorithm selected for the GD scale and the bifactor model chosen for the full test, allow 70% reduction in the length of administration, maintaining a measurement error below 0.30 on the general and 0.50 on the specific factors. Results show high correlations of the scores estimated with the adaptive algorithms and the estimates based on the full test, as well as correlations with external criteria almost equal to those generated with the full test. CONCLUSIONS: IDAS-CAT could be a reliable and fast tool for measuring internalizing spectrum.

Dysarthria-clumsy hand syndrome and multiple sequential acute limb embolisms as a form of presentation of aortic arch embolism. / Síndrome de disartria-mano torpe y embolias agudas secuenciales múltiples de las extremidades como forma de presentación de un trombo del cayado aórtico.

INTRODUCTION: Aortic arch complex atheromatosis is a source of cerebral embolism. A percentage of lacunar infarct could be of embolic etiology, especially due to microemboli of the aortic arch. CASE REPORT: We present the case of a 63-year-old hypertensive man suffering from dysarthria-clumsy hand syndrome for a right hemispheric minor ischemic stroke. The patient developed sequential acute thromboembolism of the left lower and right upper limbs. Computed tomography angiography revealed an aortic arch thrombus. Vascular surgery was successfully performed. CONCLUSION: This case highlights the importance of considering embolic sources in lacunar syndromes, especially at the level of the aortic arch.

TITLE: Síndrome de disartria-mano torpe y embolias agudas secuenciales múltiples de las extremidades como forma de presentación de un trombo del cayado aórtico.Introducción. La ateromatosis del complejo del arco aórtico es una fuente de embolia cerebral. Un porcentaje de infartos lacunares podría ser de etiología embólica, especialmente debidos a microembolias del arco aórtico. Caso clínico. Presentamos el caso de un varón hipertenso de 63 años con síndrome de disartria-mano torpe por un ictus isquémico minor hemisférico derecho. El paciente desarrolló un tromboembolismo agudo secuencial de los miembros inferior izquierdo y superior derecho. La angiografía por tomografía computarizada reveló un trombo en el arco aórtico. La cirugía vascular se llevó a cabo con éxito. Conclusión. Este caso destaca la importancia de considerar las fuentes embólicas en los síndromes lacunares, especialmente en el arco aórtico.

Unraveling Dynamic Transcriptomic Changes in Sheep's Lactating Mammary Gland Following Escherichia coli Lipopolysaccharide Exposure.

Mammary gland infections constitute a significant challenge in dairy sheep, impacting productivity and welfare. Temporal RNA-Seq provide a valuable approach to evaluate the evolution of the host defensive molecular mechanisms triggered by mastitis caused by external agents or events. This study aimed to characterize the transcriptomic response of sheep mammary glands to an intramammary inflammation induced with an Escherichia coli lipopolysaccharide (LPS) inoculation based on RNA-Seq samples generated from milk somatic cells collected at 3 time points: pre-inoculation (0 h), and 6 h and 24 h post-LPS inoculation. The differential expression analyses between the analyzed time points were performed using 2 statistical approaches: one parametric (DESeq2) and one non-parametric (Wilcoxon rank sum test). The differentially expressed genes (DEGs) commonly identified by both approaches encompass 5,872 for the 0 h versus 6 h comparison, 4,063 for the 0 h versus 24 h comparison, and 1,034 for the 6 h versus 24 h comparison. At both 6 h and 24 h, transcriptomic data highlighted a significant decrease in the expression of genes linked to metabolic processes crucial for milk protein and lipid synthesis within the mammary gland. Concurrently, increased expression of genes related to the neutrophil attraction was observed for 6 and 24 h, with differences in gene expression between DEGs with the highest expression at 6 h, related to T cell activation, type I interferon-mediated signaling pathway, and 24 h, related to cell-cell neutrophil adhesion extravasation or epithelial cell proliferation. In summary, this study reveals how the sheep mammary gland transcriptome responds dynamically to an LPS inoculation, providing a comprehensive understanding of how gene expression patterns evolve over time and shedding light on the molecular mechanisms driving the initial defensive response of the mammary gland against potential inflammatory challenges.

Analysis of apheresis outcomes in a cohort of Chilean patients treated with autologous stem cell transplantation: A single center real-world experience.

Adequate stem cell harvesting is required for autologous hematopoietic transplantation. In deficient mobilizer patients, the collection of stem cells can be challenging because of the impossibility of achieving satisfactory CD34 cell counts with GCSF + - chemotherapy. Plerixafor is a potent and expensive drug that promotes the release of stem cells from the medullary niche to the peripheral blood and allows satisfactory harvests. We performed a retrospective analysis of 370 patients with myeloma and lymphoma harvested at our institution. 99 % of patients achieved satisfactory apheresis using Plerixafor in 45 %. Satisfactory harvests were obtained in patients mobilized with GCSF or plerixafor. In patients who used plerixafor, it was necessary to perform fewer apheresis procedures (P = 0.05). In multivariate analysis, the only factor that predicted the need for plerixafor was the presence of less than 30,000 CD34 / ul on the day of apheresis (OR 0.3. p < 0.001). Since we adopted the plerixafor protocol guided by CD34 counts, the number of patients with harvest failure has decreased. In conclusion, the rational and standardized use of plerixafor favors satisfactory harvest in patients who require autologous transplantation in South-American patients.